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1
McCoy, Maurice Anthony. "Hypomagnesaemia in ruminants : incidence, clinical biochemistry and control." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.300617.
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Ricketts, David John. "Reconfiguration and modernisation of a district general hospital clinical biochemistry service." Thesis, University of Portsmouth, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.516885.
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Context: The clinical biochemistry department at the North Middlesex University Hospital successfully won funding under the pathology modernisation initiative to automate the core laboratory in 2000. Following procurement procedures, the contract was awarded to two vendors who offered an 'islands of automation' solution as opposed to the popular fully tracked solution. The automation was installed with minor process change, but process reviews occurring in 2003 with the advent of Lean Six Sigma. Methods: The Executive War College meeting in 2003 introduced new quality management tools Lean, Six Sigma and activity-based costing, to the pathology environment. These methods were incorporated into the clinical biochemistry department and the impact of these was studied over a five year period to assess if any additional benefit could be offered when compared to the implementation of automation on its own. The later being introduced using traditional process management methodology. The process review expanded to include the specimen reception area, as delays at this point had a major impact on the performance of the automated laboratory. Results: Introduction of process management tools improved turn around time for key indicators by as much as 50%, compared to automation alone, whilst removing the variation in time to result due to the pull system of samples setting a defined time for samples to arrive for analysis. The total laboratory space for clinical biochemistry was reduced by 32% allowing for the formation of a molecular laboratory and increasing the sample reception area by 133%. The avoided build cost to extend the department for these works was £265,500 .. The value added activity post process change was scored at 17.21 % which was an international best for laboratories who had been assessed using this tool. Using benchmarking data, £1,350,000 of avoided costs, in the year 2007-8, were calculated as a result of the changes made to the service. A staff survey of the changes supported the change process with positive feedback. Automation of request forms using electronic ordering show a dramatic improvement on quality compared to the hand written forms, which had a Sigma level of between 2 and 3, improving to 4.1 Sigma when the electronic requesting went live. ii Conclusion: All process tools strongly recommend taking a baseline reading of the data before making any change, this recommendation was verified as a must in this study. The advent of automation proved very popular with the staff as it removed repetitive functions and made some manual processes obsolete, thus improving morale. The impact of automation however did not improve significantly the turnaround times, but enabled sample archiving and retrieval to be less prone to error. The study found that by aligning the work processes in specimen reception to those processes in the clinical biochemistry department, this created the major benefit. Therefore a strong recommendation is that process managing of specimen reception areas is a must before undertaking any purchase of automated systems. Any delay in the laboratory is minor compared to the potential for delay that poor process can give in the pre-analytical phase. Benchmarking allowed a year on year comparison to be made, but the study highlighted the need to drill into the data and understand the service change when looking at cost per unit. This allowed the return on investment for the new technology to be assessed, in this study the return was realised in eighteen months. Benchmarking highlighted that the quality improvement that new assays provided to patient care impacted marginally on the test volumes but had a 15% impact on the non-pay budget. The use of activity-based costing compliments both Lean and Six Sigma by allowing the true cost of the work to be assessed with both value adding activity and avoided cost, the money not spent as opposed to direct cost cuts, to be calculated. The activitybased costing allowed staff to focus their jobs onto those tasks which were appropriate to their grade and identify and reduce those tasks which were not, improving job satisfaction and morale. Avoiding cost through good process change has a positive impact on both the patient and the budget, which cannot be achieved by cost improvement programmes based on a percentage change in the money allocated to the department.
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Baral, Randolph Matias. "Feline clinical biochemistry: new paradigms for interpreting results and comparing analysers." Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/13616.
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The overall aim of this project was to provide an evidence-based means for comparison of feline biochemical analytes to increase the ability to distinguish between sickness and health of cats and enhance veterinarians’ clinical decision-making. Chapter 1, the literature review, has two sections; the first outlines how traditional, population-based reference intervals are generated, followed by a description of subject-based reference limits that are being implemented in human clinical pathology. The second section describes the current approaches for method comparison of analyte values obtained from clinical pathology analysers. Since in-house biochemistry analysers are unable to be calibrated by end-users (such as veterinary hospital staff), any inherent bias in the determination of analyte values cannot be corrected (as it can for commercial laboratory analysers). Bias of in-house biochemistry equipment is well recognised, and Chapter 2 provides the first concurrent assessment of multiple analysers, using a grading system that was devised to assess constant bias and degree of proportional bias. It conclusively demonstrates that results from in-house analysers should not be directly compared to results from others, nor to those determined by commercial laboratory analysers. A potential solution may lie in the ability of correctly generated reference intervals to account for these analysers’ inherent bias. Chapter 3 demonstrates that reference intervals provided by in-house biochemistry analyser manufacturers as well as a commercial laboratory do not appear to account for the biases for all analytes and consequently may be inaccurate for local hospital population feline populations. It is now recognised in human clinical pathology, that for many biochemical analytes, traditional population-based reference intervals have limitations, as a significant change in an individual’s analyte concentration within the reference limits may still be an important medical indicator for that individual. Conversely, values outside these limits are not always clinically important for an individual. For appropriate analytes, subject-based reference values, often called ‘reference change values’ are used; these are determined from biological variation data which reflect the inherent physiological variation of these analytes within and between individuals. Chapter 4 defines the biological variation of clinical biochemical analytes in cats, determining which analytes are suited for traditional reference interval interpretation or would be better interpreted with reference change values. The high individuality found for most analytes indicate that subject-based reference values (which are determined and documented) should be used to assess feline plasma biochemistry samples. The generation of biological variation data enabled assessment of precision (repeatability) of in-house analysers in relation to this data, the recognised technique for human clinical pathology. These results are documented in Chapter 5 which found that the precision of results from these in-house and commercial laboratory analysers were generally acceptable, so large differences between repeated results from the same patient are more likely to be due to biological changes rather than analyser variation. Chapter 6 assesses the total error (based on a combination of bias and precision) of values from three in-house biochemistry analysers in relation to a commercial laboratory analyser for feline plasma using multiple quality specifications. This study required an adaptation of method comparison techniques used for human clinical pathology so that these techniques could be used with equipment that is unable to be calibrated. This chapter concludes that in-house analysers provide acceptable results and few clinical decisions would be different based on the results determined by three in-house analysers compared to those determined by the commercial laboratory. The last chapter is a discussion on the impact this research will have on veterinary practice, the projects’ limitations and future directions for this avenue of research.
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Jones, R. M. L. "Studies of proteolytic fragments of clinical interest." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354831.
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Leslie, Carolyn Elizabeth. "Studies on clinical isolates of Aspergillus Fumigatus." Thesis, Heriot-Watt University, 1985. http://hdl.handle.net/10399/1653.
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McLellan, Antony Christopher. "The glyoxalase system in clinical diabetes mellitus." Thesis, University of Essex, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333336.
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Rowan, Andrew D. "The pineapple proteinases : characterization and clinical use." Thesis, Open University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.290495.
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John, W. G. "Glycated proteins : Their measurement and clinical applications." Thesis, De Montfort University, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376968.
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Smellie, W. Stuart A. "Clinical applications of an assay for intact proinsulin." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308805.
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O'Harte, Finbarr Paul Mary. "Clinical biochemistry of cobalt deficiency in sheep with particular reference to methylmalonic acid." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336127.
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Miller, Julie. "Antibiotic-modifying enzymes and their use in clinical analysis." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302782.
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Petty, Richard Kenneth Holdsworth. "A clinical study of mitochondrial myopathies." Thesis, University of Newcastle Upon Tyne, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329160.
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Bradley, Victoria. "Determining sub-arachnoid haemorrhage in the clinical biochemistry laboratory utilising cerebrospinal fluid samples." Thesis, University of Portsmouth, 2013. https://researchportal.port.ac.uk/portal/en/theses/determining-subarachnoid-haemorrhage-in-the-clinical-biochemistry-laboratory-utilising-cerebrospinal-fluid-samples(b68c29d7-afbe-4e20-9c26-a293df652963).html.
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Introduction: Sub-arachnoid haemorrhage (SAH) occurs when cerebral artery ruptures and blood leaks out into the sub-arachnoid space. This is often a catastrophic event for the individual and morbidity and mortality rates are significantly influenced by early intervention. This makes the role of the clinical biochemistry laboratory in early diagnosis vitally important, as delays in diagnosis can have a major clinical impact. The cerebrospinal fluid (CSF) of healthy individuals is optically clear. It has, however, been recognised for over a century that it can become coloured (xanthochromia) following a cerebrovascular incident such as a SAH. This has made the main role of the clinical biochemistry laboratory in SAH diagnosis that of detecting xanthochromia in the CSF. The majority of laboratories which offer a xanthochromia screening service use the national guidelines that are based upon ultra-violet scanning spectrophotometry (350 nm to 600 nm). This analytical technique is not without its problems: it is subjective, has a possibility of inter-operator variability and due to the specialised nature of the test can take many hours or even days for a result to be issued. This project aimed to improve the current laboratory service by investigating: turnaround times, users opinions of the current service and potential alternative analytical methods. Methods: An audit of the current analytical provision was used to assess its effectiveness and in order to elucidate the service users’ perception. This was effected by a questionnaire that was distributed to service users across three different NHS Trusts in England and Wales. In an attempt to improve the laboratory service, alternatives to scanning spectrophotometry were investigated. These were selected through consideration of the nature of SAH i.e. blood is released into the subarachnoid space and the brain is damaged. Laboratory analysis therefore needed to focus on detecting the presence of blood and/or its breakdown products, any change in CSF constituents that arise as a direct consequence of blood being introduced in to the subarachnoid space or a specific analyte which would only be present if brain damage occurred. Investigation of current research into subarachnoid haemorrhage identified the following analytes as potential alternatives: CSF diazo bilirubin, CSF Ferritin, CSF protein S100 and serum protein S100. Results: The audit revealed the average turnaround time for reporting xanthochromia results to be 26 hours, with almost 20% of samples being reported as equivocal. The service user’s questionnaire revealed a general lack of awareness of current United Kingdom National External Quality Assurance Scheme (UKNEQAS) guidelines for the ‘Analysis of cerebrospinal fluid for bilirubin in suspected Subarachnoid haemorrhage’ and a lack of understanding regarding the timing of lumbar punctures. Additionally, one third of users felt that the turnaround time for results was inadequate. CSF protein S100 was found to be unsuitable due to the difficulty in achieving a suitable balance between sensitivity and specificity; at a cut-off of 0.40 μg/l sensitivity is 80% and specificity is 4%, at a cut-off of 1.60 μg/l sensitivity is 40% and specificity is 94%. Serum protein S100 was found to be unsuitable due to the difficulty in achieving a suitable balance between sensitivity and specificity at appropriate cut-offs (66 % and 73%, respectively, at a cut-off of 0.09 μg/l). When the CSF diazo bilirubin and CSF ferritin were compared to current laboratory practises using pre-defined criteria then CSF diazo bilirubin was found to be the analyte of choice to base new guidelines upon. CSF diazo bilirubin was then used as an initial ‘rule-out’ step in a new set of guidelines for the determination of SAH utilising CSF analysis. Conclusion: The new guidelines employ CSF diazo bilirubin analysis as a ‘rule-out’ step with all samples that are above the cut-off (300 nmol/l) being processed through the UKNEQAS guidelines. In order for the guidelines to be introduced and accepted, local training and education programmes for laboratory and clinical staff will need to be developed and implemented and they will need to be disseminated through publication of articles in journals relevant to both the clinical biochemistry community and requesting clinicians.
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Rocha, Susana Maria Santos. "Biological Aspects Underlying the Clinical Outcome of Hereditary Spherocytosis." Doctoral thesis, Faculdade de Farmácia da Universidade do Porto, 2009. http://hdl.handle.net/10216/63809.
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Rocha, Susana Maria Santos. "Biological Aspects Underlying the Clinical Outcome of Hereditary Spherocytosis." Tese, Faculdade de Farmácia da Universidade do Porto, 2009. http://hdl.handle.net/10216/63809.
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Melton, R. G. "Physiological properties of carboxypeptidase G2 : Polymer conjugates and their clinical application." Thesis, Birmingham City University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374679.
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Donoghue, Alan M. "Acute heat illness in underground miners : the clinical state, haematology, biochemistry and risk factors." Thesis, Curtin University, 2000. http://hdl.handle.net/20.500.11937/2196.
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Objectives - To examine the incidence, clinical state, personal risk factors, haematology and biochemistry of heat exhaustion cases occurring at a deep underground metalliferous mine. To describe the underground and surface thermal conditions associated with the occurrence of heat exhaustion cases.Methods - A one-year prospective case-series of acute heat exhaustion cases was undertaken at a deep underground metalliferous mine in tropical and Australia. A case-control study of body mass index (BMI) and maximal oxygen uptake (VO(subscript)2max) in heat exhaustion was also undertaken. A history was obtained using a structured questionnaire. Pulse rate, blood pressure, tympanic temperature and urine specific gravity were measured before treatment. Venous blood was analysed for haematological and biochemical parameters, during the acute presentation and after recovery. BMI and VO(subscript)2max were measured after recovery and in a group of controls. Psychrometric wet bulb temperature, dry bulb temperature and air velocity were measured at the underground sites where heat exhaustion had occurred. Air cooling power and psychrometric wet bulb globe temperatures were derived. Surface 24-hour mean wet bulb and dry bulb temperatures were recorded. Surface 24-hour mean wet bulb globe temperatures were derived.Results - 106 cases were studied in the case series. The incidence of heat exhaustion during the year was 43.0 cases per million man-hours. In February it was 147 cases per million man-hours. The incidence rate ratio for mines operating below 1200m compared to those operating above 1200m was 3.17. Mean estimated fluid intake was 0.64 litres/hour (SD 0.29, Range 0.08-1.50).The following were raised on acute presentation compared to recovery (P value, % of acute cases above the normal clinical range): neutrophils (P<0.001, 36%), anion gap (P<0.001, 63%), urea (P<0.001, 21%), creatinine (P<0.001, 30%), glucose (P<0.001, 15%), serum osmolality (P=0.030, 71%), creatine kinase (P=0.002, 45%), aspartate transaminase (P<0.001, 14%), lactate dehydrogenase (P<0.001, 9.5%), and ferritin (P<0.001, 26%). The following were depressed on acute presentation compared to recovery (P value, % of acute cases below the normal clinical range): eosinophils (P=0.003, 3 8%) and bicarbonate (P=0.0 11, 32%). Urea and creatinine were significantly raised in miners with heat cramps compared to miners without this symptom (P<0.001), while there was no significant difference in sodium concentration (P=0.384).Mean psychrometric wet bulb temperature was 29.0 degrees celsius (SD 2.2, Range 21.0-34.0). Mean dry bulb temperature was 37.4 degrees celsius (SD 2.4, Range 31.0-43.0). Mean air velocity was 0.54 m/s (SD 0.57, Range 0.00-4.00). Mean air cooling power was 148 W/m(subscript)2 (SD 49, Range 33-290). Mean psychrometric wet bulb globe temperature was 31.5 degrees celsius (SD 2.0, Range 25.2-35.3). Few cases (<5%) occurred at a psychrometric wet bulb temperature <25.0'C, dry bulb temperature <33.8'C, air velocity >1.56 m/s, air cooling power >248 W/m(subscript)2, or psychrometric wet bulb globe temperature <28.5 degrees Celsius.The three surface temperature variables were significantly higher on those days on which heat exhaustion occurred compared to those days on which it did not occur (P<0.001). The relative risk of heat exhaustion on days when the surface 24-hour mean wet bulb globe temperature was in the range 26.0-28.0 degrees celsius was 4.82 (95% CI 2.12-10.96).65 cases of heat exhaustion and 119 controls were studied in the case-control study. Heat exhaustion cases had a significantly higher BMI than controls (P=0.006). The odds ratios increased with BMI. For a BMI of 32.00-36.99, compared to a BMI of less than 27.00 the odds ratio was 3.63 (95% confidence interval 1.42-9.36). V0(subscript)2max was not significantly lower in cases than controls. The odds ratios for heat exhaustion increased with decreasing VO(subscript)2max, but not significantly. The sample size provided 80% power of detecting an odds ratio of 2.5 or greater.Conclusion - Heat exhaustion in underground miners is associated with hypohydration, neutrophil leukocytosis, eosinopenia, metabolic acidosis, increased glucose and ferritin, and a mild rise in CK, AST and LD. Heat cramps are associated with hypohydration but not hyponatraemia. The incidence of heat exhaustion increases during summer and at depth. An increased fluid intake is required. Heat exhaustion would be unlikely to occur if ventilation and refrigeration achieved air cooling power >250W/m2 at all underground work sites. Surface temperature data could be used at this mine to warn miners about the risk of heat exhaustion. Deep underground miners should be advised to maintain a BMI of 24-27.
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Donoghue, Alan M. "Acute heat illness in underground miners : the clinical state, haematology, biochemistry and risk factors." Curtin University of Technology, School of Public Health, 2000. http://espace.library.curtin.edu.au:80/R/?func=dbin-jump-full&object_id=11757.
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Objectives - To examine the incidence, clinical state, personal risk factors, haematology and biochemistry of heat exhaustion cases occurring at a deep underground metalliferous mine. To describe the underground and surface thermal conditions associated with the occurrence of heat exhaustion cases.Methods - A one-year prospective case-series of acute heat exhaustion cases was undertaken at a deep underground metalliferous mine in tropical and Australia. A case-control study of body mass index (BMI) and maximal oxygen uptake (VO(subscript)2max) in heat exhaustion was also undertaken. A history was obtained using a structured questionnaire. Pulse rate, blood pressure, tympanic temperature and urine specific gravity were measured before treatment. Venous blood was analysed for haematological and biochemical parameters, during the acute presentation and after recovery. BMI and VO(subscript)2max were measured after recovery and in a group of controls. Psychrometric wet bulb temperature, dry bulb temperature and air velocity were measured at the underground sites where heat exhaustion had occurred. Air cooling power and psychrometric wet bulb globe temperatures were derived. Surface 24-hour mean wet bulb and dry bulb temperatures were recorded. Surface 24-hour mean wet bulb globe temperatures were derived.Results - 106 cases were studied in the case series. The incidence of heat exhaustion during the year was 43.0 cases per million man-hours. In February it was 147 cases per million man-hours. The incidence rate ratio for mines operating below 1200m compared to those operating above 1200m was 3.17. Mean estimated fluid intake was 0.64 litres/hour (SD 0.29, Range 0.08-1.50).The following were raised on acute presentation compared to recovery (P value, % of acute cases above the normal clinical range): neutrophils (P<0.001, 36%), anion gap (P<0.001, 63%), urea (P<0.001, ++21%), creatinine (P<0.001, 30%), glucose (P<0.001, 15%), serum osmolality (P=0.030, 71%), creatine kinase (P=0.002, 45%), aspartate transaminase (P<0.001, 14%), lactate dehydrogenase (P<0.001, 9.5%), and ferritin (P<0.001, 26%). The following were depressed on acute presentation compared to recovery (P value, % of acute cases below the normal clinical range): eosinophils (P=0.003, 3 8%) and bicarbonate (P=0.0 11, 32%). Urea and creatinine were significantly raised in miners with heat cramps compared to miners without this symptom (P<0.001), while there was no significant difference in sodium concentration (P=0.384).Mean psychrometric wet bulb temperature was 29.0 degrees celsius (SD 2.2, Range 21.0-34.0). Mean dry bulb temperature was 37.4 degrees celsius (SD 2.4, Range 31.0-43.0). Mean air velocity was 0.54 m/s (SD 0.57, Range 0.00-4.00). Mean air cooling power was 148 W/m(subscript)2 (SD 49, Range 33-290). Mean psychrometric wet bulb globe temperature was 31.5 degrees celsius (SD 2.0, Range 25.2-35.3). Few cases (<5%) occurred at a psychrometric wet bulb temperature <25.0'C, dry bulb temperature <33.8'C, air velocity >1.56 m/s, air cooling power >248 W/m(subscript)2, or psychrometric wet bulb globe temperature <28.5 degrees Celsius.The three surface temperature variables were significantly higher on those days on which heat exhaustion occurred compared to those days on which it did not occur (P<0.001). The relative risk of heat exhaustion on days when the surface 24-hour mean wet bulb globe temperature was in the range 26.0-28.0 degrees celsius was 4.82 (95% CI 2.12-10.96).65 cases of heat exhaustion and 119 controls were studied in the case-control study. Heat exhaustion cases had a significantly higher BMI than controls (P=0.006). The odds ratios increased with BMI. For a BMI of 32.00-36.99, compared to a BMI of less than 27.00 the odds ratio was 3.63 (95% ++
confidence interval 1.42-9.36). V0(subscript)2max was not significantly lower in cases than controls. The odds ratios for heat exhaustion increased with decreasing VO(subscript)2max, but not significantly. The sample size provided 80% power of detecting an odds ratio of 2.5 or greater.Conclusion - Heat exhaustion in underground miners is associated with hypohydration, neutrophil leukocytosis, eosinopenia, metabolic acidosis, increased glucose and ferritin, and a mild rise in CK, AST and LD. Heat cramps are associated with hypohydration but not hyponatraemia. The incidence of heat exhaustion increases during summer and at depth. An increased fluid intake is required. Heat exhaustion would be unlikely to occur if ventilation and refrigeration achieved air cooling power >250W/m2 at all underground work sites. Surface temperature data could be used at this mine to warn miners about the risk of heat exhaustion. Deep underground miners should be advised to maintain a BMI of 24-27.
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Fry, Ian David Robert. "Oxalate analysis and its applications." Thesis, University of Surrey, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292296.
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Cook, Adrian Gerald. "Bispecific monoclonal antibodies : their potential advantages in immunoassay systems." Thesis, University of Southampton, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295751.
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Raffan, Eleanor. "Rare syndromes of perturbed insulin action and production : application of exome sequencing and characterisation of their cellular phenotypes." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648236.
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Wycherley, Darren. "The application of capillary electrophoresis and mass spectrometry to clinical and environmental problems." Thesis, Open University, 1996. http://oro.open.ac.uk/19806/.
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Using capillary electrophoresis (CE) as a separation technique has allowed analytes, previously difficult to separate by standard methods because they did not conform to requirements for GC or HPLC, to be separated with speed and great efficiency. The only requirements for CE analysis are that the sample is soluble in a liquid matrix and that analytes are present as positive or negative ions whilst in this matrix. This technique has been used here to analyse both clinical and environmental samples, some as cations and others boron-containing complexes as anions. Samples were analysed using a combination of CE alone, mass spectrometry alone and also coupled capillary electrophoresis/electrospray mass spectrometry (CE/ES). Clinically orientated analytes, dipeptides in urine and acylcamitines from blood spots were examined and peaks detected directly via uv absorbance. The environmental samples analysed included those which contained chromophoric or non-chromophoric herbicides as well as those containing diisocyanates. Analytes were either detected in their native form as with the dipeptides and chromophoric herbicides, or more typically after derivatisation to improve their absorbance characteristics. The exception was the non-chromophoric herbicides which were detected via indirect uv. CE was an experimental technique for the analysis of all these compounds, except for the dipeptides, all the others having originally been analysed using HPLC or GC methods. In each case an evaluation of the CE method was performed to determine the suitability of the method. By analysing standards in each case, it was possible to confirm that the technique was suitable for qualitative and quantitative analysis of each class of compound. CE proved to be a viable technique for the separation of all classes of compound dealt with in this thesis. However the method could not be relied upon to confirm the identity of these analytes by their migration time alone. To identify the analytes, experiments were carried out to couple CE with a mass spectrometer. Two techniques of mass spectrometry were used within this thesis, fast atom bombardment and electrospray but only electrospray ionisation mass spectrometry was used to couple to capillary electrophoresis and was the only mass spectrometric technique used to analyse clinical and environmental samples. CE instruments were successfully coupled to an electrospray mass spectrometer which then became the detector. Mass/charge ratio measurements were obtained for each analyte used and these allowed the unambiguous identification of each analyte. Other work involved using CE, ES and FAI3 mass spectrometry, to develop a new technique to detect diol containing compounds. This involved complexing the diol with a boron-containing acid to produce an anion which could then be detected using ES and FAB mass spectrometric methods. This work was viewed as a possible technique for the detection of diol containing lipids found within some body fluids.
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Harvey, Roderick David. "Studies on the clinical utility of the measurement of serum thyroglobulin in man." Thesis, University of Aberdeen, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.292621.
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Thyroglobulin (Tg) was extracted from human thyroid, purified by gel column chromatography, identified by its thyroxine content, and quantitated by accurate protein determination. The material was used for standards and a radioiodinated tracer in a radioimmmunoassay for serum thryoglobulin, and in an ELISA assay for thyroglobulin autoantibodies. The radioimmunoassay utilised a polyclonal rabbit anti-human-Tg antibody, and separation of bound and free fractions was achieved by a precipitating antiserum and centrifugation. Assay sensitivity was 1ug/1, and the inter and intra-assay CV 16-23% and 6-16% respectively. Thyroglobulin autoantibodies were measured by both radioimmunoassay and ELISA methods. Thyroglobulin autoantibodies at high titre caused interference in the Tg assay, and both falsely low and elevated results occurred depending on the assay conditions. Studies on the interference problem are described. Serum, Tg in newly presenting patients with thyrotoxic Graves' disease was usually elevated, but not in all individuals. No relationship with serum thyroid hormone levels was found. Serum Tg in patients with hypothyroidism was generally within the normal range. TSH dependent Tg release was demonstrated following acute withdrawal of triiodothyronine in a normal subject. The measurement of serum Tg as a marker for relapse following treatment of thyrotoxicosis with antithyroid drugs was assessed. Although a small group with a high probability of relapse could be identified in whom Tg levels exceeded 60ug/1, the test was generally insufficiently accurate to be clinically useful. Similarly serum Tg measurement following radioiodine treatment of thyrotoxicosis proved of no value in predicting the onset of subsequent hypothyroidism, although a characteristic biphasic release was observed. Serum Tg measurement did prove a discriminatory marker for recurrence of differentiated thyroid carcinoma in patients treated by thyroid lobectomy and suppressive thyroxine, despite the presence of potentially functioning residual normal thyroid tissue. The accuracy of the test was compared in patients treated in this way, and a group treated by more radical thyroid ablation.
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Adbeish, Idris S. "Clinical biochemistry of lipoproteins : altered expression of LDL-R and PDGF-A genes in hyperlipidaemia." Thesis, University of Reading, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307805.
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Moreton, Jennifer Anne. "The application of inductively coupled plasma source mass spectrometry to clinical biochemistry and environmental science." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242920.
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Woods, Nicole Natasha Brooks Lee R. "The role of biomedical knowledge in medical diagnosis by learners." *McMaster only, 2005.
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Hunt, C. "The clinical and biochemical effects of vitamin C supplementation in acutely ill, hospitalised elderly patients." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384613.
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Wabomba, Mukire John. "Signal and Image Processing Techniques for Environmental and Clinical Applications of Infrared Spectroscopy." Ohio University / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1040131767.
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Silva, Sueli de Oliveira. "Oxidação de melatonina de formação de N1-acetil-N2-formil-5-metoxiquinuramina: possíveis efeitos biológicos." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-27012009-134118/.
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Em trabalho anterior verificamos que neutrófilos oxidam o hormônio melatonina a N1-acetil-N2-formil-5-metoxiquinuramina (AFMK), numa reação catalisada por mieloperoxidase e dependente de ânion superóxido. Neste trabalho acompanhamos a cinética de formação de AFMK e de seu produto de deformilação N1-acetil-5-metoxiquinuramina (AMK) quando neutrófilos foram ativados por diferentes estímulos. No sentido de obtermos informações sobre a relevância biológica destas reações, avaliamos o efeito de melatonina, AFMK e AMK sobre a formação de HOCl, sobre a liberação de citocinas pró-inflamatórias (TNF-α e IL-8) e sobre a apoptose de neutrófilos. Uma forte inibição da liberação de HOCl foi observada em concentrações de melatonina igual ou superior a 0,05 mM. Embora menos efetivo, AMK também inibiu a formação de HOCl, enquanto AFMK não teve efeito. Adicionalmente mostramos que todos estes compostos inibiram a produção de TNF-α e IL-8 por neutrófilos ativados e que AFMK foi o mais potente deles. Por exemplo, enquanto 1µM de AFMK inibiu eficientemente a liberação de TNF-α, efeito similar foi obtido com melatonina apenas a partir de 1mM. O mesmo padrão de resposta foi observado na morte celular. AFMK e AMK (1mM), mas não melatonina, inibiram significativamente (aproximadamente 25%) a morte celular de neutrófilos. Nossos dados sugerem que neutrófilos são um alvo importante para AFMK e que a rota de metabolização da melatonina pode ser útil no controle da intensidade do processo inflamatório através do consumo de ERO, controle da liberação de citocinas e da sobrevida dos neutrófilos. Este conjunto de dados associados com o fato de que células mononucleares ativadas sintetizam melatonina e que o foco inflamatório é uma fonte de espécies reativas de oxigênio (ERO), levou-nos a verificar se a oxidação de melatonina ocorreria in vivo em situações inflamatórias. Para isso, analisamos amostras de liquor de pacientes com meningite viral. AFMK foi detectado em 16 das 20 amostras de liquor de pacientes com meningite viral e em nenhuma das 8 amostras controle. Das 16 amostras nas quais AFMK foi detectado, ele pôde ser quantificado em 6 (concentrações variando de 50 a 500 nM). Adicionalmente analisamos a correlação entre a presença de AFMK com alguns parâmetros inflamatórios como: celularidade, concentração de proteínas totais, TNF-α, IL-8 e IL-1β. Verificamos que todos estes parâmetros diminuíram nas amostras de liquor onde a concentração de AFMK era maior. Em conjunto, nossos resultados mostram que pelo menos parte dos efeitos antiinflamatórios descritos para melatonina pode ser originado da ação de seus produtos de oxidação. Nossos resultados contribuem significativamente para a compreensão do papel biológico da melatonina e seus produtos de oxidação na imunomodulação durante a inflamação.In a previous study we described that activated neutrophils are able to oxidize the pineal hormone melatonin to N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) in a reaction dependent on myeloperoxidase and superoxide anion. Here we followed the formation of AFMK and its deformylated product N1-acetil-5-metoxiquinuramina (AMK) when neutrophils were activated by different stimuli. The biological significance of this reaction has been one of our research interests, therefore we study the effect of melatonin, AFMK and AMK on the HOCl formation, on the release of pro-inflammatory cytokines (TNFα- and IL-8) and on the apoptosis process. Melatonin caused an almost complete inhibition of HOCl formation at concentrations up to 0.05 mM. Although less effective, AMK also inhibited HOCl formation, while AFMK had no effect. Additionally all the compounds assayed efficiently inhibited the production of TNF-α and IL-8 by activated neutrophils. Moreover, the inhibitory activity of AFMK was stronger than that of melatonin and could be observed already at 1µM. A significant inhibition of neutrophil death (approximately 25 %) was triggered by AFMK and AMK (1 mM) but not by melatonin. Our data suggest that neutrophils are an important target for AFMK and that the route of melatonin metabolism may be useful in controlling the intensity of the inflammatory process by the consumption of reactive oxygen species, control of cytokine production and neutrophils life span. These findings, associated with the efficient synthesis of melatonin by activated-mononuclear cells and the presence of reactive oxygen species in the inflammatory focus, led us to verify if inflammation triggers the oxidation of melatonin in vivo. In this way we analyzed the cerebrospinal fluid (CSF) of patients with meningitis. AFMK was detected in 16 CSF from 20 samples of patients with viral meningitis and in none of 8 control samples. From the 16 samples in which AFMK was detected, it was quantified in 6 (at the concentration range of 50 500 nM). We also analyzed the correlation between the presences of AFMK with some inflammatory parameters like: cellularity and concentration of total proteins, TNF-α, IL-8 and IL-1β. We verify that all these parameters were decreased in samples in which AFMK was in higher concentrations. Our results show that, at least part of the antiinflammatory effects described for melatonin is indeed caused by its oxidation product. These findings add a new insight in the comprehension of the biological role of melatonin and its oxidation products in immunomodulation and during inflammation.
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Bani, Rashaid Ayat H. "Clinical and Forensic Biomarkers in Human Hair." Ohio University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1407256298.
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Ramsay, Amanda. "The role of high density lipoprotein subspecies in the control of lipoprotein metabolism in relation to clinical disorders." Thesis, University of Aberdeen, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338398.
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In order to examine the role of HDL in the control of lipoprotein metabolism, the levels of HDL subspecies, other lipoproteins, apolipoproteins and fatty acids were measured in four groups of subjects presenting clinical disorders which were possibly related to their lipid profiles. (1) A monoclonal antibody was raised against apolipoprotein A-I allowing the development of an ELISA. (2) In a comparison of 43 angina patients and 61 healthy control subjects, the levels of HDL2, HDL2b and HDL2a were lower in the angina group and this was compensated for by an increase in levels of HDL3b and HDL3c. Plasma triglyceride and VLDL-cholesterol concentrations were higher in the angina group possibly giving rise to the low levels of HDL2 subspecies by their effect on HDL particle conversion. The subspecies HDL2b has been implicated in reverse cholesterol transport. (3) In a study of nine hypertriglyceridaemic subjects and 23 healthy controls there was a lower concentration of HDL2b, HDL2a and LDL-cholesterol and a higher concentration of HDL3b and VLDL-cholesterol in the hypertriglyceridaemic group. This was possibly indicative of reduced LPL activity. The resulting high levels of plasma triglyceride are known to favour the conversion of HDL2 to HDL3. These results suggest that hypertriglyceridaemic patients have a reduced ability to eliminate surplus cholesterol by reverse cholesterol transport and would therefore be at increased risk of atherosclerosis. (4) In a study of 17 violent offenders and 25 control subjects, the HDL subfraction HDL3a was higher in the offenders. The levels of the apolipoproteins E and A-IV were higher in the offender group perhaps having a role in the repair of damaged nervous tissue.
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Costa, Hugo Leonardo Riani [UNESP]. "Caracterização das alterações laboratoriais e histopatológicas associadas à obstrução uretral experimentalmente induzida em ratos." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/89277.
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A obstrução uretral é uma emergência clínica freqüente no atendimento de pequenos animais. Com a evolução do quadro, ocorre parada na filtração glomerular e, consequentemente, desenvolvem-se várias alterações nos equilíbrios hídrico, eletrolítico e ácido-básico, além do acúmulo de metabólitos nitrogenados e toxinas orgânicas. Podem ocorrer modificações histopatológicas nos rins e na bexiga. Objetivou-se, neste estudo, caracterizar prospectivamente as alterações laboratoriais e histopatológicas de ratos apresentando obstrução uretral. Para tanto, foram utilizados 21 ratos Wistar com obstrução uretral induzida. Foram realizados os seguintes exames: hemogasometria venosa e determinação dos níveis de uréia, creatinina, sódio, potássio, cloreto, cálcio e fósforo. As avaliações foram repetidas a cada 8 horas durante 24 horas. Após esse período os animais foram eutanasiados e as bexigas e os rins enviados para exame histopatológico. Entre os exames bioquímicos, foram observadas elevações estatisticamente significativas nos níveis de uréia, creatinina, fósforo, magnésio e potássio, e diminuição nos níveis de cloreto. Com relação à hemogasometria, houve diferença estatisticamente significativa entre os valores de pH, PO2, PCO2, excesso de base, saturação de oxigênio e lactato. O exame histopatológico renal revelou a presença de alterações tubulares e glomerulares, enquanto a análise histopatológica das bexigas demonstrou a presença de hemorragia, separação de fibras musculares e infiltrado inflamatório. Conclui-se que a obstrução uretral provoca alterações que podem ser detectadas nos exames laboratoriais, sendo as mesmas agravadas no decorrer do tempo. Além disso, a persistência durante 24 horas é capaz de levar a alterações morfológicas no trato urinário.
Urethral obstruction is a frequent emergency in Veterinary clinics. The persistent urethral obstruction leads to blockage of renal filtration, resulting in several alterations in fluid, electrolyte and acid-base balance, besides the accumulation of nitrogenous metabolic products and organic toxins. Histopathological changes may occur in the kidneys and urinary bladder. Thus, this study aimed to prospectively characterize renal and vesical histopathological alterations in rats due to urethral obstruction. Twenty-one male Wistar rats (Rattus norvegicus) with experimental urethral obstruction were included in the study. Venous gasometry and determination of urea, creatinine, sodium, potassium, chloride, calcium and phosporus were performed. The avaliations were repeted each 8 hours during 24 hours. After that period, the animals were euthanatized for the collection of kidneys and bladder fragments to the histopathological exam. Biochemistry exams demonstrated statiscally significant elevations for the levels of urea, creatinine, phosporus, magnesium and potassium, and a decrease for the levels of chloride. Results of gasometry also demonstrated statiscally significant changes for pH, PO2, PCO2, base excess, oxygen saturation and lactate values. Histopathology analysis revealed kidney alterations in tubular and glomerular elements. The most important alterations found in urinary bladders were transmural hemorrhage, separation of muscle fibers and neutrophilic inflammatory infiltrate. Complete urethral obstruction induces important changes that can be detected by laboratorial exams, and the alterations worsen with the course of time. Besides that, the persistent obstruction during 24 hours is able to cause morphological changes in the kidneys and urinary bladder, which can be detected using histopathological exam.
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Novais, Adriana Alonso [UNESP]. "Prevalência dos antígenos eritrocitários caninos em cães domésticos (Canis familiaris) e investigação dos parâmetros hematológicos e da ocorrência de antígenos eritrocitários em lobos-guará (Chrysocyon brachyurus) e cachorros-do-mato (Cerdocyon thos) criados no Brasil." Universidade Estadual Paulista (UNESP), 2003. http://hdl.handle.net/11449/103773.
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O propósito desse estudo foi verificar a prevalência dos antígenos eritrocitários caninos em cães domésticos criados no Brasil e compará-la com aquela descrita na literatura consultada, para cães oriundos de outros países. Além disso, verificar os valores sangüíneos normais e a ocorrência dos antígenos eritrocitários caninos em lobos-guará e cachorros-do-mato, na expectativa de adicionar novos dados sobre valores sangüíneos de referência e investigar as relações filogenéticas entre os caninos silvestres e domésticos. Para tanto, obteve-se amostras de sangue de 200 cães domésticos, sendo 150 cães mestiços e 50 Pastores Alemães, oriundos do município de Jaboticabal - São Paulo, 32 lobos-guará e 16 cachorros-do-mato, pertencentes aos zoológicos de São Carlos - SP, Rio de Janeiro - RJ, São José do Rio Preto - SP, Brasília - DF, Belo Horizonte - MG, Sorocaba - SP, e também do criadouro conservacionista da Companhia Brasileira de Metalurgia e Mineração (CBMM), localizado em Araxá - MG. A prevalência dos grupos sangüíneos encontrada para os mestiços (SRD) foi: 85 (57%) positivos para o grupo DEA 1.1; 61 (41%) positivos para o grupo DEA 1.2; 19 (13%) positivos para o grupo DEA 3; 140 (93%) positivos para o grupo DEA 4; 11 (7%) positivos para o grupo DEA 5 e 17 (11%) positivos para o grupo DEA 7. As combinações de grupos sangüíneos mais observadas foram DEA 1.1,4 (35%) e DEA 1.2,4 (32,5%). A prevalência encontrada para os Pastores Alemães foi: 32 (64%) positivos para o grupo DEA 1.1; 18 (36%) positivos para o grupo DEA 1.2; 4 (8%) positivos para o grupo DEA 3; 50 (100%) positivos para o grupo DEA 4; 7 (14%) positivos para o grupo DEA 5 e 4 (8%) positivos para o grupo DEA 7 (Figura 1). As combinações de grupos sangüíneos mais observadas foram DEA 1.1,4 (50%) e DEA 1.2,4 (28%)...
The goal of this study was to verify the prevalence of dog erythrocyte antigen (DEA) in domestic dogs reared in Brazil, in order to compare with the described prevalence found in the literature for dogs reared in other contries. Also, to verify normal blood values and the occurrence of dog erythrocyte antigen in maned wolf and crab eating dog, to investigate phylogenetic relationship between wild and domestic dogs. For this purpose, we collected anticoagulated blood samples from 200 domestic dogs (150 mixed breed and 50 German Sheepherd - GSH) from the city of Jaboticabal, in Sao Paulo state, and 32 maned wolves and 16 crab eating dogs, from zoos located in São Carlos-SP, Rio de Janeiro-RJ, São José do Rio Preto-SP, Brasília-DF, Belo Horizonte-MG, Sorocaba-SP and from a conservationist breeder called CBMM, located in Araxá/MG. The obtained prevalence of dog erythrocyte antigens in mongrels was the following: 57% positive for DEA 1.1, 41% positive for DEA 1.2, 13% positive for DEA 3, 93% positive for DEA 4, 7% positive for DEA 5 and 11% positive for DEA 7. The obtained blood group prevalence for GSH dogs was: 64% positive for DEA 1.1, 36% positive for DEA 1.2, 8% positive for DEA 3, 100% positive for DEA 4, 14% positive for DEA 5 and 8% positive for DEA 7. The most common combinations of blood groups encountered were DEA 1.1,4 (representing 50% in mongrels and 35% in GSH) and DEA 1.2,4 (representing 28% in mongrels and 32,5% in GSH. The high prevalence of DEA 1 blood group in mongrel and GSH dogs represents a favorable factor, once it reduces the risk for a transfusion reaction. The risk for a inicial transfusion reaction against groups DEA 3, DEA 5 or DEA 7 is 7,6% for mongrel and 6% for GSH dogs... (Complete abstract, access undermentioned eletronic address)
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Zhao, Linshu. "CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 8 (CEACAM8) : Purification, Characterization, Cellular and Clinical Studies." Doctoral thesis, Uppsala University, Clinical Chemistry, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4534.
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A 95-kDa protein was purified from normal human granulocytes. The protein reacted with a monoclonal antibody against CEACAM8. MALDI-Tof and MS/MS analyses revealed the protein to be a CGM6 gene product. Thus, the protein was proved to be identical to CEACAM8.
An ELISA for CEACAM8 was developed with detection range of 1-64μg/L. Data are presented on the levels of CEACAM8 in the blood of healthy individuals and patients undergoing surgery, as well as in patients with acute infection. The highly elevated levels of CEACAM8 in the blood of these patients were significantly correlated with the surface expression of CEACAM8 on neutrophils and the number of circulating neutrophils, which suggests that CEACAM8 could serve as a biological marker for granulocyte activitiy in vivo.
The cellular content of CEACAM8 in neutrophils was estimated to be 82.4 ± 8.9 ng/106 cells. Subcellular localisation and mobilisation studies showed that the majority of CEACAM8 is present in the secondary granules of human neutrophils, with a small amount on the plasma membranes. Upon stimulation, CEACAM8 translocated to the plasma membranes from the secondary granules and was also released extracellularly (5.5 ± 0.7% of the total content of CEACAM8).
In eosinophils, the cellular content of CEACAM8 was estimated to be 73.8 ± 6.0 ng/106 cells. In these cells, CEACAM8 is mainly stored in secretory vesicles. Upon activation, eosinophils released 5.1 ± 1.1% of the total content of CEACAM8.
Administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals resulted in an increased content of CEACAM8 in neutrophils on day 1, and decreased on day 4. However, the content of CEACAM8 in light membrane fractions was increased on day 4. The translocation of CEACAM8 observed in vivo after G-CSF administration is probably not directly related to this cytokine but to other cytokines such as TNF-a.
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Novais, Adriana Alonso. "Prevalência dos antígenos eritrocitários caninos em cães domésticos (Canis familiaris) e investigação dos parâmetros hematológicos e da ocorrência de antígenos eritrocitários em lobos-guará (Chrysocyon brachyurus) e cachorros-do-mato (Cerdocyon thos) criados no Brasil /." Jaboticabal : [s.n.], 2003. http://hdl.handle.net/11449/103773.
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Orientador: José Jurandir FagliariBanca: Aureo Evangelista Santana
Banca: Luis Carlos de Mattos
Banca: Aguemi Kuhayagawa
Banca: José Mauricio Barbanti Duarte
Resumo: O propósito desse estudo foi verificar a prevalência dos antígenos eritrocitários caninos em cães domésticos criados no Brasil e compará-la com aquela descrita na literatura consultada, para cães oriundos de outros países. Além disso, verificar os valores sangüíneos normais e a ocorrência dos antígenos eritrocitários caninos em lobos-guará e cachorros-do-mato, na expectativa de adicionar novos dados sobre valores sangüíneos de referência e investigar as relações filogenéticas entre os caninos silvestres e domésticos. Para tanto, obteve-se amostras de sangue de 200 cães domésticos, sendo 150 cães mestiços e 50 Pastores Alemães, oriundos do município de Jaboticabal - São Paulo, 32 lobos-guará e 16 cachorros-do-mato, pertencentes aos zoológicos de São Carlos - SP, Rio de Janeiro - RJ, São José do Rio Preto - SP, Brasília - DF, Belo Horizonte - MG, Sorocaba - SP, e também do criadouro conservacionista da Companhia Brasileira de Metalurgia e Mineração (CBMM), localizado em Araxá - MG. A prevalência dos grupos sangüíneos encontrada para os mestiços (SRD) foi: 85 (57%) positivos para o grupo DEA 1.1; 61 (41%) positivos para o grupo DEA 1.2; 19 (13%) positivos para o grupo DEA 3; 140 (93%) positivos para o grupo DEA 4; 11 (7%) positivos para o grupo DEA 5 e 17 (11%) positivos para o grupo DEA 7. As combinações de grupos sangüíneos mais observadas foram DEA 1.1,4 (35%) e DEA 1.2,4 (32,5%). A prevalência encontrada para os Pastores Alemães foi: 32 (64%) positivos para o grupo DEA 1.1; 18 (36%) positivos para o grupo DEA 1.2; 4 (8%) positivos para o grupo DEA 3; 50 (100%) positivos para o grupo DEA 4; 7 (14%) positivos para o grupo DEA 5 e 4 (8%) positivos para o grupo DEA 7 (Figura 1). As combinações de grupos sangüíneos mais observadas foram DEA 1.1,4 (50%) e DEA 1.2,4 (28%)... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The goal of this study was to verify the prevalence of dog erythrocyte antigen (DEA) in domestic dogs reared in Brazil, in order to compare with the described prevalence found in the literature for dogs reared in other contries. Also, to verify normal blood values and the occurrence of dog erythrocyte antigen in maned wolf and crab eating dog, to investigate phylogenetic relationship between wild and domestic dogs. For this purpose, we collected anticoagulated blood samples from 200 domestic dogs (150 mixed breed and 50 German Sheepherd - GSH) from the city of Jaboticabal, in Sao Paulo state, and 32 maned wolves and 16 crab eating dogs, from zoos located in São Carlos-SP, Rio de Janeiro-RJ, São José do Rio Preto-SP, Brasília-DF, Belo Horizonte-MG, Sorocaba-SP and from a conservationist breeder called CBMM, located in Araxá/MG. The obtained prevalence of dog erythrocyte antigens in mongrels was the following: 57% positive for DEA 1.1, 41% positive for DEA 1.2, 13% positive for DEA 3, 93% positive for DEA 4, 7% positive for DEA 5 and 11% positive for DEA 7. The obtained blood group prevalence for GSH dogs was: 64% positive for DEA 1.1, 36% positive for DEA 1.2, 8% positive for DEA 3, 100% positive for DEA 4, 14% positive for DEA 5 and 8% positive for DEA 7. The most common combinations of blood groups encountered were DEA 1.1,4 (representing 50% in mongrels and 35% in GSH) and DEA 1.2,4 (representing 28% in mongrels and 32,5% in GSH. The high prevalence of DEA 1 blood group in mongrel and GSH dogs represents a favorable factor, once it reduces the risk for a transfusion reaction. The risk for a inicial transfusion reaction against groups DEA 3, DEA 5 or DEA 7 is 7,6% for mongrel and 6% for GSH dogs... (Complete abstract, access undermentioned eletronic address)
Doutor
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Whitfield, David. "An investigation into the relationships between synaptic biochemistry, clinical symptoms and pathology in the Lewy body dementias and Alzheimer's disease." Thesis, King's College London (University of London), 2014. https://kclpure.kcl.ac.uk/portal/en/theses/an-investigation-into-the-relationships-between-synaptic-biochemistry-clinical-symptoms-and-pathology-in-the-lewy-body-dementias-and-alzheimers-disease(94c45525-9f7f-490b-9cb4-073420d76f22).html.
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Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) are, combined, the second most common type of dementia in the elderly but remain both poorly understood and researched. Diagnosis is based upon clinical symptoms yet there is considerable overlap between DLB, PDD and Alzheimer’s disease (AD), in terms of clinical presentation and pathology. Synapses are critical for neuronal communication and form the basis of memory and behaviour. The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline (based upon work in ZnT3- knockout mice), an observation corroborated by reports of reduced cortical zinc and ZnT3 in the brains of individuals with AD. This project utilised a cohort of AD, PDD, DLB and control brains with cognitive data and semi-quantitative scores for key behavioural symptoms (depression, agitation, hallucinations, persecution) and the principal pathologies (amyloid-beta, tau and alpha-synuclein). Semi- quantitative Western blotting was used to investigate key synaptic proteins; zinc transporter 3, PSD95, beta-III-tubulin and synaptophysin in three cortical regions. The major findings of this project were the occurrence of a loss of regulation of synaptic zinc, which predicted cognitive decline, depression and severity of amyloid-beta, tau and alpha-synuclein pathology in different cortical areas. Differences were also demonstrated in synaptic biochemistry between DLB and PDD cases, with PDD cases having a greater synaptic dysfunction. Important outcomes of this study include the potential for zinc modulation as a new target for the treatment of depression and cognitive decline in LBD, possibly through a modification of pathology, and the potential for synaptic proteins to be utilised as biomarkers for the differentiation of DLB and PDD.
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Lindmark, Eva. "Leukocytes and Coronary Artery Disease : Experimental and Clinical Studies." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2002. http://publications.uu.se/theses/91-554-5204-3/.
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Hameed, Rana Majeed. "The application of aqueous two phase systems to the analysis of protein isoforms of importance in clinical biochemistry and biopharmaceutical production." Thesis, Brunel University, 2016. http://bura.brunel.ac.uk/handle/2438/14452.
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Aqueous Phase Partitioning has a long history of applications to the analytical characterisation of biomolecules. However process applications have attracted the most interest in biotechnology where it has become widely recognized as a cost-effective technique. The main aim of this work was to explore the proposition that partition in Aqueous Two Phase Systems (ATPS) can be used as an analytical tool to detect protein isoforms and to assess the applicability of the method in clinical assays and for quality control in bioprocessing through examination of several analytical problems. The work also examined the development of automated methods of system preparation and sampling techniques to determine the partition coefficient in ATPS. The study demonstrated that the geometrical form of the phase diagram co-existence curve was of crucial importance since this directly affected the accuracy with which systems of defined Tie Line Length and Mass Ratio could be constructed. The TLL %Bias (accuracy) of a theoretical system range in the PEG1000-(NH4)2SO4 system at shorter TLL (12.2) was in the range +80.6% to -100% while at a longer TLL (53.1) the %Bias (accuracy) was reduced to +0.1% to -1.9%. At the same time the MR %Bias (accuracy) at shorter TLL (12.2) was in the range +59.5% to -21.3% while at the longer TLL (53.1) this was reduced to +2.7% to -2.6%. By contrast in the PEG8000-Dextran500 system the TLL %Bias (accuracy) at shorter TLL (13.1) was in the range +3.7% to -4.12%, while at a longer TLL (31.1) the range was +0.74% to -0.67%. The MR %Bias (accuracy) at the shorter TLL (13.1) was in the range +3.6% to -3% while at the longer TLL (31.1) the range was +1.1% to -1.4%. This illustrated that it is more difficult to work with a high degree of accuracy (e.g. %Bias <5%) close to the critical point in PEG-salt systems than in PEG-dextran systems. Two different approaches were taken to examine analytical phase partitioning. In the first approach the structure of the isoforms of a model protein (ovalbumin) were altered enzymatically. Analytical methods involving Strong Anion-Exchange chromatography were developed and applied to the separation of the ovalbumin isoforms. Removal of the phosphorylated groups (dephosphorylation of ovalbumin) was undertaken using alkaline phosphatase and de-glycosylation was attempted using neuraminidase and Endo-glycosidase F. However, both enzymatic approaches to deglycosylation were unsuccessful. Dephosphorylated isoforms were successfully produced and characterised. After partitioning in ATPS a clear difference was demonstrated between the behaviour of the native and dephosphorylated forms of ovalbumin. The mean % recovery in a PEG-salt ATPS was 99.8% (± 3.59) for the naive protein and 75.6% (± 4.03) for the dephosphorylated form. On the other hand, in a PEG3350-Dextran500 system, where solubility was maintained, a significant difference in the partition coefficient (K) of native and dephosphorylated ovalbumin was found. K for native ovalbumin was 0.85 while the partition coefficient of the dephosphorylated ovalbumin was 0.61. Analysis of covariance (ANCOVA) indicated that the regression coefficients of the respective partition isotherms were significantly different (p value < 0.05). In a second approach to examine analytical phase partitioning, chemical modification of a specific target surface amino acid of another model protein (serum albumin) was used to determine the degree of conjugation of the protein and also to determine its oxidative state. The method examined the reactivity of a free surface thiol to a wide range of labels ( (a) 2-methylsulfonyl-5-phenyl -1,3,4 oxidiazole reagent, (b) N-Ethylmaleimide (NEM) reagent, (c) 5, 5’-dithiobis (2-nitrobenzoate)(DTNB) (Ellman’s reagent), (d) N-pyrenylmaleimide (NPM) reagent, (e) Fluorescein-5-maleimide (F-5-M) Reagent). Only DTNB was found to modify the surface free thiol of serum albumin in a highly specific and quantitative manner. In the course of the development of a partitioning assay for surface free thiols of serum albumin significant oxidative properties were found to be associated with poly(ethylene glycol) PEG solutions and several attempts were made to find an oxidatively safe partitioning system by including antioxidants and by removal of contaminants by freeze drying. PEG3350-Dextran500 was found to provide an oxidatively safe environment for the development of a partitioning assay for the determination of albumin free thiols. A phase partitioning assay system capable of quantitatively resolving protein associated free thiols and low molecular weight thiols from a mixture of the two was developed. Correlation coefficients (R2) for the regression of experimentally determined protein free thiols in the presence of different levels of added LMW free thiol on the known addition of protein ranged from 0.77 to 0.83. The results demonstrated that the assay could quantify and distinguish both types of thiol in a simple two-step procedure.
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Persson, Johanna. "Hälsoundervisning : Elevers syn på hälsa inom ämnet Idrott och hälsa." Thesis, University of Kalmar, School of Human Sciences, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:hik:diva-2478.
Full textAbstract:
Fler unga människor än någonsin är idag överviktiga och stress och stressrelaterade symptom drabbar idag allt fler unga. Därför är det viktigt att unga människor får kunskaper om hur de på bästa sätt kan ta hand om sig själva.
Syftet med detta arbete är att undersöka hur elever som läser gymnasiets kurs Idrott och hälsa A ser på den hälsoundervisning de får.
Detta är relevant för alla som arbetar som idrott och hälsa lärare för att kunna hitta en jämkning mellan kursplan och elevernas tankar och förkunskaper.
Genom intervjuer och fokusintervjuer kom jag fram till att eleverna vill lära sig mer om stress och hur man hanterar stress samt om kost. Eleverna tycker däremot att idrottsläraren inte är rätt person att lära ut kunskaper om tobak.
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Tsujita, Maristela. "Estudo da S-nitrosação de Ras e participação das MAP quinases (ERK, JNK e p38) na apoptose de células THP-1 induzida por óxido nítrico." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-29042016-125624/.
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Ras é uma proteína G monomérica que converte estímulos extracelulares em sinais bioquímicos intracelulares e controla uma variedade de processos biológicos, tais como, proliferação, diferenciação, adesão e morte celular por apoptose. Além da ativação mediada por fatores de crescimento e hormônios, Ras pode ser ativado pela interação com o óxido nítrico (NO·), um radical capaz de mediar processos de sinalização. Essa interação resulta na S-nitrosação do resíduo de cisteína 118 de Ras. Assim, propusemo-nos avaliar a participação da proteína Ras e das MAP quinases: ERK1/2, JNK e p38 no processo de apoptose de células THP-1 induzida pelo doador de NO·, S-nitrosoglutationa (SNOG). Para tanto, transfectamos células THP-1 com o plasmídeo que carrega o gene que codifica para a proteína Ras mutada, na qual o resíduo de cisteína 118 foi trocado por um resíduo de serina, o que tornou Ras não responsiva ao NO·. A apoptose foi evidenciada através da formação de corpos apoptóticos, exposição de fosfatidilserina e ativação de caspase-3. A modulação da apoptose via reação de S-nitrosação foi demonstrada através da diminuição estatisticamente significativa da exposição de fosfatidilserina nas células transfectadas com o plasmídeo p21 RasC118S quando comparadas com as células selvagens e parentais. A ativação da proteína Ras ocorreu após 5, 15 e 30 minutos da adição de SNOG nas células parentais; entretanto, nas células transfectadas com o plasmídeo p21 RasC118S não observamos resposta de ativação de Ras. A avaliação das MAP quinases revelou ativação de máxima de ERK após 4 horas e ativação máxima de JNK e p38 após 2 horas de incubação com SNOG. Em relação as MAP quinases nas células transfectadas, as células p21 RasC118S apresentaram diminuição apenas da ativação ERK, quando comparadas com as células p21RasWt. A utilização dos inibidores específicos de MEK, JNK e p38; PD09895, CEP11004 e SB22004, respectivamente demonstrou que apenas a inibição de ERK diminuiu significativamente a apoptose nas células THP-1. Concluímos que na apoptose de células THP-1 estimulada por NO·, o radical livre ativa Ras via S-nitrosação, que por sua vez, recruta ERK, MAP quinase participante desta cascata de sinalização. Finalmente, demonstramos que ERK exerce papel fundamental na condução do sinal de apoptose no modelo que estudamos.Ras is a monomeric small G protein that converts intracellular stimulus into intracellular biochemical signals. Ras controls a myriad of biological processes such as, proliferation, differentiation, adhesion and cell death by apoptosis. In addition to growth factor-mediated activation of Ras, nitric oxide (NO·) directly interacts with and activates Ras via S-nitrosation on a single cysteine residue (Cys118). Therefore, we investigated the participation of Ras and of the MAP kinases (ERK, JNK and p38) in the apoptosis of THP-1 cells induced by the NO· donor S-nitrosoglutathione (SNOG). For that, we transfected THP-1 cells with a plasmid that contains the gene that codifies for the mutated Ras protein, in which the cysteine residue 118 was replaced by a serine. Apoptosis was evidenced by apoptotic bodies formation, phosphatidylserine exposition and caspase-3 activation. Parental and wild type Ras transfected-THP-1 cells (Wt) exposed phosphatidylserine upon treatment with 1.0 mM SNOG. The importance of the S-nitrosation reaction in the process was evidenced by a decrease on phosphatidylserine exposition in the cells transfected with the plasmid p21RasC118S, as compared to parental and wild type cells. Ras activation occurred within the first 30 minutes after SNOG addition to parental cells. However in p21RasC118S transfected cells, we were unable to detect activation of Ras. Regarding the MAP kinases located downstream on the Ras-mediated signaling cascade, ERK activity was maximum after 4 hours incubation with the NO· donor. JNK and p38 MAP kinase followed different kinetics, displaying maximum activity after 2 hours incubation with SNOG. The use of specific inhibitors to MEK, JNK and p38; PD09895, CEP11004 and S822004 respectively has shown that only ERK inhibition has significantly decreased THP-1 cells apoptosis. We concluded that NO· induced apoptosis in THP-1 cells activating Ras by S-nitrosation and recruiting the MAP kinase ERK, a downstream element of this signaling cascade. Furthermore, our findings support a major role for ERK in the NO· mediated apoptosis of THP-1 cells.
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Burger, Cristiani. "Lipoproteína da alta densidade (HDL) como transportadora da proteína amilóide sérica A (SAA) para sítios inflamatórios: lípides, apolipoproteínas e citocinas inflamatórias em exsudato pleural." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-06092017-122654/.
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Resultados obtidos anteriormente pelo nosso grupo mostraram que a proteína de fase aguda amilóide sérica A (SAA) é um potente estímulo para a expressão de mRNA e liberação de TNF-α, IL-1-β e IL-8 em leucócitos humanos, além de atuar como priming para a liberação de espécies reativas de oxigênio (EROs) por neutrófilos. Nosso objetivo, nesse trabalho, foi mostrar a presença de SAA em exsudatos e definir sua origem, além de verificar sua atividade pró-inflamatória in vivo. Para tanto, utilizamos soro e exsudatos pleurais de 32 pacientes com pneumonia. Mostramos primeíramente a presença da SAA no material inflamatório através de SDS-PAGE, immunoblotting e HPLC. A quantificação de SAA nas amostras foi realizada por ELISA. Nestas amostras também foram determinadas as concentrações de proteína total, proteína C reativa (PCR), apo A-I, apo A-II, apo B, colesterol total, triglicérides, TNF-α, IL-1-β e IL-8. A análise integrada dos nossos resultados indica que há uma passagem preferencial da HDL para o foco inflamatório, quando comparada as demais lipoproteínas. A SAA presente em exsudatos é originada do soro e deve sofrer intensa degradação ou associação com células. O efeito da SAA no exsudato é pró-inflamatório, sendo que esta proteína poderia ser um dos alvos para as enzimas proteolíticas e EROs presentes em exsudatos. Acreditamos que este trabalho contribua significamente para a compreensão do, ainda incerto, papel da SAA no processo inflamatório e dá nova abrangência para as funções da HDL e sua participação na reposta imune.Previous results from our lab showed that the acute phase protein serum amyloid A (SAA) is a potent stimulus for the expression of mRNA and secretion of TNF-α, IL-1-β and IL-8 from human leukocytes. Furthermore SAA primes neutrophils for the generation of reactive oxygen species (ROS). Our goal here was to show the presence of SAA in exudates and define its origin, besides the verification of its proinflammatory activity in vivo. To achieve this goal we used serum and pleural exudates from 32 patients with pneumonia. At first, we showed the presence of SAA in the exudate through SDS-PAGE, immunoblotting and HPLC. SAA was quantified by ELISA. Besides SAA, we also determined the concentrations of total protein, C reactive protein, apo A-I, apo A-II, apo B, cholesterol, triglyceride, TNF-α, IL-1-β e IL-8. The integrate analysis of our results indicates that there is a preferential leakage of HDL to the inflammatory focus when compared to other lipoproteins. SAA present in exudates is originated from serum and may be intensively degraded or associated to cells. The effect of SAA in the exudate is proinflammatory and this protein may be a target for proteolytic enzymes and for ROS present in exudates. We believed that this work adds new insights to the, yet undefined, role of SAA in the inflammatory process and gives a broader compreension to the functions of HDL and its participation in the on the immune response.
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Costa, Hugo Leonardo Riani. "Caracterização das alterações laboratoriais e histopatológicas associadas à obstrução uretral experimentalmente induzida em ratos /." Botucatu : [s.n.], 2008. http://hdl.handle.net/11449/89277.
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Orientador: Regina K. TakahiraBanca: Raimundo de Souza Lopes
Banca: André Marcelo Conceição Meneses
Resumo: A obstrução uretral é uma emergência clínica freqüente no atendimento de pequenos animais. Com a evolução do quadro, ocorre parada na filtração glomerular e, consequentemente, desenvolvem-se várias alterações nos equilíbrios hídrico, eletrolítico e ácido-básico, além do acúmulo de metabólitos nitrogenados e toxinas orgânicas. Podem ocorrer modificações histopatológicas nos rins e na bexiga. Objetivou-se, neste estudo, caracterizar prospectivamente as alterações laboratoriais e histopatológicas de ratos apresentando obstrução uretral. Para tanto, foram utilizados 21 ratos Wistar com obstrução uretral induzida. Foram realizados os seguintes exames: hemogasometria venosa e determinação dos níveis de uréia, creatinina, sódio, potássio, cloreto, cálcio e fósforo. As avaliações foram repetidas a cada 8 horas durante 24 horas. Após esse período os animais foram eutanasiados e as bexigas e os rins enviados para exame histopatológico. Entre os exames bioquímicos, foram observadas elevações estatisticamente significativas nos níveis de uréia, creatinina, fósforo, magnésio e potássio, e diminuição nos níveis de cloreto. Com relação à hemogasometria, houve diferença estatisticamente significativa entre os valores de pH, PO2, PCO2, excesso de base, saturação de oxigênio e lactato. O exame histopatológico renal revelou a presença de alterações tubulares e glomerulares, enquanto a análise histopatológica das bexigas demonstrou a presença de hemorragia, separação de fibras musculares e infiltrado inflamatório. Conclui-se que a obstrução uretral provoca alterações que podem ser detectadas nos exames laboratoriais, sendo as mesmas agravadas no decorrer do tempo. Além disso, a persistência durante 24 horas é capaz de levar a alterações morfológicas no trato urinário.
Abstract: Urethral obstruction is a frequent emergency in Veterinary clinics. The persistent urethral obstruction leads to blockage of renal filtration, resulting in several alterations in fluid, electrolyte and acid-base balance, besides the accumulation of nitrogenous metabolic products and organic toxins. Histopathological changes may occur in the kidneys and urinary bladder. Thus, this study aimed to prospectively characterize renal and vesical histopathological alterations in rats due to urethral obstruction. Twenty-one male Wistar rats (Rattus norvegicus) with experimental urethral obstruction were included in the study. Venous gasometry and determination of urea, creatinine, sodium, potassium, chloride, calcium and phosporus were performed. The avaliations were repeted each 8 hours during 24 hours. After that period, the animals were euthanatized for the collection of kidneys and bladder fragments to the histopathological exam. Biochemistry exams demonstrated statiscally significant elevations for the levels of urea, creatinine, phosporus, magnesium and potassium, and a decrease for the levels of chloride. Results of gasometry also demonstrated statiscally significant changes for pH, PO2, PCO2, base excess, oxygen saturation and lactate values. Histopathology analysis revealed kidney alterations in tubular and glomerular elements. The most important alterations found in urinary bladders were transmural hemorrhage, separation of muscle fibers and neutrophilic inflammatory infiltrate. Complete urethral obstruction induces important changes that can be detected by laboratorial exams, and the alterations worsen with the course of time. Besides that, the persistent obstruction during 24 hours is able to cause morphological changes in the kidneys and urinary bladder, which can be detected using histopathological exam.
Mestre
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Neto, Lídio Gonçalves Lima. "Polimorfismo dos genes CD14, TLR2, TLR4, IL6 e sua associação com o infarto do miocárdio em adultos jovens." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-18022014-101606/.
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O objetivo deste estudo foi avaliar a possível associação entre os polimorfismos -260C/T do gene CD14, Arg753Gln do gene TLR2, Asp299Gli e Thr39911e do gene TLR4 e -174G/C do gene IL6 com o infarto do miocárdio em adultos jovens. Para isso, foi realizado um estudo caso controle, sendo o grupo de estudo constituído por 102 pacientes que tiveram de infarto do miocárdio (34,5 ± 5 anos) e o grupo controle (35,1±8,7 anos) por 108 indivíduos sem histórico de doenças cardiovasculares. A genotipagem foi realizada pela PCRRFLP. Houve ausência de associação entre a distribuição dos genótipos dos SNPs -260C/T do gene CD14, Arg753Gln do gene TLR2, Asp299Gli e Thr39911e do gene TLR4 e -174G/C do gene IL6 entre os dois grupos estudados (p<0,05). O perfil sérico inflamatório e hematológico relacionou-se com polimorfismo -174G/C IL-6 do grupo IAM. O genótipo GG relacionou com elevação nas concentrações de PAI-1 (p<0,0001), o genótipo GC com maiores quantidades de hemácias (p=0,02) e o genótipo CC com concentrações elevadas de fibrinogênio (p<0,01) e quantidade aumentada de leucócitos (p<0,05). O genótipo CC do polimorfismo -260C/T CD14 também mostrou relação com a elevação nas concentrações de PAI-1 (0,0001) e o genótipo CT com o de fibrinogênio (p<0,01). O genótipo GG do polimorfismo -174G/C IL-6 relacionou com elevação nas concentrações de glicose (p<0,05) e o genótipo CC com diminuição nas concentrações de apoA (p<0,01), HDL (p<0,001) e elevação nas de LDL (p<0,05), colesterol total (p<0,05). O genótipo CT do polimorfismo -260C/T CD14 também relacionou com concentrações elevadas de colesterol total (p<0,0001). Em conclusão, os polimorfismos não estão relacionados com o infarto do miocárdio em jovens, porém os SNPs -260CT CD14 e -174 IL-6 parecem estar relacionados com o perfil sérico inflamatório, hematológico e bioquímico de pacientes enfartados.The objective of this study was to assess the possible association between the polymorphism - 260C/T of the gene CD14, Arg7S3Gln TLR2, Asp299Gli and Thr399lle TLR4 and - 174G/C of the gene IL6 with myocardial infarction in young adults. For that a case control study was conducted and the case group was formed by 102 patients who had myocardial infarction, and the control group by 108 individuals without history of cardiovascular disease. The genotyping was performed by PCR-RFLP. There was no association between the distribution of genotypes of SNPs - 260C/T of the gene CD14, Arg7S3Gln TLR2, Asp299Gli and Thr399lle TLR4 and -174G/C of the gene IL6 between the two groups studied (p<0.05). The serum inflammatory blood profile was related with polymorphism - 174G/C IL-6 in the group IAM. The GG genotype was linked with elevated PAI-1 concentrations (p<0.0001), the genotype GC with larger quantities of red blood cells (p=0.02) and CC genotype with high concentrations of fibrinogênio (p<0.01) and leucocytes increased quantity (p<0.05). The CC genotype of polymorphism of -260C/T CD14 also showed associated with the elevation in PAI-1 concentrations (p<0.0001) and the CT genotype with elevated fibrinogênio concentrations (p<0.01). The GG genotype of the -174G/C IL-6 polymorphism was related with elevated glucose concentrations (p<0.05) and CC genotype with decrease in the apoA (p <0.01) and HDL (p<0001) concentrations and elevation of the LDL (p <0.05), total cholesterol (p <0.05) concentrations. The CT genotype of -260C / T CD14 polymorphism also was Iinked with high total cholesterol concentrations (p <0.0001). In conclusion, the polymorphism is not associated with myocardial infarction in young patients, but the -260CT CD14 and -174 IL-6 SNPs appear to be related to the serum biochemical, hematological and inflammatory blood profile in patients that had myocardial infarction.
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Lu, Liang. "CLINICAL AND ANIMAL STUDIES OF LIPID-DERIVED PROTEIN MODIFICATIONS IN AUTISM, KIDNEY DIALYSIS, KERATITIS AND AGE-RELATED MACULAR DEGENERATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1180231149.
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Tang, Yuanyuan. "Nitric Oxide/Peroxynitrite Imbalance Induces Adhesion of Cancer Cells to Lymphatic Endothelium - Clinical Implications for Cancer Metastasis." Ohio University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1439563414.
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Borg, Mathias. "Study of the insulin-like peptide 3 in human platelets." Thesis, Linköping University, Department of Physics, Chemistry and Biology, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-21016.
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The insulin-like 3 peptide is autocrine/paracrine insulin-related hormone with a size of approximately 6kDa [1]. It mediates through a leucine richG-coupled receptor named LGR8. INSL3 is mainly expressed in human Leydig cells and is directly responsible for migration of the testis during the pre-natal period in maledevelopment. [2]
INSL3 mRNA has recently been verified in human platelets whereas no mRNA has been detected for LGR8 (by Sanofi-Aventis GmbH in Frankfurt,Germany), indicating that INSL3 might be released through paracrine functions at sites of platelet adhesion and aggregation upon a vascular injury.Furthermore, has activated platelets been shown to translate essential proteins upon activation, in a term called “signal-dependent protein synthesis”.The B-Cell lymphoma-3 protein (BCL-3) is an example of such a protein [3], and there is a possibility that INSL3 might be also.
In this thesis we wanted to detect the relaxin- like peptide 3 hormone (INSL3). (Its function, location and the timeframe of its release, when/if it issecreated in stimulated platelets).The source of platelet-derived INSL3 can be found with Western blotting and Enzyme immunoassay.
Detection of the insulin-like 3 peptide in human platelets turned out to be a difficult challenge due to the small amount of INSL3 secretion uponplatelet activation; hence the total amount of INSL3 produced might be below detection limit.
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Pereira, Edimar Cristiano. "Avaliação dos metabólitos do óxido nítrico, inibidores endógenos do óxido nítrico sintase e homocisteína na intolerância à glicose e no diabetes." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-02082017-160501/.
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A redução da biodisponibilidade óxido nítrico (•NO) tem sido responsável por complicações vasculares em algumas doenças, incluindo Diabetes Mellitus tipo 2 (DMII). A disfunção endotelial (DE) pode ser ocasionada pela baixa biodisponibilidade do •NO e estudos indicam que a hiperglicemia pode estar contribuindo para esse evento. Outro fato importante é que grande parte dos indivíduos que apresentam Intolerância à Glicose (IG) evolui para DMII. Portanto, o objetivo desse trabalho foi avaliar de que forma o estado hiperglicêmico poderia interferir sobre os metabólitos do •NO (S-nitrosotióis, nitrato + nitrito e nitrotirosina), inibidores endógenos da •NO sintase (ADMA e SDMA), homocisteína e a DE através da medida da atividade da n-acetil-β-glicosaminidase (NAG). Neste estudo participaram 140 voluntários: 12 controles (C), 32 IG e 96 DMII. A concentração de glicose foi superior nos grupos IG (109±10mg/dL) e DMII (165±66mg/dL) em relação ao grupo C (88±11mg/dL) (p<0.05). Somente o grupo DMII (8,5±1,9%; 4,57±2,78mg/dL) apresentou níveis elevados de hemoglobina glicada e frutosamina em relação ao grupo C (6,0±0,9%; 2,31±0,27mg/dL). Entretanto, os metabólitos do •NO (nitrato+nitrito, S-nitrosotióis e nitrotirosina) apresentaram concentrações elevadas nos grupos IG (35,1±12,9µM; 137±45nM; 352±104nM) e DMII (39,2±18,0µM; 143±73nM 472±231nM) em relação ao grupo C (26,6±6,2µM; 78±46nM; 260±74nM). A função endotelial também esteve alterada nos grupos IG (28,0±7,3U/L) e DMII (29,4±8,7U/L) em relação ao grupo C (21,7±3,9U/L), como indicado pela atividade da NAG. O mesmo comportamento foi observado com os inibidores endógenos de •NO (ADMA e SDMA). A concentração de homocisteína plasmática não apresentou diferença significativa entre os grupos. Os dados demonstraram que os indivíduos IG apresentaram alterações bioquímicas, relacionadas ao estresse oxidativo e à disfunção endotelial, semelhantes aos pacientes com DMII, as quais poderiam contribuir para o desenvolvimento de doenças cardiovasculares.The nitric oxide (NO) has been responsible for vascular complications in some diseases, including Diabetes Mellitus type 2 (DMII). Endothelial dysfunction (ED) may be caused by NO low bioavailability and studies indicate that the hyperglycemia may be contributing to this event. Other important fact is that a large number of individuals who present Glucose Intolerance (GI) develop DMII. Therefore, the objective of this study was to evaluate the way the hyperglycemic state could interfere upon the NO metabolites (S-nitrosotiois, nitrate + nitrite and nitrotirosine), endogen inhibitors of NO synthase (ADMA, and SDMA) and the DE using n-acetyl-β-glicosaminidase (NAG) activity measure. In this study, 140 volunteers participated: 12 as controls (C), 32 GI and 96 DMII. Glucose concentration was superior in GI group (109±10 mg/dL) and DMII group (165±66mg/dL) in relation to group C (88±11mg/dL) (p<0.05). Only DMII group (8,5±1.9%; 4,57±2,78mg/dL) showed high leveIs of glicade hemoglobin and frutosamine in relation to group C (6,0±0,9%; 2,31±0,27mg/dL). However, NO metabolites (nitrate + nitrite, S-nitrosotiois and nitrotirosine) showed high concentrations in groups GI (35,1±12,9µM; 137±45nM; 352±104nM) and DMII (39,2±18,OµM; 143±73nM; 472±231nM) in relation to group C (26,6±6,2µM; 78±46nM; 260±74nM). The endothelial function was aIso altered in groups GI (28,0±7,3U/L) and DMII (29,4±8,7U/L) in relation to group C (21,7±3,9U/L), as indicated by NAG activity. The same behavior was observed with endogen inhibitors of NO (ADMA and SDMA). Plasmatic homocystein concentration has not shown significant difference between the groups. Data has shown that the individuaIs IG presented biochemistry alterations, related to the oxidative stress and the endothelial dysfunction, similar to the patients with DMII, which could contribute to the development of cardiovascular diseases.
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Okino, Alessandra Miyuki. "Proteínas de fase aguda em exsudatos: acesso da HDL ao foco inflamatório." Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-26012015-133436/.
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A fase aguda é caracterizada pela mudança significativa nos níveis de váriasproteínas plasmáticas. As proteínas amilóide sérica A (SAA) e proteína C reativa (PCR), chamadas de proteínas de fase aguda positivas, têm sua concentração plasmática aumentada em até 1000 vezes durante a inflamação. Espera-se que estas proteínas exerçam um papel importante em algumas etapas do processo inflamatório. Para a PCR existem sólidas evidências de sua participação na ativação do sistema complemento, entretanto para a SAA, a função biológica ainda está para ser esclarecida. No plasma, a SAA encontra-se ligada à lipoproteína de densidade alta (HDL), especialmente a fração HDL3. A SAA associa-se à HDL3 através do deslocamento das apolipoproteínas,- preferencialmente a AI e pouco a AlI. Neste trabalho nos propusemos a avaliar a eficiência da passagem de SAA sérica para os focos inflamatórios. Para este fim doseamos, em 20 exsudatos pleurais e 10 exsudatos ascíticos, e respectivos soros, os seguintes parâmetros: proteínas totais (PT), SAA, PCR, apolipoproteína AI, AlI, 8, colesterol total (CT) e triacilgliceróis (TG). As relações exsudato/soro encontrados para estes parâmetros foram: SAA, 0,11 ± 0,14; PCR 0,31 ± 0,20; AI, 0,48 ± 0,26; AlI, 0,63 ± 0,29; 8, 0,46 ± 0,19; PT, 0,67 ± 0,18; CT, 0,34 ± 0,21; TG, 0,36 ± 0,22. Observamos uma forte correlação entre os níveis séricos de PCR versus SAA e entre AI versus All. Para o exsudato foi mantida a correlação forte somente entre AI versus AlI. Nas correlações entre exsudato e soro observamos correlações moderadas apenas para SAA, AlI e PT. Em função dos nossos resultados, concluímos que a proteína de fase aguda SAA tem acesso ao foco inflamatório e que o conteúdo desta proteína em exsudatos é, pelo menos em sua maioria, originário do soro .. A julgar pelos níveis de apo All encontrados no exsudatos, a permeabilidade das membranas que recobrem as cavidades pleurais e ascíticas é maior para HDL3 do que para HDL2 e LDL, fato es e que garante uma passagem eficiente de SAA para as cavidades. A SAA que tem acesso à cavidade deve sofrer extensa proteólise e/ou associar-se eficientemente às células pois a relação de concentrações exsudato/soro encontrada para SAA é menor que para as demais proteínas analisadas.Inflammation is characterized by profound changes in the serum leveis of acute phase proteins. The huge increase (up to a 1000 fold) in protein serum amyloid A (SAA) and C reactive protein (CRP) suggests that both proteins exert an important role in the inflammatory processo Although it is known the participation of CRP in the activation of the complement complex, the biological role of SAA is not clear yet. In plasma, SAA is associated to the high density lipoprotein (HDL), especially the HDL3 fraction. The association of SAA to HDL3 causes the displacement of the apolipoproteins A-ll and, especially, A-I. The goal of this study was to evaluate the efficiency of the SAA passage from serum to the inflammatory focus. With this purpose we determined total protein (TP), SAA, PC R, A-I, A-ll, apolipoprotein B (B), total cholesterol (TC) and triglicerides (TG) in 20 samples of pleural exudates and 10 samples of ascitic exudates, and respective serum samples. The ratio exudate/serum found were: SAA, 0, 11±0, 14; CRP 0,31±0,20; A-I, 0,48±O,26; A-ll, 0,63±O,29; 8, 0,46±0, 19; TP, 0,67±0,18; TC, 0,34±0,21; TG, 0,36±0,22. There was a high correlation of the serum leveis of CRP versus SAA and AI versus A-ll. A high correlation in the exudate was only found for AI versus All. The correlation between exudate and serum were moderate and were found only for SAA, A-ll and TP. In conclusion we observed that SAA has access to the exudate and that the content of SAA in the exudate is mainly originated from serum. Considering the leveis of A-ll found in the exudates, we supposed that the permeability of the membranes that cover the pleural and ascitic cavities is higher for HDL3 than for HDL2 and LDL. SAA in the inflamed pleural cavity might suffer an extensive proteolysis and/or efficient association to cells because the ratio exudate/serum found for SAA was lower than for other proteins
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Libardi, Keli Daiane Cristina. "Perfil metabólico de cordeiros Santa Inês terminados em confinamento." Universidade Estadual do Oeste do Paraná, 2014. http://tede.unioeste.br:8080/tede/handle/tede/1550.
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Previous issue date: 2014-02-28The objective of this study was to evaluate levels of food restriction followed by refeeding on the metabolic profile of lambs finished in feedlot. For this purpose, 24 male sheep were used at 20 kg body weight in a randomized and four restriction levels (0, 20, 40 and 60%) and 6 replicates per treatment design. The experiment was divided into two distinct periods of 64 days each, at the first call restriction, the rats were assigned to treatments: no restriction (ad libtum consumption remains at 10%), restriction of 20, 40 and 60% compared to consumption of the control treatment. In the second period, called the period of refeeding, food was offered ad libtum to all animals in the experiment. The variables of the metabolic profile (protein, energy, mineral and enzyme) at the beginning and end of feed restriction and the end of the intake were evaluated. For the evaluation of blood metabolites of the metabolic profile in animals, commercial laboratory kits were used. Data were analyzed using the F test of analysis of variance, when detected significant differences, regression analysis was used to study the levels of food restriction, and Tukey test for comparison between samples. In the absence of treatment effect averages relating to treatments 20, 40 and 60% restriction were calculated in the three collection periods. All statistical procedures were evaluated at 5% probability by SISVAR (2003) statistical program. It was observed that phosphorus levels were lower in animals to start the period of feed restriction, the same occurring for concentrations of urea, glucose and magnesium, which were adversely affected with the increase in the level of restriction imposed. Already in the final stages of food restriction there was a linear decrease for biochemical concentrations of urea, glucose and phosphorus; contrary, cholesterol concentrations increased linearly at the end of the period. The end of food restriction on the initiation of the restriction, negatively influenced the concentrations of triglycerides, glucose and creatinine, unlike the values of total protein, albumin, urea and cholesterol showed a significant increase with the final restrictive period. Already on feedback, there was decreasing for urea, glucose and magnesium linear behavior. In the second trial, it was found that the concentrations of total protein, globulin, total cholesterol, glucose, creatinine and phosphorus showed differences (P <0.05) between collection periods. The levels of food restriction affect protein metabolism and also interfered in the energy and mineral metabolism, and feedback resulted in changes in protein and energy metabolism
objetivo do presente trabalho foi avaliar o efeito dos níveis de restrição alimentar seguido de realimentação sobre o perfil metabólico de cordeiros terminados em confinamento. Para tanto, foram utilizados 24 cordeiros Santa Inês, aos 20 kg de peso corporal, distribuídos em delineamento inteiramente casualizado com 4 níveis de restrição (0, 20, 40 e 60%) e 6 repetições por tratamento. O experimento foi dividido em dois períodos distintos de 64 dias cada um, no primeiro denominado de restrição, os animais foram distribuídos nos tratamentos: sem restrição (consumo ad libtum com 10% de sobras), restrição de 20, 40 e 60% em relação ao consumo do tratamento controle. No segundo período, denominado de período de realimentação, o alimento foi ofertado ad libitum a todos os animais do experimento. Foram avaliadas as variáveis do perfil metabólico (proteico, energético, mineral e enzimático) ao início e ao final da restrição alimentar, e ao final do período de realimentação. Para a avaliação dos metabólitos sanguíneos do perfil metabólico nos animais, foram utilizados kits laboratoriais comerciais. Os dados foram submetidos ao teste F de análise de variância, quando detectadas diferenças significativas, a análise de regressão foi utilizada para estudo dos níveis de restrição alimentar, e teste Tukey para comparação entre coletas. Na ausência de efeito de tratamento foram calculadas médias referentes aos tratamentos 20, 40 e 60% de restrição nos três períodos de coleta. Todos os procedimentos estatísticos foram avaliados a 5% de probabilidade, pelo programa estatístico SISVAR (2003). Observou-se que os níveis de fósforo foram menores nos animais ao início do período de restrição alimentar; o mesmo ocorrendo para as concentrações de ureia, glicose e magnésio, as quais foram afetadas negativamente com o aumento do nível de restrição imposto. Já na fase final de restrição alimentar houve um decréscimo linear para as concentrações bioquímicas de ureia, glicose e fósforo; contrariamente, a concentração de colesterol aumentou linearmente no final do período restritivo. A restrição alimentar influenciou negativamente nas concentrações de triglicerídeos, glicose e creatinina, diferentemente, os valores de proteínas totais, albumina, ureia e colesterol apresentaram aumento significativo com o período restritivo. Já na realimentação, observou-se comportamento linear decrescente para ureia, glicose e magnésio. No segundo ensaio, verificou-se que as concentrações de proteínas totais, globulina, colesterol total, glicose, creatinina e fósforo apresentaram diferença (P<0,05) entre os períodos de coleta. Os níveis de restrição alimentar afetaram o metabolismo proteico e interferiram também no metabolismo energético e mineral, e a realimentação resultou em alteração no metabolismo proteico e energético
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Jalali, Sefid Dashti Mahjoubeh. "Development of a pathology-supported genetic test for improved clinical management of patients diagnosed with multiple sclerosis." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/5407.
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Thesis (MScMedSc (Pathology. Chemical Pathology))--University of Stellenbosch, 2010.Bibliography
ENGLISH ABSTRACT: The aetiology of multiple sclerosis (MS) remains largely unknown, due to its multifactorial nature with environmental and genetic factors contributing to the risk. Several investigations highlighted the important role of the genetic component influencing disease susceptibility and progression. In the present study genetic variations in the MTHFR (1298 A>C and 677 C>T) and HFE (845 G>A) genes previously, shown to affect folate and iron metabolism respectively, were studied in the context of MS. The aim of the study was to contribute the laboratory component of a pathology supported genetic testing approach used to identify a subgroup of MS patients with altered nutritional requirements due to genetic susceptibilities. The study population included 90 patients with a clinical diagnosis of MS and 49 control individuals, without any signs or symptoms of the disease, drawn from the same age- and population group. Three mutation detection systems were compared in terms of accuracy, sensitivity, cost effectiveness and ease of operation in relation to the MTHFR and HFE gene mutations analysed. Analytical validity of the genetic assays was an important consideration; therefore the respective real-time polymerase chain reaction (RT-PCR) methods were compared with direct DNA sequencing as the gold standard. The methodology included use of the ABI™ 7900HT, the Roche LightCycler® 480 II system and the Corbett Rotor-Gene™ 6000 5-plex HRM. The same genotype results were obtained for the DNA samples tested with the three RT-PCR methods. In terms of cost effectiveness, ease of operation and optimization, the Corbett Rotor-Gene™ 6000 5-plex HRM thermal cycler, with use of the ABI™ TaqMan Genotyping assays was found to be the most efficient for mutation detection using relatively small sample batches. Following successful standardization of the RT-PCR assays, genotype-phenotype correlation studies was performed in a subset of 43 MS patients with available data. Biochemical tests were previously done on blood samples at the National Health Laboratory Service (NHLS) chemical pathology laboratory at Tygerberg Academic Hospital. A novel finding of this study was that heterozygotes and homozygotes for mutation 1298 A>C in the MTHFR gene presented with lower serum iron levels (12.37 ± 5.91 μmol/l) in comparison to subjects without the C-allele (18.64 ± 7.15 μmol/l; P = 0.02). Furthermore, C-reactive protein (CRP) levels were found to be marginally significantly higher (P = 0.07) in the MTHFR 1298 A>C mutation-positive heterozygotes compared to subjects without the C-allele (6.65 ± 4.96 mg/l vs 2.93 ± 2.31 mg/l), linking inflammation to the presence of the MTHFR 1298 A>C mutation. In comparison, the MTHFR 677 C>T as well as the HFE 845 G>A mutation showed no correlation with transferrin saturation, ferritin, haemoglobin or CRP levels. The absence of increased iron status in HFE mutation carriers was in accordance previous findings suggesting altered iron metabolism in MS patients with this mutation. For the first time, high-throughput assays for functional polymorphisms in the MTHFR and HFE genes can now be offered as a routine service at the Tygerberg Academic Hospital. This application is used in combination with blood biochemistry tests as part of a comprehensive gene-based, pathology supported screening and intervention program aimed at improved quality of life in patients diagnosed with MS.
AFRIKAANSE OPSOMMING: Die etiologie van meervoudige sklerose (MS) is nog grootendeels onbekend, as gevolg van die multifaktoriale aard van die siekte, met omgewings- en genetiese faktore wat bydra tot die risiko. 'n Aantal ondersoeke het reeds die belangrikheid van die genetiese komponent vir die vatbaarheid vir die siekte en die progressie daarvan beklemtoon. In die huidige studie was genetiese variasies in die MTHFR (1298 A>C en 677 C>T) en HFE (845 G>A) gene bestudeer wat voorheen getoon het dat dit foliensuur- enystermetabolisme respektiewelik in die konteks van MS affekteer. Die doel van die studie was om die laboratorium komponent van 'n patologie-ondersteunde genetiese toets daar te stel wat gebruik kan word om 'n subgroep van MS pasiënte te identifiseer wat veranderderde voedingsbehoeftes het as gevolg van genetiese vatbaarheid. Die studiepopulasie het bestaan uit 90 pasiënte met 'n kliniese diagnose van MS en 49 kontroles sonder enige tekens of simptome van die siekte, wat ingesluit is vanuit dieselfde ouderdoms- en populasiegroep . Drie mutasie analise sisteme was vergelyk in terme van akkuraatheid, sensitwiteit, kostedoeltreffendheid en gemak van gebruik met betrekking tot die MTHFR en HFE geen mutasies. Analitiese geldigheid van die genetiese toetse was 'n belangrike oorweging; daarom was die onderskeie rieëltyd polimerase kettingreaksie (RT-PKR) metodes vergelyk met direkte DNA volgordebepaling as die goue standaard. Die metodologie het die ABI™ 7900HT, die Roche LightCycler® 480 II sisteem en die Corbett Rotor-Gene™ 6000 5-plex HRM ingesluit. Dieselfde genotipe resultate was met die verskillende metodes verkry vir die DNA monsters wat getoets is met die drie RT-PKR metodes. Wat betref kostedoeltreffendheid, gemak van gebruik en optimisering, was die gebruik van die Corbett Rotor-Gene™ 6000 5-plex HRM Thermal Cycler, met die ABI™ TaqMan Genotyping essays die mees effektief vir mutasie opsporing van relatief klein getalle monsters. Nadat die RT-PKR toetse suksesvol gestandardiseer was, was genotipe-fenotipe korrelasies uitgevoer in 'n subgroep van 43 MS pasiënte met die beskikbare data. Biochemiese toetse was voorheen gedoen op die betrokke bloedmonsters by die Nationale Gesondheid Laboratorium Diens (NHLS) se chemiese patologie laboratorium by Tygerberg Akademiese Hospitaal. 'n Nuwe bevinding van hierdie studie was dat heterosigote en homosigote vir die MTHFR 1298 A>C mutasie gepresenteer het met laer serum yster vlakke (12.37 ± 5.91 μmol/l) in vergelyking met individue sonder die C-alleel (18.64 ± 7.15 μmol/l; P = 0.02). Verder was die C-reaktiewe proteien (CRP) marginaal betekenisvol hoër (P = 0.07) in die MTHFR 1298 A>C heterosigote in vergelyking met individue sonder die C alleel (6.65 ± 4.96 mg/l vs 2.93 ± 2.31 mg/l), wat aandui dat inflammasie verhoog mag wees in die teenwoordigheid van die MTHFR 1298 A>C mutasie. In vergelyking hiermee het die MTHFR 677 C>T sowel as die HFE 845 G>A mutasies geen korrelasie met transferrien versadiging, ferritien, hemoglobien of CRP-vlakke getoon nie. Die afwesigheid van verhoogde yster status in MS pasiënte met die HFE mutasie was in ooreenstemming met vorige bevindinge wat veranderde ystermetabolisme in MS pasiënte met hierdie mutasie aangedui het. Vir die eerste keer is hoë deurvoer genetiese toetse nou vir funksionele polimorfismes in die MTHFR en HFE gene beskikbaar as 'n roetiene diens by die Tygerberg Akademiese Hospitaal. Dit kan gebruik word saam met bloed biochemiese toetse as deel van 'n omvattende geen-gebaseerde, patologie ondersteunde intervensie program wat daarop gemik is om die kwaliteit van lewe van pasiënte gediagnoseer met MS te verbeter.
Medical Research Council