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Journal articles on the topic 'Haematological adaptations'
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Rodríguez, Ferran A., Josep L. Ventura, Mireia Casas, Héctor Casas, Teresa Pagés, Ramón Rama, Antoni Ricart, Luis Palacios, and Ginés Viscor. "Erythropoietin acute reaction and haematological adaptations to short, intermittent hypobaric hypoxia." European Journal of Applied Physiology 82, no. 3 (June 13, 2000): 170–77. http://dx.doi.org/10.1007/s004210050669.
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Tobin, Barbara, Guillaume Costalat, and Gillian M. C. Renshaw. "Intermittent not continuous hypoxia provoked haematological adaptations in healthy seniors: hypoxic pattern may hold the key." European Journal of Applied Physiology 120, no. 3 (February 14, 2020): 707–18. http://dx.doi.org/10.1007/s00421-020-04310-y.
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Dänicke, Sven, Ulrich Meyer, Janine Winkler, Sebastian Ulrich, Jana Frahm, Susanne Kersten, Hana Valenta, et al. "Haematological and immunological adaptations of non-pregnant, non-lactating dairy cows to a high-energetic diet containing mycotoxins." Archives of Animal Nutrition 70, no. 1 (December 11, 2015): 1–16. http://dx.doi.org/10.1080/1745039x.2015.1117561.
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Montero, David, Adrian Cathomen, Robert A. Jacobs, Daniela Flück, Jeroen de Leur, Stefanie Keiser, Thomas Bonne, Niels Kirk, Anne-Kristine Lundby, and Carsten Lundby. "Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training." Journal of Physiology 593, no. 20 (September 14, 2015): 4677–88. http://dx.doi.org/10.1113/jp270250.
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Hervant, F., J. Mathieu, and J. Durand. "Behavioural, physiological and metabolic responses to long-term starvation and refeeding in a blind cave-dwelling (Proteus anguinus) and a surface-dwelling (Euproctus asper) salamander." Journal of Experimental Biology 204, no. 2 (January 15, 2001): 269–81. http://dx.doi.org/10.1242/jeb.204.2.269.
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The effects of long-term starvation and subsequent refeeding on haematological variables, behaviour, rates of oxygen consumption and intermediary and energy metabolism were studied in morphologically similar surface- and cave-dwelling salamanders. To provide a hypothetical general model representing the responses of amphibians to food stress, a sequential energy strategy has been proposed, suggesting that four successive phases (termed stress, transition, adaptation and recovery) can be distinguished. The metabolic response to prolonged food deprivation was monophasic in the epigean Euproctus asper (Salamandridae), showing an immediate, linear and large decrease in all the energy reserves. In contrast, the hypogean Proteus anguinus (Proteidae) displayed successive periods of glucidic, lipidic and finally lipido-proteic-dominant catabolism during the course of food deprivation. The remarkable resistance to long-term fasting and the very quick recovery from nutritional stress of this cave organism may be explained partly by its ability to remain in an extremely prolonged state of protein sparing and temporary torpor. Proteus anguinus had reduced metabolic and activity rates (considerably lower than those of most surface-dwelling amphibians). These results are interpreted as adaptations to a subterranean existence in which poor and discontinuous food supplies and/or intermittent hypoxia may occur for long periods. Therefore, P. anguinus appears to be a good example of a low-energy-system vertebrate.
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Watts, Eric. "Haematological adaptation to exercise." Clinical Hemorheology and Microcirculation 12, no. 4 (1992): 499–503. http://dx.doi.org/10.3233/ch-1992-12401.
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Corm, Selim, Ariane Leroyer, Mathieu Wemeau, Bruno Bregman, Abderrahim Oukessou, Michiel Hemels, Claude Preudhomme, Jean-Pierre Jouet, Jean-Luc Lai, and Thierry Facon. "A Retrospective Survey of Imatinib Mesylate Treatment for Chronic Myeloid Leukemia in a Northern France Region." Blood 108, no. 11 (November 16, 2006): 4800. http://dx.doi.org/10.1182/blood.v108.11.4800.4800.
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Abstract Objective: To describe the use and results of imatinib mesylate (IM) treatment for chronic myeloid leukemia (CML) in the Nord-Pas de Calais Region in Northern France (~ 4 millions inhabitants). Methods: we identified all IM treated patients (pts) within the population of all confirmed diagnosis of CML occurred during the period 1985–2004. IM resistance (haematological and cytogenetic imatinib failure and suboptimal response) was evaluated according to the European LeukemiaNet consensus. Results: 302 pts (38.6% of the global cohort of diagnosis) were included in this retrospective study. If we consider new diagnosis occurred after Januar 1st 2001, 163 pts (90.6%) have been treated by IM. At the initiation of IM: 18 pts (6%) were in advanced phase (accelerated and blastic), 245 pts (81,1%) in chronic phase (CP) (with Ph+ metaphases > 35%), 35 (11,6%) had major cytogenetic response (MCyR) obtained with interferon (IFN) or bone marrow transplantation (BMT). Four pts (1,3%) had an unknown status. The percentage of alive pts at the last update (December 31th 2005) according to the disease stage at initiation of treatment is given in the table 1.In the sample of 245 CP pts, 139 (56.7%) had been previously treated by IFN, the median CML duration prior to IM was 4.7 months [0–174], the median IM treatment duration was 31.3 months [0.5–72.3] and the median follow-up after IM initiation was 36 month [5.2–72.3]. 214 pts (87.30%) were alive at the last update with 169 (79%) still on IM and 161 (75.2%) on IM as monotherapy. The median and mean IM daily doses of alive pts are 400 mg and 409.5 mg, respectively. Seventeen pts (6.9%) stopped IM for intolerance. The haematological and cytogenetic follow-up was informative for 206 CP pts (84.1%): MCyR 155 pts (75.2%) and CCyR 144 pts (69.9%). IM resistance occurred in 73 (35.4%) of these 206 evaluable pts, including 23 (11.1%) accelerations and blastic transformations. In the subgroup of IM resistant pts 47 (64.4%) have increased their IM posology. The mean of the maximum daily dose in the resistant subgroup was 607.5 mg (median 600 mg). BCR-ABL kinase domain mutations were found in 15 (20.5%) pts amoung IM resistant population. The estimated 5-years survival rate of the CP pts is 81.3%. Previous treatment by IFN doesn’t influence significantly the survival, nor the duration of the disease before IM initiation, even if we found a trend for a better survival when this period was inferior to 6 months (5 years survival rate 90.4% vs 77.5%, p=0.16). BMT was performed for 31 pts (10.3%) including 19 pts (6.3%) after the initiation of IM therapy. Conclusion: these real life observations show the large use of IM in the last years and its great impact on the management and the survival of CML pts. IM resistance occurs in 1/3 of pts but the disease duration prior to IM is heterogeneous. An increase of IM dose has been tried in most IM resistant pts. The response to the different therapy adaptations is under study and will be presented. The vast majority of pts are still on IM therapy at the last update. Table 1
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STEPHENSON, R., D. L. TURNER, and P. J. BUTLER. "The Relationship Between Diving Activity and Oxygen Storage Capacity in the Tufted Duck (Aythya Fuligula)." Journal of Experimental Biology 141, no. 1 (January 1, 1989): 265–75. http://dx.doi.org/10.1242/jeb.141.1.265.
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For a period of 6 months, a group of eight tufted ducks (‘control’ ducks) were kept on a shallow outdoor pond and performed short dives to obtain food (maximum depth, 0.65 m; observed mean duration, 10.9 ± 0.54s). At the same time, a group of seven tufted ducks (‘dive-trained’ ducks) were kept on an adjacent deeper and partly covered pond, and performed ‘extended’ dives under the surface mesh in order to feed (maximum distance to food, 10m; observed mean dive distance, 6.0 ± 0.25 m; observed mean duration, 24.8 ± 0.58 s). At the end of this time, the calculated total usable oxygen store was approximately the same in control and dive-trained ducks (44 and 42mlO2STPDkg−1, respectively), although the relative quantities of usable oxygen in each of the three main storage sites (respiratory system, blood and skeletal muscle) differed between groups. The end-expiratory lung/air sac volume was found to be significantly smaller (P<0.01) in the dive-trained ducks (165mlBTPskg−1) than in the control ducks (232mlBTPs−1). The dive-trained ducks, however, had a significantly greater (P<001) blood volume (141mlkg−1) than the control ducks (lO7mlkg−1), although the blood oxygen capacity and several haematological indices (measured haemoglobin content, red blood cell count and haematocrit, and calculated mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration) were statistically the same in both groups. Mean corpuscular volume was significantly greater (P<0.05) in the dive-trained ducks. The myoglobin content of the myocardium was the same in both groups. The pectoralis muscle and the locomotory leg muscles, however, contained significantly higher concentrations of myoglobin in the dive-trained ducks than in the control ducks (pectoralis, P<0.05; lateral gastrocnemius and semitendinosus, P<0.01)<001). It is suggested that the anatomical adaptations which occur in response to chronic increases in diving activity may increase the aerobic diving capacity of the tufted duck by effecting a decrease in buoyancy (reduced end-expiratory lung/air sac volume) and an increase in blood oxygen storage capacity (hypervolaemia). Locomotory muscle function may be maintained in the face of decreasing oxygen delivery during extended dives by means of increased myoglobin content after dive-training.
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Savourey, Gustave, Nathalie Garcia, Yves Besnard, Angélique Guinet, Anne-Marie Hanniquet, and Jacques Bittel. "Pre-adaptation, adaptation and de-adaptation to high altitude in humans: cardio-ventilatory and haematological changes." European Journal of Applied Physiology and Occupational Physiology 73, no. 6 (July 1996): 529–35. http://dx.doi.org/10.1007/bf00357675.
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Dyomshina, O. O., M. I. Koloda, and G. O. Ushakova. "Hepato- and hemato-protective properties of α-ketoglutarate under the combined effect of water-immobilization and emotional stress." Regulatory Mechanisms in Biosystems 9, no. 4 (November 27, 2018): 508–13. http://dx.doi.org/10.15421/021876.
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This article presents the results of the combined effect of water-immobilization and emotional stress on haematological and morphological parameters of blood and liver status of rats in conditions of correction of the disorders using by α-ketoglutarate. Experimental combined stress was induced by the interchangeable effect of dry immobilization and immersion in water for 3 days under constant illumination using an artificial lighting lamp of 1,000 lux., thus achieving a combined effect of stress. Physiological adaptation and administration of 5 mg/kg of body weight of α-ketoglutarate lasted 14 days after stress induction. Haematological parameters were determined using the Automated Veterinary Hematology Analyzer PCE 90 Vet (High Technology Inc., USA), while biochemical parameters of the liver state were determined by spectrophotometric and colourimetric methods. The obtained results showed an increase in hemolysis, which was determined by a decrease in the number of erythrocytes and haemoglobin concentration in the blood of rats under the effect of the stress factors studied. A negative consequence of strengthening of hemolysis is the development of hypoxia in the liver, which causes the slowing of metabolic processes in its cells. As a result, there is an accumulation of partially oxidized products: lactate and pyruvate, increased formation of TBA-active products, and oxidative modification of proteins. During the 14 days of physiological adaptation after stress, the main indicators of blood and liver status of the rats were partially restored. A stronger recovery of redox status and improvement of the physiological state of the liver and, hence, haematological parameters, were noted for rats that received α-ketoglutarate for 14 days after stress. The revealed general positive trend indicates the stimulation of adaptation processes and the overall functioning of the antioxidant system of the liver of rats in the use of α-ketoglutarate against the background of the combined effects of water-immobilization and emotional stress.
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Ozolua, R. I., E. K. I. Omogbai, A. B. Famodu, A. B. Ebeigbe, and O. I. Ajayi. "Haematological influences of potassium adaptation in normotensive and renally-hypertensive Wistar rats." British Journal of Biomedical Science 59, no. 2 (January 2002): 80–84. http://dx.doi.org/10.1080/09674845.2002.11783639.
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Giri, Arup, Vijay Kumar Bharti*, Sahil Kalia, and Bhuvnesh Kumar. "Cardiovascular biomarkers of high altitude adaptation: Selection aid for livestock breeding." International Journal of Bioassays 5, no. 12 (November 30, 2016): 5146. http://dx.doi.org/10.21746/ijbio.2016.12.007.
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The efficiency of oxygen usage and energy metabolism is important for high-altitude adaptation and optimum performance of animals. With regards to adaptation and productivity of high yielder animals, high-altitude stress (hypobaric-hypoxia, cold stress) is a primary concern at high altitude. The cardiovascular system is an essential link in the transport of oxygen from the air to the mitochondria, and it, therefore, has an important role in acclimatisation and adaptation to the oxygen depleted environment of high altitude. These pathophysiological changes belong to the morphological, functional, and component of the cardiovascular system which can be detected as the biomarker whenever changes are found in this system. These cardiovascular biomarkers are structural, haematological, biochemical, molecular, and genetic. This lecture has reviewed the different types of cardiovascular biomarkers which are important in high altitude adaptation and therefore may be helpful in selection of adapted animals for future breeding and rearing at high altitude. Some structural biomarkers are hypertrophy of auricle and ventricle, pulmonary arterial pressure, hypertension, myocardial contractibility, hydrothorax, ascites, etc., whereas hematocrit level, blood viscosity, plateletatic, is haematological biomarkers. Cardiac troponin-I and troponin-T, brain natriuretic peptide (BNP), inflammatory markers, rennin, etc. are biochemical biomarkers. Details of these biomarkers and other related markers will be discussed in present lecture. These biomarkers concentration or levels are indicators of physiological state genetic make-up of animals of the respective environmental condition. Hence, these biomarkers along with performance and physical traits may be considered for selection high altitude adapted animals for breeding and rearing.
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Skouby, Arne P. "Haematologic Adaptation in Patients with Chronic Bronchitis and Pulmonary Insufficiency." Acta Medica Scandinavica 199, no. 1-6 (April 24, 2009): 185–90. http://dx.doi.org/10.1111/j.0954-6820.1976.tb06714.x.
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Fazio, F., S. Marafioti, F. Arfuso, G. Piccione, and C. Faggio. "Comparative study of the biochemical and haematological parameters of four wild Tyrrhenian fish species." Veterinární Medicína 58, No. 11 (December 5, 2013): 576–81. http://dx.doi.org/10.17221/7139-vetmed.
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A characteristic feature of fish is the wide physiological range of blood parameters and also the large individual variations. The aim of this study was to compare the haematological profile, glucose and lactate levels of four teleost fish species (Gobius niger, Mugil cephalus, Sparus aurata, Dicentrarchus labrax) and to establish the similarities and differences between these species which are widely present in the Tyrrhenian Sea. To this end, glucose, lactate and complete haematological profiles were determined for 25 fish from each species. Statistical analysis confirmed statistical differences in blood parameters among the four species. Our findings show a lower level of glucose and higher levels of lactate, red blood cells and haemoglobin in M. cephalus with respect to the other species. White blood cell and thrombocyte counts have the same trend and result higher in S. aurata. The differences found in this study can be attributed to the feeding behaviour, life style and adaptation of the different fish species to the habitat in which they dwell.
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PD, Katsoulos, N. Roubies, N. Panousis, E. Christaki, P. Karatzanos, and H. Karatzias. "Effects of long term feeding dairy cows on a diet supplemented with clinoptilolite on certain haematological parameters ." Veterinární Medicína 50, No. 10 (March 28, 2012): 427–31. http://dx.doi.org/10.17221/5644-vetmed.
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The effect of the dietary inclusion of clinoptilolite on the haematological parameters of dairy cows has not been studied yet; however in mice, prolonged zeolite administration causes disturbances in the adaptation of erythropoiesis in periods of increased demands. The aim of the present study was to investigate whether the long term supplementation of two levels (1.25 and 2.5%) of clinoptilolite in the concentrate feed of dairy cows has any effect on their haematological parameters. Fifty-two clinically healthy Holsteincows were randomly assigned to one of three groups according to their age and parity. The first group (group A, n = 17) was offered a concentrate feed supplemented with 1.25% clinoptilolite. The second group (group B, n = 17) was offered a concentrate feed supplemented with 2.5% clinoptilolite. The third group (group C, n = 18), which served as control, was offered the same concentrate feed without clinoptilolite supplementation. The experiment started 30 days before the expected parturition and lasted up to the end of lactation. Blood samples from individual animals were collected just before the start of experiment, at the day of calving and, thereafter, at monthly intervals. All samples were tested for packed cell volume (PCV), hemoglobin (Hb) and leukocyte count (WBC) values. The results showed that the 1.25 and 2.5% supplementation of clinoptilolite had no adverse effect on the haematological parameters tested.
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Tajchman, K. "Selected haematological indices in farmed male fallow deer (Dama dama) depending on the different conditions during the wintering period." Veterinární Medicína 64, No. 9 (September 27, 2019): 379–85. http://dx.doi.org/10.17221/3/2019-vetmed.
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Fallow deer (Dama dama) are the most common breeding species among farmed cervids in Poland. Monitoring the animals’ health, nutritional status, and welfare are highly important aspects in their breeding. Haematological variables are important indicators for comparing the physiological status of the animals and for monitoring the changes in the organism related to the adaptation to the breeding conditions. The aim of this study was to assess the impact of the day’s length and the total protein content in the diet for the farmed fallow deer on the selected haematological variables. The study demonstrated a significant decline in the mean corpuscular volume (MCV) and an increase of the mean corpuscular haemoglobin concentration (MCHC) (P < 0.05) in all the animals after the winter period. However, the animal group exposed to prolonged daylight exhibited a significant increase in the platelet distribution width (PDW) and platelet large cell ratio (P-LCR) (P < 0.05). In turn, the group receiving a lower amount of protein in the diet was characterised by a significant reduction in the platelet count (PLT) (P < 0.05). Thus, the length of daylight and the protein content of the diet for fallow deer exert a significant impact on several haematological characteristics, which may serve as indicators of an animal’s nutritional status and welfare.
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Karić, Ernes, Aida Hodžić, Amir Zahirović, Amina Hrković-Porobija, and Husein Orhan. "Biochemical and haematological parameters in dogs with Cushing’s syndrome." Veterinarska stanica 52, no. 4 (February 22, 2021): 413–19. http://dx.doi.org/10.46419/vs.52.4.5.
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The exposure of the body to stress, regardless of whether it comes from physical, chemical or emotional stimuli from the environment, causes an inadequate adaptation of the organisms which can contribute to the development of various diseases. Abnormally high blood concentrations of cortisol, known as stress hormone, lead to the development of a hormonal disorder called hyperadrenocorticism or Cushing’s syndrome. In the majority of cases, Cushing’s syndrome is diagnosed when symptoms are apparent, and screening endocrinological test confirms the existence either of increased cortisol production or decreased sensitivity of the hypothalamic-pituitary-adrenal axis to negative glucocorticoid feedback. In our research, we examined a total of 23 male and 7 female dogs that were suspected to have Cushing’s syndrome, based on history and clinical signs. A total of 15 male and 5 female dogs were positive for Cushing’s syndrome (HAC group), whereas the remaining dogs were used to form non-HAC group. Using the apparatus IDEXX “Vet Test 8008”, the following biochemical parameters were determined: glucose, urea, creatinine, phosphorus, calcium, total protein, albumin, globulin, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, and amylase. Regarding haematological parameters, the following parameters were investigated: erythrocytes, leukocytes, platelets, erythrocyte indices (MCV, MCH, MCHC, RDW), white blood cell count, haemoglobin and haematocrit, using “Laser cite vet lab Station” (IDEXX). No significant differences in haematological and biochemical blood parameters were noticed between the HAC and the non-HAC group of dogs. However, dogs suffering from Cushing’s syndrome had a higher value in the number of erythrocytes compared to the control group. The finding that has to be payed attention to is the difference in platelet count between the control group of dogs and dogs suffering from Cushing’s syndrome.
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Janicki, Bogdan, Anna Kochowicz, Mateusz Buzała, and Wiesław Krumrych. "Variability of Selected Clinical and Haematological Indices in Young Stallions During 100-Day Performance Test." Bulletin of the Veterinary Institute in Pulawy 57, no. 1 (March 1, 2013): 91–96. http://dx.doi.org/10.2478/bvip-2013-0017.
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AbstractThe study was conducted on 20 clinically healthy stallions, aged 3-4 years. The evaluation of the degree of adaptation of stallions to exercise loads in the course of a 100-d training programme was conducted three times: (I) - on the 1st d of training, (II) - on the 46th d of training, and (III) - on the 97th d of training. Rectal temperature (T) and number of heart and respiratory rates were measured. Blood was sampled before exercise (1), after exercise (2), and 30 min after rest (3). The following indices were determined in the blood: concentration of haemoglobin, haematocrit level, number of red blood cells, white blood cells, lymphocytes, neutrophils, eosinophils, basophils, monocytes, and platelets. Post-exertion changes in the evaluated indicators showed moderate intensity to the applied loads with respect to functional potential of tested horses. The effect of the standard 100-d training was to stimulate the body's adaptation to functional tasks, which was evidenced, among others, by lower variability of post-exertion T and the number of red blood cells. The highest T increase was found at the beginning of the programme (about 2.1%), whereas during the subsequent studies (II and III) it was significantly (P<0.05) lower (0.98% and 0.84%, respectively). The variability in red blood cell count in the course of training showed a downward trend (16.4%, 13.7%, and 11.0%, respectively). The results confirm the relatively low exercise loads and good health of young stallions during the 100-d performance test.
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Bhatkar, N. V. "Chromium (III) induced haematological alterations in Indian common carp, Labeo rohita (Ham.)." Journal of Applied and Natural Science 3, no. 2 (December 1, 2011): 258–63. http://dx.doi.org/10.31018/jans.v3i2.192.
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The principle source of chromium in water bodies is discharged from industries which use large amount of chromates or dichromates. The freshwater fish, Labeo rohita was used as a model in the present studies to investigate the responses to chromium metal salt contamination in water bodies as it is the most common fish consumed widely in India. Haematological tests were carried out as these are the important diagnostic tools and are equally valuable as indicators of disease or stress due to pollutants and environmental fluctuations. The fishLabeo rohita were exposed to sublethal concentration of chromium chloride for 10, 20 and 30 days to study alterations in certain haematological parameters. The parameters under study were total erythrocyte count (TEC), haemoglobin (Hb gm%), total leucocyte count (TLC), differential leucocyte count (DLC) and pack cell volume (PCV). The studies revealed that chromium chloride-treated Labeo rohita exhibited decreased levels of total erythrocyte count (TEC), haemoglobinn (Hb gm%) and PCV whereas, total leucocyte count (TLC) was increased under thestress of chromium metal The decreased WBC count found after 30 days along with depleted Hb content and RBC count indicate dysfunctioning of haemopoietic systems along with dysleucopoiesis. Leucocytosis observed after 10 and 20 days exposure has been considered to be an adaptation to meet stressful conditions by animals. Increase in macrophages and basophils appears to be protective response during chromium exposure. An increasing trend in the mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were evident in fish exposed to sublethal doses of chromium chloride when compared with the control.
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Voloshchuk, O. M., T. V. Luchyk, and G. P. Kopylchuk. "Indicators of immunoreactivity in rats under conditions of different nutrition regimen." Animal Biology 23, no. 1 (April 2021): 12–17. http://dx.doi.org/10.15407/animbiol23.01.012.
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The research deals with the integral haematological indices such as markers of immunoreactivity and phagocytic activity of neutrophils in animals kept in conditions of a nutrient imbalance. The animals were divided into four experimental groups: I — animals receiving full-value semi-synthetic ration (control group); II — animals receiving low-protein ration (LPR); III — animals receiving high-sucrose diet (HS); IV — animals receiving low-protein/high-sucrose diet (LPR/HS). It has been found that in animals kept in conditions of nutritional protein deficiency there was a disturbance of the specific immune response, as evidenced by a decrease in the immunoreactivity index and an increase in the index of neutrophils and leukocytes ratio. At the same time, no significant changes in the index of blood leukocytes shift and phagocytic activity of neutrophils were found, indicating the preservation of the non-specific immune response activity. However, in animals of this experimental group compensation of endotoxemia and a decrease in the adaptation index were observed, indicating an inhibition of the adaptive mechanisms. Similar changes in the integral haematological indices were observed in animals kept on a high-sucrose ration. It has been shown that animals consuming a low protein/high-sucrose ration have low immunological reactivity, as evidenced by a 3.4-fold decrease in the immunoreactivity index and a 1.5-fold increase in the blood leukocyte shift index, and disturbances in specific immune response (marker is an increase in the neutrophils and lymphocytes ratio), as well as a significant decrease in the phagocytic index, indicating the ineffectiveness of immune reactions involving neutrophils. At the same time, the intensification of the adaptive mechanisms and a three-fold increase in the reactive neutrophil response index indicates the subcompensation stage of endotoxemia. It is concluded that studied integral haematological parameters can be used as additional early diagnostic markers of impaired immunoreactivity and endotoxemia in animals kept in conditions of different protein and sucrose content in the diet.
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Kumar, Ch Manoj, K. S. Keerthi Vyas, and Y. Sai Krishna. "Clinical profile of dengue fever with severe thrombocytopenia and its complications: a retrospective study at a tertiary care hospital in South India." International Journal of Research in Medical Sciences 5, no. 5 (April 26, 2017): 1751. http://dx.doi.org/10.18203/2320-6012.ijrms20171543.
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Background: Dengue haemorrhagic fever is a potentially lethal illness that is universally prevalent in the tropics and has become a major health concern globally in recent decades. The clinical manifestation of dengue infection varies from asymptomatic to severe life threatening illness in the form of DHF/DSS. Dengue haemorrhagic fever or DSS may be fatal in 40% to 50% of untreated patients. A hallmark of dengue infection is severe thrombocytopenia which causes concern for the patients and treating doctors. The objective of this study was to correlate clinical profile during the evolution of dengue fever with severe thrombocytopenia (platelets <10,000/mm3), and comparing frequencies between the different clinical forms in order to predict the severity of the disease. The present study includes 40 individuals who were found to be seropositive with the detection of NS1Ag, IgM and IgG antibodies for dengue infection with severe thrombocytopenia. Early diagnosis and monitoring is largely dependent on haematological parameters. As no specific antiviral therapy is available, supportive therapy is of utmost importance.Methods: This is an observational, descriptive and retrospective study of 40 patients with clinical and serological diagnosis of dengue fever with severe thrombocytopenia (platelets<10,000/mm3), in the period from August 2015 to September 2016, who were admitted in a tertiary care hospital in South India. ELISA was performed for the detection of dengue NS1, Ig M and Ig G, haematological parameters by automated analyzer and peripheral smear, coagulation profile analysis were done.Results: Out of 40 cases with severe thrombocytopenia, 50% of the patients had classical dengue fever, 30% cases had DHF with bleeding manifests and 20% cases with DHF plasma leakage signs and 5% lead to DSS. There was lack of association studied between severe thrombocytopenia and bleeding manifestations as p value<0.065 was insignificant. However, the risk of complications increased with decreasing platelet counts in the present study.Conclusions: Thrombocytopenia was most predominant haematological discrepancy. There was no predilection for any age group or gender for thrombocytopenia or bleeding among the dengue patients. The results were relevant in assessing the severity of infection and can help by enabling the adaptation of the therapeutic conduct to the needs of individual patients.
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Habibu, B., MU Kawu, HJ Makun, T. Aluwong, LS Yaqub, MS Ahmad, M. Tauheed, and HU Buhari. "Influence of sex, reproductive status and foetal number on erythrocyte osmotic fragility, haematological and physiologic parameters in goats during the hot-dry season." Veterinární Medicína 59, No. 10 (November 27, 2014): 479–90. http://dx.doi.org/10.17221/7778-vetmed.
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The current study was aimed at evaluating the effect of heat stress (during the hot-dry period) on some physiological variables, haematology and erythrocyte osmotic fragility (EOF) in bucks, pregnant (single and twin) and lactating Red Sokoto (RS) goats. Forty apparently healthy adult goats were used for the study and were allotted to four groups [bucks (n = 10), pregnant (n = 10) dry (n = 10), and lactating (n = 10) does]. The pregnant goats were further re-grouped according to number of foetuses (single foetus, n = 5 and twins, n = 5). The temperature-humidity index and physiological variables measured were significantly higher in the afternoon compared to morning hours. Pregnant does had higher respiratory and pulse rates than the dry does, but no significant change (P > 0.05) in rectal temperature was observed between groups. On the basis of sex, bucks had lower (P < 0.05) mean corpuscular volume (MCV) than other groups, in addition to having higher (P < 0.01) mean corpuscular haemoglobin (MCH) and total leucocyte counts than dry does. Pregnant does exhibited significantly lower (P < 0.05) packed cell volume, but significantly higher (P < 0.05) MCH and mean corpuscular haemoglobin concentrations (MCHC) than lactating does. Does with a single foetus had significantly lower (P < 0.05) MCV, but higher MCHC than does with twin pregnancies. Using EOF as a biomarker of oxidative stress, erythrocytes of bucks were significantly more resistant to hypotonic haemolysis than those of dry, pregnant and lactating does, with no significant difference in EOF between does of different groups. The erythrocytes of single and twin pregnancies showed similar haemolysis pattern. In conclusion, sex, lactation, and the number of foetuses carried by pregnant does significantly influences physiological and haematological variables in RS goats during the hot-dry season. Also, during heat stress, the changes in physiological variables seem to enhance favourable adaptation by preventing an increase in rectal temperature even in twin pregnancies.
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Bird, Martin C., Andrew G. Bosanquet, Susan Forskitt, and Edward D. Gilby. "Semi-micro adaptation of a 4-day differential staining cytotoxicity (DiSC) assay for determining the in-vitro chemosensitivity of haematological malignancies." Leukemia Research 10, no. 4 (January 1986): 445–49. http://dx.doi.org/10.1016/0145-2126(86)90075-5.
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Lubrano, Carla, Giuseppe Valacchi, Palma Specchia, Lucio Gnessi, Elizaveta P. Rubanenko, Elena A. Shuginina, Arseny I. Trukhanov, Liudmila G. Korkina, and Chiara De Luca. "Integrated Haematological Profiles of RedoxStatus, Lipid, and Inflammatory Protein Biomarkers in Benign Obesity and Unhealthy Obesity with Metabolic Syndrome." Oxidative Medicine and Cellular Longevity 2015 (2015): 1–14. http://dx.doi.org/10.1155/2015/490613.
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The pathogenesis of obesity (OB) and metabolic syndrome (MetS) implies free radical-, oxidized lipid- (LOOH-), and inflammatory cytokine-mediated altered pathways in target organs. Key elements of the transition from benign OB to unhealthy OB+MetS remain unclear. Here, we measured a panel of redox, antioxidant, and inflammation markers in the groups of OB patients (67 with, 45 without MetS) and 90 controls. Both OB groups displayed elevated levels of adipokines and heavy oxidative stress (OS) evidenced by reduced levels of glutathione, downregulated glutathione-S-transferase, increased 4-hydroxynonenal-protein adducts, reactive oxygen species, and membrane-bound monounsaturated fatty acids (MUFA). Exclusively in OB+MetS, higher-than-normal glutathione peroxidase activity, tumor necrosis factor-α, and other proinflammatory cytokines/chemokines/growth factors were observed; a combination of high adipokine plasminogen activator inhibitor-1 and MUFA was consistent with increased cardiovascular risk. The uncomplicated OB group showed features of adaptation to OS such as decreased levels of vitamin E, activated superoxide dismutase, and inhibited catalase, suggesting H2O2hyperproduction. Proinflammatory cytokine pattern was normal, except few markers like RANTES, a suitable candidate for therapeutic approaches to prevent a setting of MetS by inhibition of LOOH-primed leukocyte chemotaxis/recruitment to target tissues.
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Boslooper, Karin, Peter Joosten, Nic J. G. M. Veeger, Robby Kibbelaar, Eric van Roon, Sjoerd Hovenga, Gerhard Woolthuis, Hanneke C. Kluin-Nelemans, and Mels Hoogendoorn. "A Significant Better Two Year Survival in the Very Elderly Patients with a Diffuse Large B-Cell Lymphoma (DLBCL) Who Did Complete Standard Therapy: A Population-Based Cohort Study On Treatment, Toxicity and Outcome." Blood 120, no. 21 (November 16, 2012): 2642. http://dx.doi.org/10.1182/blood.v120.21.2642.2642.
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Abstract Abstract 2642 Introduction With the aging of the population clinicians are increasingly confronted with elderly, often frail, patients with a DLBCL. While the very elderly patients, defined by the age of ≥75 year, are often excluded from clinical trials, only few prospective data in the rituximab-era are available on the outcome in this patient cohort. To asses efficacy, tolerability and safety of standard intensive rituximab-containing therapy in those patients, a descriptive population-based, cohort study was performed. Detailed information on treatment, toxicity and outcome in all patients aged ≥75 year, diagnosed with DLBCL in the Dutch province Friesland was prospectively gathered and analyzed. Methods Since 2005 all patients diagnosed with a haematological malignancy in Friesland, a province with 600.000 inhabitants, are prospectively registered and followed in a population-based registry, the HemobaseR. For this analysis data of all patients aged ≥ 75 years with a newly diagnosed DLBCL over a period of six years were retrieved from the HemobaseR. Data of clinical characteristics, treatment and its adaptations, treatment-related toxicity and outcome were obtained. Treatment modality was divided in four groups: R-CHOP chemotherapy, other rituximab-containing therapy, palliative radiotherapy and only supportive care. Follow-up was completed until 31 December 2011. Cox Proportional hazards model was used for identifying significant prognostic risk factors. Kaplan-Meier curves for each group were evaluated by a logrank test. Results From 2005 until the end of 2011 103 patients aged ≥ 75 years were diagnosed with a DLBCL. The median age was 81 years (range 75 – 96) with a slight female predominance (57%). The median observation period was 13 months (range 1 – 78) and 31 months for those still alive at time of evaluation.19 patients (19%) had stage 1 disease; in 74 patients (71%) advanced disease (stage 2–4) was reported and in 10 patients (10%) staging was incomplete. In 84 patients (81%) an age adjusted International Prognostic Index was calculated, 43% of them had an aaIPI of 2 or 3. Of the patients with stage 1 disease, 13 (68%) received three courses of R-CHOP and radiotherapy with a curative intent. Eight (62%) of them did complete this therapy. Of the other 84 patients 57 (68%) received R-CHOP chemotherapy with a curative intent. 31 (54%) of them completed at least six cycles. Ultimately 39 patients (56%), who did start with a standard therapy regimen, completed their treatment. A complete remission was achieved in 30 patients (77%). In the remaining group 10 patients (10%) received alternative, suboptimal, rituximab-based chemotherapy, 9 (9%) of patients was treated with radiotherapy. In 12 patients (11%) only supportive care was given. Severe toxicity (grade 3–4), occurred in 66% of all patients treated with rituximab-containing chemotherapy. Toxicity grade 3–4 was the main reason for receiving less then six cycles of chemotherapy (44%). Ten toxicity-related deaths (13%) were observed in patients treated with R-CHOP, with eight deaths due to infectious complications. The two-year survival was 67% for the elderly who completed chemotherapy, 25% for those treated with incomplete or inferior chemotherapy regimens and 20% for those receiving palliative radiotherapy or supportive care. In a multivariate analysis completing therapy and not age was significantly associated with a better survival (p<0.001). Conclusion Over a period of six years the majority of patients in Friesland with a DLBCL and aged ≥ 75 years was treated with a R-CHOP and 56% could complete this treatment. The ability to complete such an intensive treatment was significantly associated with a better 2-years survival (67%) compared to suboptimal chemotherapy (25%) or either palliative radiotherapy or supportive care (20%). Severe treatment-related toxicity was also observed in 66% patients, with 13% toxicity-related deaths. Age only is a poor indicator to differentiate the fit elderly patient, who will benefit from intensive therapy, from the frail. Other strategies for patient selection, such as the implication of a comprehensive geriatric assessment, should be further evaluated in very elderly patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.
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Straková, E., P. Suchý, I. Herzig, V. Šerman, and N. Mas. "The long-term administration of a clinoptilolite-supplemented feed to layers and its effect on performance, haematological parameters and metabolic profile." Czech Journal of Animal Science 53, No. 5 (May 16, 2008): 212–18. http://dx.doi.org/10.17221/311-cjas.
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120 selected layers (Bovans Goldline hybrid) aged 19 weeks with an average weight of 1 735 g were divided into two balanced groups: control group (Group C) and experimental (Group E). Layers were reared in three-tier cages with automatic watering, manual feeding, and at controlled light and temperature regimens. One cage accommodated two layers, the floor surface area was 0.1125 m<sup>2</sup> per layer. The experiment started after a 20-day adaptation period with layers aged 22 weeks (Week 22) and ended when layers were 68 weeks old (Week 68). In a period of initiation (i.e. Weeks 19–38), layers were fed the complete feeding mixture N1. Then they received the feeding mixture N2 until the end of the experiment. Feeding mixtures in both groups (C and E) had the same composition; the only difference between mixtures was that the feeding mixture in the experimental group was enriched with 1% clinoptilolite (i.e. the commercially available additive ZeoFeed). Layers received feeding mixtures and drinking water <I>ad libitum.</I> In the course of the experimental period, control layers laid 16 289 eggs while experimental layers laid 16 474 eggs. It follows from the results that the laying intensity in experimental layers was 1.7% higher as compared to control layers, i.e. the number of laid eggs in experimental layers increased by 5.6 eggs per layer. The mean weight of all laid eggs was 66.3 ± 6.25 g in the control group and 65.6 ± 5.44 g in the experimental group (<I>P</I> ≤ 0.01). Such performance was achieved at the consumption of feeding mixture being 141.7 g per laid egg in the control group and 137.6 g per laid egg in the experimental group. The consumption of feeding mixture in the experimental group was 4.1 g lower than that in the control group. The mean values of parameters monitored in blood plasma such as uric acid, cholesterol, glucose, lactose, calcium, phosphorus, ALP, and LDH in both groups of layers ranged within reference intervals, with no significant differences being detected between both groups.However, statistically significant differences between both groups were found in total plasma protein (<I>P</I> ≤ 0.01), triacylglycerol levels (<I>P</I> ≤ 0.05), and magnesium (<I>P</I> ≤ 0.01), which were elevated in the control group, and in AST (<I>P</I> ≤ 0.05) whose level in the control group was significantly lower than that in the experimental group. The results of haematological tests performed with layers’ blood revealed statistically significant changes in parameters such as the erythrocyte count (<I>P</I> ≤ 0.01), haemoglobin level (<I>P</I> ≤ 0.01), and MCHC (<I>P</I> ≤ 0.05), which were elevated in the experimental group, and in the leukocyte count (<I>P</I> ≤ 0.05), which was lower in the experimental group, as compared with the control. However, the values found varied within physiological ranges.
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Rafikova, Elmira R. "Acute Oral Toxicity of Vetom 21.77 Based on Duddingtonia Flagrans in Broiler Chickens." Macedonian Veterinary Review 42, no. 1 (March 1, 2019): 87–93. http://dx.doi.org/10.2478/macvetrev-2018-0031.
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AbstractA 14-d study was undertaken to test the acute toxicity of a new preparation Vetom 21.77 based on the predacious fungus Duddingtonia flagrans. A total of 40 healthy 5-day-old broiler chickens (Hubbard F15, 100 ± 5 g), that had previously gone through a required 5-days adaptation to the environment, were orally dosed with the drug for 5 consecutive days at different doses, after which their health status was assessed daily up to the end of the experiment. According to the results, no substantial changes in the physiological state of the chickens were detected during the experiment. Internal organs weighing revealed no statistically significant differences between the groups, though weight coefficient values of internal organs of treated chickens slightly exceeded those of the control group. Some haematological parameters were significantly higher in the treatment group, without going beyond reference ranges. All chickens used in the experiment survived the study. The preparation has not produced any toxic effect even at a higher dose (4000 µL/kg bw/day). It is concluded that Vetom 21.77 pertains to preparations of IV toxicity class.
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Witkowska-Piłaszewicz, Olga, Piotr Bąska, Michał Czopowicz, Magdalena Żmigrodzka, Ewa Szarska, Jarosław Szczepaniak, Zuzanna Nowak, Anna Winnicka, and Anna Cywińska. "Anti-Inflammatory State in Arabian Horses Introduced to the Endurance Training." Animals 9, no. 9 (August 27, 2019): 616. http://dx.doi.org/10.3390/ani9090616.
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Development of an anti-inflammatory state during physical training has been postulated in both human and equine athletes, but it is not completely understood. The aim of this study was to investigate whether endurance training changes pro- and anti-inflammatory cytokine profiles within a 20-week training season in young inexperienced endurance horses. Nine Arabian horses were examined in this prospective 20-week follow-up study. Blood samples were analysed 5 times monthly, at rest and after training sessions. Routine haematological examinations were performed. Cytokine patterns including IL-1β, IL-6, TNF-α, IL-10 mRNA expression using Real Time-PCR, and serum concentrations of IL-1β, IL-2, IL-4, IL-6, IL-17, INFγ, TNF-α, and IL-10 by ELISA test were determined. During endurance training, the most significant decrease in post-exercise cytokine type 1 levels (TNFα and IL-β) occurred within 20 weeks, beginning from the 3rd month of training. IL-6 serum level decreased after the 4th month. The results suggest that endurance training can induce advanced overall anti-inflammatory response as an adaptation to increasing workload.
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Rad S. M., Ali Hosseini, Joshua Colin Halpin, Mojtaba Mollaei, Samuel W. J. Smith Bell, Nattiya Hirankarn, and Alexander D. McLellan. "Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells." Cancers 13, no. 6 (March 11, 2021): 1229. http://dx.doi.org/10.3390/cancers13061229.
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Chimeric antigen receptor (CAR) T-cell therapy has revolutionized adoptive cell therapy with impressive therapeutic outcomes of >80% complete remission (CR) rates in some haematological malignancies. Despite this, CAR T cell therapy for the treatment of solid tumours has invariably been unsuccessful in the clinic. Immunosuppressive factors and metabolic stresses in the tumour microenvironment (TME) result in the dysfunction and exhaustion of CAR T cells. A growing body of evidence demonstrates the importance of the mitochondrial and metabolic state of CAR T cells prior to infusion into patients. The different T cell subtypes utilise distinct metabolic pathways to fulfil their energy demands associated with their function. The reprogramming of CAR T cell metabolism is a viable approach to manufacture CAR T cells with superior antitumour functions and increased longevity, whilst also facilitating their adaptation to the nutrient restricted TME. This review discusses the mitochondrial and metabolic state of T cells, and describes the potential of the latest metabolic interventions to maximise CAR T cell efficacy for solid tumours.
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Collins, Geoffrey Mark, Timothy Darren Clark, and Alexander Guy Carton. "Physiological plasticity v. inter-population variability: understanding drivers of hypoxia tolerance in a tropical estuarine fish." Marine and Freshwater Research 67, no. 10 (2016): 1575. http://dx.doi.org/10.1071/mf15046.
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Physiological plasticity and inter-population variability (e.g. local adaptation) are two key drivers in determining the capacity for species to cope with environmental change, yet the relative contribution of each parameter has received little attention. Here, we investigate the acclimation potential of two geographically distinct populations of the barramundi (Lates calcarifer) to diel hypoxia. Fish were exposed to a daily hypoxia challenge of 6h below 62% saturation, down to a minimum of 10±5% saturation, followed by a return to normoxia. Respiratory and haematological variables were assessed after 8 and 16 days of daily hypoxia exposure. Hypoxia tolerance (measured as the critical oxygen tension; [O2]crit) was not different between populations and not different from control fish after 8 days ([O2]crit=20.7±2.8% saturation), but improved similarly in both populations after 16 days ([O2]crit=16.5±3.1% saturation). This improvement corresponded with increases in haematocrit and haemoglobin, but not an increase in the mean cell haemoglobin concentration. Given the similarity of the response between these two geographically distinct populations, we conclude that hypoxia tolerance for barramundi may be more dependent on physiological plasticity than inherent variability between populations.
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Harmand, Pierre-Olivier, and Jérôme Solassol. "Thiopurine Drugs in the Treatment of Ulcerative Colitis: Identification of a Novel Deleterious Mutation in TPMT." Genes 11, no. 10 (October 16, 2020): 1212. http://dx.doi.org/10.3390/genes11101212.
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Chronic inflammatory bowel disease (IBD) includes Crohn’s disease and ulcerative colitis. Both are characterized by inflammation of part of the digestive tract lining. Azathioprine (AZA) is a well-known immunosuppressant that has been known for many years for its ability to provide long-term disease remission in IBDs, but has important side effects, most of which are related to a single nucleotide polymorphism in the gene for thiopurine methyltransferase (TPMT), which ensures the degradation and efficacy of AZA. Since a direct correlation between TPMT gene polymorphisms and the haematological toxicity of the AZA treatment has been widely demonstrated, TPMT genotyping has been made necessary prior to any introduction of AZA. The monitoring of thiopurine metabolites presents one of the factors that limit wide adaptation of these thiopurines in clinical practice. Thus, identifying patients with asymmetric metabolism could help clinicians provide an ideal treatment recommendation to improve response and reduce adverse effects. Here, we review the role of AZA in the treatment of IBD and discuss the usefulness of TPMT genotyping to guide clinical decision-making. In addition, we report the identification of a new molecular alteration, never described, TPMT mutation affecting the TPMT activity and responsible for deleterious side effects in a clinical case of a 20-year-old woman patient.
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Giammarco, M., I. Fusaro, G. Vignola, A. C. Manetta, A. Gramenzi, M. Fustini, A. Palmonari, and A. Formigoni. "Effects of a single injection of Flunixin meglumine or Carprofen postpartum on haematological parameters, productive performance and fertility of dairy cattle." Animal Production Science 58, no. 2 (2018): 322. http://dx.doi.org/10.1071/an16028.
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The objective of the present research was to evaluate the effects of a single injection of Flunixin meglumine (FM) or Carprofen postpartum on haematological indicators, productive performance and fertility of Italian Friesian dairy cattle. In total, 60 cows, including 42 multiparous and 18 primiparous, were assigned to one of the following three treatments: (1) FM (2.2 mg i.m./kg of bodyweight (BW); Meflosyl 50 mg/mL), (2) Carprofen (CA; 1.4 mg s.c./kg of BW; Rymadil 50 mg/mL) or (3) saline (control) at 2.0 mL s.c./45.5 kg of BW. All treatments were administrated by a single injection within 12 h after calving. Individual milk yield was daily recorded during the trial and composition was determined at 7, 14, 21, 28, 35 and 60 days in milk (DIM). BWs were recorded at –21 ± 5 days before calving, and 1, 7, 14, 21, 28, 35 and 60 days after calving before the morning milking. Individual blood samples were collected from each animal for haemato-biochemical evaluation 3 weeks before calving (T0) and then repeated at the following times: within 12 h after calving, immediately before the administration of the anti-inflammatory drug (FM or CA; T1), ~36 h after calving (T2), 4 days after calving (T3) and 11 days after calving (T4). At each sampling time, the rectal temperature and the heart rate were monitored. Body condition score was determined after each sampling time and at 35 and 60 DIM. FM and CA treatments did not influence rectal temperature and heart rate during the first 11 DIM; no differences in overall milk yield, milk composition and dry matter intake were found. BW and body condition score were not affected by treatments throughout the study. Treatments did not affect serum metabolite concentrations of glucose, non-esterified fatty acids, β-hydroxybutyrate, serum urea nitrogen, total protein and albumin. Control cows showed a higher culling rate (P < 0.05) than did the FM- and CA-treated cows (25% vs 15% vs 5% respectively). FM-treated multiparous cows had a significantly (P < 0.05) lower incidence of retained placenta than did control and CA-treated cows (2.3% vs 9.3% vs 14% respectively). Furthermore, a greater percentage of cows pregnant (35% vs 10%) at the first insemination (P < 0.001) in non-steroidal anti-inflammatory drug groups than in control was found. Our findings evidenced that a single injection of FM or CA to non-febrile cows immediately after parturition could positively affect the metabolic adaptation of the cows at the onset of lactation and this aspect can positively influence reproductive performances and the culling rate.
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Cappelli, Katia, Massimo Amadori, Samanta Mecocci, Arianna Miglio, Maria Teresa Antognoni, and Elisabetta Razzuoli. "Immune Response in Young Thoroughbred Racehorses under Training." Animals 10, no. 10 (October 5, 2020): 1809. http://dx.doi.org/10.3390/ani10101809.
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Training has a great impact on the physiology of an athlete and, like all stressful stimuli, can trigger an innate immune response and inflammation, which is part of a wider coping strategy of the host to restore homeostasis. The Thoroughbred racehorse is a valid animal model to investigate these changes thanks to its homogeneous training and highly selected genetic background. The aim of this study was to investigate modifications of the innate immune response and inflammation in young untrained Thoroughbred racehorses during the first training season through haematological and molecular investigations. Twenty-nine Thoroughbred racehorses were followed during their incremental 3-month sprint exercise schedule. Blood collection was performed at time 0 (T0; before starting the intense training period), 30 days after T0 (T30), and 90 days after T0 (T90). Haematological parameters (red and white blood cells, haemoglobin, and platelets) were evaluated and haematocrit (HCT), mean corpuscular haemoglobin concentration (MCHC), and red cells width distribution + standard deviation (RDW-SD) were calculated. Moreover, via RT-qPCR, we investigated the expression of, Interleukin 1β (IL-1β), Interleukin 4 (IL-4) Interleukin 6 (IL-6), Interleukin 2 (IL-2), Interleukin 3 (IL-3), Interleukin 5 (IL-5) Interleukin 8 (IL-8), Trasformig Growth Factor β and α (TGF-β), Tumor necrosis factor α (TNF-α), and Interferon γ (IFN-γ)genes. Main corpuscular volume (MCV) showed a significant (p = 0.008) increase at T90. Main corpuscular haemoglobin (MCH) and haemoglobin concentration (MCHC) values were significantly augmented at both T30 (p < 0.001) and T90 (p < 0.001). Basophils were significant increased at T30 (p = 0.02) and eosinophils were significantly increased at T90 (p = 0.03). Significant differences in gene expression were found for all the genes under study, with the exception of IFN-γ and TNF-α. In particular, IL-2 (T30, p = 0.011; T90, p = 0.015), IL-4 (T30, p = 0.009; T90, p < 0.001), and IL-8 (T30, p < 0.001; T90, p < 0.001) genes were significantly upregulated at both T30 and T90 with respect to T0, TGF-β was intensely downregulated at T30 (p < 0.001), IL-5 gene expression was significantly decreased at T90 (p = 0.001), while IL-1β (p = 0.005) and IL-3 (p = 0.001) expression was strongly augmented at the same time. This study highlighted long-term adjustments of O2 transport capability that can be reasonably traced back to exercise adaptation. Moreover, the observed changes of granulocyte numbers and functions and inflammatory cytokine gene expression confirm a major role of the innate immune system in the response to the complex of stressful stimuli experienced during the training period.
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Soares, O. A. B., G. C. Ferraz, P. Trigo, F. H. F. D'Angelis, W. H. Feringer Júnior, K. B. Nardi, F. Q. Almeida, and A. Queiroz Neto. "Comparison between specific and nonspecific tests for evaluating the physical fitness of show jumping horses." Comparative Exercise Physiology 12, no. 3 (September 15, 2016): 131–40. http://dx.doi.org/10.3920/cep160018.
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Show jumping is a century-old Olympic sport performed worldwide. However, despite the prominence of this sport, there is currently no satisfactory evaluation of the physical fitness of its horses. Our study compared two standardised exercise tests (specific and nonspecific for show jumpers) to determine the importance of a show jumping specific evaluation test. Sixteen horses were divided into two performance groups (high and low performance), and all horses performed standardised exercise tests without jumps (SET1) and with jumps (SET2). Heart rate, blood lactate, glucose, blood gas, haematological parameters, and plasma ions were measured before and after the tests, and performance indices were calculated. Both exercise tests (SET1 and SET2) resulted in changes in nearly all measured variables that were expected, based on other studies, for the duration and nature of the exercise performed. Differences between the two performance groups were observed for lactate and glucose, as well as some blood gas variables and performance indicators. These differences might have been the result of better cardiovascular and metabolic adaptation of the high performance group to the show jumping exercises. For the SET1, differences between groups were mainly noted for variables related to aerobic capacity, which suggests that this measurement is important for the evaluation of equine performance in show jumping. The SET2 was capable of detecting different horse performance levels that could not be detected by the SET1, which indicates that a specific test for show jumping (that includes jumping movements) could provide important information for the evaluation of show jumpers. Based on our findings, we recommend that the SET2 be included in future protocols for evaluating jumping horses.
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Zembron-Lacny, Agnieszka, Anna Tylutka, Eryk Wacka, Edyta Wawrzyniak-Gramacka, Dariusz Hiczkiewicz, Anna Kasperska, and Miłosz Czuba. "Intermittent Hypoxic Exposure Reduces Endothelial Dysfunction." BioMed Research International 2020 (August 19, 2020): 1–10. http://dx.doi.org/10.1155/2020/6479630.
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Intermittent exposure to hypoxia (IHE) increases the production of reactive oxygen and nitrogen species as well as erythropoietin (EPO), which stimulates the adaptation to intense physical activity. However, several studies suggest a protective effect of moderate hypoxia in cardiovascular disease (CVD) events. The effects of intense physical activity with IHE on oxi-inflammatory mediators and their interaction with conventional CVD risk factors were investigated. Blood samples were collected from elite athletes (control n=6, IHE n=6) during a 6-day IHE cycle using hypoxicator GO2 altitude. IHE was held once a day, at least 2 hours after training. In serum, hydrogen peroxide (H2O2), nitric oxide (NO), 3-nitrotyrosine (3-Nitro), proinflammatory cytokines (IL-1β and TNFα), high sensitivity C-reactive protein (hsCRP), and heat shock protein 27 (HSP27) were determined by the commercial immunoenzyme (ELISA kits) or colorimetric methods. Serum erythropoietin (EPO) level was measured by ELISA kit every day of hypoxia. IHE was found to significantly increase H2O2, NO, and HSP27 but to decrease 3NT concentrations. The changes in 3NT and HSP27 following hypoxia proved to enhance NO bioavailability and endothelial function. In the present study, the oxi-inflammatory mediators IL-1β and hsCRP increased in IHE group but they did not exceed the reference values. The serum EPO level increased on the 3rd day of IHE, then decreased on 5th day of IHE, and correlated with NO/H2O2 ratio (rs=0.640, P<0.05). There were no changes in haematological markers contrary to lipoproteins such as low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) which showed a decreasing trend in response to hypoxic exposure. The study demonstrated that IHE combined with sports activity reduced a risk of endothelial dysfunction and atherogenesis in athletes even though the oxi-inflammatory processes were enhanced. Therefore, 6-day IHE seems to be a potential therapeutic and nonpharmacological method to reduce CVD risk, especially in elite athletes participating in strenuous training.
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Wechalekar, Ashutosh D., Hugh J. B. Goodman, Julian D. Gillmore, Helen J. Lachmann, Mark Offer, Arthur R. Bradwell, and Philip N. Hawkins. "Efficacy of Risk Adapted Cyclophosphamide, Thalidomide and Dexamethasone in Systemic AL Amyloidosis." Blood 106, no. 11 (November 16, 2005): 3496. http://dx.doi.org/10.1182/blood.v106.11.3496.3496.
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Abstract The prognosis for advanced AL amyloidosis (AL) with conventional treatment remains very poor and stem cell transplantation has unacceptably high mortality (TRM). Single agent thalidomide in standard doses is poorly toleranated and has low response rates in AL (Dispenzieri et al, Amyloid10:247; 2003) and few data on the role of thalidomide based combination chemotherapy in AL are available. We report experience with a risk adapted thalidomide based combination using cyclophosphamide and dexamethasone (CTD) in 43 patients with AL amyloidosis at the National Amyloidosis Centre, UK. The regime (adapted from the UK MRC Myeloma IX trial) consisted of a 21-day cycle oral cyclophosphamide 500mg once weekly, thalidomide 200mg/day (starting dose 100mg/day, increased after 4 weeks if tolerated) continuously and dexamethasone 40mg days 1–4 and 9–12. This was risk attenuated (CTDa) in the elderly (>70yrs), heart failure >NYHA grade II or significant fluid overload to a 28-day cycle of cyclophosphamide 500mg days 1, 8 and 15, thalidomide 200mg/day (starting dose 50mg/day, 4–weekly 50mg increments as tolerated), and dexamethasone 20mg day 1–4 and 15–18. A total on 43 patients (22M:21F, median age 61yrs, range 43–79) were treated; 35 received CTD and 8 received CTDa. Median number of organs involved was 2 (1–4), including renal in 62% of patients, cardiac in 60%, hepatic in 39%. Median follow-up from treatment initiation was 7mo (0.4–35) and from diagnosis 16.5mo (0.6–69). Patients received a median of 4 cycles of treatment (1–7). The number of previous treatments was none in 39%, one in 39%, two in 14% and three in 6%. Toxicities were seen in 17 (39%) of patients (CTDa 3; CDT 14) necessitating dose reduction in 11 (25%), dexamethasone omission in 6 (14%), thalidomide omission in 1 (2%) and complete regime discontinuation in 4 (9%). The main side effects were: worsening heart failure 20%, neuropathy 11%, infections 11%, sleepiness 2%, and neutropenia, renal impairment, constipation and fatigue − 4% each with no thrombotic complications or TRM. Survival data was evaluable in all patients while response was evaluable in 35 (81%).Haematologic response was defined as follows: complete response (CR) - sustained normalisation of sFLC (serum free light chains) ratio, partial response (PR) - sustained ≥50% reduction in pre-treatment clonal isotype. There was a haematologic response in 26 (74%). 12 (34%) has a CR, 14 (40%) had a PR, 9 (25%) had no response. sFLC assays were available after every cycle in 27pts; a reduction in the clonal class of ≥25% was evident within 30days in 59% and in another 33% by day 60. An appreciable regression of amyloid was evident in 15% of the responders by SAP scintigraphy. The median survival for the cohort has not been reached at 36 months. This preliminary study shows excellent efficacy of CTD in patients with advanced AL with response rates superior to conventional intermediate dose chemotherapy. The regime appears to be safe with no treatment related mortality and tolerance appears to be better than than standard dose thalidomide alone (Dispenzieri et al, Amyloid10:247; 2003) or with dexamethasone (Pallidini et al, Blood105:7;2005). However, a quarter of the patients needed dose reduction and more stringent use of risk adaptation may improve the tolerability of this regime. Risk adapted CTD may be an alternative to standard therapies as front line treatment in AL amyloidosis.
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Ludwig, Heinz, Zdenek Adam, Roman Hajek, Richard Greil, Felix Keil, Niklas Zojer, Josef Thaler, Heinz Gisslinger, and Alois Lang. "Recovery of Renal Impairment by Bortezomib-Doxorubicin-Dexamethasone (BDD) in Multiple Myeloma (MM) Patients with Acute Renal Failure. Results from an Ongoing Phase II Study." Blood 110, no. 11 (November 16, 2007): 3603. http://dx.doi.org/10.1182/blood.v110.11.3603.3603.
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Abstract Acute renal failure (ARF) is a severe complication of MM often leading to permanent renal dysfunction and dependence on chronic hemodialysis. Reversal of kidney failure can only be achieved by fast and substantial suppression of pathogenic light-chains by effective anti-MM therapy. In a previous pilot study we were able to reverse renal impairment with bortezomib based therapy in 5 of 9 pts (Haematologica 2007). Here, we present preliminary data from an ongoing phase II study in pts with ARF using the BDD regimen. Up to now 37 pts with MM induced ARF (age: median 64 yrs, range 41–82 yrs, DS stage I: 13%, II: 10%, III: 77%; IgGλ: 18%, IgGκ: 23%; Light chainκ: 32%, Light chainλ: 27%) have been enrolled. Seventeen (46%) pts presented with de novo MM, and 20 with progressive disease. ARF was defined as reduction of GFR to <50ml/min due to MM nephropathy in newly diagnosed pts, and as reduction of GFR by >25% and to <60ml/min in pts with previously treated MM and GFR of >60ml/min within the last 4 weeks and with signs of tumor progression. Treatment regimen: Bortezomib 1.0mg/m2, d1,4,8,11, doxorubicin 9mg/m2, d1,4,8,11 until first safety analysis after enrollment of the first 5 pts and thereafter of 9mg2, d1,4, and dexamethasone 40mg d1,4,8,11. Cycles were repeated every 21 days. 22 pts have completed at least 3 cycles and are evaluable for response as yet. Overall response rate was 73% including 8 pts achieving CR, 4 nCR, 4 PR; 3 pts achieved MR. Median GFR at baseline was 17ml/min (range: 4 – 45ml/min) and improved to 45,5 ml/min (range: 11 – 134ml/min). A significant increase in GFR (>75ml/min) was achieved in 9 of the 16 pts with CR-PR while in pts with MR or NC/PD no improvement in GFR was seen. Toxicity was assessed in 25 pts including 3 pts not evaluable for response. Grade 1–2 toxicities (>10% of pts): anemia 40%, neutropenia 23%, thrombopenia 27%, fatigue 50%, infections/fever 64%, neuropathy 36%, edema 32%; diarrhea 27%, nausea 27%, mucositis 23%; Grade 3–4 toxicities: anemia 9%, neutropenia 23%, thrombopenia 9%, infections 18%, neuropathy 1%. Three of the infectious complications were due to herpes virus infections/reactivations. Three pts died during the first treatment cycle; 2 pts from pneumonia (including 1 with sepsis) and 1 pt (age 81 yrs) from myocardial infarction. This led to an adaptation of the treatment regimen including a reduction in the frequency of doxorubicin administration to days 1 and 4 (instead of d1,4,8,11), abandonment of the planned dose increase of bortezomib (to 1.3mg/m2), and addition of mandatory antibacterial and antiviral prophylaxis. In conclusion, overall anti-myeloma response rate in the 22 evaluable pts was 73%, with 12 (54%) pts achieving CR/nCR; ARF could be reverted in 9 pts. (41% of total or 56% of pts. with CR-PR). After dose reduction of the initial regimen, treatment was well tolerated in this high-risk and often multimorbid patient population. Tumor response Number of Pts (evaluable: 22) GFR (ml/min) Baseline Best response CR/nCR 12 18,2 (13–45) 62,5 (20–134) PR 4 25 (15–44) 81 (16–114) MR 3 17 (10–45) 35 (33–45) NC/PD 3 13 (4–15) 18 (11–25) CR-PR 16 GFR >75ml/min: 9 (56%)
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Oliva, Esther Natalie, Roberto Latagliata, Giorgina Specchia, Francesca Ronco, Giuliana Alimena, Domenico Pastore, Stella Impera, et al. "Quality of Life Scores Have a Prognostic Significance In Elderly AML Patients." Blood 112, no. 11 (November 16, 2008): 1949. http://dx.doi.org/10.1182/blood.v112.11.1949.1949.
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Abstract INTRODUCTION: Quality-of-life (QOL) is a patient-related outcome of increasing interest in onco-haematological setting. However, there are very few reports on QOL in elderly patients with Acute Myeloid Leukemia (AML). Prognosis of AML in elderly patients is still poor with a median survival of 9–12 months and less than 20% survival at 5 years. This is due to age-related factors and also to a higher incidence of poor-risk cytogenetics, multi-drug resistance and treatment-related mortality. The measurement of QOL at diagnosis may provide useful information regarding patient preferences and prognosis while followup measurements may indicate acceptance, adaptation and adverse effects of disease and therapy. METHODS: From 2/2003 and 2/2007, we included 113 elderly AML patients in a multicenter Italian 12-month observational study to evaluate the association of baseline QOL scores and their changes with disease factors, therapy and survival. Patients aged > 60 years (M/F 58/55, mean age 71.7 ± 5.9 yrs) from 4 Institutions with “de novo” AML according to WHO classification were evaluated from diagnosis prospectively up to 12 months. Two different questionnaires were employed: the EORTC QLQ-C30 and the QOL-E v.2. Therapeutic choice was not restricted by protocol and was given freely by the individual center. RESULTS: Forty-eight patients (43%) received intensive chemotherapy and 65 (57%) lowdose therapy or supportive care. Both age > 70 years (p=0.007) and concomitant diseases (p=0.031) had a significative impact on medical decision for palliative approaches. At diagnosis, general QOL was affected (median QOL-E standardized score 54, IQ range 47– 68, median EORTC global score 50, IQ range 42–67), loss of appetite was perceived by 75% of patients and QOL-E fatigue scores were low, indicating poorer QOL (median 45, IQ range 32–53). There was a significant correlation between fatigue and age, Hb levels and the duration of fever. In a multivariate regression model, both Hb and age indipendently predicted fatigue (linear R2 0.114, p=0.001, and linear R2 0.066, p=0,010). Most patients were given a good ECOG Performance Status (< 2) that, interestingly, did not correlate with the perception of QOL, in particular physical and functional scores. QOL scores worsened after 1 month from diagnosis but patients surviving thereafter perceived an improvement in the following months. When correcting for the effects of age, concomitant diseases and changes in Hb values, fatigue improved in patients undergoing aggressive chemotherapy while it worsened in those on standard or supportive-care (p=0.004). Median overall survival was 49 weeks (95% CI 35–63). Patients receiving aggressive therapy had a longer survival with the median not reached at 60 weeks and 72% of patients surviving versus patients receiving palliative care (median 39 weeks, 95% CI 16–63, p<0.0001). At multivariate analysis, palliative approaches (HR 2.8, 95% CI 1.4 – 5.6, p=0.003), age > 70 yrs (HR 2.4, 95%CI 1.2 – 5.0, p=0.02) and concomitant diseases (HR 2.0, 95% CI 1.1 – 3.8, p=0.044) had an independent negative prognostic impact on survival, as previously reported in many other studies. However, in order to evaluate the predictive value of QOL at diagnosis for survival, in a multivariate model corrected for age, concomitant diseases and treatment option, QOL measures that independently predicted survival were fatigue (p=0.003), global QOL (p = 0.004), physical QOL (p = 0.006) and functional QOL (p = 0.002). CONCLUSION, QOL seems to have an important role also in the elderly AML setting: though QOL is a highly subjective measurable value, we outline the role of QOL measures at diagnosis as a prognostic factor for overall survival and, thus, as a potential factor for treatment decision.
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De Matteis, Serena, Silvia Carloni, Roberta Napolitano, Michele Zanoni, Lara Gibellini, Alessandro Lucchesi, Andrea Cossarizza, and Giovanni Martinelli. "Targeting Lon Protease Activity Promotes Growth Inhibition and Apoptosis in Acute Myeloid Leukemia Cell Lines." Blood 124, no. 21 (December 6, 2014): 5130. http://dx.doi.org/10.1182/blood.v124.21.5130.5130.
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Abstract INTRODUCTION Acute myeloid leukemia (AML) is a progressive malignant disorder of the myeloid lineage of hematopoietic cells, where overall three-year survival is below 20% for patients above 65 years (1). Therapy resistance or relapsed are the main causes of mortality among these patients. The functional changes that affect mitochondria may contribute to the development of cancer (2). The mitochondrial Lon, ubiquitously expressed in human cells and tissues, seems to be involved in protein quality control and stress response pathways in mitochondria. Several stress conditions induce an upregulation of Lon that may promote tumorigenesis by inhibiting apoptosis and promoting cell proliferation, transformation and angiogenesis (3). The role of Lon in AML has not been described yet. Our study aims to investigate if the activity of the protease may be linked to AML leukemogenesis and drug resistance. In particular we tested Lon protease activity inhibitors to clarify a new pathogenetic mechanism in controlling drug responsiveness in this haematological disorder. METHODS AML cell lines Kasumi-1 (acute myeloblastic leukemia), MOLM-13 (acute monocytic leukemia) and HL-60 (acute promyelocytic leukemia) were used to perform the experiments. Lon expression was measured by RT-PCR and immunoblotting. Cell-growth was quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) were evaluated by Nitro Blue Tetrazolium (NBT) assay. For cell cycle analysis, cells were fixed with ethanol, resuspended in phosphate-buffered saline (PBS) containing 0.1mg/mL RNase A, NP40 0,15% and 100mg/mL of propidium iodide (PI) and analysed by using flow cytometry and Modfit software. The early and late apoptosis was assessed with Annexin V-FITC Apoptosis Detection kit. To measure the mitochondrial potential, JC-1 Mitochondrial Membrane Potential assay kit was used. RESULTS Lon protease was expressed at high levels in AML cell lines compared with resting or activated peripheral blood mononuclear cells and monocytes, but less than other cancer cell lines such as K562 (human erythromyeloblastoid leukemia), HDLM-2 (Hodgkin lymphoma, nuclear sclerosing), SHSY5Y (neuroblastoma), MCF7 (breast carcinoma). Based on previous works (4), which show that 2-Cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivates inhibit the Lon protease activity, we evaluated the effect of two inhibitors on cell growth and the induction of apoptosis. The leukemic cell lines were treated with CDDO and CDDO-Me (CDDO methyl-ester) at different concentrations for 24, 48 and 72h. Both compounds inhibited the cell proliferation in a dose- and time-dependent manner and induced an increase of ROS. We observed a time-dependent increase in the percentage of Annexin V+ cells after treatment with CDDO (1,25µM) and CDDO-Me (0,25µM). The induction of apoptosis after CDDO exposure was important only at 72h, while we observed a percentage of apoptosis over 60% starting from 24h of CDDO-Me treatment. Interestingly, CDDO induced a time-dependent arrest in G2/M phase in MOLM-13 cells and in G0/G1 phase in Kasumi-1 and HL-60 cells. Instead the CDDO-Me induced an alteration of all cell cycle phases, probably for its cytotoxicity. Moreover CDDO-Me caused a higher decrease in mitochondrial potential (Dψm) than CDDO in all cell lines. CONCLUSION In conclusion, these findings show that Lon protease inhibitors promote growth inhibition and apoptosis and support the concept that mitochondrial Lon may represent a novel anticancer drug target. REFERENCES 1. Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011, 29:487-494. 2. Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol. 2008, 18(4):165-73. 3. Ngo JK, Pomatto LC, Davies KJ. Upregulation of the mitochondrial Lon Protease allows adaptation to acute oxidative stress but dysregulation is associated with chronic stress, disease, and aging. Redox Biol. 2013, 1(1):258-64. 4. Bernstein SH, Venkatesh S, Li M, Lee J, Lu B, Hilchey SP, Morse KM, Metcalfe HM, Skalska J, Andreeff M, Brookes PS, Suzuki CK. The mitochondrial ATP-dependent Lon protease: a novel target in lymphoma death mediated by the synthetic triterpenoid CDDO and its derivatives. Blood. 2012, 119(14):3321-9. Disclosures Martinelli: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy; ARIAD: Consultancy.
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Jaksic, Ozren, Marija Ivic, Rajko Kusec, Zdravko Mitrovic, Mario Pirsic, Branimir Jaksic, David Cicic, and Vlatko Pejsa. "Prognostic Value of TTM with TTM Distribution and Ball Score in Relapsed/Refractory Ibrutinib Treated B-CLL - in the Real-World Setting." Blood 136, Supplement 1 (November 5, 2020): 14–15. http://dx.doi.org/10.1182/blood-2020-143030.
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There is a high number of clinical and biological parameters with impact on prognosis in B-CLL and number of successful prognostic models were developed (clinical stages, CLL IPI, MDACC score, etc.). However, rapidly changing therapeutic landscape with more successful targeted terapines with different modes of action, render most of these models developed in era of chemo and chemoimmunotherapy less useful. Recently simple prognostic score (BALL score) based on 4 parameters (LDH>UNL, B2microglobulin>5mcg/l, Hemoglobin<120 g/l in males and 110g/l in females, and time from start of last therapy- 0-1 parameters - low risk, 2-3 - intermediate risk and 4 high risk) was developed and validated in number of cohorts (Soumerai et al, Lancet Hematol). High cost of novel drugs in less affluent countries led to a higher criterion for reimbursement. Until recently in Croatia ibrutinib was reimbursed only for early relapse (less than 24 months from last therapy) or refractory disease with additional criteria for high risk disease including Rai stages III and IV or high tumor burden demonstrated by TTM score >15. TTM score (www.b-cll.org) is old, simple and continuous parameter useful for prognosis and response assessment (Jaksic B et al BJH 1980) and because it cover tumor mass in all major lymphoid compartments and allow tumor distribution assessment (Jaksic O et al, Haematologica 2001) it can be very useful for response assessment to novel agents were redistribution of lymphocytes can be significant (Jaksic O BJH 2014). In other to evaluate usefulness of novel BALL score and old TTM score in real life setting where the novel drug is available only to patients with higher risk defined by respective scores, we have evaluated series of 42 RR CLL patients treated with ibrutinib at our institution since March 2015. There were 15 females and 27 males, median age 70 years (range 53 to 82), 9 patients had 17p deletion, median TTM was 14 (range 1.2-28), 20 patients had Rai stage III/IV. Median follow up was 24 months, and maximal 64 months. Since all patients were in early relapse or refractory, we have actually used simplified BALL score based on only 3 parameters. There was no significant relationship between BALL and TTM in our patient population. In our patient cohort low risk BALL score had only 3 patients, 28 patients had intermediate risk and 11 high risk and it showed only marginal discriminative power (p=0.054) While TTM>15 did not show discriminative power (p=0.14). When we added TTM>18 as an additional parameter (point) to BALL score, this modified score (0-3 low/intermediate - 23 patients and 3-4 high risk - 19 patients) showed significant discriminative power (p=0.002) (Figure 1). Observed results indicate that: 1) performance of prognostic models may be significantly dependent on discriminative power of its components and if these components are criteria for initiation of therapy with novel agent(i.e. only high risk group defined by these parameters) it significantly lower its prognostic power, and vice versa 2) such criteria for therapy selection/initiation until these criteria are met may actually mean that we treat patients with novel agents when these are less effective. We have shown that addition of TTM significantly improves BALL score. Refinement of prognostic scores with parameters that may have predictive power for novel drugs, as well as adaptation criteria for reimbursement in future studies (including pharmacoeconomics) may further improve quality of care of B-CLL patients. Disclosures Jaksic: Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Pejsa:AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pliva: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alvogen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oktal Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees.
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Ludwig, Heinz, Elisabeth Rauch, Thomas Kuehr, Adam Zdenek, Adalbert Weissmann, Hedwig Kasparu, Eva-Maria Autzinger, et al. "Lenalidomide and Dexamethasone for Acute Light Chain-Induced Renal Failure: Final Results of a Phase II Study." Blood 124, no. 21 (December 6, 2014): 3484. http://dx.doi.org/10.1182/blood.v124.21.3484.3484.
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Abstract Background: Acute renal failure (ARF) is a frequent complication of multiple myeloma (MM) and most frequently due to clonotypic light chains (LC) causing cast nephropathy, which is associated with fast deterioration of renal function, increased risk for infections and shortened survival. Here we present the final results of a phase II study employing lenalidomide-dexamethasone as treatment for patients with acute light-chain induced ARF. Patients and methods: 35 patients with LC-induced ARF have been enrolled. Cast nephropathy was confirmed in all 15 patients who had a renal biopsy. Patients with previously unknown MM must have presented with eGFR < 50ml/min and serum creatinine ³2.0mg/dL, and those with previously established diagnosis must have had documented eGFR ³ 60ml/min and serum creatinine ≤1.2mg/dL within 6 weeks before deterioration of eGFR to < 50ml/min and of serum creatinine to ≥ 2mg/dL due to LC-induced kidney injury. Nine cycles of Lenalidomide, day 1-21, q28 days, with dose adaptation according to eGFR (eGFR 30 – 50ml/min: 10 mg daily, eGFR < 30ml/min without requiring dialysis: 15mg q 48 hrs., eGFR < 30ml/min requiring dialysis: 5 mg daily following each dialysis) and dexamethasone (Dex), 40 mg, day 1-4, 9-12 and 17-21 during the first cycle and thereafter 40 mg once weekly were planned. Renal response was defined as previously described (Dimopoulos et al, Clin Lymphoma Myeloma. 2009, Ludwig et al. JCO 2010). Results: Patient's median age was: 66 (45-87), 28 patients had newly diagnosed and 7 previously established MM. 5.7% had ISS stage II, 94.3% stage III. 18 patients had light chain myeloma, 14 IgG, and 3 IgA isotype. Adverse cytogenetics t (4; 14) ± del17q ± 1q21 were detected in 14/29 patients. 4/35 patients died and 5 discontinued therapy (3 due to AEs, 1 due to PD, and 1 due to withdrawal of consent) within the first 2 cycles, leaving 26 patients for per protocol (PP) analysis. Median follow up was 17.7 months. Responses were seen in 25/35 (71.4%) patients; 7 (20%) had CR, 3 (8.6%) VGPR, 14 (40%) PR, and 1 (2.9%) MR. Median time to first and to best myeloma response was 28, and 92 days, respectively. Median baseline concentration of involved FLC was 5.465mg/L (range: 147–42.700mg/L) and 8350mg/L (range: 234– 35.500mg/L) in patients reaching ≥PR and ≤MR, respectively, and decreased significantly to a median of 95.75mg/L (range: 11.3–5.630mg/L, p <0.001) in the former, but not in the latter group. Renal response was observed in 16 (45.7%) of 35 patients (CRrenal, 5(14.2%), PRrenal, 7(20%), MRrenal, 5(14%)). Median time to renal and to best renal response was 28 and 157 days, respectively. Median eGFR increased significantly in patients with ≥ PR from 17.1ml/min at baseline to 39.1ml/min at best response (p<0.001), and from 23.7ml/min to 26.0ml/min in patients with ≤ MR (p=0.469) (figure 1A). Median PFS and OS were 5.5 and 21.8 months in the ITT and 12.1 and 31.4 months, respectively, in the PP group (figure 1B). Grade 3/4 anemia was seen in 43%, thrombocytopenia in 23% and neutropenia in 15% patients. Other non-haematologic AEs consisted mainly of grade 3-4/5 infection in 38%/9%, and of grade 3-4/5 cardiac toxicity in 11%/9% patients. Grade 3 diarrhea and vomiting/emesis were noted in 1 patient each. Conclusion: Lenalidomide (with dose adapted to eGFR) plus initial high dose Dex during the first cycle and low dose Dex during subsequent cycles resulted in rapid reduction of involved LC within 28 days in patients with ≥ PR. Overall, 71.4% of patients had a myeloma and 45.7% a renal response. Median eGFR increased significantly in patients with ≥ PR from 17.1ml/min at baseline to 39.1ml/min. Elderly patients experienced more toxicity and had more treatment discontinuations. Figure 1A. Median eGFR in patients with CR-PR and MR-NR at baseline and at best response. Figure 1A. Median eGFR in patients with CR-PR and MR-NR at baseline and at best response. Figure 1B. PFS and OS in the intent to treat and per protocol population. Figure 1B. PFS and OS in the intent to treat and per protocol population. Disclosures No relevant conflicts of interest to declare.
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Akerman, Ashley P., Samuel JE Lucas, Chris J. Baldi, Rajesh Katare, and James D. Cotter. "Haematological adaptations to High Intensity Interval Training (HIIT) in temperate and hot environments." Extreme Physiology & Medicine 4, S1 (September 14, 2015). http://dx.doi.org/10.1186/2046-7648-4-s1-a145.
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Whitburn, Jessica, and Claire M. Edwards. "Metabolism in the Tumour-Bone Microenvironment." Current Osteoporosis Reports, July 28, 2021. http://dx.doi.org/10.1007/s11914-021-00695-7.
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Abstract Purpose of Review For solid tumours such as breast and prostate cancer, and haematological malignancies such as myeloma, bone represents a supportive home, where the cellular crosstalk is known to underlie both tumour growth and survival, and the development of the associated bone disease. The importance of metabolic reprogramming is becoming increasingly recognised, particularly within cancer biology, enabling tumours to adapt to changing environments and pressures. This review will discuss our current understanding of metabolic requirements and adaptations within the tumour-bone microenvironment. Recent Findings The bone provides a unique metabolic microenvironment, home to highly energy-intensive processes such as bone resorption and bone formation, both of which are dysregulated in the presence of cancer. Approaches such as metabolomics demonstrate metabolic plasticity in patients with advanced disease. Metabolic crosstalk between tumour cells and surrounding stroma supports disease pathogenesis. Summary There is increasing evidence for a key role for metabolic reprogramming within the tumour-bone microenvironment to drive disease progression. As such, understanding these metabolic adaptations should reveal new therapeutic targets and approaches.
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Patel, Vruti, and J. D. Lakhani. "A Cross Sectional Study to Assess the Status of Hemoglobin and Other Blood Indices among Pregnant Women Attending Tertiary Care Hospital of Vadodara." Journal of Pharmaceutical Research International, August 16, 2021, 106–11. http://dx.doi.org/10.9734/jpri/2021/v33i41a32308.
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Introduction: A number of adaptations happen in the anatomy, physiology and metabolic processes within the mother which aids in successful progression of the pregnancy. The different blood indices such as haemoglobin concentration, packed cell volume (PCV), red blood cell count; total WBC count etc. can be measured to evaluate haematological status in a pregnant woman. The hematological profile of the pregnant women has an impact on both pregnancy and its outcome. Anaemia in pregnancy can be leads to morbidity and mortality in mother and fetus. The current study was designed to determine the variation in status of hemoglobin and other blood indices in anemic and non-anemic pregnant women.
Aims ans Objectives: 1. To study the hematological and other blood indices among pregnant women, 2. To assess the degree of anemia in pregnant women, 3. To compare the Various hematological parameters between anemic and non -anemic pregnant women.
Materials and Methods: A Cross-sectional comparative descriptive survey design and quantitative approach was adopted to achieve the goal of the study. The study was conducted at the tertiary care hospital of Vadodara, Gujarat. Total 300 pregnant women were recruited and socio demographic information was collected. Hemoglobin concentration (Hb), total leucocyte count (TLC), differential leucocyte count (DLC), and platelet count, blood indices of the recruited samples were studied.Mean and SD of Haematological parameters were calculated and unpaired t-test was used to compare the pregnant anaemic women data with non-anaemic pregnant women.
Results: Out of 300, 204 pregnant women were found anemic and most of the pregnant women 84% belonged to rural area. In accordance with severity of anemia, Moderate degree of anemia was found to be highest (41%) in anemic pregnant women. Comparison of non - anaemic pregnant women with anaemic pregnant women shows significant changes in haematological parameters (p <0.05).
Conclusion: It can be concluded that there is significant changes in hematological parameters in each trimesters of pregnancy as well compare to non-anemic to anemic pregnant women. Most of the hematological changes occur in order to physiological adaptation of pregnancy but abnormal status of Haemoglobin and other blood indices cause adverse outcome of the pregnancy.
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Christou, G., E. Pagourelias, A. Deligiannis, and E. Kouidi. "Exploring the physiological determinants of marathon performance." European Journal of Preventive Cardiology 28, Supplement_1 (May 1, 2021). http://dx.doi.org/10.1093/eurjpc/zwab061.370.
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Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): ESPA 2014-2020 Background/Introduction: Long-time endurance exercise training leads to cardiovascular, respiratory, haematological and neuromuscular adaptations. The relative contribution of these adaptations to running performance in long-distance races remains to be elucidated in an integrative manner. Purpose The study of the relationship of marathon performance with anthropometric, cardiorespiratory and haematological adaptations. Methods Thirty-one marathon runners (26 males, age: 42 ± 9 years) were examined within 3 weeks before Athens marathon race (42.195 km). Assessment of training characteristics, anthropometric measurements, including height, body weight and body fat percentage, echocardiographic study, cardiopulmonary exercise testing using treadmill ergometer and blood test were performed. Results Training age was 11(1-39) years. Body fat percentage(BFP) was 17.3 ± 7.1% and body weight-indexed maximum oxygen uptake(VO2max) was 52.6 ± 8.9 mL/kg/min. Marathon race time(MRT) was 3:59:01(2:47:17-5:31:32). Among anthropometric measurements, MRT was positively associated with BFP(r= 0.561, p = 0.002) and body fat mass(r = 0.514, p = 0.005), even after adjustment for VO2max or oxygen uptake at first(VO2-VT1) or second(VO2-VT2) ventilatory threshold, implying an effect of BFP on running economy. Among echocardiographic parameters, MRT correlated negatively with right ventricular end-diastolic area(RVEDA) (r = -0.707, p < 0.001) and ratio of early to late diastolic transtricuspid flow velocity(TVE/A) (r= -0.430, p = 0.025). MRT correlated negatively with body weight-indexed VO2max (r= -0.692, p < 0.001), VO2-VT1 (r= -0.426, p = 0.019) and VO2-VT2 (r= -0.688, p < 0.001). MRT correlated negatively with maximum minute ventilation(VEmax) (r= -0.418, p = 0.022), VEmax indexed for body surface area(BSA) (r= -0.456, p= 0.011), maximum tidal volume(Vtmax) indexed for BSA(r= -0.436, p = 0.018) and oxygen uptake efficiency slope(OUES) (r= -0.529, p = 0.003). MRT was not associated with haemoglobin concentration. RVEDA correlated positively with maximum oxygen pulse (r = 0.653, p = 0.001), which is an estimate of stroke volume during exercise, and OUES(r = 0.534, p = 0.009). After performing multivariate linear regression analysis with MRT as dependent variable and BFP(standardized β=0.495, p = 0.001), RVEDA(standardized β= -0.550, p = 0.001) and Vtmax indexed for BSA(standardized β= -0.110, p = 0.418) as independent variables, only BFP and RVEDA were significant independent predictors of MRT(adjusted R2 = 0.667, p < 0.001 for the model). Conclusions The results of the present study demonstrated that the main cardiorespiratory adaptation that could predict a better marathon performance was right ventricular dilatation, through the increase in stroke volume during exercise, whereas upregulation of tidal volume during exercise was found to be a weaker predictor. The principal anthropometric determinant of marathon performance appears to be body fat percentage, via the influence on running economy. Abstract Figure 1
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de Beauchamp, Lucie, Ekaterini Himonas, and G. Vignir Helgason. "Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia." Leukemia, September 24, 2021. http://dx.doi.org/10.1038/s41375-021-01416-w.
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AbstractWhile the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells are still not eradicated with current treatments, due to various mechanisms that may contribute to therapy resistance, including cellular metabolic adaptations. In fact, recent studies have shown that LSCs and treatment-resistant cells are dependent on mitochondrial metabolism, hence rendering them sensitive to inhibition of mitochondrial oxidative phosphorylation (OXPHOS). As a result, rewired energy metabolism in leukaemic cells is now considered an attractive therapeutic target and the significance of this process is increasingly being recognised in various haematological malignancies. Therefore, identifying and targeting aberrant metabolism in drug-resistant leukaemic cells is an imperative and a relevant strategy for the development of new therapeutic options in leukaemia. In this review, we present a detailed overview of the most recent studies that present experimental evidence on how leukaemic cells can metabolically rewire, more specifically the importance of OXPHOS in LSCs and treatment-resistant cells, and the current drugs available to target this process. We highlight that uncovering specific energy metabolism dependencies will guide the identification of new and more targeted therapeutic strategies for myeloid leukaemia.
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Olenovych, O. A. "NONSPECIFIC ADAPTATIONAL REACTIONS OF ORGANISM IN PATIENTS WITH HYPOTHYROIDISM ACCORDING TO INTEGRAL HAEMATOLOGICAL INDICES." Clinical & experimental pathology 13, no. 1 (May 27, 2014). http://dx.doi.org/10.24061/1727-4338.xiii.1.47.2014.22.
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Oguntunji, Abel, Opeyemi Adetola Oladejo, Mathew Oluseyi Ayoola, Lopemi Opeoluwa Oriye, Opeyemi Olufemi Ogundijo, and Abiola Olufunke Ilufoye. "Multivariate Analysis of Thermal Adaptive Profile of Three Genetic Groups of Duck." Buletin Peternakan 44, no. 1 (February 29, 2020). http://dx.doi.org/10.21059/buletinpeternak.v44i1.46595.
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Inherent thermal adaptation in livestock is an important economic trait that cannot be overlooked, most especially in animals reared in sub-optimal thermally stressful environments. The present study explored the possibility of using multifactorial discriminant analysis (DA) to separate two duck genera {Muscovy and Common (Mallard) ducks) and their hybrid (Mule ducks) to distinct genetic groups using physiological, haematological and biochemical parameters. Data were collected after exposure of ducks to solar radiation for 90 minutes (12.00 – 13.30 hours). The result of analysis of variance indicated that genotype significantly (P<0.05) affected heamoglobin (Hb), basophil (Bas), total protein (TP), albumin (Alb), globulin (Glb), skin temperature (SKT), respiratory rate (RRT), panting rate (PTR) and rectal temperature (RTC). Stepwise DA revealed that PTR, RRT, Bas and TP in descending order were the most important parameters discriminating the three duck genotypes. The result of cross validation showed that 71.00%, 97.30% and 50.00% of Muscovy, Common and Mule ducks were correctly classified in their expected genetic group respectively. The Euclidean distance between the duck genotypes indicated that longest distance (86.507) was between Muscovy and Common (Mallard) ducks while shortest distance (12.415) was between Muscovy and Mule ducks. The results are applicable in breed adaptation studies, management, conservation and improvement programmes.
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SOUTO, Paula Lorena Grangeira, Eleonara Araújo BARBOSA, Edison MARTINS, Vera Maria Villamil MARTINS, Luciana Keiko HATAMOTO-ZERVOUDAKIS, Concepta Margaret Mcmanus PIMENTEL, and Alexandre Floriani RAMOS. "Influence of season and external morphology on thermal comfort and physiological responses in bulls from two breeds adapted to a subtropical climate." Revista Brasileira de Saúde e Produção Animal 22 (2021). http://dx.doi.org/10.1590/s1519-99402122022021.
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ABSTRACT Animals in subtropical regions can be exposed to periods of thermal stress. Locally adapted breeds are especially important in this context, but these have little information available in their natural environments. The aim of this study was to assess whether season affects thermal comfort and physiological responses to increased temperatures of two breeds of bulls in a subtropical climate. Four Angus and four Crioulo Lageano bulls were used in this study. Body and testicles measurements, skin pigmentation and thickness, hair number, length and pigmentation, respiratory rate, panting score, rectal temperature and haematological profile were recorded on three occasions in summer and winter, morning and afternoon. The surface temperature of the flank, eye and scrotum were obtained by infrared thermography. Hair coat colour was determined by CIELAB method. Thermal comfort indexes were calculated from meteorological data. Statistical analysis included analyses of variance, correlations and a partial least squares regression in determining which traits were the most important in thermal adaptability. External morphology of the bulls was important for explaining physiological changes in both seasons, but their contribution was greater in summer. Bulls experienced moderate heat stress in summer, which led to significant physiological responses, which were more pronounced in Angus bulls. The main differences in thermal adaptation found between breeds were the hair coat characteristics and respiratory rate. Despite using different mechanisms to cope with environmental challenges, all bulls were able to maintain optimal testicular thermoregulation as well as systemic normothermia throughout the seasons, showing good adaptation to the climate conditions.