Добірка наукової літератури з теми "3208 Medical physiology"

Introduction and Aim: Active and learner centred learning methods specially, self-directed learning is considered to be an important method of blended learning approach of imparting knowledge among under graduate medical students in new curriculum through integrated approach. The aim of the study is to analyse the impact and benefits of self-directed learning sessions for understanding cardio- respiratory physiology among phase one MBBS students. Design and Methods: This cross-sectional study was conducted among 250 students of Phase I MBBS for CVS and RS modules. Two groups of students were made Group A (n=125) was administered with self- directed learning sessions, while group B (n=125) was administered with normal didactic lecture session for the same topics. Following each session an objective assessment was conducted for all the topics covered in SDL and lecture sessions and the results were assessed and compared. Results: The maximum marks secured in objective assessment by Group A students post self-directed learning sessions for both cardiovascular and respiratory physiology modules were 31.2% (39/125) and 32.8% (41/125); while moderate marks were secured by 47.2% (59/125) and 48% (60/125). For assessment conducted after lecture sessions for both cardiovascular and respiratory physiology module, maximum marks were obtained by 25.6% (32/125) and 24% (30/125); while moderate marks were obtained by 21.6% (27/125) and 23.5% (29/125) respectively. Significant difference was found in the p values of marks for both modules(n=0.009) (n=0.008). The internal assessment scores showed considerable difference in the maximum marks obtained by students attending SDL sessions (80-89%) as compared to didactic learning sessions (70–79%) with p value = 0.0190, 0.01179 and 0.0192, a0.01184, respectively for both modules. Conclusion: Self-directed learning method seems to be more effective way of delivering the concept as compared to traditional lecture sessions.

Objective: The goals of this article are to (1) identify the incidence of reported laboratory abnormalities in patients in the medical intensive care unit (ICU); (2) characterize the relationship between reported laboratory abnormalities and Acute Physiology and Chronic Health Evaluation III (APACHE III) score, length of stay, and mortality; and (3) evaluate therapeutic replacement in patients with electrolyte abnormalities. Design: Retrospective chart review of all patients admitted to the medical ICU between April 1, 1993 and June 30, 1993. Setting: Large teaching institution. Participants: Patients admitted to the medical ICU (n = 116). Interventions: The following data were collected: age, sex, admitting diagnosis, serum electrolyte and laboratory parameters, APACHE HI score, length of ICU stay, and mortality. Results: Ten individual laboratory abnormalities were found in more than 30% of all patients in the medical ICU (range 32.8–59.5%). Abnormalities in four laboratory parameters were associated with undesirable patient outcomes. Patients with hypoalbuminemia had a significantly higher APACHE HI score (p < 0.05). Hypocalcemia, hypomagnesemia, and hypoalbuminemia all were associated with an increased length of stay in the ICU (p < 0.05). Overall mortality was significantly higher in patients with alkalosis (p = 0.002). Therapeutic replacement in those with low electrolyte concentrations often was delayed or missed. Fifteen to 75% of patients who had abnormally low serum electrolyte concentrations were not treated. Conclusions: A high incidence of laboratory abnormalities is reported in patients admitted to the medical ICU. Several of these abnormalities are associated with undesirable outcomes such as an increased length of ICU stay in patients with hypoalbuminemia, hypocalcemia, and hypomagnesemia and increased mortality in patients with alkalosis. Therapeutic replacement of electrolytes in patients with abnormalities often was delayed or missed.

Experiments were performed to measure the apneic threshold for CO2 and its fundamental properties in anesthetized rats under steady-state conditions. Breathing was detected from diaphragmatic electromyogram activity. Mechanical hyperventilation resulted in apnea once arterial[Formula: see text]([Formula: see text]) had fallen far enough. Apnea was not a reflex response to lung inflation because it did not occur immediately, was not prevented by vagotomy, and was reversed by raising [Formula: see text]without changing mechanical hyperventilation. The apneic threshold was measured by hyperventilating rats mechanically with O2 until apnea had occurred and then raising [Formula: see text] at constant hyperventilation until breathing reappeared. The mean[Formula: see text] level of the apneic threshold in 42 rats was 32.8 ± 0.4 Torr. The level of the threshold did not depend on the volume at which the lungs were inflated. The level of the threshold, under steady-state conditions, was the same when approached from hypocapnia as from eupnea. The level of the threshold could be raised by 9 Torr by chronic elevation of the eupneic [Formula: see text] level by 18 Torr.

In the presence of an externally applied thoracic restriction, conflicting ventilatory responses to exercise have been reported, which could be accounted for by differences in exercise protocol. Seven male subjects performed two incremental and two constant-workload ergometer tests either unrestricted or in the presence of an inelastic corset. Ventilatory variables and arterial estimates of Pco 2 were obtained breath by breath. Subjects hyperventilated in the presence of restriction during the constant-workload test (38.4 ± 3.0 vs. 32.8 ± 3.0 l/min for the average of the last 3 min of exercise, P < 0.05), whereas, at an equivalent workload during the incremental test, ventilation was similar to unrestricted values (unrestricted = 26.3 ± 1.6 vs. restricted = 27.9 ± 2.3 l/min, P = 0.36). We used a first-order linear model to describe the effects of change in workload on minute ventilation (24). When the time constants and minute ventilation values measured during unrestricted and restricted constant-workload exercise were used to predict the ventilatory response to the respective incremental exercise tests, no significant difference was observed. This suggests that hyperventilation is not seen in the restricted incremental test because the temporal dynamics of the ventilatory response are altered.

Angiotensin (ANG) can produce a biphasic arterial pressure response, i.e., an increase followed by a decrease. Because ANG type 1 (AT1) receptors mediate the pressor response to ANG, we hypothesized that the opposing depressor action is mediated by the ANG type 2 (AT2) receptors. In thiobutabarbital (Inactin)-anesthetized rats bolus injections of angiotensin III (ANG III; 100, 300, and 1,000 ng/kg iv) produced peak increases in MAP at 20 s of 13.4 +/- 1.4, 20.1 +/- 2, and 27.5 +/- 2.8 mmHg and maximum decreases in pressure at 120 s of -6.3 +/- 1.5, -6.8 +/- 2.2, and -11.4 +/- 4.9 mmHg. During blockade of the AT1 receptors with DuP 753 (losartan, 10 mg/kg) the increases in MAP were eliminated (P < 0.01), whereas the depressor responses (-24.7 +/- 8, -32.8 +/- 9.3, and -42.0 +/- 10.0 mmHg) were significantly (P < 0.05) larger. In separate groups of rats, combined blockade of both AT1 and AT2 receptors eliminated all changes in MAP in response to ANG III, whereas blockade of AT2 receptors alone enhanced the pressor response to ANG III. During AT1 receptor blockade angiotensin II also caused consistent decreases in pressure, which were inhibited during combined blockade of AT1 and AT2 receptors. Therefore, we have demonstrated that the AT2 receptors mediate a depressor response to ANG.

Smoke inhalation injuries are the leading cause of mortality from burn injury. Airway obstruction due to mucus plugging and bronchoconstriction can cause severe ventilation inhomogeneity and worsen hypoxia. Studies describing changes of viscoelastic characteristics of the lung after smoke inhalation are missing. We present results of a new smoke inhalation device in sheep and describe pathophysiological changes after smoke exposure. Fifteen female Merino ewes were anesthetized and intubated. Baseline data using electrical impedance tomography and multiple-breath inert-gas washout were obtained by measuring ventilation distribution, functional residual capacity, lung clearance index, dynamic compliance, and stress index. Ten sheep were exposed to standardized cotton smoke insufflations and five sheep to sham smoke insufflations. Measured carboxyhemoglobin before inhalation was 3.87 ± 0.28% and 5 min after smoke was 61.5 ± 2.1%, range 50–69.4% ( P < 0.001). Two hours after smoke functional residual capacity decreased from 1,773 ± 226 to 1,006 ± 129 ml and lung clearance index increased from 10.4 ± 0.4 to 14.2 ± 0.9. Dynamic compliance decreased from 56.6 ± 5.5 to 32.8 ± 3.2 ml/cmH2O. Stress index increased from 0.994 ± 0.009 to 1.081 ± 0.011 ( P < 0.01) (all means ± SE, P < 0.05). Electrical impedance tomography showed a shift of ventilation from the dependent to the independent lung after smoke exposure. No significant change was seen in the sham group. Smoke inhalation caused immediate onset in pulmonary dysfunction and significant ventilation inhomogeneity. The smoke inhalation device as presented may be useful for interventional studies.

We evaluated maximal O2 uptake (VO2max), the metabolic acidosis threshold determined by the V-slope analysis [plot of CO2 output (VCO2) as a function of oxygen uptake (VO2)], the ratio of increase in VO2 to work rate increment (delta VO2/delta WR), the upper slope (S2) of the V-slope analysis, and the VO2 for work below and above the metabolic acidosis threshold to determine whether the changes in O2 transport caused by increased carboxyhemoglobin (HbCO) affected these parameters and variables. Ten normal subjects (aged 32.8 +/- 7.1 yr) performed symptom-limited incremental exercise tests in a ramp pattern on a cycle ergometer while breathing air and air with added carbon monoxide to cause HbCO to be approximately 11% and 20%. VO2max decreased by 11.6 and 19.3%, the metabolic acidosis threshold decreased by 11.9 and 19.6%, delta VO2/delta WR decreased by 8.9 and 14.0%, and S2 increased by 13.6 and 21.8% when HbCO was increased to 11 and 20%, respectively. Most importantly, VO2 was unchanged related to work rate below the metabolic acidosis threshold during the tests with increased HbCO but was reduced at the work rates above the metabolic acidosis threshold. These findings are consistent with the concept that the metabolic acidosis threshold is synonymous with an anaerobic threshold, i.e., the latter demarcating the VO2 above which the contracting muscles are not adequately supplied with O2 but below which they are.

Twenty sedentary male university students were randomly assigned to an experimental or a control group. The experimental group trained the knee extensors of one leg by producing 30 isometric extension maximal voluntary contractions (MVC) per day, three times per week for 8 wk. After 8 wk of training, extensor MVC in the trained leg increased 32.8% (P less than 0.05), but there was no change in vastus lateralis maximal integrated electromyographic activity (IEMGmax). The most important finding was that the degree of hamstring coactivation during extension MVC decreased by approximately 20% (P less than 0.05) after the 1st wk of training. Less pronounced adaptations occurred in the untrained leg: extension MVC force increased 16.2% (P less than 0.05), hamstring coactivity decreased 13% (P less than 0.05) after 2 wk of training, and vastus lateralis IEMGmax was unchanged. The same measures in legs of the control group were not changed during the study. There were no changes in flexion MVC, biceps femoris IEMGmax, or the degree of quadriceps coactivity during flexion MVC in either leg of the control or experimental group. A reduction in hamstring coactivity in the trained and untrained legs indicates that these muscles provide less opposing force to the contracting quadriceps. We conclude that this small but significant decrease in hamstring coactivation that occurs during the early stages of training is a nonhypertrophic adaptation of the neuromuscular system in response to static resistance training of this type.

Although baroreceptors are known to reset to operate in a higher pressure range in spontaneously hypertensive rats (SHR), the total profile of dynamic arterial pressure (AP) regulation remains to be clarified. We estimated open-loop transfer functions of the carotid sinus baroreflex in SHR and Wistar Kyoto (WKY) rats. Mean input pressures were set at 120 (WKY120 and SHR120) and 160 mmHg (SHR160). The neural arc transfer function from carotid sinus pressure to efferent splanchnic sympathetic nerve activity (SNA) revealed derivative characteristics in both WKY and SHR. The slope of dynamic gain (in decibels per decade) between 0.1 and 1 Hz was not different between WKY120 (10.1 ± 1.0) and SHR120 (10.4 ± 1.1) but was significantly greater in SHR160 (13.2 ± 0.8, P < 0.05 with Bonferroni correction) than in SHR120. The peripheral arc transfer function from SNA to AP showed low-pass characteristics. The slope of dynamic gain (in decibels per decade) did not differ between WKY120 (−34.0 ± 1.2) and SHR120 (−31.4 ± 1.0) or between SHR120 and SHR160 (−32.8 ± 1.3). The total baroreflex showed low-pass characteristics and the dynamic gain at 0.01 Hz did not differ between WKY120 (0.91 ± 0.08) and SHR120 (0.84 ± 0.13) or between SHR120 and SHR160 (0.83 ± 0.11). In both WKY and SHR, the declining slope of dynamic gain was significantly gentler for the total baroreflex than for the peripheral arc, suggesting improved dynamic AP response in the total baroreflex. In conclusion, the dynamic characteristics of AP regulation by the carotid sinus baroreflex were well preserved in SHR despite significantly higher mean AP.

Preserving skeletal muscle mass is essential for maintaining optimal health throughout the lifespan. Altered skeletal muscle protein and energy metabolism, which typically occurs during the ageing process, leads to muscle degeneration, reduced strength and increased total body fat. As a result, the risk factor for chronic co-morbidities increases, highlighting the importance of preventing and/or treating decreased skeletal muscle mass and strength. While exercise, especially resistance training, is effective in slowing mass and strength loss, the search for appropriate drug therapies remains paramount with respect to global health cost and burden. In addition to this, pre-clinical evaluation of conditions like sarcopenia - the age-related loss of skeletal muscle mass and function - typically require older animals, which are timely and costly. Besides simply aged or genetically modified, there seems to be a lack of accelerated animal models of ageing that recapitulate the physiological underpinnings of conditions like sarcopenia. Thus, part of this thesis was to develop a rapid model of sarcopenia in a young mouse by combining hind limb casting (to induce rapid muscle atrophy) and castration-dependent androgen depletion (to mimic loss of testosterone seen with age). We found that these mice elicited a similar loss in muscle mass compared to middle aged ‘peri-sarcopenic’ mice and had significant detriments in slow-twitch muscle force. With the changes in the model demonstrating a loss in mass and strength, we attempted to correct this by applying a novel combination treatment which was established through three pilot studies. This combination treatment was effective at increasing muscle mass and strength; and decreasing fatigue in slow twitch muscle of healthy mice, strengthening its application in our atrophy model. Therefore, results from this thesis explored the robustness of a new animal model of sarcopenia and that our innovative combination treatment could potentially combat the problems associated with various skeletal muscle conditions.

Endothelial dysfunction is the initiating process in the development of atherosclerosis and cardiovascular disease (CVD) and is a significant predictor of future adverse cardiovascular events. Increasing evidence suggests a link between vascular function and the skeleton, an association that may be mediated by bone-derived proteins such as osteocalcin (OC). OC is an osteoblast-derived, vitamin K-dependent protein that primarily exists in two biological forms. Carboxylated osteocalcin (cOC) is involved in bone formation and undercarboxylated osteocalcin (ucOC) is suggested to be the bioactive form of the protein responsible for regulating energy metabolism and glucose homeostasis. As such, ucOC may be targeted as a therapeutic treatment for metabolic diseases such as diabetes. In humans, the association of OC with endothelial dysfunction and CVD is conflicting, with some suggesting that OC is associated with beneficial effects in the vasculature and others reporting adverse effects. Research in animals suggest that in vivo OC treatment improves vascular function. However, corresponding improvements in metabolic outcomes suggest that the improvements in vascular function may occur indirectly, due to improvements in energy metabolism. As such, the primary aim of this thesis is to investigate if ucOC has a direct biological effect on vascular function in normoglycaemic and hyperglycaemic environments in preclinical models and humans. This was examined in four studies. Study 1: Hyperglycaemia is a pathological condition that has a toxic effect on blood vessels and is a major risk factor for atherosclersosis and CVD. However, it is unclear whether the dysfunction caused by hyperglycaemia is blood vessel specific and whether the dysfunction is exacerbated by an atherogenic diet. It was important to identify which blood vessels developed dysfunction for subsequent studies to assess the vasoactive role of ucOC. Abdominal aorta, iliac and mesenteric arteries were dissected from male New Zealand White Rabbits following either a four week normal or atherogenic diet (n = 6 – 12 per group). The arteries were incubated ex vivo in normal or high glucose solutions (20 mM or 40 mM) for 2 h and isometric tension myography was used to determine endothelial-dependent vasodilation. The atherogenic diet reduced blood vessel relaxation, as measured by area under the curve (AUC), by 25% (p < 0.05) in the aorta, 17% (p = 0.06) in the iliac artery and 40% (p = 0.07) mesenteric artery. In the aorta of the atherogenic diet-fed rabbits the 20 mM glucose incubation altered EC50, thereby reducing the potency of acetylcholine (p < 0.05), and tended to reduce Emax and AUC in the normal diet-fed rabbits. Incubation of the iliac artery from atherogenic diet-fed rabbits in 40 mM glucose also altered EC50, reducing the potency of acetylcholine (p < 0.05). No dysfunction occurred in the mesentery with high glucose incubation following either the normal or atherogenic diet. High glucose-induced endothelial dysfunction appears to be blood vessel specific; the aorta may be the optimal artery to study potential therapeutic treatments of hyperglycaemia-induced endothelial dysfunction. Study 2: In Study 1, we established that acute high glucose incubations and an atherogenic diet cause endothelial dysfunction in rabbit aorta. As such, this study examined the biological effect of ucOC on blood vessel function in rabbit aorta ex vivo, as well as determining the effect of ucOC on markers of endothelial function in human cells in vitro. Isometric tension and immunohistochemistry techniques were used on the aorta of male New Zealand White Rabbits and human aortic endothelial cells (HAEC) were cultured to assess the effect of ucOC in normal and high glucose environments. Overall, ucOC, both 10 ng/ml and 30 ng/ml, did not significantly alter acetylcholine- induced blood vessel relaxation in rabbits (p > 0.05). The ucOC treatment did not cause any significant changes in the immunoreactivity of cellular signalling markers (endothelial nitric oxide synthase, protein kinase B, mammalian target of rapamycin and nitrotyrosine) in rabbit aorta (p > 0.05). In HAEC, ucOC did not attenuate endothelin 1, interleukin 6, vascular adhesion molecule 1, monocyte chemoattractant protein 1 or lactate dehydrogenase, all of which were increased in response to high glucose treatment (p > 0.05). In conclusion, the results of this study suggest that ucOC has no direct influence on endothelial function in rabbit aorta ex vivo or in human endothelial cells in vitro. Study 3: In this study we examined whether ucOC is related to blood pressure and vascular function in older adults and whether ucOC has a direct effect on endothelial function in the carotid artery of rabbits. To undertake the study, we used perfusion myography, which allows for the examination of whole vessel segments with pulsatile flow and pressure that mimics an endogenous environment. In older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 1 years). In male New Zealand White Rabbits, the vasoactivity of the carotid artery was assessed following a four week normal or atherogenic diet. An ucOC dose response curve (0.3 – 45 ng/ml) was administered following incubation of the arteries for 2 h in either normal or high glucose conditions. The concentration of ucOC was higher in normotensive older adults compared to those with stage 2 hypertension (34%, p < 0.05), particularly in women (43%, p < 0.01), but not men (p > 0.05). In all participants, higher ucOC was also associated with lower PWV (p < 0.05), but not BAFMD (p > 0.05). In rabbits, ucOC at any dose did not cause an alteration in the vasoactivity of the carotid artery, following either a normal or atherogenic diet (p > 0.05). In conclusion, ucOC is associated with vascular function in older adults, exclusively in post-menopausal women, but it has no direct effect on endothelial function in rabbit carotid arteries. Study 4: Vitamin K is a regulator of OC carboxylation, with higher vitamin K intake known to reduce circulating levels of ucOC. As ucOC was associated with vascular function in adults in Study 3, we tested the hypothesis that a suppression of ucOC following an increase in dietary vitamin K1 would exhibit a relative worsening of cardiometabolic risk factors. Men (n = 20) and women (n = 10) aged 62 ± 10 years participated in a randomised, controlled, crossover study. Participants were split into high and low responder subgroups following a four week high vitamin K1 diet (HK) of increased leafy green vegetables. High and low responders were defined based on the median percent reduction (30%) in ucOC following the HK diet. Blood pressure (resting and 24 h), arterial stiffness, plasma glucose and lipid concentrations, and serum OC forms were assessed. Following the HK diet, ucOC and ucOC/tOC were suppressed more (p < 0.01) in high responders (41% and 29% respectively) than in low responders (12% and 10% respectively). The reductions in ucOC and ucOC/tOC were not associated with changes in blood pressure, PWV, plasma glucose or lipid concentrations in the high responders (p > 0.05). The results from this study suggest that the suppression of ucOC via consumption of leafy green vegetables has no negative effects on cardiometabolic health, perhaps, in part, due to compensatory mechanisms, such as increased nitric oxide. General conclusions: Overall, the results of this thesis suggest that ucOC does not have a direct biological role in the regulation of endothelial function in rabbit arteries and human endothelial cells. In humans there is some association between ucOC and vascular function but the suppression of circulating ucOC does not influence vascular function or cardiovascular risk factors. As ucOC was not found to have a detrimental effect on vascular function, it may be targeted as a therapeutic treatment for metabolic diseases, such as T2DM, without a risk of adverse effects on the vasculature.

Chemotherapy is an effective first-line cancer-treatment to slow or even cure cancer. Despite it being widely used to treat a variety of cancers, the majority of agents used induce a myriad of serious sequalae. Recently, chemotherapy emerged as a key contributing factor to the induction of devastating wasting condition, cachexia. Cachexia involves the progressive loss of body mass, underscored by severe skeletal muscle wasting and dysfunction (skeletal myopathy). Unravelling the molecular mechanisms involved in the onset and persistence of chemotherapy-induced cachexia represents a complex scientific challenge and is of great clinical interest to identify novel drug targets and efficacious adjuvants. This thesis characterised the impact of individual chemotherapeutic agents on the skeletal muscular system of mice [doxorubicin (DOX) and irinotecan (IRI), 5-fluorouracil (5FU)] and evaluated the therapeutic efficacy of mitoprotective adjuvant candidates, sodium nitrate (with DOX) and BGP-15 (for 5FU and IRI) to protect body mass and skeletal muscle during chemotherapy. Additionally, since chemotherapeutic agents are usually administered to cancer patients in combination regimens which might escalate cachexia, we also characterised the impact of the ‘7+3’ (cytarabine and daunorubicin) chemotherapy induction regimen (CIR) utilised as standard treatment against acute myeloid leukemia. In this regard, we developed and characterised a novel murine model of AML CIR-induced cachexia. We also used this model to trace the course of cachexia during and after treatment and to evaluate whether voluntary exercise could be protective. The major findings of thesis were that the onset and severity of chemotherapy-induced cachexia is agent/regimen specific. While DOX, an anthracycline and topoisomerase-II inhibitor, and IRI, a topoisomerase- I inhibitor, induced a cachectic phenotype characterised by diminished body composition indices, and skeletal myopathy, 5FU, an anti-metabolite, did not cause cachexia. Interestingly, the multi-agent CIR induced severe cachexia. The recovery post-CIR was mixed with skeletal muscle mass returning to normal levels, while body and lean mass not completely recuperating in the 2-week recovery period. At the molecular level, the expression of key structural cytoskeletal proteins, i.e. dystrophin, were impacted by IRI and 5FU whether skeletal myopathy was observed or not. These data suggest that loss of dystrophin might be an early event in the myopathy associated with cachexia. With regard to the adjuvant candidates evaluated, sodium nitrate was not protective against DOX-induced cachexia, despite protecting against early signs of cardiomyopathy. BGP-15 displayed modest protection against IRI-induced cachexia but was not afforded the opportunity when evaluated in combination with 5FU. Alongside the CIR voluntary activity was not protective against cachexia, rather it potentiated CIR-induced cachexia, likely driven through enhanced loss of fat mass. Overall, these findings highlight that further investigation is required regarding the efficacy of mitoprotective adjuvant therapies against chemotherapy-induced cachexia.

The ability to investigate sleep is of scientific and clinical interest. Polysomnography (PSG) has long been considered the gold standard assessment for sleep physiology; however, its cost and inconvenience have spurred the development of consumer devices capable of evaluating sleep outside the laboratory. The development of dedicated consumer sleep monitoring devices, e.g., the Zeo Personal Sleep Manager, smart bands, e.g., the Microsoft Band 2 (MB2), and activity trackers, e.g., the Fitbit Charge 2 (FC2), with the ability to automatically distinguish between sleep and wakefulness has important implications for sleep research and medicine.1–3