Includes bibliography. / The presence of calcium (Ca) channels has been investigated in the apical membrane of various segments of rabbit renal tubules and in the basolateral membrane of human tubules, using the patch clamp technique. The rabbit tubule segments comprised proximal straight tubules (PST), thick ascending limbs (TAL), distal convoluted tubules (OCT), and cortical collecting ducts (CCD). The human tubule segments could not be identified, but were probably of proximal origin. The luminal surfaces of the individual tubule segments were accessed by perfusing the tubule and inserting the patch pipette through the open end or, more frequently, by tearing open the tubule to allow direct access by a patch electrode. Either Ba (90 mM) or Ca (70 mM) was used in the pipettes. Where possible, channel activity was sought in voltage clamped (30 to -60 m V) excised patches. The data were digitized at l kHz, and filtered (200- 500 Hz) by a six-pole Bessel filter.

Introduction: Polymyositis (PM), dermatomyositis (DM) and necrotising autoimmune myopathy (NAM) form part of the spectrum of idiopathic inflammatory myopathies (IIMs). Although the pathogenic mechanisms are different, the unifying feature is that of weakness caused, in some way or another, by an inflammatory attack on muscle. The mechanism by which weakness develops is still unclear, but experimental animal data suggest that dysfunction of the contractile apparatus might contribute to muscle weakness in these conditions. This study investigated the contractile function of single muscle fibres from patients with IIMs in vitro. Methods: Muscle biopsies obtained from patients with IIMs and healthy controls were dissected and chemically permeabilised. Single muscle fibres were dissected out and subjected to contractility measurement based on standard protocols utilising a permeabilised single fibre system. Specific force (SF; maximum force normalised to cross-sectional area), was calculated for each fibre and compared between the two groups. In addition, maximum shortening velocity and power output were assessed in some of the fibres, and calcium sensitivity in the rest. The myosin heavy chain composition of each fibre was determined by means of gel electrophoresis. Results: A total of 178 fibres from IIM cases and 174 fibres from controls were studied. Specific (normalised) force was 23%, 24% and 29% lower in the IIM group for all fibre types combined, type I fibres, and type IIa fibres, respectively. Shortening velocity and maximum power output were significantly higher in the IIM group for both type I and IIa fibres, compared to controls, while calcium sensitivity was higher in type IIa fibres from IIM cases than controls. Discussion: The findings from this study suggest that weakness in IIMs may, at least in part, be caused by dysfunction of the contractile apparatus leading to impaired contractile force. The higher shortening velocity, power output and calcium sensitivity in fibres from IIM cases probably represents compensatory mechanisms. Although the mechanism by which contractile function is affected has not been investigated, animal studies suggest a role for TNF-α. The findings of this study provide a basis for further investigation into the mechanisms underlying weakness in IIMs.

Increasing knowledge in physics and chemistry has stimulated research on high polymers, or to use another term, on macromolecules and on their applications in various fields. The definition of macromolecules given in 1922 by Staudinger and Fritschi states that a macromolecule is a compound with more than 1,500 atoms and with a molecular weight exceeding 10,000; dissolved it shows colloidal properties and cannot be dialyzed.

Diabetes Mellitus is a form of metabolic disease with loss or dysfunction in glycemic control. Type II Diabetes Mellitus (T2DM) is characterized by the loss of glycemic control due to developed insulin resistance. T2DM is the most common form of diabetes and a growing epidemic that is affecting 9.4% Americans and 8.5% of the population worldwide. Associated with obesity, genetic predisposition, and environmental factors such as sedentary lifestyle, uncontrolled T2DM causes hyperglycemia, eventually leading to other potential complications including hyperlipidemia, increased risk for cardiovascular diseases, nerve damage and sleep apnea. Additionally, T2DM poses a high financial burden on the USA, costing $372 billion in direct medical costs and reduced productivity. Because obesity is the main driver of insulin insensitivity of T2DM, the current standard of care for T2DM focuses on managing the weight of patients. The initial approach of weight control entails lifestyle interventions, including exercise routine and diet change, with additional glycemic control medication prescribed if the first line of intervention is not effective. T2DM management is particularly challenging in obese patients, and many anti-hyperglycemic medications currently in the market lead to weight gain, which may further add to metabolic control problems. For such a challenge, bariatric surgeries are considered as a T2DM treatment option. Roux-en-Y gastric bypass (RYGB) is the most commonly practiced bariatric surgery in the United States. RYGB is shown to be the most effective treatment for prolonged weight loss leading to metabolic and hormonal changes that ultimately improve glucose metabolism and other complications of diabetes such as hypertension. Interestingly, these beneficial effects against T2DM are observed within days after the operation, before any significant weight loss takes place. T2DM patients after undergoing RYGB showed significant improvement in insulin sensitivity and increased insulin secretion. Additionally, up to 85% of patients showed complete T2DM remission through reporting significantly lowered fasting and post prandial blood glucose levels as well as lowered HbA1c value without the use of anti-hyperglycemic medication. In addition to T2DM remissions, T2DM-related complications were improved after RYGB. Improvement in hyperlipidemia, hypertension, and sleep apnea are reported after the operation. The immediate, weight-loss independent anti-diabetic effects are resulting from the intestinal anatomic alteration from RYGB. This intestinal anatomical change leads to metabolic hormonal profile, bile acid metabolism, and gut microbiota composition. Glucagon-like peptide-1 (GLP-1) is an incretin, or a hormonal factor secreted post prandially in the small intestine, that is known to promote insulin secretion and facilitate blood glucose level regulation. A significant increase in GLP-1 level is observed after RYGB. This change is hypothesized through hindgut theory and foregut theory. Protein Tyrosine Tyrosine (PYY) is another gut hormone secreted by L-cells in the ileum-colon. PYY was appreciated as an anorexigenic appetite regulator, and recently, the hormone is recognized to play a direct role in glycemic control. Increased PYY serum level in patients after RYGB surgery is consistently reported, and this change in serum PYY explained through hindgut theory and foregut theory as PYY is co-secreted with GLP-1. The increased level of PYY is shown to improve glycemic control in T2DM through the restoration of pancreatic islet morphology and function. RYGB not only affects the gut hormonal profile, but the operation also raises total circulating bile acid concentration. Bile acids have recently been appreciated as endocrine factors that stimulate the release of GLP-1 and PYY. Changes in gastrointestinal anatomy resulting from RYGB may affect enterohepatic recirculation of bile acid, leading to the observed increase in total bile acid. An increase in total bile acids is correlated with several markers indicating normalized glycemic control and changes in the gut microbiota of the patients. The microbiota profile for T2DM patients is not fully established due to the inconsistent data reporting structures and discrepancies in reported results. Generally, decreased biodiversity in gut microbiota has been associated with increased obesity, and an increase in lipopolysaccharide-producing microbe drive the low-grade inflammation that leads to insulin resistance of the host. Reconfiguration of the gastrointestinal tract from RYGB leads to increased diversity in gut microbiota composition and markers showing improved metabolic state. Changes in gut microbiota after RYGB led to an increase in GLP-1 release through signaling pathways involving GPCRs activation and to increase in bile acids. Roux-en-Y gastric bypass deems to be a safe, effective therapeutic option for T2DM treatment for obese to severely obese patients. The exact physiological mechanism of the effects of RYGB on T2DM patients still remains elusive, but the current understanding of the effects of RYGB had led to the discovery of many potential therapeutic targets for T2DM.

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Includes abstract. / Includes bibliographical references (leaves 108-128). / Shocked trauma patients in the Intensive Care Unit undergo a powerful, neuro-endocrine stress response driven by cytokine release and the hypothalamic-pituitary-adrenal axis. The response is activated under stress by corticotropin-releasing factor (CRF), the well-known 41 amino acid peptide neuro-hormone. Evidence from animal and human studies suggests that peripheral CRF is present in the gastrointestinal tract and associated with inflammatory changes. Critically ill patients frequently display somewhat unexplained gastrointestinal dysfunction including delayed gastric emptying, ileus and increased bowel permeability. The aim of the study was to investigate the role of CRF in critically ill adults with traumatic abdominal injury compared with elective surgical patients, and describe any association of CRF levels with alterations in acute post-operative gastrointestinal function. Eight patients with haemorrhagic shock following penetrating abdominal injury and seventeen patients undergoing elective surgery for hepato-biliary disease were studied for serial plasma and intestinal tissue CRF levels using radio-immunoassay. A RT-PCR technique was used to detect mRNA for CRF in intestinal tissue. Light microscopy was used to determine the quantity and distribution of mast cells in intestinal tissue. Post-operative gastric emptying was assessed using the paracetamol absorption test and intestinal permeability by measuring urinary lactulose:mannitol ratios following a bolus of these sugars. The study was approved by University of Cape Town Human Research Ethics Committee. Informed consent (retrospectively in the case of the trauma patients), was obtained from all subjects.

Background: Skeletal muscle is highly responsive to exercise training stresses, resulting in specific performance improvements based on the type of training undertaken (66, 119). Among all the variations of exercise training there are two extremes: 1) resistance training (RT), and 2) aerobic training (AT). Concurrent training (CT) is the combination AT and RT. This combination has been shown to have positive effects on body composition through decreases in fat mass (93, 136, 181, 463) and aerobic performance (28, 56, 154, 194, 394, 421, 463). Despite these positive outcomes, there have been multiple works suggesting that the combination of these two training modalities hinders increases in strength (28, 181, 223, 420) and power (154, 420) performance and lean mass (223, 238, 404, 420). Notably, CT composed of high intensity interval training (HIIT) and RT has been shown to positively affect aerobic performance without negatively affecting strength performance in recreationally active men (56, 433, 472) and women (433). Interestingly, rhodiola rosea (RR) (34, 102, 371) and cordyceps sinensis (CS) (61) may have potential to enhance performance. Purpose: To determine the effects of CT, composed of HIIT and RT, and Shroom Tech sport (SUP), a multi-ingredient performance supplement (MIPS) containing RR and CS, on body composition, aerobic and strength performance, cardiometabolic profiles, and hormone concentrations in young recreationally active men. Methods: Recreationally active male volunteers were stratified and matched by age, total strength, relative VO2max, percent body fat, and training years; then assigned to take SUP (n=10) or a placebo (PLA) (n=11). Participants completed a 12-week CT program (4 days per week; 2 days: total body RT; 2 days: HIIT). Supplements (1 capsule (2,378mg) per 23kg) were consumed 45 minutes before each training and testing sessions and at breakfast on non-training days. Body composition, blood draws, and strength, power and aerobic performance were tested at week 0, 7, and 14. Additionally, subjects completed three-day food logs for dietary intake. Data were reported as mean ± SD. Dependent variables were assessed by two-way (group x time) analysis of variance (ANOVA). Significance was accepted at p<0.05. Results: There were no differences between groups in any of the participant characteristics. There were no significant differences in body mass index, fat free mass or percent fat free mass. However, there was a significant effect for time for percent body fat, with both groups exhibiting decreases (SUP: pre 15.5 ± 5.8% v mid 14.8 ± 7.2% v post 14.2 ± 6.6%; PLA: pre 16.2 ± 6.7% v mid 15.3 ± 6.5% v post 14.3 ± 6.4%, p=0.0065), with no significant differences between groups. Further, there were main group (p= 0.042) and time (p=0.016) effects for fat mass but no group x time interactions (SUP: pre 11.92 ± 5.28kg v mid 11.51 ± 6.22kg v post 11.10 ± 6.96 kg; PLA: pre 12.83 ± 6.55kg v mid 12.23 ± 6.61kg v post 11.32 ± 6.49kg). There were no significant differences in body segment circumferences or lean mass index (LMI). There were no changes in VO2max. Both groups improved bench (SUP: 2.6±3.0%; PLA: 5.4±5.2%) and squat (SUP: 7.2±6.6%; PLA: 8.8±5.4%) strength. There was a main effect for time in (p=0.007) and average power (p=0.004) increased over time regardless of group. Notably, significant differences were observed between groups in average bench (SUP: 28±1reps v PLA: 25±3, p<0.05) and total (bench + squat) (SUP: 61±4reps v PLA: 57±4, p<0.05) training volumes at "moderate" (72.5-77.5%) intensities. Further, SUP also attenuated decreases in average running volume at 100% calculated max speed (CMS) when compared to those at 90% CMS versus PLA (SUP:-41±83secs v PLA:-135±118, p<0.05). There were no group x time interactions in any of the hormone concentrations. Interestingly, SUP did exhibit significant decreases in cortisol levels (pre: 17.6 ± 4.6ug/dl v post: 16.6 ± 4.3ug/dl, p=0.34). There were time effects for systolic blood pressure, total cholesterol, LDL, and HDL, with decreases in total cholesterol (SUP: Pre: 152 ± 22mg/dL to Mid: 142 ± 23mg/dl to Post: 147 ± 23mg/dl v PLA: Pre: 154 ± 29mg/dl to Mid: 142 ± 22mg/dl to Post: 143 ± 22mg/dl; p=0.009), LDL (SUP: Pre: 83 ± 26mg/dL to Mid: 74 ± 14mg/dl to Post: 80 ± 26mg/dl v PLA: Pre: 82 ± 24mg/dl to Mid: 70 ± 13mg/dl to Post: 76 ± 18mg/dl; p=0.047) and HDL (SUP: Pre: 48 ± 11mg/dL to Mid: 45 ± 10mg/dl to Post: 44 ± 7mg/dl v PLA: Pre: 60 ± 12mg/dl to Mid: 55 ± 12mg/dl to Post: 54 ± 10mg/dl; p=0.013). Conclusion: Supplementation with SUP 45 minutes prior to exercise enhanced moderate intensity resistance exercise performance and max intensity HIIT performance in recreationally trained men. Additionally, 12 weeks of CT protocol consisting of progressive RT and HIIT improved strength and power performance while decreasing fat mass, however there were no differences between groups. Therefore, use of 2,378mg per 23kg SUP for 12 weeks may be beneficial for recreationally active men. / A Dissertation submitted to the Department of Nutrition, Food & Exercise Sciences in partial fulfillment of the Doctor of Philosophy. / Fall Semester 2016. / October 28, 2016. / Body Composition, Concurrent Training, Cordyceps Sinensis, Rhodiola Rosea, Strength / Includes bibliographical references. / Michael J. Ormsbee, Professor Co-Directing Dissertation; Robert J. Moffatt, Professor Co-Directing Dissertation; James Whyte, IV, University Representative; Jeong Su Kim, Committee Member.

BACKGROUND: It is well-documented that ingesting carbohydrate prior to exercise attenuates fat oxidation. However, it is yet to be established whether this effect is primarily the result of alterations in the mobilization of free fatty acids (FFA) from adipose tissue (i.e. lipolysis). Additionally, there is evidence suggesting that the glycemic index of carbohydrate influences the magnitude of the attenuation in fat oxidation. Specifically, low glycemic index carbohydrate increases fat oxidation relative to high glycemic index carbohydrate. Whether this effect is also due to alterations in adipose tissue metabolism is unknown. Finally, as increasing fat oxidation results in sparing of endogenous carbohydrate, it is possible that pre-exercise low glycemic index carbohydrate may enhance overall energy availability, particularly late in exercise, thereby enhancing endurance performance. PURPOSE: To determine the impact of pre-exercise carbohydrate of different glycemic indices on subcutaneous abdominal adipose tissue (SCAAT) metabolism and running performance. METHODS: Ten trained male runners (mass = 67.1 ± 7.4 kg, VO2max = 63.5 ± 5.3 ml∙kg-1∙min-1, 5-km personal best = 15.9 ± 3.3 min) completed three experimental trials consisting of 30 min at 60% VO2max, 30 min at 75% VO2max, and a 5-km time trial (TT). Thirty min prior to exercise, participants consumed one of three treatment beverages: 1) 75 g low glycemic index modified waxy maize starch supplement (UCAN), 2) 75 g high glycemic index sucrose- and glucose-based supplement (G), or 3) a flavor-, color-, and texture-matched non-caloric placebo (PL). SCAAT lipolysis was assessed via microdialysis. Resting and exercise gas exchange (i.e. VO2 and fuel selection patterns) was assessed via indirect calorimetry. Glucose, insulin, catecholamine, FFA, and glycerol concentrations were analyzed in whole blood and/or plasma at rest and during exercise. Perceptual responses (i.e. gastrointestinal comfort and perceived exertion) during exercise were measured via visual analog scales. Data were analyzed via magnitude-based inferences (i.e. performance, gas exchange, and perceptual responses) and null hypothesis testing (i.e. plasma and interstitial variables; p < 0.05). RESULTS: Immediately prior to exercise, blood glucose was elevated with G vs. PL (+53.0 ± 21.3 mg∙dL-1 [SD]; p = 0.000) and G vs. UCAN (+36.6 ± 24.9 mg∙dL-1; p = 0.00007). Additionally, insulin was increased prior to exercise with G vs. PL (+33.9 ± 11.0 µU∙mL-1; p = 0.000), UCAN vs. PL (+8.7 ± 4.4 µU∙mL-1; p = 0.039), and G vs. UCAN (+25.2 ± 11.0 µU∙mL-1; p = 0.000). VO2 was increased prior to exercise with G vs. PL (+19.6% ± 12.5; likelihoods [%] increase/trivial/decrease: 98/1/0) and UCAN vs PL (10.9 ± 12.2%; 86/11/2). Carbohydrate oxidation was elevated prior to exercise with G vs. PL (+200.1 ± 89.9%; 100/0/0) and G vs. UCAN (+75.5 ± 20.0%; 99/0/0). In addition, carbohydrate oxidation was enhanced at 65% VO2max with G vs. PL (22.9 ± 17.5%; 95/5/0) and UCAN vs. PL (+75.5 ± 20.0%; 75/24/1). Fat oxidation was reduced with G vs PL (-50.1 ± 26.4%; 1/2/97) and G vs. UCAN (-121 ± 74.2%; 0/0/100) prior to exercise, and with G vs. PL (-14.6 ± 9.9%; 1/5/94) and UCAN vs. PL (-9.9 ± 6.8%; 0/10/90) during exercise at 65% VO2max. While SCAAT lipolysis increased over time during exercise, there was no treatment effect. Similarly, plasma catecholamines and glycerol also increased over time but were unaffected by treatment. There was a main effect for time (p = 0.00001) and a treatment interaction (p = 0.002) for plasma FFA; however, post hoc testing revealed no significant differences between treatments. While UCAN likely attenuated abdominal cramping (-18.2 ± 14.3 units vs. PL; -10.0 ± 10.4 units vs. G), tiredness (-6.5 ± 6.6 units vs. PL), and the effort of running (-6.2 ± 5.7 units vs. G) following 60 min running, differences in TT performance were unclear and/or trivial. CONCLUSIONS: In conclusion, pre-exercise ingestion of low glycemic index modified starch attenuated the blood glucose and insulin response to feeding. Additionally, carbohydrate ingestion reduced fat oxidation, and this effect was attenuated at rest with low glycemic index carbohydrate. Despite these effects, adipose tissue metabolism and running performance were not influenced by pre-exercise carbohydrate regardless of glycemic index. / A Dissertation submitted to the Department of Nutrition, Food, and Exercise Sciences in partial fulfillment of the Doctor of Philosophy. / Spring Semester 2017. / March 6, 2017. / Fat metabolism, Glycemic Index, Insulin, Lipolysis, Microdialysis, Performance / Includes bibliographical references. / Michael J. Ormsbee, Professor Directing Dissertation; J. Michael Overton, University Representative; Lynn B. Panton, Committee Member; Jeong-Su Kim, Committee Member.

The aim of this study was to investigate the effects of Mg²⁺ pretreatment and of pharmacological inhibitors of TRPM7 channels on CP-induced cardiac injury in the isolated rat heart.