Matthew J. Sharman

IMPACT OF VICOPROFEN ON PLASMA PROENKEPHALIN PEPTIDE F CONCENTRATIONS AFTER

Peptide F [preproenkephalin (107–140)] has been shown to have stress-induced opiate-like activities with both analgesic and immune modulation characteristics.PURPOSE:The purpose of this study was to determine the effects of Vicopofen (hydrocodone bitartrate 7.5 mg with ibuprofen 200mg), ibuprofen (2

Cholesterol metabolism and transport in the pathogenesis of Alzheimer's disease

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the ɛ4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins – drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.

Comparison of a Very Low-Carbohydrate and Low-Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women

Objective: Very low-carbohydrate diets are widely used for weight loss yet few controlled studies have determined how these diets impact cardiovascular risk factors compared to more traditional low-fat weight loss diets. The primary purpose of this study was to compare a very low-carbohydrate and a low-fat diet on fasting blood lipids, LDL subclasses, postprandial lipemia, and insulin resistance in overweight and obese women. Methods: Thirteen normolipidemic, moderately overweight (body fat >30%) women were prescribed two hypocaloric (−500 kcal/day) diets for 4 week periods, a very low-carbohydrate (<10% carbohydrate) and a low-fat (<30% fat) diet. The diets were consumed in a balanced and randomized fashion. Two fasting blood draws were performed on separate days and an oral fat tolerance test was performed at baseline, after the very low-carbohydrate diet, and after the low-fat diet. Results: Compared to corresponding values after the very low-carbohydrate diet, fasting total cholesterol, LDL-C, and HDL-C were significantly (p ≤ 0.05) lower, whereas fasting glucose, insulin, and insulin resistance (calculated using the homeostatic model assessment) were significantly higher after the low-fat diet. Both diets significantly decreased postprandial lipemia and resulted in similar nonsignificant changes in the total cholesterol/HDL-C ratio, fasting triacylglycerols, oxidized LDL, and LDL subclass distribution. Conclusions: Compared to a low-fat weight loss diet, a short-term very low-carbohydrate diet did not lower LDL-C but did prevent the decline in HDL-C and resulted in improved insulin sensitivity in overweight and obese, but otherwise healthy women. Small decreases in body mass improved postprandial lipemia, and therefore cardiovascular risk, independent of diet composition.

Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women

ObjectiveTo compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK) and low-fat (LF) diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE) in overweight/obese men and women.DesignRandomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day) diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%).Subjects15 healthy, overweight/obese men (mean ± s.e.m.: age 33.2 ± 2.9 y, body mass 109.1 ± 4.6 kg, body mass index 34.1 ± 1.1 kg/m2) and 13 premenopausal women (age 34.0 ± 2.4 y, body mass 76.3 ± 3.6 kg, body mass index 29.6 ± 1.1 kg/m2).MeasurementsWeight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry), and resting energy expenditure (REE) were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person.ResultsActual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28%) and the LF (~58:22:20%) were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day) compared to the LF (1562 kcal/day) diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women. Absolute REE (kcal/day) was decreased with both diets as expected, but REE expressed relative to body mass (kcal/kg), was better maintained on the VLCK diet for men only. Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet.ConclusionThis study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss, especially in men. A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinically significant but requires further validation. These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution.

Weight loss leads to reductions in inflammatory biomarkers after a very-low-carbohydrate diet and a low-fat diet in overweight men.

In recent years, it has become apparent that low-grade vascular inflammation plays a key role in all stages of the pathogenesis of atherosclerosis. Weight loss has been shown to improve blood inflammatory markers; however, it is unknown if weight-loss diets varying in macronutrient composition differentially affect inflammatory responses. The primary purpose of the present study was to compare a very-low-carbohydrate diet and a low-fat weight-loss diet on inflammatory biomarkers in overweight men. In a randomized cross-over design, 15 overweight men (body fat, >25%; body mass index, 34 kg/m2) consumed two experimental weight-loss diets for two consecutive 6-week periods: a very-low-carbohydrate diet (<10% energy via carbohydrate) and a low-fat diet (<30% energy via fat). Both the low-fat and the very-low-carbohydrate diets resulted in significant decreases in absolute concentrations of hsTNF-alpha (high-sensitivity tumour necrosis factor-alpha), hsIL-6 (high-sensitivity interleukin-6), hsCRP (high-sensitivity C-reactive protein) and sICAM-1 (soluble intercellular cell-adhesion molecule-1). There was no significant change in absolute sP-selectin (soluble P-selectin) concentrations after either diet. Normalized inflammatory values represented as the delta change per 1 kg reduction in body mass showed a significant difference between the two diets only for sP-selectin (P<0.05). In summary, energy-restricted low-fat and very-low-carbohydrate diets both significantly decreased several biomarkers of inflammation. These data suggest that, in the short-term, weight loss is primarily the driving force underlying the reductions in most of the inflammatory biomarkers.

Androgen receptor content following heavy resistance exercise in men

The purpose of the present investigation was to examine androgen receptor (AR) content in the vastus lateralis following two resistance exercise protocols of different volume. Nine resistance-trained men (age=24.3+/-4.4 years) performed the squat exercise for 1 (SS) and 6 sets (MS) of 10 repetitions in a random, counter-balanced order. Muscle biopsies were performed at baseline, and 1h following each protocol. Blood was collected prior to, immediately following (IP), and every 15 min after each protocol for 1h. No acute elevations in serum total testosterone were observed following SS, whereas significant 16-23% elevations were observed at IP, 15, and 30 min post-exercise following MS. No acute elevations in plasma cortisol were observed following SS, whereas significant 31-49% elevations were observed for MS at IP, 15, and 30 min post-exercise. Androgen receptor content did not change 1h following SS but significantly decreased by 46% following MS. These results demonstrated that a higher volume of resistance exercise resulted in down-regulation of AR content 1h post-exercise. This may have been due to greater protein catabolism associated with the higher level of stress following higher-volume resistance exercise.

Muscle fiber characteristics in patients with peripheral arterial disease.

PURPOSE There have been conflicting reports of muscle fiber type changes in patients with peripheral arterial disease (PAD). The purpose of this study was to examine the myosin heavy chain (MHC) expression as well as histochemical changes in the gastrocnemius muscle in patients with symptomatic PAD. METHODS Needle biopsy specimens were obtained from the medial gastrocnemius of 14 subjects with PAD (mean age (+/- SD), 69.7 +/- 4.8 yr) and eight activity-matched control subjects (mean age, 65.1 +/- 6.6 yr). Ankle-brachial index was assessed using Doppler ultrasound to determine the hemodynamic status of the patients, and maximal walking performance was determined during a graded treadmill test. Expression of MHC isoforms was determined by SDS-PAGE. RESULTS The proportion of MHC I was significantly smaller in PAD than in the controls (45.6 +/- 9.1% vs 58.8 +/- 15.0%). The proportion of MHC IIx was also larger in the subjects with PAD compared with the controls (22.9 +/- 9.1% vs 16.0 +/- 11.3%). In addition, there was a significant decrease in the cross-sectional area of the type I and type IIA fibers in the subjects with PAD as well as enhanced capillary density. CONCLUSIONS This study showed a significant modification in the expression of MHC isoforms and muscle fiber type in the gastrocnemius in patients with symptomatic PAD. These results suggest that muscle ischemia resulting from PAD is an important factor in causing the adaptations in the contractile apparatus of the muscle.

High-affinity growth hormone binding protein and acute heavy resistance exercise

PURPOSE The purpose of this investigation was to examine the influence of resistance training on circulating concentrations of growth hormone binding protein (GHBP) in response to acute heavy resistance exercise. METHODS Using a cross-sectional experimental design, a group of resistance-trained men (RT, N=9, 7.9+/-1.3 yr resistance training experience) and a group of untrained men (UT, N=10) performed an acute heavy resistance exercise protocol (AHREP) consisting of 6 sets of 10 repetition maximum parallel squats. Blood samples were obtained 72 h before exercise, immediately before exercise, and 0, 15, 30, 45, and 60 min after exercise. RESULTS Significant increases (P<0.05) in GHBP, immunoreactive growth hormone (iGH), and IGF-1 were observed in both subject groups after AHREP. There were no differences (P>0.05) between groups in GHBP at rest or after AHREP. However, RT exhibited a significantly greater iGH response to AHREP than UT subjects, and significantly higher IGF-1 values at rest and after exercise. Significant positive correlations were found between GHBP and BMI, body fat, and leptin in both groups. A significant positive correlation also was observed between resting leptin and GHBP values in UT but not RT subjects. CONCLUSIONS In summary, these data indicate that resistance training does not increase blood GHBP. Nevertheless, the increases observed with IGF-1 concentrations in the resistance-trained subjects do suggest an apparent adaptation with the regulation of this hormone. If there was in fact an increase in GH sensitivity and GH receptor expression at the liver that was not detected by blood GHBP in this study, it may be possible that factors contributing to the circulating concentration of GHBP other than hepatocytes (e.g., leptin and adipocytes) may serve to mask training-induced increases in circulating GHBP of a hepatic origin, thus masking any detectable increase in GH receptor expression.

The Effects of Amino Acid Supplementation on Muscular Performance During Resistance Training Overreaching

The purpose of this study was to examine the effects of ami-no acid supplementation on muscular strength, power, and high-intensity endurance during short-term resistance training overreaching. Seventeen resistance-trained men were randomly assigned to either an amino acid (AA) or placebo (P) group and underwent 4 weeks of total-body resistance training consisting of two 2-week phases of overreaching (phase 1: 3 X 8–12 repetitions maximum [RM], 8 exercises; phase 2: 5 X 3–5RM, 5 exercises). Muscle strength, power, and high-intensity endurance were determined before (T1) and at the end of each training week (T2-T5). One repetition maximum squat and bench press decreased at T2 in P (5.2 and 3.4 kg, respectively) but not in AA, and significant increases in 1RM squat and bench press were observed at T3-T5 in both groups. A decrease in the ballistic bench press peak power was observed at T3 in P but not AA. The fatigue index during the 20-repetition jump squat assessment did not change in the P group at T3 and T5 (fatigue index = 18.6 and 18.3%, respectively) whereas a trend for reduction was observed in the AA group (p = 0.06) at T3 (12.8%) but not T5 (15.2%; p = 0.12). These results indicate that the initial impact of high-volume resistance training overreaching reduces muscle strength and power, and it appears that these reductions are attenuated with amino acid supplementation. In addition, an initial high-volume, moderate-intensity phase of overreaching followed by a higher intensity, moderate-volume phase appears to be very effective for enhancing muscle strength in resistance-trained men.

Novel promising therapeutics against chronic neuroinflammation and neurodegeneration in Alzheimer's disease.

Alzheimers disease (AD) is a progressive neurodegenerative disorder, characterized by deposition of amyloid plaques and neurofibrillary tangles, as well as microglial and astroglial activation, and, finally, leading to neuronal dysfunction and death. Current treatments for AD primarily focus on enhancement of cholinergic transmission. However, these treatments are only symptomatic, and no disease-modifying drug is available for the treatment of AD patients. This review will provide an overview of the antioxidant, anti-inflammatory, anti-amyloidogenic, neuroprotective, and cognition-enhancing effects of a variety of nutraceuticals including curcumin, apigenin, docosahexaenoic acid, epigallocatechin gallate, α-lipoic acid and resveratrol and their potential for AD prevention and treatment. We suggest that therapeutic use of these compounds might lead to a safe strategy to delay the onset of AD or slow down its progression. The continuing investigation of the potential of these substances is necessary as they are promising compounds to yield a possible remedy for this pervasive disease.