HPLC-MS identification and expression of Candida drug-resistance proteins from African HIV-infected patients.

The objective of this study was to elucidate the proteomic mechanisms of drug resistance in HIV-infected African patients. Cell membrane fractions from forty oral Candida isolates isolated from African HIV-positive patients were analysed using HPLC-MS with the aim of identifying proteins associated with their pathogenicity and drug resistance. Heat shock proteins that mediate the fungicidal activity of salivary peptides were found in all tested Candida fractions, with pH-responsive proteins associated with increased pathogenicity only being present in the three most commonly isolated species. ABC multidrug transporter efflux pumps and estrogen binding proteins were only found in C. albicans fractions, while ergosterol biosynthesis proteins were identified in four species. The combination of various adherence, invasion, upregulation and efflux pump mechanisms appear to be instrumental for the Candida host colonization and drug resistance emergence in HIV-infected individuals.

Metabolic syndrome is associated with increased seminal inflammatory cytokines and reproductive dysfunction in a case-controlled male cohort.

PROBLEM: The impact of metabolic syndrome (MetS) associated systemic inflammation on the male reproductive tract requires further investigation. METHOD OF STUDY: A cross-sectional case-controlled study design consisting of a control group (n=32) and a MetS (n=42) group was used. Variables include MetS diagnostic criterion, serum C-Reactive Protein (CRP), routine semen analysis, spermatozoa mitochondrial membrane potential (MMP) and DNA fragmentation (DF), as well as TNF-α, IL-1ß, IL6 and IL8 concentrations in serum and semen. RESULTS: Serum and seminal levels of TNF-α, IL-1ß, IL6 and IL8 were all significantly increased in the MetS group. Ejaculation volume, sperm concentration, total sperm count, progressive and total motility and vitality were significantly decreased and sperm with abnormal MMP and DF were increased in the MetS group. CONCLUSION: The results suggest that MetS is associated with decreased fertility parameters in males, as well as local reproductive tract inflammation, in the absence of leukocytospermia.

Obesity is associated with increased seminal insulin and leptin alongside reduced fertility parameters in a controlled male cohort.

BACKGROUND: Obesity appears to be associated with male reproductive dysfunction and infertility, although this has been inconsistent and inconclusive. Insulin and leptin are known mediators and modulators of the hypothalamus-pituitary-testes axis, contributing to the regulation of male reproductive potential and overall wellbeing. These hormones are also present in semen influencing sperm functions. Although abdominal obesity is closely associated with insulin resistance (hyperinsulinaemia), hyperleptinaemia and glucose dysfunction, changes in seminal plasma concentrations of insulin, leptin and glucose in obese males has not previously been investigated. METHODS: This small case controlled study assessed serum and seminal concentrations of insulin, leptin and glucose in obese (BMI > =30; n = 23) and non-obese (BMI < 30; n = 19) males. Following a detailed medical history and examination, participants meeting the inclusion criteria were entered for data analysis. Body parameters such as BMI, waist and hip circumference and the waist hip ratio were measured. Serum and semen samples were collected and assayed for insulin, leptin and glucose. Semen samples also underwent a standard semen analysis, with sperm mitochondrial membrane potential (MMP) and DNA fragmentation (DF). RESULTS: Obesity was associated with increased serum and seminal insulin and leptin, with no significant difference in seminal glucose. Serum and seminal concentrations of insulin and leptin were positively correlated. Furthermore, obesity was associated with decreased sperm concentration, sperm vitality and increased MMP and DF, with a non-significant impact on motility and morphology. CONCLUSIONS: Hyperinsulinaemia and hyperleptinaemia are associated with increased seminal insulin and leptin concentrations, which may negatively impact male reproductive function in obesity. Insulin was also found to be highly concentrated in the seminal plasma of both groups. This data will contribute to the contradictive information available in the literature on the impact of obesity and male reproduction.

Permeation of four oral drugs through human intestinal mucosa.

The pharmaceutical industry is in need of rapid and accurate methods to screen new drug leads for intestinal permeability potential in the early stages of drug discovery. Excised human jejunal mucosa was used to investigate the permeability of the small intestine to four oral drugs, using a flow-through diffusion system. The four drugs were selected as representative model compounds of drug classes 1 and 3 according to the biopharmaceutics classification system (BCS). The drugs selected were zidovudine, propranolol HCl, didanosine, and enalapril maleate. Permeability values from our in vitro diffusion model were compared with the BCS permeability classification and in vivo and in vitro gastrointestinal drug permeability. The flux rates of the four drugs were influenced by the length of the experiment. Both class 1 drugs showed a significantly higher mean flux rate between 2 and 6 h across the jejunal mucosa compared to the class 3 drugs. The results are therefore in line with the drugs' BCS classification. The results of this study show that the permeability values of jejunal mucosa obtained with the flow-through diffusion system are good predictors of the selected BCS class 1 and 3 drugs' permeation, and it concurred with other in vitro and in vivo studies.

The effect of Bach's magnificat on emotions, immune, and endocrine parameters during physiotherapy treatment of patients with infectious lung conditions.

The purpose of this study was to determine the effect of Bach's Magnificat on emotions, immune, and endocrine parameters in patients of specific infectious lung conditions. Participants (N = 40; 9 men & 31 women) ranging in age from 40 to 75 participated in the study. Patients were randomly allocated to an experimental and control group. During a 3-day period the experimental group received physiotherapy with the selected music, while the control group only received physiotherapy. ANOVA statistics indicate significant changes in the following parameters: POMS-scale, CD4+:CD8+ ratio, cortisol, and cortisol:DHEA ratio. The intervention of music demonstrates communication between the mind and body.

Antioxidant supplementation enhances neutrophil oxidative burst in trained runners following prolonged exercise.

The influence of an antioxidant vitamin supplement on immune cell response to prolonged exercise was determined using a randomized, double-blind, placebo-controlled, cross-over study. Twelve healthy endurance subjects (n = 6 male, n = 6 female; mean +/- SD for age, 30.1 +/- 6.2 yr; height, 1.76 +/- 7 m; body mass, 72.2 +/- 10.2 kg; VO2max, 63.7 +/- 12 ml x kg(-1) x min(-1)) participated in the study. Following a 3-week period during which subjects ingested a multivitamin and -mineral complex sufficient to meet the recommended daily allowance, they took either a placebo or an antioxidant vitamin supplement (containing 18 mg beta-carotene, 900 mg vitamin C, and 90 mg vitamin E) for 7 days prior to a 2-h treadmill run at 65% VO2max. Blood samples were drawn prior to and immediately following exercise. These were analyzed for neutrophil oxidative burst activity, cortisol and glucose concentrations, and white blood cell counts, as well as serum anti-oxidant vitamin concentrations. Plasma vitamin C, vitamin E, and beta-carotene concentrations significantly increased following 7-day supplementation (p < .05). In comparison to the placebo group, neutrophil oxidative burst was significantly higher following exercise (p < .05), but no differences were found in any other parameter following the 7-day supplementation period. Although the impact of exercise on neutrophil function is multifactorial, our data suggest that antioxidant supplementation may be of benefit to endurance athletes for the maintenance of this particular function of the innate immune system following the 7-day supplementation period.

Sterols and sterolins: new drugs for the immune system?

Since the discovery of glucocorticoids, we have had a single strategy for manipulating the immune system in cases of destructive diseases mediated by uncontrolled immune responses. However, long-term use of immunosuppressive drugs can lead to the threat of opportunistic infections and malignancies. As we learn more about regulatory subsets of T lymphocytes and their cytokine profiles, the thrust has been on developing new ligands that ultimately give us more site-specific control. Our group has developed a patented mixture of plant sterols and sterolins that has anti-inflammatory properties and profound immune modulating effects on subsets of CD4+ T cells. We have tested this mixture in several clinical entities and we believe that it has wide applications in reverting immune abnormalities.