Protein supplementation: the double-edged sword.

Protein supplements are widely consumed by athletes as well as young adults and teenagers going to the gym and are an excellent source to increase protein intake, build muscle mass, and enhance recovery. They are available in the form of powders, gummies, protein bars, and ready-to-drink shakes and have been shown to have effects on almost every system in the body. Subjects consuming whey protein-based supplements regularly show significantly lower systolic blood pressure, while subjects who consume soy-based protein supplements have been reported to show a significant decrease in their systolic and diastolic blood pressures. Favorable effects of soy protein consumption have been observed on the serum lipid profile, with significant decreases in serum low-density lipoprotein and triglyceride levels. Lower postprandial glucose levels have been observed in diabetic subjects as well, which can be attributed to the lower glycemic index of these supplements. This can lead to an indirect decrease in diabetes-related complications. While these supplements affect the body positively, caution has to be exercised while consuming them in excess, as they have been shown to cause hyperfiltration and increased urinary calcium excretion which can, in turn, lead to chronic kidney disease development. This article focuses on the effects of protein supplementation on the human body, with emphasis on the cardiovascular, endocrine, and renal systems.

Free and Bioavailable 25-Hydroxyvitamin D Concentrations are Associated With Disease Activity in Pediatric Patients With Newly Diagnosed Treatment Naïve Ulcerative Colitis.

Background: Vitamin D regulates intestinal epithelial and immune functions, and vitamin D receptor deficiency increases the severity of murine colitis. Bioavailable 25-hydroxyvitamin D (25(OH)D) is available to target tissues and may be a driver of immune function. The aim is to evaluate the relationship of bioavailable 25(OH)D to the clinical expression of treatment naive pediatric ulcerative colitis (UC). Methods: The PROTECT (Predicting Response to Standardized Pediatric Colitis Therapy) study enrolled children ≤17 years newly diagnosed with UC. Free and total 25(OH)D were directly measured and 25(OH)D fractions were compared with disease activity measures. Results: Data were available on 388 subjects, mean age 12.7 years, 49% female, 84% with extensive/pancolitis. The median (IQR) total 25(OH)D concentration was 28.5 (23.9, 34.8) ng/mL, and 57% of subjects demonstrated insufficient vitamin D status (25(OH)D < 30 ng/mL). We found no evidence of association between total 25(OH)D and disease activity. Regression models adjusted for age, sex, race, and ethnicity demonstrated that an increase from 25th to 75th percentile for bioavailable and free 25(OH)D were associated with a mean (95th CI) decrease in the Pediatric Ulcerative Colitis Activity Index (PUCAI) of -8.7 (-13.7, -3.6) and -3.1 (-5.0, -1.2), respectively. No associations were detected between 25(OH)D fractions and fecal calprotectin or Mayo endoscopy score. Conclusions: Vitamin D insufficiency is highly prevalent in children with newly diagnosed UC. We found associations of free and bioavailable, but not total 25(OH)D, with PUCAI. Bioavailable vitamin D may contribute to UC pathophysiology and clinical activity.

Synthesis of macromolecular systems via lipase catalyzed biocatalytic reactions: applications and future perspectives.

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz."lipases" in synthetic transformations, the resolution of pharmaceutically important small molecules including polyphenols, amides, nucleosides and their precursors, the development of macromolecular systems (and their applications as drug/gene carriers), flame retardants, polymeric antioxidants and nanocrystalline solar cells, etc.

Inflammatory Bowel Disease in Children and Adolescents.

The inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn disease, are chronic inflammatory disorders of the gastrointestinal tract most often diagnosed in adolescence and young adulthood, with a rising incidence in pediatric populations. These disorders are common enough in children that most pediatricians and other pediatric clinicians will encounter children with IBD in their general practice. Inflammatory bowel disease is caused by a dysregulated mucosal immune response to the intestinal microflora in genetically predisposed hosts. Although children can present with the classic symptoms of weight loss, abdominal pain, and bloody diarrhea, many present with nonclassic symptoms of isolated poor growth, anemia, or other extraintestinal manifestations. Once IBD is diagnosed, the goals of therapy consist of eliminating symptoms, normalizing quality of life, restoring growth, and preventing complications while minimizing the adverse effects of medications. Unique considerations when treating children and adolescents with IBD include attention to the effects of the disease on growth and development, bone health, and psychosocial functioning. The purpose of this review is to provide a contemporary overview of the epidemiologic features, pathogenesis, diagnosis, and management of IBD in children and adolescents.

Cytotoxic and radio-sensitizing effects of polyphenolic acetates in a human glioma cell line (BMG-1).

BACKGROUND AND AIMS: Polyphenolic acetates (PAs) have antioxidant/ pro-oxidant properties and can also acetylate proteins (enzymes) by a novel acetoxy drug: calreticulin transacetylase acetylation system. While PAs have been investigated as pharmacological agents for the treatment of various diseases, their potential as anti-cancer agents or their efficacy as an adjuvant in anti-cancer therapeutics remains to be explored. In the present study we investigated the cytotoxic and radio-sensitizing effects of 7, 8- diacetoxy-4-methyl coumarin (DAMC) and 7- acetoxy-4-methyl coumarin (7-AMC) in a human glioma cell line (BMG-1). METHODS: Cytotoxic and radio-sensitizing effects were investigated by studying reactive oxygen species (ROS) levels, metabolic viability, clonogenic survival, growth inhibition, cell cycle perturbation, DNA repair and cytogenetic damage, besides analyzing the histone (H3) acetylation. RESULTS: Exposure of cells to DAMC and 7-AMC for 24 h showed a dose dependent increase in toxicity as indicated by reduced metabolic viability, clonogenic survival and cell proliferation, with DAMC being more toxic than 7-AMC. The degree of radiosensitization by DAMC was also higher as compared to 7-AMC as reflected by a decrease in the clonogenicity, enhanced radiation-induced cell cycle perturbation and apoptosis. DAMC impaired the removal of radiation-induced DNA double stranded breaks (measured by γH2AX immuno- fluorescence) and enhanced the cytogenetic damage (micronuclei formation), leading to an increase in mitotic death. While DAMC alone induced pan nuclear γH2AX fluorescence, both pan nuclear and spatially restricted foci was observed with the combined treatment (DAMC + Radiation) suggesting a complex nature of DNA damage and repair. DAMC- induced cytotoxic and radio-sensitizing effects were independent of its pro-oxidant activity, whereas histone H3 lysine (9/14) hyperacetylation appeared to be a potential target, regulating cellular responses to ionizing radiation (IR). CONCLUSIONS: The polyphenolic acetate 7, 8- diacetoxy-4-methyl coumarin (DAMC) demonstrates both anticancer effects and radiosensitizing potential under in vitro conditions.

Short- and long-term regulation of 3-hydroxy 3-methylglutaryl coenzyme A reductase by a 4-methylcoumarin.

Dyslipidemia is one of the most significant risk factors for cardiovascular diseases. Cholesterol homeostasis is regulated by both the receptor-mediated endocytosis of Low Density Lipoproteins by LDL receptors and de novo cholesterol synthesis via the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase. Although statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase substrate competitors, have revolutionized the management of cardiovascular diseases by lowering serum LDL, their side effects range from myalgia to rhabdomyolysis. Treatment with antioxidant compounds could represent an efficient alternative in the modulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Indeed it has already been demonstrated that the rise in reactive oxygen species levels causes the complete dephosphorylation and, in turn activation of the enzyme. Many coumarins and their derivatives have the special ability to scavenge reactive oxygen species or show a lipid lowering potential. Here we evaluated whether the coumarin, 4-methylesculetin could exert both the ability to scavenge ROS and to modulate 3-hydroxy-3-methylglutaryl coenzyme A reductase in HepG2 cell line where the enzyme activity dysregulation induced by reactive oxygen species has already been reported. The antioxidant property of 4-methylesculetin led to the reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activation state through the increase of the enzyme phosphorylation. In addition, this coumarin showed the ability to modulate 3-hydroxy-3-methylglutaryl coenzyme A reductase protein levels both by transcriptional and degradational events independent of its antioxidant activity.

Normalization of deranged signal transduction in lymphocytes of COPD patients by the novel calcium channel blocker H-DHPM.

Investigations on the role of intracellular Ca(2+) ion concentration in the mechanism of development of COPD in smokers and non-smokers were carried out. The intracellular Ca(2+) levels were found to be increased in human lymphocytes in patients with COPD as compared to non-smokers and smokers without COPD. The investigations reveal an association in altered intracellular Ca(2+) regulation in lymphocytes and severity of COPD, by means of significant activation of Protein kinase C and inducible nitric oxide synthase (iNOS). The effect of a novel calcium channel blocker ethyl 4-(4'-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) as a potential candidate for the treatment of COPD was also investigated. H-DHPM treated cells showed a decrease in intracellular Ca(2+) level as compared to the control cells. Molecular studies were carried out to evaluate the expression profile of NOS isoforms in human lymphocytes and it was shown that H-DHPM decreases the increased iNOS in COPD along with reestablishing the normal levels of endothelial nitric oxide synthase (eNOS). The results of H-DHPM were comparable with those of Amlodipine, a known calcium channel blocker. Calcium channel blocker H-DHPM proves to be a potential candidate for the treatment of COPD and further clinical studies are required to prove its role in the treatment of pulmonary hypertension (PH).

Selective biocatalytic aminolysis of (±)-epichlorohydrin: synthesis and ICAM-1 inhibitory activity of (S)-(+)-3-arylamino-1-chloropropan-2-ols.

Regio- and enantioselective synthesis of (S)-(+)-3-arylamino-1-chloropropan-2-ols has been achieved by the epoxide ring opening of (±)-epichlorohydrin with different aromatic amines in the presence of Candida rugosa lipase. Activities of seven model (S)-(+)-3-arylamino-1-chloropropan-2-ols, out of 10 compounds synthesized, have been evaluated for the inhibition of tumor necrosis factor-α TNF-α) induced expression of intercellular adhesion molecule-1 (ICAM-1), which is one of the factors responsible for the modulation of inflammation in biological systems; (S)-(+)-1-chloro-3-(2'-chlorophenylamino)-propan-2-ol has been found to exhibit highest activity, that is, 86% inhibition of TNF-α induced expression of ICAM-1 at a concentration of 40 µg/ml.

Evaluating correlates of adolescent physical activity duration towards National Health Objectives: analysis of the Colorado Youth Risk Behavioral Survey, 2005.

BACKGROUND: While numerous studies have examined the relationships among correlates of physical activity (PA), less attention has been given to identifying the correlates of low PA duration. The main objective of the current study was to examine correlates of low PA duration, team sports participation and smoking behaviors among adolescents. METHODS: Data from the 2005 Colorado Youth Behavioral Risk Survey were analyzed using Cox proportional hazard models. We evaluated associations between two measures of low PA duration, assessed as per Healthy People 2010 (HP2010) objectives and 2008 Physical Activity Guidelines (PAG) for Americans, and smoking behaviors, participation in the physical education (PE) and team sports, controlling for age, gender and other behavioral characteristics. RESULTS: Forty percent and 70%, respectively, of adolescents did not meet the 2008 PAG and HP2010 objectives. After adjustment, smoking remained associated with failure to meet the 2008 PAG. However, no significant relationship was found with low PA duration as per the HP2010 objectives. The risk of low PA was higher among girls for both outcome measures. Likewise, adolescents who reported no participation in team sports presented a 7-fold higher risk of low PA as per the 2008 PAG and 51% higher risk of low PA as per the HP2010 objectives compared with the group with team sports participation. CONCLUSIONS: Regular participation in school PE and team sports may represent an important avenue for increasing PA duration and reducing smoking behaviors among adolescents.

7, 8-diacetoxy-4-methylcoumarin induced cell death in human tumor cells is influenced by calreticulin.

Calreticulin (CRT), an endoplasmic reticulum resident protein demonstrates transacetylase activity in presence of 7, 8 diacetoxy-4-methyl coumarin (DAMC) in vitro. To investigate the possible role of CRT and DAMC mediated protein acetylation in cells, we investigated the effects of DAMC in tumor cells with different levels of CRT. DAMC was more toxic (clonogenicity, metabolic viability and proliferation) to human glioma cells (BMG-1) expressing low endogenous CRT level as compared to head and neck carcinoma cells (KB) with a high CRT level. The cytotoxicity was accompanied by loss of mitochondrial membrane potential in both the cells, which correlated with corresponding changes in the levels of pro-apoptotic (Bax) and anti-apoptotic (NFkB) regulators. Manipulation of CRT protein level in KB cells by application of small RNA interference enhanced the sensitivity by four folds while over expression of CRT in BMG-1 cells reduced their sensitivity to DAMC by ~20% strongly suggesting the influence of CRT on DAMC induced cytotoxicity. The partial rescue of CROE cells from DAMC induced toxicity was accompanied by changes in NFkB levels and over all protein acetylation status, besides increase in the NADPH-cytochrome c reductase activity related to its well known antioxidant property. Since CRT is over-expressed in cancer cells, which are generally resistant to radio- and chemotherapy; targeting CRT transacetylase system, may be an attractive approach for increasing the efficacy of anticancer therapies.

Correlates of sexual risk behaviors among high school students in Colorado: analysis and implications for school-based HIV/AIDS programs.

Objectives of this study are to examine correlates of antecedent sexual risk exposures associated with HIV/AIDS infection among adolescents participating in the 2005 Colorado Youth Behavioral Risk Survey (CYBRS), and to determine gender differences associated with these exposures since previous studies have produced mixed findings. Variables assessing these relationships were drawn from CYBRS, 2005. We used χ2 to assess bivariate relationships and multinomial logistic regression to evaluate associations among dependent variables (sexual risk behaviors, age at first sex, and number of sexual partners in the past 3 months) and independent variables (in-school HIV/AIDS education, use of illegal substances, physically forced sex, and alcohol use). We found no significant effect of having received in-school HIV/AIDS education on all outcome measures. Compared with females, males were more likely to initiate sex at a relatively younger age, report unprotected sex with multiple partners, and drink alcohol before sexual intercourse. Among females, using 2 illegal substances increased the odds of early sexual debut by 12 times, while using ≥3 substances increased the same odds to 44-fold. Likewise, binge drinking was also associated with higher odds of having multiple partners. Hispanic ethnicity and physically forced sex variables were consistently associated with high risk sexual behaviors, early sexual initiation, and increased number of sexual partners. Efforts to control the HIV/AIDS epidemic among adolescents may need to focus on targeted interventions aimed at addressing gender- and racial/ethnic-specific risk exposures among this population group, including risk behaviors linked with lifetime physically forced sex. The need to re-examine the role of in-school HIV prevention programs to build adequate competencies among students, parents and community leaders to reduce risk exposures associated with HIV/AIDS infection among youth is emphasized.

Synthesis and antimicrobial activity of 3-arylamino-1-chloropropan-2-ols.

A series of nine 3-arylamino-1-chloropropan-2-ols 2a-2i were synthesized and their anti-fungal activity against pathogenic strains of Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger and Candida albicans, and antibacterial activity against four pathogenic bacterial strains of Salmonella typhi, Pseudomonas aeruginosa, Streptococcus pneumonae and Staphylococcus aureus were evaluated using different assay systems. 1-Chloro-3-(4'-chlorophenylamino)-propan-2-ol was found to be the most active anti-fungal compound against three pathogenic strains under study, i.e., A. fumigatus, A. flavus and A. niger; the compound showed more than 90% inhibition of growth of A. fumigatus at a concentration of 5.85 microg/ml in disc diffusion assay. Interestingly, 1-chloro-3-(4'-chlorophenylamino)-propan-2-ol did not show any toxicity up to a concentration of 4000 microg/ml. Although 1-chloro-3-(4'-chlorophenylamino)-propan-2-ol was about 8 times less active than the standard compound amphotericin B, its toxicity was many more fold less than the toxicity of amphotericin B. Further, 1-chloro-3-(2',6'-dichlorophenylamino)-propan-2-ol and 1-chloro-3-(3',5'-dichlorophenylamino)-propan-2-ol were found to be the most active compounds against C. albicans. In the anti-microbial assay, 1-chloro-3-(2',4'-dichlorophenylamino)-propan-2-ol and 1-chloro-3-(3',5'-dichlorophenylamino)-propan-2-ol were found to be the most active compounds against Salmonella typhi and 1-chloro-3-(3',4'-dichlorophenylamino)-propan-2-ol was found to be the most active compound against P. aeruginosa. Although, the activities of 1-chloro-3-(2',4'-dichlorophenylamino)-propan-2-ol and 1-chloro-3-(3',5'-dichlorophenylamino)-propan-2-ol are about half the activity of the standard anti-bacterial compound tetracycline, these compounds also were many fold less toxic than the standard drug.

Towards understanding of glycaemic index and glycaemic load in habitual diet: associations with measures of glycaemia in the Insulin Resistance Atherosclerosis Study.

Epidemiologic studies have applied the glycaemic index (GI) and glycaemic load (GL) to assessments of usual dietary intake. Results have been inconsistent particularly for the association of GI or GL with diabetes incidence. We aimed to advance understanding of the GI and GL as applied to food frequency questionnaires (FFQ) by evaluating GI and GL in relation to plasma measures of glycaemia. Included were 1255 adults at a baseline examination (1994-6) and 813 who returned for the 5-year follow-up examination. Usual diet, at both examinations, was assessed by a validated FFQ. GI and GL were evaluated in relation to average fasting glucose (two measures at each examination) and 2 h post-75 g glucose load plasma glucose (baseline and follow-up), and glycated haemoglobin (A1c; follow-up only); using generalized linear models. Correlation coefficients (r) for GI and GL related to measures of glycaemia, adjusted for total energy intake, ranged from -0.004 to 0.04 (all NS) for both examinations. Adjustment for potential confounders, for fasting glucose in models for 2 h glucose (to model incremental glucose) and for average fasting glucose in models for A1c (to account, in part, for overnight endogenous glucose production) also did not materially alter findings, nor did inclusion of data from both examinations together in linear mixed models. The present results call into question the utility of GI and GL to reflect glycaemic response to food adequately, when used in the context of usual diet. Further work is needed to quantify usual dietary exposures relative to glucose excursion and associated chronic glycaemia and other metabolic parameters.