Interaction of Lead with Calcium,Iron, and Zinc in the Biological Samples of Malnourished Children

There have been few investigations of trace elements in the urine and hair of populations exposed to high levels of arsenic (As) in drinking water. Therefore, concentrations of selected metals in urine and hair samples from a population in a study area where arsenism was endemic and a control area were determined. It was found that the median concentrations of barium (Ba), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), zinc (Zn), and As in the urine samples from the population in the study area were 3.87, 0.47, 0.50, 61.84, 26.82, 1.33, 128.45, 7.05, 1.10, 233.75, and 339.63 μg/L, respectively. The corresponding values in the urine samples from a population in the control area were 29.08, 0.19, 0.21, 27.77, 10.32, 4.61, 14.01, 2.19, 3.90, 113.92, and 20.28 μg/L, respectively. In the study area, Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, and Zn excreted in the urine were likely to be mainly derived from drinking water with high levels of arsenic. The median concentrations of Ba, Cd, Co, Cr, Cu, Mn, Mo, Ni, Pb, Zn, and As in the hair samples from the study area were 4.16, 0.03, 0.09, 1.09, 6.54, 1.97, 0.06, 0.53, 1.64, 144.28, and 1.67 mg/kg, respectively. The corresponding values from the control area were 4.76, 0.03, 0.02, 1.41, 8.31, 1.34, 0.07, 0.39, 0.86, 154.58, and 0.29 mg/kg, respectively. Significant positive correlations were observed between As and Ba, Cd, Co, Cr, Cu, Mo, Ni, Pb, and Zn in the urine in the study area. However, As was not positively associated with these metals in the hair samples. Exposure to high levels of As in drinking water increased the accumulation of Ba and Mn in the hair and the excretion of Cd, Cu, and Mo in the urine in the study area. The population in the study area might experience Cu and Mo deficiencies for an increasing excretion of Cu and Mo.     

Correlation of Calcium and Magnesium Levels in the Biological Samples of Different Types of Acute Leukemia Children

We aimed to investigate the effect of maternal exposure to NaF on mandibular bone microarchitecture and phosphocalcic plasma parameters of the offspring. For this purpose, 10-, 15-, and 21-day-old pups (n?=?6–8 per group) from two groups of mothers, control and NaF 50mg/L treated dams, were used. Plasma calcium (Ca) and phosphorus (P) levels and alkaline phosphatase activity (ALP) were measured. Fluoride concentration (F^?) in bone and in stomach content was measured using potentiometry after isothermal distillation. Morphometric, histological, and histomorphometric analyses of the jaw bones were performed. Plasma Ca and P levels and ALP activity increased in 10-day and decreased in 21-day-old pups from NaF-treated mothers. Fluoride concentration in stomach content samples of 15- and 21-day-old nursing pups from mothers exposed to NaF in their drinking water was higher compared to that observed in control dam offspring. Mandibular F^? content was higher in 21-day-old pups born to F^?-exposed dams compared to those observed in age-matched control pups. Mandibular area increased in 21-day-old pups born to treated mothers as compared to controls. Mandibular bone volume BV/TV (%) was higher in offspring from NaF-exposed dams than in controls at all the studied times. The increase in bone volume after exposure to F^? was concomitant with the increase in trabecular thickness and the decrease in trabecular separation. Altogether, our results showed that exposure to NaF during gestation and lactation increased mandibular area and bone volume of pups, with concomitant changes in phosphocalcic parameters associated with the bone modeling process.     

Validation of internal controls for gene expression analysis in the intestine of rats infected with Hymenolepis diminuta

The non-invasive parasitic cestode Hymenolepis diminuta induces hypertrophy, hyperplasia and other changes in cell activity in the intestine of rats which are indicated in the expression of mRNA. We have investigated various house-keeping genes (GAPDH, β-actin, 18S and HPRT) and other internal controls (total RNA/unit biomass, total RNA/unit length of intestine) to validate gene expression in the rat intestine after cestode infection and drug-induced neuromodulation. Variation in GAPDH, β-actin, 18S and HPRT expression was observed in rat jejunal tissue according to treatment. Total RNA/unit length of intestine was found to be the most suitable internal control for normalizing target gene mRNA expression in both infected and/or drug-induced rat intestine. This normalization method may be applied to studies of gene expression levels in intestinal tissue where hypertrophy, hyperplasia, rapid growth and cell differentiation generally occur.     

Mechanisms mediating the effects of alcohol and HIV anti-retroviral agents on mTORC1, mTORC2 and protein synthesis in myocytes

Alcoholism and acquired immune deficiency syndrome are associated with severe muscle wasting.This impairment in nitrogen balance arises from increased protein degradation and a decreased rate of protein synthesis.The regulation of protein synthesis is a complex process involving alterations in the phosphorylation state and protein-protein interaction of various components of the translation machinery and mammalian target of rapamycin(mTOR) complexes.This review describes mechanisms that regulate protein synthesis in cultured C2C12 myocytes following exposure to either alcohol or human immunodeficiency virus antiretroviral drugs.Particular attention is given to the upstream regulators of mTOR complexes and the downstream targets which play an important role in translation.Gaining a better understanding of these molecular mechanisms could have important implications for preventing changes in lean body mass in patients with catabolic conditions or illnesses.     

Both spike and background genes contribute to murine coronavirus neurovirulence

Various strains of mouse hepatitis virus (MHV) exhibit different pathogenic phenotypes. Infection with the A59 strain of MHV induces both encephalitis and hepatitis, while the highly neurovirulent JHM strain induces a fatal encephalitis with little, if any, hepatitis. The pathogenic phenotype for each strain is determined by the genetic composition of the viral genome, as well as the host immune response. Using isogenic recombinant viruses with A59 background genes differing only in the spike gene, we have previously shown that high neurovirulence is associated with the JHM spike protein, the protein responsible for attachment to the host cell receptor (J. J. Phillips, M. M. Chua, G. F. Rall, and S. R. Weiss, Virology 301:109-120, 2002). Using another set of isogenic recombinant viruses with JHM background genes expressing either the JHM or A59 spike, we have further investigated the roles of viral genes in pathogenesis. Here, we demonstrate that the high neurovirulence of JHM is associated with accelerated spread through the brain and a heightened innate immune response that is characterized by high numbers of infiltrating neutrophils and macrophages, suggesting an immunopathogenic component to neurovirulence. While expression of the JHM spike is sufficient to confer a neurovirulent phenotype, as well as increased macrophage infiltration, background genes contribute to virulence as well, at least in part, by dictating the extent of the T-cell immune response.     

Efficacy and community-effectiveness of insecticide treated nets for the control of visceral leishmaniasis: A systematic review

Visceral leishmaniasis (VL) has been targeted for elimination from Southeast Asia (SEA). The disease has been endemic in SEA, and in other parts of the world involving both humans and animals. One of the key strategies for combating VL is controlling for the vector sandfly. There are a few vector control strategies that are currently in practice. We sought to assess the efficacy and community effectiveness of insecticide treated nets (ITNs) in controlling the burden of sandfly and the occurrence of VL among humans. We conducted a systematic review following a study protocol and the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria. 6331 initial hits were retrieved from Google Scholar, Lilacs, PubMed, Science Direct, WHOlis, WHOiris and PAHOiris. 25 met the full inclusion criteria. Findings show that the insecticide impregnated bednets and the commercially treated long lasting insecticidal nets (LLINs) are effective in controlling sandflies, with mortalities as high as 75% lasting over a year; although their role in controlling VL in the community was not extensively studied, since effectiveness was usually measured with sandflies densities. Findings also show that insecticide impregnated bednets are low cost and well accepted in the community, however, early erosion of insecticides from nets could occur. Some studies also showed that killing of sandflies may not translate into reduction of VL, therefore sandfly knock down and killing data needs to be interpreted with caution. Conclusions of this review are (1) combining insecticide impregnated bednets, as targeted interventions, with another vector control measure, particularly indoor residual spraying, and in conjunction with case detection, could be the way forward to controlling VL in resource limited settings. (2) Given the current low incidence of VL in SEA, it can be difficult to further research the community effectiveness of those control measures in reducing VL.     

Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCC_inh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCC_inh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCC_inh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders.