Keratins modulate colonocyte electrolyte transport via protein mistargeting

The function of intestinal keratins is unknown, although keratin 8 (K8)–null mice develop colitis, hyperplasia, diarrhea, and mistarget jejunal apical markers. We quantified the diarrhea in K8-null stool and examined its physiologic basis. Isolated crypt-units from K8-null and wild-type mice have similar viability. K8-null distal colon has normal tight junction permeability and paracellular transport but shows decreased short circuit current and net Na absorption associated with net Cl secretion, blunted intracellular Cl/HCO3-dependent pH regulation, hyperproliferation and enlarged goblet cells, partial loss of the membrane-proximal markers H,K-ATPase-β and F-actin, increased and redistributed basolateral anion exchanger AE1/2 protein, and redistributed Na-transporter ENaC-γ. Diarrhea and protein mistargeting are observed 1–2 d after birth while hyperproliferation/inflammation occurs later. The AE1/2 changes and altered intracellular pH regulation likely account, at least in part, for the ion transport defects and hyperproliferation. Therefore, colonic keratins have a novel function in regulating electrolyte transport, likely by targeting ion transporters to their cellular compartments

Pre-treatment practices among animal bite victims attending anti-rabies clinic at a tertiary hospital, Bengaluru: A cross- sectional study

Context/Background Rabies is a neglected, vaccine-preventable, zoonotic tropical disease caused when the saliva of an infected animal comes in contact with human mucosa or skin wounds. Dog bites account for up to 99% of all human cases of rabies. Immediate, thorough wound washing with soap and water after contact with a suspected rabid animal is crucial and can save lives. Pre-treatment practices, such as application of irritants are being practiced among the bite victims

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Nutritionally Enhanced Staple Food Crops

Crop biofortification is a sustainable and cost-effective strategy to address malnutrition in developing countries. This review synthesizes the progress toward developing seed micronutrient-dense cereals and legumes cultivars by exploiting natural genetic variation using conventional breeding and/or transgenic technology, and discusses the associated issues to strengthen crop biofortification research and development. Some major QTL for seed iron and zinc, seed phosphorus, and seed phytate in common bean, rice,J;md wheat have been mapped. An iron reductase QTL associated with seed-iron ~QTL is found in common bean where the genes coding for candidate enzymes involved in phytic acid synthesis have also been mapped. Candidate genes for Ipa co segregate with mutant phenotypes identified in rice and soybean. The Gpe-B1 locus in wild emmer wheat accelerates senescence and increases nutrient remobilization from leaves to developing seeds, and another gene named TtNAM-B1 affecting these traits has been cloned. Seed iron-dense common bean and rice in Latin America; seed iron-dense common bean in eastern and southern Africa;....

Butyrate and glucose metabolism in isolated colonocytes in the developing rat colon

Background: The newborn colon is devoid of microflora, in that bacterial colonization is established after birth. Short chain fatty acids, products of bacterial fermentation, are the major energy source for colonocytes. Because it is not known whether colonocytes in the newborn can metabolize butyrate, this was examined in newborn and infant rat colon. Methods: Isolated colonocytes from rats of different perinatal ages were incubated with 14C-labeled butyrate or glucose in vitro. Complete oxidation was estimated by the production of 14C-labeled carbon dioxide, whereas intermediate metabolites were measured enzymatically. Results: Oxidation of butyrate (in micromoles per hour per milligram of protein) was highest in newborns (5.83 ± 1.76), declining to 1.32 ± 0.28 at day 10 and to 0.34 ± 0.04 in adult rats. Glucose oxidation was also highest at birth (0.39 ± 0.23), with a minor increase at approximately day 20 (weaning period) before decreasing to adult levels (0.05 ± 0). Butyrate oxidation was substantially higher than was glucose oxidation in all age groups. Production of metabolic intermediates paralleled substrate oxidation. Acetoacetate production was 4.35 ± 2.68, 2.07 ± 1.29, and 0.27 ± 0.09 nmol/hr per milligram of protein in newborns, at postnatal day 10, and in adults, respectively. The corresponding values for β-hydroxybutyrate were 3.62 ± 3.35, 0.2 ± 0.07, and 0.09 ± 0.03 nmol/hr per milligram of protein; and L-lactate production was 0.54 ± 0.52, 0.06 ± 0.04, and 0.02 ± 0 μmol/hr per milligram of protein respectively. Conclusions: Neonatal rat colon epithelial cells resemble adult colonocytes in their preference for butyrate as a metabolic substrate, indicating a constitutive expression of this property

Stimulation of sodium chloride absorption from secreting rat colon by short-chain fatty acids

Inhibition of electroneutral NaCl absorption by cyclic adenosine monophosphate (cAMP) results in fluid malabsorption in cholera. Short-chain fatty acids (SCFA) stimulate electroneutral NaCl absorption from the colon. The present study investigated effects of elevated cAMP on SCFA-stimulated NaCl absorption in rat distal colon. The effect of SCFA on fluxes of 22Na and 36Cl was studied under voltage-clamp conditions, in the presence and absence of secret agogues inducing mucosal cAMP elevation [ie, theophylline,cholera toxin (CT) and forskolin]. The effect ofbutyrate concentration on Na absorption in CT- and theophylline treated mucosa was compared with control normal mucosa. cAMP was measured in isolated colonocytes in thepresence of secretagogues with and without SCFA using aradioassay method. All secretagogues were noted to inhibit net Na absorption and to induce net Clsecretion. In the presence of SCFA, net Na absorptionwas normal, and net Cl secretion was partly reversed.The flux data indicated that NaCl absorption from secreting colon was stimulated by SCFA and that Cl secretion was partially inhibited. The effects of SCFA on NaCl absorption were similar regardless of the secret agogue used. The kinetics of butyrate stimulated Na absorption were altered by the ophylline and CT, which decreased Km(6.87 and 7.17,respectively, compared to 10.75 mM for control) and increased Vmax(4.55 and 8.33 compared to 3.45 mM/eq/cm2/hr for control). cAMP production by colonocytes in response to secretory stimuli was significantly reduced (34.4%) by butyrate but not by acetate or propionate. In conclusion, SCFA-stimulated Na absorption is up-regulated by cAMP and maybe an absorptive pathway that can be utilized in thetherapy of cholera. Effects of butyrate on cAMPgeneration are also likely to be useful in secretory diarrhea