Gut integrity and duodenal enteropathogen burden in undernourished children with environmental enteric dysfunction

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > −1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = −0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25^th, 75^th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.     

Fructose-2,6-bisphosphate in rat mesenteric lymph nodes

1. The fructose-2,6-bisphosphate (Fru-2,6-P2) content of mesenteric lymph nodes was measured in rats. 2. The effects of Fru-2,6-P2 on the activity of 6-phosphofructo-1-kinase (PFK-1) from rat mesenteric lymph nodes were also studied. 3. The affinity of the enzyme for fructose-6-phosphate was increased by Fru-2,6-P2 whereas the inhibition of the enzyme with high concentrations of ATP was released by Fru-2,6-P2. 4. The activity of lymphocyte PFK-1 was highly stimulated in a simultaneous presence of low concentrations of AMP and Fru-2,6-P2. 5. These results show that rat lymphocyte PFK-1 is highly regulated with Fru-2,6-P2 which means that glycolysis in rat lymphocytes is controlled by Fru-2,6-P2.     

Water chemistry and algal vegetation of streams in the Asir Mountains,Saudi Arabia

Surveys of water chemistry and algal vegetation at nine stream sites in the Asir Mountains, Saudi Arabia, were made in March, 1984. The waters were moderately to highly calcareous with a relatively high Mg: Ca ratio and high concentrations of reactive-Si (x = 12.2 mg l^–1) and F (x = 0.73 mg l^–1). Ammonia typically constituted about one-sixth of the inorganic nitrogen. Filamentous algae (Cladophora and/or Spirogyra) were abundant at all but one site. However two sites, Wadi Habaqah and Al Tanoumah, differed considerably from the others in their overall floristic composition, with various species of Rivulariaceae, Nostoc verrucosum, Schizothrix lardacea and certain other blue-green algae present only here. With one minor exception, heterocystous blue-green algae were absent at the other sites. Tufa was deposited at these two sites, but not elsewhere. Species which appeared to play an active role in calcification included Dichothrix gypsophila, Calothrix parietina, Cladophora glomerata and the moss Bryum sp. A community apparently not previously recorded in the literature was abundant at Wadi Habaqah. This consisted of thick mats of Cladophora glomerata, with a thin surface layer of Zygnemales and numerous colonies of Nostoc verrucosum inside, or towards the underside, of the mat.     

The identification a novel,selective, non-steroidal,functional glucocorticoid receptor antagonist

The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure–activity relationships and the process of optimisation of an initial HTS hit are also described.     

6-Phosphofructo-1-kinase isoenzymes of the jejunal mucosa of rabbit, rat and mouse

1. 6-Phosphofructo-1-kinase (PFK) isoenzymes were studied in the jejunal mucosa of rabbit, rat and mouse. 2. The rat mucosal enzyme was found to be very similar to, although not identical with, the mouse mucosal enzyme, as the physical and regulatory properties of these two enzymes were nearly similar except that the immunological studies were dissimilar. 3. PFK prepared from rabbit mucosa showed different and distinct properties from the rat and mouse mucosal PFK when studied by (NH4)2SO4-precipitation, polyacrylamide gel electrophoresis, immunological cross-reactivity and regulatory properties. 4. The difference between the rabbit enzyme and the rat or mouse enzymes is suggested to be due to the lower rate of glycolysis observed in the rabbit jejunal mucosa as the total enzyme activities of the rabbit were found to be less than half of those activities of the rat and mouse mucosa. 5. The dissimilarities among the species in mucosal isoenzymes obtained in the present study are rather expected since the term isoenzyme is now properly reserved for forms that have been shown to be genetically distinct as shown for different tissues in the same species. Such multigenic control does not appear to have been established for the same tissue in different species.     

Investigating the preventive effects of baicalin and gallocatechin against glyoxal-induced cystatin aggregation

Several mammalian proteins form pathological deposits under nonphysiological conditions that are associated with many degenerative diseases. Protein aggregation is associated with aging, as well as a variety of diseases, including cystic fibrosis, amyotrophic lateral sclerosis (ALS), and hypertrophic cardiomyopathy. There is a lack of any potential anti-amyloidogenic agents and therapeutics till date. Polyphenols have been accredited with myriad biological effects. An analysis of the effects of natural agents like baicalin (BC) and gallocatechin (GC) on aggregation process can open new avenues for the treatment of protein misfolding diseases. Thus, investigation of the effects of these flavonoids on Buffalo Heart Cystatin (BHC) aggregation induced by a reactive metabolic dialdehyde, glyoxal (GO), was taken up. Results have shown that elevated concentration of GO forms aggregates of BHC, which was characterized by an increase in the ANS fluorescence intensity, an increase in ThT fluorescence intensity, red shift in Congo red absorbance, negative ellipticity peak at 217 nm in the far-UVCD and BHC aggregates displaying by TEM. Using fluorescence spectroscopic analysis with Thioflavin T, CD and electron microscopic studies, anti-aggregation effects of polyphenols, BC and GC were analyzed. The study showed that BC and GC produced concentration-dependent anti-aggregation effects with GC producing a more pronounced effect than BC. The study proposed a mechanistic approach assuming structural constraints and specific aromatic interactions of polyphenols with sheets of BHC aggregates.     

Effects of starvation and streptozotocin-induced diabetes on the activity of phosphofructokinase in the epithelial cells of rat colon

The regulation of phosphofructokinase in the colonic mucosa of 48 h-starved and streptozotocin-induced diabetic rats was investigated. The specific activities of phosphofructokinase from colonic mucosa of starved and diabetic rats were found to be diminished compared with normal controls. The enzyme obtained from the colonic mucosa of normal, diabetic and starved rats showed sigmoidal velocity curves with respect to fructose-6-phosphate, with apparent Km values of 0.6, 0.62 and 0.7 mM, respectively. However, the present results indicated that phosphofructokinase from the epithelial cells of rat colon is not regulated in a manner similar to that of the intestinal enzyme, which was shown to be highly regulated.     

Theoretical Analysis of On-Chip Vertical Hybrid Plasmonic Nanograting

Plasmonics - A complementary metal oxide semiconductor (CMOS) compatible photonic-plasmonic waveguide with nanoscale dimensions and better optical confinement has been proposed for the infrared...