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In a randomized controlled clinical trial, the efficacy of a low-sodium low-glucose oral rehydration solution (ORS) and a low-sodium rice-based ORS was compared with standard WHO glucose ORS in the treatment of severe cholera in children aged 2-10 y. In total, 120 children were evaluated for the study, of whom 58 patients were positive for Vibrio cholerae and were included in the study. Of these 58 cases, 19 received rice-based hypo-osmolar ORS, 20 received WHO-ORS and 19 received glucose-based hypo-osmolar ORS. The clinical characteristics (age, pre-admission duration of diarrhoea, frequency of stool before admission, incidence of vomiting, body weight and volume of initial fluid requirement) were comparable in the three treatment groups. All patients received tetracycline in a dose of 50 mg/kg/d of body weight in 4 divided doses for 3 d. Conclusions: Patients who received rice-based hypo-osmolar ORS had subsequently reduced (p < 0.05) stool output, ORS consumption and diarrhoea duration than the patients who received either WHO-ORS or glucose-based hypo-osmolar ORS. [ABSTRACT FROM AUTHOR]

Unlabelled: A double-blind, randomized, controlled trial was conducted to compare the clinical efficacy of hypo-osmolar oral rehydration salts (ORS) solution (224 mmol/L) and standard ORS solution (311 mmol/L) in children with persistent diarrhoea who were prone to develop dehydration. Initially, 95 children aged between 3 and 24 mo were included in the study for overnight observation. Of these, 70 children who passed stool more than 2 g/kg/h were finally enrolled in the study and were randomly assigned either standard ORS or hypo-osmolar ORS. After decoding the identity of ORS, it was observed that 37 children were in the standard ORS group and 33 in the hypo-osmolar ORS group. Clinical parameters and microbiological findings of stool samples were comparable in the two groups at the time of enrolment. Total stool output (2.5+/-1.1 vs 3.2+/-1.6 kg; p = 0.04), duration of diarrhoea (114.8+/-38.3 vs 145.4+/-40.0 h; p = 0.002), total intake of ORS (5.4+/-1.6 vs 7.8+/-1.8 l; p = 0.002) and total fluid intake (7.9+/-2.6 vs 10.0+/-4.1 l, p = 0.01) were significantly less in the hypo-osmolar ORS group compared to the standard ORS group. However, the percentage of weight gain on recovery in the hypo-osmolar group was less compared to that of the standard ORS group, though the difference was statistically insignificant. Thirty-five (95%) children in the standard ORS and 33 (100%) children in the hypo-osmolar group recovered within 10 d of initiation of therapy and modified dietary management.Conclusion: Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating persistent diarrhoea. [ABSTRACT FROM AUTHOR]

A hospital-based case-control study was carried out to clarify the characteristics of mucoid presentation of acute enterocolitis in children. One hundred sixty-eight cases of acute mucoid enterocolitis (study population) were compared with 200 cases of watery diarrhoea and 118 cases of blood dysentery (control groups) on the basis of clinical characteristics and findings on stool examination. Study and control groups were comparable with respect to age, body weight and nutritional status. There was no significant difference in clinical characteristics (duration of diarrhoea, stool frequency, presence of vomiting, fever and dehydration) between patients suffering from mucoid enterocolitis and blood dysentery. However, watery diarrhoea patients had significantly high frequencies of vomiting (p = 0.00001) and dehydration (p = 0.00001). High numbers of microscopic red blood cells (mean ± SD: 40.8 ± 16.8) and white blood cells (40.6 ± 18.0) were present in faecal samples of the patients with mucoid enterocolitis, which is indicative of infection caused by enteroinvasive enteropathogens. Shigella was a commonly identified enteropathogen in patients with mucoid enterocolitis (40.5%) and in patients with dysentery (46.6%), with no statistically significant difference (p = 0.30). Isolation of Salmonella was statistically similar in study and control groups. However, Entamoeba histolytica was detected in significantly high frequency in patients with mucoid enterocolitis as compared to the patients with dysentery (p = 0.0004) and watery diarrhoea (p = 0.00004). Our results indicate that mucoid enterocolitis patients are infected with enteroinvasive enteropathogens, and that stool examination is useful in establishing the aetiological diagnosis. [ABSTRACT FROM AUTHOR]

The protective efficacy of an orally administered heat-killed virulent strain of Shigella flexneri 2a (5 weekly oral doses) was evaluated in 25 rabbits (14 immunized and 11 non-immunized controls) against challenge with the same strain of Shigella using the rabbit model of shigellosis. All 11 non-immunized rabbits developed bloody diarrhoea following challenge and 6 (54%) died. None of the 14 immunized rabbits developed diarrhoea (all had pellet stools) but 3 (21%) died from causes not associated with diarrhoea. Protection from diarrhoea and dysentery following oral immunization with a killed Shigella species was 100% and highly significant. Death following challenge was 2.5-fold higher in the non-immunized group (p = 0.115) but was not significant. These promising results suggest that further studies should be undertaken to develop a killed oral vaccine against shigellosis. [ABSTRACT FROM AUTHOR]

Progressive photoreceptor death occurs in blinding diseases such as retinitis pigmentosa. Myeloid differentiation primary response protein 88 (MyD88) is a central adaptor protein for innate immune system Toll-like receptors (TLR) and induces cytokine secretion during retinal disease. We recently demonstrated that inhibiting MyD88 in mouse models of retinal degeneration led to increased photoreceptor survival, which was associated with altered cytokines and increased neuroprotective microglia. However, the identity of additional molecular changes associated with MyD88 inhibitor-induced neuroprotection is not known. In this study, we used isobaric tags for relative and absolute quantification (iTRAQ) labelling followed by LC-MS/MS for quantitative proteomic analysis on the rd10 mouse model of retinal degeneration to identify protein pathways changed by MyD88 inhibition. Quantitative proteomics using iTRAQ LC-MS/MS is a high-throughput method ideal for providing insight into molecular pathways during disease and experimental treatments. Forty-two proteins were differentially expressed in retinas from mice treated with MyD88 inhibitor compared with control. Notably, increased expression of multiple crystallins and chaperones that respond to cellular stress and have anti-apoptotic properties was identified in the MyD88-inhibited mice. These data suggest that inhibiting MyD88 enhances chaperone-mediated retinal protection pathways. Therefore, this study provides insight into molecular events contributing to photoreceptor protection from modulating inflammation., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary open-angle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data for above classes of lipids. We standardized in vitro assays for rapid characterization of lipids undergoing significant diminishment in disease state. Evaluation of lipids using in vitro assays helped select a finite number of lipids that may potentially expand cellular interstitial space embedded in an artificial matrix or increase fluid flow across a layer of cells. These assays reduced a number of lipids for initial evaluation using a mouse model, DBA/2J with spontaneous IOP elevation. These lipids were then used in other mouse models for confirmation of IOP lowering potential of a few lipids that were found promising in previous assessments. Our results provide selected lipid molecules that can be pursued for further evaluation and studies that may provide insight into their function., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Purpose: Climatic droplet keratopathy (CDK) is an acquired corneal disease characterized by progressive scarring of the cornea. In several corneal diseases, matrix metalloproteinases (MMPs) are upregulated during the degradation of epithelial and stromal tissues. We investigated the levels, degree of activation and molecular forms of MMP-2, MMP-9, MMP-8 and MMP-13 and their tissue inhibitors TIMP-1 and TIMP-2 in tear fluid of patients with CDK., Methods: Seventeen CDK patients and 10 controls living in Argentine Patagonia received a complete eye examination, and MMPs and TIMP-1/2 were determined by immunofluorometric assay (IFMA), gelatin zymography and quantitative Western immunoblot analysis in tear samples., Results: The MMPs were detected mostly in their latent forms. The levels of MMP-9 and MMP-2 were found to be significantly elevated in CDK patients, whereas latent and active MMP-8 levels were significantly enhanced in controls. There was no significant difference in the level of MMP-13. TIMPs were found as part of complexes, and the TIMP-1 levels were significantly lower in patients than controls., Conclusion: Elevated MMP-2 and MMP-9 levels have been implicated in the failure of corneal re-epithelialization, and enhanced MMP-2 and MMP-9 levels in CDK patients suggest that these MMPs may play a role in corneal scarring in CDK. Elevated levels of MMP-8 suggest a defensive role for this MMP in inflammatory reactions associated with recurring corneal traumas. Decreased expression of TIMP-1 in CDK patients suggest deficient antiproteolytic shield likely to render the corneas of CDK patients vulnerable to enhanced MMPs. Overall, these data suggest a mechanistic link between MMPs and TIMP-1 level in cornea and tears with corneal scarring in CDK., (© 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.)

Increased deimination and peptidyl arginine deiminase type 2 (PAD2) expression has been observed in age-related neurodegenerative diseases without discrimination between their aging and disease component. Here, we describe reduced levels of deimination commensurate with reduced protein, mRNA and activity of peptidylarginine deiminase type 2 in the retina, optic nerve and plasma of aged rats when compared to young rats. The decrease was significant in the ganglion cell layer, inner plexiform layer and inner nuclear layer. Because our observations suggest reduced deimination is a consequence of aging, we conclude that increased deimination must be a consequence of disease. Our findings are important to understand late-onset and progressive diseases such as glaucoma, pseudoexfoliation syndrome, age-related macular degeneration and Oguchi's disease.

Background: Helicobacter pylori infection is very common in India, as in other developing countries, but few data exist on the susceptibility of H. pylori to antimicrobial agents commonly used for eradication here., Aim: To determine the antimicrobial susceptibility of H. pylori strains from Kolkata, in eastern India., Methods: A total of 67 H. pylori strains isolated from gastritis and peptic ulcer patients of Kolkata were examined in the study. Minimum inhibitory concentration to the antibiotics was determined by the agar dilution method., Results: Most of the strains (85%) were resistant to at least 8 microg/mL of metronidazole and 7.5% strains were resistant to tetracycline, which was high when compared with other reports in India. All Kolkata strains were highly sensitive to clarithromycin, furazolidone and amoxicillin., Conclusions: Our results differed significantly from the few available reports on drug sensitivity profile of H. pylori from other parts of India, namely, Hyderabad, Mumbai and Lucknow. This finding supports the need for rigorous susceptibility testing as a guide to empirical treatment and more generally, to define the resistance patterns of H. pylori in particular geographical areas.

The immobilization of F(0)F(1)-ATPase in uniform orientation is reported. The biotinylated and histidine-tagged subunits of the bacterial F(0)F(1)-ATPase complex were used for immobilization of the complex on artificial semi-permeable membranes resulting in 88+/-7.8 and 72+/-5.2% coupling of the enzymes. The immobilized enzymes retained over 90% activity. The immobilized ATPase/synthase was used for generation of ATP from ADP and P(i) at the expense of electrochemical potential energy. The re-usability, ratio of amount of enzyme immobilized to enzymic activity conferred on the membranes, ATP synthesized by assembled system and suitability of ATP generated for use in coupled enzymic reactions were determined.

The enzyme carbonic anhydrase (isoform II) from bovine and human erythrocytes was immobilized using different covalent coupling methods on inert matrices. Immobilized carbonic anhydrase may enable concentration of CO2 for Rubisco (ribulose-1,5-bisphosphate carboxylase/oxygenase)-catalysed fixation in bioreactors. In the present study the activity of carbonic anhydrase with respect to hydration of CO2 using soluble and immobilized enzymes was determined. The stability of the immobilization matrix, the properties of the immobilized enzymes subjected to a variation in operation variables and the activity profile with respect to storage are reported. Immobilization imparted greater thermal and storage stability and enhanced reusability.

Aim: To evaluate the efficacy of azithromycin in the treatment of cholera in children., Methods: A double-blind, randomized, controlled clinical trial on 80 children with acute watery diarrhoea and moderate to severe dehydration compared the efficacy of azithromycin and erythromycin in treating cholera. Data were analysed for 56 patients who were stool culture positive for Vibrio cholerae. In conjunction with rehydration therapy, 29 patients received azithromycin and 27 patients received erythromycin. Patients in the two treatment groups had comparable clinical and blood biochemical characteristics on admission., Results: Patients who received azithromycin had significantly less stool output, shorter duration of diarrhoea and lower fluid intake compared with patients who received erythromycin., Conclusion: Azithromycin appears to be superior to erythromycin for treating cholera in children.

Overexpression of the target gene in a recombinant strain of Escherichia coli has been analyzed in view of changes in the carbon-nitrogen source and as a function of C/N ratio. The rate of target gene expression varied over a range of 200%, and the yield coefficient for the target gene product changed over 400% with change in carbon source at 10 gL-1 in M9 medium. With variation in nitrogen source, however, only marginal changes (10-15%) occurred in these parameters of overexpression. Higher concentration, for example 2.5 g L-1, of any nitrogen source adversely affected heterologous expression as rate of target gene expression declined in the range 35%-50% and the yield coefficient of foreign protein decreased between 45% and 60%. A C/N ratio of 15 was found to be optimum for both parameters for overexpression and host specific parameters such as specific growth rate and observed yield coefficient for cellular growth. An analysis with respect to temperature and pH revealed that host and expression parameters were quite susceptible to changes in these factors.

In this study, pulsed-field gel electrophoresis (PFGE) was applied to determine if the Vibrio cholerae 01 strains which reappeared after being temporarily displaced in Calcutta by the 0139 serogroup were different from those isolated before the advent of the 0139 serogroup. NotI digestion generated a total of 11 different patterns among the 24 strains of V. cholerae randomly selected to represent different time frames. Among the V. cholerae 01 strains isolated after July 1993, 4 PFGE banding designated as H through K were observed with pattern H dominating. Pattern H was distinctly different from all other patterns encountered in this study including patterns A, B and C of V. cholerae 01 E1 Tor, which dominated before November 1992, and pattern F, which was the dominant V. cholerae 0139 pattern. Further, pattern H was also different from the NotI banding patterns of the representative strains of the 4 toxigenic clonal groups of V. cholerae 01 E1 Tor currently prevailing in different parts of the world. NotI fragments of the new clone of V. cholerae 01 did not hybridize with an 0139 specific DNA probe, indicating that there was no 0139 genetic material in the new clone of V. cholerae 01. Hybridization data with an 01-specific DNA probe again differentiated between the clones of V. cholerae 01 existing before the genesis of the 0139 serogroup and the 01 strains currently prevalent.

Using a mouse monoclonal antibody (MAb) 2F raised against Vibrio cholerae non-O1 heat-stable enterotoxin (NAG-ST) which also recognizes a shared epitope of Yersinia enterocolitica heat-stable enterotoxin (Y-ST), a competitive enzyme-linked immunosorbent assay (ELISA) was developed for independent detection of NAG-ST and Y-ST. There was good concordance between the Y-ST ELISA and the suckling mouse assay (SMA) for detection of Y-ST from test strains of Y. enterocolitica, and the Y-ST ELISA can effectively replace the SMA for routine detection of Y-ST. On the contrary, evaluation of the NAG-ST ELISA and the SMA using 139 strains of V. cholerae non-O1 showed discordant results and this was attributed to the presence of the suckling mice active factor(s) such as El Tor hemolysin and to the production of low amounts of NAG-ST. Concentration of culture supernatants of V. cholerae non-O1 followed by heating at 100 C was essential to obtain reproducible results by both the NAG-ST ELISA and the SMA. The ELISA developed in this study can be used for the identification of biologically active strains. While recently genetic methods such as polymerase chain reaction became available and were very reliable and simple techniques, the ELISA in this study has an advantage in detecting biologically toxic gene products of the strains. The genetic methods cannot differentiate silent STa genes which we often encounter in the case of Y. enterocolitica.

To study the genetic epidemiology of blood pressure (BP), data on 78 families were collected from a sedentary agricultural population of eastern India. The general levels of both systolic (SBP) and diastolic (DBP) blood pressures are found to be low (mean SBP = 106.41 mm Hg; mean DBP = 63.94 mm Hg). Trends of blood pressures with age are similar to those reported earlier (e.g., in the Framingham study). Environmental variables--e.g., occupation and tobacco use--do not have any direct significant effect on blood pressure variability in this population. Path analysis of family data shows a highly significant familial aggregation and yields a genetic heritability (maximum) estimate of 0.3 for both SBP and DBP. Sib-sib and mother-child correlation estimates are, respectively, 0.3 and 0.25. Father-child correlation estimates are 0.13 for SBP and near zero for DBP. A pseudopolygenic model yields the best fit to the data on SBP, while for DBP a proper resolution of various models considered could not be obtained.

1. Five prostaglandin synthesis inhibitors, indomethacin, diclofenac, mefenamic acid, ibufen and paracetamol, were found to inhibit the antinociceptive action of morphine without affecting the antinociceptive response of an equi-analgesic dose of prostaglandin E1. 2. Diclofenac was found to be the most potent and longest acting, whereas paracetamol was the least potent and shortest acting. Indomethacin, mefenamic acid and ibufen occupied an intermediate position, both in potency and duration of action. 3. The results suggest that prostaglandins may be involved in the antinociceptive action of morphine in albino rats.

Fifty-three households in a small Indian fishing community were surveyed for blood pressure, pulse rate, and anthropometric measurements (height, weight, and three skinfolds). In addition to nuclear family relationships, correlations for extended family members and in-laws living within a common household were estimated by maximum likelihood. Based on likelihood ratio tests, the hypothesis that correlations among genetically unrelated pairs from the same household are zero is rejected for systolic blood pressure. Among genetically related individuals, the degree of relationship does not affect the magnitude of the blood pressure correlations. For the anthropometric measurements, family resemblance is significant only for first-degree relatives, except that the correlation for uncle-child pairs is significant for subscapular skinfold, and brother-in-law-sister-in-law pairs resemble each other for height and weight. The results suggest that common household environment is a significant determinant of blood pressure but not fatness in this population.

1. The antinociceptive effect of prostaglandins E1, E2 and F2alpha was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E1 (PGE1) produced a dose-related antinociceptive activity. 2. The antinociceptive activities of equi-analgesic doses of morphine (7.5. mg/kg, i.p.) and PGE1 (2.0 mg/kg, i.p.) were inhibited to almost similar extents after pretreatment with drugs known to reduce central turnover of serotonin receptors, namely reserpine, fenclonine (p-chlorophenylalanine), methysergide and 5,6-dihydroxytryptamine. 3. Prostaglandin F2alpha (2.0 mg/kg, i.p.) significantly inhibited the antinociceptive effects of both morphine and PGE1. 4. The prostaglandin synthesis inhibitors, indomethacin and diclofenac, significantly inhibited morphine analgesia. 5. Probenecid markedly prolonged the duration of antinociceptive effect of morphine and the duration of PGE1-induced potentiation of subanalgesic dose of morphine. 6. The results suggest that, in albino rats, PGE1-induced antinociceptive activity is serotonin mediated and that morphine analgesia is not only mediated through serotonin but also through prostaglandins (PGE1 ?) and 5-hydroxyindole acetic acid, the serotonin metabolite.

1. Prostaglandin E1 (0.4 ml/kg, i.p.) significantly potentiated the antinociceptive action of morphine in albino rats. 2. This potentiation was significantly inhibited by pretreatment with reserpine, p-chlorophenylalanine or methysergide but not by alpha-methyl-p-tyrosine, phentolamine or propranolol. 3. The results suggest that the potentiation of morphine by prostaglandin E1 is mediated by serotonin, since it is inhibited by pharmacological agents known to reduce central turnover of serotonin receptors.