Outbreak of burn wound infections by Salmonella enterica serovar Menston and the role of disinfectant testing in finding the cause of spread.
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Burns↗
Biomedical subjects
B Mishra
Publications and source records attributed to B Mishra.
Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori.
The aim of this study was to develop a new intra-gastric floating in situ gelling system for controlled delivery of amoxicillin for the treatment of peptic ulcer disease caused by Helicobacter pylori (H. pylori). Gellan based amoxicillin floating in situ gelling systems (AFIG) were prepared by dissolving varying concentrations of gellan gum in deionized water containing sodium citrate, to which varying concentrations of drug and calcium carbonate, as gas-forming agent, was added and dissolved by stirring. The formulation variables like concentration of gellan gum and calcium carbonate significantly affected the in vitro drug release from the prepared AFIG. The in vivo H. pylori clearance efficacy of prepared AFIG in reference to amoxicillin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. AFIG showed a significant anti-H. pylori effect in the in vivo gerbil model. It was noted that the required amount of amoxicillin for eradication of H. pylori was 10 times less in AFIG than from the corresponding amoxicillin suspension. The results further substantiated that the prepared AFIG has feasibility of forming rigid gels in the gastric environment and eradicated H. pylori from the gastrointestinal tract more effectively than amoxicillin suspension because of the prolonged gastrointestinal residence time of the formulation.
Amoxicillin↗
Synthesis, pulse radiolysis, and in vitro radioprotection studies of melatoninolipoamide, a novel conjugate of melatonin and alpha-lipoic acid.
A novel conjugate of melatonin 2 and alpha-lipoic acid 4 has been prepared using DCC mediated coupling. The conjugate named melatoninolipoamide has been assigned its structure 1 on the basis of spectral analysis (UV, IR, NMR, and EI-MS). Pulse radiolysis studies of the conjugate were carried out in aqueous solutions with both oxidizing and reducing radicals. The results indicate that the melatonin moiety of the conjugate reacts preferably with oxidizing radicals and the lipoic acid moiety exhibits preferential reaction with reducing radicals. The in vitro radioprotection ability of 1 was examined by gamma-radiation induced lipid peroxidation in liposomes and hemolysis of erythrocytes, and compared the results with those of melatonin and alpha-lipoic acid. The studies suggest that the conjugate can be explored as a probable radioprotector.
Free Radicals↗
Critical interactions between TGF-beta signaling/ELF, and E-cadherin/beta-catenin mediated tumor suppression.
Inactivation of the transforming growth factor-beta (TGF-beta) pathway occurs often in malignancies of the gastrointestinal (GI) system. However, only a fraction of sporadic GI tumors exhibit inactivating mutations in early stages of cancer formation, suggesting that other mechanisms play a critical role in the inactivation of this pathway. Here, we show a wide range of GI tumors, including those of the stomach, liver and colon in elf+/- and elf+/- / Smad4+/- mutant mice. We found that embryonic liver fodrin (ELF), a beta-Spectrin originally identified in endodermal stem/progenitor cells committed to foregut lineage, possesses potent antioncogenic activity and is frequently inactivated in GI cancers. Specifically, E-cadherin accumulation at cell-cell contacts and E-cadherin-beta-catenin-dependent epithelial cell-cell adhesion is disrupted in elf+/- / Smad4+/- mutant gastric epithelial cells, and could be rescued by ectopic expression of full-length elf, but not Smad3 or Smad4. Subcellular fractionation revealed that E-cadherin is expressed mainly at the cell membrane after TGF-beta stimulation. In contrast, elf+/- / Smad4+/- mutant tissues showed abnormal distribution of E-cadherin that could be rescued by overexpression of ELF but not Smad3 or Smad4. Our results identify a group of common lethal malignancies in which inactivation of TGF-beta signaling, which is essential for tumor suppression, is disrupted by inactivation of the ELF adaptor protein.
Animals↗
Effect of pH on one-electron oxidation chemistry of organoselenium compounds in aqueous solutions.
Pulse radiolysis coupled with absorption detection has been employed to study one-electron oxidation of selenomethionine (SeM), selenocystine (SeCys), methyl selenocysteine (MeSeCys), and selenourea (SeU) in aqueous solutions. Hydroxyl radicals (*OH) in the pH range from 1 to 7 and specific one-electron oxidants Cl2*- (pH 1) and Br2*- (pH 7) have been used to carry out the oxidation reactions. The bimolecular rate constants for these reactions were reported to be in the range of 2 x 10(9) to 10 x 10(9) M(-1) s(-1). Reactions of oxidizing radicals with all these compounds produced selenium-centered radical cations. The structure and stability of the radical cation were found to depend mainly on the substituent and pH. SeM, at pH 7, produced a monomer radical cation (lambdamax approximately 380 nm), while at pH 1, a dimer radical cation was formed by the interaction between oxidized and parent SeM (lambdamax approximately 480 nm). Similarly, SeCys, at pH 7, on one-electron oxidation, produced a monomer radical cation (lambdamax approximately 460 nm), while at pH 1, the reaction produced a transient species with (lambdamax approximately 560 nm), which is also a monomer radical cation. MeSeCys on one-electron oxidation in the pH range from 1 to 7 produced monomer radical cations (lambdamax approximately 350 nm), while at pH < 0, the reaction produced dimer radical cations (lambdamax approximately 460 nm). SeU at all the pH ranges produced dimer radical cations (lambdamax approximately 410 nm). The association constants of the dimer radical cations of SeM, MeSeCys, and SeU were determined by following absorption changes at lambdamax as a function of concentration. From these studies it is concluded that formation of monomer and dimer radical cations mainly depends on the substitution, pH, and the heteroatoms like N and O. The availability of a lone pair on an N or O atom at the beta or gamma position results in monomer radical cations having intramolecular stabilization. When such a lone pair is not available, the monomer radical cation is converted into a dimer radical cation which acquires intermolecular stabilization by the other selenium atom. The pH dependency confirms the role of protonation on stabilization. The oxidation chemistry of these selenium compounds is compared with that of their sulfur analogues.
Cystine↗
RING finger-dependent ubiquitination by PRAJA is dependent on TGF-beta and potentially defines the functional status of the tumor suppressor ELF.
In gastrointestinal cells, biological signals for transforming growth factor-beta (TGF-beta) are transduced through transmembrane serine/threonine kinase receptors that signal to Smad proteins. Smad4, a tumor suppressor, is often mutated in human gastrointestinal cancers. The mechanism of Smad4 inactivation, however, remains uncertain and could be through E3-mediated ubiquitination of Smad4/adaptor protein complexes. Disruption of ELF (embryonic liver fodrin), a Smad4 adaptor protein, modulates TGF-beta signaling. We have found that PRAJA, a RING-H2 protein, interacts with ELF in a TGF-beta-dependent manner, with a fivefold increase of PRAJA expression and a subsequent decrease in ELF and Smad4 expression, in gastrointestinal cancer cell lines (P < 0.05). Strikingly, PRAJA manifests substantial E3-dependent ubiquitination of ELF and Smad3, but not Smad4. Delta-PRAJA, which has a deleted RING finger domain at the C terminus, abolishes ubiquitination of ELF. A stable cell line that overexpresses PRAJA exhibits low levels of ELF in comparison to a Delta-PRAJA stable cell line, where ELF expression is high compared to normal controls. The alteration of ELF and/or Smad4 expression and/or function in the TGF-beta signaling pathway may be induced by enhancement of ELF degradation, which is mediated by a high-level expression of PRAJA in gastrointestinal cancers. In hepatocytes, half-life (t(1/2)) and rate constant for degradation (k(D)) of ELF is 1.91 h and 21.72 min(-1) when coupled with ectopic expression of PRAJA in cells stimulated by TGF-beta, compared to PRAJA-transfected unstimulated cells (t(1/2) = 4.33 h and k(D) = 9.6 min(-1)). These studies reveal a mechanism for tumorigenesis whereby defects in adaptor proteins for Smads, such as ELF, can undergo degradation by PRAJA, through the ubiquitin-mediated pathway.
Animals↗
Reactions of biological oxidants with selenourea: formation of redox active nanoselenium.
Reactions of biological oxidizing agents, such as hydroxyl radicals ((*)OH), singlet oxygen ((1)O(2)), hydrogen peroxide (H(2)O(2)), and peroxynitrite (ONOO(-)) with selenourea were studied. The kinetics of the reactions was followed using time-resolved techniques, and the bimolecular rate constants were determined. In all these reactions, under aerated conditions, elemental red selenium was produced as one of the reaction products. The average size of the selenium particles could be controlled and stabilized in the range of 20-100 nm with the addition of bovine serum albumin (BSA) or sodium dodecyl sulfate (SDS). The particles were characterized by dynamic light scattering studies (DLS), which revealed that the size and distribution of the particles depended mainly on the amount of selenourea undergoing oxidation. Other factors such as the nature of the oxidant and the concentration of the stabilizer also are important in stabilizing the particles. Nanoselenium-reduced ABTS(*-) to colorless ABTS(2-) (ABTS = 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) and oxidized dichlorodihydrofluoresecein diacetate (DCFA) to fluorescent dichlorofluorescein (DCF) indicating its ability to participate in redox and free radical reactions. The reactivity of selenium nanoparticles with these systems varied linearly with the surface area of the particles. The studies demonstrate that selenourea undergoes oxidation with both one-electron and two-electron oxidants to produce elemental selenium, which, on stabilization to nanometer size, exhibits size-dependent redox activity.
Absorption↗
In vitro antioxidant studies and free radical reactions of triphala, an ayurvedic formulation and its constituents.
The aqueous extract of the fruits of Emblica officinalis (T1), Terminalia chebula (T2) and Terminalia belerica (T3) and their equiproportional mixture triphala were evaluated for their in vitro antioxidant activity. gamma-Radiation induced strand break formation in plasmid DNA (pBR322) was effectively inhibited by triphala and its constituents in the concentration range 25-200 microg/mL with a percentage inhibition of T1 (30%-83%), T2 (21%-71%), T3 (8%-58%) and triphala (17%-63%). They also inhibited radiation induced lipid peroxidation in rat liver microsomes effectively with IC(50) values less than 15 microg/mL. The extracts were found to possess the ability to scavenge free radicals such as DPPH and superoxide. As the phenolic compounds present in these extracts are mostly responsible for their radical scavenging activity, the total phenolic contents present in these extracts were determined and expressed in terms of gallic acid equivalents and were found to vary from 33% to 44%. These studies revealed that all three constituents of triphala are active and they exhibit slightly different activities under different conditions. T1 shows greater efficiency in lipid peroxidation and plasmid DNA assay, while T2 has greater radical scavenging activity. Thus their mixture, triphala, is expected to be more efficient due to the combined activity of the individual components.
Animals↗
Oral sustained delivery of atenolol from floating matrix tablets-formulation and in vitro evaluation.
Floating matrix tablets of atenolol were developed to prolong gastric residence time and increase drug bioavailability. Atenolol was chosen as a model drug because it is poorly absorbed from the lower gastrointestinal tract. The tablets were prepared by direct compression technique, using polymers such as hydroxypropyl methylcellulose (HPMC K15M, K4M), guargum (GG), and sodium carboxymethylcellulose (SCMC), alone or in combination, and other standard excipients. Tablets were evaluated for physical characteristics viz. hardness, swelling index, floating capacity, thickness, and weight variation. Further, tablets were evaluated for in vitro release characteristics for 8 hr. The effect of effervescent on buoyancy and drug release pattern was also studied. In vitro release mechanism was evaluated by linear regression analysis. GG- and SCMC-based matrix tablets showed significantly greater swelling indices compared with other batches. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium.
Administration, Oral↗
Fast and cheap genome wide haplotype construction via optical mapping.
We describe an efficient algorithm to construct genome wide haplotype restriction maps of an individual by aligning single molecule DNA fragments collected with Optical Mapping technology. Using this algorithm and small amount of genomic material, we can construct the parental haplotypes for each diploid chromosome for any individual. Since such haplotype maps reveal the polymorphisms due to single nucleotide differences (SNPs) and small insertions and deletions (RFLPs), they are useful in association studies, studies involving genomic instabilities in cancer, and genetics, and yet incur relatively low cost and provide high throughput. If the underlying problem is formulated as a combinatorial optimization problem, it can be shown to be NP-complete (a special case of K-population problem). But by effectively exploiting the structure of the underlying error processes and using a novel analog of the Baum-Welch algorithm for HMM models, we devise a probabilistic algorithm with a time complexity that is linear in the number of markers for an epsilon-approximate solution. The algorithms were tested by constructing the first genome wide haplotype restriction map of the microbe T. pseudoana, as well as constructing a haplotype restriction map of a 120 Mb region of Human chromosome 4. The frequency of false positives and false negatives was estimated using simulated data. The empirical results were found very promising.
Algorithms↗
An outbreak of dengue fever in periurban slums of Chandigarh, India, with special reference to entomological and climatic factors.
BACKGROUND: Dengue viral infection is one of the most important public health problem in tropical countries. AIM: An outbreak of dengue fever was investigated in a periurban slum area of Chandigarh, India, during September to December, 2002. MATERIALS AND METHODS: Blood samples from 218 patients and 30 apparently healthy contacts were tested for dengue-specific immunoglobulin M (IgM) and IgG antibodies including 80 acute samples collected within 5 days of illness were subjected for virus isolation in newborn mice. The average temperature, rainfall, and humidity of the epidemic year were compared with the number of dengue cases. STATISTICAL ANALYSIS: statistical significance was found out using c2-test. RESULTS: A total of 76 cases were positive by either dengue IgM capture assay (n = 57) or virus isolation (n = 17) or both (n = 2). Fifteen of nineteen viral isolates subjected for typing by type-specific multiplex reverse transcription-polymerase chain reaction were found to be of dengue virus. High rainfall and humidity with the temperature range from 21 degrees C to 33 degrees C during the months of August and September might have favored the breeding of mosquitoes, thus leading to an increase in the number of dengue cases in October and November, 2002. CONCLUSION: The present outbreak thus emphasizes the need for continuous sero epidemiological and entomological surveillance for the timely implementation of effective dengue control programme.
Adolescent↗
An outbreak of Japanese encephalitis in Haryana.
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Adolescent↗
Identification of flanking SSR markers for a major rice gall midge resistance gene Gm1 and their validation.
Host-plant resistance is the preferred strategy for management of Asian rice gall midge (Orseolia oryzae), a serious pest in many rice-growing countries. The deployment of molecular markers linked to gall midge resistance genes in breeding programmes can accelerate the development of resistant cultivars. In the present study, we have tagged and mapped a dominant gall midge resistance gene, Gm1, from the Oryza sativa cv. W1263 on chromosome 9, using SSR markers. A progeny-tested F2 mapping population derived from the cross W1263/TN1 was used for analysis. To map the gene locus, initially a subset of the F2 mapping population consisting of 20 homozygous resistant and susceptible lines each was screened with 63 parental polymorphic SSR markers. The SSR markers RM316, RM444 and RM219, located on chromosome 9, are linked to Gm1 at genetic distances of 8.0, 4.9 and 5.9 cM, respectively, and flank the gene locus. Further, gene/marker order was also determined. The utility of the co-segregating SSR markers was tested in a backcross population derived from the cross Swarna/W1263//Swarna, and allelic profiles of these markers were analysed in a set of donor rice genotypes possessing Gm1 and in a few gall midge-susceptible, elite rice varieties.
Animals↗
Hand washing in healthcare workers--a challenge that can be met?
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Attitude of Health Personnel↗
Indirect immunofluorescence test: role in seroepidemiology and serodiagnosis of herpes simplex viral infections.
A study was carried out to find out a) the seroprevalence of herpes simplex viral infections (HSV) in and around Chandigarh city, North India and the probable age of acquisition of infection; b) the usefulness of salivary antibody detection in seroprevalence studies; c) role of HSV immunofluorescence antibodies in the sero-diagnosis of herpes simplex encephalitis (HSE) patients. Single blood samples from 306 and paired blood and saliva samples from 48 apparently healthy individuals as well as paired blood and C.S.F. samples from 50 clinically suspected patients of HSE were included in the study proper. The subjects belonged to <6 months to > 30 years age group. Serum, saliva and C.S.F. samples were subjected to in house standardized indirect immunofluorescence test for the detection of HSV antibody. The overall seropositivity was 59.3%, which increased from 37.5% in children less than 10-years of age to 88.9% in individuals above 30 years of age (p<0.001). The maximum titer in less than 10 years children and above 10 years subjects were found to be 40 and 160 respectively. The difference in percentage positivity of HSV antibody in these groups was statistically significant (p<0.001). No difference in the seroprevalence rate was observed between different socio-economic groups and sex. Saliva in comparison to serum showed a sensitivity of 44% and specificity of 100% for the detection of HSV antibodies. Among the suspected HSE patients 4 (8%) could be serologically confirmed. This study indicated the endemicity of HSV infection in this locality. Indirect immunofluorescence test could detect intrathecal HSV antibodies in 8% of suspected HSE patients proving it to be a very useful rapid serodiagnostic tool. However, saliva testing showed limited sensitivity in HSV sero surveys.
Adolescent↗
Variable presentation of Brugada syndrome: lessons from three generations with syncope.
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Adult↗
Foundations of a query and simulation system for the modeling of biochemical and biological processes.
The analysis of large amounts of data, produced as (numerical) traces of in vivo, in vitro and in silico experiments, has become a central activity for many biologists and biochemists. Recent advances in the mathematical modeling and computation of biochemical systems have moreover increased the prominence of in silico experiments; such experiments typically involve the simulation of sets of Differential Algebraic Equations (DAE), e.g., Generalized Mass Action systems (GMA) and S-systems. In this paper we reason about the necessary theoretical and pragmatic foundations for a query and simulation system capable of analyzing large amounts of such trace data. To this end, we propose to combine in a novel way several well-known tools from numerical analysis (approximation theory), temporal logic and verification, and visualization. The result is a preliminary prototype system: simpathica/xssys. When dealing with simulation data simpathica/xssys exploits the special structure of the underlying DAE, and reduces the search space in an efficient way so as to facilitate any queries about the traces. The proposed system is designed to give the user possibility to systematically analyze and simultaneously query different possible timed evolutions of the modeled system.
Biochemical Phenomena↗
Primary splenic flexure volvulus--a case report with review of literature.
Splenic flexure is a rare site for volvulus. Very few cases have been reported in the literature. Cases mostly present with recurrent attacks of obstruction with distension of the abdomen. A case of a young female who had primary splenic plexure volvulus due to absence of ligamental attachment has been presented here. Resection of the volvulus segment with end to end anastomosis is the curative surgical treatment.
Adult↗