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Biomedical subjects

A Deb

Publications and source records attributed to A Deb.

At least 19 recordsLinked to original sources

Outbreak of cholera caused by Vibrio cholerae 01 intermediately resistant to norfloxacin at Malda, West Bengal.

During the end of September 1997, an unusual outbreak of severe dehydrating watery diarrhoea cases and deaths were reported from Malda town. Vibrio cholerae 01 El tor, the causative agent responsible for this episode was isolated from 56.5% of cases sampled. Three of the five drinking water samples were also positive for V cholerae 01. Majority of cases were adults. Isolated strains were uniformly resistant to furazolidone and intermediately to norfloxacin. Indiscriminate use of antibiotic should be discouraged for development of multidrug resistant strains.

Adult↗

Association of a disease approximating cholera caused by Vibrio cholerae of serogroups other than O1 and O139.

One hundred and six patients suffering from severe dehydrating diarrhoea were studied of whom 36 patients were positive for Vibrio cholerae. Out of 36, 15 were positive for V. cholerae O1, 10 for V. cholerae O139 and 11 for V. cholerae non-O1 non-O139. O1 and O139 were positive for the 301-bp ctxA amplicon and 471-bp tcpA amplicon indicating that the strains possessed toxigenic capability whereas no non-O1 non-O139 strain possessed ctxA or tcpA genes. Post-admission severity of purging and amount of ORS required were less in the V. cholerae non-O1 non-O139 group (P < 0.05) compared to the V. cholerae O1 and O139 groups. It appears from this study that a cholera-like clinical condition can be caused in the absence of CT as exemplified by strains of non-O1 non-O139.

Adolescent↗

Uncooked rice powder in oral rehydration solution: an alternative to glucose or cooked rice powder.

Glucose-based or rice-based ORS is the standard treatment in acute dehydrating diarrhoea. However, glucose may not be easily available in remote villages and the rice needs to be cooked for rice-based ORS. We embarked on a study to examine whether uncooked rice powder could be used as an alternative to glucose or cooked rice powder in ORS. Initially, 50 adult male patients (aged 18 to 55 yr) were randomized to receive glucose-ORS or uncooked rice ORS, in two equal groups. Subsequently, 20 male children (aged 3 to 12 yr) were also enrolled in the study and received either WHO-ORS or study ORS. All the adult patients and the children could be successfully rehydrated with ORS containing uncooked rice powder. As compared to WHO-ORS, the study ORS significantly reduced stool output (6.60 +/- 1.24 vs. 5.88 +/- 1.34 l), ORS intake (9.17 +/- 1.54 vs 8.24 +/- 1.69 l) and duration of diarrhoea (45.68 +/- 6.91 vs 41.32 +/- 6.03 h). In children also similar results were obtained. No clinical complication (e.g., vomiting, abdominal pain etc.) or abnormality in serum electrolyte concentrations was encountered either in the adults or in the children. Uncooked rice powder containing ORS can be considered as an alternative to glucose-based ORS or rice-based ORS.

Adolescent↗

Deficient cytokine signaling in mouse embryo fibroblasts with a targeted deletion in the PKR gene: role of IRF-1 and NF-kappaB.

The interferon (IFN)-induced double-stranded RNA (dsRNA)-activated Ser/Thr protein kinase (PKR) plays a role in the antiviral and antiproliferative effects of IFN. PKR phosphorylates initiation factor eIF2alpha, thereby inhibiting protein synthesis, and also activates the transcription factor, nuclear factor-kappaB (NF-kappaB), by phosphorylating the inhibitor of NF-kappaB, IkappaB. Mice devoid of functional PKR (Pkr(o/o)) derived by targeted gene disruption exhibit a diminished response to IFN-gamma and poly(rI:rC) (pIC). In embryo fibroblasts derived from Pkr(o/o) mice, interferon regulatory factor 1 (IRF-1) or guanylate binding protein (Gbp) promoter-reporter constructs were unresponsive to IFN-gamma or pIC but response could be restored by co-transfection with PKR. The lack of responsiveness could be attributed to a diminished activation of IRF-1 and/or NF-kappaB in response to IFN-gamma or pIC. Thus, PKR acts as a signal transducer for IFN-stimulated genes dependent on the transcription factors IRF-1 and NF-kappaB.

Animals↗

Double-blind, randomized clinical trial for safety and efficacy of norfloxacin for shigellosis in children.

In a randomized, double-blind clinical trial, the efficacy and safety of norfloxacin were compared with nalidixic acid in the treatment of shigellosis in children. Out of 59 cases, Shigella spp. were isolated from 8 cases in the nalidixic acid group and 14 cases in the norfloxacin group. The norfloxacin group had significantly less duration of diarrhoea and presence of blood in stool as compared to the nalidixic acid group. No joint problem was encountered in this study at up to 4 months follow-up. Norfloxacin is safe and effective and showed no cartilage toxicity on short-term follow-up.

Anti-Infective Agents↗

Efficacy of norfloxacin and doxycycline for treatment of vibrio cholerae 0139 infection.

An open randomised controlled clinical trial with 160 adults with acute watery diarrhoea and severe dehydration compared the efficacy of varying regimens of norfloxacin and doxycycline for the treatment of cholera caused by Vibrio cholerae 0139 Bengal. Data were analysed for the 111 patients who were faeces culture positive for V. cholerae 0139. In addition to rehydration therapy, 28 patients received 300 mg of doxycycline as a single dose on admission, 26 patients received norfloxacin 400 mg bd for three days, 28 patients received a single dose of 800 mg of norfloxacin and 29 patients received no antibiotic (control group). Patients in the three treatment groups and control group had comparable characteristics on admission. All three treatment groups had reduced stool output, duration of diarrhoea and fluid intake compared with the control group. Multidose norfloxacin treatment significantly reduced stool output, duration of diarrhoea and fluid requirement compared with the other regimens.

Adult↗

Roles of protein-tyrosine phosphatases in Stat1 alpha-mediated cell signaling.

Different Stat proteins are activated through phosphorylation of unique tyrosine residues in response to different cytokines and growth factors. Interferon-gamma activates Stat1 molecules that form homodimers and bind cognate DNA elements. Here we show that treatment of permeabilized cells with 200-500 microM peroxo-derivatives of vanadium, molybdenum, and tungsten results in the accumulation of constitutively phosphorylated Stat1 alpha molecules. In contrast, treatment of permeabilized cells with orthovanadate, vanadyl sulfate, molybdate, and tungstate at the same range of concentrations does not result in the accumulation of activated Stat1 alpha molecules in the absence of ligand. However, these compounds inhibit the inactivation of interferon-gamma-induced DNA-binding activity of Stat1 alpha. A 4-6-h exposure of the permeabilized cells to orthovanadate, molybdate, and tungstate, but not vanadyl sulfate, results in a ligand-independent activation of Stat1 alpha, which is blocked by the inhibition or depletion of NADPH oxidase activity in the cells, indicating that NADPH oxidase-catalyzed superoxide formation is required for the bioconversion of these metal oxides to the corresponding peroxo-compounds. Interestingly, ligand-independent Stat1 alpha activation by peroxo-derivatives of these transition metals does not require Jak1, Jak2, or Tyk2 kinase activity, suggesting that other kinases can phosphorylate Stat1 alpha on tyrosine 701.

Animals↗

A 25-kDa beta-lactam-induced outer membrane protein of Vibrio cholerae. Purification and characterization.

A 25-kDa outer membrane protein, induced following treatment of Vibrio cholerae cells with beta-lactam antibiotics and constituting about 8-10% of the total outer membrane proteins of beta-lactam-resistant mutants, has been purified to homogeneity. It is a basic (pI 8.5) protein rich in beta-sheet structure and is a homodimer, the monomers being held together by hydrophobic interactions. The effective hydrophobicity of the protein is low, and a large part of the protein is exposed on the surface of the outer membrane. The protein does not have beta-lactamase or autolytic activity and is not a penicillin-binding protein. The Stoke's radius of the 25-kDa protein (26 A) is comparable to the pore size of the V. cholerae OmpF-like porin. Proteoliposome swelling assay showed that the 25-kDa protein might block the pores of OmpF through which beta-lactam antibiotics normally enter the cells. Twenty-two amino acid residues from the N-terminal end of the 25-kDa protein have been sequenced, and a 32-mer oligonucleotide probe was synthesized using the amino acid residues 2-12. This probe was used to identify the gene encoding the 25-kDa protein. The beta-lactam-resistant cells are insensitive to changes in the osmolarity of the growth medium in contrast to the wild type cells which exhibit osmoregulation of OmpF and OmpC synthesis. All beta-lactam-resistant mutants examined are resistant to novobiocin.

Anti-Bacterial Agents↗

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study.

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging ( > 8/day), vomiting ( > 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age ( < or = 12 months; OR = 2.7, p = 0.001), frequent purging ( > 8/day; OR = 4.1, p < 0.00001), vomiting ( > 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median < or = 60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.

Acute Disease↗

Recombinant derivative of a naturally occurring non-toxinogenic Vibrio cholerae 01 expressing the B subunit of cholera toxin: a potential oral vaccine strain.

A clinical isolate of Vibrio cholerae 01 was identified which did not possess the heat-labile (CT), the heat-stable (ST) or the zonula occludens (Zot) toxin genes. Rabbit ileal loop assays showed that no other CT-like toxin was produced by this strain. The partly deleted cholera toxin gene which carries the intact gene for the B subunit was cloned and the recombinant plasmid, pURD110, was introduced into this non-toxinogenic natural human isolate. The transformed cells (strain URD2) secreted the B subunit gene product which competed with the holotoxin secreted by the hypertoxinogenic strain 569B of V. cholerae for the GM1 ganglioside binding sites in vivo. This strain can colonize the rabbit intestine as detected by the removable intestinal tie adult rabbit diarrhoea (RITARD) model. This construct has an advantage over other live oral attenuated V. cholerae strains used as vaccines in that the latter strains were made non-toxinogenic by only deleting part of the gene coding for the A subunit of cholera toxin while the strain described here is naturally non-toxinogenic.

Administration, Oral↗

Epidemic of Vibrio cholerae 0139 in Calcutta.

As one of large outbreaks of cholera-like illness in the Indian subcontinent, Calcutta and its neighbouring areas experienced an unprecedented epidemic due to a new strain of V. cholerae non-01, designated as V. cholerae 0139 Bengal, since January 1993. This epidemic predominantly affected the adult population of Calcutta as evidenced by the hospitalization of more adults at the Infectious Disease Hospital, Calcutta (IDH), which bore the main brunt of the epidemic in and around Calcutta. During the peak of the epidemic about 180 to 300 diarrhoea patients were admitted daily at the IDH. Of the 807 patients screened, 407 were positive for V. cholerae 0139 and majority (82.8%) of the cases were > 10 yr of age. Severe dehydration was recorded in 85.5 per cent of the cases.

Adult↗

Clinical profile of acute diarrhoea cases infected with the new epidemic strain of Vibrio cholerae O139: designation of the disease as cholera.

A total of 113 patients suffering from acute watery diarrhoea caused by the novel epidemic strain of Vibrio cholerae non-O1, currently assigned to a new serogroup O139, were investigated in order to determine the clinical presentation of the new epidemic strain causing outbreaks of cholera-like infection in the Indian subcontinent. Estimations of electrolyte concentration in serum and stool were also performed in a representative number of the above cases. The clinical features and blood and stool biochemical parameters of V. cholerae serogroup O139 diarrhoeal patients were indistinguishable from those in typical cholera, except for 44.3% cases infected by O139 had abdominal cramps. In view of the above, we propose to designate the disease caused by V. cholerae O139 as cholera.

Acute Disease↗