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Biomedical subjects

N Sharma

Publications and source records attributed to N Sharma.

At least 55 records · Page 3Linked to original sources
PubMed2003

Current status of drug resistance among gram-negative bacilli isolated from admitted cases in a tertiary care centre.

AIMS: To study the prevalence of drug resistance among gram-negative bacilli and susceptibility to the Cefoperazone + Sulbactam and Piperacillin + Tazobactam combination among the hospital isolates resistant to all other antimicrobial agents. METHODS: A total of 367 gram-negative bacilli isolated from various pathological samples were tested for susceptibility to antimicrobial agent by the disc diffusion technique and 300 isolates of gram-negative bacilli which were resistant to all the other antibiotics were checked for sensitivity to piperacillin + tazobactam and cefoperazone + sulbactam combination. RESULTS: Resistance to ampicillin and amoxicillin + clavulanic acid ranged from (72.1-83.8%) which was highest. Resistance to cotrimoxazole, gentamicin, netilmycin, quinolones and all the generation of cephalsporins was often above 50%. piperacillin + tazobactam combination had the lowest incidence of resistance (14 to 20.5%). CONCLUSION: Drug resistance for most of the antimicrobial agents was greater than 50% including the various generations of cephalosporins. Inefficiency of amoxicillin + clavulanic acid (resistance among 72-79.5% isolates) suggests the presence of extended spectrum beta-lactamases among the isolates. Addition of sulbactam to cefoperazone showed increased activity (resistance 27 to 34%) but piperacillin + tazobactam was the most effective combination in vitro.

Anti-Bacterial Agents↗
PubMed2003

Fatal 2,4-D (ethyl ester) ingestion.

2,4-D (2,4-dichlorphenoxyacetic acid) is widely used in agriculture and forestry to destroy broad leaved weeds (herbicide). It has a moderate mammalian toxicity and human poisoning has rarely been reported except following ingestion with suicidal intent. We report two young adults who ingested it with suicidal intent, developed neurological, cardiac, hepatic and renal toxicity and died.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2002

The effect of auricular acupuncture on anaesthesia with desflurane.

In most acupuncture studies it is difficult or even impossible to conduct a truly double-blind trial. However, this is possible when treatments are carried out on anaesthetised patients. Because acupuncture provides analgesia, we tested the hypothesis that needle stimulation of a combination of four ear acupoints would significantly reduce anaesthetic requirement. Ten healthy volunteers were anaesthetised with desflurane and randomly assigned to no treatment or acupuncture; the alternative treatment was given on a subsequent study day. Auricular acupuncture was performed with needles placed at the Shen Men, Thalamus, Tranquiliser and Master Cerebral Points on the right ear. Anaesthetic requirement, determined by the Dixon up-and-down method, was defined by the average desflurane concentration that prevented purposeful movement of the extremities in response to noxious electrical stimulation. Volunteers required a greater desflurane concentration to prevent movement on the control than on the acupuncture day: 4.9 (0.7; SD) vs. 4.4 (0.8) vol. %, p = 0.003. Acupuncture thus reduced anaesthetic requirement by 8.5 (7)%.

Acupuncture Analgesia↗
PubMed2002

Trypan blue assisted phacoemulsification in corneal opacities.

AIM: To evaluate the efficacy of trypan blue for enhancing visualisation during phacoemulsification and foldable lens implantation in cases of cataract with corneal opacities. METHODS: 11 eyes of 11 patients with nebulomacular corneal opacities involving the visual axis with partially and visually debilitating cataract underwent trypan blue assisted phacoemulsification with foldable intraocular lens implantation. The patients were followed at the first day, first week, first month, and third month postoperatively. Completion of capsulorhexis, phacoemulsification with foldable lens implantation, and postoperative best corrected visual acuity were measured. RESULTS: The dye improved visualisation of the anterior capsule and a complete capsulorhexis could be performed successfully in all eyes. In all but one eye phacoemulsification was accomplished successfully. In one eye with Fuchs' dystrophy penetrating keratoplasty was performed later. Visual acuity was < or = 6/60 preoperatively in all eyes and improved to > or = 6/24 in eight eyes postoperatively. CONCLUSION: Trypan blue assisted phacoemulsification may be performed in selected cases of corneal haze/opacification with cataract. It provides acceptable visual outcome in cases awaiting penetrating keratoplasty or in cases where it is not feasible or promising.

Adult↗
PubMed2002

Toxicity of brake oil.

Brake oil is an automobile transmission fluid composed of a mixture of toxic glycols and glycol ethers. Three cases of poisoning with toxic glycol based brake fluid are reported who presented with mild metabolic acidosis and acute renal failure. As all the cases had presented late, treatment with ethanol was not started. All of them were treated successfully with haemodialysis.

Acidosis↗
PubMed2002

Prevalence of fungal meningitis among HIV positive & negative subjects in Indore (MP state).

The aim of the study was to find out the prevalence of fungal meningitis among AIDS cases and to assess the prognosis of fungal meningitis among HIV positive & negative subjects. The study comprised of 15 & 10 cases of fungal meningitis among HIV positive & negative subjects respectively during the study period 1992-2001. India ink preparation and Gram's staining procedures were carried out on the centrifuged CSF deposits. The CSF deposits were also used for bacterial and fungal culture. In the present study the prevalence of fungal meningitis was noted among 15 (3.1%) of 483 AIDS cases. Twelve of them had cryptococcal meningitis while 3 were infected with Candida albicans. Four AIDS cases presented fungal meningitis as a primary opportunistic infection and HIV status was confirmed in 4 of them after the diagnosis of fungal meningitis. 13 of the 15 cases were in the age group 26-40 yrs while one was 55 yrs old and the other 16 month old child; these two cases had blood transfusion transmitted and vertically transmitted mode of HIV transmission respectively. Further, only two of 15 cases were females and both acquired HIV infection through blood transfusion. Overall prognosis of fungal meningitis was poor among HIV positives and 7 of the 15 cases died in hospital within 2-3 weeks after diagnosis of cryptococcal meningitis. Among HIV negative subjects, ten cases of fungal meningitis (3 with Candida albicans and 7 with Cryptococcous neoformans) were noted at our end and nine of them had immunocompromised status (3 cases of renal transplant on immunosuppressives, 3 cases neonates/infant and 2 diabetic subjects. The fungal meningitis is one of the important causes of morbidity & mortality among immunocompromised among HIV positive subjects.

AIDS-Related Opportunistic Infections↗
PubMed2001

Synthesis and antiviral activity of novel acyclic nucleoside analogues of 5-(1-azido-2-haloethyl)uracils.

We present the discovery of a novel category of 5-substituted acyclic pyrimidine nucleosides as potent antiviral agents. A series of 1-[(2-hydroxyethoxy)methyl] (5-7), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl] (8-10), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl] (11-13) derivatives of 5-(1-azido-2-haloethyl)uracil were synthesized and evaluated for their biological activity in cell culture. 1-[4-Hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azido-2-chloroethyl)uracil (12) was the most effective antiviral agent in the in vitro assays against DHBV (EC(50) = 0.31-1.55 microM) and HCMV (EC(50) = 3.1 microM). None of the compounds investigated showed any detectable toxicity to several stationary and proliferating host cells.

Animals↗
PubMed2001

Selective postoperative inhibition of gastrointestinal opioid receptors.

BACKGROUND: Postoperative recovery of gastrointestinal function and resumption of oral intake are critical determinants of the length of hospital stay. Although opioids are effective treatments for postoperative pain, they contribute to the delayed recovery of gastrointestinal function. METHODS: We studied the effects of ADL 8-2698, an investigational opioid antagonist with limited oral absorption that does not readily cross the blood-brain barrier, on postoperative gastrointestinal function and the length of hospitalization. We randomly assigned 79 patients--including 1 whose surgery was canceled--to receive one capsule containing 1 mg or 6 mg of ADL 8-2698 or an identical-appearing placebo capsule two hours before major abdominal surgery and then twice daily until the first bowel movement or until discharge from the hospital. Data were analyzed for 26 patients in each of the three groups; all received opioids for postoperative pain relief. Observers who were unaware of the group assignments evaluated the outcomes. RESULTS: Fifteen patients underwent partial colectomy and 63 underwent total abdominal hysterectomy. Patients given 6 mg of ADL 8-2698 had significantly faster recovery of gastrointestinal function than those given placebo. The median time to the first passage of flatus decreased from 70 to 49 hours (P=0.03), the median time to the first bowel movement decreased from 111 to 70 hours (P=0.01), and the median time until patients were ready for discharge decreased from 91 to 68 hours (P=0.03). Effects in the group that received 1 mg of ADL 8-2698 were less pronounced. CONCLUSIONS: Selective inhibition of gastrointestinal opioid receptors by an antagonist with limited oral absorption that does not readily cross the blood-brain barrier speeds recovery of bowel function and shortens the duration of hospitalization.

Adolescent↗
PubMed2001

Inhibition of benzo[a]pyrene- and cyclophoshamide-induced mutagenicity by Cinnamomum cassia.

Cinnamomum cassia is used as a flavoring spice with some established medicinal properties. In this study, we evaluated the antimutagenic effect of C. cassia against two mutagens, viz. benzo[a]pyrene (B[a]P) and cyclophosphamide (CP). The antimutagenic properties of C. cassia were examined by the Ames test. In vivo chromosomal aberration (CA) and micronuclei tests were also employed to assess the antimutagenic effect of C. cassia in mice after pretreatment with the extract orally for seven consecutive days. To elucidate the mechanism by which C. cassia exerts its antimutagenic effect, certain key enzymes involved in bioactivation and detoxification processes were also investigated. Changes in liver cytochrome P450 (Cyt P450), glutathione content (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and glutathione peroxidase (GPX) were evaluated in pretreated animals. It was observed in the Ames test, bone marrow chromosomal aberration assay, and micronucleus test that C. cassia exerted significant antimutagenic effects against B[a]P and CP in animals treated with the plant extract. C. cassia pretreatment decreased Cyt P450 content but increased GSH content and the activity of glutathione-dependent antioxidant enzymes, viz. GST, GR, and GPX. The present findings demonstrate that the antimutagenic potential of C. cassia could be attributed to its modulatory effect on the xenobiotic bioactivation and detoxification processes.

Administration, Oral↗
PubMed2001

Succinic acids as potent inhibitors of plasmid-borne IMP-1 metallo-beta-lactamase.

IMP-1 metallo-beta-lactamase (class B) is a plasmid-borne zinc metalloenzyme that efficiently hydrolyzes beta-lactam antibiotics, including carbapenems, rendering them ineffective. Because IMP-1 has been found in several clinically important carbapenem-resistant pathogens, there is a need for inhibitors of this enzyme that could protect broad spectrum antibiotics such as imipenem from hydrolysis and thus extend their utility. We have identified a series of 2,3-(S,S)-disubstituted succinic acids that are potent inhibitors of IMP-1. Determination of high resolution crystal structures and molecular modeling of succinic acid inhibitor complexes with IMP-1 has allowed an understanding of the potency, stereochemistry, and structure-activity relationships of these inhibitors.

Crystallography, X-Ray↗
PubMed2001

Characterization of a galactose specific adhesin of enteroaggregative Escherichia coli.

A fimbrial adhesin was identified from an enteroaggregative Escherichia coli strain. The adhesin was purified to 740-fold by sequential chromatography on an affinity matrix and gel filtration column in the FPLC system. The homogeneity of the purified protein was established by analytical isoelectrofocussing (pI 7.25). The native adhesin appeared as a high-molecular-weight aggregative protein as revealed by gel filtration chromatography on Superose 12HR10/30 column. However, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis the molecular weight of the adhesin was found to be 18 kDa and this was further confirmed by gel filtration chromatography on Superose 6HR 10/30 column presence of 6 M guanidine hydrochloride. The N-terminal 15-amino-acid sequence of the adhesin did not show homology with any of the previously reported fimbrial adhesins. The purified adhesin showed adhesion to human erythrocytes in the presence of Ca(2+) (5 mM). The optimum temperature and pH for the hemadhesion activity was found to be 25 degrees C and 6.5, respectively. The inhibition study clearly suggested that the binding site of the adhesin could recognize galactose as the specific sugar. The fluorescence of 4-methylumbelliferyl-alpha-D-galactopyranoside was quenched on binding to the adhesin and maximum reversal of fluorescence quenching was observed by competitive substitution titration with raffinose. The adhesin was found to contain one binding site per monomer for its specific sugar residue. The association constant and the free energy of binding were obtained as 3.98 x 10(5) M(-1) and -31.97 kJ/mol, respectively. The adherence of the bacteria to HEp-2 monolayer was inhibited in presence of galactose and this was further supported by a significant reduction in the bacterial adherence to the HEp-2 cells, pretreated with beta-D-galactosidase.

Adhesins, Escherichia coli↗
PubMed2001

Rpb4, a non-essential subunit of core RNA polymerase II of Saccharomyces cerevisiae is important for activated transcription of a subset of genes.

A major role in the regulation of eukaryotic protein-coding genes is played by the gene-specific transcriptional regulators, which recruit the RNA polymerase II holoenzyme to the specific promoter. Several components of the mediator complex within the holoenzyme also have been shown to affect activation of different subsets of genes. Only recently has it been suggested that besides the largest subunit of RNA polymerase II, smaller subunits like Rpb3 and Rpb5 may have regulatory roles in expression of specific sets of genes. We report here, the role of Rpb4, a non-essential subunit of core RNA polymerase II, in activation of a subset of genes in Saccharomyces cerevisiae. We have shown below that whereas constitutive transcription is largely unaffected, activation from various promoters tested is severely compromised in the absence of RPB4. This activation defect can be rescued by the overexpression of cognate activators. We have localized the region of Rpb4 involved in activation to the C-terminal 24 amino acids. We have also shown here that transcriptional activation by artificial recruitment of the TATA-binding protein (TBP) to the promoter is also defective in the absence of RPB4. Surprisingly, the overexpression of RPB7 (the interacting partner of Rpb4) does not rescue the activation defect of all the promoters tested, although it rescues the activation defect of the heat shock element-containing promoter and the temperature sensitivity associated with RPB4 deletion. Overall, our results indicate that Rpb4 and Rpb7 play independent roles in transcriptional regulation of genes.

Amino Acid Sequence↗
PubMed2001

Membrane-associated respiratory syncytial virus F protein expressed from a human rhinovirus type 14 vector is immunogenic.

Human rhinovirus (HRV) replicons have the potential to serve as respiratory vaccine vectors for mucosal immunization in humans. However, since many vaccine immunogens of interest are glycosylated, an important concern is whether HRV replicons are capable of expressing glycosylated proteins. The human respiratory syncytial virus (RSV) fusion (F) protein was chosen as a model glycoprotein and the HRV replicon DeltaP1FVP3 was generated by inserting the F protein-coding sequence in frame and in lieu of the 5' proximal 1489 nucleotides of the capsid-coding segment in the HRV-14 genome. When transfected into H1-HeLa cells, DeltaP1FVP3 replicated and led to the expression of the F protein. Inhibition with guanidine demonstrated that F-protein expression was dependent on DeltaP1FVP3 replication and did not result from translation of input RNA. Although most of the F protein remained as an immature, glycosylated precursor (F0), a readily detectable fraction of the protein was processed into the mature glycosylated subunit F1, an event known to occur within the Golgi apparatus. Packaged DeltaP1FVP3 replicons were generated in transfected HeLa cells by coexpression of homologous HRV capsid proteins using the vaccinia virus/T7 RNA polymerase hybrid system. Packaged replicon RNAs were capable of infecting fresh cells, leading to accumulation of the F protein as in RNA-transfected cells. Mice immunized with HeLa cell lysates containing F protein expressed from DeltaP1FVP3 produced neutralizing antibodies against RSV. These results indicate that an HRV-14 replicon can express a foreign glycosylated protein, providing further support for the potential of HRV replicons as a vaccine delivery system.

Animals↗
PubMed2001

Role of phospholipid transfer protein in rabbit lung development.

A 36-kDa phospholipid transfer protein (PLT-P(R)), which preferentially transfers phosphatidyl choline (PC) compared to phosphatidyl inositol (PI), was purified 827-fold from rabbit lung homogenate. Incorporation of cholesterol in unilamellar vesicles reduced the PC transfer activity of PLTP(R). Dipalmitoyl phosphatidyl choline uptake by alveolar type II cells was increased in the presence of the protein, and further enhanced in the presence of surfactant liposomes. However, a decrease in uptake was noted with cholesterol in host membranes. Incorporation of PI into host membranes had a low stimulatory effect on the process. All these effects were more pronounced in adult type II cells compared to premature, term and 3-day-old pups.

1,2-Dipalmitoylphosphatidylcholine↗