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Biomedical subjects

P K Sharma

Publications and source records attributed to P K Sharma.

At least 55 records · Page 3Linked to original sources
PubMed1998

Development and evaluation of an ideal formulation of glibenclamide by solid dispersion techniques.

An attempt was taken to develop an ideal formulation of Glibenclamide. Considering the physico-chemical nature of the drug the solid dispersion system was utilised using hydrophilic and hydrophobic carriers and formulations were made by fusion as well as solvent evaporation/co-precipitation techniques. The resulting formulations were evaluated in respect of physical nature, yield, assay content and stability. The in vitro release profiles of the formulations were compared with the marketed tablet and simple physical mixtures having same composition of drug and excipients. The effects of various carriers as well as manufacturing procedures on the in vitro release rate of drug were also studied. It is observed that a suitable blend of different batches of solid dispersions containing hydrophilic and hydrophobic carriers will give an optimum formulation with quick onset and prolonged duration of action.

Drug Stability↗
PubMed1998

Localization of hup determinants in Rhizobium sp. sesbania.

Rhizobium sp. sesbania strain SRS 78, a Hup wild type carrying three plasmids was mutagenised using Tn5-sac BR cassette and clones carrying Tn5 insertion in plasmids were identified on the basis of transfer frequency of Tn5-sac BR labelled plasmids from Rhizobium to A. tumefaciens. Neomycin sensitive (Nms) clones were isolated from clones containing Tn5 labelled plasmids by plating on sucrose (5%). Nms clones did not show loss of hup activity. Preliminary results on curing studies indicated that hup genes are located on chromosome. These results were later confirmed by southern hybridization using plasmid pKHT30 containing hup genes of Azotobacter chroococcum. None of the three plasmids showed hybridization with hup gene probe while chromosomal DNA left in the wells showed positive signal.

Bacterial Proteins↗
PubMed1997

Angioedema associated with angiotensin II receptor antagonist losartan.

Angioedema has not been associated with losartan therapy in hemodialysis patients, as it has been with angiotensin converting enzyme (ACE) inhibitors. We report the case of a hemodialysis patient who previously had angioedema after therapy with ACE inhibitors and again had angioedema while taking losartan. We suggest caution in using losartan in patients with known sensitivity to ACE inhibitors manifested by angioedema.

Angioedema↗
PubMed1996

Molecular shape, dissociation, and oxygen binding of the dodecamer subunit of Lumbricus terrestris hemoglobin.

Small angle x-ray scattering of the 213-kDa dodecamer of Lumbricus terrestris Hb yielded radius of gyration = 3.74 +/- 0.01 nm, maximum diameter = 10.59 +/- 0.01 nm, and volume = 255 +/- 10 nm3, with no difference between the oxy and deoxy states. Sedimentation velocity studies indicate the dodecamer to have a spherical shape and concentration- and Ca2+-dependent equilibria with its constituent subunits, the disulfide-bonded trimer of chains a-c and chain d. Equilibrium sedimentation data were fitted best with a trimer-dodecamer model, ln K4 = 7 (association K in liters3/g3) at 1 degrees C and 4 at 25 degrees C, providing DeltaH = -20 kcal/mol and DeltaS = 4.4 eu/mol. Oxydodecamer dissociation at pH 8.0, in urea, GdmCl, heteropolytungstate K8[SiW11O39] and of metdodecamer at pH 7, was followed by gel filtration. Elution profiles were fitted with exponentially modified gaussians to represent the three peaks. Two exponentials were necessary to fit all the dissociations except in [SiW11O39]-8. Equilibrium oxygen binding measurements at pH 6.5-8. 5, provided P50 = 8.5, 11.5-11.9 and 11.9-13.5 torr, and n50 = 5.2-9. 5, 3.2-4.9, and 1.8-2.7 for blood, Hb, and dodecamer, respectively, at pH 7.5, 25 degrees C. P50 was decreased 3- and 2-fold in approximately 100 mM Ca2+ and Mg2+, respectively, with concomitant but smaller increases in cooperativity.

Animals↗
PubMed1996

The role of the dodecamer subunit in the dissociation and reassembly of the hexagonal bilayer structure of Lumbricus terrestris hemoglobin.

The dissociation of the approximately 3500-kDa hexagonal bilayer (HBL) hemoglobin (Hb) of Lumbricus terrestris upon exposure to Gdm salts, urea and the heteropolytungstates [SiW11O39]8- (SiW), [NaSb9W21O86]18- (SbW) and [BaAs4W40O140]27- (AsW) at neutral pH was followed by gel filtration, SDS-polyacrylamide gel electrophoresis, and scanning transmission electron microscopy. Elution curves were fitted to sums of exponentially modified gaussians to represent the peaks due to undissociated oxyHb, D (approximately 200 kDa), T+L (approximately 50 kDa), and M (approximately 25 kDa) (T = disulfide-bonded trimer of chains a c, M = chain d, and L = linker chains). OxyHb dissociation decreased in the order Gdm*SCN > Gdm.Cl > urea > Gdm.OAc and AsW > SbW > SiW. Scanning transmission electron microscopy mass mapping of D showed approximately 10-nm particles with masses of approximately 200 kDa, suggesting them to be dodecamers (a+b+c)3d3. OxyHb dissociations in urea and Gdm.Cl and at alkaline pH could be fitted only as sums of 3 exponentials. The time course of D was bell-shaped, indicating it was an intermediate. Dissociations in SiW and upon conversion to metHb showed only two phases. The kinetic heterogeneity may be due to oxyHb structural heterogeneity. Formation of D was spontaneous during HBL reassembly, which was minimal (</= 10%) without Group IIA cations. During reassembly, maximal (approximately 60%) at 10 mM cation, D occurs at constant levels (approximately 15%), implying the dodecamer to be an intermediate.

Animals↗
PubMed1996

Oxygen binding properties of Eudistylia vancouverii chlorocruorin and its dodecamer subunit.

The oxygen equilibrium curves of the extracellular chlorocruorin of the polychaete Eudistylia vancouverii and its dodecamer subunit were determined over the pH range from 7.1 to 8.1 and in the presence and absence of 100 mM Mg2+. Although the chlorocruorin has a very low oxygen affinity, high cooperativity and a moderate alkaline Bohr effect (P50 = 145 mmHg, nmax = 6.9, phi = -0.44 at pH 7.1 and 25 degrees C), the dodecamer subunit has higher affinity and lower cooperativity and Bohr coefficient (P50 = 58 mmHg, nmax = 1.7, phi = -0.22). The presence of 100 mM Mg2+ increased the oxygen affinity and cooperativity of the chlorocruorin but had no significant effect on the dodecamer subunit. The oxygen binding properties of the chlorocruorin reassociated subsequent to complete dissociation in 4 M urea at neutral pH were similar to the properties of the dodecamer and not to those of the native chlorocruorin. Fitting to the Monod-Wyman-Changeux allosteric model gave KT of 0.0013 mmHg-1, Kr of 0.22 mmHg-1 and L(o) of 2.5 x 10(13) together with a size of the allosteric unit, N = 9.

Animals↗
PubMed1996

Subcutaneous phaeohyphomycosis in a renal transplant recipient: a case report and review of the literature.

Subcutaneous phaeohyphomycosis caused by dematiaceous fungi has rarely been described in immunocompromised patients. We report a case of subcutaneous infection caused by Phialophora parasitica in a renal transplant recipient. The role of early identification of the offending fungal species followed by a wide local excision in the management of such patients has been discussed.

Adult↗
PubMed1996

Are type IIIC lower extremity injuries an indication for primary amputation.

There are few large series of the long-term results of severe devascularized, open fractures to the lower extremity. Therefore, we retrospectively reviewed our experience with 35 consecutively admitted patients who sustained Gustilo Type IIIC injuries and who presented to our Reimplantation Center between 1984 and 1987. To our knowledge, this group of patients represents the largest series of this injury reported to date. The review included 21 patients who required primary amputation and 14 patients who underwent vascular, orthopedic, and delayed soft tissue reconstruction. This report details the treatment protocol used to result in our 93% success rate in the 14 patients with Type IIIC injuries who were successfully revascularized. Our initial management approach to the devascularized lower limb includes immediate revascularization with temporary shunts to minimize ischemia time, followed by revascularization with vein grafts beyond the zone of injury and external fixation. Subsequent management included liberal use of microsurgical free transplantation to overcome soft tissue defects; bone grafting as soon as infection and soft tissue coverage permitted and delayed wound closure. Our approach differs in that definitive wound closure is avoided for 4 to 6 weeks to allow resolution of myonecrosis secondary to initial ischemia and subsequent reperfusion injury. Contraindications to this aggressive revascularization approach are poor patient health before injury, completely severed limb, segmental tibial loss greater than 8 cm, ischemia time greater than 6 hours, and severance of the posterior tibial nerve.

Amputation, Surgical↗
PubMed1996

Isolation and Characterization of a Facultatively Aerobic Bacterium That Reductively Dehalogenates Tetrachloroethene to cis-1,2-Dichloroethene.

A rapidly-growing facultatively aerobic bacterium that transforms tetrachloroethene (PCE) via trichloroethene (TCE) to cis-1,2-dichloroethene (cis-1,2-DCE) at high rates in a defined medium was isolated from a contaminated site. Metabolic characterization, cellular fatty acid analysis, and partial sequence analysis of 16S rRNA showed that the new isolate, strain MS-1, has characteristics matching those of the members of the family Enterobacteriaceae. Strain MS-1 can oxidize about 58 substrates including many carbohydrates, short-chain fatty acids, amino acids, purines, and pyrimidines. It can transform up to 1 mM PCE (aqueous) at a rate of about 0.5 (mu)mol of PCE(middot) h(sup-1)(middot)mg (dry weight) of cell(sup-1). PCE transformation occurs following growth on or with the addition of single carbon sources such as glucose, pyruvate, formate, lactate, or acetate or with complex nutrient sources such as yeast extract or a mixture of amino acids. PCE dehalogenation requires the absence of oxygen, nitrate, and high concentrations of fermentable compounds such as glucose. Enterobacter agglomerans biogroup 5 (ATCC 27993), a known facultative bacterium that is closely related to strain MS-1, also reductively dehalogenated PCE to cis-1,2-DCE. To our knowledge, this is the first report on isolation of a facultative bacterium that can reductively transform PCE to cis-1,2-DCE under defined physiological conditions. Also, this is the first report of the ability of E. agglomerans to dehalogenate PCE.

Journal Article↗
PubMed1996

Isolation and characterization of a novel toluene-degrading, sulfate-reducing bacterium.

A novel sulfate-reducing bacterium isolated from fuel-contaminated subsurface soil, strain PRTOL1, mineralizes toluene as the sole electron donor and carbon source under strictly anaerobic conditions. The mineralization of 80% of toluene carbon to CO2 was demonstrated in experiments with [ring-U-14C]toluene; 15% of toluene carbon was converted to biomass and nonvolatile metabolic by-products, primarily the former. The observed stoichiometric ratio of moles of sulfate consumed per mole of toluene consumed was consistent with the theoretical ratio for mineralization of toluene coupled with the reduction of sulfate to hydrogen sulfide. Strain PRTOL1 also transforms o- and p-xylene to metabolic products when grown with toluene. However, xylene transformation by PRTOL1 is slow relative to toluene degradation and cannot be sustained over time. Stable isotope-labeled substrates were used in conjunction with gas chromatography-mass spectrometry to investigate the by-products of toluene and xylene metabolism. The predominant by-products from toluene, o-xylene, and p-xylene were benzylsuccinic acid, (2-methylbenzyl)succinic acid, and 4-methylbenzoic acid (or p-toluic acid), respectively. Metabolic by-products accounted for nearly all of the o-xylene consumed. Enzyme assays indicated that acetyl coenzyme A oxidation proceeded via the carbon monoxide dehydrogenase pathway. Compared with the only other reported toluene-degrading, sulfate-reducing bacterium, strain PRTOL1 is distinct in that it has a novel 16S rRNA gene sequence and was derived from a freshwater rather than marine environment.

Acetyl Coenzyme A↗
PubMed1996

Analgesia for acute musculoskeletal trauma: low-dose subcutaneous infusion of ketamine.

Low-dose ketamine by subcutaneous infusion (0.1 mg/kg/h) was compared in double-blind fashion with intermittent morphine (0.1 mg/kg intravenously, four-hourly) as analgesic regimen in 40 ASA-I adults after acute musculoskeletal trauma. Pain was assessed using visual analogue scales and sedation was graded on a four point rank drowsiness score. Objective cardiovascular and respiratory parameters and patient acceptability in terms of supplementary analgesia and early mobilization were also recorded. Pain relief was better with the ketamine infusion than with intermittent morphine (P < 0.001). Patients were more awake and alert with ketamine infusion as evidenced by the drowsiness score (P < 0.001). Peak expiratory flow rate improved significantly with the ketamine infusion (P < 0.05). None of the patients in ketamine group required supplementary analgesia (P < 0.001) and the patients could be easily mobilized for traction/splintage as compared with patients in the control group (P < 0.001). The incidence of nausea and vomiting in the morphine group was high (P < 0.01). The study shows that subcutaneous infusion of ketamine provides safe and effective analgesia in acute musculoskeletal trauma.

Adult↗
PubMed1996

Effect of photoinhibition and temperature on carotenoids in sorghum leaves.

Changes in carotenoid composition, CO2 assimilation and chlorophyll fluorescence due to photoinhibition at 5 degrees C and 20 degrees C were studied in 12 day and 30 day old sorghum leaves. The old leaves had a higher violaxanthin (V) content and less beta-carotene. Photoinhibition at both temperatures caused significant increases in zeaxanthin (Z) and decreases in violaxanthin. However, in young leaves the increase in zeaxanthin was greater than the decrease in violaxanthin. In young leaves the V + A + Z pool size (A = antheraxanthin) almost doubled under photoinhibitory conditions (compared to controls) while in old leaves the V + A + Z pool remained approximately constant. After photoinhibition treatment changes in the levels of the xanthophylls were restored during a recovery period both in young and old leaves. When rephotoinhibited after a 48 hr recovery period, the young plants showed better protection against photoinhibition. We suggest that in young leaves zeaxanthin is newly synthesized under photoinhibitory conditions besides being de-epoxidized from violaxanthin and that the synthesis of V + A + Z pool is higher at 20 degrees C than at 5 degrees C in both young and old leaves.

Carbon Dioxide↗
PubMed1995

Mass spectrometric composition, molecular mass and oxygen binding of Macrobdella decora hemoglobin and its tetramer and monomer subunits.

The hexagonal bilayer hemoglobin (Hb) of the leech Macrobdella decora has an equilibrium sedimentation mass of 3544(+/- 80) kDa. Maximum entropy analysis of the electrospray ionization mass spectra of the Hb show three groups of peaks: two peaks of equal intensity at approximately 17 kDa, A (16,770.1 Da) and B (16,841.9 Da); three peaks at approximately 24 kDa, C (24,340.1 Da), D (24,398.6 Da) and E (24,420.0 Da) with relative intensities of 1:6:3, respectively; and three peaks of equal intensities at approximately 33 kDa, F (32,586.0 Da), G (32,714.5 Da) and H (32,849.9 Da). Although reduction with dithiothreitol does not affect the masses of peaks A through E, the approximately 33 kDa peaks give rise to four new peaks at approximately 16 kDa, P (16,052.2 Da), Q (16,537.3 Da), R (16,666.7 Da) and S (16,792.9 Da), indicating that F, G and H represent disulfide-bonded dimers of globin chains, P + Q, P + R and P + S, respectively. The relative intensities of the three groups of peaks are (A + B) to (C + D + E) to (F + G + H) = 0.39:0.26:0.32, and the globin to linker ratio 0.71:0.29 is in good agreement with the ratio 0.72:0.28 obtained by HPLC. The largest functional subunit obtained by dissociation at pH 7 in 4 M urea, is a subunit lacking linker chains with apparent mass 63(+/- 3) kDa. The equilibrium sedimentation profile of this subunit is fitted best as a monomer-dimer-tetramer equilibrium, with association constants K1,2 = 365 l g-1 and K1,4 = 8.1 x 10(5) l3 g-3. A model of the Hb consisting of a hexagonal bilayer of 36 tetramer and 42 linker subunits provides a total mass and globin to linker ratio closest to the experimental values. Equilibrium O2 binding measurements of the native Hb and its tetramer and monomer subunits were carried out over the pH range 6.6 to 8.0 at 10 and 25 degrees C, and in the absence and presence of Na+, Mg2+ and Ca2+. The Hb exhibits a moderately high O2 affinity, P50 = 4.4 torr at pH 7.5 and 25 degrees C, a high cooperativity (n50 approximately 3) and a substantial Bohr effect, phi = delta log P50/delta pH = -0.38. The tetramer subunit has a higher affinity, lower cooperativity and smaller Bohr effect, 1.9 torr, 1.3 to 1.5 and -0.30, respectively. The monomer subunit has a much higher affinity (P50 = 0.29 torr) and no cooperativity or Bohr effect.(ABSTRACT TRUNCATED AT 400 WORDS)

Allosteric Regulation↗
PubMed1995

Double burst stimulation for monitoring neuromuscular blockade for tracheal intubation.

Responses to double burst stimulation were palpated every 15 s after intravenous administration of vecuronium 0.2 mg.kg-1 in 60 adult patients under anaesthesia. Intubating conditions and neuromuscular responses to tracheal intubation were assessed at disappearance of one or both palpable responses to double burst stimulation in groups of 30 patients randomly divided, although in group A patients, tracheal intubation could be performed at disappearance of one palpable response to double burst stimulation; 27 out of 30 patients (90%) had mild to moderate bucking on intubation. In this group, only five patients (16.66%) had good intubating conditions. In group B, where tracheal intubation was attempted at disappearance of both palpable responses, intubating conditions were good in 28 out of 30 patients (93.33%) and there was no response to tracheal intubation in 26 out of 30 patients (86.66%). Palpation of evoked response to double burst stimulation can be used to predict intubating conditions and neuromuscular response to tracheal intubation with nondepolarising muscle relaxants such as vecuronium.

Adult↗