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Biomedical subjects

R Chandra

Publications and source records attributed to R Chandra.

At least 37 records · Page 2Linked to original sources
PubMed1999

beta-Adrenergic action on wild-type and KPQ mutant human cardiac Na+ channels: shift in gating but no change in Ca2+:Na+ selectivity.

OBJECTIVE: Prior studies of the modulation of the Na+ current by sympathetic stimulation have yielded controversial results. Separation of the Na+ and Ca2+ currents poses a problem in myocyte preparations. The gating of cloned Na+ channels is different in oocytes compared with mammalian expression systems. We have examined the sympathetic modulation of the alpha-subunit of the wild-type human cardiac Na+ channel (hH1) and the long QT-associated mutant, delta KPQ, expressed in human embryonic kidney cells. METHODS: Stable cell lines of hH1 and delta KPQ were established in human embryonic kidney cells. Whole-cell and single-channel currents were measured with the patch-clamp technique. Sympathetic stimulation was effected by exposure to isoproterenol or 8-bromo-cAMP. Na+ channel activation and inactivation were determined using standard voltage clamp protocols. Ca2+:Na+ permeability ratio was determined under bi-ionic conditions. RESULTS: We observed a qualitatively different effect of sympathetic stimulation on the cardiac Na+ current from that reported in frog oocytes: activation and inactivation kinetics were shifted to more negative potentials. This shift was similar for both hH1 and delta KPQ. [delta V0.5 for inactivation: 8.3 +/- 1.7 mV, p < 0.001 (hH1); 6.8 +/- 0.9 mV, p < 0.001 (delta KPQ)]. Increased rate of closed-state inactivation contributed to the shifting of the inactivation-voltage relationship. Open-state inactivation was not affected as mean open times were unchanged. Reversal potential measurement in hH1 suggested a low Ca2+:Na+ permeability ratio of 0.017, uninfluenced by sympathetic stimulation. In delta KPQ, the size of the persistent relative to the peak current was increased with 8-bromo-cAMP from 3.0 +/- 0.7% to 4.3 +/- 0.6% (p = 0.056). CONCLUSIONS: Sympathetic stimulation exerts multiple effects on the gating of hH1. Similar effects are also seen in delta KPQ which may increase arrhythmia susceptibility in long QT syndrome by modifying the Na+ channel contribution to the action potential.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Retinoic acid in association with tin-metalloporphyrins influences heme metabolism in vivo in rats.

In the current study we report the perturbation of key enzymes of the heme metabolic pathway, i.e. delta-amino levulinic acid synthase, heme oxygenase and biliverdin reductase, in vivo by administration of retinoic acid (RA) and retinoic acid in association with tin-metalloporphyrins, viz., tin-protoporphyrin (SnPP) and tin-mesoporphyrin (SnMP) in the liver, spleen, heart and lung of rats. RA at a dosing regimen of 50,000 I.U. stimulated splenic ALA-S activity, whereas co-administration of tin-metalloporphyrins with RA antagonised the RA mediated induction of ALA-S. In the other tissues viz., liver, heart and lung our results showed a diminution of ALA-S activity on RA administration, the level of repression was further attenuated when tin-metalloporphyrins were co-administered with RA. This marked suppression of ALA-S brought forth by concurrent administration of RA and tin-metalloporphyrins is suggestive of the beneficial effect of this formulation in acute attacks of porphyria, similar to heme. Furthermore, our results emphasize that the combined dosing of RA with tin-metalloporphyrins leads to a substantial decline in bilirubin levels due to a profound inhibition of HMOX in the probed tissues. The features of the combined action of RA and tin-metalloporphyrins in vivo lead to a substantial suppression of formation of the potentially toxic metabolite bilirubin, and the enhancement of disposal of the untransformed substrate (heme) of the enzyme that is inhibited. These results define some of the characteristics of a therapeutically useful formulation and represent a new therapeutic approach for the amelioration and management of hyperbilirubinemia.

5-Aminolevulinate Synthetase↗
PubMed1999

Reasons for outpatient referrals from generalists to specialists.

OBJECTIVE: To determine the relative importance of medical and nonmedical factors influencing generalists' decisions to refer, and of the factors that might avert unnecessary referrals. DESIGN: Prospective survey of all referrals from generalists to subspecialists over a 5-month period. SETTING: University hospital outpatient clinics. PARTICIPANTS: Fifty-seven staff physicians in general internal medicine, family medicine, dermatology, orthopedics, gastroenterology, and rheumatology. MEASUREMENTS AND MAIN RESULTS: For each referral, the generalist rated a number of medical and nonmedical reasons for referral, as well as factors that may have helped avert the referral; the specialist seeing the patient then rated the appropriateness, timeliness, and complexity of the referral. Both physicians rated the potential avoidability of the referral by telephone consultation. Generalists were influenced by a combination of both medical and nonmedical reasons for 76% of the referrals, by only medical reasons in 20%, and by only nonmedical reasons in 3%. In 33% of all referrals, generalists felt that training in simple procedures or communication with a generalist or specialist colleague would have allowed them to avoid referral. Specialists felt that the vast majority of referrals were timely (as opposed to premature or delayed) and of average complexity. Although specialists rated most referrals as appropriate, 30% were rated as possibly appropriate or inappropriate. Generalists and specialists failed to agree on the avoidability of 34% of referrals. CONCLUSIONS: Generalists made most referrals for a combination of medical and nonmedical reasons, and many referrals were considered avoidable. Increasing procedural training for generalists and enhancing informal channels of communication between generalists and subspecialists might result in more appropriate referrals at lower cost.

Ambulatory Care↗
PubMed1999

The lateral pectoral flap.

The lateral pectoral flap is a new pedicled flap based on the superficial thoracic artery which arises from the subscapular artery and courses along the lateral border of pectoralis major. The flap consists of skin, subcutaneous tissue and the underlying pectoral epimysium. It has been used successfully to resurface contralateral soft tissue defects over the fingers, thumb and dorsum of the hand in eight cases. The advantages of this flap are that it provides reliable soft tissue cover to the hand, which can be kept in an elevated position resting comfortably on the contralateral pectoral region with the forearm and arm aligned conveniently in the cross-chest position. It does not interfere with clothing and dressing the lower part of the body in contrast to the groin, hypogastric or lower abdominal flaps, and it allows early ambulation. Primary closure of the donor site in the majority of cases is an added benefit.

Adolescent↗
PubMed1999

Adjunctive oral corticosteroids reduce renal scarring: the piglet model of reflux and acute experimental pyelonephritis.

PURPOSE: We investigate the efficacy of antibiotics combined with corticosteroid in diminishing post-pyelonephritic renal scarring compared to standard antibiotic therapy. MATERIALS AND METHODS: Bilateral vesicoureteral reflux was surgically created in 36 piglets (72 kidneys). A week later each bladder was inoculated by percutaneous injection with a standardized broth culture of Escherichia coli and molten paraffin. 99mTechnetium dimercapto-succinic acid (DMSA) scintigraphy was performed 3 days after introduction of urinary infection to detect the presence of acute pyelonephritis. Acute pyelonephritic lesions seen on DMSA scans were graded according to the percentage of renal zone involvement as grade 1--less than 33%, grade 2--33 to 66% and grade 3--greater than 66% involved. When pyelonephritis was present, piglets were randomized to receive either standard antibiotics or antibiotics and 2 mg./kg. prednisolone daily. 99mTechnetium-DMSA scintigraphy was repeated 2 months after completion of therapy, and the kidneys were harvested for gross and histopathological examination. Each kidney was divided into upper, middle and lower zones for correlation of pathological and imaging findings. Severity of renal scarring was then assessed using histopathological confirmation of gross anatomical findings as grade 1--less than 1, grade 2-1 to 2 and grade 3-greater than 2 cm. RESULTS: Acute pyelonephritis was induced in 136 of 216 renal zones. The sites of renal scarring corresponded anatomically to sites of acute pyelonephritis in all but 5 cases. Overall, the prevalence of post-pyelonephritic scarring was 56.6% (77 of 136) of renal zones. The severity of scarring in both groups correlated with the severity of the initial pyelonephritic lesion. Of the 31 zones that formed grade 3 renal scars the distribution of grades 1, 2 and 3 acute pyelonephritis on the initial DMSA scan was 3, 26 and 71%, respectively. Grade 3 acute pyelonephritis was more likely to result in severe (grade 3) renal scars in the control compared to the steroid treated group (59 versus 31%). Overall, acute pyelonephritis completely resolved in 40% of controls and 51% of steroid treated animals. However, only 9% of control animals with grade 3 acute pyelonephritis demonstrated complete resolution, as opposed to 28% of those receiving steroids. CONCLUSIONS: The risk of renal scarring is greatest after severe acute pyelonephritis involving greater than 66% of a renal zone. Adjunctive oral prednisolone appears to be effective in diminishing renal scarring in severely affected kidneys. In kidneys with mild and moderate acute pyelonephritis antibiotics alone appear to be equally effective in preventing scarring.

Acute Disease↗
PubMed1999

Purification and characterization of Klebsiella pneumoniae cytotoxins.

Isolation, purification and characterization of 3 new cytotoxins of a K. pneumoniae strain isolated from ready to eat pork sausage are reported. Purification process involved extraction of cytotoxins with polymyxin B sulphate, salt precipitation, gel filtration and anion exchange chromatography. Klebsiella cytotoxin (KCT) I, a glycoprotein of about 65 kDa was verocytotoxic, enterotoxic and dermonerotic. KCT II was erythemogenic, verocytotoxic and enterotoxic protein of co 55 kDa, while KCT III was about double in MW (110 kDa) hadverocytotoxicity but neither enterotoxicity nor dermatotoxicity. KCT I and II caused granulation, conglomeration, shrinkage, detachment and lysis of MDBK and Vero cells, while KCT III induced enlargement, vacuolation, granulation, multinucleolation and syncytia formation in exposed cells. All the three cytotoxins induced specific neutralizing antibodies and cytotoxins were detectable in nanogram quantities with enzyme-linked immunosorbant assay using homologous antibodies. None of the anticytotoxin cross-reacted with either heterologous Klebsiella cytotoxins or with verocytotoxic preparations of Shigella dysenteriae.

Animals↗
PubMed1999

Detection, prevalence, purification and characterization of lecithinase of Klebsiella pneumoniae.

Lecithinase activity in Klebsiella is a rare trait as out of 208 strains of Klebsiella belonging to 3 species, viz. K. pneumoniae (168), K. planticola (29) and K. oxytoca (11), only 4 strains of K. pneumoniae produced lecithinase positive colonies on egg-yolk-agar. Although cell lysates of 16 K. pneumoniae yielded positive results for lecithinase assay on egg-yolk-agar, 19 strains were detected positive for lecithinase with ELISA using anti-lecithinase serum. Release of up to 52.12% cell-bound lecithinase could be achieved with polymyxin-B treatment at 100 micrograms/ml concentration. Purified lecithinase was determined to be a high molecular weight (70 kDa), crystalizable, anionic (pI, 3.5) protein. It possessed cytolytic, haemolytic and dermonecrotic activities but did not induce fluid accumulation in rabbit ileal loop or infant mouse guts. It was inactivated by boiling, trypsin and chymotrypsin treatment and alkaline pH. Serologically, it was related to lecithinase of Aeromonas caviae and phospholipase-C of Salmonella.

Animals↗
PubMed1998

Nasal sill augmentation in adult incomplete cleft lip nose deformity using superiorly based turn over orbicularis oris muscle flap: an anatomic approach.

Adult incomplete cleft lip nose deformity is not uncommon in India. Poverty, ignorance, and parental neglect account for its late presentation. Besides the classical features of cleft lip nose deformity, the constant findings observed in this patient population have been a widened and depressed nasal sill. This is attributable to the sparse, hypoplastic, and abnormally orientated orbicularis oris muscle in the region of the sill. Failure to restore the nasal sill symmetry by suitably augmenting the sill frequently leads to unsatisfactory and asymmetric results. However, in the literature, satisfactory restoration of the nasal sill has not been given the importance it deserves while performing cleft lip rhinoplasty. We present a method of augmenting the depressed nasal sill in cases of adult incomplete nose deformity using a superiorly based orbicularis oris muscle flap, which is harvested from the soft tissues between the apex of the cleft and the nostril sill. Following de-epithelialization of the overlying skin, the exposed muscle is raised as a superiorly based flap after dissecting it from the underlying mucosa. It is folded, turned over, and tucked into the nasal sill base and anchored to the anterior nasal spine to give the desired augmentation. Satisfactory results have been obtained in 18 cases of nasal deformity associated with incomplete cleft lip. In our opinion, this technique offers a simple and effective method of augmenting the depressed sill by utilizing locally available tissues and without the need for procuring autologous tissue from distant sites.

Adolescent↗
PubMed1998

Multiple effects of KPQ deletion mutation on gating of human cardiac Na+ channels expressed in mammalian cells.

Several aspects of the effect of the KPQ deletion mutation on Na+ channel gating remain unresolved. We have analyzed the kinetics of the early and late currents by recording whole cell and single-channel currents in a human embryonic kidney (HEK) cell line (HEK293) expressing wild-type and KPQ deletion mutation in cardiac Na+ channels. The rate of inactivation increased three- to fivefold between -40 and -80 mV in the mutant channel. The rate of recovery from inactivation was increased twofold. Two modes of gating accounted for the late current: 1) isolated brief openings with open times that were weakly voltage dependent and the same as the initial transient and 2) bursts of opening with highly voltage-dependent prolonged open times. Latency to first opening was accelerated, suggesting an acceleration of the rate of activation. The delta KPQ mutation has multiple effects on activation and inactivation. The aggregate effects may account for the increased susceptibility to arrhythmias.

Animals↗
PubMed1998

Transplacental transfer of measles antibody in Delhi.

OBJECTIVE: To find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody. DESIGN: Comparison of measles antibody titres in mothers with titres in cord blood samples. METHODS: Maternal and cord blood samples from 174 full-term pregnant women of middle socio-economic status were tested for hemagglutination inhibition (HI) antibody against measles in Delhi during October 1993 to January 1995. None of the mothers had been immunized against measles. RESULTS: Antibody were undetectable in both maternal and cord samples in only 4 (2.3%) pairs. Mean maternal titre was found to be 2.94 Log2. Transplacental concentration and dilution were respectively observed in 34% and 26% of the samples. Cord titres were more often higher than the maternal values only if the maternal values were low. Overall, cord/maternal ratio of mean titre (Log2) was found to be 1.06. Although the age of the mother and parity had had no significant bearing on the transplacental transfer of measles antibody, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend = 5.4; p = 0.02). CONCLUSIONS: The study failed to show appreciable concentration of measles antibodies across the placenta.

Adolescent↗
PubMed1997

Synergistic effect of retinoic acid on Sn-PP mediated suppression of heme oxygenase activity in vivo in rats.

The present investigation is designed to probe the influence of excess retinoic acid (50,000 I.U.) and Sn-protoporphyrin (50 mumol/kg bw) along with retinoic acid on the activity patterns of the rate-limiting enzyme, heme oxygenase, of the heme catabolic pathway in the liver, spleen, kidney, brain, heart, and lung of male Wistar rats. Our results are noteworthy as SnPP is being used for the amelioration and management of hyperbilirubinemia, and they emphasize that the combined dosing of retinoic acid and SnPP attenuates the suppression of the activity of HMOX, thereby decreasing plasma bilirubin levels. The features of action of retinoic acid and SnPP together in vivo, i.e., a substantial suppression of the formation of a potentially neurotoxic metabolite, bilirubin, and the enhancement of disposal of the untransformed substrate (heme) of the enzyme that is inhibited, define some of the prerequisites of a therapeutically useful formulation.

Administration, Oral↗
PubMed1997

Immune complexes are potent inhibitors of interleukin-12 secretion by human monocytes.

We have studied the effect of immune complexes (IC) on interleukin (IL)-12 secretion by human monocytes in vitro. Two experimental models of IC were used. IC formed of tetanus toxoid and polyclonal anti-tetanus toxoid antiserum as well as heat-aggregated human serum IgG almost completely inhibited IL-12 (p70 and p40) secretion induced by interferon-gamma and lipopolysaccharide in human blood-derived monocytes. Neutralizing anti-IL-10 antibodies plus indomethacin restored IL-12 secretion in the presence of IC to a high extent, indicating that IL-10 and prostaglandin (PG) partially mediate the IC-induced inhibition of IL-12 secretion. However, neutralization of tumor necrosis factor (TNF)-alpha by specific antibodies also incompletely restored IL-12 secretion. Indeed, monocytes secrete high levels of TNF-alpha upon stimulation by IC. We found that exogenously added TNF-alpha caused a profound inhibition of monocytic IL-12 secretion in the absence of IC, again mediated via the induction of IL-10 and PG. In summary, IC inhibit IL-12 secretion via TNF-alpha-induced IL-10 and PG synthesis. We conclude that IC, typically appearing in the course of chronic inflammatory processes, may influence the balance between Th1 and Th2 responses and may thus contribute to a deprivation of cell-mediated immune responses.

Antigen-Antibody Complex↗
PubMed1997

Hydropericardium syndrome (HPS) in India: a preliminary study on the causative agent and control of the disease by inactivated autogenous vaccine.

Hydropericardium syndrome (HPS) in broiler birds of 3 to 6 weeks of age was recorded for the first time in the Haldwani area of Nainital district (UP) in India in November, 1994. The overall mortality in 6 poultry farms was 61.62 per cent. The disease was experimentally transmitted by bacteria free infected liver homogenate extract passed through membrane filters of 0.22 and 0.1 mu APD. The aetiological agent was inactivated by heat treatment at 56 degrees C for one hour and 80 degrees C for 10 min. A precipitin band was demonstrated in agar gel immunodiffusion and counter immunoelectrophoresis using infected liver homogenate extract as antigen and homologous antisera raised in the laboratory. The disease was effectively controlled by formalinised and heat inactivated autogenous vaccine prepared from the infected livers of birds which died of natural infection.

Animals↗