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Biomedical subjects

S G Kulkarni

Publications and source records attributed to S G Kulkarni.

At least 19 recordsLinked to original sources
PubMed2006

Results of a single blind, randomized, placebo-controlled clinical trial to study the effect of intravenous L-carnitine supplementation on health-related quality of life in Indian patients on maintenance hemodialysis.

BACKGROUND: Carnitine insufficiency is responsible for various co-morbid conditions in maintenance hemodialysis (MHD) patients. L-carnitine supplementation is expected to improve the quality of life (QoL) of patients on MHD. AIMS: To study the effect of L-carnitine supplementation on QoL of Indian patients on MHD. SETTING AND DESIGN: This was a single (patient) blind, randomized, placebo-controlled clinical trial conducted on patients on MHD attending hemodialysis unit of the study center. MATERIALS AND METHODS: Twenty patients on MHD suffering from hemodialysis-related symptoms were randomly assigned to receive intravenous L-carnitine 20 mg/kg or placebo after every dialysis session for 8 weeks. SF36 (Short Form with 36 questions) score for QoL, laboratory investigations and dialysis related symptoms were recorded at baseline and after 8 weeks. Improvement in QoL, laboratory parameters and dialysis related symptoms in the two groups after 8 weeks was compared. STATISTICAL ANALYSIS USED: Depending on normality of data, unpaired T test or Mann Whitney U test was used for comparison of change (8 weeks-baseline) in SF36 scores and laboratory parameters observed in the two groups. RESULTS: L-carnitine supplementation increased total SF36 score by 18.29 +/- 12.71 (95% CI: 10.41 to 26) while placebo resulted in reduction in total SF36 score by 6.4 +/- 16.39 (95% CI: -16.59 to 3.73). L-carnitine also resulted in significant increase in hemoglobin and serum albumin and decrease in serum creatinine as compared to placebo. More patients were relieved of dialysis related symptoms in L-carnitine group. CONCLUSION: Intravenous L-carnitine supplementation improves QoL in patients on MHD.

Adult↗
PubMed2000

Disposition of acetaminophen and indocyanine green in cystic fibrosis-knockout mice.

Drug treatment poses a therapeutic challenge in cystic fibrosis (CF) because the disposition of a number of drugs is altered in CF. Enhanced clearance of acetaminophen (APAP) and indocyanine green (ICG) have previously been reported in CF patients. The objective of the current study was to investigate if the CF-knockout mouse model (cftr(m1UNC)) shows altered pharmacokinetics similar to those seen in CF patients using the 2 model compounds APAP and ICG. Clearance (CL/F) of APAP and renal (CLR) and formation (CLf) clearance of acetaminophen glucuronide (AG) and acetaminophen sulfate (AS) were determined in CF-knockout mice following administration of APAP (50 mg/kg, intraperitoneal). CLR of AS was 19.5 and 12.9 (mL/min per kg) and CLf of AS was 10.4 and 6.7 mL/min per kg for homozygous and heterozygous males, respectively, which was significantly different between groups. CLR of AG was 6.3 and 4.8 mL/min per kg and CLf of AG was 9.6 and 8.9 mL/min per kg for homozygous and heterozygous males, respectively, although not reaching statistical significance. No significant differences were noted in either ClR or CLf of AG and AS in female CF mice. Plasma concentrations of ICG (10 mg/kg, intravenous) were determined over 0 to 15 minutes. Homozygous females showed a higher apparent volume of distribution (96 mL/kg) relative to heterozygous females (72 mL/kg). Similar to CF patients, a trend toward a lower Cmax was noted in homozygous male and female mice. However, contrary to human data, no significant differences in CL of ICG were noted. These results suggest that the CF-knockout mice have potential as a model for studying altered drug disposition in CF patients.

Acetaminophen↗
PubMed1999

Differential protooncogene expression in Sprague Dawley and Fischer 344 rats during 1,2-dichlorobenzene-induced hepatocellular regeneration.

Significant differences in hepatotoxic injury of 1,2-dichlorobenzene (o-DCB) have been reported (Gunawardhana, L., Sipes, I.G., 1991. Dichlorobenzene hepatotoxicity strain differences and structure activity relationships. Adv. Exp. Med. Biol. 283, 731-734; Stine, E.R., Gunawardhana, L., Sipes, I.G., 1991. The acute hepatotoxicity of the isomers of dichlorobenzene in Fischer 344 and Sprague-Dawley rats: isomer specific and strain-specific differential toxicity. Toxicol. Appl. Pharmacol. 109, 472-481; Valentovic, M.A., Ball, J. G., Anestis, D., Madan E., 1993a. Acute hepatic and renal toxicity of dichlorobenzene isomers in Fischer 344 rats. J. Appl. Toxicol. 13, 1-7; Kulkarni, S.G., Duong, H., Gomila, R., Mehendale, H.M., 1996. Strain differences in tissue repair response to 1,2-dichlorobenzene. Arch. Toxicol. 70, 714-723. Kulkarni, S.G., Warbritton, A., Bucci, T., Mehendale, H.M., 1997. Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats. Toxicology. 120, 79-88). Although, hepatotoxic injury of o-DCB is greater in Fischer 344 (F344) when compared with Sprague Dawley (S-D) rats, this interstrain difference does not transcend into any difference in lethal effects of o-DCB. Interstrain difference in compensatory tissue repair has been suggested as the underlying mechanism for the lack of strain differences in lethality (Kulkarni et al., 1996; Kulkarni et al., 1997, see these refs. above). However, the mechanism(s) for this interstrain difference in tissue repair is (are) not currently understood. The objectives of the present study were (1) to investigate if the differences in compensatory tissue repair are reflected in differential protooncogene expression in S-D versus F344 rat livers and (2) to investigate if changes in protooncogene expression could explain the decrease and delay in tissue repair response beyond a threshold of 0.6 ml o-DCB/kg. Male S-D and F344 rats (8/9 weeks old) were administered either 0.6 or 1.2 ml o-DCB/kg and changes in expression of protooncogenes c-myc (immediate early) and Ha-ras (delayed early) were examined over a time course. Findings of this study indicate that the timing and extent of c-myc and Ha-ras expression varies in the two strains following administration of o-DCB. Thus, the timing and extent of compensatory liver regeneration that ensues following o-DCB administration in S-D and F344 rats is temporally concordant with the protooncogene expression in the two strains.

Animals↗
PubMed1999

Gastric emptying of solids in long-term NSAID users: correlation with endoscopic findings and Helicobacter pylori status.

OBJECTIVE: Prostaglandins regulate gastric motor function. Inhibition of prostaglandins by nonsteroidal antiinflammatory drugs (NSAIDs) may alter gastric emptying. To study gastric emptying of solids and its relation to endoscopic findings and Helicobacter pylori in patients receiving long-term NSAIDs, we undertook this study. METHODS: Ninety-five patients with arthritis, 65 taking long-term NSAIDs (Group I) and 30 not taking NSAIDs (Group II) were studied. Presence of dyspeptic symptoms was determined using a questionnaire. Mucosal damage was determined by endoscopy. H. pylori was detected by antral biopsies for rapid urease test and histology. Gastric emptying for solids was evaluated using a scintigraphic method. Thirty healthy volunteers were used as controls for gastric emptying (Group III). Patients with peptic ulcer were excluded from the analysis of gastric emptying. Logistic regression analysis was performed to identify predictive factors for gastric emptying. RESULTS: Nineteen patients from Group I with peptic ulcers were excluded. Dyspeptic symptoms were seen in 24 (52%) Group I and seven (23%) Group II patients. Gastroduodenal erosions were seen in 10 (21.7%) Group I patients and four (13.3%) Group II patients. H. pylori was detected in 17 patients in Group I (36.9%) and Group II (56.6%). Gastric emptying was delayed in 24 (52%) Group I patients, six (20%) Group II patients (p < 0.001), and in none of the Group III controls. The mean gastric emptying times were 99.5 (15.6) min and 89 (17.7) min for Groups I and II, respectively (p < 0.05). Endoscopic damage was found with similar frequency in Group I patients with delayed or normal gastric emptying. H. pylori infection was present in 37.5% Group I patients with delayed gastric emptying and in 36.3% with normal gastric emptying (p = ns). Logistic regression analysis identified NSAID therapy as the single factor most predictive of delayed gastric emptying. CONCLUSION: Delayed gastric emptying was seen in 52% of patients on long-term NSAID therapy.

Adult↗
PubMed1997

Antimitotic intervention with colchicine alters the outcome of o-DCB-induced hepatotoxicity in Fischer 344 rats.

Although, hepatotoxic injury of 1,2-dichlorobenzene (o-DCB) is greater in Fischer 344 (F344) as compared to Sprague-Dawley (S-D) rats, this interstrain difference does not transcend into any difference in lethal effects of o-DCB. Interstrain difference in compensatory tissue repair has been suggested as the underlying mechanism for the lack of strain differences in lethality (S.G. Kulkarni, H. Duong, R. Gomila, and H.M. Mehendale, Strain differences in tissue repair response to 1,2-dichlorobenzene. Archives of Toxicology 1996; 70: 714-723). If higher tissue repair in F344 rats compensates for more severe liver injury, then antimitotic intervention after infliction of o-DCB-induced liver injury should lead to lethality in F344 rats. Colchicine (CLC, 1 mg/kg) functions as an effective antimitotic agent and does not cause any side effects apart from suppressing cellular proliferation. Two groups of male F344 rats (160-190 g) received a single dose of 0.6 ml o-DCB/kg: 30 h later one group of rats received CLC (1 mg/kg; i.p.) and the other received distilled water (1 ml/kg; i.p.). Liver injury was assessed by measuring plasma ALT and SDH activity, liver histopathology, and liver regeneration was estimated by [3H]thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) assay in both groups. Similar liver injury was noted in both the o-DCB + vehicle and o-DCB + CLC treated F344 rats at 36 h indicating that CLC does not interfere with the uptake, bioactivation and causation of injury by o-DCB. S-phase synthesis which occurred at 36 h in the o-DCB + vehicle group was blocked in the o-DCB + CLC group. CLC administration 6 h prior to S-phase stimulation selectively abolished S-phase stimulation at 36 h, and led to 50% lethality. Since the effect of CLC antimitosis was transient, S-phase synthesis occurring at 48 h was not blocked and was sustained up to 72 h thereby allowing the other 50% of rats to overcome liver injury induced by o-DCB and survive the lethal outcome. These findings suggest that a significantly higher rate of compensatory tissue repair in F344 rats enables them to overcome more severe liver injury inflicted by o-DCB.

Administration, Oral↗
PubMed1997

Retroperitoneal perforation in ulcerative colitis with mediastinal and subcutaneous emphysema.

Retroperitoneal colonic perforation in patients with ulcerative colitis is rare. We report such a case in a patient with severe ulcerative colitis without toxic dilatation in whom mediastinal and subcutaneous emphysema also developed. Unlike previously reported cases, our patient was treated conservatively with intravenous fluids, parenteral nutrition, intravenous hydrocortisone, and antibiotics. After 2 weeks, the mediastinal and subcutaneous emphysema and the retroperitoneal air completely disappeared.

Adult↗
PubMed1996

Stimulated tissue repair prevents lethality in isopropanol-induced potentiation of carbon tetrachloride hepatotoxicity.

Published reports on the alcohol potentiation of CCl4 toxicity indicate that in spite of enhanced hepatotoxicity there is no increase in lethality. The objective of this study was to investigate the mechanism involved in animal survival despite significantly enhanced liver injury. Male Sprague-Dawley rats (175-225 g) were treated with isopropanol (ISOP, 2.5 ml/kg, 25% aqueous solution, po) 24 hr prior to CCl4 (1 ml/kg, ip) administration. Plasma enzymes (ALT and SDH), hepatic glycogen levels, and [3H]thymidine (3H-T) incorporation into hepatonuclear DNA were measured during a time course (0-96 hr) after CCl4 administration. Liver sections were examined for histopathology and cell cycle progression by proliferating cell nuclear antigen (PCNA) immunohistochemistry. Maximum injury was observed at 36 hr in both the groups as indicated by elevated plasma enzyme levels and by histopathology. The extent of injury in the ISOP + CCl4 group was higher than that in the H2O + CCl4 group. Plasma enzyme activity returned to control levels by 60 hr, indicating recovery from injury in both groups. Maximum 3H-T incorporation occurred at 48 hr in both groups (ISOP + CCl4; vehicle + CCl4), indicating maximum stimulation of S-phase synthesis. PCNA studies revealed a corresponding stimulation of cell cycle progression. The wave of S-phase synthesis and cell cycle progression returned to control levels in the H2O + CCl4 group by 60 hr but continued up to 72 hr in the ISOP + CCl4 group. These findings support the hypothesis that in response to increased infliction of CCl4 injury by isopropanol, augmented stimulation of cell division and tissue repair restrain the progression of injury and restore hepatic structure and function, thereby allowing the rats to survive. Further, antimitotic intervention with colchicine (1 mg/kg, ip) led to decreased S-phase synthesis, followed by 60% lethality in the isopropanol-pretreated group in contrast to 40% lethality in the group receiving CCl4 alone (H2O + CCl4). These findings suggest that greater stimulation of tissue repair restrains the progression of ISOP-enhanced infliction of CCl4 liver injury and accounts for recovery from enhanced liver injury and animal survival. The findings are consistent with a two-stage model of toxicity wherein liver injury is linked by progression or regression of injury, which is governed by the extent of tissue repair to the final outcome.

1-Propanol↗
PubMed1996

Strain differences in tissue repair response to 1,2-dichlorobenzene.

Fischer 344 (F344) rats are reportedly 75-fold more sensitive than Sprague Dawley (S-D) rats to 1,2-dichlorobenzene (o-DCB) hepatotoxicity. Lethality studies were conducted since no information was available regarding the ultimate consequence of this sensitivity in terms of animal survival in the two strains. LD50S for o-DCB (1.66 ml/kg and 1.76 ml/kg in male F344 and S-D rats, respectively) did not differ. Several studies have shown the importance of tissue repair on animal survival following exposure to toxic chemicals. The objective of this study was to investigate if differential rates of cell division and tissue repair might explain the lack of difference in LD50 dose between the two strains despite higher hepatotoxic injury in F344 rats. Age-matched male S-D and F344 rats were administered o-DCB (0.2, 0.6, 1.2 ml/kg, i.p.); injury and tissue repair occurring as two dynamic but opposing events were measured over time. Liver injury was assessed by measuring plasma alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities and by liver histopathology. Higher plasma ALT elevations were observed in F344 rats following administration of 0.2 and 0.6 ml o-DCB/kg. Using SDH as a marker of liver injury, the strain difference was evident only at 0.2 ml o-DCB/kg. Liver regeneration was estimated by 3H-thymidine incorporation into hepatonuclear DNA and via proliferating cell nuclear antigen (PCNA) assay. Prompt and significantly higher hepatocellular regeneration beginning at 36 h was evident in F344 rats following administration of 0.2 and 0.6 ml o-DCB/kg. The significantly higher depletion of hepatic glycogen observed in F344 rats following administration of 0.2 and 0.6 ml o-DCB/kg occurred without significant changes in plasma glucose and is consistent with highly stimulated tissue repair seen in these rats at the corresponding doses. However, increasing the dose further to 1.2 ml o-DCB/kg results in a delayed (S-phase synthesis begins at 48 h) and diminished response to o-DCB. These findings suggest that a significantly higher rate of tissue repair in F344 rats helps them overcome higher liver injury inflicted by o-DCB. This differential in tissue repair in the two strains may play a vital role in equalizing the ultimate outcome of toxicity in the two strains.

Animals↗
PubMed1996

Long-term anti-inflammatory drug use and Helicobacter pylori infection: a clinical, endoscopic and histological study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori are independent risk factors for gastroduodenal damage and peptic ulcer. OBJECTIVE: To study the frequency and effect of H pylori infection on gastroduodenal mucosa in patients on long-term NSAID use. METHODS: A total of 125 subjects were studied: 65 patients (Group 1) on NSAID therapy (> 6 months), 30 patients (Group 2) with arthritic disorders prior to starting NSAID therapy, and 30 healthy volunteers (Group 3). Dyspeptic symptoms were evaluated using a questionnaire. All patients underwent endoscopy and antral and duodenal biopsies were obtained to assess the extent of gastroduodenal damage and H pylori status. RESULTS: H pylori infection was less frequent in Group 1 (37%) compared to Group 2 (57%, p = ns) and 3 (60%, p < 0.05). Among Group 1 patients, H pylori infection did not increase the risk of gastroduodenal damage (52% vs 45%) or ulceration (32% vs 27%). Group 1 patients with H pylori infection were more likely to be symptomatic (48% vs 27%) and have chronic active gastritis (76% vs 12%) and chronic active duodenitis (68% vs 5%). Gastric metaplasia was seen only in patients with H pylori infection, chronic active gastritis and duodenitis. Chemical gastritis was observed more commonly in Group 1 (34% vs 3%) compared to Group 2; its was not seen in Group 3. H pylori infection was less commonly observed in patients with chemical gastritis (8% vs 50%). CONCLUSION: Patients on long-term NSAIDs are not at increased risk of H pylori infection. Presence H pylori infection is not associated with increased risk of gastroduodenal damage in these patients. H pylori infection correlated with presence of chronic active gastritis, and NSAID with presence of chemical gastritis.

Anti-Inflammatory Agents↗
PubMed1995

Percutaneous renal biopsy using Monopty needle.

Forty six percutaneous renal biopsies (thirty one native and fifteen transplant kidneys) were performed using the Monopty needle, compared with equal number of biopsies performed using the Travenol Tru-cut needle. The core length of samples obtained ranged from 3-16 mm using Monopty and 5-13 mm using Tru-cut. Adequate tissue was obtained in 65.5% and 80.4% of cases with the use of Monopty and Tru-cut respectively. Both the needles gave equal number of reuses. The use of Tru-cut needle was associated with serious complications like gross haematuria requiring blood transfusions and perinephric haematoma in ten cases whereas only two cases developed haematuria when the Monopty needle was used. In view of its greater safety we have switched over to using the Monopty needle for percutaneous renal bipsies.

Arteriovenous Fistula↗