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Biomedical subjects

T Joseph

Publications and source records attributed to T Joseph.

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

Mechanics, energetics, and crossbridge kinetics of rabbit diaphragm during congestive heart failure.

Crossbridge (CB) properties were investigated in isolated diaphragm of rabbits during congestive heart failure (CHF, n=9) induced by chronic volume and pressure overload. This model induced cardiac hypertrophy and heart failure. Controls (C) were prepared (n=14). Compared to C, peak tension in CHF fell by 57% in twitch and by 40% in tetanus; Vmax declined by 47% in twitch and by 48% in tetanus. Our study provided an analytical means of calculating from A. F. Huxley's equations the rate constants for CB attachment and detachment, CB single force (II), CB number per mm3 (m'), peak mechanical efficiency (Effmax), and turnover rate of myosin ATPase (kcat); m', II, and Effmax were lower in CHF than in C in both twitch and tetanus. The marked decline in m' and II accounted for the fall in diaphragm strength. In the overall population of C and CHF, Effmax was linearly related to II. Conversely, there was no relationship between Vmax and kcat. Dissociation between Vmax and kcat might be explained by the crucial role attributed to two apparently nonconserved surface 'loops' on the motor domain of myosin head.

Animals↗
PubMed1998

Synergistic effect of flunarizine and sodium valproate on seizure thresholds elicited by cortical stimulation in conscious rats.

The effect of flunarizine (FLU) and sodium valproate (SV) alone and in combination were examined for their effects on seizure thresholds elicited by cortical stimulation in conscious rats. Two different pharmacodynamic parameters could be distinguished viz, the threshold for localised seizures (TLS) defined as the current (mu A) required to elicit forelimb clonus and the threshold for generalised seizure (TGS), defined as the current (mu A) required to elicit vigorous clonic activity without a tonic component. In preliminary neuro-behavioral studies on rats, the most favourable combination was FLU 10 mg/kg i.p. and SV 200 mg/kg i.p., which produced anticonvulsant efficacy with minimal neurotoxicity. With FLU alone, SV alone and the combination of FLU and SV, the mean % change +/- SEM from baseline values over a period of 6 h were for TLS: 3.8 +/- 0.8, 23.9 +/- 3.7, and 29.8 +/- 2.1; and for TGS 5.5 +/- 0.7, 15.6 +/- 2.7 and 190.9 +/- 22.7 respectively, indicating that FLU alone had no effect on TLS or TGS, SV significantly elevated TLS but had no effect on TGS and the combination of FLU plus SV produced a synergistic elevation of both TLS and TGS-the intensity of effect being more on TGS than on TLS. This model provides a new dimension to the profiling of two anticonvulsant agents with different mechanisms of anticonvulsant activity and offers predictive criteria for protective effects on clinical manifestations of partial or generalised tonic clonic seizure.

Animals↗
PubMed1998

Influence of caffeine on pharmacokinetic profile of sodium valproate and carbamazepine in normal human volunteers.

The present study evaluates effect of pharmacokinetic interaction between caffeine (300 mg) in three divided doses with sodium valproate (400 mg) and carbamazepine (200 mg) given as single doses, in normal human volunteers, using a open cross over design. Both the serum concentration of sodium valproate and pharmacokinetic parameters remained unaltered, as against significant reduction in plasma concentration and area under the concentration curve of carbamazepine following the coadministration of caffeine. Also, the plasma t 1/2 (of carbamazepine was prolonged by two folds and bioavailability reduced by about 32% in presence of caffeine. The results are of clinical significance as xanthine consumption may have to be restricted in patients on carbamazepine therapy and this aspect may need further investigation.

Anticonvulsants↗
PubMed1998

Attenuation of ECS-induced retrograde amnesia by using an herbal formulation.

Earlier research indicated the efficacy of a complex herbal formulation in the attenuation of electroconvulsive shock (ECS)-induced amnestic deficits in rats; this study sought to ascertain whether a simplified herbal formulation (Memorin; Phyto-Pharma, India) also was effective. Rats pretreated for a fortnight with Memorin (200 mg/kg/day) or vehicle were exposed to a passive-avoidance learning paradigm in a shuttle box. The next day, the rats were administered two true or sham ECSs, 5 h apart; recall of the pre-ECS learning was reassessed on the following day. ECS was found to produce significant retrograde amnesia (p < 0.002). Memorin attenuated the ECS-induced amnesia (p = 0.00003) without influencing the ECS seizure duration. The clinical implications of these findings are discussed.

Amnesia↗
PubMed1998

Additive anticonvulsant effect of flunarizine and sodium valproate on electroshock and chemoshock induced seizures in mice.

The efficacy of Flunarizine (FLU), a calcium channel blocker, in combination with conventional antiepileptic drugs, phenytoin (PHT), carbamazepine (CBZ), sodium valproate (VPA), and ethosuximide (ESM), at ED50 doses, were examined for protective effects against maximal electroshock seizures (MES) and pentylenetetrazol (PTZ) induced seizures in mice. In both models, only VPA and FLU showed significantly enhanced protection, which was additive ie. 100% protection. In the MES test, though FLU combined with PHT did show a slightly enhanced protection (66.6%), with CBZ there was no enhancement as compared to either drug alone. In the PTZ test, FLU with ESM showed 83% protection this however was not statistically significant. The findings of this study in mice suggest that FLU would be a suitable candidate for add-on therapy with VPA for clinical epilepsy.

Animals↗
PubMed1998

[Implantation of coronary stents in diabetic patients. Short- and medium-term clinical results].

Coronary balloon angioplasty is associated with a high incidence of restenosis in diabetics and of revascularisation of the culprit lesion and increased long-term mortality. The authors report the short and medium-term results of coronary stenting in diabetics. Between May 1995 and April 1997, 2,182 patients underwent coronary stenting. This population included 272 diabetics : 58 insulin-dependent and 214 non-insulin dependent (oral antidiabetics). Stents were implanted in vessels with mean diameters of 3 mm and over. During the hospital period, the complication rate (mortality, non-fatal myocardial infarction, emergency coronary bypass surgery, subacute thrombosis of the stent) was comparable in non-diabetics, insulin-dependent and non-insulin-dependent diabetics (2.55, 0 and 2.0% respectively). One patient (0.5%) died and another (0.5%) had non-fatal myocardial infarction (thrombosis of the stent) in the non-insulin-dependent group. No complications were observed in the insulin-dependent diabetic group. The mean clinical follow-up of 13 months (3-26 months) was respected in 93 and 97% of diabetics. The non-fatal myocardial infarction rate and revascularisation of the culprit lesion were comparable in the insulin and non-insulin-dependent groups (0 versus 0.5% and 8.2 versus 10.5% respectively) but global mortality was higher in the insulin-dependent diabetics (9.3 versus 2.4%).

Aged↗
PubMed1997

[Cardiomyopathy induced by catecholamines in neuroblastoma].

BACKGROUND: Cardiovascular disorders associated with neural crest tumors are congenital malformations rather than cardiomyopathies. CASE REPORT: A 18 month-old girl developed heart failure one week after discovery of an adrenal neuroblastoma with excessive secretion of catecholamines. Investigation showed dilated cardiomyopathy without myocardial hypertrophy. Besides chemotherapy, the patient was given nitrous derivatives, diuretics and converting enzyme inhibitor. His cardiac condition gradually improved so that partial resection of the tumor was possible 2 years later. CONCLUSIONS: The cardiomyopathy presented by this patient is possibly catecholamine-induced even though catecholamines usually results in myocardial hypertrophy rather than dilated cardiomyopathy. The reason why such a cardiomyopathy has never been reported in patients with neuroblastoma remains unclear.

Adrenal Gland Neoplasms↗
PubMed1997

Developmental changes in crossbridge properties and myosin isoforms in hamster diaphragm.

The aim of this study was to determine the effects of maturation on crossbridge properties and myosin isoform composition in hamster diaphragm muscle. Diaphragm strips were obtained at postnatal Days 1 and 8 and in adults (10 to 12 wk). Peak isometric tension and maximum unloaded shortening velocity (Vmax) increased with age (p < 0.001). The single crossbridge force (pi), the total number of crossbridges normalized per cross-sectional area (m x 10(9)/mm2), the turnover rate of myosin ATPase (kcat), and peak mechanical efficiency (Effmax) were calculated from Huxley's equations. The value of m increased significantly from birth to adulthood (p < 0.001), with no changes in pi or Effmax; kcat increased significantly only after the first week postpartum. There was a strong linear relationship between peak isometric tension and m (p < 0.001). Conversely, changes in Vmax were not related to kcat. Myosin electrophoresis showed that neonatal bands and slow myosin isoforms (S) were present at birth. The number of fast adult myosin isoforms increased progressively from birth to adulthood, whereas S increased during the first week postpartum. In conclusion, development changes in diaphragm muscle force and myosin isoform composition were associated with changes in crossbridge number and kinetics, with no changes in the average force per crossbridge or in mechanical efficiency.

Age Factors↗
PubMed1997

Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery.

The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.

Adult↗
PubMed1997

Safety pharmacology of a combination of tinidazole and oxyphenonium bromide.

The effect of a combination of 150 mg tinidazole (CAS 19387-91-8) and 1 mg oxyphenonium bromide (CAS 50-10-2), referred to as the combination, was examined in various animal species to assess its safety. In mice and rats, the combination in the dose range 30-1000 mg/kg p.o. or 250 mg/kg i.p. did not produce behavioural or neurological changes, nor did it influence pentobarbital sleeping time, though, alcohol sleeping time was altered. In anaesthetised dogs, neither blood pressure, ECG, heart rate, respiration or gastrointestinal motility was affected after single intraduodenal administration of the combination 20 and 50 mg/kg or after chronic oral administration of 25 mg/kg daily for 15 days. In isolated organs, viz. perfused rabbit heart, guinea-pig ileum and rat ileum no significant changes were observed following various doses of the combination, compared to tinidazole and oxyphenonium bromide given alone in corresponding concentrations. In conclusion, the pharmacological profile of the aforementioned combination in the dosages employed in mice, rats, guinea-pigs, rabbits and dogs shows that it is safe and well tolerated.

Animals↗
PubMed1997

Influence of adenosine, dipyridamole, adenosine antagonists and antiepileptic drugs on EEG after discharge following cortical stimulation.

The effects of adenosine (100 nM, icv), dipyridamole (DPM, 5 mg/kg, i.p.), adenosine A1 receptor antagonist 8-cyclopentyl-theophylline (8-CPT, 10 mg/kg, i.p.), and aminophylline (AMP) and caffeine (CAF) (at equivalent doses of 35 mg/kg, i.p.), were examined in rats. Anti-epileptic drugs (AEDs) were also administered i.p., viz, carbamazepine (CBZ, 10 mg/kg); phenobarbitone (PB, 10 mg/kg); phenytoin (PHT, 20 mg/kg); valproic acid (VPA, 300 mg/kg); and diazepam (DZP, 10 mg/kg), to study their effects on EEG after discharge (AD) and postictal depression (PID) induced by cortical stimulation. The AD parameters: (1) duration of EEG-AD (sec) and (2) number of spikes was noted both during pre and post drug treatment sessions. Adenosine and DPM had no special effects on AD parameters but showed significant prolongation of PID. All the adenosine antagonists, 8-CPT, AMP and CAF produced significant prolongation of AD duration, increase in number of spikes and reduced the duration of PID to a significant extent. Interestingly, some of the AEDs, viz. CBZ, VPA and DZP showed abolition of all the EEG-AD parameters whereas PB and PHT failed to show any significant effect. The results confirm previous findings on involvement of adenosine in postictal events.

Adenosine↗
PubMed1997

Determination of anticonvulsant effects on seizure thresholds using ramp generated cortical stimulation in conscious rats.

The purpose of this investigation was to evaluate the new technique of direct cortical stimulation in conscious rats, using ramp generated pulse trains. In rats with electrodes permanently implanted in the frontoparietal cortex, twice daily stimulation for a fortnight, with ramp shaped trains of 2 msec duration, frequency 50 Hz, ramp time 200 sec and incrementing 5 microA per 0.1 sec yielded reproducible convulsive thresholds which could be repeated at short intervals over a period of time. Two different pharmacodynamic parameters viz Threshold for Localized Seizures (TLS) and Threshold for Generalised Seizure (TGS) could be distinguished. TLS is defined as the current (microA) required to elicit forelimb clonus or minimal restricted seizure activity and at the 14th session was found to be 650 +/- 91 microA (n = 14). TGS is defined as the current (microA), at which forceful clonic jerks and vigorous clonic activity without the tonic component occurred, and at the 14th session was found to be 1059 +/- 171 microA (n = 23). The effect of (doses, mg/kg, ip),phenytoin (PHY)10, carbamazepine (CBZ) 10 and 20; sodium valproate (SV) 300 and ethosuximide (ESM) 200 were studied on the TLS and TGS (n = 6). PHY, CBZ and SV significantly elevated both TLS and TGS, whereas ESM was ineffective. PHY and CBZ elevated thresholds within 0.5 hr and continued for 5 to 6 hr. For SV, significant elevation of TLS and TGS commenced at 5 to 10 min and lasted about 4 hr. Comparison of these results with conventional methods, suggests that this model provides a new dimension to profiling anticonvulsant compounds, with better extrapolation to clinical situations.

Animals↗
PubMed1996

Sequence heterogeneity of Nef transcripts in HIV-1-infected subjects at different stages of disease.

Nef transcripts were analyzed from peripheral blood mononuclear cells of 10 HIV-1-infected subjects with 9-822 CD4+ lymphocytes/cu mm, including 4 individuals with a probable common source infection. There was no relationship between the phylogenetic position of the various nef sequences and the disease state of the person from whom they were derived. The nef open reading frame was disrupted in all three clones from only 1 subject. Functional analyses of a representative clone from each of the remaining 9 subjects showed that all nef alleles were capable of CD4 cell surface down-regulation, but only three nef alleles suppressed the induction of IL-2 transcription.

Amino Acid Sequence↗
PubMed1996

Pyridoxine 4'-alpha- and 5'-alpha-D-glucosides are taken up and metabolized by isolated rat liver cells.

Uptake and metabolism of pyridoxine-4'-alpha-D-glucoside and pyridoxine-5'-alpha-D-glucoside by freshly isolated rat liver cells were studied using the membrane filtration method. The presence of the pyridoxine-alpha-glucosides at either 0.5 or 5.0 micromol/L had no inhibitory effect on the uptake of pyridoxine (0.5 micromol/L) by hepatocytes. The amount of pyridoxine-alpha-glucoside transported into the cells was only 10-12% of that of pyridoxine. The initial rates of uptake of the pyridoxine-alpha-glucosides were linear with concentrations up to 50 micromol/L. On entry into the cells, 78% of pyridoxine-5'-alpha-glucoside and 15% of the pyridoxine-4'-alpha-glucoside were hydrolyzed at the end of 60 min. Because pyridoxine-5'-alpha-glucoside is hydrolyzed readily and does not interfere with the transport of pyridoxine, the glucoside, if present in animal- or plant-derived foods, may be available as a source of vitamin B-6.

Animals↗
PubMed1996

Mechanical and energetic effects of cromakalim on guinea pig left ventricular papillary muscle.

The mechanical and energetic effects of the adenosine triphosphate-sensitive potassium channel opener cromakalim at 50 microM and 100 microM were determined on guinea pig left ventricular papillary muscles and compared with those of low calcium concentration (n = 9 in each group). Both concentrations of cromakalim induced a negative inotropic effect (decrease in maximum shortening velocity at preload only and maximum extent of muscle shortening at preload only, P < .01 and P < .001 at 50 and 100 microM, respectively; maximum isometric active force normalized per cross-sectional area during the isometric twitch, P < .001; positive peak of the isometric force derivative normalized per cross-sectional area, P < .001) and a negative lusitropic effect (decrease in maximum lengthening velocity at preload only and negative peak of the isometric force derivative normalized per cross-sectional area, P < .01 and P < .001 at 50 and 100 microM, respectively). At 100 microM, the decrease in relaxation parameters was more marked than that in contraction parameters under isotonic conditions, as shown by the decrease in the slope of the relationship between peak lengthening velocity and maximum extent of muscle shortening (P < .01); this result reflects an intrinsic negative relaxant effect. No relaxant effect was found under isometric conditions at either concentration. The mechanical effects of low calcium were similar to those of cromakalim 100 microM, which suggests that the drug acted mainly by reducing the cellular calcium entry. Despite the negative mechanical effect of cromakalim, mechanical efficiency was preserved. This could partly explain the cardioprotective effect of cromakalim during ischemia.

Action Potentials↗
PubMed1996

Correlation between the severity of symptoms in organophosphorus poisoning and cholinesterase activity (RBC and plasma) in humans.

This study was undertaken to examine the correlation, if any, between the inhibition of red blood cell cholinesterase (RBC ChE), plasma cholinesterase (PChE) and cerebrospinal fluid acetyl cholinesterase (CSF AChe) and the severity of symptoms in patients poisoned with organophosphorus (OP) compounds. Baseline values of the cholinesterases (RBC, Plasma & CSF) were established in our laboratory using a modified colorimetric method. OP poisoned patients were divided into 3 groups - mild, moderate and severe based on clinical symptoms. We observed a severity dependent inhibition of both RBC ChE and PChE, in acute poisoning. Sequential post exposure estimations of the ChEs upto 5 days not reveal any rise in the values though there was substantial clinical improvement. Our findings therefore indicate that the correlation of ChE values with severity of symptoms are applicable only in the initial stages of acute poisoning. AChE could not be detected in CSF in two severely neurotoxic patients who subsequently expired. The clinical significance of this observation needs to be examined further.

Cholinesterases↗
PubMed1996

Higher AUCs on oral administration of omeprazole and felodipine in Indian volunteers--are they clinically important?

Bioavailability studies with single oral doses of omeprazole 20 mg (enteric coated formulation) and felodipine 10 mg (extended release formulation) were performed in Indian volunteers to confirm that adequate plasma concentrations are obtained in Indian subjects. Plasma samples were analysed by chromatographic methods. The AUCs of omeprazole were about 3 fold higher and those of felodipine 2 fold higher than AUCs reported in Western subjects. This has no toxicological implications with respect to omeprazole, but whether lower dose of omeprazole may be sufficient in Indian patients with acid related diseases would require acid inhibition studies. In the case of felodipine the higher AUCs in Indian subjects suggest a need for a lower strength formulation (2.5 mg) to fine-titrate the dosage to obtain optimal antihypertensive effects with minimal adverse effects.

Administration, Oral↗