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Biomedical subjects

S D Seth

Publications and source records attributed to S D Seth.

At least 37 records · Page 2Linked to original sources
PubMed1995

Comparative bioavailability of two brands of ciprofloxacin.

Twelve adult healthy volunteers participated on two occasions in a cross-over study with an interval of 30 days. The bioavailability of ciprofloxacin 500 mg administered as single oral dose was compared in preparation A (Indian, Torrent) and preparation B (Imported, Bayer). The drug was administered early morning on an empty stomach. Blood samples were collected at 1/2,1,2,4,6,8,12 and 24 hours. Plasma levels of ciprofloxacin were determined by HPLC. Time taken to achieve peak plasma concentration (Tmax) was 2 hours (A) and 1.67 +/- 0.49 hours (B). Maximum plasma concentration (Cmax) ranged from 1.8 to 5.1 ug/ml (mean 3.08 +/- 0.99 ug/ml) for 'A' and 2.08 to 5.5 mu g/ml (mean 3.58 +/- 1.37 mu g/me for 'B'. Area under plasma concentration time curve ranged from 30.91 to 118.27 ug/ml/hr (mean 59.97 +/- 26.68 ug/ml/hr) in 'A' and 36.52 to 108.05 (mean 62.80 +/- 22.33 ug/ml/hr) in 'B' which is more than reported in Western literature. Large bioavailability of ciprofloxacin in the present study suggests the need to be cautious while treating patients with renal problems and to use lower doses in Indian patients to achieve desirable results. However, there was no significant difference in the pharmacokinetic parameters between the two brands (Paired 't' test and Wilcoxon Sign Rank test). It is therefore, concluded that both the preparations are comparable in terms of bioavailability.

Administration, Oral↗
PubMed1994

Role of aspirin in modulating myocardial ischemic reperfusion injury.

The role of low-dose aspirin (3 mg/kg, i.v.) in attenuating ischemic reperfusion injury was studied in a canine model. Regional ischemia for 40 min was produced by temporary occlusion of the left anterior descending coronary artery and thereafter reperfusion instituted for 3 h. Mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive (+) LV dP/dtmax and negative (-) LV dP/dtmax were monitored along with myocardial adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate. Following reperfusion, there was a significant fall in (i) MAP, (ii) (+) LV dP/dtmax and (iii) (-) LV dP/dtmax. LVEDP was corrected after about 2 h of reperfusion. Replenishment of only myocardial CP occurred, without any change in ATP and glycogen, although lactate accumulation was corrected. Aspirin administered 15 min before reperfusion (post-treatment) caused normalisation of LVEDP within 15 min and prevented any deterioration in (-) LV dP/dtmax, although it had no effect on MAP and (+) LV dP/dtmax. After 3 h of reperfusion (post-treatment), myocardial ATP, CP, glycogen and lactate contents became normal. The number of premature ventricular complexes was significantly reduced after aspirin treatment. The present study indicates that low-dose aspirin post-treatment can ameliorate at least some of the deleterious consequences of reperfusion injury of the myocardium.

Adenosine Triphosphate↗
PubMed1994

Reduced urinary kallikrein excretion in human renovascular hypertension caused by nonspecific aortoarteritis and other disorders.

In this study urinary kallikrein excretion was measured using the kininogenase bioassay technique in 12 normal volunteers and 23 patients with angiographically-proven renovascular hypertension (RVHT). In 13 of these (group I), RVHT was due to nonspecific aortoarteritis (NSAA) and in 10 (group II) due to other causes. Urinary kallikrein (UKa) excretion was significantly lower in patients, with values still lower in NSAA. PRA was high in both the groups in comparison with controls; however, the levels were significantly lower in group I compared with group II. Finding of both UKa and PRA lower in group I is suggestive of long standing hypertension becoming volume dependent with nephrosclerotic changes in the kidney. These results point to decreased renal kallikrein-kinin system activity as a feature of NSAA that probably contributes chiefly to the maintenance of the hypertensive state. Normalisation of BP with restoration of UKa and PRA towards normal in three patients of group I and five in group II further support the role of UKa not only when over activity of renin-angiotensin system is responsible for RVHT as in group II but also in group I when the hypertension becomes volume dependent.

Adolescent↗
PubMed1994

Isoniazid and acetylisoniazid kinetics in serum and urine in pulmonary primary complex with intermittent regimen.

Twenty patients, 1 through 13 years of age from Pediatric Tuberculosis Clinic of All India Institute of Medical Sciences, New Delhi, suffering from pulmonary primary complex (PPC) were investigated for serum and urine concentrations of isoniazid (INH) and acetylisoniazid (AcINH). Patients were put on an intermittent regimen - 2HR, 4H2R2, INH (H) was given in a dose of 10 mg/kg/day for first 2 months (the daily dose phase), followed by 20 mg/kg/dose in biweekly phase of regimen for rest of the 4 months, whereas, rifampicin (R) was given as 12 mg/kg in both daily as well as biweekly phases. In the biweekly phase of regimen, after 7 days of biweekly administration of drugs, INH and AcINH concentrations were estimated by HPLC at 0,1,3,5 and 7 hours in serum, and at 0-3, 3-6, 6-12 and 12-24 hour-intervals of drug administration in urine. Peak concentrations of INH and AcINH (Mean +/- SD) were 2.6 +/- 1.8 and 5.5 +/- 2.6 micrograms/ml in serum (Cmax), and 5.7 +/- 4.8 and 21.5 +/- 12.1 mg in urine, respectively. Time to achieve Cmax (Tmax), for INH and AcINH were 1 and 5 hours respectively while time of peak concentration in urine for INH was 3-6 hours and for AcINH 6-12 hours. The half-life (T1/2) of INH was 4.5 hours and area under serum-concentration time-curve (AUC0-7h) was 20.7 micrograms/ml/h (mean values). In biweekly phase (4H2R2) of regimen, just before administration of next dose, 0 hour (or 72 hours) concentration of INH was estimated at 0.47 +/- 0.3 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Recovery from reperfusion injury in intact canine heart by nifedipine.

Effect of nifedipine post-treatment (100 micrograms/kg slow bolus followed by 3 micrograms/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (I) (20 min.) followed by 1 hr of reperfusion (R) was studied in pentobarbitone-anaesthetized open-chest coronary ligated dogs. In the control group, 1 hr of reperfusion failed to cause any significant recovery of the depressed LVdP/dtmax and that of the elevated LVEDP (LVdP/dtmax, pre-ischemic: 2720 +/- 90 mm Hg/sec., 20 min. of I: 2410 +/- 120 mm Hg/sec and 60 min. of R: 2210 +/- 130 mm Hg/sec. LVEDP, pre-ischemic: 5.25 +/- 0.2 mm Hg, 20 min. of I: 10.5 +/- 0.9 mm Hg and 60 min. of R: 7.5 +/- 0.5 mm Hg). However, 1 hr of reperfusion caused a significant recovery of ischemia-induced depletion of myocardial creatine phosphate (CP) content only, but not that of ATP. On post-treatment with nifedipine (i.e., infusion started just before reperfusion), there was a significant recovery in LVEDP (8.25 +/- 0.6 mm Hg after 20 min. of ischemia to 5.0 +/- 0.4 mm Hg after 1 hr of reperfusion) and there was no further deterioration in LVdP/dtmax, as observed in untreated dogs. More significantly, nifedipine caused a near normal recovery of both ATP and CP contents of the affected myocardium. Therefore, the present study shows that post-ischemic administration of nifedipine prevented reperfusion injury of the ischemic myocardium, as evidenced by both functional and metabolic recovery.

Adenosine Triphosphate↗
PubMed1993

Serum concentrations of rifampicin and isoniazid in tuberculosis.

Ninety-four patients, 1-13 years of age suffering from different types of tuberculosis were investigated for serum rifampicin (RIF) and isoniazid (INH) concentrations using microbiological and fluorimetric methods, respectively. Of these, 64 (68.1%) had pulmonary primary complex (PPC); 20 (21.3%) progressive primary disease (PPD) and 10 (10.6%) tuberculous meningitis (TBM). Patients with PPC, PPD and TBM were given two-drug (6HR), three drug (2HRZ, 4HR) and four drug (2SHRZ, 4HRE, 3HE) regimens, respectively. RIF and INH were administered in a dose of 12 and 10 mg/kg/day, respectively. After 10-12 days of continuous therapy, their serum concentrations were estimated at 0, 2, 4, 6, 8 hours for RIF and 0, 1, 3, 5, 7 hours for INH. For RIF, the time to achieve maximum concentrations (Tmax) was 2 hours, range of mean of maximum concentration (Cmax) 3.38 to 3.88 micrograms/ml, terminal half life elimination (T1/2) 3.03 to 3.81 hours and area under serum concentration curve (AUC) 0-8 hours 24.7 to 28.3 micrograms/ml hours in different forms of tuberculosis. INH had a Tmax of 1 h, Cmax 4.38 to 8.17 micrograms/ml, T1/2 4.0 to 4.98 hours and AUC 0-7 hours 34.1 to 57.5 micrograms/ml hours. The concentrations achieved at 7-8 hours with these dosages were much above those required for therapeutic efficacy (minimum inhibitory concentration), being 50 to 250 times for RIF and 35-60 times for INH. We recommend pharmacokinetic studies with lower doses of RIF and INH for less toxic, equally effective and cheaper antitubercular chemotherapy.

Adolescent↗
PubMed1993

Effect of verapamil post-treatment in myocardial reperfusion injury.

Effect of verapamil post-treatment (0.2 mg/kg bolus, followed by 0.01 mg/kg/min infusion) on the functional and metabolic changes of the heart after a brief regional ischemia (20 min) followed by 1 hr of reperfusion was studied in open-chest pentobarbitone anaesthetized dogs. In control dogs 1 hr of reperfusion failed to cause any improvement of depressed myocardial contractility (LVdP/dtmax and LVEDP) caused by 20 min of ischemia, which confirmed the earlier reported phenomenon of 'Stunned Myocardium'. Myocardial ischemia caused a significant loss of high-energy phosphate (HEP) content of the affected myocardium (ATP decreased by 60% and CP decreased by 75% of non-ischemic level). Following 1 hr of reperfusion, myocardial ATP was not replenished, though creatine phosphate became near normal. When verapamil was administered just before reperfusion, it showed a profound beneficial effect on the incidence of fatal reperfusion arrhythmias. At the end of 1 hr of reperfusion in this group, the recovery of the myocardial contractility was incomplete, but a significant replenishment of the myocardial HEP content was observed. Thus verapamil post-treatment can prevent reperfusion-induced myocardial injury but functional recovery may be delayed due to the drug's inherent direct myocardial depressant effect.

Adenosine Triphosphate↗
PubMed1991

Isoproterenol fails to produce myocardial necrosis in streptozotocin-induced diabetic rats.

Biochemical alterations in the hearts of non-diabetic and 5 weeks of streptozotocin-induced diabetic rats following isoproterenol (ISO) administration were compared. Serum lactate dehydrogenase (LDH) and myocardial adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycogen were used as indices of myocardial injury. Hearts from diabetic rats (blood glucose greater than 350 mg/dl), before ISO administration, had normal lactate levels but significantly low high-energy phosphate (HEP) levels and high glycogen levels in comparison to non-diabetic rats. No difference was observed in serum LDH levels between these two groups. ISO administration to non-diabetic rats caused myocardial necrosis as evidenced by a significant depletion of myocardial glycogen and HEPs along with significant myocardial lactate accumulation and an increase in serum LDH. However, the hearts from diabetic rats failed to show any significant HEP depletion, accumulation of lactate and leakage of LDH into serum following ISO-administration, though myocardial glycogen level was significantly lowered. These observations, in conjunction with earlier reports, point to the hypothesis that, in diabetes, there are certain alterations in the sarcolemma which hamper the process by which ISO causes myocardial necrosis.

Animals↗
PubMed1991

Modulation of morphine induced antinociception by intracerebroventricularly administered captopril.

Captopril when administered intracerebroventricularly (icv) in doses of 100, 300, 500 and 1000 micrograms induced a dose dependent antinociceptive effect in rats. Naloxone pretreatment (10 mg/kg, ip) completely antagonised antinociceptive effect of captopril, suggesting thereby the involvement of brain enkephalinergic system. Captopril 300 micrograms, icv potentiated the antinociceptive effect of morphine in intact animals. The bilateral adrenalectomy did not have any effect on this potentiation as against the reported blockade of potentiation in adrenalectomized animals when captopril was administered by systemic route. Thus potentiation of morphine induced antinociception by icv captopril is unlikely to be exerted through an effect on adrenal function and is most likely due to increased brain enkephalin levels.

Analgesics↗
PubMed1990

Increased brainstem angiotensin-I levels in chronic 2 KIC hypertensive rats.

A study was undertaken on the role of brainstem renin-angiotensin system in maintenance of hypertension in chronic renovascular hypertensive rats. Hypertension was induced by unilateral renal artery clamping, while the contralateral kidney was left intact (2 KIC). Blood pressure (BP), plasma renin activity (PRA) and brainstem angiotensin (ang-I) levels were measured after 24 days, in hypertensive and sham-operated animals. In separate subgroups of these animals, the effect of intracerebroventricular administration of captopril on the parameters listed was studied. The results showed high ang-I levels in 2 KIC rats as compared to controls (P less than 0.05). Captopril administration (500 micrograms/50 microliters icv) caused a fall in BP and increase in brainstem ang-I levels (P less than 0.01). In control animals, however, captopril produced a rise in BP without any significant change in brainstem ang-I levels. Peripheral plasma renin activity was normal, despite significant sodium retention in 2 KIC rats. The results are suggestive of activation of brainstem renin-angiotensin system (RAS) in chronic 2 KIC hypertension.

Angiotensin I↗
PubMed1989

Effects of dilazep in evolving myocardial infarction in dogs: a biochemical study.

Mongrel dogs of either sex with ligation of their left anterior descending coronary artery were employed for the present study to investigate the biochemical basis of the cardioprotective action of dilazep. Dilazep (0.2 mg/kg intravenous) was administered 20 minutes after coronary arterial occlusion. Ligation of the artery for 40 minutes increased the tissue lactate concentration and decreased the adenosine triphosphate molecules within the occluded bed. Dilazep decreased the lactate concentration and improved the adenosine triphosphate content of this bed significantly. Dilazep also lowered the tissue cyclic adenosine monophosphate concentration and free fatty acid extraction of the ischemic myocardium as studied 40 minutes after coronary arterial ligation. It can be inferred that less free fatty acid extraction and calcium antagonistic action of dilazep helps in restoring mitochondrial function. Furthermore, decreased tissue lactate concentration resulted after better perfusion of the occluded bed and helped in greater generation of adenosine triphosphate molecules. These favorable biochemical and metabolic changes contribute to the cardioprotective action of dilazep.

Adenosine Triphosphate↗
PubMed1989

Opposing effect of apomorphine on antinociceptive activity of morphine: a dose-dependent phenomenon.

Apomorphine, when administered intracerebroventricularly (0.05 mg/kg) to rats, increased tail-flick latency (a spinal nociceptive response). However, intraperitoneal administration at doses of 1, 3 and 10 mg/kg had no effect, probably because of a tonic supraspinal inhibitory influence on spinal dopaminergic neurones involved in segmental nociceptive processes. Depending on the doses administered, intraperitoneal administration of apomorphine exhibited opposite effects on antinociceptive activity of morphine. Pretreatment with a low dose of apomorphine (1 mg/kg) attenuated, whereas, a high dose (10 mg/kg) potentiated morphine-induced antinociception. Dopamine antagonists, in doses that preferentially block autoreceptors, i.e., haloperidol (0.1 mg/kg, i.p.) and (-)-sulpiride (5 mg/kg, i.p.), antagonised the attenuation of morphine antinociception by a low dose of apomorphine, while treatment with a high dose of haloperidol (1 mg/kg, i.p.) and pimozide (1.25 mg/kg, i.p.) completely antagonised the potentiating effect of a high dose of apomorphine on the antinociceptive activity of morphine. The attenuation of morphine antinociception thus appears to be due to decreased dopaminergic activity as a result of preferential dopamine autoreceptor stimulation by a low dose of apomorphine, whereas potentiation with a high dose of apomorphine is caused by enhanced dopaminergic activity via postsynaptic receptor stimulation.

Animals↗
PubMed1989

Effect of intracerebroventricular administration of angiotensin II on emetic reflex in dogs.

Area postrema is rich in angiotensin II receptors and intravenous (iv) administration of angiotensin II has been reported to elicit emesis. However, in the present study intracerebroventricular (icv) administration of angiotensin II up to a dose of 10 micrograms failed to elicit emesis. It is suggested that presence of a cerebrospinal fluid-brain barrier in area postrema most probably prevents access of icv angiotensin II to its receptors which are otherwise accessible on iv administration.

Angiotensin II↗
PubMed1989

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.

Animals↗