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S S Chatterjee

Publications and source records attributed to S S Chatterjee.

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

Damaged neuronal energy metabolism and behavior are improved by Ginkgo biloba extract (EGb 761).

The standardized extract EGb 761 from the dried green leaves of Ginkgo biloba is a complex mixture of ingredients with an uniquely broad spectrum of pharmacological activities on the central nervous system e.g. in memory enhancing properties and in the regulation of cerebral glucose/energy metabolism. To test these effects on both behavioral and metabolic brain parameters, the animal model of intracerebroventricular (i.c.v.) streptozotocin (STZ) treatment was used. To quantify the experimental data more precisely, animals that were good performers were separated from poor performers by means of the holeboard test before i.c.v. administration of STZ. Good performers only were considered for the study. After a 1-week training period on the holeboard improvement was seen in all animals in learning, memory and cognition, and the improvement was maintained over the investigation period of 12 weeks in the control group. In this group, the energy pool in the cerebral parietotemporal cortex was found to be large and the energy turnover high. After triplicate i.c.v. STZ injection, working memory (WM), reference memory (RM), and passive avoidance (PA) behavior fell off and continued to deteriorate throughout the investigation period. Otherwise there were no significant differences in locomotor activity, excluding the possibility that activity per se might have contributed to the behavioral abnormalities. These were accompanied by a permanent deficit in cerebral energy metabolism. The ongoing deterioration in behavior and the maintained deficit in cerebral energy metabolism occurring after a triplicate i.c.v. STZ injection were significantly slowed down by EGb761. The deficits in learning, memory and cognition were partially compensated, and the disturbances in cerebral energy metabolism returned to almost completely normal values. These findings underscore the beneficial effect of EGb761 that had been reported in dementia disorders.

Adenosine Triphosphate↗
PubMed1998

The putative cognitive enhancer KA-672.HCl is an uncompetitive voltage-dependent NMDA receptor antagonist.

KA-672.HCl (KA-672) is a new substance demonstrating anti-dementia properties. It shows modulatory effects on several neurotransmitter systems known to be affected in patients with Alzheimer's disease. In this study the action of KA-672 on the NMDA receptors was examined by applying patch clamp techniques to acutely isolated hippocampal neurons. KA-672 antagonizes NMDA responses in a voltage-dependent manner. At a holding potential of -90 mV the IC50 value for the blocking action of KA-672 was 20+/-7 microM. This action of KA-672 is independent on the concentration either of agonist or coagonist of NMDA receptor. Ketamine, which interacts with the PCP center, does not occlude the action of KA-672. Evidently, KA-672.HCl is a weak NMDA receptor-operated channel blocker. This property may account for its pharmacological profile.

Animals↗
PubMed1998

Hyperforin as a possible antidepressant component of hypericum extracts.

We demonstrate that the phloroglucinol derivative hyperforin is not only the major lipophilic chemical constituent of the medicinal plant Hypericum perforatum (St. John's wort) but also a potent uptake inhibitor of serotonin (5-HT), dopamine (DA), noradrenaline (NA), GABA and L-Glutamate with IC50 values of about 0.05-0.10 microg/ml (5-HT, NA, DA, GABA) and about 0.5 microg/ml (L-glutamate) in synaptosomal preparations. Furthermore, potencies of two different hypericum extracts in two conventional pharmacological paradigms useful for the detection of antidepressants (behavioral despair, learned helplessness), closely correlate with their hyperforin contents. In addition, most till now known neuropharmacological properties of the clinically used hypericum extracts can also be demonstrated with pure hyperforin. It appears, therefore, that this non-nitrogenous constituent is a possible major active principle responsible for the observed clinical efficacies of the extract as an antidepressant and that it could also be a starting point for drug discovery projects engaged in the search of psychoactive drugs with novel mode of action.

Animals↗
PubMed1998

Antidepressant activity of hypericum perforatum and hyperforin: the neglected possibility.

Efforts leading to the identification of hyperforin as an antidepressive component of therapeutically used alcoholic hypericum extracts are described and discussed. Initially, the effects of this unique and major constituent of the herb were detected in peripheral organs using in vitro models and an extract was obtained by supercritical extraction of the herb by carbon dioxide. These extracts are highly enriched in hyperforin (38.8%) and are devoid of hypericines and numerous other components of alcoholic extracts. Studies with such an extract and with isolated hyperforin indicated that this acylphloroglucinol derivative can inhibit serotonin-induced responses and uptake of this neurotransmitter in peritoneal cells. Assuming that the effects of hyperforin were due to its actions on serotoninergic 5-HT3/5-HT4 receptors, further studies were conducted to investigate its effects on the CNS. These efforts revealed its antidepressant activity in the behavioral despair test and led to the working hypothesis that hyperforin and serotoninergic mechanisms are involved in the antidepressant activities of alcoholic hypericum extracts. The observations made during this study also indicate that hyperforin is the major, but not the only antidepressive component of alcoholic extracts.

Animals↗
PubMed1998

Activity profiles of two hyperforin-containing hypericum extracts in behavioral models.

The behavioral activity profile of a therapeutically used alcoholic hypericum extract containing hyperforin (4.5%) in rodent models was compared with that of an experimental CO2 extract devoid of hypericines but highly enriched in hyperforin (38.8%). The antidepressant activities of 50, 150 and 300 mg/ kg/day of the alcoholic extract were similar to those of 5, 15 and 30 mg/kg/day respectively of the CO2 extract. The ethanol extract in the same dose range potentiated dopaminergic behavioral responses, whereas these effects were either absent or less pronounced in the CO2 extract treated groups. By contrast, serotoninergic effects of the CO2 extract were more pronounced than those of the alcoholic extract. These and various other observations made during the study confirm that although the antidepressant action of hypericum extracts depends on their hyperforin contents, their spectrums of central activity are due to other component(s). Our working hypothesis that hyperforin and serotoninergic mechanisms are involved in the therapeutically observed antidepressant activities of hypericum extracts is in agreement with these observations.

Animals↗
PubMed1998

Oral bioavailability of hyperforin from hypericum extracts in rats and human volunteers.

Validated analytical methods suitable for determining hyperforin in plasma after administration of alcoholic Hypericum perforatum extracts containing hyperforin are described. After oral administration of 300 mg/kg Hypericum extract (WS 5572, containing 5% hyperforin) to rats maximum plasma levels of approximately 370 ng/ml (approx. 690 nM) were reached after 3 h, as quantified by a HPLC and UV detection method. Estimated half-life and clearance values were 6 h and 70 ml/min/kg respectively. Since therapeutic doses of Hypericum extracts are much lower than that used in rats, a more sensitive LC/MS/MS method was developed. The lower limit of quantification of this method was 1 ng/ml. Using this method, plasma levels of hyperforin could be followed for up to 24 h in healthy volunteers after administration of film coated tablets containing 300 mg hypericum extracts representing 14.8 mg hyperforin. The maximum plasma levels of approximately 150 ng/ml (approx. 280 nM) were reached 3.5 h after administration. Half-life and mean residence time were 9 and 12 h respectively. Hyperforin pharmacokinetics were linear up to 600 mg of the extract. Increasing the doses to 900 or 1200 mg of extract resulted in lower Cmax and AUC values than those expected from linear extrapolation of data from lower doses. Plasma concentration curves in volunteers fitted well in an open two-compartment model. In a repeated dose study, no accumulation of hyperforin in plasma was observed. Using the observed AUC values from the repeated dose study, the estimated steady state plasma concentrations of hyperforin after 3 x 300 mg/day of the extract, i.e., after normal therapeutic dose regimen, was approximately 100 ng/ml (approx. 180 nM).

Administration, Oral↗
PubMed1997

Phospholipid breakdown and choline release under hypoxic conditions: inhibition by bilobalide, a constituent of Ginkgo biloba.

A marked increase of choline release from rat hippocampal slices was observed when the slices were superfused with oxygen-free buffer, indicating hypoxia-induced hydrolysis of choline-containing phospholipids. This increase of choline release was suppressed by bilobalide, an ingredient of Ginkgo biloba, but not by a mixture of ginkgolides. The EC50 value for bilobalide was 0.38 microM. In ex vivo experiments, bilobalide also inhibited hypoxia-induced choline release when given p.o. in doses of 2-20 mg/kg 1 h prior to slice preparation. The half-maximum effect was observed with 6 mg/kg bilobalide. A similar effect was noted after p.o. administration of 200 mg/kg EGb 761, a ginkgo extract containing approximately 3% of bilobalide. We conclude that ginkgo extracts can suppress hypoxia-induced membrane breakdown in the brain, and that bilobalide is the active constituent for this effect.

Animals↗
PubMed1997

[In vitro and in vivo studies on the cardioprotective action of oligomeric procyanidins in a Crataegus extract of leaves and blooms].

Cardioprotective effects of a standardized extract from leaves with flowers of Crataegus (WS-1442; content of oligomeric procyandins [OPC]: 18.75%) have recently been demonstrated in an ischemia-reperfusion model in rats. Further studies were now conducted to clarify the mechanism of action and to identify active constituents involved in these effects of WS-1442. Exhausting partitioning between ethyl acetate/water and successive ultrafiltration of the aqueous layer led to the quantitative recovery of three fractions, which were tested for their in vitro radical scavenging (RS) and human neutrophil elastase (HNE) inhibitory activity. The lipophilic ethylacetate-soluble fraction A, enriched in flavone derivatives and constituting 14.9% of WS-1442, was as active as WS-1442 in inhibiting HNE. However, its RS activity was only about half that of the primary extract. Although 67.9% of WS-1442 was recovered in a water-soluble low molecular weight fraction B, this fraction displayed only weak RS and HNE inhibiting activity. In contrast, the RS and HNE inhibiting potencies of an essentially flavone-free and OPC-rich fraction C (21.3% of WS-1442) were significantly higher (inhibition of lipid peroxidation: IC50 0.3 microgram/ml; inhibition of HNE: IC50 0.84 microgram/ml) as those of WS-1442. The RS and HNE inhibitory activities of the extract and those of its fractions correlated well with their OPC-content but not with their concentration of flavonols. These results demonstrate that OPCs of Crataegus extracts possess stronger radical scavenging activities than flavone derivatives or other constituents. In addition, the oligomeric components are potent inhibitors of HNE. Oral administration of 20 mg/kg/d of the OPC-rich fraction C to rats afforded similar protection against ischemia-reperfusion induced pathologies as treatment with WS-1442 at a dose of 100 mg/kg/d. These observations indicate that radical scavenging and elastase inhibitory activities could indeed be involved in the observed cardioprotective effects of WS-1442, and demonstrate that OPCs are major orally active constituents of WS-1442. Thus, Crataegus extracts used therapeutically for cardiovascular diseases should be analyzed and standardized for their OPC-content.

Animals↗
PubMed1996

Eye changes in non-specific aorto-arteritis.

Non-specific aorto-arteritis or Takayasu's arteritis is fairly common and has been reported from all parts of India. The disease presents with various eye symptoms such as transient or permanent blindness, headache and signs including neovascularisation, retinal anastomosis, rubeosis iridis, cataracts. Eye manifestations depend on stage of disease and degree of involvement of cervical arteries. This review consists of an indepth impression of eye involvement in non-specific aorto-arteritis.

Eye Diseases↗
PubMed1996

Studies on prosthetic valve function--a transesophageal echocardiographic assessment.

Haemodynamic assessment was done by colour flow mapping and Doppler interrogation by both Transthoracic (TTE) and Transesophageal echocardiography (TEE) in 40 consecutive patients (mean age 36.6 +/- 12.35 years) with prosthetic valves. There were 30 cases of mitral (MVR) and 12 aortic (AVR) valve replacement. Major purpose of the study was to detect the sensitivity of TEE in detecting prosthetic valve malfunction particularly in comparison to TTE. Pannus was detected in 3 and 8 cases of MVR (p < 0.01) by TTE and TEE respectively; however, TEE was found to be of equal status in detecting pannus over AV (2 cases). Physiological regurgitation in MVR and AVR was detected in 13% and 25% by TTE and 20% and 33% by TEE respectively. Paravalvular leak was detected in 3 cases of MVR by TEE compared to only case by TTE. Though it is difficult to deduce any specific conclusion from this small number of patients, there is definite trend to higher sensitivity in detecting disorders with TEE specially for mitral prostheses.

Adult↗
PubMed1995

Effects of methysticin on three different models of seizure like events studied in rat hippocampal and entorhinal cortex slices.

Methysticin is one of the constituents of Piper methysticum which possesses anticonvulsant and neuroprotective properties. Its effects on different in vitro seizure models were tested using extracellular recordings in rat temporal cortex slices containing the hippocampus and the entorhinal cortex. Elevating [K+]0 induced seizure-like events with tonic and clonic electrographic phases in area CA1. Lowering [Ca2+]0 caused recurrent seizure like episodes with large negative field potential shifts. Lowering Mg2+ induced short recurrent discharges in area CA3 and CA1 while ictaform events lasting for many seconds were induced in the subiculum, entorhinal and temporal neocortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the subiculum, entorhinal and temporal cortex changed their characteristics after one to two hours to late recurrent discharges. In a concentration-range from 10 to 100 microM methysticin reversibly blocked all these types of epileptiform activity. Decreases in [Ca2+]0 and associated slow field potentials evoked by repetitive stimulation of the stratum radiatum or the alveus remained almost unaffected by methysticin. A paired pulse stimulus paradigm used to test for effects of methysticin on synaptically evoked transient field potentials in normal medium revealed interference with mechanisms involved in frequency potentiation. While responses to alvear stimulation were largely unaffected, the responses to a paired pulse stimulus to stratum radiatum were depressed over the whole range of tested stimulus intervals. The findings suggest that methysticin has effects on different patterns of epileptiform activity possibly by interfering with processes responsible for frequency potentiation.

Animals↗
PubMed1995

Effects of the anticonvulsant losigamone and its isomers on the GABAA receptor system.

We conducted in vitro studies to clarify the possible involvement of GABAA receptor-mediated processes in the anticonvulsant effects of losigamone and its optical isomers AO-242 (+ losigamone) and AO-294 (- losigamone). In binding experiments with cortical and cerebellar membrane preparations of rat brain, < or = 100 microM losigamone did not affect the specific binding of [3H]GABA, [3H]flunitrazepam, or [35S]t-butyl-bicyclophosphorothionate (TBPS) to their receptors. Losigamone, however, in concentrations of 10(-8)-10(-5) M, stimulated 36Cl influx into spinal cord neurons in the absence of exogenous GABA. This effect was inhibited by the GABA antagonists bicuculline (BIC) and picrotoxin (PIC). Losigamone 10(-5) M potentiated the effect of a suboptimal concentration of exogenous GABA 10(-5) M on 36 Cl influx. Both isomers of losigamone likewise stimulated 36Cl influx into spinal cord neurons, and these effects were similarly antagonized by BIC and PIC. Losigamone and its optical isomers AO-294 and AO-242 antagonized potassium-induced hyperexcitability in rat hippocampal slices concentration dependently. There were no clear differences in the potencies of losigamone, AO-242, or AO-294. However, AO-294 and AO-242 differed significantly in their ability to suppress TBPS-induced hyperexcitability of hippocampal slices. Such observations demonstrate that although losigamone does not bind to GABA, benzodiazepine (BZD) or PIC binding sites of the neuronal chloride channel, it is capable of stimulating 36Cl influx in the spinal cord neurons by a GABA-sensitive mechanism and at a side distant from the GABA channel.

Animals↗
PubMed1995

Risk factors and angiographic profile of coronary artery disease in young.

A total of 124 patients of ischaemic heart disease under 40 years of age (96 with myocardial infarction and 28 with angina) were studied for risk factors of coronary artery disease. Electrocardiogram, treadmill test, lipid profile and coronary arteriography were done in all cases. Smoking (56.4%) and hyperlipidaemia (30.6%) emerged as the major risk factors. Further stratification of lipid profile revealed that predictive value of hypercholesterolaemia could be enhanced by considering the different ratios of lipoproteins and indices of atherogenicity. Coronary arteriography revealed a preponderance of single vessel disease (48.4%)-left anterior descending being most commonly involved (71.8%). Increase in low density lipoprotein fraction was related to multivessel involvement.

Adult↗
PubMed1994

An aggregate brain cell culture model for studying neuronal degeneration and regeneration.

Rotation-mediated aggregating cell cultures from fetal rat telencephalons containing glial and neuronal cells mature in a fashion comparable to that known to occur in brain in vivo. Large aggregates of 300-500 microM diameters can now reproducibly be cultivated and maintained for more than 40 days in a well defined serum free medium. Validity of the use of such cultures for in vitro studies of various physiological, pharmacological and toxicological phenomenon has already been demonstrated. In this communication some observations suggesting the usefulness of such cultures for pharmacological studies clarifying the possible effects of drugs and other agents on excitatory amino acid induced pathological processes will be presented. The advantages and limitations of the use of aggregated brain cell culture based models for the development of agents potentially useful for the treatment of aging and dementia will also be discussed.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1994

Evaluation of the greater omentum in the treatment of experimental lymphedema.

Despite advances in microsurgery, the most suitable operation for primary lymphedema remains unclear. A variety of tissue transplants and artificial substances have been used to facilitate drainage of peripheral lymph. The greater omentum, for example, has absorptive lymph draining capability, fights infection, and is expendable for the abdomen. Previous attempts to use the omentum in treatment of clinical lymphedema have, however, been disappointing. This discrepancy between theory and outcome prompted us to reevaluate the role of the omentum in the treatment of chronic lymphedema. In rabbits, mobilization of omentum was carefully examined by three separate techniques and the presence of natural lymph nodal-venous (L-V) shunts determined by an injection of Evans blue into the omentum with sampling later of plasma from the gastroepiploic venous blood. In dogs after promotion of unilateral chronic hindlimb lymphedema by soft tissue excision and sclerosis, the results of four methods of omental transplantation with or without L-V shunt for relief of lymphedema were compared. The results in rabbits suggest that although the greater omentum can be lengthened without jeopardizing its blood supply, it is inappropriate to lengthen it based on blood vascular arcades alone because the omental lymphatics do not strictly follow these arcades in the more distal portion, and with elongation, may be interrupted even though the blood supply remains intact. Moreover, because there is no natural L-V shunt within the greater omentum, the addition of a L-V shunt in dogs in addition to omental transplantation seems to increase effectiveness of the omentum for draining hindlimb lymph after its autotransplantation.

Animals↗
PubMed1994

Autotransplantation of the greater omentum in the treatment of chronic lymphedema.

We evaluated the use of transplantation of the greater omentum in the management of chronic lymphedema in 21 patients. The omentum provides a large surface with fluid absorbing capability and potentially therefore is useful in management of patients with primary or hypoplastic peripheral lymphatics. Based on the angio- and lymphangio-architecture of the gastroepiploic architecture, we used large segments of greater omentum as a free autotransplant with microrevascularization to the femoral or axillary artery and vein thereby avoiding technical drawbacks of a pedicle graft with the feeding vessels traversing the abdomen. Elongation of the omentum must be done properly because omental lymphatic arcades do not consistently follow the blood vascular arcades in its more distal part. Accordingly, if not properly mobilized the blood supply may be retained whereas the lymph circulation is interrupted. We combined omental implantation with lymph nodal-venous anastomoses using an omental vein with a nearby systemic venous tributary. In 19 of the 21 patients followed from 3 months to 2 years after operation, remission of lymphedema was good (reduction in swelling more than 50%) in 14 patients and satisfactory in 5 (approximately 25-50% reduction in swelling) with improvement gradually increasing with the passage of time.

Adolescent↗
PubMed1994

Effect of intravenous streptokinase on left ventricular function following acute myocardial infarction--an echocardiographic study.

160 patients with first attack of acute myocardial infarction (AMI), admitted within 6 hours after onset of chest pain, were divided into two groups--80 receiving intravenous streptokinase (IVSK, Gr. I) an 80 being treated without IVSK (GR. II). They were studied for pre-discharge (12.5 +/- 2.5 days-post admission) echocardiographic LV function. Gr. I pts received 1.5 million units of IVSK within 6 hrs of onset of chest pain, alongwith beta-blockers, aspirin and heparin unless contraindicated. Gr. II received all these except IVSK alongwith conventional therapy. Highly significant (P < 0.001) improvement was noted in the end-diastolic volume (EDV), end-systolic volume (ESV), Ejection fraction (EF) and regional wall motion score (RWMS) in the anterior wall (AW) AMI group when treated early with IVSK. In the inferior wall (IW) AMI group significant decrease was observed in the EDV and ESV (P < 0.001) and RWMS (P < 0.05), but the difference was not statistically significant for EF. Early high-dose short term IVSK infusion is thus associated with highly significant improvement in LV functions--regional as well as global--especially in AW AMI; in IWAMI the improvement is less marked.

Echocardiography↗