PubMed Health⌕ Search

Biomedical subjects

S Kindler

Publications and source records attributed to S Kindler.

18 recordsLinked to original sources
PubMed1992

Hormone responses to fenfluramine and placebo challenge in endogenous depression.

Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.

Adult↗
PubMed1992

Enhanced serotonergic responsivity following electroconvulsive therapy in patients with major depression.

Prolactin release in response to fenfluramine hydrochloride (60 mg orally) and placebo was evaluated in 18 medication-free patients with RDC major depressive disorder, endogenous subtype, before and after a series of bilateral treatments with ECT. Before ECT, fenfluramine induced a twofold increase in plasma prolactin levels. This response was significantly enhanced after the ECT series, while baseline prolactin levels and response to the placebo challenge were not altered. There was no significant difference in plasma fenfluramine and norfenfluramine levels during the pre- and post-ECT challenges. These findings suggest that ECT enhances central serotonergic responsivity and extend to depressed patients pre-clinical observations regarding the effect of electroconvulsive shock on serotonergic function.

Depressive Disorder↗
PubMed1992

Effect of hypophysectomy on rat preadipocyte replication and differentiation.

The effects of hypophysectomy, which results in decreased fat pad weight, fat cell number, and new fat cell formation, on preadipocyte replication were examined. Perirenal and epididymal preadipocytes were cultured from hypophysectomized, sham-operated and unoperated 3-month-old rats. In cloned preadipocytes, hypophysectomy resulted in a 19% decrease in cloning efficiency and a 60% reduction in cell number after 3 weeks in culture. Perirenal cells underwent more extensive replication than epididymal cells. The mechanism of reduced replication following hypophysectomy differed from that of donor site: hypophysectomy resulted in an increased percentage of cells which underwent 2 or fewer population doublings at the expense of cells capable of more than 2 doublings. However, donor site had little effect specifically on these slowly replicating preadipocytes; rather, perirenal preadipocytes underwent more extensive replication than epididymal cells because of the higher percentage of preadipocytes capable of 13 or more doublings in perirenal fat pads. Hypophysectomy did not result in decreased differentiation of preadipocytes. These observations are in accord with the hypothesis that hypophysectomy reduces fat cell number in maturing rats partly through an effect on preadipocyte replicative capacity. Additionally, it seems that more than one form of preadipocyte exists, the various forms having differing susceptibilities to factors such as pituitary function and anatomic site.

Adipose Tissue↗
PubMed1992

Current concepts in the pharmacological treatment of obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic and often disabling disease. OCD is characterised by intrusive, unwanted and persistently recurring mental events (obsessions) that usually evoke discomfort or anxiety, and/or repetitive ritualistic behaviours (compulsions) that are aimed at reducing discomfort and anxiety. However, the compulsions succeed only in achieving transient relief, followed by a growing sense of pressure. 10 years ago, OCD was considered a rare and treatment-refractory disorder. Recent well designed studies document a lifetime prevalence rate for OCD of more than 2% in the general population. The outlook for patients with OCD has changed in the last decade, with many well controlled studies showing that OCD patients respond to specific behavioural and pharmacological treatments. The specific form of behavioural therapy is in vivo exposure coupled with response prevention. Only serotonin reuptake inhibitors, such as clomipramine, fluoxetine and fluvoxamine, are effective in the treatment of both depressed and not depressed OCD patients. Fluoxetine and fluvoxamine lack the anticholinergic side effects of clomipramine and, thus, provide an alternative treatment for patients who cannot tolerate clomipramine. Other nonserotonergic antidepressants (tricyclics and monoamine oxidase inhibitors) and anxiolytic agents have not been found to be consistently effective in this disorder. Insufficient data on the efficacy of neuroleptics and their potentially irreversible side effects limit their use in OCD patients. Behavioural and the pharmacological treatment are complementary, and a combination of the 2 therapies is apparently more effective than either modality alone.

Clomipramine↗
PubMed1991

Reminiscing as a technique in the group psychotherapy of depression: a comparative study.

Reminiscing as a technique of group psychotherapy for severely depressed hospitalized patients was found by patients and staff to be more efficacious than the traditional reflective non-directive group psychotherapy approach. The therapeutic potential of reminiscing in combatting depressed mood was supported by the present findings. The suitability of reminiscing to the difficult task of handling groups of severely depressed hospitalized patients was demonstrated.

Depressive Disorder↗
PubMed1990

Molecular structure of microtubule-associated protein 2b and 2c from rat brain.

Full length cDNA clones encoding microtubule-associated proteins (MAP) 2b and 2c from rat brain have been isolated and sequenced. The cDNA fragments spanning the coding regions for both MAP2b and MAP2c were assembled and expressed in Escherichia coli. The mobility of these bacterial expressed proteins in sodium dodecyl sulfate gels is identical to that of MAP2b and MAP2c from rat brain. The protein sequence of rat MAP2b has been compared to the full length sequence from mouse and the partial sequence from human high molecular weight MAP2. This comparison has revealed that MAP2b is composed of several highly conserved domains flanked by domains with extensive sequence divergence. Two of the conserved domains, found either at the NH2 or COOH terminus, overlap with the binding domain for the regulatory subunit of the cAMP-dependent protein kinase II and the microtubule-binding domain, respectively. A third homologous domain of unknown function lies in a central region of MAP2b. Secondary structure prediction suggests that the portion of MAP2b which extends from the microtubule surface is composed of an extensive number of alpha-helices separated by small turns which may account for the extended yet flexible structure of MAP2. Interestingly, the 4000-base pair deletion from the middle of MAP2b which generates MAP2c not only removes these helices, but also this third highly conserved MAP2b domain.

Amino Acid Sequence↗
PubMed1988

Lithium modulation of second messenger signal amplification in man: inhibition of phosphatidylinositol-specific phospholipase C and adenylate cyclase activity.

The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

Adenylyl Cyclase Inhibitors↗
PubMed1988

Cyclic AMP second-messenger signal amplification in depression.

Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Adult↗
PubMed1987

Conditioned avoidance acquisition and extinction following repeated electroconvulsive shock: strain effect and response to vasopressin.

Male albino rats (Sabra strain) were exposed to electroconvulsive shock (ECS) once daily for periods ranging from 1 to 13 days, and proactive effects on conditioned avoidance response (CAR) acquisition and extinction were studied. CAR acquisition was intact following both single and repeated ECS, but extinction was accelerated by multiple ECS administration. These findings resembled the effect of repeated ECS on anterograde memory function in humans and confirmed previous observations based on a passive avoidance paradigm. However, extinction was not accelerated in a different rat strain (LC2). Parallel open field activity measures suggested that these findings were not related to ECS-induced alterations in locomotor activity. Administration of arginine vasopressin prior to each ECS, or following acquisition sessions, as well as 1-desamino-8-D-arginine vasopressin administration following acquisition sessions, did not ameliorate ECS-induced deficits in the Sabra rats. Differences between the present paradigm of ECS administration and those in which positive effects of vasopressin and other neuropeptides have been reported are discussed. The potential research applications of a rodent model of ECS-induced memory impairment that parallels deficits encountered in the clinical context are considered.

Animals↗
PubMed1986

Excessive proliferation in culture of reverted adipocytes from massively obese persons.

Differentiated omental adipocytes from lean and massively obese persons lost their spherical shape in culture and regained the ability to replicate. In propagating culture, reverted cells from each group multiplied to a greater extent than corresponding stromal adipocyte precursors. Reverted adipocytes from the massively obese proliferated at significantly higher rates than those from lean subjects. Reverted cells derived from 1-2 adipocytes also revealed these differences.

Adipose Tissue↗
PubMed1986

The formation of 5 alpha-reduced androgens in stromal cells from human breast adipose tissue.

The present study was designed to determine if stromal cells derived from human breast adipose tissue contain 5 alpha-reductase activity, and to study the effect of 5 alpha-reduced androgens on aromatase activity under basal and cortisol stimulated conditions. Stromal cells were prepared from breast adipose tissue obtained at the time of surgery from four patients. The cells were isolated after collagenase digestion and were cultured in alpha-minimum essential medium with 15% fetal calf serum. Studies were carried out between days 4 and 11 of the third subculture in the presence or absence of cortisol (10(-6) M). Metabolism of androstenedione (A) was studied over a period of 8 h after addition of medium containing 20 X 10(6) dpm (100 pM) [3H]A. The cells metabolized A to estrone (E1), testosterone (T), 5 alpha-androstane 3, 17-dione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone. On day 7 of culture, product formation expressed as percent conversion of A per 1 X 10(6) cells ranged as follows: E1, 0.02-0.13; T, 0.12-0.36; 5 alpha-A-dione, 2.05-9.91; and a fraction containing AND and dihydrotestosterone, 0.38-0.59. In the presence of cortisol the rate of cell growth was decreased by 25% to 50%. The formation of E1 increased 150- to 1500-fold and AND formation increased 2- to 8-fold. There was no consistent change in the formation of 5 alpha-A-dione and T. The addition of 5 alpha-A-dione (10(-6) M) to the culture medium at the time of assay resulted in greater than 90% inhibition of E1 formation under both basal and cortisol stimulated conditions. The studies indicate that adipose tissue is an important site for the formation of 5 alpha-reduced androgens.

Adipose Tissue↗
PubMedDate not supplied

Effect of imipramine treatment on the prolactin response to fenfluramine and placebo challenge in depressed patients.

As an index of central serotonergic function, plasma prolactin response to fenfluramine (60 mg orally) and placebo challenge was examined in 10 depressed patients before and after treatment with imipramine 200 mg/day for 3 weeks. Although baseline prolactin levels were not altered by imipramine, the prolactin response to fenfluramine was significantly (P = 0.01) increased compared to the response in the untreated state. The response to placebo was also enhanced but this effect was of lesser magnitude and not statistically significant. These findings complement previous reports and suggest that tricyclic antidepressant treatment enhances serotonergically mediated neuroendocrine responses.

Adult↗