ABSTRACT
We have earlier demonstrated that NMDA receptor antagonists possess antidepressant effect and also they show a synergism with imipramine. The present study attempts to investigate whether NMDA receptor antagonists also interact with selective serotonin reuptake inhibitors. The study was conducted in albino mice using shock-induced depression model. The mice were placed on a grid floor and shock delivered were of 2 sec duration with a 9 sec interval for 1 h. Twenty four hours later depression was measured by an open field test followed by a forced swimming test. Presentation of inescapable foot shock significantly reduced ambulation (from 159.50 +/- 5.42 to 80.50 +/- 4.61) and rearing (from 22.10 +/- 2.15 to 11.30 +/- 1.32) in the open field arena and increased immobility duration in the forced swimming test (from 82.20 +/- 3.51 to 158.90 +/- 4.61). Pretreatment with fluvoxamine, MK-801, ketamine and the combination of fluvoxamine with either of the NMDA antagonists antagonised shock-induced depression. Haloperidol and ketanserin pretreatment modified the effect of these agents. These findings suggest an interaction of NMDA receptor antagonists with fluvoxamine, and an involvement of brain dopaminergic and tryptaminergic mechanisms in the behavioural suppression observed after inescapable foot shock.
Subject(s)
Animals , Depression/drug therapy , Dizocilpine Maleate/therapeutic use , Drug Synergism , Electroshock , Excitatory Amino Acid Antagonists/therapeutic use , Female , Fluvoxamine/therapeutic use , Ketamine/therapeutic use , Male , Mice , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Selective Serotonin Reuptake Inhibitors/therapeutic useABSTRACT
In the past few years, literature has accumulated describing manifestation of seizures following administration of certain antidepressants. Such reports are of particular importance because depression is a frequent psychiatric problem associated with epilepsy. Therefore, in the view of the fact that NMDA receptor antagonists have been reported to reduce behavioural deficits and have been shown to be anticonvulsant, it was considered imperative to study their antidepressant effect using shock-induced depression model in mice. Presentation of inescapable foot shock significantly reduced ambulation and rearing in the open field arena and increased immobility duration in the FST. Pretreatment with imipramine, MK 801 and ketamine significantly prevented the effect of shock. Also, the combination of imipramine with either of the NMDA antagonists antagonised the effect of shock. Haloperidol, prazosin and ketanserin pretreatment modified the effect of these agents. These findings suggest an antidepressant effect of the NMDA receptor antagonists, and a complexity of neurotransmitter mechanisms, which are responsible for the occurrence of behavioural effects in shock-induced depression model.
Subject(s)
Animals , Antidepressive Agents, Tricyclic/pharmacology , Depression/drug therapy , Disease Models, Animal , Electroshock , Female , Imipramine/pharmacology , Male , Mice , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitorsABSTRACT
Research into phospholipid signaling continues to flourish, as more and more bioactive lipids and proteins are being identified and their actions characterised. The Pleckstrin homology (PH) domain is one such newly recognized protein module thought to play an important role in intracellular signal transduction. The tertiary structures of several PH domains have been determined, some of them complexed with ligands and on the basis of structural similarities between PH domains and lipid binding proteins it has been suggested that PH domains may be binding to lipophilic molecules. In fact many of the proteins that contain this domain can interfere with the membrane association. This review examines the specificity of this binding and illustrates the importance of charge-charge interactions in PIP2-PH domain complex formation. The precise physiological functions of PH domain in vivo remains to be explored therefore this review examines the biochemical aspects of the interaction of PH domains with phospholipid breakdown mediated products and proto-oncogenic serine-threonine kinase (Akt), protein tyrosine kinases, which have been found to be a target of phospholipid second messengers. Thus, number of cellular processes mediated by this way, ranging from insulin signaling and protein synthesis to differentiation and cell survival are regulated by this intracellular signaling protein module.
Subject(s)
Blood Proteins/metabolism , Phospholipases/metabolism , Phospholipids/metabolism , Phosphoproteins , Signal Transduction , src Homology DomainsABSTRACT
The present study has been conducted to assess social and behavioural factors predisposing individuals suffering from sexually transmitted diseases to seek treatment and the role of the health provider in them. Out results showed that the demographic, socio-economic and behavioural characteristics of patients seeking treatment at alternative places and those attending the referral hospital in the first instance were comparable. Inhibition, time and distance were important considerations for selecting a health facility. Private clinics were the most preferred (72.4%) source of treatment. In 60.3% of cases written prescriptions were not given and advice regarding treatment of sexual partner was not there in any of the cases. 98.3% of the patients lacked awareness about their disease and 91.4% patients about the treatment they were receiving.
Subject(s)
Adolescent , Adult , Female , Health Knowledge, Attitudes, Practice , Health Services Accessibility , Humans , India , Male , Middle Aged , Patient Acceptance of Health Care/psychology , Prospective Studies , Surveys and Questionnaires , Sexually Transmitted Diseases/psychology , Social ClassSubject(s)
Adult , Aged , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Antihypertensive Agents/adverse effects , Blood Pressure/drug effects , Cough/chemically induced , Drug Tolerance , Enalapril/adverse effects , Female , Follow-Up Studies , Headache/chemically induced , Humans , Hypertension/drug therapy , Male , Middle Aged , Sex FactorsABSTRACT
Ampicillin elimination was studied in geriatric and younger subjects, 10 in each group. The geriatric subjects had higher serum concentration and elimination half-life of the drug. The plasma clearance and urinary excretion of the drug were significantly reduced in them when compared to younger subjects. Urinary excretion of the drug had significant correlation with creatinine clearance of the subjects.
Subject(s)
Adult , Aged , Aging/blood , Ampicillin/pharmacokinetics , Developing Countries , Humans , India , Middle Aged , Reference ValuesABSTRACT
The endogenous creatinine clearance test was done in 14 Type I and 15 Type II poorly controlled diabetic patients and compared with respective age matched healthy volunteers. Type I diabetics had significantly lower creatinine clearance rate, body mass index and serum albumin levels when compared to their control group. In Type II diabetics these values remained unaltered. Both Type I and Type II diabetics had significantly higher blood sugar and glycosylated haemoglobin levels. The creatinine clearance rate had significant positive correlation with patients' body mass index and serum albumin levels. This suggests that the undernutrition of Type I diabetics may be responsible for the decreased creatinine clearance.