Drugs online research references
Acta Otolaryngol Suppl. 1997;528:37-40.
Effect of histamine on intracellular Ca2+ concentration in guinea pig isolated vestibular hair cells.
Tomoda K, Nagata M, Harada N, Iwai H, Yamashita T.
Department of Otolaryngology, Kansai Medical University, Osaka, Japan.
The present study examined the effects of histamine in the guinea pig isolated vestibular hair cells (VHCs) by measuring the dynamic changes of intracellular free calcium ion ([Ca2+]i) concentration using calcium sensitive dye Fura-2. The histamine-induced calcium response in VHCs was markedly increased at the concentration of 10 microM histamine in the presence of extracellular Ca2+, while in the absence of extracellular Ca2+, a slow increase of [Ca2+]i was evident. Receptor specificity of the response to histamine was examined: promethazine (H1 receptor antagonist), cimetidine (H2 receptor antagonist) and thioperamide (H3 receptor antagonist) completely blocked the histamine-induced calcium response at the concentrations of 2.5 microM, 1.0 microM and 1.0 nM, respectively. The responses were mediated by H1, H2 and H3 receptors and resulted in a rise of [Ca2+]i due to an influx of Ca2+ from the extracellular space and a release from intracellular stores. Our preliminary data suggest that under immuno-pathological conditions of the inner ear, histamine released from the mast cells distributed in the endolymphatic sac may act through receptors located on the vestibular hair cell membrane and may regulate the cell function and the signal transduction in the vestibular nerve-hair cell afferent system.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9288234&dopt=Abstract
Am J Forensic Med Pathol. 1997 Sep;18(3):246-50.
Site-to-site variability of drug concentrations in skeletal muscle.
Williams KR, Pounder DJ.
Department of Forensic Medicine, University of Dundee, Scotland.
The homogeneity of drug concentrations in skeletal muscle was assessed in eight fatal overdoses. Ten to 30 random samples were taken from leg muscle weighing 1,650 to 7,985 g. For cases involving paracetamol the mean muscle-to-blood ratio ranged from 0.1 to 1.1 (n = 4) for amitriptyline 1.1 to 3.6 (n = 3), and for dothiepin 0.8 to 2.1 (n = 2). The coefficient of variance was large for all drugs, ranging from 10.5 (carbamazepine) to 50 (thioridazine). Skeletal muscle is not homogeneous with respect to drug concentrations in fatal overdose cases. Of 16 instances of drug detection in blood 2 (nortriptyline and promethazine) were not detected in muscle. Muscle-to-blood drug ratios varied significantly among cases, possibly influenced by survival time after drug ingestion. Quantitative interpretations of muscle drug levels present significant difficulties. However, skeletal muscle can be used for qualitative corroboration of blood analyses and is a suitable specimen for drug detection where none other is available.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9290870&dopt=Abstract
Gen Physiol Biophys. 1997 Mar;16(1):3-14.
Effect of phenothiazines on activated macrophage-induced luminol-dependent chemiluminescence.
Traykov T, Hadjimitova V, Goliysky P, Ribarov S.
Department of Biophysics, Sofia University School of Medicine, Bulgaria.
The inhibitory effect of some phenothiazine neuroleptics (chlorpromazine, levomepromazine, thioridazine, promethazine and trifluoperazine) on the ability of rat peritoneal macrophages to produce O2- during phagocytosis was investigated. The superoxide radical release was estimated by measuring the luminol-dependent chemiluminescence (CL). The effect of drugs was studied in the concentration range of 0.1-100 mumol/l. Additional experiments to determine the ability of the drugs to scavenge O2- were carried out. They included measuring the effect of phenothiazines on the luminol-dependent CL in systems with enzymatically (xanthine-xanthine oxidase) and non-enzymatically (KO2) generated O2-. The ability of phenothiazines to scavenge O2- was additionally tested by a "non-luminescence" method in which the superoxide concentration was determined spectrophotometrically by the reduction of nitro blue tetrazolium to formazan. All drugs tested decreased significantly CL of stimulated macrophages at concentrations greater than 1 mumol/l. The C50 values were between 0.45 and 1.74 mumol/l. Also phenothiazines were found to act as scavengers of O2-. However, this effect occurred at significantly higher drug concentrations. The C50 values for 50% scavenging of O2- in systems with different sources of O2- were in the concentration range of 5-160 mumol/l. These results suggested that phenothiazines predominantly affected the ability of macrophages to produce O2- during phagocytosis. The findings may provide some insight into the untoward effects of the drugs tested.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9290939&dopt=Abstract
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