A linear relationship between lamotrigine and GABA in cerebrospinal fluid [Beyin omurilik sıvısında lamotrijin ve GABA arasında lineer ilişki]

The γ-amino butyric acid (GABA)-mediated neurotransmission is useful in treating conditions like anxiety, sleep disturbances, depression and bipolar disorders. The aim of the present study is to supply evidence about neurochemical effects of acute lamotrigine treatment on GABA and L-glutamic acid levels in the cerebrospinal fluid of Wistar Albino rats and the involvement of cholinergic system. The day after the placement of concentric microdialysis probes into the lateral ventricles of rats, microdialysis experiments were performed in conscious rat model. The rats either received intraperitoneal injections of physiological saline or 20 mg/kg lamotrigine. For assessing the cholinergic involvement 0.5 mg/kg physostigmine or 2 mg/kg atropine sulfate pre-treatments were given prior to lamotrigine injection. GABA, L-glutamic acid and lamotrigine concentrations in the dialysates were analyzed using High Performance Liquid Chromatography. Saline produced no change in GABA or L-glutamic acid levels, but lamotrigine treatment significantly elevated GABA concentrations (p<0.05). Pre-treatment with physostigmine or atropine sulfate did not affect either GABA or L-glutamic acid levels siginificantly. Physostigmine or atropine sulfate pre-treatments did not affect the lamotrigine-induced GABA levels. The results may imply that lamotrigine-induced GABA plays a role in the pharmacological effects of lamotrigine where a linear relationship exists between lamotrigine and GABA. However, central cholinergic system fails to affect lamotrigine-induced GABA release

Herbal product use patterns and possible herb-drug interactions among older adults in Turkey

Background: Traditional and Complementary medicine use is on the increase universally. In this descriptive study, the aim is to evaluate the frequency and determinants of herbal product use, as well as determine possible drug-herb interactions among older individuals who live in rural and urban areas. Methods: The study was carried out with individuals 65 years or older in one urban and five rural neighborhoods in Bursa, Turkey. The data was collected during face-to-face interviews using a questionnaire comprising 43 questions. The participants were asked about the drugs and herb/herbal products they use and then the possible drug-herb interactions were evaluated using Micromedex (R). Results: Among the participants, 82.2 % reported using at least one drug regularly, and 18.3 % used at least one herb/herbal product in the past year (rural 26.1 %, urban 13.4 %). Most commonly used herb/herbal products were plane tree leaves and black cumin. Herbal product use was seen more among those experiencing difficulties accessing health care and living alone. Among those using drug and herb/herbal products concurrently, the possible drug-herb interaction rate was 7.5 %. Conclusions: Physicians providing health care services to geriatric populations should inquire about usage of drugs and herbs. Conventional medicine should be made accessible to every older adult, and it should be ensured that they do not have to resort to complementary therapies that could harm their health

Distinct functional muscarinic receptors in guinea-pig gallbladder, ileum and atria

Objective. The contractile responses of guinea-pig gallbladder smooth muscle cells have been suggested to be mediated by M-3 and M-4 muscarinic receptors by different research groups. Therefore, in the present study, several pharmacological properties of cholinergic functions in guinea-pig gallbladder, guinea-pig ileum (mediated via M-3 receptors), and guinea-pig and rat atria (mediated via Mt receptors) were compared, Methods: The isometric contractions of isolated guinea-pig ileum, guinea-pig gallbladder, guinea-pig and rat atrial strips in in vitro organ bath were recorded on a polygraph and the effects of carbachol, oxotremorine, McN-A-343, and clozapine have been investigated. Results: Three muscarinic receptor agonists, carbachol, oxotremorine and McN-A-343 showed different order of potencies in their negative inotropic effects and contractile actions in guinea-pig gallbladder suggesting that functional muscarinic receptors in the gallbladder are distinct from those in the atria, and similar to M-4-subtypes. Clozapine which was shown to have antagonistic affinity for muscarinic M-1, M-2, M-3 and M-5, but partial agonistic affinity for muscarinic M-4 receptors, contracted gallbladder concentration-dependently. On the other hand, clozapine antagonised carbachol-induced ileal and gallbladder contractions and negative inotropic effects indicating that it acts like a partial agonist in the gallbladder. Conclusion: It was concluded that the contractile muscarinic receptors of guinea-pig gallbladder are distinct from those of atria (M-2) and ileum (M-3), but seem to be of M-4 subtype. (C) 1999 Academic Press

Cyp3a4 *1b gene polymorphism in coronary artery disease patients with obesity undergoing statin treatment

Objective: Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality worldwide and statins are frequently prescribed in the treatment of CAD to help lower blood cholesterol levels. Since the main enzyme involved in the metabolism of statins is CYP3A4, we aimed to investigate the effect of CYP3A4 * 1B genotypes on plasma lipid profile in Turkish cardiovascular disease subjects with and without obesity taking statin. Materials and Methods: The study group consisted of 85 cardiovascular disease patients who were prescribed statins and had routine biochemical analysis data. Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) assay was performed for genotyping of CYP3A4 *1B (rs2740574) polymorphism. Results: Genotype distribution of CYP3A4 *1B polymorphism was found for homozygous wild (AA) and homozygous polymorphic (GG) genotypes as 94.1% and 5.9%, respectively. We did not detect patients with heterozygous genotype in our study group. We found that the mean LDL-c, TG and TC levels were higher in patients with CYP3A4 *1B GG compared to the AA genotype. The frequency of CYP3A4 *1B GG genotype frequency (9.5%) was detected higher in the obese patients compared to the non-obese patients (7.7%) (χ2=0.037, p=0.85). Conclusion: Our results demonstrate that CYP3A4 *1B homozygous polymorphic genotype distribution tends to be higher in obese patients compared to non-obese patients with cardiovascular disease which may point to *1B allele having a slight effect on serum lipids during statin therapy. Ad-ditional studies with higher samples are needed for evaluating the role of CYP3A4 *1B on lipids in patients under statin therapy. © 2021 Bentham Science Publishers

Impact of a short postgraduate course in rational pharmacotherapy for general practitioners

Aims The impact of a short postgraduate course on rational pharmacotherapy planning behaviour of general practitioners (GP) was investigated via a face-to-face interview with 25 GPs working at health centres in Istanbul. Methods GPs were randomly allocated to control and intervention groups. Intervention group attended a 3-day-training program preceded and followed by a written exam to plan treatment for simulated cases with a selected indication. The participants' therapeutic competence was also tested at the post-test for an unexposed indication to show the transfer effect of the course. In addition, patients treated by these GP's were interviewed and the prescriptions were analysed regarding rational use of drugs (RUD) principles at the baseline, 2 weeks and 4 months after the course. Results At the baseline there was not any significant difference between the control and intervention groups in terms of irrational prescribing habits. The questionnaires revealed that the GPs were not applying RUD rules in making their treatment plans and they were not educating their patients efficiently. Training produced a significant improvement in prescribing habits of the intervention group, which was preserved for 4 months after the course. However, very low scores of the pretest indicate the urgent necessity for solutions. Conclusions Training medical doctors on RUD not only at the under- but also at the postgraduate level deserves attention and should be considered by all sides of the problem including academia, health authorities and medical associations

Muscarinic M-2 receptors are not primarily involved in the contraction of guinea-pig gallbladder smooth muscle

The presence of M-1-M-4 receptors in guinea-pig gallbladder smooth muscle cells has been reported recently. The majority of these receptors are said to be of M-2 subtype. However, there are controversial reports about the functional muscarinic receptors that mediate contraction in this tissue. Similar to gallbladder, it was claimed that M-4 receptors mediate guinea-pig uterine contractions, but these receptors have appeared to be of M-2 subtypes later. Therefore, the antagonistic affinities of three M-2-selective muscarinic antagonists were determined in contraction and radioligand binding experiments in guinea-pig gallbladder in the present study. The antagonistic affinity Values (pK(i)) of gallamine, tripitramine and imperialine were as follows, respectively: 6.28+/-0.15, 8.65+/-0.10 and 6.55+/-0.07 against 0.250 nM [H-3]QNB binding. All three antagonists displaced the concentration-response curves to carbachol to the right in parallel without affecting the maximum responses. The pA(2) values obtained from constrained Schild plots (-log K-B) were 4.14+/-0.18 for gallamine, 6.79+/-0.09 for tripitramine, and 7.02+/-0.09 for imperialine. The antagonistic affinity values of gallamine, tripitramine and imperialine for M-2 receptors are reported to be 6.3, 9.6, 7.7, respectively. The pA(2) values obtained in this study clearly indicate that the primary muscarinic receptors involved in carbachol-induced guinea-pig gallbladder contraction are not of M-2 subtype. The poor correlation between the antagonistic affinity values of these antagonists obtained at radioligand binding (pK(i)) and contraction (pA(2)) experiments also support the conclusion that the majority of muscarinic receptors which have been reported to be of M-2 do not mediate the contractile responses. (C) 1999 Academic Press

Association of PD-1 and PDL-1 gene polymorphisms with colorectal cancer risk and prognosis

Background Programmed Cell Death-1 (PD-1) together with Programmed Death Ligand 1 (PDL-1) have crucial roles in anti-tumor immune response, cancer susceptibility and prognosis. Since PD-1 and PDL-1 have been considered as important genetic risk factors in cancer development and their functions can be affected by polymorphic sites, we investigated the effects of PD-1 rs2227981, rs2227982, rs36084323 and PDL-1 rs2282055, rs822336 gene polymorphisms on colorectal cancer (CRC) risk and prognosis in Turkish subjects. Methods and results Our study group consisted of 5-FU or Capacitabine prescribed CRC diagnosed patients and healthy controls. Genotype analyses of PD1 and PDL-1 polymorphisms were performed with Agena MassARRAY platform. rs36084323 CT genotype frequency was found to be higher in controls compared to cases (p C polymorphism might be useful in predicting CRC prognosis. PDL-1 rs2282055 T > G polymorphism might be useful in predicting both CRC risk and prognosis. Further studies should be conducted in larger and different populations to clear the roles of PD-1 and PDL-1 polymorphisms in CRC risk and prognosis

The effects of CYP2C9 and VKORC1 gene polymorphisms on warfarin maintenance dose in Turkish cardiac patients

Aim: Our aim was to examine the effect of CYP2C9 and VKORC1 polymorphisms on warfarin dose requirements in Turkish patients. Materials & methods: 24 warfarin prescribed patients were included and analyzed for eight VKORC1 and 6 CYP2C9 polymorphisms in the study. Results: Patients with CYP2C9 *1/*1 and VKORC1 -1639 GG and GA genotypes required higher warfarin doses in comparison to wild type VKORC1 genotype. Patients with CYP2C9 *1/*3 and VKORC1 -1639 GG genotypes simultaneously, required the lowest dose of warfarin (4.64 mg/day). Patients with CYP2C9 *1/*1 and VKORC1 9041 AA genotype were found to require higher warfarin doses. Conclusion: Our results provide additional evidence to support the hypothesis that CYP2C9 *2, *3, VKORC1 9041 G > A polymorphisms explain considerable proportion of inter-individual variability in warfarin dose requirement