The Endogenous Cannabinoid Anandamide Inhibits Cromakalim-Activated K+ Currents in Follicle-Enclosed Xenopus Oocytes

The effect of the endogenous cannabinoid anandamide on K+ currents activated by the ATP-sensitive potassium (KATP) channel opener cromakalim was investigated in follicle-enclosed Xenopus oocytes using the two-electrode voltage-clamp technique. Anandamide (1–90 μM) reversibly inhibited cromakalim-induced K+ currents, with an IC50 value of 8.1 ± 2 μM. Inhibition was noncompetitive and independent of membrane potential. Coapplication of anandamide with the cannabinoid type 1 (CB1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR 141716A) (1 μM), the CB2 receptor antagonist N-[(1S)endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) (1 μM), or pertussis toxin (5 μg/ml) did not alter the inhibitory effect of anandamide, suggesting that known cannabinoid receptors are not involved in anandamide inhibition of K+ currents. Similarly, neither the amidohydrolase inhibitor phenylmethylsulfonyl fluoride (0.2 mM) nor the cyclooxygenase inhibitor indomethacin (5 μM) affected anandamide inhibition of K+ currents, suggesting that the effects of anandamide are not mediated by its metabolic products. In radioligand binding studies, anandamide inhibited the specific binding of the KATP ligand [3H]glibenclamide in the oocyte microsomal fractions, with an IC50 value of 6.3 ± 0.4 μM. Gonadotropin-induced oocyte maturation and the cromakalim-acceleration of progesterone-induced oocyte maturation were significantly inhibited in the presence of 10 μM anandamide. Collectively, these results indicate that cromakalim-activated K+ currents in follicular cells of Xenopus oocytes are modulated by anandamide via a cannabinoid receptor-independent mechanism and that the inhibition of these channels by anandamide alters the responsiveness of oocytes to gonadotropin and progesterone

Re-emergence of genotype G9 during a five-and-a-half-year period in Turkish children with rotavirus diarrhea.

This study was done to understand the dynamics of rotavirus genotype distribution in Turkish children. Samples were collected from January 2006 through August 2011 from children at a hospital in Ankara. Rotavirus was detected in 28 % (241/889) of the samples. Genotype G9P[8] was predominant (28 %), followed by G1P[8] (16.3 %) and G2P[8] (15.9 %). G9 was absent in the samples from 2006 and 2007 and then re-emerged in 2008 and increased gradually. Phylogenetic analysis showed that Turkish G9 rotaviruses of the present study formed a sublineage with strains from Italy and Ethiopia, possibly indicating spread of a clone in these countrie

Re-emergence of genotype G9 during a five-and-a-half-year period in Turkish children with rotavirus diarrhea

This study was done to understand the dynamics of rotavirus genotype distribution in Turkish children. Samples were collected from January 2006 through August 2011 from children at a hospital in Ankara. Rotavirus was detected in 28 \% (241/889) of the samples. Genotype G9P{[}8] was predominant (28 \%), followed by G1P{[}8] (16.3 \%) and G2P{[}8] (15.9 \%). G9 was absent in the samples from 2006 and 2007 and then re-emerged in 2008 and increased gradually. Phylogenetic analysis showed that Turkish G9 rotaviruses of the present study formed a sublineage with strains from Italy and Ethiopia, possibly indicating spread of a clone in these countries

The efficacy and tolerability of glecaprevir/pibrentasvir treatment in a real-world chronic hepatitis C patients cohort

Background and Aim: The aims of the present study were to evaluate the real-life efficacy and tolerability of glecaprevir (GLE)/pibrentasvir (PIB) in the treatment of patients with chronic hepatitis C (CHC). Materials and Methods: Between May 2019 and May 2022, 686 patients with CHC, treated with GLE/PIB combination from 21 participating centers in Turkiye, were enrolled in the study. Results: All patients were Caucasian, and their median age was 56 years. At the start of GLE/PIB treatment, the median serum Hepatitis C virus RNA and serum alanine amino transaminase (ALT) levels were 6.74 log10 IU/mL and 47 U/L, respectively. Fifty-three percent of the patients were infected with genotype 1b, followed by genotype 3 (17%). Diabetes was the more common concomitant disease. The sustained virological response (SVR12) was 91.4% with intent-to-treat analysis and 98.5% with per protocol analysis. The SVR12 rates were statistically significant differences between the patients who were i.v. drug users and non-user (88.0% vs. 98.8%, p=0.025). From the baseline to SVR12, the serum ALT levels and Model for End-Stage Liver Disease score were significantly improved (p<0.001 and p=0.014, respectively). No severe adverse effect was observed. Conclusion: GLE/PIB is an effective and tolerable treatment in patients with CHC

Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study

Familial Mediterranean fever (FMF) is an autosomal recessive disease that is prevalent among eastern Mediterranean populations, mainly non-Ashkenazi Jews, Armenians, Turks, and Arabs. Since a large proportion of all the FMF patients in the world live in Turkey, the Turkish FMF Study Group (FMF-TR) was founded to develop a patient registry database and analyze demographic, clinical, and genetic features. The cohort was composed of 2838 patients (mean age, 23.0 +/- 13.33 yr; range, 2-87 yr), with a male:female ratio of 1.2:1. There was a mean period of 6.9 +/- 7.65 years from disease onset to diagnosis; the period was about 2 years shorter for each decade since 1981. Ninety-four percent of patients were living in the central-western parts of the country; however, their familial origins (70% from the central-eastern and Black Sea regions) reflected not only the ongoing east to west migration, but also the historical roots of FMF in Turkey. Patients' clinical features included peritonitis (93.7%), fever (92.5%), arthritis (47.4%), pleuritis (31.2%), myalgia (39.6%), and erysipelas-like erythema (20.9%). Arthritis, arthralgia, myalgia, and erysipelas-like erythema were significantly more frequent (p < 0.001) among patients with disease onset before the age of 18 years. Genetic analysis of 1090 patients revealed that M694V was the most frequent mutation (51.4%), followed by M680I (14.4%) and V726A (8.6%). Patients with the M694V/M694V genotype were found to have an earlier age of onset and higher frequencies of arthritis and arthralgia compared with the other groups (both p < 0.001). In contrast to other reported studies, there was no correlation between amyloidosis and M694V homozygosity in this cohort. However, amyloidosis was still remarkably frequent in our patients (12.9%), and it was prevalent (27.8%) even among the 18 patients with a disease onset after age 40 years. Twenty-two patients (0.8%) had nonamyloid glomerular diseases. The high prevalence of vasculitides (0.9% for polyarteritis nodosa and 2.7% for Henoch-Schonlein purpura) and high frequency of pericarditis (1.4%) were striking findings in the cohort. Phenotype II cases (those patients with amyloidosis as the presenting or only manifestation of disease) were rare (0.3% or less). There was a high rate of a past diagnosis of acute rheumatic fever, which suggested a possible misdiagnosis in children with FMF presenting with recurrent arthritis. To our knowledge, this is the largest series of patients with FMF reported from 1 country. We describe the features of the disease in the Turkish population and show that amyloidosis is still a substantial problem