Characterization of relaxant mechanism of H2S in mouse corpus cavernosum

The aim of this study was to investigate the mechanism of H₂S‐induced relaxation in mouse corpus cavernosal tissue. l ‐cysteine (10^?6 × 10^?3 mol/L) and exogenous H₂S (NaHS; 10^?6 to 10^?3 mol/L) induced concentration‐dependent relaxation. l ‐cysteine‐induced relaxations was reduced by d,l ‐propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l ‐cysteine induced relaxations, but not of those of H₂S diminished in endothelium‐denuded tissues. N^ω‐nitro‐l ‐arginine (l ‐NA; 10^?4 mol/L), a nitric oxide synthase inhibitor, and ODQ (10^?4 mol/L), a guanylyl cyclase inhibitor, increased the H₂S‐induced relaxation. Zaprinast (5 × 10^?6 mol/L) and sildenafil (10^?6 mol/L), phosphodiesterase inhibitors, inhibited H₂S‐induced relaxation. Adenylyl cyclase inhibitors N‐ethylmaleimide (2.5 × 10^?5 mol/L) and SQ22536 (10^?4 mol/L) reduced relaxation to H₂S. Also, H₂S‐induced relaxation was reduced by KCl (50 mmol/L), 4‐aminopyridine (10^?3 mol/L), a K_v inhibitor, glibenclamide (10^?5 mol/L), a K_ATP inhibitor or barium chloride (10^?5 mol/L), a K_IR inhibitor. However, H₂S‐induced relaxation was not influenced by apamin (10^?6 mol/L), a SK_Ca²⁺ inhibitor, charybdotoxin (10^?7 mol/L), an IK_Ca²⁺ and BK_Ca²⁺ inhibitor or combination of apamin and charybdotoxin. Nifedipine (10^?6 mol/L), an L‐type calcium channel blocker and atropine (10^?6 mol/L), a muscarinic receptor blocker, inhibited H₂S‐induced relaxation. However, H₂S‐induced relaxation was not influenced by ouabain (10^?4 mol/L), a Na⁺/K⁺‐ATPase inhibitor. This study suggests that H₂S endogenously synthesizes from l ‐cysteine by CSE endothelium‐dependent in mouse corpus cavernosum tissue, and exogenous H₂S may cause endothelium‐independent relaxations via activation of K channels (K_ATP channel, K_V channels, K_IR channels), L‐type voltage‐gated Ca²⁺ channels, adenylyl cyclase/cAMP pathway and muscarinic receptor, and there is the interaction between H₂S and NO/cGMP.     

Urinary methylmalonic acid levels in patients with acute ischemic stroke

ObjectivesVitamin B-12 and folate deficiency are common, especially in people aged 55 or over, and accompanied by elevated methylmalonic acid (MMA) and homocysteine concentrations. The aims of the study were to investigate the relationship between serum vitamin B-12, homocysteine, folate, erythrocyte folate and urinary MMA in patients with ischemic stroke, and to develop a simple screening HPLC method for the measurement of urinary MMA.Design and methodsTwenty-eight patients aged 55 years and over with ischemic stroke and 23 age- and sex- matched healthy controls were included in the study. Serum vitamin B-12 and folate were measured by immunoassay; serum total homocysteine and urinary MMA concentrations by HPLC.ResultsThere was no significant difference in vitamin B-12, folate and homocysteine concentrations between the patient and control groups. Urinary MMA concentrations and erythrocyte folate levels were significantly higher in patients than controls. There was a significantly negative correlation between vitamin B-12 and MMA.ConclusionsIncreased urinary MMA excretion is associated with ischemic stroke and it may more robustly reflect vitamin B-12 deficiency in patients with ischemic stroke. The method used in this study is eligible for routine urinary MMA measurements.     

Epidemiology and cost implications of candidemia,a 6‐year analysis from a developing country

Surveillance of candidemia is essential to monitor trends in species distribution and change in the incidence and antifungal resistance. In this study, we aimed to investigate prevalence, resistance rates, antifungal utilization and costs. A 6‐year retrospective analysis of the data belonging to patients with candidemia hospitalized between 2010 and 2016 was performed. The annual usage of fluconazole and caspofungin and the usage of these antifungals in different units were described in defined daily doses (DDD) per 1000 patient days. In total, 351 patients of candidemia were included. Median age of the patients was 45 (0‐88) and 55.1% of them were male. Overall, 48.1% of the candidemia episodes (169/351) were due to C. albicans, followed by C. parapsilosis (25.1%), C. glabrata (11.7%). Length of hospital stay was longer with a median of 20 days among patients with non‐albicans candidemia. Presence of a central venous catheter was found to be an associated risk for candidemia caused by non‐albicans strains. Annual incidence of candidemia increased from 0.10 to 0.30 cases/1000 patient days. Antifungal use was increased over years correlated with the cost paid for it. The policy against candidemia should be specified by each institution with respect to candidemia prevalence, resistance rates, antifungal use and costs.     

The effect of varenicline on heart rate variability in healthy smokers and nonsmokers

Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist. In this study, we assessed the effects of varenicline on heart rate variability (HRV). Thirty subjects were included in the randomized, double-blind, placebo-controlled, crossover study. Varenicline or placebo was administered in two different testing sessions. Time domain parameters and power spectral analysis of HRV were assessed in the supine position and during handgrip exercise before and after the participants were given placebo or varenicline. Fifteen healthy non-smokers (NS) and fifteen healthy smokers (S) were included in the study. There were no statistically significant differences among any of the time domain parameters obtained before and after placebo administration or between the S and NS groups with respect to varenicline administration. In frequency domain analyses, normalized HF (high-frequency) powers were significantly higher in the S group than in the NS group (before placebo, NS:6.57±3.58 vs. S:13.85±7.50, p=0.002, after placebo, NS:6.33±3.89 vs. S:10.82±4.88, p=0.007). After varenicline administration, the normalized HF power was significantly higher (NS:6.65±4.34 vs. S:11.06±4.52, p=0.01), and the ratio of LF (low-frequency) to HF was significantly lower (NS:8.44±5.89 vs. S:4.97±4.60, p=0.02) in the S group than in the NS group. Administration of a single dose of varenicline significantly increased the LF/HF ratio (5.83±2.69 vs. 8.44±5.89) in the NS group, but in the S group, there were no significant differences related to any of the time or frequency domain parameters. We concluded that a single dose of varenicline does not affect HRV in healthy smokers but that it may alter HRV when administered at a therapeutic dose to healthy non-smokers during mild sympathetic stimulation.     

Evoked myotonia can be “dialed‐up” by increasing stimulus train length in myotonic dystrophy type 1

It is unknown how evoked myotonia varies with stimulus frequency or train length, or how it compares to voluntary myotonia in myotonic dystrophy type 1 (DM1). First dorsal interosseous (FDI) tetanic contractions evoked by trains of 10–20 ulnar nerve stimuli at 10–50 HZ were recorded in 10 DM1 patients and 10 normals. For comparison, maximum voluntary handgrip contractions were also recorded. An automated computer program placed cursors along the declining (relaxation) phase of the force recordings at 90% and 5% of peak force (PF) and calculated relaxation times (RTs) between these points. For all stimulus frequencies and train lengths, evoked RTs were much shorter, and evoked PFs were much greater in normals than in DM1. In normals, evoked RT was independent of stimulus frequency and train length, while in DM1 RT was longer for train lengths of 20 stimuli (mean: 9 s in DM1; 0.20 in normals) than for 10 stimuli (mean: 3 s in DM1, 0.19 in normals), but it did not change with stimulus frequency. In both groups PF increased greatly as stimulus frequency rose from 10–50 HZ but only slightly as train length rose from 10–20 stimuli. Voluntary handgrip RT (mean: 1.9 s) was less than evoked FDI RT (mean: 9 s). In DM1, evoked RT can be “dialed up” by increasing stimulus train length. Evoked myotonia testing utilizing a stimulus paradigm of at least 20 stimuli at 30–50 HZ may be useful in antimyotonic drug trials, particularly when grip RT is normal or equivocal. Muscle Nerve, 2010