Do penile haemodynamics change in the presence of hydrogen sulphide (H2 S) donor in metabolic syndrome-induced erectile dysfunction?

Erectile dysfunction (ED) is defined in relation to the metabolic syndrome (metS). Hydrogen sulphide (H2 S), a gasotransmitter, has been revealed to get involved in hypertension, insulin secretion and regulation of vascular tone especially in erectile physiology. This study aimed to investigate the effect of H2 S on metS-induced ED. Animals were divided into two groups as control and metS, which were fed with standard diet or 60% high-fructose diet for 10 weeks respectively. The metS model was evaluated with biochemical analyses, waist circumference/tibia length ratio and HOMA index. Penile hemodynamic parameters were evaluated by the measurement of intracavernous pressure/mean arterial pressure ratio during cavernous nerve stimulation in the presence and absence of intracavernous injection of NaHS (100 µg/50 µl) and its control 0.9%NaCl (50 µl) in both groups. H2 S levels were measured in penile tissues by methylene blue assay. H2 S levels were significantly decreased in the penile tissues of the metS group. Decreased intracavernous pressure/mean arterial pressure ratio improved after intracavernous administration of NaHS in the metS group. These results suggest the significant role of H2 S in the metS-induced erectile dysfunction that could be a new therapeutic target.

Effects of the dopamine D3 receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin in hyperthyroidism-induced premature ejaculation rat model.

Various factors are involved in the aetiology of premature ejaculation (PE). Hyperthyroidism is one of the causes of acquired PE, but the exact mechanism by which it causes the disorder is not yet understood. The aim of this study was to evaluate the role of the dopaminergic system in hyperthyroidism-induced PE by the intracerebroventricular microinjection of the preferentially active dopamine receptor agonist 7-hydroxy-2-(di-N-propylamino) tetralin (7-OH-DPAT) in a rat model of this disorder. Wistar rats were randomly divided into hyperthyroid and control groups, and ejaculation was induced by the ICV administration of 7-OH-DPAT. To evaluate the emission and expulsion phases of ejaculation, measurements of seminal vesicle pressure (SVP) and electromyographic recordings of the bulbospongiosus muscle were taken. The interval between the 7-OH-DPAT administration and the first ejaculation was significantly less in the hyperthyroid group (p < .01) than in the control group, and the maximum amplitude of the SVP values revealed a statistically significant difference between the groups (p < .01). The intervals between contractions of the seminal vesicle and bulbospongiosus muscles were also significantly less in the hyperthyroid group (p = .0187) than in the control group. No other results differed significantly between the groups. This study determined that hyperthyroidism altered only the emission phase of ejaculation.

Soluble guanylyl cyclase activators increase the expression of tolerance to morphine analgesic effect.

OBJECTIVES: It is aimed to investigate the effects of guanylyl cyclase activation and inhibition on acute morphine antinociception and the development of tolerance to its effect. BACKGROUND: Nitric oxide-soluble guanylyl cyclase signal transduction cascade suggested to play an important role in the development of tolerance to antinociceptive effects of morphine. METHODS: Nociception was evaluated by tail flick and hot plate tests in male Wistar rats. The analgesic effects of intraperitoneal protoporphyrin IX (PPIX; an activator of soluble guanylyl cyclase), 3-morpholinosydnonimine hydrochloride (SIN-1; NO donor and activator of guanylyl cyclase), S-Nitroso-N-acetylpenicillamine (SNAP; an activator of guanylyl cyclase), 3,3-Bis (amino ethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18; NO donor activating guanylyl cyclase) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; an inhibitor of guanylyl cyclase) alone or in combination with subcutaneous morphine injection were evaluated. Their effects on morphine tolerance development were evaluated by giving these agents 20 minutes prior to twice daily morphine injection during tolerance development for 5 days. On day 6, the expression of morphine tolerance was determined. RESULTS: PPIX, SIN-1, SNAP and NOC-18 significantly increased expression of morphine tolerance while ODQ decreased. CONCLUSION: These data suggested that sGC activators have a significant role in tolerance to the analgesic effect of morphine (Tab. 1, Fig. 4, Ref. 29).

Pharmaceutical risk management in Turkey: the first national overview.

Risk management plans and actions aim to limit the known risks of drugs and provide valuable data to evaluate actual risks and pre-disposing factors for adverse drug reactions. In this study, it is aimed to evaluate and summarize the risk management actions in Turkey between 2005 and 2013 for the first time. The drugs monitored with a risk management plan and actions taken are evaluated by examining the records of the Turkish Pharmaceuticals and Medical Devices Agency retrospectively. Various risk management actions such as provision of information, summary of product characteristics and patient information leaflets, direct communication with healthcare professionals, patient and physician brochures, change of the legal status of the drug, education of doctors and pharmacists, control of number and validity of prescriptions, using informed consent forms, using "drug safety surveillance form" for the TNF blockers (firstly on the world), using web-based monitoring system, web-based prescription and web-based adverse reaction monitoring system were used for safe use of drugs during and after authorization in Turkey. Although, most of the actions are similar to those of international health authorities, the remaining are specific to the conditions of Turkey such as "drug safety surveillance form" for the TNF blockers.

The effects of L type calcium channels on the electroencephalogram recordings in WAG/RIJ rat model of absence epilepsy.

BACKGROUND: Epilepsy is one of the most important central nervous system disorder and 1% of the total world population suffers from this disorder which require a chronic drug treatment. Most of the researchers suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges but the role of L type calcium channels has not been clarified in absence epilepsy. AIM: In this study, it is aimed to investigate the antiepileptic effects of nifedipine, an L type calcium channel blocker and BAY K8644, an L type calcium channel opener in a genetic model of absence epilepsy in WAG/Rij rats. MATERIALS AND METHODS: Thirty two WAG/Rij rats were allocated into four groups; sham (only saline injected), only nifedipine (an L type calcium channel blocker) injected group (40 µg/2 µl; 60 µg/2 µl; 80 µg/2 µl), only BAY K8644 (1,4 Dihydro-2,6-dimethyl-5-nitro-4-trifluoromethyl- phenyl-3-pyridine carboxylic acid methyl ester) (L-type Ca2+-channel activator) injected group (40 µg/2 µl; 60 µg/2 µl; 80 µg/2 µl) and combination of their most effective doses BAY K8644 (60 µg/2 µl) after nifedipine (60 µg/2 µl) injected group. All agents were given by intracerebroventricular injection. The beta, alpha, theta and delta wave ratios of electroencephalogram recordings and the frequency and duration of SWDs (spike and wave discharges) were analyzed and compared between four groups. RESULTS: Nifedipine increased the number and duration of spike wave discharges whereas BAY K8644 decreased both of them. When BAY K8644 was given after nifedipine, there was no significant difference with control group. CONCLUSIONS: L type calcium channels play an activator role on spike wave discharges and have positive effects on the duration and frequency.

FRAIL Scale: an independent predictor of in-hospital mortality among older adults.

OBJECTIVE: To screen for geriatric syndromes in older in-hospital patients and investigate their relationship with mortality. PATIENTS AND METHODS: Demographic data, comorbidities, and medical history of the patients were recorded. Anthropometric measurements were obtained at 72 hours after hospital admission. The Mini Nutritional Assessment-Short Form, strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F) sarcopenia screening questionnaire, Katz Activities of Daily Living scale, Lawton-Brody instrumental activities of daily living scale, the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale and the Eating Assessment Test-10 (EAT-10) screening test were used to assess geriatric syndromes. All patients were evaluated for delirium, pain, falls, polypharmacy, sleep disorders, incontinence, and pressure injury by the same researcher. RESULTS: A total of 85 patients were included in the study. The mean age was 75±7 years (range: 66-97). During hospital follow-up, 15.3% (n=13) of the patients died and 84.7% (n=72) were discharged. The median length of stay was 19 days (range: 3-126 days). In the multivariate analysis, frailty (hazard ratio: 2.67, 95% CI: 1.41-5.06, p=0.003) was found to be associated with in-hospital mortality. CONCLUSIONS: Frailty is an independent risk factor for in-hospital mortality in older adults.

The effect of frailty in older community-dwelling outpatients with atrial fibrillation: a new score HAS-BLED-F (rail).

OBJECTIVE: This study aims to determine the effect of frailty on thromboembolic events (TEE) and bleeding in older patients with non-valvular atrial fibrillation (AF). PATIENTS AND METHODS: Patients aged ≥65 years who were diagnosed as having non-valvular AF in a geriatric outpatient clinic between June 2015 and February 2021 were included in the study. Frailty, the risk of thrombosis secondary to AF, and the risk of bleeding as a complication of AF treatment were evaluated using the FRAIL scale, and CHA2DS2-VASc and HAS-BLED scores, respectively. RESULTS: Out of 83 patients included in the study, 72.3% were frail and 21.7% were pre-frail. TEE was observed in 14.5% (n=12) and bleeding was observed in 25.3% (n=21) of the patients. A total of 21 (25.3%) patients had a history of bleeding. There was no difference between the normal, pre-frail, and frail groups in terms of TEE and bleeding history (p=0.112 and p=0.571, respectively). In multivariate analysis, mortality decreased with the use of apixaban; frailty and malnutrition were found to increase mortality (p=0.014, p=0.023, and p=0.020, respectively). HAS-BLED-F score was obtained as a result of the sum of the patients' HAS-BLED and FRAIL scores to predict the bleeding risk. A HAS-BLED-F score of ≥6 predicted the risk of bleeding with 90.5% sensitivity and 40.3% specificity. CONCLUSIONS: Frailty is not associated with a statistically significant increase in the risk of thromboembolic events or bleeding in patients with non-valvular AF. HAS-BLED-F score can be used to better predict the risk of bleeding in frail patients.

Time-course changes of nLDL-induced erectile dysfunction.

Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg-1 nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.

Reduction of paraquat toxicity in maize leaves by benzyladenine.

The protective effect of a cytokinin benzyladenine (BA), against toxicity of paraquat (PQ), a widely used herbicide and a well-known oxidative stress inducer, was investigated in the leaves of maize. Maize leaves have been pretreated with BA at concentrations of 1, 10 and 100 microM and afterwards treated with PQ. At all concentrations tested, BA retarded PQ-induced decreases in chlorophyll, carotenoid and ascorbic acid contents. Pretreatment with 10 and 100 microM of BA significantly increased superoxide dismutase (SOD) activity after 8 h of PQ treatment but there was no significant change in SOD activity in the leaves pretreated with BA at 12 and 24 h. However, peroxidase activity significantly increased in 100 microM of BA pretreated leaves. Results indicate that pretreatment with BA reduce PQ toxicity and BA-treated plants might become more tolerant against oxidative stress.

Effects of fluoxetine and LY 367265 on tolerance to the analgesic effect of morphine in rats.

Morphine is widely used to treat chronic pain, however its utility is hindered by the development of tolerance to its analgesic effects. The aim of this study was to investigate effects of fluoxetine, a specific serotonin (5-HT) reuptake inhibitor, and LY 367265, an inhibitor of the 5-HT transporter and 5-HT2A receptor antagonist, on tolerance induced to the analgesic effect of morphine in rats. The study was carried out on male Wistar Albino rats (weighing 170-190 g). To constitute morphine tolerance, animals received morphine (50 mg/kg; s.c.) once daily for 3 days. After last dose of morphine, injected on day 4, morphine tolerance was evaluated. The analgesic effects of fluoxetine (10 mg/ kg; i.p.), LY 367265 (3 mg/kg; i.p.) and morphine were considered at 30-min intervals by tail-flick and hot-plate tests. The results showed that fluoxetine and LY 367265 significantly attenuated the development and expression of morphine tolerance. The maximal antinociceptive effects were obtained 30 min after administration of fluoxetine and 60 min after administration of LY 367265. In conclusion, we observed that co-injection of morphine with fluoxetine and LY 367265 increased the analgesic effects of morphine and delayed development of tolerance to morphine analgesia.