Comparison of the safety and efficacy of the on-demand use of sertraline,dapoxetine, and daily use of sertraline in the treatment of patients with lifelong premature ejaculation: A prospective randomised study

This study compared the safety and efficacy of the on-demand (OD) use of sertraline (50 mg), sertraline (100 mg) and dapoxetine (30 mg), and the daily use of sertraline (50 mg) in the treatment of patients with premature ejaculation (PE). This prospective randomised study involved 120 lifelong PE patients (intravaginal ejaculatory latency time [IELT]: <1 min; Arabic Index of Premature Ejaculation [AIPE] score: < 30) without secondary causes of PE, identified between March 2018 and May 2020. Patients were divided into 4 groups (30 patients per group) and treated for 8 weeks. Assessments were conducted using the AIPE form as a diagnostic tool. Sertraline (50 mg, daily; 196.7 ± 115.5 s) and sertraline (100 mg, OD; 173.3 ± 97.0 s) had similar IELT and AIPE scores. The latter groups had better results in comparison with sertraline (50 mg, OD; 100.5 ± 54.4 s) and dapoxetine (93.7 ± 53.5 s; p < 0.01). Sertraline (100 mg, OD) had a similar efficacy to that of sertraline (50 mg, daily) and was more effective than sertraline (50 mg, OD) and dapoxetine (30 mg, OD). Sertraline (100 mg, OD) can be considered in the treatment of lifelong PE treatment, having tolerable side effects.     

Impact of intra-operative doppler ultrasound assistance during microsurgical varicocelectomy on operative outcome and sperm parameters

The microsurgical varicocelectomy is the gold standard treatment with a low recurrence rate and less postoperative complications. We compared the surgical outcomes and difficulty in intra-operative vascular Doppler ultrasound-assisted microscopic varicocelectomy (IVDU-MV) with MV in primary and recurrent varicocele. A total of 228 infertile patients with clinically palpable varicocele were included in the study. One hundred fifteen patients were operated on with the standard MV approach, whereas the other 113 patients were operated on with IVDU-MV. Perioperative outcomes, sperm parameters and operative difficulty of the procedure were evaluated. The operative times were significantly shorter for the IVDU-MV group for primary and recurrent varicocele (p = .001). Mean number of veins ligated for primary and recurrent varicocele was significantly higher in the IVDU-MV group than in the MV group (6 ± 1.4 vs. 4.8 ± 1.8 and 3.7 ± 0.9 vs. 2.9 ± 1.2; p < .01). The increase in mean sperm motility was significantly higher in the IVDU-MV group for both primary and recurrent varicocelectomy patients (p < .05). A significant number of IVDU-MV procedures were described as easy in both primary and recurrent varicocelectomy procedures (p = .006). The use of Doppler ultrasound(US) revealed advantages in ligating veins, preserving arteries and improving sperm motility and facilitates the operation for the surgeon, especially during recurrent varicocele repair .     

Melatonin prevents deterioration of erectile function in streptozotocin-induced diabetic rats via sirtuin-1 expression

A review of the literature indicated that sirtuin-1 expression, a regulator of nitric oxide bioavailability in erectile dysfunction (ED) after melatonin therapy, has not yet been investigated. The objective of this study was to evaluate the protective effects of melatonin for erectile function with sirtuin-1 protein expression in type 1 diabetic rat models. Fifty male Sprague Dawley rats were placed into five groups. Except for those in the control group (C), each animal received a single dose (60 mg/kg) of streptozotocin to induce diabetes. The animals were placed into the diabetes (D) group, insulin (I) group (6 U/kg/day), melatonin (Mel) group (10 mg kg⁻¹ day⁻¹) and combined treatment (I + Mel) group. Ten weeks later, the serum testosterone levels, intracavernosal pressure (ICP), mean arterial pressure (MAP), malondialdehyde (MDA), cyclic guanosine monophosphate (c-GMP), 8-hydroxydeoxyguanosine (8-OHdG), nitric oxide synthase (NOS), caspase-3 activity, sirtuin-1 and endothelial nitric oxide synthase (eNOS) protein expression and histological findings were assessed. The mean ICP/MAP ratio for the D group was lower than the mean ratios for the other groups. The treatment groups, particularly the I + Mel group, exhibited lower 8-OHdG and MDA levels and caspase-3 activity than the D group. The sirtuin-1 and eNOS expression and cavernosal tissue (CT) histology seemed to have been preserved by the melatonin and/or insulin therapy. These results were indicative of a profound protective effect of melatonin by the activation of sirtuin-1 protein expression against hyperglycemia-induced oxidative CT injury.     

Diurnal leptin secretion is intact in male hypogonadotropic hypogonadism and is not influenced by exogenous gonadotropins

Circulating leptin shows a pulsatile secretory pattern along with a nocturnal rise. We have previously shown that circulating leptin concentrations are high in males with untreated idiopathic hypogonadotropic hypogonadism (IHH). However, circadian leptin secretion in IHH before and after gonadotropin treatment is not known. Thus, we studied 14 adult males with IHH who had no history of previous hormonal therapy, and 12 age- and body mass index-matched healthy men. Plasma leptin concentrations were measured with 1-h intervals for 24 h before and 6 months after gonadotropin treatment. The 24-h mean leptin concentration showed a significant decrease, from 11.78 +/- 1.908 microg/liter at baseline to 10.85 +/- 1.939 microg/liter after 6 months of therapy (z = 3.107; P = 0.002). Before and after treatment, 24-h mean leptin concentrations were also significantly higher in the patient group when compared with controls (4.275 +/- 0.711 microg/liter) (z = 5.938; P = 0.0001). Hourly leptin levels demonstrated a diurnal pattern in hypogonadal patients, a surge in the midday, and a peak just after midnight, and this pattern did not differ before and after treatment. We observed a similar diurnal pattern in the control subjects too. Leptin levels were negatively and significantly correlated with free testosterone and total testosterone levels both before (r = -0.656, P = 0.011; and r = -0.639, P = 0.014, respectively) and after (r = -0.537, P = 0.048; and r = -0.563, P = 0.036, respectively) gonadotropin administration. Our observations suggest that the diurnal rhythm of leptin is intact in males with IHH, and short-term gonadotropin treatment does not effect its diurnal rhythm. Moreover, testosterone produced under the influence of the gonadotropin treatment led to decreases in the leptin levels.     

NF‐κB activation mediates LPS‐or zymosan‐induced hypotension and inflammation reversed by BAY61‐3606, a selective Syk inhibitor,in rat models of septic and non‐septic shock

We have previously demonstrated that the activation of the spleen tyrosine kinase (Syk)/inhibitory‐κB (IκB)‐α/nuclear factor‐κB (NF‐κB) p65 signalling pathway contributes to hypotension and inflammatory response in a rat models of zymosan (ZYM)‐induced non‐septic shock. The purpose of this study was to further examine the possible mechanism underlying the effect of inhibition of Syk by BAY61‐3606 via NF‐κB activity at the level of nuclear translocation regarding the production of vasodilator and proinflammatory mediators in lipopolysaccharide (LPS) (septic)‐ and ZYM (non‐septic)‐induced shock. Administration of LPS (10 mg/kg, ip) or ZYM (500 mg/kg, ip) to male Wistar rats decreased mean arterial pressure and increased heart rate that was associated with an increase in the activities of cyclooxygenase and nitric oxide synthase, tumour necrosis factor‐α, and interleukin‐8 levels, and NF‐κB activation and nuclear translocation in sera and/or cardiovascular and renal tissues. BAY61‐3606 (3 mg/kg, ip), the selective Syk inhibitor, given 1 hour after LPS‐ or ZYM injection reversed all the above‐mentioned effects. These results suggest that Syk contributes to the LPS‐ or ZYM‐induced hypotension and inflammation associated with transactivation of NF‐κB in septic and non‐septic shock.     

Full Genome of batCoV/MinFul/2018/SriLanka,a Novel Alpha-Coronavirus Detected in Miniopterus fuliginosus,Sri Lanka

Coronaviruses (CoV) are divided into the genera α-CoVs, β-CoVs, γ-CoVs and δ-CoVs. Of these, α-CoVs and β-CoVs are solely capable of causing infections in humans, resulting in mild to severe respiratory symptoms. Bats have been identified as natural reservoir hosts for CoVs belonging to these two genera. Consequently, research on bat populations, CoV prevalence in bats and genetic characterization of bat CoVs is of special interest to investigate the potential transmission risks. We present the genome sequence of a novel α-CoV strain detected in rectal swab samples of Miniopterus fuliginosus bats from a colony in the Wavul Galge cave (Koslanda, Sri Lanka). The novel strain is highly similar to Miniopterus bat coronavirus 1, an α-CoV located in the subgenus of Minunacoviruses. Phylogenetic reconstruction revealed a high identity of the novel strain to other α-CoVs derived from Miniopterus bats, while human-pathogenic α-CoV strains like HCoV-229E and HCoV-NL63 were more distantly related. Comparison with selected bat-related and human-pathogenic strains of the β-CoV genus showed low identities of ~40%. Analyses of the different genes on nucleotide and amino acid level revealed that the non-structural ORF1a/1b are more conserved among α-CoVs and β-CoVs, while there are higher variations in the structural proteins known to be important for host specificity. The novel strain was named batCoV/MinFul/2018/SriLanka and had a prevalence of 50% (66/130) in rectal swab samples and 58% (61/104) in feces samples that were collected from Miniopterus bats in Wavul Galge cave. Based on the differences between strain batCoV/MinFul/2018/SriLanka and human-pathogenic α-CoVs and β-CoVs, we conclude that there is a rather low transmission risk to humans. Further studies in the Wavul Galge cave and at other locations in Sri Lanka will give more detailed information about the prevalence of this virus.     

The role of posterior instrumentation and fusion after anterior radical debridement and fusion in the surgical treatment of spinal tuberculosis: experience of 127 cases

Long periods of immobilization, progressive kyphosis and graft failure are the major postoperative problems encountered after anterior radical surgical treatment for tuberculosis of the spine. Posterior fusion and instrumentation can be an effective solution for these problems. Effectiveness of posterior fusion and instrumentation was investigated in this study on the basis of the cases with anterior procedure only, and with combined anterior-posterior procedures. One hundred twenty-seven cases of tuberculosis of the spine were surgically treated between 1987 and 1995. All had either 1 or more of conditions such as spinal cord compression and neurological deficit, vertebral body collapse and kyphosis, or wide paravertebral abscess unresponsive to medical treatment. Of these, 57 had only anterior radical procedure between the years 1987 and 1993. Seventy cases had posterior instrumentation and fusion after the anterior procedure between the years 1991 and 1995. In about two third of the patients (81) autogenous iliac strut graft and in one third of them (40) autogenous fibular strut graft (cases with more than 2 level involvement) was used along with rib grafts after debridement. Twenty-one of the 57 patients who had only anterior procedure demonstrated a postoperative increase of kyphosis of more than 10 degrees. Increased kyphosis was due to graft slippage in 3, resorption in 2 and subsidence in 16 patients. No such increase or graft failure was noted in cases of combined anterior-posterior procedure. The difference in terms of kyphosis was found to be statistically significant (P=0.047). Anterior radical debridement and strut graft is the golden standard in the surgical treatment of spinal tuberculosis, but it should always be accompanied by posterior instrumentation and fusion to shorten the immobilization period and hospital stay, obtain good and long lasting correction of kyphosis, and prevent further collapse and graft failure.     

Prevalence of endothelial nitric oxide synthase E298D polymorphism in Turkish patients with essential hypertension

AimsOur aim was to evaluate the effects of endothelial nitric oxide synthase (eNOS) E298D polymorphism in obesity variables and essential hypertension (eHT) development risk. The genotype frequencies of E298D polymorphism in eHT patients and non-hypertensive (non-HT) controls (proven to have normal coronaries angiographically) were analyzed for their association with demographic and obesity related data of the eHT patients and controls.Materials and methodseNOS gene E298D genotypes were determined with qPCR.ResultsThe eNOS E298D polymorphism frequencies for 298E/E, 298E/D and 298D/D genotypes were respectively as 41.1%, 44.6%, 14.3% in subjects eHT and 52.8%, 38.9%, 8.3% in the non-HT groups. The combined E298D homozygous polymorphic and heterozygous genotypes were found to have a decreasing effect on serum total-cholesterol levels in comparison to wild-type genotypes in eHT patients but not controls.ConclusionsOur results support the idea that, the eNOS E298D polymorphism, which is not associated with hypertension, may increase the risk of hypertension when associated with high serum total-cholesterol levels.