The effect of chronic alpha-methyldopa upon sexual function in the adult male rat

Erectile impotence is a commonly reported undesired side effect in patients treated for hypertension with alpha-methyldopa. However, the mechanism of that dysfunction has not been determined. In this study we report the effect of 12 days of daily intraperitoneal injections, 300 mg./kg., of alpha-methyldopa on adult male, Long-Evans rats and their age-matched saline controls. The effect of the drug upon copulation, penile reflexes and tissue catecholamines was measured. The results showed significant differences between control and experimental animals in all parameters studied. Tests of copulatory ability showed significant decreases in mounts from 5.8 +/- 1.6 (mean +/- standard error) to 3.1 +/- 1.3; penile intromissions from 27.0 +/- 3.8 to 4.8 +/- 1.9; and ejaculations from 2.1 +/- 0.3 to 1.1 +/- 0.6 per 30 minute test period. Penile reflexes measured as erection and cup formation showed similar significant reductions. The norepinephrine content of the penile corpora in the controls was 0.460 +/- 0.084 ng./mg. wet weight and 0.112 +/- 0.022 ng./mg. wet weight in the experimental group. There were similar significant reductions of norepinephrine content in the vas deferens of these animals 32.95 +/- 4.31 ng./mg. and 0.25 +/- 0.1 ng./mg. wet weight in the control and experimental groups respectively.     

Oral risperidone with lorazepam versus oral zuclopenthixol with lorazepam in the treatment of acute psychosis in emergency psychiatry: a prospective, comparative, open-label study

Acutely psychotic patients presenting as psychiatric emergencies with aggression or agitation are often administered conventional antipsychotics intramuscularly. However, patients view intramuscular administration as coercive, and conventional antipsychotics are often associated with adverse events. In this open study, consecutive adult patients presenting with an acute exacerbation of schizophrenia or other psychotic disorder were assigned to oral risperidone 2-6 mg/day (n = 48) or oral zuclopenthixol 20-50 mg/day (n = 27) for 7-14 days. Lorazepam (either oral or intramuscular) was administered to both groups as needed. Patients were assessed regularly until day 14 or discharge. Mean Positive And Negative Syndrome Scale (PANSS) aggression scores (sum of item scores on excitement, poor impulse control, hostility and uncooperativeness) decreased steadily and similarly in both groups; the mean changes from baseline were statistically significant at days 10 and 14 and at study end-point. The mean decrease at study end-point in the PANSS component score for hostility was statistically significant in the risperidone group, but not in the zuclopenthixol group. Social Dysfunction and Aggression Scale aggression scores and Clinical Global Impression scores decreased significantly and similarly in both groups. Overall, 18.7% of patients showed minor extrapyramidal symptoms during the study, but only 16.7% of risperidone-treated patients, compared to 59.3% of zuclopenthixol-treated patients, received anti-parkinsonian medication (p < 0.001). Lorazepam was administered to all of the patients assigned to risperidone and to 89% of those assigned to zuclopenthixol. Oral risperidone plus lorazepam is a convenient, effective and well-tolerated alternative to conventional antipsychotics for the treatment of acute psychosis in emergency psychiatry.     

Clinical outcomes of atypical extra-esophageal reflux symptoms following laparoscopic antireflux surgery

Introduction  

While it is well established that antireflux surgery is effective in relieving typical gastroesophageal reflux disease (GERD) symptoms such as heartburn and regurgitation, it is currently unclear whether atypical symptoms (cough, hoarseness, wheeze) foreshadow a less satisfactory outcome following laparoscopic antireflux surgery (LARS). The purpose of this study is to critically analyze the clinical outcomes of atypical symptoms in patients undergoing LARS.     

Collagen type I:III ratio of the gastroesophageal junction in patients with paraesophageal hernias

Background  

The purpose of this study was to examine the biological environment of the esophageal hiatus through analysis of the collagen content within the gastrohepatic ligament (GHL), gastrophrenic ligament (GPL), and phrenoesophageal ligament (PEL) in patients with type I hiatal hernias (HH) and type III paraesophageal hernias (PEH).     

Evaluation of acute fixation strength of absorbable and nonabsorbable barrier coated mesh secured with fibrin sealant

Introduction  

The purpose of this study was to evaluate the acute fixation strength of fibrin sealant as an alternative fixation method for laparoscopic ventral hernia repair (LVHR) when utilized with absorbable and nonabsorbable barrier meshes.     

The sphingosine‐1‐phosphate pathway is upregulated in response to partial urethral obstruction in male rats and activates RhoA/Rho‐kinase signalling

OBJECTIVES

To examine the effect of partial urethral obstruction (PUO) on the sphingosine‐1‐phosphate (S1P, a bioactive lipid shown to modulate smooth muscle, SM) pathway in the bladders of male rats, and to determine the effect of PUO on the RhoA/Rho‐kinase (ROK) pathway, and whether there is a molecular cross‐talk with the S1P pathways associated with bladder overactivity (S1P1‐S1P3, where S1P1 is associated with nitric oxide‐mediated SM relaxation, and S1P2 and S1P3 receptors are associated more with SM contraction via the ROK pathway).

MATERIALS AND METHODS

In all, 20 male rats were divided into two groups and underwent PUO or a sham operation (control). After 2 weeks all rats were killed humanely and bladder specimens used for in vitro organ‐bath physiological contractility studies, and for mRNA and protein analyses of major S1P/ROK pathway constituents via real‐time polymerase chain reaction and Western blotting, respectively. In addition, early‐passage SM cells were transfected with recombinant sphingosine kinase (SPHK, the enzyme that converts sphingosine to S1P).

RESULTS

Bladders from PUO rats had greater mRNA expression of the S1P2 and S1P3 receptors, as well as SPHK1, than the sham controls (4.78, 2.04 and 2.72 times, respectively). PUO rats also had significantly greater expression of RhoA and ROKα (1.76 and 2.19 times, respectively). Western blotting and organ‐bath contractility studies showed similar changes at the protein and in vitro functional level, with an increased contractility of bladder strips from PUO rats to exogenous S1P. Transfection of SPHK into isolated SM cells increased ROK expression.

CONCLUSIONS

We show for the first time that the S1P signalling pathway is significantly upregulated in response to PUO in male rats at both the molecular and in vitro functional levels, correlating with an activation of the RhoA/ROK pathway. Further, we provide novel data that SPHK overexpression increases ROK expression in vitro, suggesting a novel hypothesis of S1P‐induced bladder overactivity in the mechanism for PUO‐induced bladder dysfunction and the S1P signalling pathway as a possible therapeutic target for bladder overactivity.