Effect of Selective 5-Hydroxytryptamine-3 Receptor and Neurokinin-1 Receptor Antagonists on Hemodynamic Changes and Arrhythmogenic Potential in Patients Receiving Chemotherapy: A Retrospective, Observational Study.

Background: Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce electrocardiographic changes. This study examined the effect of anti-emetic medications on arrhythmogenic potential and hemodynamic alterations. Methods: We considered patients aged 18 or above receiving chemotherapy between June 2013 and December 2013. Patients were grouped by anti-emetic medication: intravenous granisetron (Group G), oral aprepitant plus IV granisetron (Group AG), IV palonosetron (Group P), and oral aprepitant plus IV palonosetron (Group AP). We recorded blood pressure and electrocardiography initially and at the thirtieth minute post-medication, focusing on P dispersion, QTc dispersion, and systolic/diastolic blood pressure alterations. Results: The study included 80 patients (20 per group). Baseline systolic/diastolic blood pressure and P dispersion showed no significant variance. However, the baseline QTc dispersion was significantly lower in Groups P and AP than G and AG. The thirtieth-minute systolic/diastolic blood pressures were significantly lower than the baseline for Groups AG and AP, and the heart rates decreased in all groups. Group P showed significantly fewer blood pressure changes. Conclusions: We found no arrhythmogenic potential linked to granisetron, palonosetron, and aprepitant. Hypotension was more frequent at 30 min post-medication in granisetron or aprepitant recipients. Considering no hypotension occurred when using palonosetron alone, this treatment was deemed safer.

The roles of galectin-3 and galectin-4 in the idiopatic Parkinson disease and its progression.

OBJECTIVES: Idiopathic Parkinson's Disease is a neurodegenerative disease caused by the loss of cells that secrete dopamine in the basal ganglia. Galectins are multipotent, evolutionarily conserved, cell surface glycoconjugated and crosslinked carbohydrate-binding proteins. The roles of these proteins in the diagnosis of the disease have been investigated. PATIENT AND METHODS: Patients who were diagnosed with idiopathic Parkinson's disease were classified as early (stage 1-2) and advanced stage (stage 3-5) according to the Hoehn-Yahr classification. In addition, voluntary cases without parkinson disease constituted the control group. Serum samples of consecutive Parkinson patients and age and gender matched healthy controls were used to measure serum galectin-3 and serum galectin-4 levels. The levels were compared between Parkinson's patients and control groups and early and advanced stage Parkinson's groups. RESULTS: Thirty age and gender-matched healthy controls and 60 parkinson patients were enrolled in the study. Serum galectin-3 levels were lower in controls compared with patients (892.9 (168.2-2416.3) vs. 2271.8 (375.9-9673.4), respectively, P < 0.01). Serum galectin-3 levels were related to Hoehn-Yahr stages and (r: 0.691, P < 0.001). The early stage group (20 patients) had lower serum galectin-4 levels compared with advanced stages (40 patients) (197.97 ± 46.42 vs. 334.263 ± 37, respectively, P < 0.01). Serum galectin-4 levels were also lower in controls compared with patients 185.1 (116.2-313.3) vs. 282.3 (156.9-984.8), respectively, P < 0.01. ROC analysis showed that serum galectin-3 and galectin-4 were statistically significant in the identification of Parkinson disease and advanced stages. The results were significant for galectin-3 (AUC: 0.89, SE: 0.034, P < 0.001 and CI: 0.823-0.958; P < 0.001) and for galectin-4 (AUC: 0.758, SE: 0.05, P < 0.001). CONCLUSION: Serum galectin-3 and galectin-4 may be potential noninvasive markers for the identification of Parkinson disease and advanced stages.

Effects of hydrogen sulphide donor, sodium hydrosulphide treatment on the erectile dysfunction in L-NAME-induced hypertensive rats.

Men with hypertension often develop erectile dysfunction (ED). The present study aimed to examine the effects of sodium hydrosulphide (NaHS), a hydrogen (H2 S) donor, treatment on ED in nitric oxide synthase (NOS) inhibitor (L-NAME)-induced hypertensive rats. Forty adult Sprague-Dawley rats were divided into four groups: control, NaHS (0.037 mg kg day-1 )-treated control, L-NAME-induced hypertension (40 mg kg day-1 ) and NaHS-treated L-NAME-induced hypertension. The ratio of intracavernosal pressure to mean arterial pressure and isometric tension of corpus cavernosum (CC) were measured. The penile expression of endothelial and neuronal NOS (eNOS and nNOS), inflammation markers [nuclear factor kappa B (NF-κB) and inhibitor kappa B alpha (IκBα)], H2 S-producing enzymes[cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE)], the smooth muscle/collagen ratio and H2 S concentrations were determined. The blood pressure was significantly increased in the hypertensive group, but not reversed by NaHS. The erectile response in hypertensive rats was partially prevented by NaHS. The relaxation response to electrical field stimulation was increased in CC from NaHS-treated hypertensive rats. NaHS treatment restored decreased protein expression of eNOS, nNOS and CSE as well as smooth muscle/collagen ratio and H2 S levels and increased NF-κB and IκBα protein expression in the penile tissue of hypertensive rats. NaHS promoted the recovery of erectile responses in hypertensive rats by improvement of neuronal function and downregulation of fibrosis and NF-κB signalling.

Intracavernous Injection of Human Umbilical Cord Blood Mononuclear Cells Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats.

INTRODUCTION: Erectile dysfunction (ED) worsens in men with diabetes. Human umbilical cord blood (HUCB), because of its widespread availability and low immunogenicity, is a valuable source for stem cell-based therapies. AIM: To determine the effect of intracavernous injection of HUCB mononuclear cells (MNCs) on ED in rats with diabetes induced by streptozotocin. METHODS: Thirty adult male Sprague-Dawley rats were equally divided into three groups: (i) control, (ii) diabetes induced by streptozotocin (35 mg/kg intravenously for 8 weeks), and (iii) diabetic rats treated with MNCs (1 × 106 cells by intracavernosal injection). The HUCB-MNCs isolated by the Ficoll-Hypaque technique were obtained from eight healthy donors and administered to diabetic rats after 4 weeks. MAIN OUTCOME MEASURES: The ratio of intracavernosal pressure to mean arterial pressure ratio; the protein expression of endothelial and neuronal markers, such as von Willebrand factor, neuronal nitric oxide synthase, hypoxia-inducible factor-1α, and vascular endothelium growth factor; and the relative area of smooth muscle to collagen using western blotting and Masson trichrome staining were determined. RESULTS: Diabetic rats demonstrated a significantly decreased ratio of intracavernosal pressure to mean arterial pressure (0.26 ± 0.04; P < .01) and treatment with MNCs restored erectile function in diabetic rats (0.67 ± 0.05) compared with control rats (0.56 ± 0.02). In bath studies, neurogenic relaxant and contractile responses were significantly decreased in diabetic cavernosal tissues, which were restored by treatment. The ratio of smooth muscle to collagen was partly recovered by treatment, whereas von Willebrand factor levels were not altered in any group. Neuronal nitric oxide synthase and vascular endothelium growth factor levels were decreased, which were not restored by treatment. Increased hypoxia-inducible factor-1α protein expression in the diabetic group was completely normalized in MNC-treated diabetic samples. CONCLUSION: These results suggest that HUCB-MNC treatment can enhance the recovery of erectile function and promote numerous activities such the contribution of the hypoxia-inducible factor-1α and von Willebrand factor pathway to the neurogenic erectile response of diabetic rats. HUCB-MNCs in the healing process could involve an adaptive regenerative response and appear to be a potential candidate for cell-based therapy in ED of men with diabetes. It is evident that HUCB could provide a realistic therapeutic modality for the treatment of diabetic ED.

Median and Ulnar Neuropathy Assessment in Parkinson's Disease regarding Symptom Severity and Asymmetry.

Background. While increasing evidence suggests comorbidity of peripheral neuropathy (PNP) and Parkinson's disease (PD), the pathogenesis of PNP in PD is still a debate. The aim of this article is to search the core PD symptoms such as rigidity and tremor as contributing factors to mononeuropathy development while emphasizing each individual patient's asymmetric symptom severity. Methods. We studied 62 wrists and 62 elbows of 31 patients (mean age 66.48 ± 10.67) and 64 wrists and 64 elbows of 32 age-gender matched healthy controls (mean age 62.03 ± 10.40, p = 0.145). The Hoehn and Yahr disability scale and Unified Parkinson's Disease Rated Scale were used to determine the severity of the disease. Results. According to electrodiagnostic criteria, we confirmed median neuropathy in 16.12% (bilateral in two-thirds of the patients) and ulnar neuropathy in 3.22% of the PD group. While mean age (p = 0.003), age at PD onset (p = 0.019), and H&Y scores (p = 0.016) were significant, tremor and rigidity scores were not. The comparison of the mean indices of electrophysiologic parameters indicated subclinical median and ulnar nerve demyelination both at the wrist and at the elbow in the patient groups where a longer disease duration and mild tremor and rigidity scores are prominent, remarkably. Conclusion. A disease related peripheral neurodegeneration beyond symptom severity occurs in PD.