Platelet nitric oxide synthase is activated by tyrosine dephosphorylation: possible role for SHP-1 phosphatase

BACKGROUND: Endothelial nitric oxide synthase (eNOS) activity in endothelial cells is regulated by post-translational phosphorylation of critical serine, threonine and tyrosine residues in response to a variety of stimuli. However, the post-translational regulation of eNOS in platelets is poorly defined. OBJECTIVES: We investigated the role of tyrosine phosphorylation in the regulation of platelet eNOS activity. METHODS: Tyrosine phosphorylation of eNOS and interaction with the tyrosine phosphatase SHP-1 were investigated by coimmunoprecipitation and immunoblotting. An in vitro immunoassay was used to determine eNOS activity together with the contribution of protein tyrosine phosphorylation. RESULTS: We found platelet eNOS was tyrosine phosphorylated under basal conditions. Thrombin induced a dose- and time-dependent increase in eNOS activity without altering overall level of tyrosine phosphorylation, although we did observe evidence of minor tyrosine dephosphorylation. In vitro tyrosine dephosphorylation of platelet eNOS using a recombinant protein tyrosine phosphatase enhanced thrombin-induced activity compared to thrombin alone, but had no effect on endothelial eNOS activity either at basal or after stimulation with bradykinin. Having shown that dephosphorylation could modulate platelet eNOS activity we examined the role of potential protein phosphatases important for platelet eNOS activity. We found SHP-1 protein tyrosine phosphatase, co-associated with platelet eNOS in resting platelets, but does not associate with eNOS in endothelial cells. Stimulation of platelets with thrombin increased SHP-1 association with eNOS, while inhibition of SHP-1 abolished the ability of thrombin to induce elevated eNOS activity. CONCLUSIONS: Our data suggest a novel role for tyrosine dephosphorylation in platelet eNOS activation, which may be mediated by SHP-1.     

Do vascular surgery patients need a cardiology work-up? A review of pre-operative cardiac clearance guidelines in vascular surgery.

OBJECTIVES: to outline the appropriate pre-operative cardiac work-up for patients who are scheduled for major peripheral vascular surgery. DESIGN: review of the literature. MATERIALS AND METHODS: a review of the literature focusing on studies that have correlated the pre-operative cardiac work-up patients receive to the cardiac morbidity and mortality following vascular surgery. Only studies with level A evidence were included. RESULTS: peri-operative beta blockade has been shown to decrease cardiac complications after vascular surgery in all risk groups. Non-invasive cardiac testing is only necessary for patients in the intermediate/high risk group. Coronary revascularization should only be considered after a positive non-invasive cardiac test. CONCLUSIONS: patients must be risk stratified pre-operatively based on history and physical examination. Low risk patients should receive peri-operative beta blockade only with no further non-invasive testing. On the other hand, intermediate and high risk patients should undergo non-invasive cardiac testing before going to the operating room.     

Is there relationship between serum uric acid levels and lower urinary tract symptoms,prostate volume,and PSA in men without cancer? A prospective population-based study

There are conflicting results about uric acid (UA) effect on the prostate. We investigated the relationship between UA and PSA, free PSA, prostate volume and international prostate symptoms score (IPSS) in benign prostate hyperplasia (BPH). This study was conducted in BPH men without cancer who were referred for annual health workup (N = 910) from 2017 to 2020. The mean ages were 67.28 ± 9.2 years. UA was positively related to IPSS and PSA (r = 0.210, p = .023 and r = 0.156, p = .041 respectively) and also negatively related to free/total PSA ratio (r = −0.332, p = .01) but not related to prostate volume (r = 0.036, p = .696). After adjustment for age, BMI and prostate volume, there were significant relationships between hyperuricaemia and PSA, free/total PSA ratio, and IPSS (95% CI: 0.254–1.645, OR = 0.647, p = .039; 95% CI: 0.076–0.899, OR = 0.270, p = .033 and 95% CI: 1.011–3.386, OR = 1.851, p = .038 respectively). These results should be considered during the general assessment of the patients with BPH. The findings raise the possible hypothesis of relationship between serum UA with IPSS and PSA which should be investigated by future studies.     

Human Linguatulosis Caused by Linguatula serrata in the City of Kerman,South-eastern Iran- Case Report

Human linguatulosis poses an important medical and veterinary concern in endemic countries. Animals, as reservoir host, play a major role in transmission of infestation and epidemiology of the disease. This study reports a case of human linguatulosis caused by Linguatula serrata in the city of Kerman, South-eastern Iran. A woman suffering from upper respiratory symptoms is presented. The patient consumed raw liver of sheep who was admitted to the Afzalipour University Hospital in Kerman for the symptoms of upper respiratory tract. In microscopic examination of the nasopharyngeal discharge, L. serrata was detected. This report has future medical implication in precise diagnosis of L. serrata in patients with complaints of nasopharyngeal symptoms.     

Cardiovascular Effects of Medical Marijuana: A Systematic Review

Utilization of marijuana as a medicinal agent is becoming increasingly popular, and so far, 25 states have legalized it for medical purposes. However, there is emerging evidence that marijuana use can result in cardiovascular side effects, such as rhythm abnormalities, syncope/dizziness, and myocardial infarction, among others. Further, there are currently no stringent national standards or approval processes, like Food and Drug Administration (FDA) evaluation, in place to assess medical marijuana products. This review includes the largest up-to-date pooled population of patients with exposure to marijuana and reported cardiovascular effects. Although purported as benign by many seeking to advance the use of marijuana as an adjunctive medical therapy across the country, marijuana is associated with its own set of cardiovascular risks and deserves further definitive study and the same level of scrutiny we apply in research of all other types of medications. When used as a medicinal agent, marijuana should be regarded accordingly, and both clinical providers and patients must be aware of potential adverse effects associated with its use for early recognition and management.     

Characteristics and outcomes of recurrent atrial fibrillation after prior failed pulmonary vein isolation

Journal of Interventional Cardiac Electrophysiology - The mechanisms for atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) catheter ablation are unclear. Non-PV organized...