Metabolic alterations such as insulin resistance are thought to underlie the endothelial dysfunction and low grade inflammation found in morbid obesity. Twenty-six morbidly obese patients, aged 39.0 +/- 10.0 (mean +/- sd), were evaluated before and 4.2 +/- 0.8 months after bariatric surgery. A marked increment in the insulin sensitivity index (S(I)) and the endothelium-dependent vasodilatory response in a dorsal hand vein was observed after weight loss following bariatric surgery. Circulating levels of E-selectin, P-selectin, plasminogen activator inhibitor-1, and von Willebrand factor, which were higher than those in the control group, decreased significantly after surgery. Plasma vascular cell adhesion molecule-1, angiotensin-converting enzyme, intercellular adhesion molecule-1, thrombomodulin, and plasma and intraplatelet cGMP levels did not change after weight loss. All inflammatory markers were higher in morbidly obese patients. After surgery, C- reactive protein and sialic acid diminished, whereas circulating levels of IL-6, TNF-alpha, and its soluble receptors did not. Positive correlations were found between changes in adiposity and S(I) and changes in C-reactive protein and between changes in sialic acid and changes in endothelial function. In conclusion, a marked improvement in S(I), endothelial function, and low grade inflammation was observed in the weight-losing, morbidly obese patients after bariatric surgery. S(I) and adiposity appear to play roles in obesity-related, low grade inflammation that contribute to the endothelial dysfunction observed in morbid obesity.

We have conducted a prospective double blind randomized and placebo controlled clinical study in 20 patients with shoulder pain syndrome caused by supraspinatus tendinitis to determine whether transdermal nitroglycerin (NTG) has analgesic action in this condition. In a randomized manner we used a 5-mg NTG (Nitroplast) patch per day over 3 days or similar placebo patches applied in the most painful area. Patients were evaluated before treatment was initiated and after 24 and 48 h. The assessment was made blindly by the same clinical investigator. The follow-up showed a significant decrease in intensity of pain at 24 h (7.05 +/- 0.4 to 4.5 +/- 0.5) and 48 h (2 +/- 0.3) in the NTG group (P < 0.003). No changes were observed in the placebo group. The mean pain duration, activity of the extremity and hours of sleep also improved in the NTG group, with no significant modification in the placebo group. Two patients experienced headache as a side effect 24 h after treatment was started. Patients in the NTG group remained free of symptoms when they were assessed 15 days later. We conclude that NTG is useful in the treatment of shoulder pain syndrome caused by supraspinatus tendinitis and that this treatment could be a useful approach to the management of this common disturbance and probably also in other tendon musculoskeletal disorders.

No abstract

Endothelium plays a central role in the regulation of regional blood flow through the release of certain vasoactive substances. We conducted this study to test whether an increase in the production of nitric oxide (NO) metabolites, atrial natriuretic peptide (ANP) and plasma and intraplatelet cyclic guanosine 3':5' monophosphate (cGMP) is involved in the adaptation to chronic exercise in physically trained people and in the vasodilatation induced by acute physical exercise. We studied one group of 10 trained athletes and another group of 10 untrained people. We measured plasma levels of nitrites, nitrates and cGMP and intraplatelet levels of cGMP, as an indicator of intracellular guanylate cyclase activity, and ANP before and after a maximal treadmill test. Resting cardiac rate (CR) and systolic blood pressure (SBP) were lower in the athlete group than in the control group (73.8 +/- 3.6 vs. 92 +/- 5.9; P < 0.02 and 110 +/- 2.58 vs. 118 +/- 3.27; P < 0.02 respectively). SBP did not show differences between groups after the exercise test. Diastolic blood pressure (DBP) at rest was lower in the athlete group (71 +/- 1.79 vs. 80.5 +/- 3.53; P < 0.03) and the decrease after maximal exercise was more pronounced in this group (64 +/- 2.67 vs. 74.5 +/- 3.2; P < 0.02). Basal plasma nitrites were 4.9 +/- 0.8 in the athlete group and 1.9 +/- 0.3 in the control group (P < 0.05). After exercise, test differences between groups remained (P < 0.05). Nitrates were significantly higher in the group of athletes and did not show exercise-related changes. Plasma levels of cGMP and ANP increased in both groups after the treadmill test, with no differences between groups. Among the athletes, cGMP increased from 1.11 +/- 0.1 to 2.6 +/- 0.4 (P < 0.001), whereas in the untrained group plasma cGMP rose from 1.14 +/- 0.09 to 1.86 +/- 0.2 (P < 0.01). There was a significant correlation between the increases in plasma cGMP and the atrial natriuretic peptide in both groups (r = 0.91, P < 0.0002, for athletes; and r= 0.68, P < 0.04, for control group). The intraplatelet concentration of cGMP did not show differences between groups and did not change after exercise. In conclusion, we have found increased basal levels of plasma nitrite and nitrate in trained subjects. Exercise does not produce differences in the increments of these metabolites. Therefore, we speculate the release of nitric oxide is not augmented by exercise in trained athletes.

Aims Endothelin-1 is a potent endogenous vasoconstrictor that acts on the endothelin A (ET A ) receptor. The dose-response and time-course of the dilator effect of the ET A receptor antagonist, BQ-123, was investigated in the forearm of healthy volunteers. Methods Forearm blood flow was measured using mercury-in rubber strain gauge venous occlusion plethysmography. Results Following intra-arterial infusion of BQ-123 (50 nmol min −1 ) for 5 min, forearm blood flow increased by approximately 60% over the next 60 minutes; lower doses were without significant effect. The degree of dilatation was similar to that observed in previous studies using 20-fold larger doses. Conclusions This study confirms that basal endothelin-1 has a role in the physiological regulation of vascular tone. It is possible that at low doses, BQ-123 might be a more sensitive pharmacological tool for the detection of abnormal endothelin-1 mediated constriction.

L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients.

Plasma AM and cAMP are increased in type 1 diabetic patients with renal insufficiency. Creatinine clearance (CrClc) and duration of the disease are related to plasma AM levels in these patients.

No abstract