Effects of poor glucose handling on arterial stiffness and left ventricular mass in normal children.

AIM: Cardiovascular risk factors can be present in children and young adults. We previously found abnormal microvascular function in children who had glucose intolerance and insulin resistance. The aim of the present study was to investigate whether they also have abnormalities in left ventricular mass (LVM) and arterial stiffness. METHODS: We measured heart dimensions and LVM using echocardiography, and arterial stiffness using pulse wave analysis in 23 children with good glucose handling (postfeeding glucose: 3.9 to 5 mmol/L) and 21 with poor glucose handling (7.7 to 11.4 mmol/L). RESULTS: The time to pulse reflection was slightly shorter in the poorer glucose handlers (mean+/-SD: 143+/-10 vs 153+/-20 ms, P=0.04), suggestive of increased arterial stiffness. Also in this group, there were significant relationships between intraventricular septal thickness, blood pressure and body mass index, but not in the normal glucose handlers. CONCLUSIONS: We have found that normal children who are in the lowest quintile of glucose tolerance in comparison with their peers are exhibiting the first signs of arterial stiffening. In addition, we have seen the beginnings of a relationship between blood pressure, body mass index and left ventricular enlargement in this group. While these changes may not yet be clinically significant, their emergence might be further evidence of early predisposition to cardiovascular disease.     

N-Phenylethyl Amitriptyline in Rat Sciatic Nerve Blockade

Background: The antidepressant amitriptyline is commonly used orally for the treatment of chronic pain, particularly neuropathic pain, which is thought to be caused by high-frequency ectopic discharge. Among its many properties, amitriptyline is a potent Na+ channel blocker in vitro, has local anesthetic properties in vivo, and confers additional blockade at high stimulus-discharge rates (use-dependent blockade). As with other drug modifications, adding a phenylethyl group to obtain a permanently charged quaternary ammonium derivative may improve these advantageous properties.

Methods: The electrophysiologic properties of N-phenylethyl amitriptyline were assessed in cultured neuronal GH3 cells with the whole cell mode of the patch clamp technique, and the therapeutic range and toxicity were evaluated in the rat sciatic nerve model.

Results: In vitro, N-phenylethyl amitriptyline at 10 [mu]m elicits a greater block of Na+ channels than amitriptyline (resting block of approximately 90%vs. approximately 15%). This derivative also retains the attribute of amitriptyline in evoking high-degree use-dependent blockade during repetitive pulses. In vivo, duration to full recovery of nociception in the sciatic nerve model was 1,932 +/- 72 min for N-phenylethyl amitriptyline at 2.5 mm (n = 7) versus 72 +/- 3 min for lidocaine at 37 mm (n = 4; mean +/- SEM). However, there was evidence of neurotoxicity at 5 mm.     

Why is the age-standardized incidence of low-trauma fractures rising in many elderly populations?

Low-trauma fractures of elderly people are a major public health burden worldwide, and as the number and mean age of older adults in the population continue to increase, the number of fractures is also likely to increase. Epidemiologically, however, an additional concern is that, for unknown reasons, the age-standardized incidence (average individual risk) of fracture has also risen in many populations during the recent decades. Possible reasons for this rise include a birth cohort effect, deterioration in the average bone strength by time, and increased average risk of (serious) falls. Literature provides evidence that the rise is not due to a birth cohort effect, whereas no study shows whether bone fragility has increased during this relatively short period of time. This osteoporosis hypothesis could, however, be tested if researchers would now repeat the population measurements of bone mass and density that were made in the late 1980s and the 1990s. If such studies proved that women's and men's age-standardized mean values of bone mass and density have declined over time, the osteoporosis hypothesis would receive scientific support. The third explanation is based on the hypothesis that the number and/or severity of falls has risen in elderly populations during the recent decades. Although no study has directly tested this hypothesis, a great deal of indirect epidemiologic evidence supports this contention. For example, the age-standardized incidence of fall-induced severe head injuries, bruises and contusions, and joint distortions and dislocations has increased among elderly people similarly to the low-trauma fractures. The fall hypothesis could also be tested in the coming years because the 1990s saw many research teams reporting age- and sex-specific incidences of falling for elderly populations, and the same could be done now to provide data comparing the current incidence rates of falls with the earlier ones.     

Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study.

BACKGROUND: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). METHODS: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery. RESULTS: Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed. CONCLUSIONS: The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results.     

A double blind comparison of diclofenac and indomethacin in the treatment of ankylosing spondylitis

During almost 12 years of development and clinical trials, diclofenac sodium has been shown to be both effective and safe as a new nonsteroidal antiinflammatory drug (NSAID) for the treatment of rheumatic diseases including ankylosing spondylitis (AS). We compared the safety and efficacy of 75, 100, or 125 mg/day of diclofenac with the same doses of indomethacin in a multicenter, randomized, parallel group trial in patients with AS. A single blind placebo washout period of 2 days to 2 weeks preceded the 13-week double blind treatment period. Both diclofenac and indomethacin produced significant (p less than 0.001) improvement from baseline for all 14 efficacy variables analyzed. There were no significant between treatment differences. Differences favored diclofenac in the frequency and the severity of adverse experiences reported and in the frequency of complaints affecting the central nervous system.