Endothelial nitric oxide synthase genotype modulates the improvement of coronary blood flow by pravastatin: a placebo-controlled PET study

The objective was to study whether coronary blood flow or its response to pravastatin are affected by genetic variation in the endothelial nitric oxide synthase (eNOS) gene. Vascular endothelial nitric oxide maintains endothelium-dependent vasodilatation and also mediates antithrombotic actions. Its formation is catalyzed by eNOS, a constitutive enzyme, which has a polymorphic site in intron 4 (4a/b). Some clinical studies have suggested an association of the rare a-allele of eNOS with coronary artery disease and myocardial infarction. We carried out a double-blind placebo-controlled study involving 43 men (aged 35+/-4 years), who were randomized to receive either 40 mg/day pravastatin ( n=21) or placebo ( n=22) for 6 months. Myocardial blood flow was measured by positron emission tomography (PET) using (15)O-labeled water. PET was performed at rest and after stimulation by adenosine infusion. PET and lipid analyses were carried out at baseline and after 6 months. eNOS genotyping was done by PCR. At baseline there were no differences in basal or adenosine-stimulated coronary blood flow between subjects with either eNOS bb or ba genotypes. At the end of the study genotypes reacted differently between pravastatin and placebo groups with respect to the change in adenosine-stimulated flow (ANCOVA P=0.008). More specifically, after pravastatin treatment the adenosine-stimulated flow increased by 54.5% in men with the eNOS ba genotype, whereas in the men with the bb genotype no significant change in flow was observed ( P=0.002 for ba versus bb). In the placebo group there were no significant changes in blood flow from the baseline values ( P=0.916 for ba versus bb). After pravastatin treatment both genotype groups showed a similar decrease in serum total cholesterol and low-density lipoprotein cholesterol ( P<0.00001 for both). Our results suggest that adenosine-stimulated myocardial perfusion improves after treatment with pravastatin in subjects with the eNOS ba genotype but not in those with the bb genotype. This effect is not dependent on the decrease of serum cholesterol.     

Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans

Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21–30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity.     

Onchocerca volvulus microfilariae avoid complement attack by direct binding of factor H

The filarial parasite Onchocerca volvulus is the causative agent of river blindness. The adult worms produce microfilariae (mf), which are responsible for the disease pathogenesis; mf activate the complement system, but the activation stops before the formation of terminal complement complexes. Because of the arrest of complement activation, this study analyzed binding of the main alternative pathway regulator, factor H (fH), to the mf. The mf bound fH after incubation in nonimmune human serum or with purified radiolabeled fH. In the presence of factor I, mf-bound fH promoted the cleavage of complement 3 molecule b (C3b) to iC3b. An analysis with recombinant constructs of fH showed that the C-terminal short consensus repeats (SCRs) 8-20 of fH bound to mf, whereas the N-terminal SCRs 1-7 containing the complement-regulatory domains in SCRs 1-5 did not. Thus, mf of the nematode O. volvulus may evade human complement by binding fH and by promoting inactivation of C3b into iC3b.     

Smoking may impair the bone protective effects of nutritional calcium: a population-based approach

Postmenopausal women were randomly selected to investigate the effects of smoking on prevention of bone loss with nutritional calcium. DXA was performed twice, and smoking and calcium intake habits were inquired through the mail in 954 women. Smoking dampened the bone protective effects of nutritional calcium. This may reflect the pathophysiology underlying smoking-induced bone loss postmenopause. This study evaluated the effect of smoking on the bone protective properties of nutritional calcium. Of the random sample of 954 peri- and postmenopausal women selected from the Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort (n = 13,100) in Kuopio, Finland, 182 had smoked at some time (ever smokers) and 772 had never smoked. Women were divided in tertiles according to self-reported dairy nutritional calcium intake (mg/day): < 648 (1st), 648-927 (2nd), > 927 (3rd). Bone mineral density at lumbar spine (LS) and femoral neck (FN) was measured with DXA at baseline in 1989-1991 and at the 5-year follow-up in 1994-1997. In a linear regression model, nutritional calcium intake did not predict annual bone loss in smokers. These results were similar in the subanalysis on 71 current smokers (at both baseline and 5-year measurements) and on 85 past smokers. In never smokers, a statistically significant linear trend was observed between calcium intake and annual bone loss at LS, but at FN only after adjustment for age, weight, hormone replacement therapy (HRT), and other covariates. In analysis of covariance (ANCOVA), no differences in bone loss rate were observed between calcium intake tertiles among smokers. In nonsmokers, the annual bone loss rate was lower in the second (-0.41%) and the third (-0.35%) tertile compared with the first tertile (-0.61%) at LS (p < 0.05) and lower in the third tertile (-0.55%) than in first tertile (-0.72%) at FN after adjustment for age, weight, HRT, and other covariates (p < 0.05). When smokers were added to the nonsmoker group, the differences in bone loss rate between calcium intake tertiles disappeared. In addition, in ANCOVA, the term of interaction between smoking and calcium intake was statistically significant at LS only. In conclusion, smoking seems to impair the bone protective effects of nutritional calcium in postmenopausal women, more clearly in LS than FN.     

Soluble Adhesion Molecules and Myocardial Injury during Coronary Artery Bypass Grafting

Abstract Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery. Leukocyte-endothelial binding followed by neutrophil migration appears to play a central role. These interactions are mediated by adhesion molecules on the surface of activated cells. The present study compared the perioperative levels of soluble adhesion molecules after coronary artery bypass grafting (CABG) in patients with or without cardiopulmonary bypass (CPB). Altogether, 9 patients underwent off-pump revascularization and 11 did so with CPB. Plasma levels of soluble adhesion molecules sE-selectin and sP-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before anesthesia induction and 1, 4, and 20 hours after reperfusion to the myocardium. The baseline plasma levels of the adhesion molecules were similar in the two groups. Perioperative levels of sE-selectin remained the same and did not differ between groups. Plasma sP-selectin increased in both groups, the change being significantly greater in the CPB group than that in the off-pump group (p = 0.001). Plasma sICAM-1 decreased during an early stage after CABG with CPB, recovering at 4 hours after reperfusion; and a significant increase in ICAM-1 was observed 20 hours later. In the off-pump group, sICAM-1 levels did not change at 1 and 4 hours after reperfusion but increased 20 hours later. Postoperative creatine kinase–muscle bound (CK-MB) levels were significantly higher in the CPB group than in the off-pump group (p = 0.001). The change in sP-selectin levels also showed a correlation with CK-MB values (r = 0.676, p = 0.001). The results indicated that off-pump revascularization is associated with reduced endothelial activation and myocardial injury.     

Reproduction,blood and plasma parameters and gill histology of vendace (Coregonus albula L.) in long-term exposure to acidity and aluminum

Vendace were exposed to pHs 4.75 and 5.25 with or without added aluminum (200 microg=7.4 micromol AlL(-1)) from late endogenous vitellogenesis in July through the spawning period. At the normal time of spawning, when 48% of the control females had already released their eggs, 50% of females at pH 4.75+Al had completely unovulated oocytes. The final proportions of completely ovulated females were 14%, 36%, 25%, 61%, and 81% at pH 4.75+Al, pH 4.75, pH 5.25+Al, pH 5.25, and in the control group, respectively. Delayed testes regression was seen in males at pH 4.75+Al. A clear decrease in plasma Na(+) and Cl(-) and an increase in blood glucose concentration was detected only near spawning time, from October to November, coincident with Al accumulation inside the gill tissue. It is concluded that seasonal changes, probably related to reproductive physiology or to the decrease in water temperature, are associated with the increase in Al toxicity in vendace.     

Bioabsorbable miniplating versus metallic fixation for metacarpal fractures

Bioabsorbable implants offer an attractive alternative to metallic implants to stabilize small bone fractures in the hand. Self-reinforced bioabsorbable miniplating for metacarpal fractures was studied in bones from cadavers and compared with standard metallic fixation methods. One hundred twelve fresh-frozen metacarpals from humans had three-point bending and torsional loading after transverse osteotomy followed by fixation using seven methods: (1) dorsal and (2) dorsolateral 2-mm self-reinforced polylactide-polyglycolide 80/20 plating, (3) dorsal and (4) dorsolateral 2-mm self-reinforced poly-L/DL-lactide 70/30 plating, (5) dorsal 1.7-mm titanium plating, (6) dorsal 2.3-mm titanium plating, and (7) crossed 1.25-mm Kirschner wires. In apex dorsal and palmar bending, dorsal self-reinforced polylactide-polyglycolide and poly-L/DL-lactide plates provided stability comparable with dorsal titanium 1.7-mm plating. When the bioabsorbable plates were applied dorsolaterally, apex palmar rigidity was increased and apex dorsal rigidity was decreased. Bioabsorbable platings resulted in higher torsional rigidity than 1.7-mm titanium plating and in failure torque comparable with 2.3-mm titanium plating. Low-profile selfreinforced polylactide-polyglycolide and poly-L/DL-lactide miniplates provide satisfactory biomechanical stability for metacarpal fixation. These findings suggest that bioabsorbable miniplating can be used safely in the clinical stabilization of metacarpal and phalangeal fractures.     

Occurrence of chronic disease in former top-level athletes. Predominance of benefits,risks or selection effects?

Former elite athletes from most sports disciplines have lower overall morbidity risk and enjoy better self-rated health in later years compared with the general population and matched controls who were healthy at young age. This is seen particularly among former endurance athletes who have a lower incidence of coronary heart disease and type 2 diabetes mellitus. Most often data are available only for men. Based on the available data, participation in elite sports cannot be regarded as an overall health hazard. However, aside from a high risk of acute injury in specific sports, possible negative effects of long-standing athletic activity on the development of osteoarthritis should not be neglected. It should also be remembered that elite athletes are a biologically and genetically select group who are not representative of the population at large. Given the nature of the available data, the possible health consequences of recent changes in different characteristics of sports, such as training practices, professionalism and use of doping, cannot be properly predicted.