Interleukin-6 -174 G/C promoter polymorphism and effects of fenofibrate and simvastatin on inflammatory markers in hypercholesterolemic patients.

To evaluate whether the interleukin-6 (IL-6) -174 G/C polymorphism might alter the effects of micronized fenofibrate or simvastatin therapy on inflammatory markers, we measured IL-6, C-reactive protein, CD40 ligand, adhesion molecules, P-selectin and monocyte chemoattractant protein-1 in hypercholesterolemic patients both before and after a 30-day treatment. Serum IL-6 levels were significantly higher in patients with the GC or CC genotypes (P=0.04). The presence of the C allele was associated with greater absolute reduction of IL-6 levels (P=0.04) following fenofibrate treatment. There was no significant association between the -174 G/C IL-6 polymorphism and the effects of simvastatin treatment. A relationship between the -174 G/C IL-6 polymorphism and the anti-inflammatory action of fenofibrate reported might be useful in the optimization of the treatment regimen in patients receiving this class of drugs.     

In vivo PET imaging of cardiac presynaptic sympathoneuronal mechanisms in the rat.

The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans. METHODS: We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves. RESULTS: At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%. CONCLUSION: Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans.     

Effect of estrogens on bone marrow adipogenesis and Sirt1 in aging C57BL/6J mice

Age-related bone loss has been associated with high levels of marrow adipogenesis. Estrogens (E₂) are known to regulate the differentiation of marrow precursors into osteoblasts, however, their role in bone marrow adipogenesis remain unknown. E₂ regulate adipocyte differentiation in subcutaneous and visceral fat through interaction with other nuclear receptors. This interaction has not been assessed in bone marrow adipocytes in vivo. In this study, we compared two groups of animals, young and old, after either oophorectomy (OVX) or oophorectomy plus E₂ (OVX + E₂) replacement. We found that absence of E₂ was associated with higher levels of PPARγ and lower levels of Sirt1 most significantly in the old group. In addition, old mice responded better to E₂ replacement in terms of reducing adipogenesis and PPARγ expression as well as increasing levels of Sirt1 expression. Our findings represent a new understanding of the role of E₂ in age-related bone loss, which could be mediated through the regulation of Sirt1 expression within the bone marrow. In addition, this evidence suggests that old individuals may show a better response to E₂ administration in terms of reverting the high levels of marrow fat seen in age-related bone loss.     

Modified Epworth Sleepiness Scale in Chinese children with obstructive sleep apnea: a retrospective study

Background and objective  The purpose of this study is to assess whether Chinese children with high apnea–hypopnea index (AHI) are sleepier by a modified Epworth Sleepiness Scale (ESS). Materials and methods  Records were retrospectively reviewed. We included children who were between 3 and 12 years old, admitted for overnight polysomnogram because of suspected obstructive sleep apnea syndrome (OSAS). A modified ESS was used to assess excessive daytime sleepiness (EDS) of the children. Results  One hundred ninety-two Chinese children were included. Children with high AHI, defined as AHI > 5.0, were sleepier than children with AHI less than or equal to 5. After adjustment by age, gender, and obesity, children with high AHI remained significantly sleepier. Modified ESS was significantly correlated with AHI (rho = 0.124, 95% CI = 0.004–0.281). Modified ESS score of >8 was the best cutoff point with the sensitivity and specificity of 0.29 and 0.91, respectively. The odds ratio of children with modified ESS > 10 having high AHI was 4.231 (95%CI = 1.248 to 14.338) and children with modified ESS > 8 had the highest odds ratio, 4.295(95%CI = 1.66 to 11.1), of having high AHI. Conclusion   Chinese children with high AHI appear to be sleepier than children with low AHI. Children with suspected OSAS and high modified ESS, i.e., ESS > 8, had significantly higher odds ratio of having high AHI. Increased sleepiness is a specific but not a sensitive symptom in snoring children with high AHI. Screening for EDS in snoring children may help us identify those with high AHI and prioritize the management of those children. All authors worked and the study was carried out in Kwong Wah Hospital in Hong Kong. There was no conflict of interest and no specific source of funding for the study.     

The effect of apomorphine on regional cerebral blood flow in schizophrenia

A double-blind, placebo-controlled crossover study of the effects of apomorphine on regional cerebral blood flow (rCBF) during a prefrontal cortex activation task was undertaken to explore the role of dopamine on cortical function. The subjects were eight drug-free, chronically psychotic patients; six patients had schizophrenia. In each, apomorphine increased the relative prefrontal flow. The results suggest that enhanced prefrontal dopamine activity may reverse deficits in prefrontal cortex metabolism in schizophrenia.     

A patient with right and left atrial membranes: the role of transesophageal echocardiography and magnetic resonance imaging in diagnosis

A patient who had right and left atrial membranes was examined. The diagnosis and the hemodynamic significance of both membranes were detailed by transesophageal echocardiography and were confirmed by magnetic resonance imaging. Transesophageal imaging was found to be superior to routine echocardiography in visualization of these atrial structures.