Selective COX2 inhibition improves whole body and muscular insulin resistance in fructose‐fed rats

Background The effects of cyclooxygenase‐1 (COX1) and cyclooxygenase‐2 (COX2) inhibition on insulin resistance in subjects with the metabolic syndrome remain elusive. Aims of this study were to examine the effects of COX1 and COX2 inhibitors on whole body and muscular insulin resistance in fructose‐fed rats, an animal model of the metabolic syndrome. Materials and methods The rats on regular or 60% fructose‐enriched diets for 6 weeks were further divided into rats combined with or without piroxicam (a selective COX1 inhibitor) or celecoxib (a selective COX2 inhibitor) treatment for an additional 2 weeks. Euglycaemic hyperinsulinaemic clamp (EHC) with a tracer dilution method was performed at the end of the study. Results The present result showed that fructose‐induced increases in systolic blood pressure and fasting plasma insulin levels were significantly suppressed in rats treated with celecoxib but not piroxicam. In the EHC period, celecoxib significantly reversed fructose‐induced decreases in whole body glucose uptake, mainly by glucose storage. Hepatic glucose production and whole body glycolysis were not significantly changed among groups. Celecoxib but not piroxicam significantly reversed fructose‐induced decreases in glycogen synthase activities in red and white quadriceps muscles and insulin‐stimulated membrane GLUT4 recruitment in soleus muscles. Celecoxib and piroxicam both significantly diminished fructose‐induced increases in plasma thromboxane B2 and 6‐keto prostaglandin (PG) F1α; but only celecoxib treatment significantly attenuated a fructose‐induced increase in 8‐isoprostane levels. Plasma PGE metabolites were not different among groups. Conclusions This study demonstrates that a therapeutic dose of celecoxib, but not piroxicam, could significantly attenuate fructose‐induced whole body and muscular insulin resistance in rats.     

The needs of family caregivers of frail elders during the transition from hospital to home: a Taiwanese sample

The needs of family caregivers of frail elders during the transition from hospital to home: a Taiwanese sample This study explored the needs of family caregivers during the transition from hospital to home. Data from 37 face-to-face interviews with 16 caregivers before discharge and at 2 weeks and 1 month after discharge were subjected to constant comparative analysis. Findings revealed changes in family caregivers' needs during the discharge transition. While preparing to take caregiving responsibility, caregivers reported a need for various types of information. After the discharge, but before home caregiving settled into a pattern, they needed help with caregiving practices. After reaching a pattern for providing family care, caregivers frequently reported needs for continuous emotional support. These findings provide a basis for transitional care services such as discharge planning and home health care services.     

Regulation of hypoxia-inducible factor-1alpha by cyclical mechanical stretch in rat vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) are exposed to hormonal and mechanical stress in vivo. Hormonal factors have been shown to affect hypoxia-inducible factor-1alpha (HIF-1alpha). How mechanical stress affects the regulation of HIF-1alpha in VSMCs has not been reported previously, and therefore we sought to investigate the regulation of HIF-1alpha by cyclical mechanical stretch in cultured rat VSMCs. Rat VSMCs grown on a flexible membrane base were stretched by vacuum to 20% of the maximum elongation at 60 cycles/min. The levels of HIF-1alpha protein began to increase as early as 2 h after stretch was applied and reached a maximum of 2.8-fold over the control by 4 h. Real-time PCR showed that the levels of HIF-1alpha mRNA increased 2.1-fold after cyclical stretch for 4 h. Cyclical mechanical stretch also increased the immunohistochemical labelling of HIF-1alpha in VSMCs after cyclical stretch for 4 h. The phosphorylation of p42/p44 mitogen-activated protein kinase (MAP kinase) increased after stretch and this was inhibited by the MAP kinase kinase inhibitors PD98059 and U0126. PD98059 and U0126 also blocked HIF-1alpha gene expression induced by cyclical stretch. In conclusion, cyclical mechanical stretch activates the gene expression of HIF-1alpha in cultured VSMCs and this mechanical effect is possibly mediated by the p42/p44 MAP kinase kinase pathway.     

Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction

BackgroundCardiac hypertrophy is a common response to pressure overload and leads to left ventricular (LV) dysfunction. Thrombomodulin (TM), an endothelial anticoagulant protein, was found to have direct effects on cellular proliferation and inflammation. We examined the TM expression in cardiomyocytes during cardiac hypertrophy and investigated its physiological significance.Methods and ResultsTM expression was evaluated in cardiomyocytes from hearts of mice that underwent transverse aortic constriction (TAC). The effects of recombinant TM protein on cardiomyocytes apoptosis and related signaling pathways were examined. Recombinant TM protein was administered continuously in mice that underwent TAC, and serial LV function was determined. There was significant TM expression in cardiomyocytes during cardiac hypertrophy elicited by TAC in mice. TM treatment decreased doxorubicin-induced apoptosis of cardiomyocytes and increased the Bcl-2/Bax ratio. It also increased cardiomyocytes hypertrophy, expression of atrial natriuretic peptide, and significantly activated the extracellular signal–regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (Akt) signaling pathways in cardiomyocytes. Continuous TM supply after TAC prevented the progression of LV contractile dysfunction in mice.ConclusionsTM treatment decreased cardiomyocyte apoptosis and maintained LV contractile function in response to pressure overload.     

Short-Term Red Wine Consumption Promotes Differential Effects on Plasma Levels of High-Density Lipoprotein Cholesterol, Sympathetic Activity, and Endothelial Function in Hypercholesterolemic, Hypertensive, and Healthy Subjects

OBJECTIVES:

To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls.

METHODS:

Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake.

RESULTS:

Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7% (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group.

CONCLUSIONS:

Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine.     

Corpus callosotomy in a patient of hemimegalencephaly and Lennox-Gastaut syndrome

We report the case of a girl with hemimegalencephaly (HME) and Lennox-Gastaut syndrome (LGS) treated by callosotomy at 1 year of age. Over 10 years, her seizure frequency and severity decreased markedly. Hemispherectomy is the main surgical option for HME although HME appears to correlate with a less favorable seizure outcome. However, the clinical presentation of LGS and possible generalized cortical dysplasia, which is indicative of a secondarily generalized epilepsy, might predict a favorable surgical outcome of corpus callosotomy in patients of HME, as in our case.     

Prenatal depiction of angioarchitecture of an aneurysm of the vein of Galen with three-dimensional color power angiography.

A fetus with a large supratentorial cyst and cardiomegaly was encountered at 33 weeks of gestation. The cyst appeared as an aneurysmal, fluid-filled structure extending posteriorly with a finger-like appendage. Using color flow mapping, we disclosed rapid in-and-out blood flow with marked turbulence within the cyst. For evaluation of its blood supply and venous drainage of the vascular malformation, a three-dimensional reconstruction of the power Doppler image was conducted. The results revealed that the vascular malformation was supplied by a small contralateral aneurysm from the branches of Willis' circle, draining posteriorly into an abnormal falcine sinus and then into the superior sagittal sinus. No other fetal abnormality such as hydrocephalus or hydrops was discovered. The prenatal diagnosis of an aneurysm of the vein of Galen was made on the basis of the gray-scale, color Doppler findings, and also the angioarchitecture obtained by three-dimensional power Doppler imaging. The woman was admitted at 37 weeks of gestation due to labor onset and delivered the baby via the vaginal route without complication. Postnatal angiography and magnetic resonance imaging confirmed the diagnosis of an aneurysm of the vein of Galen, and the angioarchitecture depicted it before birth. We suggest that three-dimensional power Doppler ultrasonography may assist in the diagnosis of an aneurysm of the vein of Galen, and precisely delineate the complicated corresponding vasculature. This may guide postnatal management and predict the prognosis more accurately.     

Randomized prospective study comparing routine versus selective use of sonography of the complete calf in patients with suspected deep venous thrombosis

OBJECTIVE: We compared patient outcomes using two protocols: one routinely and the other selectively evaluating the calves completely during sonographic assessment of the lower extremities in patients with suspected deep venous thrombosis. SUBJECTS AND METHODS: In this randomized prospective study, patients were assigned to two groups. In one group, the deep calf veins were routinely evaluated in their entirety, and in the other group the calf was not evaluated unless the patient had symptoms or physical signs in the calf, in which case only the areas of symptoms or physical signs were evaluated. Patients were followed up for 3 months by medical record review, physician surveys, and telephone calls. An adverse outcome was a propagated deep venous thrombosis into the thigh or a pulmonary embolus. Examination times were recorded when possible. RESULTS: Of the 235 patients in the group in which the deep calf veins were routinely evaluated, we saw no adverse outcomes (0.0%; 97.5% one-sided confidence interval [CI], 0.6-1.6%). Of the 261 patients in the group in which the calf was only evaluated if there were signs or symptoms, we saw two adverse outcomes (0.8%; 95% CI, 0.1-2.7%). CONCLUSION: We found no significant difference in adverse outcomes in patients undergoing a protocol in which the deep calf veins were routinely evaluated or a protocol in which the calf was evaluated only if physical signs or symptoms were present.     

Intrauterine diagnosis of heterotaxy syndrome

Background Heterotaxy syndrome, including right isomerism and left isomerism, is characterized by an abnormal symmetry of the viscera and veins and is frequently associated with complex cardiac anomalies. We sought to define the feasibility of in utero diagnosis and the postnatal outcome. Methods Patients with heterotaxy syndrome were identified from 579 fetal echocardiograms performed from January 1994 to December 1998. The diagnosis was made on the basis of the fetal echocardiographic findings and was confirmed with autopsy or postnatal evaluation. Results A total of 25 fetuses with right isomerism and 4 with left isomerism constitute the study population. The pregnancies of 7 fetuses (6 right and 1 left isomerism) were terminated before the 24th gestational week and subjected to autopsy. Twelve fetuses (10 right and 2 left isomerism) were lost to follow-up. Nine with right isomerism and 1 with left isomerism were delivered and underwent palliation. Among them, 5 patients (56%) with right isomerism died and more than half of the deaths occurred during infancy. The major cardiac anomalies detected and confirmed with postnatal evaluation or autopsy in fetuses with right isomerism were total anomalous pulmonary venous connection (6/15; 40%), common atrium (15/15; 100%), complete atrioventricular canal (15/15; 100%), double outlet right ventricle (15/15; 100%), and pulmonary stenosis (11/15; 73%). The major cardiac anomalies in fetuses with left isomerism were interruption of inferior vena cava (2/2; 100%), common atrium (1/2; 50%), and complete atrioventricular canal (1/2; 50%). Undetected lesions with fetal echocardiogram were abnormal pulmonary venous return to systemic veins in 1 case (sensitivity, 83%; 5/6; and specificity, 90%; 9/10) and outflow obstruction in 1 case (sensitivity, 91%; 11/12; and specificity, 67%; 2/3). Different patterns of rhythm disturbances were identified: supraventricular tachycardia in 1 case with right isomerism and sinus bradycardia with junctional rhythm in 3 cases with left isomerism (2 of them lost to follow-up). After birth, another 2 patients with right isomerism had supraventricular tachycardia, and 1 with left isomerism had sinus bradycardia develop at age 2 years. Conclusion Heterotaxy syndrome is usually detected in fetuses with the sonographic cardiac abnormalities. Visualization of the pulmonary venous return and outflow obstruction and characterization of the rhythm disturbances are feasible. However, in spite of prenatal diagnosis, the prognosis remains poor. (Am Heart J 2002;143:1002-8.)