Health-related quality of life following surgical attenuation of congenital portosystemic shunts versus healthy controls.

OBJECTIVES: To design a health-related quality of life questionnaire for dogs with congenital portosystemic shunts, use it in a cohort of dogs treated with suture attenuation and compare results with those obtained from a healthy control cohort. MATERIALS AND METHODS: Data were collected from the hospital records of dogs treated with suture ligation of an intrahepatic or extrahepatic congenital portosystemic shunt at two referral centres. Owners were asked to complete a questionnaire assessing their dog's health-related quality of life preoperatively (retrospectively) and at the time of follow-up. Owners of control dogs also completed the questionnaire. RESULTS: One hundred and twenty-eight dogs with congenital portosystemic shunts and 131 control dogs were recruited. Median follow-up time was 64 months (range 19.7 to 157.2). The median long-term health-related quality of life score was excellent for both intrahepatic and extrahpatic shunt cases and similar to that of control dogs. The long-term portosystemic shunt clinical sign scores for both intrahepatic and extrahepatic congenital portosystemic shunt dogs were significantly worse than the those of the control group. CLINICAL SIGNIFICANCE: Suture attenuation of congenitial portosystemic shunts is associated with an excellent health-related quality of life score at long-term follow-up.

Coordinated existence of multiple gangliosides is required for cartilage metabolism.

OBJECTIVE: Gangliosides, ubiquitously existing membrane components that modulate transmembrane signaling and mediate cell-to-cell and cell-to-matrix interactions, are key molecules of inflammatory and neurological disorders. However, the functions of gangliosides in the cartilage degradation process remain unclear. We investigated the functional role of gangliosides in cartilage metabolism related to osteoarthritis (OA) pathogenesis. DESIGN: We generated knockout (KO) mice by targeting the ß1, 4-N-acetylgalactosaminyltransferase (GalNAcT) gene, which encodes an enzyme of major gangliosides synthesis, and the GD3 synthase (GD3S) gene, which encodes an enzyme of partial gangliosides synthesis. In vivo OA and in vitro cartilage degradation models were used to evaluate the effect of gangliosides on the cartilage degradation process. RESULTS: The GalNAcT and GD3S KO mice developed and grew normally; nevertheless, OA changes in these mice were enhanced with aging. The GalNAcT KO mice showed significantly enhanced OA progression compared to GD3S mice in vivo. Both GalNAcT and GD3S KO mice showed severe IL-1α-induced cartilage degradation ex vivo. Phosphorylation of MAPKs was enhanced in both GalNAcT and GD3S KOs after IL-1α stimulation. Gangliosides modulated by GalNAcT or GD3S rescued an increase of MMP-13 induced by IL-1α in mice lacking GalNAcT or GD3S after exogenous replenishment in vitro. CONCLUSION: These data show that the deletion of gangliosides in mice enhanced OA development. Moreover, the gangliosides modulated by GalNAcT are important for cartilage metabolism, suggesting that GalNAcT is a potential target molecule for the development of novel OA treatments.

Regulation of G protein-coupled receptor kinases by phospholipids.

G protein coupled-receptor (GPCR) kinases (GRKs) initiate the deactivation of GPCRs by phosphorylating their cytoplasmic loops and C-terminal tails. They are regulated not only by allosteric interactions with activated GPCRs, but also by the membrane environment itself. Herein we describe how the various GRKs are recruited to lipid bilayers and, where evident, how specific anionic phospholipids help regulate their activity. Using crystal structures representing each of the three vertebrate GRK subfamilies, we map the lipid binding sites in order to better understand how these enzymes are oriented at the cell surface. This analysis suggests that GRKs bind lipid and active GPCRs in a coordinated manner.

Episodic plate separation and fracture infill on the surface of Europa. Galileo Imaging Team.

Images obtained by the Voyager spacecraft revealed dark, wedge-shaped bands on Europa that were interpreted as evidence that surface plates, 50-100 km across, moved and rotated relative to each other. This implied that they may be mechanically decoupled from the interior by a layer of warm ice or liquid water. Here we report similar features seen in higher resolution images (420 metres per pixel) obtained by the Galileo spacecraft that reveal new details of wedge-band formation. In particular, the interior of one dark band shows bilateral symmetry of parallel lineaments and pit complexes which indicates that plate separation occurred in discrete episodes from a central axis. The images also show that this style of tectonic activity involved plates < 10 km across. Although this tectonic style superficially resembles aspects of similar activity on Earth, such as sea-floor spreading and the formation of ice leads in polar seas, there are significant differences in the underlying physical mechanisms: the wedge-shaped bands on Europa most probably formed when lower material (ice or water) rose to fill the fractures that widened in response to regional surface stresses.

Relation of blood pressure, serum lipids, and smoking to the risk of cerebral stroke. A longitudinal study in Eastern Finland.

The impact of blood pressure, serum cholesterol and triglycerides, and smoking on the risk of cerebral infarction and other stroke was studied by a longitudinal design. A random sample of the population aged 35-59 years in two counties of Eastern Finland was examined in 1972, with a participation rate of 92 per cent. In subjects (both sexes) standardized epidemiological measurements on blood pressure, height, weight, and serum lipids were made and questionnaire data were obtained on smoking. The cohort was followed for seven years by means of national hospital discharge and death certificate registers. During the follow-up 77 men and 65 women had a cerebral stroke. Based on multiple logistic risk function analysis, age, smoking, blood pressure, and history of previous stroke and diabetes turned out to be independent predictors of both cerebral infarction and other strokes in men. Diastolic blood pressure of 100 mm Hg or more was associated with a 1.9-fold (90% CI = 1.1-3.6) risk of cerebral infarction in men and 2.5-fold (90% CI = 1.1-5.6) risk in women with no previous stroke. In men 37% (90% CI = 21-53%) of all cerebral strokes were attributable to systolic blood pressure of 150 mm Hg or more and 27% (90% CI = 11-42%) to diastolic blood pressure of 95 mm Hg or more.

Effect of guar gum on body weight and serum lipids in hypercholesterolemic females.

The effect of guar gum (15 g/day) on serum lipids and body weight of middle-aged hypercholesterolemic females was studied in a double-blind controlled trial. No consistent changes were observed in serum cholesterol, triglycerides or HDL cholesterol in patients taking guar gum, placebo or no medication at all. A highly significant decrease in body weight (62.9 +/- 2.1 vs. 60.4 +/- 2.2 kg, p < 0.0005, paired comparison) was seen in subjects receiving guar gum, whereas body weight remained constant in the other two groups. It is concluded that the daily ingestion of 15 g of guar gum results in a permanent weight loss, but does not influence serum lipids in females with hypercholesterolemia.