Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes.

AIMS: To compare long-term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes. METHODS: This was a double-blind, multicentre, comparative, parallel group trial in 283 patients with Type 2 diabetes, who were randomized to receive 1-year treatment with pioglitazone 30-45 mg/day or gliclazide 80-320 mg/day. Drug dose was titrated on the basis of self-monitored blood glucose (SMBG) measurements and HbA1c values. The 1-year changes in HbA1c, fasting blood glucose (FBG), insulin, HOMA-S (HOmeostatic Model Assessment) and SMBG were compared. In a subgroup of patients (n = 10), systemic glucose production and utilization were determined by a combination of isotopic (deuterated glucose) and clamp techniques. RESULTS: In both groups, there were similar decreases in HbA1c (pioglitazone: -0.79%; gliclazide: -0.79%) and FBG (pioglitazone: -1.0 mmol/l; gliclazide: -0.7 mmol/l), whereas the slope of the reduction of fasting blood glucose was different between groups (P = 0.004). Insulin levels as well as insulin resistance assessed using HOMA-S decreased significantly only after pioglitazone treatment (-11.94 pmol/l and -1.03, respectively, both P = 0.002 vs. baseline). A significantly greater reduction in systemic glucose production was observed in the pioglitazone group (-2.48 micromol/kg/min, P = 0.042) than in the gliclazide group (-1.02 micromol/kg/min). A few, mild adverse events occurred in both groups. CONCLUSIONS: A comparable decrease in HbA1c and FBG was observed with pioglitazone and gliclazide. However, with pioglitazone there was a continuous decrease in FBG over 1 year, whereas gliclazide failed to maintain a similar trend. This favourable effect of pioglitazone was due to its insulin-sensitizing effect and ability to decrease systemic glucose production.     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

Tenotomy prevents the functional improvement of a muscle reinnervated with a chronically severed nerve

During the early stages of nerve implantation, we followed the dynamic properties of the lateral gastrocnemius muscle of the rat, reinnervated with an acutely or chronically severed peroneal nerve. The aim of this study was to ascertain whether (1) the better functional recovery of a muscle reinnervated by a chronically severed foreign nerve is present from the onset of reinnervation, and (2) whether such functional improvement is due to the conditioning lesion effect. Our results indicate that better functional recovery is already apparent one week after nerve implantation, and it is due to the conditioning lesion effect, since tenotomy prevents such improvement. The tenotomy effect underlines the fact that some environmental factors concerning the target tissue, and not only the predegenerated nerve, are involved in the conditioning effect. © 1995 Wiley-Liss, Inc.     

Analysis of circulating gammadelta T cells in children affected by IgE-associated and non-IgE-associated allergic atopic eczema/dermatitis syndrome

Recent studies have suggested that not only alphabeta(+) T cells, but also the less common gammadelta(+) T cells may play a role as effectors and immunoregolatory cells in the development and perpetuation of allergic inflammation. The objective of this study was to focus on the role of gammadelta(+) T cells in atopic dermatitis (AD), a chronic relapsing inflammatory disease of the skin, often associated with allergic bronchial asthma. The present study employed flow cytometric analysis to compare numbers and phenotypic characteristics of gammadelta(+) T cells in the peripheral blood of children with atopic dermatitis and age-matched healthy controls. The percentage of circulating Vgamma 9Vdelta2(+) T lymphocytes was significantly increased in AD patients with respect to the age-matched controls, with a positive correlation with clinical score severity. The prevalent phenotype in both AD patients and controls was CD45RO(+), with no differences observed in the percentage of Vdelta2(+) CD45RO(+) between these groups. Conversely, memory CD45RO(+) CD62L(+) Vdelta2(+) lymphocytes were significantly lower in AD patients. Furthermore, naive circulating Vdelta2(+) T lymphocytes were significantly lower in AD children than in aged-matched controls. No correlation was observed between circulating Vgamma 9Vdelta2(+) expansion and IgE serum levels. It was concluded that an association exists between the levels of circulating gammadelta(+) T lymphocytes and atopic dermatitis, with a positive correlation with clinical score but no link with IgE serum levels. The pathophysiological role of gammadelta T lymphocytes in atopic dermatitis awaits further investigation.     

Value of culture of pus via percutaneous drainage under sonographic guidance in diagnosis and therapy of pyogenic liver abscess

Pyogenic hepatic abscess is often a serious disease, whose rates of cure are proportional to the timeliness of treatment and the correct use of antibiotics. The final choice of antibiotics should be guided by the results of a culture. Local cultures of pus are more often positive than blood cultures It is essential to plan an effective treatment regimen when dealing with immunocompromised patients. Our results, regarding 85 patients with pyogenic liver abscess, 19 of which were immunocompromised, seen at our Department from 1980 to 1992, indicate that planning the therapy on the base of blood culture alone means a 78% risk of inappropriate treatment.     

Hepatitis and cholestasis in infancy: clinical and nutritional aspects

A major complication of cholestasis is fat malabsorption related to decreased intestinal bile acids, which leads to malnutrition and fat-soluble vitamin deficiency. The impaired excretion of bile acids leads to a low intraluminal micellar concentration that causes long-chain triglyceride lipolysis and absorption to be ineffective. Medium-chain triglycerides (MCTs) are more readily absorbed when there are low concentrations of bile acids and therefore are a good source of fat calories; MCTs can be administered as MCT-containing formulas. In those children who are unable to take sufficient calories by mouth, it is important to start nocturnal enteral feeding to improve nutritional status. In infants with cholestasis, the absorption of fat-soluble vitamins (A, D, E and K) that require bile acids is also impaired, and supplementation is mandatory. Vitamin K deficiency may be responsible for hypoprothrombinaemia, which may lead to bleeding diathesis, Vitamin K (phytomenadione) should therefore be promptly administered intravenously, at a dose of 1 mg. Chronic vitamin E (α-tocopherol) deficiency is associated with a progressive neuromuscular syndrome that can cause cerebellar ataxia, areflexia and peripheral neuropathy. Supplements are given orally in doses of 3–5 times the normal requirement if cholestasis is incomplete. In complete cholestasis, supplements must be given intramuscularly at monthly intervals. In infants who fail to thrive, dietary supplements of carbohydrate polymers and MCTs are required.