Subcongenic analysis of a quantitative trait locus affecting body weight and glucose metabolism in zinc transporter 7 (znt7)-knockout mice.

BACKGROUND: A genome-wide mapping study using male F2 zinc transporter 7-knockout mice (znt7-KO) and their wild type littermates in a mixed 129P1/ReJ (129P1) and C57BL/6J (B6) background identified a quantitative trait locus (QTL) on chromosome 7, which had a synergistic effect on body weight gain and fat deposit with the znt7-null mutation. RESULTS: The genetic segment for body weight on mouse chromosome 7 was investigated by newly created subcongenic znt7-KO mouse strains carrying different lengths of genomic segments of chromosome 7 from the 129P1 donor strain in the B6 background. We mapped the sub-QTL for body weight in the proximal region of the previously mapped QTL, ranging from 47.4 to 64.4 megabases (Mb) on chromosome 7. The 129P1 donor allele conferred lower body weight gain and better glucose handling during intraperitoneal glucose challenge than the B6 allele control. We identified four candidate genes, including Htatip2, E030018B13Rik, Nipa1, and Atp10a, in this sub-QTL using quantitative RT-PCR and cSNP detection (single nucleotide polymorphisms in the protein coding region). CONCLUSIONS: This study dissected the genetic determinates of body weight and glucose metabolism in znt7-KO mice. The study demonstrated that a 17-Mb long 129P1 genomic region on mouse chromosome 7 conferred weight reduction and improved glucose tolerance in znt7-KO male mice. Among the four candidate genes identified, Htatip2 is the most likely candidate gene involved in the control of body weight based on its function in regulation of lipid metabolism. The candidate genes discovered in this study lay a foundation for future studies of their roles in development of metabolic diseases, such as obesity and type 2 diabetes.

[Bedside thrombelastography. Cost reduction in cardiac surgery]. / "Bedside"-Thrombelastographie. Kostenreduktion in der Herzchirurgie.

BACKGROUND: Demographic changes and aggressive medication with platelet aggregation inhibitors have resulted in a marked increase in blood and coagulation product expenditure and costs in cardiac surgery. We analyzed the bedside coagulation test (ROTEM) in order to verify clot forming quality and to find a cost-effective treatment algorithm. PATIENTS AND METHODS: Annual treatment costs of all cardiosurgical patients were retrospectively analyzed before (729 patients) and after (693 patients) implementation of the bedside ROTEM test. Cumulative numbers and costs of platelet concentrates (PltC), fresh frozen plasma (FFP), red blood cell units (RBC), and the coagulation factors prothrombin complex concentrates (PCC), recombinant factor VIIa (rFVIIa), factor XIII (FXIII), and fibrinogen were assessed. Average monthly numbers and costs were compared. The number of rethoracotomies and early mortality were assessed and compared in both periods. RESULTS: After ROTEM implementation cumulative RBC expenditure showed a 25% decrease and PltC a 50% decrease. FFP expenditure remained unchanged. PCC, FXIII were markedly reduced (-80%) while rFVIIa was entirely omitted. Fibrinogen, however, showed a two-fold increase. Cumulative average monthly costs of all blood products decreased from 66,000 EUR to 45,000 EUR (-32%). Coagulation factor average monthly costs decreased from 60,000 EUR to 30,000 EUR (-50%) yielding combined savings of 44%. In contrast, average monthly costs for ROTEM were 1,580 EUR. The total number of rethoracotomies decreased from 6.6% to 5.5% while early mortality (5.9%; 6.0%) remained stable. CONCLUSIONS: Cumulative costs for treatment of perioperative coagulation disorders were reduced by bedside ROTEM analysis to achieve a selective substitution management. Saved costs for blood and coagulation products clearly outweighed the expenses of ROTEM. Adequate differential coagulation management can therefore be cost-effective.

Increased prevalence of class I integrons in Escherichia coli, Klebsiella species, and Enterobacter species isolates over a 7-year period in a German university hospital.

The prevalence of integrons in five enterobacterial species was analyzed in 900 blood culture isolates from 1993, 1996, and 1999. Remarkably, the prevalence increased from 4.7% in 1993 to 9.7% in 1996 and finally to 17.4% in 1999 (P < 0.01). Within 7 years the combined percentage of P1 strong promoters and P1 weak plus P2 active promoters with high transcription efficacies has increased from 23.1 to 33.3 and finally 60% (P < 0.05).

Long-term ethanol self-administration with repeated ethanol deprivation episodes changes ethanol drinking pattern and increases anxiety-related behaviour during ethanol deprivation in rats.

In order to study the dynamics of ethanol drinking behaviour, male Wistar rats were given the free choice between tap water, and 5, 10 and 20% ethanol solutions. After 8 weeks of continuous access, the animals were repeatedly deprived of the ethanol solutions for 3 days every 4 weeks. In the first experiment, drinking patterns were recorded for 24 h with an electronic drinkometer device, at different time-points of ethanol experience and after an ethanol deprivation episode. The preference for more highly concentrated ethanol solutions as well as ethanol consumption increased with continuing ethanol experience. Furthermore, after the ethanol deprivation episode, the animals immediately and preferentially drank from the 20% ethanol solution, the most highly concentrated ethanol solution offered. Additionally, the number of drinking bouts, particularly at the 10 and 20% ethanol solutions, was increased during the first hour after ethanol re-presentation. In a second experiment, the effects of repeated ethanol deprivation experience, inherent in this self-administration paradigm, on anxiety-related behaviour were tested on the elevated plus-maze. Repeated ethanol deprivation proved to be more anxiogenic than the first deprivation experience. Taken together, these findings suggest that ethanol deprivation is anxiogenic in long-term voluntarily ethanol-drinking rats, which is increased by repeated ethanol deprivation experience. The possibility that anxiety during ethanol deprivation might contribute to the 'relapse'-like drinking behaviour is discussed.

Forced opiate withdrawal under anaesthesia augments and prolongs the occurrence of withdrawal signs in rats.

A newly developed treatment for rapid detoxification of opiate addicts is the use of continuous naloxone/naltrexone administration under general anaesthesia. This method is now introduced in several European countries despite the fact that there is only spare evidence for its effectiveness. Here we report on the assessment of withdrawal symptoms in morphine-dependent rats which received continuous naloxone administration combined with barbiturate anaesthesia. Morphine-dependent rats were implanted with osmotic minipumps filled with either saline or naloxone (delivering 0.5 mg/kg per hour) under barbiturate anaesthesia (lasting for 8 h). Animals were tested daily for the occurrence of withdrawal signs for the subsequent 7 days. All signs of withdrawal which are frequently observed in rats undergoing morphine withdrawal such as body weight loss, diarrhea, writhing, teeth chattering and wet dog shakes were significantly augmented and observed over longer time periods in morphine-dependent animals treated continuously with naloxone versus rats receiving saline. The present study demonstrates that continuous naloxone treatment under anaesthesia worsen and prolongs the detoxification phase in rats. This conflicts with reported clinical observations, and strongly suggests a need for controlled clinical studies before this method enters the everyday clinical routine.