Thyroid hormone stimulates hepatic IGF-I mRNA expression in a bony fish,the tilapia Oreochromis mossambicus,in vitro and in vivo

To gain more knowledge about the physiological regulation of hepatic insulin-like growth factor-I (IGF-I) production in bony fish, we examined the potential influence of thyroid hormone (T3, 3,5,3'-triiodothyronine) on the expression of IGF-I in the liver of the tilapia Oreochromis mossambicus, using in vitro and in vivo methods. The in vitro experiments were performed using a recently established primary hepatocyte cell culture and IGF-I expression was determined by means of semiquantitative RT-PCR. T3 (100 nM) significantly enhanced the synthesis rate of IGF-I mRNA in short (>8h) and long (>42h) time courses. The stimulating effect of T3 was detected already after 1h. After 4h, the IGF-I mRNA expression was more than 150% of the starting amount. In long time courses, after 6h the IGF-I mRNA value was about 170% of that in untreated cells and at the end of the experiment, it was still three times higher than in the control. In addition, the increase in IGF-I mRNA expression evoked by T3 (1 nM to 1 microM) was dose-dependent. In the in vivo approach, 10 individuals of tilapia received 4 daily intraperitoneal injections of T3 (6 microg/g body weight). IGF-I mRNA was assessed using dot blot technique with a tilapia specific IGF-I cRNA probe. The T3 treatment led to an increase of the IGF-I mRNA level up to 45% in the liver compared to the untreated animals. In conclusion, our results show that T3 directly stimulates the hepatic production of IGF-I in the tilapia in vitro and in vivo and indicate that in tilapia liver regulatory mechanisms seem to exist, as they are discussed for mammals.     

Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stentgrafts versus bare stents

In patients with liver cirrhosis, implantation of a transjugular intrahepatic shunt (TIPS) leads to reduction of portal pressure, but not of mortality compared with other therapies. The high stenosis rates of conventional bare stents causes high reintervention rates and costs and may be correlated with poor survival. ePTFE-covered stentgrafts provide much improved patency rates, but their impact on survival is unclear. All suitable patients receiving either bare TIPS (419/466) or undergoing implantation of ePTFE endoprostheses (89/100) in several centers in Austria up to 2002 were included in this retrospective analysis. Both patient groups were compared regarding survival with Kaplan-Meier and Cox regression analysis. Unmatched and 1:1-matched survival analyses were performed. Patients undergoing ePTFE stentgraft implantation had significantly higher survival rates in all analyses. The 3-month, 1-year, and 2-year survival rates were 93%, 88%, and 76% for the ePTFE-group and 83%, 73%, and 62% for conventional TIPS patients, respectively. The matched survival analyses validated these findings. The model of the stent, patient age, and Child-Pugh Class (CPC) were independent predictors of survival. In conclusion, patients undergoing ePTFE-endoprosthesis implantation had higher survival rates within 2 years after TIPS-implantation. This may be the result of improved patency rates after correct placement (up to the inferior caval vein [ICV]) of the ePTFE stentgraft. These data should be validated in a prospective series.     

Overexpression of Polo-like kinase 1 is a common and early event in pancreatic cancer.

BACKGROUND: There is abundant evidence from in vivo and in vitro studies that Polo-like kinase 1 (PLK1) plays a crucial role in the regulation of proliferative activity of normal and malignant cells. Therefore, PLK1 has been proposed as a new target for antineoplastic treatment strategies. METHODS: We conducted an immunohistochemical expression study for PLK1 on 86 cases of pancreatic adenocarcinoma as well as on 5 cases of chronic pancreatitis. Additionally, we investigated the correlation of PLK1 expression levels with clinicopathological data and patient survival. RESULTS: PLK1 was found overexpressed in pancreatic neoplasia as early as in pancreatic intraepithelial neoplasia III lesions, whereas benign acinar pancreatic parenchyma and ductal epithelia showed only focal PLK1 positivity. Invasive pancreatic adenocarcinomas were PLK1 positive in 47.7% of cases. No correlation of PLK1 positivity and the extent of tumour spread was evident, nor did PLK1 expression correlate with tumour grade or patient prognosis. Prognostic factors in our study cohort were nodal status and tumour grade. CONCLUSIONS: The fact that half of the invasive pancreatic carcinomas strongly overexpressed PLK1 indicates that inhibition of this mitotic key regulator might represent a rewarding approach in the treatment of early and late pancreatic carcinoma.     

Echocardiographic findings in former professional cyclists after long-term deconditioning of more than 30 years.

BACKGROUND: In professional cyclists, typical changes include reversible dilatation of atria and left ventricle (LV), LV hypertrophy but normal diastolic function. Data on long-term outcome are limited. METHODS: Of all 134 former Swiss professional cyclists (PC) participating >or=1x in the professional bicycle race Tour de Suisse from 1955 to 1975, 62 (42%) were recruited for a prospective case control study. The PC and a control group of 62 golfers (matched for age, gender, hypertension, present physical activity) were screened [clinical examination, history, echocardiography, measurement of proBNP (normal <227 pg/mL)]. RESULTS: The interval since the last bicycle race as PC was 38 (15-49) years. Average age at exam was equal in controls and PC (66+/-6 vs 66+/-7 years; P = 0.73). Percentage of participants undergoing >4 h of endurance training per week was identical (P = 0.72). Total kilometers (km) on the bicycle were higher in PCs with 311,000 (60,000-975,000) than in controls (2500 [0-120,000]; P < 0.0001). PC had larger atrial volume indices (P = 0.002) and tended to have higher LV muscle mass indices (P = 0.07). Multiple regression analysis identified the total number of bicycle km as an independent factor for LV muscle mass. For left atrial size, heart rate at rest, age, years since the last bicycle race and the current hours of endurance training were identified as independent predictors. Long axis function of both ventricles (systolic velocities of mitral and tricuspid annulus) was decreased in PC (P 相似文献   

Das Delir im höheren Lebensalter

Delirium is a common, serious medical and often life-threatening condition in elderly in-patients. Delirium can develop primarily or secondarily related to other medical conditions and lead to hospital admission. The pathogenesis is still not fully known and is usually addressed as multifactorial. Alterations in neurotransmitters have a key role in this process. The incidence varies by setting up to 90%. Delirium is associated with increased short- and long-term mortality, iatrogenic complications, functional decline, and future development of cognitive impairment or dementia. Delirium is also associated with longer hospital stays, higher hospital and total health system costs, and an increasing rate of nursing home admissions. A structured diagnostic and therapeutic process is recommended. Delirium should become a quality indicator for hospital medicine; however, many research questions still exist.     

Improved quality of life in patients with refractory or recidivant ascites after insertion of transjugular intrahepatic portosystemic shunts

BACKGROUND AND AIMS: A substantial proportion of patients with chronic hepatitis C virus infection have persistently normal serum transaminase levels. The aim of this study was to assess the efficacy and safety of interferon plus ribavirin combination therapy in this population. METHODS: In this prospective open trial 152 patients with biopsy-proven chronic hepatitis C were enrolled, 32 of whom had persistently normal alanine aminotransferase levels (group A). The remaining 120 patients served as a comparison (group B). Patients were treated for 12 months with 4.5 million units of interferon-alpha(2a) thrice weekly in combination with ribavirin 1,000 or 1,200 mg daily. They were followed up for at least 6 months after therapy. Serum hepatitis C RNA was detected by polymerase chain reaction and quantified by a branched DNA assay. RESULTS: At the end of treatment, 12 (37.5%) and 48 patients (40%) were negative for HCV-RNA in groups A and B, respectively (p = 0.33). After 24 weeks of follow-up, 9 patients (28%) from group A and 36 patients (30%) from group B were still HCV-RNA negative (p = 0.4). Treatment was well tolerated by both groups. There were no alanine transferase elevations among group A patients during therapy. CONCLUSION: Interferon-ribavirin combination therapy was safe and induced a sustained virologic response in a significant proportion of patients with chronic hepatitis C and repeatedly normal serum transaminase levels.     

Correction by CSF-1 of defects in the osteopetrotic op/op mouse suggests local, developmental, and humoral requirements for this growth factor

Mice that are mutant at the op locus have a severe deficiency of mononuclear phagocytes due to an inactivating mutation in the CSF-1 (macrophage colony-stimulating factor, M-CSF) gene. op/op mice are toothless, possessing skeletal abnormalities, a low body weight, and compromised fertility; they are osteopetrotic due to a deficiency of osteoclasts. The congenital osteopetrosis, toothless phenotype, osteoclast deficit, and the defects in splenic and femoral macrophages were corrected by routes of administration of human recombinant CSF-1 that maintained normal circulating CSF-1 concentrations. Early restoration of circulating CSF-1 was required for rescue of the toothless phenotype, but only partially restored body weight. In contrast, the deficiencies of pleural and peritoneal cavity macrophages and the reduced female fertility were not corrected by restoration of circulating CSF-1. These results suggest that although circulating CSF-1 is required for osteoclast and macrophage production, local synthesis and action of the growth factor are important for certain target cell populations.