Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes

Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-alpha/beta, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade.     

A microplate-based enzymatic assay for the simultaneous determination of phenylalanine and tyrosine in serum

BACKGROUND: Several methods have been reported for the quantitation of phenylalanine (Phe) or tyrosine (Tyr) in blood, but the simultaneous determination of Phe and Tyr usually requires sophisticated equipment. Here we describe a simple and reliable microplate assay for measurement of Phe and Tyr in serum of patients with phenylketonuria (PKU). METHODS: Serum was deproteinised and incubated with phenylalanine ammonia-lyase at 37 degrees C for 2 h. Phe and Tyr were converted to trans-cinnamate and trans-coumarate, respectively, which were determined UV spectrophotometrically. RESULTS: The assay demonstrated linearity up to 3200 micromol/l Phe and 640 micromol/l Tyr. The sensitivity of the assay was 15 micromol/l for Phe and 5 micromol/l for Tyr. Analytical recovery was 105% and 97% for Phe and Tyr, respectively. The between-run coefficient of variation (CV) varied with concentration but was 4.7-18.8% for Phe and 4.2-8.8% for Tyr. The within-run CV was 2.7% for Phe and 6.5% for Tyr. Results obtained with the assay correlated well with those of an ion exchange chromatographic method. CONCLUSIONS: This novel assay is sensitive, accurate, precise and suitable for routine monitoring of PKU patients.     

IgG antibodies against microorganisms and atopic disease in Danish adults: the Copenhagen Allergy Study

BACKGROUND: Seropositivity to food-borne and orofecal microorganisms (hepatitis A virus, Helicobacter pylori, and Toxoplasma gondii ), which are considered to be markers of poor hygiene, has been reported to be associated with a lower prevalence of atopy. In contrast, colonization of the gut with Clostridium difficile, a potential intestinal bacterial pathogen, in early childhood may be associated with a higher prevalence of atopy. OBJECTIVE: The objective of this study was to investigate the association between atopy and exposure to 2 groups of food-borne and orofecal microorganisms: (1) markers of a poor hygiene and (2) intestinal bacterial pathogens. METHODS: A cross-sectional population-based study of 15- to 69-year-olds living in Copenhagen, Denmark, was carried out in 1990 to 1991. Atopy was defined as a positive test result for specific IgE to at least 1 of 6 inhalant allergens. Exposure to microorganisms was assessed as IgG seropositivity to microorganisms. RESULTS: Seropositivity to 2 or 3 markers of poor hygiene (hepatitis A virus, H pylori, and T gondii ) was associated with a lower prevalence of atopy (adjusted odds ratio, 0.5; 95% CI, 0.3 to 0.8). In contrast, seropositivity to 2 or 3 intestinal bacterial pathogens (C difficile, Campylobacter jejuni, and Yersinia enterocolitica ) was associated with a higher prevalence of atopy (adjusted odds ratio, 1.7; 95% CI, 1.2 to 2.6). CONCLUSION: Exposure to markers of poor hygiene was associated with a lower prevalence of atopy, whereas exposure to intestinal bacterial pathogens was associated with a higher prevalence of atopy. These findings raise the hypothesis that different groups of food-borne and orofecal microorganisms may have different effects on the risk of atopy.     

On the increased risk of developing late-onset epilepsy for patients with major affective disorder

BACKGROUND: Based on register data we wanted to investigate whether patients with a diagnosis of affective disorder are at increased risk of developing epilepsy compared to other medically ill control groups. METHODS: By linkage of public hospital registers covering the whole of Denmark from 1977 to 1993, using ICD-8 diagnoses, three study cohorts were identified: Patients with first affective disorder episodes (mania and depression), patients with first osteoarthritis and patients with first diabetes discharge. Time to first diagnosis of epilepsy was estimated with the use of survival analysis. RESULTS: A total of 164,227 patients entered the study base: 13,748 patients with mania or depression, 81,380 patients with osteoarthritis and 69,149 patients with diabetes. The risk of getting a diagnosis of epilepsy was increased for patients with affective disorder compared with the risk for the control groups. However, the increased risk seemed to be due to the effect of comorbid alcohol or drug abuse and not to the effect of the affective illness itself. LIMITATIONS: The results only apply to hospitalised patients. Diagnoses are not validated for research purposes. CONCLUSION: Patients with a diagnosis of affective disorder have an increased risk of developing epilepsy in later life. In patients with affective disorder, comorbid alcoholism/drug abuse seriously increased the risk of a subsequent diagnosis of epilepsy.     

Detection of chromosomal imbalances in hepatocellular carcinoma

Hepatocellular carcinoma is the most common malignant tumor of the liver. The discrimination between well-differentiated hepatocellular carcinoma and reactive lesions and benign tumors may be difficult, especially when performed on the basis of needle biopsies. A promising means of solving this problem is provided by chromosomal analysis of imbalances in hepatocellular carcinoma. This article describes the different approaches to ascertain differential diagnosis by chromosomal studies in a reliable and cost-effective manner. It is shown that in situ hybridization techniques provide a reliable means of defining chromosome alterations. These techniques allow the detection of genetic gains and losses of defined chromosomes in a histopathological context and can serve as a helpful tool in establishing diagnosis of liver cell proliferation.     

Sub-classification of low-grade cerebellar astrocytoma: is it clinically meaningful?

OBJECTIVES: The objectives were to identify prognostic factors for the survival of children with cerebellar astrocytoma, and to evaluate the reproducibility and prognostic value of histological sub-classification and grading. METHODS: Children aged 0-14 years treated in Denmark for a cerebellar astrocytoma in the period 1960-1984 were included and followed until January 2001 or until their death. The histological specimens from each patient were reviewed for revised grading and classification according to three different classification schemes: the WHO, the Kernohan and the Daumas-Duport grading systems. RESULTS: The overall survival rate was 81% after a follow-up time of 15-40 years. The significant positive prognostic factors for survival were "surgically gross-total removal" of the tumour at surgery and location of the tumour in the cerebellum proper as opposed to location in the fourth ventricle. No difference in survival time was demonstrated when we compared pilocytic astrocytoma and fibrillary astrocytoma. Moreover, we found that the Kernohan and the WHO classification systems had no predictive value and that the Daumas-Duport system is unsuitable as a prognostic tool for low-grade posterior fossa astrocytomas. CONCLUSION: Discordant observations due to interobserver variability make histological sub-classification of low-grade cerebellar astrocytomas in children insufficient for predicting prognosis and biological behaviour. Similar survival rates in a population of paediatric low-grade cerebellar astrocytomas of grades I and II indicate that tumour grade has no prognostic significance within this group of patients. "Surgically gross-total removal", especially if the tumour is located in the fourth ventricle is of the highest importance for long-term survival. Histological sub-classification of the tumours has no predictive value.