Relative bioactivity of alpha- and gamma-tocopherol calculated from respiration parameters in rat liver mitochondria

In experiments with male wistar rats the influence of dl-alpha-tocopherol as well as dl-gamma-tocopherol on both the respiration of liver mitochondria and membrane lipid peroxidation has been investigated. For a test period of 8 weeks the animals were fed isoenergetic diets containing either no vitamin E or 46 mg d-alpha-tocopherol equivalents/kg diet as dl-alpha-tocopherol (60 ppm) or dl-gamma-tocopherol (480 ppm). The diets contained 6% of a synthetic triglyceride mixture rich in polyunsaturated fatty acids (about 60%). The measurements of the P/O ratios and corresponding respiratory control index (RCI) values for several substrates (alpha-ketoglutarate, malate/glutamate, succinate) indicated that under vitamin E-deficient conditions the mitochondria showed an increased respiratory intensity accompanied with an elevated lipid peroxidation. The oxidative phosphorylation itself was not affected. These deficiency symptoms could be normalized by the applied amounts of both tocopherols. In this respect dl-gamma-tocopherol showed a more distinct bioactivity than previously proposed. Based on the investigated parameters we calculated for dl-gamma-tocopherol an average bioactivity of 28% compared to that of dl-alpha-tocopherol.     

Effect of intermittent versus continuous energy restriction on weight loss,maintenance and cardiometabolic risk: A randomized 1-year trial

Background & aims

Long-term adherence to conventional weight-loss diets is limited while intermittent fasting has risen in popularity. We compared the effects of intermittent versus continuous energy restriction on weight loss, maintenance and cardiometabolic risk factors in adults with abdominal obesity and ≥1 additional component of metabolic syndrome.

Overweight,obesity and the risk of LADA: results from a Swedish case–control study and the Norwegian HUNT Study

Aims/hypothesis

Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.

Methods

Analyses were based on incident cases of LADA (n?=?425) and type 2 diabetes (n?=?1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI.

Results

In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD.

Conclusions/interpretation

Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

     

Effect of ultrasound-guided interstitial laser photocoagulation on benign solitary solid cold thyroid nodules - a randomised study

AIM: To evaluate the efficacy of ultrasound (US)-guided interstitial laser photocoagulation (ILP) on thyroid function, nodule size and patient satisfaction in benign solitary solid cold thyroid nodules by comparing one ILP session with no treatment in a prospective randomised study. MATERIALS AND METHODS: Thirty euthyroid outpatients with a benign solitary solid and a scintigraphically cold thyroid nodule causing local discomfort were assigned to one session of ILP (n = 15) or observation (n = 15) and followed for 6 months. Thyroid nodule volume and total thyroid volume were assessed by US and thyroid function was determined by routine assays before and during follow-up. Pressure and cosmetic complaints before and at 6 months were evaluated on a visual analogue scale. ILP was performed under US guidance and with an output power of 2.5-3.5 W. RESULTS: In the ILP group, the nodule volume decreased from 8.2 ml (6.1; 11.9) (median; quartiles) to 4.8 ml (3.0; 6.6) after 6 months (P = 0.001). The overall median reduction was 44% (37; 52), which correlated with a significant decrease in pressure symptoms as well as cosmetic complaints. In the control group, a non-significant increase in median nodule volume of 7% (0; 34) after 6 months was seen. No major side-effects were seen in the ILP group. There was no correlation between thermal energy deposition and nodule volume reduction. Thyroid function was unaltered throughout. CONCLUSION: US-guided ILP, given as a single treatment, resulted in a satisfactory clinical response in the majority of patients with a benign solitary solid cold thyroid nodule, and may become a clinically relevant alternative to surgery in selected patients.     

The relationship between hospital or operator volume and outcomes of coronary patients undergoing percutaneous coronary interventions

Summary The relationship between volume and outcome in medicine has been intensively investigated in the last few decades. The large amount of accumulated data demonstrates that for many surgical or non-surgical procedures and medical conditions, patients being treated in high-volume hospitals or by high-volume physicians have lower mortality rates and better quality of life compared to those treated by low-volume hospitals or by low-volume physicians. Although the degree of the relationship between high volume and better outcome varies, it is persistent across a wide range of procedures and conditions.Percutaneous coronary interventions (PCIs) have an important impact on public health, given the frequency of coronary heart disease for which these procedures are performed. Studies carried out before and after the advent of stents on the relationship between volume and outcome for PCIs have almost consistently reported that performance of PCIs in high-volume institutions or by high-volume operators is associated with improved outcomes for patients, regardless of the specific indication for PCI.For those procedures for which a relationship between high volume and better outcome has been clearly demonstrated, patients as well as their referring physicians should be informed that patients can benefit both in terms of reduced mortality and improved quality of life if they are treated by high-volume health care providers. Consequently, for these procedures, a health care policy aiming at their concentration in high-volume institutions should be strongly considered.     

Elevated GLUT 1 level in crude muscle membranes from diabetic Zucker rats despite a normal GLUT 1 level in perineurial sheaths

Summary Recently, we demonstrated that approximately 60 % of GLUT 1 in a crude membrane fraction of rat skeletal muscle originates from perineurial sheaths. To study the in vivo regulation of GLUT 1 expression in different tissues in muscles, we measured the level of GLUT 1 in crude muscle membranes and in perineurial sheaths in diabetic (fa/fa) Zucker rats and lean controls, with and without metformin treatment. The GLUT 1 concentration in perineurial sheaths was identical in all four groups of rats, both when measured by quantitative immunofluorescence and by immunoblotting and densitometry. In a fraction of crude membranes of soleus muscles GLUT 1 expression was more than two-fold higher in (fa/fa) rats than in lean controls (p<0.005). Metformin treatment significantly elevated GLUT 1 in control rats (p<0.05) and tended to decrease GLUT 1 in diabetic rats (p<0.075). The expressions of GLUT 1 and GLUT 4 in crude muscle membranes were inversely correlated (p<0.01), and GLUT 1 expression correlated positively with fasting glucose (p<0.05). In conclusion, GLUT 1 expression in perineurial sheaths is unaffected by alterations in glucose homeostasis and by the genes responsible for obesity and diabetes in the Zucker rat. GLUT 1 expression in a crude membrane fraction of soleus muscle is increased in the diabetic animals, likely due to an increased expression in muscle cells proper. [Diabetologia (1994) 37: 443–448] Received: 17 June 1993 and in revised form: 19 November 1993     

Sonographic,manometric, and myographic evaluation of the anal sphincters morphology and function

PURPOSE: A direct comparison of anal sphincter physiology (muscle performance and anatomy-muscle thickness) has not yet been undertaken but may be of importance in patients with defecation disorders. METHODS: We evaluated 15 healthy volunteers by means of anorectal manometry to determine pressure functions of the internal and external anal sphincter. Transcutaneous electromyography was recorded to assess the electrical activity of the external anal sphincter. Thickness of the anal sphincter muscles was measured sonographically from within the anal canal with dorsal projection using a 7.5-MHz 360° rectal panorama scanner. RESULTS: It was shown that neither is the muscle thickness of the external anal sphincter during rest (6.26±1.02 mm) or during squeezing (7.40±1.39 mm) correlated to its squeeze pressure (138.8±15.2 mmHg), nor is the diameter of the internal anal sphincter (2.09±0.58 mm) correlated to its resting pressure (61.1±15.2 mmHg). Finally, the thicker the internal anal sphincter muscle, the lower the electrical activity of the external anal sphincter during squeezing (r=0.74,P <0.001). CONCLUSION: It is concluded that both manometry to assess sphincter function and sonography to determine sphincter morphology are important measures in the evaluation of continence function.     

Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome

Objective: The objective of this study was to analyze the incidence of immunohistochemically detectable p53 protein accumulation in epithelial ovarian carcinomas and to correlate these data with the clinical outcome so as to clarify further the role of p53 mutations in prognosis with these patients.Methods: Tumor tissues from 179 patients with epithelial ovarian carcinoma were used for immuno-histochemical analysis with monoclonal antibody DO1 and BP 53-12-1 on formalin-fixed, paraffin-embedded tissue.Results: A total of 78 cases (44%) showed positive nuclear p53 staining. The p53-positive cases were found in all histological types of epithelial ovarian tumors. p53 staining was found in tumors of all stages with a higher percentage of positive cases in stage IV ovarian carcinomas (not significant). Poorly differentiated carcinomas showed a significantly higher percentage of p53 protein expression than did highly differentiated tumors (P=0.0002). Clinical follow-up of up to 14 years (median 25 months) showed a slightly but not significantly shortened disease-free and overall survival time for patients with p53-positive epithelial ovarian carcinomas.Conclusions: We conclude from our data that p53 expression in ovarian carcinoma is associated with poor differentiation but not with the disease being in an advanced stage. There was a tendency for shortened disease-free and overall survival for patients with p53-positive tumors.