No evidence of tachyphylaxis for insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) in subjects with type 2 diabetes, their first-degree relatives, or in healthy subjects.

BACKGROUND, AIMS: In patients with type 2 diabetes, the lost insulinotropic effect of the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is more apparent after continuous versus bolus administration. To test whether the difference might be explained by rapid tachyphylaxis in response to elevated concentrations of GIP, and whether patients with type 2 diabetes and their relatives are more susceptible to tachyphylaxis than healthy subjects. PATIENTS AND METHODS: In a two-way crossover design, insulinotropic responses to repeated bolus injection (50 pmol/kg body weight at 30 and 120 min) and continuous infusion of GIP (2 pmol.kg-1.min-1 from 30 to 180 min) under hyperglycaemic clamp conditions (8.5 mmol/l) was compared in age- gender- and weight-matched patients with type 2 diabetes, first degree relatives of such patients, and healthy subjects. RESULTS: Insulin secretory responses to the first and second GIP bolus were not significantly different in any of the subject groups. Subjects with type 2 diabetes had a significant relative impairment versus healthy subjects with continuous (C-peptide, -13.2 %, p < 0.05), but not with repeated bolus administration of GIP (+11.1 %, n.s.). First-degree relatives tended to hyper-secrete insulin with bolus or continuous administrations of GIP. CONCLUSIONS: Rapid tachyphylaxis in response to continuous exposure to slightly supraphysiological concentrations of GIP does not explain the reduced insulinotropic response to GIP infusions in patients with type 2 diabetes or their first-degree relatives.

High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice.

OBJECTIVE: Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein signatures during high-fat diet (HF)-mediated development of hepatic insulin resistance. METHODS: We induced hepatosteatosis by feeding C3HeB/FeJ male mice an HF enriched with long-chain polyunsaturated C18:2n6 fatty acids for 7, 14, or 21 days. Longitudinal changes in hepatic insulin sensitivity were assessed via the euglycemic-hyperinsulinemic clamp, in membrane lipids via t-metabolomics- and membrane proteins via quantitative proteomics-analyses, and in hepatocyte morphology via electron microscopy. Data were compared to those of age- and litter-matched controls maintained on a low-fat diet. RESULTS: Excess long-chain polyunsaturated C18:2n6 intake for 7 days did not compromise hepatic insulin sensitivity, however, induced hepatosteatosis and modified major membrane lipid constituent signatures in liver, e.g. increased total unsaturated, long-chain fatty acid-containing acyl-carnitine or membrane-associated diacylglycerol moieties and decreased total short-chain acyl-carnitines, glycerophosphocholines, lysophosphatidylcholines, or sphingolipids. Hepatic insulin sensitivity tended to decrease within 14 days HF-exposure. Overt hepatic insulin resistance developed until day 21 of HF-intervention and was accompanied by morphological mitochondrial abnormalities and indications for oxidative stress in liver. HF-feeding progressively decreased the abundance of protein-components of all mitochondrial respiratory chain complexes, inner and outer mitochondrial membrane substrate transporters independent from the hepatocellular mitochondrial volume in liver. CONCLUSIONS: We assume HF-induced modifications in membrane lipid- and protein-signatures prior to and during changes in hepatic insulin action in liver alter membrane properties - in particular those of mitochondria which are highly abundant in hepatocytes. In turn, a progressive decrease in the abundance of mitochondrial membrane proteins throughout HF-exposure likely impacts on mitochondrial energy metabolism, substrate exchange across mitochondrial membranes, contributes to oxidative stress, mitochondrial damage, and the development of insulin resistance in liver.

All-reflective, highly accurate polarization rotator for high-power short-pulse laser systems.

We present the setup of a polarization rotating device and its adaption for high-power short-pulse laser systems. Compared to conventional halfwave plates, the all-reflective principle using three zero-phase shift mirrors provides a higher accuracy and a higher damage threshold. Since plan-parallel plates, e.g. these halfwave plates, generate postpulses, which could lead to the generation of prepulses during the subsequent laser chain, the presented device avoids parasitic pulses and is therefore the preferable alternative for high-contrast applications. Moreover the device is easily scalable for large beam diameters and its spectral reflectivity can be adjusted by an appropriate mirror coating to be well suited for ultra-short laser pulses.

Osteopontin deficiency protects against obesity-induced hepatic steatosis and attenuates glucose production in mice.

AIMS/HYPOTHESIS: Obesity is strongly associated with the development of non-alcoholic fatty liver disease (NAFLD). The cytokine osteopontin (OPN) was recently shown to be involved in obesity-induced adipose tissue inflammation and reduced insulin response. Accumulating evidence links OPN to the pathogenesis of NAFLD. Here we aimed to identify the role of OPN in obesity-associated hepatic steatosis and impaired hepatic glucose metabolism. METHODS: Wild-type (WT) and Opn (also known as Spp1) knockout (Opn (-/-)) mice were fed a high-fat or low-fat diet to study OPN effects in obesity-driven hepatic alterations. RESULTS: We show that genetic OPN deficiency protected from obesity-induced hepatic steatosis, at least in part, by downregulating hepatic triacylglycerol synthesis. Conversely, absence of OPN promoted fat storage in adipose tissue thereby preventing the obesity-induced shift to ectopic fat accumulation in the liver. Euglycaemic-hyperinsulinaemic clamp studies revealed that insulin resistance and excess hepatic glucose production in obesity were significantly attenuated in Opn (-/-) mice. OPN deficiency markedly improved hepatic insulin signalling as shown by enhanced insulin receptor substrate-2 phosphorylation and prevented upregulation of the major hepatic transcription factor Forkhead box O1 and its gluconeogenic target genes. In addition, obesity-driven hepatic inflammation and macrophage accumulation was blocked by OPN deficiency. CONCLUSIONS/INTERPRETATION: Our data strongly emphasise OPN as mediator of obesity-associated hepatic alterations including steatosis, inflammation, insulin resistance and excess gluconeogenesis. Targeting OPN action could therefore provide a novel therapeutic strategy to prevent obesity-related complications such as NAFLD and type 2 diabetes.

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes.

AIMS: The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. METHODS: A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. RESULTS: Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. CONCLUSIONS: A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.

Actin complexes in the cell nucleus: new stones in an old field.

Actin is a well-known protein that has shown a myriad of activities in the cytoplasm. However, recent findings of actin involvement in nuclear processes are overwhelming. Actin complexes in the nucleus range from very dynamic chromatin-remodeling complexes to structural elements of the matrix with single partners known as actin-binding proteins (ABPs). This review summarizes the recent findings of actin-containing complexes in the nucleus. Particular attention is given to key processes like chromatin remodeling, transcription, DNA replication, nucleocytoplasmic transport and to actin roles in nuclear architecture. Understanding the mechanisms involving ABPs will definitely lead us to the principles of the regulation of gene expression performed via concerting nuclear and cytoplasmic processes.

Nuclear myosin is ubiquitously expressed and evolutionary conserved in vertebrates.

Nuclear myosin I (NMI) is a single-headed member of myosin superfamily localized in the cell nucleus which participates along with nuclear actin in transcription and chromatin remodeling. We demonstrate that NMI is present in cell nuclei of all mouse tissues examined except for cells in terminal stages of spermiogenesis. Quantitative PCR and western blots demonstrate that the expression of NMI in tissues varies with the highest levels in the lungs. The expression of NMI is lower in serum-starved cells and it increases after serum stimulation. The lifespan of NMI is longer than 16 h as determined by cycloheximide translation block. A homologous protein is expressed in human, chicken, Xenopus, and zebrafish as shown by RACE analysis. The analysis of genomic sequences indicates that almost identical homologous NMI genes are expressed in mammals, and similar NMI genes in vertebrates.

Removal of Ocular Artifacts from EEG: A Comparison of Adaptive Filtering Method and Regression Method Using Simulated Data.

We recently proposed an adaptive filtering method for removing ocular artifacts from EEG recordings. In this study, the accuracy of this method is evaluated quantitatively using simulated data and compared with the accuracy of the time domain regression method. The results show that when transfer of ocular signal to EEG channel is frequency dependent, or when there is a time delay, the adaptive filtering method is more accurate in recovering the true EEG signals.

Megaplex DNA typing can provide a strong indication of the authenticity of ancient DNA amplifications by clearly recognizing any possible type of modern contamination.

Recent experiments revealed the perfect applicability of megaplex typing by autosomal short tandem repeats (STRs) to degraded DNA. The advantages of megaplex approaches lie in reduced amounts of sample material that are necessary and in remarkable time saving. Furthermore, megaplex typing clearly recognizes possible contaminations and thus has a large potential for indicating authenticity in ancient DNA analysis. This is demonstrated by three examples in which various types of contaminations could clearly be identified as such and even traced back to their origin. This would have been impossible using control samples, due to the sporadic nature of these types of contaminations.

[Isolated hyoid bone fracture]. / Die isolierte Zungenbeinfraktur.

We present a rare case of isolated hyoid bone fracture caused by direct trauma. We will describe the mechanism of injury, how to find diagnosis and our treatment.

Dupuytren's contracture.

Dupuytren's contracture is a fibroproliferative disorder of autosomal dominant inheritance that most commonly affects men over age 60 who are of Scandinavian, Irish, or eastern European descent. Local microvessel ischemia in the hand and specific platelet-derived and fibroblast growth factors act at the cellular level to promote the dense myofibroblast population and altered collagen profiles seen in affected tissue. Surgical treatment depends to some degree on patient preference and a clear understanding of the possible complications and considerable postoperative therapy commitment. Operative management is appropriate when metacarpophalangeal or proximal interphalangeal joint contracture exceeds 30 degrees. A volar zigzag Brunner incision in the digit and palm provides reliable exposure and leads to predictable healing in most cases. The mainstay of postoperative hand therapy is early active-flexion range-of-motion exercises to restore grip strength. A nighttime extension splint is often used for several months postoperatively to maintain the correction achieved in the operating room. Early recurrence of disease is most common in individuals with Dupuytren's diathesis; use of full-thickness skin grafts may be helped for these patients.

[Abdominal actinomycosis]. / Die abdominelle Aktinomykose.

Twelve years after adnexectomy, performed for actinomycosis of the left ovary, a 32-year-old woman developed abdominal and back pain. A solid tumour was palpated in the left lower abdomen. Colon contrast examination revealed a subtotal stenosis in the sigmoid colon, while sonography showed a complete stenosis of the left ureter with left hydronephrosis. Relaparotomy demonstrated a stone-hard tumour at the rectosigmoid junction, which involved the right ovary and ureter, as well as having infiltrated the retroperitoneum, predominantly on the left. After resection of the sigmoid colon, uterus and right ovary, as well as of the ureteric stenosis with reanastomosis, the further course was without complication. Histological examination confirmed actinomycosis of the left ovary, sigmoid colon and pelvic mesocolon. Therapy with amoxycillin, 500 mg three times daily, was started. As the patient had worn an intrauterine pessary for several years, primary infection of the uterus with spread into the abdominal cavity via tube and ovaries is likely to have been the course of events. The recurrence was probably caused by reactivation of residual actinomycetes in the retroperitoneum and pelvic mesocolon.

[Complicated aneurysm of the splenic artery]. / Das komplizierte Lienalis-Aneurysma.

For 2 1/2 years after sustaining blunt trauma to the abdomen a 51-year-old woman had experienced episodes of pain, recently with throbbing, in the left upper quadrant. A smooth, circumscribed, painless tumour filling the left upper and mid-abdomen was palpable under the left costal margin. Ultrasound revealed a 12 x 11 cm space-occupying mass with cystic-fluid components, at first interpreted as a blood-containing pseudocyst. Computed tomography demonstrated a connection with the splenic artery. Digital subtraction angiography established the diagnosis of an aneurysm of the splenic artery arising immediately beyond its origin from the coeliac trunk. Splenectomy and resection of the aneurysm were performed. Total removal of the aneurysm was not undertaken because the dorsal aspect of the aneurysm wall was very thick and fused with the retroperitoneum. The postoperative course was unremarkable. The genesis of splenic aneurysm often remains unexplained. Its occurrence after blunt abdominal trauma is exceedingly rare.

[The dynamic condylar screw (DCS) in proximal femoral fractures. Initial experiences]. / Die "dynamische" Kondylenschraube (DCS) bei proximalen Femurfrakturen. Erste Erfahrungen.

Beginning January 1st 1987 19 fractures of the proximal femur were stabilized utilizing the "dynamic condylar screw" (DCS). During or after reduction of the fracture the DCS is accomplished by a supporting plate. In the cases we applied the DCS hitherto employment of a bone distractor of complementary cancellous bone graft has been mandatory. Although we feel encouraged by our preliminary results the DCS will have to undergo arduous clinical trial.

[ Papillary and peripapillary bile duct injuries during gastrectomy]. / Papilläre und peripapilläre Gangverletzungen anlässlich von Magenresektionen.

During subtotal gastrectomy in 3 patients injury of the papilla and/or pancreatic and common bile duct occurred. Diagnostic and therapeutic problems of these life threatening intraoperative complication are discussed.

Effects of positive end-expiratory pressure (PEEP) ventilation on the exocrine pancreas in minipigs.

The effect of positive end-expiratory pressure (PEEP) ventilation on the pancreas was studied in 22 anesthetized minipigs. Five pigs were treated with intermittent positive pressure ventilation (IPPV) for 21 h (Group I) and six pigs were treated with a PEEP of 15 cm H2O for 21 h (Group II). We next explored the influence of PEEP ventilation while stimulating the pancreas with Ceruletide, a synthetic cholecystokinin (CCK) analog, at 2.3 micrograms/kg per h.i.v. for 3 h. Ventilation with IPPV for 4 h (n = 5, group III) was compared with PEEP of 15 cm H2O for 4 h (n = 6, group IV). Changes in serum-lipase were observed in all groups. The average lipase level rose from 12.6 U/l to 67 U/l group I and from 15.1 U/l to 129.2 U/l in group II (P = 0.025 for group I vs group II). In group IV (PEEP and Ceruletide), the mean lipase level rose about six times more than in group III (IPPV and Ceruletide). The difference was significant (P less than 0.00005). By three-factor ANOVA analysis, effects due to the drug (P less than 0.000006) and to PEEP (P less than 0.038) as well as a threefold interaction could be demonstrated, i.e., using Ceruletide a greater PEEP effect on lipase than without the drug (P less than 0.023) took place. There were no significant histological changes of the pancreas in groups I and III. In group II (21 h PEEP), vacuolization of acinar cells was evident; on the ultrastructural level, indication was given that these vacuoles derived both from the Golgi apparatus and from fusion of individual zymogen granules. In group IV (PEEP and Ceruletide), the focal appearance of fatty-tissue necrosis and acinar cells as well as hemorrhage of the gland was observed. We conclude that PEEP ventilation impairs the function of the pancreas and produces even more deleterious effects when the gland is stimulated. These effects should be considered when PEEP is used in clinical practice in the treatment of acute pancreatitis.

[Malignant teratoma of the thyroid gland]. / Das maligne Teratom der Schilddrüse.

Two years after a bilateral subtotal thyroidectomy because of nodular goitre a 45-year-old woman noticed a firm nodule on the right side of her neck. Because malignant cells were suspected on cytological examination of a fine-needle biopsy, thyroidectomy was performed which revealed an immature malignant teratoma of the thyroid. A 4 cm local recurrence was noted by computed tomography only three weeks later. Despite chemotherapy (four cycles of vinblastine, cisplatin and bleomycin), radiotherapy to the neck (total dose of 60 Gy) and surgical excision of the infiltrated sternocleidomastoid muscle, bone, liver and lung metastases occurred within 10 months. Four weeks later the patient died of global cardiac failure and tumour cachexia.

[Luxations in the sternoclavicular joint]. / Luxationen im Sternoklavikulargelenk.

Primary open reduction and fixation with Kirschner wires and/or fascia lata or PDS is recommended in the treatment of acute traumatic luxations of the sternoclavicular joint. If not bent or secured against migration, K-wires may be the reason for lethal postoperative complications. We report on 7 own patients with luxation of the sternoclavicular joint and discuss the problems in diagnosis, operative and postoperative treatment of this rare lesion.

[Fibrolamellar liver cell cancer. A case report]. / Das fibrolamelläre Leberzellkarzinom. Ein Fallbericht.

Fibrolamellar hepatocellular carcinoma of the liver is a rare variant of hepatocellular carcinoma with characteristic morphological patterns and a good prognosis. Preoperatively the tumor is rarely diagnosed. Surgical treatment is resection, hemihepatectomy or transplantation of the liver. We report a case of a 51 years old patient with fibrolamellar hepatocellular carcinoma of the liver.