Azeotropic drying free [(18)F]FDG synthesis and its application to a lab-on-chip platform.

A very simple and time-saving cartridge-based drying technique for [(18)F]fluoride allows for an efficient [(18)F]FDG synthesis using protic solvents and high water content. This novel method has been adapted to a lab-on-chip synthesis platform mitigating the standard azeotropic drying process and demonstrating a proof of concept towards reduced hardware complexity for such systems.

The effect of inactivated Lactobacillus LB fermented culture medium on symptom severity: observational investigation in 297 patients with diarrhea-predominant irritable bowel syndrome.

INTRODUCTION: Little is known about the intensity of symptoms of diarrhea-predominant IBS (IBS-D) or the consequences of the disease on patients' health-related quality of life (HRQOL). This observational investigation assessed the symptoms (abdominal pain, bloating, number of stools per day, and stool consistency), impact on HRQOL, and consequence on anal continence in 297 patients with IBS-D before and after 1 month of probiotic treatment with Lacteol (inactivated Lactobacillus LB plus fermented culture medium). METHODS: Functional assessment using a standardized visual analogue scale in order to quantify abdominal pain, bloating, and quality of life before and after 1 month of treatment with 2 capsules/day of Lacteol. The number of symptomatic days per week, number of stools, consistency of stools, secondary fecal incontinence rate, and potential trigger effect of food were quantified. A χ2 test was used to compare qualitative data and the variance of quantitative criteria was analyzed. RESULTS: The pain score decreased from 4.46±0.15 on a scale of 0-10 before treatment to 2.8±0.14 after treatment (p<0.0001). Bloating decreased from 4.49±0.18 to 2.5±0.15 on a scale of 0-10 (p<0.0001). The HRQOL score, which is inversely correlated with quality of life, decreased from 5.99±0.14 to 3.92±0.16 (p<0.0001). In this cohort study, the fecal incontinence rate secondary to diarrhea was clearly higher than that of the general population: 18% versus a prevalence of 9-10%, according to different studies. The mean number of stools per week decreased from 17.59 to 12.83 after treatment (p<0.0001). Before treatment, 54% of patients had watery stools and 46% had smooth stools; at the end of treatment, only 18.5% of patients still had watery stools, and 34% had normal stools. 52% of patients attributed their symptoms to their diet: 34% to vegetables, 29% to fruit, 15% to milk, 15% to fat, 6% to peppers and spices, and 4% to sugar. CONCLUSION: This observational investigation shed new light on patients with IBS-D, the HRQOL of which is altered by a fecal incontinence rate twice as high as that of the general population. Correlation with diet is confirmed by 1 out of 2 patients reporting poor tolerance of fiber and dairy products. Nutritional management should thus be part of these patients' treatment. Inactivated Lactobacillus LB plus fermented culture medium is a probiotic drug that has been used by physicians for a long time to treat patients with diarrhea. Strongly concentrated, it has no side effects and seems to help these patients. Due to a strong placebo effect in patients with this pathology, however, a controlled study is necessary to confirm this result.

Large-area, uniform, high-spatial-frequency ripples generated on silicon using a nanojoule-femtosecond laser at high repetition rate.

Large-area high-spatial-frequency patterns (HSFLs) of λ/6 periodicity have been generated by a nanojoule-femtosecond laser scanning technique (80 MHz, 170 fs, 700-950 nm) at the silicon-air interface. The excellent large-area uniformity allowed reproducible and accurate measurements of the periodicity. Variation of experimental parameters as illumination geometry, and pulse energy and number showed no influence on the ripple spacing. A wavelength dependence was observed and compared to current models of HSFL formation. A particular second-harmonic model was found to match the results best but needs to take into account transient changes in the refractive index under laser exposure. A second-harmonic mechanism is further supported by direct spectroscopic observation.

Fatty acids as metabolic mediators in innate immunity.

BACKGROUND: Increasing data support the hypothesis of a local and systemic crosstalk between adipocytes and monocytes mediated by fatty acids. The aim of this study was to characterize the immunomodulatory effects of a large panel of fatty acids on cytokines and chemokines in monocytic THP-1 cells and primary human monocytes. We tested whether anti-inflammatory fatty acids are able to inhibit the binding of lipopolysaccharide (LPS) to its receptor, toll-like receptor/MD-2 (TLR4/MD-2). MATERIALS AND METHODS: Resistin, monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor (TNF) were measured by enzyme-linked immunosorbent assay. Proteins were analysed by Western blot. A designed Flag-tagged TLR4/MD-2 fusion protein (LPS trap) was used to investigate the effect of fatty acids on binding of LPS to its receptor. In 30 patients with type 2 diabetes mellitus (T2D), the correlation of serum triglyceride levels with LPS-induced monocyte activation was analysed. RESULTS: Eleven fatty acids investigated exerted differential effects on the monocytic release of cytokines and chemokines. Eicosapentaenoic acid had potent anti-inflammatory effects on human primary monocytes and THP-1 cells; 100 and 200 microM eicosapentaenoic acid dose-dependently inhibited LPS binding to the LPS trap. LPS-induced release of monocytic MCP-1 and TNF was significantly and positively correlated with serum triglyceride levels in 30 patients with T2D. CONCLUSIONS: Monocytic activation is differentially regulated by fatty acids and depends on triglyceride levels in T2D. The main finding of the present study shows that eicosapentaenoic acid inhibits the specific binding of LPS to TLR4/MD-2. Eicosapentaenoic acid represents a new anti-inflammatory LPS-antagonist.

Adiponectin downregulates CD163 whose cellular and soluble forms are elevated in obesity.

BACKGROUND: CD163 is a monocyte/macrophage specific receptor whose soluble form (sCD163) is elevated in inflammatory diseases. Obesity is associated with chronic inflammation and low adiponectin, an anti-inflammatory adipokine. Adiponectin, 5-aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR) and metformin activate the AMP-kinase that exerts anti-inflammatory effects, and the influence of adiponectin and these drugs on monocytic CD163 was analysed, and cellular and sCD163 were determined in obesity and type 2 diabetes. MATERIALS AND METHODS: Monocytes were incubated with adiponectin, AICAR or metformin. Furthermore, monocytes and serum were obtained from type 2 diabetic patients (T2D), overweight (defined as a body mass index > or = 25 kg m(-2)) and normal-weight (NW) controls. CD163 was analysed by immunoblot and sCD163 was measured by enzyme-linked immunosorbent assay in the supernatants of the monocytes and in serum. RESULTS: In monocytes, adiponectin reduced cellular and surface CD163, whereas sCD163 was not altered in the corresponding supernatants. Further, metformin and AICAR downregulated CD163. Monocytic CD163 was higher in T2D and obesity, whereas sCD163 in the supernatants was not elevated and neither correlated with serum sCD163 nor systemic adiponectin. There was a positive correlation of monocytic sCD163 with serum but not with monocytic IL-6. In the serum of obese controls and T2D patients, sCD163 was significantly higher compared to NW donors and was positively associated with systemic IL-6. CONCLUSIONS: This study indicates that monocytic CD163 and systemic sCD163 are elevated in T2D and obesity. Adiponectin reduces CD163 in vitro, but additional factors related to obesity like IL-6 may be more relevant in vivo.

Peritoneal fluid adipokines: ready for prime time?

BACKGROUND: Visceral adipose tissues secret a variety of adipokines; however, it is not known whether they are present in the peritoneal fluid. It was the aim of this study to investigate peritoneal fluid concentrations of novel (cartonectin, omentin) and classical adipokines (leptin, adiponectin, resistin, visfatin) in patients with ascites. MATERIAL AND METHODS: Ninety-six patients (71 men and 25 women) undergoing paracentesis were included. Of these, 76 suffered from liver cirrhosis. Adipokines were measured by enzyme-linked immunosorbent assay or Western blot. RESULTS: Each adipokine was detected in ascites with a broad range. Serum-ascites ratios (SAR) correlated with clinical and laboratory parameters. The main variables influencing peritoneal fluid adipokine concentrations were body mass index (BMI), local inflammation, systemic inflammation and serum adipokine concentrations. Resistin was significantly higher in patients with peritonitis and showed a positive correlation with peripheral leucocytes (white blood cell count). Leptin was correlated with the underlying disease. Visfatin correlated with peripheral white blood cell and C-reactive protein levels. Omentin expression was correlated with ascitic leucocyte count, ascitic albumin concentration and low albumin SAR. BMI was correlated positively with ascitic leptin levels and cartonectin protein levels. CONCLUSIONS: Peritoneal fluid adipokine concentrations are characterized by individual SARs, depend on the presence of peritonitis, and correlate with underlying disease, BMI and systemic inflammation. The data open a new field of research on the role of the peritoneum and visceral adipokines in gastrointestinal diseases.

Serum levels of adiponectin are associated with diabetic retinopathy and with adiponectin gene mutations in Caucasian patients with diabetes mellitus type 2.

INTRODUCTION: Even diabetic patients with excellent glycemic control can develop diabetic complications very early. Possibly, not only the degree of glycemic control, but other factors as well are responsible for the development of diabetic microangiopathy. Since adiponectin represents an adipocyte-specific secretory protein modulating endothelial cell functions, it was the aim of the present study to investigate the role of adiponectin serum levels as well as adiponectin gene polymorphisms in the development of diabetic retinopathy. METHODS: A population based cohort of caucasian patients (n=523) with type 2 diabetes mellitus was recruited from an epidemiological field survey. Serum adiponectin levels were determined by ELISA. Genotypes of the Tyr111His and the Gly15Gly polymorphism were determined by PCR-based RFLP analysis. Diabetic retinopathy was graded by fundus photography. RESULTS: The data demonstrate, that a) the Tyr111His (T-->C) polymorphism influences adiponectin serum levels, b) adiponectin serum levels do correlate with the prevalence of diabetic retinopathy, and c) patients heterozygous for the +45 T-->G (Gly15Gly) polymorphism show a lower prevalence of diabetic retinopathy. Furthermore, we could generate the proof of principle that adiponectin is detectable in the fluid of the human vitreous body. SUMMARY: Adiponectin gene polymorphisms influence adiponectin serum levels and elevated adiponectin serum levels are associated with diabetic retinopathy in patients with diabetes mellitus type 2. Therefore, endothelial cell modulating adiponectin should be further investigated as a candidate gene in the development and progression of retinopathy associated with type 2 diabetes mellitus.

Interfering effects of insulin, growth hormone and glucose on adipokine secretion.

INTRODUCTION: Cell culture media with high glucose concentration are normally used. Data on the secretion of the adipokines adiponectin and resistin from adipocytes in response to insulin and growth hormone (GH) both under normo- and hyperglycemic conditions are not available. It was the aim of the study to investigate the impact of standard metabolic conditions (normo-/hyperglycemia, normo-/hyperinsulinemia) and of GH on the secretion of adiponectin and resistin. MATERIAL AND METHODS: 3T3-L1 preadipocytes were differentiated into adipocytes and then incubated under normoglycemia (100 mg/dl), hyperglycemia (450 mg/dl), in combination with insulin (0, 0.2, 2.0 nM) and/or GH (1 nM). Adiponectin and resistin secretion was measured by ELISA. RESULTS: Insulin significantly stimulates adiponectin and resistin secretion under normo- and hyperglycemia. Hyperglycemia PER SE stimulates adiponectin and resistin secretion both in the absence and presence of low or high insulin concentrations. GH stimulates adiponectin secretion both under normoglycemic and hyperglycemic conditions. Whereas insulin does not modulate GH-induced adiponectin secretion under normoglycemia, insulin augments adiponectin release under hyperglycemia. GH stimulates resistin secretion only under normoglycemia, but not under hyperglycemic conditions. Since scavenger receptor B-I expression did not change, these effects are specific and not caused by a simple enhancement of adipocyte differentiation. DISCUSSION: Glucose, insulin and growth hormone have significant and interfering effects on the secretion of resistin and adiponectin. Several of the well-known in vivo phenomena such as diurnal variation or effects of re-feeding and weight-loss might be explained by direct effects of these hormones on adipocytes. Finally, when effects of hormones on adipocyte function are investigated, it is a prerequisite to take glucose levels of the cell culture media into account.

[Plantar Lisfranc dislocation fracture]. / Plantare Lisfranc-Luxationsfraktur.

We report a 30-year-old patient suffering a plantar dislocation fracture after he dropped a heavy weight on his foot. The patient was treated immediately after diagnosis was secured by CT scan. Median approach and dermatofasciotomy of the foot were followed by anatomic reduction of the fractures and the Lisfranc dislocation and fixed by internal osteosynthesis. After 3 months the patient was able to ambulate pain free without walking aids. Plantar dislocation is a very rare direction of comminuted Lisfranc dislocation fractures. The outcome may be favorable with early reduction and stable internal fixation of the fractures. One always has to be aware of the major soft tissue trauma associated with complex Lisfranc dislocation fractures.

Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue.

Genomic structure, promoter region, amino acid sequence and exon-specific primer combinations of the human omentin gene are presented. Omentin mRNA expression differs between omental adipose tissue probes from patients with chronic inflammatory bowel diseases such as Crohn's disease. Sequence comparisons revealed a 100% identity of omentin with human intelectin. Based on this, omentin might be a new adipocytokine playing a role in the defense against intestinal bacterial translocation in the context of Crohn's disease.

[Efficacy of endoscopic pneumatic dilatation in achalasia. Medium-term results]. / Efficacité de la dilatation pneumatique perendoscopique dans l'achalasie. Résultats à moyen terme.

During a seven-year period, thirty patients with achalasia of the esophagus were treated by pneumatic dilatation without complications. Only twenty patients could be followed with a mean follow of 32 +/- 23 months after their initial dilatation. Excellent to good results were obtained in more than 75 p. cent of the group. Most patients have not required a further dilatation. This study suggest to propose a regular supervision of these patients by clinical examination, esophageal manometry and endoscopy.

Synthesis of plasmalemmal glycoproteins in intestinal epithelial cells. Separation of Golgi membranes from villus and crypt cell surface membranes; glycosyltransferase activity of surface membrane.

The relationship between Golgi and cell surface membranes of intestinal cells was studied. These membranes were isolated from intestinal crypt cells and villus cells. The villus cell membranes consisted of microvillus membrane, a Golgi-rich fraction, and two membrane fractions interpreted as representing lateral-basal membranes. The villus cell microvillus membrane was purified by previously published techniques while the other membranes were obtained from isolated cells by differential centrifugation and density gradient velocity sedimentation. The two membrane fractions obtained from villus cells and considered to be lateral-basal membranes were enriched for Na+,K+-ATPase activity, but one also showed enrichment in glycosyltransferase activity. The Golgi membrane fraction was enriched for glycosyltransferase activity and had low to absent Na+,K+-ATPase activity. Adenylate cyclase activity was present in all membrane fractions except the microvillus membrane but co-purified with Golgi rather than lateral-basal membranes. Electron microscopy showed that the Golgi fraction consisted of variably sized vesicles and cisternalike structures. The two lateral-basal membrane fractions showed only vesicles of smaller, more uniform size. After 125I labeling of isolated intact cells, radioactivity was found associated with the lateral-basal and microvillus membrane fractions and not with the Golgi fraction. Antibody prepared against lateral-basal membrane fractions reacted with the surface membrane of isolated villus cells. The membrane fractions from isolated crypt cells demonstrated that all had high glycosyltransferase activity. The data show that glycosyltransferase activity, in addition to its Golgi location, may be a significant property of the lateral-basal portion of the intestinal villus cell plasma membrane. Data obtained with crypt cells support earlier data and show that the crypt cell surface membrane possesses glycosyltransferase activity.