Plasma 25-hydroxyvitamin D and its genetic determinants in relation to incident type 2 diabetes: a prospective case-cohort study

It is unclear whether vitamin D lowers risk of type 2 diabetes (T2D). In an observational study, we assessed the prospective association between plasma 25-hydroxyvitamin D (25(OH)D) and incident T2D, and evaluated whether it holds up for genetically determined elevated 25(OH)D. We used a case-cohort study nested within the German arm of the European Prospective Investigation into Cancer. From a total cohort of 53,088 participants with a mean follow-up of 6.6 years, we identified a random subcohort of 2,121 participants (57 % women) and 1,572 incident cases of T2D. 25(OH)D was measured in baseline plasma samples retrieved from frozen storage. Mean plasma 25(OH)D in the subcohort was 47.1 (5th–95th percentile 19.6–80.7) nmol/L. After controlling for age, sex, center, season of blood draw, education, and lifestyle, the hazard of T2D decreased across increasing plasma concentrations of 25(OH)D (P linear trend <0.0001). The association became non-linear after adjustment for BMI and waist circumference (P non-linearity <0.0001), with the inverse association being restricted to participants with 25(OH)D concentrations below ~45 nmol/L (hazard ratio per 5 nmol/L higher 25(OH)D 0.91, 95 % CI 0.84–0.98). A score predicting genetically determined plasma 25(OH)D by weighting four independent single-nucleotide polymorphisms by their effect on 25(OH)D, explained 3.7 % of the variance in 25(OH)D. The hazard ratio (95 % CI) per 5 nmol/L higher genetically predicted 25(OH)D was 0.98 (0.89–1.08) in the entire study sample and 1.06 (0.93–1.21) in the sub-sample with 25(OH)D <45 nmol/L. This latter finding casts doubt on a strong causal association of 25(OH)D with T2D, but further research in large-scale consortia is needed.     

Patient cooperation in treatment with removable appliances: a model of patient noncompliance with treatment implications

The uncooperative or noncompliant patient presents a substantial problem during treatment with removable orthopedic/orthodontic appliances. Frequently, the uncooperative patient is labeled as having a poor or defiant attitude toward orthodontic treatment. In contrast to this attitude model of patient noncompliance, this article presents an analysis of uncooperative behavior in terms of behavior-environment relationships. The authors bring together backgrounds of expertise in both clinical psychology and orthodontics. The behavioral model presented is applied to clinical orthodontic patients undergoing treatment with removable functional appliances. Preliminary research findings suggest that the behavioral model described is a successful system for the introduction of a removable device to be worn by the patient. The techniques described also are useful for the previously uncooperative patient undergoing remedial treatment. Another major benefit of using this strategy is found in the response of the children's parents. The approach reduces the potential for and frequency of parent-child conflicts over dental health. Currently, a small sample of children are being treated by the behavioral method. Both parents and patients are involved. A specific schedule for wearing of a removable appliance is identified, along with parental observations and rewards based on patient compliance. Once the youngster is regularly meeting criteria, the program is altered to increase the desired response of appliance wear. The behavioral model has implications for various aspects of orthodontic care, including the use of such appliances as the Fr?nkel, Bionator, headgear, intraoral elastics, and proper lip posture. On the basis of this functional analysis of behavior, implications for treatment and prevention of noncompliance in orthodontic patients are discussed.     

Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.

OBJECTIVE: Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage renal disease (ESRD) and is associated with increased morbidity and mortality. Means to reduce elevated homocysteine concentrations is supplementation with folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for optimized treatment are subject of debate. Therefore, the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared. DESIGN: Patients received 3 times per week either 2 tablets of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6), 2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin B6), or placebo for a period of 12 weeks with control of total homocysteine (tHcy) levels at baseline, and at 4, 8, and 12 weeks. SETTING: The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis. RESULTS: Preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo. However, tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION: The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone. Nevertheless, hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation, in contrast with results obtained in healthy volunteers.     

Plasma resistin levels and risk of myocardial infarction and ischemic stroke

CONTEXT: Resistin is a hormone that has been linked to insulin resistance, inflammatory processes, and coronary heart disease in case-control studies; however, prospective data on the association between plasma resistin levels and future risk of cardiovascular disease are lacking. OBJECTIVE: The objective of the study was to investigate the association between plasma resistin levels and risk of future myocardial infarction (MI) and ischemic stroke (IS) in a large prospective cohort. METHODS: We investigated the association between plasma resistin levels and risk of MI and IS in a case-cohort design among 26,490 middle-aged subjects from the European Investigation into Cancer and Nutrition-Potsdam Study without history of MI or stroke at time of blood draw. Plasma resistin levels were measured in baseline blood samples of 139 individuals who developed MI, 97 who developed IS, and 817 individuals who remained free of cardiovascular events during a mean follow-up of 6 yr. RESULTS: After multivariable adjustment for established cardiovascular risk factors including C-reactive protein, individuals in the highest compared with the lowest quartile of plasma resistin levels had a significantly increased risk of MI (relative risk 2.09; 95% confidence interval 1.01-4.31; P for trend = 0.01). In contrast, plasma resistin levels were not significantly associated with risk of IS (relative risk 0.94; 95% confidence interval 0.51-1.73; P for trend = 0.88). CONCLUSION: Our data suggest that high plasma resistin levels are associated with an increased risk of MI but not with risk of IS. Further studies are needed to evaluate the predictive value of plasma resistin levels for cardiovascular disease.     

Effect of drugs on homocysteine concentrations

Many studies conducted over the last two decades have shown that drug treatment for common medical conditions may have an adverse effect on plasma total homocysteine (tHcy) concentrations. The mechanism for the effects of individual drugs on tHcy concentrations is frequently unknown, as the mechanism of action of the drug may not be established, or the drug is typically administered in combination with other drugs. Some drugs are believed to alter tHcy concentrations by interfering in the metabolism of folate or vitamins B (12) or B (6) or by altering renal function, but the underlying mechanisms for the effects on tHcy concentrations of many drugs remains to be discovered. Several widely used drugs, such as lipid-lowering drugs (like fibrates and niacin) or oral hypoglycemic drugs (like metformin), insulin, drugs used in rheumatoid arthritis, and anticonvulsants cause elevated tHcy concentrations. Sex hormones have variable effects on tHcy levels, and N-acetylcysteine lowers tHcy. The mechanisms of action of drugs on tHcy concentrations and strategies to avoid tHcy elevation have been studied. Assuming that the association of tHcy with cardiovascular disease is causal, this article focuses on the adverse effect on tHcy levels of fibrates, statins and niacin, antihypertensive drugs, metformin, methotrexate and sulfasalazine, anticonvulsant drugs, and levodopa and reviews strategies to avoid such effects. The clinical significance, if any, of these adverse effects on plasma tHcy concentrations remains to be determined.     

Coupling a sensory hair-cell bundle to cyber clones enhances nonlinear amplification

The vertebrate ear benefits from nonlinear mechanical amplification to operate over a vast range of sound intensities. The amplificatory process is thought to emerge from active force production by sensory hair cells. The mechano-sensory hair bundle that protrudes from the apical surface of each hair cell can oscillate spontaneously and function as a frequency-selective, nonlinear amplifier. Intrinsic fluctuations, however, jostle the response of a single hair bundle to weak stimuli and seriously limit amplification. Most hair bundles are mechanically coupled by overlying gelatinous structures. Here, we assayed the effects of mechanical coupling on the hair-bundle amplifier by combining dynamic force clamp of a hair bundle from the bullfrog’s saccule with real-time stochastic simulations of hair-bundle mechanics. This setup couples the hair bundle to two virtual hair bundles, called cyber clones, and mimics a situation in which the hair bundle is elastically linked to two neighbors with similar characteristics. We found that coupling increased the coherence of spontaneous hair-bundle oscillations. By effectively reducing noise, the synergic interplay between the hair bundle and its cyber clones also enhanced amplification of sinusoidal stimuli. All observed effects of coupling were in quantitative agreement with simulations. We argue that the auditory amplifier relies on hair-bundle cooperation to overcome intrinsic noise limitations and achieve high sensitivity and sharp frequency selectivity.     

In heavy drinkers, fatty acid ethyl esters remain elevated for up to 99 hours

BACKGROUND: Both medical and forensic needs require reliable detection of earlier ethanol intake after the disappearance of ethanol from blood. The esters of ethanol with free fatty acids (FAEEs) are candidate markers of this kind. However, it is unknown whether FAEEs can serve as a marker for a single prior ethanol intake. In addition, the period for which FAEEs are elevated is unknown. Therefore, we measured FAEEs in heavy drinkers admitted to detoxification, and in healthy subjects after a drinking experiment. METHODS: Blood from 30 heavy drinkers was obtained for up to 5 days during a detoxification period in a psychiatric hospital. In addition, 17 healthy subjects who participated in a drinking experiment and who were abstinent thereafter gave blood during a similar time period for analysis of FAEEs. Fatty acid ethyl esters were measured by gas chromatography-mass spectroscopy. RESULTS: Heavy drinkers had much higher ethanol and FAEEs concentrations than healthy subjects; however, in both groups, FAEEs decreased rapidly during the first day. Only in heavy drinkers, elevated concentrations of FAEEs were observed at days 2 to 4. Concentrations of FAEEs were not associated with serum triglycerides or patients' body mass index. CONCLUSIONS: It is concluded that kinetics of FAEEs are different in heavy drinkers compared with healthy subjects and that FAEEs are of limited value for the detection of prior single ethanol intake.     

Recovery from respiratory failure after decompression laparotorny for severe acute pancreatitis

We present three cases of patients (at the age of 56 years,49 years and 74 years respectively) with severe acute pancreatitis (SAP),complicated by intra-abdominal compartment syndrome (ACS) and respiratory insufficiency with limitations of mechanical ventilation.The respiratory situation of the patients was significantly improved after decompression laparotomy (DL) and lung protective ventilation was re-achieved.ACS was discussed followed by a short review of the literature.Our cases show that DL may help patients with SAP to recover from severe respiratory failure.     

Postprandial lipid and carbohydrate responses after the ingestion of a casein-enriched mixed meal

BACKGROUND: Postprandial lipemia is markedly modulated when carbohydrates are added to a fatty meal. The effect of added protein is less known, however, and the data are controversial. OBJECTIVE: We investigated the effects of casein added to various fat-rich meals in the absence and presence of oligosaccharides. DESIGN: Four different test meals were given to 24 healthy volunteers: 1) fat alone, consisting of 3 g cream/kg body wt; 2) fat plus 75 g oligosaccharides; 3) fat plus 50 g sodium caseinate; and 4) a combination of all 3 components. Blood samples were taken before the meals and 1, 2, 3, 4, 5, 6, 7, and 8 h thereafter. The variables measured were serum free fatty acids, arginine, glucose, insulin, and C-peptide as well as triacylglycerol in serum, in chylomicrons, and in VLDL. Gastric emptying was monitored with the use of a (13)C breath test. RESULTS: Addition of oligosaccharides resulted in the known delay and reduction in postprandial lipemia. Casein caused additional effects: chylomicrons were further reduced and delayed, independently of gastric emptying. C-peptide and insulin, as expressed by their areas under the curves, were raised not only during the early response to the glucose load but also in the postabsorptive state. Concentrations of free fatty acids, which were markedly suppressed by 24% after oligosaccharides alone, were lowered a further 20% after the addition of casein. CONCLUSIONS: Casein added to a fatty meal lowers free fatty acids markedly in the postprandial and postabsorption phases, probably via its insulinotropic activity. Postprandial lipemia is also moderately reduced.     

Effects of ATP and derivatives on neuropile glial cells of the leech central nervous system

We investigated the effects of ATP (adenosine 5'-triphosphate) and derivatives on leech neuropile glial cells, focusing on exposed glial cells. ATP dose-dependently depolarized or hyperpolarized neuropile glial cells in situ as well as exposed neuropile glial cells. These potential shifts varied among cells and repetitive ATP application did not change their amplitude, duration or direction. In exposed neuropile glial cells, ATP most frequently induced a Na(+)-dependent depolarization and decreased the input resistance. The agonist potency ATP > ADP (adenosine 5'-diphosphate) > AMP (adenosine 5'-monophosphate) > adenosine indicates that P2 purinoceptors mediate this depolarization. The P2Y agonist 2-methylthio-ATP mimicked the ATP-induced depolarization, whereas the P2Y antagonist PPADS (pyridoxal-phosphate-6-azophenyl-2', 4'-disulphonic acid) reduced it. P2X agonists were without effect. Because the P1 antagonist 8-SPT (8-(p-sulphophenyl)-theophylline) also depressed ATP-induced depolarizations and some ATP-insensitive glial cells responded to adenosine, we suggest coexpression of metabotropic P2Y and P1 purinoceptors. The ATP-induced depolarization requires activation of Na(+) channels or nonselective cation channels, whereas the ATP-induced hyperpolarization indicates activation of K(+) channels. ATP also increased the intracellular Ca(2+) concentration ([Ca(2+)](i)), that is independent of Ca(2+) influx but reflects intracellular Ca(2+) release possibly triggered by IP(3) formation. ADP and AMP also increased [Ca(2+)](i), but were less efficient than ATP; adenosine and 2-methylthio-ATP did not affect [Ca(2+)](i). In view of the mobilization of intracellular Ca(2+), ATP is clearly different from other leech neurotransmitters, because it enables intracellular Ca(2+) signaling without causing prominent changes in glial membrane potential. Thus disturbance of the extracellular microenvironment and the demand for metabolic energy are minimized.