Fundamentals about onset and progressive disease character of type 2 diabetes mellitus

ResearchGate is a world wide web for scientists and researchers to share papers, ask and answer questions, and find collaborators. As one of the more than 15 million members, the author uploads research output and reads and responds to some of the questions raised, which are related to type 2 diabetes. In that way, he noticed a serious gap of knowledge of this disease among medical professionals over recent decades. The main aim of the current study is to remedy this situation through providing a comprehensive review on recent developments in biochemistry and molecular biology, which can be helpful for the scientific understanding of the molecular nature of type 2 diabetes. To fill up the shortcomings in the curricula of medical education, and to familiarize the medical community with a new concept of the onset of type 2 diabetes, items are discussed like: Insulin resistance, glucose effectiveness, insulin sensitivity, cell membranes, membrane flexibility, unsaturation index (UI; number of carbon-carbon double bonds per 100 acyl chains of membrane phospholipids), slow-down principle, effects of temperature acclimation on phospholipid membrane composition, free fatty acids, energy transport, onset of type 2 diabetes, metformin, and exercise. Based on the reviewed data, a new model is presented with proposed steps in the development of type 2 diabetes, a disease arising as a result of a hypothetical hereditary anomaly, which causes hyperthermia in and around the mitochondria. Hyperthermia is counterbalanced by the slow-down principle, which lowers the amount of carbon-carbon double bonds of membrane phospholipid acyl chains. The accompanying reduction in the UI lowers membrane flexibility, promotes a redistribution of the lateral pressure in cell membranes, and thereby reduces the glucose transporter protein pore diameter of the transmembrane glucose transport channel of all Class I GLUT proteins. These events will set up a reduction in transmembrane glucose transport. So, a new blood glucose regulation system, effective in type 2 diabetes and its prediabetic phase, is based on variations in the acyl composition of phospholipids and operates independent of changes in insulin and glucose concentration. UI assessment is currently arising as a promising analytical technology for a membrane flexibility analysis. An increase in mitochondrial heat production plays a pivotal role in the existence of this regulation system.     

Tremor analysis in two normal cohorts.

OBJECTIVE: Quantitative tremor analyses using almost identical methods were compared between two independent large normal cohorts, to separate robust measures that may readily be used diagnostically from more critical ones needing lab-specific normalization. METHODS: Hand accelerometry and surface EMG from forearm flexors and extensors were recorded with (500 and 1000 g) and without weight loading under postural conditions in 117 and 67 normal volunteers in two different specialty centers for movement disorders in Germany. RESULTS: Tremor amplitude (total power) and frequency fell within a similar range but differed significantly. A significant reduction of tremor frequency under 1000 g weight load (>1 Hz), and a lack of rhythmic EMG activity at the tremor frequency in around 85-90% of the recordings were robust findings in both centers. CONCLUSIONS: The differences in frequency and total power indicate that these measures critically depend on the details of the recording conditions being slightly different between the two centers. Thus each lab needs to establish its own normative data. We estimate that at least 25 normal subjects have to be recorded to obtain normal values. The reduction of tremor frequency under load and lacking tremor-related EMG activity were well reproducible allowing a differentiation of physiological from low amplitude pathological tremor. SIGNIFICANCE: This study provides a framework for more standardized tremor analyses in clinical neurophysiology.     

A persisting secular trend for body measurements in Dutch children. The Oosterwolde 11 study

To investigate whether the secular trend for growth in Dutch children still exists, the Oosterwolde I study of 1980 was repeated in 1989. A persisting secular trend was visible for height while the z scores of body proportions show no change during the past 10 years, which suggests that there is no change in the timing of puberty.     

A retrospective study to determine the risk of red cell alloimmunization and transfusion during pregnancy

A retrospective review of post-delivery antibody records was performed at a teaching hospital and a community hospital to determine the frequency of new red cell alloantibody production and transfusion during pregnancy. If alloantibody was undetected at delivery, it was assumed that alloimmunization had not occurred. When antibody was detected, a chart review was performed to determine if the antibody was present at the beginning of the pregnancy or was newly produced during the pregnancy. A total of 17,568 pregnancies were reviewed. Antibody was detected at delivery in 948 (5.4%) cases, of which 89.5 percent (848/948) involved passive anti-D or clinically insignificant antibodies. The remaining 100 pregnancies involved clinically significant IgG antibodies. In 58 pregnancies, the antibody was detected in the first trimester, and in 42, new antibody production occurred during the pregnancy. Thus, the prevalence of new antibody production during pregnancy was 0.24 percent (95% confidence interval [CI], 0.17-0.32). Transfusion records indicated that the prevalence of transfusions during pregnancy was 0.09 percent (95% CI, 0.04-0.14). None of the women with new alloantibody formation during their pregnancies required transfusion; hence, new alloantibody production and the need for transfusion appear to be independent events. The probability of these events occurring together was 2.1 × 10(-6), or 1 in 500,000 deliveries.     

Post-ischemic administration of diazoxide attenuates long-term microglial activation in the rat brain after permanent carotid artery occlusion

Diazoxide is a putative mitochondrial, ATP-sensitive potassium channel opener that has been implicated in neuroprotection in cerebral ischemia. Administered as pretreatment, diazoxide can attenuate ischemia-related neuronal injury, but little is known about the potential neuroprotective properties of the drug when it is given after the onset of an ischemic insult. In a previous study, we applied diazoxide after imposing chronic cerebral hypoperfusion by means of permanent, bilateral occlusion of the common carotid arteries (2VO) in rats. We observed that ischemia-induced learning impairment assessed in the Morris water maze, and microglial activation visualized by immunocytochemistry, were prevented by diazoxide as determined at 13 weeks after 2VO. However, dimethyl sulfoxide, the organic solvent of diazoxide also prevented memory deficits, without any effect on microglial activity. Therefore, we have repeated our experiments with the use of an inorganic solvent, aqueous NaOH solution in order to clarify the effect of diazoxide independent of dimethyl sulfoxide. The present results demonstrated that diazoxide alone did not improve learning performance, but it prevented microglial activation in the hippocampus 13 weeks after the onset of 2VO. These data provide evidence that post-treatment with diazoxide is not effective in impeding a long-term memory deficiency, but it can attenuate ischemia-induced microglial activation, independently of the solvent used.