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Rob NM Weijers 《World journal of diabetes》2020,11(5):165-181
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. 相似文献
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E. J. Carlisle J. D. Allen W. G. Kernohan W. Leahey A. A. Adgey 《British journal of pharmacology》1990,100(3):530-534
1. The effects of anti-arrhythmic drugs on the power spectrum of established ventricular fibrillation induced by endocardial electrical stimulation, have been studied in greyhounds anaesthetized with sodium pentobarbitone (35 mg kg-1, i.v.). 2. In dogs receiving no drug, initial recording of ventricular fibrillation showed a dominant frequency of 9.9 +/- 0.7 Hz (lead II) and 10.0 +/- 0.6 Hz (endocardium). After 3.3 min the frequency had fallen to 4.0 +/- 0.4 Hz in lead II, but remained high in the endocardium (10.7 +/- 0.5 Hz). 3. Lignocaine significantly reduced the dominant frequency for fibrillation recorded from lead II at (0-80 s), and for endocardial fibrillation at (0-200 s). 4. Pretreatment with propranolol or bretylium had little effect on the time course of the dominant frequency of fibrillation in lead II or the endocardium. 5. Verapamil prevented the fall in frequency seen in lead II after 80 s in the no drug group. A significantly higher frequency was maintained in both lead II (14.7 +/- 0.9 Hz) and the endocardium (14.8 +/- 0.9 Hz) for 3.3 min, compared with the no drug group (P less than 0.01). 6. Activation of fast sodium channels may determine the rapid frequency of the initial stages of ventricular fibrillation. The rapid fall in dominant frequency in lead II after fibrillation for 80 s can be prevented by calcium channel blockade and may be due to intracellular accumulation of calcium. 相似文献
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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. 相似文献
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Atrophoderma of Pasini and Pierini (APP) is a rare and distinctive form of dermal atrophy of uncertain origin. In only one previous report have immunopathologic methods been used to study a case of atrophoderma of Pasini and Pierini, and on the basis of the results obtained it was concluded that immunologic mechanisms were relevant to the pathogenesis of the condition. A detailed investigation of a case of atrophoderma of Pasini and Pierini was conducted using immunofluorescence and immunoperoxidase techniques. The epidermal Langerhans cells were abundant and expressed polyclonal immunoglobulin M on the cell-surface membrane. Biopsy of the same lesion was repeated 6 months later and revealed staining for immunoglobulins A and M and also for C3. This pattern of staining could not be reproduced in a range of other atrophic or scarring cutaneous lesions. Immunophenotypic analysis of the mild perivascular mononuclear cell infiltrate revealed an aberrant T-cell phenotype of uncertain significance. 相似文献
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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. 相似文献