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.     

Analysis and management of chronic testicular pain

A total of 45 patients was seen in consultation between May 1980 and April 1989 for chronic unilateral or bilateral orchialgia, defined as intermittent or constant testicular pain 3 months or longer in duration that significantly interferes with the daily activities of the patient so as to prompt him to seek medical attention. We analyzed 34 patients available for followup in terms of socioeconomic parameters, etiology and duration of pain, associated urological symptomatology, specific treatment and results of therapy. Of the patients 31 underwent surgical treatment after failing medical management (24 orchiectomies, 10 epididymectomies, 5 orchiopexies and 1 hydrocelectomy). Of 10 patients who underwent epididymectomy 9 underwent subsequent orchiectomy as definitive treatment. Of 15 patients who underwent inguinal orchiectomy 11 (73%) reported complete relief of pain, while 4 had partial relief. Of the 9 patients who underwent scrotal orchiectomy 5 (55%) reported complete relief of pain, 3 had partial relief and 1 denied improvement. On the basis of these results we recommend inguinal orchiectomy as the procedure of choice for the management of chronic testicular pain when conservative measures are unsuccessful.     

New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol

Twenty-two days after administration by intravenous bolus, of 50 mg of adriamycin to several patients we found concentrations of adriamycin and adriamycinol of the order of 100 pcg/ml. In theory, however, with a terminal half-life of 30 h, the plasma levels of adriamycin and adriamycinol should be close to 0.1 pcg/ml. Further pharmacokinetic investigation was therefore necessary. We have retained for this study nine male patients, aged between 53 and 69 years who received 25 to 50 mg of adriamycin by slow intravenous injection. The HPLC method permitted the detection of 50 pcg/ml of adriamycin and adriamycinol, with the possibility of monitoring their elimination during 120 h (and in one case during 160 h). The terminal half-lives of elimination estimated in 8 patients were respectively 110 +/- 52 h for adriamycin and 92 h 50 min +/- 43 h for adriamycinol. Surface ratios under adriamycinol curves against calculated adriamycin was 1.10 +/- 0.26. Plasma levels found during the To in certain patients correspond to the end of the drug elimination of the previous treatment. It is difficult with a half-life to 110 h to predict the effects of residual concentrations of adriamycin and adriamycinol.