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.     

Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study.

BACKGROUND: The inflammatory cascade has been hypothesized to be an important mechanism of post-ischaemic myocardial reperfusion injury and several studies demonstrated that C1 esterase inhibitor (C1-INH) is effective in post-ischaemia myocardial protection. Therefore, we aimed to investigate prospectively in a randomised double-blind study the cardioprotective effects of C1-INH in ST segment elevation myocardial infarction (STEMI) in patients who underwent emergent reperfusion with coronary artery bypass grafting (CABG). METHODS: In this study, we enrolled 80 patients affected with STEMI who underwent emergent CABG. Patients were assigned in two groups (C1-INH group: receive 1000 UI of C1-INH; and placebo group: receive a saline solution). The effects of C1-INH on complement inhibition, myocardial cell injury extension and clinical outcome were studied. Haemodynamic data and myocardial function were monitored. C1-INH, C3a, C4a complement activation fragments and cardiac troponin I (cTnI) serum levels were measured before, during and after surgery. RESULTS: Patient characteristics were not different between the two groups. The overall in-hospital mortality rate was 6.2%. No statistical significant difference was observed between the two groups with regard to early mortality (p=0.36). Statistical significant difference between the two groups was showed for cardiopulmonary bypass support (p=0.04), administration of high dose of inotropes drugs (p=0.001), time of intubation (p=0.03), intensive care unit (ICU) stay (p=0.04) and in-hospital stay (p=0.03). A significant improvement in mean arterial pressure (p=0.03), cardiac index (p=0.02) and stroke volume (p=0.03) was showed in C1-INH group versus placebo group. The serum cTnI levels were significantly low in the C1-INH group versus placebo group after reperfusion, during the observation period. Plasma levels of C3a and C4a complement fragments were reduced significantly in C1-INH group. No drugs-related adverse effects were observed. CONCLUSIONS: The inhibition of the classic complement pathway by C1-INH appears to be an effective mean of preserving ischaemic myocardium from reperfusion injury as demonstrated by low serum cTnI levels in C1-INH group. Therefore, the use of C1-INH during CABG as a rescue therapy in STEMI patients is probably an effective treatment to inhibit complement activity and to improve cardiac function and haemodynamic performance without impacting early mortality. Large randomised study should be performed to support our results.     

Uniportal vs standard three-port VATS technique for spontaneous pneumothorax: comparison of post-operative pain and residual paraesthesia.

OBJECTIVE: VATS using the conventional three ports is currently the technique of choice for blebectomy/bullectomy for spontaneous pneumothorax. However, the procedure has recently been shown to have neurological complications related to the port sites. Uniportal VATS has recently been proposed as an alternative to conventional three-port VATS. It is anticipated that the single incision will predispose to a lower incidence of neurological complications. METHODS: We report our initial single surgeon experience of uniportal VATS (n = 16) and provide a comparison of post-operative pain and residual paraesthesia to conventional three-port procedures (n = 19) for the same pathology. RESULTS: In both groups, the pneumothorax pathology was principally primary. There was no difference between the groups in terms of age, spirometry, tissue resected, drainage time and inpatient stay. A difference was, however, noted in inpatient pain scores. The uniportal group had a lower median score of 0.4 (visual analogue range 0-4) while the three-port technique reported 0.8 (P = 0.06, Mann-Whitney test). The maximum score trend was similar (1.4 vs. 2.6, respectively, P < 0.001, Mann-Whitney test). Follow-up for uniportal and three-port VATS averaged 9.4+/-6.6 and 32.1+/-9.9 months, respectively. One patient in the three-port group had a pneumothorax recurrence. Three-port VATS also had a higher residual pain score (0.5) compared to uniportal VATS (0.3). Of clinical significance was the incidence of neurological complications. Eighty-six percent of uniportal patients reported no symptoms. The remaining experienced only mild 'numbness' or 'swelling'. However, in the three-port group, only 42% reported no symptoms. A similar number experienced 'numbness'. Two females described sexual dysfunction due to altered breast sensitivity. Seventeen percent (2/12) reported 'pins and needles'. CONCLUSIONS: Uniportal VATS appears to be tolerable, safe and efficient in treating spontaneous pneumothorax in our series. Moreover, post-operative pain and paraesthesia incidence was lower than three-port VATS. Prospective randomised trials are important to evaluate this technique.     

Reconstruction of a transmetatarsal amputation stump using a salvaged peroneal artery fasciocutaneous flap from the opposite leg: A case report

During lower extremity amputation, the objective is to provide a functional residual limb that permits maximum patient mobility and independence. Preservation of length of the fore part of the foot using salvageable tissue from the amputated part in young patients prevents equines deformity and revision of amputation to a higher level. This can be achieved using tissue available from the amputated part. The spare part concept in reconstructive surgery should be integrated into the trauma algorithm to avoid additional donor site morbidity. Reported here is a young adult patient with crush injuries to both feet, which resulted in amputations. A fasciocutaneous flap raised from one extremity was used to facilitate transmetatarsal amputation stump length preservation of the other extremity.