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.     

Combination of flavone acetic acid (FAA) with adriamycin,cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells

Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.     

Dupuytren disease of the sole]

The authors discuss the essence of Dupuytren disease occurring in the plantar aponeurosis with literary surveys. They briefly outline the essence of the well-known different theories which endeavour to explain the causes of the development of this disease of unknown etiology. In their article, they deal with its clinical manifestation, histological changes and therapeutical possibilities in connection with the 5 cases treated by them.     

Management of lung and bone metastases from thyroid cancers of differentiated structures

During a period of thirty years (1959-1989) 374 patients underwent surgery for differentiated thyroid carcinoma at the 1st Department of Surgery of the University Medical School in Debrecen. Distant metastases were found in the lungs or bones in 36 patients (9.6%). In 20 patients the first clinical sign of the primary disease was the distant metastasis. The aspects of surgical treatment depended on whether the metastases were solitary or multiple, capable or uncapable of radioiodine uptake. Whereas the majority of pulmonary metastases respond well to 131I-treatment the therapy of bone metastases is multidisciplinary. The 5-year survival rate was 47%, the 10-year one 19%.     

Mycobacterium marinum infection of the hand and wrist. Results of conservative treatment in twenty-four cases

Inadequate débridement, extensive scarring, and breakdown of the wound have been commonly encountered after surgical débridement has been employed as the initial treatment of infection with Mycobacterium marinum involving the deep structures of the hand. Because of our disappointment with the results of this form of treatment, from 1982 to 1986 we treated twenty-four patients who had such an infection with rifampicin and ethambutol after a diagnostic biopsy was done. Surgical treatment was deferred until it was determined that the infection had not been controlled by the chemotherapy. The clinical outcome for these patients could be divided into three patterns: eleven patients (Group I) had a good result with no complications, three patients (Group II) had delayed healing of the wound, and ten patients (Group III) did not have a good response to conservative treatment and required one or more surgical débridements. Complications were sometimes associated with use of the drugs, and loss of visual acuity was a concern in three patients. In twenty-one (87 per cent) of the patients, at follow-up the function of the treated hand was equal to that of the other hand. Persistent pain, a discharging sinus, and previous local injection of steroids were unfavorable prognostic factors. If these factors are present, surgical débridement is advised.