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.     

Treatment of myofascial trigger points in common shoulder disorders by physical therapy: A randomized controlled trial [ISRCTN75722066]

Background  

Shoulder disorders are a common health problem in western societies. Several treatment protocols have been developed for the clinical management of persons with shoulder pain. However available evidence does not support any protocol as being superior over others. Systematic reviews provide some evidence that certain physical therapy interventions (i.e. supervised exercises and mobilisation) are effective in particular shoulder disorders (i.e. rotator cuff disorders, mixed shoulder disorders and adhesive capsulitis), but there is an ongoing need for high quality trials of physical therapy interventions. Usually, physical therapy consists of active exercises intended to strengthen the shoulder muscles as stabilizers of the glenohumeral joint or perform mobilisations to improve restricted mobility of the glenohumeral or adjacent joints (shoulder girdle). It is generally accepted that a-traumatic shoulder problems are the result of impingement of the subacromial structures, such as the bursa or rotator cuff tendons. Myofascial trigger points (MTrPs) in shoulder muscles may also lead to a complex of symptoms that are often seen in patients diagnosed with subacromial impingement or rotator cuff tendinopathy. Little is known about the treatment of MTrPs in patients with shoulder disorders.     

Growth hormone signalling: sprouting links between pathways, human genetics and therapeutic options.

Our molecular understanding of growth hormone-induced signal transduction has improved significantly over the past decades. At the same time, human population genetics and the analysis of genetically engineered animals have led to the discovery of genes that control specific aspects of the overall growth process. Although, currently, growth disorders are still diagnosed and treated on empirical bases, it might soon be possible to stratify patients predominantly by genetic defect, with treatment based on our molecular understanding of the role of the affected gene in the disease.     

Reactivation of dormant lumbar methicillin-resistant Staphylococcus aureus osteomyelitis after 12 years.

The adequate treatment of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis has intrigued clinicians for some time. As the resistance of these pathogens, coupled with the increase in community-acquired cases, continues steadily to rise, clinicians are finding it useful to employ multi-modal approaches for efficacious treatment. The authors present a single case report of a patient with recurrent MRSA osteomyelitis, lumbar paraspinal and epidural abscess. He was found to have decreased muscle strength and was hyporeflexic in the involved extremity. Serum testing demonstrated MRSA bacteremia. Neuroimaging studies revealed evidence of paraspinal abscess and a presumed herniated nucleus pulposus at the L5/S1 interspace with significant nerve root compromise. Despite antimicrobials, his symptoms persisted, necessitating surgical exploration. At surgery, paraspinal and epidural abscesses were encountered and debrided; however, no herniated disc was visualized. This case demonstrates the diagnostic and therapeutic dilemmas with which these lesions present. We postulate that the MRSA osteomyelitis/discitis pathogens were walled off in the disc space and subsequently inoculated the soft tissues with ensuing bacteremia. We concur that antimicrobial treatment should be the first line of therapy for these patients; however, surgical debridements and cautious spinal instrumentation should be employed where appropriate.     

Interobserver and interstudy variability of myocardial blood flow and flow-reserve measurements with nitrogen 13 ammonia-labeled positron emission tomography

Background  

Experimental studies have shown that positron emission tomography (PET) with ¹³N-labeled ammonia provides accurate quantification of regional myocardial blood flow (MBF) under rest and stress conditions. To establish the clinical utility of this method, the interobserver variability and the temporal variability of serial measurements of blood flow and coronary flow reserve (CFR) must be known. This study investigated the interobserver and temporal reproducibility of ¹³N-labeled PET for measurement of MBF and CFR.     

Ecology of a Southern Ohio stream receiving fly ash pond discharge: Changes from acid mine drainage conditions

Prior to 1975, Stingy Run was a third-order tributary of Kyger Creek, which empties into the Ohio River at Mile 260 (Gallia County, Ohio). Both streams drained strip mine refuse areas and physicochemical measurements indicated acidicmine drainage conditions (e.g., low pH). A depauperate macroinvertebrate community, dominated by a few acid-tolerant taxa, was found in both streams and no fishes were collected. In 1974, Stingy Run was impounded to form a fly ash pond which contains fly ash sluiced from Ohio Power Company's General James M. Gavin coal-fired power plant. Physicochemical and biological sampling during 1975–1986 indicated marked changes in the aquatic ecology of Stingy Run between 1) pre-impoundment and post-impoundment conditions; and 2) effluent pH control treatments after impoundment. Fly ash discharge eliminated acidicmine drainage characteristics in Stingy Run and lower Kyger Creek. After impoundment, net spinning caddisflies and a few dipteran taxa dominated the Stingy Run benthic community, reflecting changes in functional niches likely due to improved habitat and greater food availability. Replacement of acid feed by CO₂ injection for effluent pH control and changes in ash pond chemistry occurred concomitant with elimination of a substrate floc; increased species richness and densities of invertebrates were subsequently observed. In Stingy Run, species richness and diversity of fishes increased from 1983 to 1986, reflecting improved water quality and increased benthic production after impoundment. Many of these fishes are opportunistic feeders on drifting insects.     

Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue.

(11)C-meta-Hydroxyephedrine (HED) is used in cardiac PET as an index of norepinephrine (NE) reuptake transporter (NET) density and synaptic NE levels. Whereas cardiac uptake is well documented, tracer retention in other tissues with rich noradrenergic innervation is unclear. Dysfunctional sympathetic nervous system (SNS) function in extracardiac metabolic storage tissues (i.e., adipose tissue and skeletal muscle) and endocrine organs contributes to several disorders. The aim of this study was to determine the potential of HED as an index of NE function in brown adipose tissue, lung, pancreas, skeletal muscle, and kidney by identifying NET-specific retention and determining the presence of radiolabeled metabolites. METHODS: Male Sprague-Dawley rats were administered HED and sacrificed at 30 min after tracer injection. Tissues were rapidly excised and counted for radioactivity, and relative tracer retention was quantified. Pretreatment with NET inhibitors established specific HED accumulation. The effect of elevated NE was tested by subcutaneous minipump NE infusion or inhibition of monoamine oxidase. Column-switch high-performance liquid chromatography (HPLC) was used to analyze the presence of radiolabeled metabolites in heart, brown adipose tissue, pancreas, and plasma. RESULTS: NET-specific retention was observed in heart, brown adipose tissue, lung, and pancreas but not in liver, skeletal muscle, or kidney. A dose-dependent response of HED accumulation to treatments elevating NE levels was established in tissues exhibiting specific uptake. At 30 min after tracer administration, HPLC analysis revealed 93%-95% of total radioactivity signal derived from unchanged HED in heart, pancreas, and brown adipose tissue compared with 61% +/- 8% unchanged HED in plasma. CONCLUSION: In addition to the heart, lung, pancreas, and brown adipose tissue exhibit specific and NE-responsive uptake of HED, supporting the potential for novel PET studies of SNS integrity in these tissues.