A plasma inhibitor of the renin-antirenin reaction and the in vitro generation of angiotensin I

In the course of studies designed to develop a radioimmunoassay system for the detection of renin, we have identified in human plasma a potent inhibitor that interferes with the renin-antirenin reaction. Utilizing gel filtration, this renin-antirenin inhibitory activity was found to have the same molecular size as renin substrate. However, it could be separated from renin substrate by ion-exchange chromatography. When fractions containing this activity were tested in an in vitro system containing renin and renin substrate, they were found to inhibit the generation of angiotensin I.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22129/1/0000557.pd

Production and use of 6He, 7Be, 8Li, 12B and metastable nuclear beams

A low energy (few MeV/nucleon), modest flux (104-107/s) radioactive nuclear beam (RNB) facility has been in operation for approximately three years at the University of Notre Dame Van de Graaff accelerator. This facility utilizes a compact superconducting solenoid lens, designed at the University of Michigan, with adjustable apertures to produce momentum-analyzed secondary beams via the direct transfer and other methods. Useable beams of 6He, 7Be, 8Li, 12B, 18F and to our knowledge the first isomeric beam, 18mF, have been produced and a first generation of RNB experiments has been successfully completed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29368/1/0000438.pd

Muscle Mitochondrial ATP Synthesis and Glucose Transport/Phosphorylation in Type 2 Diabetes

BACKGROUND: Muscular insulin resistance is frequently characterized by blunted increases in glucose-6-phosphate (G-6-P) reflecting impaired glucose transport/phosphorylation. These abnormalities likely relate to excessive intramyocellular lipids and mitochondrial dysfunction. We hypothesized that alterations in insulin action and mitochondrial function should be present even in nonobese patients with well-controlled type 2 diabetes mellitus (T2DM). METHODS AND FINDINGS: We measured G-6-P, ATP synthetic flux (i.e., synthesis) and lipid contents of skeletal muscle with (31)P/(1)H magnetic resonance spectroscopy in ten patients with T2DM and in two control groups: ten sex-, age-, and body mass-matched elderly people; and 11 younger healthy individuals. Although insulin sensitivity was lower in patients with T2DM, muscle lipid contents were comparable and hyperinsulinemia increased G-6-P by 50% (95% confidence interval [CI] 39%–99%) in all groups. Patients with diabetes had 27% lower fasting ATP synthetic flux compared to younger controls (p = 0.031). Insulin stimulation increased ATP synthetic flux only in controls (younger: 26%, 95% CI 13%–42%; older: 11%, 95% CI 2%–25%), but failed to increase even during hyperglycemic hyperinsulinemia in patients with T2DM. Fasting free fatty acids and waist-to-hip ratios explained 44% of basal ATP synthetic flux. Insulin sensitivity explained 30% of insulin-stimulated ATP synthetic flux. CONCLUSIONS: Patients with well-controlled T2DM feature slightly lower flux through muscle ATP synthesis, which occurs independently of glucose transport /phosphorylation and lipid deposition but is determined by lipid availability and insulin sensitivity. Furthermore, the reduction in insulin-stimulated glucose disposal despite normal glucose transport/phosphorylation suggests further abnormalities mainly in glycogen synthesis in these patients

Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2

Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

In-vivo dosimetry for gynaecological brachytherapy: Physical and clinical considerations

Introduction: The study aimed to estimate the dosimetric uncertainty using diodes (PTW/Germany) for a high-dose rate Iridum-192 source under clinical conditions. Finally, the role of in-vivo dosimetry for cervix cancer patients was evaluated. Material and methods: First, diode calibration and factors influencing diode response were investigated and phantom studies compared doses measured and computed by the treatment planning system. Based on that, the uncertainty for diode measurements was estimated to be 7% (1 sigma). Secondly, 55 applications of patients with cervix carcinoma were evaluated. Doses in rectum and bladder were measured and compared to the computed doses and differences were calculated. If the differences exceeded 10% the corresponding shift in probe position was evaluated. Additionally, the in-vivo dosimetry data were compared to doses at the ICRU 38 [ICRU Report No. 38, dose and volume specification for reporting intracavitary therapy in gynaecology. In: Chassagne D, Dutreix A, Almond P, Burgers J, Busch M, Joslin C editors. International commissioning on radiation units and measurements. Bethesda: 1985.] reference points for rectum and bladder. Results: In patients, in-vivo dosimetry resulted in differences between calculated and measured doses ranging from -31 to +90% (mean 11%) for the rectum and from -27 to +26% (mean 4%) for the bladder. Shifts in probe position of 2.5 mm for the rectal probe and 3.5 mm for the bladder probe caused dose differences exceeding 10%. The dose at the ICRU rectum reference point was underestimated by the calculated doses at probe position ranging from -61 to 156% (mean 29%). The dose to the ICRU bladder reference point was underestimated by the calculated dose ranging from 12 to 162% (mean 58%). Conclusion: The study shows that diode accuracy and reproducibility is sufficient for clinical applications. For accurate in-vivo dosimetry geometric conditions are of outmost importance. It is recommended that in-vivo dosimetry should be performed in addition to computation. (c) 2005 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 77 (2005) 310-317