Reactive oxygen species cause diabetes-induced decrease in renal oxygen tension

Aims/hypothesis Augmented formation of reactive oxygen species (ROS) induced by hyperglycaemia has been suggested to contribute to the development of diabetic nephropathy. This study was designed to evaluate the influence of streptozotocin (STZ)-induced diabetes mellitus, as well as the effects of preventing excessive ROS formation by -tocopherol treatment, on regional renal blood flow, oxygen tension and oxygen consumption in anaesthetized Wistar Furth rats.Methods Non-diabetic and STZ-diabetic rats were investigated after 4 weeks with or without dietary treatment with the radical scavenger DL--tocopherol (vitamin E, 5%). A laser-Doppler technique was used to measure regional renal blood flow, whilst oxygen tension and consumption were measured using Clark-type microelectrodes.Results Renal oxygen tension, but not renal blood flow, was lower throughout the renal parenchyma of diabetic rats when compared to non-diabetic control rats. The decrease in oxygen tension was most pronounced in the renal medulla. Renal cellular oxygen consumption was markedly increased in diabetic rats, predominantly in the medullary region. Diabetes increased lipid peroxidation and protein carbonylation in the renal medulla. Treatment with -tocopherol throughout the course of diabetes prevented diabetes-induced disturbances in oxidative stress, oxygen tension and consumption. The diabetic animals had a renal hypertrophy and a glomerular hyperfiltration, which were unaffected by -tocopherol treatment.Conclusions/interpretation We conclude that oxidative stress occurs in kidneys of diabetic rats predominantly in the medullary region and relates to augmented oxygen consumption and impaired oxygen tension in the tissue.Abbreviations ROS Reactive oxygen species - TBARS thiobarbituric acids reactive substances - NO nitric oxide - STZ streptozotocin     

The Moxus Modular metabolic system evaluated with two sensors for ventilation against the Douglas bag method

This study evaluated the Moxus metabolic system with the Douglas bag method (DBM) as criterion. Reliability and validity were investigated in a wide range of ventilation and oxygen uptake and two sensors for determining ventilation were included. Thirteen well-trained athletes participated in one pre-test and four tests for data collection, exercising on a cycle ergometer at five submaximal powers (50–263 W) and at $ V{\text{O}}_{{2{ \hbox{max} }}} $ . Gas exchange variables were measured simultaneously using a serial setup with data collected on different days in an order randomized between Moxus with pneumotachometer (MP) and turbine flowmeter (MT) sensors for ventilation. Reliability with both sensors was comparable to the DBM. Average CV (%) of all exercise intensities were with MP: 3.0 ± 1.3 for VO₂, 3.8 ± 1.5 for VCO₂, 3.1 ± 1.2 for the respiratory exchange ratio (RER) and 4.2 ± 0.8 for V _E. The corresponding values with MT were: 2.7 ± 0.3 for VO₂, 4.7 ± 0.4 for VCO₂, 3.3 ± 0.9 for RER and 4.8 ± 1.4 for V _E. Validity was acceptable except for small differences related to the determination of ventilation. The relative differences in relation to DBM at the powers including $ V{\text{O}}_{2\hbox{max} } $ were similar for both sensors with the ranges being: +4 to ?2 % for V _E, +5 to ?3 % for VO₂ and +5 to ?4 % for VCO₂ while RER did not differ at any power. The Moxus metabolic system shows high and adequate reliability and reasonable validity over a wide measurement range. At a few exercise levels, V _E differed slightly from DBM, resulting in concomitant changes in VO₂ and VCO₂.     

In Vivo Evaluation and Dosimetry Estimate for a High Affinity Affibody PET Tracer Targeting PD-L1

Molecular Imaging and Biology - In vivo imaging of programmed death ligand 1 (PD-L1) during immunotherapy could potentially monitor changing PD-L1 expression and PD-L1 expression heterogeneity...     

A double-blind, placebo-controlled trial to assess the efficacy of quetiapine fumarate XR in very heavy-drinking alcohol-dependent patients

Background: Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol‐dependent population of very heavy drinkers. Methods: In this double‐blind, placebo‐controlled trial, 224 alcohol‐dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization. Results: No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy‐drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%). Conclusions: This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy‐drinking alcohol‐dependent patients.     

A retrospective evaluation of iatrogenic dental root damage with predrilled vs drill-free bone anchor screws for intermaxillary fixation

Abstract – Aims: The aim of this study was to retrospectively evaluate iatrogenic dental root damage, caused by two different techniques that utilized bone anchor screws, for intermaxillary fixation (IMF) in orofacial trauma. Materials and methods: The techniques used included either predrilled or drill‐free bone anchor screws. A total of 123 patients who required IMF were evaluated (97 men and 26 women). Sixty‐four patients were treated in the predrilled group, and 59 patients were treated in the drill‐free group. The data were collected over an 8‐year period and were analyzed using crosstabs and Fisher’s exact test. Results: Injuries to dental roots were found only in the predrilled group. Twenty‐nine patients (45.3%) were injured at the time of surgery. One year after surgery, 10 patients (15.6%) had permanently injured dental roots. There was a significant difference in injury rates between the predrilled and drill‐free groups 1 year after surgery (P < 0.001). Conclusion: There is an increased potential risk of iatrogenic injury and permanent damage to the dental roots when a technique that involves predrilled holes for bone anchor screws is used.