Amelioration of exosome and mesenchymal stem cells in rats infected with diabetic nephropathy by attenuating early markers and aquaporin-1 expression

Abstract Diabetic nephropathy (DN) is a prevalent diabetic microvascular condition. It is the leading cause of kidney disease in the advanced stages. There is no currently effective treatment available. This research aimed to investigate the curative potentials of exosomes isolated from mesenchymal stem cells affecting DN. This study was performed on 70 male adult albino rats. Adult rats were randomized into seven groups: Group I: Negative control group, Group II: DN group, Group III: Balanites treated group, Group IV: MSCs treated group, Group V: Exosome treated group, Group VI: Balanites + MSCs treated group and Group VII: Balanites + exosome treated group. Following the trial period, blood and renal tissues were subjected to biochemical, gene expression analyses, and histopathological examinations. Results showed that MDA was substantially increased, whereas TAC was significantly decreased in the kidney in the DN group compared to normal health rats. Undesired elevated values of MDA levels and a decrease in TAC were substantially ameliorated in groups co-administered Balanites aegyptiacae with MSCs or exosomes compared to the DN group. A substantial elevation in TNF-α and substantially diminished concentration of IGF-1 were noticed in DN rats compared to normal health rats. Compared to the DN group, the co-administration of Balanites aegyptiacae with MSCs or exosomes substantially improved the undesirable elevated values of TNF-α and IGF-1. Furthermore, in the DN group, the mRNA expression of Vanin-1, Nephrin, and collagen IV was significantly higher than in normal healthy rats. Compared with DN rats, Vanin-1, Nephrin, and collagen IV Upregulation were substantially reduced in groups co-administered Balanites aegyptiacae with MSCs or exosomes. In DN rats, AQP1 expression was significantly lower than in normal healthy rats. Furthermore, the groups co-administered Balanites aegyptiacae with MSCs or exosomes demonstrated a substantial increase in AQP1 mRNA expression compared to DN rats

Morning administration of 0.4 U/kg/day insulin glargine 300 U/mL provides less fluctuating 24-hour pharmacodynamics and more even pharmacokinetic profiles compared with insulin degludec 100 U/mL in type 1 diabetes

Abstract Aim To compare steady state pharmacodynamic and pharmacokinetic profiles of insulin glargine 300U/mL (Gla-300) with insulin degludec 100U/mL (Deg-100) in people with type 1 diabetes. Methods This single-centre, randomized, double-blind crossover euglycaemic clamp study included two parallel cohorts with fixed once-daily morning dose regimens. For both insulins participants received 0.4 ( n =24) or 0.6U/kg/day ( n =24), before breakfast, for 8 days prior to the clamp. The main endpoint was within-day variability (fluctuation) of the smoothed glucose infusion rate (GIR) over 24 hours (GIR-smFL 0–24 ). Results Gla-300 provided 20% less fluctuation of steady state glucose infusion rate profiles than Deg-100 over 24 hours at 0.4U/kg/day (GIR-smFL 0–24 treatment ratio 0.80 [90% confidence interval: 0.66 to 0.96], P =0.047), while at the dose of 0.6U/kg/day the difference between insulins was not statistically significant (treatment ratio 0.96 [0.83 to 1.11], P =0.603). Serum insulin concentrations appeared more evenly distributed with both dose levels of Gla-300 versus the same doses of Deg-100, as assessed by relative 6-hour fractions of the area under the curve within 24 hours. Both insulins provided exposure and activity until 30 hours (end of clamp). Conclusion Gla-300 provides less fluctuating steady state pharmacodynamic profiles (i.e. lower within-day variability) and more evenly distributed pharmacokinetic profiles, compared with Deg-100 in a once-daily morning dosing regimen of 0.4U/kg/day

Forced vital capacity (FVC), peaked expiratory flow rate (PEFR), are additional parameters in the assessment of the reversibility test.

Background: Spirometry is an important test performed in patients expect to have airway obstruction, assessment of intense reaction to inhalers (the trial of reversibility of airway blockade) is a normally utilized technique in clinical and academic studies. The consequences of this test are utilized to make choices on treatment, consideration, exclusion from diagnosis and other research think about, and for analytic marking [asthma versus chronic obstructive airway disease (COPD)]. Usually, the (FEV1) or (FVC) standards before and after giving of the bronchodilator are compared and the adjustment is processed to distinguish variations from the norm in lung volumes and air flow. Objective: The aim of this study was to investigate the effectiveness of FVC and PEFR as further constraints to evaluate bronchodilator reaction in asthmatic peoples with severe or moderate airflow blockade. Patients and methods: This study is cross sectional study performed in Baghdad teaching hospital where one hundred patient were enrolled in this study patients were detected with asthma and confirm airway blockade according to (GINA) guide lines. The pulmonary function for all members was investigated with a convenient spirometer (spiro-lab3 Spirometer) as stated by those measures from claiming American thoracic particular social order, The mean and standard deviation results of the predicted% values pulmonary function test were also used for comparisons were measured by t-test. A p-value of ≤ 0.05 considered to be significant statistically. Results: The post bronchodilator (post –BD) results of FVC, PEFR are greater than pre- bronchodilator where are statistically significant P value = 0.00. the amount of the changes of FVC post (BD) was more than 400ml from pre (BD) and the amount of the changes of PEFR post (BD) more than 1000ml from the pre (BD) both were p-value = 0.00. Conclusion: The asthmatic patients with moderate and severe airway obstruction, we observed that FVC and PEFR is a valuable important limit to FEV1 to evaluate reversibility reaction Keyword: forced vital capacity(FVC), peaked expiratory flow rate (PEFR), spirometry and forced expiratory volume in 1st second (FEV1)

Epidural Hematoma Following Cervical Spine Surgery.

STUDY DESIGN: A multicentered retrospective case series. OBJECTIVE: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. METHODS: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. RESULTS: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment (P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. CONCLUSION: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ(2) tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date

Reference ranges for Doppler indices of umbilical and fetal middle cerebral arteries and cerebroplacental ratio: systematic review.

OBJECTIVE: To assess studies reporting reference ranges for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR), using a set of predefined methodological quality criteria for study design, statistical analysis and reporting methods. METHODS: This was a systematic review of observational studies in which the primary aim was to create reference ranges for UA and MCA Doppler indices and CPR in fetuses of singleton gestations. A search for relevant articles was performed in MEDLINE, EMBASE, CINAHL, Web of Science (from inception to 31 December 2016) and references of the retrieved articles. Two authors independently selected studies, assessed the risk of bias and extracted the data. Studies were scored against a predefined set of independently agreed methodological criteria and an overall quality score was assigned to each study. Linear multiple regression analysis assessing the association between quality scores and study characteristics was performed. RESULTS: Thirty-eight studies met the inclusion criteria. The highest potential for bias was noted in the following fields: 'ultrasound quality control measures', in which only two studies demonstrated a comprehensive quality-control strategy; 'number of measurements taken for each Doppler variable', which was apparent in only three studies; 'sonographer experience', in which no study on CPR reported clearly the experience or training of the sonographers, while only three studies on UA Doppler and four on MCA Doppler did; and 'blinding of measurements', in which only one study, on UA Doppler, reported that sonographers were blinded to the measurement recorded during the examination. Sample size estimations were present in only seven studies. No predictors of quality were found on multiple regression analysis. Reference ranges varied significantly with important clinical implications for what is considered normal or abnormal, even when restricting the analysis to the highest scoring studies. CONCLUSIONS: There is considerable methodological heterogeneity in studies reporting reference ranges for UA and MCA Doppler indices and CPR, and the resulting references have important implications for clinical practice. There is a need for the standardization of methodologies for Doppler velocimetry and for the development of reference standards, which can be correctly interpreted and applied in clinical practice. We propose a set of recommendations for this purpose. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd