Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

BACKGROUND: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. MATERIAL AND METHODS: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. RESULTS: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. CONCLUSIONS: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Comparison between levels of Homocysteine, Interleukin-6 and Interleukin-10 in severe cases of Egyptian COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is the reason of an outbreak of respiratory illnesses ranging from typical cold to severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome. We intended to compare levels of IL-6, IL-10, and homocysteine in the sera of severe COVID-19 Egyptian patients and connect them with the extent of the illness. This cross-sectional study included 90 COVID-19 Egyptian patients. They included 45 non severe cases (group 1) and 45 severe cases (group 2). There was statistically significantly increase in IL-6 in group 2 (median = 7.05, IQR = 6.2 - 7.9; p < 0.001) in comparison to group 1 (median = 4.96, IQR = 4.5 - 5.8) and statistically significantly increase in IL-10 in group 2 (154.1 ± 73.3) in comparison to group 1 (47.04 ± 23.8; p < 0.001). There were no variations in the examined groups' homocysteine levels (p= 0.318). Furthermore, there was statistically substantial positive connection (r=0.30) between IL-6 and AST (p=0.046) and between IL-10 and HCT (r = 0.37, p=0.012). In addition, data of other studied parameters are presented. In conclusion, IL-6 and IL-10 could be proposed for follow up of COVID-19 patients and to detect cases before progressing to a severe disease stage.

Evaluation of circulating miR-16-5p and miR-223-5p in association with musculoskeletal ultrasonography seven-joint score in the assessment of rheumatoid arthritis activity.

Rheumatoid arthritis (RA) is characterized by ongoing joint destruction. MicroRNAs (miRs) are blood-based biomarkers linked to RA pathogenesis. The musculoskeletal ultrasonography seven-joint score (US7) is an objective tool to assess RA activity. We aimed to evaluate miR-223 and miR-16 roles in monitoring RA activity and to investigate if there is a link between their plasma levels and US7 score. This study enrolled 76 RA patients classified according to Disease Activity Score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 38) and active cases (n = 38). Each patient's joint was scored for synovial proliferation (gray-scale ultrasound 'GSUS7') and vascularization (power Doppler ultrasound 'PDUS7'). Real-time quantitative PCR was used to measure the expression levels of miR-16 and miR-223 in plasma. When compared to inactive group, the active group revealed significant upregulation of miR-16 and miR-223, (P = 0.001 and P = 0.02, respectively). miR-16 and miR-223 levels were correlated with synovitis PDUS7 (r = 0.34, p < 0.01 and r= 0.25, P = 0.03, respectively). miR-16 was also positively correlated with synovitis GSUS7 (r= 0.42, p < 0.001). miR-223 upregulation discriminated active from inactive RA patients at AUC = 0.64, with 76% sensitivity and 50% specificity at cutoff > 2.8-fold change), whereas miR-16 distinguished the two groups at AUC = 0.78 with 87% sensitivity and 53% specificity at cutoff >38.27-fold change. In conclusion, upregulated miR-16 may have more potential to serve as activity biomarkers than miR-223 in RA. The miR-16 level was linked to synovitis GSUS7 and synovitis PDUS7 changes but miR-223 only linked to synovitis PDUS.

Correlations between serum testosterone and irisin levels in a sample of Egyptian men with metabolic syndrome; (case-control study).

BACKGROUND: Metabolic syndrome (MetS) in men is a common problem. Several studies highlight that testosterone deficiency is associated with metabolic disorders that may be explained by "myokines". Irisin is an adipo-myokine that has beneficial metabolic effects. AIM: To evaluate serum testosterone in a sample of Egyptian men with MetS diagnosed by NCEP ATP III, and correlate it with serum irisin level. METHODS: A total of 90 men (60 with MetS and 30 healthy age-matched controls) participated in the study. Testosterone level is estimated by an automated system, Irisin level was measured by ELISA. RESULTS: Circulating irisin was positively correlated with serum testosterone and was significantly lower in patients with MetS. CONCLUSION: This study highlights the effect of serum testosterone on irisin formation from skeletal muscle. Recommendations; treatments of MetS may include testosterone supplementation. Further studies are needed to elucidate this association.

Detection of soluble urokinase type plasminogen activator receptors in children with gingivitis and normal subjects.

BACKGROUND: Gingivitis is a reversible condition; however, if left untreated, it progresses to periodontitis, which a serious infection that leads to bone destruction. Soluble urokinase-type plasminogen activator receptor (suPAR) measurement may be of value in the early assessment of gingivitis in children, thereby minimizing risk of tooth loss. OBJECTIVES: In this observational study, we assessed salivary and serum concentrations of suPAR for the diagnosis of gingivitis and correlation of salivary suPAR with the periodontal clinical parameters. METHODS: Ninety children participated in the study, with 20 healthy subjects as controls and 70 patients with gingivitis. The gingivitis group was divided into mild, moderate, and severe cases. According to the gingival index (GI), salivary and serum samples were analyzed for the suPAR and C-reactive protein levels using an enzyme-linked immunosorbent assay. RESULTS: The salivary suPAR was significantly higher in patients with gingivitis (10.8 ± 2.9 ng/mL) than in the control group (7.0 ± 1.1 ng/mL) as P < 0.001. SuPAR was correlated with gingivitis severity. It was 7.7 ± 1.5 1 ng/mL in mild cases, 10.9 ± 1.2 ng/mL in moderate cases, and 14.4 ± 0.9 ng/mL in severe cases. The difference was significantly high (P < 0.001) between the groups; however, the difference between the mild cases and the control was nonsignificant as P < 0.066. The salivary suPAR was correlated with periodontal clinical parameters, which included GI and simple oral hygiene index (SOHI). Conversely the serum suPAR was not correlated with the salivary suPAR or the periodontal clinical parameters. CONCLUSION: The results of the present study demonstrated that the salivary suPAR is increased in proportionate with the degree of severity of gingivitis in children. Moreover, salivary suPAR was correlated with the periodontal clinical parameters.

Admission Levels of Serum P-Selectin and IL-6 Can Predict Development of Deep Venous Thrombosis in Hospitalized Covid-19 Patients.

Background and Aim: Deep venous thrombosis (DVT) of the lower extremities is common in Covid-19 patients. Interleukin (IL)-6 and P-selectin were found to be elevated in Covid-19 patients. The current study aimed to evaluate P-selectin and IL6 in Covid-19 patients with DVT and to explore its relation to clinical and laboratory parameters in those patients. Patients and methods: The present retrospective study included 150 hospitalized COVID-19 patients diagnosed on the basis of a positive result of reverse-transcriptase polymerase chain reaction (RT-PCR) test. Laboratory assessments were included for IL-6 and P selectin assessments via enzyme-linked immunosorbent assay. The primary outcome of the present study was the development of DVT detected by Doppler ultrasound (DU) evaluation of the lower extremities during the admission. Results: The present study included 150 hospitalized Covid-19 patients. DVT was developed in 59 patients (39.3%). DVP patients had significantly higher levels of P selectin [76.0 (63.0-87.0) versus 63.0 (54.3-75.0), p < 0.001] and IL-6 [37.0 (27.0-49.0) versus 18.5 (13.5-31.5), p < 0.001]. ROC curve analysis revealed good performance of P selectin [AUC (95% CI): 0.72 (0.64-0.81)] and IL-6 [AUC (95% CI): 0.79 (0.71-0.86)] in identification of DVT. Logistic regression analysis identified the presence of severe disease [OR (95% CI): 9.016 (3.61-22.49), p < 0.001], elevated P selectin [OR (95% CI): 1.032 (1.005-1.059), p = 0.018] and elevated IL-6 [OR (95% CI): 1.062 (1.033-1.091), p < 0.001] as significant predictors of DVT development in multivariate analysis. Conclusion: The present study identified a probable role of elevated P-selectin and IL-6 levels in the DVT development in hospitalized Covid-19 patients.

Correlation of serum apelin level with carotid intima-media thickness and insulin resistance in a sample of Egyptian patients with type 2 diabetes mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a growing health problem in Egypt, with a significant impact on morbidity and mortality. Measurement of the carotid Intima-media thickness (CIMT) allows early detection of atherosclerotic blood vessel diseases. Apelin is an adipose tissue-derived hormone that may be associated with insulin resistance (IR). This study aimed to assess the level of serum apelin in patients with T2DM and its relation to IR and CIMT. Materials and Methods: A case-control study was conducted on 60 patients with T2DM and 30 healthy controls. T2DM was diagnosed based on American Diabetes Association criteria. The study was carried out at Al-Zahraa University Hospital, Cairo, Egypt, through the period from June to December 2019. The laboratory investigations included serum apelin and blood glucose hemostasis markers. CIMT was assessed using B-mode ultrasonography. Results: Patients' group had a statistically significant higher apelin level than healthy controls (407.96 ± 291.07 versus 83.32 ± 10.55 ng/dL, P < 0.001). The correlation analysis showed that the serum apelin level correlated positively with glycemic indices, body weight, and waist circumference (P < 0.05). At cutoff value of >96 ng/dL, the serum apelin exhibited a sensitivity of 98.3% and specificity of 96.7%, positive predictive value of 98.1%, and negative predictive value of 96.5%, with a diagnostic accuracy of 95.1%. Serum apelin correlated positively with CIMT (r = 0.296, P = 0.022). Logistic regression analysis showed that systolic and diastolic blood pressures, Homeostasis Model Assessment of IR, and CIMT were independent predictors of serum apelin. Conclusion: Serum apelin may be correlated with the degree of carotid atherosclerosis and hence can be used as a prognostic biomarker.

Brain-derived neurotrophic factor in relation to central obesity in children with sleep disordered breathing.

INTRODUCTION: Sleep disordered breathing (SDB) represents common comorbidities of childhood obesity leading to interrupted sleep and sleep deprivation. Sleep deprivation alters secretion of brain-derived neurotrophic factor (BDNF), which is an appetite regulator. However, little is known about the relation between BDNF and central obesity in children with SDB. The aim of the study was to evaluate BDNF level and anthropometric indices in relation to SDB in children with obesity. MATERIAL AND METHODS: A prospective case-control study was conducted on 30 children with obesity (BMI > 95th percentile) and 30 healthy lean children (BMI 5th-85th percentile). Polysomnographic, anthropometric data and BDNF serum level were obtained from all included children. Serum level of BDNF and anthropometric indices of obesity were assessed in relation to SDB in children with obesity. Regression analysis was done to determine predictors for SDB in children with obesity. RESULTS: In comparison to healthy controls, anthropometric indices of central obesity were significantly higher while BDNF was significantly lower in obese children, especially those with SDB. Respiratory disturbance index has a significant positive correlation with anthropometric indices of central obesity and a significant negative correlation with BDNF level. Central obesity and decreased BDNF were associated with 2-fold increased risk for SDB. Waist circumference/height ratio and neck circumference/height ratio have 89.5%, 75% sensitivity and 81.23%, 84.62% specificity at a cutoff point > 0.62, > 0.24 respectively for prediction of SDB in children with obesity. CONCLUSIONS: Central obesity and decreased BDNF represent independent predictors for SDB in children with obesity. Anthropometric indices adjusted to height are a simple screening tool for SDB in obese children.