Comparative study of the efficacy of captopril, simvastatin, and L-carnitine as cardioprotective drugs in children with type 1 diabetes mellitus: a randomised controlled trial.

OBJECTIVES: To assess the efficacy and safety of captopril, simvastatin, and L-carnitine as cardioprotective drugs in children with type 1 diabetes mellitus on different echocardiographic parameters, electrocardiographic parameter, lipid profile, and carotid intima-media thickness. METHODS: This randomised controlled trial was conducted on 100 children with type 1 diabetes mellitus for more than 3 years during the period from September 2018 to June 2020. Fifty healthy children of matched age and sex served as a control group. The patients were randomly assigned into four groups (25 children each): no-treatment group who received no cardioprotective drug, simvastatin group who received simvastatin (10-20 mg/day), captopril group who received captopril (0.2 mg/kg/day), and L-carnitine group who received L-carnitine (50 mg/kg/day) for 4 months. Lipid profile, serum troponin I, carotid intima-media thickness, and echocardiographic examinations were performed on all included children before and after the treatment. RESULTS: Total cholesterol and low-density lipoprotein were significantly decreased in children who received simvastatin or L-carnitine. Triglycerides significantly decreased only in children who received simvastatin. High-density lipoprotein significantly increased in simvastatin and L-carnitine groups only. Serum troponin I decreased significantly in all the three treatment groups. Carotid intima-media thickness showed no significant change in all treatment groups. Echocardiographic parameters significantly improved in simvastatin, L-carnitine, and captopril groups. CONCLUSION: Captopril, simvastatin, and L-carnitine have a significant beneficial effect on cardiac functions in children with type 1 diabetes mellitus. However, only simvastatin and L-carnitine have a beneficial effect on the lipid profile. The drugs were safe and well tolerated.Clinical trial registration: The clinical trial was registered at www.clinicaltrial.gov (NCT03660293).

Effect of treatment with direct antiviral agents (DAAs) on glycemic control in patients with type 2 diabetes mellitus & hepatitis C virus genotype 4.

BACKGROUND AND AIMS: It is widely recognized that chronic hepatitis C is a metabolic disease that is strongly associated with type 2 diabetes mellitus (T2DM) and insulin resistance (IR). The evidence behind the effect of Direct Anti-Viral Agents (DAAs) therapy on T2DM is conflicting. The aim of the present study was to evaluate the effect of treatment with DAAs on glycemic control in patients with type-2 diabetes mellitus and chronic hepatitis C virus genotype 4. METHODS: This study was a prospective study that conducted on 100 patients with chronic hepatitis C and Type-2 diabetes mellitus, selected from Kafr El-Sheikh Liver Research Center treated with Direct Anti-Viral Agents (DAAs) during the period from September 1, 2017 to last of August 2018. All patients in the study were subjected to the following: Full history taking stressing on the age, gender, previous treatment; clinical examination and laboratory investigations. HBA1C was assessed before and after DAAs treatment. RESULTS: In the present study, there was a significant decrease of baseline fasting blood glucose levels after treatment when compared with before treatment. Also, there was a significant decrease of 2 h post prandial blood glucose after treatment when compared with before treatment. There was significant decrease of HBA1c levels after treatment when compared with before treatment. CONCLUSIONS: DAAs treatment significantly improved the fasting blood glucose and help better glycemic control. This study augments the importance and the benefits of new Direct Anti-Viral Agents interferon free regimens in diabetic HCV infected patients.

Serum Ferritin level, microalbuminuria and non-alcoholic fatty liver disease in type 2 diabetic patients.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) was considered one of the most common causes of chronic liver disease and is considered the hepatic manifestation of type 2 diabetes mellitus (T2DM). The factors that lead to marked fibrosis and liver cell injury in NAFLD are still remaining undiscovered. PATIENTS AND METHODS: This study included (40) type 2 diabetic patients with NAFLD and (40) diabetic patients without NAFLD beside 15 healthy persons as a control group. All of them were subjected to full history taking, thorough clinical examination with especial stress on body weight (BW), height, body mass index (BMI), waist-hip ratio, blood pressure. Laboratory tests included serum total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL) and high-density lipoprotein (HDL), fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG), serum Ferritin and urine microalbuminuria (MAU). RESULTS: Duration of diabetes, BW, BMI and blood pressure were significantly higher in NAFLD group (P = 0.001). FBG, PBG, TC, TG, LDL, serum Ferritin and MAU were significantly increased in NAFLD group with significant difference between two studied groups as regard HDL. There was a highly significant correlation between serum Ferritin with BW, BMI, duration of diabetes, TC, TG, LDL and MAU. There was a significant correlation between serum Ferritin with age, waist hip ratio, duration of diabetes, SBP, FBG, PBG and HDL. There was a significant correlation between MAU and age, weight, BMI, waist hip ratio, duration of diabetes, DBP, FBG TC, TG, LDL and HDL. CONCLUSION: NAFLD is a common liver disorder in diabetic patients. NAFLD is significantly associated with microalbuminuria and elevated serum Ferritin.

Nerve growth factor, neuropeptides and cutaneous nerves in atopic dermatitis.

INTRODUCTION: Neurogenic components, as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) with the neuroimmunocutaneous system as they modify the functions of immunoactive cells in the skin. Nerve growth factor (NGF) is the best-characterized member of the neurotrophin family. Both NGF and neuropeptides (NPs) may be associated with the disease pathogenesis. AIM: This study aims to evaluate the plasma level of NGF and NPs in AD patients and correlate them with the disease activity and nerve changes in the skin by electron microscopy. MATERIALS AND METHODS: Plasma levels of NGF and vasoactive intestinal peptide (+VIP) were measured by an immunoenzymatic assay while plasma levels of calcitonine gene related peptide (CGRP) and neuropeptide Y (NPY) were measured by radioimmunoassay in 30 AD patients in comparison to 10 normal non-atopic controls. Electron microscopic study was done in 10 AD patients. RESULTS: It has been found that there is significant increase of plasma levels of NGF and NPs in AD patients compared with controls. There is a positive correlation between the plasma levels of NGF and disease activity (correlation coefficient = 0.750, P<0.005). There is a significant correlation between the number of Schwann axon complex, evidenced by electron microscopic examination and plasma level of NGF in AD patients. CONCLUSION: It has been concluded that these neurogenic factors; NGF and NPs modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. NGF might be considered as a marker of the disease activity.

Role of Foxp3 and regulatory CD4+CD25+ T-lymphocytes in bronchial asthma.

Regulatory T cells (Tregs) are thought to have a critical role in the suppression of immune responses. In addition to the prevention of the development of autoimmunity, they are thought to have a role in the prevention of allergic responses to environmental allergens. Foxp3 is transcription factor (Foxp3), which is predominantly expressed by CD4+ CD25+ T cells, and may correlates with the suppressive activity of these cells. This study assesses the immunoregulatory role of CD4+CD25+ T-lymphocytes in peripheral blood of asthmatic children and possible role of Foxp3 mRNA expression. The study included thirty children, 10 with acute asthmatic exacerbation, 10 during rest state with no asthma manifestation and 10 apparently healthy children. T-regs, and Foxp3 mRNA were investigated using Flowcytometry and RT-PCR respectively. Early morning sputum was also collected for determination of eosinophillia. Significant increase in the percent of CD4+CD25+ was found in acute asthmatic as compared to stable asthmatic cases (23.3 +/- 3.74% vs 13.97% +/- 1.18%), and in acute asthmatic group than control group (13.97% +/- 1.18% vs 8.12 +/- 1.65%), (P < 0.001). Similarly, significant increase in Foxp3 mRNA expression was found in acute asthmatic cases as compared to stable and control children (P < 0.001). A significant positive correlation was found between Foxp3 mRNA expression and the percent of CD4+CD25+ T cells in all studied groups (r = 0.91 P = 0.01). It is concluded that regulatory CD4+CD25+ T-cells may play a critical role in maintaining suppression and protection against allergic bronchial asthma and that Foxp3 may be important in the development of these cells.

Study of gene expression of CD30 variant (CD30v) and CD30 ligand (CD30L) in acute leukemia.

Proliferation of malignant lymphohematopoietic cells is thought to be regulated by a number of surface molecules on tumour cells whose expression may contribute to neoplastic transformation. In this work, reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the gene expression (mRNA) of CD30 variant (CD30v) and CD30 Ligand (CD30L) on the peripheral blood mononuclear cells (PBMCs) of 15 healthy individuals as a control group, 15 patients with newly diagnosed acute myeloid leukemia (AML) and 15 patients with newly diagnosed acute lymphocytic leukemia (ALL). The results revealed that simultaneous positive expression of both CD30v and CD30L was found in 46.7%, 40% and 53.3% of whole leukemic patients and those with AML and ALL respectively, with significant difference from controls in whom no expression was found (P=0.007, 0.021 and 0.005, respectively). Patients with positive expression of CD30v and CD30L were found to have significantly increased blast cell % (p<0.001), increased total leucocytic count (P<0.001) and decreased platelets count (P<0.001) than those with negative expression. No significant difference in expression could be noticed in relation to age (p>0.05), sex (P=0.998.) or hemoglobin (Hb) level (P=0.20). As regard to immunophenotypes of ALL, positive expression was found to be significantly higher in B-cell than T-cell subtype (77.8% versus 16.7%, P=0.02). It could be concluded that frequent expression of CD30V and CD30L was detected only in newly diagnosed cases of AML and ALL, but not in healthy individuals. Positive expression was also significantly associated with more aggressive disease and with B-cell than T-cell subtypes. These results suggested a possible role of these molecules in pathogenesis of such hematopoietic malignancy. Further studies are needed for better understanding of the involved mechanisms.

Evaluation of natural killer cells as diagnostic markers of early onset neonatal sepsis: comparison with C-reactive protein and interleukin-8.

This study was conducted on thirty-seven neonates and healthy neonates (sixteen full term and fourteen preterm). The study aimed at revealing the role played by the NK cells in neonatal sepsis and evaluating the sensitivity of NK cell number and cytotoxicity as diagnostic markers in infants with suspected early neonatal sepsis compared with the circulating cytokine IL-8 and CRP levels. All samples of peripheral blood lymphocytes were subjected to determination of CD16 and CD56 positive cells using flow cytometry and NK cytotoxicity using the standard 4h 51Cr release assay. Sera were separated to measure IL-8 using ELISA. Determination of CRP, using turbdimetric assay, as well as blood cultures were done for patient's group only. Out of the 37 cases of suspected early neonatal sepsis, 16 were given final diagnosis of sepsis. Seven infants (43.8%) in the sepsis group had culture-proven diagnosis, one of which had meningitis. The median CRP value was significantly higher in sepsis group (88 mg/L; range: 17-159 mg/L) compared with that in non-septic group (15.4 mg/L; range: 7.6-23.2 mg/L, p < 0.001) only 12-60 h after admission. On the other hand, newborns in the sepsis group had significantly higher serum levels of IL-8 (median 310 pg/mL; range: 37-583 pg/ml) at study entry than that in the non septic group (median 63 pg/mL; range: 32-94 pg/ml, P < 0.001). On admission, the NK activity, rather than the number of CD16 and CD56 positive cells was much affected where NK cytotoxicity was significantly lower in sepsis group (3.4 +/- 2.1%, range 0.9-7%) than that of the nonseptic group (18.3 +/- 6.7%: range 10.7- 25.3%, p < 0.01) and healthy neonates (23.8 +/- 4.7%: range 12.2-32.3%, p < 0.001). We may conclude that defective NK cell activity rather than NK cell number plays an important role in susceptibility to early onset neonatal sepsis. Evaluation of NK cytotoxicity as a marker in early diagnosis of neonatal sepsis reveals that the sensitivity, specificity and predictive values of reduced NK cytotoxicity (10% killing) was higher than both of CRP and IL-8, either individually or in combination. Additionally, reduced NK cytotoxicity showed high correlation with the severity and outcome of neonatal sepsis. Our data raise the possibility that the addition of NK cell activity to the standard work-up of critically ill patients with suspected sepsis could increase diagnostic certainty and generate an improved patient management.