INCREASED URINARY 8-OXO-7,8-DIHYDRO-2′-DEOXYGUANOSINE EXCRETION IN A SAMPLE OF EGYPTIAN CHILDREN WITH BETA THALASSEMIA MAJOR: MARKER FOR LIPID PEROXIDATION-INDUCED DNA DAMAGE

Objective: The objective of this research was to evaluate oxidative stress status in children with β-thalassemia major.Methods: Our study was conducted in children with β-thalassemia aged from 5 to 15 years. Investigate the urinary excretion of human 8-oxo-7,8- dihydro-2′-deoxyguanosine, which will be analyzed by enzyme-linked immunosorbent assay. To investigate serum levels of antioxidant enzymes include glutathione s-transferase (GST) and catalase (CAT).Results: We found a significant elevation of the urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine level with p=0.001 compared to control group, a significant reduction of both GST and CAT p=0.05 and 0.03, respectively, compared to control group. There was a significant negative correlation between urinary 8-oxo-7,8-dihydro-2′-deoxyguanisine and CAT level, r=−0.378, p=0.016, hemoglobin - r=−0.610, p=0.001, hematocrit (%) - r=−0.478, p=0.002, while a significant positive correlation between urinary 8-oxo-7,8-dihydro-2′-deoxyguanisine and alanine aminotransferase - r=0.547, p=0.001, and serum ferritin - r=0.391, p=0.013. There was a significant negative correlation between CAT and serum ferritin - r=−0.320, p=0.44.Conclusion: We conclude that the strongly increased urinary excretion 8-oxo-7,8=dihydro-2′-deoxyguanisine indicates elevated lipid peroxidation induced DNA damage in internal organs such as the liver. These highly pro mutagenic lesions may contribute to the increased risk of thalassemia patients to develop hepatocellular carcinoma

The synaptic ribbon is a site of phosphatidic acid generation in ribbon synapses.

Ribbon synapses continuously transmit graded membrane potential changes into changes of synaptic vesicle exocytosis and rely on intense synaptic membrane trafficking. The synaptic ribbon is considered central to this process. In the present study we asked whether tonically active ribbon synapses are associated with the generation of certain lipids, specifically the highly active signaling phospholipid phosphatidic acid (PA). Using PA-sensor proteins, we demonstrate that PA is enriched at mouse retinal ribbon synapses in close vicinity to the synaptic ribbon in situ. As shown by heterologous expression, RIBEYE, a main component of synaptic ribbons, is responsible for PA binding at synaptic ribbons. Furthermore, RIBEYE is directly involved in the synthesis of PA. Using various independent substrate binding and enzyme assays, we demonstrate that the B domain of RIBEYE possesses lysophosphatidic acid (LPA) acyltransferase (LPAAT) activity, which leads to the generation of PA from LPA. Since an LPAAT-deficient RIBEYE mutant does not recruit PA-binding proteins to artificial synaptic ribbons, whereas wild-type RIBEYE supports PA binding, we conclude that the LPAAT activity of the RIBEYE(B) domain is a physiologically relevant source of PA generation at the synaptic ribbon. We propose that PA generated at synaptic ribbons likely facilitates synaptic vesicle trafficking.journal articleresearch support, non-u.s. gov't2011 Nov 02importe

URINARY MARKERS OF OXIDATIVE DNA DAMAGE IN TYPE 1 DIABETIC CHILDREN: RELATION TO MICROVASCULAR COMPLICATIONS

  Objective: Type 1 diabetes mellitus (T1DM) is a widespread metabolic disease, which frequently carries with it a significant impact on human health. Oxidative damage and tissue inflammation have been claimed to be a typical pathogenic component for the progression of diabetic complications. We aim in this study to explore the relation of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) (as a marker of nucleic acid oxidation) to microvascular complications in T1DM.Methods: A case–control study, enrolling 45 T1DM children and an equivalent number of healthy subjects, was performed. Full clinical examination and anthropometric measurement were performed to all subjects. Urinary assessment for 8-oxodG and albumin was done in addition to blood sampling for lipid profile and glycated Hb (HbA1c) assay. Complete ocular examination for assessment of diabetic retinopathy (DR) was also done.Results: Levels of urinary 8-oxodG, serum cholesterol, triglycerides, and low-density lipoprotein in cases were significantly higher than non-diabetics; these levels were likewise higher in uncontrolled T1DM patients in comparison with well-controlled T1DM subjects. Urinary 8-oxodG and HbA1c were significantly higher in diabetic patients with albuminuria and DR compared to patients without complications. Significant positive correlation was found between 8-oxodG with HbA1c (r=0.8, p<0.01), diastolic blood pressure (DBP) (r=0.4, p=0.02), and cholesterol (r=0.4, p=0.05).Conclusion: Urinary 8-oxodG was found to be a reliable marker for assessing oxidative DNA damage in T1DM and can be used in the determination of microvascular complications related to diabetes

Protein Energy Wasting in a Sample of Egyptian Children on Regular Hemodialysis: Relation to Anorexigenic Hormones

BACKGROUND: Increased incidence of pediatric end-stage renal disease (ESRD) with associated serious consequences indicating a major public health problem. Malnutrition and uremic wasting are leading causes of growth impairment and increasing morbidity and mortality of pediatric ESRD patients, predominantly those on regular hemodialysis (HD). Ghrelin and obestatin, which are known appetite regulatory hormones, might have a pivotal role in uremic wasting and growth impairment in hemodialyzed children. AIM: The aim of the present study was to measure serum unacylated ghrelin (UAG) and obestatin and to investigate their roles in the growth impairment of Egyptian hemodialyzed children. SUBJECTS AND METHODS: The study included 50 hemodialyzed and 40 healthy children recruited from the Department of Nephrology, Pediatric Hospital, Ain Shams University. Full clinical examination and measurement of anthropometric indices were done. Routine labs were done as well, with an assessment of serum levels of obestatin, UAG, and insulin by enzyme linked immunosorbent assay. Furthermore, we determined fasting serum glucose and lipid profile with the calculation of homeostasis model assessment for insulin resistance (HOMA-IR). RESULTS: Anthropometric measurements were statistically significantly decreased in the hemodialyzed group than that of the control group (p < 0.05). Weight z-score was the most affected anthropometric parameter (37 patients = 74% with underweight and 13 patients = 26% with normal weight). The hemodialyzed children showed a significant increase of UAG, obestatin, insulin, glucose, HOMA-IR, and TG, while a significant decrease of HDL-cholesterol and albumin (p < 0.01). UAG had a negative correlation with Wt-z score, Ht z-score, fat mass %, albumin, and TG while obestatin was inversely correlated to Wt-z score, BMI z-score, waist circumference, and waist-height ratio (W/H). CONCLUSION: UAG and obestatin hormones were elevated in a group of Egyptian children on regular HD. These hormones were strongly related to the impairment of renal functions, and anthropometric parameters, dyslipidemia, hypoalbuminemia, and insulin resistance in these pediatric hemodialyzed patients

Pentraxin 3: A Potential Novel Predictor for Neonatal Pulmonary Hypertension

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a serious neonatal problem which has a high mortality rate even with advanced modes of mechanical ventilation. Pentraxin 3 is one of the long pentraxins, which plays an essential role in regulation of cell proliferation and angiogenesis. AIM: This study aims to assess serum pentraxin 3 levels in neonates with pulmonary arterial hypertension and compare them in those who have other congenital heart diseases and healthy neonates. Also, we intended to evaluate serum levels of CRP as a mediator of inflammation in the studied groups. METHODS: The study is a case-control study. Cases were recruited from El Galaa Teaching Hospital, classified into three groups; each group had thirty cases. The first one: cases with pulmonary hypertension (PHT), the second one: cases with congenital heart diseases (CHD) without pulmonary hypertension and the third group included healthy neonates. All participants were subjected to full history taking and full clinical examination. Diagnosis of congenital heart disease and pulmonary hypertension was made according to echocardiographic ï¬ndings by pediatric cardiologist using echocardiography machine. Laboratory investigations included measurement of serum pentraxin 3, Routine CBC, CRP. RESULTS: This study found that the mean serum pentraxin 3 in PHT neonates was significantly higher than that of the control and CHD neonates (p ≤ 0.001, p = 0.02 respectively). Also, the mean Pentraxin3 of the CHD neonates was significantly higher than that of the control (p = 0.06). Also, the mean CRP of the PHT neonates was significantly higher than that of the control (p = 0.01). Regression analysis showed that Pentraxin3 was the main predictor of PAP (P = 0.01). CONCLUSION: Serum pentraxin 3 is significantly elevated in neonates with pulmonary hypertension, so measurement of pentraxin 3 levels in neonates may be valuable as a predictor for pulmonary hypertension in neonates

Stability and Release Kinetics of an Advanced Gliclazide-Cholic Acid Formulation: The Use of Artificial-Cell Microencapsulation in Slow Release Targeted Oral Delivery of Antidiabetics

Introduction: In previous studies carried out in our laboratory, a bile acid (BA) formulation exerted a hypoglycaemic effect in a rat model of type-1 diabetes (T1D). When the antidiabetic drug gliclazide (G) was added to the bile acid, it augmented the hypoglycaemic effect. In a recent study, we designed a new formulation of gliclazide-cholic acid (G-CA), with good structural properties, excipient compatibility and exhibits pseudoplastic-thixotropic characteristics. The aim of this study is to test the slow release and pH-controlled properties of this new formulation. The aim is also to examine the effect of CA on G release kinetics at various pH values and different temperatures. Method: Microencapsulation was carried out using our Buchi-based microencapsulating system developed in our laboratory. Using sodium alginate (SA) polymer, both formulations were prepared: G-SA (control) and G-CA-SA (test) at a constant ratio (1:3:30), respectively. Microcapsules were examined for efficiency, size, release kinetics, stability and swelling studies at pH 1.5, pH 3, pH 7.4 and pH 7.8 and temperatures of 20 and 30 °C. Results: The new formulation is further optimised by the addition of CA. CA reduced microcapsule swelling of the microcapsules at pH 7.8 and pH 3 at 30 °C and pH 3 at 20 °C, and, even though microcapsule size remains similar after CA addition, percent G release was enhanced at high pH values (pH 7.4 and pH 7.8, p < 0.01). Conclusion: The new formulation exhibits colon-targeted delivery and the addition of CA prolonged G release suggesting its suitability for the sustained and targeted delivery of G and CA to the lower intestine

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic