Abstract Vitamin D deficiency (VDD) and anemia are both public health nutrition concerns. An association between VDD and anemia has been suggested in various healthy and diseased populations. The ...current study aimed to elucidate the effect of VDD on iron status in children with type I diabetes mellitus (T1DM). The study recruited two groups of children with T1DM: control group comprised of 38 T1DM children with sufficient vitamin D (> 30 ng/ml) and a case group, consisted of 52 T1DM children with VDD (< 20 ng/ml). Both groups had comparable gender, age, BMI, and disease duration. The laboratory measurements included analysis of blood indices, markers of iron metabolism, hepcidin and inflammatory markers included interleukin 6 (IL-6) and C-reactive protein (CRP). Compared to control group, T1DM children with VDD differs specifically in terms of some markers of blood indices, such as decreased hemoglobin and increased red blood cell distribution width. Moreover, decreased serum iron, ferritin, total iron-binding capacity and transferrin along with elevated inflammatory markers were observed in case group. Results of the study indicated that VDD had increased the risk of iron deficiency anemia in children with T1DM as well as inflammatory related anemia. Furthermore, in T1DM children, VDD had raised the incidence of both absolute and functional iron deficiency, with greater incidence of the former. This study may indicate that VDD may be a risk factor that may worsen iron deficiency anemia in T1DM.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse ...effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Blood–brain barrier (BBB) efflux transporters' overexpression hinders antiepileptic drug brain entry. Breast cancer resistance protein (BCRP) is a major BBB efflux transporter. In the present work, ...BCRP's role as a mechanism that might contribute to drug-resistant epilepsy (DRE) in a mouse model of acute seizures was studied with further assessment of the effect of its inhibition by ko143 and metformin (MET) on lamotrigine (LTG) bioavailability and efficacy. 42 male mice divided into 6 groups: G1: Normal control, G2: LTG-injected healthy mice: LTG 20 mg/kg i.p., G3: Acute seizures (A.S) mice: Pentylenetetrazole (PTZ) 50 mg/kg i.p., G4: LTG-treated A.S mice: LTG 20 mg/kg + PTZ 50 mg/kg i.p., G5: Ko143 + LTG treated A.S mice: Ko143 15 mg/kg i.p. before LTG + PTZ, G6: MET + LTG treated A.S mice: MET 200 mg/kg i.p. before LTG + PTZ. Seizures severity, serum, brain LTG, and brain BCRP were assessed. PTZ group experienced the highest seizure frequency and brain BCRP expression. Ko143 and MET groups showed a significant decrease in brain BCRP with subsequent improvement in brain LTG level and better seizure control. BCRP has a significant role in epilepsy resistance and its inhibition with ko143 or MET adds value to DRE management.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Blood transfusion (BT) is essential in treating sickle cell disease (SCD); however, it leads to iron overload (IO) and oxidative stress. We studied the relationship between oxidative stress, iron ...status parameters, hepcidin mRNA gene expression, and IO in SCD patients.
We classified all SCD patients (n = 90) into two groups: Group I, 45 children (s.ferritin ≥ 938 ng/mL) and Group II, 45 children (s.ferritin < 938 ng/mL). A total of 55 children, age and sex matched, participated as a control group. Malondialdehyde (MDA), nitrite, s.iron, s.total iron-binding capacity (sTIBC), transferrin saturation %, s.ferritin, s.hepcidin, and hepcidin mRNA gene expression were assessed.
Among SCD BT-dependent patients (>3 times/year), 63% were from Group I and 37% from Group II, p < .01. The two patient groups had significantly lower s.hepcidin and hepcidin gene expression than controls (p < .001). TIBC, s.iron, s.ferritin, transferrin saturation %, ferritin/hepcidin ratio, and MDA levels were higher among SCD patients than controls (p < .001). Group I had higher mean level of ferritin/hepcidin ratio and MDA than Group II (p < .01). The higher level of MDA and increased frequency of BT were the significant predicting risk factors for IO (p < .05). A receiver-operating characteristic curve indicates that MDA is the outstanding significant biomarker for high level of s.ferritin with subsequent IO progression.
MDA may serve as a biomarker of oxidative stress and IO in SCD patients. This result paid attention for urgent initiation of antioxidant and chelation therapy on detecting increased MDA level.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Renal tubulointerstitium plays an important role in the development and progression of diabetic nephropathy. The aim of this study was to assess serum cystatin C and 2 renal tubular enzymes, ...neutrophil gelatinase associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG), as screening markers for early renal dysfunction in patients with type 2 diabetes mellitus (T2DM). ROC curve analysis showed that urinary NAG is the most sensitive marker of microalbuminuria and early renal damage with sensitivity of 83.3%, while serum cystatin C was the most sensitive and specific marker of macroalbuminuria and damage progress with sensitivity of 70.8% and specificity of 83.3% versus 70.6% and 83.3% for uNGAL; and 64.7% and 66.7% for NAG, respectively. Our data indicate that urinary NAG is the most sensitive marker for early renal damage in diabetic patients. However, for damage progress, serum cystatin C is the most sensitive and specific marker for follow-up and monitoring renal dysfunction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
Lupus nephritis (LN) is a potentially devastating outcome of systemic lupus erythematosus (SLE). It is important to identify reliable, non-invasive methods to assess the kidneys in patients with SLE. ...The aim of the study was to measure the level of novel markers of renal involvement in these patients and assess their correlation with disease activity and damage. Sixtyone patients with SLE (33 adults and 28 juvenile) were included in the study. Fifty-two ageand sex-matched healthy individuals served as controls. Full history taking, thorough clinical examination and laboratory investigations were performed and disease activity and damage were assessed for all patients. Renal bio-markers including serum cystatin C, urinary neutrophil gelatinase-associated lipocalin (UNGAL) and N-acetyl-beta-D-glucosaminidase (UNAG) were assessed in patients and controls. There was a significant increase in serum cystatin C, UNGAL and UNAG levels in the adult SLE patients compared with controls (P = 0.000, P = 0.013 and P = 0.018, respectively); serum cystatin C and UNGAL levels were higher in the juvenile patients compared with controls (P = 0.038 and P = 0.000, respectively). Serum cystatin C significantly correlated with the damage index, renal biopsy class and negatively with the serum albumin; UNGAL correlated with albuminuria and the level of nephritis and UNAG negatively correlated with serum albumin level. Our study suggests that serum cystatin C, UNGAL and UNAG are important markers of LN and both cystatin C and UNAG would help in predicting the renal biopsy class.
We investigated the association between polymorphisms of the angiotensin converting enzyme-1 (ACE-1) and angiotensin II type one receptor (AT1RA1166C) genes and the causation of renal disease in 76 ...advanced chronic kidney disease (CKD) pediatric patients undergoing maintenance hemodialysis (MHD) or conservative treatment (CT). Serum ACE activity and creatine kinase-MB fraction (CK-MB) were measured in all groups. Left ventricular mass index (LVMI) was calculated according to echocardiographic measurements. Seventy healthy controls were also genotyped.
The differences of D allele and DI genotype of ACE were found significant between MHD group and the controls (p = 0.0001). ACE-activity and LVMI were higher in MHD, while CK-MB was higher in CT patients than in all other groups. The combined genotype DD v/s ID+II comparison validated that DD genotype was a high risk genotype for hypertension .~89% of the DD CKD patients were found hypertensive in comparison to ~ 61% of patients of non DD genotype(p = 0.02). The MHD group showed an increased frequency of the C allele and CC genotype of the AT1RA1166C polymorphism (P = 0.0001). On multiple linear regression analysis, C-allele was independently associated with hypertension (P = 0.04).
ACE DD and AT1R A/C genotypes implicated possible roles in the hypertensive state and in renal damage among children with ESRD. This result might be useful in planning therapeutic strategies for individual patients.
The functional apolipoprotein E (Apo E) gene polymorphism could be used as a determinant of outcome of HCV infection. This study aimed to demonstrate the impact of Apo E genotype on the response to ...HCV combined therapy. Material and methods: The study has been implemented on 125 individuals with persistent HCV infection and 120 cases with sustained virologic response (SVR). All participants were genotyped for ApoE gene polymorphism by a real-time quantitative PCR (qPCR). Results: Statistically significant differences were demonstrated regarding the Apo E genotypes between the two groups (P-value < .001) where the frequency of E3E3 was significantly higher among the chronic HCV-patients while E3E4 and E4E4 genotypes frequencies were higher among the SVR-subjects group and E3E3 genotype was associated with increased risk of chronicity (OR 4.7; 95% CI 1.9–12.1, P-value < .001). Moreover, There were statically significant differences regarding E3 and E4 alleles frequencies, where E3 allele display a higher frequency among the chronic HCV-patient group while the SVR-subjects group showed higher frequency of E4 allele and the carriers of E3 allele have 1.4 times more risk to develop chronicity than those with E4 allele (OR 1.4; 95% CI 1.0–2.0, P-value < .05). Meanwhile the protective E2 allele was absent in all infected participants. Conclusion: This study supports the hypothesis of the protective impact of Apo E4 allele that favors viral clearance of HCV infection and its recovery after combined therapy, while the Apo E3 allele is considered as a particular risk factor for the chronicity in HCV patients and resistance to therapy. Whereas the Apo E2 allele confers a resistance to HCV infection at a time of exposure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background An essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the ...role of Fas − 670A/G and Fas Ligand (FasL) − 843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients. Methods In 47 pediatric kidney transplant recipients and 20 healthy controls, Fas − 670A/G and FasL − 843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured. Results Serum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25 ± 298.64 pg/ml vs 143.17 ± 44.55 pg/ml, p = 0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70 ± 279.87 pg/ml vs 507.85 ± 342.80 pg/ml, p = 0.56). Fas − 670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. ( P > 0.05 for all). FasL − 843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR ( P > 0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P = 0.03). FasL − 843C/T alleles were significantly different between patients with and without AR ( P = 0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR. Conclusion This study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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