Effect of Transplanted Bone Marrow on Spleen of Irradiated Pregnant Rats and Their Fetuses.

<b>Background and Objective:</b> Prenatal ionizing radiation exposure may hinder fetal and embryonic growth depending on the dose and gestational age. The current study's objective was to discover how bone marrow transplants affected the spleens of pregnant rats that had been subjected to γ (Gamma) radiation. <b>Materials and Methods:</b> Sixty rats that were pregnant were separated into five different groups, each with 6 females. The pregnant rats in the second Group were exposed to 2Gy of γ-rays. Group III; pregnant rats subjected to 2Gy of γ-rays, followed by an intraperitoneal injection of newly prepared bone marrow transplantation (BMT). The fifth Group were exposed to 2Gy γ-rays and received 1 dosage of BMT an hour later. Spleen samples from the pregnant rats as well as their fetuses were taken for histological and histochemical analyses. <b>Results:</b> Gamma rays damaged the splenic tissue of women and their fetuses on days 7 or 14 of pregnancy in a variety of histological and histochemical ways, although bone marrow transplantation significantly reduced the damage. Treated mothers with bone marrow post-radiation showed a noticeable recovery in spleen of their fetuses. Improved spleen architecture was accompanied by appearance of normal content of collagen, polysaccharides and total protein in the fetal spleen tissue especially on day 7 of gestation. <b>Conclusion:</b> Bone marrow transplantation can lessen the damage caused by gamma radiation.

Involvement of ADGRV1 Gene in Familial Forms of Genetic Generalized Epilepsy.

Background: Genetic generalized epilepsies (GGE) including childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and GGE with tonic-clonic seizures alone (GGE-TCS), are common types of epilepsy mostly determined by a polygenic mode of inheritance. Recent studies showed that susceptibility genes for GGE are numerous, and their variants rare, challenging their identification. In this study, we aimed to assess GGE genetic etiology in a Sudanese population. Methods: We performed whole-exome sequencing (WES) on DNA of 40 patients from 20 Sudanese families with GGE searching for candidate susceptibility variants, which were prioritized by CADD software and functional features of the corresponding gene. We assessed their segregation in 138 individuals and performed genotype-phenotype correlations. Results: In a family including three sibs with GGE-TCS, we identified a rare missense variant in ADGRV1 encoding an adhesion G protein-coupled receptor V1, which was already involved in the autosomal recessive Usher type C syndrome. In addition, five other ADGRV1 rare missense variants were identified in four additional families and absent from 119 Sudanese controls. In one of these families, an ADGRV1 variant was found at a homozygous state, in a female more severely affected than her heterozygous brother, suggesting a gene dosage effect. In the five families, GGE phenotype was statistically associated with ADGRV1 variants (0R = 0.9 103). Conclusion: This study highly supports, for the first time, the involvement of ADGRV1 missense variants in familial GGE and that ADGRV1 is a susceptibility gene for CAE/JAE and GGE-TCS phenotypes.

Increased Serum Levels of Asymmetric Dimethylarginine and Symmetric Dimethylarginine and Decreased Levels of Arginine in Sudanese Patients with Essential Hypertension.

INTRODUCTION: Essential hypertension (EH) is a disease caused by various environmental and genetic factors. Nitric oxide (NO) is important for the functional integrity of the endothelium. It is produced in endothelial cells by endothelial NO synthase (eNOS) that mediates the conversion of the amino acid arginine into NO and citrulline. Asymmetric dimethylarginine (ADMA) acts as an inhibitor of eNOS. In contrast, symmetric dimethylarginine (SDMA) has no direct effect on eNOS but plays an important role competing with arginine for transport across the amino acid transporter. ADMA and SDMA have been found to play a central role in the development of cardiovascular diseases. Serum ADMA levels may serve as a future diagnostic marker and a target of therapy in hypertensive patients in the Sudanese population. This study aimed to investigate the relation between serum arginine, ADMA, and SDMA levels with EH in the Sudanese population. METHODS: Patients (n = 260) with established hypertension and controls (n = 144) with normal blood pressure were included in this case-control study. Serum blood samples were analyzed for arginine, ADMA, and SDMA, using high-performance liquid chromatography-tandem mass spectrometry. Other laboratory data were measured using routine methods. Mann-Whitney's U test and χ2 tests were used for continuous and categorical data, respectively. A multivariate logistic regression analysis was conducted to investigate the independent effect of multiple variables on the development of hypertension. RESULTS: Serum arginine levels were significantly lower in the patient group than in the control group (p < 0.001). ADMA and SDMA levels were significantly higher in the patient group than the control group (p < 0.001, p = 0.001, respectively). Multivariate logistic regression analysis showed that only older age, being a male, and arginine levels are independent factors controlling the development of hypertension (p < 0.001, p < 0.001, and p = 0.046, respectively). ADMA and SDMA levels were not independent factors for the development of hypertension. CONCLUSIONS: This study demonstrated increased serum levels of ADMA and SDMA and decreased arginine levels in Sudanese patients with EH. Lowering serum ADMA levels or increasing the arginine levels might be a novel therapeutic target in these individuals.

Association of NOS3 gene polymorphisms with essential hypertension in Sudanese patients: a case control study.

BACKGROUND: Essential hypertension (EH) is influenced by various environmental and genetic factors. Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). EH has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are rs1799983 in exon 7 (encoding Glu298Asp), a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region. This study aims to investigate the association between these three polymorphisms in the NOS3 gene and EH in Sudanese patients. METHODS: Hypertensive patients (n = 157) > 18 years of age with established hypertension from various hospitals in Khartoum, and controls (n = 85) > 18 years of age and with blood pressure measurements <140/90, were included in this case control study. Genotypes at the NOS3 variants were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Genotype and allele frequencies were compared between the two groups by χ2 analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). P values <0.05 were considered statistically significant. RESULTS: The rs2070744 polymorphism in NOS3 was found to be associated with EH in the Sudanese population as the patients group had higher frequency of CC genotype compared with the controls (6.6% vs 6.1%, p = 0.02). Considering a dominant inheritance model, the frequency of TC + CC genotypes in patients was significantly higher than that in the control subjects (52.6% vs 34.1%, respectively; p < 0.01), with an odds ratio (95% CI) of 2.14 (1.23-3.74). In addition, the C allele was more frequent in the patients than the control group (29.6% vs 20%, p = 0.03, OR = 1.84 (1.15-2.93)). The c allele of intron 4 VNTR was reported in >1% of the Sudanese population under study. CONCLUSION: The results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population. The c allele of intron 4 VNTR is not rare in the Sudanese population.