Adil Mergani | University Of Gezira (original) (raw)
Papers by Adil Mergani
International Journal of Clinical Medicine
Lecture Notes in Computer Science, 2001
Invited Papers.- The Metalanguage ?prolog and Its Implementation.- A Scalable Architecture for Pr... more Invited Papers.- The Metalanguage ?prolog and Its Implementation.- A Scalable Architecture for Proof-Carrying Code.- Parameterized Logic Programs where Computing Meets Learning.- Functional Programming.- Proving Syntactic Properties of Exceptions in an Ordered Logical Framework.- A Higher-Order Colon Translation.- Compiling Lazy Functional Programs Based on the Spineless Tagless G-machine for the Java Virtual Machine.- Logic Programming.- A Higher-Order Logic Programming Language with Constraints.- Specifying and Debugging Security Protocols via Hereditary Harrop Formulas and ?Prolog ? A Case-study ?.- An Effective Bottom-Up Semantics for First-Order Linear Logic Programs.- Functional Logic Programming.- A Framework for Goal-Directed Bottom-Up Evaluation of Functional Logic Programs.- Theoretical Foundations for the Declarative Debugging of Lazy Functional Logic Programs.- Adding Linear Constraints over Real Numbers to Curry.- A Complete Selection Function for Lazy Conditional Narrowing.- An Abstract Machine Based System for a Lazy Narrowing Calculus.- Incremental Learning of Functional Logic Programs.- Types.- A General Type Inference Framework for Hindley/Milner Style Systems.- Monadic Encapsulation with Stack of Regions.- Well-Typed Logic Programs Are not Wrong.- Program Analysis and Transformation.- A Framework for Analysis of Typed Logic Programs.- Abstract Compilation for Sharing Analysis.- A Practical Partial Evaluator for a Multi-Paradigm Declarative Language.- A Simple Take on Typed Abstract Syntax in Haskell-like Languages.- Calculus.- A simply typed context calculus with first-class environments.- Refining the Barendregt Cube using Parameters.
Journal of Drug Delivery and Therapeutics, 2021
Background: Vitamin D plays a role in critical cellular processes such as apoptosis, cell develop... more Background: Vitamin D plays a role in critical cellular processes such as apoptosis, cell development, and division. The Fok1 polymorphism in the VRD gene is T/C resulting in larger vitamin D receptor protein with lesser expression activity. Fok1 polymorphism is thought to be linked to many diseases including diabetes mellitus, cancers, and rheumatoid arthritis. The snipe also provides effective and sensitive diagnostic and predictive tools and affected by differences in ethnicity and individuals' life style. This study reports on the frequency and distribution of Fok1 SNP among healthy Sudanese transplantation donors. Method: This cross sectional study was conduct in National Cancer Institute University of Gezira, Sudan. One hundred and forty six healthy Sudanese transplantation donors were enrolled in this study. Two ml of venous blood was collected from each participant and stored at -20 till DNA extraction. Qaigen kit was used for DNA extraction. VDR Fok1 was genotyped by CT...
Clinical and Medical Investigations, 2016
Small proportion of malaria infected individuals develops severe clinical phenotypes while other ... more Small proportion of malaria infected individuals develops severe clinical phenotypes while other doesn't. Cerebral malaria (CM) is a selective phenotype of severe malaria that may clusters in certain families. The main purpose of this study was to localize the gene(s) that control(s) the susceptibility to cerebral malaria in a large inbred Sudanese family with sex members having CM. A total of 58 microsatellite markers were typed in the family. Linkage analysis was done by two-point linkage analysis based on a recessive model under 50% of penetrance. There was no markers with a lod score ≥ 3.0 which is the criterion for significant linkage in families. However, one marker (D3S1580) on chromosome 3 with maximum lod scores of 1.40 at recombination fraction (θ at 0.00). This may indicated that a suggestive or inexclusive linkage of cerebral malaria to chromosome 3q27-29 region.
Genetics and Molecular Research, 2015
Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in... more Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in protection against products of oxidative stress and against electrophiles. Glutathione S-transferase mu (GST-M1) and theta (GST-T1) are isoforms of glutathione transferase enzymes that participate in the metabolism of a wide range of chemicals. Deletion variants that are associated with a lack of enzyme function exist at both these loci. The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are very high in most of the populations studied to date. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 genotypes among the Turabah population in Saudi Arabia in comparison with the data published for some other Arabic populations. The subjects consisted of 164 unrelated healthy individuals from the Turabah population. GST genotyping was performed by multiplex polymerase chain reaction-based A.A. Mansour et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16863-16871 (2015) methods. The GSTM1 deletion homozygosity was 56.1% and GSTT1 deletion homozygosity was 20.7%, while the GSTM1 and GSTT1 doubledeletion homozygosity was 11.0%. Comparison with published data from Bahraini, Lebanese, and Tunisian populations demonstrated no significant difference for GSTM1 between these populations. The GSTT1 null-allele frequency was significantly lower than those for the Lebanese and Tunisian populations (P = 0.001) but similar to that for the Bahraini population (P = 0.099). Characterization of GST genetic polymorphisms in the Saudi population may aid in genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and the pharmacogenetics of chemotherapy.
Introduction: Malaria parasite resistant to Chloroquine poses severe and increasing health proble... more Introduction: Malaria parasite resistant to Chloroquine poses severe and increasing health problems in tropical countries. Monitoring the drug resistance by implementing the molecular markers may be essential to overcome the problem, therefore this study aims to assess the Chloroquine resistance of Plasmodium Falciparum parasite in central Sudan, using molecular markers. Methods: One hundred and seventy six patients were confirmed P. falciparaum positive. Sixty-four were selected and only forty patients completed the follow-up. In vivo sensitivity assay was used accompanied with standard regimen of Chloroquine phosphate. DNA was extracted from blood on filter paper (day 0) and was used to amplify two genes P. Falciparum transporters gene Pfcrt and multi-drug resistant gene-1 Pfmdr-1. Results: Among forty patients, 54% responded to Chloroquine regimen with adequate clinical response (ACR), however, 46% showed treatment failure. All treatment failures were treated with Artemether or Quinine. The amplification of Pfcrt gene (n, 18) and Pfmdr 1 gene (n, 29), had shown that 72% of Pfcrt T76 were mutant allele, 22% were K76 wild-type, however, only 5% were mixed alleles T/K. while Pfmdr 1 gene (n, 29) revealed that 55% were wild genotype N 86, 38% were mutant Y 86, and 7% were mixed alleles Y/ N 86. Conclusion: The high frequency of the mutant Pfcrt 76T gene among P. Falciparum isolates was consistent with in vivo study supports the hypothesis that Pfcrt 76T gene could be used as predictive marker for Chloroquine susceptibility in epidemiological surveys. Key words: P. Falciparum , drug resistance, in vivo , PFCRT, PFMDR 1and RFLP
Malaria parasite resistant to chloroquine poses severe health prob- lems in tropical countries, M... more Malaria parasite resistant to chloroquine poses severe health prob- lems in tropical countries, Molecular markers for monitoring the drugs resistance may be essential to overcome the problem. Forty patients out of 176 were completed in vivo sensitivity assay. The DNA was used to assess the prevalence of mutations of chloroquine resistance P. falciparum strains Pfcrt K76T, Pfmdr-1, N86Yand the prevalence of mutation of sulfadoxine-pyrimethamine strains dhfr and dhps genes. Twenty two (54%) responded very well to chloroquine regimen with adequate clinical response (ACR), however, 18/40 (46%) were found to be chloroquine resistant. The in vitro assay showed that 32 (80%) of the isolates were resistant to Chloroquine. Thirteen (72%) isolates have shown mutation in Pfcrt T76, and 4 (22%) have the wild-type of Pfcrt K76, however, only 5% has mixed alleles of wild and mutant genotype Pfcrt T/K. Screening of the mutations of Pfmdr 1 Y86N revealed that 16 (55%) having the wild genotype, 11 (...
The Open Tropical Medicine Journal, 2010
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2003
Hepatology, 2015
Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate im... more Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P 5 0.003; odds ratio [OR] 5 2), and CC, TT of rs2064501 (P 5 0.01; OR 5 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P 5 0.0007; OR 5 8.2], rs2064501 TT [P 5 0.02; OR 5 3.1]), and Brazilians (rs6570136 GG [P 5 0.003; OR 5 26], rs2064501 TC, TT (P 5 0.03; OR 5 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P 5 0.007; OR 5 1.7], rs2064501 TT, TC (P 5 0.004; OR 5 2.4]). Conclusions: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis.
Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its asso... more Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its association with predisposition of certain diseases may be of geographical and ethnical important. In this study we investigated distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism in Turabah population. Genotyping of eNOS VNTR was done by PCR in 225 unrelated individuals from population living in Turabah province. The allele/and genotype frequencies of the polymorphism were tested for Hardy-Weinberg equilibrium (WBE) and compared to two Arabic populations (Egyptian and Tunisians) using Chi Square Goodness-of-Fit test. The study revealed that; the alleles and genotypes distribution of eNOS VNTR 27-bp polymorphism showed a significant difference from these expected frequencies indicating that the population is not in Hardy-Weinberg equilibrium. comparing alleles and genotypes frequencies in study population with those of Tunisian and Egyptian populations had demonstrated significa...
Journal of vector borne diseases, 2015
BACKGROUND & OBJECTIVES Cerebral malaria is considered a leading cause of neuro-disability in sub... more BACKGROUND & OBJECTIVES Cerebral malaria is considered a leading cause of neuro-disability in sub-Saharan Africa among children and about 25% of survivors have long-term neurological and cognitive deficits or epilepsy. Their development was reported to be associated with protracted seizures, deep and prolonged coma. The study was aimed to determine the discharge pattern and to identify potential and informative predictors of neurological sequelae at discharge, complicating childhood cerebral malaria in central Sudan. METHODS A cross-sectional prospective study was carried out during malaria transmission seasons from 2000 to 2004 in Wad Medani, Sinnar and Singa hospitals, central Sudan. Children suspected of having cerebral malaria were examined and diagnosed by a Pediatrician for clinical, laboratory findings and any neurological complications. Univariate and multiple regression model analysis were performed to evaluate the association of clinical and laboratory findings with occurr...
Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is ... more Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p < 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-␥ levels were associated with a marked reduction of the risk of fibrosis (p ؍ 0.01; OR, 0.1); in contrast, high TNF-␣ levels were associated with an increased risk (p ؍ 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-␥ production. These results with observations in experimental models strongly suggest that IFN-␥ plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-␣ may aggravate the disease.
Imperial journal of interdisciplinary research, 2016
Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its asso... more Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its association with predisposition of certain diseases may be of geographical and ethnical important. In this study we investigated distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism in Turabah population. Genotyping of eNOS VNTR was done by PCR in 225 unrelated individuals from population living in Turabah province. The allele/and genotype frequencies of the polymorphism were tested for Hardy-Weinberg equilibrium (WBE) and compared to two Arabic populations (Egyptian and Tunisians) using Chi Square Goodness-of-Fittest. The study revealed that; the alleles and genotypes distribution of eNOS VNTR 27-bp polymorphism showed a significant difference from these expected frequencies indicating that the population is not in Hardy-Weinberg equilibrium. comparing alleles and genotypes frequencies in study population with those of Tunisian and Egyptian populations had demonstrated significa...
Gezira Journal of Health Sciences, 2005
Objectives: 1-To evaluate the effect of Praziquantel (PZQ) therapy on the regression of liver fib... more Objectives: 1-To evaluate the effect of Praziquantel (PZQ) therapy on the regression of liver fibrosis in an endemic population. 2-To determine the factors controlling the regression of hepatic fibrosis (e.g. gender, age and grade of fibrosis). Material and methods: An association study of a cohort of one hundred seventy seven Sudanese patients infected with Schistosoma mansoni (82 males 46%, 95 females 54%) was conducted to evaluate the factors controlling the regression of liver fibrosis 39 months after treatment with PZQ using ultrasound evaluation. SPSS (Statistical Package for Social Science) software was used for statistical analysis. Chi- Square was used to compare the two phenotypes (regression and progression) in the study subjects. Results: PPF was regressed in 63 patients (36%) from higher grades of fibrosis to lower ones. While in 24 patients (13 %) the disease progressed to higher grades. In addition, the grade of PPF did not change in 90 patients (51%). The mean value...
The Journal of Infectious Diseases
Background. Visceral leishmaniasis (kala-azar, KA) is the most severe form of leishmaniasis, char... more Background. Visceral leishmaniasis (kala-azar, KA) is the most severe form of leishmaniasis, characterized by fever, weight loss, hepatosplenomegaly, and lymphadenopathy. During an outbreak of KA in Babar El Fugara (Sudan), 5.7% of cured patients displayed relapses, with familial clustering in half the cases. Methods. We performed whole-exome sequencing on 10 relapsing individuals and 11 controls from 5 nuclear families. Results. Rare homozygous and compound-heterozygous nonsense (c.1213C > T, rs139309795, p.Arg405*) and missense (c.701A > G, rs143439626, p.Lys234Arg) mutations of the alkylglycerol monooxygenase (AGMO) gene were associated with KA relapse in 3 families. Sequencing in additional family members confirmed the segregation of these mutations with relapse and revealed an autosomal dominant mode of transmission. These mutations were detected heterozygous in 2 subjects among 100 unrelated individuals with KA who never relapsed after cure, suggesting incomplete penetrance of AGMO deficiency. AGMO is expressed in hematopoietic cells, and is strongly expressed in the liver. AGMO modulates PAF production by mouse macrophages, suggesting that it may act through the PAF/PAF receptor pathway previously shown to have anti-Leishmania activity. Conclusions. This is the first demonstration that relapses after a first episode of KA are due to differences in human genetic susceptibility and not to modifications of parasite pathogenicity.
American Journal of Infectious Diseases, 2016
Polymorphisms in the regulatory regions of cytokine genes may not only increase susceptibility to... more Polymorphisms in the regulatory regions of cytokine genes may not only increase susceptibility to some infectious diseases but also affect the course and prognosis of the disease. TNF-α is considered an important Th1 cytokines that plays critical roles in control of Brucella infection and in macrophage activation. In this study, we are going to analyze the relationship of two polymorphisms in TNF-α and the inherited susceptibility/resistance to brucellosis in population of Makkah region. A cases-control association study was conducted in 69 individuals with human Brucellosis and 112 healthy individuals. Genotyping of TNF-308G>A and-857C>T polymorphism in both patients and healthy controls was done by PCR-RFLP method and were assessed for potential associations with susceptibility for human brucellosis and their mode of penetrance. The findings indicate an increased risk of TNF-α-308 A allele for human brucellosis reliable with the recessive genetic model of penetrance (Odd Ratio: 3.222, 95% CI: 1.008-5.702, P = 0.018). There is no association between susceptibility of human brucellosis and TNF-α-857 C/T polymorphism was observed. The protective role of TNF-α-857 C/T polymorphism against human brucellosis in this study population could not be excluded.
Biochemical genetics, 2016
Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative ... more Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative stress resulting from accumulation of free radicals in body's tissues, which especially affects beta cells in pancreas and is an important factor in the development of diabetes and its complications. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that play important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case-control study, we investigated the role of GSTP1 Ile105Val polymorphism in predisposition to T2DM in patients from Tarabah province, Saudi Arabia. The polymorphism was screened by PCR-RFLP in 90 T2DM patients and 87 healthy controls. The genotypes and alleles frequencies in cases and controls were assessed using Cochran-Armitage trend test and odds ratios (ORs), and 95 % confidence intervals (CIs) in different genetic models of inheritance were calculated. Our data indicate that G allele (Val) is associated with an i...
Mycetoma is a major mycological health problem in many tropical and subtropical areas and Sudan i... more Mycetoma is a major mycological health problem in many tropical and subtropical areas and Sudan is considered the mycetoma homeland. In the Sudan, Mycetoma is endemic in Central, and Western parts of the country. It affects different ethnic groups with evidence of familial trends. The frequency of HLA-DRB1 and HLADQB1 alleles in Sudanese patients with eumycetoma (n=53) and matched healthy control (n=31) was determined using polymerase chain reaction-Sequence specific primer (PCR-SSP) technique. The frequency of HLA-DRB1*13 allele was significantly higher in mycetoma patients (P<0.044) while the frequency of HLA DQB1*06 was not significantly higher in the patients compared with the control group (P<0.460). On the other hand, a non-significant increase in the frequencies of HLA-DRB1*4, HLA-DRB1*7 alleles were detected in patients when compared with the controls, p=0.498, OR=1.0209, 95%IC, 0.372-3.931 and p=0.434, OR=1.381, 95%IC, 0.387-4.924, respectively. Several alleles showed non-significant association with the presence/ absence of clinical mycetoma,
International Journal of Clinical Medicine
Lecture Notes in Computer Science, 2001
Invited Papers.- The Metalanguage ?prolog and Its Implementation.- A Scalable Architecture for Pr... more Invited Papers.- The Metalanguage ?prolog and Its Implementation.- A Scalable Architecture for Proof-Carrying Code.- Parameterized Logic Programs where Computing Meets Learning.- Functional Programming.- Proving Syntactic Properties of Exceptions in an Ordered Logical Framework.- A Higher-Order Colon Translation.- Compiling Lazy Functional Programs Based on the Spineless Tagless G-machine for the Java Virtual Machine.- Logic Programming.- A Higher-Order Logic Programming Language with Constraints.- Specifying and Debugging Security Protocols via Hereditary Harrop Formulas and ?Prolog ? A Case-study ?.- An Effective Bottom-Up Semantics for First-Order Linear Logic Programs.- Functional Logic Programming.- A Framework for Goal-Directed Bottom-Up Evaluation of Functional Logic Programs.- Theoretical Foundations for the Declarative Debugging of Lazy Functional Logic Programs.- Adding Linear Constraints over Real Numbers to Curry.- A Complete Selection Function for Lazy Conditional Narrowing.- An Abstract Machine Based System for a Lazy Narrowing Calculus.- Incremental Learning of Functional Logic Programs.- Types.- A General Type Inference Framework for Hindley/Milner Style Systems.- Monadic Encapsulation with Stack of Regions.- Well-Typed Logic Programs Are not Wrong.- Program Analysis and Transformation.- A Framework for Analysis of Typed Logic Programs.- Abstract Compilation for Sharing Analysis.- A Practical Partial Evaluator for a Multi-Paradigm Declarative Language.- A Simple Take on Typed Abstract Syntax in Haskell-like Languages.- Calculus.- A simply typed context calculus with first-class environments.- Refining the Barendregt Cube using Parameters.
Journal of Drug Delivery and Therapeutics, 2021
Background: Vitamin D plays a role in critical cellular processes such as apoptosis, cell develop... more Background: Vitamin D plays a role in critical cellular processes such as apoptosis, cell development, and division. The Fok1 polymorphism in the VRD gene is T/C resulting in larger vitamin D receptor protein with lesser expression activity. Fok1 polymorphism is thought to be linked to many diseases including diabetes mellitus, cancers, and rheumatoid arthritis. The snipe also provides effective and sensitive diagnostic and predictive tools and affected by differences in ethnicity and individuals' life style. This study reports on the frequency and distribution of Fok1 SNP among healthy Sudanese transplantation donors. Method: This cross sectional study was conduct in National Cancer Institute University of Gezira, Sudan. One hundred and forty six healthy Sudanese transplantation donors were enrolled in this study. Two ml of venous blood was collected from each participant and stored at -20 till DNA extraction. Qaigen kit was used for DNA extraction. VDR Fok1 was genotyped by CT...
Clinical and Medical Investigations, 2016
Small proportion of malaria infected individuals develops severe clinical phenotypes while other ... more Small proportion of malaria infected individuals develops severe clinical phenotypes while other doesn't. Cerebral malaria (CM) is a selective phenotype of severe malaria that may clusters in certain families. The main purpose of this study was to localize the gene(s) that control(s) the susceptibility to cerebral malaria in a large inbred Sudanese family with sex members having CM. A total of 58 microsatellite markers were typed in the family. Linkage analysis was done by two-point linkage analysis based on a recessive model under 50% of penetrance. There was no markers with a lod score ≥ 3.0 which is the criterion for significant linkage in families. However, one marker (D3S1580) on chromosome 3 with maximum lod scores of 1.40 at recombination fraction (θ at 0.00). This may indicated that a suggestive or inexclusive linkage of cerebral malaria to chromosome 3q27-29 region.
Genetics and Molecular Research, 2015
Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in... more Glutathione-S-transferases (GST) are key phase II detoxifying enzymes that play critical roles in protection against products of oxidative stress and against electrophiles. Glutathione S-transferase mu (GST-M1) and theta (GST-T1) are isoforms of glutathione transferase enzymes that participate in the metabolism of a wide range of chemicals. Deletion variants that are associated with a lack of enzyme function exist at both these loci. The frequencies of homozygous GSTM1 and GSTT1 deletion carriers are very high in most of the populations studied to date. The aim of this study was to investigate the frequencies of GSTM1 and GSTT1 genotypes among the Turabah population in Saudi Arabia in comparison with the data published for some other Arabic populations. The subjects consisted of 164 unrelated healthy individuals from the Turabah population. GST genotyping was performed by multiplex polymerase chain reaction-based A.A. Mansour et al. ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16863-16871 (2015) methods. The GSTM1 deletion homozygosity was 56.1% and GSTT1 deletion homozygosity was 20.7%, while the GSTM1 and GSTT1 doubledeletion homozygosity was 11.0%. Comparison with published data from Bahraini, Lebanese, and Tunisian populations demonstrated no significant difference for GSTM1 between these populations. The GSTT1 null-allele frequency was significantly lower than those for the Lebanese and Tunisian populations (P = 0.001) but similar to that for the Bahraini population (P = 0.099). Characterization of GST genetic polymorphisms in the Saudi population may aid in genetic studies on the association of GSTM1 and GSTT1 polymorphisms with disease risks and the pharmacogenetics of chemotherapy.
Introduction: Malaria parasite resistant to Chloroquine poses severe and increasing health proble... more Introduction: Malaria parasite resistant to Chloroquine poses severe and increasing health problems in tropical countries. Monitoring the drug resistance by implementing the molecular markers may be essential to overcome the problem, therefore this study aims to assess the Chloroquine resistance of Plasmodium Falciparum parasite in central Sudan, using molecular markers. Methods: One hundred and seventy six patients were confirmed P. falciparaum positive. Sixty-four were selected and only forty patients completed the follow-up. In vivo sensitivity assay was used accompanied with standard regimen of Chloroquine phosphate. DNA was extracted from blood on filter paper (day 0) and was used to amplify two genes P. Falciparum transporters gene Pfcrt and multi-drug resistant gene-1 Pfmdr-1. Results: Among forty patients, 54% responded to Chloroquine regimen with adequate clinical response (ACR), however, 46% showed treatment failure. All treatment failures were treated with Artemether or Quinine. The amplification of Pfcrt gene (n, 18) and Pfmdr 1 gene (n, 29), had shown that 72% of Pfcrt T76 were mutant allele, 22% were K76 wild-type, however, only 5% were mixed alleles T/K. while Pfmdr 1 gene (n, 29) revealed that 55% were wild genotype N 86, 38% were mutant Y 86, and 7% were mixed alleles Y/ N 86. Conclusion: The high frequency of the mutant Pfcrt 76T gene among P. Falciparum isolates was consistent with in vivo study supports the hypothesis that Pfcrt 76T gene could be used as predictive marker for Chloroquine susceptibility in epidemiological surveys. Key words: P. Falciparum , drug resistance, in vivo , PFCRT, PFMDR 1and RFLP
Malaria parasite resistant to chloroquine poses severe health prob- lems in tropical countries, M... more Malaria parasite resistant to chloroquine poses severe health prob- lems in tropical countries, Molecular markers for monitoring the drugs resistance may be essential to overcome the problem. Forty patients out of 176 were completed in vivo sensitivity assay. The DNA was used to assess the prevalence of mutations of chloroquine resistance P. falciparum strains Pfcrt K76T, Pfmdr-1, N86Yand the prevalence of mutation of sulfadoxine-pyrimethamine strains dhfr and dhps genes. Twenty two (54%) responded very well to chloroquine regimen with adequate clinical response (ACR), however, 18/40 (46%) were found to be chloroquine resistant. The in vitro assay showed that 32 (80%) of the isolates were resistant to Chloroquine. Thirteen (72%) isolates have shown mutation in Pfcrt T76, and 4 (22%) have the wild-type of Pfcrt K76, however, only 5% has mixed alleles of wild and mutant genotype Pfcrt T/K. Screening of the mutations of Pfmdr 1 Y86N revealed that 16 (55%) having the wild genotype, 11 (...
The Open Tropical Medicine Journal, 2010
Transactions of the Royal Society of Tropical Medicine and Hygiene, 2003
Hepatology, 2015
Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate im... more Interleukin (IL)-22 acts on epithelia, hepatocytes, and pancreatic cells and stimulates innate immunity, tissue protection, and repair. IL-22 may also cause inflammation and abnormal cell proliferation. The binding of IL-22 to its receptor is competed by IL-22 binding protein (IL-22BP), which may limit the deleterious effects of IL-22. The role of IL-22 and IL-22BP in chronic liver diseases is unknown. We addressed this question in individuals chronically infected with schistosomes or hepatitis C virus (HCV). We first demonstrate that schistosome eggs stimulate production of IL-22 transcripts and inhibit accumulation of IL22-BP transcripts in schistosome-infected mice, and that schistosome eggs selectively stimulate production of IL-22 in cultures of blood leukocytes from individuals chronically infected with Schistosoma japonicum. High IL-22 levels in cultures correlated with protection against hepatic fibrosis and portal hypertension. To test further the implication of IL-22/IL-22BP in hepatic disease, we analyzed common genetic variants of IL22RA2, which encodes IL-22BP, and found that the genotypes, AA, GG of rs6570136 (P 5 0.003; odds ratio [OR] 5 2), and CC, TT of rs2064501 (P 5 0.01; OR 5 2), were associated with severe fibrosis in Chinese infected with S. japonicum. We confirmed this result in Sudanese (rs6570136 GG [P 5 0.0007; OR 5 8.2], rs2064501 TT [P 5 0.02; OR 5 3.1]), and Brazilians (rs6570136 GG [P 5 0.003; OR 5 26], rs2064501 TC, TT (P 5 0.03; OR 5 11]) infected with S. mansoni. The aggravating genotypes were associated with high IL22RA2 transcripts levels. Furthermore, these same variants were also associated with HCV-induced fibrosis and cirrhosis (rs6570136 GG, GA [P 5 0.007; OR 5 1.7], rs2064501 TT, TC (P 5 0.004; OR 5 2.4]). Conclusions: These results provide strong evidence that IL-22 protects against and IL-22BP aggravates liver fibrosis and cirrhosis in humans with chronic liver infections. Thus, pharmacological modulation of IL-22 BP may be an effective strategy to limit cirrhosis.
Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its asso... more Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its association with predisposition of certain diseases may be of geographical and ethnical important. In this study we investigated distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism in Turabah population. Genotyping of eNOS VNTR was done by PCR in 225 unrelated individuals from population living in Turabah province. The allele/and genotype frequencies of the polymorphism were tested for Hardy-Weinberg equilibrium (WBE) and compared to two Arabic populations (Egyptian and Tunisians) using Chi Square Goodness-of-Fit test. The study revealed that; the alleles and genotypes distribution of eNOS VNTR 27-bp polymorphism showed a significant difference from these expected frequencies indicating that the population is not in Hardy-Weinberg equilibrium. comparing alleles and genotypes frequencies in study population with those of Tunisian and Egyptian populations had demonstrated significa...
Journal of vector borne diseases, 2015
BACKGROUND & OBJECTIVES Cerebral malaria is considered a leading cause of neuro-disability in sub... more BACKGROUND & OBJECTIVES Cerebral malaria is considered a leading cause of neuro-disability in sub-Saharan Africa among children and about 25% of survivors have long-term neurological and cognitive deficits or epilepsy. Their development was reported to be associated with protracted seizures, deep and prolonged coma. The study was aimed to determine the discharge pattern and to identify potential and informative predictors of neurological sequelae at discharge, complicating childhood cerebral malaria in central Sudan. METHODS A cross-sectional prospective study was carried out during malaria transmission seasons from 2000 to 2004 in Wad Medani, Sinnar and Singa hospitals, central Sudan. Children suspected of having cerebral malaria were examined and diagnosed by a Pediatrician for clinical, laboratory findings and any neurological complications. Univariate and multiple regression model analysis were performed to evaluate the association of clinical and laboratory findings with occurr...
Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is ... more Hepatic periportal fibrosis, which affects 5-10% of subjects infected by Schistosoma mansoni, is caused by the T cell-dependent granuloma that develop around schistosome eggs. Experimental models of infection have shown that granuloma and fibrosis are tightly regulated by cytokines. However, it is unknown why advanced periportal fibrosis occurs only in certain subjects. The goal of the present study was to evaluate the cytokine response of S. mansoni-infected subjects with advanced liver disease in an attempt to relate susceptibility to periportal fibrosis with an abnormal production of cytokines that regulate granuloma and fibrosis. Fibrosis was evaluated by ultrasound on 795 inhabitants of a Sudanese village in which S. mansoni is endemic: advanced periportal fibrosis was observed in 12% of the population; 35% of the affected subjects exhibited signs of portal hypertension. Age (odds ratio (OR), 11.5), gender (OR, 4.2), and infection levels (OR, 2.2) were significantly (p < 0.01) associated with hepatic fibrosis. Cytokines produced by egg-stimulated blood mononuclear cells from 99 subjects were measured (75 with no or mild fibrosis; 24 subjects with advanced fibrosis). Multivariate analysis of cytokine levels showed that high IFN-␥ levels were associated with a marked reduction of the risk of fibrosis (p ؍ 0.01; OR, 0.1); in contrast, high TNF-␣ levels were associated with an increased risk (p ؍ 0.05; OR, 4.6) of periportal fibrosis. Moreover, infection levels were negatively associated with IFN-␥ production. These results with observations in experimental models strongly suggest that IFN-␥ plays a key role in the protection of S. mansoni-infected patients against periportal fibrosis, whereas TNF-␣ may aggravate the disease.
Imperial journal of interdisciplinary research, 2016
Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its asso... more Different population distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism and its association with predisposition of certain diseases may be of geographical and ethnical important. In this study we investigated distribution of 27 bp-VNTR in intron4 of eNOS gene polymorphism in Turabah population. Genotyping of eNOS VNTR was done by PCR in 225 unrelated individuals from population living in Turabah province. The allele/and genotype frequencies of the polymorphism were tested for Hardy-Weinberg equilibrium (WBE) and compared to two Arabic populations (Egyptian and Tunisians) using Chi Square Goodness-of-Fittest. The study revealed that; the alleles and genotypes distribution of eNOS VNTR 27-bp polymorphism showed a significant difference from these expected frequencies indicating that the population is not in Hardy-Weinberg equilibrium. comparing alleles and genotypes frequencies in study population with those of Tunisian and Egyptian populations had demonstrated significa...
Gezira Journal of Health Sciences, 2005
Objectives: 1-To evaluate the effect of Praziquantel (PZQ) therapy on the regression of liver fib... more Objectives: 1-To evaluate the effect of Praziquantel (PZQ) therapy on the regression of liver fibrosis in an endemic population. 2-To determine the factors controlling the regression of hepatic fibrosis (e.g. gender, age and grade of fibrosis). Material and methods: An association study of a cohort of one hundred seventy seven Sudanese patients infected with Schistosoma mansoni (82 males 46%, 95 females 54%) was conducted to evaluate the factors controlling the regression of liver fibrosis 39 months after treatment with PZQ using ultrasound evaluation. SPSS (Statistical Package for Social Science) software was used for statistical analysis. Chi- Square was used to compare the two phenotypes (regression and progression) in the study subjects. Results: PPF was regressed in 63 patients (36%) from higher grades of fibrosis to lower ones. While in 24 patients (13 %) the disease progressed to higher grades. In addition, the grade of PPF did not change in 90 patients (51%). The mean value...
The Journal of Infectious Diseases
Background. Visceral leishmaniasis (kala-azar, KA) is the most severe form of leishmaniasis, char... more Background. Visceral leishmaniasis (kala-azar, KA) is the most severe form of leishmaniasis, characterized by fever, weight loss, hepatosplenomegaly, and lymphadenopathy. During an outbreak of KA in Babar El Fugara (Sudan), 5.7% of cured patients displayed relapses, with familial clustering in half the cases. Methods. We performed whole-exome sequencing on 10 relapsing individuals and 11 controls from 5 nuclear families. Results. Rare homozygous and compound-heterozygous nonsense (c.1213C > T, rs139309795, p.Arg405*) and missense (c.701A > G, rs143439626, p.Lys234Arg) mutations of the alkylglycerol monooxygenase (AGMO) gene were associated with KA relapse in 3 families. Sequencing in additional family members confirmed the segregation of these mutations with relapse and revealed an autosomal dominant mode of transmission. These mutations were detected heterozygous in 2 subjects among 100 unrelated individuals with KA who never relapsed after cure, suggesting incomplete penetrance of AGMO deficiency. AGMO is expressed in hematopoietic cells, and is strongly expressed in the liver. AGMO modulates PAF production by mouse macrophages, suggesting that it may act through the PAF/PAF receptor pathway previously shown to have anti-Leishmania activity. Conclusions. This is the first demonstration that relapses after a first episode of KA are due to differences in human genetic susceptibility and not to modifications of parasite pathogenicity.
American Journal of Infectious Diseases, 2016
Polymorphisms in the regulatory regions of cytokine genes may not only increase susceptibility to... more Polymorphisms in the regulatory regions of cytokine genes may not only increase susceptibility to some infectious diseases but also affect the course and prognosis of the disease. TNF-α is considered an important Th1 cytokines that plays critical roles in control of Brucella infection and in macrophage activation. In this study, we are going to analyze the relationship of two polymorphisms in TNF-α and the inherited susceptibility/resistance to brucellosis in population of Makkah region. A cases-control association study was conducted in 69 individuals with human Brucellosis and 112 healthy individuals. Genotyping of TNF-308G>A and-857C>T polymorphism in both patients and healthy controls was done by PCR-RFLP method and were assessed for potential associations with susceptibility for human brucellosis and their mode of penetrance. The findings indicate an increased risk of TNF-α-308 A allele for human brucellosis reliable with the recessive genetic model of penetrance (Odd Ratio: 3.222, 95% CI: 1.008-5.702, P = 0.018). There is no association between susceptibility of human brucellosis and TNF-α-857 C/T polymorphism was observed. The protective role of TNF-α-857 C/T polymorphism against human brucellosis in this study population could not be excluded.
Biochemical genetics, 2016
Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative ... more Type 2 diabetes mellitus is characterized by chronic hyperglycemia and associated with oxidative stress resulting from accumulation of free radicals in body's tissues, which especially affects beta cells in pancreas and is an important factor in the development of diabetes and its complications. Glutathione S-transferases (GSTs) are a family of antioxidant enzymes that play important roles in decreasing ROS species and act as a kind of antioxidant defense. In a case-control study, we investigated the role of GSTP1 Ile105Val polymorphism in predisposition to T2DM in patients from Tarabah province, Saudi Arabia. The polymorphism was screened by PCR-RFLP in 90 T2DM patients and 87 healthy controls. The genotypes and alleles frequencies in cases and controls were assessed using Cochran-Armitage trend test and odds ratios (ORs), and 95 % confidence intervals (CIs) in different genetic models of inheritance were calculated. Our data indicate that G allele (Val) is associated with an i...
Mycetoma is a major mycological health problem in many tropical and subtropical areas and Sudan i... more Mycetoma is a major mycological health problem in many tropical and subtropical areas and Sudan is considered the mycetoma homeland. In the Sudan, Mycetoma is endemic in Central, and Western parts of the country. It affects different ethnic groups with evidence of familial trends. The frequency of HLA-DRB1 and HLADQB1 alleles in Sudanese patients with eumycetoma (n=53) and matched healthy control (n=31) was determined using polymerase chain reaction-Sequence specific primer (PCR-SSP) technique. The frequency of HLA-DRB1*13 allele was significantly higher in mycetoma patients (P<0.044) while the frequency of HLA DQB1*06 was not significantly higher in the patients compared with the control group (P<0.460). On the other hand, a non-significant increase in the frequencies of HLA-DRB1*4, HLA-DRB1*7 alleles were detected in patients when compared with the controls, p=0.498, OR=1.0209, 95%IC, 0.372-3.931 and p=0.434, OR=1.381, 95%IC, 0.387-4.924, respectively. Several alleles showed non-significant association with the presence/ absence of clinical mycetoma,