Faculty of Medicine and Surgery

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REGRESSION OF LIVER FIBROSIS IN SCHISTOSOMA MANSONI INFECTED SUDANESE SUBJECTS AFTER PRAZIQUANTEL TREATMENT
(Gezira Journal Of Health Sciences, 2005) Rahoud, Siddig A.; Mergani, Adil; Khamis, Ammar H.; Saeed, Osman K.; Ali, Qurashi Mohamed; Dessein, Alain J.; Elwali. Nasr Eldin M. A.
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 values of portal vein diameter (PVD), splenic vein diameter (SVD), and index liver size (ILS) in subjects in whom PPF regressed after treatment were significantly lower than in subjects in whom the disease was progressed (P < .0001, P = .031, and P = .003 respectively).The progression of hepatic fibrosis in males (n = 15, 18 %) was greater than that of females (n = 9, 9 %). Patients who showed regression of PPF or progression of the disease tend to cluster in certain families. Conclusion: Our study indicated that regression and stabilization of PPF after PZQ therapy is controlled by gender, age, grade of fibrosis, and possibly inherited factors.
Lower succinyl-CoA:3-ketoacid-CoA transferase (SCOT) and ATP citrate lyase in pancreatic islets of a rat model of type 2 diabetes: Knockdown of SCOT inhibits insulin release in rat insulinoma cells
(journal homepage: www.elsevier.com/locate/yabbi, 2010) Hasan,Noaman M; Longacre,Melissa J; Ahmed,Mohammed Seed; Kendrick,Mindy A; Gu,Harvest; Ostenson,Claes-Goran; Fukao,Toshiyuki; MacDonald,Michael J
Succinyl-CoA:3-ketoacid-CoA transferase (SCOT) is a mitochondrial enzyme that catalyzes the reversible transfer of coenzyme-A from acetoacetyl-CoA to succinate to form acetoacetate and succinyl-CoA. mRNAs of SCOT and ATP citrate lyase were decreased 55% and 58% and enzyme activities were decreased >70% in pancreatic islets of the GK rat, a model of type 2 diabetes. INS-1 832/13 cells were transfected with shR- NAs targeting SCOT mRNA to generate cell lines with reduced SCOT activity. Two cell lines with >70% knockdown of SCOT activity showed >70% reduction in glucose- or methyl succinate-plus-b-hydroxybu- tyrate-stimulated insulin release. Less inhibition of insulin release was observed with two cell lines with less knockdown of SCOT. Previous studies showed knockdown of ATP citrate lyase in INS-1 832/13 cells does not lower insulin release. The results further support work that suggests mitochondrial pathways involving SCOT which supply acetoacetate for export to the cytosol are important for insulin secretion.
Effects of gum Arabic ingestion on body mass index and body fat percentage in healthy adult females: two-arm randomized, placebo controlled, double-blind trial
(Nutrition Journal, 2012) Babiker, Rasha; Merghani, Tarig H; Elmusharaf, Khalifa; Badi, Rehab M; Lang, Florian; Saeed, Amal M
Background: Gum Arabic (acacia Senegal) is a complex polysaccharide indigestible to both humans and animals. It has been considered as a safe dietary fiber by the United States, Food and Drug Administration (FDA) since the 1970s. Although its effects were extensively studied in animals, there is paucity of data regarding its quantified use in humans. This study was conducted to determine effects of regular Gum Arabic (GA) ingestion on body mass index and body fat percentage among healthy adult females. Methods: A two-arm randomized, placebo controlled, double-blind trial was conducted in the Department of Physiology at the Khartoum University. A total of 120 healthy females completed the study. They were divided to two groups: A test group of 60 volunteers receiving GA (30 gm /day) for 6 weeks and a placebo group of 60 volunteers receiving pectin (1 gm/day) for the same period of time. Weight and height were measured before and after intervention using standardized height and weight scales. Skin fold thickness was measured using Harpenden Skin fold caliper. Fat percentage was calculated using Jackson and Pollock 7 caliper method and Siri equation. Results: Pre and post analysis among the study group showed significant reduction in BMI by 0.32 (95% CI: 0.17 to 0.47; P<0.0001) and body fat percentage by 2.18% (95% CI: 1.54 to 2.83; P<0.0001) following regular intake of 30 gm /day Gum Arabic for six weeks. Side effects caused by GA ingestion were experienced only in the first week. They included unfavorable viscous sensation in the mouth, early morning nausea, mild diarrhea and bloating abdomen. Conclusions: GA ingestion causes significant reduction in BMI and body fat percentage among healthy adult females. The effect could be exploited in the treatment of obesity.
Increased expression of adenylyl cyclase 3 in pancreatic islets and central nervous system of diabetic Goto-Kakizaki rats
(Journaltandfonline, 2012) Ahmed,Mohammed Seed; Kovoor,Abraham; Nordman,Sofia; Abu Seman,Norhashimah; Gu,Tianwei; Efendic,Suad; Brismar,Kerstin; Östenson,Claes-Göran; Gu,Harvest F
Adenylyl cyclase 3 (AC3) is expressed in pancreatic islets of the Goto-Kakizaki (GK) rat, a spontaneous animal model of type 2 diabetes (T2D), and also exerts genetic effects on the regulation of body weight in man. In addition to pancreatic islets, the central nervous system (CNS) plays an important role in the pathogenesis of T2D and obesity by regulating feeding behavior, body weight and glucose metabolism. In the present study, we have investigated AC3 expression in pancreatic islets, striatum and hypothalamus of GK rats to evaluate its role in the regulation of glucose homeostasis. GK and Wistar rats at the age of 2.5 mo were used. A group of GK rats were implanted with sustained insulin release chips for 15 d. Plasma glucose and serum insulin levels were measured. AC3 gene expression levels in pancreatic islets, striatum and hypothalamus were determined by using real-time RT-PCR. Results indicated that plasma glucose levels in Wistar rats were found to be similar to insulin-treated GK rats, and significantly lower compared with non-treated GK rats. AC3 expression levels in pancreatic islets, striatum and hypothalamus of GK rats were higher compared with Wistar rats, while the levels were intermediate in insulin-treated GK rats. The AC3 expression display patterns between pancreatic islets and striatum-hypothalamus were similar. The present study thus provides the first evidence that AC3 is overexpressed in the regions of striatum and hypothalamus of brain, and similarly in pancreatic islets of GK rats suggesting that AC3 plays a role in regulation of glucose homeostasis via CNS and insulin secretion.
Effects of gum Arabic ingestion on body mass index and body fat percentage in healthy adult females: two-arm randomized, placebo controlled, double-blind trial
(Nutrition Journal, 2012) Babiker,Rasha; Merghani,Tarig H; Elmusharaf,Khalifa; Badi,Rehab M; Lang,Florian; Saeed,Amal M
Background: Gum Arabic (acacia Senegal) is a complex polysaccharide indigestible to both humans and animals. It has been considered as a safe dietary fiber by the United States, Food and Drug Administration (FDA) since the 1970s. Although its effects were extensively studied in animals, there is paucity of data regarding its quantified use in humans. This study was conducted to determine effects of regular Gum Arabic (GA) ingestion on body mass index and body fat percentage among healthy adult females. Methods: A two-arm randomized, placebo controlled, double-blind trial was conducted in the Department of Physiology at the Khartoum University. A total of 120 healthy females completed the study. They were divided to two groups: A test group of 60 volunteers receiving GA (30 gm /day) for 6 weeks and a placebo group of 60 volunteers receiving pectin (1 gm/day) for the same period of time. Weight and height were measured before and after intervention using standardized height and weight scales. Skin fold thickness was measured using Harpenden Skin fold caliper. Fat percentage was calculated using Jackson and Pollock 7 caliper method and Siri equation. Results: Pre and post analysis among the study group showed significant reduction in BMI by 0.32 (95% CI: 0.17 to 0.47; P<0.0001) and body fat percentage by 2.18% (95% CI: 1.54 to 2.83; P<0.0001) following regular intake of 30 gm /day Gum Arabic for six weeks. Side effects caused by GA ingestion were experienced only in the first week. They included unfavorable viscous sensation in the mouth, early morning nausea, mild diarrhea and bloating abdomen. Conclusions: GA ingestion causes significant reduction in BMI and body fat percentage among healthy adult females. The effect could be exploited in the treatment of obesity.
Genetic Association of Adrenergic Receptor Alpha 2a with Obesity and Type 2 Diabetes
(Original Article EPIDEMIOLOGY/GENETICS, 2013) La ̊ ngberg,Ewa-Carin; Ahmed,Mohammed Seed; Efendic,Suad; Gu,Harvest F; Ostenson,Claes-Goran
Objective: The sympathetic nervous system (SNS) is linked to glucose, lipid, and protein metabolism. The a2A-adrenergic receptor (ADRA2A) is involved in the SNS and mediates inhibition of insulin secretion and lipolysis. The association of ADRA2A single-nucleotide polymorphisms (SNPs) with obesity and/or type 2 diabetes (T2D) was investigated. Design and Methods: Genotyping was performed in a case–control study of 1,177 Swedish individuals, including lean and obese subjects with normal glucose tolerance (NGT) and T2D patients. ADRA2A mRNA expression was measured in pancreatic islets isolated from T2D patients and nondiabetic subjects. Results: SNP rs553668 was associated with T2D in men (odds ratio [OR] 1⁄4 1.47; 95% confidence interval [CI] 1⁄4 1.08–2.01; P 1⁄4 0.015) but this association was lost after adjusting for age and for body mass index (BMI). Associations were also detected when comparing obese NGT and lean NGT subjects (OR 1⁄4 1.49; 95% CI 1⁄4 1.07–2.07; P 1⁄4 0.017), and in obese (OR 1⁄4 1.62; 95% CI 1⁄4 1.06–2.49; P 1⁄4 0.026), but not in lean T2D. In women, multiple logistic regression regarding SNP rs521674 demonstrated an increased OR of 7.61 (95% CI 1⁄4 1.70–34.17; P 1⁄4 0.008) for T2D when including age as a covariant. Correcting for BMI removed the significant association. When age was included in the model, association also found when obese T2D patients were compared with lean NGT subjects (P 1⁄4 0.041). ADRA2A mRNA expression in human pancreatic islets was detectable, but with no statistically significant difference between the diabetic and the control groups. Conclusions: ADRA2A genetic polymorphisms are mainly associated with obesity and possibly with T2D in a Swedish population.
Expression of Protein Kinase C Isoforms in Pancreatic Islets and Liver of Male Goto- Kakizaki Rats, a Model of Type 2 Diabetes
(PLOS ONE journal, 2015) Ahmed,Mohammed Seed; Pelletier,Julien; Leumann,Hannes; Gu,Harvest F; Östenson,Claes-Göran
Protein kinase C (PKC) is a family of protein kinases controlling protein phosphorylation and playing important roles in the regulation of metabolism. We have investigated expres- sion levels of PKC isoforms in pancreatic islets and liver of diabetic Goto-Kakizaki (GK) rats with and without insulin treatment to evaluate their association with glucose homeostasis. mRNA and protein expression levels of PKC isoforms were assessed in pancreatic islets and liver of Wistar rats and GK rats with or without insulin treatment. PKCα and PKCζ mRNA expressions were down-regulated in islets of GK compared with Wistar rats. PKCα and phosphorylated PKCα (p-PKCα) protein expressions were decreased in islets of GK compared with insulin-treated GK and Wistar rats. PKCζ protein expression in islets was reduced in GK and insulin-treated GK compared with Wistar rats, but p-PKCζ was decreased only in GK rats. Islet PKCε mRNA and protein expressions were lower in GK compared with insulin-treated GK and Wistar rats. In liver, PKCδ and PKCζ mRNA expres- sions were decreased in both GK and insulin-treated GK compared with Wistar rats. Hepatic PKCζ protein expression was diminished in both GK rats with and without insulin treatment compared with Wistar rats. Hepatic PKCε mRNA expression was down-regulated in insulin- treated GK compared with GK and Wistar rats. PKCα, PKCε, and p-PKCζ expressions were secondary to hyperglycaemia in GK rat islets. Hepatic PKCδ and PKCζ mRNA expressions were primarily linked to hyperglycaemia. Additionally, hepatic PKCε mRNA expression could be under control of insulin.
Why Did Sudanese End Stage Renal Failure Patients Refuse Renal Transplantation?
(Open Journal of Nephrology, 2015) Banaga,Amin S; Mohammed,Elaf B; Siddig,Rania M; Salama,Diana E; Elbashir,Sara B; Khojali,Mohamed O; Babiker,Rasha A; Elmusharaf,Khalifa; Homeida,Mamoun M
Renal transplantation remains the most effective treatment of End Stage Renal Failure (ESRF). In this cross sectional study we explore the reasons behind refusal of renal transplantation among adults’ Sudanese haemodialysis patients. The subjects of the study are ESRF adults’ patients on regular haemodialysis treatment in 15 haemdoialysis centres in Khartoum/Sudan. All patients who are on regular haemodialysis were interviewed by questionnaire to explore the reasons of refusal of renal transplantation. A total of 1583 ESRF adults’ patients on regular haemodialysis have been participated in the study, 381 (24.1%) patients refused kidney transplantation. The mean age of patients refusing kidney transplantation was (58.5 + 15.1 years); 77.4% of them were ≥50 years old, 59.2% were males and 88.1% were unemployed, patients older than 50 years old and unemployed are tend to refuse renal transplantation (P < 0.001). The main reason of refusal was that the patients refuse to accept kidney from living donors (34.8%). 17.6% of patients de- cline kidney transplantation because of financial reason, 18.1% of patients refused to do trans- plantation because of fear of transplant surgery, 15.7% of patients believe that kidney transplan- tation is against their religious values, 11.9% of patients refused transplantation because they don’t have enough knowledge on renal transplantation, only 0.5% of patients refuse transplanta- tion because of side effect of immunosuppressive drugs. In conclusion, in this study we found that elderly and unemployed ESRF patients tend to refuse renal transplantation, the most important reason behind refusal of renal transplantation is refusal of accepting kidney donation from living related donors. This reflects the need for development of cadaveric donors program in the Sudan. ESRF patients need education and counseling on renal transplantation.
Causes of end stage renal failure among haemodialysis patients in Khartoum State/Sudan
(2015) Banaga,Amin S. I; Mohammed,Elaf B; Siddig,Rania M; Salama,Diana E; Elbashir,Sara B; Khojali,Mohamed O; Babiker,Rasha A; Elmusharaf,Khalifa; Homeida,Mamoun M
Background: End stage renal failure (ESRF) has become a major health problem in Sub Saharan Africa (SSA). There were limited data about causes of ESRF in the Sudan. Methods: This is a cross sectional hospital based descriptive study. The subjects of the study are ESRF adults’ patients on regular haemodialysis treatment in 15 haemdoialysis centres in Khartoum State—Sudan. Clinical and epidemio- logical data were obtained from 1583 patients. The medical files of each patient were reviewed to identify the cause of ESRF. Concerning the causes of ESRF, diabetes was diagnosed based on the past medical history and result of the glucose tolerance test, hypertension was diagnosed based on past history of hypertension based on blood pressure of more than 140/90 mmHg, glomerulonephritis was diagnosed based on results of previous kidney biopsies and on clinical grounds, polycystic kidney disease and obstructive uropathy were diagnosed based on abdominal ultrasound and other imaging modalities, sickle cell anaemia was diagnosed based on the result of haemoglobin electrophoresis, systemic lupus erythematosus was diagnosed based on the clinical criteria in addition to lab results of auto antibod- ies, and analgesic nephropathy was diagnosed based on past medical history of chronic analgesic drugs usage with no other identifiable risk factors. We included all ESRF patients on regular haemodialysis treatment. We excluded ESRF patients less than 18 years old. Results: The results showed that the mean age of ESRF Patients was 49 ± 15.8 (years) and 63.4 % were male and 76.3 % were unemployed. The mean duration of haemodialysis is 4.38 ± 4.24 (years). The most common cause of ESRF in our patients was hypertension (34.6 %) followed by chronic glomerulonephritis (17.6 %), diabetes mellitus (12.8 %), obstructive uropathy (9.6 %), autosomal dominant poly cystic kidney disease (ADPKD) (4.7 %), chronic pyelonephritis (4.6 %), analgesic nephropathy (3.5 %). However in (10.7 %) no cause was found. In patient aged less than 40 years old the leading cause of ESRF was glomerulonephritis (29.3 %) followed by hypertension (25 %). In patient aged between 40 to 60 years old the leading cause of ESRF was hypertension (38.5 %) followed by diabetes mellitus (14 %). In patient aged older than 60 years the leading cause of ESRF was hypertension (38.4 %) followed by diabetes mellitus (23.3 %). Conclusions: ESRF in Sudan affects the economically productive age group; unemployment rate among ESRF patients is high. The study showed that hypertension is a leading cause of ESRF in Sudan followed by chronic glomer- ulonephritis. Hypertension and diabetes mellitus are the leading causes of ESRF among patients over 40 years old.
Incidence of gastric carcinoma at King Faisal Specialist Hospital- Jeddah Saudi Arabia: a hospital-based study
(Integrative Molecular Medicine, 2016) Alahmadi, Raha; Hamour, Osman; Al-Enizi, H; Tashkandi, A.
Stomach cancer is the fifth most common cancer worldwide, and the third leading cause of death from cancer making up 7% of cases and 9% of deaths. The present study aimed at providing an image of the incidence of gastric carcinoma, with all its epidemiological and pathological characteristics including their trends during the last decade in a tertiary care hospital in the western region of Saudi Arabia. After obtaining an Institutional Review Board approval to conduct this retrospective study in King Faisal Specialist Hospital, a tertiary care institution in the western part of Saudi Arabia; the charts of 76 consecutive patients diagnosed with gastric cancer between January 2002 and 2013, were abstracted. Forty seven patients were included in the study. The charts were reviewed for demographic data, clinical data, diagnostic tools, endoscopic location of the tumour, size of the tumour, the imaging performed, the pathological features, the treatment given, and the final outcome. Forty seven patients were included in the study, thirty three (70%) of them were males, and the mean age of all patients was 57.55 ± 19.24 years. Forty three of the patients (91.5%) had intestinal type, thirty two (68.1%) had poorly differentiated cancer. Fourteen out of the 47 had palliative chemotherapy and twenty two patients out of 47 underwent surgery with curative intent. Two out of the 22 who had surgery received neoadjuvant chemotherapy, while only 7 had adjuvant chemotherapy. Fifteen out of the 22 who underwent surgery died, seven out of the 22 had a recurrence. Median overall survival for the 47 patients was 7 months, and the overall survival for the 22 patients who underwent surgery was 24 months. The median overall survival for the 25 patients, who did not undergo surgery was 2 months (Log rank, p-value=0.0005). Gastric cancer is among the deadliest forms of cancer in Saudi Arabia, with gradual increase in the incidence over the last decade, but its incidence still considered low in comparison to other countries worldwide. The outcome of our patients was poor, and we believe this is due to late presentation in the majority of our patients. Surgery is the mainstay of treatment for resectable gastric cancer, while perioperative and adjuvant chemotherapy, as well as chemoradiation, can improve outcome of resectable gastric cancer with extended lymph node dissection. Further research is required to study the epidemiology and the pathological features and the mode of presentation of gastric cancer in the Kingdom of Saudi Arabia.
Adenylate cyclase 3: a new target for anti-obesity drug development
(obesity reviews, 2016) Wu,L; Shen,C; Ahmed,M. Seed; Östenson,C.-G; Gu,H. F
Obesity has become epidemic worldwide, and abdominal obesity has a negative im- pact on health. Current treatment options on obesity, however, still remain limited. It is then of importance to find a new target for anti-obesity drug development based upon recent molecular studies in obesity. Adenylate cyclase 3 (ADCY3) is the third member of adenylyl cyclase family and catalyses the synthesis of cAMP from ATP. Genetic studies with candidate gene and genome-wide association study approaches have demonstrated that ADCY3 genetic polymorphisms are associated with obesity in European and Chinese populations. Epigenetic studies have indi- cated that increased DNA methylation levels in the ADCY3 gene are involved in the pathogenesis of obesity. Furthermore, biological analyses with animal models have implicated that ADCY3 dysfunction resulted in increased body weight and fat mass, while reduction of body weight is partially explained by ADCY3 activa- tion. In this review, we describe genomic and biological features of ADCY3, sum- marize genetic and epigenetic association studies of the ADCY3 gene with obesity and discuss dysfunction and activation of ADCY3. Based upon all data, we suggest that ADCY3 is a new target for anti-obesity drug development. Further investiga- tion on the effectiveness of ADCY3 activator and its delivery approach to treat ab- dominal obesity has been taken into our consideration.
Pharmacological Modulations of the Serotonergic System in a Cell-Model of Familial Alzheimer’s Disease
(Journal of Alzheimer’s Disease, 2016) Tajeddinna,Walid; Persson,Torbjorn; Garridoa,Javier Calvo; Ahmed,Mohammed Seed; Maiolia,Silvia; Vijayaraghavan,Swetha; Kazokoglua,Mehmet Selim; Fernandez,Cristina Parrado; Yoshitaked,Takashi; Kehrd,Jan; Francisb,Paul; Winblada,Bengt; Hoglund ,Kina; Mingueza,Angel Cedazo; Aarsland,Dag
Serotonin (5-HT) plays a central role in the integrity of different brain functions. The 5-HT homeostasis is regulated by many factors, including serotonin transporter (SERT), monoamine oxidase enzyme (MAO), and several 5-HT receptors, including the 5-HT1B. There is little knowledge how the dynamics of this system is affected by the amyloid- (A) burden of Alzheimer’s disease (AD) pathology. SH-SY5Y neuroblastoma cells transfected with the amyloid precursor protein (APP) gene containing the Swedish mutations causing familial AD (APPswe), were used as a model to explore the effect of A pathology on 5-HT1B and related molecules including the receptor adaptor protein (p11), SERT and MAOA gene expression, and MAOA activity after treatment with selective serotonin reuptake inhibitor (SSRI) (sertraline), and a 5-HT1B receptor antagonist. Sertraline led more than 70 fold increase of 5-HT1B gene expression (p < 0.001), an increased serotonin turnover in both APPswe and control cells and reduced intracellular serotonin levels by 75% in APPswe cells but not in controls (p > 0.05). Treatment with the 5-HT1B receptor antagonist increased SERT gene-expression in control cells but not in the APPswe cells. 5-HT and 5-HT1B antagonist treatment resulted in different p11 expression patterns in APPswe cells compared to controls. Although MAOA gene expression was not changed by APPswe overexpression, adding 5-HT lead to a significant increase in MAOA gene expression in APPswe but not control cells. These findings suggest that the sensitivity of the 5-HT1B receptor and related systems is affected by APPswe overexpression, with potential relevance for pharmacologic intervention in AD. This may at least partly explain the lack of effect of SSRIs in patients with AD and depression.
Association of Platelet Serotonin Levels in Alzheimer’s Disease with Clinical and Cerebrospinal Fluid Markers
(Journal of Alzheimer’s Disease, 2016) Tajeddinna,Walid; Fereshtehnejad,Seyed-Mohammad; Ahmed,Mohammed Seed; Yoshitaked,Takashi; Kehr,Jan; Shahnaz,Tasmin; Milovanovic,Micha; Behbahani,Homira; Hoglund ,Kina; Winblad,Bengt; Cedazo-Minguez,Angel; Jelic,Vesna; Jaremo,Petter; Aarsland,Dag
Introduction: Serotonin (5-HT) is involved in the pathology of Alzheimer’s disease (AD). Objective: We aimed to measure 5-HT level in platelets in AD and explore its association with cerebrospinal fluid (CSF), AD biomarkers (amyloid- 1-42 (A42), total tau (t-tau), and phosphorylated tau (p-tau)), and clinical symptoms. Methods: 15 patients with AD and 20 patients with subjective cognitive impairment (SCI) were included. 5-HT metabolites were measured, in a specific fraction, using high performance liquid chromatography with electrochemical detection (HPLC- ECD). Results: Significantly lower 5-HT concentrations were observed in AD patients compared to SCI patients both after normal- ization against total protein (p = 0.008) or platelet count (p = 0.019). SCI patients with lower 5-HT level have higher AD CSF biomarkers, total tau (p = 0.026) and tau/A42 ratio (p = 0.001), compared to those with high 5-HT levels. Conclusion: AD patients have reduced platelet 5-HT levels. In SCI, lower 5-HT content was associated with a higher AD-CSF biomarker burden.
Prevalence and Presentation of Tuberculosis among Hemodialysis Patients in Khartoum, Sudan
(Saudi Journal of Kidney Diseases and Transplantation, 2016) Banaga,Amin S. I; Siddiq,Nihad K; Alsayed,Randa T; Babiker,Rasha; Elmusharaf,Khalifa
ABSTRACT. Tuberculosis (TB) is a major health problem in the developing countries. There are limited data about the prevalence of TB patients on maintenance hemodialysis (HD) in Sudan. The aim of this study is to identify the prevalence and presentation of TB among Sudanese maintenance HD patients. This is a hospital-based descriptive study. The participants of the study are all HD patients distributed in 13 HD centers in Khartoum and Khartoum North Provinces in Sudan. All patients attended the HD centers from November 1, 2014 to February 1, 2015, were interviewed by a questionnaire focused on personal and clinical data. Those who were diagnosed as having active TB were studied regarding their clinical presentation, presence of comorbidities, site of TB, and methods used on diagnosis. The total number of HD patients during the study period was 1328 patients. We found 19 patients who already diagnosed and treated for TB infec- tion. The prevalence rate of TB among HD patients is 1.4%. The mean age of patient was 44.53 ±8.69 years, 89.5% of them were males. The majority of them have comorbidities: 31.6%% have hypertension and 21.1% have diabetes. Extrapulmonary TB was the major presentation (57.9%) mainly tuberculous lymphadenitis (26.3%). The pulmonary presentation was found to be 42.1%. The diagnosis of TB was supported by microbiological evidence of alcohol acid-fast Bacilli pre- sent in sputum smear (21%), histological diagnosis (31.6%), polymerase chain reaction (21%), and imaging in (26.3%). Patients on maintenance HD are at an increased risk of TB and diagnosis of TB among HD patients need a high index of suspicion. There is a great need for establishing a screening scheme for TB among HD patients and further epidemiological studies are needed to fully evaluate this problem.
Hereditary spastic paraplegias: identification of a novel SPG57 variant affecting TFG oligomerization and description of HSP subtypes in Sudan
(European Journal of Human Genetics, 2016) Elsayed,Liena EO; Mohammed,Inaam N; Hamed,Ahlam AA; Elseed,Maha A; Johnson,Adam; Mairey,Mathilde; Mohamed,Hassab Elrasoul SA; Idris,Mohamed N; Salih,Mustafa AM; El-sadig,Sarah M; Koko,Mahmoud E; Mohamed,Ashraf YO; Raymond,Laure; Coutelier,Marie; Darios,Frédéric; Siddig,Rayan A; Ahmed,Ahmed KMA; Babai,Arwa MA; Malik,Hiba MO; Omer,Zulfa MBM; Mohamed,Eman OE; Eltahir,Hanan B; Magboul,Nasr Aldin A; Bushara,Elfatih E; Elnour,Abdelrahman; Rahim,Salah M Abdel; Alattaya,Abdelmoneim; Elbashir,Mustafa I; E Ibrahim,Muntaser; Durr,Alexandra; Audhya,Anjon; Brice,Alexis; Ahmed,Ammar E; Stevanin,Giovanni
Hereditary spastic paraplegias (HSP) are the second most common type of motor neuron disease recognized worldwide. We investigated a total of 25 consanguineous families from Sudan. We used next-generation sequencing to screen 74 HSP- related genes in 23 families. Linkage analysis and candidate gene sequencing was performed in two other families. We established a genetic diagnosis in six families with autosomal recessive HSP (SPG11 in three families and TFG/SPG57, SACS and ALS2 in one family each). A heterozygous mutation in a gene involved in an autosomal dominant HSP (ATL1/SPG3A) was also identified in one additional family. Six out of seven identified variants were novel. The c.64C4T (p.(Arg22Trp)) TFG/SPG57 variant (PB1 domain) is the second identified that underlies HSP, and we demonstrated its impact on TFG oligomerization in vitro. Patients did not present with visual impairment as observed in a previously reported SPG57 family (c.316C4T (p.(Arg106Cys)) in coiled-coil domain), suggesting unique contributions of the PB1 and coiled-coil domains in TFG complex formation/function and a possible phenotype correlation to variant location. Some families manifested marked phenotypic variations implying the possibility of modifier factors complicated by high inbreeding. Finally, additional genetic heterogeneity is expected in HSP Sudanese families. The remaining families might unravel new genes or uncommon modes of inheritance.
Evaluation of the toxic influence of vitamin E (dl-alpha-tocopheryl acetate) and treatment with aqueous extracts of cinnamon or anise on lipid profile and liver functions of female wistar rats
(International Journal of Medicine, 2017) Ibrahim ,Sabah A. E; Sabahelkhier,Murwan K
The toxic effects of vitamin E and its treatment with aqueous extracts of Cinnamon or anise on lipid profile and liver functions of female wistar rats were examined for six weeks during September 2016 at labs in al-Neelain University. 18 rats were divided into six groups: 1. negative control group (sunflower oil), 2. Positive control group and rest groups given (1500 mg/Kg/BW/day of Vitamin E). After two hours, the four treated groups received a low dose (2.13g/Kg) and a high dose (3.20g/Kg) 20g/Kg from Cinnamon aqueous extract (CAE) and Anise aqueous extract (AAE). At the end rats were sacrificed then serum and liver tissues were analyzed. Vitamin E toxic dose had caused a significant increase in serum Triglycerides (TG), Alanine amino transferase (ALT) levels, while it decreased the levels of High- density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC) and Aspartate amino transferase (AST). All treatments decreased TG and ALT levels. CAE low dose significantly increased TC, LDL and HDL levels. CAE high dose caused a significant decrease in AST, TC, and LDL. Both doses of AAE, caused significant increases on AST levels, and only anise low dose caused a signif- icant decrease on TC and LDL levels. Vitamin E toxic dose caused severe fatty change in liver histology, which was near normal in both doses of CAE with a small necrosis in a low dose. Only AAE low dose normalized the liver. To conclude Vitamin E oral administration with a dose of (1500 mg/Kg) induced liver injury with an elevation in ALT and TG levels, which was significantly ameliorated by both treatments. Cinnamon was better than anise in ameliorating the toxicity. Cinnamon high dose was better than Cinnamon low dose; in contrast anise low dose was better than Anise high dose.
Metabolic effects of Gum Arabic (Acacia Senegal) in patients with Type 2 Diabetes Mellitus (T2DM): Randomized, placebo controlled double blind trial
(2017) Babiker,Rasha; Elmusharaf,Khalifa; Keogh,Michael B; Banaga,Amin S. I; Saeed,Amal M
Background: Gum Arabic (GA) is a water-soluble dietary fiber, indigestible to both humans and animals. While GA currently does not have any therapeutic potential, it has nutritional value and some effects on metabolism of glucose and lipids. Thus, the aim of this study is to assess the effect of GA on serum level of glucose, lipids, and the BMI in type 2 diabetic patients. Methods: A double-blind randomized placebo-controlled trial took place at Academy Charity Teaching Hospital (ACTH) in Sudan between August 2014 to February 2015. The trial was conducted in type 2 diabetic patients who were on regular oral hypoglycemic drugs and had HbA1C ≥ 6.5%. Patients excluded from the study included those on insulin, any patient with a metabolic or gastrointestinal disease, and any patient with history of drug addiction and alcoholism. Other patients excluded were patients who had previous allergic reactions to GA in addition to patients who were pregnant or planned for conception within 6 months. 120 patients were invited to participate in this trial. 100 patients gave consent and were randomized to GA and placebo groups. The GA group was given 30 g of Acacia Senegal and the placebo group was given 5 g of placebo daily for 3 months. The outcomes assessed were primarily the effect of GA on glucose levels in addition to the effects on levels of lipids and BMI in type 2 diabetic patients. Results: The GA group showed significant reduction in fasting plasma glucose (FPG) and HbA1c (P<0.05) within the GA group. Moreover, GA supplementation improved lipid profiles; decreased LDL-Cholesterol by 5.95%, total Cholesterol by 8.28% and triglyceride by 10.95% from baseline levels. HDL-Cholesterol showed significant increase by 19.89% within GA group (P<0.05), BMI was decreased significantly by 2.06% (95% CI: −0.98; −0.16), P<0.05). Conclusions: Gum Arabic is a dietary supplement for improving nutrition of type 2 diabetic patients; it has demonstrated a good effect on improving their poor glycemic control. It has also shown improvement in the levels of the lipids and the BMI. Further studies are needed in obese and pre-diabetic patients to evaluate GA therapeutic potentials.
Intra-familial phenotypic heterogeneity in a Sudanese family with DARS2-related leukoencephalopathy, brainstem and spinal cord involvement and lactate elevation: a case report
(BMC Neurology, 2018) Yahia,Ashraf; Elsayed,Liena; Babai,Arwa; Salih,Mustafa A; El-Sadig,Sarah Misbah; Amin,Mutaz; Koko,Mahmoud; Abubakr,Rayan; Idris,Razaz; Taha,Shaimaa Omer M.A; Elmalik,Salah A; Brice,Alexis; Ahmed,Ammar Eltahir; Stevanin,Giovanni
Background: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL, OMIM #611105) is a genetic disease of the central nervous system characterized by lower limb spasticity, cerebellar ataxia and involvement of the dorsal column. The disease is caused by mutations in the DARS2 gene but has never been reported in sub-Saharan Africa so far. Case presentation: Two siblings, aged 18 years and 15 years, from a consanguineous family presented with pyramidal signs and symptoms since infancy and developmental delay. Whole exome sequencing of the proband identified two compound heterozygous variants (NM_018122.4:c.1762C > G and c.563G > A) in DARS2. Sanger sequencing confirmed the presence of the mutations and their segregation in trans in both patients and in their elder sister (aged 20 years), who showed only brisk reflexes and mild lower limb spasticity. Surprisingly, in contrast to her subtle clinical presentation, the elder sister had abnormal MRI features and serum lactate levels comparable to her ill sisters. Conclusion: This report illustrates intra-familial phenotypic variation in LBSL and provides an example of a marked dissociation between the clinical and radiological phenotypes of the disease. This may have implications for the detection of mutation carriers in LBSL.
Effect of Gum Arabic (Acacia Senegal) supplementation on visceral adiposity index (VAI) and blood pressure in patients with type 2 diabetes mellitus as indicators of cardiovascular disease (CVD): a randomized and placebo-controlled clinical trial
(Lipids in Health and Disease, 2018) Babiker, Rasha; Elmusharaf, Khalifa; Keogh, Michael B.; Saeed, Amal M.
Background: There is a strong association between cardiometabolic risk and adipose tissue dysfunction with great consequences on type 2 diabetic patients. Visceral Adiposity Index (VAI) is an indirect clinical marker of adipose tissue dysfunction. Gum Arabic (GA) is a safe dietary fiber, an exudate of Acacia Senegal. Gum Arabic had shown lipid lowering effect in both humans and animals. The aim of this trial was to determine the effect of GA supplementation on anthropometric obesity marker, Visceral Adiposity Index (VAI) and blood pressure in patients with type 2 diabetes mellitus. Methods: This randomized, double blinded, placebo controlled trial recruited a total of 91 type 2 diabetic patients (73 females, 18 males), age (mean ±SD) 50.09±9.3 years on hypoglycemic agents and were randomly assigned into two groups, either to consume 30 g of GA or 5 g of placebo daily for 3 months. Anthropometric obesity markers were measured and indices were calculated. Blood pressure was measured and high density lipoprotein (HDL) and triglycerides (TG) were determined in fasting blood samples at the start and end of the study period. Results: After intervention, Gum Arabic decreased BMI and VAI significantly (P < 0.05) in GA group by 2 and 23.7% respectively. Body adiposity index significantly decreased by 3.9% in GA group while there were no significant changes in waist circumference or waist-to-hip ratio (WHR). Systolic blood pressure significantly decreased by 7.6% in GA group and by 2.7% in placebo group from baseline with no significant changes in diastolic blood pressure in the two groups. Conclusion: Gum Arabic consumption at a dose of 30 g/d for 3 months may play an effective role in preventing weight gain and modulating adipose tissue dysfunction in type 2 diabetic patients, although no effect has been shown in waist-to-hip ratio
Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family
(BMC Medical Genetics, 2018) Elsayed,Liena E. O; Mohammed,Inaam N; Hamed,Ahlam A. A; Elseed,Maha A; Salih,Mustafa A. M; Yahia,Ashraf; Siddig,Rayan A; Amin,Mutaz; Koko,Mahmoud; Elbashir,Mustafa I; Ibrahim,Muntaser E; Brice,Alexis; Ahmed,Ammar E; Stevanin,Giovanni
Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in PLA2G6. The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent. Case presentation: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found in PLA2G6. It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members. Conclusion: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients’ phenotype). Therefore this variant can be currently annotated as “pathogenic”. This is the first study to report mutations in PLA2G6 gene in patients from Sudan.