Genetic variability of CYP2D6, CYP3A4 and CYP3A5 among the Egyptian population.

Aim: This study investigated major allelic variants of CYP2D6, CYP3A4 and CYP3A5 in Egyptians, an Arabic population for which there is little information regarding these important pharmacogenes. Patients & methods:CYP2D6*2, *4, *5, *10, *41 and gene copy number variation, as well as CYP3A4*22 and CYP3A5*3 were determined with commercially available TaqMan assays in 145 healthy study participants. Results: The CYP2D6 alleles identified suggest that the prevalence of poor metabolizers is low as none were found among the 145 subjects investigated. The frequency for CYP3A5 nonexpressers was 74.5% and the CYP3A4*22 allele frequency was low at 2.0%. Conclusion: These preliminary findings indicate that pharmacogene variation in Egyptians is different from those of other Middle Eastern/Arabic populations and warrants further investigation.

Enteric parasites can disturb leptin and adiponectin levels in children.

INTRODUCTION: Infection by intestinal parasites in childhood may be the main cause of many health-related problems in developed countries such as anemia, anorexia, loss of appetite, retarded growth and development. The aim of the present study was to assess the effect of different intestinal parasites on white adipose tissue hormones. MATERIAL AND METHODS: Eighty-one children infected by different parasites and 35 apparently healthy children were enrolled in this study. All patients and controls were subjected to clinical examination, measurement of body mass index (BMI) and laboratory examination. RESULTS: For BMI percentiles, there was a significant increase in serum leptin level (p = 0.042) and a significant decrease in serum adiponectin level (p = 0.039) in uninfected children, whereas there were no significant changes in the infected group (p = 0.068 and 0.082 respectively). A significant increase in leptin and decrease in adiponectin levels were observed for E. histolytica, Strongyloides and E. histolytica and Giardia infections compared to the control group (p = 0.047, 0.035 and 0.019 for leptin, and p = 0.025, 0.038 and 0.041 for adiponectin, respectively). CONCLUSIONS: The infection by some intestinal parasites may deregulate the secretion of leptin and adiponectin and also affect the absorption of some nutrients which can disturb the BMI and cause anorexia.

Impact of ApoE genotypes variations on Toxoplasma patients with dementia.

BACKGROUND: Toxoplasma deprives host neuron cells from cholesterol and leads to its ability to potentiate dementia. ApoE intermediates neuronal transmission of cholesterol, which is a key constituent for axonal development, redesigning occasions that are important for education and synaptic arrangement, development of memory and repair of neuron. The aim of this work is to investigate the effect of ApoE genotypes on dementia associated with neurodegeneration in latent Toxoplasma gondii in elderly population. METHODS: This study comprised: 133 patients with dementia (78 were positive for toxoplasma IgG and 55 were negative) and 95 subjects as control group without dementia (30 were positive for toxoplasma IgG and 65 were negative). All of them were subjected to a cognitive assessment, T. gondii seropositivity (ELISA) and determination of ApoE allelic forms (PCR). RESULTS: The ApoE genotype distribution shows that the most predominant genotype is ApoE3/3 and the most widely recognized allele is E3. Both patients and control were further divided into Toxoplasma IgG positive group (n=108) and Toxoplasma IgG negative group (n=120). ApoE4 non carrier, ApoE 2/3 and ApoE 3/3 alleles have highly significant differences (P<0.001) between dementia and non-dementia patients in Toxoplasma infected patients in comparison to non-infected ones. CONCLUSION: Toxoplasma positive patients have more risk to develop dementia regardless ApoE4 carriage.

Adipocytokines in Patients with Chronic Kidney Disease Stage 5.

BACKGROUND: Chronic kidney disease (CKD) leading to kidney failure and end stage renal disease (ESRD) is a common health problem associated with wasting syndrome characterized by inadequate nutrient intake and decrease tissue anabolism and/or catabolism. In CKD adipokines, especially leptin and adiponectin (ADPN), accumulate in serum due to reduced renal clearance. Although, rapidly growing, knowledge of adipocytokines is limited and much is still unknown of the altered adipocytokine pattern in patients with impaired renal function. The aim of this study is to assess the adipocytokines, leptin, and adiponectin in relation to weight loss in pediatric patients with CKD stage-5 treated conservatively (CT) or undergoing maintenance hemodialysis (MHD). METHODS: 41 CKD stage-5 patients and 20 healthy controls were included in this study. Serum levels of leptin and adiponectin were determined by ELISA. Leptin gene expression was analyzed using quantitative real time-polymerase chain reactions (QPCR). RESULTS: Patients had significantly elevated ADPN levels and non significantly elevated serum leptin levels as compared to controls (p < 0.001, p = 0.354, respectively). Leptin gene expression and body mass index (BMI) were highly significantly reduced in CKD stage-5 compared to controls (p < 0.001 for each). There were no significant differences between patients treated conservatively and those undergoing MHD with respect to all studied parameters. Finally, univariate logistic regression analysis revealed no association between leptin, ADPN, and weight loss in CKD stage-5 patients. CONCLUSIONS: The present study showed non significantly elevated or even normalized serum leptin levels, elevated serum adiponectin level and reduced leptin gene expression in CKD stage-5 patients as compared to healthy controls. Patients had significantly lower weight than healthy controls but there was no association between leptin, adiponectin, and weight loss in CKD stage-5 studied patients so, further studies are needed to clarify the role of the two adipokines in body weight loss in those patients.

A simple diagnostic index comprising epithelial membrane antigen and fibronectin for hepatocellular carcinoma.

UNLABELLED: Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC). RESULTS: A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC. CONCLUSIONS: A four-marker index may improve the early detection of HCC with a high degree of accuracy.

Biochemical evaluation of hyaluronic acid in breast cancer.

BACKGROUND: The latest experimental studies on human cancer diseases have observed the bioactive role of hyaluronic acid (HA) during carcinogenesis. HA is a component of the extra-cellular matrix (ECM). It is closely correlated with tumor cell growth, proliferation, and metastasis. The present study aimed to evaluate the biochemical role of HA and its degrading enzymes and products in breast cancer (BC) patients under therapy treatment. METHODS: An ELISA method was used to determine HA levels and standard spectrophotometric techniques were used to estimate the activities of HA degrading enzymes hyaluronidase (HAS), N-acetyl-beta-D-glucosminidase (NAG), and beta-glucuronidase (beta-Glu) and the concentration of both glucoseamine (G-Amine) and glucuronic acid (GA) as degrading products in blood sera of 50 BC patients before and after chemotherapy treatment and in blood sera of 40 healthy women as controls. Statistical analyses were performed by a statistical package for social sciences (SPSS, version 15.0). RESULTS: Elevated serum HA levels, increased HAS, NAG, and beta-Glu activities and high concentrations of G-Amine and GA were significantly found (p < 0.001) in patients before treatment compared to controls. After all BC patients had received the first chemotherapy course, HA and its previous degrading parameters were significantly decreased (p < 0.001) in post-treated patients compared to pre-treated patients. CONCLUSIONS: Hyaluronic acid and its degrading enzymes and products can be considered a biomarker for early detection of recurrent disease and also for monitoring the effective therapeutic follow up of BC patients.

Erythrocyte phosphatidylserine exposure in ß-thalassemia.

[ABS]Phospholipid asymmetry is well maintained in erythrocyte (RBC) membranes with phosphatidylserine (PS) exclusively present in the inner leaflet. Eryptosis, the suicidal death of RBCs, is characterized by cell shrinkage, membrane blebbing, and cell membrane phospholipids scrambling with PS exposure at the cell surface. Erythrocytes exposing PS are recognized, bound, engulfed, and degraded by macrophages. Eryptosis thus fosters clearance of affected RBCs from circulating blood, which may aggravate anemia in pathological conditions. Thalassemia patients are more sensitive to the eryptotic depletion and osmotic shock which may affect RBC membrane phospholipid asymmetry. We aimed in this work to determine the RBC PS exposure in splenectomized and nonsplenectomized ß-thalassemia major (ß-TM) patients and correlate it with the clinical presentation and laboratory data. RBCs were stained for annexin V to detect phosphatidylserine (PS) exposure in 46 ß-TM patients (27 splenectomized and 19 nonsplenectomized) compared to 17 healthy subjects as a control group. We observed a significant increase in RBC PS exposure in ß-TM patients compared to control group (P = .0001). Erythrocyte PS exposure was significantly higher in splenectomized ß-TM patients compared with nonsplenectomized ß-TM patients (P = .001). No correlation was found between RBC PS exposure and clinical or hematological data of ß-TM patients, but there was a positive correlation between RBC PS exposure and ferritin level in ß-TM patients have higher levels of RBC PS exposure, and splenectomy was shown to aggravate RBC PS exposure without aggravation of anemia.

Role of interleukin-8 and oxidative stress in patients with hepatocellular carcinoma.

BACKGROUND: The rate of hepatocellular carcinoma (HCC) is increasing in Egypt where the major risk factor is chronic infection with hepatitis C virus (HCV). The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant public health implications worldwide. The objective of this study is to investigate the role of interleukin-8, alpha-fetoprotein (AFP), oxidative stress markers, and some trace elements in Egyptian patients with hepatocellular carcinoma infected with hepatitis C virus. METHODS: This study comprised 40 patients with HCC (20 with cirrhosis and 20 without cirrhosis) and 20 patients with hepatitis C virus. They were 39 males and 21 females with ages ranging from 22 to 71 years. Twenty apparently healthy volunteers with matched age and sex were taken as control group. Serum concentration levels of IL-8 and AFP were measured using an enzyme-linked immunosorbent assay (ELISA). Antioxidants were measured using spectrophotometric analysis and trace elements by using atomic absorption spectrophotometry. RESULTS: A highly significant elevation was found in interleukin-8, alpha- fetoprotein, iron, and malondialdehyde in patients with HCC compared to control subjects. On the other hand, serum levels of reduced glutathione, catalase, superoxide dismutase, total antioxidant capacity, and zinc were significantly decreased in patients with HCC compared to control subjects. A positive correlation was found between serum level of IL-8 and each of GSH (r = -0.534 and p = 0.000), SOD (r = -0.295 and p = 0.021), CAT (r = -0.545 and p = 0.000), and Zn (r = 0.422 and p = 0.001) in all patient groups. CONCLUSIONS: The ability to measure IL-8 in serum could be useful as a marker of HCC in patients. The levels of antioxidants such as CAT, SOD, and GSH in HCC patients when compared to control groups play a vital and important role in the prevention of liver cancer. Interleukin-8, some antioxidants (MDA, GSH, CAT and SOD), and some trace elements (Fe and Zn) might be simultaneously evaluated in order to enhance the detection of HCC.

Prognostic implication of BAALC gene expression in adult acute myeloid leukemia.

BACKGROUND: Recently various molecular markers and global gene expression profiling have been investigated to improve risk profile characterization of AML with normal cytogenetics. Our main objective is to investigate the prognostic impact of brain and acute leukemia, cytoplasmic (BAALC) expression in AML with normal karyotype. METHODS: BAALC expression was analysed using quantitative real time (QRT) PCR. RESULTS: High expression was detected in 22 of 45 patients (48.9%) and its expression did not correlate with the clinical parameters of patients. High BAALC expressers had significantly lower incidence of CR (22.7% vs. 73.9%; p = 0.001), higher mortality rate (72.1% vs. 39.1%; p = 0.023), showed significantly shorter DFS (mean 4.5 vs. 13.21 months, p < 0.001), and inferior overall survival (7.02 vs. 15.02 months, p < 0.001). Multivariable analysis confirmed high BAALC expression as an independent risk factor for DFS and OS. CONCLUSIONS: BAALC expression is an important prognostic factor in AML patients with normal karyotype and its incorporation into novel risk-adapted therapeutic strategies will improve the currently disappointing cure rate of this group of patients.

Serum Survivin and TP53 Gene Expression in Children with Acute Lymphoblastic Leukemia.

BACKGROUND: The aim of this study was to detect the prognostic significance of survivin level and the expression of total p53 in acute lymphoblastic leukemia (ALL) and its correlation to patients' outcome. METHODS: Sixty two children newly diagnosed with acute lymphoblastic leukemia were treated with chemotherapy and followed up for 2 years or until death. Twenty apparently healthy volunteers with matched age and sex were taken as control. Survivin protein was measured by quantitative sandwich enzyme immunoassay and total human p53 was measured by Flow cytometry in peripheral blood at diagnosis and at complete remission. RESULTS: A highly significant elevation (P<0.0001) was found in survivin protein and total p53 levels in acute lymphoblastic leukemia children patients at diagnosis compared to controls. At complete remission a significant decrease of the two indices were found in ALL patients compared to those at diagnosis (P<0.0001). Survivin protein and total p53 was significantly higher in non-survived compared to survived group (P<0.0001 & P=0.016, respectively). A positive correlation was found between survivin level and total human p53 level in children with ALL (r=0.501 & P<0.0001). CCONCLUSION: survivin protein is related to anti-apoptotic proteins and its high expression lead to unsuccessful treatment of ALL. Survivin and TP53 are new prognostic tools in ALL, independent of age and sex.

Nosocomial infections and fever of unknown origin in pediatric hematology/oncology unit: a retrospective annual study.

BACKGROUND: pediatric hematology/oncology patients are faced with an increased risk of nosocomial infections (NIs) that vary in different populations and different institutions with considerable morbidity and mortality. This study was undertaken to assess the frequency and patterns of NIs in 1564 pediatric patients and to determine the prevalence of causative organisms and their antimicrobial sensitivity. METHODS: a retrospective analysis was made in the patients admitted between January 2007 and January 2008 to the pediatric hematoloy/oncology unit of Mansoura University, Egypt. The 1564 patients showed 2084 admissions and 27 092 inpatient days. The Centers for Disease Control and Prevention criteria were used as a standard definition for NI. RESULTS: the overall rate of NIs in all patients and neutropenic patients was 8.6 and 25.3 per 1000 patient-days respectively. The frequent sites of NIs were blood stream (42.7%), the respiratory system (25.3%), the urinary system (22.2%) and the central nervous system (9.8%), whereas nosocomial fever of unknown origin constituted 52.9% of cases. The incidence of NIs was significantly higher during neutropenic days (P<0.001). Gram-positive organisms represented 64.5% of pathogens (Staphylococci 71.5%, Streptococci 16%, and pneumococci 7%), and Gram-negative organisms represented 30% (E. coli 48.6%, Klebsiella 15.7%, Pseudomonas 35.7%, and C. albicans 5.5%). Positive cultures were more frequent in summer (July to September). Susceptibility of isolated organisms was relatively low (cefoperazone/sulbactam 49.9%, amikacin 35.9%, imipenem/cilastin 34.4%, cefoperazone 33.6%, and vancomycin 36.5%). Methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci represented 30%, 45% and 75% of isolated S. aureus, Gram-negative organisms and Enterococci, respectively. CONCLUSIONS: blood stream infection and fever of unknown origin are the most common nosocomial infections in pediatric hematology/oncology patients with a higher risk during neutropenic days. Isolated organisms are multi-drug resistant, predominantly Gram-positive pathogens with a high incidence of methicillin-resistant S. aureus, extended spectrum beta lactamase and vancomycin resistant enterococci organisms.

Carcinoembryonic antigen, alpha-fetoprotein, and prostate-specific antigen in the sera of industrial workers exposed to phenol, formaldehyde, urea, and mixed vapors.

Exposure to certain industrial agents has been thought to have carcinogenic potential, both for employees who work closely with agents and for the general population that comes into contact with them. The objective of the present study is to evaluate the changes at the cellular level or at the level of cellular metabolism products present in the biological fluid, and to detect early stages of the carcinogenic process resulting from the exposure of industrial environmental hazards. Carcinoembryonic antigen (CEA), alpha-fetoproteins (AFP), and prostate-specific antigen (PSA) were measured in sera of workers (n = 51), who were divided into 4 groups: group I, workers exposed to phenol; group II, workers exposed to formaldehyde; group III, workers exposed to urea; and group IV, workers exposed to mixed vapor, plus a reference control healthy group (n = 15). The results showed that 75% of the workers exposed to phenol, 75% of the workers exposed to urea, 83.3% of workers exposed to formalin, and 92.3% of the workers exposed to mixed vapors had raised values of serum CEA (S-CEA) above normal value of the control group. Also, 23% of workers exposed to mixed vapors, 44% of workers exposed to formalin, 50% of workers exposed to phenol, and 62.5% of workers exposed to urea had raised values of serum AFP (S-AFP) above normal value of control group. Finally, 16.6% of workers exposed to phenol, 23% of workers exposed to mixed vapors, and 33.3% of workers exposed to formalin had raised values of serum PSA (S-PSA) above the normal value of control group; there were no raised values of S-PSA in workers exposed to urea. No significant difference was found in the activities of AST and ALT in group I, but a highly significant increase was found in the AST activities for groups II and IV and the ALT activities for groups III and IV. A significant difference was found in the activity of ALT in group II and in AST for group III. There was no significant difference in the levels of albumin in groups I, II, and III, whereas albumin levels were significantly decreased in group IV. No significant change was found in the level of urea and creatinine in all groups except for group III, where serum levels of creatinine were significantly decreased. From our findings, we concluded that S-CEA can be used as an important prognostic screening marker for early prediction for malignancy, and for management of workers with lung cancer who are exposed to the environmental hazards in industrial factories. Furthermore, S-AFP can be used also as a biomarker if it is carried out and correlated with S-CEA.

Evaluation of serum levels of p53 in hepatocellular carcinoma in Egypt.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-induced death. Somatic mutation of the p53 gene is the most common genetic abnormality so far described in human cancer and there is evidence that supports a high level of p53 alterations in HCC. The aim of this study was to investigate serum levels of p53 in Egyptian patients with HCC, and its relation to other prognostic factors such as tumor grade, alpha-fetoprotein (AFP), and liver function tests in an attempt to clarify their significance in the pathogenesis of the disease. Liver function tests were carried out and AFP and p53 levels were measured for all individuals studied. Our results show that detection of p53 increased the frequency of HCC prediction from 79.5% to 86.3%. Moreover, significant positive correlation between p53 and tumor size (cm) for tumor grade II and III was identified. In conclusion, serum concentration of p53 protein may be a convenient and useful non-invasive screening test for prediction of HCC.