Adipocyte fatty acid-binding protein (FABP4) as a potential biomarker for predicting metabolically driven low-grade and organ damage in thalassemia syndromes.

Adipocyte fatty acid-binding protein (A-FABP; FABP4) plays a significant role in the pathogenesis and progression of metabolically driven low-grade inflammation and organ damage. This study aimed to evaluate the performance of circulating FABP4 as a predictive and diagnostic biomarker for thalassemia-associated cardiometabolic events. This case-control study enrolled 50 adults with ß-thalassemia and 30 age-, sex-, and body mass index-matched controls. Participants underwent a comprehensive evaluation, including complete blood count, liver and kidney function tests, serum blood glucose, lipid profile, and ferritin levels, pelviabdominal ultrasound, ECG, and echocardiography after taking a full medical history and conducting a clinical examination. Serum levels of FABP4 were measured using an Enzyme-Linked-Immunosorbent-Assay. The diagnostic performance of FABP4 was assessed using receiver operator characteristic (ROC) curve analysis to determine optimal values for excluding and confirming cardiometabolic metflammation. The thalassemia cohort exhibited a statistically significant higher concentration of FABP4 compared to the control group (p-value < 0.001). Positive correlations were found between FABP4 and ferritin serum levels above 800 or 1000 ug/L, as well as with ALT, TGS, and LDL (p-value < 0.05). Circulating FABP4 was identified as a statistically significant risk factor for thalassemia-associated cardiometabolic comorbidities (OR = 84.00, 95%CI:18.6-378.6, p-value < 0.001). ROC analysis determined that the FABP4 exclusionary cut-off value > 2.30 ng/ml could effectively discriminate between thalassemia-associated adverse metaflammation and controls, while the FABP4 confirmatory cut-off value was > 2.58 ng/ml. In conclusion, circulating FABP4 appears to be a potential risk factor for predicting progression to cardiometabolic events in thalassemia-associated adverse metaflammation. FABP4 holds promise as a diagnostic and prognostic biomarker for disease monitoring and risk stratification. Further validation through large-scale, multicenter, prospective studies is warranted.

Genotype Hemophilia Screening Program Identified 2 Novel Variants Including a Novel Variant (c.5816-2A > G) Causing a Pathogenic Variant of the Factor 8 Gene.

Establishing a national screening program for hemophilia patients is highly encouraged by the World Health Organization and the World Federation of Hemophilia. Hence, this study aimed to analyze the variant spectrum of F8 and F9 genes in Arab hemophilia patients. Molecular genetic and sequencing studies were performed on a cohort of 135 Saudi hemophilia patients. Out of all screened hemophilia patients (97 hemophilia A and 39 hemophilia B), 15 (11.1%) were positive for inversion 22 and 4 (3%) for inversion 1. Out of a total of 32 (23.7%) substitution/deletion mutations, 2 novel variants were identified: a novel splice acceptor site missense mutation (c.5816-2A > G) causing a pathogenic variant of the F8 gene and another splicing site point mutation in intron/exon 23 (g.164496G > A). The frequent F8 variants were (c.409A > C, p.T137P) in exon 4, (c.760A > G) in exon 6, and (c.1835G > C, p.R612P) in exon 12, while the frequent F9 variants were (c.580A > G) in exon 6 and (c.880C > T) in exon 8. These study data will enrich the spectrum of the genetic databases in the Arab population that could be applied in the future for national genetic counseling.

Screening of subclinical functional hemoglobin and red blood cell abnormalities among blood donors of Fayoum University Hospital in Egypt: Are RET-He, and IRF useful screening tools?

BACKGROUND: The effectiveness of red cell transfusion in a given blood unit that relied on both quantity and quality of donated cells undoubtedly affects prognostic outcomes. OBJECTIVE: We aimed to determine the frequency of subclinical functional hemoglobin and red cell abnormalities in donated blood of Fayoum University Hospital in Egypt. Additionally, to assess the usefulness of reticulocyte mean hemoglobin content (RET-He) and immature reticulocyte fraction (IRF) as screening measures for such abnormalities. MATERIAL AND METHODS: This cross-sectional study enrolled 200 volunteer blood donors who met the national standard criterion of blood donation. Complete blood count with reticulocyte parameters, serum ferritin, sickling test, G6PD assay, Mentzer index, and naked-eye single tube red cell osmotic fragility test were carried out. RESULTS: Functional red cell abnormalities represented 44 % of this cohort. Out of them, 4.5 % had iron deficiency, 11 % had a positive sickling test, 19 % had G6PD deficiency, and 9.5 % had suspicious thalassemia. The sensitivity and specificity test for RET-He in selective identification of functional hemoglobin abnormalities in donated blood were 83.3 % and 61.2 %, respectively at a cutoff value of 26.9. Though there was no statistically significant effect of RET-He on the selective detection of G6PD deficiency, IRF had a statistically significant high level with a p-value of 0.04. CONCLUSION: Subclinical functional red cell abnormalities seem to be prevalent among blood donors. Reticulocyte/ erythrocyte indices could be useful screening tools for red cell abnormalities. Further studies are required for assessing the impact of transfusing such abnormalities to neonates and other critical recipients.

Seroprevalence of SARS-CoV-2 immunoglobulin G antibody during COVID-19 pandemic in Fayoum District, Egypt: a community-based pilot survey.

Introduction: controlling the worldwide pandemic, coronavirus disease (COVID-19), could be impossible due to the hesitancy about the available vaccines and the difficulty to implement strict restrictions. Little information is available about herd immunity in the highly vulnerable region of North East Africa, Egypt. The objective of this study was to assess the seroprevalence of SARS-CoV-2 during the pandemic in one of the highly vulnerable populations in Egypt, the Fayoum district of Fayoum Governorate. Additionally, to assess the predictive value of symptoms and other associated risk factors towards a positive COVID-19 test. Methods: in this cross-sectional community-based pilot study, immunoglobulin G (IgG) antibodies that are specific for the SARS-CoV-2 spike (S1-RBD) protein were tested during the period from February 2021 to July 2021. Results: out of 155 participants, 60.6% were SARS-CoV-2 seropositive. Out of symptomatic and asymptomatic individuals, 76.5% and 56.2% were seropositive, respectively. Surprisingly, only one individual had received the COVID-19 vaccine. Previous history of COVID-19; such as symptoms and gender are statistically significant predictors of high seroconversion independent of age, comorbidities, and level of education. Conclusion: this study which disclosed unexpectedly high SARS-CoV-2 seroconversion among the Egyptians, might provide a clear insight into COVID-19 transmission patterns and state of immunity. Further study with a larger sample size on a large scale is required to represent the whole local population.

Lead (Pb) and cadmium (Cd) blood levels and potential hematological health risk among inhabitants of the claimed hazardous region around Qaroun Lake in Egypt.

BACKGROUND: Lead (Pb) and cadmium (Cd) heavy metals are considered potentially hazardous toxins which cause serious health problems. Many studies reported that the water of Qaroun Lake in Fayoum, Egypt with its fish farms was contaminated with Pb and Cd above permissible levels. However, there is a lack of studies addressing levels of these toxic metals among inhabitants. OBJECTIVES: We aimed to evaluate blood levels of Pb and Cd and their potential health risk among inhabitants around Qaroun Lake. MATERIALS AND METHODS: This case-control study estimated Pb and Cd blood levels among 190 individuals from two destinations (near and far away) of Qaroun Lack using an atomic absorption spectrometer after full history taking and routine checkup investigations; Full blood count, serum ferritin, liver enzyme (ALT), and creatinine levels. RESULTS: There was a significant difference between blood levels of Pb and Cd heavy metals of inhabitants from near and far away Qaroun Lake destinations (p-value < 0.001). The majority of inhabitants around Qaroun Lake had Pb and Cd blood levels above permissible levels (100% and 60% respectively). Critical levels out of them were 12.1% and 30.3% respectively. In comparison to inhabitants faraway Qaroun Lake, three individuals (2.4%) had Cd above the permissible level, while all of them (100%) had Pb level within the permissible level. There were no statistically significant differences between the two sampled populations as regards hemoglobin level, ALT, creatinine, and ferritin serum levels (p-value > 0.05). The difference between studied populations regarding types of anemia was not statistically significant. Subclinical leucopenia was higher in the population near Qaroun Lake when compare to inhabitants far from the lake (13.6% vs. 4.8%, p-value 0.032). CONCLUSION: Bio-monitoring of populations exposed to Pb and Cd hazardous substances could help in generating an early warning system to reduce the disease burden associated with their toxicity.

Seroprevalence of SARS-CoV-2 immunoglobulin G antibody during COVID-19 pandemic in Fayoum District, Egypt: a community-based pilot survey

Introduction: controlling the worldwide pandemic, coronavirus disease (COVID-19), could be impossible due to the hesitancy about the available vaccines and the difficulty to implement strict restrictions. Little information is available about herd immunity in the highly vulnerable region of North East Africa, Egypt. Objectives: to assess the seroprevalence of SARS-CoV-2 during the pandemic in one of the highly vulnerable populations in Egypt, Fayoum district of Fayoum Governorate. Additionally, to assess the predictive value of symptoms and other associated risk factors towards a positive COVID-19 test. Methods: in this cross-sectional community-based pilot study, immunoglobulin G (IgG) antibodies that are specific for the SARS-CoV-2 spike (S1-RBD) protein were tested during the period from February 2021 to July 2021. Results: out of 155 participants, 60.6% were SARS-CoV-2 seropositive. Out of symptomatic and asymptomatic individuals, 76.5% and 56.2% were seropositive, respectively. Surprisingly, only one individual had received the COVID-19 vaccine. Previous history of COVID-19; such as symptoms and gender are statistically significant predictors of high seroconversion independent of age, comorbidities, and level of education. Conclusion: this study which disclosed unexpectedly high SARS-CoV-2 seroconversion among the Egyptians, might provide a clear insight into COVID-19 transmission patterns and state of immunity. Further study with a larger sample size on a large scale is required to represent the whole local population.

Hematologic reference intervals for healthy adult Saudis in Riyadh.

BACKGROUND: Laboratory hematological tests are widely used in clinical practice to assess health and disease conditions. Reference ranges provided by laboratory reports are considered the most authoritative medical tools to assist in the decision-making phase. International standards institutes recommend that reference ranges be established for each region. OBJECTIVES: Provide reference values of routine hematological parameters in Saudi adults according to age and gender. DESIGN: Cross-sectional SETTING: Central province of Saudi Arabia. PATIENTS AND METHODS: Apparently healthy Saudi adults were subjected to laboratory testing of routine hematological parameters (full blood count, hemostatic profile, and serum hematinics), after completing a detailed health medical questionnaire. MAIN OUTCOME MEASURES: Hematological reference values based on the local population. SAMPLE SIZE AND CHARACTERISTICS: 637 after screening 827 potentially healthy Saudi adults with ages ranging from 15 to 65 years. RESULTS: The reference values of routine hematological parameters for the full population and by gender are presented with 90% CI as the lower and upper limits. Reference ranges mostly differed from universal established ranges shown in textbooks. CONCLUSION: The reference ranges of routine hematologic parameters for accurate assessment and appropriate management will help improve the routine clinical care of the adult Saudi population. LIMITATIONS: Difficulty in assessing health status of participants, who could have subclinical illnesses not reflected in the evaluated blood measurement. Lack of ability to eliminate individuals who might be carriers for haemoglobinopathies. Studies with larger sample sizes from different areas of the country are required to achieve a more accurate representation of the whole Saudi population. CONFLICT OF INTEREST: None.

Potential impact of gut Lactobacillus acidophilus and Bifidobacterium bifidum on hepatic histopathological changes in non-cirrhotic hepatitis C virus patients with different viral load.

BACKGROUND: Composition of gut microbiota has recently been suggested as a key factor persuading the pathogenesis of numerous human diseases including hepatic cirrhosis. OBJECTIVE: To evaluate the potential impact of Lactobacillus acidophilus and Bifidobacterium bifidum microbiota on the progression of hepatic histopathological changes among patients with non-cirrhotic chronic hepatitis C (HCV) infection with different viral load. Additionally, to assess fecal composition of Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota genotypes MATERIAL AND METHODS: This study was carried out on 40 non-cirrhotic chronically infected HCV patients, and 10 healthy-controls. Liver biopsy and HCV genomic viral load were assessed for all patients after full clinical examination. Lactobacillus acidophilus ATCC-4356 and Bifidobacterium bifidum ATCC-11863 microbiota were assessed in all fecal samples using PCR assay, after counting total lactic acid bacteria. RESULTS: There was a significantly higher difference between the count of both total lactic acid and Lactobacillus acidophilus of healthy controls compared to patients (P-value < 0.001). Though the count of total lactic acid bacteria, and Lactobacillus acidophilus were higher in the cases with early stage of fibrosis (score ≤ 1) compared to those with score > 1, there were no statistically significant differences with both the serum level of hepatitis C viremia (P = 0.850 and 0.977 respectively) and the score of fibrosis (P = 0.246 and 0.260 respectively). Genotypic analysis for the composition of the studied microbiota revealed that diversity was higher in healthy controls compared to patients. CONCLUSIONS: The progression of hepatic fibrosis in HCV chronically infected patients seems to be plausible based on finding the altered Lactobacillus acidophilus and Bifidobacterium bifidum gut microbiota composition. Thus, modulation of these microbiota seems to be a promising target for prevention and control of HCV infection.

Association between circulating MicroRNAs (hsa-miR-92a-1* and hsa-miR-454) and multiple sclerosis phenotypes and activity status.

Efficient diagnosis of multiple sclerosis (MS) disease along with early prediction of its progression will ultimately lead to better management, control of complications and improvement of therapeutic outcomes and patient's well-being. Blood based biomarkers like circulating microRNAs represent a non- invasive, fast, and easily measured markers with a promising potential. This work intended to assess the relative expression of circulating hsa-miR-454 and hsa-miR-92a-1* as a diagnostic and prognostic tool among Egyptian MS patients in terms of correlation to disease type and severity. hsa-miR-454 and hsa-miR-92a-1* relative expression was measured in the plasma of 31 MS patients, relapsing remitting MS (RRMS, n=21) and progressive MS (PMS, n=10) and 20 age and sex matched normal controls by using reverse transcription followed by real time PCR. Disease severity assessment was done in the form of patient expanded disability status scale (EDSS) evaluation. Relative expression of hsa-miR-454 and hsa-miR-92a-1* did not show a statistically significant difference between MS cases and controls. However, hsa-miR-454 was significantly higher among RRMS patients in comparison to PMS patients (P = 0.04). Additionally, both markers showed a statistically significant upregulation among patients in disease exacerbation in comparison to patients in remission (P = < 0.01) and both showed a negative correlation with EDSS. In conclusion, microRNAs may represent potential valuable non-invasive biomarkers for assessment of MS type (RRMS vs PMS), as well as for prediction of disease activity and severity in MS patients.

Genetic variations in tumor ecrosis factor related apoptosis-inducing ligand receptor-1 (TRAIL-R1) gene and the susceptibility to b-cell non-hodgkin lymphoma (B-NHL) in Egypt.

BACKGROUND: Dysregulated apoptosis is a hallmark of cancer development and progression. TRAIL and its receptors (R1 and R2) are key players in the extrinsic apoptotic pathway. Genetic alteration or blockade of TRAIL-R1 may alter its apoptotic function, and subsequently provide growth advantage to neoplastic cells. OBJECTIVE: to investigate the possible association between -C626G, -A683C and -A1322G single nucleotide polymorphisms (SNPs) of TRAIL-R1 gene and the susceptibility to B-NHL in a cohort of Egyptians. METHODS: Genotypic analysis was performed for 100 newly diagnosed B-NHL patients and 150 age and gender matched healthy controls. RESULTS: The polymorphic alleles of -C626G and -A1322G conferred almost twofold increased risk of B-NHL (OR = 1.76; 95%CI = 1.01-3.22 and OR = 1.89; 95%CI = 1.01-3.75 respectively). There was no statistical difference in the distribution of TRAIL-R1-A683C alleles/genotypes between B-NHL patients and controls. B-NHL risk increased when -C626G and -A1322G polymorphic genotypes were co-inherited (OR = 3.57; 95%CI = 1.29-9.84). The risk conferred by -C626G SNP increased for DLBCL (OR = 3.39, 95% CI: 1.61-7.16). CONCLUSION: TRAIL-R1-C626G and -A1322G polymorphisms could be considered as molecular risk factors for B-NHL especially DLBCL. The data provided by the current study constitute an initial millstone towards developing a large-scale dataset for genetic variations that could contribute to lymphomagenesis in Egyptian population.

Screening hemostatic defects in Saudi University students with unexplained menorrhagia: a diagnosis, which could be missed.

Bleeding disorders are a common cause of unexplained menorrhagia in adolescents. However, there is lack of information provided on Arab girls. To estimate the prevalence of coagulation factor deficiencies and platelet dysfunction among Saudi university students with unexplained menorrhagia. In this cross sectional study, 463 adolescent girls surveyed for having heavy menses for further evaluation of underlying bleeding tendencies using screening standardized questionnaire. Only 109 girls out of the total 463 girls reported menorrhagia and were included in the evaluation. All girls with menorrhagia were evaluated by Pictorial blood assessment chart (PBAC) for precise evaluation of menstrual blood loss (PBAC score >100), had underwent pelvic ultrasonography and screening of hemostatic abnormalities (complete blood count, PFA-100, PT, aPTT, vWF:RCo, vWF:Ag, coagulation factors assay). On the basis of the score of PBAC more than 100, 25.6% (28/109) of adolescent women (age ranged: 17-25 years old) had confirmed menorrhagia. In 30.8% of them, an ultimate diagnosis of bleeding tendency or hemostatic abnormality was detected [five cases of probable von Willebrand disease (vWD) or low level of vWF:Ag and/or vWF:RCo, two cases of probable platelet dysfunction, and one case of factorV (FV) deficiency]. Anemia was found in 39.28% (11/28) of them; however, only 4 (36%) had received iron supplements. Our study demonstrated that hemostatic defects are not uncommon in Saudi adolescent women presenting with menorrhagia but mostly unrecognized and untreated. It is probably advisable to screen women with menorrhagia for these defects.

Implication of HMOX1 and CCR5 genotypes on clinical phenotype of Egyptian patients with sickle cell anemia.

Sickle cell disease (SCD) is a relatively common inherited hemolytic anemia among individuals of African descent. Genetic factors might clarify clinical diversity of the disease and variations in treatment response. Some researchers investigated heme oxygenase-1 (HMOX1) or chemokine receptor 5 (CCR5Δ32) genotypes among SCD patients and their correlation with fetal hemoglobin (HbF) and disease severity. However, there are no such records among Arab nations. We aimed to estimate the prevalence of the HMOX1-413 A>T (rs2071746) and CCR5Δ32 (rs333) polymorphisms, and to assess their effect on SCD phenotype and HbF level among Egyptian patients. Polymerase chain reaction assay was used to determine these polymorphisms among 100 SCD patients and 100 healthy controls. Though not statistically significant, the frequency of individual carrying HMOX-1 polymorphic AT and TT genotypes in both patient and control groups was 92% and 85% respectively. Regarding CCR5Δ32 polymorphisms, all SCD patients harbored the wild genotype (100%), while the heteromutant genotype was encountered in 2% of our controls. Patients harboring mutant HMOX-1 had a less frequent vaso-occlusive crisis (VOC)/lifetime, less VOC in the last year, less incidence of stroke, less frequency of hospitalization, and responded more frequently to hydroxyurea with statistically significant differences (p = 0.028, 0.007, 0.046, 0.007, and 0.011 respectively). No significant associations with HbF level or other hematologic parameters were encountered among our cohort. Our study results suggest a protective effect of mutant HMOX-1 genotypes in ameliorating the phenotypic severity of the disease. HMOX1-413 A>T (rs2071746) polymorphisms might prove to be a prognostic marker among Egyptian SCD, but not CCR5Δ32 (rs333) polymorphisms.

Control of ß-sitosterol biosynthesis under light and watering in desert plant Calotropis procera.

Most scientific studies on Calotropis procera refer to the plant as an important source of pharmaceutical compounds and its valuable benefits in medicine. One of the most important substances in this plant is the potential immunostimulant ß-sitosterol (BS) that acts in improving human health. This study focused on the effects of lighting before and after irrigation on the BS accumulation pathway namely steroid biosynthesis. Studying the enzymes in BS biosynthetic pathway indicated the upregulation at dawn and predusk of the SMT2 and SMO2 genes encoding sterol methyltransferase 2 and methylsterol monooxygenase, two key enzymes in BS accumulation in C. procera. The results almost indicated no regulation at the different time points of the CYP710A gene encoding sterol 22-desaturase, an enzyme that acts in depleting ß-sitosterol towards the biosynthesis of stigmasterol. RNA-Seq data was validated via quantitative RT-PCR and results were positive. The data of ultra-performance liquid chromatography-tandem mass spectrometry analysis with regard to BS accumulation also aligned with those of RNA-Seq analysis. We focused on the effects of light before and after watering on BS accumulation in C. procera. Our results show that BS accumulation is high at dawn in both dehydrated and well-watered condition. While, the BS was dramatically decrease at midday in well-watered plants. This increase/decrease in BS content is correlated with rates of expression of SMT 2 gene. This gene is a key convertor between the different branches in the cardiac glycoside biosynthesis. Accordingly, it could be suggested that BS (or one of the descendent product) may play an important role in C. procera tolerance to drought/light intensity conditions.

Molecular Screening for Malaria among Blood Donors in a WHO Claimed Region of Egypt, Fayoum Governorate.

BACKGROUND: Transfusion-transmitted malaria is undoubtedly a potential health hazard for blood recipients. Egypt is still on the prevention of reintroduction phase of malaria control program. Fayoum Governorate is considered one of the high-risk foci in Egypt due to its geology. However, no studies have been reported to evaluate the current status of subclinical Plasmodium infection based on sensitive molecular techniques. Moreover, screening of malaria is not listed within screening protocols of blood-borne pathogens in Fayoum blood banks. OBJECTIVE: To assess the current prevalence of subclinical Plasmodium infection among blood donors of Fayoum inhabitants for transfusion biosafety. To predict any possibility of the reemergence of malaria in the governorate and the effectiveness of malaria control measures. METHODS: A cross-sectional survey was conducted on 400 apparently healthy blood-donors in blood transfusion center of Fayoum University hospital from Jun 2012 to Jan 2013. Conventional PCR was used to detect the 18 S ssrRNA Plasmodium gene. RESULTS: All Fayoum inhabitants' blood donors' samples were negative for Plasmodium infection. CONCLUSIONS: Current applied control, and preventive measures are valid in the context of blood transfusion biosafety in Fayoum blood banks and, therefore, the implementation of a routine malaria screening test in Fayoum blood banks is not merited at this time.

Characterization of differential antibody production against hepatitis C virus in different HCV infection status.

BACKGROUND: The Centers for Disease Control and Prevention (CDC) issued an update on hepatitis C virus (HCV) testing approach, in which it omitted the use of recombinant immunoblot assay (RIBA) in the diagnostic algorithm and recommended that future studies are needed to evaluate the performance of HCV testing without RIBA. As Egypt has the highest prevalence of HCV worldwide, we aimed to evaluate the value of RIBA in HCV testing in a high prevalence population. Our objective was to clarify whether enzyme linked immunosorbent assay (ELISA) anti-HCV signal-to-cutoff (S/CO) ratios were able to discriminate true positive from false positive anti-HCV antibody status and to evaluate the role of RIBA in solving this problem which may lead to a redefined strategy for diagnosis of HCV infection. Our second objective was to elucidate the effects of different HCV peptides of both structural and non-structural proteins on the humoral immune response to HCV infection. METHODS: The current study drew results from 167 individuals divided into three groups: Group I: included 77 HCV antibody positive (ELISA) high risk health care workers (HCW), Group II: included 56 presumably uninfected individuals who showed normal liver enzymes, negative HCV RNA and were asymptomatic. Their ELISA HCV antibody S/C ratio ranged from 0.9 to <5. Group III: included 34 patients enrolled from outpatient clinics of Ain Shams Hospital with persistent viral replication, elevated liver enzymes, and chronic HCV related liver disease. All study participants were assessed for the presence of anti-HCV antibodies by 3(rd) generation ELISA which was confirmed by RIBA. RESULTS: Interpreting the results of both ELISA and RIBA together, false positive results were highly significantly increased in HCW when compared with the other two groups. Indeterminate and false negative results were only found in the presumably uninfected group. For differentiated antibody responses by RIBA, chronic HCV cases had the highest frequency of positive antibody response to core peptides while the presumably uninfected group had the lowest. Antibody response to E2 was found less frequently in chronic cases than Core 1, Core 2 and NS3. The specific antibody response to the different HCV peptides showed the same distribution of frequencies in both chronic HCV cases and the presumably uninfected individuals with the chronic cases having the highest frequencies. This distribution was different from the HCW. The most evident difference was the reaction towards NS3 which was the highest antibody producing peptide in chronic HCV and presumably uninfected individuals whereas in HCW Core1 was the highest. CONCLUSION: The HCV antibody immunoblot assay (RIBA) is still necessary for the detection of false positive cases which can occur quite frequently in countries of high prevalence as Egypt. Indeterminate RIBA results indicate a waning antibody response in elderly individuals who recovered from previous or distant HCV infection.

Role of regulatory CD4+CD25+ Foxp3 T cells in bronchial asthma in Egyptian children.

CD4+CD25+high Foxp3 regulatory T (Treg) cells are known to play a key role in balancing immune response to maintain peripheral tolerance against harmless antigens or allergens. Defective immunological suppression by CD4+CD25+high Foxp3 Treg cells can be a cause of the inflammation that leads to an allergic condition such as asthma. The aims of the study are to (1) determine CD4+CD25+high Foxp3 Treg cells frequency in the peripheral blood of children with and without asthma; and (2) investigate the association between CD4+CD25+high Foxp3 Treg cells frequency with disease severity and corticosteroid therapy. Sixty asthmatic children with varying disease severity (20 mild, 20 moderate and 20 severe) were enrolled in the study. Severe asthmatic children were further subdivided into two groups, one on corticosteroid therapy and the other was not on corticosteroid. Twenty age and sex matched healthy children were enrolled as controls. Number of circulating CD4+CD25+high Foxp3 Tregs were measured using flow cytometry. Our finding demonstrates that children with asthma had a significant decrease of CD4+CD25high Foxp3 Treg cells and Tregs/T effectors ratio in peripheral blood compared to children without asthma. Patients with moderate asthma demonstrated lower frequency of CD4+CD25+high Foxp3 Treg cells compared to mild and severe asthmatic patients. Those on corticosteroid therapy revealed significant increase in CD4+CD25+high Foxp3 Treg cells and decrease in T effectors. It is concluded that asthmatic children have decreased number of CD4+CD25+high Foxp3 Treg cells leading to increase in effectors cells which mediate inflammation in the airways. Corticosteroid therapy plays a role in elevating number of CD4+CD25+high Foxp3 Treg cells and maintaining its suppressor function.

Effect of surgically-induced weight loss on inflammatory mediators and peripheral blood monocyte CD11b expression in morbid obesity.

Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers. Expression and release of inflammation-related adipokines, generally, rise as adipose tissue expands. In the present study we evaluated the level of serum mediators concerned in inflammation and monocyte activation (TNF-alpha, hs-CRP, MCP-1) together with percentage of CD11-b expression on monocytes in a group of morbidly obese individuals (n = 20) before and (3-6 months) after restrictive surgery, and in 15 healthy normal weight individuals. Serum MCP-1, TNF-alpha and hs-CRP were assayed by enzymatic immunoassay, while the percentage of CD11b expression on monocytes was assayed by flow cytometry. The total lipid profile and random blood glucose levels were also assessed. Morbidly obese individuals ( before surgical weight loss) had significantly increased levels of MCP-1, TNF-alpha, hs-CRP, CD11b expression on monocytes as compared to controls (P < 0.01). Levels of MCP-1, TNF-alpha, hs-CRP were significantly decreased 3 to 6 months after restrictive surgery than before the operation (P < 0.01). hs-CRP, MCP-1 and TNF-alpha were positively correlated versus each other. TNF-alpha and hs-CRP also showed positive correlation with the body mass index. Our data suggested that the studied serum and monocyte parameters may link obesity with systemic inflammation and metabolic disorders. The interactions of MCP-1, CD11b and other inflammatory parameters might provide the basis for development of new therapies for this syndrome.

A comparative study of two angiogenic factors: vascular endothelial growth factor and angiogenin in induced sputum from asthmatic children in acute attack.

BACKGROUND: Angiogenesis is a prerequisite for airway remodeling in bronchial asthma. Several factors may play important roles in inflammation and angiogenesis through effects on inflammatory cell infiltration or neovascularization. OBJECTIVES: (1) To determine the levels of vascular endothelial growth factor (VEGF) and angiogenin in sputum supernatants of asthmatic children during the acute attack and 6 weeks after start of therapy; and (2) to correlate their levels with the degree of asthma severity. SUBJECTS AND METHODS: Twenty asthmatic children with acute attack (mean age, 9.6 +/- 3.5 years [+/- SD]) and 12 sex- and age-matched healthy control children were enrolled in the study. Sputum supernatants were collected for determination of VEGF and angiogenin levels. Serum samples were withdrawn for IgE measurement. The above tests were performed using an enzyme-linked immunosorbent assay. The FEV1 was measured using spirometry. VEGF, angiogenin, and FEV1 estimations were repeated for asthmatic children 6 weeks after start of therapy. RESULTS: During the acute attack, asthmatic children had significantly higher levels of VEGF and angiogenin than in healthy control children (p < 0.001). VEGF and angiogenin levels showed more elevation with increase in asthma severity (p < 0.001). A significant positive correlation existed between both angiogenic factors (r = 0.98, p < 0.001). A negative significant correlation was found between FEV1 percentage of predicted and both VEGF (r = -0.99, p < 0.001) and angiogenin (r = -0.97, p < 0.001). A nonsignificant correlation was found between serum IgE and sputum VEGF (r = 0.09, p > 0.05). Although there was a significant decrease in the levels of both VEGF and angiogenin after 6 weeks of treatment with corticosteroid inhalation therapy, the levels did not reach normal control levels (p < 0.001 and p < 0.05, respectively). CONCLUSIONS: Our results show that both VEGF and angiogenin levels were elevated in children with acute asthma. The study also suggests that increased severity of bronchial asthma in children is associated with the expression of both angiogenic factors, which are implicated in asthma pathogenesis. After 6 weeks of therapy, the levels of both angiogenic factors showed significant decrease.