Sayed Abdelwahab - Academia.edu (original) (raw)

Papers by Sayed Abdelwahab

Research paper thumbnail of Prevalence of Methicillin Resistant Staphylococcus aureus among Egyptian Patients after Surgical Interventions

Surgical Infections

Abstract Background: Staphylococcus aureus (S. aureus) is isolated frequently from surgical site ... more Abstract Background: Staphylococcus aureus (S. aureus) is isolated frequently from surgical site infections and other soft tissue infections. There are limited data examining the prevalence of methicillin resistant S. aureus (MRSA) among Egyptian patients after surgery. The current study determined the prevalence of MRSA isolated from surgical site and soft tissue infections at Minia University Hospital (MUH), determined their susceptibility to β-lactams and other antimicrobials, and examined their mecA gene expression. Methods: A total of 208 hospitalized patients attending the General Surgery Department at MUH were enrolled and all had skin and soft tissue infections (SSTIs) of different causes. These 208 patients (143 males and 65 females) were suffering from surgical site infection (SSI; n=82), diabetic foot (n=52), abscess (n=45), or burn (n=29) infections. Samples were cultured on different media for isolation and identification of S. aureus and the isolates were screened for ...

Research paper thumbnail of P-B10 Egyptian healthcare workers and Hepatitis C virus vaccines

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2016

Research paper thumbnail of Occult hepatitis C virus infection among Egyptian hemodialysis patients

Journal of medical virology, Jan 7, 2016

Occult Hepatitis C Virus (HCV) infection (OCI) was reported in an apparently disease-free state i... more Occult Hepatitis C Virus (HCV) infection (OCI) was reported in an apparently disease-free state in the absence of liver disease, anti-HCV and HCV-RNA in the serum. The existing data examining the clinical significance of OCI and its potential as a source of HCV infection among hemodialysis patients are very limited. We examined the presence of OCI among patients on maintenance hemodialysis at Minia Governorate, Egypt; an HCV endemic country. A total of 81 subjects with negative markers for HCV were enrolled. HCV-RNA was tested in PBMCs by real-time PCR. For the 81 subjects, the average dialysis duration was 32.7 ± 21.7 months and the average ALT level (± SD) was 26 ± 12 U/L while that of AST was 29 ± 16 U/L. Out of the 81 subjects, three (3.7%) were HCV-RNA positive in PBMCs in the absence of serum anti-HCV and HCV-RNA indicating OCI. The viral load of the OCI subjects ranged from 172 to 4150 IU/ml. History of liver disease was positive in one of the three positive patients. These r...

Research paper thumbnail of Risk factors for hepatitis C virus infection among Egyptian healthcare workers in a national liver diseases referral centre

Transactions of the Royal Society of Tropical Medicine and Hygiene, Dec 22, 2011

Little is known about the prevalence of hepatitis C virus (HCV) among healthcare workers (HCW) in... more Little is known about the prevalence of hepatitis C virus (HCV) among healthcare workers (HCW) in Egypt, where the highest worldwide prevalence of HCV exists. The prevalence of HCV, hepatitis B virus and Schistosoma mansoni antibodies was examined in 842 HCWs at the National Liver Institute in the Nile Delta, where >85% of patients are HCV antibodypositive. The mean age of HCWs was 31.5 years and they reported an average of 0.6 ± 1.2 needlesticks/HCW/year. The prevalence of anti-HCV, hepatitis B surface antigen (HBsAg) and co-infection was 16.6%, 1.5% and 0.2%, respectively. HCV-RNA was present in 72.1% of anti-HCV-positive HCWs, and all but one subject were infected with HCV genotype 4. Schistosoma mansoni antibodies were present in 35.1%. The anti-HCV rate increased sharply with age and employment duration, but not among those with needlestick history. After adjusting for other risk factors, the anti-HCV rate was higher among older HCWs [P < 0.001; risk ratio (RR) = 1.086, 95% CI 1.063-1.11], males (P = 0.002; RR = 1.911, 95% CI 1.266-2.885) and those with rural residence (P < 0.001; RR = 2.876, 95% CI 1.830-4.52). Occupation (P = 0.133), duration of employment (P = 0.272) or schistosomal antibody positivity (P = 0.152) were not significant risk factors for anti-HCV positivity. In conclusion, although one in six HCWs had been infected with HCV, the infections were more likely to be community-acquired and not occupationally related.

Research paper thumbnail of Design, Synthesis, and Molecular Docking of Novel Pyrrolooxazepinediol Derivatives with Anti-Influenza Neuraminidase Activity

Archiv der Pharmazie, Jan 17, 2015

A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starti... more A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starting from l-tartaric acid, which was transformed into anhydride which then reacted with allylamine in xylene to afford the imide 2. The target molecules 12-15 were achieved via ring-closing metathesis with the Grubbs catalyst, followed by reduction of the carbonyl group and deprotection of hydroxyl groups. Finally, catalytic hydrogenation of the double bond afforded the title compounds 12-15. Molecular docking study of the title compounds 12-15 was carried out against neuraminidase as the target enzyme, in an attempt to understand the mechanism of action of the tested compounds as potential neuraminidase inhibitors. Molecular docking of the target compounds showed that all tested compounds bind to the active site of neuraminidase, with moderate to high binding energy. Compounds 12-15 were examined for their antiviral activity against H5N1 virus (A/chicken/Egypt/1/2008). Oseltamivir phospha...

Research paper thumbnail of Bagley, K.C., Abdelwahab, S.F., Tuskan, R.G., Fouts, T.R. & Lewis, G.K. Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway. J. Leukoc. Biol. 72, 962-969

Journal of Leukocyte Biology

Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella ... more Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella pertussis. PT is a powerful mucosal adjuvant whose cellular target and mechanism of action are unknown; however, emerging evidence suggests that dendritic cells (DC) may be a principal adjuvant target of PT. Here, we investigate the mechanism underlying the effects of these toxins on human monocyte-derived DC (MDDC) in vitro. We found that the effects of PT and AT on MDDC, including maturation, are mediated by cyclic adenosine monophosphate (cAMP). In this regard, adenosine 5'-diphosphate-ribosylation-defective derivatives of PT failed to induce maturation of MDDC, whereas dibutyryl-cAMP (d-cAMP) and Forskolin mimic the maturation of MDDC and dominant inhibition of cytokine production induced by these toxins. Also, cAMP-dependent kinase inhibitors blocked the ability of PT, AT, d-cAMP, and Forskolin to activate MDDC. Taken together, these results show that the effects of PT and AT on...

Research paper thumbnail of Interleukin 28B.rs12979860 genotype does not affect hepatitis C viral load in Egyptians with genotype 4 chronic infection

Archives of Virology, 2015

Several host and viral factors affect the natural history of Hepatitis C Virus (HCV) infection. I... more Several host and viral factors affect the natural history of Hepatitis C Virus (HCV) infection. Interleukin 28B (IL28B).rs12979860 single nucleotide polymorphism (SNP) was found to predict viral clearance with and without therapy. Subjects with the CC (favorable) genotype of IL28B.rs12979860 were more likely to spontaneously clear the infection and respond favorably to therapy. These data suggest that subjects with the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;favorable&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; CC genotype might have a lower viral load when compared to those with the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;unfavorable&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; TT genotype. Therefore, we examined the effect of IL28B.rs12979860 SNP on HCV viral load and clearance among HCV-infected Egyptians. This cross sectional study was conducted on 375 HCV antibody-positive subjects. Detection and quantification of HCV-RNA was determined by RT-PCR. IL28B.rs12979860 genotyping was performed using SYBR green real-time PCR and specific primers. Of 375 HCV-antibody positive subjects, 239 (63.7 %) had chronic HCV infection while the remaining 136 (36.3 %) subjects had spontaneously cleared the virus. The frequency of IL28-B CC, CT, and TT genotypes among spontaneous resolvers were 54.4 %, 39.0 %, and 6.6 % while among the chronically infected subjects, they were 31.4 %, 49.8 %, and 18.8 %, respectively. As expected, IL28 genotype predicted spontaneous HCV clearance (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The average HCV viral loads were 1.5 ± 0.69 x 10(6), 0.62 ± 0.11 x 10(6) and 0.51 ± 0.14 x 10(6) IU/ml among chronic subjects with the IL28B.rs12979860 CC, CT and TT genotypes, respectively (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). In conclusion, our results show that IL28B.rs12979860 genotype does not affect viral load among chronic HCV infected Egyptians. These findings further confirm the complexity of viral host interactions in determining HCV infection outcome.

Research paper thumbnail of Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response

Archives of Virology, 2015

The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous ... more The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous hepatitis C virus (HCV) clearance and treatment response. The distribution and correlation of an IL28B.rs12979860 single-nucleotide polymorphism (SNP) with HCV-specific cell-mediated immune (CMI) responses among Egyptian healthcare workers (HCWs) is not known. We determined this relationship in 402 HCWs who serve a patient cohort with ~85 % HCV prevalence. We enrolled 402 HCWs in four groups: group 1 (n = 258), seronegative aviremic subjects; group 2 (n = 25), seronegative viremic subjects; group 3 (n = 41), subjects with spontaneously resolved HCV infection; and group 4 (n = 78), chronic HCV patients. All subjects were tested for an HCV-specific CMI response using an ex-vivo interferon-gamma (IFNγ) ELISpot assay with nine HCV genotype-4a overlapping 15-mer peptide pools corresponding to all of the HCV proteins. All subjects were tested for IL28B.rs12979860 SNP by real-time PCR. An HCV-specific CMI was demonstrated in ~27 % of the seronegative aviremic HCWs (group 1), suggesting clearance of infection after low-level exposure to HCV. The frequency of IL28B.rs12979860 C allele homozygosity in the four groups was 49 %, 48 %, 49 %, and 23 %, while that of the T allele was 14 %, 16 %, 12 and 19 %, respectively, suggesting differential distributions among subjects with different HCV status. As reported, IL28B.rs12979860 predicted the outcome of HCV infection (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), but we did not find any relationship between the IL28B genotypes and the outcome of HCV-specific CMI responses in the four groups (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). The data show differential IL28B.rs12979860 genotype distribution among Egyptian HCWs with different HCV status and could not predict the outcome of HCV-specific CMI responses.

Research paper thumbnail of Prevalence of anti-HEV IgM among blood donors in Egypt

The Egyptian journal of immunology / Egyptian Association of Immunologists, 2011

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis (AVH) in developing countries.... more Hepatitis E virus (HEV) is a common cause of acute viral hepatitis (AVH) in developing countries. In Egypt; where up to 80% of the inhabitants of rural villages have anti-HEV antibodies denoting past infection, most of these infections are asymptomatic with little evidence that the infection causes AVH. There are accumulating reports which suggest potential risk of HEV transmission by blood transfusion. However, detection of serological markers for HEV infection or HEV RNA in Egyptian blood banks is not routinely performed. 760 blood samples from apparently healthy donors at the National blood bank were tested for markers of acute HEV infection to estimate the seroprevalence of acute HEV infection, and potential risk of infection by blood transfusion. They included 124 females (16.82%) and 636 males (83.68%), with a mean age of 23.8 +/- 5.3 years and mean ALT value of 23.3 +/- 13.2 IU/ml. Samples were tested as pools of 10 subjects. Pools with highest reactivity were retested indivi...

Research paper thumbnail of Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway

Journal of leukocyte biology, 2002

Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella ... more Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella pertussis. PT is a powerful mucosal adjuvant whose cellular target and mechanism of action are unknown; however, emerging evidence suggests that dendritic cells (DC) may be a principal adjuvant target of PT. Here, we investigate the mechanism underlying the effects of these toxins on human monocyte-derived DC (MDDC) in vitro. We found that the effects of PT and AT on MDDC, including maturation, are mediated by cyclic adenosine monophosphate (cAMP). In this regard, adenosine 5'-diphosphate-ribosylation-defective derivatives of PT failed to induce maturation of MDDC, whereas dibutyryl-cAMP (d-cAMP) and Forskolin mimic the maturation of MDDC and dominant inhibition of cytokine production induced by these toxins. Also, cAMP-dependent kinase inhibitors blocked the ability of PT, AT, d-cAMP, and Forskolin to activate MDDC. Taken together, these results show that the effects of PT and AT on...

Research paper thumbnail of ‘Self-Protection’ of Individual CD4+ T Cells against R5 HIV-1 Infection by the Synthesis of Anti-Viral CCR5 Ligands

PLoS ONE, 2008

It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8 + and CD4 + T c... more It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8 + and CD4 + T cells can block the infection of activated CD4 + T cells by R5 and dual-tropic isolates of HIV-1. By contrast, because CD4 + T cells can be infected by HIV-1 and at least some subsets secrete anti-viral CCR5 ligands, it is possible that these ligands protect against HIV-1 via autocrine as well as paracrine pathways. Here we use a model primary CD4 + T cell response in vitro to show that individual CD4 + T cells that secrete anti-viral CCR5 ligands are 'self-protected' against infection with R5 but not X4 strains of HIV-1. This protection is selective for CD4 + T cells that secrete anti-viral CCR5 ligands in that activated CD4 + T cells in the same cultures remain infectable with R5 HIV-1. These data are most consistent with an autocrine pathway of protection in this system and indicate a previously unappreciated selective pressure on the emergence of viral variants and CD4 + T cell phenotypes during HIV-1 infection.

Research paper thumbnail of Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians

Hepatology International, 2015

Background/purpose Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; ... more Background/purpose Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; also known as interleukin 28B; IL28B) gene are associated with spontaneous hepatitis C virus (HCV) clearance. Interferon lambda 4 (IFNL4).ss469415590, in linkage disequilibrium (LD) with IFNL3.rs12979860 among the Caucasian population, has recently been identified as a potential functional variant. Our objective was to assess the LD between IFNL3.rs12979860 and IFNL4.ss469415590 and to compare their effect on the outcome of HCV infection among Egyptians, mainly infected with HCV genotype 4. Methods One-hundred and eighty-five Egyptian HCV patients (77 spontaneous resolvers and 108 chronic subjects), and 122 healthy controls were genotyped for both IL28B.rs12979860 and IFNL4.ss469415590. Logistic regression models including factors with univariate association with the outcome of infection were calculated for each genetic marker. The LD was also calculated for the 122 healthy controls.

Research paper thumbnail of Exposure to hepatitis C virus induces cellular immune responses without detectable viremia or seroconversion

The American journal of tropical medicine and hygiene, 2005

Sporadic cases of cell-mediated immunity (CMI) in persons exposed to hepatitis C (HCV) but eviden... more Sporadic cases of cell-mediated immunity (CMI) in persons exposed to hepatitis C (HCV) but evidently uninfected have been reported. To further define this, we measured CMI in individuals without evidence of HCV infection, that is, negative for HCV-antibodies (anti-HCV) and RNA, residing in a rural Egyptian community where prevalence of anti-HCV was 24%. Cell-mediated immunity (CMI) measured by interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay, confirmed by intracellular staining using flow cytometry, against HCV peptides was measured in seronegative individuals with high-risk (HR) and low-risk (LR) exposures to HCV. Thirteen of 71 (18.3%) HR subjects but only 1 of 35 (2.9%) LR subjects had detectable CMI (P = 0.032). These data are compatible with the hypothesis that exposures to HCV may lead to development of HCV-specific CMI without anti-HCV and ongoing viral replication. We speculate induced CMI clears HCV sometimes when anti-HCV is not detectable, and HCV-spe...

Research paper thumbnail of Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection

Journal of virology, 2005

Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that ... more Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. Beta-defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 microg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select beta-defensins, especially human beta-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that beta-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV co...

Research paper thumbnail of Antigen stimulation induces HIV envelope gp120-specific CD4+ T cells to secrete CCR5 ligands and suppress HIV infection

Virology, 2007

CD4 + T cells are critical for effective immune responses against HIV, but they are also the main... more CD4 + T cells are critical for effective immune responses against HIV, but they are also the main cell type targeted by the virus. To investigate the key factors that could protect these cells from infection, we evaluated the capacity of HIV gp120-specific human CD4 + T cells to produce chemokines that inhibit HIV and determined their contribution in suppressing infection in the cells. Antigen stimulation of the CD4 + T cells elicited production of high amounts of CCR5 chemokines MIP-1α (CCL3), MIP-1β (CCL4), and RANTES (CCL5). Production of these CCR5 ligands was more readily and reproducibly detected than that of IFN-γ or IL-2. Importantly, in association with secretion of the CCR5 ligands, antigen stimulation made these CD4 + T cells more resistant to CCR5-tropic HIV-1. Conversely, in the absence of antigen stimulation, the cells were readily infected by the virus, and after infection, their capacity to produce MIP-1β and IFN-γ rapidly declined. Thus, vaccines that trigger HIV-specific CD4 + T cells to elicit robust and rapid production of anti-viral chemokines would be advantageous. Such responses would protect virus-specific CD4 + T cells from HIV infection and preserve their critical functions in mounting and maintaining long-lasting immunity against the virus.

Research paper thumbnail of Changing Patterns of Drug-Resistant Shigella Isolates in Egypt

Microbial Drug Resistance, 2014

Background: The emergence of multidrug resistance (MDR) is a serious problem in treating shigello... more Background: The emergence of multidrug resistance (MDR) is a serious problem in treating shigellosis. There are limited existing data examining the change in the antimicrobial resistance profile of Shigella in Egypt. We previously reported that 58% of the Shigella isolates in Egypt were resistant to at least one member of the three different antimicrobial groups. This study was performed to determine the antimicrobial resistance profile of Shigella, determine their possible mechanisms of resistance, and compare their resistance profile to those reported 20 years ago. Patients and Methods: Stool samples were collected from 500 subjects and processed for the isolation and identification of Shigella. The susceptibility of the isolates to 11 different antimicrobials was determined using the disc diffusion method. Results: Of 500 stool cultures, 24 (4.8%) samples were positive for Shigella. There was a high percentage of resistance to ampicillin (88%), tetracycline (83%), and sulfamethoxazole-trimethoprim (75%). Also, there was a moderate percentage of resistance to chloramphenicol (46%), streptomycin (42%), ceftazidime (33%), and cefotaxime (25%). A lower percentage of resistance was recorded for amikacin, nalidixic acid (17% each), and ofloxacin (7%), while no resistance was found to ciprofloxacin (0%). Twenty-one of the isolates (88%) were resistant to at least three different antimicrobial groups (indicating MDR). The average number of antimicrobial agents to which the Shigella isolates were resistant was 4.3±1.4, while it was 3.4±1.5 in the same locality in 1994. Conclusion: These data demonstrate that there is a marked increase in MDR and change in the resistance patterns of Shigella over the past 20 years.

Research paper thumbnail of Increased quinolone resistance among typhoid Salmonella isolated from Egyptian patients

The Journal of Infection in Developing Countries, 2014

Introduction: Typhoid fever is endemic in Egypt; and quinolones are the empirical treatment of ch... more Introduction: Typhoid fever is endemic in Egypt; and quinolones are the empirical treatment of choice. There are very limited data reporting quinolone resistance among Egyptian typhoidal Salmonella isolates. We previously reported that all typhoidal Salmonella were sensitive to quinolones. This study aimed to isolate and identify typhoidal Salmonella from cases suffering from enteric fever at Minia Governorate, Egypt, determine their quinolone resistance patterns, compare them to those reported 20 years ago, and test gyrA mutation as a possible mechanism for quinolone resistance. Methodology: Stool samples from Widal-positive subjects were screened by culture on suitable media and were identified biochemically. The identified isolates were tested for resistance against three representatives of the first three quinolone generations, namely nalidixic acid (NAL), levofloxacin (LEV), and norfloxacin (NOR). The gyrA gene was amplified and sequenced to detect point mutation(s) conferring quinolone resistance. Results: Out of 230 stool samples (from patients with Widal anti-O titers of ≥ 1/160), 40 isolates were S. enterica serovar Typhi (97.5%) and Paratyphi A (2.5%). Six (15%) isolates were resistant to at least one of the quinolones, compared to 0% in 1993. In this regard, 15%, 7.5%, and 2.5% of the isolates were resistant to NAL, both NAL and LEV, and all three quinolones tested, respectively. Sequencing of the gyrA gene revealed point mutations at position 83 and/or 87 of the gyrA gene only among the resistant isolates. Conclusion: There has been an increase in quinolone-resistant typhoidal Salmonella in Egypt over time.

Research paper thumbnail of T cells are depleted in HCV-Induced hepatocellular carcinoma patients: possible role of apoptosis and p53

The Egyptian journal of immunology / Egyptian Association of Immunologists, 2006

Egypt has possibly the highest Hepatitis C Virus (HCV) prevalence worldwide. A high proportion of... more Egypt has possibly the highest Hepatitis C Virus (HCV) prevalence worldwide. A high proportion of HCV infections become chronic and lead to liver cirrhosis and hepatocellular carcinoma (HCC). The cellular and molecular mechanisms behind HCV infection complication are not completely understood although apoptosis has been implicated in this process. Using flowcytometry, we examined whether T lymphocyte; isolated from patients with HCV and HCV-associated HCC (HCV-HCC); are predestined in vivo to undergo spontaneous apoptosis. Also, the role of p53; a key protein in apoptotic process; in the development of HCC was examined. Our data showed that T cells were severely depleted in HCV-HCC patients and its spontaneous apoptosis was higher in patient groups as compared to normal controls. In addition, p53 expression in liver tissue (determined by ELISA) was higher in the HCC patient groups as compared to normal controls and correlated well with the HCC grade. In conclusion, HCV infection ind...

Research paper thumbnail of Cross reactive cellular immune response to HCV genotype 1 and 4 antigens among genotype 4 exposed subjects

PloS one, 2014

Hepatitis C Virus (HCV) infection is a global health burden particularly in Egypt, where HCV geno... more Hepatitis C Virus (HCV) infection is a global health burden particularly in Egypt, where HCV genotype 4a (GT-4a) predominates. The prevention and control of HCV infection will remain a challenge until the development of an effective vaccine that protects against different genotypes. Several HCV GT-1-based vaccines are in different stages of clinical trials, but antigenic differences could make protection against other genotypes problematic. In this regard, data comparing the cell-mediated immune (CMI) response to different HCV genotypes are limited. We aimed to ex vivo investigate whether GT-1-based vaccine may protect against HCV GT-4 infections. This was carried out on samples collected from genotype 4 infected/exposed subjects. The CMI responses of 35 subjects; infected with HCV GT-4/or who had spontaneously-resolved the infection and 10 healthy control subjects; to two sets of seven HCV overlapping 15-mer peptide pools derived from both genotypes; and covering most of the viral ...

Research paper thumbnail of HIV-1 transgenic rats develop T cell abnormalities

Virology, 2004

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility... more HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-g following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC À CD62L À ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naïve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/ memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process. D 2004 Elsevier Inc. All rights reserved.

Research paper thumbnail of Prevalence of Methicillin Resistant Staphylococcus aureus among Egyptian Patients after Surgical Interventions

Surgical Infections

Abstract Background: Staphylococcus aureus (S. aureus) is isolated frequently from surgical site ... more Abstract Background: Staphylococcus aureus (S. aureus) is isolated frequently from surgical site infections and other soft tissue infections. There are limited data examining the prevalence of methicillin resistant S. aureus (MRSA) among Egyptian patients after surgery. The current study determined the prevalence of MRSA isolated from surgical site and soft tissue infections at Minia University Hospital (MUH), determined their susceptibility to β-lactams and other antimicrobials, and examined their mecA gene expression. Methods: A total of 208 hospitalized patients attending the General Surgery Department at MUH were enrolled and all had skin and soft tissue infections (SSTIs) of different causes. These 208 patients (143 males and 65 females) were suffering from surgical site infection (SSI; n=82), diabetic foot (n=52), abscess (n=45), or burn (n=29) infections. Samples were cultured on different media for isolation and identification of S. aureus and the isolates were screened for ...

Research paper thumbnail of P-B10 Egyptian healthcare workers and Hepatitis C virus vaccines

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2016

Research paper thumbnail of Occult hepatitis C virus infection among Egyptian hemodialysis patients

Journal of medical virology, Jan 7, 2016

Occult Hepatitis C Virus (HCV) infection (OCI) was reported in an apparently disease-free state i... more Occult Hepatitis C Virus (HCV) infection (OCI) was reported in an apparently disease-free state in the absence of liver disease, anti-HCV and HCV-RNA in the serum. The existing data examining the clinical significance of OCI and its potential as a source of HCV infection among hemodialysis patients are very limited. We examined the presence of OCI among patients on maintenance hemodialysis at Minia Governorate, Egypt; an HCV endemic country. A total of 81 subjects with negative markers for HCV were enrolled. HCV-RNA was tested in PBMCs by real-time PCR. For the 81 subjects, the average dialysis duration was 32.7 ± 21.7 months and the average ALT level (± SD) was 26 ± 12 U/L while that of AST was 29 ± 16 U/L. Out of the 81 subjects, three (3.7%) were HCV-RNA positive in PBMCs in the absence of serum anti-HCV and HCV-RNA indicating OCI. The viral load of the OCI subjects ranged from 172 to 4150 IU/ml. History of liver disease was positive in one of the three positive patients. These r...

Research paper thumbnail of Risk factors for hepatitis C virus infection among Egyptian healthcare workers in a national liver diseases referral centre

Transactions of the Royal Society of Tropical Medicine and Hygiene, Dec 22, 2011

Little is known about the prevalence of hepatitis C virus (HCV) among healthcare workers (HCW) in... more Little is known about the prevalence of hepatitis C virus (HCV) among healthcare workers (HCW) in Egypt, where the highest worldwide prevalence of HCV exists. The prevalence of HCV, hepatitis B virus and Schistosoma mansoni antibodies was examined in 842 HCWs at the National Liver Institute in the Nile Delta, where >85% of patients are HCV antibodypositive. The mean age of HCWs was 31.5 years and they reported an average of 0.6 ± 1.2 needlesticks/HCW/year. The prevalence of anti-HCV, hepatitis B surface antigen (HBsAg) and co-infection was 16.6%, 1.5% and 0.2%, respectively. HCV-RNA was present in 72.1% of anti-HCV-positive HCWs, and all but one subject were infected with HCV genotype 4. Schistosoma mansoni antibodies were present in 35.1%. The anti-HCV rate increased sharply with age and employment duration, but not among those with needlestick history. After adjusting for other risk factors, the anti-HCV rate was higher among older HCWs [P < 0.001; risk ratio (RR) = 1.086, 95% CI 1.063-1.11], males (P = 0.002; RR = 1.911, 95% CI 1.266-2.885) and those with rural residence (P < 0.001; RR = 2.876, 95% CI 1.830-4.52). Occupation (P = 0.133), duration of employment (P = 0.272) or schistosomal antibody positivity (P = 0.152) were not significant risk factors for anti-HCV positivity. In conclusion, although one in six HCWs had been infected with HCV, the infections were more likely to be community-acquired and not occupationally related.

Research paper thumbnail of Design, Synthesis, and Molecular Docking of Novel Pyrrolooxazepinediol Derivatives with Anti-Influenza Neuraminidase Activity

Archiv der Pharmazie, Jan 17, 2015

A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starti... more A series of novel pyrrolo[2,1-b][1,3]oxazepine-8,9-diol derivatives 12-15 were synthesized starting from l-tartaric acid, which was transformed into anhydride which then reacted with allylamine in xylene to afford the imide 2. The target molecules 12-15 were achieved via ring-closing metathesis with the Grubbs catalyst, followed by reduction of the carbonyl group and deprotection of hydroxyl groups. Finally, catalytic hydrogenation of the double bond afforded the title compounds 12-15. Molecular docking study of the title compounds 12-15 was carried out against neuraminidase as the target enzyme, in an attempt to understand the mechanism of action of the tested compounds as potential neuraminidase inhibitors. Molecular docking of the target compounds showed that all tested compounds bind to the active site of neuraminidase, with moderate to high binding energy. Compounds 12-15 were examined for their antiviral activity against H5N1 virus (A/chicken/Egypt/1/2008). Oseltamivir phospha...

Research paper thumbnail of Bagley, K.C., Abdelwahab, S.F., Tuskan, R.G., Fouts, T.R. & Lewis, G.K. Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway. J. Leukoc. Biol. 72, 962-969

Journal of Leukocyte Biology

Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella ... more Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella pertussis. PT is a powerful mucosal adjuvant whose cellular target and mechanism of action are unknown; however, emerging evidence suggests that dendritic cells (DC) may be a principal adjuvant target of PT. Here, we investigate the mechanism underlying the effects of these toxins on human monocyte-derived DC (MDDC) in vitro. We found that the effects of PT and AT on MDDC, including maturation, are mediated by cyclic adenosine monophosphate (cAMP). In this regard, adenosine 5'-diphosphate-ribosylation-defective derivatives of PT failed to induce maturation of MDDC, whereas dibutyryl-cAMP (d-cAMP) and Forskolin mimic the maturation of MDDC and dominant inhibition of cytokine production induced by these toxins. Also, cAMP-dependent kinase inhibitors blocked the ability of PT, AT, d-cAMP, and Forskolin to activate MDDC. Taken together, these results show that the effects of PT and AT on...

Research paper thumbnail of Interleukin 28B.rs12979860 genotype does not affect hepatitis C viral load in Egyptians with genotype 4 chronic infection

Archives of Virology, 2015

Several host and viral factors affect the natural history of Hepatitis C Virus (HCV) infection. I... more Several host and viral factors affect the natural history of Hepatitis C Virus (HCV) infection. Interleukin 28B (IL28B).rs12979860 single nucleotide polymorphism (SNP) was found to predict viral clearance with and without therapy. Subjects with the CC (favorable) genotype of IL28B.rs12979860 were more likely to spontaneously clear the infection and respond favorably to therapy. These data suggest that subjects with the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;favorable&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; CC genotype might have a lower viral load when compared to those with the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;unfavorable&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; TT genotype. Therefore, we examined the effect of IL28B.rs12979860 SNP on HCV viral load and clearance among HCV-infected Egyptians. This cross sectional study was conducted on 375 HCV antibody-positive subjects. Detection and quantification of HCV-RNA was determined by RT-PCR. IL28B.rs12979860 genotyping was performed using SYBR green real-time PCR and specific primers. Of 375 HCV-antibody positive subjects, 239 (63.7 %) had chronic HCV infection while the remaining 136 (36.3 %) subjects had spontaneously cleared the virus. The frequency of IL28-B CC, CT, and TT genotypes among spontaneous resolvers were 54.4 %, 39.0 %, and 6.6 % while among the chronically infected subjects, they were 31.4 %, 49.8 %, and 18.8 %, respectively. As expected, IL28 genotype predicted spontaneous HCV clearance (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The average HCV viral loads were 1.5 ± 0.69 x 10(6), 0.62 ± 0.11 x 10(6) and 0.51 ± 0.14 x 10(6) IU/ml among chronic subjects with the IL28B.rs12979860 CC, CT and TT genotypes, respectively (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). In conclusion, our results show that IL28B.rs12979860 genotype does not affect viral load among chronic HCV infected Egyptians. These findings further confirm the complexity of viral host interactions in determining HCV infection outcome.

Research paper thumbnail of Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response

Archives of Virology, 2015

The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous ... more The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous hepatitis C virus (HCV) clearance and treatment response. The distribution and correlation of an IL28B.rs12979860 single-nucleotide polymorphism (SNP) with HCV-specific cell-mediated immune (CMI) responses among Egyptian healthcare workers (HCWs) is not known. We determined this relationship in 402 HCWs who serve a patient cohort with ~85 % HCV prevalence. We enrolled 402 HCWs in four groups: group 1 (n = 258), seronegative aviremic subjects; group 2 (n = 25), seronegative viremic subjects; group 3 (n = 41), subjects with spontaneously resolved HCV infection; and group 4 (n = 78), chronic HCV patients. All subjects were tested for an HCV-specific CMI response using an ex-vivo interferon-gamma (IFNγ) ELISpot assay with nine HCV genotype-4a overlapping 15-mer peptide pools corresponding to all of the HCV proteins. All subjects were tested for IL28B.rs12979860 SNP by real-time PCR. An HCV-specific CMI was demonstrated in ~27 % of the seronegative aviremic HCWs (group 1), suggesting clearance of infection after low-level exposure to HCV. The frequency of IL28B.rs12979860 C allele homozygosity in the four groups was 49 %, 48 %, 49 %, and 23 %, while that of the T allele was 14 %, 16 %, 12 and 19 %, respectively, suggesting differential distributions among subjects with different HCV status. As reported, IL28B.rs12979860 predicted the outcome of HCV infection (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), but we did not find any relationship between the IL28B genotypes and the outcome of HCV-specific CMI responses in the four groups (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05). The data show differential IL28B.rs12979860 genotype distribution among Egyptian HCWs with different HCV status and could not predict the outcome of HCV-specific CMI responses.

Research paper thumbnail of Prevalence of anti-HEV IgM among blood donors in Egypt

The Egyptian journal of immunology / Egyptian Association of Immunologists, 2011

Hepatitis E virus (HEV) is a common cause of acute viral hepatitis (AVH) in developing countries.... more Hepatitis E virus (HEV) is a common cause of acute viral hepatitis (AVH) in developing countries. In Egypt; where up to 80% of the inhabitants of rural villages have anti-HEV antibodies denoting past infection, most of these infections are asymptomatic with little evidence that the infection causes AVH. There are accumulating reports which suggest potential risk of HEV transmission by blood transfusion. However, detection of serological markers for HEV infection or HEV RNA in Egyptian blood banks is not routinely performed. 760 blood samples from apparently healthy donors at the National blood bank were tested for markers of acute HEV infection to estimate the seroprevalence of acute HEV infection, and potential risk of infection by blood transfusion. They included 124 females (16.82%) and 636 males (83.68%), with a mean age of 23.8 +/- 5.3 years and mean ALT value of 23.3 +/- 13.2 IU/ml. Samples were tested as pools of 10 subjects. Pools with highest reactivity were retested indivi...

Research paper thumbnail of Pertussis toxin and the adenylate cyclase toxin from Bordetella pertussis activate human monocyte-derived dendritic cells and dominantly inhibit cytokine production through a cAMP-dependent pathway

Journal of leukocyte biology, 2002

Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella ... more Pertussis toxin (PT) and adenylate cyclase toxin (AT) are AB enterotoxins produced by Bordetella pertussis. PT is a powerful mucosal adjuvant whose cellular target and mechanism of action are unknown; however, emerging evidence suggests that dendritic cells (DC) may be a principal adjuvant target of PT. Here, we investigate the mechanism underlying the effects of these toxins on human monocyte-derived DC (MDDC) in vitro. We found that the effects of PT and AT on MDDC, including maturation, are mediated by cyclic adenosine monophosphate (cAMP). In this regard, adenosine 5'-diphosphate-ribosylation-defective derivatives of PT failed to induce maturation of MDDC, whereas dibutyryl-cAMP (d-cAMP) and Forskolin mimic the maturation of MDDC and dominant inhibition of cytokine production induced by these toxins. Also, cAMP-dependent kinase inhibitors blocked the ability of PT, AT, d-cAMP, and Forskolin to activate MDDC. Taken together, these results show that the effects of PT and AT on...

Research paper thumbnail of ‘Self-Protection’ of Individual CD4+ T Cells against R5 HIV-1 Infection by the Synthesis of Anti-Viral CCR5 Ligands

PLoS ONE, 2008

It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8 + and CD4 + T c... more It is well established that paracrine secretion of anti-viral CCR5 ligands by CD8 + and CD4 + T cells can block the infection of activated CD4 + T cells by R5 and dual-tropic isolates of HIV-1. By contrast, because CD4 + T cells can be infected by HIV-1 and at least some subsets secrete anti-viral CCR5 ligands, it is possible that these ligands protect against HIV-1 via autocrine as well as paracrine pathways. Here we use a model primary CD4 + T cell response in vitro to show that individual CD4 + T cells that secrete anti-viral CCR5 ligands are 'self-protected' against infection with R5 but not X4 strains of HIV-1. This protection is selective for CD4 + T cells that secrete anti-viral CCR5 ligands in that activated CD4 + T cells in the same cultures remain infectable with R5 HIV-1. These data are most consistent with an autocrine pathway of protection in this system and indicate a previously unappreciated selective pressure on the emergence of viral variants and CD4 + T cell phenotypes during HIV-1 infection.

Research paper thumbnail of Influence of IFNL3.rs12979860 and IFNL4.ss469415590 polymorphism on clearance of hepatitis C virus infection among Egyptians

Hepatology International, 2015

Background/purpose Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; ... more Background/purpose Single-nucleotide polymorphisms (SNPs) around the interferon lambda 3 (IFNL3; also known as interleukin 28B; IL28B) gene are associated with spontaneous hepatitis C virus (HCV) clearance. Interferon lambda 4 (IFNL4).ss469415590, in linkage disequilibrium (LD) with IFNL3.rs12979860 among the Caucasian population, has recently been identified as a potential functional variant. Our objective was to assess the LD between IFNL3.rs12979860 and IFNL4.ss469415590 and to compare their effect on the outcome of HCV infection among Egyptians, mainly infected with HCV genotype 4. Methods One-hundred and eighty-five Egyptian HCV patients (77 spontaneous resolvers and 108 chronic subjects), and 122 healthy controls were genotyped for both IL28B.rs12979860 and IFNL4.ss469415590. Logistic regression models including factors with univariate association with the outcome of infection were calculated for each genetic marker. The LD was also calculated for the 122 healthy controls.

Research paper thumbnail of Exposure to hepatitis C virus induces cellular immune responses without detectable viremia or seroconversion

The American journal of tropical medicine and hygiene, 2005

Sporadic cases of cell-mediated immunity (CMI) in persons exposed to hepatitis C (HCV) but eviden... more Sporadic cases of cell-mediated immunity (CMI) in persons exposed to hepatitis C (HCV) but evidently uninfected have been reported. To further define this, we measured CMI in individuals without evidence of HCV infection, that is, negative for HCV-antibodies (anti-HCV) and RNA, residing in a rural Egyptian community where prevalence of anti-HCV was 24%. Cell-mediated immunity (CMI) measured by interferon-gamma (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay, confirmed by intracellular staining using flow cytometry, against HCV peptides was measured in seronegative individuals with high-risk (HR) and low-risk (LR) exposures to HCV. Thirteen of 71 (18.3%) HR subjects but only 1 of 35 (2.9%) LR subjects had detectable CMI (P = 0.032). These data are compatible with the hypothesis that exposures to HCV may lead to development of HCV-specific CMI without anti-HCV and ongoing viral replication. We speculate induced CMI clears HCV sometimes when anti-HCV is not detectable, and HCV-spe...

Research paper thumbnail of Human beta-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection

Journal of virology, 2005

Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that ... more Beta-defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. Beta-defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 microg/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select beta-defensins, especially human beta-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that beta-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV co...

Research paper thumbnail of Antigen stimulation induces HIV envelope gp120-specific CD4+ T cells to secrete CCR5 ligands and suppress HIV infection

Virology, 2007

CD4 + T cells are critical for effective immune responses against HIV, but they are also the main... more CD4 + T cells are critical for effective immune responses against HIV, but they are also the main cell type targeted by the virus. To investigate the key factors that could protect these cells from infection, we evaluated the capacity of HIV gp120-specific human CD4 + T cells to produce chemokines that inhibit HIV and determined their contribution in suppressing infection in the cells. Antigen stimulation of the CD4 + T cells elicited production of high amounts of CCR5 chemokines MIP-1α (CCL3), MIP-1β (CCL4), and RANTES (CCL5). Production of these CCR5 ligands was more readily and reproducibly detected than that of IFN-γ or IL-2. Importantly, in association with secretion of the CCR5 ligands, antigen stimulation made these CD4 + T cells more resistant to CCR5-tropic HIV-1. Conversely, in the absence of antigen stimulation, the cells were readily infected by the virus, and after infection, their capacity to produce MIP-1β and IFN-γ rapidly declined. Thus, vaccines that trigger HIV-specific CD4 + T cells to elicit robust and rapid production of anti-viral chemokines would be advantageous. Such responses would protect virus-specific CD4 + T cells from HIV infection and preserve their critical functions in mounting and maintaining long-lasting immunity against the virus.

Research paper thumbnail of Changing Patterns of Drug-Resistant Shigella Isolates in Egypt

Microbial Drug Resistance, 2014

Background: The emergence of multidrug resistance (MDR) is a serious problem in treating shigello... more Background: The emergence of multidrug resistance (MDR) is a serious problem in treating shigellosis. There are limited existing data examining the change in the antimicrobial resistance profile of Shigella in Egypt. We previously reported that 58% of the Shigella isolates in Egypt were resistant to at least one member of the three different antimicrobial groups. This study was performed to determine the antimicrobial resistance profile of Shigella, determine their possible mechanisms of resistance, and compare their resistance profile to those reported 20 years ago. Patients and Methods: Stool samples were collected from 500 subjects and processed for the isolation and identification of Shigella. The susceptibility of the isolates to 11 different antimicrobials was determined using the disc diffusion method. Results: Of 500 stool cultures, 24 (4.8%) samples were positive for Shigella. There was a high percentage of resistance to ampicillin (88%), tetracycline (83%), and sulfamethoxazole-trimethoprim (75%). Also, there was a moderate percentage of resistance to chloramphenicol (46%), streptomycin (42%), ceftazidime (33%), and cefotaxime (25%). A lower percentage of resistance was recorded for amikacin, nalidixic acid (17% each), and ofloxacin (7%), while no resistance was found to ciprofloxacin (0%). Twenty-one of the isolates (88%) were resistant to at least three different antimicrobial groups (indicating MDR). The average number of antimicrobial agents to which the Shigella isolates were resistant was 4.3±1.4, while it was 3.4±1.5 in the same locality in 1994. Conclusion: These data demonstrate that there is a marked increase in MDR and change in the resistance patterns of Shigella over the past 20 years.

Research paper thumbnail of Increased quinolone resistance among typhoid Salmonella isolated from Egyptian patients

The Journal of Infection in Developing Countries, 2014

Introduction: Typhoid fever is endemic in Egypt; and quinolones are the empirical treatment of ch... more Introduction: Typhoid fever is endemic in Egypt; and quinolones are the empirical treatment of choice. There are very limited data reporting quinolone resistance among Egyptian typhoidal Salmonella isolates. We previously reported that all typhoidal Salmonella were sensitive to quinolones. This study aimed to isolate and identify typhoidal Salmonella from cases suffering from enteric fever at Minia Governorate, Egypt, determine their quinolone resistance patterns, compare them to those reported 20 years ago, and test gyrA mutation as a possible mechanism for quinolone resistance. Methodology: Stool samples from Widal-positive subjects were screened by culture on suitable media and were identified biochemically. The identified isolates were tested for resistance against three representatives of the first three quinolone generations, namely nalidixic acid (NAL), levofloxacin (LEV), and norfloxacin (NOR). The gyrA gene was amplified and sequenced to detect point mutation(s) conferring quinolone resistance. Results: Out of 230 stool samples (from patients with Widal anti-O titers of ≥ 1/160), 40 isolates were S. enterica serovar Typhi (97.5%) and Paratyphi A (2.5%). Six (15%) isolates were resistant to at least one of the quinolones, compared to 0% in 1993. In this regard, 15%, 7.5%, and 2.5% of the isolates were resistant to NAL, both NAL and LEV, and all three quinolones tested, respectively. Sequencing of the gyrA gene revealed point mutations at position 83 and/or 87 of the gyrA gene only among the resistant isolates. Conclusion: There has been an increase in quinolone-resistant typhoidal Salmonella in Egypt over time.

Research paper thumbnail of T cells are depleted in HCV-Induced hepatocellular carcinoma patients: possible role of apoptosis and p53

The Egyptian journal of immunology / Egyptian Association of Immunologists, 2006

Egypt has possibly the highest Hepatitis C Virus (HCV) prevalence worldwide. A high proportion of... more Egypt has possibly the highest Hepatitis C Virus (HCV) prevalence worldwide. A high proportion of HCV infections become chronic and lead to liver cirrhosis and hepatocellular carcinoma (HCC). The cellular and molecular mechanisms behind HCV infection complication are not completely understood although apoptosis has been implicated in this process. Using flowcytometry, we examined whether T lymphocyte; isolated from patients with HCV and HCV-associated HCC (HCV-HCC); are predestined in vivo to undergo spontaneous apoptosis. Also, the role of p53; a key protein in apoptotic process; in the development of HCC was examined. Our data showed that T cells were severely depleted in HCV-HCC patients and its spontaneous apoptosis was higher in patient groups as compared to normal controls. In addition, p53 expression in liver tissue (determined by ELISA) was higher in the HCC patient groups as compared to normal controls and correlated well with the HCC grade. In conclusion, HCV infection ind...

Research paper thumbnail of Cross reactive cellular immune response to HCV genotype 1 and 4 antigens among genotype 4 exposed subjects

PloS one, 2014

Hepatitis C Virus (HCV) infection is a global health burden particularly in Egypt, where HCV geno... more Hepatitis C Virus (HCV) infection is a global health burden particularly in Egypt, where HCV genotype 4a (GT-4a) predominates. The prevention and control of HCV infection will remain a challenge until the development of an effective vaccine that protects against different genotypes. Several HCV GT-1-based vaccines are in different stages of clinical trials, but antigenic differences could make protection against other genotypes problematic. In this regard, data comparing the cell-mediated immune (CMI) response to different HCV genotypes are limited. We aimed to ex vivo investigate whether GT-1-based vaccine may protect against HCV GT-4 infections. This was carried out on samples collected from genotype 4 infected/exposed subjects. The CMI responses of 35 subjects; infected with HCV GT-4/or who had spontaneously-resolved the infection and 10 healthy control subjects; to two sets of seven HCV overlapping 15-mer peptide pools derived from both genotypes; and covering most of the viral ...

Research paper thumbnail of HIV-1 transgenic rats develop T cell abnormalities

Virology, 2004

HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility... more HIV-1 infection leads to impaired antigen-specific T cell proliferation, increased susceptibility of T cells to apoptosis, progressive impairment of T-helper 1 (Th1) responses, and altered maturation of HIV-1-specific memory cells. We have identified similar impairments in HIV-1 transgenic (Tg) rats. Tg rats developed an absolute reduction in CD4 + and CD8 + T cells able to produce IFN-g following activation and an increased susceptibility of T cells to activation-induced apoptosis. CD4 + and CD8 + effector/memory (CD45RC À CD62L À ) pools were significantly smaller in Tg rats compared to non-Tg controls, although the converse was true for the naïve (CD45RC + CD62L + ) T cell pool. Our interpretation is that the HIV transgene causes defects in the development of T cell effector function and generation of specific effector/ memory T cell subsets, and that activation-induced apoptosis may be an essential factor in this process. D 2004 Elsevier Inc. All rights reserved.