Clinical significance of viral markers testing by ELISA and Individual Donation Nucleic Acid Testing (ID-NAT) for blood screening in blood bank: Single center study in Egypt.

Prevention of transfusion-transmitted viral infections and insurance of safe blood transfusion are the main goals of all blood banks worldwide. Despite the high sensitivity and specificity of currently used enzyme linked immunosorbent assay (ELISA) for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) testing, viral transmission could still occur during the window period. Introducing viral individual donation nucleic acid testing (ID-NAT) can greatly decrease such risk providing an additional layer in securing blood transfusion. We aimed to assess the clinical significance of viral markers testing by ELISA and ID-NAT for blood screening in the Blood Bank of Suez Canal University Hospital. We studied all donations (2132) collected during a two-months period. Blood donor samples were screened by ELISA and ID-NAT tests for HBV, HCV, and HIV. Serological testing results for HCV by ELISA revealed 2,122 (99.5 %) negative donations compared to 2,131 (99.95 %) negative donations by ID-NAT testing. Of the positive ELISA samples, only one was NAT positive. For HBV ELISA testing, 2,115 (99.2 %) donations were negative, also by ID-NAT testing 2,115 (99.2 %) donations were HBV DNA negative. Out of the negative ELISA samples, two samples were ID-NAT reactive donors which were missed by serology assay being in the window period. HIV ELISA testing revealed negative 2,130 (99.9 %) donations while ID-NAT testing showed 2,131 (99.95 %) negative donations and one positive donation. In conclusion, this is the first study carried out in the Suez Canal and Sinai region, Egypt to assess the importance of ID-NAT implementation. The introduction of ID-NAT in blood banks is an effective method for increasing safety of the blood transfusion.

Mechanisms for Positive Bielschowsky Head Tilt Testing in Horizontal Strabismus.

PURPOSE: To elucidate the induced effects of horizontal strabismus on the Bielschowsky Head Tilt Test (BHTT). DESIGN: Prospective clinical study. METHODS: Prospective analysis of BHTT testing in 85 patients with exotropia and 71 patients with esotropia who were examined in a strabismus clinic. RESULTS: Eighty-four of 85 patients with exotropia (98.82%) showed a positive BHTT with an induced hyperdeviation on the side of the tilt (to both sides in 67% and to one side in 32%). Fifty-seven of 71 patients with esotropia (80.2%) showed a positive BHTT with an induced hypodeviation on the side of the tilt (to both sides in 57.7% and to one side in 22.5%). These induced vertical deviations were greater in patients with larger horizontal deviations and in those with constant rather than intermittent deviations; however, they were not influenced by the presence or absence of associated primary oblique muscle overaction. CONCLUSIONS: Exotropia and esotropia produce hyperdeviations during BHTT testing, with a hyperdeviation on the side of the tilt observed in patients with exotropia, and hypotropia on the side of the tilt observed in patients with esotropia. These diametrical results are not attributable to any preexistent alteration of neurologic output inherent to these two forms of horizontal strabismus or to associated torsion. Rather, they arise directly from the altered anatomical positions of the two eyes, which cause the eyes to approximate their visual axes more closely to the vertical rectus muscles (in exotropia) and the oblique muscles (in esotropia), enabling the vertical actions of specific cyclovertical muscles to predominate in response to altered utricular output generated by the BHTT.

Screening for SARS-CoV-2 IgM and IgG antibodies among healthcare workers: A single-center study in Egypt.

Coronavirus disease 2019 (COVID-19) pandemic has become a global public health disaster, spreading throughout the world. In order to accurately determine the extent of the pandemic, it is important to accurately identify the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). This study intended to determine the prevalence of SARS-CoV-2 infection among HCWs and examine its correlation with the demographic characteristics of the study participants prior to the implementation of the vaccination campaign. In this cross-sectional study included 431 HCWs from Suez Canal University Hospital in Ismailia, Egypt. Their sera were screened for SARS-CoV-2 antibodies using a one-step novel coronavirus (COVID-19) IgM/IgG antibody test from Artron, Canada. Positive cases were then confirmed using nasal swab real-time reverse transcriptase PCR from Viasure, Spain. Of the 431 study participants, 254 (58.9%) were males and 177 (41.1%) females. The majority of participants, 262 (60.8%), were younger than 30 years old, 150 (34.8%) between 30 and 40 years old, and only 19 (4.4%) older than 40 years old. Out of the total samples, 26 (6%) tested positive for SARS-CoV-2 IgM, while 19 (4.4%) tested positive for both IgM and IgG. The majority of the samples, 386 (89.6%), tested negative for both IgG and IgM. There was no association between the prevalence of SARS-CoV-2 and either sex or age of study participants. In conclusion, during the study period, the prevalence of SARS-CoV-2 infection among healthcare workers at Suez Canal University Hospital in Egypt was relatively low. Additionally, there was no significant correlation observed between the prevalence of positive cases and either age or sex.

COVID-19 anti immunoglobulin G antibodies serum levels among health care workers post COVID -19 vaccination: A single center study.

Coronavirus disease 2019 (COVID-19) pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The post vaccination immune response differs between individuals especially health care workers who are the first line of defense to combat this disease. Our aim was to measure levels of anti-IgG antibodies titer post COVID-19 vaccination among health care workers in Suez Canal University Hospital. The study included 141 healthcare workers. Of these, 54 were physicians, 80 nurses, 6 health service workers, and one security guard. We used the Roche Elecsys Anti-SARS-CoV-2 assay for serological detection of IgG. Seropositive was found in 96.5% of the participants, and 43.3% of them had evidence of the prior history of COVID-19 infection. The highest titers of IgG in sera were found in the youngest age groups (20 - <35) years with a mean of 335.1 U/ ml. Participants who received the Sinovac vaccine had the highest mean IgG titer, 354.6U/ml; followed by Sinopharm (mean 352.15 U/ml) then Pfizer and Moderna (311.7U/ml) and AstraZeneca vaccine had the least mean level (267.31U/ml). Fatigue was the most significant short side effect occurring with 34% of the participants. In conclusion, there was a significant rising in serum IgG titer post-vaccine, and better antibody response in those previously infected with COVID-19. The post-COVID-19 vaccine serum IgG titers were affected by age, prior history of COVID-19 infection, and type of vaccine while short side effects post-vaccination may be affected by age and type of the vaccine.

Comparison of human immunodeficiency virus and syphilis results in pooled sera versus individual samples of blood donors attending suez canal university hospital.

Egypt is one of the countries where sexually transmitted diseases like human immunodeficiency virus (HIV) and syphilis are least prevalent. HIV and syphilis count less than one percent of total Egyptian population. An ELISA protocol for pooling serum samples is simple and may provide a way to reduce the cost and time needed for analysis. This study aimed to investigate the applicability and reliability of testing pooled sera of blood donors for HIV and syphilis compared to testing their individual sera and to assess the cost-effectiveness of this procedure. The study included 75 sera from randomly selected blood donors attending Suez Canal University hospital. Sera were screened by two ELISA kits, HIV Ag-Ab ELISA kit, and syphilis total antibody ELISA kit. Screening protocols were done by two sequential steps. At first, samples in pools of five were screened for both HIV and syphilis then, samples in positive pools were individually retested. There was no significant difference between the mean optical density for samples tested HIV and syphilis positive either individually or in pooled sera. There was no difference between the number of individual sera, tested positive for both HIV and syphilis and their pooled sera results (100 % positivity). There was significant decrease of the mean cost in one pool of 5 samples (16.5 L. E) in comparison to 5 individual samples (82.5 L. E) by HIV ELISA. Also, there was significant decrease of the mean cost in one pool of 5 samples (16 L.E) in comparison to 5 individual samples (80 L.E) by syphilis ELISA. In conclusion, the studied pooling protocol appeared reliable and can save up to 80 % of the cost for testing either HIV or syphilis by regular procedures.

Evaluation of blood and biochemical parameters of COVID-19 patients in Suez Canal University Hospital; A retrospective study.

INTRODUCTION: The severe acute respiratory syndrome coronavirus 2 (SARS CoV2-CoV-2) viral outbreak in Wuhan (China) caused thousands of confirmed cases and deaths around the world. Severe viral pneumonia with respiratory failure and death are the ultimate consequence of infection. AIM: This study aimed to evaluate the regularly performed standard laboratory parameters that can assist in COVID-19 case identification and establish an effective approach to help care and management of (COVID-19) patients. METHODOLOGY: COVID-19 (n = 129) patients were hospitalized in the Suez Canal University Hospital and were retrospectively examined. Laboratory parameters were gathered from patients upon admission (n = 129) during the period from the 20th of June to 15th of August 2020. SARS-CoV-2 cases were diagnosed clinically and radiologically by chest Computed Tomography (CT) and confirmed by RT-PCR. RESULTS: The results showed that COVID-19 survivors exhibited lower hemoglobin (Hb) and hematocrit (HCT), while showed higher Red Cell Distribution Width (RDW), neutrophil lymphocyte ratio (NLR), and lymphocytes. Logistic regression analysis showed that age greater than 60 years old, neutrophilia and high NLR were associated with more deaths. CONCLUSION: Monitoring of lymphopenia, neutrophilia and NLR may help categorizing patients who may need Intensive care.

Assessment of angiotensin converting enzyme gene polymorphism in patients with psoriasis.

Psoriatic patients had diversity of clinical presentations and complications. Psoriasis can have significant interference with the patient's quality of life, recovery, and outcome. Some evidences suggest that the angiotensin converting enzyme (ACE) is present in the skin of psoriatic patients. This study intended to assess the patterns of ACE insertion/deletion (ACE ID) polymorphism and the levels of serum ACE among psoriatic patients in comparison to normal controls. The study included two groups: 20 patients with psoriasis and 20 apparently healthy adults with negative family history of psoriasis as a control group. Psoriasis area and severity index (PASI) was used to measure of severity of psoriasis. In both groups, ACE ID gene polymorphism was assessed by quantitative real-time polymerase reaction and serum ACE levels was evaluated using an enzyme-linked immunosorbent assay. ACE ID genotype was significantly higher among the psoriatic group in comparison to the control group (40.0% versus 15.0%, respectively, p=0.016). D allele was significantly higher among the psoriatic group than the control group (25.0% versus 7.5%, respectively, p=0.034). ACE ID genotype carried significantly higher risk in psoriatic group versus control group (OR=3.8). The D allele carried higher risk in psoriatic group versus control group (OR=4.1). ACE serum levels were significantly higher among the psoriatic group compared to the control group (87.4±7.03 versus 2.3±0.7, respectively; p < 0.001). We concluded that ACE ID gene polymorphism may be considered as a risk factor for developing psoriasis.

Convalescent plasma in COVID-19: renewed focus on the timing and effectiveness of an old therapy.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic that has strained health care systems worldwide and resulted in high mortality. The current COVID-19 treatment is based on supportive and symptomatic care. Therefore, convalescent plasma (CP), which provides passive immunization against many infectious diseases, has been studied for COVID-19 management. To date, a large number of randomized and non-randomized clinical trials as well as many systematic reviews have revealed conflicting results. This article summarizes the basic principles of passive immunization, particularly addressing CP in COVID-19. It also evaluates the effectiveness of CP as a therapy in patients with COVID-19, clinical trial reports and systematic reviews, regulatory considerations and different protocols that are authorized in different countries to use it safely and effectively. An advanced search was carried out in major databases (PubMed, Cochrane Library, and MEDLINE) and Google Scholar using the following key words: SARS-CoV-2, COVID-19, convalescent plasma, and the applied query was "convalescent plasma" AND "COVID-19 OR SARS-CoV-2". The results were filtered and duplicate data were removed. Collective evidence indicates that two cardinal players determine the effectiveness of CP use, time of infusion, and quality of CP. Early administration of CP with high neutralizing anti-spike IgG titer is hypothesized to be effective in improving clinical outcome, prevent progression, decrease the length of hospital stay, and reduce mortality. However, more reliable, high quality, well-controlled, double-blinded, randomized, international and multicenter collaborative trials are still needed.

Assessment of human parvovirus B19 infection in Egyptian hemodialysis patients.

INTRODUCTION: Parvovirus B19V has been shown to be associated with end-stage renal disease (ESRD) with increased risk of post-infection anemia, especially in hemodialysis (HD) patients. This effect may be due to immunosuppression, insufficient erythropoietin, or short lifespan of red blood cells. Therefore, parvovirus infection should be investigated in this group of patients suffering from anemia or pancytopenia. We assessed the frequency of parvovirus B19 in HD patients attending Suez Canal University Hospital and analyzed the correlation of this infection with hematological parameters in those patients compared with normal individuals. METHODS: We recruited 80 ESRD patients on hemodialysis and 70 healthy controls. History-taking, full examination, and complete blood count (CBC) were performed for all study subjects. Parvovirus B19 detection was performed through polymerase chain reaction (PCR), which included the QIAamp DNA Mini Kit for extracting DNA, which was amplified using TaqMan Universal Master Mix and detected using TaqMan MGB probes by real-time PCR using Rotor Gene Analyzer (6000). FINDINGS: HD patients had a significantly higher frequency of B19V infection than the control group (p = .02). We also found that parvovirus B19-infected HD patients had significantly lower CBC values than uninfected patients. CONCLUSION: The frequency of parvovirus B19 was significantly higher in HD patients and was associated with lower hematological parameters than in uninfected patients, suggesting a significant role of this virus in the pathogenesis of anemia and/or pancytopenia in ESRD.

Clinical significance of golgi protein-73 as a diagnostic marker for Egyptian patients with colorectal cancer: Preliminary study.

BACKGROUND: Colorectal cancer is one of the most common cancers and the leading cause of cancer-related death worldwide. Early diagnostic methods help in therapeutic success and higher survival rate. Golgi protein 73 (gp73) could help in diagnosis of colorectal cancer at an earlier stage. AIM: A case-control study aimed to assess serum level of golgi protein 73 (gp73) as a liquid biopsy marker in Egyptian colorectal cancer patients. METHODS AND RESULTS: In the current study, ninty (90) patients were included and classified into three groups; thirty (30) patients with Colorectal cancer (CRC) as study group; 30 patients (20 patients with irritable bowel disease and 10 patients with rectal polyps) as pathological control and 30 healthy adult individuals as normal control. The diagnosis was based on the history, clinical, laboratory, endoscopic, and histological data. Golgiprotein 73 (GP73) was measured by ELISA immunoassay Kit. Serum GP73 level was higher in CRC patients than pathological control group and normal control group with high sensitivity and specificity p < .005. CONCLUSION: GP73 alone or combined with Carcinoembryonic antigen (CEA) may be good diagnositic marker in CRC. However large studies are warranted on different stages of the disease to assess its diagnostic and prognositic value.

Screening for Human Parvovirus B19 Infection in Egyptian Family Replacement Blood Donors.

Up till now, screening for human parvovirus B19 is not routine in national Egyptian blood bank strategy. Blood samples were collected from 500 healthy blood donors within the age range from 18 to 45 years old attending the blood bank of Suez Canal University Hospital, Ismailia, Egypt. Sera were separated and stored at - 20 °C. Serum samples were screened for anti-human parvovirus B19 IgM and IgG antibodies and B19 genome using ELISA and real-time PCR respectively. Frequency of B19 IgM and B19 IgG antibodies was 6.20%, and 80.20% respectively, and the prevalence of B19 genome was 3.00%. There is a high frequency of human parvovirus B19 among Egyptian blood donors; therefore, serological screening for B19 is warranted.

Serum level of interleukin-22 in patients with cutaneous warts: A case-control study.

BACKGROUND: Warts are viral cutaneous infections caused by human papilloma virus (HPV), presented by verrucous growth over the skin surface. The immune response is considered to play a crucial role in HPV clearance. It depends on intact cellular immunity including natural killer (NK) cell and cytotoxic T cells. It has been clarified that T-helper (Th) 1 cytokines (interleukin (IL)-2, interferon-γ, and tumor necrosis factor-a) and IL-17 are involved in HPV clearance. IL-22 is one of IL-10 family of cytokines produced by NK cells, Th1, Th17, and Th22 cells. In the skin, IL-22 reduces keratinocyte cornification and enhances keratinocyte production of antimicrobial peptides. IL-22 overexpression has been demonstrated in various viral infections and skin inflammatory disorders. AIM: The aim of this study was to assess serum levels of IL-22 in patients with warts and its association with their different clinical characteristics. METHODS: The study included 20 patients with warts and 20 control subjects. Serum concentration of IL-22 was measured by enzyme-linked immune sorbent assay. RESULTS: Serum levels of IL-22 were significantly higher in patients with warts than in control subjects (P < .001). The levels were significantly higher in patients with recurrent warts after prior treatment than in patients with first-time warts (P = .007). Moreover, a significant positive correlation was detected between serum levels of IL-22 and the number of warts (P = .017). CONCLUSION: Serum level of IL-22 was elevated in patients with warts. Thus, IL-22 may have a crucial role in the antiviral immune response against this infection.

Evaluation of Golgi Protein 73 (GP73) as a Potential Biomarkers for Hepatocellular Carcinoma.

BACKGROUND: Early detection of hepatocellular carcinoma is very important in the treatment which is feasible. Alpha-fetoprotein plus ultrasound in surveillance programs is controversial. GP73 is a protein. Golgi increase significantly in the sera of patients with hepatitis B virus and HCV-related HCC, providing a marker for its early detection. The aim is to detect serum Golgi protein 73 (GP73) in patients with cirrhosis and with hepatocellular carci-noma (HCC), and to determine its sensitivity and specificity as a screening tool for the detection of HCC. METHODS: A case control study was conducted in four groups of 32 participants each: 1- healthy controls; 2 - chronic liver disease; 3 - decompensated liver disease; 4 - HCC group. The HCC group included 25 males and 7 females with a mean age of 58 ± 7 years, fulfilling diagnostic criteria for HCC. GP73 was estimated in the serum samples taken from the HCC group and control groups. RESULTS: GP73 was elevated in patients with HCC and liver cirrhosis. Serum level was very high in HCC patients (p < 0.01) when compared with the other studied groups. GP73 had a sensitivity of 96.9% and specificity of 96.9% at a cutoff value of 17.5 ng/mL when compared with α-fetoprotein (AFP) that showed a sensitivity of 75% and specificity of 92% at a cutoff value of 9.4 ng/mL. CONCLUSIONS: GP73 can be used as a screening tool for the detection of HCC with higher diagnostic performance than AFP.

Human equilibrative nucleoside transporter-1 and deoxycytidine kinase can predict gemcitabine effectiveness in Egyptian patients with Hepatocellular carcinoma.

BACKGROUND: Several biomarkers of gemcitabine effectiveness have been studied in cancers, but less so in hepatocellular carcinoma (HCC), which is identified as the fifth most common cancer worldwide. Investigation of human equilibrative nucleoside transporter-1 (HENT-1) and deoxycytidine kinase (DCK), genes involved in gemcitabine uptake and metabolism, can be beneficial in the selection of potential cancer patients who could be responding to the treatment. AIM: To study HENT-1 and DCK gene expression in HCC patients with different protocols of treatment. METHODS: Using real-time PCR, we analyzed expression levels of HENT-1 and DCK genes from peripheral blood samples of 109 patients (20 controls & 89 HCC patients) between March 2015 and March 2017. All the 89 HCC patients received the antioxidants selenium (Se) and vitamin E (Vit.E) either alone (45 patients) or in combination with gemcitabine (24 patients) or radiofrequency ablation (RFA) (20 patients). RESULTS: There was a significant increase in HENT-1 expression levels in HCC patients treated with Se and Vit.E alone as compared to controls (P Ë‚ .0001), while there was no significant difference between HCC patients treated with gemcitabine or RFA as compared to controls. In contrast, expression of DCK was significantly increased in all groups of HCC patients as compared to controls (P Ë‚ .0001). CONCLUSIONS: HENT-1 and DCK mRNA expressions are important markers of HCC and for GEM effect and GEM sensitivity in patients with HCC. This could be beneficial in the selection of HCC patients sensitive to gemcitabine to avoid subjecting resistant patients to unnecessary chemotherapy.

Inducible Nitric Oxide Synthase Polymorphism In Hepatitis C Patients Treated With Interferon Based-Treatment As A Predictor of Early Virological Response.

HCV infection represented a foremost communal health trouble and Egypt has the largest epidemic of HCV in the world with prevalence of 14.7% for HCV antibody and 9.8% HCV-RNA. Nitric oxide (NO) is a signaling molecule participated in inhibiting of microbial diseases. Pro-inflammatory stimuli can trigger resting cells to produce inducible nitric oxide synthase ((iNOS) also referred to as (NOS2), which is very crucial for host response to contagious agents. NOS2A gene haplotypes has been associated with a number of diseases. This study aimed to assess the relation between NOS2A gene haplotypes and HCV treatment response in pegylated interferon alpha /ribavirin (PEG-IFN /RBV) in chronic HCV patients (CHC) in an attempt to find a predictor biomarker to detect poor responders to therapy. DNA was extracted from blood samples and subjected to detection of NOS2A gene haplotypes using real time PCR. Non-responder patients showed statistically significant higher percentages of unclassified haplotypes than responder patients (85.7% versus 58.6%, respectively) (P < 0.0001) and of haplotypes 4 and 5 (GTT and ATC) than non-responder patients (25.7% and 14.3% versus 0% and 0%, respectively) (P < 0.0001). The NOS2A gene haplotypes were not associated with response to PEG-IFN /RBV at 12th week Early Virological Response (EVR). In conclusion, NOS2A gene haplotypes are not considered predictors of response to PEG-IFN /RBV treatment. Further studies are required to elucidate predictor markers.

Interleukin-22 and Chemokine Interferon γ -Inducible-10 (IP-10) Levels in Chronic Hepatitis C Patients and Treatment Response to Pegylated Interferon and Ribavirin Therapy.

IL-22 plays a vital role in improving hepatic damage by targeting hepatocytes that express high levels of IL-22 receptor1. IP-10 is a chemokine that recruit mononuclear cells to liver parenchyma and improves the host immune response against hepatitis C virus. The study targeted 27 patients with chronic HCV who received pegylated Interferon and Ribavirin. IL-22 and IP-10 serum levels were measured by Elisa. The level of the serum IL-22 is higher in HCV patients groups receiving the antiviral treatment compared to control group and its levels significantly increased with response to treatment. The level of the serum IP-10 is higher in HCV patients groups compared to control group and its level significantly decreased with effective antiviral treatment. In conclusion, IL-22 and IP-10 levels could be used with a high sensitivity and specificity during antiviral treatment of HCV infected patients as predictive markers for treatment response.

Multiple intra-familial transmission patterns of hepatitis B virus genotype D in north-eastern Egypt.

The transmission rate of intra-familial hepatitis B virus (HBV) and mode of transmission were investigated in north eastern Egypt. HBV infection was investigated serologically and confirmed by molecular evolutionary analysis in family members (N = 230) of 55 chronic hepatitis B carriers (index cases). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prevalence was 12.2% and 23% among family members, respectively. HBsAg carriers were prevalent in the age groups; <10 (16.2%) and 21-30 years (23.3%). The prevalence of HBsAg was significantly higher in the family members of females (19.2%) than males (8.6%) index cases (P = 0.031). HBsAg and anti-HBc seropositive rates were higher significantly in the offspring of females (23%, 29.8%) than those of the males index cases (4.3%, 9.8%) (P = 0.001, 0.003), as well as higher in the offspring of an infected mother (26.5, 31.8%) than those of an infected father (4.7%, 10.5%) (P = 0.0006, 0.009). No significant difference was found in HBsAg seropositive rates between vaccinated (10.6%) and unvaccinated family members (14.8%). Phylogenetic analysis of the preS2 and S regions of HBV genome showed that the HBV isolates were of subgenotype D1 in nine index cases and 14 family members. HBV familial transmission was confirmed in five of six families with three transmission patterns; maternal, paternal, and sexual. It is concluded that multiple intra-familial transmission routes of HBV genotype D were determined; including maternal, paternal and horizontal. Universal HBV vaccination should be modified by including the first dose at birth with (HBIG) administration to the newborn of mothers infected with HBV.

Circulating endothelial cells as a marker of vascular dysfunction in patients with systemic lupus erythematosus by real-time polymerase chain reaction.

CONTEXT: Systemic lupus erythematosus (SLE) is associated with an increased risk of atherosclerosis; endothelial dysfunction represents the first step in its pathogenesis. OBJECTIVE: To assess endothelial dysfunction in SLE by circulating endothelial cells (CECs) and to characterize SLE-specific factors that contribute to its appearance. DESIGN: Case-control study was conducted on 60 subjects, divided into 2 groups: group A (30 patients with SLE) and group B (30 healthy sex- and age-matched controls). Total cholesterol, triglycerides, antinuclear antibodies, anti-double-stranded DNA antibodies, and C3 were determined in all patients. Systemic lupus erythematosus activity was assessed using the SLE Disease Activity Index. Endothelial function was assessed by means of flow-mediated dilation of the brachial artery using B-mode ultrasonography and relative quantification of CD 146 mRNA by real-time polymerase chain reaction. RESULTS: The group of SLE patients was formed of 20 females and 10 males, with a mean age of 31.16 ± 9.69 years. The values of SLE-specific tests and SLE Disease Activity Index were represented by anti-double-stranded DNA antibodies 160 ± 40.5, C3 68.91 ± 11.91 mg/dL, total cholesterol 188.66 ± 49.63 mg/dL, triglycerides 143.41 ± 46.26 mg/dL, and SLE Disease Activity Index 12.66 ± 3.70. Values for flow-mediated dilation were 8.85% ± 2.02% (group A) and 20.33% ± 6.19% (group B), P < .001, and CECs were 300 ± 40.5 µL⁻¹ blood (group A) and 10 ± 2.5 µL⁻¹ blood (group B). The statistical analysis showed a strong inverse correlation between CECs and SLE Disease Activity Index, a strong correlation between CECs and C3, a strong correlation between CECs and anti-double-stranded DNA antibodies, and a moderate inverse correlation between CECs and total cholesterol. CONCLUSION: Endothelial dysfunction is present in SLE patients even in the absence of traditional cardiovascular risk factors due to disease activity.

The prognostic value of p53 mutation in pediatric marrow hypoplasia.

BACKGROUND: The tumor suppressor gene p53 is involved in the control of cell proliferation, particularly in stressed cells. p 53 gene mutations are the most frequent genetic event found in human cancers. Fanconi Anemia (FA) is the most common representative of inherited bone marrow failure syndromes (IBMFS) with a leukemic propensity. P 53 DNA alteration has not been studied before in Egyptian children with FA. PATIENTS AND METHODS: we investigated p53 mutation in the bone marrow and peripheral blood of forty children, FA (n = 10), acquired aplastic anemia (AAA) (n = 10), and immune thrombocytopenia (ITP) as a control (n = 20), using real-time PCR by TaqMan probe assay. RESULTS: Mutation of p53 gene was demonstrated in the BM of 90% (9/10) of children with FA, compared to 10% (1/10) in AAA (p < 0.001), while, no p53 DNA mutation was seen in the control group. A positive correlation between DNA breakage and presence of p53 mutation was seen in FA (p < 0.02, r0.81). CONCLUSION: mutation of p53 gene in hypoplastic marrow especially FA may represent an early indicator of significant DNA genetic alteration with cancer propensity.

Novel role of curcumin combined with bone marrow transplantation in reversing experimental diabetes: Effects on pancreatic islet regeneration, oxidative stress, and inflammatory cytokines.

Therapeutic utility of bone marrow transplantation in diabetes is an attractive approach. However, the oxidative stress generated by hyperglycemia may hinder ß-cell regeneration. The present study was undertaken to investigate the therapeutic potential of curcumin, a dietary spice with antioxidant activity, bone marrow transplantation, and their combined effects in the reversal of experimental diabetes. Diabetes was induced in mice by multiple low doses of streptozotocin. After the onset of diabetes, mice were treated with curcumin (10 mM; 100 µl/mouse, i.p., for 28 days) or received a single bone marrow transplantation (10(6) un-fractionated bone marrow cells), or both. Parameters of diabetes, integrity of pancreatic islets, pancreatic oxidative stress markers, and serum pro-inflammatory cytokines, were evaluated. Treatment with either curcumin or bone marrow transplantation significantly reversed streptozotocin-induced hyperglycemia/glucose intolerance, hypoinsulinemia, and damage of pancreatic islets. Interestingly, combination of curcumin and bone marrow transplantation elicited the most profound alleviation of such streptozotocin-evoked anomalies; including islet regeneration/insulin secretion. On the other hand, curcumin, either alone or combined with bone marrow transplantation, blunted the pancreatic lipid-peroxidation, up-regulated activities of the antioxidant enzymes, and suppressed serum levels of TNF-α and IL-1ß. Curcumin and single bone marrow transplantation proved their therapeutic potential in reversing diabetes when used in combination. Curcumin, via its antioxidant and anti-inflammatory effects, evidently enhanced the ability of bone marrow transplantation to regenerate functional pancreatic islets. Hence, the use of natural antioxidants combined with other therapeutic regimens to induce pancreatic regeneration is a promising strategy in the management of diabetes.