Monocyte chemotactic protein and response to pegylated interferon-alpha-2A treatment in patients with chronic hepatitis C [CHC] genotype 4

The prevalence of hepatitis C virus [HCV] infection varies across the world, with the highest number of infections reported in Egypt. Monocyte chemotactic protein-1 [MCP-1] is a potent chemokine, and its hepatic expression is up-regulated during chronic HCV infection. Fifty naive patients with chronic hepatitis C in National Hepatology and Tropical Medicine Research Institute and 20 healthy volunteers as controls were enrolled in a prospective study designed with strict inclusion criteria to nullify the effect of confounding variables and further minimize selection bias. Fifty naïve patients were treated with PEG-IFN-a2b, at a dose of 180lg/kg subcutaneously every week plus ribavirin at a dose of 1000- 1200 mg/day, according to the patient's body weight, for 48 weeks. Quantification of HCV-RNA by real-time PCR and MCP-1 by ELISA were performed for every patient and controls. There was a statistically significant difference between patients and control group as regards the quantity of MCP-1 [P <0.05] [Mann-Whitney test] [P =0.004]. There was a significant difference between responders and nonresponses regarding MCP-1 [P < 0.05], responders showed a higher percentage of cases with initial MCP-1< 306 [P < 0.05]. We conclude the importance of the detection of MCP-1 expression at the start of therapy as a factor for assessing the likelihood of HCV genotype 4 patients to achieving a sustained virological response to treatment with IFN-a2 in combination with ribavirin

K469E polymorphism of the intercellular adhesion molecule-1 gene in Egyptians with coronary heart disease

The initial step in atherosclerosis is the adhesion of leukocytes to activated endothelial cells mediated by intercellular adhesion molecule-1 [ICAM-1]. This study aimed to investigate the association of K469E polymorphism of the ICAM-1 gene and soluble ICAM-1 [sICAM-1] serum level with coronary heart disease [HD] in Egyptian subjects. Using a case-control design, we studied 100 patients with CHD, including 73 patients with acute myocardial infarction [MI] and 27 with unstable angina [UA]. The control groups consisted of 50 healthy subjects with normal left ventricular function. All participants were genotyped for the ICAM-1 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] method. Serum sICAM-1 was measured by enzyme-linked immunoassay [ELISA]. In CHD patients, the frequencies of K genotype [KK and EK] were significantly higher when compared to controls [P<.001] and were associated with an increased risk of disease development [OR=3.8, 95% CI: 1.7 to 8.5; P=.001]. K genotype frequencies in patients with MI showed no significant difference when compared to patients with UA [P=.121]. Serum sICAM-1 levels were comparable between CHD patients and controls [P=.37] and between MI and UA patients [P=.23]. There were no significant differences in sICAM-1 levels than women [P=.004]. ICAM-1 gene polymorphism in codon 469 is associated with a risk for CHD development in Egyptian subjects. Serum sICAM-1 is not influenced by this polymorphism and is not necessarily elevated in CHD

Effect of cisplatin on the cerebellar cortex and spinal cord of adult male albino rat and the possible role of vitamin e: light and electron microscopic study

The nervous system is frequently the site of symptomatic toxicity of antineoplastic agents. Cisplatin is a widely used potent chemotherapeutic agent that is highly neurotoxic. It has been proven that it is able to generate reactive oxygen species and inhibit the activity of antioxidant enzymes. This study was carried out to demonstrate the neurotoxic effects of cisplatin on the structure of adult rat cerebellar cortex and motor neurons of the anterior horn of the spinal cord and to evaluate the role of vitamin E which has been shown to ameliorate nephro, oto and neurotoxicities induced by cisplatin. Thirty adult male albino rats weighing 200-250 gm were divided into three groups: Group [I]: Kept as a control. Group [II]: Animals treated with cisplatin at a dose of 4 mg/kg twice weekly by intraperitoneal injection, for one month. Group [III]: Animals treated with vitamin E at a dose of 100 mg/kg by intramuscular injection in concomitant with cisplatin twice weekly for one month. Animals were sacrificed and their cerebellar cortex and spinal cords were processed for light and electron microscopy. Morphometrical and statistical study was done for the mean number, as well as the mean surface area of Purkinje cells and mean surface area of their nuclei. The histological approach revealed marked degenerative changes in the Purkinje cells and motor neurons of cisplatin treated animals [GII]. Some of these cells appeared irregular with deeply stained cytoplasm and pykontic nuclei. Ultrastructural examination showed Purkinje cells with cellular distortion, damaged organelles and irregular nuclei with electron dense karyoplasms. Degenerative changes in the motor neurons and blood capillaries of the anterior horn of spinal cord of the same group were frequently observed. Morphometric evaluations demonstrated significant decrease in the mean number and the mean surface area of nuclei and cell bodies of Purkinje cells. These structural and morphometrical alterations were much less observed in concomitant use of vitamin E with cisplatin [GIII]. Cerebellar cortex and spinal cord motor neurons are considered target areas of cisplatin neurotoxicity, while vitamin E, when used in combination with cisplatin displays a protective action against neurotoxicity

Association of tumor necrosis factor-alpha polymorphisms with susceptibility and clinical outcomes of rheumatic heart disease

To examine the association of tumor necrosis factor-alpha [TNF-alpha] gene polymorphisms with rheumatic heart disease [RHD] and valve damage, and their influence on TNF-alpha production and disease outcome. We performed this cross-sectional study at Kasr El-Aini Hospital, Cairo University, Cairo, Egypt, from December 2008 to October 2009. Eighty children with chronic RHD and valve affection, and 50 controls were included. Patients with any other diseases or complications were excluded. Blood samples [5 ml] were collected. Genotyping for TNF-alpha polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Serum TNF-alpha was measured by enzyme-linked immunosorbent assay. Serum TNF-alpha was significantly increased in RHD compared with controls [p=0.00003]. The TNF-alpha-238 adenine [AA] [p=0.036] and-308AA [p=0.003] genotypes were more frequent in RHD patients than in controls, and were associated with increased production of TNF-alpha [p=0.00001 for 238AA] and [p=0.001 for 308AA]. Both polymorphisms contributed to increased susceptibility for RHD [-308AA and adenine guanine [AG], odds ratio [OR]=4.72 [95% confidence interval [CI] 2.03-11.05], p=0.0001]; [-238 AA and AG, OR=2.33 [CI: 1.05-5.19], p=0.035]. The presence of-308AA was associated with mitral [p=0.001] and multivalvular [p=0.003] lesions and was more prevalent in moderate [p=0.001], and severe [p<0.001] cases than in controls. The-238AA variant was associated with mitral lesions [p=0.04] and severe cases [p=0.05] as compared with controls. The TNF-alpha-238G/A and-308G/A polymorphisms were associated with susceptibility to RHD and increased production of TNF-alpha. Both polymorphisms were related to valve damage, and a more severe outcome of RHD

Factor V Leiden and prothrombin G20210A gene mutations in women with a history of thrombosis during pregnancy relation to pregnancy outcomes for mother and fetus

To investigate the presence of factor V Leiden [FVL], and prothrombin gene mutations [PRT], protein C and protein S in pregnant women with a previous history of thromboembolism, and evaluate their impact on maternal and fetal outcomes. This study was carried out at Ain Shams University Hospital, Cairo, Egypt between January 2006 to March 2008. The study included 15 pregnant females without a history of thromboembolism [control group], and 25 pregnant females with a history of previous thromboembolism during pregnancy, and puerperium [patient group]. Identification of FVL and PRT mutations by real-time quantitative polymerase chain reaction, and estimation of protein C and S activity by functional clotting assay were performed. Regarding the control group; one patient had FVL mutation [6.6%], and one had decreased protein C activity [6.6%]. As regard the patient group 13/25 [52%] bad normal genotype, and 12/25 [48%] expressed abnormal genotype either FVL or PRT G20210A, or both. Also 3/25 [12%] patients had decreased protein C activity, and 2/25 [8%] had decreased protein S. The intrauterine growth retardation [IUGR] less than the tenth percentile was more in the patients group [48%] compared to the control group [33%], while there was no statistically significant difference between both groups on preeclampsia, placental abruption, abortion, or IUGR less than the fifth percentile. The FVL was not associated with any adverse outcomes, while the PRT mutation was significantly associated with IUGR less than the fifth percentile. The results of this study shows that good monitoring of fetal growth is mandatory for all carriers of the PRT gene mutation

Study of adrenomedullin in children with heart failure

Congestive heart failure [CHF] is the end stage of many diseases of the heart and is a major cause of morbidity and mortality among children. CHF is a common, serious and treatable disease so great efforts should be made to manage it correctly. Adrenomedullin [ADM] is a multifunctional peptide with a wide range of actions related to cardiovascular homeostasis. ADM receptors are highly expressed in the heart. ADM may play some important role in the pathophysiologic make up of CHF. This study was conducted on 50 infants and children with CHF of cardiac etiology divided into 3 groups: Group I, rheumatic heart disease patients [RHD], Group II, congenital heart disease patients [CHD] and Group III, myocardial heart disease patients [MYHD]. Then healthy matched age and gender children were taken as controls. All patients were subjected to: full history taking, clinical physical examination, chest X-ray, ECG, echocardiography and routine laboratory investigations including complete blood count, blood gases, pH, sodium, potassium, serum calcium, AST and ALT. Adrenomedullin was assayed using enzyme immunoassay method. Results revealed that plasma level of ADM was highest in Group I [RHD] patients followed by Group II [CHD] then Group III [MYHD] indicating a role played by underlying etiological cardiac disease in the pathophysioloy of CHF and ADM level. As regards to Group I [RHD] the plasma level of ADM was significantly higher in patients with combined mitral and aortic valve affection than those with isolated mitral valve affection rather than isolated affection of aortic valve. In Group II [CHD] the cyanotic patients had significantly higher plasma ADM level than the acyanotic patients. Concerning Group III [MYHD] ADM level was significantly higher in patients with dilated cardiomyopathy compared to those with myocarditis. The plasma level of ADM was significantly elevated in proportion to the severity of CHF; cases with NYHA [New York Heart Association] Class IV [Servere CHF] had the highest plasma ADM levels followed by NYHA Class III [moderate CHF] cases then NYHA Class II [mild CHF]. ADM is involved in the pathophysiolgic make up of HF. It is not only a biochemical marker for evaluating the severity of HF, but also an independent prognostic indicator of this syndrome. An improved understanding of the role of ADM in HF might lead to the development of promising therapeutic agents for the treatment of patients with this syndrome

Short-term growth and bone turnover in children with persistent asthma during inhaled steroid therapy

Although the change in therapy of bronchial asthma towards inhaled corticosteroids [ICS] is supported by both pathophysiological findings and efficacy data, its safety is often questioned. Many pediatricians are still concerned about the potential adverse effects of long-term treatment with inhaled corticosteroids, particularly on growth. As a result, this class of medication remains underused in children in many countries. The objective of this study is to compare the formation and degradation markers of bone turnover in asthmatic children who are using inhaled fluticasone propionate [FP]. The present study included 45 asthmatic children, of the age group 6-12 years, They were divided into two groups: Group 1: 26 patient with mild to moderate persistent asthma, receiving FP via pressurized metered dose inhalers [pMDI] at dosages equal to or below 200 mcg/day and Group II: 19 patients with moderate to severe persistent asthma, receiving FP at doses above 200 mcg/day. The study also included 14 healthy, nonatopic, non-asthmatic children as controls. All asthmatic children were subjected to: full medical history taking, symptom score calculation, thorough clinical examination, anthropometric measurements, Peak expiratory flow rate [PEFR] monitoring as well as pulmonary function testing before and after treatment, laboratory investigations including CBC with absolute eosinophilic count [AEC] calculation and total serum IgE once, serum calcium, phosphorous, alkaline phosphatase. Carboxy terminal of procollagen I [PICP] and Carboxy terminal telopeptide of type I collagen [ICTP] by radioimmunoassay as markers for bone formation and degradation respectively, before and after treatment with inhaled FP for 6 months. PICP and ICTP were also assessed once in controls. The results of the present work demonstrated a statistically significant decrease in asthma symptom score in both groups, as well as improvement of all asthma symptoms. A statistically significant increase in mean weight and height was observed in both groups that was within the normal percentiles. However, no statistically significant increase in mean body mass index [BMI] was demonstrated in either group. As regards pulmonary functions, a statistically significant increase in mean Forced expiratory volume in the first second [FEV[1]] Forced expiratory volume in the first second/Forced vital capacity [FEV[1]/FVC] and Forced expiratory flow through the midportion of the FVC [FEF[25-75]] was detected after treatment. No statistically significant difference between pre-and post-treatment mean values of serum calcium, phosphorous, and alkaline phosphatase was demonstrated. However, a statistically significant decrease was observed in post-treatment mean values of both PICP and ICTP as compared to pretreatment values with a significant positive correlation between both analytes implying a decrease in rate of bone turnover. No suppression of statural growth should occur in asthmatic children treated with inhaled FP if used at the conventional doses tailored to disease severity. A slowing down of bone turnover rate may occur, which is coupled for both formation and degradation markers. PICP and ICTP are sensitive markers that might be early indicators for potential growth suppression