Mohamed Shaarawy

Endocrine profile and semen characteristics in male smokers

Research that involves study of both the endocrine profile and the sperm of groups of smokers and nonsmokers who are not selected for possible fertility problems is needed in order to determine more clearly whether smoking has an effect on them. This criterion was used in the choice of the clinical material in the present investigation. 2 groups of healthy volunteer men were selected. The 1st group consisted of 25 smokers who were smoking more than 20 cigarettes daily. The 2nd group consisted of 20 nonsmokers. The ages of both groups ranged from 25-35 years. In proof of their fertility, each man had fathered at least 2 children. 10 milliliters of blood was obtained from each subject. Serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) were determined by specific radioimmunoassay (RIA), and the polyethylene glycol method for precipitating the bound fraction was used. Serum T was determined by double-antibody RIA and 125I-labeled T. Serum F was determined fluorometrically. 2 24 hour urine collections from each case were assayed in duplicate for urinary pregnanediol, pregnanitriol, 17-oxogenic steroids, and 17-oxosteroids. Full seminography was conducted for each man. The levels of serum FSH and F in male smokers were significantly higher than those of nonsmokers. Serum T was significantly lower in the former group. Serum LH did not vary significantly in either group. The levels of urinary 17-oxogenic steroids and pregnanetriol in male smokers were significantly elevated. Those of urinary 17-oxosteroids were significantly decreased when compared with the corresponding levels of nonsmokers. Urinary pregnandiol did not differ significantly in either group. Sperm initial motility was significantly decreased in smokers, and the percentage of abnormal forms of spermatozoa was significantly elevated. There was no significant difference in sperm count between smokers and nonsmokers.

Maternal serum and amniotic fluid cytokines in patients with preterm premature rupture of membranes with and without intrauterine infection

Objectives: To evaluate the role of interleukins (IL‐1, IL‐6), tumor necrosis factor α (TNFα) and for the first time interferon gamma (IFNγ) and epidermal growth factor (EGF) in the pathogenesis of premature rupture of membranes (PROM) with and without confirmed intrauterine infection. Methods: Amniotic fluid was retrieved by transabdominal amniocentesis from 30 patients with PROM and 20 normal pregnant women with intact membranes of matched gestational age. Microbial state of amniotic cavity included culture for aerobic and anaerobic bacteria, mycoplasmas and ureaplasma whether or not clinical signs of chorioamnionitis were present. Maternal serum and amniotic fluid IL‐1, IL‐6, TNFα and IFNγ concentrations were determined by the corresponding immunoradiometric assay, whereas EGF concentration was determined by a specific radioimmunoassay. Results: Nearly all cases of PROM with infection revealed elevated amniotic fluid cytokines (IL‐1β, IL‐6, TNFα, IFNγ, EGF) whereas half of them revealed elevated serum cytokines. In cases of PROM without confirmed infection, there were no significant changes of maternal serum cytokines, whereas two‐thirds of them revealed elevated amniotic fluid cytokines. Conclusions: The rise of cytokines in amniotic fluid of cases of PROM with infection may represent: (a) enhanced macrophage activity for immunosurveillance of the fetus; (b) a preparatory step for the initiation of labor; and (c) a valuable tests for diagnosing chorioamnioitis. The mechanism responsible for PROM in the presence or absence of infection is likely to be of different nature.

Enhanced expression of cytokines may play a fundamental role in the mechanisms of immunologically mediated recurrent spontaneous abortion

Objectives. To determine circulatory levels of 1L‐1 β, TNFα, IFN‐γ and Neopterin in immunologically mediated recurrent abortion. Design. Blood samples were withdrawn from both groups of first trimester recurrent abortion and controls for the determination of serum IL‐lβ, TNFα, IFN‐γ by the corresponding IRMA and serum neopterin by a double antibody RIA. Setting. Department of Obstetrics & Gynecology, Cairo University Hospitals. Patients. Thirty pregnant women in their first trimester who presented with inevitable abortion with history of at least 3 prior spontaneous consecutive abortions, in addition to twenty‐three pregnant women in their first trimester presented with their first miscarriage due to chromosomal anomalies (controls). Every attempt was made to eliminate the possible known contributing factors of recurrent abortion except for the presence of cervical mucus sperm antibodies which were present in 24 out of 30 cases. Interventions. None. Results. Serum ILiβ, TNFα and IFN‐γ levels of the abortion group were significantly elevated when compared to the corresponding levels of controls. The incidence of abnormal high values of these cytokines varied between 40 to 70%. There was no significant difference of serum neopterin between abortion and control groups. The increase of IFNγ, the most active principle inducing neopterin release, was below the concentration needed for neopterin stimulation. Conclusions. In view of the proven findings that cytokines do have detrimental effects on implantation, trophoblast proliferation, embryo development and fetal survival, our results suggest a potential mechanism of immunologic recurrent abortion which involves the secretion of IL‐iβ. TNFα, IFNγ and other cytokines by activated endometrial lymphocytes and macrophages in response to either trophoblast or sperm antigens and these cytokines could partially defuse or penetrate into the systemic circulation.

Thrombomodulin, plasminogen activator inhibitor type 1 (PAI-1) and fibronectin as biomarkers of endothelial damage in preeclampsia and eclampsia

Objective: Preeclampsia has been recently suggested to be an endothelial cell disorder. This study was initiated to determine the levels of various biomarkers of endothelial damage in preeclampsia and eclampsia. Methods: Blood samples were withdrawn from 70 pregnant women in their third trimester grouped as 25 mild preeclampsia, 15 severe preeclampsia, 10 eclampsia and 20 normotensive healthy women (controls) for the determination of thrombomodulin by ELISA, PAI‐1 by urokinase method and fibronectin by radial immunodiffusion. Results were statistically analyzed by Students t‐test. Results: Circulation levels of PAI‐1, thrombomodulin and fibronectin were increased with increasing severity of the disease. Thrombomodulin was the only parameter which did not change significantly in mild preeclampsia. The average percent increments in preeclampsia and eclampsia were 63%, 102% and 132%, respectively. Conclusions: These results demonstrate that fibronectin may be a more valuable biomarker than thrombomodulin and PAI‐1 for the assessment of endothelial damage in preeclampsia and eclampsia.

Maternal serum transforming growth factor beta-2 in preeclampsia and eclampsia, a potential biomarker for the assessment of disease severity and fetal outcome.

Objective: The emerging role of transforming growth factor β in hypertension, kidney disease, and trophoblast differentiation promoted our interest in evaluating the clinical value of assaying maternal serum TGF-β2 levels in pregnancies complicated by preeclampsia and eclampsia. We wished to determine these levels in relation to the severity of the disease, the degree of renal involvement, and fetal outcome. Methods: A prospective study was carried out in 50 pregnant patients with preeclampsia (PE) and eclampsia and these women were compared to 20 pregnant normotensive controls. Preeclamptic patients were subdivided into 20 cases of mild PE, 20 cases of severe PE, and 10 cases of eclampsia. Maternal serum levels of TGF-β2 were determined in all cases by enzyme immunoassay. Maternal serum creatinine and uric acid were measured, together with an assessment of fetal well being, using the Biophysical Profile Score. Results: Maternal serum TGF-β2 levels were significantly increased in cases of severe preeclampsia and eclamsia compared to controls. This increase was positively correlated with elevated levels of serum creatinine and uric acid, as well as poor biophysical profile scores (BPS), and low birth weight (LBW). Conclusion: Measurement of maternal serum TGF-β2 levels in preeclampsia may be a useful biomarker for the assessment of the severity of disease and fetal outcome in PE.

Biomarkers of Intrinsic Angiogenic and Anti-angiogenic Activity in Patients with Endometrial Hyperplasia and Endometrial Cancer

Serum vascular endothelial growth factor (VEGF) and endostatin were determined in postmenopausal women, including 72 with endometrial cancer, 27 with endometrial hyperplasia and 30 healthy controls. Serum VEGF levels in endometrial hyperplasia (142+/-18 ng/ml, mean +/- SE) and endometrial cancer stages I (291+/-22), II (623+/-68) and stage III-IV (1527+/-119) were significantly higher than the mean for controls (12+/-1.6). Serum endostatin levels in endometrial hyperplasia (149+/-19 ng/ml), endometrial cancer stages I (320+/-41), II (644+/-86) and stage III-IV (1253+/-114) were also significantly higher than the mean for controls (13+/-2.4). Elevated values of VEGF above the non-malignant level were encountered in 7% (stage I), 37% (stage II) and 100% (stage III-IV) of endometrial cancers. The corresponding figures for endostatin were 37%, 59 and 100%, respectively. These results demonstrate that the circulating levels of both markers correlated with tumor stage and apparently tumor burden. Serum VEGF and endostatin levels decreased significantly after treatment, followed by marked elevations at clinical relapse. The VEGF endostatin ratio was higher in the advanced stages ( > 1.0) than in the early stages of endometrial carcinoma (< 1.0). indicating that the balance of angiogenic stimulators and inhibitors may regulate metastasis and access tumor progression.

Radical-scavenging antioxidants in pre-eclampsia and eclampsia

Objective: Increased free‐radical activity may be implicated in the pathogenesis of pre‐eclampsia and knowledge of the response of the antioxidant systems is limited in pre‐eclampsia and lacking in eclampsia. Accordingly, this study was initiated to assess total antioxidant status in pre‐eclampsia and eclampsia. Method: Thirty‐five patients with pre‐eclampsia (20 mild and 15 severe), 10 patients with eclampsia and 20 normotensive women (controls) with singleton gestations in the third trimester participated in this study. Their freshly drawn blood was assayed for total antioxidant status colorimetrically using incubation mixture of ABTS, a peroxidase (metmyoglobin) and H2O2. In addition, serum fibronectin was determined by radial immunodiffusion. Result: Serum total antioxidant status levels in mild and severe pre‐eclampsia and eclampsia were significantly lower than that of healthy pregnant women (controls). The mean percent decreases amounted to 22%, 40% and 59%, respectively, indicating the propensity of these patients to oxidative stress. Conclusion: These results demonstrate that radical‐scavenging antioxidants are consumed by the increased free‐radical activity in pre‐eclampsia. The mechanisms by which free radicals are involved in endothelial dysfunction and renal injury are explained as evidenced by significant negative correlation of fibronectin and positive correlation of creatinine clearance with total antioxidants.

Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis

OBJECTIVE To determine whether leptin is involved in bone remodeling in patients with postmenopausal osteoporosis. DESIGN Cross-sectional study. SETTING Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University. PATIENT(S) Ninety postmenopausal osteoporotic women (37 obese and 53 nonobese) and 30 healthy premenopausal women from the same clinic served as controls. Lumbar spine bone mineral density (LS-BMD) of osteoporotic patients was more than 2.5 SD below the normal mean of healthy premenopausal women. MAIN OUTCOME MEASURE(S) Serum levels of leptin, osteocalcin (OC), bone alkaline phosphatase (B-ALP), urinary deoxypyridinoline (DPyr), and N-telopeptide of type 1 collagen (NTX) as well as LS-BMD using dual energy X-ray absorptiometry (DEXA). RESULT(S) The serum leptin level in obese postmenopausal osteoporotic patients was significantly increased compared with nonobese osteoporotic patients. There were no significant differences of bone formation markers (B-ALP, OC), bone resorption markers (DPyr, NTX), or LS-BMD between the obese and nonobese groups. There were no significant correlations between serum leptin and any biomarkers of bone turnover and BMD. CONCLUSION(S) In postmenopausal osteoporotic patients with increased bone turnover, serum leptin concentration is not correlated with BMD or with the biomarkers of bone formation or bone resorption.

Leptin and Gestational Weight Gain: Relation of Maternal and Cord Blood Leptin to Birth Weight

Objectives: To determine maternal serum leptin concentrations throughout normal pregnancy, as well as cord blood leptin concentration, and to correlate serum and cord blood leptin levels with gestational weight gain and birth weight, respectively. Methods: This study comprised 52 normal pregnant women, including 11 in the first, 19 in the second, and 22 in the third trimester, in addition to 30 healthy, fertile nonpregnant women of comparable age and with normal body mass index (BMI). Maternal blood and fetal cord blood samples were withdrawn from the normal, healthy pregnant women and the nonpregnant controls for hte determination of serum leptin by a specific radioimmunoassay. Results: Maternal serum leptin concentrations in the first trimester did not differ significantly from those of healthy nonpregnant control subjects, whereas leptin concentrations in the second and third trimesters were elevated significantly. There were significant positive correlations between maternal serum leptin concentration and gastational age, gestational weight, and BMI. Cord blood leptin concentration correlated positively with birgh weight and third trimester maternal serum leptin. Conclusion: Elevated serum leptin is associated with maternal adiposity and risk of developing large for gastational age infants.

Plasma endothelin-1 and mean arterial pressure in the prediction of pre-eclampsia

Objective: To determine whether increased first trimester plasma endothelin‐1 and/or increased midtrimester mean arterial blood pressure detected in pregnant women who are free of symptoms can predict the subsequent development of pre‐eclampsia. Method: Eighty pregnant women were successfully followed from 10 weeks gestation until delivery. Pre‐eclampsia and eclampsia developed in 29 and 2 women, respectively, whereas 49 women remained normotensive. Plasma endothelin‐1 was determined in the first trimester (10–12 weeks gestation) by a competitive radioimmunoassay. Result: First trimester plasma endothelin‐1 levels in pregnant women who subsequently developed mild, severe pre‐eclampsia and eclampsia were significantly higher than those of pregnant women who remained normotensive. The release of endothelin‐1 increases with the severity of the disease, age, body mass index and mean arterial blood pressure. The predictive values of plasma endothelin‐1 for pre‐eclampsia were: sensitivity 96.8%, specificity 51%, positive predictive value 55.5% and negative predictive value 91%, whereas those of MAP were 48.4, 45, 35.7 and 58%, respectively. Conclusion: Determination of first trimester plasma endothelin level may be a valuable marker to identify 55.5% of individuals at high risk of developing pre‐eclampsia, if combined with midtrimester MAP, the positive predictive value increases to 68.2%.