Elevated serum Bcl-2 in children with temporal lobe epilepsy

Intractable temporal lobe epilepsy (TLE) is associated with alterations in expression of apoptosis-associated signaling molecules in the temporal lobe. Bcl-2 is an anti-apoptotic molecule which has previously been reported to be raised in patient's brain and serum. In the present study we examined serum Bcl-2 protein levels as a surrogate marker of apoptosis-associated signaling in children with non lesional TLE. Serum Bcl-2 levels were found to be higher in patients with TLE than controls. The serum level correlated to seizure variables including, duration of disease, frequency of seizures, and disease severity. The impact of epilepsy on cognition was assessed using total score intelligence quotient (IQ). IQ was found to be lower than controls and negatively correlated to serum Bcl-2. These findings support serum Bcl-2 levels as a marker of seizure burden and cognition in children with epilepsy.     

Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia

Preeclampsia is a pregnancy‐related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia, and reduced uterine perfusion pressure (RUPP). RUPP causes imbalance between the anti‐angiogenic factors soluble fms‐like tyrosine kinase‐1 and soluble endoglin and the pro‐angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia‐inducible factor, reactive oxygen species, and angiotensin AT₁ receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, smooth muscle and various components of the extracellular matrix. Generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels causes decreases in endothelium‐derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin‐1 and thromboxane A2. Enhanced mechanisms of vascular smooth muscle contraction, such as intracellular Ca²⁺, protein kinase C, and Rho‐kinase cause further increases in vasoconstriction. Changes in matrix metalloproteinases and extracellular matrix cause inadequate vascular remodeling and increased arterial stiffening, leading to further increases in vascular resistance and hypertension. Therapeutic options are currently limited, but understanding the molecular determinants of microvascular dysfunction could help in the design of new approaches for the prediction and management of preeclampsia.     

Human chronic fascioliasis: hepatitis B and C among infected cases

Sera from one hundred and fifty three chronic Fasciola cases were screened for the presence of HB markers (HBsAg, anti HBc and anti HBs) and anti HCV using ELISA technique. Quantitative stool examination and estimation of liver enzymes (AST-ALT-bilirubin) levels of the study population were performed. HBsAg was present in 5 (3.3%), anti HBs in 13 (8.5%), HBexposed (HBex) in 44 (28.8%) and anti HCV in 13 (8.5%) of examined sera. HBV and HCV markers were significantly higher among older age groups. Concerning familial aggregation of hepatitis markers, 7 (15.9%) of the 44 HBex cases had two individuals per family who had evidence of exposure to HBV. No significant change in Fasciola GMEC and liver function tests have been noticed.     

Potential effect of new (E)‐4‐hydroxy ‐N’‐(1‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐3‐yl) ethylidene) benzohydrazide against acute myocardial infarction: Haemodynamic,biochemical and histological studies

This study aimed to explore the cardioprotective effect of new synthesized coumarin (E)‐4‐hydroxy‐N’‐(1‐(7‐hydroxy‐2‐oxo‐2H‐chromen‐3‐yl) ethylidene) benzohydrazide denoted (Hyd.Cou) against myocardial infarction disorders. Male Wistar rats were divided into four groups; Control, isoproterenol (ISO), ISO + Acenocoumarol (Ac) and ISO + Hyd.Cou. Results showed that the ISO group exhibited serious alteration in EGC pattern, significant heart hypertrophy (+33%), haemodynamic disturbance and increase in plasma rate of CK‐MB, LDH and troponin‐T by 44, 53, and 170%, respectively, as compared to Control. Moreover, isoproterenol induced a rise in plasma angiotensin‐converting enzyme activity (ACE) by 49%, dyslipidaemia, and increased thiobarbituric acid‐reactive substances (TBARS) by 117% associated with decrease in the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) by 46% and 58%, respectively in myocardium. Interestingly, the molecular docking calculation demonstrated strong interactions of Hyd.Cou with the receptors of the protein disulphide isomerase (PDI) which could highlight the antithrombotic effect. Moreover, Hyd.Cou improved plasma cardiac dysfunction biomarkers, mitigated the ventricle remodelling process and alleviated heart oxidative stress damage. Overall, Hyd.Cou prevented the heart from the remodelling process through inhibition of ACE activity and oxidative stress improvement.     

Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause

Cardiovascular disease (CVD) is more prevalent in postmenopausal than premenopausal women, suggesting vascular protective effects of estrogen. Also, experimental studies have demonstrated beneficial effects of estrogen in improving vascular function and reducing vascular injury. However, clinical trials including HERS I, HERS II, WHI and WISDOM have demonstrated minimal beneficial vascular effects of menopausal hormone therapy (MHT) in postmenopausal women with CVD. The discrepancies between the experimental findings and clinical data may be related to the vascular estrogen receptors (ER), the type, route of administration, or dosage of MHT, and subject's age. Vascular ERs mediate both genomic and non-genomic effects of estrogen on the endothelium, vascular smooth muscle (VSM), and extracellular matrix (ECM). Postmenopausal changes in vascular ER structure, polymorphisms, amount, subcellular location, affinity or signaling could modify their responsiveness to estrogen and thereby the outcome of MHT. Recent investigations and patents have been centered on developing new ER modulators and alternatives for the traditional natural and synthetic forms of MHT which carry the risk of invasive breast cancer and venous thromoboembolism. Phytoestrogens may have similar effects as traditional MHT and have not demonstrated harmful side effects. Specific estrogen receptor modulators (SERMs) such as raloxifene and tamoxifen have also been tested. ER agonists that selectively target ERalpha, ERbeta and perhaps GPR30 may modify specific vascular signaling pathways. Also, the dose, route of administration, and timing of MHT are integral to optimizing the beneficial effects and minimizing the side effects of MHT. Progesterone, testosterone and modulators of their specific receptors may also affect the overall vascular effects of MHT in estrogen-deficiency states associated with menopause.