ألقى أ.د.علاء الدين عيسي الأستاذ بقسم الأسماك- كلية الطب البيطري - جامعة القاهرة ورشة عمل تحت عنوان :An update on aquatic animal medicine : educational and research perspectives
Introduction: In Egypt, disorders of sex development (DSD) constitute a significant entity among the birth defect list. Previous studies have reported that end organ androgen unresponsiveness, i.e. Androgen resistance, was the most prevalent underlying mechanism among Egyptian 46,XY DSD cases. Based on cytogenetic and hormonal diagnostic criteria as well as few sporadic case reports, it was proposed that androgen receptor (AR) defects [i.e. Androgen insensitivity syndrome (AIS), OMIM#300068] might constitute a major etiology within this category. However, this has never been systematically ascertained through an AR molecular diagnostic approach. Aim of the Work: The current study aimed to assess the role of AR mutations as an underlying etiology among a sample of Egyptian 46,XY DSD pediatric patients presenting with androgen end organ unresponsiveness. Patients and Method: In the current study, 21 children [age<18years] with male undermasculinization due to androgen end organ unresponsiveness were selected from 46,XY DSD cases. The selection criteria included ambiguous genital phenotype or genitalia discordant to the genotypic sex; 46,XY Karyotype and normal testicular response to HCG stimulation in prepubertal patients or normal basal testosterone (T) levels in postpubertal subjects. Molecular studies of the AR entailed PCR amplification for screening of major deletions/ insertions, single stranded conformational polymorphism (SSCP) screening for point mutations in the AR 2-8 exons followed by sequencing of these exons for all cases. Results: The results showed that none had major deletions/insertions. Five exons out of 147 (3.4%) showed abnormal SSCP migrational patterns. Out of those 5, two mutations in two Egyptian patients were detected by sequencing. The first was R840G (Arginine 840 glycine), in exon 7 (The ligand binding domain). The other was A596T (Alanine 596 Threonine) in exon 3 (The DNA binding domain). Conclusion:, This study shows that AR mutation is an uncommon underlying etiology among Egyptian paediatric 46,XY cases.
Abstract. The present study aimed to investigate the potential role of leptin in the progression of breast cancer and the associated cell proliferation signalling pathway(s). A total of 44 female patients diagnosed with breast cancer and 24 healthy donors from Ain Shams University Hospitals (Cairo, Egypt) were enrolled in the present study. The present study assessed leptin expression in breast cancer tissues at the gene and protein level using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and immunohistochemistry. The results demonstrate that the expression of leptin was significantly higher in tissue of breast cancer samples from obese patients than overweight and control samples (P<0.001). ELISA results indicated a significant increase (P<0.001) of leptin expression in obese patients. To investigate whether there is any difference in leptin expression between the peripheral and tumor microenvironment blood of patients with breast cancer, the concentration of leptin was assessed in plasma from both using ELISA assays. The results demonstrated a statistically significant increase in the level of leptin in plasma samples from the tumor microenvironment of obese patients with estrogen receptor positive (ER+) breast cancer, compared with peripheral plasma samples. Furthermore, the leptin gene was overexpressed in obese ER+ breast cancer tissue. RT‑qPCR was also performed to assess the expression of genes involved in proliferation pathways including leptin receptor (LEPR), aromatase, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription‑3 (STAT3). A positive association between leptin expression, LEPR, aromatase, MAPK and STAT3 was detected in tissue samples of patients with breast cancer. The current study concluded that leptin may enhance breast cancer progression by inducing the expression of JAK/STAT3, ERK1/2 and estrogen pathways in obese patients breast cancer.
The effects of the non-selective beta-blocker propranolol (CAS 525-66-6) and the cardioselective drug atenolol (CAS 29122-68-7) on serum glucose, insulin levels and some serum lipid components, were compared in normal and diabetic rats receiving glibenclamide. The two beta-blockers, when administered concurrently with glibenclamide in normal rats, exerted a significant hypoglycemic effect (p < 0.01), while in diabetic rats the two drugs caused a more significant decrease (p < 0.001 and p < 0.01, resp.). Serum insulin levels were mainly unaffected by the two beta-blockers. Propranolol was found to exhibit a hypolipidemic effect in diabetic rats when administered alone or in combination with glibenclamide. In comparison atenolol, when used alone, exerted a significant increase in triglycerides and total lipid levels (p < 0.05) in normal rats. This effect was masked when atenolol was administered concurrently with glibenclamide, but a hypercholesterolemic effect (p < 0.01) was noticed. Paradoxically in diabetic rats, atenolol caused a significant decrease (p < 0.05) in triglycerides level, while its combined use with glibenclamide showed no effect.
Captopril was effective in the long term reduction of serum sodium and aldosterone in normotensive rats, the addition of HCT produced a further decrease in serum sodium and was also useful in preventing hypokalemia produced by HCT. On the other hand, the concurrent therapy with Diclofenac attenuated the hypotensive effect of Captopril and HCT, it was observed that to combine Diclofenac with captopril was more beneficial as regards the metabolic parameters.
The effect of methanol on some of the lipid components in serum was studied in rats. Methanol was administered by stomach tube in doses of 2 and 6 ml/kg b.wt daily for 21 and 6 days, respectively. Methanol was found to accumulate lipids; thus, cholesterol, phospholipids and triglycerides increased significantly. Concurrently, modification of the lipoid content of organs has been considered. It was concluded that methanol and not only formate, is toxic to rats, inspite of the alleged difference in routes of its metabolism in primates and rodents.
The effect of long-term treatment of chloroquine (CAS 54-05-7) (20 mg/kg body weight) on serum lipid components and its relation to to the retinotoxic effect was studied in albino rats. Chloroquine was found to form lamellar lysosome-like structures within the photoreceptive layer, as well as the pigment epithelium and neurooretinal layers. Biochemically, hypolipidemia in the serum was observed mainly due to the decrease in phospholipid portion. It was hypothesized that due to the inhibition of the degradation process in the defective lysosomes, the retinal cells were denied the re-use of their own phospholipids, and thereby resort to their uptake from the serum.
The long- and short-term effects of chloroquine (CAS 54-05-7) on glucose metabolism in rats were assessed. The long-term chronic chloroquine administration (5 and 10 mg/kg b.w. 6 days a week for 6 months) caused a decrease in serum glucose, insulin, calcium, potassium and protein levels, while the glucagon level increased. The short-term acute effect of chloroquine administration (10 mg/kg b.w. 6 days for one week) caused an improvement in glucose tolerance as shown by the decrease in glucose and insulin curves after an oral glucose tolerance test. This was accompanied by an increase in insulin activity, corrected insulin response, and glucose tolerance parameter and a decrease in glucose and insulin areas. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased, too, indicating an increase which provides the needed energy for overcoming the injurious effect of chloroquine.
