Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber’s rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

Background: Acute pancreatitis (AP) is a self-limiting condition to a widespread, deadly multi-organ failure that can resultin death.Objectives: To compare the protective effect of alpha lipoic acid (ALA) and Coenzyme (Q10) in an experimental rat modelof L-arginine-induced AP.Materials (Subjects): Forty adult male albino rats were randomized equally into 4 groups: (i) The control group; (ii) The APgroup received L-Arginine by intraperitoneal (IP) injection in two doses of 2 g/kg body weight each, 1 hour apart, (iii) TheALA+AP group was injected with L-Arginine and intramuscular (IM) injection of ALA in two doses of 60mg/kg body weight;1 hour before L-arginine injection and 24 hours after the second dose of L-arginine; (iii) The Coenzyme Q10+AP group wasinjected with L-Arginine and IM injection of Q10 in two doses of 30mg/kg body weight; 1 hour before L-arginine injection and24 hours after the second dose of L-arginine. Histological, immunohistochemical for HSP70 and NF-κB, and morphometricstudies were done followed by statistical analysis.Results: AP group showed significant distortion of the pancreatic acini with obvious cellular damage while those treated byALA and Coenzyme Q 10 especially ALA showed significant pancreatic tissue improvement as shown by HSP70 and NF-κBimmunoexpressing.Conclusions: ALA and Q 10 therapy proved a clear protective effect in suppressing experimentally generated AP in malealbino rats, but the improvement was more obvious with ALA.

Background: The aim of the present work was to elucidate the possible protective role of Verapamil (VPM) and Dantrolene (Da) in controlling experimentally induced early acute pancreatitis (AP) in male albino rats. Materials & Methods: Thirty- two adult male wistar-albino rats were divided randomly into: Group I (Control group; n. 8). Group II ((AP) group; n.24): 8 for each experimental subgroup: Subgroup (IIa) untreated AP: each was injected intraperitoneal (IP) by 250mg L- arginine/100g body weight. Subgroup (IIb) AP treated with VPM: each was pre-treated with VPM (0.25mg/100g body weight) by IP injection an hour before L-arginine induction. Subgroup (IIc) AP treated with Da: each was pre-treated with Da (1mg/100g body weight) by IP injection an hour before induction. Twenty-four hours following L-arginine injection, the rats were sacrificed by cervical dislocation under anesthesia by IP injection of pentobarbital at dose of 50mg/Kg body weight. Serological assessment of serum lipase and amylase, histological, histochemical, immunohistochemical and morphometric studies were done. Biochemical Study for Malondialdehyde (MDA), catalase, trypsin and Tumor necrosis factor alpha (TNFα) assessment by quantitative polymerase chain reaction (qPCR) were performed. All studies were followed by statistical analysis. Results: Subgroup IIa showed morphological changes indicating inflammation and degeneration that regressed in subgroups IIb & IIc with more obvious regression in subgroup IIb. The mean values of serum (s) amylase and lipase indicated a significant increase in AP subgroup compared to control and treated subgroups also a significant decrease was found in verapamil subgroup versus dantrolene subgroups. Morphometric and biochemical quantitative values were confirmative. Conclusions: Verapamil and Dantrolene therapy proved definite protective effect, more obvious in response to verapamil, in controlling experimentally induced early AP in male albino rats.

Background: Nicotine is the most important component of cigarettes and considers a strong carcinogen. Quercetin (QCT) is potent anticancer and antioxidant agent. Both nicotine and QCT can pass the placenta and appear in breast milk.Aim: To study the possible protective role of QCT on nicotine induced liver and kidney structural damage of neonates.Materials and Methods: Eighteen pregnant female albino rats were divided into 3 groups. The control group was injected subcutaneously (SC) by distilled water. The nicotine group was injected SC by nicotine (6mg/kg/d). Nicotine and QCT group was injected by nicotine and take simultaneously QCT orally (302 mg/kg/day). Twelve male neonates were taken from each group and divided into two subgroups (a and b). Offspring subgroups (1a, 2a, 3a) were sacrificed 2 weeks postnatal and offspring subgroups (1b, 2b, 3b) were sacrificed 4 weeks postnatal. By end of experiment, liver and kidney specimens were processed for histological and immunological studies.Results: In nicotine group, neonates' liver showed hepatocytes with pyknotic nuclei and vacuolated cytoplasm. Portal area showed more than one bile duct and cellular infiltrates. QCT and nicotine group showed moderate restoration of hepatic architecture especially in subgroup 3a. Transforming growth factor -β immnnoexpression was increased in nicotine group indicating liver damage while decreased in nicotine and QCT group, indicating some improvement. Neonates' kidney of nicotine group showed shrunken glomeruli, congestion of peritubular capillaries and homogenous eosinophilic material in tubular lumina. In nicotine and QCT group, there was minimal renal tissue improvement. Immunoexpression of COX-2 was much in kidney tissue of nicotine group indicating kidney damage, while in nicotine and QCT group, it was less expressed. Conclusion: Maternal QCT administration has a moderate role to protect neonatal liver against damage produced by maternal nicotine injection while this protective role was less in kidney.

Background & Objectives: Overweight patients meet obvious anatomical changes in the appearance of their skin and consequently morphological changes are expected. Weight loss in a massive manner results in redundancy of the skin following sleeve gastrectomy. The current work targeted to determine impact of morphological and morphoquantitative changes of epidermis, dermal fibers and endogenous stem cells (SCs) on surgical outcome in female patients with class III overweight and those with weight loss in a massive manner subjected to sleeve gastrectomy.Patients &Methods: Skin biopsies were obtained from excised skin during surgical intervention in thirty female patients, classified into three groups (10 patients for each group). Normal weight group presented with history of no weight loss who have done abdominoplasty. Morbid obesity (MO) group who have done sleeve gastrectomy. Massive weight loss (MWL) group presented with history of massive weight loss after sleeve gastrectomy and were submitted to abdominoplasty. Skin specimens were taken during abdominoplasty after surgical excision of excess abdominal skin in 1st and 3rd groups and during sleeve operation from wound edge in the 2nd group. Sections were subjected to histologic, biochemical, Phenotypic, morphoquantitative studies and quantitative polymerase chain reaction (qPCR). Results: Wound complications that occurred in MWL patients, were less in MO patients, and some of them required reoperation due to recurrence of redundancy. Associated phenotypic and morphometric changes in epidermal barrier, dermal fibers, degeneration marker and endogenous SCs were less evident in MO patients. Conclusions: Patients presenting with MWL following sleeve gastrectomy should accept higher complication rates and revisional procedures for recurrent redundancy due to altered skin behaviour. The beneficial therapeutic outcome could be related to the plasticity of skin SCs to transdifferentiate into adult skin cells of epidermal barrier and dermal fibers responsible for skin integrity.