Toxic effects arising from selenium and deferasirox interaction in the biological system

This investigation was conducted to evaluate the effect of deferasirox on selenium toxicity in male rat organs. After 50 days of selenium administration, all the rats showed toxicity symptoms. After poisoning, deferasirox was given orally to rats during 10 days. The results show that toxicity symptoms were unexpectedly increased. The new symptoms of toxicity after deferasirox administration were including loss of body hairs, yellowish discoloration of hair, weakness, brown spot on their skin, enlargement of the spleen and shrinking of sex organs. Selenium and iron concentrations were determined by GFAAS and FAAS, respectively. The results indicate the poisoned rats with selenium that received deferasirox as a drug, shown serious symptoms such as exacerbate toxicity, reduction in iron concentration, anemia and even death after a few days of deferasirox administration.     

Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.Key Words: Malaria, Interleukin-18, Plasmodium berghei, Histopathology     

An in vitro study on the effect of vinca alkaloid,vinorelbine, on chromatin histone,HMGB proteins and induction of apoptosis in mice non-adherent bone marrow cells

Context: Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one. Objective: To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro. Materials and methods: Non-adherent bone marrow cells were isolated and exposed to various concentrations (0–160?µg/ml) for 4?h at 23?°C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed. Result: The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89?KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells. Conclusion: Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis.     

Correlation between expression of MMP-9 and MMP-3 in Helicobacter pylori infected patients with different gastroduodenal diseases

Background and study aims

Helicobacter pylori (H. pylori) has been implicated in the pathogenesis of most important gastro-duodenal diseases, such as gastritis, peptic ulcer disease (PUD) and gastric cancer. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in the gastric mucosa, but the role of MMP-3 and MMP-9 in infected patients with H. pylori have not been clearly defined yet. We examined mucosal MMP-3 and MMP-9 mRNA levels in gastric mucosa of H. pylori infected patients and evaluated the effects of virulence factors cagA and vacA allelic variants on these levels. We also determined correlation between mucosal MMP-3 and MMP-9 mRNA levels and types of disease.

Clinical outcome with half-dose depot triptorelin is the same as reduced-dose daily buserelin in a long protocol of controlled ovarian stimulation for ICSI/embryo transfer: a randomized double-blind clinical trial (NCT00461916)

BACKGROUND: Traditional doses of depot GnRH agonist may be excessive for ovarian stimulation. We compared half-dose depot triptorelin (Group I) with reduced-dose daily buserelin (Group II) in a long protocol ICSI/embryo transfer through a double-blind randomized clinical trial. METHODS: Controlled ovarian stimulation (COS) was started by a pretreatment with oral contraceptives for 21 days. Then, 182 patients were randomized into two groups of 91. Group I received 1.87 mg triptorelin depot i.m. followed by daily s.c. injections of saline. Group II (reduced-dose protocol) received a bolus injection of i.m. saline followed by daily s.c. injections of 0.5 mg buserelin, which was then reduced to 0.25 mg at the start of human menopausal gonadotrophin stimulation. When transvaginal ultrasound showed at least two follicles of 16-20 mm diameter, HCG was given and ICSI was performed 40-42 h later. RESULTS: No significant differences were seen in the mean (SD) number of follicles at HCG administration, as our primary outcome [10.3 (4.4) in Group I versus 11.1 (4.2) in Group II, P = 0.180, mean difference = 0.86, 95% confidence interval 0.39-2.11]. The other early results of COS, clinical and ongoing pregnancy rates, or early pregnancy loss were also not significantly different between the groups. Group I endured longer stimulation period [11.2 (1.8) days versus 10.6 (1.9), P = 0.030]. CONCLUSIONS: Clinical outcomes were not significantly different between Group I and Group II.     

Fabrication of hybrid scaffold based on hydroxyapatite-biodegradable nanofibers incorporated with liposomal formulation of BMP-2 peptide for bone tissue engineering

In the present study, we fabricated an efficient, simple biomimetic scaffold to stimulate osteogenic differentiation of mesenchymal stem cells (MSCs). Electrospun poly L-lactic acid nanofibers were employed to mimic the nanofibrillar structure of bone proteins and coated with hydroxyapatite nanoparticles to simulate bone minerals. Thereafter, we regulated the release pattern of BMP-2 peptide through covalent attachment of an optimized liposomal formulation to the scaffold. The fabricated platform provided a sustained release profile of BMP-2 peptide up to 21?days while supporting cellular attachment and proliferation without cytotoxicity. In-vitro results confirmed the superiority of the scaffold containing liposomes through enhancement of growth and differentiation of MSCs. Ectopic bone formation model exhibited significant localized initiation of bone formation of liposome incorporated scaffold. Consequently, these findings demonstrated that our designed platform with modified release properties of BMP-2 peptide considerably promoted osteogenic differentiation of MSCs making it a unique candidate for bone regeneration therapeutics.     

Potential Cardioprotective Effects of Sumac Capsule in Patients With Hyperlipidemia: A Triple-Blind Randomized,Placebo-Controlled Crossover Trial

Objective: Alternative medicine and herbal drugs have been taken into account for managing cardiovascular risk factors. Sumac (Rhus coriaria L.) is rich in biologically active ingredients known to improve cardiovascular health. We investigated the effect of sumac on systolic (SBP) and diastolic (DBP) blood pressure, flow-mediated dilation (FMD), body mass index (BMI), and serum concentrations of lipids and fasting blood sugar (FBS) in participants with hyperlipidemia in a triple-blind randomized placebo- controlled crossover trial.

Methods: Thirty adults with dyslipidemia (mild to moderate elevation of plasma total cholesterol and/or triglycerides [TG; total cholesterol ≥ 6.0 mmol/L or TG ≥ 1.7 mmol/L and TG ≤ 5.0 mmol/L]) were assigned randomly to a sumac or a placebo group. Participants in the sumac group received sumac capsules (500 mg/twice daily) for the first 4 weeks, followed by 2 weeks’ washout period; the patients were then switched to a 4-week interval and received placebo for 4 weeks in the second period. The placebo group received these treatments in reverse order. FMD, BMI, SBP, DBP, lipids, and FBS were measured at baseline and after each period.

Results: Differences between placebo group and sumac group (placebo-sumac) were significantly decreased for BMI (0.21 ± 0.075 kg/m²), SBP (1.87 ± 0.83 mm Hg), DBP (1.32 ± 0.46 mm Hg), and total cholesterol (14.42 ± 4.95 mmol/L) and significantly increased for FMD (?0.23% ± 0.065%). Plasma level of TG did not change significantly across the treatment.

Conclusion: Sumac consumption may decrease cardiovascular risk factors in persons with mild to moderate hyperlipidemia.     

Synthesis of fluorene and/or benzophenone O-oxime ethers containing amino acid residues and study of their cardiovascular and antibacterial effects

The syntheses and biological studies of O-oxime ethers having α-amino acid residues as new analogs of IPS-339 have been described. In this synthesis, the reaction of fluorene and/or benzophenone O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of amino acid with O-oxime ether adducts led to synthesis of new analogs of IPS-339. The products were examined for their cardiovascular property. It was demonstrated that 2-(3-(9H-fluoren-9-ylideneaminooxy)-2-hydroxypropylamino)-3-methyl-butanoic acid as the most potent compound substantially reduces the heart rate of dogs. Compounds were also evaluated for their in vitro antibacterial activity against some Gram-negative and Gram-positive bacteria. The antibacterial screening proved the considerable antibacterial activity against both groups of bacteria. The docking analysis demonstrated the appropriate fitting of 2-(3-(9H-fluoren-9-ylideneaminooxy)-2-hydroxy-propylamino)-3-methyl-butanoic acid in human β₂-adrenergic receptor active site. Potential drug toxicity for some active compounds has also been predicted.