The Concentration and Partitioning of Heavy Metals in Surface Sediments of the Maharlu Lake,SW Iran

In this study, an assessment is made of the environmental impacts of heavy metal concentration and fractionation in bed sediments of the saline Maharlu Lake, SW Iran. Total elemental analysis indicated that sediments were highly enriched in Pb and Cd. Sequential extraction analysis revealed that salt of the lake is probably highly contaminated with Cd, Pb, and Co. Due to the oxidizing conditions of the lake, the organic matter fraction of the elements was not significant. In all sediments, Cd, Pb, Co, Mn, and Zn were strongly associated with exchangeable plus carbonate fractions, with mean percentage of 76.4%, 65.3%, 56%, 40.9%, and 34.3%, respectively. On average, the percentage of Ni associated with the sum of the exchangeable and carbonate fractions was 19.8%. Cr, Fe, and Cu fractionation indicated that these metals are environmentally inert and immobile. Statistical relationships among metal fractions and sediment properties showed that Cd, Pb, Zn, Ni, Co, and Mn were mainly from recent anthropogenic sources, while such sources were less important for Cr, Cu, and Fe. The latter metals represented natural geochemical levels.     

Preparation and Investigation of Sustained Drug Delivery Systems Using an Injectable, Thermosensitive, In Situ Forming Hydrogel Composed of PLGA–PEG–PLGA

In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(D,L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol-gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA-PEG1500-PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12.     

Ligation of the jugular veins does not result in brain inflammation or demyelination in mice

An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and ^99mTc-exametazime to assess for structural and hemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and hemodynamic disturbances in the brain on Tc99m-exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and hemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis.     

Assessment of Feasibility of Maillard Reaction between Baclofen and Lactose by Liquid Chromatography and Tandem Mass Spectrometry, Application to Pre Formulation Studies

The aim of this study was to determine any possible, baclofen–lactose Maillard reaction products. Granules and tablets of baclofen and lactose were prepared and maintained in heat ovens for a certain time period. The effects of lactose type, addition of magnesium stearate, and water were monitored. Heated lactose and baclofen were analyzed using reverse-phase HPLC. Liquid chromatography tandem mass spectroscopy revealed nominal mass values consistent with baclofen–lactose, early-stage Maillard reaction condensation products (ESMRP). Multiple reaction monitoring confirmed the presence of ESMRP as well. FTIR analysis proved the formation of imine bond. The results indicated that baclofen undergoes a Maillard-type reaction with lactose.     

Mammalian Target of Rapamycin (mTOR) and S6 Kinase Down-regulate Phospholipase D2 Basal Expression and Function

The mammalian target of rapamycin (mTOR) and S6 kinase (S6K) pathway is essential for cell differentiation, growth, and survival. Phospholipase D2 (PLD2) plays a key role in mTOR/S6K mitogenic signaling. However, the impact of PLD on mTOR/S6K gene expression is not known. Here we show that interleukin-8 (IL-8) increases mRNA expression levels for PLD2, mTOR, and S6K, with PLD2 preceding mTOR/S6K in time. Silencing of PLD2 gene expression abrogated IL-8-induced mTOR/S6K mRNA expression, whereas silencing of mTOR or S6K gene expression resulted in large (>3-fold and >5-fold, respectively) increased levels of PLD2 RNA, which was paralleled by increases in protein expression and lipase activity. Treatment of cells with 0.5 nm rapamycin induced a similar trend. These results suggest that, under basal conditions, PLD2 expression and concomitant activity is negatively regulated by the mTOR/S6K signaling pathway. Down-regulation of PLD2 was confirmed in differentiated HL-60 leukocytes overexpressing an mTOR-wild type, but not an mTOR kinase-dead construct. At the cellular level, overexpression of mTOR-wild type resulted in lower basal cell migration, which was reversed by treatment with IL-8. We propose that IL-8 reverses an mTOR/S6K-led down-regulation of PLD2 expression and enables PLD2 to fully function as a facilitator for cell migration.     

Structure based design of a series of potent and selective non peptidic PTP-1B inhibitors

A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphatase.     

Solid Phase Radioimmunoassay for Identification of Herpesvirus hominis Types 1 and 2 from Clinical Materials

A solid phase radioimmunoassay (RIA) was developed for typing Herpesvirus hominis (HVH) strains isolated from clinical materials, and it also proved to be applicable to the direct detection and typing of HVH antigen in human and animal brain tissue. The procedure utilized virus-infected human fetal diploid cells or brain tissue smears in the bottom of 1-dram glass vials, antigen was detected through the use of intermediate HVH antisera produced in rabbits or hamsters and cross-absorbed with the HVH heterotype, and (125)I-labeled anti-species (rabbit or hamster) globulins produced in goats were used for detection of immune complexes. The cross-absorbed HVH antisera could be used at high dilutions in the RIA test, and they reacted with marked type-specificity in the RIA system. Specificity of the test was also improved by determining and using optimal concentrations of intermediate sera and of (125)I-labeled anti-species globulins. Results of typing HVH isolates by the RIA procedure agreed in all instances with those obtained by direct fluorescent antibody staining with cross-absorbed conjugates. The RIA procedure was effective and more sensitive than direct fluorescent antibody for demonstrating and typing HVH antigen directly in smears of infected human brain tissue.     

Phage display-derived antibody fragments against conserved regions of VacA toxin of Helicobacter pylori

Applied Microbiology and Biotechnology - Infection with Helicobacter pylori may result in the emergence of gastric adenocarcinoma. Among various toxins assisting pathogenesis of H. pylori,...