Major histocompatibility complex class II inhibits fas antigen-mediated gastric mucosal cell apoptosis through actin-dependent inhibition of receptor aggregation

Escape from normal apoptotic controls is thought to be essential for the development of cancer. During Helicobacter pylori infection, the leading cause of gastric cancer, activation of the Fas antigen (Fas Ag) apoptotic pathway is responsible for early atrophy and tissue loss. As disease progresses, metaplastic and dysplastic glands arise which express Fas Ag but are resistant to apoptosis and are believed to be the precursor cells for adenocarcinoma. In this report, we show that one mechanism of acquired Fas resistance is inhibition of receptor aggregation via a major histocompatibility complex class II (MHCII)-mediated, actin-dependent mechanism. For these studies we used the well-described C57BL/6 mouse model of Helicobacter pylori and Helicobacter felis infection. Under normal conditions, Fas Ag is expressed at low levels, and MHCII expression on gastric mucosal cells is negligible. With infection and inflammation, both receptors are upregulated, and 6.1% of gastric mucosal cells express MHCII in combination with Fas Ag. Using the rat gastric mucosal cell line RGM-1 transfected with murine Fas Ag and MHCIIalphabeta chains, we demonstrate that MHCII prevents Fas receptor aggregation and inhibits Fas-mediated signaling through its effects on the actin cytoskeleton. Depolymerization of actin with cytochalasin D allows receptors to aggregate and restores Fas sensitivity. These findings offer one mechanism by which gastric mucosal cells acquire Fas resistance.     

Chemoprevention by pyrimethamine

The goal of the current research was to investigate the chemopreventive potency of an antimalaria drug, pyrimethamine, in in vitro conditions. The fibrosarcoma (WEHI-164) cell line was used for evaluating cytotoxicity, matrix metalloproteinase 2 (MMP-2) activity, and apoptosis. Pyrimethamine and methotrexate were used at concentrations of 0-8 µg/ml in triplicate and 2-fold dilutions. MMP-2 activity was assessed using zymoanalysis method. For assessment of apoptosis, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used. Cytotoxicity analysis of pyrimethamine showed a greater tolerability than methotrexate at concentrations of 1-8 µg/ml. The dose-dependent inhibitory effect of pyrimethamine on MMP-2 activity was significantly less than that of methotrexate at concentrations of 1-8 µg/ml. Moreover, the rate of apoptosis for pyrimethamine-treated cells at different doses (0.1, 1, and 10 µg/ml) was 3.30%, 9.42%, and 11.32%, respectively. Our data suggest that pyrimethamine enables suppression of MMP-2 activity and induces apoptosis that could be assumed for chemoprevention therapy.     

Comparison between swallowing and chewing of garlic on levels of serum lipids,cyclosporine, creatinine and lipid peroxidation in Renal Transplant Recipients

Abstract Hyperlipidemia and increased degree of oxidative stress are among the important risk factors for Atherosclerosis in renal transplant recipients (RTR). The Medical treatment of hyperlipidemia in RTR because of drugs side effects has been problematic, therefore alternative methods such as using of Garlic as an effective material in cholesterol lowering and inhibition of LDL Oxidation has been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients with stable renal function were selected and divided into 2 groups. They took one clove of garlic (1 gr) by chewing or swallowing for two months, after one month wash-out period, they took garlic by the other route. Results indicated that although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood pressure did not change, Systolic blood pressure decreased from138.2 to 132.8 mmHg (p=0.001) and Malondialdehyde (MDA) decreased from 2.4 to1.7 nmol/ml (p=0.009) by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl (p=0.03), triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008), MDA decreased from 2.5 to 1.6 nmol/ml (p=0.001), systolic blood pressure decreased from 137.5 to 129.8 mmHg (p=0.001), diastolic blood pressure decreased from 84.6 to 77.6 mmHg (p=0.001) and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03) by chewing route too. However HDL, LDL and cyclosporine serum levels had no significant differences by both of swallowing and chewing routes. We conclude that undamaged garlic (swallowed) had no lowering effect on lipid level of serum. But Crushed garlic (chewed) reduces cholesterol, triglyceride, MDA and blood pressure. Additionally creatinine reduced without notable decrease in cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating effect of garlic.     

Monitoring of National Drug Policy (NDP) and its standardized indicators; conformity to decisions of the national drug selecting committee in Iran

Background  

Pharmaceuticals have made an important contribution to global reductions in morbidity and mortality. To help save lives and improve health, it is important to be sure about equity to access to drugs, drug efficacy, quality and safety, and rational use of drugs, which are standardized National Drug Policy (NDP) objectives. NDP's indicators are useful to evaluate the pharmaceutical system performance in a country. Iran has adapted a National Drug List (NDL). Since management of drug supply in Iran takes place only for drugs that have been selected in NDL and this list is selected by the member of Iran Drug Selecting Committee (IDSC), thus evaluation of IDSC's decision making during last 5 years is an appropriate way to evaluate the implementation of drug supply system in the country.     

Subliminal attentional modulation in crowding condition

In the crowding phenomenon, recognition of a visual target is impaired by other similar visual stimuli (distracters) presented near the target. This effect may be due largely to insufficient resolution of spatial attention. We showed that attention could subliminally enhance orientation selective adaptation to illusory lines in the crowding condition where target-distractor separation is beyond the limit of spatial resolution of attention. Despite the traditionally held close link between attention and awareness, here we provided evidence for subliminal attentional modulation for orientation stimuli that could not have been consciously perceived.     

Novel expression and characterization of lymphatic vessel endothelial hyaluronate receptor 1 (LYVE-1) by conjunctival cells

PURPOSE: Lymphatic vessel endothelial hyaluronic acid receptor (LYVE-1) is a newly discovered lymphatic-specific marker. To date, there is no report of its expression on conjunctival cells. The purpose of this study was to investigate the expression of LYVE-1 in normal conjunctiva, to phenotype LYVE-1+ cells, and to study changes in their expression levels during corneal inflammation. METHODS: Flat-mounted conjunctivae or cross sections of eyeballs were harvested from BALB/c mice (6-8 weeks of age) for immunofluorescent confocal microscopic studies. RESULTS: The data demonstrate, for the first time, that in addition to its expression on lymphatic vessels, LYVE-1 was expressed on CD45+, CD11b+, and CD31- conjunctival cells, indicating a bone-marrow-derived monocytic lineage. Surprisingly, the number of cells that expressed LYVE-1 decreased during corneal inflammation, in conjunction with ingrowth of lymphatics into the cornea. CONCLUSIONS: A new population of monocytic cells has been found to express LYVE-1 in normal conjunctiva. These cells that normally express LYVE-1 may act as a reservoir for lymphangiogenesis and cell recruitment when the immune system is challenged.     

Radiotherapy-induced ocular surface disease

Today radiation is routinely used as a therapeutic modality for select tumors of the orbit, adnexa, paranasal sinus, and nasopharynx. Despite significant improvements in mechanisms of delivery and protective shielding, acute and chronic complications of radiation can affect different segments of the eye. In this report, we provide an overview of ocular damage secondary to radiotherapy. We identify the characteristic clinical changes and underlying pathophysiologic mechanisms involving the ocular surface and provide a rational approach to their prevention and treatment.     

Development of a simple analytical methodology for determination of glucosamine release from modified release matrix tablets

A simple spectrophotometric method for determination of glucosamine release from sustained release (SR) hydrophilic matrix tablet based on reaction with ninhydrin is developed, optimized and validated. The purple color (Ruhemann purple) resulted from the reaction was stabilized and measured at 570 nm. The method optimization was essential as many procedural parameters influenced the accuracy of determination including the ninhydrin concentration, reaction time, pH, reaction temperature, purple color stability period, and glucosamine/ninhydrin ratio. Glucosamine tablets (600 mg) with different hydrophilic polymers were formulated and manufactured on a rotary press. Dissolution studies were conducted (USP 26) using deionized water at 37+/-0.2 degrees C with paddle rotation of 50 rpm, and samples were removed manually at appropriate time intervals. Under given optimized reaction conditions that appeared to be critical, glucosamine was quantitatively analyzed and the calibration curve in the range of 0.202-2.020 mg (r=0.9999) was constructed. The recovery rate of the developed method was 97.8-101.7% (n=6). Reproducible dissolution profiles were achieved from the dissolution studies performed on different glucosamine tablets. The developed method is easy to use, accurate and highly cost-effective for routine studies relative to HPLC and other techniques.     

Transscleral diode laser therapy for cyclodialysis cleft induced hypotony

In order to evaluate the efficacy of transscleral diode laser therapy for treatment of cyclodialysis cleft associated with ocular hypotony, transscleral diode laser therapy was used in two patients with cyclodialysis cleft. It was applied over the cleft area in two rows of 14 applications in a post-traumatic patient and of 8 applications in a post-trabeculectomy patient at a power setting of 2500 mW and duration of 2000 msec. The clefts were closed with restoration of normal intraocular pressure and recovery of visual function in both patients. Transscleral diode laser therapy seems to be a safe, simple and non-invasive method for closure of the cyclodialysis clefts, especially in patients inappropriate for argon laser photocoagulation and those with opaque cornea.