Quercetin induces apoptosis and necroptosis in MCF-7 breast cancer cells.

OBJECTIVE: This study investigated the quercetin (Que) effects on growth of MCF-7 human cancer breast cell line and its cellular death mechanism. BACKGROUND: Quercetin has been found to be very efficacious against many different types of cancer cells. However, the study is not sufficiently powered to demonastrate anticancer mechanisms. METHODS: MCF-7cells were treated by 50 µM/ ml of Que for 48 hours. MCF-7 cells were also pretreated with 10 Μm ZVAD (apoptosis inhibitor) or 3 mM Nec-1 (necroptosis inhibitor) for evaluation of cell death induced by apoptosis or necroptosis. RESULTS: MTT and clonogenicity assays revealed that the Que induced a significant increase in cell viability and proliferation in presence of Nec-1 in comparison to the presence of ZVAD (p < 0.05). Que also increased apoptosis as revealed by DAPI staining and morphology evaluations. Following Que treatment Bcl-2 expression was significantly decreased while Bax expression was significantly increased. Que in presence of Nec-1 decreased expression of Bax gene, reduced apoptotic index, increased cell viability and proliferation of MCF-7 cells in comparison to absence of Nec-1. MCF-7 cells showed a significantly increased expression of RIPK1 and RIPK3 in response to Que plus ZVAD in comparison to absence of ZVAD. CONCLUSION: Our results revealed that the high Que toxicity for breast cancer cells depends on multiple cell death pathways, which involve mainly necroptosis (Fig. 6, Ref. 21).

Systemic prednisolone versus topical tranexamic acid for prevention of rebleeding in patients with traumatic hyphema: A randomized clinical trial.

PURPOSE: To compare the efficacy of systemic prednisolone and topical tranexamic acid (TA) on the rate of rebleeding in patients with macroscopic traumatic hyphema (MTH). METHOD: In a randomized clinical trial, patients with MTH were randomized to receive oral prednisolone (OP group) or topical TA drops (TA group). Comprehensive ophthalmic examinations including slit lamp examination and fundoscopy, intraocular pressure (IOP), best-corrected visual acuity (BCVA) and check for rebleeding were performed in all cases. RESULTS: Ninety eyes of 90 patients were included, and 45 patients were allocated into each group. Age, sex, IOP, BCVA and grade of hyphema were not different between groups. Rebleeding in the TA group (2 patients, 4.4%) occurred less frequently than in the OP group (7 patients, 15.6%), but this difference did not reach statistical significance (P=0.081). However, there was a significant difference between the two groups over time in terms of absorption of the MTH (P<0.001). CONCLUSION: Topical TA appears promising in the management of macroscopic traumatic hyphema.

Development of a model to assess environmental performance, concerning HSE-MS principles.

The main objective of the present study was to develop a valid and appropriate model to evaluate companies' efficiency and environmental performance, concerning health, safety, and environmental management system principles. The proposed model overcomes the shortcomings of the previous models developed in this area. This model has been designed on the basis of a mathematical method known as Data Envelopment Analysis (DEA). In order to differentiate high-performing companies from weak ones, one of DEA nonradial models named as enhanced Russell graph efficiency measure has been applied. Since some of the environmental performance indicators cannot be controlled by companies' managers, it was necessary to develop the model in a way that it could be applied when discretionary and/or nondiscretionary factors were involved. The model, then, has been modified on a real case that comprised 12 oil and gas general contractors. The results showed the relative efficiency, inefficiency sources, and the rank of contractors.

Design and study of ibuprofen disintegrating sustained-release tablets comprising coated pellets.

One challenge in tableting of sustained-release multiparticulates is maintaining the desired drug release after compaction. The aim of this study was to design sustained-release ibuprofen tablets which upon oral ingestion rapidly disintegrate into sustained-release pellets in which the integrity of the pellet core and/or coat is preserved. First free films composed of Eudragit RS 30D and RL 30D in 4:1 ratio and containing different levels of triethyl citrate (TEC) were prepared and tested to optimize the plasticizer level. Cured Eudragit based pellets with 60% ibuprofen loading which in our previous study showed proper mechanical properties for compression were coated with Eudragit RS 30D/RL 30D (4:1) containing 20% triethyl citrate at different coating levels. The mechanical properties of the coated pellets were tested. Polymer coated pellets were compacted into tablets either alone or with a blend of excipients comprising Avicel, PEG 4000, cross-linked PVP. A 3(2) full factorial design was used to optimize the filler blend composition. Effects of pellet to filler ratio, compression force and granulation of filler on tablet characteristics were investigated. Results of mechanical test showed that the coating of cured pellets had no significant effect on yield point and elastic modulus of the pellets. In the case of 5% coating level sustained release of ibuprofen over a period of 24h was achieved. The results obtained from tableting procedure showed that by selecting suitable filler blend (60% Avicel, 10% cross-linked PVP and 30% PEG 4000), compression force, and granulation of filler it was possible to prepare sustained-release tablets containing high ratio of coated pellets (even 80%) with desirable strength, disintegration time, and drug release rate. It was observed that compression force, pellet to filler ratio, composition of filler blend and granulation of fillers had no effect on drug release rate from compacted pellets but had significant influence on tablet strength, friability, and disintegration time. SEM graphs and in vitro release profiles for compacted pellets showed no apparent damage to the coated pellets as a result of the compaction process.

Thermal treating as a tool to produce plastic pellets based on Eudragit RS PO and RL PO aimed for tableting.

A 3(2) full-factorial design was used for preparation of pellets using extrusion-spheronization technique. Independent variables were %ibuprofen (40, 60, 80) and %Eudragit RS PO/RL PO (0, 50, 100). In all formulations 3% w/w PVP K30 and 10% Avicel PH101 were also used. The pellets were cured in oven at 60 degrees C for 24h. The evaluated responses were crushing strength or yield point, elastic modulus and mean dissolution time (MDT) of pellets. The cured pellets were also compressed at 15kN compaction force and then observed under scanning electron microscope. It was shown that the cured pellets containing 40% or 60% drug exhibited a plastic deformation without any fracture under mechanical tests. The curing process resulted in significant decrease in the elastic modulus of the pellets. The SEM of the compressed pellets were also confirmed the plastic behavior of these pellets. The transition of pellet behavior from brittle to plastic upon curing was due to shift of Eudragit structure from glassy to rubbery state which was supported by DSC studies. However pellets with 80% drug showed brittle properties even after curing due to presence of less amount of Eudragit in their structure. Increasing the ratio of Eudragit RS in the pellets decreased the yield point and elastic modulus of cured pellets containing 40% or 60% drug, indicating more plastic behavior of these pellets. This was attributed to lower Tg of Eudragit RS than Eudragit RL. The curing process also retarded drug release from pellets and increased MDT. Increasing the ratio of Eudragit RS in the pellets increased MDT in cured pellets containing 40% or 60% drug but had no effect in pellets with 80% drug. Overall the results of this study revealed that thermal treating is a proper tool to produce plastic ibuprofen pellets based on Eudragit RS PO and Eudragit RL PO.

Preparation and characterization of ibuprofen pellets based on Eudragit RS PO and RL PO or their combination.

The aim of this study was to assess the application of Eudragit RL PO and RS PO and their combination for production of ibuprofen pellets by extrusion-spheronization. The pellets were prepared based on full factorial design. Independent variables were % ibuprofen (40, 60, 80), the ratio of Eudragit RS to Eudragit RL (1:0, 1:1, 0:1) and % PVP (1, 3, 5). The evaluated responses were mean dissolution time (MDT), crushing strength and elastic modulus of pellets. Surface characteristics, sphericity and aspect ratio of pellets were also evaluated. Linear regression and response surface modeling was used for analyzing results. It was shown that the amount of water required to prepare a proper wet mass was affected by composition of formulations. The required amount of water decreased with increasing drug load and percent of PVP. It was also shown that formulations containing Eudragit RL need more water. Increasing percent of PVP slightly decreased MDT and elastic modulus but had negligible effect on crushing strength. Increasing the percent of ibuprofen up to 60% decreased MDT but beyond that increased MDT. Increasing the percent of ibuprofen also decreased elastic modulus of pellets. Eudragit RL PO compare with Eudragit RS PO resulted in pellets with high crushing strength; however, Eudragit type did not have a significant effect on elastic modulus.

Preparation and evaluation of pellets using acacia and tragacanth by extrusion-spheronization.

BACKGROUND AND THE PURPOSE OF THE STUDY: Extrusion-spheronization is an established technique for the production of pellets for pharmaceutical applications. In this study, the feasibility and influence of the incorporation of acacia, by itself and in combination with tragacanth, on the ability of formulations containing 2 model of drugs (ibuprofen and theophylline) to form spherical pellets by extrusion-spheronization was investigated. MATERIAL AND METHODS: Formulations containing different ratios of acacia and tragacanth (8:2, 9:1, and 10:0) and different drug concentrations (20%, 40%, and 60%) were prepared, on the basis of a 3(2) full factorial design. Pellet properties, such as aspect ratio, sphericity (image analysis), crushing strength and elastic modulus (mechanical tests), mean dissolution time, and dissolution profiles were evaluated. The effect of particular factors on responses was determined by linear regression analysis. RESULTS: The sphericity, drug release rate, and the mechanical properties of the pellets were affected by the amounts and types of the drugs, and the ratio of the gums. Acacia, relative to tragacanth, produced pellets with higher mechanical strength and a faster drug release rate. Addition of small amounts of tragacanth to ibuprofen formulations resulted in matrix pellets with slow drug release. CONCLUSION: The results showed that acacia and tragacanth can be used successfully as 2 natural binders in the pellet formulations.

Relationship of soil terrestrial radionuclide concentrations and the excess of lifetime cancer risk in western Mazandaran Province, Iran.

The main goal of this study is to lay out the map of the soil radionuclide activity concentrations and the terrestrial outdoor gamma dose rates in the western Mazandaran Province of Iran, and to present an evaluation scheme. Mazandaran Province was selected due to its special geographical characteristics, high population density and the long terrestrial and aquatic borders with the neighbouring countries possessing nuclear facilities. A total of 54 topsoil samples were collected, ranging from the Nour to Ramsar regions, and were based on geological conditions, vegetation coverage and the sampling standards outlined by the International Atomic Energy Agency. The excess lifetime cancer risks (ELCRs) were evaluated and the coordinates of sampling locations were determined by the global positioning system. The average terrestrial outdoor gamma dose rate was 612.38 ± 3707.93 nGy h(-1), at 1 m above the ground. The annual effective gamma dose at the western part of Mazandaran Province was 750 µSv, and the ELCR was 0.26 × 10(-2). Soil samples were analysed by gamma spectrometry with a high-purity germanium detector. The average (226)Ra, (232)Th, (40)K and (137)Cs activities were 1188.50 ± 7838.40, 64.92 ± 162.26, 545.10 ± 139.42 and 10.41 ± 7.86 Bq kg(-1), respectively. The average soil radionuclide concentrations at the western part of Mazandaran Province were higher than the worldwide range. The excess lifetime risks of cancer and the annual effective gamma doses were also higher than the global average.

Road traffic noise model.

BACKGROUND: The recognition of road traffic noise as one of the main sources of environmental pollution has led to develop models that enable to predict noise level from fundamental variables. Traffic noise prediction models are required as aids for designing roads and highways. In addition, sometimes are used in the assessment of existing or envisaged changes in traffic noise conditions. In this paper a statistical modelling approach has been used for predicting road traffic noise in Iranian road conditions. METHODS: The study was performed during 2005-2006 in Hamadan city, in the west of Iran. The data set consisted of 282 noise measurements. The entire data set was utilized to develop a new model for Iranian condition using regression analysis. RESULTS: The developed model has twelve explanatory variables in order to achieve a proper fit for measured values of Leq (r2= 0.913). CONCLUSION: The proposed road traffic noise model can be effectively used as a decision support tools for prediction of traffic noise index of Leq(30min), in Iran's cities.

Oral nicotinamide reduces serum phosphorus,increases HDL, and induces thrombocytopenia in hemodialysis patients: a double-blind randomized clinical trial

Background: Recently, nicotinamide has been suggested as an effective drug for hyperphosphatemia in hemodialysispatients. The authors assessed the efficacy and safety ofnicotinamide in these patients with lower doses and longer duration than other studies. Methods: Forty eight patients with fasting serum phosphorus >5 mg/dl enrolled in this randomized clinical trial study and were randomly assigned to two equal-sized groups of nicotinamide or placebo. The study lasted 8 weeks. In the first four weeks, nicotinamide was administered at 500 mg/day, and in the second four weeks at 1,000 mg/day. Blood samples were tested at baseline, week 4, and week 8. Results: In nicotinamide group, the mean phosphorus level decreased from5.9 ± 0.58 mg/dl to 4.77 ± 1.43 mg/dl in week 4 (P = 0.002)and to 4.66 ± 1.06 mg/dl in week 8 (P = 0.000). The mean calcium-phosphorus product decreased significantly with the same pattern as phosphorus. High-density lipoprotein level increased from 42.46 ± 8.01 mg/dl to 55.71 ± 11.88mg/dl in week 4 (P = 0.000) and to 65.25 ± 20.18 mg/dl in week 8 (P = 0.000). Levels of serum calcium, uric acid, SGOT, SGPT, and iPTH didn’t change significantly. Compared to baseline, the platelet counts were decreased in both week 4 and week 8. No significant changes were observed in placebo group. Conclusions: In our patients, nicotinamide effectively decreased phosphorus, increased high-density lipoprotein, and caused thrombocytopenia. Since nicotinamide lowered platelet counts and caused thrombocytopenia in lower doses than other studies in these patients, it is necessary to plan other studies for assessing the safety of the drug especially in different populations (AU)

Antecedentes: Recientemente, se ha sugerido que la nicotinamida es un fármaco eficaz para la hiperfosfatemia en pacientes en hemodiálisis. Los autores evaluaron la eficacia y la seguridad de la nicotinamida en estos pacientes con dosis más bajas y mayor duración que en otros estudios. Métodos: Cuarenta y ocho pacientes con fósforo sé-rico en ayunas >5 mg/dl participaron en este estudio clínico aleatorio y fueron asignados al azar a dos grupos de igual tamaño uno de los cuales recibiría nicotinamida y el otro, placebo. El estudio duró 8 semanas. En las primeras4 semanas, se les administraron 500 mg de nicotinamida al día, y en el segundo período de 4 semanas se aumentó la dosis a 1.000 mg/día. Se tomaron muestras de sangre en la primera, quinta y novena semanas. Resultados: En el grupo de la nicotinamida, el nivel de fósforo se redujo de 5,9± 0,58 a 4,77 ± 1,43 mg/dl en la quinta semana (p = 0,002) y a 4,66 ± 1,06 mg/dl en la novena semana (p = 0.000). El producto calcio-fósforo se redujo significativamente siguiendo el mismo patrón que el fósforo. El nivel de HDL aumentó de 42,46 ± 8,01 a 55,71 ± 11,88 mg/dl en la quinta semana (p = 0,000) y a 65,25 ± 20,18 mg/dl en la novena semana (p = 0,000). Los niveles de calcio sérico, ácido úrico, TGO, TGP e iPTH no cambiaron de manera significativa. En comparación con la primera semana, el recuento de plaquetas en la quinta y novena semana disminuyó. No se observaron cambios significativos en el grupo placebo. Conclusiones: En nuestros pacientes, la nicotinamida disminuyó de forma efectiva el fósforo, aumentó el HDL, y causó trombocitopenia. Como la nicotinamida redujo el recuento de plaquetas y causó trombocitopenia en dosis más bajas que en otros estudios con estos pacientes, es necesario planificar más estudios para evaluar la seguridad del fármaco, especialmente en diferentes poblaciones (AU)