Antiangiogenic activity of xanthomicrol and calycopterin, two polymethoxylated hydroxyflavones in both in vitro and ex vivo models

Our previous studies had shown xanthomicrol and calycopterin, two plant-derived flavonoids, to have selective antiproliferative activity against some malignant cell lines. The present study is focused on the investigation of antiangiogenic potential of these two flavonoids, using in vitro and ex vivo models. Xanthomicrol and calycopterin were found to have potent inhibitory effects on microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to completely block microvessel sprouting at 10 μg/mL, and calycopterin suppressed microvessel outgrowth by 89 at 5 μg/mL. Suramin and thalidomide, used at 20 μg/mL as positive controls, inhibited microvessel formation by 23 and 64, respectively. The flavones also inhibited endothelial cell tube formation and human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 μg/mL. In order to delineate the underlying mechanisms of antiangiogenic activity of these flavones, we investigated the influences of xanthomicrol and calycopterin on expression of vascular endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF) in endothelial cells. These flavones were able to inhibit VEGF expression at 0.5, 5, and 10 μg/mL, but they had little or no effect on b-FGF expression. These findings suggest that xanthomicrol and calycopterin possess potent antiangiogenic activities, which may be due to their inhibitory influences on VEGF expression. Copyright © 2014 John Wiley & Sons, Ltd

Exponential renormalization

Moving beyond the classical additive and multiplicative approaches, we present an "exponential" method for perturbative renormalization. Using Dyson's identity for Green's functions as well as the link between the Faa di Bruno Hopf algebra and the Hopf algebras of Feynman graphs, its relation to the composition of formal power series is analyzed. Eventually, we argue that the new method has several attractive features and encompasses the BPHZ method. The latter can be seen as a special case of the new procedure for renormalization scheme maps with the Rota-Baxter property. To our best knowledge, although very natural from group-theoretical and physical points of view, several ideas introduced in the present paper seem to be new (besides the exponential method, let us mention the notions of counterfactors and of order n bare coupling constants).Comment: revised version; accepted for publication in Annales Henri Poincar

Interaction between ketoconazole, amphotericin B and terbinafin and three diazenumdiolates in concomitant uses against some fugal species

A checkerboard broth microdilution method was performed to investigate the in vitro antifungal activities of three diazeniumdiolates derivatives (DETA/NO, DPTA/NO, DEA/NO) alone and in combination with ketoconazole, amphotricin B or terbinafine against five Candida species, Cryptococcus neoformance and four dermatophyte strains. MICs and MLCs were recorded, and synergy was calculated by using fractional inhibitory and fractional lethal concentration index. DETA/NO with a half-life of 57h at 25°C showed antifungal activity against all tested dermatophyte species (MIC 0.150 to 2.5mg/ml), DPTA/NO with a half life of 3h at 37°C showed antifungal activity against five species of Candida and Cryptococcus neoformans, and DEA/NO with a half life of 2 min at 37°C and 16 min at 25° C did not show antifungal activity against tested strains. Combinations of DPTA-NO with either ketoconazole or amphotericin B were either synergistic or indifferent for all tested strain of Candida and Cryptococcus neoformance. DETA/NO was unable to enhance the antifungal activity of terbinafine against dermatophyte strains. Even where no synergistic activity was achieved, there was still a decrease in the MIC of one or both drugs which were used in combination. Antagonism was observed between terbinafine and DETA-NO against Trichophyton rubrum. Our result suggests that DETA/NO and DPTA/NO may be useful for development of new therapeutic strategies for treatment of dermatophyte and Candida infections. Clinical studies are warranted to elucidate the potential utility of these combination therapies

Evaluation of the frequency of the IL-28 polymorphism (rs8099917) in patients with chronic hepatitis C using zip nucleic acid probes, Kerman, Southeast of Iran

Polymorphisms in the region of the interleukin IL-28 gene on chromosome 19 have been related with clearance of hepatitis C virus (HCV), a major human pathogen responsible for chronic hepatitis, cirrhosis and hepatocellular carcinoma. About 3 of the world's population is infected with HCV. The long-term response to therapy is influenced by many host and viral factors, and recent evidence has indicated that some host genetic polymorphisms related to IL-28 are the most powerful predictors of virological response in patients with HCV. This study assessed frequency of the IL-28 polymorphism (rs8099917) in 50 patients (39 men and 11 women ) with chronic hepatitis C using ZNA probe real time PCR new method . All patients were tested for genotype of HCV and the HCV viral load. In parallel, the levels of SGOT, SGPT and ALK enzymes were assessed. Treatment using Peg-interferon alpha with ribavirin was conducted for patients and subsequently samples were collected to detect any change in viral load or liver enzyme rates. The overall frequency of the TT allele is 74, TG allele 20 and GG allele 6 and the percent of patients who had T allele was 84. Clear reduction in viral load and liver enzymes was reported in patients with the T allele. Especially for genotype 1 which is relatively resistant to treatment, these alleles may have a role in this decline. In conclusion, we showed that IL-28 polymorphism rs8099917 strongly predicts virological response in HCV infection and that real-time PCR with Zip nucleic acid probes is a sensitive, specific and rapid detection method for detection of SNPs which will be essential for monitoring patients undergoing antiviral therapy

Development of micellar electro kinetic chromatography for the separation and quantitation of L-valine, L-leucine, L-isoleucin and L-phenylalanine in human plasma and comparison with HPLC

Phenylketonuria (PKU) and Maple Syrup Urine Disease (MSUD) are two inborn metabolic diseases which are carried by autosomal recessive genes in man. These genetic errors result in accumulation of phenylalanine (in PKU) or valine, leucine and isoluecin (in MSUD). At high concentrations, amongst other problems, these amino acids cause mental retardation. However if detected early after birth, using special diets and other forms of therapy, mental abnormalities can be prevented. As a result in many countries screening of infants for MSUD and PKU, by measuring plasma amino acids has become a routine neonatal test. Capillary Electrophoresis (CE) assays have a number of advantages over the traditional chromatography techniques (such as GC or HPLC). These include low cost, high speed of analysis and high resolution. These characteristics, make CE an ideal method for the screening of inborn errors of metabolism. We developed a CE assay based on pre-column derivatisation of amino acids with phenylisothiocyanate. This conjugate has strong absorbance at 254 nm. CE was carried out using a Spectraphoresis 1000 instrument, fitted with 40 cm of a 25 μm capillary, at 17°C. A running voltage of 18KV was used to separate the amino acid mixture in an electrophoretic buffer containing 45 mM imidazole, 6 mM borate and 208 mM SDS, fixed at pH 9 with 2-N-morpholino ethane sulfonic acid. The assay was calibrated using various concentrations of amino acid standards. LOD, LOQ, recovery, inter-day and intra-day variations of the assay were determined. Also, levels of the 4 amino acids in normal and abnormal plasma were determined and compared with HPLC. © 2007 Asian Network for Scientific Information

Study on physico-chemical properties of the Iranian waters in the Oman Sea

The characteristics physicochemical studies in the northern part of the Oman Sea and Strait of Hormuz within the Iranian waters were conducted during 2007 and 2009.The project was implemented using Ferdous research vessel and with the cooperation of Chah Bahar Research Center. The sampling area included the whole stretch of the Iranian waters along the northern part of the Oman Sea from the northeast of the Iranian marine border of 30 miles Bay of Chabahar to the mouth of the Hormuz Strait in Hormuzgan province. Along this stretch 10 equally distributed transects at a distance of 30 miles away from each other were designated, 4 main sampling stations at a distance of 10 miles from one another were fixed at each transect. Sampling was conducted twice a year ( spring and autumn 2007 and 2009).Physicochemical parameters of water such as temperature, density, salinity, turbidity, dissolved oxygen, pH, EC and chlorophyll-a were recorded at stations using CTD multiparameter probe. Nutrients samples were collected by multi water sampler and were measured by spectrophotometric method. According to achieved results; we can point out to the following outlines below: The beginning of thermocline layer starts in the regional Iranian Territorial Waters of Oman Sea; located at approximate depth of 10m; in spring, 20-40m; in autumn, and at 100m depth in winter; seasons, with an average difference in temperature of 10˚C; between surface and deeper layers. In another word, permanent thermocline exists annually in this body of water; where only the point of start, and the fracture width of thermocline layer; alter with alteration of seasons. Horizontal and vertical distribution of electrical conductivities, obey exactly from thermal degree structure; in such a way that, with increase in temperature; they increase, and with decrease in temperature; they decrease. Level of salinity increase from east to west, but it decrease; from surface to deeper layers. In deeper regions, especially in the midway east of the Oman Sea; the level of salinity in the deeper waters from 150-300m, there is a considerable increase observed in salinity, due to very high salinity waters of The Persian Gulf; that are entering the Sea of Oman, via the Striate of Hormouz from the bottom; where they are having their effect following the whole length of the Sea of Oman; through their path. The level of water density from offshore to onshore, and from surface to deeper levels increase in such a way that; its average in surface layers is 24g/cm^3, and at 400m depth; is 29g/cm^3, and at 600m; reaches to 30g/cm^3. The level of Chlorophyll-a in surface waters, in the northeastern midway; is higher than the northwestern midway of the Sea of Oman, and it decreases from inshore to offshore waters, but its vertical distribution; has caused somehow in a way, that the highest distribution and concentration of chlorophyll-a; to be formed in deeper layers, between about 20-40m depths. Then by the increase in water depth, its concentration decreases drastically; reaching zero in magnitude. Concentration of dissolved oxygen is higher in spring in comparison to that of autumn, and the highest level is achieved in water layers located at 10-40m depth (where the level of chlorophyll-a is higher). In addition to which, that its vertical structure; shows the existence of a permanent oxycline layer at this region, in a way that; by seasonal alterations (similar to that of thermocline layer), only the point of start and that of the thickness of oxycline layer changes. The layer of oxycline is established from seawaters; located at 10m depth in spring, and at20-40m waters in autumn; whereas the same layer is formed at 100m seawaters in winter, and then by water depth increase; it reaches crisis condition. The highest level of water pH; has been achieved in the spring of year 2009 (1388 Iranian Calendar), where some northern and northwestern regions of the Strait of Hormouz; were suffering from the remnants of red tide occurrences (~8.5), where the pH level decreased from water surface, and its vertical alteration trend; obeyed to that of the same for temperature and chlorophyll-a vertical structure, especially for dissolved oxygen parameter, where the maximum decrease was recorded coinciding with formation of oxycline layer. The level of water turbidity increased from offshore to inshore direction, but it decreased from water surface to depth for the Sea of Oman. But nutrient levels increased; at surface water layers from offshore to inshore, and from west to east, for the same body of water. In addition to that, concentration of nutrients in autumn (after monsoon); were more than that of, spring season (before monsoon), where; concentration of their vertical structure increase from water surface toward deeper sections

A new potentiometric sensor for determination and screening phenylalanine in blood serum based on molecularly imprinted polymer

Methods routinely utilized for detection of phenylalanine in new-born blood consist of enzymatic assays, lacking sensitivity and HPLC assays which are expensive and timeconsuming to conduct. We, here, report for the first time, the construction of a phenylalanine sensitive electrode, on the basis of a selective molecularly imprinted polymer, offering sensitivity, economy and ease of use for the measurement of phenylalanine. The sensor was constructed of a graphite-rod electrode which was coated by MIP embedded polymer base made from polyvinyl chloride and plasticizer mixture, dissolved in THF. At optimized conditions the electrode revealed a Nernstian response 29.73 ± 1.0 mV decade-1 in a concentration range of 1 � 10�� to 1 � 10-4 M with detection limit of 5 � 10�� M. The potential response of the electrode was constant in the pH range of 4.0�7.5. The electrode unfolded a response time of ~20 sec. The selectivity coefficient of the sensor towards a number of different amino acids with molecular similarities and some metal ions was evaluated. The sensor was successfully used for determination of phenylalanine in blood serum and the results were in good compatibility with HPLC method. © 2019, Iranian Journal of Pharmaceutical Research. All rights reserved

Development of a rheological model for polymeric fluids based on FENE model

Rheological models for polymer solutions and melts based on the finitely extensible non-linear elastic (FENE) dumbbell theory are reviewed in this study. The FENE-P model that is a well-known Peterlin approximation of the FENE model, indicates noticeable deviation from original FENE predictions and also experimental results, especially in the transient flow. In addition, both FENE and FENE-P models have some shortcomings from the point of view of theory. To overcome these shortcomings, a new approximation of the FENE spring force has been established. It has been used to develop a modified constitutive rheological model for polymeric fluids. In the procedure of modeling, the effect of non-affine deformation is introduced into the new model. Comparison between the model predictions and experimental data presented in the literature for transient and steady shear flow of polystyrene indicates that this modified model can predict the rheological behavior of polymeric fluids with a great accuracy. The newly developed modified model could predict different slopes that can cover the behavior of most of the polymeric fluids

Conjugated linoleic acid stimulates apoptosis in RH and tehran strains of Toxoplasma gondii, in vitro

Background: The aim of this study was to evaluate the effects of conjugated linoleic acid (CLA) on apoptosis of tachyzoites of T. gondii, RH strain (type I) and the cyst-forming Tehran strain (type II) in vitro. Methods: Toxoplasma strains were injected into the peritoneal cavity of BALB/c mice. The Tehran strain forms cysts in the brain of mice. Bradyzoites within the cysts are reactivated to proliferative tachyzoites, by dexamethasone. Tachyzoites were aspirated from the peritoneum of infected mice, and the percentage of viable parasites was estimated with trypan blue staining. Tachyzoites were inoculated into HeLa cells cultivated in DMEM medium. Different concentrations of CLA were evaluated on T. gondii in HeLa cells by the tetrazolium (MTT) colorimetric assay. Differentiation between apoptosis and cell death was determined by flow cytometry using Annexin V and propidium iodide (PI) double staining. The statistical analysis performed by GraphPad Prism version 6.00. Results: CLA induces apoptosis in virulent (RH) and avirulent (Tehran) strains of T. gondii. The results of MTT indicated that CLA could decrease the proliferation of tachyzoites of both strains in HeLa cells. Conclusion: Conjugated linoleic acid has anti-toxoplasmacidal activity on tachyzoites of T. gondii. Therefore, we recommended further studies on this component in order to achieve a new drug against the parasite. © 2015, Tehran University of Medical Sciences (TUMS). All rights reserved

Lower Serum Level of Anti-tetanus Toxin Antibodies in Patients with Type 2 Diabetes Mellitus

Aim: to evaluate the serum levels of anti-tetanus toxin antibodies (anti-TTA) in patients with type 2 diabetes mellitus (DM) and in a control group. Methods: totally, 100 patients with type 2 DM and 100 age-and sex-matched healthy individuals were enrolled to study. The presence of type 2 DM confirmed according to the clinical and para-clinical criteria such as fasting plasma glucose above 126 mg/dl. A peripheral blood sample was collected from all subjects. The serum samples of participants tested for the levels of anti-TTA by ELISA method. The serum antitoxin concentration ≥0.1 IU/mL was considered as a protective level of antibody. Results: the seroprotective rate in healthy group was significantly higher than diabetic group (99% vs. 92%; p40 years was also lower in comparison to those with age 5 years (3.91±0.35 IU/ml vs 2.85±0.38 IU/ml; p40 years and in diabetic patients with disease duration >5 years . Key words: immunity, tetanus, antibody, type 2 diabetes