Prediction of HBF-0259 interactions with hepatitis B Virus receptors and surface antigen secretory factors

Hepatitis B virus (HBV) is an etiological agent of viral hepatitis, which may lead to cirrhosis, and hepatocellular carcinoma. Current treatment strategies have not shown promising effect to date but various complications such as, drug toxicity-resistance have been reported. Study on newly discovered compounds, with minimal side effects, as specific HBV inhibitors is a fundamental subject introducing new biologic drugs. Here, we aimed to, by prediction, estimate interactions of HBF-0259 as a non-toxic anti-HBV compound on inhibiting the HBV through either interaction with the viral entry or HBsAg secreting factors using In Silico procedure. Molecular docking was performed by Hex 8.0.0 software to predict the interaction energy (Etot) between HBF-0259 and known cellular factors involved in HBV entry and HBsAg secreting factors. Hex 8.0.0 also employed to create protein–protein complexes. These interactions were then used to analyze the binding site of HBF-0259 within the assumed receptors by MGLTools software. Finally, the amino acid sequences involved in this interaction were aligned for any conservancy. Here, we showed that HBF-0259 Etot with CypA (–545.41 kcal/mol) and SCCA1 (499.68 kcal/mol), involved in HBsAg secretion and HBV integration, respectively, was higher than other interactions. Furthermore, HBF-0259 predicted interaction energy was even higher than those of CypA inhibitors. In addition, we claim that preS1 and/or preS2 regions within HBsAg are not suitable targets for HBF-0259. HBF-0259 has higher interaction energy with CypA and SCCA1, even more than other known receptors, co-receptors, viral ligands, and secretory factors. HBF-0259 could be introduced as potent anti-viral compound in which CypA and or SCCA1, as previously shown, are involved. © 2016 Indian Virological Societ

Designing optimal controllers for nonlinear frames by considering the effect of response feedback

AbstractThe effect of response feedback on designing optimal controllers for nonlinear frames has been studied. Different combinations of response feedback have been used in the performance index. The Newmark based nonlinear instantaneous optimal control algorithm has been used as the control algorithm in controlling the response of an eight-story bilinear hysteretic frame subjected to white noise excitation and real earthquakes, and controlled by either eight actuators or a single actuator. While the objective has been to minimize the maximum control force for reducing the maximum drift to below the yielding level, the distributed genetic algorithm (DGA) has been used to determine the proper set of weighting matrices in the performance index. Results show that the performance of the active control system depends on the combination of response feedback, where the velocity feedback has been more effective than acceleration and displacement. Also, although using the full feedback of response in the performance index leads to the design of optimal controllers that require the smallest control force, it is costlier, because it requires more online measurements. Finally, it has been concluded that amongst all possibilities, using only velocity feedback can provide the best results regarding the maximum required control force and online measurement, simultaneously

Oil characteristics and fatty acid profile of seeds from three varieties of date palm (Phoenix dactylifera) cultivars in Bushehr-Iran

Studies were conducted on properties of seed oils extracted from three date palm (Phoenix dactylifera) varieties Shahabi, Shekar and Kabkab, grown in Bushehr-Iran. The primary objective of this study was to extract seed-oil from the three native date varieties and then analyzed their fatty acids (FAs). Also the chemical parameters of PV, AV, p-anisidin, and Totox values of oils, as indicators of the quality and safety, and oxidative status of edible oils, as well as refractive index as an objective method for evaluation of rancidity were also evaluated. Date seeds are approximately 10% of the fruits weight. Seeds contained about 8.5% fat that can serve as a useful source of fatty acids to replace other vegetable oils. The following mean of values from the three varieties were obtained from samples: peroxide value (1.05), acid value (1.4), p-anisidine value (2.54), Totox (4.64) and refractive index (1.46). Also, flame ionization based detection gas chromatography (GC-FID) revealed that oleic acid was the primary fatty acid in all varieties. It was followed by lauric, myristic, palmitic, linoleic and stearic acids and trace amounts of the other fatty acids like undecylic, capric, nonanoic (pelargonic) and caprylic acids. Depending on the regional industry, these data suggest that the potential applications of date seed oil for humans and animals are feeding, cosmetic formulations such as in body creams, shaving soap and shampoos, and pharmaceutical products.Keywords: Seed oil (Phoenix dactylifera), fatty acid, gas chromatograph

Serum biochemical status and morphological changes in mice ovary associated with copper oxide nanoparticles after thiamine therapy

Introduction: Nanoparticles (NPs) can induce inflammatory responses and oxidative stress and are also cytotoxic to the genital organs of animals after exposure. The aim of this study was to assess the effects of copper oxide (CuO) and CuO NPs alone and in combination with thiamine on the ovaries of mice and on antioxidant enzymes.Methods: Sixty adult mice were randomly divided into five groups. Group A served as the control. Group B received CuO NPs and group C received CuO at 0.2 mL/kg intraperitoneally (IP). Mice in groups D and E respectively received CuO and CuO NPs along with thiamine (30 mg/L) therapy. The responses of the ovaries to the treatments were appraised by histopathology studies. The values for catalase (CAT), superoxide dismutase (SOD), and lipid peroxidation were determined after 20 days of treatment.Results: The degree of degeneration and apoptosis of the different zones within the ovaries were recorded in groups B and C. The decrease in CAT value and increase in SOD activity were significant for groups B and C at 20 days compared to the control group. The thiobarbituric acid reactive substances (TBARS) level in groups B, C and E were significantly higher at 20th day when compared with control group. The groups treated with thiamine showed histopathological and enzymatic results that were similar to those of the control group.Conclusion: These findings suggest the combination of CuO NPs and CuO with thiamine improves serum enzyme activity and has positive effects on the ovary

Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance

Inherited distal renal tubular acidosis (dRTA) is caused by impaired urinary acid excretion resulting in hyperchloremic metabolic acidosis. Although the glomerular filtration rate (GFR) is usually preserved, and hypertension and overt proteinuria are absent, it has to be considered that patients with dRTA also suffer from chronic kidney disease (CKD) with an increased risk for adverse pregnancy-related outcomes. Typical complications of dRTA include severe hypokalemia leading to cardiac arrhythmias and paralysis, nephrolithiasis and nephrocalcinosis. Several physiologic changes occur in normal pregnancy including alterations in acid-base and electrolyte homeostasis as well as in GFR. However, data on pregnancy in women with inherited dRTA are scarce. We report the course of pregnancy in three women with hereditary dRTA. Complications observed were severe metabolic acidosis, profound hypokalemia aggravated by hyperemesis gravidarum, recurrent urinary tract infection (UTI) and ureteric obstruction leading to renal failure. However, the outcome of all five pregnancies (1 pregnancy each for mothers n. 1 and 2; 3 pregnancies for mother n. 3) was excellent due to timely interventions. Our findings highlight the importance of close nephrologic monitoring of women with inherited dRTA during pregnancy. In addition to routine assessment of creatinine and proteinuria, caregivers should especially focus on acid-base status, plasma potassium and urinary tract infections. Patients should be screened for renal obstruction in the case of typical symptoms, UTI or renal failure. Furthermore, genetic identification of the underlying mutation may (a) support early nephrologic referral during pregnancy and a better management of the affected woman, and (b) help to avoid delayed diagnosis and reduce complications in affected newborns

Determination of mebudipine in human plasma by liquid chromatography�tandem mass spectrometry

In previous studies, mebudipine, a dihydropyridine calcium channel blocker, showed a considerable potential to be used in cardiovascular diseases. The aim of the current study was to develop a valid method using reversed-phase high performance liquid chromatography coupled with electrospray ionization mass spectrometry to assay mebudipine in the human plasma. Separation was achieved on a Zorbax Eclipse® C18 analytical column using a mobile phase consisted of methanol/water (90:10, v/v). The flow rate was 0.6 mL/min and carbamazepine was used as an internal standard (IS). This method involved the use of M +Na+ ions of mebudipine and IS at m/z 411 and 259, respectively with the selected ion monitoring (SIM) mode. There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r2>0.99) between 5 to 100 ng/mL. The mean extraction efficiency was about 84% and the limit of quantification for mebudipine was 5 ng/mL in plasma. The coefficient of variation and error at all of the intra-day and inter-day assessments were less than 11%. The results indicated that this method is a fast, accurate, sensitive, selective and reliable method for the determination of mebudipine in the human plasma. The assay method has been successfully used to estimate plasma concentration of mebudipine after the oral administration of 2.5 mg tablet in healthy adults. © 2015 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services

The fluctuations of physicochemical factors and phytoplankton populations of Urmia Lake, Iran

Urmia Lake is one of the two large hypersaline lakes in the world which have Artemia. It is located in northwest of Iran. Due to a decrease in water inflow and volume, the salinity of Urmia Lake has reached to more than 300 g.l-1 since 2001. The increased salinity has greatly influenced biological aspects of the lake, and caused the lake undergoes at critical conduction. The aim of the present study was to investigate the distribution fluctuations of phytoplanktons and selected physicochemical factors in relation to Artemia distribution in Urmia Lake during 8 months. Statistical analysis of mean values of ion concentrations and phytoplankton abundance indicated significant differences among sampling months. The minimum and maximum values for the selected factors were, as Cl- 176.2-201.3 g.l-1 , CO2 95-175mg.l-1 , dissolved oxygen (DO) 0.1-2.8 mg.l-1 , HCO3 - 144-496 mg.l-1 , PO42+ 104-875 mg.l-1, NO3- 330-4104 mg.l-1, NO2- 4-21.5 mg.l-1, SO42- 10490-29840 mg.l-1, Ca2+ 561-1606 mg.l-1, Mg2+ 3649-14587 mg.l-1 while water hardness was 21000- 62000 mg.l-1. Fourteen phytoplankton genera included Bacillariophyceae (10 genera),Chlorophyceae (2 genera) and Cyanophyceae (2 genera) were identified during sampling period. The smallest average density of phytoplankton 97249 L-1 was observed in December 2005 and the greatest average density 481983 L-1 in August 2005. Dunaliella sp. composed 92.1% of the lake's phytoplankton. Statistical analysis of phytoplanktons fluctuations showed a significant difference among different months (p< 0.05)

Association of variable number of tandem repeats in endothelial nitric oxide synthase gene with coronary artery disease

Endo-derived nitric oxide (NO) is synthesized from L-arginine by endothelium nitric oxide synthase (eNOS). Since reduced NO synthesis has been implicated in the development of coronary atherosclerosis; we hypothesized that polymorphisms of NOS gene might be associated with increased susceptibility to this disorder and coronary artery disease (CAD). We studied the 27 base pair tandem repeat polymorphism in intron4 of the endothelial nitric oxide synthase (eNOS) gene in 141 unrelated CAD patients with positive coronary angiograms in Shahid Rajaee Heart Hospital and 159 age matched control subjects without a history of symptomatic CAD. The study protocol was approved by the Iran University of Medical Sciences Ethics Committee. The eNOS gene intron4a/b VNTR polymorphism was analyzed by polymerase chain reaction. The plasma lipids levels and other risk factors were also determined. The genotype frequencies for eNOS4b/b, eNOS4a/b and eNOS4a/a were 68.8, 29.1 and 2.1 in CAD subjects, and 81, 18.4 and 0.6 in control subjects, respectively. The genotype frequencies differed significantly between the two groups (�2= 6.38 P= 0.041). The frequency of the allele was 16.7 in CAD subjects and 9.8 in control subjects and was significantly higher in the patients (�2= 6.18 P= 0.013, odds ratio=1.84). Plasma lipids, except HDL-C were also remarkablely increased in CAD group

C-reactive protein and coronary calcium score association in coronary artery disease

Background: Both high-sensitivity C-reactive protein (hs-CRP) and spiral computed tomography coronary artery calcium score (CCS) are valid markers of cardiovascular risk. It is unknown whether hs-CRP is a marker of atherosclerotic burden or whether it reflects a process leading to acute coronary events. Methods and Results: We studied the relation between hs-CRP and CCS in 143 patients that were candidates for coronary artery bypass grafting (CABG). In our cross-sectional study, we found no significant association between hs-CRP and CCS in bivariate (p = 0.162) and multivariate (p = 0.062) analysis, but in patients who did not use statins this association was positive and significant in bivariate analysis (p = 0.001), and in multivariate analysis this association was negative and significant (p = 0.008). Conclusions: High-sensitivity CRP was not correlated with CCS. The relation between CRP and clinical events might not be related to atherosclerotic burden. Measures of inflammation, such as hs-CRP, and indices of atherosclerosis, such as CCS, are likely to provide distinct information regarding cardiovascular risk. Copyright © 2008 Via Medica

Fluctuation in density of ciliates in Bukan dam reservoir, Zarrinehrud, Iran

The abundance and species composition of ciliates were analyzed in the Bukan Dam Reservoir (West Azerbaijan, Iran) from January to December 2008. Surface water samples were collected at monthly intervals from the middle (Stations 1 and 3) and shallow (Stations 2 and 4) areas of the lake. Three samples were taken in the water column using a 5-litre sampler. Totally 30 liters water was collected, 200 ml of which was fixed immediately with 8.6 ml of a saturated HgCl2 solution and stained with 0.04% bromophenol blue. Three subsamples were counted in a 5-ml chamber and examined with a microscope (100 x) as well as Chlorophyll a and a few ecological parameters such as dissolved oxygen, pH, transperancy and water temperature were measured. Totally 50 ciliates species were found in Bukan Dam Reservoir. Regarding the density, a high-density period was detected from January to April with a mean density of 2.86 x 103 cells.l-1 Ciliata at stations 1 and 3 and 4.16 x 103 cells.l-1 at stations 2 and 4. The high density of ciliate in summer may be due to the increase in the density of bacteria and moderate metazooplankton as a result of the appearance of non-edible algae . The ciliata occurring at the highest densities were Coleps tessellates, Didinium nasutum, Paradileptus elephantinus, Stentor polymorphus, Zosterograptus labiatus, Paramecium bursaria, Cyclidium citrullus, Vorticella campanula, Halteria grandinella and Aspidisca costata. The maximum and minimum chlorophyll a values observed at the reservoir water were 10.39 µg.l-l and 1.0 µg.l-l being obtained in May and Octobor respectively