Sesquiterpene lactone and diterpene constituents of helianthus annuus

One new furanoheliangolide derivative, 4,5-dihydroniveusin A, as well as the known compounds niveusin B and argophyllin A and B, were isolated from a Texas population of Helianthus annuus. Three previously characterized diterpene acids, grandifloric acid, ciliaric acid and 17-hydroxy-ent-isokaur-15(16)-en-19-oic acid were the principal constituents of this population.     

Effect of penicillin G-induced epileptic seizures on hemorheological parameters in rats

Normally, cerebral blood flow (CBF) is quantitatively coupled to cerebral metabolic rate like other tissues and maintained basically by altering vascular geometry and appropriate perfusion pressure. However, the rheological properties of the blood are important factors for effective tissue perfusion. Although a lot of studies have reported that hemorheological parameters are affected by a wide range of pathophysiological conditions, to our knowledge no research related to the effects of epileptic seizures on hemorheological parameters has been carried out. Thus, the aim of this study was to explore possible changes in rheological parameters including red blood cell (RBC) deformability, rigidity and aggregation, whole blood and plasma viscosity during epileptic seizures induced by penicillin G in rats. Eighteen female albino rats were divided into three groups that included sham operated controls (Group S), epileptic group (Group E), intraperitoneal penicillin group (Group IPP). Epilepsy was induced by intracortical injections of penicillin G. Hemorheological studies had been carried out 3 h after the induction of epilepsy. Among the studied hemorheological parameters, only RBC deformability was found to be different in the E group compared to S group. Epileptic seizures led to an increase in RBC deformability in the E group. In conclusion, these results suggest that in addition to an increase in CBF, RBC deformability may also improve to better match brain metabolic demands during seizures.     

Chronic Fluoride Exposure Has a Role in Etiology of Coronary Artery Ectasia: Sialic Acid/Glycosaminoglycan Ratio

The sialic acid/glycosaminoglycan ratio was determined in 35 coronary artery ectasia patients and 35 control subjects to determine the possible role of fluoride in the etiology of the disease. The coronary artery ectasia patients and controls were selected from subjects who underwent coronary angiography. The mean serum sialic acid level was significantly lower in patients with coronary artery ectasia (CAE) than in controls (340.3 ± 28.6 vs. 427.0 ± 15.9 μg/mL, respectively; p < 0.001). The mean serum glycosaminoglycan level was significantly higher in patients with CAE than in controls (5,013.1 ± 158.6 vs. 3,833.6 ± 237.1 μg/mL, respectively; p < 0.001). The sialic acid/glycosaminoglycan ratio in patients with coronary artery ectasia was significantly lower than in controls (0.068 ± 0.007 vs. 0.111 ± 0.005; p < 0.001). There was more than 38.7% reduction in this ratio in patients with CAE when compared with controls. We demonstrated that chronic fluoride exposure has an important role in pathogenesis of coronary artery ectasia.     

Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients

A relationship between hormones and seizures has been reported in animals and humans. Therefore, the purpose of this study was to investigate the association between serum levels of prolactin, nesfatin-1 and ghrelin measured different times after a seizure or non-epileptic event and compared with controls. The study included a total of 70 subjects, and of whom 18 patients had secondary generalized epilepsy (SGE), 16 patients had primary generalized epilepsy (PGE), 16 patients exhibited paroxysmal event (psychogenic) and 20 healthy males were control subjects. The first sample was taken within 5 min of a seizure, with further samples taken after 1, 24, and 48 h so long as the patient did not exhibit further clinically observable seizures; blood samples were taken once from control subjects. Prolactin was measured immediately using TOSOH Bioscience hormone assays. Nesfatin-1 and ghrelin peptides were measured using a commercial immunoassay kit. Patients suffering from focal epilepsy with secondary generalization and primary generalized epilepsy presented with significantly higher levels of serum prolactin and nesfatin-1 and lower ghrelin levels 5 min, 1 and 24 h after a seizure than patients presenting with paroxysmal events (psychogenic) and control subjects; the data were similar but not statistically significant after 48 h. The present study suggests that increased serum prolactin and nesfatin-1 concentrations, decreased ghrelin concentrations could be used as markers to identify patients that have suffered a recent epileptic seizure or other paroxysmal event (psychogenic).     

Cardiopulmonary bypass as a cause of free radical-induced oxidative stress and enhanced blood-borne isoprostanes in humans

Free radicals are believed to be involved in postsurgery-related complications. We studied whether cardiopulmonary bypass (CPB) operation has any immediate impact on the initiation of oxidative stress and inflammatory response by measuring isoprostanes and prostaglandin F2alpha during and 24 h following CPB. The levels of 8-iso-PGF2alpha (a major F2-isoprostane and biomarker of oxidative stress) and 15-keto-dihydro-PGF2alpha (a major metabolite of PGF2alpha and biomarker of inflammatory response) were measured in frequently collected plasma samples before, during, and up to 24 h postsurgery in 21 patients. 8-Iso-PGF2alpha levels significantly increased within 3 min (p <.0001) and continued until 50 min (p <.0001) during CPB. On the contrary, no significant increase of inflammatory response indicator, 15-keto-dihydro-PGF2alpha was found during and up to 24 h postoperatively. These findings establish an increased free radical-induced oxidative stress activity rather than inflammatory response after CPB.     

Encapsulation of Pt-labelled DNA Molecules inside Carbon Nanotubes

Experiments on encapsulating Pt--labelled DNA molecules inside multiwalled carbon nanotubes (MWCNT) were performed under temperature and pressure conditions of 400K and 3 Bar. The DNA-CNT hybrids were purified via agarose gel electrophoresis and analyzed via high resolution transmission electron microscopy (HR-TEM) and energy dispersive X-ray spectroscopy (EDX). The results showed that the Pt-labelled DNA molecules attached to the outside walls of CNTs could be removed by electrophoresis. The HR-TEM and EDX results demonstrated that 2-3% of the Pt-labelled DNA molecules were successfully encapsulated inside the MWCNTs. The experimental study complements our previous molecular dynamics simulations on encapsulation of single stranded DNA oligonucleotides inside single wall carbon nanotubes under similar conditions in water. The van der Waals interaction between CNT and Pt-labelled DNA is believed to be the main driving force for this phenomenon. The DNA-CNT molecular complex could be further explored for potential applications in bio-nanotechnology.     

Prevalence of extended-spectrum beta-lactamases produced by nosocomial isolates of Enterobacteriaceae in Trakya University Hospital,Turkey

The prevalence of extended-spectrum beta-lactamase (ESBL) production by 194 nosocomial isolates of Enterobacteriacea recovered from 1995 to 1999 was investigated. The ESBL production was determined by the double-disk synergy test and was confirmed by the E-test ESBL strip. Twenty-three isolates (21 Klebsiella pneumoniae, one Escherichia coli, one Providencia rettgeri) were found as ESBL-producers (11.8%). These isolates were also usually resistant to non-betalactam antibiotics. Most of them contained a beta-lactamase with a pI of 7.6. All the strains conjugally transferred their ESBLs to recipient E. coli. Contrary to others, ESBL-producing K. pneumoniae strains isolated in 1999 were resistant to ciprofloxacin, and had the identical plasmid profiles suggestive of an outbreak. Ciprofloxacin resistance in these strains could not be transferred. In conclusion, K. pneumoniae was the main ESBL-producing species among nosocomial isolates of Enterobacteriacae in our hospital.     

Exome sequences and multi‐environment field trials elucidate the genetic basis of adaptation in barley

Broadening the genetic base of crops is crucial for developing varieties to respond to global agricultural challenges such as climate change. Here, we analysed a diverse panel of 371 domesticated lines of the model crop barley to explore the genetics of crop adaptation. We first collected exome sequence data and phenotypes of key life history traits from contrasting multi‐environment common garden trials. Then we applied refined statistical methods, including some based on exomic haplotype states, for genotype‐by‐environment (G×E) modelling. Sub‐populations defined from exomic profiles were coincident with barley's biology, geography and history, and explained a high proportion of trial phenotypic variance. Clear G×E interactions indicated adaptation profiles that varied for landraces and cultivars. Exploration of circadian clock‐related genes, associated with the environmentally adaptive days to heading trait (crucial for the crop's spread from the Fertile Crescent), illustrated complexities in G×E effect directions, and the importance of latitudinally based genic context in the expression of large‐effect alleles. Our analysis supports a gene‐level scientific understanding of crop adaption and leads to practical opportunities for crop improvement, allowing the prioritisation of genomic regions and particular sets of lines for breeding efforts seeking to cope with climate change and other stresses.     

Whole-exome sequencing reveals damaging gene variants associated with hypoalphalipoproteinemia

Low levels of high density lipoprotein-cholesterol (HDL-C) are associated with an elevated risk of arteriosclerotic coronary heart disease. Heritability of HDL-C levels is high. In this research discovery study, we used whole-exome sequencing to identify damaging gene variants that may play significant roles in determining HDL-C levels. We studied 204 individuals with a mean HDL-C level of 27.8 ± 6.4 mg/dl (range: 4–36 mg/dl). Data were analyzed by statistical gene burden testing and by filtering against candidate gene lists. We found 120 occurrences of probably damaging variants (116 heterozygous; four homozygous) among 45 of 104 recognized HDL candidate genes. Those with the highest prevalence of damaging variants were ABCA1 (n = 20), STAB1 (n = 9), OSBPL1A (n = 8), CPS1 (n = 8), CD36 (n = 7), LRP1 (n = 6), ABCA8 (n = 6), GOT2 (n = 5), AMPD3 (n = 5), WWOX (n = 4), and IRS1 (n = 4). Binomial analysis for damaging missense or loss-of-function variants identified the ABCA1 and LDLR genes at genome-wide significance. In conclusion, whole-exome sequencing of individuals with low HDL-C showed the burden of damaging rare variants in the ABCA1 and LDLR genes is particularly high and revealed numerous occurrences in HDL candidate genes, including many genes identified in genome-wide association study reports. Many of these genes are involved in cancer biology, which accords with epidemiologic findings of the association of HDL deficiency with increased risk of cancer, thus presenting a new area of interest in HDL genomics.     

Development of stability indicating HPLC method for the separation and validation of enantiomers of miconazole

A selective and sensitive stability indicting HPLC method was developed for the analysis of enantiomers of miconazole. For this purpose, six different polysaccharide‐based chiral columns were evaluated. Optimization was performed using several polar organic and alcohol‐hydrocarbon mobile phases. As a result of optimization studies, the analysis was carried out using Lux Cellulose‐3, methanol as a mobile phase at a flow rate of 1 mL·min^?1, and the detection wavelength was arranged to 230 nm. Developed method has been fully validated according to International Council on Harmonization guidelines. Method was found linear in the concentration range of 1 to 200 μg·mL^?1. Coefficient of determination (R²) was calculated as 0.9996, intraday precision of the method was found with the RSD% of 0.56, and the recovery of the method was calculated close to 100%. Furthermore, some other validation parameters like specificity, selectivity, LOD, and LOQ were also investigated. Stability indicating capability of this method was shown by forced degradation studies, and the run time for each analysis was less than 6 minutes. As a result, simple, fast, reliable HPLC method was developed for the separation and determination of the enantiomers of miconazole. Applicability of the developed method was shown with the application of marketed pharmaceutical preparations.