Plasma pharmacokinetics, faecal excretion and efficacy of pyrantel pamoate paste and granule formulations following per os administration in donkeys naturally infected with intestinal strongylidae

The plasma disposition, faecal excretion and efficacy of two formulations of pyrantel pamoate in donkeys were examined in a controlled trial. Three groups of seven donkeys received either no medication (control) or pyrantel paste or granule formulations at horse dosage of 20mg/kg B.W. (equals 6.94 mg/kg PYR base) of body weight. Heparinized blood and faecal samples were collected at various times between 1 and 144 h after treatment. The samples were analysed by high-performance liquid chromatography. The last detectable plasma concentration (tmax) of paste formulation was significantly earlier (36.00 h) compared with granule formulation (46.29 h). Although, there was no significant difference on terminal half lives (t1/2: 12.39 h vs. 14.86 h), tmax (14.86 h vs. 14.00) and MRT (24.80 h vs. 25.44 h) values; the Cmax (0.09 ??g/ml) AUC (2.65 ??gh/ml) values of paste formulation were significantly lower and smaller compared with those of granule formulation (0.21 ??g/ml and 5.60 ??gh/ml), respectively. The highest dry faecal concentrations were 710.46 ??g/g and 537.21 ??g/g and were determined at 48 h for both paste and granule formulation of PYR in donkeys, respectively. Pre-treatment EPG of 1104, 1061 and 1139 were observed for the control, PYR paste and PYR granule groups, respectively. Pre-treatment EPG were not significantly different (P>0.1) between groups. Post-treatment EPG for both PYR treatment groups were significantly different (P95% efficacy) until day 28. In all studied donkeys, coprocultures performed at day-3 revealed the presence of Cyathostomes, S. vulgaris. Faecal cultures performed on different days from C-group confirmed the presence of the same genera. Coprocultures from treated animals revealed the presence of few larvae of Cyathostomes

Optical coherence tomography of retinal and choroidal layers in patients with familial hypercholesterolaemia treated with lipoprotein apheresis

PURPOSE: Detect and quantify morpho-functional alterations of the retina and choroid in patients affected by familial hypercholesterolemia (FH) treated with lipoprotein apheresis (LA) using optic coherence tomography (OCT) and optic coherence tomography-angriography (OCTA). DESIGN: Observational study. SUBJECTS: To be diagnosed: A group of 20 patients (40 eyes) being clinically and genetically diagnosed as FH and under treatment (FH-Group)", for at least 2 years, was compared to a control group of 20 healthy subjects (40 eyes), with a normal lipid profile and no ocular disease (CT-Group). METHODS: Participants were studied with the slit lamp, binocular indirect fundoscopy, OCT and OCTA. MAIN OUTCOME MEASURES: Best corrected visual acuity (BVCA), spherical equivalent (SE), intraocular pressure (IOP), central macular thickness (CMT), choroidal thickness (CHT), retinal nerve fiber layer in four quadrants (RNFL (Superior = Sup; Inferior = Inf; Nasal = Nas Temporal = Temp), and the mean value across the four quadrants (RNFL G), foveal avascular zone (FAZ) and vascular density (VD). RESULTS: FH subjects had smaller RNFL superiorly (108 ± 19,38 μm OD/111 ± 16,56 μm OS FH-Group vs 127 ± 7,42 μm OD/129 ± 14,64 μm OS CT-Group; P < 0,001 for both OD and OS) and inferiorly (108 ± 23,58 μm OD/115 ± 17,33 μm OS FH-Group vs 128 ± 18,15 μm OD/133 ± 17,38 μm OS CT-Group; P = 0,002 OD; P = 0,001 OS). G RNFL was consequently smaller (93 ± 12,94 μm OD/94 ± 10,49 μm OS FH-Group vs 101 ± 9,01 μm OD/101 ± 10,20 μm OS CT-Group; P = 0,03 OD; P = 0,02 OS). FH subjects had a larger FAZ (0,31 ± 0,08 mm2 OD/0,33 ± 0,10 mm2 in OS FH-Group vs 0,21 ± 0,05 mm2 OD/0,21 ± 0,07 mm2 OS CT-Group; P < 0,001 OD; P = 0,002 OS). CONCLUSIONS: Early signs of retinal vessel damage in FH patients can be detected and quantified with OCT and OCTA

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus

Preventing Prostate Biopsy Complications: to Augment or to Swab?

Aims for Improvement The aim of this study was to determine the antibiotic prophylaxis associated with the fewest infectious complications following prostate biopsy Determining the safest method allows the Jefferson Department of Urology to modify its biopsy protocol and improve the rate of post-biopsy complication

The effect of carboxylate position on the structure of a metal organic framework derived from cyclotriveratrylene

Two cyclotriveratrylene-based ligands H3L1 and H3L2 have been synthesised using microwave heating and used in the formation of 1 [Zn2(L1)(DMA)2(CH3COO)] and 2 [Zn6(L2)4(DMA)6(H2O)5] (DMA = N,N-dimethylacetamide). 1 displays an unusual trigonal paddlewheel node geometry, while Zn(II) paddlewheels are observed in 2. However the stacking of CTV molecules in 1 is replaced by an uncommon molecular capsule structure in 2

Hypoxia-inducible factor-1α gene polymorphisms and cancer risk: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The results from the published studies on the association between <it>hypoxia-inducible factor -1α </it>(HIF-1α) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between <it>HIF-1α </it>1772 C/T and 1790 G/A polymorphisms and cancer.</p> <p>Methods</p> <p>The meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.</p> <p>Results</p> <p>For the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P_{heterogeneity}< 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P_{heterogeneity}= 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P_{heterogeneity}= 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P_{heterogeneity}= 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P_{heterogeneity}= 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P_{heterogeneity}= 0.41, respectively. The frequency of the <it>HIF-1α </it>1790 A allele was very low and only two studies were included in the breast cancer subgroup.</p> <p>Conclusions</p> <p>Our meta-analysis suggests that the <it>HIF-1α </it>1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.</p

Association between forgone care and household income among the elderly in five Western European countries – analyses based on survey data from the SHARE-study

Background. Studies on the association between access to health care and household income have rarely included an assessment of 'forgone care', but this indicator could add to our understanding of the inverse care law. We hypothesize that reporting forgone care is more prevalent in low income groups. Methods. The study is based on the 'Survey of Health, Ageing and Retirement in Europe (SHARE)', focusing on the non-institutionalized population aged 50 years or older. Data are included from France, Germany, Greece, Italy and Sweden. The dependent variable is assessed by the following question: During the last twelve months, did you forgo any types of care because of the costs you would have to pay, or because this care was not available or not easily accessible? The main independent variable is household income, adjusted for household size and split into quintiles, calculating the quintile limits for each country separately. Information on age, sex, self assessed health and chronic disease is included as well. Logistic regression models were used for the multivariate analyses. Results. The overall level of forgone care differs considerably between the five countries (e.g. about 10 percent in Greece and 6 percent in Sweden). Low income groups report forgone care more often than high income groups. This associ

Understanding the adsorption process in ZIF-8 using high pressure crystallography and computational modelling

Understanding host–guest interactions and structural changes within porous materials is crucial for enhancing gas storage properties. Here, the authors combine cryogenic loading of gases with high pressure crystallography and computational techniques to obtain atomistic detail of adsorption-induced structural and energetic changes in ZIF-8

Mucociliary and long-term particle clearance in airways of patients with immotile cilia

Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients