Synthesis and characterization of dextran esters as coating or matrix systems for oral delivery of drugs targeted to the colon

Different dextran esters with various degrees of substitution (1, 2 and 3) were synthesized by esterification reaction, with three acid anhydrides: acetic anhydride, propionic anhydride, and butyric anhydride, separately. These modified polysaccharides were characterized by FT-IR, 1H NMR and 13C NMR spectroscopies. Enzymatic degradation of biopolymers by dextranase was also studied. The polymers showing the best degradation profiles were chosen to design blended free films in combination with a polymethacrylate (Eudragit® RS 30D) as a sustained release system for targeting to the colon. These free films were evaluated by permeability of theophylline used as tracer in different in vitro media of the gastro intestinal tract, in presence or in absence of dextranase. From these studies, it was concluded that dextran esters having the lower degree of substitution and constituted of short carbohydrate chains showed the best and significant enzymatic degradation and could be used as a promising carrier for specific colon drug delivery system.Keywords: Colon-Specific Drug Delivery; Polysaccharides; Dextran; Dextranase; Dextran esters; Enzymatic Degradation; Eudragit® RS 30D; Sid-by-side diffusion cel

Pulsating B-type stars in the young open cluster h Persei (NGC 869)

We announce the discovery of six Beta Cephei stars and many other variable stars in the young open cluster h Persei (NGC 869). The cluster seems to be very rich in variable B-type stars, similarly to its twin, Chi Persei (NGC 884).Comment: 5 pages, 5 figures, Proc. HELAS-II conference, Goettingen, 20-24 August 200

The effect of protozoa on the bacterial composition and hydrolytic activity of the roe deer rumen.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. The purpose of this study was to compare the effect of the presence of protozoa in the rumen of wild roe deer (Capreolus capreolus) on the bacteria composition and digestion rate of the main carbohydrates of forage. The research material involved rumen content and rumen fluid, which were collected in the autumn-winter season, from eight adult males of roe deer with an average body mass of 22.6 kg. The microscopic analysis demonstrated that there were only protozoa in 50% of the animals sampled. Qualitative analysis revealed the presence of protozoa belonging to the genus Entodinium. The density of protozoal population varied from 6.5 to 38.7 × 105/mL rumen fluid. The analysis of bacteria composition indicated that protozoa did not have an effect on bacterial diversity. Furthermore, the results of hydrolytic activity revealed that the fastest digestion of carbohydrates was for pectin, while the slowest was inulin. The pH and redox potential in the rumen varied from 5.9 to 6.1 and from −248.1 to −251.1 mV, respectively. In summary, the presence of protozoa in the rumen of wild roe deer does not have an effect on the bacterial population and has no effect on the digestion rate of carbohydrates in the rumen

Prenatal exposure to fine particles and polycyclic aromatic hydrocarbons and birth outcomes : a two-pollutant approach

Background Previous epidemiologic studies have considered the effects of individual air pollutants on birth outcomes, whereas a multiple-pollutant approach is more relevant to public health policy. Objectives The present study compared the observed effect sizes of prenatal fine particulate matter ( PM2.5) and polycyclic aromatic hydrocarbons (PAH) (a component of PM2.5) exposures on birth outcome deficits, assessed by the single vs. two-pollutant approaches. Methods The study sample included 455 term infants born in Krakow to non-smoking mothers, among whom personal exposures to PM2.5 and PAH were monitored in the second trimester of pregnancy. The exposure effect estimates (unstandardized and standardized regression coefficients) on birth outcomes were determined using evant covariates. Results In the single-pollutant approach, each pollutant was inversely associated with all birth outcomes. The effect size of prenatal PAH exposure on birth weight and length was twice that of PM2.5, in terms of standardized coefficients. In the two-pollutant approach, the negative effect of PM2.5 on birth weight and length, adjusted for PAH exposure, lost its significance. The standardized effect of PAH on birth weight was 10-fold stronger ($\beta$ = -0.20, $\rho$ = 0.004) than that estimated for PM2.5 ($\beta$ = -0.02, $\rho$ = 0.757). Conclusion The results provide evidence that PAH had a greater impact on several measures of fetal development, especially birth weight, than PM2.5. Though in the singlepollutant models PM2.5 had a significant impact on birth outcomes, this effect appears to be mediated by PAH

Obtención de shortenings cero-trans con alta estabilidad termo-oxidativa por transesterificación enzimática

Novel zero-trans frying shortenings were formed by enzymatic transesterification by exploring a palm stearin and canola oil mixture and stearic acid as substrates. Both immobilized (Novozym 435, Lipase PS “Amano” IM) and non-immobilized (Lipomod TM 34P) enzymes were applied as biocatalysts. Palmitic acid, the fatty acid which defines the proper type of crystal formation, was present at the 15% level in the reaction mixtures. The novel structured lipids had comparable physical properties and offered similar frying performance to those of commercial shortening. Needle-shaped crystals were predominant both in the transesterification products and the commercial frying shortening. Furthermore, solid fat content profiles of the zero-trans structured lipids produced by Novozym 435 and Lipase PS “Amano” IM were close to those of the commercial shortening.Los innovadores shortenings cero-trans para frituras se obtenían por transesterificación enzimática utilizando como sustratos una mezcla de estearina de palma con aceite de cánola y ácido esteárico. Tanto las enzimas inmovilizadas (Novozym 435, Lipase PS “Amano” IM) como las no inmovilizadas (Lipomod TM 34P) fueron aplicadas como biocatalizadores. El contenido de ácido palmítico, el ácido graso que define el tipo adecuado de formación cristalina, fue del 15% en las mezclas de reacción. Los lípidos estructurados innovadores tenían propiedades físicas comparables a los shortenings comerciales y estabilidad de oxidación térmica similar en proceso de fritura. Los cristales en forma de aguja predominaban tanto en los productos de transesterificación como en los shortenings para frituras disponible en el mercado. Además, los perfiles de contenido de grasa sólida de los lípidos estructurados cero trans producidos por Novozym 435 y Lipase PS “Amano” IM eran similares a los perfiles de los shortenings comerciales

Effect of three common SNPs in 5′-flanking region of LEP and ADIPOQ genes on their expression in Polish obese children and adolescents

Genes encoding adipokines are considered as candidates for human obesity. In this study we analyzed the expression of leptin (LEP) and adiponectin (ADIPOQ) genes in relation to common 5′-flanking or 5′UTR variants: -2548G>A (LEP), 19A>G (LEP) and -11377C>G (ADIPOQ) in Polish obese children and adolescents. Relative transcription levels in the subcutaneous adipose tissue (real time RT–PCR) and serum protein concentrations (RIA) were measured in 48 obese subjects with known genotypes at three polymorphic sites and in five non-obese controls. None of the studied polymorphisms altered significantly the expression. Significantly elevated relative transcription levels of the LEP gene (P < 0.05) and serum leptin concentrations (P < 0.01) were recorded in obese patients, when compared with the non-obese controls, but such differences were not found for the ADIPOQ gene. Interestingly, the leptin to adiponectin protein concentration ratio (L/A) was approximately sevenfold higher in obese children and adolescents when compared with the non-obese controls (P < 0.001). Taking into consideration the observed relationship between the genotypes and the gene expression level we suggest that these SNPs are not conclusive markers for predisposition to obesity in Polish children and adolescents. On the other hand, we confirmed that the leptin to adiponectin gene expression ratio (L/A) is an informative index characterizing obesity

Estimating progression-free survival in patients with glioblastoma using routinely collected data

Glioblastoma (GBM) represents 80% of all primary malignant brain tumours in adults. Prognosis is poor, and there is a clear correlation between disease progression and deterioration in functional status. In this pilot study we assess whether we can estimate disease progression and progression free survival (PFS) from routinely collected electronic healthcare data. We identified fifty patients with glioblastoma who had chemo-radiotherapy. For each patient we manually collected a reference data set recording demographics, surgery, radiotherapy, chemotherapy, follow-up and death. We also obtained an electronic routine data set for each patient by combining local data on chemotherapy/radiotherapy and hospital admissions. We calculated overall survival (OS) and PFS using the reference data set, and estimated them using the routine data sets using two different methods, and compared the estimated measures with the reference measures. Overall survival was 68% at 1 year and median OS was 12.8 months. The routine data correctly identified progressive disease in 37 of 40 patients and stable disease in 7 of 10 patients. PFS was 7.4 months and the estimated PFS using routine data was 9.1 and 7.8 months with methods 1 and 2 respectively. There was acceptable agreement between reference and routine data in 49 of 50 patients for OS and 35 of 50 patients for PFS. The event of progression, subsequent treatment and OS are well estimated using our approach, but PFS estimation is less accurate. Our approach could refine our understanding of the disease course and allow us to report PFS, OS and treatment nationally

Loss of Prestin Does Not Alter the Development of Auditory Cortical Dendritic Spines

Disturbance of sensory input during development can have disastrous effects on the development of sensory cortical areas. To examine how moderate perturbations of hearing can impact the development of primary auditory cortex, we examined markers of excitatory synapses in mice who lacked prestin, a protein responsible for somatic electromotility of cochlear outer hair cells. While auditory brain stem responses of these mice show an approximately 40 dB increase in threshold, we found that loss of prestin produced no changes in spine density or morphological characteristics on apical dendrites of cortical layer 5 pyramidal neurons. PSD-95 immunostaining also showed no changes in overall excitatory synapse density. Surprisingly, behavioral assessments of auditory function using the acoustic startle response showed only modest changes in prestin KO animals. These results suggest that moderate developmental hearing deficits produce minor changes in the excitatory connectivity of layer 5 neurons of primary auditory cortex and surprisingly mild auditory behavioral deficits in the startle response

Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel