Synthesis and Physical Studies of the Organic Salts of Pindolol: Pindolol Benzoate and Pindolol 2-Methoxyphenylacetate

In order to investigate the formation of organic salts of drugs, two salts of pindolol were prepared using salt-forming agents which were crystalline and suitable for physical studies in the solid state. The stoichiometry of the products, pindolol benzoate and pindolol 2-methoxyphenylacetate, was established by elemental analysis. The precipitates formed were assessed by differential scanning calorimetry (DSC), thermogravimetry (TG), x-ray powder diffractometry (XRPD) and Fourier transform-infrared spectrometry (FT-IR). According to the TG and DSC curves, there was no water of crystallization in the precipitates, and the products were thermally stable. Both precipitates gave one sharp melting endotherm which differed from the endotherms of the starting compounds. The x-ray dipaction pattern of the precipitates direred clearly from those of the starting materials, acid and base. The products showed absorption by FT-IR typical of carboxylic acid salts at about 1640-1540 cm^-1. The carbonyl absorption indicative of the carboxylic acid group of benzoic acid or 2-methonyphenylacetic acid was not detectable in the spectra of the precipitates. All this indicates that two new crystalline organic salts (1:1) were formed during the syntheses.     

The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration

Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, with a particular focus on the role of Piezo1 in controlling myogenic precursor activity and skeletal muscle regeneration and vascularization. The disclosed effects reported by pharmacological activation of Piezo1 channels with the selective agonist Yoda1 indicate a potential impact of Piezo1 channel activity in skeletal muscle regeneration, which is disrupted in various muscular pathological states. All findings reported so far agree with the idea that Piezo1 channels represent a novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating skeletal muscle disorders characterized by an impairment of tissue regenerative potential.     

Determination of the sources of indoor PM2.5 in Amsterdam and Helsinki

Daily PM2.5 samples were repeatedly collected (1-8 times) in the homes of elderly nonsmoking individuals with coronary heart disease in Amsterdam, The Netherlands (33 individuals) and Helsinki, Finland (44 individuals). Sources of indoor PM2.5 were evaluated using a two-way multilinear engine model. Because the indoor elemental data lacked a traffic marker, separation of traffic related PM was attempted by combining the indoor data with fixed site outdoor data that also contained NO. Six outdoor sources, including long-range transport (LRT), urban mixture, oil combustion, traffic, sea-salt, and soil were identified, and three indoor sources were resolved: resuspension, potassium-rich and copper-rich sources. The average contribution of the indoor factors was 6% (1.1 microg m(-3)) and 22% (2.4 microg m(-3)) in Amsterdam and Helsinki, respectively. The highest longitudinal correlations between source-specific outdoor and indoor PM2.5 concentrations were found for LRT and urban mixture; the median R was above 0.6 for most sources. The longitudinal correlations were lower in Helsinki than in Amsterdam. Indoor-generated PM2.5 was not related to ambient concentrations. We conclude that using outdoor and indoor data together improved the source apportionment of indoor PM2.5. The results support the use of fixed site outdoor measurements in epidemiological time-series studies on outdoor air pollution.     

Processing of rye bran influences both the fermentation of dietary fibre and the bioconversion of lignans by human faecal flora in vitro

Plant lignans are converted to mammalian forms, enterodiol and enterolactone, in the colon. Enhanced plasma or urinary enterolactone levels have been associated with lowered risk of cardiovascular diseases and breast cancer. Processed rye bran and its fractions were compared to ascertain the fermentation rates of fermentable carbohydrates and the bioconversion of lignans. Rye bran was extruded and treated with a food‐grade xylanase. Part of the xylanase‐treated rye bran was separated into a soluble rye bran extract and an insoluble residue, and a part of the xylanase‐treated rye bran was freeze‐dried without separation. All the samples were digested by pepsin and pancreatin and subsequently fermented with a human faecal inoculum in vitro. The consumption of carbohydrates, the productions of short‐chain fatty acids (SCFA), enterodiol and enterolactone were followed as a function of time. The soluble rye bran extract showed the fastest fermentation rate and the highest extent of fermentation determined as the consumption of neutral sugar residues (arabinose, xylose and glucose), the production of SCFA and the formation of enterodiol and enterolactone. Xylanase treatment enhanced the fermentation rate of extruded rye bran. An even a higher fermentation rate was observed for rye bran extract containing soluble carbohydrates. The amount of enterolactone precursors in rye seemed to be too low for enterolactone formation using an amount of substrate suitable for carbohydrate fermentation. However, xylanase treatment enhanced the availability of plant lignans from rye bran, as enterodiol formation was increased by the use of xylanase. Copyright © 2005 Society of Chemical Industry     

BET Inhibition Upregulates SIRT1 and Alleviates Inflammatory Responses

Control of histone acetylation is a part of the epigenetic mechanism that regulates gene expression and chromatin architecture. The members of the bromodomain and extra terminal domain (BET) protein family are a group of epigenetic readers that recognize histone acetylation, whereas histone deacetyl‐ ases such as sirtuin 1 (SIRT1) function as epigenetic erasers. We observed that BET inhibition by the specific inhibitor JQ1 upregulated SIRT1 expression and activated SIRT1. Moreover, we observed that BET inhibition functionally reversed the pro‐inflammatory effect of SIRT1 inhibition in a cellular lung disease model. SIRT1 activation is desirable in many age‐related, metabolic and inflammatory diseases; our results suggest that BET protein inhibition would be beneficial in treatment of those conditions. Most importantly, our findings demonstrate a novel mechanism of SIRT1 activation by inhibition of the BET proteins.     

Volatile compounds of Baltic herring analysed by dynamic headspace sampling–gas chromatography–mass spectrometry

European Food Research and Technology - The effect of storage time at 6&;nbsp;°C on the volatile compounds of Baltic herring was studied using the dynamic headspace–gas...     

The association of distress and sleeping problems with physicians’ intentions to change profession: The moderating effect of job control.

The present study examined whether job control moderated the association between stress indicators (distress and sleeping problems) and intentions to change profession among 2,650 Finnish physicians. Ordinal logistic regression analysis was applied. The authors found that high levels of distress and sleeping problems were associated with higher levels of intentions to change profession, whereas high job control was associated with lower levels of intentions to change profession even after adjusting for the effects of gender, age, and employment sector. In addition, high job control was able to mitigate the positive association that distress and sleeping problems had with intentions to change profession. Our findings highlight the importance of offering more job control to physicians to prevent unnecessary physician turnover. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Guidance in computer-supported collaborative inquiry learning: Capturing aspects of affect and teacher support in science classrooms

International Journal of Computer-Supported Collaborative Learning - Technology-enhanced collaborative inquiry learning has gained a firm position in curricula across disciplines and educational...     

Technology, human, and society centred visions of the future of technology

In this article we look at the conceptions computing professionals have of the future. We studied these conceptions by analysing 31 essays on the future published in theCommunications of the ACM. We found the future was envisioned from three different perspectives: in addition to a technology centred perspective the authors also used human centred and society centred perspectives, but region centred and organisation centred perspectives were missing. I assume the visions of these individuals of future technology represent the culture of the computing field as they are published in one of the top computer science journals.     

Assessment of bioavailability and effects of chemicals due to remediation actions with caging mussels (Anodonta anatina) at a creosote-contaminated lake sediment site

A study was conducted at Lake J?ms?nvesi in Central Finland, to identify the potential ecotoxicological risks of the remediation operation of a creosote-/PAH-contaminated lake sediment, made by capping during the years 1998-1999. Mussels (Anodonta anatina) were deployed to the lake at the same time as the remediation operation was started in November 1998. The contaminated area (0.5 ha) was covered by a filter geotextile (polypropylene), gravel and sand (1-1.5m) which were spread out on the ice and let to sink onto the bottom of the lake when the ice melted in May 1999. The possible impacts of capping to the adjacent environment were assessed from mussels exposed and particulate material settled (SPM) to collectors placed on the lake bottom. Mussel tissue, SPM, the water inside the collector were analyzed for polycyclic aromatic compounds (PAH)-compounds. Biological endpoints included body condition, glycogen and protein contents of adductor muscle. Mussels and SPM exposed downstream to the contaminated site (Site 3) contained the highest total PAH concentrations. Biota-sediment accumulation factors of acenaphthene, phenanthrene, anthracene, fluoranthene, pyrene and benzo(a)anthracene of mussels varied from 0.79 to 1.45. The glycogen and protein concentrations were lowest in adductor muscle from mussels exposed to conditions at Site 3. Concentrations of some PAH-compounds were found distinctly increased adjacent to the remediated area, possibly due to the agitation of contaminated sediment due to the capping. It is also possible that resuspension of sediment around remediated area (containing some PAHs) spread the deposited PAH-compounds.