2,3-Dichloro-1,4-hydroquinone 2,3-dichloro-1,4-benzoquinone monohydrate: a quinhydrone-type 1:1 donor-acceptor [D-A] charge-transfer complex

In the crystal structure of the title compound (systematic name: 2,3-dichlorobenzene-1,4-diol 2,3-dichlorocyclohexa-2,5-diene-1,4-dione monohydrate), C(6)H(4)Cl(2)O(2)center dot C(6)H(2)Cl(2)O(2)center dot H(2)O, the 2,3-dichloro-1,4-hydroquinone donor (D) and the 2,3-dichloro-1,4-benzoquinone acceptor (A) molecules form alternating stacks along [100]. Their molecular planes [maximum deviations for non-H atoms: 0.0133 (14) (D) and 0.0763 (14) angstrom (A)] are inclined to one another by 1.45 (3)degrees and are thus almost parallel. There are pi-pi interactions involving the D and A molecules, with centroid-centroid distances of 3.5043 (9) and 3.9548 (9) angstrom. Intermolecular O-H center dot center dot center dot O hydrogen bonds involving the water molecule and the hydroxy and ketone groups lead to the formation of two-dimensional networks lying parallel to (001). These networks are linked by C-H center dot center dot center dot O interactions, forming a three-dimensional structure.

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs

To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg(-1)) as a positive control, followed by TDB (52.5 mug h(-1)) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL(-1) (+/-1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 degrees C (+/-0.48) at 1h after IVB administration and 51.63 degrees C (+/-1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect.

Effect of oral donepezil on intraocular pressure in normotensive Alzheimer patients

Donepezil, a selective acetylcholinesterase (AChE) inhibitor, has been shown to reduce intraocular pressure (IOP) in ocular normotensive rabbit eyes. The aim of this investigation was to evaluate the effect of oral donepezil on IOP and pupil diameter after mid-term oral treatment in normotensive persons. Thirty-two newly diagnosed Alzheimer patients with normal IOP and no further antiglaucomatous treatment were included in the study. IOP and pupil diameter were evaluated before and 4 weeks after daily intake of 5 mg donepezil. IOP and pupil diameter were significantly lower/smaller after 4 weeks of treatment. The mean IOP of all 63 eyes was 14.1 mmHg before and 12.8 mmHg after treatment (8.8% reduction). Mean pupil diameter constricted from 3.9 to 3.6 mm (-7.4%). These findings show that donepezil, and, possibly, other selective AChE inhibitors, can potentially be used to treat glaucoma. They are also known to have neuroprotective effects in Alzheimer's, and, therefore, might have an additional therapeutic benefit.

Characterization of apxIVA, a new RTX determinant of Actinobacillus pleuropneumoniae

A fourth type of RTX determinant was identified in Actinobacillus pleuropneumoniae and was designated apxIVA. When expressed in Escherichia coli, recombinant ApxIVA showed a weak haemolytic activity and co-haemolytic synergy with the sphingomyelinase (beta-toxin) of Staphylococcus aureus. These activities required the presence of an additional gene, ORF1, that is located immediately upstream of apxIVA. The apxIVA gene product could not be detected in A. pleuropneumoniae cultures grown under various conditions in vitro; however, pigs experimentally infected with A. pleuropneumoniae serotypes 1, 5 and 7 started to produce antibodies that reacted with recombinant ApxIVA 14 d post-infection, indicating that apxIVA is expressed in vivo. In addition, sera from pigs naturally and experimentally infected with any of the serotypes all reacted with recombinant ApxIVA. The apxIVA gene from the serotype 1 A. pleuropneumoniae type strain Shope 4074T encodes a protein with a predicted molecular mass of 202 kDa which has typical features of RTX proteins including hydrophobic domains in the N-terminal half and 24 glycine-rich nonapeptides in the C-terminal half that bind Ca2+. The glycine-rich nonapeptides are arranged in a modular structure and there is some variability in the number of modules in the ApxIVA proteins of different serotypes of A. pleuropneumoniae. The deduced amino acid sequences of the ApxIVA proteins have significant similarity with the Neisseria meningitidis iron-regulated RTX proteins FrpA and FrpC, and to a much lesser extent with other RTX proteins. The apxIVA gene could be detected in all A. pleuropneumoniae serotypes and seems to be species-specific. Although the precise role of this new RTX determinant in pathogenesis of porcine pleuropneumonia needs to be determined, apxIVA is the first in vivo induced toxin gene that has been described in A. pleuropneumoniae.

Coffee consumption attenuates short-term fructose-induced liver insulin resistance in healthy men.

BACKGROUND Epidemiologic and experimental data have suggested that chlorogenic acid, which is a polyphenol contained in green coffee beans, prevents diet-induced hepatic steatosis and insulin resistance. OBJECTIVE We assessed whether the consumption of chlorogenic acid-rich coffee attenuates the effects of short-term fructose overfeeding, dietary conditions known to increase intrahepatocellular lipids (IHCLs), and blood triglyceride concentrations and to decrease hepatic insulin sensitivity in healthy humans. DESIGN Effects of 3 different coffees were assessed in 10 healthy volunteers in a randomized, controlled, crossover trial. IHCLs, hepatic glucose production (HGP) (by 6,6-d2 glucose dilution), and fasting lipid oxidation were measured after 14 d of consumption of caffeinated coffee high in chlorogenic acid (C-HCA), decaffeinated coffee high in chlorogenic acid, or decaffeinated coffee with regular amounts of chlorogenic acid (D-RCA); during the last 6 d of the study, the weight-maintenance diet of subjects was supplemented with 4 g fructose · kg(-1) · d(-1) (total energy intake ± SD: 143 ± 1% of weight-maintenance requirements). All participants were also studied without coffee supplementation, either with 4 g fructose · kg(-1) · d(-1) (high fructose only) or without high fructose (control). RESULTS Compared with the control diet, the high-fructose diet significantly increased IHCLs by 102 ± 36% and HGP by 16 ± 3% and decreased fasting lipid oxidation by 100 ± 29% (all P < 0.05). All 3 coffees significantly decreased HGP. Fasting lipid oxidation increased with C-HCA and D-RCA (P < 0.05). None of the 3 coffees significantly altered IHCLs. CONCLUSIONS Coffee consumption attenuates hepatic insulin resistance but not the increase of IHCLs induced by fructose overfeeding. This effect does not appear to be mediated by differences in the caffeine or chlorogenic acid content. This trial was registered at clinicaltrials.gov as NCT00827450.

Hormonally defined pancreatic and duodenal neuroendocrine tumors differ in their transcription factor signatures: expression of ISL1, PDX1, NGN3, and CDX2

We recently identified the transcription factor (TF) islet 1 gene product (ISL1) as a marker for well-differentiated pancreatic neuroendocrine tumors (P-NETs). In order to better understand the expression of the four TFs, ISL1, pancreatico-duodenal homeobox 1 gene product (PDX1), neurogenin 3 gene product (NGN3), and CDX-2 homeobox gene product (CDX2), that mainly govern the development and differentiation of the pancreas and duodenum, we studied their expression in hormonally defined P-NETs and duodenal (D-) NETs. Thirty-six P-NETs and 14 D-NETs were immunostained with antibodies against the four pancreatic hormones, gastrin, serotonin, calcitonin, ISL1, PDX1, NGN3, and CDX2. The TF expression pattern of each case was correlated with the tumor's hormonal profile. Insulin-positive NETs expressed only ISL1 (10/10) and PDX1 (9/10). Glucagon-positive tumors expressed ISL1 (7/7) and were almost negative for the other TFs. Gastrin-positive NETs, whether of duodenal or pancreatic origin, frequently expressed PDX1 (17/18), ISL1 (14/18), and NGN3 (14/18). CDX2 was mainly found in the gastrin-positive P-NETs (5/8) and rarely in the D-NETs (1/10). Somatostatin-positive NETs, whether duodenal or pancreatic in origin, expressed ISL1 (9/9), PDX1 (3/9), and NGN3 (3/9). The remaining tumors showed labeling for ISL1 in addition to NGN3. There was no association between a particular TF pattern and NET features such as grade, size, location, presence of metastases, and functional activity. We conclude from our data that there is a correlation between TF expression patterns and certain hormonally defined P-NET and D-NET types, suggesting that most of the tumor types originate from embryologically determined precursor cells. The observed TF signatures do not allow us to distinguish P-NETs from D-NETs.

Performance and metabolic profile of dairy cows during a lactational and deliberately induced negative energy balance with subsequent realimentation

Homeorhetic and homeostatic controls in dairy cows are essential for adapting to alterations in physiological and environmental conditions. To study the different mechanisms during adaptation processes, effects of a deliberately induced negative energy balance (NEB) by feed restriction near 100 d in milk (DIM) on performance and metabolic measures were compared with lactation energy deficiency after parturition. Fifty multiparous cows were studied in 3 periods (1=early lactation up to 12 wk postpartum; 2=feed restriction for 3 wk beginning at 98+/-7 DIM with a feed-restricted and control group; and 3=a subsequent realimentation period for the feed-restricted group for 8 wk). In period 1, despite NEB in early lactation [-42 MJ of net energy for lactation (NE(L))/d, wk 1 to 3] up to wk 9, milk yield increased from 27.5+/-0.7 kg to a maximum of 39.5+/-0.8 kg (wk 6). For period 2, the NEB was induced by individual limitation of feed quantity and reduction of dietary energy density. Feed-restricted cows experienced a greater NEB (-63 MJ of NEL/d) than did cows in early lactation. Feed-restricted cows in period 2 showed only a small decline in milk yield of -3.1+/-1.1 kg and milk protein content of -0.2+/-0.1% compared with control cows (30.5+/-1.1 kg and 3.8+/-0.1%, respectively). In feed-restricted cows (period 2), plasma glucose was lower (-0.2+/-0.0 mmol/L) and nonesterified fatty acids higher (+0.1+/-0.1 mmol/L) compared with control cows. Compared with the NEB in period 1, the decreases in body weight due to the deliberately induced NEB (period 2) were greater (56+/-4 vs. 23+/-3 kg), but decreases in body condition score (0.16+/-0.03 vs. 0.34+/-0.04) and muscle diameter (2.0+/-0.4 vs. 3.5+/-0.4 mm) were lesser. The changes in metabolic measures in period 2 were marginal compared with the adjustments directly after parturition in period 1. Despite the greater induced energy deficiency at 100 DIM than the early lactation NEB, the metabolic load experienced by the dairy cows was not as high as that observed in early lactation. The different effects of energy deficiency at the 2 stages in lactation show that metabolic problems in early lactating dairy cows are not due only to the NEB, but mainly to the specific metabolic regulation during this period.

Babesia capreoli infections in alpine chamois (Rupicapra r. Rupicapra), roe deer (Capreolus c. Capreolus) and red deer (Cervus elaphus) from Switzerland

Five cases of fatal babesiosis in free-ranging chamois (Rupicapra r. rupicapra) attributed to infections with Babesia capreoli were recently recorded in two regions of the Swiss Alps. To investigate the ecologic factors that possibly lead to those fatal B. capreoli infections in chamois, blood, ticks, and demographic data of 46 roe deer (Capreolus c. capreolus), 48 chamois, and nine red deer (Cervus elaphus) were collected in 2006 and 2007 in both affected regions. Whereas no parasitic inclusions were found by microscopical examination of blood smears, B. capreoli was identified by polymerase chain reaction/sequencing in blood of 12 roe deer (26%, 95% confidence interval [CI]: 14.3-41.1), one chamois (2%, CI: 0-6.1), and one red deer (11%, CI: 0.3-48.2). Prevalence of B. capreoli was significantly higher in roe deer compared with chamois (P<0.001). All 214 ticks were identified as Ixodes ricinus, and significantly more roe deer (63%, CI: 47.5-76.8) were infested compared with chamois (21%, CI: 10.5-35.0, P<0.001). Overall, prevalences of both tick infestation and Babesia infection increased significantly (P<0.001) with decreasing altitude, and Babesia-positive samples were detected significantly more often from animals with tick infestation compared with animals without ticks (P = 0.040). Our results indicate that roe deer may play an important reservoir role for B. capreoli. It is hypothesized that the expansion of the presumed vector I. ricinus to higher elevations and its increased abundance in overlapping habitats of roe deer and chamois may favor the spillover of B. capreoli from roe deer to chamois.

Improving a gas ion source for C-14 AMS

For more than 4 years, gaseous samples of 1-50 mu g carbon have been routinely measured with the gas ion source of the small AMS (Accelerator Mass Spectrometer) facility MICADAS (Mini CArbon DAting System) at ETH Zurich. The applied measurement technique offers a simple and fast way of C-14 measurements without the need of sample graphitization. A major drawback of gaseous C-14 measurements, however, is the relatively low negative ion current, which results in longer measurement times and lower precision compared to graphitized samples. In December 2009, a new, improved Cs sputter ion source was installed at MICADAS and we began to optimize conditions for the measurement of gaseous samples. C-12(-) currents from the new ion source were improved from initially 3 to 12-15 mu A for routine measurements and the negative ion yield was increased by a factor of 2, reaching 8 on average during routine operation. Moreover, the new measurement settings enable a doubled CO2 flow, thus substantially reducing measurement times. The achieved performance allows closing the sample size gap between gaseous and solid samples and makes the gas ion source a promising tool for dating with a measurement precision of 5 parts per thousand on samples as small as 50 mu g carbon. (C) 2012 Elsevier B.V. All rights reserved.

Intercomparison of C-14 Analysis of Carbonaceous Aerosols: Exercise 2009

Radiocarbon analysis of the carbonaceous aerosol allows an apportionment of fossil and non-fossil sources of airborne particulate matter (PM). A chemical separation of total carbon (TC) into its subfractions organic carbon (OC) and elemental carbon (EC) refines this powerful technique, as OC and EC originate from different sources and undergo different processes in the atmosphere. Although C-14 analysis of TC, EC, and OC has recently gained increasing attention, interlaboratory quality assurance measures have largely been missing, especially for the isolation of EC and OC. In this work, we present results from an intercomparison of 9 laboratories for C-14 analysis of carbonaceous aerosol samples on quartz fiber filters. Two ambient PM samples and 1 reference material (RM 8785) were provided with representative filter blanks. All laboratories performed C-14 determinations of TC and a subset of isolated EC and OC for isotopic measurement. In general, C-14 measurements of TC and OC agreed acceptably well between the laboratories, i.e. for TC within 0.015-0.025 (FC)-C-14 for the ambient filters and within 0.041 (FC)-C-14 for RM 8785. Due to inhomogeneous filter loading, RM 8785 demonstrated only limited applicability as a reference material for C-14 analysis of carbonaceous aerosols. C-14 analysis of EC revealed a large deviation between the laboratories of 28-79 as a consequence of different separation techniques. This result indicates a need for further discussion on optimal methods of EC isolation for C-14 analysis and a second stage of this intercomparison.