Induction of cell proliferation in the rat liver by the short-term administration of ethyl tertiary-butyl ether

In the present study, in continuation of our previous experiment in order to investigate the mode of action (MOA) of ethyl tertiary-butyl ether (ETBE) hepatotumorigenicity in rats, we aimed to examine alterations in cell proliferation, that are induced by short-term administration of ETBE. F344 rats were administered ETBE at doses of 0, and 1,000 mg/kg body weight twice a day by gavage for 3, 10, 17 and 28 days. It was found that the previously observed significant increase of P450 total content and hydroxyl radical levels after 7 days of ETBE administration, and 8-OHdG formation at day 14, accompanied by accumulation of CYP2B1/2B2, CYP3A1/3A2, CYP2C6, CYP2E1 and CYP1A1 and downregulation of DNA oxoguanine glycosylase 1, was preceded by induction of cell proliferation at day 3. Furthermore, we observed an increase in regenerative cell proliferation as a result of ETBE treatment at day 28, followed by induction of cell cycle arrest and apoptosis by day 14. These results indicated that short-term administration of ETBE led to a significant early increase in cell proliferation activity associated with induction of oxidative stress, and to a regenerative cell proliferation as an adaptive response, which could contribute to the hepatotumorigenicity of ETBE in rats.     

Intravenous sufentanil‐midazolam versus sevoflurane anaesthesia in medetomidine pre‐medicated Himalayan rabbits undergoing ovariohysterectomy

ObjectiveTo compare physiological effects of sufentanil-midazolam with sevoflurane for surgical anaesthesia in medetomidine premedicated rabbits.Study designProspective, randomized controlled experimental study.AnimalsEighteen female Himalayan rabbits, weight 2.1 ± 0.1 kg.MethodsPremedication with 0.1 mg kg⁻¹ medetomidine and 5 mg kg⁻¹ carprofen subcutaneously, was followed by intravenous anaesthetic induction with sufentanil (2.3 μg mL⁻¹) and midazolam (0.45 mg mL⁻¹). After endotracheal intubation, anaesthesia was maintained with sufentanil-midazolam (n = 9) or sevoflurane (n = 9). Ovariohysterectomy was performed. Intermittent positive pressure ventilation was performed as required. Physiological variables were studied perioperatively. Group means of physiologic data were generated for different anaesthetic periods. Data were compared for changes from sedation, and between groups by anova. Post-operatively, 0.05 mg kg⁻¹ buprenorphine was administered once and 5 mg kg⁻¹ carprofen once daily for 2–3 days. Rabbits were examined and weighed daily until one week after surgery.ResultsSmooth induction of anaesthesia was achieved within 5 minutes. Sufentanil and midazolam doses were 0.5 μg kg⁻¹ and 0.1 mg kg⁻¹, during induction and 3.9 μg kg⁻¹ hour⁻¹ and 0.8 mg kg⁻¹ hour⁻¹ during surgery, respectively. End-tidal sevoflurane concentration was 2.1% during surgery. Assisted ventilation was required in nine rabbits receiving sufentanil-midazolam and four receiving sevoflurane. There were no differences between groups in physiologic data other than arterial carbon dioxide. In rabbits receiving sevoflurane, mean arterial pressure decreased pre-surgical intervention, heart rate increased 25% during and after surgery and body weight decreased 4% post-operatively. Post-operative problems sometimes resulted from catheterization of the ear artery.ConclusionSevoflurane and sufentanil-midazolam provided surgical anaesthesia of similar quality. Arterial blood pressure was sustained during sufentanil-midazolam anaesthesia and rabbits receiving sevoflurane lost body weight following ovariohysterectomy. Mechanical ventilation was required with both anaesthetic regimens.Clinical relevanceAnaesthesia with sufentanil-midazolam in medetomidine premedicated healthy rabbits is useful in the clinical and the research setting, as an alternative to sevoflurane.     

Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signaling pathway

Procyanindin extract (PE) is a mixture of polyphenols, mainly procyanidins, obtained from grape seed with putative antiinflammatory activity. We evaluated the PE effect on RAW 264.7 macrophages stimulated with lipopolysaccharide plus interferon-gamma that show a rapid enhanced production of prostaglandin E2 (PGE2) and nitric oxide (NO). Our results demonstrated that PE significantly inhibited the overproduction of NO, dose and time dependently. PE caused a marked inhibition of PGE2 synthesis when administered during activation. Moreover, PE pretreatment diminished iNOS mRNA and protein amount dose dependently (10-65 microg/mL). PE (65 microg/mL) pretreatment inhibited NFkappaB (p65) translocation to nucleus by nearly 40%. Trimeric and longer oligomeric-rich procyanidin fractions from PE (5-30 microg/mL) inhibited iNOS expression but not the monomeric forms catechin and epicatechin. Thus, we show that the degree of polymerization is important in determining procyanidin effects. PE was considerably a more effective inhibitor of NO biosynthesis (IC50 = 50 microg/mL) in comparison to other antiinflammatories, such as aspirin (3 mM), indomethacin (20 microM), and dexamethasone (9 nM). In conclusion, PE modulates inflammatory response in activated macrophages by the inhibition of NO and PGE2 production, suppression of iNOS expression, and NFkB translocation. These results demonstrate an immunomodulatory role of grape seed procyanidins and thus a potential health-benefit in inflammatory conditions that exert an overproduction of NO and PGE2.     

Physiological and metabolic properties of a digestion-resistant maltodextrin, classified as type 3 retrograded resistant starch

There is a growing interest in highly fermentable dietary fibers having the potential to reduce risks of disease through the production of short-chain fatty acids (SCFA). Recently a digestion-resistant retrograded maltodextrin (RRM), classified as type 3 resistant starch was developed. Systematic work to determine its molecular and physiological properties was carried out to determine (1) the fraction resistant to digestion in vitro and in vivo, (2) its postconsumption effect on blood glucose in healthy volunteers, and (3) its in vitro fermentation pattern, at different ages, by use of pooled fresh human fecal inoculum. RESULTS: The digestion resistant fraction obtained in vivo from ileostomy patients (59.4%) is similar to that obtained by the AOAC method for measuring retrograded resistant starch (59.7%). The relative glycemic response after consumption of 50 g of RRM was 58.5% compared to glucose set as 100%. When exposed to colonic microbiota, in vitro obtained indigestible fractions behave similarly to those obtained in vivo in ileostomy patients. Fermentation of RRM and production of butyric acid is negligible during the first months of life but develops subsequently during weaning. In adults, RRM fermentation results in a high yield of SCFA, with butyrate representing 21-31 mol % of total SCFA. The high yield of SCFA during colonic fermentation, observed from weaning age on, as well as the potential to help reduce glycemic load may be of benefit to a number of health-related functions in the host. Further study on clear clinical end points is warranted.     

Model studies on acrylamide generation from glucose/asparagine in aqueous glycerol

Acrylamide formation from asparagine and glucose in different ratios in neutral glycerol/water mixtures was found to increase with decreasing water activity (0.33 < or = aw < or = 0.71 investigated) and increasing temperature (120 degrees C < or = T < or = 160 degrees C investigated). The initial rate of acrylamide formation was found to be approximately proportional to the asparagine concentration for an excess of asparagine, but less dependent on an excess of glucose. A steady-state concentration of acrylamide was established at 160 degrees C after 1 h for aw = 0.33 (30 microg x L-1 for GLU:ASN = 10:1, 11 microg x L-1 for GLU:ASN = 1:1, and 130 microg x L-1 for GLU:ASN = 1:10) and for aw = 0.47 (15 microg x L-1 for GLU:ASN = 10:1 and 80 microg x L-1 for GLU:ASN = 1:10), suggesting a protection by glucose against acrylamide degradation. The energy of activation, as estimated from the temperature dependence of the initial rate, increased with decreasing aw despite a higher rate of formation of acrylamide at low aw. For high aw, water elimination from a reaction intermediate is suggested to be rate determining. For low aw, the increase in energy of activation (and enthalpy of activation) is accordingly counteracted by a more positive entropy of activation, in agreement with decarboxylation as rate determining at low aw.     

Synthesis and antifungal activity of a series of N-substituted [2-(2,4-dichlorophenyl)-3-(1,2,4-triazol-1-yl)]propylamines

A series of N-mono- or N, N-disubstituted [2-(2,4-dichlorophenyl-3-(1,2,4-triazol-1-yl)]propylamines and N-[2-(2,4-dichlorophenyl-3-(1,2,4-triazol-1-yl)propyl]amides were synthesized and tested for their fungicidal activity in vitro and in vivo against a group of plant pathogenic fungi. Some compounds exhibited a fairly good in vitro activity. The replacement of the ether group of tetraconazole with a secondary or tertiary amino group leads to compounds that maintain the antifungal activity on several phytopathogenic fungi, provided that the substituents are not too bulky or lipophilic. The allyl, propargyl, and cyclopropyl groups appear particularly suitable. Although these compounds have some structural similarities with terbinafine and naftifine, which act as squalene epoxidase inhibitors, they maintain the usual mechanism of action of the other triazoles.     

Bioaccessibility and antioxidant activity stability of phenolic compounds from extra-virgin olive oils during in vitro digestion

The impact of an in vitro procedure that mimics the physiochemical changes occurring in gastric and small intestinal digestion on the bioaccessibility and antioxidant activity of phenols from 10 extra-virgin olive oil samples was assessed. Extra-virgin olive oil phenols were totally extracted in the aqueous phase, which reproduces gastric fluids during the digestion procedure. A linear bioaccessibility model, based on tyrosol behavior in model oil samples, was used to estimate the bioaccessibility index (BI%) of extra-virgin olive oil phenols. The BI% varied amongst samples from a maximum of 90% to a minimum of 37%, thus indicating that only a fraction of phenols can be considered bioaccessible. The specific antioxidant activity of olive oil phenols proved to be negatively affected by the digestion procedure. By computing a principal component analysis, it was possible to show that differences in the potential bioactive effect of extra-virgin olive oil samples were related to different phenolic profiles.     

Evaluation of 2-alkylcyclobutanones in irradiated cured pork products during vacuum-packed storage

The 2-Alkylcyclobutanones (2-ACBs) content was determined in three Italian cured pork products (salame Milano, coppa, and pancetta) irradiated at different targeted irradiation doses (2, 5, and 8 kGy) during vacuum-packed storage. Among 2-ACBs, three different compounds were investigated, namely, 2-dodecylcyclobutanone, 2-tetradecylcyclobutanone, and 2-(tetradec-5'-enyl)cyclobutanone. 2-ACBs were absent from the nonirradiated samples, whereas their content increased with irradiation dose. Their presence was recorded occasionally at 2 kGy and constantly at higher irradiation doses (5 and 8 kGy). The plot of 2-ACBs content against targeted irradiation doses showed an exponential relationship. The effect of vacuum-packed storage time on the 2-ACBs content was dependent on the irradiation dose. During vacuum-packed storage for up to 60 days, the 2-ACBs content remained unchanged in the cured pork products irradiated at 2 and 5 kGy, whereas a significant increase was observed in the pork products irradiated at 8 kGy.     

Trade-offs and synergies in management of two co-occurring specialist squash pests

Journal of Pest Science - Co-occurring herbivorous pests may have shared or divergent responses to plant- and insect- derived cues, creating challenges for effective pest management in...     

Surveys on Coxiella burnetii infections in Swedish cattle,sheep, goats and moose

Background

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Prevalence data in ruminant species are important to support risk assessments regarding public and animal health. The aim was to investigate the presence of or exposure to C. burnetii in cattle, sheep, goats and moose, and to compare two enzyme-linked immunosorbent assays (ELISAs). National surveys of antibodies against C. burnetii were performed for dairy cattle (n=1537), dairy goats (n=58) and sheep (n=518). Bovine samples consisted of bulk milk, caprine of pooled milk, and ovine of pooled serum. Antibodies were investigated in moose samples (n=99) from three regions. A one-year regional cattle bulk milk survey was performed on the Isle of Gotland (n=119, four occasions). Cattle, sheep and goat samples were analysed with indirect ELISA and moose samples with complement fixation test. For the sheep, goat, and parts of the cattle survey, samples were run in parallel by ELISAs based on antigens from infected ruminants and ticks. Bulk milk samples from the regional cattle survey and vaginal swabs from a subset of the sheep herds (n=80) were analysed for the agent by polymerase chain reaction. Spatial clustering was investigated in the national cattle survey.

Results

The prevalence of antibodies in dairy herds was 8.2% with large regional differences. High risk clusters were identified in the southern regions. The prevalence among dairy herds on the Isle of Gotland varied from 55.9% to 64.6% and 46.4% to 58.9.0% for antibodies and agent, respectively, overall agreement between agent and antibodies was 85.2%. The prevalence of antibodies in sheep was 0.6%, the agent was not detected the vaginal swabs. Antibodies were not detected in goats or moose, although parts of the moose samples were collected in an area with high prevalence in cattle. The overall agreement between the two ELISAs was 90.4%.

Conclusions

The prevalence of antibodies against C. burnetii in dairy cattle in Sweden shows large regional differences. The results suggest that C. burnetii is a rare pathogen among Swedish moose, dairy goat and sheep. ELISAs based on ruminant and tick antigen performed in a similar manner under Swedish conditions.