Reversal of arterial oxygen desaturation with the use of an oxygen concentrator during injectable anaesthesia in feral cats positioned in the Trendelenburg, dorsal or lateral surgical position.

INTRODUCTION: This study observed the effects of oxygen supplementation, via an oxygen concentrator, on peripheral arterial blood oxygenation (SpO2) measured by pulse oximetry in anaesthetised cats undergoing spay in three different surgical positions. A total of 192 female feral cats were investigated for a large-scale trap-neuter-release program. Cats were anaesthetised with an intramuscular combination of butorphanol (0,4 mg / kg), ketamine (7-10 mg / kg) and medetomidine (0,03-0,05 mg / kg). Cats were randomly allocated to undergo spay in either Trendelenburg (TR) (70° downward head tilt), lateral (LR) or dorsal (DR) recumbency. Cats were breathing spontaneously either room air or 2 L/minute oxygen via a tight-fitting face mask. Pulse rate (in beats per minute), respiratory rate (in breaths per minute) and SpO2 (in percentage) were measured at baseline in left lateral recumbency and afterwards continuously after being positioned in allocated surgical position. At the end of surgery, cats were placed again in left recumbency, and all parameters were re-evaluated after five minutes. Overall, 33 % of cats showed severe arterial oxygen desaturation (SpO2 < 90 %) at baseline when breathing room air. When oxygen was supplemented during the procedure, arterial oxygen desaturation resolved in all cats. At the end of the procedure, 29 % of cats were hypoxaemic when oxygen was not supplemented, with an overall higher percentage of hypoxaemic cats in TR as compared to DR and LR recumbencies. All cats recovered well from surgery and were released within 24 hours post-anaesthesia. Arterial oxygen desaturation is frequent in cats anaesthetised with injectable anaesthesia for spay under field conditions. Oxygen supplementation administered via a tight-fitting mask resolved arterial oxygen desaturation in this feral cat population regardless of the surgical position and therefore oxygen supplementation is recommended in any case.

INTRODUCTION: Cette étude a observé les effets d'une supplémentation en oxygène, via un concentrateur d'oxygène, sur l'oxygénation du sang artériel périphérique (SpO2) mesurée par oxymétrie de pouls chez des chats anesthésiés subissant une stérilisation dans trois positions chirurgicales différentes. Au total, 192 chats sauvages femelles ont été examinés dans le cadre d'un programme de piégeage, de stérilisation et de remise en liberté à grande échelle. Les chats ont été anesthésiés avec une combinaison de butorphanol (0,4 mg / kg), de kétamine (7­10 mg / kg) et de médétomidine (0,03­0,05 mg / kg) appliquée par voie intramusculaire. Les chats ont été répartis au hasard pour subir une stérilisation en position de Trendelenburg (TR) (inclinaison de la tête de 70° vers le bas), en décubitus latéral (LR) ou en décubitus dorsal (DR). Les chats respiraient spontanément soit de l'air ambiant, soit de l'oxygène à raison de 2 L/minute par l'intermédiaire d'un masque facial bien ajusté. Le pouls (en battements par minute), la fréquence respiratoire (en respirations par minute) et la SpO2 (en pourcentage) ont été mesurés au départ en décubitus latéral gauche, puis en continu après avoir été placés dans la position chirurgicale attribuée. À la fin de l'opération, les chats ont été replacés en décubitus latéral gauche et tous les paramètres ont été réévalués au bout de cinq minutes. Dans l'ensemble, 33 % des chats présentaient une désaturation sévère en oxygène artériel (SpO2 < 90 %) au départ lorsqu'ils respiraient de l'air ambiant. Lorsque de l'oxygène a été ajouté pendant la procédure, la désaturation en oxygène artériel s'est résorbée chez tous les chats. À la fin de l'intervention, 29 % des chats étaient hypoxémiques lorsque l'oxygène n'était pas administré, avec un pourcentage global plus élevé de chats hypoxémiques en décubitus dorsal qu'en décubitus latéral. Tous les chats se sont bien remis de l'opération et ont été libérés dans les 24 heures suivant l'anesthésie. La désaturation en oxygène artériel est fréquente chez les chats anesthésiés par injection pour la stérilisation dans des conditions de terrain. La supplémentation en oxygène administrée via un masque étanche a résolu la désaturation en oxygène artériel dans cette population de chats sauvages, quelle que soit la position chirurgicale et la supplémentation en oxygène est donc recommandée dans tous les cas.

Hepatotoxic combination effects of three azole fungicides in a broad dose range.

Single active substances of pesticides are thoroughly examined for their toxicity before approval. In this context, the liver is frequently found to be the main target organ. Since consumers are generally exposed to multiple residues of different active substances via the diet, it is important to analyse combinations of active substances for potential mixture effects. For the (tri-)azoles, a group of agricultural fungicides and antifungal drugs, combination effects on the liver are likely because of a similar mode of action. Hepatotoxic effects of mixtures of two triazoles (cyproconazole and epoxiconazole) and an imidazole (prochloraz) were investigated in a 28-day feeding study in rats at three dose levels ranging from a typical toxicological reference value to a clear effect dose. Test parameters included organ weights, clinical chemistry, histopathology and morphometry. In addition, molecular parameters were investigated by means of pathway-focused gene expression arrays, quantitative real-time PCR and enzyme activity assays. Effects were compared to those caused by the individual substances as observed at the same dose levels in a previous study. Mixture effects were substantiated by increases in relative and absolute liver weights, histopathological findings and alterations in clinical chemistry parameters at the top dose level. On the molecular level also at lower dose levels, additive effects could be observed for the induction of several cytochrome P 450 enzymes (Cyp1a1, Cyp2b1, Cyp3a2), transporters (Abcb1a, Abcc3) and of genes encoding for enzymes involved in fatty acid or phospholipid metabolism (Ppargc1a, Sc4 mol). In most cases, treatment with mixtures caused a more pronounced effect as compared to the individual substances. However, the assumption of dose additivity was in general sufficiently conservative to cover mixture effects observed under the conditions of the present study.

Mixture effects of azole fungicides on the adrenal gland in a broad dose range.

Consumers are exposed to low concentrations of a variety of pesticide residues in or on food. Some of them might interfere with the endocrine system. While each individual active substance has been extensively tested for toxicity and safety, potential combination effects possibly resulting from combined exposure to different pesticides have seldomly been tested so far, especially in vivo. Since the adrenal gland is a key endocrine organ, we investigated if and how substances of a group of fungicides presumed to interfere with the biosynthesis of steroid hormones affect this organ when applied individually and in combination in a broad dose range. A 28-day feeding study was conducted in Wistar rats by using three (tri)azole fungicides considered to potentially affect the endocrine system (cyproconazole, epoxiconazole and prochloraz) individually at five dose levels, ranging from 0.9ppm to 2400ppm, and in combination at three dose levels. The parameters analysed included classical toxicology (pathology, histopathology, clinical chemistry) and molecular toxicology endpoints (gene expression arrays and quantitative real time PCR e.g. of Star, HSD3ß, Cyp11a1, Cyp11b1, Cyp11b2, Cyp 21, ApoE), as well as hormone analysis. A dose-dependent decrease in the adrenal gland weight of rats treated with epoxiconazole alone, which was accompanied by an atrophy of the adrenal gland as well as by an increase in the serum cholesterol level and which only became statistically significant at the top dose levels, was observed. These effects were attenuated in the combination experiments, although the same epoxiconazole concentration was used.

Investigations on the possible impact of a glyphosate-containing herbicide on ruminal metabolism and bacteria in vitro by means of the 'Rumen Simulation Technique'.

AIMS: This study was performed in a well-established in vitro model to investigate whether the application of a glyphosate-containing herbicide might affect the bacterial communities and some biochemical parameters in a cow's rumen. METHODS AND RESULTS: The test item was applied in two concentrations (high and low) for 5 days. In a second trial, fermentation vessels were inoculated with Clostridium sporogenes before the high dose was applied. Effluents were analysed by biochemical, microbiological and genetic methods. A marginal increase in short-chain fatty acid production and a reduction in NH3 -N were observed. There were minor and rather equivocal changes in the composition of ruminal bacteria but no indications of a shift towards a more frequent abundance of pathogenic Clostridia species. Clostridium sporogenes counts declined consistently. CONCLUSIONS: No adverse effects of the herbicide on ruminal metabolism or composition of the bacterial communities could be detected. In particular, there was no evidence of a suspected stimulation of Clostridia growth. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic activity of glyphosate resulting in microbial imbalances has been postulated. In this exploratory study, however, intraruminal application of concentrations reflecting potential exposure of dairy cows or beef cattle did not exhibit significant effects on bacterial communities in a complex in vitro system. The low number of replicates (n = 3/dose) may leave some uncertainty.

Combination effects of azole fungicides in male rats in a broad dose range.

Two 28-day feeding studies were performed in male rats to investigate combination effects of azole fungicides in a broad dose range. Following separate administration of cyproconazole, epoxiconazole, prochloraz, propiconazole, and tebuconazole at five dose levels, the first three compounds were selected to be administered in two different mixtures at three dose levels including very low doses. Here we present the data obtained by clinical observations, pathology, histopathology, clinical chemistry and haematology. The liver was the common main target organ of all compounds and their mixtures. In addition, epoxiconazole exhibited an effect on the adrenals. Furthermore, food consumption and efficiency and body weight (gain) were affected. Adverse effects of the combinations were observed at dose levels at which the individual substances caused similar effects. No evidence of adverse effects was found at dose levels below the previously established NOAELs. Our findings indicate that the concept of dose additivity appears sufficiently protective for risk assessment of the fungicides examined. Besides toxicological testing, tissue residues of the azole compounds in liver, testis and kidney were determined revealing remarkable differences following administration of the single substances and of the mixtures.

Application of omics data in regulatory toxicology: report of an international BfR expert workshop.

Advances in omics techniques and molecular toxicology are necessary to provide new perspectives for regulatory toxicology. By the application of modern molecular techniques, more mechanistic information should be gained to support standard toxicity studies and to contribute to a reduction and refinement of animal experiments required for certain regulatory purposes. The relevance and applicability of data obtained by omics methods to regulatory purposes such as grouping of chemicals, mode of action analysis or classification and labelling needs further improvement, defined validation and cautious expert judgment. Based on the results of an international expert workshop organized 2014 by the Federal Institute for Risk Assessment in Berlin, this paper is aimed to provide a critical overview of the regulatory relevance and reliability of omics methods, basic requirements on data quality and validation, as well as regulatory criteria to decide which effects observed by omics methods should be considered adverse or non-adverse. As a way forward, it was concluded that the inclusion of omics data can facilitate a more flexible approach for regulatory risk assessment and may help to reduce or refine animal testing.

Hepatotoxic effects of (tri)azole fungicides in a broad dose range.

The toxicological relevance of effects observed at molecular stage, which occur at dose levels well below classical no-observed adverse effect levels is currently subject to controversial scientific debate. While the importance of molecular effects for the identification of a mode of action or an adverse outcome pathway is undisputed, their impact for other regulatory purposes remains uncertain. Here, we report the results of a 28-day rat-feeding study including three widely used hepatotoxic (tri)azole fungicides (cyproconazole, epoxiconazole and prochloraz) administered individually at five dose levels, ranging from slightly above the reference values to a clear toxic effect dose. Parameters analysed included pathology, histopathology, clinical chemistry and particularly effects on the molecular level. Since azole fungicides are considered to cause liver toxicity by a mechanism involving the constitutive androstane receptor (CAR), a known CAR activator (phenobarbital, PB) was administered to investigate potential similarities between triazoles and PB-mediated liver toxicity by pathway-focused gene expression analysis. Our results show an increase in liver weights and additionally histopathological changes (hepatocellular hypertrophy) for all substances at the top dose levels. The effects on liver weight were most pronounced for cyproconazole by which also the animals receiving the next lower dose were affected. In addition, vacuolisation of hepatocytes was observed at the top dose level. No such findings were obtained with any substance at lower doses to which consumers and operators might be exposed to. In contrast, the expression of sensitive marker genes (like some cytochrome-P-450 isoforms) was significantly affected also at the lower dose levels. While some of these changes, like the induction of genes related to fatty acid and phospholipid metabolism (e.g. Fasn, Fat/Cd36, Ppargc1a) or xenobiotic metabolism (Cyp1a1, Cyp2b1, Cyp3a2), could be associated with high dose effects like hepatocellular vacuolisation or hypertrophy, a histopathological correlate was lacking for others.

Assessment of three approaches for regulatory decision making on pesticides with endocrine disrupting properties.

Recent EU legislation has introduced endocrine disrupting properties as a hazard-based "cut-off" criterion for the approval of active substances as pesticides and biocides. Currently, no specific science-based approach for the assessment of substances with endocrine disrupting properties has been agreed upon, although this new legislation provides interim criteria based on classification and labelling. Different proposals for decision making on potential endocrine disrupting properties in human health risk assessment have been developed by the German Federal Institute for Risk Assessment (BfR) and other regulatory bodies. All these frameworks, although differing with regard to hazard characterisation, include a toxicological assessment of adversity of the effects, the evaluation of underlying modes/mechanisms of action in animals and considerations concerning the relevance of effects to humans. Three options for regulatory decision making were tested upon 39 pesticides for their applicability and to analyze their potential impact on the regulatory status of active substances that are currently approved for use in Europe: Option 1, based purely on hazard identification (adversity, mode of action, and the plausibility that both are related); Option 2, based on hazard identification and additional elements of hazard characterisation (severity and potency); Option 3, based on the interim criteria laid down in the recent EU pesticides legislation. Additionally, the data analysed in this study were used to address the questions, which parts of the endocrine system were affected, which studies were the most sensitive and whether no observed adverse effect levels were observed for substance with ED properties. The results of this exercise represent preliminary categorisations and must not be used as a basis for definitive regulatory decisions. They demonstrate that a combination of criteria for hazard identification with additional criteria of hazard characterisation allows prioritising and differentiating between substances with regard to their regulatory concern. It is proposed to integrate these elements into a decision matrix to be used within a weight of evidence approach for the toxicological categorisation of relevant endocrine disruptors and to consider all parts of the endocrine system for regulatory decision making on endocrine disruption.

False positive detection of peanut residue in liquid caramel coloring using commercial ELISA kits.

Initial food industry testing in our laboratory using enzyme-linked immunosorbent assay (ELISA) methods indicated that the darkest caramel color (class IV) unexpectedly contained traces of peanut protein, a potential undeclared allergen issue. Caramel production centers on the heating of sugars, often glucose, under controlled heat and chemical processing conditions with other ingredients including ammonia, sulfite, and/or alkali salts. These ingredients should not contain any traces of peanut residue. We sought to determine the reliability of commercially available peanut allergen ELISA methods for detection of apparent peanut residue in caramel coloring. Caramel color samples of classes I, II, III, and IV were obtained from 2 commercial suppliers and tested using 6 commercially available quantitative and qualitative peanut ELISA kits. Five lots of class IV caramel color were spiked with a known concentration of peanut protein from light roasted peanut flour to assess recovery of peanut residue using a spike and recovery protocol with either 15 ppm or 100 ppm peanut protein on a kit-specific basis. A false positive detection of peanut protein was found in class IV caramel colors with a range of 1.2 to 17.6 parts per million recovered in both spiked and unspiked liquid caramel color samples. ELISA kit spike/recovery results indicate that false negative results might also be obtained if peanut contamination were ever to actually exist in class IV caramel color. Manufacturers of peanut-free products often test all ingredients for peanut allergen residues using commercial ELISA kits. ELISA methods are not reliable for the detection of peanut in class IV caramel ingredients and their use is not recommended with this matrix.

Effects of fentin hydroxide on reproduction of the Japanese quail (Coturnix coturnix japonica).

In a one-generation reproductive study, the fungicidal compound triphenyltin hydroxide (fentin) was administered to adult Japanese quail for 6 weeks at dietary levels of 3 and 30 ppm. Reproduction was significantly impaired in the high-dose group. The principal adverse finding was a marked increase in embryonic mortality, resulting in a lower hatch rate. Furthermore, a reduction in egg production was observed with ongoing duration of treatment. Most of the other reproduction-related parameters were not affected. The in ovo losses are assumed to result from a direct toxic effect of the test substance on chick embryos. At the low dietary level, reproduction was not altered. In contrast to the obvious reproductive toxicity, there was only limited evidence of adverse treatment-related findings in the adult birds. However, because such minor effects as an increase in mean liver weight, which was accompanied by macroscopic liver findings and a decrease in T4 serum concentration, were still seen at 3 ppm, a no-observed-effect level could not be established.

Effects of vinclozolin on spermatogenesis and reproductive success in the Japanese quail (Coturnix coturnix japonica).

In a one-generation reproduction study, the major agricultural fungicide vinclozolin was administered to adult Japanese quail for a period of 6 weeks at dietary levels of 125 and 500 ppm. Fertility and reproductive performance were not affected up to the highest concentration, although the examination of additional endpoints in the drakes (spermatid count, histology of the testis) provided some evidence of an inhibition of spermatogenesis at both dietary concentrations. Likewise, there were no indications of systemic toxicity in the adult birds. Plasma hormone concentrations (estradiol, testosterone, progesterone, T3, and T4) showed a large interindividual variance but treatment-related differences between the groups could not be established. There were no clear-cut indications of antiandrogenic effects in quail, although a limited transfer of the test substance into the eggs was proven.

Moisture content and particle size of dehydrated egg yolk affect lipid and cholesterol extraction using supercritical carbon dioxide.

Egg yolk was spray-dried under conditions to produce a small particle size powder and a large particle size powder. Particle size was determined using a Nikon Optiophot microscope. Spray-dried egg yolk was also adjusted to various moisture levels as follows: control (2 to 4% moisture), 7% moisture, and 12% moisture. Supercritical carbon dioxide extraction (SCE) of each of these moisture treatments at 45 C/306 atm using 30 g CO2/g of sample was completed. For the particle size study, 45 g CO2/g of sample at 45 C/306 atm was utilized. Particle size exhibited a significant effect on cholesterol and lipids extracted using SCE. As moisture content of dried egg yolk increased to 7%, there was a significant increase in lipids extracted using supercritical carbon dioxide. Moisture content had no significant effect on cholesterol extraction. After extracting SCE higher moisture spray-dried egg yolk, sponge cake volume was significantly reduced compared to that of the control. The reduced sponge cake volume may be due to protein denaturation.

Wuchereria bancrofti in Tanzania: microfilarial periodicity and effect of blood sampling time on microfilarial intensities.

The circadian periodicity of Wuchereria bancrofti microfilarial (mf) intensities in peripheral blood was analysed in a group of infected individuals from an endemic community in north-eastern Tanzania. The mf density was quantified at two-hourly intervals for 24 hours. A clear nocturnal periodic pattern was observed. Mathematical analysis of the data indicated a peak at 0152 h and a periodicity index of 117.5. A periodicity equation was developed describing the average relation between mf intensity and hour of the day for the study area. Based on the observed periodicity pattern, the effect of blood sampling before peak time is discussed, and the importance of taking sampling time into consideration when analysing data from epidemiological studies is emphasized. A simple method is devised which can be used to adjust for the influence of time on mf intensities, in studies where accurate information on mf intensities is necessary, and where it is impossible to obtain all samples at peak time.

Antimicrobial susceptibility of 278 streptococcal blood isolates to seven antimicrobial agents.

A total of 278 streptococci isolated from blood (including 66 strains of Streptococcus pneumoniae) were tested for their MIC to penicillin G, gentamicin, rifampicin, clindamycin, erythromycin, vancomycin and teicoplanin to determine the current state of resistance among streptococci isolated from blood at a University Hospital in Copenhagen, Denmark, and thereby to assess alternative treatment for patients who are infected with a penicillin-resistant streptococcal strain or allergic to penicillin. Danish Blood Sensitivity Agar and the Etest were used. Overall, resistance to penicillin among Streptococcus mitis strains was 44.4% (37% intermediately susceptible and 7.4% resistant). As penicillin resistance in S. mitis may be an early indication of emerging penicillin resistance among other streptococcal species, this finding is a matter of concern. Except for this observation, penicillin remains the best and a safe choice for treatment of streptococcal infection. For alternative treatment when the patient is allergic to penicillin and for prophylaxis, the usual recommendation is macrolide antibiotics or clindamycin. The majority of non-enterococcal groups of streptococci remain sensitive to erthromycin and clindamycin, but the antibiotic susceptibility pattern is unpredictable without testing the isolates, so empirical therapy or prophylaxis may fail.

Supercritical carbon dioxide extraction of lipids and cholesterol from dehydrated chicken meat.

Supercritical carbon dioxide (SC-CO2) extraction was studied for removal of lipids and cholesterol from dried chicken meat powder and chunks. Two combinations of pressure and temperature were used: 299 atm and 45 C, and 381 atm and 55 C, both providing a fluid density of .90 g/cm3. For a given quantity of CO2, at the higher temperature and pressure, significantly (P < .05) more lipids and cholesterol were extracted from the powder. At 381 atm and 55 C, approximately 89% of the lipids and 90% of the cholesterol were removed from the dehydrated chicken meat powder. With respect to the chunk chicken meat, about 93% of the lipids and 82% of the cholesterol were extracted at 299 atm and 45 C. It seemed that the SC-CO2 extraction process was more efficient when chunks were used. Protein was concentrated as cholesterol and lipids were removed by SC-CO2 extraction of both chicken meat types, and Hunterlab L values increased but aL values decreased, indicating a lighter color with less redness. This research indicated that SC-CO2 extraction holds promise for substantially reducing lipids and cholesterol in chicken meat.

The health status and health care utilization of deaf and hard-of-hearing persons.

OBJECTIVE: To evaluate whether health habits, self-reported health status, and communication with physicians play a role in the known altered health care utilization patterns of deaf and hard-of-hearing persons. DESIGN: A cross-sectional survey. Respondents were given the choice of completing either a self-administered written survey or an American Sign Language interview-administered survey. POPULATION: Eighty-seven deaf and hard-of-hearing members of various organizations serving this population in southeastern Michigan and 88 hearing patients from a family practice clinic in the same area. RESULTS: Deaf and hard-of-hearing persons visit physicians more frequently (P = .01), have a lower incidence of ever smoking tobacco (P < .0006) and of alcohol use (P = .04), have more difficulties communicating with physicians (P < .001), have trouble understanding physicians (P < .001), and feel less comfortable with physicians (P < .001). Lower current tobacco use among deaf and hard-of-hearing persons was only seen in persons who were not educated beyond high school. Increased frequency of physician visits for deaf and hard-of-hearing persons was especially noticeable in the group of persons 60 years of age and older. Our finding that use of interpreters is associated with increased utilization and decreased understanding suggests deaf and hard-of-hearing patients presenting with interpreters warrant more focused attention from physicians. Reasons for seeing physicians did not explain the difference in frequency of physician visits between the two groups. CONCLUSIONS: Deaf and hard-of-hearing persons report a lower subjective health status and higher physician utilization, as well as substantial communication difficulties with physicians. They also report better health-related behaviors, namely less use of tobacco and alcohol. The use of interpreters did not decrease physician utilization or improve the understanding of physicians by these persons. Overall, our results underscore the fact that deaf and hard-of-hearing persons constitute a minority population that experiences considerable difficulties in the patient-physician relationship.