No abstract

Implementing a mandatory protocol for treating adult patients with diabetic ketoacidosis decreases intensive care and hospital lengths of stay and time to anion gap closure and ketone clearance, without increasing the rate of hypoglycemia.

No abstract

A systematic review of the literature has been conducted and studies reporting investigations of genotoxicity biomarkers in pesticide workers have been assessed with view to establishing whether there was evidence for any risk to those using pesticides approved in the United Kingdom. Each of the studies was evaluated using a set of criteria drawn up by members of the UK Committee of Mutagenicity based upon the guidelines proposed by the International Programme on Chemical Safety (IPCS) working group [R. J. Albertini, D. Anderson, G. R. Douglas, L. Hagmar, K. Hemminki, F. Merlo, A. T. Natarajan, H. Norppa, D. E. Shuker, R. Tice, M. D. Waters and A. Aitio (2000) Mutat. Res., 463, 111-172]; 24 out of 70 studies met the criteria for inclusion in the substantive evaluation. Positive findings were compared with occupational practices and evidence of exposure to specific pesticides with view to developing hypotheses for further consideration. Seventeen of the 24 studies reported positive findings, although in the majority of these the magnitude of increase was small. There was some limited evidence that the use of benzimidazoles was more consistently associated with positive findings. However, limitations in the data, particularly evidence of exposure, did not allow definitive conclusions to be drawn. Also, it was noted that the use (or not) of personal protective equipment (PPE) was not well documented and in the few studies in which its use was reported, the findings were more likely to be positive in the absence of PPE usage. An independent epidemiological review concluded that all studies were of limited design, particularly with regards to study size, the assessment of subject selection and potential recruitment bias. Variance in genotoxicity indices in the control population and a lack of understanding of the factors influencing this variability complicate attempts to characterize positive responses. More substantive data are needed in this respect so that the significance of relatively small increases in biomonitoring indices can be accurately assessed. Once these data are available, a study in workers using benzimidazoles would be appropriate.

A review of risk factors affecting background rates of micronuclei and chromosomal aberration (CA) formation in peripheral blood lymphocytes (PBLs) was undertaken with a view to aiding the interpretation of genotoxicity biomonitoring studies. Both endogenous factors and those due to methodological variation were evaluated. Background variation of other indices of genotoxicity in PBLs (specifically 8-hydroxy-deoxyguanosine and comet assays) were also considered as these data likely reflect overlapping causes of DNA damage and may provide some indicators for future research areas. A number of host risk factors, namely age, gender, smoking, vitamin B(12) and folate status, were identified for which there is strong or sufficient evidence that they impact on background levels of genotoxicity biomarkers. Evaluation of these factors should be routinely included in genotoxicity biomonitoring studies. Although data on the influence of smoking is somewhat inconsistent, because of its known association with cancer and DNA damage, it is also classified as a high-risk factor. A number of other factors were identified for which there is weak or insufficient evidence including alcohol consumption, disease conditions and infections, physical exercise, body mass index and genotype. The review shows that the evaluation of biomonitoring studies of genotoxicity is complex and there is a need to improve study designs by setting an a priori hypothesis, collecting good exposure data and stratifying groups appropriately, using appropriate power calculations before initiating biomonitoring studies, and collecting information on appropriate risk factors. There is a need for further collaborative work and the establishment of centres of excellence on genotoxicity biomonitoring. If these measures are achieved, then it would be possible to use the data from biomonitoring studies in risk assessments to derive risk management measures.

-Ketamine is widely used in equine anaesthesia. Beside its anaesthetic and analgesic properties, ketamine possesses a cytokine-modulating activity. However, to date, no data are available regarding the inhibitory effect of ketamine on the cytokine response in horses. In horses, cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) play a pivotal role in the pathogenesis of equine endotoxaemia following gastrointestinal disorders. Hence, the objective of this study was to assess the influence of ketamine on LPS-induced TNF-α and IL-6 formation in an equine macrophage cell line (eCAS cells). The results demonstrate a cytokinemodulating activity of ketamine in an equine cell line, suggesting a beneficial role for ketamine in the treatment of equine endotoxaemia. ketamine / cytokine / equine endotoxaemia / eCAS

When challenged with allergens and pro-inflammatory agents, such as Aspergillus fumigatus (AF), hay dust solution (HDS) and lipopolysaccharide (LPS), the innate immune response will not only activate the immune system but also increase the amount of pro-inflammatory cytokines in the bronchoalveolar space. The aim of this study was to assess the response of equine alveolar macrophages to different aerosolized challenges and to investigate the differences in this response between horses susceptible or nonsusceptible to recurrent airway obstruction (RAO). Seven susceptible and 5 nonsusceptible horses were challenged with saline, LPS, HDS, or AF, and bronchoalveolar lavage (BAL) cytology, total cell counts, and lung function were assessed. In addition, alveolar macrophages were isolated 6 and 24 hours after challenge, and macrophage mRNA expression of tumor necrosis factor (TNF)-alpha and interleukins (IL) IL-1beta, IL-6, IL-8, and IL-10 were measured by means of real-time (RT) polymerase chain reaction (PCR). There was a significant difference in lung function, neutrophil ratios, and total cell counts in the bronchoalveolar lavage fluid between RAO-susceptible and nonsusceptible horses. In addition, the expression of TNF-alpha, IL-1beta, and IL-8 by alveolar macrophages after challenges were higher in susceptible horses, than in nonsusceptible horses. In contrast, I1-6, considered an anti-inflammatory cytokine, showed a higher expression in nonsusceptible horses 6 hours after inhalation challenge with allergens and pro-inflammatory antigens. These data suggest that the differences between susceptible and nonsusceptible horses to RAO are not only dependent on adaptive immunity but also start with an innate immune response.

The aminoglycoside gentamicin is often used in equine practice. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity, in equine patients, particularly after repeated dosing. The aim of the study was to investigate first in vitro the mechanisms contributing to the renal toxicity of gentamicin and to identify sensitive biomarkers indicating proximal tubule damage. To this end, the kidney-derived cell lines LLC-PKI and MDCK were treated with gentamicin at different concentrations. Toxicity was assessed by measuring the release of gamma-glutamyl transferase (GGT), and the production of reactive oxygen species (ROS). Cell viability was measured using Alamar blue (AB) and Neutral red (NR) cytotoxicity assays. Gentamicin exerted a dose-dependent toxicity. Primarily, loss of brush border membrane integrity, indicated by GGT leakage, and an increased ROS production were observed. As GGT was found to be a sensitive marker for gentamicin-induced renal cell injury, in the subsequent in vivo experiments, in which ponies were given gentamicin (3.0 mg/kg bw three times daily and 4.5 mg/kg bw twice daily) for five consecutive days, plasma levels and the urinary excretion of GGT and creatinine were measured and the GGT:creatinine ratio was calculated. Elevated GGT levels in urine following gentamicin therapy were observed, but this enzyme leakage was transient and returned to baseline values after cessation of therapy. It could thus be concluded that even a conservative dose regimen of gentamicin did not result in significant renal toxicity in healthy ponies.