Involvement of hepatic xenobiotic related genes in bromadiolone resistance in wild Norway rats, Rattus norvegicus (Berk.)

To examine the role of xenobiotic relevant genes in bromadiolone resistance in wild Norway rats (Rattus norvegicus) we compared the constitutive liver gene expression and expression upon bromadiolone administration in bromadiolone resistant and anticoagulant susceptible female rats using a LNA microarray and quantitative PCR. Resistant rats showed significantly higher constitutive expression of the cytochrome P450 genes Cyp2c13 and Cyp3a2 and lower expression of Cyp2e1 and Gpox1 compared to the susceptible rats. The Cyp1a2, Cyp2c13, Cyp2e1, Cyp3a2 and Cyp3a3 genes were significantly higher expressed in resistant than susceptible rats upon bromadiolone exposure. To establish how bromadiolone affected xenobiotic gene expression in the two strains we compared bromadiolone expression profiles to saline profiles of both strains. Bromadiolone mediated significant up-regulation of Cyp2e1 and Cyp3a3 expression in the resistant rats whereas the rodenticide conferred down-regulation of Cyp2e1, Cyp3a3 and Gpox1 and induction of Cyp2c12 expression in susceptible rats. Cyp2c13 and Cyp3a2 expression were markedly suppressed in both strains upon treatment. This suggests that xenobiotic relevant enzymes play a role in bromadiolone resistance in the Norway rat. A high constitutive expression of Cyp2c13 and Cyp3a2 and induction of Cyp1a2, Cyp2e1 and Cyp3a3 expression during bromadiolone exposure may increase the resistance to bromadiolone presumably by facilitating increased detoxification and decreased liver injury.     

Intratesticular and subcutaneous lidocaine alters the intraoperative haemodynamic responses and heart rate variability in male cats undergoing castration

ObjectiveTo evaluate the usefulness of intratesticular and subcutaneous lidocaine in alleviating the intraoperative nociceptive response to castration, measured by pulse rate (PR) and mean arterial pressure (MAP), and to test the applicability of heart rate variability (HRV) analysis in assessing this response.Study designRandomized, controlled, observer-blinded experimental trial.AnimalsThirty-nine healthy male cats admitted for castration.MethodsOne group received general anaesthesia and served as control group (GA), while the treatment group (LA) additionally received local anaesthesia (lidocaine 2 mg kg^?1) intratesticularly and subcutaneously. PR and MAP were recorded at anaesthesia baseline (T0), treatment (T1), incision left testicle (T2), traction on spermatic cord (T3), tightening of the autoligature and resection of the cord (T4), incision on the right side (T5), traction on spermatic cord (T6), and tightening of the autoligature and resection of cord (T7). HRV analysis was divided into three 5-minute intervals: baseline (H0), treatment (H1), and surgery (H2).ResultsThere were significant increases in PR and MAP for both groups during surgery from T3 onwards; however, the increase in the treatment group (LA) was significantly lower than for the control group (GA). For HRV analysis, significant differences were found between groups in the following parameters during surgery: TP (total power), VLF (very low frequency), SDNN (standard deviation of NN intervals [=the interval between two consecutive R-waves in the ECG]), and TI (triangular index), which were lower in the LA group. Mean NN was significantly lower in the GA group, whereas LF (low frequency) and LFn (low frequency, normalized value) were lower in the LA group. HF (high frequency) and HFn (high frequency, normalized value) decreased significantly from H1 to H2 in both groups.Conclusions and clinical relevanceThe study showed that the nociceptive response to surgery was alleviated by the use of intratesticular and subcutaneous lidocaine and that HRV analysis is a promising research tool to estimate intraoperative nociception in cats during general anaesthesia.     

Mast cell tumours and other skin neoplasia in Danish dogs - data from the Danish Veterinary Cancer Registry

Background

The Danish Veterinary Cancer Registry (DVCR) was established in May 2005 to gather information about neoplasms in the Danish dog and cat populations. Practitioners from more than 60 clinics throughout Denmark have submitted data on these species. The objectives of the current study were, with a special focus on mast cell tumours (MCT) to investigate the occurrence, gender distribution, biological behaviour, locations, types, the diagnostic method used and treatment of skin neoplasms in dogs based on information reported to the DVCR.

Methods

From May 15^th 2005 through February 29^th 2008, reports on a total of 1,768 canine cases of neoplasia in the skin, subcutis or adnexa were submitted.) Of these, 765 cases (43%) were confirmed by cytology or histopathology.

Results

The majority of dogs had a benign neoplasm (66%) while 21% were cases of malignant neoplasia. The most commonly encountered malignant neoplasms were MCT and soft tissue sarcomas and for benign neoplasms, lipomas and histiocytomas were the most common. The location of the neoplasms were primarily in the cutis, subcutis or in the perianal region. The occurrence, gender distribution, biological behaviour and location of canine skin neoplasias in Denmark were similar to earlier reports, although some national variations occurred. A correlation between grade of MCT and the proportion of cases treated surgically was observed.

Conclusions

Population based cancer registries like the DVCR are of importance in the collection of non-selected primary information about occurrence and distribution of neoplasms. The DVCR provides detailed information on cases of skin neoplasms in dogs and may serve as a platform for the study of sub-sets of neoplastic diseases (e.g. MCT) or subgroups of the canine population (e.g. a specific breed).     

Evaluation of skin erythema by use of chromametry and image analysis of digital photographs after intradermal administration of histamine in dogs

OBJECTIVE: To investigate whether the degree of erythema during an induced erythematous reaction, the histamine skin test reaction, can be assessed objectively by use of chromametry and image analysis of digital photographs. ANIMALS: 9 pet dogs (6 Golden Retrievers and 3 yellow Labrador Retrievers). PROCEDURE: Histamine phosphate was injected intradermally, and erythema of the wheal reaction was evaluated during the hour that followed. This was done by use of clinical scores, chromametry, and image analysis of digital photographs. Method reproducibility was tested for visual evaluation of printouts of digital photographs and for image analysis of the same photographs. RESULTS: The coefficient of variation of the technically derived erythema values was < 10%. The reproducibility of image analysis was high and the range of agreement between observers narrow. Using chromametry, it was not possible to differentiate between various degrees of erythema intensity as visually perceived. In contrast, use of image analysis of digital photographs enabled discrimination of slight erythema from moderate and marked erythema. The dynamics of reaction measured by chromametry followed the clinical observation. CONCLUSIONS AND CLINICAL RELEVANCE: Chromametric values are comparable to those obtained by visual inspection. As the result of standardized conditions, chromametry is preferred over digital photography.     

Splanchnic metabolism of volatile fatty acids absorbed from the washed reticulorumen of steers

Six steers fitted with a ruminal cannula and chronic indwelling catheters in the mesenteric artery, mesenteric vein, hepatic portal vein, hepatic vein, as well as in the right ruminal vein were used to study metabolism of VFA absorbed from buffers in the emptied and washed reticulorumen. [2-(13)C]Acetate was infused into a jugular vein to study portal-drained visceral (PDV) uptake of arterial acetate, hepatic unidirectional uptake of acetate, and whole-body irreversible loss rate (ILR). Isobutyrate was infused into the right ruminal vein to calibrate VFA fluxes measured in the portal vein. On sampling days, the rumen was emptied and incubated in sequence with a 0-buffer (bicarbonate buffer without VFA), a VFA-buffer plus continuous intraruminal infusion of VFA, and finally another 0-buffer. Ruminal VFA absorption was determined as VFA uptake from the VFA-buffer and metabolic effects determined as the difference between metabolite fluxes with VFA-buffer and 0-buffers. Steady absorption rates of VFA were maintained during VFA-buffer incubations (4 h; 592+/-16, 257+/-5, 127+/-2, 17+/-<1, 20+/-<1 mmol/h, respectively, of acetate, propionate, butyrate, isovalerate, and valerate). The portal flux of acetate corrected for PDV uptake of arterial acetate accounted for 105+/-3% of the acetate absorption from the rumen, and the net portal flux of propionate accounted for 91+/-2% of propionate absorption. Considerably less butyrate (27+/-3%) and valerate (30+/-3%) could be accounted for in the portal vein. The sum of portal VFA and 3-hydroxybutyrate as well as lactate represented 99+/-3% of total VFA acetyl units and 103+/-2% of VFA propionyl units. Estimates are maximum because no accounting was made for lactate derived from glycolysis in the PDV. The net splanchnic flux of VFA, lactate, 3-hydroxybutyrate, and glucose accounted for 64+/-2% of VFA acetyl units and 34+/-5% of VFA propionyl units. Results indicate that there is a low "first-pass" uptake of acetate and propionate in the ruminal epithelium of cattle, whereas butyrate and valerate are extensively metabolized, though seemingly not oxidized to carbon dioxide in the epithelium but repackaged into acetate, 3-hydroxybutyrate, and perhaps other metabolites. When PDV "second-pass" uptake of arterial nutrients is accounted for, PDV fluxes of VFA, lactate, and 3-hydroxybutyrate represent VFA production in the gastrointestinal tract and thereby VFA availability to the ruminant animal.