A novel MCT1 and MCT4 dual inhibitor reduces mitochondrial metabolism and inhibits tumour growth of feline oral squamous cell carcinoma

Monocarboxylate transporters (MCTs) support tumour growth by regulating the transport of metabolites in the tumour microenvironment. High MCT1 or MCT4 expression is correlated with poor outcomes in human patients with head and neck squamous cell carcinoma (HNSCC). Recently, drugs targeting these transporters have been developed and may prove to be an effective treatment strategy for HNSCC. Feline oral squamous cell carcinoma (OSCC) is an aggressive and treatment‐resistant malignancy resembling advanced or recurrent HNSCC. The goals of this study were to investigate the effects of a previously characterized dual MCT1 and MCT4 inhibitor, MD‐1, in OSCC as a novel treatment approach for feline oral cancer. We also sought to determine the potential of feline OSCC as a large animal model for the further development of MCT inhibitors to treat human HNSCC. In vitro, MD‐1 reduced the viability of feline OSCC and human HNSCC cell lines, altered glycolytic and mitochondrial metabolism and synergized with platinum‐based chemotherapies. While MD‐1 treatment increased lactate concentrations in an HNSCC cell line, the inhibitor failed to alter lactate levels in feline OSCC cells, suggesting an MCT‐independent activity. In vivo, MD‐1 significantly inhibited tumour growth in a subcutaneous xenograft model and prolonged overall survival in an orthotopic model of feline OSCC. Our results show that MD‐1 may be an effective therapy for the treatment of feline oral cancer. Our findings also support the further investigation of feline OSCC as a large animal model to inform the development of MCT inhibitors and future clinical studies in human HNSCC.     

Polymorphisms in major histocompatibility complex genes and its associations with milk quality in Murrah buffaloes

Tropical Animal Health and Production - Animal breeding programs have used molecular genetic tools as an auxiliary method to identify and select animals with superior genetic merit for milk...     

Evaluation of efficacy of several disinfectants against Campylobacter jejuni strains by a suspension test

The objective of this study was to determine the efficacy of 16 active compounds and 11 commercial disinfectants against Campylobacter jejuni. Two reference strains (one of avian origin and the other isolated from bovine) and two avian field strains were tested in suspension test in the presence and absence of serum. Chloramine-T, povidone–iodine (1% available iodine), cetylpiridinium chloride, ethanol, isopropanol, chlorhexidine digluconate, formaldehyde, phenol, and 10 of the 11 commercial formulations (eight of them based on quaternary ammonium compounds) showed an excellent disinfectant capability, resulting in the highest level of reduction (>6-log₁₀) in colony-forming units of the four C. jejuni strains compared regardless of the presence or absence of organic material. These compounds might be helpful in the adoption of environmental control measures against C. jejuni.     

Fell Pony syndrome in a pony in North America

A 5-week-old Fell Pony colt was examined for fever, lethargy, and anemia. The colt had been lethargic for 1 week before examination, had continued to nurse, had a temperature of 104°F (40°C), and was treated with ceftiofur (5 mg/kg IM q12h). Approximately 36 hours before examination, the colt developed watery diarrhea. Blood work performed by the referring veterinarian on the day of admission revealed a PCV of 10%.     

Association between limb conformation and retention of sows through the second parity

OBJECTIVE: To determine the association between limb conformation scores in gilts and retention through the second parity. ANIMALS: 961 gilts. PROCEDURE: Gilts were monitored for 1 year. Baseline data recorded were conformation scores for the forelimbs and hind limbs and backfat thickness. Primary outcome was time to removal from a herd, and the secondary outcome was time to removal as a result of lameness. RESULTS: 662 of 961 (68.89%) females remained in herds through the second parity, whereas 299 (31.11%) were removed before the second parity. Survival time for females on the basis of conformation scores for the forelimbs and hind limbs differed significantly for total sow removals and removals as a result of lameness. Females with poor conformation scores for the hind limbs had an increased risk of being removed, compared with risk for females with better conformation scores. Risk of removal specifically as a result of lameness increased as conformation score for the hind limbs became poorer. Proportion of the total population that was removed and could be attributed to undesirable limb conformation was 16.13% for forelimbs and 12.90% for hind limbs. CONCLUSIONS AND CLINICAL RELEVANCE: Females with undesirable conformation were removed earlier than females with desirable conformation. This was particularly true for females with low conformation scores for the hind limbs. Selection of gilts on the basis of limb conformation may result in reduced attrition of females and improved performance of herds over time.     

Comparison of a camera - software system and typical farm management for detecting oestrus in dairy cattle at pasture

AIM: To compare the sensitivity, specificity, predictive values and accuracy of detection of oestrus using a novel oestrus detection strip (ODS) and a camera-software device (CSD) with typical farm management practices of visual observation and use of tail paint in dairy cattle at pasture. METHODS: Dairy cows (n = 480) in a seasonal-calving herd managed at pasture under typical commercial conditions in New Zealand were stratified by age, body condition score and days in milk, then randomly allocated to one of two groups prior to the planned start of mating (PSM). Tail paint was applied to all cows and oestrus detected by visual observation of oestrous behaviour and removal of paint, by farm staff. One group (n = 240) was fitted with ODS and also monitored for signs of oestrus using a CSD, while the Control group (n = 240) was monitored using tail paint and visual observations only. Cows detected in oestrus were artificially inseminated (AI), and pregnancy status determined using rectal palpation and ultrasonography, 51-52 days after the end of a 55-day A period. Results of pregnancy diagnosis were used to confirm the occurrence of oestrus, and the sensitivity, specificity, predictive value and accuracy of detection of oestrus compared between oestrus detection methods. RESULTS: The sensitivity and accuracy of oestrus detection in the Control group, using visual observation and tail paint, were low. Compared with the Control group, detection of oestrus using the ODS and CSD resulted in greater sensitivity (85% vs 78%; p = 0.006), specificity (99.6% vs 98.0%; p < 0.001), positive predictive value (PPV; 88% vs 51%; p < 0.001) and overall accuracy (99.0% vs 98.0%; p < 0.001). Negative predictive value (NPV) did not differ significantly between groups (99.4% vs 99.3%; p = 0.28). Pregnancy rate to first service was higher in the CSD group than in the Control group (72% vs 39%; p < 0.05). Use of the CSD significantly increased the cumulative proportion of cows pregnant to AI over the breeding period (p = 0.044). CONCLUSION AND CLINICAL RELEVANCE: The ODS and CSD was satisfactory for detection of oestrus in seasonal calving dairy herds grazing on pasture and could improve the sensitivity and accuracy of detection of oestrus in herds where these are low.     

An investigation into the role of Chlamydophila spp. in bovine upper respiratory tract disease

An outbreak of upper respiratory tract disease was investigated in a group of 17 housed home-bred calves on a mixed dairy, beef and sheep farm in Devon. Conjunctival swabs were collected and tested for Chlamydophila spp. DNA using a PCR test that detects Chlamydophila abortus and Chlamydophila psittaci. Six of the calves tested gave a positive result. Further epidemiological observations and laboratory testing indicated that the adult dairy cows, from which the affected calves originated, were the most likely source of infection.     

Trends in the incidence of tuberculosis in possums and livestock, associated with differing control intensities applied to possum populations

AIM: To determine the trap-catch index (an estimate of abundance) of brushtail possum (Trichosurus vulpecula) populations infected with bovine tuberculosis (Tb; Mycobacterium bovis) that must be achieved, and the length of time such an index must be maintained, for Tb to be eliminated from possum populations and adjacent livestock. METHODS: Between 1997-1998 and 2000-2001, trap-catch surveys of possum populations naturally infected with Tb and subjected to population-control measures were undertaken at four forest sites and two farmland sites. At the same time, possum carcasses were collected at these sites and their Tb status determined, and all contiguous cattle and deer herds were Tb tested and abattoir slaughter data for these herds were interrogated. RESULTS: Trap-catch surveys indicated that numbers of possums on the farmland sites surveyed were usually very low and well below the control targets set (i.e. a 5% trap catch or approximately 0.5-1 possum/ha) for the study. In contrast, trap-catch surveys undertaken in forest sites indicated possum numbers were more variable, and often recovered rapidly from control operations to exceed control targets within 1-3 years. The annual rate of recovery of possum populations in half of the forest population surveys undertaken exceeded published intrinsic rates of increase for possums. The overall prevalence of Tb in possum populations was < or =1.9% at 5/6 sites, and was 6.5% at the sixth site. Juvenile possums infected with Tb were trapped within but near the edge of control zones and appeared to represent an immigrant source of infection. Mature infected possums survived control operations apparently by having home ranges in uncontrolled patches within control areas. Infection in possums appeared to be eliminated from one study site by the intensive control undertaken, but elimination at other sites appeared less likely. Levels of Tb in livestock on or adjacent to the study sites fell by at least 50% during the study, and cattle in one area tested clear for the first time in 20 years. CONCLUSIONS: Initial control of possums in forest appeared to achieve national control targets set by the Animal Health Board (AHB), despite trap-catch data often providing misleading population estimates. Such targets were often exceeded within 1-3 years. By comparison, possum control on farmland appeared to maintain populations at very low levels, while control on forest margins maintained populations at intermediate levels. Control was least effective in deep forest where human access was most difficult. Intensive population control measures appeared to have led to a reduced incidence of Tb in livestock at 3/4 sites, and elimination of Tb in livestock at one site. This result supports modelling studies that predict the eradication of Tb from possums through ongoing intensive control and may explain the lower success achieved with earlier less-intensive possum control.     

Evaluation of IgG subclass responses against Dermatophagoides farinae allergens in healthy and atopic dogs

A semiquantitative chemiluminescent Western blot analysis system was developed and validated to evaluate antigen-specific IgG subclass responses to electrophoretically separated proteins of Dermatophagoides farinae in healthy and atopic dogs. Both groups mounted similar D. farinae-specific IgG1 and IgG4 responses to multiple antigens, but IgG2 and IgG3 responses were difficult to detect. The most commonly recognized bands in both groups were 18 and 98 kDa antigens for IgG1 and 18, 45, 66, 98, 130 and 180 kDa for IgG4. The number of bands recognized per dog did not differ significantly, but significantly more atopic dogs had an IgG1 response to a 180 kDa protein. The overall D. farinae-specific IgG1 and IgG4 responses were slightly higher, but not significantly different, in the healthy group. The results suggest that some antigens produced by D. farinae can induce different subclass responses. However, as most of these responses are seen in both healthy and atopic dogs, they are likely to merely represent recognition of foreign proteins presented to the immune system, rather than involvement in the pathogenesis of atopic dermatitis. The role of the 180 kDa antigen warrants further study.     

Detection of chlamydiae in boar semen and genital tracts

Chlamydiae cause abortion and reproductive disorders in sows. Although organisms can infect the male genital tract, little is known about the disease situation in boars. Hence, we examined the prevalence of chlamydial infection in semen and genital tracts of boars. Samples collected from Swiss boars (group A: n=42), and boars from Germany (group B: n=39) were examined by bacteriology, LPS-ELISA, immunohistochemistry (IHC) and polymerase chain reaction (PCR). The latter methodology involved use of three PCR assays including 16Sig rDNA, IGS-S (intergenic spacer 16S/23S-Short) and IGS-L (intergenic spacer 16S/23S-Long) PCR for comparison methods. PCR sensitivity and the presence of potential PCR inhibitors were determined by spiking semen with Chlamydophila (Cp.) abortus DNA. Detection limits of the 16Sig and IGS-S PCR were 10 templates, while the IGS-L PCR was less sensitive (100 templates). Of 25 semen samples that were collected from group A, one semen sample was positive for Cp. psittaci and two were positive for Chlamydia-like organisms by 16Sig PCR. Screening of sera from Swiss boars revealed three animals with positive reactions in the LPS-ELISA, although we failed to detect chlamydiae within organs of these or sera-negative animals by IHC or IGS-S PCR. In group B, 10 ejaculates were positive for Chlamydia (C.) suis and two were positive for Chlamydia-like organisms by 16S PCR. The identification of DNA from Chlamydia-like organisms in semen from both groups of boars was surprising and a role for these bacteria in reproductive diseases requires further assessment. In conclusion, the prevalence of chlamydial infection was low in group A animals indicating that venereal transmission may not be significant for Chlamydia-associated reproductive diseases in pigs, although rare cases may occur.