Impact of the COVID-19 Pandemic on the Welfare of Animals in Australia.

We report on the various responses in Australia during 2020 to minimize negative impacts of the COVID-19 pandemic on the welfare of animals. Most organizations and individuals with animals under their care had emergency preparedness plans in place for various scenarios; however, the restrictions on human movement to contain the spread of COVID-19, coupled with the economic impact and the health effects of COVID-19 on the skilled workforce, constituted a new threat to animal welfare for which there was no blueprint. The spontaneous formation of a national, multisectoral response group on animal welfare, consisting of more than 34 organizations with animals under their care, facilitated information flow during the crisis, which helped to mitigate some of the shocks to different organizations and to ensure continuity of care for animals during the pandemic. We conclude that animal welfare is a shared responsibility, and accordingly, a multisectoral approach to animal welfare during a crisis is required. Our experience demonstrates that to safeguard animal welfare during crises, nations should consider the following: a national risk assessment, clear communication channels, contingency plans for animal welfare, a crisis response group, and support systems for animal care providers. Our findings and recommendations from the Australian context may inform other countries to ensure that animal welfare is not compromised during the course of unpredictable events.

Maternal rat serum concentrations of dimethadione do not explain intra-litter differences in the incidence of dimethadione-induced birth defects, including novel findings in foetal lung.

To investigate mechanisms of chemical-induced congenital heart defects (CHD) we have developed a rat model using dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant, trimethadione (TMD). Dosing pregnant rats with 300mg/kg DMO every 12h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses) produces a mean 74% incidence of CHD with inter litter variability ranging from 40 to 100%. The goal of this study was to determine if the variability in maternal serum concentrations of DMO on GD 14, a surrogate marker for total exposure, was related to the inter-litter differences in teratogenic outcomes. To test this hypothesis, pregnant rats were dosed as described above and serum levels of DMO assessed on GD 14. On GD 21, foetuses were collected by caesarean section, assessed for a number endpoints and the outcomes were correlated with the GD 14 serum concentrations of DMO. DMO exposure was associated with decreased foetal body weight, increased incidence of sternal defects and CHD, but these endpoints were not meaningfully correlated with maternal concentrations of DMO. Novel findings were decreased viability as measured one-hour following caesarean section, and delayed alveolar maturation. The major conclusions from these studies were first, that serum DMO concentrations on GD 14 did not predict teratogenicity, and second, delayed lung development may contribute to the decreased survival of foetuses at the time of caesarean section.

Evidence against the involvement of chronic cerebrospinal venous abnormalities in multiple sclerosis. A case-control study.

OBJECTIVE: Multiple sclerosis (MS) is a chronic neurodegenerative disease of the CNS. Recently a controversial vascular hypothesis for MS, termed chronic cerebrospinal venous insufficiency (CCSVI), has been advanced. The objective of this study was to evaluate the relative prevalence of the venous abnormalities that define CCSVI. METHODS: A case-control study was conducted in which 100 MS patients aged between 18-65 y meeting the revised McDonald criteria were randomly selected and stratified into one of four MS subtypes: relapsing/remitting, secondary progressive, primary progressive and benign. Control subjects (16-70 y) with no known history of MS or other neurological condition were matched with the MS cases. All cases and controls underwent ultrasound imaging of the veins of the neck plus the deep cerebral veins, and magnetic resonance imaging of the neck veins and brain. These procedures were performed on each participant on the same day. RESULTS: On ultrasound we found no evidence of reflux, stenosis or blockage in the internal jugular veins (IJV) or vertebral veins (VV) in any study participant. Similarly, there was no evidence of either reflux or cessation of flow in the deep cerebral veins in any subject. Flow was detected in the IJV and VV in all study participants. Amongst 199 participants there was one MS subject who fulfilled the minimum two ultrasound criteria for CCSVI. Using MRI we found no significant differences in either the intra- or extra-cranial venous flow velocity or venous architecture between cases and controls. CONCLUSION: This case-control study provides compelling evidence against the involvement of CCSVI in multiple sclerosis.

Analgesic targets: today and tomorrow.

Pain is recognized as a multifactorial sensory experience that is wholly unpleasant. It can vary in intensity from mild to severe and its duration can be anything from transient to persistent. Today we know so much more about the peripheral nociceptor as the primary detection apparatus for painful stimuli. We also understand in far greater detail the neurochemical mechanisms that occur at the level of the spinal cord and the complex interplay that exists between excitatory and inhibitory neural pathways. As a consequence of the assembly of this new body of evidence there are clear pointers that direct our attention to receptors, signaling pathways, enzymes and ion channels that all have the potential to be targets for novel, effective analgesics. The purpose of this review is to highlight some of the knowledge that has been assembled on this subject in recent years.

Inhibition of COX pathway in experimental myocardial infarction.

Release of inflammatory mediators within the ischemic myocardium has long been thought to contribute to myocardial damage and dysfunction. Myocardial infarction (MI) and congestive heart failure (CHF) were induced in rats by ligating the left coronary artery. Animals were treated with the selective cyclooxygenase-2 (COX-2) inhibitor-5,5-dimethyl-3-(3-fluorophenyl1)-4-(4-methyl-sulphonyl-2(5H)-fluranone (DFU), low-, high-dose acetyl salicylic acid (aspirin), or vehicle for 3 months. Strong immunoreactivity for COX-2 was detected in the cardiomyocytes, vascular endothelial cells, and macrophages in the infarcted myocardium. Compared to the vehicle, treatment with DFU significantly reduced left ventricular end-diastolic pressure, central venous pressure, lung wet/dry ratio and infarct size, and improved cardiac contractility (P < 0.05). In comparison, treatment with low or high doses of aspirin did not significantly impact any of these parameters. These findings demonstrate that induction of myocardial COX-2 in rats with CHF secondary to MI contributes to the cardiac injury and dysfunction associated with this disease, and that therapy aimed at inhibiting this enzymatic pathway at the onset of the disease may be beneficial in the treatment of MI and CHF.

Cyclooxygenase-2 (COX-2) in acute myocardial infarction: cellular expression and use of selective COX-2 inhibitor.

Our previous work has shown strong expression of COX-2 in the myocardium of patients with end-stage ischemic heart failure. The purpose of this study was to determine the cellular expression of this enzyme in the setting of acute myocardial infarction (AMI) and determine the role of COX-2 in experimental animals using a selective COX-2 inhibitor. Experimental AMI was induced in rats by ligating the left coronary artery. Animals were either treated with a selective COX-2 inhibitor (5 mg x kg(-1) x day(-1)) or vehicle. Three days after ligation, cardiac function was assessed and infarct size was determined. Myocardial specimens were immunostained with antiserum to COX-2. Plasma concentration of prostanoids was measured by enzyme immunoassay. There was strong expression of COX-2 in the myocytes, endocardium, vascular endothelial cells, and macrophages in the infarcted zone of the myocardium. In contrast, little expression was seen in the myocardium of control rats. Animals treated with the COX-2 inhibitor showed a significant improvement in left ventricular (LV) end-diastolic pressure (P < 0.05) and LV systolic pressure (P < 0.01), and a reduction in infarct size (P < 0.05). Inhibition of COX-2 significantly decreased plasma concentration of thromboxane B2 (P < 0.05); however, it did not affect 6-keto-prostaglandin F1alpha. Induction of COX-2 during AMI appears to contribute to myocardial injury, and treatment with the specific inhibitor of the enzyme ameliorated the course of the disease.