Small molecules in the venom of the scorpion Hormurus waigiensis

Despite scorpion stings posing a significant public health issue in particular regions of the world, certain aspects of scorpion venom chemistry remain poorly described. Although there has been extensive research into the identity and activity of scorpion venom peptides, non-peptide small molecules present in the venom have received comparatively little attention. Small molecules can have important functions within venoms; for example, in some spider species the main toxic components of the venom are acylpolyamines. Other molecules can have auxiliary effects that facilitate envenomation, such as purines with hypotensive properties utilised by snakes. In this study, we investigated some non-peptide small molecule constituents of Hormurus waigiensis venom using LC/MS, reversed-phase HPLC, and NMR spectroscopy. We identified adenosine, adenosine monophosphate (AMP), and citric acid within the venom, with low quantities of the amino acids glutamic acid and aspartic acid also being present. Purine nucleosides such as adenosine play important auxiliary functions in snake venoms when injected alongside other venom toxins, and they may have a similar role within H. waigiensis venom. Further research on these and other small molecules in scorpion venoms may elucidate their roles in prey capture and predator defence, and gaining a greater understanding of how scorpion venom components act in combination could allow for the development of improved first aid

Detecting Emerging Diseases in Farm Animals through Clinical Observations

Clinical observations will allow early detection of emerging diseases in animal to enhance response time and capabilities

Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial

<div><p>Background</p><p>Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2) is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1) and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.</p><p>Methods and findings</p><p>To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v.) infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d) or terlipressin (single 2-mg i.v. bolus), and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow.</p><p>Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT/eNOS/NO signaling pathway in the kidney. In the randomized clinical study, infusion of serelaxin for 120 min increased total renal arterial blood flow by 65% (95% CI 40%, 95%; <i>p <</i> 0.001) from baseline. Administration of serelaxin was safe and well tolerated, with no detrimental effect on systemic blood pressure or hepatic perfusion. The clinical study’s main limitations were the relatively small sample size and stable, well-compensated population.</p><p>Conclusions</p><p>Our mechanistic findings in rat models and exploratory study in human cirrhosis suggest the therapeutic potential of selective renal vasodilation using serelaxin as a new treatment for renal dysfunction in cirrhosis, although further validation in patients with more advanced cirrhosis and renal dysfunction is required.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01640964" target="_blank">NCT01640964</a></p></div

Development of a novel monitoring and surveillance system for endemic animal diseases in New Zealand : dissertation submitted in partial fulfilment of the requirements for the degree of Masters of Veterinary Studies (Epidemiology) at Massey University, Turitea, Palmerston North, New Zealand

Disease surveillance of animal populations has taken on renewed importance. The literature regarding disease surveillance systems, particularly with respect to animal diseases is summarised in section 1. Section 2 explores three potential sources of dairy cattle endemic disease data, with a view to utilising this data within the national disease surveillance system and as a model for gathering data from other animal species. Disease records stored on farm computers were retrospectively sourced from forty dairy farmers, from paper records of their servicing veterinary practices and from laboratory records held by the practice for these same farmer's animals. In this way, the loss of data on recorded disease events from farmer to veterinarian to animal health laboratory could be quantified and characterised. Frequency and magnitude of veterinary activity on farms was also quantified, as an indicator of "coverage" of the dairy cattle population, with respect to disease surveillance capability. As expected farmers recorded the largest number of disease events (14.6 per 1000 cow months at risk, the veterinary practitioners the next (5.2 per 1000 cow months) and animal health laboratories the least (0.58 per 1000 cow months). Twenty-five percent of farmers did not record any disease data. Of those farmers who did record diseases, 84% of records were cases of lameness or mastitis. Farmers rarely recorded veterinary diagnoses. When lameness and mastitis were excluded, veterinary records gave the highest rate (3.6 per 1000 cow months) and spectrum of diseases events recorded. Veterinary records had a high (22%) percentage of undiagnosed or unspecified cases when compared to farmer records. Veterinary practices visited the farms on average 17.8 times per year and handled on average 156 cows per 1000 cow months. The animal health laboratories made positive disease diagnoses at a rate of 0.24 per 1000 cow months. Approximately half of these were milk samples for routine culture and sensitivity testing. Veterinary practice records offer valuable information for monitoring the temporal and spatial pattern of disease events on farms. Section 3 outlines elements of a prototype palmtop recording system (VetPAD), which offers easy standardised data capture. Section 4 explores a possible future for Veterinary Practitioner Assisted Disease Surveillance (VetPAD) using a syndromic disease reporting approach