Dose confirmation studies for monepantel, an amino-acetonitrile derivative, against fourth stage gastro-intestinal nematode larvae infecting sheep

Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Nine dose confirmation studies were conducted in Australia, New Zealand and Switzerland to confirm the minimum therapeutic oral dose of monepantel to control fourth stage (L4) gastro-intestinal nematode larvae in sheep (target species were Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus battus, Nematodirus filicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum). In each study, sheep infected with a defined selection of the target nematodes were treated with 2.5 mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. The results demonstrate high (95 < 100%) efficacy of monepantel when administered orally to sheep at 2.5 mg/kg for most species tested. Efficacy levels against N. spathiger and O. venulosum were variable and failed to meet the required regulatory standard (≥90%) in some studies. Efficacy was demonstrated against L4 stages of nematodes known to be resistant to either benzimidazole and/or levamisole anthelmintics (macrocyclic lactone resistant isolates were not available for testing). The broad-spectrum activity of monepantel against L4 larvae of common gastro-intestinal nematodes in sheep and its favorable safety profile represents a significant advance in the treatment of parasitic gastro-enteritis in this animal species. No adverse effects related to treatment with monepantel were observed.     

The Great Sydney Water Crisis of 1998

This paper traces the history of the contamination of Sydney's water supply between July and September 1998, its impact and consequences. Routine testing found persistently high readings of Cryptosporidium and Giardia in the water supply. After initial official inactivity, health warnings were issued leading to comprehensive boil water alerts. The paper examines the issues of scientific uncertainty and the response of the Government to the crisis. In particular, the paper examines the establishment and course of the Sydney Water Inquiry, chaired by Peter McClellan, QC, which delivered its final report in December 1998. The recommendations of the Inquiry are assessed, in particular the establishment of an independent catchment management authority, augmentation of treatment processes, and upgraded monitoring and research. Implementation of the recommendations by the Government by legislative and executive act is also addressed. Finally, the lessons to be learned are discussed, especially care of the catchment and restrictions on certain types of development within it. Postcript: Amazingly, no one got sick!     

Healing characteristics of deep digital flexor tenorrhaphy within the digital sheath of horses

OBJECTIVE: To describe the healing characteristics of deep digital flexor tenorrhaphy within the digital sheath. STUDY DESIGN: Experimental study. ANIMALS: Five mature horses. METHODS: Right thoracic limb, deep digital flexor tenorrhaphy was performed within the digital sheath. Limbs were cast in partial flexion using a short limb cast for 6 weeks. Next, extended heel shoes were used for limb support for 14 weeks. Healing was evaluated by sequential ultrasonographic examinations, and limb use was evaluated by force plate analysis. At 26 weeks, mechanical strength and morphologic characteristics of the repair site were evaluated. RESULTS: Gap (mean, 0.93 cm.) formation was evident in unloaded limbs at 3 weeks. This increased markedly by 6 weeks and was 5 cm at 26 weeks. Demarcation between the deep and superficial flexor tendons decreased as the transected ends adhered to the dorsal surface of the superficial flexor tendon. The intrathecal space was reduced by fibrous tissue. Mean maximum load to failure of the repair tissue was 4,616 +/- 3,556 N, with a mean stress of 12.99 +/- 2.78 MPa. The repair consistently failed at the adhesion between the transected tendon and the superficial flexor tendon. CONCLUSIONS: Intrathecal tenorrhaphy with external coaptation (in partial limb flexion) for 6 weeks resulted in gap healing, fibrous adhesion between the deep and superficial flexor tendons, fibrous tissue reduction of the intrathecal space, and a pasture-sound horse at 26 weeks. CLINICAL RELEVANCE: Without improved methods for immobilizing the deep digital flexor tendon, intrathecal tenorrhaphy is unlikely to result in first intention tendon healing.     

Algal-Derived Halogenated Sesquiterpenes from Laurencia dendroidea as Lead Compounds in Schistosomiasis Environmental Control

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (−)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.     

Abortion, stillbirth, neonatal death, and nutritional myodegeneration in a rabbit breeding colony

Vitamin E deficiency was found to be the cause of reproductive failure and nutritional myodegeneration in a rabbit breeding colony. The diagnosis was based on the low vitamin E concentration of doe liver (5.73 micrograms/g) associated with myodegeneration of tongue, skeletal muscle, and heart and the absence of other abnormal microbiologic and parasitologic findings. Supplementation of the diet with wheat germ oil returned the does' fertility to normal, and abortion, stillbirth, and neonatal death ceased.     

Studies on the aetiology of hydropericardium syndrome (Angara disease) in broilers.

The study was carried out to determine the aetiological agent(s) associated with hydropericardium syndrome (Angara disease) in broilers in Pakistan. The results indicate that in addition to adenovirus some other agent is involved in causing the disease but that this agent requires co-infection by an adenovirus for the reproduction of the typical signs of the syndrome. The nature of this agent remains unknown because no discrete virus or virus-like particle could be seen by electron microscopy.     

Metabolic alterations in dogs with osteosarcoma

OBJECTIVE: To evaluate changes in resting energy expenditure (REE) as well as protein and carbohydrate metabolism in dogs with osteosarcoma (OSA). ANIMALS: 15 weight-stable dogs with OSA that did not have other concurrent metabolic or endocrine illness and twelve 1-year-old sexually intact female Beagles (control dogs). PROCEDURES: Indirect calorimetry was performed on all dogs to determine REE and respiratory quotient (RQ). Stable isotope tracers (15N-glycine, 4.5 mg/kg of body weight, IV; 6,6-deuterium-glucose, 4.5 mg/kg, IV as a bolus, followed by continuous-rate infusion at 1.5 mg/kg/h for 3 hours) were used to determine rate of protein synthesis and glucose flux in all dogs. Dual-energy x-ray absorptiometry (DEXA) scans were performed to determine total body composition. RESULTS: Accounting for metabolic body size, REE in dogs with OSA was significantly higher before and after surgery, compared with REE of healthy control dogs. The RQ values did not differ significantly between groups. Dogs with OSA also had decreased rates of protein synthesis, increased urinary nitrogen loss, and increased glucose flux during the postoperative period. CONCLUSIONS AND CLINICAL RELEVANCE: Alterations in energy expenditure, protein synthesis, urinary nitrogen loss, and carbohydrate flux were evident in dogs with OSA, similar to results documented in humans with neoplasia. Changes were documented in REE as well as protein and carbohydrate metabolism in dogs with OSA. These changes were evident even in dogs that did not have clinical signs of cachexia.