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Coles, G.

Publications and source records attributed to Coles, G..

3 recordsLinked to original sources

Advantageous prebiotic effects in ruminants of semi-refined chelates of dibasic cations with three-and four-carbon organic acids.

Providing a semi-refined chelate of magnesium with mixed organic acids gave controlled magnesium supplementation of equivalent effectiveness to conventional uncontrolled administration of MgO in regard to prevention of milk fever in dairy cows. The supplement was palatable and supplementation produced no adverse health effects as adjudged by veterinary supervision. Monitoring productivity of cows provided with the supplement compared with controls indicated that the use of the supplement provided a paranutritional improvement in feed utilisation, resulting in a significant increase in milk solids yield of up to 23% through the period of supplementation, together with an improvement in body reserves sufficient to sustain a continuing milk solids yield advantage of up to 5% for two months after cessation of feeding. Since this increase in productivity was achieved without an increase in feed intake, use of the experimental supplement is considered to have resulted in a prebiotic effect in ruminant fermentation and consequently a commensurate reduction in methane intensity of production. Important Note on history of projectThe investigations reported in this paper were conducted under strict, independent veterinary supervision. This was because the responsible animal ethics committee first stated that the proposed study of the efficacy of a novel means of meeting magnesium supplemental requirements was of no academic interest, and refused to assess an application for ethics approval on those grounds. When the first experiment reported suggested the possibility of a prebiotic effect, the committee said that because there was no prior publication of such an effect in ruminants, the experimental hypothesis could not be sustained. This was despite the fact that prebiotic effects were well-known in humans and monogastric animals. As a consequence, the Committee refused to assess the research. Subsequent investigations (e.g https://peerj.com/articles/18103) clearly indicate that the material under investigation could exert the prebiotic effect seen in monogastrics. In light of the present interest in inhibition of methanogenesis, the results reported below are of particular interest, requiring that they be placed in the public domain. Note that across both experiments, no adverse events related to administration of the prebiotic were observed by the veterinarian. Conduct of the investigations reported has been compared with the ARRIVE guidelines, and found to be compliant.

physiology↗

First evaluation and detection of ivermectin resistance in gastrointestinal nematodes of sheep and goats in South Darfur, Sudan

In Sudan, resistance to benzimidazoles has been reported recently in cattle and goats from South Darfur. Herein, ivermectin efficacy against gastrointestinal nematodes (GINs) was evaluated in sheep and goats in three study areas in South Darfur. The faecal egg count reduction test (FECRT) was used to evaluate the efficacy of ivermectin in sheep and goats naturally infected with GINs in the region of Bulbul (goats: n=106), Kass (goats: n=40) and Nyala (Domaia (sheep: n=47, goats: n=77) and the University farm (goats: n=52)), using different treatment plans, and the efficacy was evaluated 12 days after treatment. Ivermectin efficacy was also evaluated in goats experimentally infected using local Haemonchus contortus isolates from Kass and Nyala. Nematodes surviving ivermectin treatment in goats in Bulbul and Nyala were harvested and larvae used to infect worm-free male sheep (n=6, [≤]6 months old). Infected sheep were dosed subcutaneously with ivermectin every eight days with increasing doses from 0.2 mg/kg to 1.6 mg/kg bodyweight (bw). Reduced ivermectin efficacy was identified in sheep and goats in the four study locations. Using a paired statistic, the efficacy of a therapeutic dose in sheep was 75.6% (90% upper credible limit (UCrL): 77.5%), while twice the recommended dose led to a reduction of 92.6% (90% UCrL: 93.3%). In goats, the FECRs of a therapeutic dose were 72.9 - 95.3% (90% UCrL range: 73.6 - 95.7%) in Bulbul, Nyala Domaia, Nyala University farm and Kass. Twice the dose recommended for goats in Bulbul revealed a 90% UCrL of 87.6%. All post-treatment faecal cultures contained only Haemonchus spp. larvae. The experimental infection trials in sheep and goats supported our findings from field trials and calculated upper 90% CrL of below 98.9%. For the first time highly ivermectin resistant H. contortus populations have been identified in sheep and goats in Sudan, and resistance was experimentally confirmed.

zoology↗

Anti-GD2 antibody disrupts GD2:Siglec-7 interactions and synergizes with CD47 blockade to mediate tumor eradication

The disialoganglioside GD2 is consistently overexpressed in neuroblastoma and osteosarcoma, and is variably expressed in other sarcomas, gliomas, neuroendocrine tumors, and epithelial cancers. Anti-GD2 antibodies have improved the survival rates of patients with neuroblastoma only when administered as part of intense chemotherapy-based cytotoxic regimens, which are associated with debilitating late effects including hearing loss, growth retardation, and secondary leukemias. Despite broad expression of GD2 on osteosarcoma, anti-GD2 antibody has not mediated significant antitumor activity in that disease or any other GD2+ cancers. CD47 is a checkpoint molecule overexpressed on tumor cells that inhibits macrophage activity, and CD47 blockade has demonstrated promising clinical activity in early human trials. We investigated whether anti-CD47 antibody could enhance the efficacy of anti-GD2 antibody in neuroblastoma and other GD2+ malignancies. We demonstrate substantial synergy of these two agents, resulting in the recruitment of tumor associated macrophages (TAMs) to mediate robust and durable anti-tumor responses. The responses are driven by GD2-specific factors that reorient the balance of macrophage activity towards phagocytosis of tumor cells, including disruption of a newly described GD2:Siglec-7 axis. These results demonstrate the unique synergy of combining anti-GD2 with anti-CD47, which has the potential to significantly enhance outcomes for children with neuroblastoma and osteosarcoma and will soon be investigated in a first-in-human clinical trial.

immunology↗