piperidines and Rodent-Diseases

Leech attachment is a common nuisance to outdoor recreationists and farmers in aquatic environments. Consequences include bleeding, infection, and, rarely, death. Methods to prevent leech attachment are anecdotal and individual; effective repellent formulations with universal applicability are needed. In this study, icaridin is demonstrated to be repellent and toxic to aquatic leech, and formulation of icaridin loading nitrocellulose (Icar-Nitr) is proposed as a new leech repellent. The nitrocellulose provided sustained drug release and waterproof properties. One optimal formulation, 10-Icar-Nitr, proved effective for leech repelling in aquatic environment. Using a rat model, the same formulation also showed removal and killing after leech attachment. The nitrocellulose reduced percutaneous absorption of icaridin, and 10-Icar-Nitr showed good biocompatibility. This study provides a potential new and practicable strategy for prevention and removal against leech attachment and bites.

Topics: Animals; Bites and Stings; Collodion; Insect Repellents; Piperidines; Rats; Rodent Diseases

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic neoplasm. Mutations in src homology 2 domain-containing phosphatase 2 (SHP2; encoded by PTPN11), which recently have been identified in canine HS tumour cells, could be attractive therapeutic targets for SHP099, an allosteric inhibitor of SHP2. Here, molecular characteristics of wild-type SHP2 and four SHP2 mutants (p.Ala72Gly, p.Glu76Gln, p.Glu76Ala and p.Gly503Val), including one that was newly identified in the present study, were investigated. Furthermore, in vivo effects of SHP099 on a HS cell line carrying SHP2 p.Glu76Ala were examined using a xenograft mouse model. While SHP2 Glu76 mutant cell lines and SHP2 wild-type/Gly503 mutant cell lines are highly susceptible and non-susceptible to SHP099, respectively, a cell line carrying the newly identified SHP2 p.Ala72Gly mutation exhibited moderate susceptibility to SHP099. Among recombinant wild-type protein and four mutant SHP2 proteins, three mutants (SHP2 p.Ala72Gly, p.Glu76Gln, p.Glu76Ala) were constitutively activated, while no activity was detected in wild-type SHP2 and SHP2 p.Gly503Val. Activities of these constitutively activated proteins were suppressed by SHP099; in particular, Glu76 mutants were highly sensitive. In the xenograft mouse model, SHP099 showed anti-tumour activity against a SHP2 p.Glu76Ala mutant cell line. Thus, there was heterogeneity in molecular characteristics among SHP2 mutants. SHP2 p.Glu76Ala and perhaps p.Glu76Gln, but not wild-type SHP2 or SHP2 p.Gly503Val, were considered to be oncogenic drivers targetable with SHP099 in canine HS. Further studies will be needed to elucidate the potential of SHP2 p.Ala72Gly as a therapeutic target of SHP099 in canine HS.

Topics: Animals; Disease Models, Animal; Dog Diseases; Dogs; Heterografts; Histiocytic Sarcoma; Mice; Mutation; Neoplasms; Piperidines; Pyrimidines; Rodent Diseases

Piperine, a trans-trans-isomer of 1-piperoyl-piperidine, was tested in combination with mupirocin for antimicrobial activity against Staphylococcus aureus strains including meticillin-resistant S. aureus. The combination markedly reduced the MIC of mupirocin and also lowered the mutation frequency. Enhanced accumulation and efflux of ethidium bromide from wild-type and mutant (Mup(r)-1) strains in the presence of piperine indicated that inhibition of efflux could be a possible mechanism of potentiation of mupirocin activity by piperine. The combination of piperine with mupirocin in a dermal infection model of mice showed better in vivo efficacy when compared with the commercially available formulation of 2 % mupirocin.

Topics: Alkaloids; Animals; Anti-Bacterial Agents; Bacterial Proteins; Benzodioxoles; Disease Models, Animal; Drug Synergism; Enzyme Inhibitors; Ethidium; Female; Membrane Transport Proteins; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Mupirocin; Piperidines; Polyunsaturated Alkamides; Rodent Diseases; Staphylococcal Infections; Treatment Outcome

Acute outbreaks of diarrhoea with high mortality rates are frequently observed in rabbits. Amongst various aetiological factors Escherichia coli or its toxins have been found to be commonly incriminated. Sulphonamides or antibiotics are used to treat rabbits with bacterial diarrhoea. The result of the antibiotic treatment is moderately successful. We had good results using oral rehydration treatment in combination with loperamide hydrochloride (Immodium) in a colony of rabbits with E. coli diarrhoea.

Topics: Acute Disease; Animals; Combined Modality Therapy; Diarrhea; Fluid Therapy; Loperamide; Piperidines; Rabbits; Rodent Diseases