Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Functional involvement of L-type calcium channels and cyclic nucleotide-dependent pathways in cadmium-induced myometrial relaxation in rats.

Modulation of myometrial spontaneity by cadmium (Cd) and its regulatory pathways was studied in rat uterus in the absence and presence of blockers of different signaling pathways. Isometric tension in myometrial strips, under a resting tension of 1 g, mounted in organ bath containing Ringer-Locke solution (RLS) continuously aerated with carbogen, was measured using data acquisition system-based physiograph and Lab Chart Pro V7.3.7 software. Mean integral tension was measured for 8 min. Cd (1 nM-0.1 mM) not only produced concentration-dependent inhibitory effect on rat myometrium but it (10 µM) also significantly ( p < 0.05) inhibited calcium chloride and BAY K-8644-induced myometrial contraction. Glybenclamide (10 µM), 4-aminopyridine (1 mM), and propranolol (10 µM) failed to significantly attenuate Cd-induced inhibitory responses, while L-NAME (0.1 mM), 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 25 µM), and 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536; 1 µM) significantly ( p < 0.05) produced inhibitory effects on Cd-induced myometrial relaxation. Phenylephrine (1 nM-10 µM) and salbutamol (0.01 nM-0.1 µM)-induced relaxant effects on rat myometrium were significantly potentiated by 10 µM Cd. Thus based on the results of present functional study, it may be inferred that inhibitory effects of Cd on rat myometrium are mediated through blockade of L-type calcium channels and activation of NOS-NO-sGC and/or AC-cAMP pathways.