Cardioprotection via the skin: nociceptor-induced conditioning against cardiac MI in the NIC of time.

Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9-T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-α. The similarity of the neuroanatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease. NEW & NOTEWORTHY This study shows that an electrical stimulus to skin sensory nerves elicits a very powerful cardioprotection against myocardial infarction. This stimulus works by a neurogenic mechanism similar to that previously elucidated for remote cardioprotection of trauma. Nociceptor-induced conditioning is equally potent when applied before ischemia or at reperfusion and has great potential clinically.

Effects of aqueous extract of Capsicum frutescens (Solanaceae) against the fish ectoparasite Ichthyophthirius multifiliis.

Ichthyophthirius multifiliis is an important fish ectoparasite that often results in significant economic losses to freshwater aquaculture. The search of alternative substances to control infections of I. multifiliis became stringent after malachite green, an effective and widely used chemotherapeutant, is banned on fish farms because of its carcinogenicity and teratogenicity. In this study, the effects of the aqueous extract of Capsicum frutescens, which is readily available and affordable, were evaluated under in vitro and in vivo conditions. The results in the in vitro conditions showed that the aqueous extracts of C. frutescens with the ratios (V (SS)/V (T)-V (SS), the volume of stock solution; V (T), the volume of total solution) of 1:32 and 1:64 led to more than 70 % mortality of I. multifiliis theronts during 4 h of exposure and significantly reduced the survival of the tomonts and the total number of theronts released by the tomonts within 22 h (P < 0.05). A 96-h bioassay was carried out to determine the acute toxicity of the aqueous extract of C. frutescens to goldfish. No visible effect was observed in the treatments with the aqueous extracts of C. frutescens with the ratios (V (SS)/V (T)) of 1:32, 1:64 and 1:128, while in the other treatments, the erratic behaviour of fish was noted. In addition, in vitro tests demonstrated that the aqueous extract of C. frutescens had an adverse effect on I. multifiliis trophonts in situ. Fish treated with the aqueous extracts of C. frutescens in ratios V (SS)/V (T) of 1:32 and 1:64 carried significantly fewer parasites than the control and the other treatments (P < 0.05). These results suggest, therefore, that aqueous extracts of C. frutescens have potential for the control of ichthyophthiriasis in the aquaculture industry, though further phytochemical studies will need to be performed for isolation and identification of the active compounds.