Animals that specialise in blood feeding have particular challenges in obtaining their meal, whereby they impair blood hemostasis by promoting anticoagulation and vasodilation in order to facilitate feeding. These convergent selection pressures have been studied in a number of lineages, ranging from fleas to leeches. However, the vampire bat (Desmondus rotundus) is unstudied in regards to potential vasodilatory mechanisms of their feeding secretions (which are a type of venom). This is despite the intense investigations of their anticoagulant properties which have demonstrated that D. rotundus venom contains strong anticoagulant and proteolytic activities which delay the formation of blood clots and interfere with the blood coagulation cascade. In this study, we identified and tested a compound from D. rotundus venom that is similar in size and amino acid sequence to human calcitonin gene-related peptide (CGRP) which has potent vasodilatory properties. We found that the vampire bat-derived form of CGRP (i.e., vCGRP) selectively caused endothelium-independent relaxation of pre-contracted rat small mesenteric arteries. The vasorelaxant efficacy and potency of vCGRP were similar to that of CGRP, in activating CGRP receptors and Kv channels to relax arteriole smooth muscle, which would facilitate blood meal feeding by promoting continual blood flow. Our results provide, for the first time, a detailed investigation into the identification and function of a vasodilatory peptide found in D. rotundus venom, which provides a basis in understanding the convergent pathways and selectivity of hematophagous venoms. These unique peptides also show excellent drug design and development potential, thus highlighting the social and economic value of venomous animals.

Irvine JC, Ravi RM, Kemp-Harper BK, Widdop RE. Nitroxyl donors retain their depressor effects in hypertension. Am J Physiol Heart Circ Physiol 305: H939 -H945, 2013. First published July 12, 2013 doi:10.1152/ajpheart.00630.2012, the redox congener of nitric oxide, has numerous vasoprotective actions including an ability to induce vasodilation and inhibit platelet aggregation. Given HNO is resistant to scavenging by superoxide and does not develop tolerance, we hypothesised that HNO would retain its in vivo vasodilatory action in the setting of hypertension. The in vitro and in vivo vasodilator properties of the HNO donors Angeli's salt (AS) and isopropylamine/NONOate (IPA/NO) were compared with the NOḋ onor diethylamine/NONOate (DEA/NO) in spontaneously hypertensive rats (SHR) and normotensive [Wistar-Kyoto (WKY) rats]. AS (10, 50, and 200 g/kg), IPA/NO (10, 50, and 200 g/kg), and DEA/NO (1, 5, and 20 g/kg) caused dose-dependent depressor responses in conscious WKY rats of similar magnitude. Depressor responses to AS and IPA/NO were significantly attenuated (P Ͻ 0.01) after infusion of the HNO scavenger N-acetyl-L-cysteine (NAC), confirming that AS and IPA/NO function as HNO donors in vivo. In contrast, responses to DEA/NO were unchanged following NAC infusion. Depressor responses to AS and IPA/NO in conscious SHR retained their sensitivity to the inhibitory effects of NAC (P Ͻ 0.01), yet those to DEA/NO in SHR were significantly (P Ͻ 0.05) enhanced following NAC infusion. Importantly, depressor responses to AS, IPA/NO, and DEA/NO were preserved in hypertension and vasorelaxation to AS and DEA/NO, in isolated aorta, unchanged in SHR as compared with WKY rats. This study has shown for the first time that HNO donors exert antihypertensive effects in vivo and may, therefore, offer a therapeutic alternative to traditional nitrovasodilators in the treatment of cardiovascular disorders such as hypertension. nitric oxide; vasorelaxation; blood pressure; Angeli's salt; isopropylamine/NONOate THE VASOACTIVE PROPERTIES of nitric oxide (NO) donors such as glyceryl trinitrate (GTN) are well recognized, and nitrovasodilators have been used clinically to treat disorders such as angina, heart failure, and hypertension for more than 100 years (26). Yet NO can exist in different redox states, and although the physiological activity of NO has been traditionally attributed to its uncharged form (NO˙), it is becoming increasingly apparent that nitroxyl (HNO), the reduced and protonated congener of NO˙, exhibits distinct pharmacology from NO( 13) and may itself have significant therapeutic potential.The unique actions of HNO, as compared with its redox sibling, are readily apparent in the cardiovascular system. Thus, unlike NO˙, HNO increases myocardial contractility (via direct thiol interaction) (28,29) and is protective in the setting of acute experimental heart failure (23, 28). The positive cardiac inotropic actions of HNO are complemented by its ability to cause vasodilatation and unload the heart (19, 24, 28).Indeed HNO serv...

No abstract

Kikuchi-Fujimoto disease also known as necrotizing lymphadenitis is a rare, self limiting cause of lymphadenitis with unknown etiology and pathogenesis. The clinical signs and symptoms include cervical lymphadenopathy, fever, less frequent chills, night sweats, arthralgia, rash, weight loss and symptoms of respiratory infections. Diagnosis is often based on histopathological studies involving lymph node. It is often misdiagnosed with SLE, Lymphoma etc. There is no treatment guidelines given for KFD after diagnosis it is often limited to treat the symptoms but in severe cases corticosteroids can be given. Here we discuss a 14yr old female patient presented with evening rise of temperature and significant weight loss of approximately 5kg. Along with that she has also complained about bilateral axillary swelling of small size with pain. The final diagnosis was based on lymph node biopsy indicating Kikuchi-Fujimoto disease also the laboratory values were also elevated. After diagnosis patient was treated with symptomatically and the condition of the patient also improved. Although Kikuchi-Fujimoto disease can be misdiagnosed with other diseases, a systematic diagnostic approach is needed. Since there is no specific guidelines available for the management of Kikuchi-Fujimoto disease, further studies are needed to conduct the therapeutic option and its long term outcome.