Ferritin 1 silencing effect in Rhipicephalus sanguineus sensu lato (Acari: Ixodidae) during experimental infection with Ehrlichia canis.

Rhipicephalus sanguineus sensu lato (s.l.) is a very common ectoparasite of domestic dogs able to transmit several pathogens of human and veterinary importance. Tick infestations and tick-borne diseases (TBDs) remain a serious and persistent problem, due to the lack of efficient control measures. It is therefore vital that novel approaches to control are pursued. Whilst vaccination is recognised as a potential control method to reduce tick infestation, no anti-R. sanguineus vaccine is available. Ticks depend on their blood meals to obtain nutrients and to achieve sexual maturity, which exposes them to vast amounts of iron. Although an essential molecule for several biological processes, its excess can lead to oxidative stress. Iron homeostasis is achieved with the help of iron-binding proteins called ferritins, among others, present in several tick tissues and developmental stages. These evolutionarily conserved proteins regulate iron homeostasis by storing and releasing iron in a controlled manner. In this study the R. sanguineus ferritin 1 gene was silenced through RNA interference (RNAi) in adult females exposed to an experimental infection with Ehrlichia canis. The purpose of this study was to assess the role of this protein in tick feeding, ovary development, oogenesis, and pathogen acquisition. Our data has shown that silencing ferritin 1 alters tick competence to normally engorge and causes morphologic and histochemical changes in the ovaries (OV) and oocytes. Furthermore, our data revealed that no E. canis DNA was found in either experimental group. Determining the function of molecules that act in key biological processes, such as blood digestion or reproduction, and that could be considered potential tick antigens will contribute towards the improvement of current control measures against these ectoparasites and the pathogens they vector.

Molecular, biological, and morphometric comparisons between different geographical populations of Rhipicephalus sanguineus sensu lato (Acari: Ixodidae).

In this study, different geographical populations of Rhipicephalus sanguineus sensu lato were compared by molecular, biological, and morphometric methods. Phylogenetic trees were constructed using 12S and 16S rDNA sequences and showed two distinct clades: one composed of ticks from Brazil (Jaboticabal, SP), Cuba (Havana) Thailand (Bangkok) and the so-called "tropical strain" ticks. The second clade was composed of ticks from Spain (Zaragoza), Argentina (Rafaela, Santa Fe) and the so-called "temperate strain" ticks. Morphometric analysis showed good separation between females of the two clades and within the temperate clade. Males also exhibited separation between the two clades, but with some overlap. Multiple biological parameters revealed differences between the two clades, especially the weight of the engorged female. These results confirm the existence of at least two species under the name "R. sanguineus".

Hyoscine-N-butylbromide premedication on cardiovascular variables of horses sedated with medetomidine.

OBJECTIVE: To evaluate the effects of intravenous (IV) or intramuscular (IM) hyoscine premedication on physiologic variables following IV administration of medetomidine in horses. STUDY DESIGN: Randomized, crossover experimental study. ANIMALS: Eight healthy crossbred horses weighing 330 ± 39 kg and aged 7 ± 4 years. METHODS: Baseline measurements of heart rate (HR), cardiac index (CI), respiratory rate, systemic vascular resistance (SVR), percentage of patients with second degree atrioventricular (2(o) AV) block, mean arterial pressure (MAP), pH, and arterial partial pressures of carbon dioxide (PaCO2 ) and oxygen (PaO2 ) were obtained 5 minutes before administration of IV hyoscine (0.14 mg kg(-1) ; group HIV), IM hyoscine (0.3 mg kg(-1) ; group HIM), or an equal volume of physiologic saline IV (group C). Five minutes later, medetomidine (7.5 µg kg(-1) ) was administered IV and measurements were recorded at various time points for 130 minutes. RESULTS: Medetomidine induced bradycardia, 2(o) AV blocks and increased SVR immediately after administration, without significant changes in CI or MAP in C. Hyoscine administration induced tachycardia and hypertension, and decreased the percentage of 2(o) AV blocks induced by medetomidine. Peak HR and MAP were higher in HIV than HIM at 88 ± 18 beats minute(-1) and 241 ± 37 mmHg versus 65 ± 16 beats minute(-1) and 192 ± 38 mmHg, respectively. CI was increased significantly in HIV (p ≤ 0.05). Respiratory rate decreased significantly in all groups during the recording period. pH, PaCO2 and PaO2 were not significantly changed by administration of medetomidine with or without hyoscine. CONCLUSION AND CLINICAL RELEVANCE: Hyoscine administered IV or IM before medetomidine in horses resulted in tachycardia and hypertension under the conditions of this study. The significance of these changes, and responses to other dose rates, requires further investigation.

Cardiovascular therapeutics targets on the NO-sGC-cGMP signaling pathway: a critical overview.

In a brief overview, in NO-sGC-cGMP signaling in a blood vessel, l-arginine is converted in the endothelium monolayer by the endothelial nitric oxide synthase (eNOS) to NO which diffuses into both the vessel lumen and the vessel wall, thereby activating soluble guanylate cyclase (sGC). Heme-dependent sGC stimulators and hem-independent sGC activators increase the cellular cGMP concentration via the direct activation of sGC, which results in both vasorelaxation and inhibition of platelet aggregation. Studies of the 90's definitively established the role of endothelium in all cardiovascular diseases, which were associated with endothelial dysfunction by impaired release of endothelium-derived relaxing factors with consequent risk of spasm and thrombosis. The rationale of this review is based on the fact that the discovery of NO changed the concepts of cardiovascular disease mechanisms. However, considering the jargon "from the bench to clinical practice" we concluded that a potential therapeutic revolution did not follow the pathophysiological revolution. The review is focused on general aspects without regard for advanced research aspects, and designed in two main groups: the NO/cGMP positive stimulators and blockers as "future and encouraging" new therapeutic drugs. The potential vasodilators include 1) NOS uncoupling; 2) NOS enhancers (AVE compounds); 3) NO donors (nitrovasodilators); 4) NO-independent activators (BAY compounds), and; 5) PDE5 inhibitors. The potential vasoconstrictors include 1) NOS-blockers (L-NAME, L-NMMA); 2) sGC-blockers (methylene blue), and; 3) PDEs. Few texts, selected by excellence and relevance, were crucial and considerably facilitated the elaboration of this text, in addition to our own experimental and clinical experience working on vasoplegic endothelium dysfunction.