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Background: Canine-mediated human rabies deaths typically occur in poor and rural populations with limited access to rabies biologics: vaccine and immunoglobulin. A critical aspect of reducing rabies deaths is understanding how these countries procure, deliver, and forecast rabies biologics. Vietnam is one of the few endemic countries where biologics is widely available. However, a formal evaluation of its current rabies biologics distribution system has not been conducted., Methods: In 2017, we conducted a formal evaluation of Vietnam's rabies biologics distribution system. Our goals were (1) to identify centers providing rabies biologics (2) identify costs to the patient and centers and (3) assess the rabies biologic procurement and delivery system at eligible district and provincial centers (provides and orders biologics for itself and other centers directly from the manufacture). To conduct the formal evaluation, we developed a standardized survey that was distributed to centers., Results: Of the 780 designated rabies biologics centers in Vietnam, 659 (84%) of them provide rabies immunoglobulin (eRIG), vaccine, or both. Of the 177 eligible centers, 90% (160) responded to the survey. The average costs to patients were $8.45 (range: 5.43-12.77) for one dose of IM injection, $13.90 (range: 11.86-16.71) for domestic eRIG, and $23 (21.11-27.11) for imported eRIG. Respondents reported experiencing delays in receiving vaccine in 50 centers and eRIG in 14 centers within the past year. Respondents stated their top three challenges in providing biologics were: delays or shortages from manufactures, lack of funds to pay for biologics, and the high cost of biologics., Conclusions and Relevance: Despite the wide availability of biologics in Vietnam, more work is needed to provide affordable and reliable supply of biologics to patients. This includes the expansion of ID injection use throughout the country to lower vaccine demand, and decrease the costs to centers and patients. Furthermore, a more coordinated effort to share biologics among centers, possibly through a more centralized system at the provincial level may alleviate delays and shortages., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We investigated the antiplatelet activity of indirubin-3'-monoxime (I3O) and the underlying mechanisms. In a rat carotid artery injury model, oral administration (20 mg/kg/day) of I3O for 3 days significantly prolonged occlusion time, and ADP- and collagen-induced platelet aggregation. In washed platelets in vitro, I3O potently inhibited collagen-induced platelet aggregation by suppressing phospholipase Cγ2 (PLCγ2) phosphorylation, subsequently blocking diacylglycerol and arachidonic acid (AA) formation, P-selectin secretion and the production of thromboxane B2. Platelet aggregation induced by phorbol-12-myristate 13-acetate, a protein kinase C (PKC) activator, was inhibited by I3O. Both I3O and U0126, an extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor, markedly reduced collagen-induced phosphorylation of ERK1/2 and p47, resulting in the blockade of cyclooxygenase (COX)-mediated AA metabolite production in AA-treated platelets. I3O suppressed phosphorylation of JNK, p38, GSK-3β, and AKT. I3O inhibited glycoprotein VI (GPVI), as a collagen receptor, by suppressing the phosphorylation of tyrosine kinase Syk of GPVI and the phosphorylation of PLCγ2 and ERK1/2 stimulated by convulxin, as a specific stimulator. Our results indicate that an antiplatelet effect of I3O is due to the suppression of GPVI-mediated signaling pathways. In collagen-stimulated platelets, ERK1/2 phosphorylation is adenylyl cyclase-dependent and leads to the modulation of PKC-p47 signaling and COX-1-mediated AA-metabolic pathways., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We examined the effects of murrayafoline-A (1-methoxy-3-methylcarbazole, Mu-A), which is isolated from the dried roots of Glycosmis stenocarpa, on cell shortenings and L-type Ca2+ currents (ICa,L) in rat ventricular myocytes. Cell shortenings and ICa,L were measured using the video edge detection method and patch-clamp techniques, respectively. Mu-A transiently increased cell shortenings in a concentration-dependent manner with an EC50 of ~20 μM. The maximal effect of Mu-A, approximately 175% of the control, was observed at ≥100 μM. The positive inotropic effect of Mu-A (25 μM) reached a maximum after ~2-min exposures, and then decayed after a ~1-min steady-state. During the Mu-A-induced positive inotropy, the rate of contraction was accelerated, whereas the rate of relaxation was not significantly altered. To understand the possible mechanism for the Mu-A-induced positive inotropy, the ICa,L was assessed. Mu-A transiently enhanced the ICa,L. Concentration-dependence of the increase in ICa,L by Mu-A was similar to that of positive inotropic effect of Mu-A. The maximal effect of Mu-A (25 μM) on ICa,L was observed at 2-3 min after the application of Mu-A. A partial inhibition of ICa,L using verapamil (1 μM) induced a right shift of concentration-response curve of the positive inotropic effect of Mu-A and significantly attenuated the effect. These results suggest that Mu-A may transiently enhance contractility, at least in part, by increasing the Ca2+ influx through the L-type Ca2+ channels in rat ventricular myocytes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Monopterus albus, a swamp eel inhabiting the freshwaters of South East Asia, relies on an extensive vascularisation of the buccal cavity, pharynx and anterior oesophagus for gas exchange, while the gills are much reduced. In the present study we describe the macro-circulation in the cephalic region and the vascularisation of the buccal cavity of M. albus using vascular fillings and micro-computed tomography (μCT). We also show that M. albus has the capacity to use the buccal cavity for aquatic gas exchange, being able to maintain normal arterial blood gas composition, blood pressure, heart rate and cardiac output throughout 10h of forced submergence. M. albus therefore can be characterised as a facultative air-breather. Because M. albus aestivates for many months in moist mud during the dry season we characterised in vivo cardiovascular function during exposure to anoxia as well as the effects of anoxia on in vitro contractility of strip preparations from atria and ventricle. Both studies revealed a low anoxia tolerance, rendering it unlikely that M. albus can survive prolonged exposure to anoxia., (Copyright © 2012 Elsevier Inc. All rights reserved.)