BackgroundDaboia siamensis (Eastern Russell’s viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell’s viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand against D. siamensis venoms from four geographical locales: Myanmar, Taiwan, China and Thailand.Methodology/Principle findingsThe D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all four geographical venom variants neutralized by both the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. These in vitro findings translated into therapeutic efficacy in vivo, as the D. siamensis monovalent antivenom was found to effectively protect against the lethal effects of all four geographical venom variants preclinically. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 μg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity and prevented renal morphological changes, although lower doses had no therapeutic effect.Conclusions/SignificanceThis study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russell’s viper. However, only the early delivery of high antivenom doses appears to be capable of preventing venom-induced nephrotoxicity.

BackgroundDaboia siamensis(Eastern Russell’s viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell’s viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand againstD. siamensisvenoms from three geographical locales: Myanmar, Taiwan and Thailand.Methodology/ Principle findingsTheD. siamensismonovalent antivenom displayed extensive recognition and binding to proteins found inD. siamensisvenom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also usesD. siamensisvenom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all three geographical venom variants neutralized by both theD. siamensismonovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. Assessments ofin vivonephrotoxicity revealed thatD. siamensisvenom (700 µg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration ofD. siamensismonovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity, although lower doses had no therapeutic effect.Conclusions/SignificanceThis study highlights the potential broad geographical utility of the ThaiD. siamensismonovalent antivenom for treating envenomings by the Eastern Russell’s viper. However, only the early delivery of high antivenom doses appear capable of preventing venom-induced nephrotoxicity.Author summarySnakebite is a major public health concern in rural regions of the tropics. The Eastern Russell’s viper (Daboia siamensis) is a medically important venomous snake species that is widely distributed in Southeast Asia and Southern China, including Taiwan. Envenoming byD. siamensiscauses several systemic pathologies, most notably acute kidney failure and coagulopathy. The administration of antivenom is the mainstay therapeutic for treating snakebite, but in remote areas of Myanmar and Southern China access to antivenom is limited, and can result in the use of inappropriate, non-specific, antivenoms and treatment failure. Therefore, maximizing the utility of available efficacious antivenom is highly desirable. In this study, we investigated the utility of the widely available Thai Red Cross antivenoms for binding to and neutralizingD. siamensisvenoms sourced from three distinct locales in Asia. Since the effectiveness and antivenom dose required to preventD. siamensisvenom-induced nephrotoxicity has been controversial, we also examined the preclinical efficacy ofD. siamensisantivenom at preventing this pathology in experimentally envenomed anaesthetised animals. Our findings suggest that monovalent antivenom from Thailand, which is clinically effective in this country, has highly comparable levels of immunological binding andin vitroneutralization toD. siamensisvenoms from Taiwan and Myanmar. We also show that the early administration of high therapeutic doses of antivenom are likely required to neutralize nephrotoxins and thus prevent acute renal failure following envenoming. Our findings suggest that certain Thai Red Cross antivenoms likely have wide geographical utility againstD. siamensisvenom and therefore may be useful tools for managing snakebite envenomings by this species in the absence of available locally manufactured therapeutics.

Tetrahydrocurcumin (THC) has been shown to possess anti-angiogenic activities. This study aims to investigate the effects of THC on adipose angiogenesis and expression of angiogenic factors that occurs in 60% high-fat diet-induced obese mice. Male ICR mice were randomly divided into 3 groups: mice fed with a low-fat diet (LFD group); mice fed with very high fat diet (VHFD group), and mice fed with VHFD supplemented with THC (300 mg/kg/day orally)(VHFD+THC group) for 6 weeks. Body weight (BW), food intake, fasting blood sugar (FBS), lipid profiles and visceral fats weight (VF) were measured. The microvascular density (MVD), VEGF, MMP-2 and MMP-9 expressions were evaluated. The VHFD group had significantly increased total cholesterol, triglyceride, food intake, BW, VF, VF/BW ratio, adipocyte size and the number of crown-liked structures as compared to LFD group. THC supplementation markedly reduced these parameters and adipocyte hypertrophy and inflammation in white adipose tissues. MVD, VEGF, MMP-2 and MMP-9 were over-expressed in the VHFD group. However, THC supplementation decreased MVD and reduced expression of VEGF, MMP-2 and MMP-9. In conclusion, THC suppressed angiogenesis in adipose tissue by the downregulation of VEGF, MMP-2 and MMP-9. With its effects on lipid metabolism as well as on food consumption, THC could contribute to lower visceral fat and body weight. Overall, our study demonstrated the potential benefit of THC in mitigating obesity and associated metabolic disorders along with elucidated the suppression of adipose angiogenesis as one of its underlying mechanisms.Author summaryConceptualization, B.Y, U.S., P.P., N.D., N.S. and N.M3.; methodology, B.Y., U.S., P.P., N.D., N.S., N.M3., and C.C; validation, B.Y., U.S., P.P., N.D., N.S., N.M1., and N.M3.; formal analysis, B.Y., U.S, N.S., N.M1., N.P., and N.M3; investigation, B.Y., U.S, N.S., N.M1., N.P., and N.M3.; resources, B.Y. and C.C.; data curation, B.Y. and N.M1.; writing—original draft preparation, BY; writing—review and editing, B.Y; visualization, B.Y., U.S., P.P., and N.D.; supervision, B.Y.; project administration, B.Y., U.S., P.P., N.S., and N.P.; funding acquisition, B.Y., U.S., P.P., N.S., and N.P.

Covid-19 pandemic has disrupted traditional face-to-face human physiology teaching for students at Faculty of Medicine, Thammasat university, Pathumthani, Thailand since February 2020. Online curriculum for both lectures and laboratory sessions were developed to continue the education. This work compared the effectiveness of online physiology labs to the traditional onsite counterparts for 120 dental and pharmacy sophomore students during 2020 academic year. The method used was a Microsoft Team synchronous online laboratory experience consisted of eight topics. Faculty lab facilitators created protocol, video script, online assignments and instruction note. Group lab instructions prepared and delivered the content for recording and led student discussion. Data recording and live discussion were synchronized and executed. The response rate for the control (2019) and study groups (2020) were 36.89 and 60.83%, respectively. The control group reported higher satisfaction, compared to the online study group. The online group rated the laboratory online experience with equal satisfaction to that would be of an onsite lab experience. Onsite control group reported 55.26% satisfaction with equipment instrument while only 32.88% online group voiced their approval on this measure. It was understandable because the excitement in physiology work relied heavily on experiences the work (p<0.05). With the same difficulty index of both academic year examination papers, the non-significant different of academic performance of the control and study (59.50±13.50 and 62.40±11.43, respectively showed the effectiveness of our online synchronous physiology lab teaching. The conclusion was physiology learning experience could be appreciated online when a good design was achieved.