粤西茂名地区毒蛇咬伤的流行病学特征研究

目的 探讨茂名地区毒蛇咬伤的流行病学特征.方法 收集2014～2019年我院收治的毒蛇咬伤患者1625例的临床资料,对毒蛇种类、性别、年龄、咬伤部位、咬伤地点、伤后就诊时间、住院时间进行统计分析.结果 茂名地区主要致伤毒蛇为竹叶青蛇和眼镜蛇;受伤患者以41～70岁男性多见;被咬伤部位主要为腕关节、踝关节以下;咬伤地点多...     

防治蛇伤药物矮冷水花制剂的研究

寻麻科植物矮冷水花系我区挖掘的防治蛇伤民间草药.取其干全草制成酒剂和散剂。适合于多种毒蛇咬伤的治疗.经试验研究,制定了酒剂和散剂的制备工艺高质量标准。矮冷水花制剂疗效确切,副作用小,工艺简便,是个适合于广大农村推广应用的防治蛇伤草药制剂。     

毒蛇咬伤的社区医院处理对策

目的总结39例毒蛇咬伤患者的社区医院处理经验。方法对39例毒蛇咬伤患者的临床资料进行回顾性分析。结果39例中,治愈20例,好转13例,无死亡病例}转送上级医院6例,转诊率15．38％,治愈率51．28％,总有效率84．62％。结论毒蛇咬伤社区医院处理对策,关键在于准确地辨别蛇种和判断病情,熟练使用相应的抗蛇毒血清和中医中药治疗。     

Integrating human behavior and snake ecology with agent-based models to predict snakebite in high risk landscapes

Snakebite causes more than 1.8 million envenoming cases annually and is a major cause of death in the tropics especially for poor farmers. While both social and ecological factors influence the chance encounter between snakes and people, the spatio-temporal processes underlying snakebites remain poorly explored. Previous research has focused on statistical correlates between snakebites and ecological, sociological, or environmental factors, but the human and snake behavioral patterns that drive the spatio-temporal process have not yet been integrated into a single model. Here we use a bottom-up simulation approach using agent-based modelling (ABM) parameterized with datasets from Sri Lanka, a snakebite hotspot, to characterise the mechanisms of snakebite and identify risk factors. Spatio-temporal dynamics of snakebite risks are examined through the model incorporating six snake species and three farmer types (rice, tea, and rubber). We find that snakebites are mainly climatically driven, but the risks also depend on farmer types due to working schedules as well as species present in landscapes. Snake species are differentiated by both distribution and by habitat preference, and farmers are differentiated by working patterns that are climatically driven, and the combination of these factors leads to unique encounter rates for different landcover types as well as locations. Validation using epidemiological studies demonstrated that our model can explain observed patterns, including temporal patterns of snakebite incidence, and relative contribution of bites by each snake species. Our predictions can be used to generate hypotheses and inform future studies and decision makers. Additionally, our model is transferable to other locations with high snakebite burden as well.     

Gedunin Inactivates the Co-chaperone p23 Protein Causing Cancer Cell Death by Apoptosis

Pharmacological inhibition of Hsp90 is an exciting option for cancer therapy. The clinical efficacy of Hsp90 inhibitors is, however, less than expected. Binding of the co-chaperone p23 to Hsp90 and induced overexpression of anti-apoptotic proteins Hsp70 and Hsp27 are thought to contribute to this outcome. Herein, we report that the natural product gedunin may provide a new alternative to inactivate the Hsp90 machine. We show that gedunin directly binds to p23 and inactivates it, without overexpression of Hsp27 and relatively modest induction of Hsp70. Using molecular docking and mutational analysis, we mapped the gedunin-binding site on p23. Functional analysis shows that gedunin inhibits the p23 chaperoning activity, blocks its cellular interaction with Hsp90, and interferes with p23-mediated gene regulation. Cell treatment with gedunin leads to cancer cell death by apoptosis through inactivation of p23 and activation of caspase 7, which cleaves p23 at the C terminus. These results provide important insight into the molecular mechanism of action of this promising lead compound.     

A systematic protocol for the characterization of Hsp90 modulators

Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA.     

Antimalarial activities of gedunin and 7-methoxygedunin and synergistic activity with dillapiol

Gedunin from Cedrela odorata (Meliaceae), a potent in vitro antimalarial agent, was investigated for its in vivo efficacy in CD‐1 mice infected with Plasmodium berghei. When orally administered at 50 mg kg‐1 day‐1 for 4 days, gedunin was able to suppress the parasitaemia level by 44%. However, no clear dose‐response effects were observed in the 0–100 mg kg‐1 day‐1 dose range. Preliminary pharmacokinetics in Sprague‐Dawley rats showed poor absorption. However, a binary treatment of 50 mg kg‐1 day‐1 gedunin with 25 mg kg‐1 day‐1 dillapiol, a cytochrome P450 inhibitor, increased parasitaemia clearance in mice to 75%. A clear dose‐response was observed in the 0–50 mg kg‐1 day‐1 gedunin dose range when administration was combined with 25 mg kg‐1 day‐1 dillapiol. In addition, 7‐methoxygedunin, a semi‐synthetic derivative which is more stable to degradation than gedunin, suppressed the level in mice by 67% at 50 mg kg‐1 day‐1. When administered at this dose in combination with 25 mg kg‐1 day‐1 dillapiol, clearance increased to 80%. These results demonstrate the potentialefficacy of antimalarial drugs and phytomedicines based on gedunin and the value of the combination therapy.     

Effect of triterpenoids and limonoids isolated from Cabralea canjerana and Carapa guianensis (Meliaceae) against Spodoptera frugiperda (J. E. Smith)

The activities of two triterpenoids, ocotillone and cabraleadiol, and four limonoids, methyl angolensate, 3-beta-deacetylfissinolide, 7-deacetoxy-7-oxogedunin, and beta-photogedunin, isolated from arillus of Carapa guianensis and fruits and seeds of Cabralea canjerana (Meliaceae), were evaluated against the fall armyworm Spodoptera frugiperda. Gedunin was used as a positive control. 7-Deacetoxy-7-oxogedunin and beta-photogedunin reduced the pupal weight as occurred with gedunin. Cabraleadiol, 3-beta-deacetylfissinolide, and 7-deacetoxy-7-oxogedunin prolonged the larval phase similar to the control (gedunin) of approximately 1.2 days at 50.0 mg kg(-1). The highest insecticidal activity was obtained for beta-photogedunin.     

Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents

Human pancreatic α-amylase (HPA) inhibitors offer an effective strategy to lower postprandial hyperglycemia via control of starch breakdown. Limonoids from Azadirachta indica known for their therapeutic potential were screened for pancreatic α-amylase inhibition, a known anti-diabetic target. Studies were carried out to reveal their mode of action so as to justify their hypoglycemic potential. Of the nine limonoids isolated/semi-synthesized from A.indica and screened for α-amylase inhibition, azadiradione and exhibited potential inhibition with an IC₅₀ value of 74.17 and 68.38 μM, respectively against HPA under in vitro conditions. Further screening on AR42J α-amylase secretory cell line for cytotoxicity and bioactivity revealed that azadiradione and gedunin exhibited cytotoxicity with IC₅₀ of 11.1 and 13.4μM. Maximal secreted α-amylase inhibition of 41.8% and 53.4% was seen at 3.5 and 3.3μM, respectively. Michaelis-Menten kinetics suggested a mixed mode of inhibition with maltopentaose (K _i 42.2, 18.6 μM) and starch (K _i ′ 75.8, 37.4 μM) as substrate with a stiochiometry of 1:1 for both azadiradione and gedunin, respectively. The molecular docking simulation indicated plausible π-alkyl and alkyl-alkyl interactions between the aromatic amino acids and inhibitors. Fluorescence and CD confirmed the involvement of tryptophan and tyrosine in ligand binding to HPA. Thermodynamic parameters suggested that binding is enthalpically and entropically driven with ΔG° of -21.25 kJ mol^-1 and -21.16 kJ mol^-1 for azadiradione and gedunin, respectively. Thus, the limonoids azadiradione and gedunin could bind and inactivate HPA (anti-diabetic target) and may prove to be lead drug candidates to reduce/control post-prandial hyperglycemia.     

Snakebites in Two Rural Districts in Lao PDR: Community-Based Surveys Disclose High Incidence of an Invisible Public Health Problem

BackgroundThe Lao PDR (Laos) is one of the least developed countries in Asia with an estimated 25% of the population living in poverty. It is the habitat of some highly venomous snakes and the majority of the population earns their living from agricultural activities. Under these circumstances the incidence of snakebites is expected to be high.MethodsTwo cross-sectional, community-based surveys were performed in Champone and Phin district, Savannakhet province, Lao PDR to estimate snakebite incidence. Multistage random sampling was used. In the first stage approximately 40% of all villages in each district were randomly selected. In the second stage 33% of all households in each village were randomly chosen. Members of the selected households were interviewed about snakebites during the previous 12 months.ResultsThirty-five of 9856 interviewees reported a snakebite in a 12 month period in Champone district and 79 of 7150 interviewees in Phin district. The estimated incidence is 355 snakebites per 100,000 persons per year and 1105 per 100,000 in Champone and Phin district respectively. All snakebite victims received treatment by traditional healers or self-treatment at home and nobody went to a hospital. Incidence of snakebites, calculated on the basis of hospital records of 14 district hospitals and Savannakhet provincial hospital, ranged from 3 to 14 cases per 100,000 persons per year between 2012 and 2014.ConclusionIncidence of snakebites is high in rural communities in Laos with significant regional differences. Poverty most likely contributes significantly to the higher number of snakebites in Phin district. Hospital statistics profoundly underestimates snakebite incidence, because the majority of snakebite victims receive only treatment by traditional healers or self-treatment in their village. There is an urgent need to train medical staff and students in management of snakebite patients and make snake antivenom available to cope effectively with this important public health problem in order to prevent fatalities and disabilities.     

毒蛇咬伤早期尿,血部分指标改变与肾功能的关系

目的 探讨毒蛇咬伤早期对肾功能的影响。方法对６７例蛇伤患者进行尿液分析和血液生化相关指标的观察。结果 约一半蛇伤患者尿ＰＲＯ和ＢＬＤ阳性,１／１０左右的患者尿ＬＥＵ阳性;全部病例血清Ｎａ、ＢＵＮ和Ｃｒ变化不大,蝰蛇伤和银环蛇伤出血Ｋ偏低。结论 毒蛇咬伤早期可使肾脏受到一定程度的影响,但肾功能变化并不严重,其影响在３种蛇伤之间有差别。     

(-)-3,5-Dicaffeoyl-muco-quinic acid isolated from Aster scaber contributes to the differentiation of PC12 cells: through tyrosine kinase cascade signaling

Aster scaber T. (Asteraceae) has been used in traditional Korean and Chinese medicine to treat bruises, snakebites, headaches, and dizziness. (-)-3,5-Dicaffeoyl-muco-quinic acid (DQ) isolated from A. scaber induced neurite outgrowth in PC12 cells. It has been reported that the activation of the extracellular signal regulated kinase 1/2 (Erk 1/2) and phosphoinositide 3 (PI3) kinase plays a crucial role in the NGF-induced differentiation of PC12 cells. This study showed that the effect of DQ on neurite outgrowth is mediated via the Erk 1/2 and PI3 kinase-dependent pathways like NGF. Furthermore, DQ stimulated the phosphorylation of Trk A. Overall, DQ elicited the differentiation of PC12 cells through Trk A phosphorylation followed by Erk 1/2 and PI3 kinase activation.     

湖北鹤峰县蛇伤流行病学研究

为摸清我县蛇伤发病情况,对全县进行了初步调查.调查时间是1989年至1991年三年;调查人口20.3万人.蛇伤数213人,平均年发病率为0.35‰.其中男性161例占75.59%.死亡2例,死亡率0.94%.蛇伤高峰在5至8月.受伤者绝大多数是农民(97.65%).受伤部位多为下肢(78.40%).受伤地点多在山林中(40.85%)和山间小路上(38.03%),致伤蛇种主要是蝮蛇(40.85%)和烙铁头蛇(33.80%),其次是竹叶青蛇(13.62%)和五步蛇(8.45%).本地对人危害最大的是五步蛇。     

Analgesic Effect of Photobiomodulation on Bothrops Moojeni Venom-Induced Hyperalgesia: A Mechanism Dependent on Neuronal Inhibition,Cytokines and Kinin Receptors Modulation

BackgroundEnvenoming induced by Bothrops snakebites is characterized by drastic local tissue damage that involves an intense inflammatory reaction and local hyperalgesia which are not neutralized by conventional antivenom treatment. Herein, the effectiveness of photobiomodulation to reduce inflammatory hyperalgesia induced by Bothrops moojeni venom (Bmv), as well as the mechanisms involved was investigated.Conclusion/SignificanceThese data demonstrate that LLLT interferes with mechanisms involved in nociception and hyperalgesia and modulates Bmv-induced nociceptive signal. The use of photobiomodulation in reducing local pain induced by Bothropic venoms should be considered as a novel therapeutic tool for the treatment of local symptoms induced after bothropic snakebites.     

Identifying Intraspecific Variation in Venom Yield of Chinese Cobra(Naja atra) from Ten Populations in Mainland China

Detailed information on venom yield is helpful in preparing antivenoms and treating snakebites, but such information is lacking for many species of venomous snakes. The Chinese cobra(Naja atra) is a large sized, venomous snake commonly found in southeastern China, where it causes a heavy burden of snakebites. To examine the effects of various factors(morphology, sex, age, season, and geographical origin) on the venom yield in this snake, we collected venom samples of 446 individuals(426 adults and 20 neonates) from 10 populations of N. atra over an eightyear period. We used two variables, lyophilized venom mass(venom yield) and solid content of venom(% solids), to quantify the venom yield. We used linear regression analysis to check if venom yield was related to morphological factors, one-way ANOVA and one-way ANCOVA to detect the sexual, ontogenetic, and geographic variation in venom yield, and repeated-measures ANOVA to examine seasonal shifts in venom yield. Our results indicate that venom yield of N. atra is positively related to the morphological traits examined, with male snakes expelling more venom than females. Venom yield in N. atra was age-related, with elder snakes always expelling more venom than younger ones. Geographic variation in venom yield was also observed, while seasonal variation was not. The solid content of venom was lower in males than in females, but this was not related to morphology, season, age, or geography. Our findings suggest that venom yield in N. atra is influenced by multiple factors, as well as by the interactions among these factors.     

Inhibition of Naja nigricolis (Reinhardt) venom protease activity by Luffa egyptiaca (Mill) and Nicotiana rustica (Linn) extracts

Luffa egyptiaca and Nicotiana rustica are used in traditional medicine to treat snakebites and were evaluated for inhibitory activities on Naja nigricolis venom protease. The aqueous and ethanolic extracts of L. egyptiaca significantly reduced the maximum velocity (Vmax) and the computed index of physiological efficiency (Kcat) of the enzyme in a dose dependent fashion. The protease activity was non-competitively inhibited by the aqueous extract of N. rustica with the Vmax significantly decreased and the K(M) remained unchanged. However, the N. rustica ethanol extract completely inhibited the protease activity. Ethyl acetate fractions partitioned from ethanol extracts of both plants were also found to completely inhibit the N. nigricolis venom protease activity at 0.1 and 0.05%. The use of these plants could be important in the treatment of snakebites.     

Snakebite mortality in India: a nationally representative mortality survey

Background

India has long been thought to have more snakebites than any other country. However, inadequate hospital-based reporting has resulted in estimates of total annual snakebite mortality ranging widely from about 1,300 to 50,000. We calculated direct estimates of snakebite mortality from a national mortality survey.

Methods and Findings

We conducted a nationally representative study of 123,000 deaths from 6,671 randomly selected areas in 2001–03. Full-time, non-medical field workers interviewed living respondents about all deaths. The underlying causes were independently coded by two of 130 trained physicians. Discrepancies were resolved by anonymous reconciliation or, failing that, by adjudication.A total of 562 deaths (0.47% of total deaths) were assigned to snakebites. Snakebite deaths occurred mostly in rural areas (97%), were more common in males (59%) than females (41%), and peaked at ages 15–29 years (25%) and during the monsoon months of June to September. This proportion represents about 45,900 annual snakebite deaths nationally (99% CI 40,900 to 50,900) or an annual age-standardised rate of 4.1/100,000 (99% CI 3.6–4.5), with higher rates in rural areas (5.4/100,000; 99% CI 4.8–6.0), and with the highest state rate in Andhra Pradesh (6.2). Annual snakebite deaths were greatest in the states of Uttar Pradesh (8,700), Andhra Pradesh (5,200), and Bihar (4,500).

Conclusions

Snakebite remains an underestimated cause of accidental death in modern India. Because a large proportion of global totals of snakebites arise from India, global snakebite totals might also be underestimated. Community education, appropriate training of medical staff and better distribution of antivenom, especially to the 13 states with the highest prevalence, could reduce snakebite deaths in India.     

毒蛇咬伤急救治疗的研究（附256例报告）

目的研究能随身携带自救、互救,局部注射治疗蛇咬伤的新方法。方法使用配置有胰、糜蛋白酶及抗过敏、抗炎等药物的“急救药盒”。结果２５６例全部治愈,对各种毒蛇咬伤治愈率达１００％。结论胰、糜蛋白酶治疗毒蛇咬伤使用方法简便,易于保存和携带。     

The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths

Background

Envenoming resulting from snakebites is an important public health problem in many tropical and subtropical countries. Few attempts have been made to quantify the burden, and recent estimates all suffer from the lack of an objective and reproducible methodology. In an attempt to provide an accurate, up-to-date estimate of the scale of the global problem, we developed a new method to estimate the disease burden due to snakebites.

Methods and Findings

The global estimates were based on regional estimates that were, in turn, derived from data available for countries within a defined region. Three main strategies were used to obtain primary data: electronic searching for publications on snakebite, extraction of relevant country-specific mortality data from databases maintained by United Nations organizations, and identification of grey literature by discussion with key informants. Countries were grouped into 21 distinct geographic regions that are as epidemiologically homogenous as possible, in line with the Global Burden of Disease 2005 study (Global Burden Project of the World Bank). Incidence rates for envenoming were extracted from publications and used to estimate the number of envenomings for individual countries; if no data were available for a particular country, the lowest incidence rate within a neighbouring country was used. Where death registration data were reliable, reported deaths from snakebite were used; in other countries, deaths were estimated on the basis of observed mortality rates and the at-risk population. We estimate that, globally, at least 421,000 envenomings and 20,000 deaths occur each year due to snakebite. These figures may be as high as 1,841,000 envenomings and 94,000 deaths. Based on the fact that envenoming occurs in about one in every four snakebites, between 1.2 million and 5.5 million snakebites could occur annually.

Conclusions

Snakebites cause considerable morbidity and mortality worldwide. The highest burden exists in South Asia, Southeast Asia, and sub-Saharan Africa.     

Point-of-care infrared thermal imaging for differentiating venomous snakebites from non-venomous and dry bites

BackgroundLocal envenomation following snakebites is accompanied by thermal changes, which could be visualized using infrared imaging. We explored whether infrared thermal imaging could be used to differentiate venomous snakebites from non-venomous and dry bites.MethodsWe prospectively enrolled adult patients with a history of snakebite in the past 24 hours presenting to the emergency of a teaching hospital in southern India. A standardized clinical evaluation for symptoms and signs of envenomation including 20-minute whole-blood clotting test and prothrombin time was performed to assess envenomation status. Infrared thermal imaging was done at enrolment, 6 hours, and 24 hours later using a smartphone-based device under ambient conditions. Processed infrared thermal images were independently interpreted twice by a reference rater and once by three novice raters.FindingsWe studied 89 patients; 60 (67%) of them were male. Median (IQR) time from bite to enrolment was 11 (6.5–15) hours; 21 (24%) patients were enrolled within 6 hours of snakebite. In all, 48 patients had local envenomation with/without systemic envenomation, and 35 patients were classified as non-venomous/dry bites. Envenomation status was unclear in six patients. At enrolment, area of increased temperature around the bite site (Hot spot) was evident on infrared thermal imaging in 45 of the 48 patients with envenomation, while hot spot was evident in only 6 of the 35 patients without envenomation. Presence of hot spot on baseline infrared thermal images had a sensitivity of 93.7% (95% CI 82.8% to 98.7%) and a specificity of 82.9% (66.3% to 93.4%) to differentiate envenomed patients from those without envenomation. Interrater agreement for identifying hot spots was more than substantial (Kappa statistic >0.85), and intrarater agreement was almost perfect (Kappa = 0.93). Paradoxical thermal changes were observed in 14 patients.ConclusionsPoint-of-care infrared thermal imaging could be useful in the early identification of non-venomous and dry snakebites.