北方地区蝮蛇咬伤致DIC样综合征的临床研究

目的：探讨北方地区蝮蛇咬伤引起DIC样综合征的临床表现及预后情况。方法：对2010-06-2011-09来本院就诊的97例蝮蛇咬伤病例进行回顾性分析,对其中确诊为DIC样综合征的9例病例进行血小板计数及凝血系统指标D-二聚体、血浆凝血酶原时间、活化部分凝血活酶时间、血浆纤维蛋白原及凝血酶时间检测及分析。结果：北方地区蝮蛇咬伤后DIC样综合征的发生率约为9.3%;9例患者分别于伤后1～8d内出现DIC现象,持续时间约2～7d,均无临床DIC表现。结论：北方地区蝮蛇咬伤可引起患者凝血及纤溶系统异常,出现DIC样综合征。     

Secreted Phospholipases A2 of Snake Venoms: Effects on the Peripheral Neuromuscular System with Comments on the Role of Phospholipases A2 in Disorders of the CNS and Their Uses in Industry

Neuro- and myotoxicological signs and symptoms are significant clinical features of envenoming snakebites in many parts of the world. The toxins primarily responsible for the neuro and myotoxicity fall into one of two categories—those that bind to and block the post-synaptic acetylcholine receptors (AChR) at the neuromuscular junction and neurotoxic phospholipases A₂ (PLAs) that bind to and hydrolyse membrane phospholipids of the motor nerve terminal (and, in most cases, the plasma membrane of skeletal muscle) to cause degeneration of the nerve terminal and skeletal muscle. This review provides an introduction to the biochemical properties of secreted sPLA₂s in the venoms of many dangerous snakes and a detailed discussion of their role in the initiation of the neurologically important consequences of snakebite. The rationale behind the experimental studies on the pharmacology and toxicology of the venoms and isolated PLAs in the venoms is discussed, with particular reference to the way these studies allow one to understand the biological basis of the clinical syndrome. The review also introduces the involvement of PLAs in inflammatory and degenerative disorders of the central nervous system (CNS) and their commercial use in the food industry. It concludes with an introduction to the problems associated with the use of antivenoms in the treatment of neuro-myotoxic snakebite and the search for alternative treatments.     

Snake Venom Proteomics,Immunoreactivity and Toxicity Neutralization Studies for the Asiatic Mountain Pit Vipers,Ovophis convictus,Ovophis tonkinensis,and Hime Habu,Ovophis okinavensis

Snakebite envenomation is a serious neglected tropical disease, and its management is often complicated by the diversity of snake venoms. In Asia, pit vipers of the Ovophis species complex are medically important venomous snakes whose venom properties have not been investigated in depth. This study characterized the venom proteomes of Ovophis convictus (West Malaysia), Ovophis tonkinensis (northern Vietnam, southern China), and Ovophis okinavensis (Okinawa, Japan) by applying liquid chromatography-tandem mass spectrometry, which detected a high abundance of snake venom serine proteases (SVSP, constituting 40–60% of total venom proteins), followed by phospholipases A₂, snake venom metalloproteinases of mainly P-III class, L-amino acid oxidases, and toxins from other protein families which were less abundant. The venoms exhibited different procoagulant activities in human plasma, with potency decreasing from O. tonkinensis > O. okinavensis > O. convictus. The procoagulant nature of venom confirms that consumptive coagulopathy underlies the pathophysiology of Ovophis pit viper envenomation. The hetero-specific antivenoms Gloydius brevicaudus monovalent antivenom (GbMAV) and Trimeresurus albolabris monovalent antivenom (TaMAV) were immunoreactive toward the venoms, and cross-neutralized their procoagulant activities, albeit at variably limited efficacy. In the absence of species-specific antivenom, these hetero-specific antivenoms may be useful in treating coagulotoxic envenomation caused by the different snakes in their respective regions.     

Herbal medicine used by the community of Koneba district in Afar Regional State,Northeastern Ethiopia

BackgroundPastoral communities of the Afar people in northeastern Ethiopia use medicinal plants for various health problems. However, very limited scientific documents are found addressing ethnomedicinal knowledge of the community.ObjectiveThis study aimed at documenting herbal medicine and the associated knowledge from Koneba district of Afar Regional State, Ethiopia.MethodsPurposive sampling method was used to select study sites and key informants. General informants were selected through simple random sampling methods. Semi-structured interviews and guided field walk were used to collect data while Informant Consensus Factor (ICF), Fidelity Level (FL) and Preference Ranking were used to analyze and verify data.ResultsA total of 67 medicinal plant species used to treat humans and livestock ailments were recorded and collected. Thirteen medicinal plant species were mentioned as effective medicine against snake bite (ICF; 0.68) while nine species used to treat malaria, common cold and fever (ICF: 0.67). Cyphostemma adenocaule (Steud. ex A.Rich.) Desc. ex Wild & R.B.Drumm. was the most preferred species used to combat snakebite, which was prevalent in the area.ConclusionSnake bite, malaria, common cold and fever are common health problems in the study area. Efficient use of herbal medicine has minimized the impact of these diseases.     

湿润烧伤膏联合自体微粒皮种植治疗毒蛇咬伤创面疗效分析

目的 分析探讨湿润烧伤膏联合自体微粒皮种植治疗毒蛇咬伤创面的临床效果。方法 给予2020年9月至2021年8月龙岩市中医院收治的15例毒蛇咬伤患者在全身综合治疗的基础上采用湿润烧伤膏联合自体微粒皮种植治疗局部创面,观察创面愈合情况。结果 微粒皮种植2周后,创面肿胀、分泌物、气味、肉芽组织颜色评分均明显低于治疗前(Z=-5.036、-4.845、-5.068、-4.769,P均<0.001),创面面积明显小于治疗前(t=6.311,P<0.001)。治疗期间,所有患者均未发生脏器功能衰竭、血栓等并发症。出院后随访3个月～2年,愈后皮肤生长良好,功能正常。结论 湿润烧伤膏联合自体微粒皮种植可有效促进毒蛇咬伤创面愈合,疗效显著,临床应用价值较高。     

Evaluation of a Treatment Algorithm for Tsushima Mamushi (Gloydius tsushimaensis) Snakebites,after Its Introduction to Tsushima Island,Nagasaki, Japan

Objective Tsushima mamushi (Gloydius tsushimaensis) is an endemic species of snake inhabiting only Tsushima Island, a remote Japanese island. We conducted a multicenter, retrospective study of G. tsushimaensis bites for the first time and developed a treatment algorithm that unified treatment on the island and is still in use today. Methods This is a multicenter, retrospective study comparing 72 cases from January 2005 to December 2018, before the introduction of the algorithm, and 12 cases from January 2019 to December 2020, after its introduction. Results There was no significant decrease in the maximum grade of symptoms after the introduction of the algorithm, but there was a decreasing trend (p=0.057). Conversely, the median of the maximum creatinine kinase levels was 343.5 IU/L (interquartile range: 115.5-4,745.5) before the algorithm''s introduction and significantly lower (142.5; interquartile range: 111.3-163) after the algorithm''s introduction (p=0.042). After the algorithm''s introduction, the disseminated intravascular coagulation merger rate and the acute kidney injury incidence both dropped to 0%, from 9.7% and 6.9%, respectively, before the algorithm''s introduction. There was no significant difference in the length of hospital stay before versus after the algorithm''s introduction. Conclusion This study showed that the treatment algorithm can be safely and quickly applied. The algorithm''s effectiveness is expected to be strengthened by the accumulation of more cases in the future.     

Neutrophil Gelatinase–Associated Lipocalin Acts as a Robust Early Diagnostic Marker for Renal Replacement Therapy in Patients with Russell’s Viper Bite–Induced Acute Kidney Injuries

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase–associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies.     

Pharmacological activity of Costus spicatus in experimental Bothrops atrox envenomation

Context: Medicinal plants encompass a rich source of active compounds that can neutralize snake venoms or toxins. Costus spicatus (Jacq.) Sw. (Costaceae) is used by the Amazonian population to treat inflammation, pain and other pathological manifestations.

Objective: To evaluate the influence of C. spicatus aqueous extract on edema, peritonitis, nociception, coagulation, haemorrhage and indirect haemolytic activity induced by Bothrops atrox venom (BAV).

Materials and methods: Dried and pulverized leaves were extracted with distilled water. Envenoming was induced by administration of B. atrox snake venom in Swiss Webster mice. The experimental groups consisted of BAV (at the minimum dose to induce measurable biological responses) and C. spicatus extract (CSE, 1.25, 2.5, 5.0, 7.5 and 10?mg/kg/25?μl phosphate-buffered saline) administered individually and in combination (BAVCSE). PBS was used as a control. In vitro assays were also conducted in order to evaluate phospholipase A2 coagulant activities (indirect haemolytic method).

Results: CSE significantly reduced the venom-induced edema and nociception at all concentrations tested and inhibited migration of inflammatory cells at the three least concentrations (5.0, 7.5 and 10?mg/kg/25?μl PBS). CSE was not effective in inhibiting coagulant, haemorrhagic and indirect haemolytic activities of the venom.

Discussion and conclusion: The data suggest that CSE could exhibit a central mechanism for pain inhibition, and may also inhibit prostaglandin synthesis. These findings corroborate the traditional administration of C. spicatus decoction to treat inflammatory disorders, including those caused by B. atrox envenomation.     

Engineering Venom’s Toxin-Neutralizing Antibody Fragments and Its Therapeutic Potential

Serum therapy remains the only specific treatment against envenoming, but anti-venoms are still prepared by fragmentation of polyclonal antibodies isolated from hyper-immunized horse serum. Most of these anti-venoms are considered to be efficient, but their production is tedious, and their use may be associated with adverse effects. Recombinant antibodies and smaller functional units are now emerging as credible alternatives and constitute a source of still unexploited biomolecules capable of neutralizing venoms. This review will be a walk through the technologies that have recently been applied leading to novel antibody formats with better properties in terms of homogeneity, specific activity and possible safety.     

Omics Meets Biology: Application to the Design and Preclinical Assessment of Antivenoms

Snakebite envenoming represents a neglected tropical disease that has a heavy public health impact worldwide, mostly affecting poor people involved in agricultural activities in Africa, Asia, Latin America and Oceania. A key issue that complicates the treatment of snakebite envenomings is the poor availability of the only validated treatment for this disease, antivenoms. Antivenoms can be an efficacious treatment for snakebite envenoming, provided they are safe, effective, affordable, accessible and administered appropriately. The shortage of antivenoms in various regions, particularly in Sub-Saharan Africa and some parts of Asia, can be significantly alleviated by optimizing the use of current antivenoms and by the generation of novel polyspecific antivenoms having a wide spectrum of efficacy. Complementing preclinical testing of antivenom efficacy using in vivo and in vitro functional neutralization assays, developments in venomics and antivenomics are likely to revolutionize the design and preclinical assessment of antivenoms by being able to test new antivenom preparations and to predict their paraspecific neutralization to the level of species-specific toxins.