Epidemiological, clinical and therapeutic aspects of Bothrops asper bites

Bothrops asper inflicts the majority of snakebites in Central America and in the northern regions of South America, mostly affecting young agricultural workers in rural settings. This species is capable of provoking severe envenomings associated with local and systemic manifestations. The main clinical features are: local edema, ecchymoses, blisters, dermonecrosis, myonecrosis, defibrinogenation, thrombocytopenia, systemic bleeding, hypotension and renal alterations. In addition, soft-tissue infection, acute renal failure, compartmental syndrome, central nervous system hemorrhage and, in pregnant women, abortion, fetal wastage and abruptio placentae have been described as complications. Intravenous administration of antivenom constitutes the mainstay in the therapy. Antivenoms composed of either whole IgG or F(ab′)₂ fragments, manufactured in Brazil, Colombia, Costa Rica and Mexico, have been tested in controlled clinical trials, and rational protocols for antivenom administration have been developed. In addition to antivenom therapy, a number of ancillary interventions are recommended in the treatment of B. asper bites.     

Epidemiological and clinical survey of scorpionism in Khuzestan province, Iran (2003)

Epidemiological and clinical survey of scorpion envenomation was carried out by statistical method of stratified cluster random sampling in Khuzestan, the southern province of Iran, cross-sectionally. We analyzed 12,150 cases recorded in Emergency Unit of the hospitals of six cities in Khuzestan province during the year 2003. The prevalence rate of human scorpion stings in the province is 3.1/1000 inhabitants. The percentage of prevalence in selected cities was as follows: Masjed-Soleiman (27.1%), Ramhormoz (26.6%), Izeh (15.3%), Shush (12%), Baghmalek (11.7%), and Behbahan (7.3%). The scorpions, responsible for the majority of stings in Khuzestan province of Iran were identified as 53.3% yellow (Mesobuthus eupeus, Hottentotta saulcyi, Odonthobuthus doriae and Hemiscorpius lepturus), and 17.4% black (Androctonus crassicauda and Hottentotta schach), and 29.3% unknown colors. Most stings occurred throughout the year, however, the highest and lowest frequency occurs in June (16.0%) and February (0.6%), respectively. Nocturnal envenomations (60.9%) were more common than diurnal (39.1%), and 39.3% of stings were on the hands and 37.3% on the feet. Most envenomings were mild (74.5%) that all evolved to cure, except for three deaths. Envenomation was characterized by local pain (63.3%), erythema (10.1%), vomiting (1.3%), restlessness (0.6%), hyperthermia (0.5%), sweating (0.4%), and spasmic (0.3%). With respect to the outcoming results, scorpionism in Khuzestan province of Iran is a public health problem, which needs to be monitored carefully by the government.     

Report of the 4th international conference on envenomations by snakebites and scorpion stings in Africa, Dakar, April 25–29, 2011

The authors present a summary of the proceedings and the recommendations of the the 4th International Conference on Envenomations by Snakebites and Scorpion Stings in Africa, held from April 25th to 29th in Dakar. After a two day training workshop for Senegalese health personnel on the most relevant aspects of the management of envenomations, about 270 participants met to share their experiences in the field. Nearly a hundred oral and poster contributions concerning the epidemiology of snakebites and scorpion stings in Africa, the composition and action of venoms, as well as the manufacture and use of antivenoms, were presented and discussed. The last day was devoted to an institutional debate joining experts, representatives of national health authorities and concerned professionals (physicians, pharmacists, nurses and traditional healers) as well as members of the pharmaceutical industry, to discuss and elaborate a set of recommendations. It was agreed that it is necessary to improve knowledge of the epidemiological situation by case reporting. Quality control of anivenoms and procedures for their registration at the level of national health authorities should aim at improving the distribution of safe and effective antivenoms in peripheral health centers, which bear the heaviest burden of cases. It was also recommended that adequate training of health personnel in all aspects of medical management of envenomations should constitute a priority. Finally, financing mechanisms to ensure an equitable distribution of resources must be sought, as well as the constitution of a network of African experts were discussed at length.     

The burden of bites and stings management: Experience of an academic hospital in the Kingdom of Saudi Arabia

PurposeThe main aim of this study is to estimate the economic burden and prevalence of bites and stings injuries in Saudi Arabia.MethodsA retrospective, cross-sectional study was conducted at King Saud University Medical City (KSUMC) for all bites and stings cases presented to the Emergency Department (ED) between the period June 2015 and May 2019.ResultsA total of 1328 bites and stings cases were treated in the ED at KSUMC. There were 886 insect bites and stings cases, 376 animal bites, 22 human bites, 34 scorpion stings, and ten snakebites. Most cases were reported in April - June. Females account for 62% of the reported cases, and the mean age was 24 years old. The total management cost of bite and sting cases during the study period was 3.4 million Saudi Riyal (SR). The spending cost of the management of animal bites was the highest as it cost 1,681,920.76 SR, followed by insect's management costing 1,228,623.68 SR.ConclusionBites and stings have a considerable health care burden on our society. Although the vast majority of the cases were not associated with a severe life-threatening condition, many were visit ED and associated with high medical costs. Increased awareness of the hazards of animal-related injuries, especially during spring and summer, where most cases take place may lower its incidence and decrease EDs visits.     

Enzyme immunoassays in brown snake (Pseudonaja spp.) envenoming: detecting venom, antivenom and venom-antivenom complexes.

Although a commercial snake venom detection kit (SVDK) is available to distinguish between the five major snake groups in Australia, there is no assay for quantifying venom or antivenom concentrations in envenomed patients. Serum samples were obtained from patients with brown snake (Pseudonaja spp.) envenoming before and after the administration of antivenom and patients with suspected brown snake bites but no evidence of envenoming. Enzyme immunoassays (EIAs) were developed for free venom, free antivenom and the venom-antivenom complex. Standard samples measured in duplicate had a coefficient of variation of less than 10%. The EIA for venom was able to detect brown snake venom down to concentrations of 3 ng/mL. A high baseline absorbance was measured in some patients that did not change with the addition of excess antivenom to the samples. In these patients, the baseline absorbance was subtracted from all measurements to calculate the true venom concentration. The EIA for brown snake antivenom had a limit of detection of 20 microg/mL, but 50 microg/mL was used as a cut-off based on assays in patients who had not received antivenom. The EIA for venom-antivenom complexes was unable to detect these at the low venom concentrations that occurred in patients. Quantification of venom and antivenom will help to determine the dose of antivenom required to bind venom and to establish appropriate end points for antivenom treatment.     

Epidemiological and clinical characteristics of scorpionism in Colima, Mexico (2000-2001).

We analyzed 13,223 clinical records of patients treated for scorpion sting in hospitals of the Mexican Institute of Public Health and the Ministry of Health in the state of Colima, Mexico, during the years 2000-2001. A database containing demographic, epidemiological and clinical information was constructed and analyzed retrospectively. Patients were classified in the categories as mild (49.2%), moderate (33.8%) and severe (17.0%) according to commonly accepted standards. Most common symptoms recorded were local pain (94.7%), local paresthesia (67.2%), pruritus/itching (54.3%), sensation of a lump or hair in the throat (47.3%), and sialorrhoea (27.7%). The median time from sting to admission to the emergency room (patient delay) was 33min (interquartile range: 12-60). We found that older and clinically severe patients were significantly associated with longer times of admission to the emergency room. Age was significantly associated with clinical severity: the age group 0-10 years included a higher proportion of severe cases than the group 11 years and older. In four cases, patients died. An educational campaign to inform the population about the importance of receiving prompt attention following a scorpion sting has potential value in reducing complications in the emergency room.     

Local envenoming by the Western hognose snake (Heterodon nasicus): A case report and review of medically significant Heterodon bites

A case of clinically significant local envenoming resulting from a bite inflicted by a Western hognose snake, Heterodon nasicus, is described. The patient was bitten while offering a juvenile mouse to a captive snake. The snake maintained a grip on the patient's arm (left anticubital fossa) for several minutes. The bite resulted in marked edema, ecchymoses, lymphadenopathy, cutaneous signs suggestive of mild cellulitis and blister formation. There were no systemic effects. Recovery was complete after approximately five months. Several documented Heterodon sp. bites with significant clinical effects are reviewed. This common xenodontine colubrid must be considered capable of inflicting medically significant bites. It is currently unclear whether the pathological changes associated with these bites are due to specific Duvernoy's secretion components, Type I hypersensitivity or a combination of these. The influence of the feeding response on the severity of clinical effects is considered as is the discrepancy between experimentally verified pharmacological activities of Duvernoy's secretions from Heterodon sp. and medical sequelae of documented bites. Although hognose snakes may uncommonly produce medically significant bites, they should not be considered dangerous or venomous. Captive specimens should be handled carefully, particularly when offered food.     

不同地域东亚钳蝎蝎毒的双向电泳鉴定

摘要 目的利用蛋白质组学中双向电泳技术,定性鉴定、分析不同地域东亚钳蝎蝎毒活性的差别,探索不同产地蝎毒的蛋白质组成及功能差异。方法将不同产地的冷冻干燥蝎毒粉经溶解、除盐、浓缩后测定蝎毒蛋白质含量,进行定量的蝎毒鉴定。采用pH梯度等电聚焦和SDS PAGE凝胶电泳技术分离蝎毒蛋白质。银染后通过凝胶成像系统获得双向电泳凝胶图谱,用PD Quest图像分析软件比较分析,确定差异的特征蛋白点,从而定性鉴定不同产地蝎毒。结果获得3个样品的蛋白质指纹图谱。分别检测出80,69和77个点,特征差异蛋白点依次为56,46和55个。结论不同产地的东亚钳蝎蝎毒通过双向电泳分离蛋白后,表现出明显不同的蛋白点分布。     

Isolation,characterisation and complement fixation activity of acidic polysaccharides from Argemone mexicana used as antimalarials in Mali

ContextGlobal studies on Argemone mexicana L. (Papaveraceae) traditionally used against malaria in Mali are limited to its low-mass compounds activities, and little information on its bioactive polysaccharides is available.ObjectiveThis study determines the structure and the immunomodulatory activity of polysaccharides from aerial parts of A. mexicana.Materials and methodsAcidic polysaccharides from this plant material named HMAmA1 and HMAmA2 were isolated from water extracts. Their monosaccharide composition was determined by gas chromatography. Glycosidic linkages were determined using GC-MS. NMR was also applied. The polymers were tested for effects on the human complement system in vitro at different doses.ResultsThe monosaccharide composition showed that the two polysaccharides contained in different amounts the following monomers: arabinose, rhamnose, galactose, and galacturonic acid. Overall structural analysis showed the presence of a low ratio of 1,2-linked rhamnose compared to 1,4-linked galacturonic acid with arabinogalactans substituted on position 4 of rhamnose. NMR data showed the presence of galacturonans alternated by rhamnogalacturonans bearing arabinose and galactose units. α-Linkages were found for l-arabinose, l-rhamnose and d-galacturonic acid, while β-linkages were found for d-galactose. The two polysaccharides exhibited strong complement fixation activities, with HMAmA1 being the highest potent fraction. ICH₅₀ value of HMAmA1 was 5 µg/mL, compared to the control BPII being 15.9 µg/mL.Discussion and conclusionsPolysaccharides form A. mexicana presented a complement fixation effect. The complement system is an important part of the immune defense, and compounds acting on the cascade are of interest. Therefore, these polymers may be useful as immunodulatory agents.     

Epidemiological and clinical characteristics of scorpionism in children in Sanliurfa, Turkey.

The epidemiological and clinical findings of scorpion stings in Sanliurfa region of Turkey were evaluated in this investigation from May to September 2003, because of the high incidence of scorpionism cases during this season. Scorpion envenomation is an important health problem in all South-eastern Anatolia, specifically in Sanliurfa. The sting cases mostly occurred in the month of July (37.6%) when yearly temperature is the highest. Scorpion species causing the envenomation in children were not identified. More of the patients were adolescents (54.1%). Most of the stings were seen in exposed extremities (87.7%), mainly in the upper limbs (47.1%). One single village, Birecik, had the highest number of incidents (36.5%). Patients at the emergency units showed signs of local and systemic effects, but no lethality occurred. Local and autonomic nervous system effects were most frequently characterized by local pain, hyperemia, swelling, burning, hypotension, hypertension, dry mouth, thirst and sweating. We propose that public awareness and physician readiness combined with the availability of effective antivenom significantly reduced lethality in this region.     

Scorpion venom (Odontobuthus doriae) induces apoptosis by depolarization of mitochondria and reduces S-phase population in human breast cancer cells (MCF-7)

Venom of some species of scorpions induces apoptosis and arrests proliferation in cancer cells. This is an important property that can be harnessed and can lead to isolation of compounds of therapeutic importance in cancer research. Cytotoxicity was investigated using MTT reduction and confirmed with lactate dehydrogenase release following venom exposure. Apoptosis was evaluated with determination of mitochondrial membrane potential, reactive nitrogen species assay, measurement of Caspase-3 activity and DNA fragmentation analysis. To confirm that venom can inhibit DNA synthesis in proliferating breast cancer cells, immunocytochemical detection of BrdU incorporation was done. Our results demonstrated that venom of Odontobuthus doriae not only induced apoptosis but lead to the inhibition of DNA synthesis in human breast cancer cells (MCF-7). Cell viability decreased with parallel increment of LDH release in dose dependent manner after treatment with varying concentrations of venom. Moreover, venom depleted cellular antioxidants evidenced by depression of GSH and Catalases and concomitantly increased reactive nitrogen intermediates (RNI). These events were related to the depolarization of mitochondria and associated Caspase-3 activation following venom treatment in a concentration dependent manner. Finally, fragmentation of nuclear DNA following venom treatment confirmed the apoptotic property of the said venom. These results suggest that venom of O. doriae can be potential source for the isolation of effective anti-proliferative and apoptotic molecules.     

Experimental envenoming of mice with venom from the scorpion Centruroides limpidus limpidus: differences in mortality and symptoms with and without antibody therapy relating to differences in age, sex and strain of mouse

C57Bl/6J and BALB/cAnN inbred strains of mice differed significantly in mortality and symptoms when intoxicated subcutaneously with one LD₅₀ of venom from Centruroides limpidus limpidus. Higher mortality was observed in C57Bl/6J than in BALB/cAnN. Also, C57Bl/6J mice more quickly developed muscular and respiratory collapse whilst BALB/cAnN mice were hyperactive before dying. Also, the symptoms in the survivors lasted for 24 h in C57Bl/6J and for 2 h in BALB/cAnN. The age and sex of mice were also related to mortality: younger mice were more resistant than older mice and females were more susceptible than males, especially in the younger groups. Antivenom (horse F(ab′)₂) administration 5–10 min after envenoming of mice with one LD₅₀ rescued 60% of BALB/cAnN and 52% of C57Bl/6J mice, respectively. Results indicate that genetic background, gender and age differences are of consequence in the pathogenesis of C. limpidus scorpion envenomation in mice, and that timely treatment with active antivenom F(ab′)₂ saves a significant fraction of intoxicated mice without statistically significant distinction of strains.     

Snakebites in Hungary—Epidemiological and clinical aspects over the past 36 years

Epidemiological and clinical aspects of snakebites in Hungary between 1970 and 2006 were surveyed. A total of 97 cases were recorded from 21 species, including the two native vipers, Vipera berus and Vipera ursinii, and various exotic species represented by Viperidae, Elapidae, and Colubridae. Bites by native species on laymen are uncommon (17 cases) and present trivial clinical manifestations. Compared with the consequences of native Vipera cases, bites by exotic species often resulted in severe or life-threatening envenomations. These cases were treated with antivenom administration, plasmapheresis, fasciotomy, and amputation. There were two fatalities caused by V. berus and Agkistrodon contortrix. Both of these cases were inflicted in snake-handlers with a previous history of Viperidae bites and the cause of deaths are attributed to anaphylactic reactions as a consequence of hypersensitivity to the venom. Snake-handlers and their physicians face a major challenge due to the diversity and severity of signs and symptoms following exotic venomous snakebites, and the risk of anaphylaxis or anaphylactoid reactions in patients with repeated exposure to snake venom and antivenom. Highly dangerous venomous snake species continue to appear in collections of Hungarian snake-handlers.     

Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events,clinical aspects,and pharmacotherapy options

Introduction: Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used.

Areas covered: This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH.

Expert opinion: Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.     

Purification and N-terminal sequence of a serine proteinase-like protein (BMK-CBP) from the venom of the Chinese scorpion (Buthus martensii Karsch)

A serine proteinase-like protein was isolated from the venom of Chinese red scorpion (Buthus martensii Karsch) by combination of gel filtration, ion-exchange and reveres-phase chromatography and named BMK-CBP. The apparent molecular weight of BMK-CBP was identified as 33kDa by SDS-PAGE under non-reducing condition. The sequence of N-terminal 40 amino acids was obtained by Edman degradation. The sequence shows highest similarity to proteinase from insect source. When tested with commonly used substrates of proteinase, no significant hydrolytic activity was observed for BMK-CBP. The purified BMK-CBP was found to bind to the cancer cell line MCF-7 and the cell binding ability was dose-dependent.