Venoms of Iranian Scorpions (Arachnida, Scorpiones) and Their Potential for Drug Discovery.

Scorpions, a characteristic group of arthropods, are among the earliest diverging arachnids, dating back almost 440 million years. One of the many interesting aspects of scorpions is that they have venom arsenals for capturing prey and defending against predators, which may play a critical role in their evolutionary success. Unfortunately, however, scorpion envenomation represents a serious health problem in several countries, including Iran. Iran is acknowledged as an area with a high richness of scorpion species and families. The diversity of the scorpion fauna in Iran is the subject of this review, in which we report a total of 78 species and subspecies in 19 genera and four families. We also list some of the toxins or genes studied from five species, including Androctonus crassicauda, Hottentotta zagrosensis, Mesobuthus phillipsi, Odontobuthus doriae, and Hemiscorpius lepturus, in the Buthidae and Hemiscorpiidae families. Lastly, we review the diverse functions of typical toxins from the Iranian scorpion species, including their medical applications.

Myocarditis and Early Markers of Cardiac Response Associated with Scorpion Stings in Children.

INTRODUCTION: A clinical course ranging from mild local findings to life-threatening systemic findings may occur after scorpion stings. The purpose of this study was to identify priority markers indicating scorpion sting-related cardiac involvement. METHODS: Our study was performed between July 2014, and September 2015 in the Çukurova University medical faculty pediatric emergency department, in Adana, Turkey. Patients admitted with scorpion sting-related cardiac involvement and a control group consisting of patients with no scorpion sting-related cardiac involvement were included in the study. Troponin I at time of presentation and at 6 and 24 h, N-terminal prohormone of brain natriuretic peptide (NTproBNP), ejection fraction as determined by echocardiography at 24 h, and peak and end of T wave (Tp-e) and Tp-e/QTc ratios with echocardiography at 24 h were evaluated. RESULTS: A patient group consisting of 7 cases of scorpion envenomation-related myocarditis and a control group of 30 cases of scorpion intoxication without myocarditis findings were enrolled. Statistically significantly high glucose, white blood cell values, creatine kinase MB, troponin I, and NTproBNP values were identified in the scorpion sting-related myocarditis group (P<0.05). Ejection fractions determined by echocardiography at time of presentation were significantly lower in the patients with myocarditis compared with the control group (P<0.05). A statistically significant difference was identified between Tp-e/corrected QT interval (QTc) ratios investigated in DI and V2 derivations in patient and control group echocardiograms (P<0.05). CONCLUSIONS: We think that use can be made of NTproBNP in addition to echocardiography and troponin I in the early diagnosis of scorpion sting-related myocarditis and that Tp-e and Tp-e/QTc ratios identified via echocardiography can be used as early markers; however, further studies with larger numbers are needed to confirm this.

Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain.

BmK I, purified from the venom of scorpion Buthus martensi Karsch (BmK), is a receptor site-3-specific modulator of voltage-gated sodium channels (VGSCs) and can induce pain-related behaviors in rats. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 contributes to most of the sodium current underlying the action potential upstroke in dorsal root ganglia (DRG) neurons and may serve as a critical ion channel targeted by BmK I. Herein, using electrophysiological, molecular, and behavioral approaches, we investigated whether the aberrant expression of Nav1.8 in DRG contributes to generation of pain induced by BmK I. The expression of Nav1.8 was found to be significantly increased at both mRNA and protein levels following intraplantar injection of BmK I in rats. In addition, the current density of TTX-R Nav1.8 sodium channel is significantly increased and the gating kinetics of Nav1.8 is also altered in DRG neurons from BmK I-treated rats. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, are significantly alleviated through either blockade of the Nav1.8 sodium channel by its selective blocker A-803467 or knockdown of the Nav1.8 expression in DRG by antisense oligodeoxynucleotide (AS-ODN) targeting Nav1.8 in rats. Finally, BmK I was shown to induce enhanced pain behaviors in complete freund's adjuvant (CFA)-inflamed rats, which was partly due to the over-expression of Nav1.8 in DRG. Our results suggest that functional up-regulation of Nav1.8 channel on DRG neurons contributes to the development of BmK I-induced pain in rats.

Impact of scorpion stings on electrocardiographic changes and relationship with body oxidant and antioxidant status.

OBJECTIVE: To investigate electrocardiogram changes due to scorpion stings and association between oxidative stress index, body oxidant/antioxidant system and the electrocardiogram changes. METHODS: The study was conducted at the Faculty of Medicine, Gaziantep University, Turkey, between May 2009 and October 2010. It comprised 44 patients admitted to the emergency department for scorpion sting, and a control group of matched age and gender of 20 persons. Electrocardiograms were taken promptly in the most painful phases of the patients. Cardiac parametres were measured. Erythrocyte packages were prepared to detect toxin/antioxidant levels. SPSS 18 was used for statistical analysis. RESULTS: Of the 44 patients, 22 (50%) were male. Overall average age of the patients was 45.22 +/- 17.99 years. None of the patients required intensive care and none of them had limb losses. Cardiac parametres of the patients in electrocardiogram were higher (p < 0.05). Difference between those with changed electrocardiogram and unchanged electrocardiogram in terms of the values of total antioxidant status, total oxidant status, and oxidative stress index, were not statistically significant (p > 0.05). CONCLUSION: Scorpion stings associated with electrocardiogram changes. The mechanism of this relationship is not related with the status of body oxidative stress index and body oxidant and antioxidant capacity. Some parametres warrant further study in terms of potential serious arrhythmias in scorpionism.

Bites and Stings: Exotic Causes of Stroke in Asia.

BACKGROUND: Many unusual and fascinating causes of stroke are seen in Asia. Although rarely encountered in the Western world, such cases are seen not so infrequently by neurologists, physicians, and other healthcare workers in Asian countries. This article highlights some of these intriguing causes of stroke such as snakebite, scorpion stings, and bee and wasp stings. SUMMARY: Snakebite is a neglected tropical disease of global importance affecting over 5 million people each year, and scorpion stings and bee and wasp stings affect over a million people worldwide every year. Strokes due to these uncommon causes predominantly affect young males in their most productive years, and many victims die or remain with residual disability with significant socioeconomic consequences to the affected families and society. Both ischaemic and haemorrhagic strokes are seen, with ischaemic strokes being more common. Many unanswered questions remain regarding the pathophysiological mechanisms, clinical spectrum, and the natural history of stroke due to these causes. Antivenom is effective in snake envenoming, antivenom and prazosin are effective in scorpion envenoming, and treatment of anaphylaxis and allergy is recommended in systemic reactions due to bee or wasp stings. However, there are no treatment guidelines or expert recommendations to guide the management of stroke in these patients, and there are no data on the safety and efficacy of stroke-specific treatments such as antiplatelet therapy, thrombolysis or endovascular treatment. KEY MESSAGES: More research is clearly needed to unravel the complexities related to stroke following snakebite, scorpion envenoming, and bee and wasp stings, and to guide the development of optimal stroke treatment strategies in these unusual situations. Awareness of these exotic stroke aetiologies is important in early recognition and appropriate management of patients presenting with stroke symptoms in Asian countries, and in global travellers from the region. International collaborations would go a long way in improving our understanding of these rare but fascinating causes of stroke.

The roles of some scorpions, Hemiscorpius lepturus and Androctonus crassicauda, in a scorpionism focus in Ramhormorz, southwestern Iran.

Scorpion stings are a common and important health problem in Iran, particularly in south and southwestern Iran, including the province of Khuzestan. In the area of Khuzestan near the city of Ramhormoz, Hemiscorpius lepturus (Scorpionida: Hemiscorpioiidae) and Androctonus crassicauda (Buthidae) are present. Ramhormoz is in southwestern Iran and is one of the most important foci of the scorpion sting problem. The current study was carried out to gain both epidemiological and medical information about scorpion stings in and around the city of Ramhormoz. In total, 179 people who were admitted to the Emergency Department of Ramhormoz Imam Khomeini Hospital during 2008 and 2009 after being stung by scorpions were monitored. Epidemiological and medical parameters including sex of the victim; the part of the body stung; the month when stung; the biochemical parameters comprising blood sugar (BS), blood urea nitrogen (BUN), and creatinine (CR); hematological parameters including white blood cells (WBC), count blood cells (CBC), red blood cells (RBC), hemoglobin (Hb), hematocrit (HCT), platelet (PLT); and urine analysis including hemoglobinuria were recorded. The current study showed that most of the victims were stung by H. lepturus, while very few were stung by A. crassicaud, but in over half of the cases the species was not known. Stings were most common from May to Aguust. 73% of the victims were female. The limbs were the part of the body most likely to be stung. Hemogobinuria was very common in H. lepturus victims.

Pediatric scorpion envenomation in the United States: morbidity, mortality, and therapeutic innovations.

In the Southwestern United States, the venom of the scorpion Centruroides sculpturatus (common name bark scorpion) can cause serious and potentially fatal neurotoxicity, with young children most vulnerable to its effects. Historically, advances in the quality of supportive care have made significant improvements in morbidity and mortality. In recent years, the development of effective antivenom therapies has changed the landscape of caring for these patients. This article reviews the background, pathophysiology, diagnosis, and treatment options for C. sculpturatus envenomation. Recent advances in immunotherapy and subsequent implications for pediatric emergency care providers are discussed.

Induced pathophysiological alterations by the venoms of the most dangerous Moroccan scorpions Androctonus mauretanicus and Buthus occitanus: A comparative pathophysiological and toxic-symptoms study.

Scorpion envenomation is a serious public health issue. Androctonus mauretanicus (Am) and Buthus occitanus (Bo) are the most dangerous scorpions in Morocco. Despite their medical relevance, no study has yet related their kinetics of symptom apparition and the consequent tissue disorders at the same interval post-injection. This work achieved the first comparative pathophysiological and toxic-symptoms study between the Am and Bo venoms from a biochemical, toxicological and physiopathological standpoint. The activity of venoms and their subletal dose were determined by administration of increasing concentrations of the venoms. 30, 60 and 120 min following the experimental envenomation in mice, the profile of clinical symptoms was underlined and the main organs: brain, heart, lungs, liver and kidneys were removed for histological examination. The Am venom is a rich source of proteins and three-times more toxic than the Bo. The most observed clinical symptoms are neurological and cardiopulmonary. The Am venom caused histopathological alterations at 30, 60, and 120 min which were more important than the Bo. This study highlighted that both venoms exhibited a strong toxicity with variable intensities. Moreover, we showed the presence of correlation between the level of histopathological disorders observed and the intensity of signs appeared at the same time following venom inoculation.

Scorpion envenomation and antivenom therapy.

Scorpion envenomation is a dangerous and common global event that can result in a variety of toxic clinical effects. These are typically managed with supportive care or antivenom. Antivenom use is controversial because of conflicting evidence of effectiveness for adrenergic toxicity. However, both controlled and uncontrolled studies have shown that antivenom is effective in resolving neuromotor toxicity associated with envenomations by the scorpions of genus Centruroides.

Comparison of the Scorpionism Caused by Centruroidesmargaritatus, Tityuspachyurus and Tityus n. sp. aff. metuendus Scorpion Venoms in Colombia.

Among other scorpion species, Colombia has two genera of the Buthidae family Centruroides and Tityus, considered to be dangerous to humans. This research shares scientific knowledge aiming to a better understanding about the pathophysiological effects of such venoms. The venom of the three species: Centruroides margaritarus, Tityus pachyurus, and T. n. sp. aff. metuendus with biomedical interest were studied. An initial pre-glycemic sample was taken from ICR mice. They were later intraperitoneally inoculated with doses of 35% and 70% of LD50 of total venom. Poisoning signs were observed during a 6-h period to determine the level of scorpionism. After observation, a second glycemic sample was taken, and a histopathological evaluation of different organs was performed. This work revealed that all three venoms showed considerably notorious histopathological alterations in main organs such as heart and lungs; and inducing multiple organ failure, in relation to the glycemia values, only C. margaritatus and T. n. sp. aff. metuendus showed significant changes through manifestation of hyperglycemia. According to the Colombian scorpionism level; signs were mild to severe affecting the autonomous nervous system.

Scorpion sting: N-terminal fragment of proB-type natriuretic peptide as an early predictor of pediatric cardiotoxicity.

AIM OF THE WORK: This prospective study was conducted to evaluate the clinical reliability of N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) in identifying patients with cardiotoxicity in the early hours following scorpion sting. SUBJECTS AND METHODS: This study involved 483 children aging between 2-17 years who were admitted to Minia University Poisoning Control Center from 1st January 2010 to 31st December 2019 with a history of scorpion sting, and on clinical evaluation symptoms were manifested. All subjects were clinically examined, investigated for NT-proBNP and CPK-MB on admission, 6 h and 24 h post-envenomation; and subjected to 24 h cardiac monitoring with periodic ECG every 6 h. RESULTS: Assessment of CPK-MB levels showed a significant increase in all moderate to severe cases 6 h post-envenomation. Assessment of NT-proBNP levels showed a significant increase in all moderate to severe cases on admission and 6 h post-envenomation. Moreover, there was a significant decrease in the NT-proBNP level after 24 h compared with that measured on admission. The sensitivity of NT-proBNP for the diagnosis of myocardial injury at hospital admission was significantly higher than that of CPK-MB. CONCLUSION: NT-proBNP may be a valuable and sensitive laboratory biomarker to predict cardiotoxicity of scorpion sting in the early hours.

Terrestrial venomous animals, the envenomings they cause, and treatment perspectives in the Middle East and North Africa.

The Middle East and Northern Africa, collectively known as the MENA region, are inhabited by a plethora of venomous animals that cause up to 420,000 bites and stings each year. To understand the resultant health burden and the key variables affecting it, this review describes the epidemiology of snake, scorpion, and spider envenomings primarily based on heterogenous hospital data in the MENA region and the pathologies associated with their venoms. In addition, we discuss the venom composition and the key medically relevant toxins of these venomous animals, and, finally, the antivenoms that are currently in use to counteract them. Unlike Asia and sub-Saharan Africa, scorpion stings are significantly more common (approximately 350,000 cases/year) than snakebites (approximately 70,000 cases/year) and present the most significant contributor to the overall health burden of envenomings, with spider bites being negligible. However, this review also indicates that there is a substantial lack of high-quality envenoming data available for the MENA region, rendering many of these estimates speculative. Our understanding of the venoms and the toxins they contain is also incomplete, but already presents clear trends. For instance, the majority of snake venoms contain snake venom metalloproteinases, while sodium channel-binding toxins and potassium channel-binding toxins are the scorpion toxins that cause most health-related challenges. There also currently exist a plethora of antivenoms, yet only few are clinically validated, and their high cost and limited availability present a substantial health challenge. Yet, some of the insights presented in this review might help direct future research and policy efforts toward the appropriate prioritization of efforts and aid the development of future therapeutic solutions, such as next-generation antivenoms.

Hand ulceration.

In the American Southwest, a common problem can be diagnosed with the knowledge of the local environment and its inhabitants.

What's eating you? the South African fattail scorpion revisited.

Worldwide, there are more than 3250 deaths a year related to scorpion stings. With the increasing popularity of exotic and dangerous pets, American physicians are more likely to see exotic scorpion envenomations. Although adults are stung more often, children experience more severe envenomation.

Unusual presentations of scorpion envenomation.

Scorpions are nocturnal arthropods that inject their venom through the victims' skin by stingers. By the envenomation, clinical manifestations in a wide spectrum may occur, including pain at one side and death because of severe cardiopulmonary or neurological abnormalities. Sometimes the victim cannot describe the insect or does not remember even being stung after the event. We present two cases of scorpion envenomation with different and rare clinical situations with a short review of the literature.

Severe bark scorpion envenomation in adults.

INTRODUCTION: The preponderance of medical literature regarding severe bark scorpion envenomation describes pediatric patients; however, the majority (>66%) of annual poison center calls pertain to adults. This retrospective review sought to evaluate the clinical manifestations of adults with severe Centruroides sculpturatus envenomation and determine if significant morbidity occurred. METHODS: This is a retrospective review of adults presenting to a single tertiary referral center with Grade-III or Grade-IV scorpion envenomation from 1 January 2007 to 3 March 2013. The primary objective is to describe clinical findings, treatment strategies, complications and short-term outcomes. RESULTS: Thirty-three patients were included; 61% were female (20/33), average age was 40.7 (19-81) years. The average time to healthcare facility was 142 (14-720) minutes. The most common signs and symptoms of envenomation were: pain/paresthesias 94%, opsoclonus 82%, excessive motor activity 76%, visual disturbance 76%. Benzodiazepines 85% (29/33) and opioids 83% (28/33) were the most frequently used agents to control envenomation. Cardiac evaluation was performed in 24% of patients, 6% were pregnant and underwent fetal monitoring, 6% were intubated and 3% developed rhabdomyolysis. Average length of stay (LOS) was 28.3 (1.5-307) hours; 58% (19/33) required hospital admission. Four patients had LOS >48 h, with pre-existing cardiac disease, substance misuse disorder, acute ethanol withdrawal and medical errors identified as factors contributing to prolonged LOS. CONCLUSIONS: Bark scorpion envenomation in adults may be severe, necessitating medical intervention and hospital admission. Comorbid conditions and complications arising from treatment may contribute to prolonged LOS.

Second Dose of Scorpion Antivenom in Children with Indian Red Scorpion (Mesobuthus tamulus) Sting Envenomation.

OBJECTIVE: To study the effect of the second dose of scorpion antivenom in children with non-resolving or worsening scorpion sting envenomation. METHODS: 72 children aged ≤12 years with scorpion sting envenomation grade 2 and above were enrolled. 61 received the first dose of three vials of antivenom at admission (group A). Children with persistent/worsening envenomation at 6 hours received the second dose (group B). The time required for resolution of autonomic symptoms, myocardial dysfunction, predictors of the second dose and side effects were studied. RESULTS: The mean time taken for resolution of autonomic symptoms were similar in GroupA and B (4.1 vs. 5.3 hours, P=0.452), and of myocardial dysfunction was shorter in Group A (10.8 vs. 37.6 hours, P=0.019). On regression analysis, abnormal echocardiography at admission was found to be a significant predictor of the second dose (OR=27.6, 95% CI, 4.7-162.5; P=<0.001). CONCLUSION: Children with severe scorpion sting envenomation with abnormal echocardiography may require a higher dose of scorpion antivenom.

Approach to scorpion stings in pregnancy: A retrospective case series and literature review.

OBJECTIVE: Scorpion stings remain a serious health problem in many parts of the world. There is very limited information regarding the effects of therapies delivered for scorpion stings in pregnant women on the mother and fetus. They can cause acute conditions such as fetal loss, preterm delivery, or placental abnormalities and can also result in other conditions that may have an effect on the baby in the long term. MATERIALS AND METHODS: In this study the medical records of 24 pregnant women who were admitted to the emergency room at Suruç State Hospital due to scorpion stings between January 1, 2013 and January 1, 2014 were retrospectively reviewed. Age, gestational week, monthly distribution of the cases, type of delivery, status of the fetus, affected body sites, and local and systemic findings were evaluated. The clinical severity of each case was assessed using Abroug's classification. A fetal biophysical profile test was administered in pregnant women above 24 weeks of gestation. The newborns underwent follow-up for mental and motor functions in the pediatric department at three-month intervals for 12 months. RESULTS: 24 patients, with a mean age of 26.1 ± 2.4 years, were included in the study. The most common region stung by scorpions was Lower extremity (58.3%). The most common symptom occurred in cases was immediate localized pain (58%). In terms of gestational age, 41.6% of scorpion sting were within the third trimester. Biophysical profile scores were 8 and above. Only symptomatic treatment, without use of anti-venom, was done to all the patients in this study. And neither death nor major sequel happened. CONCLUSION: Scorpion stings during pregnancy may not have significant adverse effects on the fetus and the mother. Decisions regarding the use of anti-venom in pregnant women should be considered carefully when only limited safety information, especially in those patients with only local symptoms.