Black Scorpion (Tityus obscurus) Fatalities in Guyana and a Literature Review.

BACKGROUND: More than 1500 scorpion species exist worldwide, with a few scorpion species potentially lethal to humans. About 1 million stings annually result in >3000 deaths, but the incidence and mortality vary greatly by species and location. Physicians working internationally must recognize that resulting toxidromes vary significantly by region. Over the past few decades, South America has reported relatively few deaths and low case mortality rates from envenomations. In Guyana, a small tropical country on its northeast coast, they have been extremely rare. A sudden fatal case cluster suggests an extension of the black scorpion's habitat, an increase in venom toxicity, or both. CASE REPORTS: During a 12-month period, Guyana experienced 3 deaths, including 1 adult, from black scorpion (Tityus obscurus) envenomation. The 30-year-old man and 2 young children experienced the same symptom complex, initially appearing well except for pain at the sting site. They soon developed persistent emesis and leukocytosis. All were flown from remote jungle areas to the only public tertiary care hospital where they received maximal available medical support. They gradually developed profound cardiopulmonary failure requiring ventilation and, eventually, dysrhythmias. None had hyperglycemia or pancreatitis, and they had no neurologic abnormalities until developing progressive obtundation immediately before intubation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Scorpion envenomation symptoms, outcomes, and treatment are geographically specific. Patients benefit when clinicians recognize the worldwide variations in grading systems and treatment options, which we discuss and compare to our patients.

Pharmacokinetics and Biodistribution of Rhopalurus junceus Scorpion Venom in Tumor-Bearing Mice after Intravenous and Oral Administration

Background: Rhopalurus junceus scorpion venom has shown potential for anticancer treatment. However, there are no scientific evidence about venom pharmacokinetic (PK) and biodistribution (BD) in tumor-bearing mice. Methods: 131I-labeled venom was administrated by intravenous (IV) and oral (PO) routes at the single dose of 12.5 mg/kg. Mice were sacrificed and blood samples, major organs, and tumor were taken at 10, 20, 40, 90, 180, 300, 480, and 1440 min. Results: For IV route, maximum peak concentration (Cmax), elimination half-lives, total body clearance (CL), distribution volume (Vd), mean residence time (MRT), and area under curve (AUC) were 21.77 ± 2.45 %Dosis•h/mL, 12.65 ± 2.1 h, 4.59 ± 0.23 mL/h, 83.80 ± 12 mL, 12.49 ± 2.71 h, and 21.77 ± 2.45 %Dosis•h/mL, respectively. For PO route, they were 0.60 ± 0.07 %Dosis•h/mL, 9.33 ± 1.35 h, 36.94 ± 4.01 mL/h, 497.33 ± 30 mL, 12.40 ± 1.87 h, and 6.89 ± 1.18 %Dosis•h/mL, respectively. PK parameters (Cmax, CL, Vd, and AUC) showed significant differences between IV and PO routes. Bioavailability was 31.6 ± 4% for PO dose. Kidney, stomach, liver, and lung for IV and stomach, kidney, spleen, and lung for PO routes showed the major uptakes for 131I-labeled venom. In tumor tissue, after the maximum uptake for both routes, there was a consistent behavior of radioactivity respect to the major organs during the first 480 min. Conclusion: The PK and BD of R. junceus venom in mice depend on the administration route. These data represent a starting point for future experiments with this scorpion venom in experimental models of cancer.

Ultrasensitive sensing of Androctonus australis hector scorpion venom toxins in biological fluids using an electrochemical graphene quantum dots/nanobody-based platform.

Rapid and sensitive detection of low levels of scorpion venom toxins in biological fluids is of tremendous importance for decision-taking in cases of envenomation by scorpions stings. In Tunisia, at least 1200 severe envenomation cases by Androctonus australis hector (Aah) scorpion stings were reported annually. In this work, we report on a novel electrochemical immuno-sandwich to detect the Aah50 toxic fraction within the Aah scorpion venom using the bispecific nanobody format specially designed to highly recognize and neutralize the two most toxic molecules in the AahG50 venom fraction (i.e. AahI and AahII toxins), graphene quantum dots (GQDs) constructed on the surface carbon screen-printed electrodes. Hydroquinone/H2O2/peroxidase system was used to amplify the current in order to achieve the detection of low levels of AahG50. Electrochemical studies revealed a high sensitivity toward the AahG50 with a sensitivity of 18.2 nA mL pg-1 and a picomolar limit of detection as low as 0.55 pg mL-1. The platform exhibits very good metrological performances such as repeatability, reproducibility, selectivity and long storage stability. Matrix effect was found to be insignificant as demonstrated by assays performed in human blood serum and urine.

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

Study of severe scorpion envenoming following subcutaneous venom injection into dogs: Hemodynamic and concentration/effect analysis.

To evaluate the dose-effects of Androctonus australis hector (Aah) venom injected subcutaneously on hemodynamics and neurohormonal secretions, 10 anesthetized and ventilated mongrel dogs, were split in two groups (n = 5/group). Subcutaneous injection was done with either 0.2 mg/kg or 0.125 mg/kg of the purified G50 scorpion toxic fraction. Hemodynamic parameters using right heart catheter were recorded and plasma concentrations of catecholamine, troponin, and serum toxic fraction were measured sequentially from baseline to 120 min. We identified the dose of toxic fraction evoking characteristic hemodynamic perturbation of severe envenomation, the time-lapse to envenomation, and the associated plasma level. The injection of 0.125 mg/kg toxic fraction was not associated with significant variations in hemodynamic parameters, whereas the 0.2 mg/kg dose caused envenomation characterized by significant increase in plasma catecholamines, increased pulmonary artery occluded pressure, mean arterial pressure, and systemic vascular resistance (p < 0.05), in association with sustained decline in cardiac output (p < 0.001). Envenomation occurred by the 30th minute, and the corresponding concentration of toxic fraction was 1.14 ng/ml. The current experiment allowed the identification of the sub-lethal dose (0.2 mg/kg) of the toxic fraction of Aah administered by the subcutaneous route. Two parameters with potential clinical relevance were also uncovered: the time-lapse to envenomation and the corresponding concentration of toxic fraction.

Determination of BmKCT-13, a chlorotoxin-like peptide, in rat plasma by LC-MS/MS: application to a preclinical pharmacokinetic study.

A novel chlorotoxin-like toxin derived from Buthus martensii Karsch, namely BmKCT-13, is a potential candidate for glioma therapy and highly homologous to the chlorotoxin (CTX) derived from the venom of the scorpion Leiurus quinquestriatus. In this study, a simple, sensitive, and robust analytical method based on liquid chromatography-tandem mass spectrometry has been developed for the determination of BmKCT-13 in rat plasma using CTX as internal standard (IS). After sample preparation by protein precipitation with 0.1% formic acid in methanol, chromatography was performed on a Hanbon Dubhe C18 column (150 mm × 2.1 mm, 5 µm, and 100 Å) using a gradient elution with 0.1% formic acid in water and methanol. Mass spectrometry involved positive electrospray ionization and multiple reaction monitoring of the transitions at m/z 780.2→69.9 for BmKCT-13 and m/z 800.2→69.7 for CTX. The method was linear over the concentration range 10-1000 ng/mL with a lower limit of quantification of 10 ng/mL. Intra- and inter-day precision (expressed as relative standard deviation, RSD) were ≤8.1 and ≤7.9%, respectively, with intra-and inter-day accuracy of 94.5-99.0%. Recoveries of BmKCT-13 and IS were more than 65% and matrix effects were not significant. Stability studies showed that BmKCT-13 was stable under a variety of storage conditions. The method was successfully applied to a pharmacokinetic study involving intravenous administration of BmKCT-13 to rats.

Effectiveness of Centruroides scorpion antivenom compared to historical controls.

BACKGROUND: Envenomation by North American scorpions of genus Centruroides is associated with a syndrome of neurotoxicity and respiratory compromise that disproportionately affects rural children. Severe scorpion envenomation is rare, which makes treatment difficult to study using conventional controlled clinical trials; and small-scale placebo-controlled trials conducted in tertiary centers are of limited generalizability to the community setting. Open label studies, although safer and easier to conduct, are of limited value unless a suitable comparator group is used. Historical controls may be appropriate when concurrent controls are not feasible or ethical. METHODS: A successful placebo-controlled, double-blind clinical trial design was adapted for community use in Arizona and Mexico. A comparator population was established by replacement of the placebo group with a retrospective cohort and preservation of criteria for inclusion, exclusion, dosing and endpoint assessment. Study endpoints were selected to demonstrate the clearest possible difference between treatment groups, while minimizing confounders. Results were summarized and endpoints were directly compared between groups and with the prior double-blind study. RESULTS: The clinical syndrome remained evident in 95.9% of the historical cohort (93/97) 4 h after admission, and their cumulative dose of midazolam given between baseline and discharge was 5.29 ± 8.68 mg/kg (range 0-62.8). Among 78 prospectively treated cases, none received midazolam and only 2 (2.8%) remained symptomatic at 4 h. Venom was detectable in the plasma of all antivenom recipients tested, and it dropped by 90% of baseline in 95% of cases studied. CONCLUSIONS: The results of this pragmatic study strongly support the findings of the double-blind, placebo controlled clinical trial of the same antivenom. Recipients of antivenom at rural sites improved at a rate similar to that in the intensive care (ICU) setting, and historical cases resolved at a rate similar to that for untreated ICU controls. Use of antivenom in the primary care setting appeared to be safe and effective and to eliminate the need for intensive care or for transport to a tertiary care center, in all subjects prospectively studied.

Serum TNF-α levels reflect the clinical severity of envenomation following a Hemiscorpius lepturus sting.

Hemiscorpius lepturus (H. lepturus), found in south-western areas of Iran and south of Iraq, is considered to be the most dangerous scorpion in the region, and poses a significant risk to the health of the indigenous population due to the unique, clinical manifestations associated with its sting.. In the present study, 36 patients from the Khuzestan province in the southwest of Iran, displaying varying degrees of envenomation following an H. lepturus scorpion sting, were admitted to hospital. Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) were measured using double-ligand, enzyme-linked, immunosorbent assay (ELISA) kits, and were compared with 30 healthy controls and ten age-matched patients stung by the Mesobuthus eupeus (M. eupeus) scorpion, a less dangerous species that produces primarily neurotoxic manifestations. Blood samples from M. eupeus and H. lepturus victims were taken on admission, and from H. lepturus-stung patients six hours after serotherapy with multivalent anti-venom. When compared to healthy volunteers, with the exception of TNF-α, significantly higher serum cytokine levels were measured in patients following M. eupeus envenomation. However, all three groups of H. lepturus-stung patients showed significantly, and in a severity-related manner, higher mean values for all the interleukins that were measured, including TNF-α, when compared with M. eupeus-stung cases. Six hours after serotherapy, there was a greater reduction in cytokine and TNF-α levels in patients classed as having mild symptoms, in comparison with patients classed as having moderate to severe symptoms. The results of the present study suggest that, unlike M. eupeus, the toxic manifestations observed following being stung by H. lepturus are associated with increased serum TNF-α levels and correlate positively with the clinical severity of the symptoms. Furthermore, serotherapy is only effective when administered to mild cases of H. lepturus scorpion envenomation.

Chemical re-engineering of chlorotoxin improves bioconjugation properties for tumor imaging and targeted therapy.

Bioconjugates composed of chlorotoxin and near-infrared fluorescent (NIRF) moieties are being advanced toward human clinical trials as intraoperative imaging agents that will enable surgeons to visualize small foci of cancer. In previous studies, the NIRF molecules were conjugated to chlorotoxin, which results in a mixture of mono-, di-, and trilabeled peptide. Here we report a new chemical entity that bound only a single NIRF molecule. The lysines at positions 15 and 23 were substituted with either alanine or arginine, which resulted in only monolabeled peptide that was functionally equivalent to native chlorotoxin/Cy5.5. We also analyzed the serum stability and serum half-life of cyclized chlorotoxin, which showed an 11 h serum half-life and resulted in a monolabeled product. Based on these data, we propose to advance a monolabeled chlorotoxin to human clinical trials.

Hematological and biochemical profiles of rats submitted to experimental poisoning with Tityus serrulatus venom / Perfis hematológicos de ratos submetidos ao envenenamento escorpiônico experimental por Tityus serrulatus

The hematological and biochemical profiles of newly weaned rats submitted to experimental poisoning with T. serrulatus venom were evaluated. Fifteen recently weaned male Wistar rats (mean weight 130g) were distributed into three equal groups (n = 5). Animals in the control group (group A) received a subcutaneous injection of 400μL of ultra-pure water, while those in the experimental groups received, by identical route, 400μL of a solution containing 100μg (group B) or 450μg (group C) of scorpion venom dissolved in ultra-pure water. Red blood cells indexes, and differential leukocyte and total platelet counts were determined, together with levels of serum glucose, urea, creatinine, lactic dehydrogenase, aspartate aminotransferase, amylase, insulin, and cortisol. No significant differences between the control and experimental groups regarding red blood cells indexes were found. In contrast, significant increases (P<0.05) in neutrophils, lymphocytes, and monocytes were observed in animals from groups B and C compared with the control group, while the number of platelets decreased. Serum glucose concentration remained unchanged in all groups, but important alterations were observed in the values of urea and creatinine. The results show that scorpion venom was detrimental to renal function as demonstrated by the altered urea and creatinine levels. Pancreatic function was also impaired, as revealed by the increase in amylase activity and the reduction in insulin levels.

Avaliaram-se os perfis hematológico e bioquímico de ratos recém-desmamados submetidos ao envenenamento experimental com veneno de Tityus serrulatus. Quinze ratos Wistar machos, média de peso de 130g, foram distribuídos aleatoriamente em três grupos (n = 5). Os animais do grupo-controle A foram inoculados com 400μL de água ultrapura, os do grupo experimental B receberam 400μL de uma solução contendo 100μg de veneno e os do grupo experimental C receberam 400μL de uma solução contendo 450μg de veneno. Foram determinados os índices da série vermelha, a contagem total e diferencial dos leucócitos e a contagem total de plaquetas, bem como os níveis da desidrogenase lática, aspartato aminotransferase, amilase, glicose, ureia, creatinina, cortisol e insulina. Não houve diferenças significativas entre o grupo-controle e os experimentais com relação aos índices da série vermelha. Foram observados aumentos significativos (P<0,05) no número de neutrófilos, linfócitos e monócitos nos ratos dos grupos B e C, enquanto o número de plaquetas diminuiu. A concentração de glicose permaneceu inalterada em todos os grupos, mas foram observadas importantes alterações nos valores séricos de ureia e creatinina. Esses resultados mostraram que o veneno de escorpião comprometeu o funcionamento dos rins. Como demonstrado pelo aumento da atividade da amilase sérica e a redução dos níveis de insulina, a função pancreática também foi afetada.

Clinical pathology alterations in pregnant and non-pregnant rats following scorpion envenomation.

Scorpion envenomation is a growing problem in many countries, especially among women and children. Existing diagnostic criteria are not sufficiently specific to allow antivenin administration in the absence of a confirmed scorpion sting. This study was performed to evaluate conventional haematological and serum chemical measurements as potential indices of scorpion envenomation. Adult, cycling nulliparous and near-term primiparous, white Wistar rats received a single subcutaneous injection of crude venom (600 µg/kg) from the Buthidae scorpion (Buthus occitanus tunetanus). All envenomed rats were observed for external signs and symptoms of toxicity until necropsy, which entailed terminal blood collection at either 0.5, 1, 2, or 4 hr after venom administration (n = 6 per reproductive state per time-point) for evaluation of selected clinical chemistry and haematological analytes. Control cohorts (matched for age and reproductive state) received saline injections subcutaneously and were necropsied at 0.5 hr. Almost all envenomed rats but no control animals displayed physical symptoms of intoxication, including agitation, mastication with hypersalivation, and/or vocalizing. Reproducible alterations in clinical pathology parameters were lacking in venom-treated rats regardless of reproductive status, although modest but significant Rho correlations suggested that mild haemoconcentration, haemolysis, renal function deficits and possibly coagulation difficulties developed over time.

Hemograma de cães submetidos ao envenenamento experimental por Tityus serrulatus / Canine blood profile after experimental envenomation by Tityus serrulatus

Avaliou-se o hemograma de 12 cães adultos, saudáveis (14,2±5,4kg) após a inoculação de veneno do escorpião amarelo (Tityus serrulatus). Os animais foram distribuídos em dois grupos (G), com seis em cada: os do GI foram usados como controle e receberam 0,5mL de salina tamponada com fosfato (PBS) por via subcutânea (SC) na face medial da coxa esquerda (FMCE), e os do GII receberam veneno liofilizado do T. serrulatus (250µg/kg) diluído em PBS por via SC na FMCE. Foram realizadas colheitas de sangue com anticoagulante EDTA a 10 por cento antes da inoculação do veneno (T0) e após 2h, (T1), 6h (T2), 12h (T3), 24h (T4), 48h (T5) e 72h (T6), para contagem de eritrócitos, leucócitos e plaquetas em aparelho contador eletrônico e esfregaços sanguíneos para contagem diferencial de leucócitos. Houve aumento significativo (P<0,05) dos valores de eritrócitos, volume globular e hemoglobina 2h e 6h após o envenenamento, devido à contração esplênica decorrente da dor local causada pelo veneno e pela liberação de catecolaminas. Foi observada leucocitose por aumento significativo (P<0,05) de neutrófilos e linfócitos 2h e 6h após o envenenamento. Concluiu-se que o veneno de Tityus serrulatus na dose de 250µg/kg, é capaz de aumentar os valores do eritrograma e do leucograma dos cães, provavelmente devido à dor local, com liberação de catecolaminas.

The canine blood profile after scorpion envenomation was evaluated using 12 healthy mongrel male dogs (14.2±5.4kg) distributed in two groups, with six animals in each: group I (control group) and group II (venom group). The lyophilized yellow scorpion (Tityus serrulatus) venom (250µg/kg) diluted in 0.5mL phosphate buffered saline (PBS) was given to group II animals by subcutaneous injection, in the medial face of the left thigh. Group I animals received only 0.5mL of PBS, by subcutaneous injection, in the medial face of the left thigh. Blood samples were collected with EDTA before (T0) and 2 (T1), 6 (T2), 12 (T3), 24 (T4), 48 (T5), and 72h (T6) after envenomation. Significant increases (P<0.05) in erythrocytes counting, hematocrit and hemoglobin concentration, 2 and 6h after envenomation were observed. Leukocytosis with significant increases (P<0.05) of neutrophils and lymphocytes 2 and 6h after envenomation was found. Then, T. serrulatus venom may induce alterations in blood profile in dogs, probably due to spleen contraction evoked by pain and catecholamines releasing.

Serum levels and urine detection of Centruroides sculpturatus venom in significantly envenomated patients.

INTRODUCTION: Envenomation by Centruroides sculpturatus can cause systemic signs and symptoms requiring treatment. The toxicokinetics of C. sculpturatus venom has not been described. METHODS: Venom components were separated for cross-reactivity testing. Serum and urine collected from three patients envenomated by C. sculpturatus had venom levels determined by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Western blot analysis indicated recognition of C. sculpturatus venom by Alacramyn, an equine F(ab')(2) antivenom developed against Centruroides scorpion venoms, including C. sculpturatus. Serum venom levels in ng/mL with post-envenomation times in minutes (min) were as follows: 85-year-old woman = 8.2 (approximately 150), 2.8 (515), 1.6 (1,200); 14-month-old girl = 29.7 (approximately 50), 5.0 (729); 3-year-old girl = 11.1 (approximately 313), urine venom level of 9.0 (approximately 490). CONCLUSION: There is sufficient venom cross-antigenicity among different Centruroides species to allow this ELISA technique with Alacramyn to determine serum and urine C. sculpturatus venom concentrations in envenomated patients.

Neurohormonal activation in severe scorpion envenomation: correlation with hemodynamics and circulating toxin.

We studied the effects of scorpion (Androctonus australis hector) venom on hemodynamics and on the release of catecholamines, neuropeptide Y (NPY), endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in dog model of severe scorpion envenomation. Nine mongrel anesthetized dogs were submitted to mechanical ventilation through intubation and were administered intravenously purified dried scorpion venom (Androctonus autstralis) 0.05 mg/kg. Measurements including pulmonary artery catheter derived parameters, serum toxin levels and humoral variables were performed at baseline (before venom injection) and 5, 15, 30 and 60 min after venom injection. Humoral variables included: serum lactate, epinephrine (EP), norepinephrine (NE), NPY, ET-1 and ANP plasma concentrations. Scorpion venom caused rapid and transient increase of mean arterial pressure (MAP) and PAOP associated with a marked and sustained decline in cardiac output (-55% at 60 min; P < 0.001). Hemodynamic changes were associated with a rapid and significant increase of all measured hormones. The highest increase was for NE (28-fold) and EP (25-fold). MAP was closely correlated with NE and less significantly correlated with toxin levels. Similarly, significant correlation was observed between PAPO and ANP plasma levels. These findings support the implication of excessive catecholamines release in hemodynamic disturbances of severe SE and suggest that NPY and ET-1 could be involved in this process. Serum toxin does not appear to consistently contribute to these effects. Through its correlation with PAOP, ANP could be a reliable and useful marker of cardiac dysfunction in SE.

Best evidence topic report. Scorpion envenomation: does antivenom reduce serum venom concentrations?

A short cut review was carried out to determine if anitvenom reduces serum venom concentrations. Using the reported search, 69 papers were found, of which four presented the best evidence to answer the clinical question. The author, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Direct vs. mediated effects of scorpion venom: an experimental study of the effects of a second challenge with scorpion venom.

OBJECTIVE: To assess the respective roles of venom and of catecholamines following scorpion envenomation and to verify whether a second challenge with scorpion venom induces the same consequences than a first one. DESIGN AND SETTING: Controlled animal study in a university research laboratory. SUBJECTS: Anesthetized and ventilated dogs. INTERVENTIONS: Fifteen dogs received intravenously a sublethal dose of scorpion venom (0.05 mg/kg). In the reenvenomated group (n=5) a second venom challenge with one-half sublethal venom dose was performed 30 min after the first one. The control group (n=10) received saline. Five additional animals served as sham. MEASUREMENTS AND RESULTS: Plasma toxin and catecholamine levels and a set of usual hemodynamic measurements were repeatedly measured in the first hour following envenomation. In the reenvenomated group another set of measurements was performed 5 min after the second challenge. Changes in toxin, catecholamines, and the main hemodynamic parameters were compared between the study groups. Initial peak toxin levels were similar in the two groups. They induced a striking increase in circulating catecholamines, a fall in heart rate, and an increase in mean arterial and pulmonary artery occluded pressures and in systemic vascular resistance. In the reenvenomated group the second challenge with scorpion venom achieved a toxin blood level similar to the first peak. However, it was not associated with a significant effect either on catecholamines release or on hemodynamics. Subsequent trends in hemodynamic changes were similar to those observed in the control group. CONCLUSIONS: These data emphasize the limited role of direct effects of scorpion venom on the cardiovascular system and the key role of catecholamines.

Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab')2 extrusion mechanism from blood to tissues.

Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab')(2) extrusion mechanism from blood to tissues. We measured pharmacokinetic parameters for T. discrepans venom in rams. Forty, 75 or 100 microg/kg venom were injected subcutaneously in the inner side of the thigh. Plasma venom content (venenemia) was determined by enzyme-linked immunosorbent assay (ELISA) from 0 to 300 min after injecting venom. Venenemia was fit to a three-compartment model (inoculation site, plasma and extra vascular extracellular space), it was assumed that the venom may also be irreversibly removed from plasma. Calculated time course of venom content shows that at any time no more that 30% of the venom is present in plasma. Venenemia peaks at 1h and decays afterwards. Fluorescently labelled antivenom [horse anti-TityusF(ab')(2) or fraction antigen binding, immuglobulin without Fc chain covalently bound to fluorescine or fluorescamine] pharmacokinetics was determined. Although F(ab')(2) molecular weight is >/=10 times bigger that toxin's, the rate of outflow of F(ab')(2) from blood to tissues was approximately 4 times faster than the venom's outflow. Venom content in the injection site decays exponentially for >6h, this prediction was confirmed immunohistochemically. Only approximately 5% of the venom is eliminated in 10h; approximately 80% of the venom is in the tissues after 2h and remains there for >10h.

The kinin system in the envenomation caused by the Tityus serrulatus scorpion sting.

Several lines of evidence in experimental animals indicate that the kinin system may participate in the pathogenesis of envenomation by the Tityus serrulatus (Ts) scorpion sting, but there are no studies in humans with regard to this system. In this study, we evaluated the plasma levels of high-molecular (HKg) and low-molecular (LKg) weight kininogens (detected by ELISA), the activities of plasma or tissue kallikreins and kininase II (enzymatic action upon selective substrates), and the Ts plasma venom levels (ELISA). A total of 27 patients (12 males) aged 12-72 were evaluated immediately at hospital admittance. According to the severity of envenomation, patients were classified as mild (n = 15), moderate (n = 8), and severe cases (n = 4). Controls were paired for age and sex. Plasma venom levels were associated with the severity of envenomation. Severe cases presented lower levels of LKg in relation to mild and controls. Inverse correlations were seen between LKg levels and the venom concentration. The results of this study suggested that the kinin system may participate in the pathogenesis of human Ts envenomation and knowledge about this system may be useful to develop new strategies to reduce the damage caused by scorpion envenomation.

Dose-dependent serum biochemical alterations in Wistar albino rats after Palamneus gravimanus (Indian black scorpion) envenomation.

Palamneus gravimanus envenomated rats showed dose-dependent alterations in serum biochemical parameters. Sub lethal doses of 100, 200, and 400 microg/kg of P. gravimanus venom were injected intramuscularly into rats. Blood samples were collected by heart puncture before and 4 h after crude venom administration. Serum was analyzed for glucose, blood urea nitrogen (BUN), uric acid, total protein, cholesterol, sodium, potassium, inorganic phosphorus, alkaline phosphatase, aspartate aminotransferase (AST-SGOT), alanine amino-transferase (ALT-SGPT), lactate dehydrogenase (LDH), and creatinine phosphokinase (CPK). Statistically significant increases in serum levels of glucose, creatinine, AST, ALT, BUN, CPK, and LDH and significant decreases in serum levels of total protein, uric acid, cholesterol, calcium, and potassium 4 h after venom administration could be due to the toxic action of P. gravimanus venom on certain organs in rats.