The gut microbiota and microbial metabolites are associated with tail biting in pigs.

Tail biting is an abnormal behaviour that causes stress, injury and pain. Given the critical role of the gut-microbiota in the development of behavioural problems in humans and animals, the aim of this study was to determine whether pigs that are biters, victims of tail biting or controls (nine matched sets of pigs) have a different microbiota composition, diversity and microbial metabolite profile. We collected faecal and blood samples from each individual for analysis. The gut microbiota composition was most different between the biter and the control pigs, with a higher relative abundance of Firmicutes in tail biter pigs than the controls. Furthermore, we detected differences in faecal and plasma short chain fatty acids (SCFA) profiles between the biter and victim pigs, suggesting physiological differences even though they are kept in the same pen. Thus, in addition to supporting an association between the gut microbiota and tail biting in pigs, this study also provides the first evidence of an association between tail biting and SCFA. Therefore, further research is needed to confirm these associations, to determine causality and to study how the SCFA profiles of an individual play a role in the development of tail biting behaviour.

Engineered action at a distance: Blood-meal-inducible paralysis in Aedes aegypti.

BACKGROUND: Population suppression through mass-release of Aedes aegypti males carrying dominant-lethal transgenes has been demonstrated in the field. Where population dynamics show negative density-dependence, suppression can be enhanced if lethality occurs after the density-dependent (i.e. larval) stage. Existing molecular tools have limited current examples of such Genetic Pest Management (GPM) systems to achieving this through engineering 'cell-autonomous effectors' i.e. where the expressed deleterious protein is restricted to the cells in which it is expressed-usually under the control of the regulatory elements (e.g. promoter regions) used to build the system. This limits the flexibility of these technologies as regulatory regions with useful spatial, temporal or sex-specific expression patterns may only be employed if the cells they direct expression in are simultaneously sensitive to existing effectors, and also precludes the targeting of extracellular regions such as cell-surface receptors. Expanding the toolset to 'non-cell autonomous' effectors would significantly reduce these limitations. METHODOLOGY/PRINCIPAL FINDINGS: We sought to engineer female-specific, late-acting lethality through employing the Ae. aegypti VitellogeninA1 promoter to drive blood-meal-inducible, fat-body specific expression of tTAV. Initial attempts using pro-apoptotic effectors gave no evident phenotype, potentially due to the lower sensitivity of terminally-differentiated fat-body cells to programmed-death signals. Subsequently, we dissociated the temporal and spatial expression of this system by engineering a novel synthetic effector (Scorpion neurotoxin-TetO-gp67.AaHIT) designed to be secreted out of the tissue in which it was expressed (fat-body) and then affect cells elsewhere (neuro-muscular junctions). This resulted in a striking, temporary-paralysis phenotype after blood-feeding. CONCLUSIONS/SIGNIFICANCE: These results are significant in demonstrating for the first time an engineered 'action at a distance' phenotype in a non-model pest insect. The potential to dissociate temporal and spatial expression patterns of useful endogenous regulatory elements will extend to a variety of other pest insects and effectors.

Identification of the source of blood meals in mosquitoes collected from north-eastern Australia.

BACKGROUND: More than 70 arboviruses have been identified in Australia and the transmission cycles of most are poorly understood. While there is an extensive list of arthropods from which these viruses have been recovered, far less is known about the non-human hosts that may be involved in the transmission cycles of these viruses and the relative roles of different mosquito species in cycles of transmission involving different hosts. Some of the highest rates of human infection with zoonotic arboviruses, such as Ross River (RRV) and Barmah Forest (BFV) viruses, occur in coastal regions of north-eastern Australia. METHODS: Engorged mosquitoes collected as a part of routine surveillance using CO2-baited light traps in the Rockhampton Region and the adjoining Shire of Livingstone in central Queensland, north-eastern Australia, were analysed for the source of their blood meal. A 457 or 623 nucleotide region of the cytochrome b gene in the blood was amplified by PCR and the amplicons sequenced. The origin of the blood was identified by comparing the sequences obtained with those in GenBank®. RESULTS: The most common hosts for the mosquitoes sampled were domestic cattle (26/54) and wild birds (14/54). Humans (2/54) were an infrequent host for this range of mosquitoes that are known to transmit arboviruses causing human disease, and in an area where infections with human pathogens like RRV and BFV are commonly recorded. The blood meals identified in the most abundant vector analysed, Culex annulirostris, were from 10 different vertebrate hosts. The notable detection of chimpanzee blood in two mosquitoes, presumably obtained from a nearby zoo, extends the known range of hosts for this species. Culex quinquefasciatus and Cx. sitiens fed almost exclusively on a variety of bird species. CONCLUSIONS: While human-mosquito-human transmission of arboviruses like RRV can occur, this study highlights the potential importance of zoonotic cycles of transmission, including avian species, of arboviruses that are indigenous to Australia. Further studies on larger samples of blood-engorged mosquitoes are required to validate the trends observed herein. Moreover, serological and virological evidence that the hosts on which the mosquitoes are feeding are being infected with arboviruses of interest are required.

Clinicopathologic abnormalities associated with increased animal triage trauma score in cats with bite wound injuries: 43 cases (1998-2009).

OBJECTIVE: To document the clinical and clinicopathologic changes in cats presenting with trauma from bite wounds, identify common abnormalities associated with bite wounds, and to determine whether the calculated animal trauma triage (ATT) score is related to any clinicopathologic abnormalities. DESIGN: Retrospective descriptive study. SETTING: University veterinary teaching hospital. ANIMALS: Forty-three client-owned cats that presented for bite wounds to a large, urban, veterinary hospital between 1998 and 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pertinent history, physical examination findings, results of biochemical testing, and outcome were extracted from medical records. Animal triage trauma score was calculated based on the physical examination at presentation in cats with adequate available information. Patients were classified as having either a low (<5) ATT (n = 20) or a high (≥5) ATT (n = 23) score. Male cats were overrepresented (65.1%), and a majority of cats had outdoor access (53.4%). Low venous blood pH (P = 0.047), high plasma lactate concentration (P = 0.018), and low ionized calcium concentration (P = 0.004) were associated with higher ATT scores. CONCLUSIONS: There is a significant association between low venous blood pH, high plasma lactate concentration, and low ionized calcium concentration and higher ATT scores at presentation in cats suffering from bite wounds. Early recognition of these abnormalities may help to identify more severely injured patients.

Which mosquitoes (Diptera: Culicidae) are candidates for DNA extraction in forensic practice?

Mosquitoes can be of importance in forensic context as a source of the perpretator's DNA. The aim of this study was to find how can we optimize the selection of appropriate mosquito individuals. The study was based on the data of 177833 trapped female mosquitoes and 105236 individuals which were collected directly from human skin. The mean human-specific biting willingness value of Aedes species was the highest (mean: 0.8). Significant differences were found between the human-specific biting willingness value variances of Aedes and Culex (p=0.0117) and barely significant differences between Anopheles and Culiseta (p = 0.5412), as well as between Aedes and Culiseta genera (p = 0.0562). Culiseta species showed the lowest human-specific biting willingness values (mean = 0.16). The mean of the human-specific biting willingness values of univoltine and multivoltine mosquitoes were 0.43 and 0.37 which means no significant difference between the variances of the two groups (p = 0.625). The mean of the human-specific biting willingness values of the predominantly mammal biting and non-mammal biting mosquitoes were 0.45 and 0.03 with a very significant difference (p<0.0001). Only five mosquito species have a relative biting risk index equal or more than 0.03 in Hungary, namely of Aedes vexans (0.43), Ochlerotatus cantans: (0.25), Ochlerotatus sticticus: (0.11), Culex modestus: (0.07) and Aedes cinereus: (0.03). It can be concluded that the mean human-specific biting willingness of mosquitoes depends on the genera, the host preference and it is independent of the annual number of generations or the breeding habitat preference. The relative biting risk index reflects the actual and annual relative abundances and the usefulness and availability of a mosquito for legal purposes reducing the financial and time requirements of the investigations.

Dynamic variations in platelet counts may reflect the severity and prognosis of stingray injuries in the early phase.

There is often a delay in offering quality and prompt treatment after a stingray sting. We present 3 cases of stings and discuss the Poisoning Severity Score (PSS) and a simple tool to assess the severity of such injuries. A 34-year-old man, who worked as an aquarium keeper, presented a wound on the left fifth digit caused by a stingray. Acute myocardial injury and rhabdomyolysis were detected. After 6weeks, the wound had almost healed. A 27-year-old man who experienced a stingray injury on the left second digit recovered without sequelae after 5weeks. A 45-year-old man with a history of diabetes, who was accidentally stung in the right palm by a stingray, experienced rhabdomyolysis and returned to work after 2months. We performed debridement, administered the tetanus toxoid and antibiotics, and immersed the wounded hand in warm water (about 43°C) for all three cases. Meanwhile, patients with rhabdomyolysis were administered intravenous hydration. Upon presentation at the emergency department, we recorded the severity of the injury by using PSS. We found that relatively high PSSs were associated with lower platelet counts that happen due to various adverse events. We suggest that dynamic changes in platelet counts may be associated with the severity of the injury. Furthermore, lower platelet counts in the normal or abnormal range may indicate poor prognoses.

Detecting multiple DNA human profile from a mosquito blood meal.

Criminal traces commonly found at crime scenes may present mixtures from two or more individuals. The scene of the crime is important for the collection of various types of traces in order to find the perpetrator of the crime. Thus, we propose that hematophagous mosquitoes found at crime scenes can be used to perform genetic testing of human blood and aid in suspect investigation. The aim of the study was to obtain a single Aedes aegypti mosquito profile from a human DNA mixture containing genetic materials of four individuals. We also determined the effect of blood acquisition time by setting time intervals of 24, 48, and 72 h after the blood meal. STR loci and amelogenin were analyzed, and the results showed that human DNA profiles could be obtained from hematophagous mosquitos at 24 h following the blood meal. It is possible that hematophagous mosquitoes can be used as biological remains at the scene of the crime, and can be used to detect human DNA profiles of up to four individuals.

Animal toxins and renal ion transport: Another dimension in tropical nephrology.

Renal vascular and tubular ion channels and transporters involved in toxin injury are reviewed. Vascular ion channels modulated by animal toxins, which result in haemodynamic alterations and changes in blood pressure, include ENaC/Degenerin/ASIC, ATP sensitive K channels (KATP ), Ca activated K channels (Kca) and voltage gated Ca channels, mostly L-type. Renal tubular Na channels and K channels are also targeted by animal toxins. NHE3 and ENaC are two important targets. NCC and NKCC may be involved indirectly by vasoactive mediators induced by inflammation. Most renal tubular K channels including voltage gated K channels (Kv1), KATP , ROMK1, BK and SK are blocked by scorpion toxins. Few are inhibited by bee, wasp and spider venoms. Due to small envenoming, incomplete block and several compensatory mechanisms in renal tubules, serum electrolyte charges are not apparent. Changes in serum electrolytes are observed in injury by large amount of venom when several channels or transporters are targeted. Envenomings by scorpions and bees are examples of toxins targeting multiple ion channels and transporters.

Reconhecimento materno na Unidade de Cuidado Intensivo Neonatal / Reconocimiento materno en la Unidad de Cuidado Intensivo Neonatal / Mother recognition in the Neonatal Intensive Care Unit

RESUMO Objetivo: analisar experiências maternas em Unidade de Cuidado Intensivo Neonatal, com foco nas relações de reconhecimento. Método: estudo qualitativo, desenvolvido na perspectiva da hermenêutica gadameriana, fundamentado no conceito honnethiano de reconhecimento. Foram entrevistadas, em profundidade, dez mães de crianças internadas em Unidade de Cuidado Intensivo Neonatal. Resultados: há comprometimentos no processo de reconhecimento materno na unidade e, como desdobramento, surgem sentimentos de obrigação e insegurança para o cuidado do filho e fragilidades na autoestima. Conclusão: as interações com os profissionais de saúde e as normas e protocolos ali existentes promovem vulnerabilidades e comprometem o reconhecimento e a autonomia materna. .

RESUMEN Objetivo: analizar la experiencia derivada de la maternidad en la Unidad de Cuidados Intensivos Neonatales, centrándose en las relaciones de reconocimiento. Método: estudio cualitativo, desarrollado desde la perspectiva de la hermenéutica de Gadamer, basado en el concepto honnethiano de reconocimiento. Fueron entrevistados en profundidad diez madres de niños ingresados en una Unidad de Cuidados Intensivos Neonatales. Resultados: existen deficiencias en el proceso de reconocimiento materno en la UCIN y, por consiguiente, surgen sentimientos de inseguridad y obligación de cuidar de su hijo resultando en debilidades en su autoestima. Conclusión: las interacciones con profesionales de la salud en la unidad y las normas y protocolos allí existentes llevan a vulnerabilidades y comprometen el reconocimiento y autonomía materna. .

ABSTRACT Objective: analyze the maternal experience in a neonatal intensive care unit, focusing on relations of recognition. Method: a qualitative study, built on the perspective of Gadamer’s hermeneutics, based on Honneth’s concept of recognition. In-depth interviews were conducted with 10 mothers of children admitted to a neonatal intensive care unit. Results: failures were reported in the process of mother recognition in the unit, with consequent feelings of insecurity and obligation to child care, resulting in fragility of self-esteem. Conclusion: interactions with health professionals in the NICU and its standards and protocols cause vulnerabilities and affect maternal recognition and autonomy. .

Evidence for a link between tail biting and central monoamine metabolism in pigs (Sus scrofa domestica).

Tail biting in pigs is a major welfare problem within the swine industry. Even though there is plenty of information on housing and management-related risk factors, the biological bases of this behavioral problem are poorly understood. The aim of this study was to investigate a possible link between tail biting, based on behavioral recordings of pigs during an ongoing outbreak, and certain neurotransmitters in different brain regions of these pigs. We used a total of 33 pigs at a farm with a long-standing problem of tail biting. Three equally big behavioral phenotypic groups, balanced for gender and age were selected, the data thus consisting of 11 trios of pigs. Two of the pigs in each trio originated from the same pen: one tail biter (TB) and one tail biting victim (V). A control (C) pig was selected from a pen without significant tail biting in the same farm room. We found an effect of tail biting behavioral phenotype on the metabolism of serotonin and dopamine, with a tendency for a higher 5-HIAA level in the prefrontal cortex (PFC) of TB compared to the other groups, while V pigs showed changes in both serotonin and dopamine metabolism in the striatum (ST) and limbic cortex (LC). Trp:BCAA and Trp:LNAA correlated positively with serotonin and 5-HIAA in the PFC, but only in TB pigs. Furthermore, in both ST and LC, several of the neurotransmitters and their metabolites correlated positively with the frequency of bites received by the pig. This is the first study indicating a link between brain neurotransmission and tail biting behavior in pigs with TB pigs showing a tendency for increased PFC serotonin metabolism and V pigs showing several changes in central dopamine and serotonin metabolism in their ST and LC, possibly due to the acute stress caused by being bitten.

Tail biting in pigs: blood serotonin and fearfulness as pieces of the puzzle?

Tail biting in pigs is a widespread problem in intensive pig farming. The tendency to develop this damaging behaviour has been suggested to relate to serotonergic functioning and personality characteristics of pigs. We investigated whether tail biting in pigs can be associated with blood serotonin and with their behavioural and physiological responses to novelty. Pigs (n = 480) were born in conventional farrowing pens and after weaning at four weeks of age they were either housed barren (B) or in straw-enriched (E) pens. Individual pigs were exposed to a back test and novel environment test before weaning, and after weaning to a novel object (i.e. bucket) test in an unfamiliar arena. A Principal Component Analysis on behaviours during the tests and salivary cortisol (novel object test only) revealed five factors for both housing systems, labeled 'Early life exploration', 'Near bucket', 'Cortisol', 'Vocalizations & standing alert', and 'Back test activity'. Blood samples were taken at 8, 9 and 22 weeks of age to determine blood platelet serotonin. In different phases of life, pigs were classified as tail biter/non-tail biter based on tail biting behaviour, and as victim/non-victim based on tail wounds. A combination of both classifications resulted in four pig types: biters, victims, biter/victims, and neutrals. Generally, only in phases of life during which pigs were classified as tail biters, they seemed to have lower blood platelet serotonin storage and higher blood platelet uptake velocities. Victims also seemed to have lower blood serotonin storage. Additionally, in B housing, tail biters seemed to consistently have lower scores of the factor 'Near bucket', possibly indicating a higher fearfulness in tail biters. Further research is needed to elucidate the nature of the relationship between peripheral 5-HT, fearfulness and tail biting, and to develop successful strategies and interventions to prevent and reduce tail biting.

Jejunal morphology and blood metabolites in tail biting, victim and control pigs.

Tail biting has several identified feeding-related risk factors. Tail biters are often said to be lighter and thinner than other pigs in the pen, possibly because of nutrition-related problems such as reduced feed intake or inability to use nutrients efficiently. This can lead to an increase in foraging behavior and tail biting. In this study, a total of 55 pigs of different ages were selected according to their tail-biting behavior (bouts/hour) and pen-feeding system to form eight experimental groups: tail-biting pigs (TB), victim pigs (V) and control pigs from a tail-biting pen (Ctb) and control pen (Cno) having either free access to feed with limited feeding space or meal feeding from a long trough. After euthanasia, a segment of jejunal cell wall was cut from 50 cm (S50) and 100 cm (S100) posterior to the bile duct. Villus height, crypt depth and villus : crypt ratio (V : C) were measured morphometrically. Blood serum concentration of minerals and plasma concentration of amino acids (AA) was determined. Villus height was greater in Cno than Ctb pigs in the proximal and mid-jejunum (P < 0.05), indicative of better ability to absorb nutrients, and increased with age in the proximal jejunum (P < 0.001). Serum mineral concentration of inorganic phosphate (Pi) and calcium (Ca) was lower in Ctb compared with Cno pigs, and that of Pi in V compared with all the other pigs. Many non-essential AA were lower in pigs from tail-biting pens, and particularly in victim pigs. Free access feeding with shared feeding space was associated with lower levels of essential AA in blood than meal feeding with simultaneous feeding space. Our data suggest that being a pig in a tail-biting pen is associated with decreased jejunal villus height and blood AA levels, possibly because of depressed absorption capacity, feeding behavior or environmental stress associated with tail biting. Victim pigs had lower concentrations of AA and Pi in plasma, possibly as a consequence of being bitten.

Long-term analysis of Irukandji stings in Far North Queensland.

INTRODUCTION: We reviewed the occurrence, trends, definition and severity of the Irukandji syndrome for the Cairns region of North Queensland, Australia. METHODS: A retrospective analysis of patient files from two sources was conducted: historic accounts kept by Dr Jack Barnes for the period 1942 to 1967, and records from the Emergency Unit in Cairns Base Hospital for 1995 to 2007. RESULTS: There has been a significant increase in the length of the Irukandji season since it was first reliably recorded (15 days in 1961; 151 days in 2002); however, annual numbers of envenomations were highly variable. Traditionally, greater frequencies of Irukandji stings were reported at onshore as opposed to offshore locations. However, in recent years this trend has reversed, potentially because of increased safety protocols for beach regions. Mean Troponin I levels were higher in offshore reef envenomations compared to those from islands or coastal regions. In terms of morphine-equivalent doses, patients given fentanyl received significantly greater opioid doses compared to those given morphine or pethidine. Opioid dosage was indicative of syndrome severity and correlated with other physiological parameters measured. Five major symptoms were associated with Irukandji syndrome: pain, nausea/vomiting, diaphoresis, headache and shortness of breath. Pain was the overwhelming symptom, followed closely by nausea/vomiting. CONCLUSIONS: The duration of the Irukandji season appears to be increasing. Conversely the number of envenomings appears to be decreasing, possibly because of improved beach management in recent years. Offshore envenomings appear to have a higher potential for more severe envenomings with five associated major symptoms.

Implication of haematophagous arthropod salivary proteins in host-vector interactions.

The saliva of haematophagous arthropods contains an array of anti-haemostatic, anti-inflammatory and immunomodulatory molecules that contribute to the success of the blood meal. The saliva of haematophagous arthropods is also involved in the transmission and the establishment of pathogens in the host and in allergic responses. This survey provides a comprehensive overview of the pharmacological activity and immunogenic properties of the main salivary proteins characterised in various haematophagous arthropod species. The potential biological and epidemiological applications of these immunogenic salivary molecules will be discussed with an emphasis on their use as biomarkers of exposure to haematophagous arthropod bites or vaccine candidates that are liable to improve host protection against vector-borne diseases.

Serial plasma glucose changes in dogs suffering from severe dog bite wounds.

The objective of this study was to describe the changes in plasma glucose concentration in 20 severely injured dogs suffering from dog bite wounds over a period of 72 hours from the initiation of trauma. Historical, signalment, clinical and haematological factors were investigated for their possible effect on plasma glucose concentration. Haematology was repeated every 24 hours and plasma glucose concentrations were measured at 8-hourly intervals post-trauma. On admission, 1 dog was hypoglycaemic, 8 were normoglycaemic and 11 were hyperglycaemic. No dogs showed hypoglycaemia at any other stage during the study period. The median blood glucose concentrations at each of the 10 collection points, excluding the 56-hour and 64-hour collection points, were in the hyperglycaemic range (5.8- 6.2 mmol/l). Puppies and thin dogs had significantly higher median plasma glucose concentrations than adult and fat dogs respectively (P < 0.05 for both). Fifteen dogs survived the 72-hour study period. Overall 13 dogs (81.3 %) made a full recovery after treatment. Three of 4 dogs that presented in a collapsed state died, whereas all dogs admitted as merely depressed or alert survived (P = 0.004). The high incidence of hyperglycaemia can possibly be explained by the "diabetes of injury" phenomenon. However, hyperglycaemia in this group of dogs was marginal and potential benefits of insulin therapy are unlikely to outweigh the risk of adverse effects such as hypoglycaemia.

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.

Antivenom efficacy or effectiveness: the Australian experience.

Despite widespread use of antivenoms, many questions remain about their effectiveness in the clinical setting. The almost universal acceptance of their value is based mainly on in vitro studies, animal studies and human observational studies. Numerous examples exist where they demonstrate clear benefit, such as consumption coagulopathy in viper envenoming, prevention of neurotoxicity in Australasian elapid bites, systemic effects in scorpion and funnel-web spider envenoming. There are also concerns about the quality and efficacy of some antivenoms. However, it is important not to confuse the efficacy of antivenom, defined as its ability to bind and neutralise venom-mediated effects under ideal conditions, and the effectiveness of antivenom, defined as its ability to reverse or prevent envenoming in human cases. There are numerous potential reasons for antivenom failure in human envenoming, of which antivenom inefficacy is only one. Other important reasons include venom-mediated effects being irreversible, antivenom being unable to reach the site of toxin-mediated injury, or the rapidity of onset of venom-mediated effects. A number of recent studies in Australia bring into question the effectiveness of some antivenoms, including snake antivenom for coagulopathy, redback spider and box jellyfish antivenoms. Despite brown snake antivenom being able to neutralise venom induced clotting in vitro, use of the antivenom in human envenoming does not appear to change the time course of coagulopathy. However, it is important that apparent antivenom ineffectiveness in specific cases is correctly interpreted and does not lead to a universal belief that antivenom is ineffective. It should rather encourage further studies to investigate the underlying pathophysiology of envenoming, the pharmacokinetics of venoms and antivenoms, and ultimately the effectiveness of antivenom based on snake type, clinical effects and timing of administration.