Search Results (21)

Mamba (Dendroaspis species) snakebites are critical medical emergencies across sub-Saharan Africa. Envenomings can result in the rapid onset of complex neurotoxic symptoms, often leading to high rates of mortality without timely intervention with antivenom. The ancestral state of mambas is the green coloured, forest dwelling type, with the tan/grey coloured, savannah dwelling D. polylepis (Black Mamba) representing a derived state both ecologically and morphologically. However, it has not been tested whether these changes are paralleled by changes in venom biochemistry or if there are differential molecular evolutionary patterns. To fill these knowledge gaps, this study evaluated the neurotoxic effects of all Dendroaspis species venoms using the chick biventer cervicis nerve-muscle preparation, assessed the neutralizing efficacy of three antivenoms commercially available in Africa, and reconstructed the molecular evolutionary history of the toxin types to ascertain whether some were unique to particular species. All Dendroaspis venoms demonstrated potent flaccid-paralysis due to postsynaptic neurotoxicity. The only exception was D. angusticeps venom, which conversely exhibited spastic-paralysis due to presynaptic/synaptic neurotoxicity characterised by potentiation of acetylcholine presynaptic release and sustained synaptic activity of this neurotransmitter. Antivenom efficacy varied significantly. All three antivenoms neutralized to some degree the flaccid-paralysis postsynaptic effects for all species, with D. viridis venom being the best neutralized, and this pattern extended to all the antivenoms. However, neutralisation of flaccid-paralysis postsynaptic effects unmasked spastic-paralysis presynaptic/synaptic neurotoxicity within non-angusticeps venoms. Spastic-paralysis presynaptic effects were poorly neutralized for all species by all antivenoms, consistent with prior clinical reports of poor neutralisation of spastic-paralytic effects. Geographic variation in D. polylepis venom was evident for the relative neutralisation of both spastic-paralysis presynaptic/synaptic and flaccid-paralysis postsynaptic/synaptic neurotoxic pathophysiological effects, with differential neutralization capabilities noted between the Kenyan and South African populations studied. Molecular phylogenetic analyses confirmed spastic-paralysis and flaccid- paralysis toxins to be a trait that emerged in the Dendroaspis last common ancestor, with all species sharing all toxin types. Therefore, differences in venoms’ pathophysiological actions between species are due to differential expression of toxin isoforms rather than the evolution of species-specific novel toxins. Our findings highlight the synergistic nature of flaccid-paralysis postsynaptic and spastic-paralysis presynaptic/synaptic toxins, while contributing significant clinical and evolutionary knowledge of Dendroaspis venoms. These data are crucial for the continued development of more effective therapeutic interventions to improve clinical outcomes and for evidence-based design of clinical management strategies for the envenomed patient. Full article

Butter clams (Saxidomus gigantea) are a staple in the subsistence diets of Alaskan Native communities and are also harvested recreationally. This filter–feeding species can accumulate saxitoxins (STXs), potent neurotoxins produced by late spring and summer blooms of the microalga Alexandrium catenella. The consumption of tainted clams can cause paralytic shellfish poisoning (PSP). Traditional beliefs and early reports on the efficacy of removing clam siphons have created the impression that cleaning butter clams by removing certain tissues makes them safe to eat. However, the toxin distribution within clams can vary over time, making the practice of cleaning butter clams unreliable. This study tested the effectiveness of the cleaning methods practiced by harvesters on Kodiak Island, Alaska. Specifically, butter clams were cleaned by removing different tissues to produce samples of “edible” tissues that were tested for STX content. The results were compared to historical data from a study conducted in Southeast Alaska from 1948 to 1949. Using these data, the risk for an average–sized man and woman consuming 200 g of edible tissue was calculated. The results showed that for clams containing >200 µg STX–equivalents 100 g edible tissue⁻¹, no cleaning method reduced the concentration of STXs in the remaining tissue below the regulatory limit. Meals containing >900 µg STX–equivalents 100 g edible tissue⁻¹ posed a substantial risk of moderate or severe symptoms. No cleaning method assured that untested butter clams are safe to eat. Full article

As a significant zoonotic disease, rabies poses substantial economic challenges for the livestock sector, highlighting the need for effective wildlife monitoring as part of a One Health approach. This study documents the first case of paralytic rabies in a lowland tapir (Tapirus terrestris) at the Guaycolec Wildlife Station in Formosa, Argentina. The 12-year-old male tapir exhibited neurological symptoms, including limb paralysis and dysphagia, leading to its death. The rabies virus was confirmed through direct immunofluorescence, virus isolation in BHK-21 cells, and molecular diagnostics via real-time RT-PCR and conventional PCR. Antigenic variant 3, associated with Desmodus rotundus, was identified. Histopathological examination revealed non-suppurative encephalitis with lymphocytic perivascular cuffs, neuronal vacuolization, and acidophilic intracytoplasmic inclusion bodies in the grey matter. This case underscores the importance of expanded surveillance for non-traditional hosts, as it demonstrates the potential for rabies transmission in changing environments. The findings highlight the need to maintain epidemiological surveillance systems at the wildlife–livestock–human interface and to develop targeted control strategies to mitigate the spread of rabies, particularly in areas where vampire bat populations are subject to anthropogenic pressures. Comprehensive monitoring and early detection are essential for effective rabies management in both wildlife and urban contexts. Full article

Background: Ectropion is a common eyelid problem and is defined as eversion of the eyelid margin and typically involves the lower eyelid. The main acquired causes of ectropion include involutional, cicatricial, paralytic, and mechanical. A severe manifestation of ectropion is tarsal ectropion, where much of the tarsal conjunctiva is visible, often with keratinization of the conjunctiva. causes. Common techniques for ectropion repair include horizontal tightening of the lid with lateral tarsal strip or Bick procedure, lateral tarsorraphy, inverting sutures and the sub-orbicularis oculi fat lift. However, all surgical techniques are prone to ectropion recurrence. We review the techniques for ectropion repair and describe a novel adjunctive technique called the superotemporal skin transposition (STS), which is well suited for patients with recurrent or tarsal ectropion. Methods: The STS is combined with a lateral tarsal strip or Bick procedure. For the STS, all of the anterior lamellae of the lateral lower lid is retained. The posterior lamellae is sutured to the lateral orbital tubercle. A triangular bed of skin is excised superotemporally, and the lower lid anterior lamellae is transposed and secured with multiple sutures. The STS can be combined with inverting sutures, or skin graft for cicatricial cases. Results: We used the STS with Bick procedure and optional inverting sutures on 23 patients, 4 of whom required bilateral ectropion repair. At 1–6 month followup all patients achieved satisfactory outcomes with a well-positioned eyelid and improved symptoms. The STS had more lateral cutaneous scarring than with a Bick procedure alone, but patients did not find this objectionable. No reoperations were required. Conclusion: The STS is a straightforward and useful adjunct for patients with severe, recurrent or tarsal ectropion. Further studies are needed to determine the long-term efficacy of this technique. Full article

Saxitoxin (STX) causes high toxicity by blocking voltage-gated sodium channels, and it poses a major threat to marine ecosystems and human health worldwide. Our work evaluated the neurotoxicity and chronic toxicology of STX to Caenorhabditis elegans by an analysis of lifespan, brood size, growth ability, reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels, and the overexpression of green fluorescent protein (GFP). After exposure to a series of concentrations of STX for 24 h, worms showed paralysis symptoms and fully recovered within 6 h; less than 5% of worms died at the highest concentration of 1000 ng/mL for first larval stage (L1) worms and 10,000 ng/mL for fourth larval stage (L4) worms. Declines in lifespan, productivity, and body size of C. elegans were observed under the stress of 1, 10, and 100 ng/mL STX, and the lifespan was shorter than that in controls. With STX exposure, the productivity declined by 32–49%; the body size, including body length and body area, declined by 13–18% and 25–27%, respectively. The levels of ROS exhibited a gradual increase over time, accompanied by a positive concentration effect of STX resulting in 1.14–1.86 times higher levels compared to the control group in L4 worms. Conversely, no statistically significant differences were observed between L1 worms. Finally, after exposure to STX for 48 h, ATP levels and GFP expression in C. elegans showed a significant dose-dependent increase. Our study reports the first evidence that STX is not lethal but imposes substantial oxidative stress on C. elegans, with a dose-responsive relationship. Our results indicated that C. elegans is an ideal model to further study the mechanisms underlying the fitness of organisms under the stress caused by paralytic shellfish toxins including STX. Full article

Post-polio syndrome (PPS) is characterized by recrudescence or worsening of motor neuron disease symptoms decades after recovery from acute paralytic poliovirus infection, i.e., poliomyelitis. PPS afflicts between 25% and 40% of poliomyelitis survivors and mimics motor neuron diseases (MNDs), such as amyotrophic lateral sclerosis (ALS), due to its selective impairment, degeneration, or death of motor neurons in the brainstem and spinal cord. Herein, we report a case of PPS in a 68-year-old man with a remote history of bulbar and cervical cord involvement by poliomyelitis, review the relevant literature, and contrast the salient histopathologic features that distinguish our case of PPS from ALS. Full article

Phytoplankton are photosynthetic microorganisms in aquatic environments that produce many bioactive substances. However, some of them are toxic to aquatic organisms via filter-feeding and are even poisonous to humans through the food chain. Human poisoning from these substances and their serious long-term consequences have resulted in several health threats, including cancer, skin disorders, and other diseases, which have been frequently documented. Seafood poisoning disorders triggered by phytoplankton toxins include paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), amnesic shellfish poisoning (ASP), diarrheic shellfish poisoning (DSP), ciguatera fish poisoning (CFP), and azaspiracid shellfish poisoning (AZP). Accordingly, identifying harmful shellfish poisoning and toxin-producing species and their detrimental effects is urgently required. Although the harmful effects of these toxins are well documented, their possible modes of action are insufficiently understood in terms of clinical symptoms. In this review, we summarize the current state of knowledge regarding phytoplankton toxins and their detrimental consequences, including tumor-promoting activity. The structure, source, and clinical symptoms caused by these toxins, as well as their molecular mechanisms of action on voltage-gated ion channels, are briefly discussed. Moreover, the possible stress-associated reactive oxygen species (ROS)-related modes of action are summarized. Finally, we describe the toxic effects of phytoplankton toxins and discuss future research in the field of stress-associated ROS-related toxicity. Moreover, these toxins can also be used in different pharmacological prospects and can be established as a potent pharmacophore in the near future. Full article

Phycotoxins occur in various marine and freshwater environments, and can accumulate in edible species such as fish, crabs, and shellfish. Human exposure to these toxins can take place, for instance, through consumption of contaminated species or supplements and through the ingestion of contaminated water. Symptoms of phycotoxin intoxication include paralysis, diarrhea, and amnesia. When the cause of an intoxication cannot directly be found, a screening method is required to identify the causative toxin. In this work, such a screening method was developed and validated for marine and freshwater phycotoxins in different matrices: fish, shellfish, water, and food supplements. Two LC methods were developed: one for hydrophilic and one for lipophilic phycotoxins. Sample extracts were measured in full scan mode with an Orbitrap high resolution mass spectrometer. Additionally, a database was created to process the data. The method was successfully validated for most matrices, and in addition, regulated lipophilic phycotoxins, domoic acid, and some paralytic shellfish poisoning toxins could be quantified in shellfish. The method showed limitations for hydrophilic phycotoxins in sea water and for lipophilic phycotoxins in food supplements. The developed method is a screening method; in order to confirm suspected compounds, comparison with a standard or an additional analysis such as NMR is required. Full article

Background: Mucopolysaccharidosis type III (MPS III, Sanfilippo disease) is a life-limiting recessive lysosomal storage disorder caused by a deficiency in the enzymes involved in degrading glycosaminoglycan heparan sulfate. MPS III is characterized by progressive deterioration of the central nervous system. Respiratory tract infections have been reported as frequent and as the most common cause of death, but gastrointestinal (GI) manifestations have not been acknowledged as a cause of concern. The aim of this study was to determine the incidence of GI problems as a primary cause of death and to review GI symptoms reported in published studies. Methods: Causes of death from 221 UK death certificates (1957–2020) were reviewed and the literature was searched to ascertain reported GI symptoms. Results: GI manifestations were listed in 5.9% (n = 13) of death certificates. Median (IQR) age at death was 16.7 (5.3) years. Causes of death included GI failure, GI bleed, haemorrhagic pancreatitis, perforation due to gastrostomies, paralytic ileus and emaciation. Twenty-one GI conditions were reported in 30 studies, mostly related to functional GI disorders, including diarrhoea, dysphagia, constipation, faecal incontinence, abdominal pain/distension and cachexia. Conclusions: GI manifestations may be an under-recognized but important clinical feature of MPS III. Early recognition of GI symptoms and timely interventions is an important part of the management of MPS III patients. Full article

Botulinum toxins or neurotoxins (BoNTs) are the most potent neurotoxins known, and are currently extensively studied, not only for their potential lethality, but also for their possible therapeutic and cosmetic uses. Currently, seven types of antigenically distinct toxins are known and characterized, produced by a rod-shaped bacterium, Clostridium botulinum. Human poisoning by botulism (presenting with severe neuromuscular paralytic disease) is usually caused by toxins A, B, E, and F type. Poisoning from contaminated food preparations is the most common cause of noniatrogenic botulism. The spores are highly resistant to heat but are easily destroyed at 80 °C for thirty minutes. Type A and B toxins are resistant to digestion by the enzymes of the gastrointestinal system. After their entry, BoNTs irreversibly bind to cholinergic nerve endings and block the release of acetylcholine from the synapses. In contrast, in wound botulism, the neurotoxin is instead product by the growth of C. botulium in infected tissues. The contamination by BoNT inhalation does not occur by a natural route but it is certainly the most dangerous. It can be caused by the dispersion of the botulinum toxin in the atmosphere in the form of an aerosol and therefore can be deliberately used for bioterrorist purposes (e.g., during CBRN (chemical, biological, radiological, and nuclear) unconventional events). In addition, BoNTs are currently used to treat a variety of diseases or alleviate their symptoms, such as the onabotulinumtoxinA for migraine attacks and for cosmetic use. Indeed, this paper aims to report on updated knowledge of BoNTs, both their toxicological mechanisms and their pharmacological action. Full article

Although it had been reported that Israeli acute paralysis virus (IAPV) can cause systemic infection in honey bees, little is known about how it establishes this infection and results in the typical symptoms, paralysis and trembling. Here, we used our previously constructed IAPV infectious clone to investigate viral loads in different tissues of honey bees and further identify the relation between tissue tropism and paralytic symptoms. Our results showed that tracheae showed a greater concentration of viral abundance than other tissues. The abundance of viral protein in the tracheae was positively associated with viral titers, and was further confirmed by immunological and ultrastructural evidence. Furthermore, higher viral loads in tracheae induced remarkable down-regulation of succinate dehydrogenase and cytochrome c oxidase genes, and progressed to causing respiratory failure of honey bees, resulting in the appearance of typical symptoms, paralysis and body trembling. Our results showed that paralysis symptoms or trembling was actually to mitigate tachypnea induced by IAPV infection due to the impairment of honey bee tracheae, and revealed a direct causal link between paralysis symptoms and tissue tropism. These findings provide new insights into the understanding of the underlying mechanism of paralysis symptoms of honey bees after viral infection and have implications for viral disease prevention and specific therapeutics in practice. Full article

Background: The incidence of poliovirus has been significantly reduced by as much as 99.9% globally. Alongside this, however, vaccine-associated paralytic poliomyelitis has emerged. Previously, our team reported in the Lésio-Louna-Léfini Nature Reserve (Republic of Congo) the presence of a new Enterovirus C (Ibou002) in a male gorilla that was put away because of clinical symptoms of facial paralysis. This new virus, isolated was from the stool samples of this gorilla but also from the excrement of an eco-guardian, is very similar to Coxsackievirus (EV-C99) as well as poliovirus 1 and 2. We hypothesised that these symptoms might be due to poliovirus infection. To test our hypothesis, we developed and optimised a non-invasive immunoassay for the detection of Enterovirus-specific antibodies in gorilla faeces that could be useful for routine serosurveillance in such cases. Methods: In order to assess the potential role of poliovirus infection, we have developed and optimised a protocol, based on the lyophilisation and solubilisation of small volumes of stool extracts from 16 gorilla and 3 humans, to detect specific antibodies by western blot and ELISA. Results: First, total immunoglobulins were detected in the concentrated stool extracts. Specific antibodies were then detected in 4/16 gorilla samples and 2/3 human samples by western blot using both the polio vaccine antigen and the Ibou002 antigen and by ELISA using the polio vaccine antigen. Humoral responses were greater with the Ibou002 antigen. Conclusion: We therefore suggest that this recombinant virus could lead to a polio-like disease in the endangered western lowland gorilla. The development of a non-invasive approach to detect microorganism-specific immunoglobulins from faecal samples opens numerous prospects for application in zoonotic infectious diseases and could revolutionise the screening of animals for important emerging infections, such as Ebola fever, rabies and coronavirus infections. Full article

Out of control proliferation of toxic phytoplankton, called harmful algal blooms (HABs), have a significant economic impact on bivalve aquaculture and harvesting in coastal waters. Some phytotoxins, such as paralytic shellfish toxins (PSTs), are of concern due to the life-threatening symptoms they can cause. Development of rapid and low-cost screening tools would be a welcome addition to the laboratory methodologies employed in routine monitoring programs. However, most of the assays and biosensors for the screening of PSTs, are restricted to a single target, saxitoxin (STX), which is the most potent PST. The present study aimed at developing an assay for the detection of N-sulfocarbamoyl PST—GTX5, which is one of the most abundant toxins in bivalves during G. catenatum blooms as found on the Portuguese coast. Enzymatic assay employing PSTs’ transforming enzyme—carbamoylase—was proposed. Carbamoylase was extracted and purified from the surf clam S. solida. Carbamoylase displayed similar specificity to both carbamate (STX) and N-sulfocarbamate toxins (GTX5 and C1+2) converting them into decarbamoyl saxitoxin (dcSTX) and decarbamoyl gonyautoxins 2+3 (dcGTX2+3), respectively. The enzymatic assay involved hydrolysis of GTX5 by carbamoylase and quantification of the product of enzymatic reaction, dcSTX, using a potentiometric chemical sensor. A potentiometric sensor with plasticized PVC membrane that displayed sensitivity to dcSTX and selectivity in the presence of GTX5 was employed. Enzymatic assay allowed determination of GTX5 in the concentration range from 0.43 to 3.30 µmolL⁻¹, which encompasses levels of GTX5 in contaminated bivalve extracts with toxicities above PSTs regulatory limits. The feasibility of the carbamoylase-based potentiometric assay for detection of GTX5 was demonstrated. Full article

Paralytic shellfish poisoning (PSP) is precipitated by a family of toxins produced by harmful algae, which are consumed by filter-feeding and commercially popular shellfish. The toxins, including saxitoxin, neosaxitoxin, and gonyautoxins, accumulate in shellfish and cause intoxication when consumed by humans and animals. Symptoms can range from minor neurological dysfunction to respiratory distress and death. There are over 40 different chemical congeners of saxitoxin and its analogs, many of which are toxic and many of which have low toxicity or are non-toxic. This makes accurate toxicity assessment difficult and complicates decisions regarding whether or not shellfish are safe to consume. In this study, we describe a new antibody-based bioassay that is able to detect toxic congeners (saxitoxin, neosaxitoxin, and gonyautoxins) with little cross-reactivity with the low or non-toxic congeners (decarbamoylated or di-sulfated forms). The anti-saxitoxin antibody used in this assay detects saxitoxin and neosaxitoxin, the two most toxic congers equally well, but not the relatively highly toxic gonyautoxins. By incorporating an incubation step with L-cysteine, it is possible to convert a majority of the gonyautoxins present to saxitoxin and neosaxitoxin, which are readily detected. The assay is, therefore, capable of detecting the most toxic PSP congeners found in commercially relevant shellfish. The assay was validated against samples whose toxicity was determined using standard HPLC methods and yielded a strong linear agreement between the methods, with R2 values of 0.94–0.96. As ELISAs are rapid, inexpensive, and easy-to-use, this new commercially available PSP ELISA represents an advance in technology allowing better safety management of the seafood supply and the ability to screen large numbers of samples that can occur when monitoring is increased substantially in response to toxic bloom events Full article

Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future. Full article