Xizhen Wu, Guixiang Wang, Jiangbing Qiu, Aifeng Li, Philipp Hess
Harmful algal blooms (HABs) formed by toxic microalgae have seriously threatened marine ecosystems and food safety and security in recent years. Among them, Karenia selliformis has attracted the attention of scientists and society due to its acute and rapid neurotoxicity in mice. Herein, the growth and gymnodimine A (GYM-A) production of K. selliformis were investigated in diverse culture systems with different surface-to-volume (S/V) ratios and nitrogen/phosphorus concentrations. The results showed that the specific growth rates (μ), maximal cell yields, and GYM-A production levels of K. selliformis increased with higher S/V, but no significant differences were observed under different culture volumes with the same S/V, which indicated that light penetration and gas exchange in the seawater culture systems actually influenced the growth and GYM-A production of K. selliformis. The maximum cell density and photosynthetic efficiency of K. selliformis decreased under nitrogen (N) and phosphorus (P) deficiency, suggesting that the growth of K. selliformis was significantly inhibited by the deficiency in N or P. Both N and P limitation conditions, especially P deficiency, promoted the cellular GYM-A quotas of K. selliformis. In this study, a scientific basis is provided for understanding the effects of culture systems and nutrient concentrations on the growth and toxin production of K. selliformis.
{"title":"Effects of Culture Systems and Nutrients on the Growth and Toxin Production of <i>Karenia selliformis</i>.","authors":"Xizhen Wu, Guixiang Wang, Jiangbing Qiu, Aifeng Li, Philipp Hess","doi":"10.3390/toxins16120518","DOIUrl":"10.3390/toxins16120518","url":null,"abstract":"<p><p>Harmful algal blooms (HABs) formed by toxic microalgae have seriously threatened marine ecosystems and food safety and security in recent years. Among them, <i>Karenia selliformis</i> has attracted the attention of scientists and society due to its acute and rapid neurotoxicity in mice. Herein, the growth and gymnodimine A (GYM-A) production of <i>K. selliformis</i> were investigated in diverse culture systems with different surface-to-volume (S/V) ratios and nitrogen/phosphorus concentrations. The results showed that the specific growth rates (μ), maximal cell yields, and GYM-A production levels of <i>K. selliformis</i> increased with higher S/V, but no significant differences were observed under different culture volumes with the same S/V, which indicated that light penetration and gas exchange in the seawater culture systems actually influenced the growth and GYM-A production of <i>K. selliformis</i>. The maximum cell density and photosynthetic efficiency of <i>K. selliformis</i> decreased under nitrogen (N) and phosphorus (P) deficiency, suggesting that the growth of <i>K. selliformis</i> was significantly inhibited by the deficiency in N or P. Both N and P limitation conditions, especially P deficiency, promoted the cellular GYM-A quotas of <i>K. selliformis</i>. In this study, a scientific basis is provided for understanding the effects of culture systems and nutrient concentrations on the growth and toxin production of <i>K. selliformis</i>.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aflatoxin M1 (AFM1) exposure through dairy products is associated with adverse health effects, including hepatotoxicity and carcinogenicity. Therefore, the AFM1 presence in milk and dairy products is strictly regulated. In this context, the current work focuses on the investigation of different competitive enzyme immunoassay configurations for the determination of AFM1 in milk with high sensitivity and short assay duration. Amongst the configurations tested, the one based on incubation of the anti-AFM1 specific antibody along with the calibrators/samples and a biotinylated conjugate of AFM1 with bovine serum albumin (BSA) in microwells coated with a secondary antibody provided a six-fold lower detection limit than the configuration involving immobilized AFM1-BSA conjugate and liquid phase antibody. The detection limit achieved was 5.0 pg/mL, with a dynamic range of up to 2.0 ng/mL. The assay was repeatable with intra- and inter-assay coefficients of variations lower than 3.2% and 6.5%, respectively, and accurate with recovery values from 87.5 to 108%. Moreover, the assay was completed in 1.5 h. The excellent analytical characteristics and short analysis time make the proposed assay suitable for use by the food industry. Furthermore, the proposed configuration could be employed to enhance the detection sensitivity of competitive immunoassays for other low-molecular-weight analytes.
{"title":"Sensitive Aflatoxin M1 Detection in Milk by ELISA: Investigation of Different Assay Configurations.","authors":"Dimitra Kourti, Michailia Angelopoulou, Panagiota Petrou, Sotirios Kakabakos","doi":"10.3390/toxins16120515","DOIUrl":"10.3390/toxins16120515","url":null,"abstract":"<p><p>Aflatoxin M1 (AFM1) exposure through dairy products is associated with adverse health effects, including hepatotoxicity and carcinogenicity. Therefore, the AFM1 presence in milk and dairy products is strictly regulated. In this context, the current work focuses on the investigation of different competitive enzyme immunoassay configurations for the determination of AFM1 in milk with high sensitivity and short assay duration. Amongst the configurations tested, the one based on incubation of the anti-AFM1 specific antibody along with the calibrators/samples and a biotinylated conjugate of AFM1 with bovine serum albumin (BSA) in microwells coated with a secondary antibody provided a six-fold lower detection limit than the configuration involving immobilized AFM1-BSA conjugate and liquid phase antibody. The detection limit achieved was 5.0 pg/mL, with a dynamic range of up to 2.0 ng/mL. The assay was repeatable with intra- and inter-assay coefficients of variations lower than 3.2% and 6.5%, respectively, and accurate with recovery values from 87.5 to 108%. Moreover, the assay was completed in 1.5 h. The excellent analytical characteristics and short analysis time make the proposed assay suitable for use by the food industry. Furthermore, the proposed configuration could be employed to enhance the detection sensitivity of competitive immunoassays for other low-molecular-weight analytes.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhuo Chen, Rui Chen, Xin Ma, Wenzi Wu, Qixin Huang, Wenxin Ye, Chulong Wu, Bin Yao, Jianhong Xu, Lichun Qian
Aflatoxin B1 is a prevalent secondary hazardous metabolite generated by fungus present in feed ingredients and the surrounding environment: enzymes are currently being recognized as an efficient and promising approach to reducing the associated risks. The objective of this study was to assess the effects of varying doses of enzyme complexes on several parameters in laying hens that were exposed to aflatoxin. During an 8-week experiment, a total of 288 Yukou Jingfen No.6 laying hens were placed into four groups. These groups included a group treated with toxins (CON group) and groups supplemented with compound enzyme complexes at doses of 250 g/t (E1 group), 500 g/t (E2 group), and 1000 g/t (E3 group). The E2 and E3 groups exhibited a statistically significant 2.6% increase in egg production rate compared to the CON group (p < 0.05). In addition, the E2 group showed significant improvements in both the feed-to-egg ratio and egg weight (p < 0.05). In addition, the E2 and E3 groups showed improved hutch unit and egg white height compared to the control group (p < 0.05). The E2 and E3 groups showed a substantial rise in liver health indicators, namely serum alanine transaminase (ALT) and alkaline phosphatase (ALP) activity. On the other hand, malondialdehyde (MDA) was lowered, and total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC) were raised. These findings were statistically significant (p < 0.05). The E2 and E3 groups showed notable enhancements in intestinal morphology, as evidenced by a rise in villus height and a decrease in crypt depth in all segments of the intestine (p < 0.05). Furthermore, analysis of 16S rRNA sequencing revealed that these participants had a higher prevalence and variety of microorganisms in their gut microbiota. More precisely, there was a significant rise in the abundance of Bacteroidota and a decline in Firmicutes at the level of the phylum. In general, the inclusion of the enzyme complex had advantageous impacts on performance, egg quality, intestinal morphology, intestinal barrier function, and intestinal flora in laying hens. Our results indicate that toxin-degrading enzymes, when used as feed additives, play a significant role in mitigating AFB1 contamination in diets and improving the production performance of laying hens.
{"title":"A Multi-Enzyme Complex That Mitigates Hepatotoxicity, Improves Egg Production and Quality, and Enhances Gut and Liver Health in Laying Hens Exposed to Trace Aflatoxin B<sub>1</sub>.","authors":"Zhuo Chen, Rui Chen, Xin Ma, Wenzi Wu, Qixin Huang, Wenxin Ye, Chulong Wu, Bin Yao, Jianhong Xu, Lichun Qian","doi":"10.3390/toxins16120517","DOIUrl":"10.3390/toxins16120517","url":null,"abstract":"<p><p>Aflatoxin B<sub>1</sub> is a prevalent secondary hazardous metabolite generated by fungus present in feed ingredients and the surrounding environment: enzymes are currently being recognized as an efficient and promising approach to reducing the associated risks. The objective of this study was to assess the effects of varying doses of enzyme complexes on several parameters in laying hens that were exposed to aflatoxin. During an 8-week experiment, a total of 288 Yukou Jingfen No.6 laying hens were placed into four groups. These groups included a group treated with toxins (CON group) and groups supplemented with compound enzyme complexes at doses of 250 g/t (E1 group), 500 g/t (E2 group), and 1000 g/t (E3 group). The E2 and E3 groups exhibited a statistically significant 2.6% increase in egg production rate compared to the CON group (<i>p</i> < 0.05). In addition, the E2 group showed significant improvements in both the feed-to-egg ratio and egg weight (<i>p</i> < 0.05). In addition, the E2 and E3 groups showed improved hutch unit and egg white height compared to the control group (<i>p</i> < 0.05). The E2 and E3 groups showed a substantial rise in liver health indicators, namely serum alanine transaminase (ALT) and alkaline phosphatase (ALP) activity. On the other hand, malondialdehyde (MDA) was lowered, and total superoxide dismutase (T-SOD) and total antioxidant capacity (T-AOC) were raised. These findings were statistically significant (<i>p</i> < 0.05). The E2 and E3 groups showed notable enhancements in intestinal morphology, as evidenced by a rise in villus height and a decrease in crypt depth in all segments of the intestine (<i>p</i> < 0.05). Furthermore, analysis of 16S rRNA sequencing revealed that these participants had a higher prevalence and variety of microorganisms in their gut microbiota. More precisely, there was a significant rise in the abundance of <i>Bacteroidota</i> and a decline in <i>Firmicutes</i> at the level of the phylum. In general, the inclusion of the enzyme complex had advantageous impacts on performance, egg quality, intestinal morphology, intestinal barrier function, and intestinal flora in laying hens. Our results indicate that toxin-degrading enzymes, when used as feed additives, play a significant role in mitigating AFB<sub>1</sub> contamination in diets and improving the production performance of laying hens.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cláudio Matusse, Zelda Lucamba, João Bila, Custódia Macuamule, Ana Sampaio, Sandra Afonso, Armando Venâncio, Paula Rodrigues
Aflatoxins constitute a significant risk in staple foods produced in African countries. This research aimed to analyze the total aflatoxin (AFT) contamination of various staple foods in Angola and Mozambique. A total of 233 samples of corn, peanuts, beans, rice, and cassava flour collected from farmers or local markets from the province of Cuanza Sul, Angola, and the provinces of Gaza and Inhambane, South Mozambique, were analyzed for the presence of AFT using the lateral flow strip method via AgraStrip® Pro WATEX® (Romer). The results showed that, from all matrices, the highest incidence and level of AFT were found in corn produced in Mozambique, with medians ranging from 6.5 to 66.5 µg/kg, with the samples showing values as high as 9200 µg/kg. Levels higher than the maximum admissible levels recommended by the Codex Alimentarius Commission for cereals and pulses (15 µg/kg) were observed in up to 90% of the corn samples, depending on the province. Corn produced in Angola showed lower amounts of AFT, with medians ranging from 1.2 to 7.7 µg/kg. Considering the maximum admissible levels for AFT recommended by the European Commission and the Codex Alimentarius Commission for cereals and pulses, the level of AFT contamination in staple food produced and consumed in the studied provinces is high and constitutes a public health risk for the population. Therefore, risk mitigation strategies are urgently needed.
{"title":"Aflatoxin Contamination of Various Staple Foods from Angola and Mozambique.","authors":"Cláudio Matusse, Zelda Lucamba, João Bila, Custódia Macuamule, Ana Sampaio, Sandra Afonso, Armando Venâncio, Paula Rodrigues","doi":"10.3390/toxins16120516","DOIUrl":"10.3390/toxins16120516","url":null,"abstract":"<p><p>Aflatoxins constitute a significant risk in staple foods produced in African countries. This research aimed to analyze the total aflatoxin (AFT) contamination of various staple foods in Angola and Mozambique. A total of 233 samples of corn, peanuts, beans, rice, and cassava flour collected from farmers or local markets from the province of Cuanza Sul, Angola, and the provinces of Gaza and Inhambane, South Mozambique, were analyzed for the presence of AFT using the lateral flow strip method via AgraStrip<sup>®</sup> Pro WATEX<sup>®</sup> (Romer). The results showed that, from all matrices, the highest incidence and level of AFT were found in corn produced in Mozambique, with medians ranging from 6.5 to 66.5 µg/kg, with the samples showing values as high as 9200 µg/kg. Levels higher than the maximum admissible levels recommended by the Codex Alimentarius Commission for cereals and pulses (15 µg/kg) were observed in up to 90% of the corn samples, depending on the province. Corn produced in Angola showed lower amounts of AFT, with medians ranging from 1.2 to 7.7 µg/kg. Considering the maximum admissible levels for AFT recommended by the European Commission and the Codex Alimentarius Commission for cereals and pulses, the level of AFT contamination in staple food produced and consumed in the studied provinces is high and constitutes a public health risk for the population. Therefore, risk mitigation strategies are urgently needed.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matteo Antonio Sacco, Saverio Gualtieri, Alessandro Pasquale Tarallo, Maria Cristina Verrina, Angela Carbone, Wandamaria Mazzuca, Santo Gratteri, Isabella Aquila
Mycotoxins, specifically aflatoxin B1 (AFB1), ochratoxin A (OTA), trichothecenes (TCNs), and patulin, are a group of secondary metabolites that can contaminate food, leading to severe health implications for humans. Their detection and analysis within forensic toxicology are crucial, particularly as they can be implicated in cases of poisoning, foodborne illnesses, or lethal chronic exposure. However, little is known about the application that mycotoxins could have in forensic investigations and especially about the possibility of extracting and quantifying these molecules on tissues or post-mortem fluids collected at autopsy. We propose a review of the scientific literature on autopsy case studies in which the presence of mycotoxins on cadavers in cases of acute and chronic exposure has been investigated and identified. This review demonstrates how the analysis of mycotoxins on cadavers could be fundamental in the study of mushroom poisonings or even in the investigation of the chronic effects of mycotoxins on the human organism, by virtue of the known carcinogenic and mutagenic effects of many of them. This paper aims to explore the multifaceted role of mycotoxins within forensic sciences, focusing on their detection methods, implications in criminal contexts, and their potential as forensic evidence, thereby underscoring the critical importance they could assume in post-mortem toxicology, public health prevention, and forensic investigations.
{"title":"The Role of AFB1, OTA, TCNs, and Patulin in Forensic Sciences: Applications in Autopsy, Criminal Investigations, and Public Health Prevention.","authors":"Matteo Antonio Sacco, Saverio Gualtieri, Alessandro Pasquale Tarallo, Maria Cristina Verrina, Angela Carbone, Wandamaria Mazzuca, Santo Gratteri, Isabella Aquila","doi":"10.3390/toxins16120514","DOIUrl":"10.3390/toxins16120514","url":null,"abstract":"<p><p>Mycotoxins, specifically aflatoxin B1 (AFB1), ochratoxin A (OTA), trichothecenes (TCNs), and patulin, are a group of secondary metabolites that can contaminate food, leading to severe health implications for humans. Their detection and analysis within forensic toxicology are crucial, particularly as they can be implicated in cases of poisoning, foodborne illnesses, or lethal chronic exposure. However, little is known about the application that mycotoxins could have in forensic investigations and especially about the possibility of extracting and quantifying these molecules on tissues or post-mortem fluids collected at autopsy. We propose a review of the scientific literature on autopsy case studies in which the presence of mycotoxins on cadavers in cases of acute and chronic exposure has been investigated and identified. This review demonstrates how the analysis of mycotoxins on cadavers could be fundamental in the study of mushroom poisonings or even in the investigation of the chronic effects of mycotoxins on the human organism, by virtue of the known carcinogenic and mutagenic effects of many of them. This paper aims to explore the multifaceted role of mycotoxins within forensic sciences, focusing on their detection methods, implications in criminal contexts, and their potential as forensic evidence, thereby underscoring the critical importance they could assume in post-mortem toxicology, public health prevention, and forensic investigations.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous proteomic studies of viperid venom revealed that it is mainly composed of metalloproteinases (SVMPs), serine proteinases (SVSPs), phospholipase A2 (PLA2), and C-type lectins (CTLs). However, other proteins appear in minor amounts that affect prey and need to be identified. This study aimed to identify novel toxic proteins in the venom gland transcriptome of Bothrops asper and Bothrops jararaca, using data from NCBI. Bioinformatics tools were used to assemble, identify, and compare potentially novel proteins in both species, and we performed functional annotation with BLASTX against the NR database. While previous assemblies have been performed for B. jararaca, this is the first assembly of the B. asper venom gland transcriptome. Proteins with potentially novel functions were identified, including arylsulfatase and dihydroorotate dehydrogenase, among others, that could have implications for venom toxicity. These results suggest that the identified proteins may contribute to venom toxic variation and provide new opportunities for antivenom research. The study improves the understanding of the protein composition of Bothrops venom and suggests new possibilities for the development of treatments and antivenoms.
{"title":"Exploring the Venom Gland Transcriptome of <i>Bothrops asper</i> and <i>Bothrops jararaca</i>: De Novo Assembly and Analysis of Novel Toxic Proteins.","authors":"Joseph Espín-Angulo, Doris Vela","doi":"10.3390/toxins16120511","DOIUrl":"10.3390/toxins16120511","url":null,"abstract":"<p><p>Previous proteomic studies of viperid venom revealed that it is mainly composed of metalloproteinases (SVMPs), serine proteinases (SVSPs), phospholipase A2 (PLA2), and C-type lectins (CTLs). However, other proteins appear in minor amounts that affect prey and need to be identified. This study aimed to identify novel toxic proteins in the venom gland transcriptome of <i>Bothrops asper</i> and <i>Bothrops jararaca</i>, using data from NCBI. Bioinformatics tools were used to assemble, identify, and compare potentially novel proteins in both species, and we performed functional annotation with BLASTX against the NR database. While previous assemblies have been performed for <i>B. jararaca</i>, this is the first assembly of the <i>B. asper</i> venom gland transcriptome. Proteins with potentially novel functions were identified, including arylsulfatase and dihydroorotate dehydrogenase, among others, that could have implications for venom toxicity. These results suggest that the identified proteins may contribute to venom toxic variation and provide new opportunities for antivenom research. The study improves the understanding of the protein composition of <i>Bothrops</i> venom and suggests new possibilities for the development of treatments and antivenoms.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Botulinum toxin type A1 is a first-line treatment for adult and pediatric spasticity. However, when considering the quantity of 150 kDa neurotoxin protein in relation to patient weight and the maximum recommended dose for treating adult and pediatric patients with spasticity, several concerns arise. First, the therapeutic margin (the ratio of the actual maximum quantity of toxin recommended for treating adult spasticity to its median lethal dose) appears to be relevant. Second, there is no consistency between adult and pediatric dosing of botulinum toxin type A1 for spasticity. The third point concerns the suitability of the recommended doses for treating spasticity in pediatric patients. Based on the average body weight of American children and adolescents, the maximum weight-based doses for abobotulinumtoxinA and onabotulinumtoxinA could be administered to children as young as 9 years old. Additionally, the maximum weight-based dose for incobotulinumtoxinA could be administered to children as young as 6 years old. The final point concerns managing the maximum dose of BoNT/A1 in pediatric patients with spasticity who weigh more than 25 kg for incobotulinumtoxinA, or more than 34 kg for abobotulinumtoxinA and onabotulinumtoxinA. No labeled recommendations are given on the weight cut-off for transitioning to adult dosing in pediatric patients.
{"title":"Are We Missing Something About the Maximum Dosing of Botulinum Toxin Type A1 in Adult and Pediatric Patients with Spasticity?","authors":"Alessandro Picelli, Rita Di Censo, Stefano Tamburin, Nicola Smania, Mirko Filippetti","doi":"10.3390/toxins16120513","DOIUrl":"10.3390/toxins16120513","url":null,"abstract":"<p><p>Botulinum toxin type A1 is a first-line treatment for adult and pediatric spasticity. However, when considering the quantity of 150 kDa neurotoxin protein in relation to patient weight and the maximum recommended dose for treating adult and pediatric patients with spasticity, several concerns arise. First, the therapeutic margin (the ratio of the actual maximum quantity of toxin recommended for treating adult spasticity to its median lethal dose) appears to be relevant. Second, there is no consistency between adult and pediatric dosing of botulinum toxin type A1 for spasticity. The third point concerns the suitability of the recommended doses for treating spasticity in pediatric patients. Based on the average body weight of American children and adolescents, the maximum weight-based doses for abobotulinumtoxinA and onabotulinumtoxinA could be administered to children as young as 9 years old. Additionally, the maximum weight-based dose for incobotulinumtoxinA could be administered to children as young as 6 years old. The final point concerns managing the maximum dose of BoNT/A1 in pediatric patients with spasticity who weigh more than 25 kg for incobotulinumtoxinA, or more than 34 kg for abobotulinumtoxinA and onabotulinumtoxinA. No labeled recommendations are given on the weight cut-off for transitioning to adult dosing in pediatric patients.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Animal venoms contain a huge variety of bioactive molecules-namely, toxins-with an almost combinatorial spectrum of biological activities [...].
动物的毒液含有各种各样的生物活性分子——也就是毒素——几乎是生物活性的组合谱[…]。
{"title":"Toxins from Animal Venom-A Rich Source of Active Compounds with High Pharmacological Potential.","authors":"Ekaterina N Lyukmanova, Zakhar O Shenkarev","doi":"10.3390/toxins16120512","DOIUrl":"10.3390/toxins16120512","url":null,"abstract":"<p><p>Animal venoms contain a huge variety of bioactive molecules-namely, toxins-with an almost combinatorial spectrum of biological activities [...].</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ian D Cameron, Louise Ada, Maria Crotty, Mithu Palit, Lydia Huang, John Olver, Steven G Faux, Senen Gonzales, Brian Anthonisz, Malcolm Bowman, Yuriko Watanabe, Yan Chow, Rachel Milte, Julie Ratcliffe, Coralie K English, Natasha A Lannin
We examined the effect of botulinum toxin-A on upper limb impairments and activity limitations in chronic stroke. This study is a secondary analysis of control group data from a national, multicenter, Phase III randomized trial with a masked outcome assessment. We studied 71 stroke survivors who received a botulinum toxin-A injection in any muscle(s) that crosses the wrist due to significant spasticity after a stroke greater than 3 months previously. We measured upper limb activity, spasticity, range of motion, grip strength, pain and other outcomes at injection and three months later. The median difference between injection and 3 months later was 0.0 blocks/s (interquartile range (IQR) 0.0) on the Box and Block Test, 0/4 (IQR 1) on the Tardieu Scale, 4 degrees (IQR 26) of wrist extension, 0.0 kg (IQR 2) of grip strength, 0.0 (IQR 1.5) on the 10 cm visual analogue scale for pain, 0/100 (IQR 21) on the 10 cm visual analogue scale for overall health, 0/3 (IQR 0) for self-care and -2 (IQR 8) for burden of care. In chronic stroke survivors who have little activity in their upper limb, botulinum toxin-A is not effective in improving any measured outcomes and does not appear to be clinically justified in this population with severe activity limitations.
{"title":"The Lack of Effect of Botulinum Toxin-A on Upper Limb Activity in Chronic Stroke: A Short Report from the InTENSE Trial.","authors":"Ian D Cameron, Louise Ada, Maria Crotty, Mithu Palit, Lydia Huang, John Olver, Steven G Faux, Senen Gonzales, Brian Anthonisz, Malcolm Bowman, Yuriko Watanabe, Yan Chow, Rachel Milte, Julie Ratcliffe, Coralie K English, Natasha A Lannin","doi":"10.3390/toxins16120510","DOIUrl":"10.3390/toxins16120510","url":null,"abstract":"<p><p>We examined the effect of botulinum toxin-A on upper limb impairments and activity limitations in chronic stroke. This study is a secondary analysis of control group data from a national, multicenter, Phase III randomized trial with a masked outcome assessment. We studied 71 stroke survivors who received a botulinum toxin-A injection in any muscle(s) that crosses the wrist due to significant spasticity after a stroke greater than 3 months previously. We measured upper limb activity, spasticity, range of motion, grip strength, pain and other outcomes at injection and three months later. The median difference between injection and 3 months later was 0.0 blocks/s (interquartile range (IQR) 0.0) on the Box and Block Test, 0/4 (IQR 1) on the Tardieu Scale, 4 degrees (IQR 26) of wrist extension, 0.0 kg (IQR 2) of grip strength, 0.0 (IQR 1.5) on the 10 cm visual analogue scale for pain, 0/100 (IQR 21) on the 10 cm visual analogue scale for overall health, 0/3 (IQR 0) for self-care and -2 (IQR 8) for burden of care. In chronic stroke survivors who have little activity in their upper limb, botulinum toxin-A is not effective in improving any measured outcomes and does not appear to be clinically justified in this population with severe activity limitations.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Apolka Szentirmay, Zsófia Molnár, Patrik Plank, Miklós Mézes, Attila Sajgó, Attila Martonos, Tímea Buzder, Miklós Sipos, Lili Hruby, Zsuzsanna Szőke, Levente Sára
The effect of mycotoxin exposure on follicular fluid composition and reproductive outcomes in women undergoing in vitro fertilisation (IVF) was investigated in this study. Twenty-five patients were included, and follicular fluid and serum samples were analysed for various mycotoxins. Principal observations:1. Mycotoxin presence: All examined mycotoxins were detected in follicular fluid. Follicular fluid (ff) levels: Deoxynivalenol (DON), alfa-Zearalenol (α-ZOL), Zearalenone (ZEN), and total aflatoxin (AFs) were significantly higher in follicular fluid than in serum. 2. Follicular fluid and reproductive outcomes: A positive correlation was observed between the ratio of oocytes to total follicles and the follicular Fumonisin B1 (FB1) levels. Multiple linear regression analysis revealed a significant relationship between DON and T-2/HT-2 toxins (T2/HT2) levels in the follicular fluid. 3. Hormone levels: Follicular 17-beta estradiol (E2) and progesterone (P4) levels were higher than the serum levels. Follicular P4 correlated with serum P4 and Anti-Müllerian hormone (AMH) levels. In contrast, follicular E2 did not correlate with plasma E2 levels. 4. Mycotoxin-hormone interactions: A positive correlation was observed between follicular P4 and T2/HT2 toxin levels, whereas a negative correlation was found between ffE2 and ffT2/HT2, and a positive correlation was found between ZEN and E2. Conclusion: This study elucidated the presence of various mycotoxins in the follicular fluid and their potential influence on reproductive outcomes. Further research is warranted to clarify the specific mechanisms underlying these effects and develop strategies for detecting mycotoxin exposure in women undergoing IVF.
{"title":"The Potential Influence of the Presence of Mycotoxins in Human Follicular Fluid on Reproductive Outcomes.","authors":"Apolka Szentirmay, Zsófia Molnár, Patrik Plank, Miklós Mézes, Attila Sajgó, Attila Martonos, Tímea Buzder, Miklós Sipos, Lili Hruby, Zsuzsanna Szőke, Levente Sára","doi":"10.3390/toxins16120509","DOIUrl":"10.3390/toxins16120509","url":null,"abstract":"<p><p>The effect of mycotoxin exposure on follicular fluid composition and reproductive outcomes in women undergoing in vitro fertilisation (IVF) was investigated in this study. Twenty-five patients were included, and follicular fluid and serum samples were analysed for various mycotoxins. Principal observations:1. Mycotoxin presence: All examined mycotoxins were detected in follicular fluid. Follicular fluid (ff) levels: Deoxynivalenol (DON), alfa-Zearalenol (α-ZOL), Zearalenone (ZEN), and total aflatoxin (AFs) were significantly higher in follicular fluid than in serum. 2. Follicular fluid and reproductive outcomes: A positive correlation was observed between the ratio of oocytes to total follicles and the follicular Fumonisin B1 (FB1) levels. Multiple linear regression analysis revealed a significant relationship between DON and T-2/HT-2 toxins (T2/HT2) levels in the follicular fluid. 3. Hormone levels: Follicular 17-beta estradiol (E2) and progesterone (P4) levels were higher than the serum levels. Follicular P4 correlated with serum P4 and Anti-Müllerian hormone (AMH) levels. In contrast, follicular E2 did not correlate with plasma E2 levels. 4. Mycotoxin-hormone interactions: A positive correlation was observed between follicular P4 and T2/HT2 toxin levels, whereas a negative correlation was found between ffE2 and ffT2/HT2, and a positive correlation was found between ZEN and E2. Conclusion: This study elucidated the presence of various mycotoxins in the follicular fluid and their potential influence on reproductive outcomes. Further research is warranted to clarify the specific mechanisms underlying these effects and develop strategies for detecting mycotoxin exposure in women undergoing IVF.</p>","PeriodicalId":23119,"journal":{"name":"Toxins","volume":"16 12","pages":""},"PeriodicalIF":3.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11728479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}