scholarly journals Toxemia in Human Naturally Acquired Botulism

Toxins ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 716
Author(s):  
Christine Rasetti-Escargueil ◽  
Emmanuel Lemichez ◽  
Michel R. Popoff
Keyword(s):  
Severe Disease ◽  
Disease Onset ◽  
High Specificity ◽  
Mouse Bioassay ◽  
Serum Samples ◽  
Wound Botulism ◽  
Food Borne ◽  
Autoimmune Neuropathy ◽  
Infant Botulism

Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in food, botulism by intestinal colonization (infant botulism and intestinal toxemia botulism in infants above one year and adults), and wound botulism. A rapid laboratory confirmation of botulism is required for the appropriate management of patients. Detection of BoNT in the patient’s sera is the most direct way to address the diagnosis of botulism. Based on previous published reports, botulinum toxemia was identified in about 70% of food-borne and wound botulism cases, and only in about 28% of infant botulism cases, in which the diagnosis is mainly confirmed from stool sample investigation. The presence of BoNT in serum depends on the BoNT amount ingested with contaminated food or produced locally in the intestine or wound, and the timeframe between serum sampling and disease onset. BoNT levels in patient’s sera are most frequently low, requiring a highly sensitive method of detection. Mouse bioassay is still the most used method of botulism identification from serum samples. However, in vitro methods based on BoNT endopeptidase activity with detection by mass spectrometry or immunoassay have been developed and depending on BoNT type, are more sensitive than the mouse bioassay. These new assays show high specificity for individual BoNT types and allow more accurate differentiation between positive toxin sera from botulism and autoimmune neuropathy patients.

The Toxicity Testing of Cyanobacterial Toxins In Vivo and In Vitro by Mouse Bioassay: A Review

2021 ◽  
Vol 21 ◽  
Author(s):  
Hamed Ahari ◽  
Bahareh ‎ Nowruzi ◽  
Amir Ali Anvar ◽  
Samaneh Jafari Porzani
Keyword(s):  
Toxicity Testing ◽  
High Specificity ◽  
Immunological Methods ◽  
Water Bloom ◽  
Mouse Bioassay ◽  
Cell Extracts ◽  
Specificity And Sensitivity ◽  
Main Technique

: Different biological methods based on bioactivity are available to detect cyanotoxins, including neurotoxicity, immunological interactions, hepatotoxicity, cytotoxicity, and enzymatic activity. The mouse bioassay is the first test employed in laboratory cultures, cell extracts, and water bloom materials to detect toxins. It is also used as a traditional method to estimate the LD50. Concerning the ease of access and low cost, it is the most common method for this purpose. In this method, a sample is injected intraperitoneally into adult mice, and accordingly, they are assayed and monitored for about 24 hours for toxic symptoms. The toxin can be detected using this method from minutes to a few hours; its type, e.g., hepatotoxin, neurotoxin, etc., can also be determined. However, this method is nonspecific, fails to detect low amounts, and cannot distinguish between homologues. Although the mouse bioassay is gradually replaced with new chemical and immunological methods, it is still the main technique to detect the bioactivity and efficacy of cyanotoxins using LD50 determined based on the survival time of animals exposed to the toxin. In addition, some countries oppose animal use in toxicity studies. However, high cost, ethical considerations, low-sensitivity, non-specificity, and prolonged processes persuade researchers to employ chemical and functional analysis techniques. The qualitative and quantitative analyses, as well as high specificity and sensitivity, are among the advantages of cytotoxicity tests to investigate cyanotoxins. The present study aimed at reviewing the results obtained from in-vitro and in-vivo investigations of the mouse bioassay to detect cyanotoxins, including microcystins, cylindrospermopsin, saxitoxins, etc.

Involvement of functional autoantibodies against vascular receptors in systemic sclerosis

2010 ◽  
Vol 70 (3) ◽  
pp. 530-536 ◽  
Author(s):  
Gabriela Riemekasten ◽  
Aurélie Philippe ◽  
Melanie Näther ◽  
Torsten Slowinski ◽  
Dominik N Müller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Systemic Sclerosis ◽  
Transforming Growth Factor ◽  
Solid Phase ◽  
Biological Effects ◽  
Severe Disease ◽  
Study Cohort ◽  
Serum Samples ◽  
Related Mortality

BackgroundSystemic sclerosis (SSc) features autoimmunity, vasculopathy and tissue fibrosis. The renin-angiotensin and endothelin systems have been implicated in vasculopathy and fibrosis. A role for autoantibody-mediated receptor stimulation is hypothesised, linking three major pathophysiological features consistent with SSc.MethodsSerum samples from 478 patients with SSc (298 in the study cohort and 180 from two further independent cohorts), 372 healthy subjects and 311 control-disease subjects were tested for antibodies against angiotensin II type 1 receptor (AT1R) and endothelin-1 type A receptor (ETAR) by solid phase assay. Binding specificities were tested by immunoprecipitation. The biological effects of autoantibodies in microvascular endothelial cells in vitro were also determined, as well as the quantitative differences in autoantibody levels on specific organ involvements and their predictive value for SSc-related mortality.ResultsAnti-AT1R and anti-ETAR autoantibodies were detected in most patients with SSc. Autoantibodies specifically bound to respective receptors on endothelial cells. Higher levels of both autoantibodies were associated with more severe disease manifestations and predicted SSc-related mortality. Both autoantibodies exert biological effects as they induced extracellular signal-regulated kinase 1/2 phosphorylation and increased transforming growth factor β gene expression in endothelial cells which could be blocked with specific receptor antagonists.ConclusionsFunctional autoimmunity directed at AT1R and ETAR is common in patients with SSc. AT1R and ETAR autoantibodies could contribute to disease pathogenesis and may serve as biomarkers for risk assessment of disease progression.

scholarly journals SAT0253 ANTI-NEUTROPHIL CYTOPLASMATIC ANTIBODIES PREDATE SYMPTOM ONSET OF ANCA-ASSOCIATED VASCULITIS. A CASE-CONTROL STUDY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1069.2-1070
Author(s):  
E. Berglin ◽  
A. J. Mohammad ◽  
J. Dahlqvist ◽  
C. Eriksson ◽  
J. Sjöwall ◽  
...  
Keyword(s):  
Cause Of Death ◽  
Symptom Onset ◽  
Severe Disease ◽  
Disease Onset ◽  
Control Sample ◽  
Discharge Summary ◽  
Serum Samples ◽  
Blood Samples ◽  
Anca Associated Vasculitis ◽  
Time Point

Background:Presence of anti-neutrophil cytoplasmatic autoantibodies (ANCA) is important for the diagnosis of ANCA-associated vasculitis (AAV) and reflects on-going immune processes. The timing of the antibody development and its contribution to disease is not well established.Objectives:To investigate the presence of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA in blood samples collected from healthy individuals who subsequently developed AAV.Methods:The Swedish National Patient Register of inpatient care and the Swedish Cause of Death Register were used to identify individuals assigned ICD codes for AAV (1) in the discharge summary or cause of death, respectively. The resulted cohort was then linked to the registers of 4 different biobanks to identify those with available predating blood samples. Diagnoses of AAV were confirmed and time point for onset of symptoms was identified by reviewing all available case records (1); 68 were classified as granulomatosis with polyangiitis (GPA), 14 as microscopic polyangiitis (MPA), and 4 as eosinophilic GPA (EGPA). The 86 cases (36 males, 50 females) had a mean (SD) age of 51.9 (16.9) years at sampling, with ≥1 sample (26% plasma, 74% serum samples). The sampling time point before onset of symptoms was mean (SD); 4.4 (3.1) years. Serum and plasma control samples (n=198; 82 males, 116 females; mean age (SD); 52.0 (16.5) years) were identified and matched for sex, age and date of sampling. The samples were first screened for ANCA using high sensitive ELISA (ORGANTEC diagnostika, Germany) and samples close to or above cut-off level were further analysed for capture PR3- and capture MPO-ANCA (ELISA; SVAR Life Science, Sweden). For each case one control sample was included for the ANCA specificity tests. Statistical calculations were performed using SPSS software.Results:In ANCA-screen 36.0% of the cases and 2.6 % of controls tested positive (p<0.001). 23/52 (44.2%) of the cases were PR3-ANCA positive (OR 56.3; 95% CI 7.26-436.62) and 8/52 (15.4%) were MPO-ANCA positive (OR 4.18; 95% CI 1.05-16.62). The mean (SD) predating time for PR3-ANCA positivity was 3.73 (3.49) years and for MPO-ANCA positivity 2.11 (1.46) years. Cases with positive predating PR3-ANCA were younger (46.0±19.4 vs 65.6±12.0 years; P<0.001) than cases with a negative predating PR3-ANCA. MPO-ANCA positive vs. MPO-ANCA negative pre-dating cases had more often severe disease (kidney/lung/peripheral nervous system) (OR 15.08; 95% CI 1.68—135.54) at disease onset. Furthermore, predating MPO-ANCA positive vs predating PR3-ANCA positive cases had significantly more often severe manifestations at disease onset (87.5% vs 28.6%; p<0.05). Cases positive vs. negative for MPO-ANCA in predating samples were less often classified as GPA (37.5% vs 86.4%; p<0.01) and more often as MPA (62.5% vs 13.6%; p<0.05).Conclusion:The production of both PR3 and MPO-ANCA starts already years before onset of symptoms of AAV. Presence of MPO-ANCA appeared closer to symptom onset and with more severe disease presentation. Differences in the disease phenotype and disease severity were evident between the two ANCA serotypes.References:[1]Watts et al. Ann Rheum Dis 2007;66:222-22Acknowledgments: :Vasculitis Foundation, USADisclosure of Interests:Ewa Berglin: None declared, Aladdin J Mohammad Speakers bureau: lecture fees from Roche and Elli Lilly Sweden, PI (GiACTA study), Johanna Dahlqvist: None declared, Catharina Eriksson: None declared, Johanna Sjöwall: None declared, Solbritt Rantapää Dahlqvist: None declared

scholarly journals The dynamic antibody responses on COVID-19 patients with different severity: A retrospective research

2020 ◽  
Author(s):  
Wanrong Lu ◽  
Ping Wu ◽  
Liang He ◽  
Yifan Meng ◽  
Peng Wu ◽  
...  
Keyword(s):  
Regression Models ◽  
Severe Disease ◽  
Disease Onset ◽  
Antibody Responses ◽  
Clinical Severity ◽  
Serum Samples ◽  
Logistic Regression Models ◽  
The Difference ◽  
Igg Level

Abstract ObjectivesWe aimed to explore the association between dynamic antibody responses and the clinical severity of COVID-19. MethodsWe collected complete follow-up data of 777 pathogen-confirmed COVID-19 patients with corresponding IgG/IgM testing results. ResultsWe found the overall positive rates of IgG and IgM in severe patients were slightly higher than those in non-severe patients. In addition, higher IgG levels were detected in severe patients compared with non-severe patients (P=0.026). Through further analysis, our results showed that the statistical difference in the IgG only significant in serum samples taken ≤14 days from disease onset (P<0.001). In 74 patients who taken detection more than three times, by analyzing the antibody expression levels at different time points, we found that the difference between IgG was more obvious than that of IgM among severe/non-severe patients. In multivariate logistic regression models, after adjusting for cofactors, the higher anti-SARS-CoV-2 IgG level before 14 days from disease onset was independently associated with severe disease in COVID-19 (OR=1.310, 95%CI= 1.137-1.509).ConclusionWe observed differences in antibody responses among COVID-19 patients with different disease severity. A high IgG level in the first 14 days from disease onset might positively associate with severe disease.

Botulism, gas gangrene, and clostridial gastrointestinal infections

2020 ◽  
pp. 1120-1126
Author(s):  
Dennis L. Stevens ◽  
Michael J. Aldape ◽  
Amy E. Bryant
Keyword(s):  
Stomach Contents ◽  
Gas Gangrene ◽  
Gastrointestinal Infections ◽  
Blurred Vision ◽  
Food Treatment ◽  
Wound Botulism ◽  
Food Borne ◽  
Infant Botulism ◽  
Microbial Toxin ◽  
Ordinary Cooking

Human botulism is caused by seven serological types of C. botulinum, which is ubiquitously distributed in the soil. Poisoning usually results from ingestion of preformed toxin in food, although this is rapidly inactivated at ordinary cooking temperatures, but it can also result from contaminated wounds. C. botulinum toxin binds irreversibly to the neuromuscular junction and is the most lethal known microbial toxin. There are five forms of clinical botulism: food-borne botulism; wound botulism; infant botulism; adult enteric infectious botulism; and inhalational botulism. Clinical presentation is with symptoms suggesting gastrointestinal tract illness, followed by neurological symptoms including diplopia, blurred vision, dizziness, and difficulty with speech or swallowing, leading on to generalized flaccid paralysis. The diagnosis can be confirmed by testing for botulinum toxin in the patient’s serum, urine, or stomach contents, or in the suspect food. Treatment requires supportive care, which may continue for many months.

scholarly journals Human Botulism in France, 1875–2016

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 338 ◽  
Author(s):  
Christine Rasetti-Escargueil ◽  
Emmanuel Lemichez ◽  
Michel R. Popoff
Keyword(s):  
Severe Disease ◽  
Meat Products ◽  
Second World War ◽  
Small Scale ◽  
Food Hygiene ◽  
World War ◽  
Food Borne ◽  
Infant Botulism ◽  
The 19Th Century ◽  
Second World

Botulism is a rare but severe disease which is characterized by paralysis and inhibition of secretions. Only a few cases had been reported at the end of the 19th century in France. The disease was frequent during the second world war, and then the incidence decreased progressively. However, human botulism is still present in France with 10–25 cases every year. Food-borne botulism was the main form of botulism in France, whereas infant botulism (17 cases between 2004 and 2016) was rare, and wound and inhalational botulism were exceptional. Type B was the prevalent botulism type and was mainly due to consumption of home-made or small-scale preparations of cured ham and to a lesser extent other pork meat products. In the recent period (2000–2016), a wider diversity of botulism types from various food origin including industrial foods was reported. Severe cases of type A and F botulism as well as type E botulism were more frequent. Albeit rare, the severity of botulism justifies its continued surveillance and recommendations to food industry and consumers regarding food hygiene and preservation practices.

A Physiologic Regulator of Collagen-Induced Platelet Aggregation: Inhibition by Clq

1981 ◽  
Vol 45 (02) ◽  
pp. 110-115 ◽  
Author(s):  
György Csákó ◽  
Eva A Suba
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Platelet Reactivity ◽  
High Specificity ◽  
Turbidimetric Method ◽  
Specific Manner ◽  
Aggregation Inhibition ◽  
Different Tissues

SummaryPlatelet aggregations were studied by a turbidimetric method in citrated human platelet-rich plasmas (PRP) in vitro. Human Clq inhibited the aggregations caused by collagens derived from different tissues and species. Clq was needed by weight in comparable quantities to collagen for neutralizing the aggregating effect. The dependence of the inhibitory reaction on the preincubation of platelets with Clq and the differences in the occurrence of aggregating substances in supernatants of PRP triggered with collagen in the presence or absence of Clq, confirmed that Clq exerts its effect by preventing fixation of collagen to platelets. In addition, the high specificity of the inhibitory action of Clq for collagen-induced platelet aggregation was demonstrated by results obtained for testing a variety of aggregating agents in combination with Clq and/or collagen.Since normal concentrations of Clq in the blood are in the range of inhibitory doses of Clq for collagen-induced platelet aggregations in vitro and upon activation of complement Clq is known to dissociate from Cl, it is proposed that Clq may participate in a highly specific manner in regulating platelet reactivity to collagen in vivo.

Enzyme Promiscuous Activity: How to Define it and its Evolutionary Aspects

2020 ◽  
Vol 27 (5) ◽  
pp. 400-410
Author(s):  
Valentina De Luca ◽  
Luigi Mandrich
Keyword(s):  
Gene Evolution ◽  
Sequence Divergence ◽  
High Specificity ◽  
Industrial Applications ◽  
Point Of View ◽  
Enzyme Promiscuity ◽  
Primary Activity ◽  
Starting Point ◽  
Main Activity

: Enzymes are among the most studied biological molecules because better understanding enzymes structure and activity will shed more light on their biological processes and regulation; from a biotechnological point of view there are many examples of enzymes used with the aim to obtain new products and/or to make industrial processes less invasive towards the environment. Enzymes are known for their high specificity in the recognition of a substrate but considering the particular features of an increasing number of enzymes this is not completely true, in fact, many enzymes are active on different substrates: this ability is called enzyme promiscuity. Usually, promiscuous activities have significantly lower kinetic parameters than to that of primary activity, but they have a crucial role in gene evolution. It is accepted that gene duplication followed by sequence divergence is considered a key evolutionary mechanism to generate new enzyme functions. In this way, promiscuous activities are the starting point to increase a secondary activity in the main activity and then get a new enzyme. The primary activity can be lost or reduced to a promiscuous activity. In this review we describe the differences between substrate and enzyme promiscuity, and its rule in gene evolution. From a practical point of view the knowledge of promiscuity can facilitate the in vitro progress of proteins engineering, both for biomedical and industrial applications. In particular, we report cases regarding esterases, phosphotriesterases and cytochrome P450.

Prospective Application of Aptamer-based Assays and Therapeutics in Bloodstream Infections

2020 ◽  
Vol 20 (10) ◽  
pp. 831-840
Author(s):  
Weibin Li
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Diagnosis ◽  
Bloodstream Infections ◽  
High Specificity ◽  
Peptide Sequence ◽  
High Morbidity ◽  
Specificity And Sensitivity ◽  
Prospective Application ◽  
Small Molecule Therapeutics

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.

Personalized stratification of back to work risk amidst COVID-19: A machine learning approach (Preprint)

2020 ◽  
Author(s):  
Carson Lam ◽  
Jacob Calvert ◽  
Gina Barnes ◽  
Emily Pellegrini ◽  
Anna Lynn-Palevsky ◽  
...  
Keyword(s):  
Machine Learning ◽  
High Risk ◽  
Learning Algorithm ◽  
Severe Disease ◽  
High Specificity ◽  
Population Level ◽  
The United States ◽  
Health Condition ◽  
Available P ◽  
Severe Illness

BACKGROUND In the wake of COVID-19, the United States has developed a three stage plan to outline the parameters to determine when states may reopen businesses and ease travel restrictions. The guidelines also identify subpopulations of Americans that should continue to stay at home due to being at high risk for severe disease should they contract COVID-19. These guidelines were based on population level demographics, rather than individual-level risk factors. As such, they may misidentify individuals at high risk for severe illness and who should therefore not return to work until vaccination or widespread serological testing is available. OBJECTIVE This study evaluated a machine learning algorithm for the prediction of serious illness due to COVID-19 using inpatient data collected from electronic health records. METHODS The algorithm was trained to identify patients for whom a diagnosis of COVID-19 was likely to result in hospitalization, and compared against four U.S policy-based criteria: age over 65, having a serious underlying health condition, age over 65 or having a serious underlying health condition, and age over 65 and having a serious underlying health condition. RESULTS This algorithm identified 80% of patients at risk for hospitalization due to COVID-19, versus at most 62% that are identified by government guidelines. The algorithm also achieved a high specificity of 95%, outperforming government guidelines. CONCLUSIONS This algorithm may help to enable a broad reopening of the American economy while ensuring that patients at high risk for serious disease remain home until vaccination and testing become available.

Sign in / Sign up

Export Citation Format

Share Document