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1.
Appl Microbiol Biotechnol ; 105(21-22): 8297-8311, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34609523

RESUMO

Staphylococcus aureus is a serious pathogen unleashing its virulence through several classes of exotoxins such as hemolysins and enterotoxins. In this study, we designed a novel multi-antigen subunit vaccine which can induce innate, humoral and cellular immune responses. Alpha hemolysin, enterotoxins A and B were selected as protective antigens for combining into a triple antigen chimeric protein (HAB). Immunoinformatics analysis predicted HAB protein as a suitable vaccine candidate for inducing both humoral and cellular immune responses. Tertiary structure of the HAB protein was predicted and validated through computational approaches. Docking studies were performed between the HAB protein and mice TLR2 receptor. Furthermore, we constructed and generated recombinant HAB (r-HAB) protein in E. coli and studied its toxicity, immunogenicity and protective efficacy in a mouse model. Triple antigen chimeric protein (r-HAB) was found to be highly immunogenic in mouse as the anti-r-HAB hyperimmune serum was strongly reactive to all three native exotoxins on Western blot. In vitro toxin neutralization assay using anti-r-HAB antibodies demonstrated > 75% neutralization of toxins on RAW 264.7 cell line. Active immunization with r-HAB toxoid gave ~ 83% protection against 2 × lethal dosage of secreted exotoxins. The protection was mediated by induction of strong antibody responses that neutralized the toxins. Passive immunization with anti-r-HAB antibodies gave ~ 50% protection from lethal challenge. In conclusion, in vitro and in vivo testing of r-HAB found the molecule to be nontoxic, highly immunogenic and induced excellent protection towards native toxins in actively immunized and partial protection to passively immunized mice groups. KEY POINTS: • HAB protein was computationally designed to induce humoral and cellular responses. • r-HAB protein was found to be nontoxic, immunogenic and protective in mouse model. • r-HAB conferred protection against lethal challenge in active and passive immunization.


Assuntos
Toxinas Bacterianas , Toxemia , Animais , Anticorpos Antibacterianos , Toxinas Bacterianas/genética , Enterotoxinas , Escherichia coli/genética , Camundongos , Camundongos Endogâmicos BALB C , Staphylococcus aureus , Toxoides
2.
Avian Dis ; 65(1): 10-17, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-34339116

RESUMO

Septicemia-toxemia (sep/tox) falls under U.S. Department of Agriculture (USDA) food safety Category 1 and is the most common and economically significant cause of broiler carcass condemnations. Hepatic lesions are considered a possible consequence of septicemia and associated bacterial contamination of the carcass. Thus, these lesions are considered an indicator of sep/tox (sep/tox hepatitis). This study was undertaken to analyze the histologic lesions preceding grossly visible liver lesions leading to condemnation because of sep/tox at the processing plant. Livers from carcasses of broilers condemned by USDA inspectors for sep/tox were used to establish microscopic and gross criteria of end-stage sep/tox hepatitis. Following the characterization of sep/tox hepatitis, broilers from a farm with a history of sep/tox condemnations were submitted for postmortem examination and bacteriologic investigation at four intervals during the final 20 days of production. Five healthy and five clinically ill chickens were submitted from four houses at 18, 25, 32, and 38 days of production (160 total). Microscopic lesions representing hepatic perisinusoidal myofibroblast proliferation (HPMP), periportal extramedullary granulopoiesis (PEMG), splenic follicular histiocytosis, and bone marrow cellularity (BMC) were graded subjectively for each bird, and subjective grading was evaluated with digital quantitative techniques. Perisinusoidal hepatic stellate cell morphology and progressive transformation of these cells into myofibroblasts was confirmed by immunohistochemistry for smooth muscle actin and desmin. Aerobic cultures of livers and gall bladders from sep/tox birds yielded no growth of bacteria associated with septicemia. Mild to severe HPMP was observed in all age groups, representing 28% of examined birds. Increases in inflammatory cells observed by PEMG and BMC were positively correlated with progressive HPMP and end-stage sep/tox hepatitis in broiler chickens.


Assuntos
Proliferação de Células , Galinhas , Hepatite Animal/patologia , Fígado/patologia , Miofibroblastos/fisiologia , Doenças das Aves Domésticas/patologia , Síndrome de Resposta Inflamatória Sistêmica/veterinária , Animais , Hepatite Animal/virologia , Doenças das Aves Domésticas/virologia , Sepse/veterinária , Sepse/virologia , Síndrome de Resposta Inflamatória Sistêmica/patologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Toxemia/veterinária , Toxemia/virologia
3.
Toxins (Basel) ; 12(11)2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33202855

RESUMO

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.


Assuntos
Toxinas Botulínicas/sangue , Botulismo/sangue , Toxemia/sangue , Animais , Humanos , Intestinos/microbiologia , Ferimentos e Lesões/sangue
4.
BMJ Case Rep ; 13(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878836

RESUMO

We report a case of profound, symptomatic hyponatraemia in association with pre-eclamptic toxaemia (PET) in a 38-year-old nulliparous woman with type 1 diabetes mellitus. This patient developed hypertension and proteinuria at 31+6 weeks' gestation and was admitted for management of pre-eclampsia. Severe headache, visual disturbance and nausea were associated with a hyponatraemia of 115 mmol/L followed by ketoacidosis. This was reversed through fluid restriction, supplementation with 1.8%-3.0% hypertonic saline and a volume-reduced variable-rate insulin infusion. Clinical stability was achieved and she was subsequently worked up for an induction of labour for worsening pre-eclampsia. Hyponatraemia in the context of PET has been previously reported as rare. However, it has complications that may significantly compound the sequelae of severe PET. We propose that specific and focused monitoring of serum sodium levels should become common practice in the management of women with this condition to allow for timely, measured correction of abnormalities.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Hiponatremia/diagnóstico , Pré-Eclâmpsia/diagnóstico , Toxemia/diagnóstico , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hiponatremia/sangue , Hiponatremia/etiologia , Hiponatremia/terapia , Insulina/administração & dosagem , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/terapia , Gravidez , Solução Salina Hipertônica/administração & dosagem , Índice de Gravidade de Doença , Toxemia/sangue , Toxemia/etiologia , Toxemia/terapia , Resultado do Tratamento
5.
Res Vet Sci ; 130: 73-78, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32146378

RESUMO

Pregnancy toxemia (PT) is considered one of the most common metabolic diseases with high impact on the production of small ruminants. The objective of this study was investigate possible myocardial damage in goats affected with PT by the determination of serum myocardial biomarkers CK-MB and cTnI. A total of 44 goats affected with PT, and 10 apparently healthy goats (control group or CG) were used in the study. In goats with PT, the serum concentrations of cTnI (0.43 ng/mL) were significantly higher than that in CG goats (0.06 ng/mL). Although CK-MB showed no significant difference, it was approximately three times higher in animals with PT. The serum concentrations of insulin were significantly lower in PT goats (5.03 ppmol/L) compared to CG goats (10.66 pmol/L). The serum concentrations of cortisol in PT goats (155.41 nmol/L) were significantly higher than that in CG goats (36.58 nmol/L). Results of this study indicate that a clinically significant myocardial damage might occur in goats affected with PT leading to significant elevations in values of cTnI and CK-MB. Therefore, these parameters could be used as a potential prognostic indicator in goats affected with this important disease.


Assuntos
Biomarcadores/metabolismo , Doenças das Cabras/metabolismo , Miocárdio/metabolismo , Pré-Eclâmpsia/veterinária , Animais , Feminino , Cabras , Pré-Eclâmpsia/metabolismo , Gravidez , Toxemia/metabolismo , Toxemia/veterinária
6.
Toxins (Basel) ; 12(2)2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31991691

RESUMO

Intoxication with botulinum neurotoxin can occur through various routes. Foodborne botulism results after consumption of food in which botulinum neurotoxin-producing clostridia (i.e., Clostridium botulinum or strains of Clostridium butyricum type E or Clostridium baratii type F) have replicated and produced botulinum neurotoxin. Infection of a wound with C. botulinum and in situ production of botulinum neurotoxin leads to wound botulism. Colonization of the intestine by neurotoxigenic clostridia, with consequent production of botulinum toxin in the intestine, leads to intestinal toxemia botulism. When this occurs in an infant, it is referred to as infant botulism, whereas in adults or children over 1 year of age, it is intestinal colonization botulism. Predisposing factors for intestinal colonization in children or adults include previous bowel or gastric surgery, anatomical bowel abnormalities, Crohn's disease, inflammatory bowel disease, antimicrobial therapy, or foodborne botulism. Intestinal colonization botulism is confirmed by detection of botulinum toxin in serum and/or stool, or isolation of neurotoxigenic clostridia from the stool, without finding a toxic food. Shedding of neurotoxigenic clostridia in the stool may occur for a period of several weeks. Adult intestinal botulism occurs as isolated cases, and may go undiagnosed, contributing to the low reported incidence of this rare disease.


Assuntos
Botulismo , Enteropatias , Toxemia , Adulto , Botulismo/diagnóstico , Botulismo/microbiologia , Botulismo/terapia , Clostridium botulinum , Microbioma Gastrointestinal , Humanos , Enteropatias/diagnóstico , Enteropatias/microbiologia , Enteropatias/terapia , Toxemia/diagnóstico , Toxemia/microbiologia , Toxemia/terapia
7.
Rev. med. Risaralda ; 25(2): 77-82, jul.-dic. 2019. tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1115750

RESUMO

Resumen Introducción: La fisiopatología de la preeclampsia no está dilucidada por completo, diferentes índices plaquetarios dentro de los que se incluye el ancho de distribución plaquetaria (ADP) podrían ser utilizado para predecir la severidad en esta condición. Objetivo: Analizar el comportamiento del ADP en el desarrollo de severidad en preeclampsia en mujeres atendidas en la unidad de medicina materno-fetal del Hospital Simón Bolívar de Bogotá, Colombia. Materiales y métodos: Estudio de corte trasversal analítico en 105 pacientes con trastorno hipertensivo asociado al embarazo, preeclampsia y preeclampsia severa. Se analizó el comportamiento del ADP en una población de mujeres hipertensas con preeclampsia mediante una curva de análisis ''Receiver Operating Characteristic'' (ROC) para estimar la sensibilidad, tasa de falsos positivos, razón de probabilidad positiva y negativa de la prueba como marcador de desarrollo de severidad Resultados: El ADP tuvo un ascenso significativo mayor en pacientes donde su progresión de enfermedad desarrollaron características de severidad. En la curva ROC el área bajo la curva para del ADP como predictor de severidad en la preeclampsia fué de 0.68 Conclusión: El ADP es un índice plaquetario que aumentó significativamente en las mujeres con preeclampsia con características de severidad. El ADP podría ser un marcador para la predicción de severidad de la preeclampsia.


Abstract Introduction: The pathophysiology of preeclampsia is not completely elucidated. Different platelet indices, including the platelet distribution width (PDW), could be used to predict the severity of this condition. Objective: To analyze the behavior of PDW in the severity development of preeclampsia in women treated in the maternal-fetal medicine unit of Hospital Simón Bolívar in Bogotá, Colombia. Materials and methods: This is an analytical cross-sectional study in 105 patients with hypertensive disorder associated with pregnancy, preeclampsia and severe preeclampsia. We analyzed the behavior of PDW in a population of hypertensive women with preeclampsia using a curve of analysis '' Receiver Operating Characteristic '' (ROC) to estimate the sensitivity, false positive rate, positive and negative likelihood ratio of the test as a marker of development of severity Results: PDW had a higher significant increase in patients where their disease progression developed severity characteristics. In the ROC curve, the area under the curve for PDW as a predictor of severity in preeclampsia was 0.68. Conclusion: PDW is a platelet index that increased significantly in women with preeclampsia with severity characteristics. PDW could be a marker for the prediction of severity of preeclampsia.


Assuntos
Humanos , Feminino , Gravidez , Pré-Eclâmpsia , Toxemia , Transtornos Plaquetários , Perinatologia , Difosfato de Adenosina , Estudos Transversais , Progressão da Doença , Área Sob a Curva
8.
Rev Inst Med Trop Sao Paulo ; 61: e49, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531627

RESUMO

This manuscript reports a case of intestinal toxemia botulism in an adult with recently diagnosed metastatic colon cancer in whom botulism symptoms began 23 days after hospital admission. Representing the rarest form of botulism presentation in clinical practice, this infectious disease may have developed due to a cluster of predisposing factors that favored Clostridium botulinum colonization and the endogenous production of neurotoxins, among which are previous use of broad-spectrum antibiotics and colon changes related to the development of the neoplasia. This case highlights the importance of considering intestinal toxemia botulism in the differential diagnosis of a patient presenting with symmetrical descending flaccid paralysis, since immediate treatment with botulinum antitoxin may improve clinical outcomes.


Assuntos
Botulismo/diagnóstico , Neoplasias do Colo/complicações , Infecção Hospitalar/microbiologia , Enteropatias/microbiologia , Toxemia/diagnóstico , Botulismo/complicações , Evolução Fatal , Fezes/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Toxemia/complicações
9.
Anal Bioanal Chem ; 411(12): 2493-2509, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30911800

RESUMO

Inhalation of Bacillus anthracis spores can cause a rapidly progressing fatal infection. B. anthracis secretes three protein toxins: lethal factor (LF), edema factor (EF), and protective antigen (PA). EF and LF may circulate as free or PA-bound forms. Both free EF (EF) and PA-bound-EF (ETx) have adenylyl cyclase activity converting ATP to cAMP. We developed an adenylyl cyclase activity-based method for detecting and quantifying total EF (EF+ETx) in plasma. The three-step method includes magnetic immunocapture with monoclonal antibodies, reaction with ATP generating cAMP, and quantification of cAMP by isotope-dilution HPLC-MS/MS. Total EF was quantified from 5PL regression of cAMP vs ETx concentration. The detection limit was 20 fg/mL (225 zeptomoles/mL for the 89 kDa protein). Relative standard deviations for controls with 0.3, 6.0, and 90 pg/mL were 11.7-16.6% with 91.2-99.5% accuracy. The method demonstrated 100% specificity in 238 human serum/plasma samples collected from unexposed healthy individuals, and 100% sensitivity in samples from 3 human and 5 rhesus macaques with inhalation anthrax. Analysis of EF in the rhesus macaques showed that it was detected earlier post-exposure than B. anthracis by culture and PCR. Similar to LF, the kinetics of EF over the course of infection were triphasic, with an initial rise (phase-1), decline (phase-2), and final rapid rise (phase-3). EF levels were ~ 2-4 orders of magnitude lower than LF during phase-1 and phase-2 and only ~ 6-fold lower at death/euthanasia. Analysis of EF improves early diagnosis and adds to our understanding of anthrax toxemia throughout infection. The LF/EF ratio may also indicate the stage of infection and need for advanced treatments.


Assuntos
Antraz/patologia , Antígenos de Bactérias/sangue , Bacillus anthracis/patogenicidade , Toxinas Bacterianas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Infecções Respiratórias/patologia , Espectrometria de Massas em Tandem/métodos , Toxemia/patologia , Trifosfato de Adenosina/metabolismo , Animais , Antraz/sangue , Estudos de Casos e Controles , AMP Cíclico/biossíntese , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Humanos , Limite de Detecção , Macaca mulatta , Reação em Cadeia da Polimerase , Infecções Respiratórias/sangue , Toxemia/sangue , Toxemia/microbiologia
11.
Anaerobe ; 53: 50-55, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29920342

RESUMO

The epsilon toxin (Etx) produced by Clostridium perfringens type B and D causes severe enterotoxaemia associated with a general edema and neurological alterations, leading to subsequent death and is listed as one of the most lethal toxins. Currently employed vaccines against C. perfringens epsilon toxin include toxoid based vaccines. Use of peptide vaccines has become an interesting approach for vaccination after the successful licensing of peptide vaccines against Haemophilus influenza, Neisseria meningitides and Streptococcus pneumonia that have demonstrated the potential and effectiveness of these vaccines. Therefore, the present study was undertaken to develop a peptide based vaccine against epsilon toxin. Peptides were selected on the basis of epitope mapping by making 35 overlapping peptides of 15 amino acid residues in length specific to the primary amino acid sequence of the toxin, with a 7 amino acid residues overlaps between sequential peptides. Chemically synthesized peptides that were recognised by the antibody against the full length epsilon toxin were further assessed for vaccine potential. The selected peptides were chemically conjugated to partially reduced tetanus toxoid (TT) using of N-succinimidyl-3(2-pyridyldithio) propionate. Immunization of BALB/c mice with TT-peptide conjugates by sub-cutaneous route induced sustained high level mixed immune response as analyzed by antibody isotyping. Immunoblot analysis and ELISA clearly indicated generation of Etx-specific antibodies. Further, neutralization studies with the antisera generated against the TT-conjugated peptide(s) demonstrated that the antisera were able to neutralize the lethal dose of epsilon toxin in vitro demonstrating its potential as a promising vaccine candidate against enterotoxaemia.


Assuntos
Adjuvantes Imunológicos/farmacologia , Toxinas Bacterianas/imunologia , Vacinas Bacterianas/imunologia , Toxoide Tetânico/farmacologia , Toxemia/prevenção & controle , Adjuvantes Imunológicos/química , Animais , Anticorpos Antibacterianos/sangue , Anticorpos Neutralizantes/sangue , Antitoxinas/sangue , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/síntese química , Vacinas Bacterianas/genética , Infecções por Clostridium/prevenção & controle , Ensaio de Imunoadsorção Enzimática , Feminino , Immunoblotting , Injeções Subcutâneas , Camundongos Endogâmicos BALB C , Testes de Neutralização , Toxoide Tetânico/química , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/química , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
12.
Crit Care Med ; 46(4): 658-660, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29538122
13.
Pol J Vet Sci ; 21(4): 665-671, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30605278

RESUMO

The presence of lipopolysaccharide (LPS) in blood induces an inflammatory response which leads to multiple organ dysfunction and numerous metabolic disorders. Uncontrolled, improper or late intervention may lead to tissue hypoxia, anaerobic glycolysis and a disturbance in the acid -base balance. The effects of LPS-induced toxemia on biological and immunological markers were well studied. However, parameters such as base excess, ions, and acid-base balance were not fully investigated. Therefore, the objective of this study was to examine these blood parameters collectively in LPS-induced inflammatory toxemia in rat's model. After induction of toxemia by injecting LPS at a rate of 5 mg/kg body weight intravenously, blood was collected from the tail vein of twenty rats and immediately analyzed. After 24 hours, the animals were sacrificed and the blood was collected from the caudal vena cava. The results revealed that the levels of pH, bicar- bonate, partial pressure of oxygen, oxygen saturation, Alveolar oxygen, hemoglobin, hematocrit, magnesium (Mg2+), and calcium (Ca2+) were significantly decreased. On the other side, the levels of Base excess blood, Base excess extracellular fluid, partial pressure of carbon dioxide, lactate, Ca2+/Mg2+, potassium, and chloride were significantly increased compared to those found pre toxemia induction. However, sodium level showed no significant change. In conclusion, Acute LPS-toxemia model disturbs acid-base balance, blood gases, and ions. These parameters can be used to monitor human and animal toxemic inflammatory response induced by bacterial LPS conditions to assist in the management of the diagnosed cases.


Assuntos
Hematócrito , Hemoglobinas/efeitos dos fármacos , Ácido Láctico/sangue , Lipopolissacarídeos/toxicidade , Toxemia/sangue , Toxemia/induzido quimicamente , Animais , Masculino , Ratos , Ratos Sprague-Dawley
14.
Ann Clin Microbiol Antimicrob ; 16(1): 61, 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28923072

RESUMO

BACKGROUND: Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. A recent report suggested that cancer chemotherapy might increase the risk for the intestinal toxemia botulism in both adults and children. CASE PRESENTATION: We report a 5-year-old boy, who developed general muscle weakness, constipation, ptosis and mydriasis during the third induction therapy for relapsed acute myeloid leukemia. He had recent histories of multiple antibiotic therapy for bacteremia and intake of well water at home. Repeated bacterial cultures identified Clostridium botulinum producing botulinum neurotoxin A. Botulinum toxin A was isolated from his stools at 17, 21, and 23 days after the onset. Symptoms were self-limiting, and were fully recovered without anti-botulinum toxin globulin therapy. CONCLUSION: This is the second report of a pediatric case with cancer chemotherapy-associated intestinal toxemia botulism. Our case provides further evidence that the immunocompromised status due to anti-cancer treatments increases the risk for the development of botulism at all ages in childhood.


Assuntos
Botulismo/complicações , Clostridium botulinum/patogenicidade , Intestinos/microbiologia , Leucemia/complicações , Leucemia/tratamento farmacológico , Toxemia/complicações , Antibacterianos/farmacologia , Bacteriemia/tratamento farmacológico , Infecções Bacterianas , Toxinas Botulínicas , Toxinas Botulínicas Tipo A/isolamento & purificação , California , Pré-Escolar , Clostridium botulinum/isolamento & purificação , Clostridium botulinum/metabolismo , Tratamento Farmacológico , Fezes/química , Fezes/microbiologia , Humanos , Masculino , Doenças Raras
15.
Clin Infect Dis ; 66(suppl_1): S99-S102, 2017 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-29293935

RESUMO

We report a laboratory-confirmed case of adult intestinal toxemia botulism in an allogeneic hematopoietic stem cell transplantation (allo-HCT) recipient. Onset of symptoms occurred within the hospitalized setting, making this case particularly unique. Botulism may have arisen because of significant intestinal disruption and compromise, and not directly from immune compromise.


Assuntos
Botulismo/complicações , Transplante de Células-Tronco Hematopoéticas , Complicações Pós-Operatórias/microbiologia , Toxemia/microbiologia , Adulto , Clostridium botulinum/isolamento & purificação , Humanos , Intestinos/microbiologia , Tempo de Internação , Masculino , Transplante Homólogo
18.
Toxins (Basel) ; 8(5)2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-27153087

RESUMO

Clostridium difficile infection (CDI) has significant clinical impact especially on the elderly and/or immunocompromised patients. The pathogenicity of Clostridium difficile is mainly mediated by two exotoxins: toxin A (TcdA) and toxin B (TcdB). These toxins primarily disrupt the cytoskeletal structure and the tight junctions of target cells causing cell rounding and ultimately cell death. Detectable C. difficile toxemia is strongly associated with fulminant disease. However, besides the well-known intestinal damage, recent animal and in vitro studies have suggested a more far-reaching role for these toxins activity including cardiac, renal, and neurologic impairment. The creation of C. difficile strains with mutations in the genes encoding toxin A and B indicate that toxin B plays a major role in overall CDI pathogenesis. Novel insights, such as the role of a regulator protein (TcdE) on toxin production and binding interactions between albumin and C. difficile toxins, have recently been discovered and will be described. Our review focuses on the toxin-mediated pathogenic processes of CDI with an emphasis on recent studies.


Assuntos
Proteínas de Bactérias , Toxinas Bacterianas , Enterotoxinas , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/toxicidade , Toxinas Bacterianas/química , Toxinas Bacterianas/genética , Toxinas Bacterianas/toxicidade , Infecções por Clostridium , Enterotoxinas/química , Enterotoxinas/genética , Enterotoxinas/toxicidade , Humanos , Toxemia
19.
Mol Immunol ; 70: 140-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26774054

RESUMO

Clostridium perfringens beta (CPB) and iota (CPI) toxaemias result in some of the most lethal forms of haemorrhagic and necrotic enteritis and sudden death syndrome affecting especially neonates. While CPB enterotoxemia is one of the most common forms of clostridial enterotoxemia, CPI enterotoxemia though putatively considered to be rare is an emerging cause of concern. The similarities in clinical manifestation, gross and histopathology findings of both types of toxaemias coupled to the infrequency of CPI toxaemia might lead to symptomatic misidentification with Type C resulting in therapeutic failure due to habitual administration of CPB anti-toxin which is ineffective against CPI. Therefore in the present study, to generate a composite anti-toxin capable of neutralizing both toxaemias, a novel bivalent chimera r-Cpib was constructed by splicing the non-toxic C terminal binding regions of CPB and CPI, via a flexible glycine linker (G4S) by overlap-extension PCR. The fusion protein was characterized for its therapeutic abilities toward CPI and CPB toxin neutralizations. The r-Cpib was found to be non-toxic and could competitively inhibit binding of CPB to host cell receptors thereby reducing its cytotoxicity. Immunization of mice with r-Cpib generated specific antibodies capable of neutralizing the above toxaemias both in vitro and in vivo. Caco-2 cells exposed to a mixture of anti-r-Cpib sera and native CPI or CPB, displayed significantly superior protection against the respective toxins while passive challenge of mice with a similar mixture resulted in 83 and 91% protection against CPI and CPB respectively. Alternatively, mice exposed to a mixture of sham sera and native toxins died within 2-3 days. This work thus demonstrates r-Cpib as a novel bivalent fusion protein capable of efficient immunotherapy against C. perfringens CPI and CPB toxaemia.


Assuntos
ADP Ribose Transferases/imunologia , Toxinas Bacterianas/imunologia , Infecções por Clostridium/imunologia , Imunoterapia/métodos , Proteínas Recombinantes de Fusão/imunologia , Toxemia/imunologia , Sequência de Aminoácidos , Animais , Western Blotting , Células CACO-2 , Clostridium perfringens , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Proteínas Recombinantes de Fusão/síntese química
20.
Klin Khir ; (5): 77-80, 2015 May.
Artigo em Ucraniano | MEDLINE | ID: mdl-26419044

RESUMO

In 76 injured persons with deep and superficial burns, having area from 3 to 65% of the total body surface and ageing 5-16 yrs old, there was investigated the impact of early surgical treatment on the metabolic intoxication severity in accordance to content of the oxidatively modified proteins carbonyl groups in the blood serum, and of a ceruloplasmin, what was considered as integral express-index of the organism antioxidant system state. Changes of these indices in ambustial disease of middle severity have witnessed a sufficiently compensated reaction of organism: of severe and extremely severe one--there were noted a deficiency of the organism antioxidant defense; and in stages of toxemia and septicotoxemia--attrition of the organism oxidant reserves and danger of the septic complications occurrence. Conduction of early surgical intervention have guaranteed maintenance of a ceruloplasmin content in stages of toxemia and septicotoxemia on the level of healthy persons, relief of the ambustial disease course, absence of critical metabolic intoxication and carbonyl stress, reduction of the septic complications rate in 1.5 times.


Assuntos
Queimaduras/cirurgia , Procedimentos Cirúrgicos Dermatológicos , Transplante de Pele , Lesões dos Tecidos Moles/cirurgia , Toxemia/cirurgia , Adolescente , Queimaduras/metabolismo , Queimaduras/patologia , Ceruloplasmina/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Carbonilação Proteica , Índice de Gravidade de Doença , Pele/metabolismo , Pele/patologia , Pele Artificial , Lesões dos Tecidos Moles/complicações , Lesões dos Tecidos Moles/metabolismo , Lesões dos Tecidos Moles/patologia , Toxemia/complicações , Toxemia/metabolismo , Toxemia/patologia , Transplante Autólogo
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