RESUMO
OBJECTIVE: Neisseria gonorrhoeae is identified as a national challenge due to emerging antimicrobial resistance. The Centers for Disease Control and Prevention (CDC) sexually transmitted diseases (STD) Treatment guidelines are updated to address emerging concerns. The aims of this study were 1) to determine the proportion of cases that were adherent to two aspects of the treatment guidelines: antimicrobial treatment and follow-up recommendations and 2) to evaluate differences in adherence based on clinical location. STUDY DESIGN: A retrospective review of medical records was performed for the first positive N. gonorrhoeae tests identified in subjects between May 2011 and December 2013 at a large urban academic medical centre. We hypothesised that provider adherence to STD treatment and prevention guidelines was better at STD specialised clinics than non-specialised settings. METHODS: Adherence to CDC STD treatment guidelines was determined for both treatment and prevention management. Demographic, testing differences, and appropriate treatment and follow-up between speciality and non-speciality clinics were evaluated using chi-squared, Fisher's exact, and Student's t-test, when appropriate. RESULTS: During the study period, 542/714 positive tests were analysed. Healthcare provider adherence to antimicrobial management guidelines was 82% during the study period. Adherence to the guidelines was 76% and 88% for the 2010 and 2012 time periods, respectively. Non-adherence to recommendations included lack of dual therapy for N. gonorrhoeae in speciality clinics and incorrect dose in non-speciality clinics. Appropriate preventive follow-up was identified in only 31% of cases. Both speciality clinics and non-speciality clinics had errors related to partner therapy. CONCLUSIONS: Providers in speciality clinics were more adherent to the guidelines compared with providers at other clinical sites. Significant lack of adherence was identified in the follow-up management of N. gonorrhoeae. Evaluation of treatment errors may help improve medical management of N. gonorrhoeae.
Assuntos
Gonorreia/terapia , Fidelidade a Diretrizes/estatística & dados numéricos , Neisseria gonorrhoeae/isolamento & purificação , Guias de Prática Clínica como Assunto , Centros Médicos Acadêmicos , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , Centers for Disease Control and Prevention, U.S. , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Estudos Retrospectivos , Estados Unidos , Serviços Urbanos de Saúde , Adulto JovemRESUMO
Experimental induction of most autoimmune diseases appears to depend on the activation of CD4+ T helper cells, while CD8+ lymphocytes may have a role in disease progression. To study the role of CD4+ and CD8+ T cell subsets in T cell-dependent autoimmunity, mice lacking CD4 or CD8 molecules after gene targeting were injected with cardiac myosin to induce organ specific autoimmune myocarditis. Mice homozygous for the CD8 mutation (CD8-/-) developed significantly more severe disease as compared to CD4+/-CD8+/- controls. Surprisingly, CD4-/- mice developed autoimmune myocarditis with infiltration of TCR alpha beta +CD4-CD8- T cells in the heart tissue and appearance of autoantibodies. These data demonstrate that the lack of CD4+ or CD8+ T cells has no significant influence on the initiation of autoimmune myocarditis. CD4+ and CD8+ cells regulate disease severity and these results may explain the occurrence of autoimmunity in CD4 immunodeficiencies.
Assuntos
Doenças Autoimunes/imunologia , Complexo CD3/imunologia , Antígenos CD8/imunologia , Miocardite/imunologia , Miocárdio/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Autoanticorpos/análise , Doenças Autoimunes/patologia , Complexo CD3/genética , Antígenos CD8/genética , Cruzamentos Genéticos , Feminino , Homozigoto , Imunoglobulina G/imunologia , Masculino , Camundongos , Camundongos Endogâmicos , Miocardite/patologia , Miocárdio/patologia , Miosinas/imunologiaRESUMO
Chlamydia infections are epidemiologically linked to human heart disease. A peptide from the murine heart muscle-specific alpha myosin heavy chain that has sequence homology to the 60-kilodalton cysteine-rich outer membrane proteins of Chlamydia pneumoniae, C. psittaci, and C. trachomatis was shown to induce autoimmune inflammatory heart disease in mice. Injection of the homologous Chlamydia peptides into mice also induced perivascular inflammation, fibrotic changes, and blood vessel occlusion in the heart, as well as triggering T and B cell reactivity to the homologous endogenous heart muscle-specific peptide. Chlamydia DNA functioned as an adjuvant in the triggering of peptide-induced inflammatory heart disease. Infection with C. trachomatis led to the production of autoantibodies to heart muscle-specific epitopes. Thus, Chlamydia-mediated heart disease is induced by antigenic mimicry of a heart muscle-specific protein.
Assuntos
Doenças Autoimunes/microbiologia , Proteínas da Membrana Bacteriana Externa/imunologia , Infecções por Chlamydia/imunologia , Chlamydia/imunologia , Mimetismo Molecular , Miocardite/microbiologia , Cadeias Pesadas de Miosina/imunologia , Transferência Adotiva , Sequência de Aminoácidos , Animais , Antígenos de Bactérias/química , Antígenos de Bactérias/imunologia , Autoanticorpos/biossíntese , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Linfócitos B/imunologia , Proteínas da Membrana Bacteriana Externa/química , Linfócitos T CD4-Positivos/imunologia , Infecções por Chlamydia/complicações , Chlamydia trachomatis/imunologia , Ilhas de CpG , Humanos , Imunização , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Miocardite/imunologia , Miocardite/patologia , Miocárdio/imunologia , Miocárdio/patologia , Cadeias Pesadas de Miosina/química , Oligodesoxirribonucleotídeos/imunologia , Homologia de Sequência de AminoácidosRESUMO
BACKGROUND: Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. AIM: To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. METHODS: A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. FINDINGS: Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). CONCLUSION: Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical.
Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Uso de Medicamentos , Hospitais Pediátricos , Assistência de Longa Duração , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Estudos Retrospectivos , Adulto JovemRESUMO
Immunization with cardiac myosin induces T cell-mediated myocarditis in genetically predisposed mice and serves as a model for autoimmune heart disease. This study was undertaken to identify pathogenic epitopes on the myosin molecule. Our approach was based on the comparison of the pathogenicity between cardiac (alpha-)myosin and soleus muscle (beta-)myosin. We show that alpha-myosin is the immunodominant isoform and induces myocarditis at high severity and prevalence whereas beta-myosin induces little disease. Therefore the immunodominant epitopes of alpha-myosin must reside in regions of different amino acid sequence between alpha- and beta-myosin isoforms. Cardiac myosin peptides corresponding to these regions of difference were synthesized and tested for their ability to induce inflammatory heart disease. Three pathogenic peptides were identified. One peptide that is located in the head portion of the molecule induced severe myocarditis, whereas two others that reside in the rod portion possessed only minor pathogenicity. The identification of pathogenic epitopes on the cardiac myosin molecule will allow detailed studies on the recognition of this antigen by the immune system and might be used to downmodulate ongoing heart disease.
Assuntos
Doenças Autoimunes/imunologia , Mapeamento de Epitopos , Miocardite/imunologia , Miosinas/imunologia , Sequência de Aminoácidos , Animais , Doenças Autoimunes/etiologia , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Miocardite/etiologia , Miocárdio/metabolismo , Miocárdio/patologia , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/imunologia , RatosRESUMO
BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of sudden cardiac death. In certain mouse major histocompatibility complex (MHC) backgrounds, myocarditis and inflammatory cardiomyopathy can be triggered by immunization with heart muscle-specific proteins. Similarly, chronic heart disease in humans has been linked to certain HLA alleles, such as HLA-DQ6. However, there is no experimental evidence showing that human MHC class II molecules and peptides derived from human proteins are involved in the pathogenesis of myocarditis and DCM. METHODS AND RESULTS: We generated double CD4- and CD8-deficient mice transgenic for human CD4 (hCD4) and human HLA-DQ6 to specifically reconstitute the human CD4/DQ6 arm of the immune system in mice. Transgenic hCD4 and HLA-DQ6 expression rendered genetically resistant C57BL/6 mice susceptible to the induction of autoimmune myocarditis induced by immunization with cardiac myosin. Moreover, we identified heart-specific peptides derived from both mouse and human alpha-myosin heavy chains capable of inducing inflammatory heart disease in hCD4 and HLA-DQ6 double transgenic mice but not in hCD4 single transgenic littermates. The autoimmune inflammatory heart disease induced by the human heart muscle-specific peptide in hCD4 and HLA-DQ6 double transgenic mice shared functional and phenotypic features with the disease occurring in disease-susceptible nontransgenic mice. CONCLUSIONS: Our data provide the first genetic and functional evidence that human MHC class II molecules and a human alpha-myosin heavy chain-derived peptide can cause inflammatory heart disease and suggest that human inflammatory cardiomyopathy can be caused by organ-specific autoimmunity. The humanized mice generated in this study will be an ideal animal model to further elucidate the pathogenesis of inflammatory heart disease and facilitate the development of rational treatment strategies.
Assuntos
Doenças Autoimunes/imunologia , Antígenos CD4/imunologia , Antígenos HLA-DQ/imunologia , Miocardite/imunologia , Cadeias Pesadas de Miosina/imunologia , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Antígenos CD4/genética , Suscetibilidade a Doenças/imunologia , Antígenos HLA-DQ/genética , Humanos , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout/genética , Camundongos Transgênicos/genética , Miocardite/genética , Miocardite/metabolismo , Miocárdio/metabolismo , Miosinas/imunologia , Fragmentos de Peptídeos/imunologia , Fenótipo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune disease. This concept is exemplified in the Obese strain (OS) chicken model which develops a spontaneous autoimmune thyroiditis closely resembling human Hashimoto disease. Three modulating factors are specifically addressed, viz. (a) the lower threshold of OS thyroid epithelial cells for the gamma-interferon-induced MHC class II antigen expression as compared to normal controls, (b) the decreased glucocorticoid tonus of the OS and (c) the presence of a new endogenous virus (ev 22) locus in the OS that has so far not been found in any normal strain and which seems to influence the glucocorticoid-mediated immunoregulatory process.
Assuntos
Tireoidite Autoimune/etiologia , Animais , Galinhas , Glândulas Endócrinas/imunologia , Feminino , Antígenos de Histocompatibilidade Classe II , Interferon gama/farmacologia , Masculino , Glândula Tireoide/imunologia , Tireoidite Autoimune/genética , Tireoidite Autoimune/microbiologiaRESUMO
Immunization with cardiac myosin in complete Freund's adjuvant (CFA) induces severe autoimmune myocarditis in A H-2 congenic mouse strains. The disease shares a variety of characteristics with Coxsackie-virus B3 (CB3)-induced myocarditis and is strongly associated with high-titered autoantibodies to cardiac myosin. Using the spot ELISA-technique, we demonstrate here that in cardiac myosin-immunized mice myosin autoantibodies were not only produced within the spleen, but also at the site of the autoimmune attack, i.e., within the inflammatory heart infiltrate. At the level of single plasma cells we further showed that a substantial part of the myosin autoantibodies was specific for the cardiac myosin isoform, thereby supporting previous serologic data. The finding that cells of the inflammatory heart infiltrate significantly contribute to autoantibody production might explain why the occurrence of high-titered myosin autoantibodies is restricted to mice which develop the disease.
Assuntos
Autoanticorpos/biossíntese , Doenças Autoimunes/imunologia , Miocardite/imunologia , Miosinas/imunologia , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imunização , Imunoglobulina G/biossíntese , Isotipos de Imunoglobulinas , Camundongos , Miocardite/induzido quimicamente , Miocárdio/imunologia , Baço/imunologiaRESUMO
F1-hybrids of Obese strain (OS) chickens, afflicted with spontaneous autoimmune thyroiditis (SAT), and normal, inbred CB chickens, do not develop severe thyroiditis. About 50% of these crosses show circulating autoantibodies to thyroglobulin (TgAAb), but the thyroid glands are only slightly infiltrated, suggesting that the target organ is not susceptible to autoimmune attack. In the present study we show that despite this mild infiltration TgAAb are only synthesized by lymphoid cells within the thyroid gland. Furthermore, we demonstrate that immunization with chicken thyroglobulin (Tg) in complete Freund's adjuvant causes severe experimental autoimmune thyroiditis (EAT) in F1(OSxCB) hybrids.
Assuntos
Autoanticorpos/biossíntese , Tireoidite Autoimune/imunologia , Animais , Galinhas , Cruzamentos Genéticos , Modelos Animais de Doenças , Tireoglobulina/imunologiaRESUMO
Dilated cardiomyopathy is a prevalent cause of progressive heart disease and sudden death, and most patients with cardiomyopathy have a history of viral myocarditis. Coxsackie B3 (CB3) picornaviruses can be detected in as many as 50% of these patients and CB3 infections have been epidemiologically linked to chronic heart disease. Several clinical and experimental studies suggest that chronic stages of disease are mediated by an autoimmune response against heart muscle myosin. Human heart disease can be mimicked in mice using cardiac myosin as autoantigen. Murine cardiac myosin-induced myocarditis is an organ-specific autoimmune disease and mediated by CD4+ T cells that recognize a myosin-specific peptide in association with MHC class II molecules. Here, the recent discovery of autoimmune epitopes derived from the alpha isoform of cardiac myosin, the functional roles of surface receptor and signal transduction molecules, and the molecular mechanisms of target organ susceptibility will be discussed.
Assuntos
Doenças Autoimunes/imunologia , Miocardite/imunologia , Sequência de Aminoácidos , Animais , Células Apresentadoras de Antígenos/imunologia , Antígenos CD/metabolismo , Doenças Autoimunes/patologia , Antígenos CD8/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Dados de Sequência Molecular , Miocardite/patologia , Miosinas/imunologia , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral , Linfócitos T/imunologiaRESUMO
BACKGROUND: Correctly diagnosing tuberculosis (TB) in children is critical to provide appropriate treatment and to detect undiagnosed source cases. However, diagnosing TB in children may be difficult. OBJECTIVE: We sought to determine whether Amplicor, a Food and Drug Administration-approved polymerase chain reaction (PCR) assay used to detect Mycobacterium tuberculosis in sputum and computerized tomography (CT) would facilitate the diagnosis of TB in children. We also examined the applicability of the Centers for Disease Control and Prevention clinical case definition for TB. SETTING: A university-affiliated pediatric hospital in New York City. SUBJECTS: From March, 1995, to November, 1997, 27 children < 15 years of age (mean age, 3.9 years) were evaluated for suspected TB. RESULTS: M. tuberculosis was cultured from 5 of 76 (6.6%) gastric aspirate specimens, and PCR detected M. tuberculosis DNA in 3 (4.1%) of these specimens. There was poor correlation between culture and PCR because 6 specimens were discordant. CT scans were diagnostic of mediastinal or hilar adenopathy in 6 children with equivocal or negative chest radiographs and confirmed adenopathy in 8 others. Six children received alternative diagnoses. CONCLUSIONS: We conclude that the commercially available PCR technology had very limited utility in detecting M. tuberculosis from gastric aspirates, but CT scans were useful in assessing pediatric patients with suspected TB.
Assuntos
Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adolescente , Centers for Disease Control and Prevention, U.S. , Criança , Pré-Escolar , Meios de Cultura , DNA Bacteriano/análise , Feminino , Suco Gástrico/microbiologia , Infecções por HIV/microbiologia , Humanos , Lactente , Recém-Nascido , Masculino , Mycobacterium tuberculosis/genética , Reação em Cadeia da Polimerase/métodos , Tomografia Computadorizada por Raios X , Teste Tuberculínico , Tuberculose Pulmonar/diagnóstico por imagem , Estados UnidosRESUMO
We describe a nosocomial rotavirus outbreak among pediatric cardiology patients and the impact of a prospective, laboratory-based surveillance program for rotavirus in our university-affiliated, quartenary-care pediatric hospital in New York City. Improved compliance with infection control and case-finding among patients and healthcare workers halted the outbreak.
Assuntos
Infecção Hospitalar/virologia , Surtos de Doenças , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/virologia , Hospitais Pediátricos , Humanos , Técnicas Imunoenzimáticas , Lactente , Masculino , Cidade de Nova Iorque/epidemiologia , Vigilância da PopulaçãoRESUMO
Staphylococcus epidermidis has become an increasingly important pathogen as the cause of serious postoperative infection after heart and orthopedic surgery. We studied the susceptibilities of 80 blood, sternotomy, and hip isolates to vancomycin, cefazolin, cefuroxime, oxacillin, erythromycin, ciprofloxacin, and ofloxacin. The MIC90 of methicillin-susceptible isolates was 4 micrograms/ml for cefazolin and cefamandole, 8 micrograms/ml for cefuroxime, and 4 micrograms/ml for vancomycin. At 48 hr the MIC90 rose to 32 micrograms/ml for cefazolin and greater than 128 micrograms/ml for cefuroxime, and remained at 4 micrograms/ml for cefamandole and vancomycin. The MIC90 of methicillin-resistant isolates at 48 hr was 16 micrograms/ml cefamandole, 64 micrograms/ml cefazolin, greater than 128 micrograms/ml cefuroxime, and 4 micrograms/ml vancomycin. Ciprofloxacin and ofloxacin inhibited the majority of isolates at 1 microgram/ml, and vancomycin at 4 micrograms/ml. The new peptolide, daptomycin, also inhibited S. epidermidis at less than or equal to 1 microgram/ml.
Assuntos
Cefalosporinas/farmacologia , Infecções Estafilocócicas/microbiologia , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Cefamandol/farmacologia , Cefazolina/farmacologia , Cefuroxima/farmacologia , Coagulase , Humanos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Oxacilina/farmacologia , Staphylococcus/enzimologia , Staphylococcus epidermidis/enzimologia , Vancomicina/farmacologiaRESUMO
Methicillin resistance in staphylococci is an increasing problem both for Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), which cause infections of the heart and after central nervous system surgery. Resistance seems to be due primarily to production of altered penicillin-binding proteins. The present study determined whether a combination of beta-lactamase inhibitor sulbactam and ampicillin or sulbactam and cefazolin would inhibit MRSA and MRSE. Sulbactam, ampicillin and cefazolin at 32 micrograms/ml did not inhibit MRSA or MRSE. At 8 micrograms/ml of each agent all isolates were inhibited. Synergy of sulbactam and ampicillin could be demonstrated against MRSA by the agar fixed ratio method, checkerboard dilution and by killing curves. This suggests that in certain situations MRSA and MRSE may be effectively eliminated by this method.
Assuntos
Ampicilina/farmacologia , Proteínas de Bactérias , Hexosiltransferases , Meticilina/farmacologia , Ácido Penicilânico/farmacologia , Resistência às Penicilinas , Peptidil Transferases , Staphylococcus/efeitos dos fármacos , Proteínas de Transporte/biossíntese , Cefazolina/farmacologia , Sinergismo Farmacológico , Muramilpentapeptídeo Carboxipeptidase/biossíntese , Proteínas de Ligação às Penicilinas , SulbactamRESUMO
Fosfomycin inhibits bacterial cell wall synthesis at the initial stage. It can act synergistically with beta-lactams. The effect of the combination of fosfomycin and selected penicillins and cephalosporins against staphylococci, Pseudomonas aeruginosa, Pseudomonas cepacia and selected Gram-negative bacteria was determined. Synergy was determined by agar dilution and checkerboard titration methods; synergy was defined as an FIC index less than or equal to 0.5 and partial synergy greater than 0.5 to 0.75. Concentrations of drugs used were those that would be reached in man by intravenous and oral routes. Fosfomycin combined with nafcillin and with cefotaxime against staphylococci showed synergy for most isolates. For methicillin-resistant Staphylococcus aureus, synergy or partial synergy was found for 90% of isolates. Synergy was less frequently found with Staphylococcus epidermidis. The MICs for S. aureus were reduced from greater than or equal to 32 micrograms/ml to less than or equal to 1 microgram/ml. Fosfomycin was synergistic with ticarcillin, piperacillin, azlocillin, ceftazidime, aztreonam and imipenem against 31 to 61% of P. aeruginosa. MICs were reduced from greater than or equal to 128 micrograms/ml to 8-32 micrograms/ml, depending upon the agent. Although fosfomycin acted synergistically with azlocillin, piperacillin and ceftazidime against some P. cepacia, most often there was an indifferent interaction and MICs were in the resistant range, greater than or equal to 128 micrograms/ml. The interaction of fosfomycin and ampicillin was synergistic against a number of strains of Enterobacteriaceae, Proteus vulgaris and Providencia rettgeri, yielding MICs in an achievable range. The combination of fosfomycin with beta-lactams may be clinically useful in selected situations, particularly for methicillin-resistant staphylococci and beta-lactam-resistant P. aeruginosa.
Assuntos
Antibacterianos/farmacologia , Fosfomicina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Combinação de Medicamentos , Sinergismo Farmacológico , Meticilina/farmacologia , Resistência às PenicilinasRESUMO
Alterations in the volume, density, connectivity and functional activation of white matter tracts are reported in some individuals with autism and may contribute to their abnormal behaviors. The BTBR (BTBR T+tf/J) inbred strain of mouse, is used to model facets of autism because they develop low social behaviors, stereotypical and immune changes similar to those found in people with autism. Previously, it was thought a total absence of corpus callosal interhemispheric connective tissues in the BTBR mice may underlie their abnormal behaviors. However, postnatal lesions of the corpus callosum do not precipitate social behavioral problems in other strains of mice suggesting a flaw in this theory. In this study we used digital pathological methods to compare subcortical white matter connective tracts in the BTBR strain of mice with those found in the C57Bl/6 mouse and those reported in a standardized mouse brain atlas. We report, for the first time, a novel connective subcortical interhemispheric bridge of tissue in the posterior, but not anterior, cerebrum of the BTBR mouse. These novel connective tissues are comprised of myelinated fibers, with reduced myelin basic protein levels (MBP) compared to levels in the C57Bl/6 mouse. We used electrophysiological analysis and found increased inter-hemispheric connectivity in the posterior hemispheres of the BTBR strain compared with the anterior hemispheres. The conduction velocity was slower than that reported in normal mice. This study shows there is novel abnormal interhemispheric connectivity in the BTBR strain of mice, which may contribute to their behavioral abnormalities.
Assuntos
Transtorno Autístico/patologia , Encéfalo/patologia , Corpo Caloso/patologia , Lateralidade Funcional , Fibras Nervosas Mielinizadas/patologia , Análise de Variância , Animais , Encéfalo/anormalidades , Modelos Animais de Doenças , Eletroencefalografia , Ensaio de Imunoadsorção Enzimática , Feminino , Processamento de Imagem Assistida por Computador , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Básica da Mielina/metabolismo , Neuroimagem , Análise EspectralRESUMO
Polychlorinated biphenyls (PCBs) are persistent lipophilic environmental contaminants which are found in fatty tissues of humans and wild-life alike. Maternal transfer of PCBs to offspring is easily achieved across the placenta and via lactation. In male rats, perinatal PCB exposure induces behavioral abnormalities, in addition to hypothyroxinemia and white matter changes. There are sex differences in white matter volume synthesis and density in adult and aged rodents. Yet whether PCB exposure effects on white matter are sex-specific is unclear, because the previous studies were conducted in male offspring. Furthermore, although hypothyroxinemia induced by PCB exposure is thought to trigger white matter changes, PCBs also affect interleukin-6 (IL-6) expression, and IL-6 regulates white matter growth. We hypothesized that perinatal PCB exposure would have sex-specific effects on white matter development associated with altered IL-6 levels. We found that female offspring had higher levels of myelin basic protein (MBP) than males did, at postnatal day (PND) 7, 18 and 21. PCB exposure induced hypothyroxinemia in males and females at PND7, 14, 21, and 42. PCB exposure also increased MBP and reduced glial fibrillary acidic protein (GFAP) levels in males at PND21, but had the opposite effect in females. In addition, at PND14 and 21, PCB exposure elevated IL-6 levels in male offspring only. The induction of sex-specific changes in white matter proteins, in the absence of sex differences in thyroxine levels after PCB exposure, suggests that serum thyroxine levels do not directly contribute to the white matter alterations. Instead, IL-6 may contribute to increased MBP levels in males, whereas in females estromimetic and thyromimetic PCB metabolites may affect white matter development. This data adds to an increasing body of literature showing that perinatal insults induce sex-specific effects in offspring.