RESUMO
Giardia lamblia is the most frequently identified protozoan cause of intestinal infection. Over 200 million people are estimated to have acute or chronic giardiasis, with infection rates approaching 90% in areas where Giardia is endemic. Despite its significance in global health, the mechanisms of pathogenesis associated with giardiasis remain unclear, as the parasite neither produces a known toxin nor induces a robust inflammatory response. Giardia colonization and proliferation in the small intestine of the host may, however, disrupt the ecological homeostasis of gastrointestinal commensal microbes and contribute to diarrheal disease associated with giardiasis. To evaluate the impact of Giardia infection on the host microbiota, we used culture-independent methods to quantify shifts in the diversity of commensal microbes throughout the gastrointestinal tract in mice infected with Giardia We discovered that Giardia's colonization of the small intestine causes a systemic dysbiosis of aerobic and anaerobic commensal bacteria. Specifically, Giardia colonization is typified by both expansions in aerobic Proteobacteria and decreases in anaerobic Firmicutes and Melainabacteria in the murine foregut and hindgut. Based on these shifts, we created a quantitative index of murine Giardia-induced microbial dysbiosis. This index increased at all gut regions during the duration of infection, including both the proximal small intestine and the colon. Giardiasis could be an ecological disease, and the observed dysbiosis may be mediated directly via the parasite's unique anaerobic fermentative metabolism or indirectly via parasite induction of gut inflammation. This systemic alteration of murine gut commensal diversity may be the cause or the consequence of inflammatory and metabolic changes throughout the gut. Shifts in the commensal microbiota may explain observed variations in giardiasis between hosts with respect to host pathology, degree of parasite colonization, infection initiation, and eventual clearance.
Assuntos
Disbiose/parasitologia , Microbioma Gastrointestinal , Giardíase/fisiopatologia , Intestino Delgado/parasitologia , Animais , Feminino , Giardia lamblia , Interações Hospedeiro-Patógeno , Intestino Delgado/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Carga ParasitáriaRESUMO
Gut infections often lead to epithelial cell damage followed by a healing response. We examined changes in the epithelial cell cytoskeleton and the involvement of host adaptive immunity in these events using an in vivo model of parasitic infection. We found that both ezrin and villin, key components of the actin cytoskeleton comprising the brush border (BB) of intestinal epithelial cells (IECs), underwent significant post-translational changes following gut infection and during the recovery phase of gut infection. Intriguingly, using mice lacking either CD4(+) or CD8(+) T-cell responses, we demonstrated that the mechanisms by which ezrin and villin are regulated in response to infection are different. Both ezrin and villin undergo proteolysis during the recovery phase of infection. Cleavage of ezrin requires CD4(+) but not CD8(+) T cells, whereas cleavage of villin requires both CD4(+) and CD8(+) T-cell responses. Both proteins were also regulated by phosphorylation; reduced levels of phosphorylated ezrin and increased levels of villin phosphorylation were observed at the peak of infection and correlated with reduced BB enzyme activity. Finally, we show that infection also leads to enhanced proliferation of IECs in this model. Cytoskeletal remodeling in IECs can have critical roles in the immunopathology and healing responses observed during many infectious and non-infectious intestinal conditions. These data indicate that cellular immune responses can be significant drivers of these processes.
Assuntos
Citoesqueleto/metabolismo , Células Epiteliais/metabolismo , Imunidade Celular , Mucosa Intestinal/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Calpaína/metabolismo , Movimento Celular/imunologia , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Feminino , Giardia lamblia/imunologia , Giardíase/imunologia , Giardíase/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/parasitologia , Intestinos/imunologia , Intestinos/parasitologia , Camundongos , Camundongos SCID , Proteínas dos Microfilamentos/metabolismo , Fosforilação , Transporte Proteico , ProteóliseAssuntos
Balantidíase/veterinária , Balantidium/fisiologia , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/epidemiologia , Animais , Balantidíase/tratamento farmacológico , Balantidíase/epidemiologia , Bovinos , Paquistão/epidemiologia , Publicações Periódicas como Assunto , Prevalência , Rios , Sus scrofa/parasitologiaRESUMO
Giardia lamblia is a ubiquitous parasite that causes diarrhoea. Effective control of Giardia infections in mice has been shown to involve IgA, T cells, mast cells and IL-6. We now show that Tumour necrosis factor alpha (TNFalpha) also plays an important role in the early control of giardiasis. Mice treated with neutralizing anti-TNFalpha antibodies or genetically deficient in TNFalpha were infected with the G. lamblia clone GS/(M)-H7. In both cases, mice lacking TNFalpha had much higher parasite numbers than controls during the first 2 weeks of infections. However, anti-parasite IgA levels, mast cell responses, and IL-4 and IL-6 mRNA levels do not appear significantly altered in the absence of TNFalpha. In addition, we show that mice infected with G. lamblia exhibit increased intestinal permeability, similar to human Giardia infection, and that this increase occurs in both wild-type and TNFalpha deficient mice. We conclude that TNFalpha is essential for host resistance to G. lamblia infection, and that it does not exert its effects through mechanisms previously implicated in control of this parasite.
Assuntos
Giardia lamblia/patogenicidade , Giardíase/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Modelos Animais de Doenças , Impedância Elétrica , Feminino , Giardia lamblia/imunologia , Giardíase/parasitologia , Humanos , Mucosa Intestinal/parasitologia , Mucosa Intestinal/fisiologia , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The protozoan parasite Giardia lamblia synthesizes a diverse and surprisingly abundant array of sterile transcripts unable to code for proteins. Random sampling of cDNAs from two evolutionarily divergent Giardia strains indicates that approximately 20% of cDNAs in the libraries represent polyadenylated sterile transcripts. RNase protection analysis and northern blot hybridization of three sterile transcript loci demonstrated that both the sterile transcript and a complementary mRNA were made in each case, further categorizing these sterile transcripts as antisense transcripts. Investigation of the genomic loci for these same three sterile antisense transcripts showed typical transcription units for the sense transcripts, but still failed to reveal a usable open reading frame for the sterile antisense transcripts. 5'-RACE mapped the transcription start site for one of the sterile antisense transcripts to an AT-rich region, as is typical for GIARDIA: It is unclear whether these sterile transcripts represent errors in transcription or whether they have regulatory functions within the cell, although preliminary investigations failed to reveal evidence for a role in developmental gene regulation. In either case, the presence of such a large pool of sterile antisense transcripts is dramatic evidence of the unusual molecular machinery of the early diverging protist G.lamblia.
Assuntos
Giardia lamblia/genética , RNA não Traduzido/genética , Animais , Sequência de Bases , Northern Blotting , Cisteína Endopeptidases/genética , DNA Complementar/química , DNA Complementar/genética , DNA de Protozoário/química , DNA de Protozoário/genética , Regulação da Expressão Gênica no Desenvolvimento , Giardia lamblia/crescimento & desenvolvimento , Dados de Sequência Molecular , NADH NADPH Oxirredutases/genética , Fases de Leitura Aberta/genética , Biossíntese de Proteínas , RNA Helicases/genética , RNA Mensageiro/genética , Análise de Sequência de DNA , Transcrição GênicaRESUMO
Giardia lamblia, one of the earliest diverging eukaryotes and a major cause of diarrhea world-wide, has unusually short intergenic regions, raising questions concerning its regulation of gene expression. We have approached this issue through examination of the alpha2-tubulin promoter and in particular investigated the function of an AT-rich element surrounding the transcription start site. Its placement and the ability of this sequence to direct transcription initiation in the absence of any other promoter elements is similar to the initiator element in higher eukaryotes. However, the sequence diversity of extremely short (8-10 bp) initiator elements is surprising, as is their ability to independently direct substantial levels of transcription. We also identified a large AT-rich element located between -64 and -29 bp upstream of the transcriptional start site and show using both deletions and site-specific mutations of this region that sequences between -60 and the start of transcription are important for promoter strength; interestingly this AT-rich sequence is not highly conserved among different Giardia promoters. These data suggest that while the overall structure of the core promoter has been conserved throughout eukaryotic evolution, significant variation and flexibility is allowed in element consensus sequences and roles in transcription. In particular, the short and diverse sequences that function in transcription initiation in Giardia suggest the potential for relaxed transcriptional regulation.
Assuntos
Genoma de Protozoário , Giardia lamblia/genética , Tubulina (Proteína)/genética , Animais , Sequência de Bases , Deleção de Genes , Giardia lamblia/química , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Regiões Promotoras Genéticas , Transcrição Gênica/genéticaRESUMO
The two-neutron halo nucleus (14)Be has been investigated in a kinematically complete measurement of the fragments ((12)Be and neutrons) produced in dissociation at 35 MeV/nucleon on C and Pb targets. Two-neutron removal cross sections, neutron angular distributions, and invariant mass spectra were measured, and the contributions from electromagnetic dissociation (EMD) were deduced. Comparison with three-body model calculations suggests that the halo wave function contains a large nu(2s(1/2))(2) admixture. The EMD invariant mass spectrum exhibited enhanced strength near threshold consistent with a nonresonant soft-dipole excitation.
RESUMO
Immune evasion is frequently cited as the main reason for antigenic variation in pathogenic microorganisms. To better understand the role of switching of variant-specific surface proteins (VSPs) in Giardia lamblia-host interactions, antigenic variation during infections of mice and gerbils was examined, using clones that predominantly expressed unique VSPs. As expected, VSPs were selected against during infections of immunocompetent hosts. In contrast, in immunodeficient hosts, some VSPs were selected for and others were selected against. These diverse patterns of selection demonstrate that there are host-VSP interactions that exert both positive and negative selective pressures on parasites, independent of the adaptive immune response. Furthermore, selection was dependent on both the particular VSP and the host. Thus, the large number of VSP genes in G. lamblia may allow the parasite to infect multiple different hosts, and antigenic variation could be a mechanism to expand the parasite's host range.
Assuntos
Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Giardia lamblia/imunologia , Giardíase/parasitologia , Animais , Variação Antigênica , Feminino , Gerbillinae , Interações Hospedeiro-Parasita , Imunocompetência , Terapia de Imunossupressão , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos SCIDRESUMO
Protozoan parasites of the genus Leishmania undergo a complex life cycle involving transmission by biting sand flies and replication within mammalian macrophage phagolysosomes. A major component of the Leishmania surface coat is the glycosylphosphatidylinositol (GPI)-anchored polysaccharide called lipophosphoglycan (LPG). LPG has been proposed to play many roles in the infectious cycle, including protection against complement and oxidants, serving as the major ligand for macrophage adhesion, and as a key factor mitigating host responses by deactivation of macrophage signaling pathways. However, all structural domains of LPG are shared by other major surface or secretory products, providing a biochemical redundancy that compromises the ability of in vitro tests to establish whether LPG itself is a virulence factor. To study truly lpg(-) parasites, we generated Leishmania major lacking the gene LPG1 [encoding a putative galactofuranosyl (Gal(f)) transferase] by targeted gene disruption. The lpg1(-) parasites lacked LPG but contained normal levels of related glycoconjugates and GPI-anchored proteins. Infections of susceptible mice and macrophages in vitro showed that these lpg(-) Leishmania were highly attenuated. Significantly and in contrast to previous LPG mutants, reintroduction of LPG1 into the lpg(-) parasites restored virulence. Thus, genetic approaches allow dissection of the roles of this complex family of interrelated parasite virulence factors, and definitively establish the role of LPG itself as a parasite virulence factor. Because the lpg1(-) mutant continue to synthesize bulk GPI-anchored Gal(f)-containing glycolipids other than LPG, a second pathway distinct from the Golgi-associated LPG synthetic compartment must exist.
Assuntos
Glicoconjugados/fisiologia , Glicoesfingolipídeos/fisiologia , Leishmania major/patogenicidade , Animais , Glicosilação , Glicosilfosfatidilinositóis/metabolismo , Leishmania major/metabolismo , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , VirulênciaRESUMO
The presence of normal bacterial flora in the intestinal tract is thought to protect against colonization by pathogens. Only a few specific examples of this protection have been demonstrated for bacterial pathogens and protozoan infections. Mice from one commercial breeding farm were found to be less susceptible to infection with Giardia lamblia than were isogenic mice from another facility. When mice were housed together, resistance to infection was readily transferred to normally susceptible mice. After resistant mice were treated with neomycin, differences in susceptibility to infection were shown to be due to differences in the resident flora present in these mice. These results suggest the possible use of probiotic therapy for prevention of G. lamblia infections and may help explain some of the variability of outcomes seen in G. lamblia infections in humans.
Assuntos
Antibiose , Giardia lamblia , Giardíase/microbiologia , Intestinos/microbiologia , Animais , Antibacterianos/uso terapêutico , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Neomicina/uso terapêuticoRESUMO
We have studied immune mechanisms responsible for control of acute Giardia lamblia and Giardia muris infections in adult mice. Association of chronic G. lamblia infection with hypogammaglobulinemia and experimental infections of mice with G. muris have led to the hypothesis that antibodies are required to control these infections. We directly tested this hypothesis by infecting B-cell-deficient mice with either G. lamblia or G. muris. Both wild-type mice and B-cell-deficient mice eliminated the vast majority of parasites between 1 and 2 weeks postinfection with G. lamblia. G. muris was also eliminated in both wild-type and B-cell-deficient mice. In contrast, T-cell-deficient and scid mice failed to control G. lamblia infections, as has been shown previously for G. muris. Treatment of wild-type or B-cell-deficient mice with antibodies to CD4 also prevented elimination of G. lamblia, confirming a role for T cells in controlling infections. By infecting mice deficient in either alphabeta- or gammadelta-T-cell receptor (TCR)-expressing T cells, we show that the alphabeta-TCR-expressing T cells are required to control parasites but that the gammadelta-TCR-expressing T cells are not. Finally, infections in mice deficient in production of gamma interferon or interleukin 4 (IL-4) and mice deficient in responding to IL-4 and IL-13 revealed that neither the Th1 nor the Th2 subset is absolutely required for protection from G. lamblia. We conclude that a T-cell-dependent mechanism is essential for controlling acute Giardia infections and that this mechanism is independent of antibody and B cells.
Assuntos
Giardia lamblia/imunologia , Giardíase/imunologia , Linfócitos T/imunologia , Doença Aguda , Animais , Anticorpos/administração & dosagem , Linfócitos B/imunologia , Antígenos CD4/imunologia , Giardia lamblia/isolamento & purificação , Giardíase/parasitologia , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/parasitologia , Interferon gama/deficiência , Interferon gama/genética , Interleucina-13/farmacologia , Interleucina-4/deficiência , Interleucina-4/genética , Interleucina-4/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Receptores de Antígenos de Linfócitos T alfa-beta/deficiência , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T gama-delta/deficiência , Receptores de Antígenos de Linfócitos T gama-delta/genética , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Susceptibility to the human autoimmune disease IDDM is strongly associated with those haplotypes of the major histocompatibility complex (MHC) carrying DQB1 alleles that do not encode aspartic acid at codon 57. Similarly, in a spontaneous animal model of this disease, the NOD mouse, the genes of the MHC play an important role in the development of diabetes. The DQB1 homolog in NOD mice, I-Ab(g7), encodes a histidine at codon 56 and a serine at codon 57, while all other known I-Ab alleles encode proline and aspartic acid, respectively, at these positions. We therefore mutated the NOD I-Ab allele to encode proline at position 56 and aspartic acid at position 57 and introduced this allele onto the NOD genetic background to study the effect of these substitutions on susceptibility to diabetes. No transgenic mice developed diabetes by 8 months of age, and transgenic mice had markedly reduced lymphocytic infiltration in the pancreas compared with nontransgenic littermates. Furthermore, splenocytes from transgenic mice failed to proliferate or secrete gamma-interferon in response to a panel of beta-cell autoantigens, although the mice did produce beta-cell specific antibodies. Interestingly, the proportion of IgG1 and IgE relative to IgG2a comprising these autoantibodies was much greater in transgenic mice compared with nontransgenic control mice. Finally, T-cells from transgenic mice inhibited the adoptive transfer of diabetes to irradiated recipients. This inhibition was partially reversed by treatment of the recipients with a combination of anti-interleukin (IL)-4 and anti-IL-10 monoclonal antibodies. Thus, a transgenic class II MHC allele encoding aspartic acid at B57 prevents diabetes, in part, by promoting the production of IL-4 and IL-10, which interfere with the effector phase of the diabetic process.
Assuntos
Diabetes Mellitus Tipo 1/prevenção & controle , Antígenos HLA-DQ/genética , Antígenos de Histocompatibilidade Classe II/genética , Mutagênese Sítio-Dirigida , Animais , Autoantígenos/imunologia , Autoimunidade , Citocinas/biossíntese , Diabetes Mellitus Tipo 1/genética , Feminino , Cadeias beta de HLA-DQ , Ilhotas Pancreáticas/imunologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Linfócitos T/imunologiaRESUMO
Giardia lamblia is an early diverging eukaryote which causes gastrointestinal disease throughout the world. Different subgroups of Giardia have been defined based on several biochemical and genetic criteria. We have developed a method for stably introducing DNA into the nuclei of the parasite using puromycin acetyltransferase (pac) as a dominant selectable marker. Transfected circular DNAs were maintained as episomes in the isolate WB, a representative of one Giardia subgroup. When input DNAs were linearized, integration was observed to occur by homologous recombination producing gene replacements in this isolate. In isolate GS, which represents a different subgroup, both linear and circular transfected DNAs were integrated into the genome by homologous recombination. In GS, linear DNA again produced gene replacements, while circular DNA produced duplicative integration events. The failure of GS to replicate episomes may reflect differences in the structure or recognition of DNA replication origins between these subgroups. A plasmid shuttle vector was also developed for expression of other genes in Giardia lamblia. Utilizing the green fluorescent protein as a reporter gene in the WB isolate, we show that gene expression from this vector correlated with plasmid copy number over a range of two orders of magnitude. Together these tools should greatly enhance our ability to study both the basic biology and the pathogenesis of this ubiquitous parasite.
Assuntos
Giardia lamblia/genética , Plasmídeos , Recombinação Genética , Transfecção , Acetiltransferases/genética , Animais , Resistência a Medicamentos/genética , Marcadores Genéticos , Proteínas de Fluorescência Verde , Proteínas Luminescentes/biossíntese , Proteínas Luminescentes/genética , Seleção Genética , Triose-Fosfato Isomerase/genéticaRESUMO
Susceptibility to IDDM is strongly associated with major histocompatibility complex (MHC) class II genotypes. Nonobese diabetic (NOD) mice develop a similar autoimmune diabetes and have a unique MHC class II I-A allele that is required for the development of diabetes. A number of groups have shown that the introduction of resistant MHC class II alleles as transgenes into the NOD mouse protects from diabetes. We made control transgenic NOD mice, expressing their own I-Abetag7 molecule as a transgene. One of two lines of these mice showed a reduced incidence of diabetes, without any change in T-cell proliferative response to a number of diabetes autoantigens or any change in insulitis severity. This line developed a subtle decrease in the percentage of splenic B-cells that progressed with age. This defect was not associated with any other phenotypic abnormalities. Our findings suggest that assessment of splenic B-cell number is necessary in interpretation of the effects of MHC class II transgenes on the development of diabetes in the NOD mouse.
Assuntos
Diabetes Mellitus Tipo 1/genética , Antígenos de Histocompatibilidade Classe II/genética , Alelos , Animais , Autoantígenos , Doenças Autoimunes/genética , Linfócitos B/imunologia , Linfócitos B/patologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Eosinofilia , Contagem de Linfócitos , Camundongos , Camundongos Endogâmicos NOD , Camundongos Transgênicos , Baço/patologia , Linfócitos T/imunologiaRESUMO
OBJECTIVE: The impact of major social policy decisions on community health is rarely considered or analyzed. This article describes the association of major community and health resource use in relation to the distribution of monthly welfare payments. METHODS: A descriptive, retrospective study was performed using existing accessible databases in the city of Vancouver, British Columbia (BC), and St. Paul's Hospital, a tertiary care, downtown institution. The mean numbers of admissions or responses per week and per day related to the monthly welfare check issue day in 1993 were collected from the following health agencies: the BC Ambulance Service, the Vancouver Fire Department, the BC Coroner's Office, the Vancouver Detox Center, the Vancouver City Police Jail for public drunkenness, and St. Paul's Hospital ED. RESULTS: Comparison of weekly events for non-payweeks vs the week starting on welfare payday (mean +/- SD) are; St. Paul's ED, 949 +/- 51 vs 993 +/- 81 (p = 0.10); Detox Center observation admissions, 29 +/- 5.6 vs 40 +/- 7.3 (p < 0.001); Vancouver Fire Department medical responses, 453 +/- 44 vs 527 +/- 45 (p < 0.001); BC Ambulance Service responses, 3,338 +/- 101 vs 3,634 +/- 85 (p < 0.001); and coroner-reported deaths, 8.8 +/- 3.0 vs 13.6 +/- 2.6 (p < 0.0001). CONCLUSIONS: As measured in multiple independent databases, there is a significant increase in morbidity and mortality in the week after the distribution of monthly welfare paychecks.
Assuntos
Serviços Médicos de Emergência/estatística & dados numéricos , Assistência Pública , Política Pública , Intoxicação Alcoólica , Colúmbia Britânica/epidemiologia , Política de Saúde , Pesquisa sobre Serviços de Saúde , Humanos , Morbidade , Mortalidade , Estudos Retrospectivos , Fatores de TempoRESUMO
Aluminum is a neurotoxin and in susceptible species induces a neurofibrillary pathology characterized by argentophilic masses in neuronal perikarya and in axonal spheroids. These inclusions are known to contain neurofilament proteins. Using immunocytochemistry and immunoblotting, we demonstrate that tau is a component of these aluminum-induced neurofibrillary tangles (Al-NFTs) in rabbits. Double-label immunocytochemistry experiments reveal co-localization of phosphorylated neurofilaments (using SMI31) and tau (using tau-1, tau-5, AT8, and PHF-1) in the perikaryal Al-NFTs. Non-phosphorylated tau (detected using tau-1) occupies a smaller area of the Al-NFT than the total pool of tau proteins (detected using tau-5). The area of total tau and non-phosphorylated tau immunolabeling in the Al-NFT increases as the size of the Al-NFT (i.e., the proportion of cell area occupied by the Al-NFT) increases. The proportion of cell area (outside of the Al-NFT) occupied by tau (as indicated by tau-5) decreases as the area of tau in the Al-NFT increases and as the size of the Al-NFT in the cell increases. Immunoblotting experiments demonstrate 1) the specificity of the tau antibody labeling and verify a lack of cross-reactivity of the tau-5 antibody to neurofilament proteins in rabbit tissue; and 2) no alterations in the levels of tau resulting from aluminum-treatment. These data suggest that as the size of the Al-NFT in a cell increases there is less tau in the neuronal perikarya. Therefore, there may be less tau in the perikarya available to perform normal functions such as microtubule polymerization and stabilization. Tau and neurofilament proteins are perturbed in a number of neurodegenerative disorders such as Alzheimer's disease, diffuse Lewy body disease, and Parkinson's disease. Aluminum-induced neurofibrillary pathology may provide a model to study perturbation in tau and neurofilaments, their phosphorylation and deposition into pathological inclusions.
Assuntos
Alumínio/intoxicação , Emaranhados Neurofibrilares/efeitos dos fármacos , Neurotoxinas/intoxicação , Proteínas tau/metabolismo , Animais , Especificidade de Anticorpos , Quelantes , Immunoblotting , Imuno-Histoquímica , Doença dos Neurônios Motores/induzido quimicamente , Emaranhados Neurofibrilares/metabolismo , Fosforilação , Coelhos , Medula Espinal/metabolismoRESUMO
In susceptible species, aluminum induces cytoskeletal changes in which neurofilaments accumulate in neuronal cell bodies and proximal axonal enlargements. To determine if microtubule-associated proteins (MAPs) are altered in this model, we examined the spinal cords of aluminum- and saline-treated control rabbits at several time points after treatment. Transient decreases in tau and MAP2 immunoreactivity in neurons in aluminum-intoxicated rabbits were demonstrated with immunocytochemistry. An antibody directed against Alzheimer's disease paired helical filaments labeled neurons in aluminum-treated rabbits but not controls. MAP5 immunoreactivity in the cell body cytoplasm was displaced by aluminum-induced tangles. The transient decreases in MAP2 and tau immunoreactivity did not reflect alterations in protein levels measured using immunoblotting. The transient antigenic changes in tau and MAP2 may reflect conformational changes in these cytoskeletal proteins. Aluminum-induced pathology provides a model for studying perturbations in MAPs and neurofilament proteins that are characteristic of many human neurodegenerative diseases such as Alzheimer's disease, diffuse Lewy body disease, Parkinson's disease, and amyotrophic lateral sclerosis.
Assuntos
Alumínio/toxicidade , Proteínas Associadas aos Microtúbulos/metabolismo , Emaranhados Neurofibrilares/ultraestrutura , Neurônios/patologia , Neurotoxinas/toxicidade , Medula Espinal/patologia , Doença de Alzheimer/patologia , Animais , Feminino , Humanos , Imuno-Histoquímica , Proteínas Associadas aos Microtúbulos/análise , Microtúbulos/efeitos dos fármacos , Microtúbulos/patologia , Microtúbulos/ultraestrutura , Emaranhados Neurofibrilares/efeitos dos fármacos , Emaranhados Neurofibrilares/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Coelhos , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Proteínas tau/análiseRESUMO
This paper describes the survey results reporting demographic profiles, behaviours, opinions beliefs, attitudes and intentions related to condom use for three Canadian ethnocultural communities (Latin American, English-speaking Caribbean and South Asian) participating in the Ethnocultural Communities facing AIDS Study. Specific recommendations are presented for HIV-prevention programming based on the research results (AU).
Assuntos
Humanos , Feminino , Masculino , Adulto , Etnicidade , Síndrome da Imunodeficiência Adquirida/etnologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Preservativos/estatística & dados numéricos , Atitude Frente a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Motivação , Análise Multivariada , Assunção de Riscos , Comportamento Sexual , Comportamento Social , Sudeste Asiático/etnologia , Indonésia/etnologia , América Latina/etnologia , CanadáRESUMO
The aim of this study was to understand the intention to use a condom for each instance of sexual intercourse with a new partner in three of Canada's non-dominant ethnocultural communities: Latin American (N=346), English-speaking Caribbean (N=358), and South Asian (N=355). All respondents were recruited from multiple ethnocultural venues using predetermined sampling frames and quotas for each community. Anonymous questionnaire assessing culturally specific theoretical constructs were completed. This paper presents the methodology and the main findings. The high quality of the results of this study demonstrate the advantage of establishing strong partnerships with members of communities being studied (AU)
Assuntos
Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Preservativos/estatística & dados numéricos , Etnicidade , Emigração e Imigração , Inquéritos e Questionários , Papel (figurativo) , Estudos de Amostragem , Fatores de Tempo , Comportamento SocialRESUMO
This paper presents the results of Phase 11 of the Ethnocultural Communities facing AIDS Study, the sociocultural investigation of factors contributing to risk behaviour associated wih HIV/AIDS in six ethnocultural communities in Canada in three urban sites. In Vancouver, the South Asian and Chinese communities were studied, the Horn of Africa and English-speaking Caribbean communities in Toronto and the Latin American and Arab-speaking communities in Montreal. Results demonstrated that there are common elements across these ethnocultural communities that increase the risk for HIV transmission. HIV/AIDS awareness and prevention in ethnocultural communities must address sociocultural differences, particularly sex role differences between men and women in terms of power within relationships to negotiate for safer sexual practices (AU).