RESUMO
OBJECTIVES: To describe the most common ocular lesions and demonstrate the frequency of ophthalmic involvement in a group of cats with systemic sporotrichosis. ANIMALS STUDIED: Two hundred seventy-four cats diagnosed with systemic sporotrichosis. The inclusion criteria included previous positive cytopathological examination, histopathological examination, or fungal culture. PROCEDURES: In a prospective case-control study, 274 cats diagnosed with systemic sporotrichosis underwent ophthalmic evaluation and received treatment for systemic sporotrichosis. Of these animals, 63 had ocular abnormalities which were recorded, and conjunctivitis was scored from 0 to 5. Diagnostic techniques utilized included fungal culture, as well as cytopathological (10 eyes; 10 cats), and histopathological examination of the palpebral conjunctiva and eyes (2 eyes). RESULTS: Cytopathological and histopathological examination of the conjunctiva, as well as fungal culture, proved to be important tests for the detection of Sporothrix sp. Five cats without the evidence of ophthalmic abnormalities also had a positive fungal culture. The identified ocular lesions in animals with systemic sporotrichosis included increased serous discharge (79 eyes; 53 cats), blepharoconjunctivitis (33 eyes; 25 cats), conjunctivitis (39 eyes, 20 cats), blepharitis (9 eyes; 8 cats), uveitis (5 eyes; 3 cats), and Florida keratopathy-like lesions (2 eyes; 1 cat). CONCLUSION: Sporotrichosis should be considered a differential diagnosis for conjunctivitis and blepharoconjunctivitis, especially in endemic areas. Fungal culture and cytopathology of ocular discharge and histopathological examinations of the conjunctiva are important for the diagnosis of ophthalmic sporotrichosis, although not all cats underwent laboratory testing in this study. Ocular discharge could be a source of contagion transmission.
Assuntos
Doenças do Gato , Conjuntivite , Opacidade da Córnea , Esporotricose , Animais , Gatos , Esporotricose/diagnóstico , Esporotricose/veterinária , Estudos de Casos e Controles , Conjuntivite/diagnóstico , Conjuntivite/veterinária , Túnica Conjuntiva , Opacidade da Córnea/veterinária , Doenças do Gato/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Data suggest a relationship between sexual dysfunction, mainly erectile dysfunction in men, and worse disease progression in Parkinson's disease (PD). There is scant evidence on the correlates of sexual activity in PD patients. By involving a subgroup of 355 patients from the PRIAMO (Parkinson Disease Non Motor Symptoms) study, the present 24-month longitudinal prospective analysis aims to demonstrate that the presence of active sexual life is associated with disease progression in early PD. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models showed that gastrointestinal symptoms [odds ratio 0.56, 95% confidence interval (CI) 0.39-0.82, P = 0.003] and apathy (odds ratio 0.42, 95% CI 0.29-0.63, P < 0.001) were less likely to be associated with sexual activity in men. Analysis also demonstrated that sexual activity in men was associated with lower motor disability (coefficient -2.881, 95% CI -4.732 to -1.030, P = 0.002), better quality of life (coefficient -24.196, 95% CI -44.884 to -3.508, P = 0.022; coefficient 0.083, 95% CI 0.023-0.143, P = 0.006) and lower depression scores (coefficient -1.245, 95% CI -2.104 to -0.387, P = 0.004). No association was shown in women. CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients suggesting that sexual activity is associated with lower motor and non-motor disability as well as with better quality of life in men. These findings should prompt movement disorders specialists to periodically inquiry about their patients' sexual life.
Assuntos
Transtornos dos Movimentos/etiologia , Doença de Parkinson/psicologia , Comportamento Sexual/psicologia , Adulto , Idade de Início , Idoso , Apatia , Estudos de Coortes , Avaliação da Deficiência , Progressão da Doença , Feminino , Gastroenteropatias/etiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Estudos Prospectivos , Qualidade de Vida , Caracteres Sexuais , Resultado do TratamentoRESUMO
INTRODUCTION: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), previously known as hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) or pigmentary orthochromatic leukodystrophy (POLD), is the most frequent non-vascular adult-onset leukoencephalopathy. It is caused by autosomal dominant mutations in CSF1R gene. Recently, also autosomal recessive mutations in AARS2 gene were found to be the cause of an adult-onset leukodystrophy with axonal spheroids. Our aim was to achieve a genetic diagnosis in a cohort of CSF1R-negative patients, performing a sequence analysis of AARS2 gene. MATERIAL AND METHODS: AARS2 sequencing was performed in 38 CSF1R-negative patients with clinical and magnetic resonance imaging (MRI) findings of adult-onset leukoencephalopathy. RESULTS: Three patients carrying AARS2 compound heterozygous mutations have been found. All patients were female with ovarian failure and leukoencephalopathy. In 2 patients, MRI findings were consistent with previous reports while the third patient showed focal white matter (WM) lesions in the centrum semiovale and the corpus callosum in the absence of extensive involvement and rarefaction of the WM. MRI spectroscopy showed the presence of increased lactate in 2 patients, thus linking AARS2-related leukoencephalopathy with other mitochondrial leukoencephalopathies with high levels of cerebral lactate. CONCLUSION: We recommend screening for mutations in AARS2 gene in CSF1R-negative patients, also in the absence of a clear family history and peculiar MRI findings. Our results also suggest that findings of conventional MRI and MR spectroscopy may be useful in prompting the genetic screening.
Assuntos
Alanina-tRNA Ligase/genética , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/genética , Imageamento por Ressonância Magnética/métodos , Mutação/genética , Doenças Ovarianas/diagnóstico por imagem , Doenças Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Corpo Caloso/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodosRESUMO
BACKGROUND AND PURPOSE: New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non-motor subtypes and models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the present 24-month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non-motor burden as well as lower health-related quality of life. METHODS AND RESULTS: Multivariable mixed-effect logistic regression models controlling for demographic and clinical variables showed that the following NMS domains were associated with urinary dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.67-3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18-4.17, P = 0.013), skin (OR 1.81, 95% CI 1.06-3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34-3.16, P = 0.001), pain (OR 1.85, 95% CI 1.21-2.83, P = 0.004), fatigue (OR 2.40, 95% CI 1.56-3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72-4.52, P < 0.001) and respiratory (OR 1.82, 95% CI 1.02-3.23, P = 0.039). Analysis also demonstrated that urinary dysfunction was associated with higher motor disability (coefficient 1.73, 95% CI 0.68-2.78, P = 0.001) and lower health-related quality of life (coefficient -0.05, 95% CI -0.08 to -0.02, P < 0.001, and coefficient -3.49, 95% CI -5.21 to -1.77, P < 0.001) but not with more severe cognitive disability (coefficient -0.34, 95% CI -0.92 to 0.24, P = 0.251). CONCLUSIONS: This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non-motor disability as well as lower health-related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.
Assuntos
Progressão da Doença , Fadiga/complicações , Doença de Parkinson/complicações , Qualidade de Vida , Transtornos Urinários/complicações , Idoso , Apatia/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Sono/fisiologiaRESUMO
To cause infections microbes need to evade host defense systems, one of these being the evolutionarily old and important arm of innate immunity, the alternative pathway of complement. It can attack all kinds of targets and is tightly controlled in plasma and on host cells by plasma complement regulator factor H (FH). FH binds simultaneously to host cell surface structures such as heparin or glycosaminoglycans via domain 20 and to the main complement opsonin C3b via domain 19. Many pathogenic microbes protect themselves from complement by recruiting host FH. We analyzed how and why different microbes bind FH via domains 19-20 (FH19-20). We used a selection of FH19-20 point mutants to reveal the binding sites of several microbial proteins and whole microbes (Haemophilus influenzae, Bordetella pertussis, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Borrelia burgdorferi, and Borrelia hermsii). We show that all studied microbes use the same binding region located on one side of domain 20. Binding of FH to the microbial proteins was inhibited with heparin showing that the common microbial binding site overlaps with the heparin site needed for efficient binding of FH to host cells. Surprisingly, the microbial proteins enhanced binding of FH19-20 to C3b and down-regulation of complement activation. We show that this is caused by formation of a tripartite complex between the microbial protein, FH, and C3b. In this study we reveal that seven microbes representing different phyla utilize a common binding site on the domain 20 of FH for complement evasion. Binding via this site not only mimics the glycosaminoglycans of the host cells, but also enhances function of FH on the microbial surfaces via the novel mechanism of tripartite complex formation. This is a unique example of convergent evolution resulting in enhanced immune evasion of important pathogens via utilization of a "superevasion site."
Assuntos
Bactérias/metabolismo , Candida albicans/metabolismo , Fator H do Complemento/metabolismo , Bactérias/genética , Bactérias/imunologia , Bactérias/patogenicidade , Sítios de Ligação , Bordetella pertussis/genética , Bordetella pertussis/imunologia , Bordetella pertussis/metabolismo , Bordetella pertussis/patogenicidade , Borrelia/genética , Borrelia/imunologia , Borrelia/metabolismo , Borrelia/patogenicidade , Candida albicans/genética , Candida albicans/imunologia , Candida albicans/patogenicidade , Membrana Celular/metabolismo , Ativação do Complemento , Fator H do Complemento/química , Haemophilus influenzae/genética , Haemophilus influenzae/imunologia , Haemophilus influenzae/metabolismo , Haemophilus influenzae/patogenicidade , Humanos , Ligação Proteica , Estrutura Terciária de Proteína , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/imunologia , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidade , Staphylococcus aureus/genética , Staphylococcus aureus/imunologia , Staphylococcus aureus/metabolismo , Staphylococcus aureus/patogenicidade , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/metabolismo , Streptococcus pneumoniae/patogenicidadeRESUMO
Dermatophytosis caused by Microsporum canis is a heterogeneous disease with variable clinical manifestations. M. canis is a zoophilic dermatophyte and the most frequent fungi isolated from dogs, cats and children in Brazil. The aim of this study was to investigate the genetic variability of M. canis isolates from different animal species using two microsatellite markers, namely, McGT(13) and McGT(17), and to correlate the results with the clinical and epidemiological patient data in Brazil. The study included a global set of 102 M. canis strains, including 37 symptomatic cats, 35 asymptomatic cats, 19 human patients with tinea, 9 asymptomatic dogs and 2 symptomatic dogs. A total of 14 genotypes were identified, and 6 large populations were distinguished. There was no correlation between these multilocus genotypes and the clinical and epidemiological data, including the source, symptomatology, clinical picture, breed, age, sex, living conditions and geographic location. These results demonstrate that the use of microsatellite polymorphisms is a reliable method for the differentiation of M. canis strains. However, we were unable to demonstrate a shared clinical and epidemiological pattern among the same genotype samples.
Assuntos
Doenças do Gato/microbiologia , Dermatomicoses/epidemiologia , Dermatomicoses/veterinária , Doenças do Cão/microbiologia , Variação Genética , Microsporum/classificação , Microsporum/genética , Adulto , Animais , Brasil/epidemiologia , Gatos , Criança , Pré-Escolar , Análise por Conglomerados , DNA Fúngico/genética , Dermatomicoses/microbiologia , Cães , Feminino , Genótipo , Humanos , Masculino , Repetições de Microssatélites , Microsporum/isolamento & purificação , Epidemiologia Molecular , Tipagem Molecular , Técnicas de Tipagem MicológicaAssuntos
Neurite do Plexo Braquial/etiologia , Dissecação da Artéria Vertebral/complicações , Adulto , Neurite do Plexo Braquial/diagnóstico por imagem , Feminino , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Humanos , Imageamento por Ressonância Magnética , Dissecação da Artéria Vertebral/diagnóstico por imagemRESUMO
Leptospirosis, the most common zoonotic infection worldwide, is a multi-system disorder affecting the kidney, liver, and lungs. Infections can be asymptomatic, self-limiting or progress to multi-organ system failure and pulmonary hemorrhage. The incidence of canine and human leptospirosis is steadily increasing worldwide. At least sixty-four Leptospira species and several hundred lipopolysaccharide-based serovars have been defined. Preventive vaccines are available for use in veterinary medicine and limited use in humans in some countries. All commercially available vaccines are bacterin formulations that consist of a combination of laboratory cultivated strains of different lipopolysaccharide serotypes. The development of a broadly protective subunit vaccine would represent a significant step forward in efforts to combat leptospirosis in humans, livestock, and companion animals worldwide. Here we investigate the potential of General secretory protein D (GspD; LIC11570), a secretin, to serve as a possible antigen in a multi-valent vaccine formulation. GspD is conserved, expressed in vitro, antigenic during infection and elicits antibody with complement independent bactericidal activity. Importantly, antibody to GspD is bactericidal against diverse Leptospira species of the P1 subclade. Epitope mapping localized the bactericidal epitopes to the N-terminal N0 domain of GspD. The data within support further exploration of GspD as a candidate for inclusion in a next generation multi-protein subunit vaccine.
RESUMO
Lyme disease (LD), the most common tick-borne disease of canines and humans in N. America, is caused by the spirochete Borreliella burgdorferi. Subunit and bacterin vaccines are available for the prevention of LD in dogs. LD bacterin vaccines, which are comprised of cell lysates of two strains of B. burgdorferi, contain over 1000 different proteins and cellular constituents. In contrast, subunit vaccines are defined in composition and consist of either outer surface protein (Osp)A or OspA and an OspC chimeritope. In this study, we comparatively assessed antibody responses to OspA and OspC induced by vaccination with all canine bacterin and subunit LD vaccines that are commercially available in North America. Dogs were administered a two-dose series of the vaccine to which they were assigned (3 weeks apart): Subunit-AC, Subunit-A, Bacterin-1, and Bacterin-2. Antibody titers to OspA and OspC were determined by ELISA and the ability of each vaccine to elicit antibodies that recognize diverse OspC proteins (referred to as OspC types) assessed by immunoblot. While all of the vaccines elicited similar OspA antibody responses, only Subunit-AC triggered a robust and broadly cross-reactive antibody response to divergent OspC proteins. The data presented within provide new information regarding vaccination-induced antibody responses to key tick and mammalian phase antigens by both subunit and bacterin LD canine vaccine formulations.
Assuntos
Antígenos de Bactérias/imunologia , Antígenos de Superfície/imunologia , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Lipoproteínas/imunologia , Vacinas contra Doença de Lyme/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Formação de Anticorpos , Borrelia burgdorferi/imunologia , Doenças do Cão/imunologia , Doenças do Cão/prevenção & controle , Cães , Feminino , Doença de Lyme/prevenção & controle , Doença de Lyme/veterinária , Masculino , Vacinação/veterináriaRESUMO
Lyme disease (LD) is a tick-transmitted disease caused by Borreliella burgdorferi (Bb). Temporal studies of maternal antibody (Ab) profiles in Bb infected pregnant dogs and their pups have not been conducted. In this study, Ab profiles of a client-owned Bb C6 Ab positive Rottweiler and her nine pups were assessed. The dam presented with lameness 12 days prior to parturition and was C6 Ab positive with a Quant C6 Ab concentration of 237U/mL. Treatment with amoxicillin was initiated and 11 days later nine pups were delivered. Screening of the sera from the dam and pups against Bb cell lysates and a panel of antigens revealed similar immunoreactivity profiles. While antigen-specific IgG and IgM reactivity persisted in the dam for at least 7 months, a rapid decline in IgG specific for BBA36, BBK53, BB0238, BBA73 and outer surface protein (Osp) E in the pups occurred between days 29 and 52 post-parturition. In contrast, Ab specific for DbpA and the diagnostic antigens VlsE (C6) and OspF, remained elevated in the pups. Sera from the dam displayed potent complement-dependent bactericidal activity against Bb. Sera from the pups was also bactericidal but primarily through a complement-independent mechanism. Lastly, single dose vaccination of the dam at day 51 post-parturition with a LD subunit vaccine consisting of OspA and an OspC chimeritope triggered a broad anti-OspC Ab response indicative of an anamnestic response. Although this study focused on a single case, these findings add to our knowledge of maternal Ab profiles and will aid the interpretation of serological assays in pups delivered by a Bb C6 Ab positive dog.
Assuntos
Borrelia burgdorferi/imunologia , Doenças do Cão/diagnóstico , Vacinas contra Doença de Lyme/imunologia , Doença de Lyme/veterinária , Animais , Anticorpos Antibacterianos/sangue , Doenças do Cão/tratamento farmacológico , Doenças do Cão/imunologia , Cães , Feminino , Doença de Lyme/diagnóstico , Doença de Lyme/imunologia , Ontário , Vacinação/veterináriaRESUMO
Persistent infections caused by high-risk human papillomavirus (HR-HPV) are important, for the development of cervical lesions, but environmental and genetic factors are also related in the process of carcinogenesis. Among the genetic factors, the genetic variants of HR-HPV appear to be related to the risk of persistent infections. Therefore, the present study investigates variants of HPV31 E5 oncogene in cervical scraping samples from Brazilian women to assess their functional and structural effects, in order to identify possible repercussions of these variants on the infectious and carcinogenic process. Our results detected nucleotide changes previously described in the HPV31 E5 oncogene, which may play a critical role in the development of cancer due to its ability to promote cell proliferation and signal transmission. In our study, the interaction percentage of the 31E5 sequence generated by the Immune Epitope Server database and the Analysis Resource (IEDB) allowed us to include possible immunogenic epitopes with the MHC-I and MHC-II molecules, which may represent a possible relationship between protein suppression of the immune system. In the structural analysis of the HPV31 E5 oncoprotein, the N5D, I48 V, P56A, F80I and V64I polymorphisms can be found inserted within transmembrane regions. The P56A mutation has been predicted to be highly stabilizing and, therefore, can cause a change in protein function. Regarding the interaction of the E5 protein from HPV31 with the signaling of NF-kB pathway, we observed that in all variants of the E5 gene from HPV-31, the activity of the NF-kB pathway was increased compared to the prototype. Our study contributes to a more refined design of studies with the E5 gene from HPV31 and provides important data for a better understanding of how variants can be distinguished under their clinical consequences.
Assuntos
Colo do Útero/virologia , Variação Genética , Papillomavirus Humano 31/classificação , Papillomavirus Humano 31/genética , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Feminino , Células HEK293 , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas Oncogênicas Virais/classificação , Infecções por Papillomavirus/virologia , Filogenia , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Quinase Induzida por NF-kappaBRESUMO
Familial hemiplegic migraine type 2 (FHM-2) and common types of migraine show phenotypic similarities which may indicate a common neurobiological background. The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we tested the hypothesis that ATP1A2 mutations in patients with FHM-2 are associated with hypersensitivity to NO-cGMP pathway. Eight FHM-2 patients with R202Q, R763C, V138A and L764P mutations and nine healthy controls received intravenous infusions of 0.5 mug kg(-1) min(-1) glyceryl trinitrate (GTN) over 20 min. We recorded the following variables: headache intensity on a verbal rating scale; mean flow velocity in the middle cerebral artery (V(meanMCA)) by transcranial Doppler; diameter of the superficial temporal artery (STA) by ultrasound. The primary end-points were differences in incidence of migraine headache and area under the curve (AUC) for headache score during an immediate phase (0-120 min) and a delayed phase (2-14 h) after start of infusion. We found no difference in the incidence of reported migraine between FHM-2 patients, 25% (two out of eight), and controls, 0% (0 out of nine) (95% confidence interval -0.06, 0.56) (P = 0.21). The AUC(headache) in the immediate (P = 0.37) and delayed (P = 0.09) phase was not different between patients and controls. The GTN infusion resulted in a biphasic response in patients. During the immediate phase, the median peak headache occurred at 30 min and tended to be higher in patients, 1 (0, 3.8), than in controls, 0 (0, 1) (P = 0.056). During the delayed phase, the median peak headache occurred 4 h after the start of the infusion and was significantly higher in patients, 2.5 (0, 3), than in controls, 0 (0, 0) (P = 0.046). We found no difference in the AUC(VmeanMCA) (P = 0.77) or AUC(STA) (P = 0.53) between FHM-2 patients and controls. GTN infusion failed to induce more migraine in FHM-2 patients than in controls. The pathophysiological pathways underlying migraine headache in FHM-2 may be different from the common types of migraine.
Assuntos
Enxaqueca com Aura/genética , Enxaqueca com Aura/metabolismo , Óxido Nítrico/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Circulação Cerebrovascular , GMP Cíclico/metabolismo , Feminino , Genótipo , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/fisiologia , Enxaqueca com Aura/induzido quimicamente , Nitroglicerina , Artérias Temporais/fisiologia , VasodilatadoresRESUMO
OBJECTIVE: To estimate prevalence of Parkinson's disease (PD) and other types of parkinsonism in the Aeolian Archipelago, Sicily. METHODS: We studied the frequency of PD and other types of parkinsonism in the Aeolian Archipelago (population 13,431). All potential cases were identified from available medical information sources. To ensure the completeness of the case-findings, a screening questionnaire was also mailed to residents aged 40 years and over. Subjects were considered prevalent if they fulfilled the SNES diagnostic criteria for PD, on prevalence day (January 1, 2001). RESULTS: We identified 17 patients with parkinsonism from medical sources, and 4 from mail-survey. Prevalence for all types of parkinsonism was 156.3/100,000 (95% CI 99.4-234.8). Fourteen subjects fulfilled diagnostic criteria for PD giving a crude prevalence of 104.2/100,000 (95% CI 59.4-170.7) and 422.5/100,000 in the population aged 60 years and over. CONCLUSIONS: Prevalence of all types of parkinsonism and PD found in the Aeolian Archipelago is lower than that previously reported in Sicily.
Assuntos
Doença de Parkinson/epidemiologia , Transtornos Parkinsonianos/classificação , Transtornos Parkinsonianos/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Sicília/epidemiologiaRESUMO
Dementia is a common complication of Parkinson's disease (PD). It correlates significantly with the presence of cortical, limbic or nigral Lewy bodies, mainly constituted of alpha-synuclein. Mutations of the alpha-synuclein gene (SNCA) have been linked to rare familial forms of PD, while association studies on the promoter polymorphisms have given conflicting results in sporadic patients. We have performed a case control study to investigate whether genetic variability in the promoter of the alpha-synuclein gene could predispose to dementia in PD. A total of 114 demented patients and 114 non-demented patients with sporadic PD were included in the study. Six polymorphic loci (including the Rep1 microsatellite) in the promoter of the SNCA gene were examined. Each marker, taken individually, did not show association to dementia and no significant differences were observed in the inferred haplotype frequencies of demented and non-demented patients. Our data suggest the lack of involvement of the SNCA promoter in the pathogenesis of dementia in PD. Further studies in other populations are needed to confirm these results.
Assuntos
Demência/genética , Haplótipos , Doença de Parkinson/genética , Regiões Promotoras Genéticas , alfa-Sinucleína/genética , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
Treponema denticola is a proteolytic-anaerobic spirochete whose abundance in the subgingival crevice correlates with periodontal disease severity. Treponema denticola evades serum-mediated killing through the binding of factor H (FH), a negative regulator of the complement system. The T. denticolaFH receptor has been identified as FhbB, an 11.4kDa immunodominant lipoprotein. Three distinct subfamilies of FhbB proteins have been delineated and designated as FhbB1, FhbB2 and FhbB3. In this study we demonstrate that all FhbB variants bind human plasminogen (Plg). Competitive binding analyses revealed that FH and Plg do not compete for binding. Binding studies with FhbB135405 site-directed amino acid substitution mutants demonstrated that the interaction domains for FH and Plg on FhbB are separable. Inhibition of Plg-FhbB binding by ε-aminocaproic acid (a lysine analog) indicates that binding is mediated by electrostatic interactions that presumably occur with Lys binding sites contained within Plg "Kringle" domains 1, 2, 4 or 5. Similar to that demonstrated for FH, Plg can also serve as a substrate for the T. denticola protease, dentilisin. The in vivo consequences of dentilisin-mediated cleavage of Plg remained to be determined. The data presented demonstrate that FhbB is a multi-functional protein that may contribute to virulence through several mechanisms including immune evasion, manipulation of the host immune response, adherence or tissue invasion.
Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Bactérias/metabolismo , Fator H do Complemento/imunologia , Fator H do Complemento/metabolismo , Plasminogênio/metabolismo , Treponema denticola/imunologia , Treponema denticola/metabolismo , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/genética , Sítios de Ligação/imunologia , Complemento C3b/metabolismo , Fator H do Complemento/genética , Humanos , Evasão da Resposta Imune/imunologia , Lipoproteínas/metabolismo , Modelos Moleculares , Peptídeo Hidrolases/metabolismo , Ligação Proteica/imunologia , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismoRESUMO
We describe clinical and imaging features of a patient with sporadic progressive ataxia and palatal tremor (PAPT) of unknown etiology. There was hypertrophy of bilateral inferior olivary nuclei with hyperintense T2-weighted signal and mild cerebellar atrophy at brain magnetic resonance imaging. 18F-fluoro-2-desoxy-d-glucose positron emission tomography scanning (FDG-PET) showed hypometabolism in the red nucleus, external globus pallidus and precuneus while FP-CIT-SPECT imaging revealed mild and progressive loss of striatal dopaminergic terminals. Our findings suggest that in idiopathic PAPT involvement of the dentato-rubro-olivary pathway occurs along with some dopaminergic dysfunction.
Assuntos
Doenças dos Gânglios da Base/fisiopatologia , Ataxia Cerebelar/fisiopatologia , Dopamina/deficiência , Dissinergia Cerebelar Mioclônica/fisiopatologia , Mioclonia/fisiopatologia , Gânglios da Base/metabolismo , Gânglios da Base/patologia , Gânglios da Base/fisiopatologia , Doenças dos Gânglios da Base/diagnóstico por imagem , Doenças dos Gânglios da Base/patologia , Ataxia Cerebelar/diagnóstico por imagem , Ataxia Cerebelar/patologia , Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/patologia , Doenças Cerebelares/fisiopatologia , Núcleos Cerebelares/metabolismo , Núcleos Cerebelares/patologia , Núcleos Cerebelares/fisiopatologia , Diagnóstico Diferencial , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dissinergia Cerebelar Mioclônica/diagnóstico por imagem , Dissinergia Cerebelar Mioclônica/patologia , Mioclonia/diagnóstico por imagem , Mioclonia/patologia , Vias Neurais/metabolismo , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Núcleo Olivar/metabolismo , Núcleo Olivar/patologia , Núcleo Olivar/fisiopatologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Tomografia por Emissão de Pósitrons , Núcleo Rubro/metabolismo , Núcleo Rubro/patologia , Núcleo Rubro/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
INTRODUCTION: Several gender differences have been reported in Parkinson's Disease (PD). We evaluated the burden of non-motor symptoms (NMS) in PD and the possible gender differences in their occurrence. METHODS: The FRAGAMP study is a large multicenter case-control study. PD patients and controls underwent a face-to-face interview and a neurological examination performed by trained neurologists. Presence of NMS was investigated using a standardized questionnaire; cognitive impairment and depression were assessed using the Mini Mental State Examination and the Hamilton Depression Rating Scale respectively. RESULTS: 585 PD patients (59.5% men) and 481 controls (34.9% men) were enrolled in the study. All NMS were significantly more frequent among PD patients than controls. PD women showed a significantly higher frequency of depression and urinary disturbances than parkinsonian men; a close frequency among PD women and men was recorded for hallucination, cognitive impairment and sleep disorders. Nonetheless, with respect to the control population, according to logistic regression stratified by sex and adjusted by age, PD men showed a stronger positive significant association with almost all NMS compared to women, excepting for urinary disturbances. The strongest association among PD men was recorded for cognitive impairment (adjusted OR 5.44 for men and 2.82 for women) and depression (adjusted OR 30.88 for men and 12.72 for women). CONCLUSIONS: With respect to the general population, presence of NMS was stronger associated with male gender. Our data suggest that the presence of NMS among PD men is more strictly due to the neurodegenerative processes related to PD.
Assuntos
Gastroenteropatias/fisiopatologia , Doença de Parkinson/fisiopatologia , Caracteres Sexuais , Transtornos do Sono-Vigília/fisiopatologia , Idoso , Estudos de Casos e Controles , Transtorno Depressivo , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Doença de Parkinson/psicologia , Fatores de Risco , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/psicologiaRESUMO
This paper reports the preliminary results obtained by Electron Paramagnetic Resonance (EPR) measurements on films of IRGANOX® 1076 phenols with and without low content (5% by weight) of gadolinium oxide (Gd2O3) exposed in the thermal column of the Triga Mark II reactor of LENA (Laboratorio Energia Nucleare Applicata) of Pavia (Italy). Thanks to their size, the phenolic films here presented are good devices for the dosimetry of beams with high dose gradient and which require accurate knowledge of the precise dose delivered. The dependence of EPR signal as function of neutron dose was investigated in the fluence range between 10(11) cm(-2) and 10(14) cm(-2). Linearity of EPR response was found and the signal was compared with that of commercial alanine films. Our analysis showed that gadolinium oxide (5% by weight) can enhance the thermal neutron sensitivity more than 18 times. Irradiated dosimetric films of phenolic compound exhibited EPR signal fading of about 4% after 10 days from irradiation.
Assuntos
Espectroscopia de Ressonância de Spin Eletrônica/métodos , Nêutrons , Fenóis/química , CalibragemRESUMO
A Campylobacter jejuni gene, designated hup, that appears to encode a homolog of the histone-like DNA-binding protein, HU, has been cloned, sequenced and expressed in Escherichia coli. Immunoblotting and in vitro transcription/translation analyses revealed a 11-kDa protein that was produced by recombinant plasmids containing hup. The gene contains an open reading frame (ORF) sufficient to encode a protein of 98 amino acids (aa) with a calculated molecular mass of 10,267 Da and a predicted isoelectric point of 10.1. The deduced aa sequence of the protein, designated HCj, exhibits considerable sequence identity with members of the HU family of proteins from other eubacterial species. The transcription start point was identified by primer extension analysis and appropriately spaced promoter sequences were found which exhibit considerable similarity to E. coli and Bacillus promoters. Southern hybridization analyses indicate that C. jejuni has a single copy of hup.
Assuntos
Proteínas de Bactérias/genética , Campylobacter jejuni/genética , Proteínas de Ligação a DNA/genética , Genes Bacterianos , Sequência de Aminoácidos , Sequência de Bases , Northern Blotting , Southern Blotting , Clonagem Molecular , Eletroforese , Escherichia coli/genética , Expressão Gênica , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Alinhamento de SequênciaRESUMO
The ATP-dependent protease Lon (La) of Escherichia coli degrades abnormal proteins and is involved in the regulation of capsular polysaccharide synthesis. In addition, mutations in the E. coli lon gene suppress temperature-sensitive mutations in other genes. The lon gene of Borrelia burgdorferi, encoding a homolog of the Lon protease, has been cloned and sequenced. The gene encodes a protein of 806 amino acids. The deduced amino acid sequence of the B. burgdorferi Lon protease shares substantial sequence identity with those of other known Lon proteases. The transcription start point of the B. burgdorferi lon gene was identified by primer extension analysis and the potential promoter did not show similarities to the consensus heat-shock promoter in E. coli. The 5'-end of the B. burgdorferi lon gene appears to suppress the temperature-sensitive phenotype of an E. coli lpxA mutant.