RESUMO
INTRODUCTION: Patients with familial early-onset dementia (EOD) pose a unique opportunity for gene identification studies. METHODS: We present the phenotype and whole-exome sequencing (WES) study of an autosomal dominant EOD family. Candidate genes were examined in a set of dementia cases and controls (n = 3712). Western blotting was conducted of the wild-type and mutant protein of the final candidate. RESULTS: Age at disease onset was 60 years (range 56 to 63). The phenotype comprised mixed amnestic and behavioral features, and parkinsonism. Cerebrospinal fluid and plasma biomarkers, and a positron emission tomography amyloid study suggested Alzheimer's disease. WES and the segregation pattern pointed to a nonsense mutation in the TRIM25 gene (p.C168*), coding for an E3 ubiquitin ligase, which was absent in the cohorts studied. Protein studies supported a loss-of-function mechanism. DISCUSSION: This study supports a new physiopathological mechanism for brain amyloidosis. Furthermore, it extends the role of E3 ubiquitin ligases dysfunction in the development of neurodegenerative diseases. HIGHLIGHTS: A TRIM25 nonsense mutation (p.C168*) is associated with autosomal dominant early-onset dementia and parkinsonism with biomarkers suggestive of Alzheimer's disease. TRIM25 protein studies support that the mutation exerts its effect through loss of function. TRIM25, an E3 ubiquitin ligase, is known for its role in the innate immune response but this is the first report of association with neurodegeneration. The role of TRIM25 dysfunction in development of amyloidosis and neurodegeneration merits a new line of research.
Assuntos
Doença de Alzheimer , Amiloidose , Demência , Transtornos Parkinsonianos , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Códon sem Sentido , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Transtornos Parkinsonianos/diagnóstico por imagem , Transtornos Parkinsonianos/genética , Proteínas Amiloidogênicas , Biomarcadores , Proteínas com Motivo Tripartido/genética , Fatores de Transcrição/genéticaRESUMO
Water radiolysis involves chemical decomposition of the water molecule into free radicals after exposure to ionizing radiation. These free radicals have deleterious effects on normal cell physiology. Carboxylated nanodiamonds (cNDs) appear to modulate the deleterious effects of γ-irradiation on the pathophysiology of red blood cells (RBCs). In the present work, the antioxidant activity of hydrated cNDs (h-cNDs) on limiting oxidative damage (the water radiolysis effect) by γ-irradiation was confirmed. Our results show that h-cNDs have remarkable free radical scavenging ability and preserve the enzymatic activity of catalase after γ-irradiation. The underlying mechanism through which nanodiamonds exhibit antioxidant activity appears to depend on their colloidal stability. This property of detonation synthesized nanodiamonds is improved after carboxylation, which in turn influences changes in the hydrogen bond strength in water. The observed stability of h-cNDs in water and their antioxidant activity correlates with their protective effect on RBCs against γ-irradiation.
RESUMO
Brazil has 9 million ha of sugarcane, 85% of which are located in the Center-South area of the country. Field trials and surveys around the globe have shown that ratoon stunt disease (RSD), caused by Leifsonia xyli subsp. xyli, can severely reduce tonnage yield. Previous small-scale studies in Brazil have demonstrated RSD infection in all varieties, with values varying from 25 to 68%. Nevertheless, the prevalence and severity of RSD in commercial fields had not previously been assessed. To address this issue, we surveyed 13,173 ha in 1,154 fields of the eight main sugarcane varieties of the Center-South area, taking 92,114 samples from 50 mills in five different states. Our data showed that 10% of fields were infected, and that 58% of mills had at least one RSD-infected field. The variety RB92579 had the highest proportion of infected fields (17%) and, on average, the prevalence and severity in these fields was high compared with other varieties. RB867515, the most cultivated in Brazil, showed infection in 6.2% of sampled fields (5.5% of sampled area) causing an estimated annual economic loss of over US$1 million. This was the first time the economic importance of RSD on Brazilian commercial sugarcane production was estimated. The Cerrado region had the highest prevalence of RSD: 16% of fields, 17% of the cultivated area, and 82% of mills. The use of diseased planting material was identified in 9% of plant cane fields, representing 10% of the cultivated area. Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
RESUMO
BACKGROUND: Patients with primary progressive aphasia (PPA) usually develop significant behavioral disturbances with progression of the disease. We tested our clinical observation that development of disruptive agitation is more likely in semantic than in nonfluent PPA and examined which clinical variables could be associated with this behavior. METHODS: We retrospectively analyzed neuropsychiatric scores and the need for behavioral treatments in semantic PPA (n = 41) and nonfluent PPA (n = 39) cases and compared first (1-3 years since the onset of symptoms) and last (5-13 years since the onset) evaluations. Clinical variables and laterality of temporal atrophy were associated with symptoms in semantic PPA cases. RESULTS: The semantic PPA group developed more frequent (p = 0.03) and intense agitation (p = 0.0008) and had a greater need for antipsychotic drugs (p = 0.001) than the nonfluent PPA group. Presence of agitation was clearly associated with psychotic symptoms (delusions/hallucinations) but was not associated with gender, age at onset, duration of the disease, or laterality of temporal atrophy. In contrast, nonfluent PPA cases were more frequently depressed and treated with antidepressants (p = 0.0007). There were no differences in anxiety, irritability, apathy, perseverations, hyperorality, or abnormal motor behavior. CONCLUSIONS: Semantic PPA in advanced disease is frequently associated with agitation and psychotic symptoms with fewer mood symptoms, while nonfluent PPA maintains a high prevalence of depression. This implies different treatment and care and support needs for each group.
Assuntos
Afasia Primária Progressiva/psicologia , Delusões/etiologia , Depressão/etiologia , Afasia Primária Progressiva não Fluente/psicologia , Agitação Psicomotora/etiologia , Idoso , Atrofia , Delusões/diagnóstico , Depressão/diagnóstico , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Agitação Psicomotora/diagnóstico , Estudos Retrospectivos , Lobo TemporalRESUMO
AIMS: Bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae (Psa) is currently the major threat to its commercial production worldwide. In 2011, the most virulent type (Psa3) was detected for the first time in Northwest-Spain, in the province of Pontevedra. In 2013 surveys, leaves and flower buds with mild symptoms were observed in Actinidia deliciosa 'Hayward' vines in an orchard at the province of A Coruña, suggesting the presence of P. syringae pv. actinidifoliorum (Psaf). METHODS AND RESULTS: Isolates obtained from such orchard were characterized by morphological, biochemical and physiological tests, fatty acids (FA) profile and molecular tests (PCR, BOX-PCR, duplex PCR, multiplex PCR, real-time PCR, PCR-C, phytotoxins, housekeeping and effector genes). Pathogenicity tests were also carried out on plants and fruits of A. deliciosa 'Hayward' and on different cultivated plants and fruits. Results demonstrated the presence of P. syringae pv. actinidifoliorum in Spain. CONCLUSIONS: The work provides new information on the pathovar P. syringae pv. actinidifoliorum, which has only been found previously in New Zealand, Australia and France. SIGNIFICANCE AND IMPACT OF STUDY: The results are relevant for taxonomy of isolates of P. syringae from kiwifruit, especially those of low virulence not belonging to pathovar actinidiae.
Assuntos
Actinidia/microbiologia , Frutas/microbiologia , Doenças das Plantas/microbiologia , Pseudomonas syringae , Pseudomonas syringae/genética , Pseudomonas syringae/isolamento & purificação , Pseudomonas syringae/patogenicidadeRESUMO
BACKGROUND: In recent years, a benign variant of frontotemporal lobar degeneration (FTLD) has been recognized, with a particularly slow progression of cognitive deficits and scarce frontotemporal atrophy or hypoperfusion in neuroimaging studies. Patients with FTLD have been considered "phenocopies," with an underlying nondegenerative neurologic process. RESULTS: We report the first family with three affected members having benign FTLD associated with C9ORF72 gene hexanucleotide expansion. Onset of symptoms occurred during the fifth decade, with naming and memory problems as the main features. Two siblings have stabilized at mild cognitive impairment or incipient dementia for more than a decade, and remain quite independent for their activities of daily living at the current ages of 69 and 65 years, respectively. Their mother's cognitive deterioration evolved slowly during >30 years. CONCLUSION: This family demonstrates that a benign evolution can be part of the growing spectrum of clinical phenotypes associated with neurodegenerative diseases caused by the C9ORF72 hexanucleotide expansion. Screening of this genetic marker should be considered in cases with this slow deterioration, especially if there is a family history.
Assuntos
Expansão das Repetições de DNA , Degeneração Lobar Frontotemporal/genética , Proteínas/genética , Idade de Início , Idoso , Encéfalo/patologia , Proteína C9orf72 , Colestase , Feminino , Degeneração Lobar Frontotemporal/patologia , Humanos , Masculino , Linhagem , Fenótipo , PneumoniaRESUMO
BACKGROUND: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. METHODS: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. RESULTS: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. CONCLUSIONS: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.
Assuntos
Demência Frontotemporal , Masculino , Humanos , Feminino , Progranulinas/genética , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Virulência , Mutação/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genéticaRESUMO
BACKGROUND AND PURPOSE: Decreased plasma progranulin levels are a very specific marker for the diagnosis of frontotemporal lobar degeneration (FTLD) caused by mutations in the progranulin gene (GRN). A frequent neuroimaging pattern in this type of dementia is asymmetric cortical atrophy. The aim of this study was to screen for GRN-linked FTLD in cases with different cortical dementia phenotypes and asymmetric perisylvian atrophy. METHODS: Progranulin plasma levels were analyzed in a variety of FTLD phenotypes (n = 71), dementia of the Alzheimer type (DAT) (n = 22) and probable Lewy body dementia (n = 8), both latter groups presented with asymmetric perisylvian atrophy. A group of elderly controls (n = 29) and DAT cases with symmetric atrophy (n = 33) were also analyzed. The GRN gene was sequenced in cases with lower plasma levels. RESULTS: Four cases with clinical FTLD phenotypes and plasma levels below 70 ng/ml were found to carry different GRN mutations: M1?, C139R, a point mutation in the splice donor site of intron 3 (A89VfsX41), and a deletion in exon 9 (A303AfsX57), this latter one being a new mutation. Thirteen cases with levels between 72 and 85 ng/ml did not show pathogenic changes in the GRN gene. None of the cases with asymmetric atrophy and clinical phenotypes other than FTLD had GRN mutations. CONCLUSIONS: Asymmetric perisylvian atrophy is not likely to predict progranulin-linked FTLD unless it is associated with a consistent FTLD clinical phenotype.
Assuntos
Demência/sangue , Demência/patologia , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Idoso , Idoso de 80 Anos ou mais , Atrofia , Demência/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Degeneração Lobar Frontotemporal/sangue , Degeneração Lobar Frontotemporal/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Masculino , Mutação , Fenótipo , ProgranulinasRESUMO
INTRODUCTION: Bisphosphonates are used worldwide to treat osteoporosis and, thus, to prevent fractures. Though they have been proven in clinical trials to avoid some fractures, their effectiveness in reducing hip fractures is unclear. The aim of the present study was to explore the relationship between bisphosphonate use and hip fracture trends in Spain. METHODS: For this purpose, an ecologic study spanning 2002 to 2008 was conducted in Spain. Consumption data were obtained from the Spanish Ministry of Health and Social Policy. The number of hip fractures was obtained from hospital discharges; annual hip fracture rates were determined and standardized using the Spanish 2002 population census. A linear regression was performed between fracture rate and use of bisphosphonates; R(2) and Pearson correlation coefficient were calculated. RESULTS: From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. In the same period, the crude hip fracture rate increased from 2.85 to 3.02 cases per 1,000 inhabitants older than 50 years; however, when age standardized rates were estimated, the rate declined from 2.85 to 2.79. Analyzed by sex, the standardized rate for men slightly increased from 1.45 to 1.48, while for women the rate significantly dropped from 4.00 to 3.91. CONCLUSION: A small effect of bisphosphonates on hip fracture rates can not be ruled out; however, other factors might partially explain this decline. Assuming this medication was the only cause for hip fracture rate reduction, the elevated medication cost to avoid a single hip fracture makes it necessary to explore less expensive interventions.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas do Quadril/prevenção & controle , Osteoporose/tratamento farmacológico , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores Sexuais , Espanha/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Low-temperature neutron diffraction experiments at [Formula: see text] GPa have been conducted to investigate the magnetic structures of metallic Holmium at high pressures by employing a long d-spacing high-flux diffractometer and a Paris-Edinburgh press cell inside a cryostat. We find that at [Formula: see text] GPa and [Formula: see text] K, no nuclear symmetry change is observed, keeping therefore the hexagonal closed packed (hcp) symmetry at high pressure. Our neutron diffraction data confirm that the ferromagnetic state does not exist. The magnetic structure corresponding to the helimagnetic order, which survives down to 5 K, is fully described by the magnetic superspace group formalism. These results are consistent with those previously published using magnetization experiments.
Assuntos
Demência Frontotemporal/genética , Doença dos Neurônios Motores/genética , Doença dos Neurônios Motores/psicologia , Mutação/genética , Proteínas Serina-Treonina Quinases/genética , Idoso , Estudos de Casos e Controles , Europa (Continente) , Feminino , Demência Frontotemporal/complicações , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
BACKGROUND: : Finding variables that predict decline or stability in persons with amnestic mild cognitive impairment (aMCI) is an important step in identifying subjects in prodromal stages of dementia. This study tests a clinical observation suggesting that aMCI cases with better-preserved recognition skills, despite similar delayed recall deficits, are more likely to remain functionally stable. METHODS: : A cohort of 210 cases with aMCI, diagnosed with standardized criteria that had been followed up for 48 ± 12 months (range: 36-100), were divided into two groups according to their initial recognition memory discrimination index (DI) on the Hopkins Verbal Learning Test (DI ≥ or <8). We compared the two groups according to demographic and neuropsychological variables, cerebral small vessel disease, and outcome (progression to dementia versus stability as aMCI). RESULTS: : Thirty-seven percent progressed to dementia. In the group with the higher DI scores (n = 107), only 21.5% of the cases converted, compared with 52.4% of lower scorers (n = 103; Fisher's test: p < 0.0001). Progression to dementia occurred significantly later in cases with higher DI (50 ± 17 versus 26 ± 11 months in cases with impaired DI, Mann-Whitney test, U statistic = 1092.5, p < 0.0001). The group with lower DI showed a threefold-increased rate of progression to dementia. A multivariate regression model revealed DI, delayed recall, age, and family history of dementia as the strongest predictors of dementia, in this order. CONCLUSIONS: : The aMCI patients with better-preserved recognition at baseline have a more benign prognosis. Detection of these cases may aid in isolating other aMCI cases that are already in prodromal stages of AD and in selecting more homogeneous groups for clinical trials.
Assuntos
Amnésia/psicologia , Disfunção Cognitiva/psicologia , Rememoração Mental , Reconhecimento Psicológico , Fatores Etários , Idoso , Amnésia/complicações , Amnésia/genética , Apolipoproteínas E/genética , Disfunção Cognitiva/complicações , Disfunção Cognitiva/genética , Progressão da Doença , Saúde da Família , Feminino , Seguimentos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricosRESUMO
INTRODUCTION: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). OBJECTIVE: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. PATIENTS AND METHODS: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. RESULTS: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection > 2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. CONCLUSIONS: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.
Assuntos
Poliomielite , Síndrome Pós-Poliomielite , Progressão da Doença , Fadiga , Feminino , Humanos , Poliomielite/complicações , Síndrome Pós-Poliomielite/complicações , Síndrome Pós-Poliomielite/diagnóstico , Síndrome Pós-Poliomielite/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Visual hallucinations are a core feature of dementia with Lewy bodies (DLB) and have been proposed as being part of a narcolepsy-like REM sleep disorder. Selective loss of hypothalamic hypocretin-producing neurons is common to both narcolepsy and the spectrum of Lewy body diseases. We hypothesized that the genetic marker associated with narcolepsy, the HLA class II DR2-DQ6 haplotype, could confer some degree of susceptibility to brainstem-hypothalamic damage leading to the manifestation of visual hallucinations. METHODS: We examined HLA class II haplotypes in 30 patients with prominent visual hallucinations in the context of clinical criteria for DLB and in 30 patients affected by a cortical-type dementia without hallucinations. RESULTS: No significant differences were found in the distribution of DR and DQ antigens. CONCLUSIONS: We conclude that hypothalamic vulnerability in different diseases is not mediated by a common HLA haplotype.
Assuntos
Demência/genética , Demência/psicologia , Genes MHC da Classe II/genética , Antígenos HLA/genética , Alucinações/genética , Alucinações/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos HLA-DQ , Antígenos HLA-DR , Haplótipos , Humanos , Doença por Corpos de Lewy/genética , Doença por Corpos de Lewy/psicologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the efficacy of the solar water disinfection (SODIS) method for inactivating Cryptosporidium parvum oocysts in turbid waters using 1.5 l polyethylene terephthalate (PET) bottles under natural sunlight. METHODS: All experiments were performed at the Plataforma Solar de Almería, located in the Tabernas Desert (Southern Spain) in July and October 2007. Turbid water samples [5, 100 and 300 nephelometric turbidity units (NTU)] were prepared by addition of red soil to distilled water, and then spiked with purified C. parvum oocysts. PET bottles containing the contaminated turbid waters were exposed to full sunlight for 4, 8 and 12 h. The samples were then concentrated by filtration and the oocyst viability was determined by inclusion/exclusion of the fluorogenic vital dye propidium iodide. Results After an exposure time of 12 h (cumulative global dose of 28.28 MJ/m(2); cumulative UV dose of 1037.06 kJ/m(2)) the oocyst viabilities were 11.54%, 25.96%, 41.50% and 52.80% for turbidity levels of 0, 5, 100 and 300 NTU, respectively, being significantly lower than the viability of the initial isolate (P < 0.01). CONCLUSIONS: SODIS method significantly reduced the potential viability of C. parvum oocysts on increasing the percentage of oocysts that took up the dye PI (indicator of cell wall integrity), although longer exposure periods appear to be required than those established for the bacterial pathogens usually tested in SODIS assays. SODIS.
Assuntos
Cryptosporidium parvum/efeitos da radiação , Desinfecção/métodos , Água Doce/parasitologia , Luz Solar , Purificação da Água/métodos , Animais , Cryptosporidium parvum/crescimento & desenvolvimento , Cryptosporidium parvum/isolamento & purificação , Cryptosporidium parvum/metabolismo , Relação Dose-Resposta à Radiação , Nefelometria e Turbidimetria , Oocistos/crescimento & desenvolvimento , Oocistos/efeitos da radiação , Polietilenotereftalatos/farmacocinética , TemperaturaRESUMO
Species belonging to the genera Cryptosporidium are recognized as waterborne pathogens. Solar water disinfection (SODIS) is a simple method that involves the use of solar radiation to destroy pathogenic microorganisms that cause waterborne diseases. A notable increase in water temperature and the existence of a large number of empty or partially excysted (i.e. unviable) oocysts have been observed in previous SODIS studies with water experimentally contaminated with Cryptosporidium parvum oocysts under field conditions. The aim of the present study was to evaluate the effect of the temperatures that can be reached during exposure of water samples to natural sunlight (37-50 degrees C), on the excystation of C. parvum in the absence of other stimuli. In samples exposed to 40-48 degrees C, a gradual increase in the percentage of excystation was observed as the time of exposure increased and a maximum of 53.81% of excystation was obtained on exposure of the water to a temperature of 46 degrees C for 12 h (versus 8.80% initial isolate). Under such conditions, the oocyst infectivity evaluated in a neonatal murine model decreased statistically with respect to the initial isolate (19.38% versus 100%). The results demonstrate the important effect of the temperature on the excystation of C. parvum and therefore on its viability and infectivity.
Assuntos
Cryptosporidium parvum/fisiologia , Cryptosporidium parvum/efeitos da radiação , Desinfecção/métodos , Oocistos/efeitos da radiação , Luz Solar , Animais , Criptosporidiose/parasitologia , Criptosporidiose/patologia , Cryptosporidium parvum/patogenicidade , Modelos Animais de Doenças , Camundongos , Oocistos/crescimento & desenvolvimento , Temperatura , Água/parasitologiaRESUMO
The G protein-coupled receptor kinase 2 (GRK2) phosphorylates and desensitizes ligand-activated G protein-coupled-receptors. Here, evidence is shown for a novel role of GRK2 in regulating chemokine-mediated signals. The presence of increased levels of GRK2 in human embryonic kidney (HEK) 293 cells produced a significant reduction of the extracellular signal-regulated kinase (ERK) response to CCL2. This effect is independent of its role in receptor phosphorylation because the kinase-deficient mutant GRK2K220R was able to reduce this response, and ERK activation by CCR2BIX, a phosphorylation-defective receptor mutant, was also inhibited by GRK2. Constructs containing the Galpha(q)-binding RGS-like RH domain of GRK2 or its Gbetagamma-binding domain could not reproduce the inhibition, thus revealing that GRK2 acts downstream of G proteins. Interestingly, chemokine-driven mitogen-activated protein kinase kinase (MEK) stimulation is not affected in cells overexpressing GRK2 or GRK2K220R or in splenocytes from heterozygous GRK2 mice, where reduced kinase levels correlate with enhanced ERK activation by chemokines. We find GRK2 and MEK in the same multimolecular complex, thus suggesting a mechanism for GRK2 regulation of ERK activity that involves a direct or coordinate interaction with MEK. These results suggest an important role for GRK2 in the control of chemokine induction of ERK activation at the level of the MEK-ERK interface.
Assuntos
Quimiocina CCL2/farmacologia , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases de Receptores Adrenérgicos beta/metabolismo , Animais , Células Cultivadas , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Transgênicos , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica , Subunidades Proteicas/metabolismo , Quinases de Receptores Adrenérgicos beta/genéticaRESUMO
INTRODUCTION: Patients presenting sequelae of poliomyelitis may present new symptoms, known as post-polio syndrome (PPS). OBJECTIVE: To identify the clinical and functional profile and epidemiological characteristics of patients presenting PPS. PATIENTS AND METHODS: We performed a retrospective study of 400 patients with poliomyelitis attended at the Institut Guttmann outpatient clinic, of whom 310 were diagnosed with PPS. We describe patients' epidemiological, clinical, and electromyographic variables and analyse the relationships between age of poliomyelitis onset and severity of the disease, and between sex, age of PPS onset, and the frequency of symptoms. RESULTS: PPS was more frequent in women (57.7%). The mean age at symptom onset was 52.4 years, and was earlier in women. Age at primary infection >2 years was not related to greater poliomyelitis severity. The frequency of symptoms was: pain in 85% of patients, loss of strength in 40%, fatigue in 65.5%, tiredness in 57.8%, cold intolerance in 20.2%, dysphagia in 11.7%, cognitive complaints in 9%, and depressive symptoms in 31.5%. Fatigue, tiredness, depression, and cognitive complaints were significantly more frequent in women. Fifty-nine percent of patients presented electromyographic findings suggestive of PPS. CONCLUSIONS: While the symptoms observed in our sample are similar to those reported in the literature, the frequencies observed are not. We believe that patients' clinical profile may be very diverse, giving more weight to such objective parameters as worsening of symptoms or appearance of weakness; analysis of biomarkers may bring us closer to an accurate diagnosis.
RESUMO
This work describes the evaluation of a glass ceramic (55S41C4P-1300) as a potential substrate for bone tissue engineering. For that purpose, the capacity of mesenchymal stem cells (MSCs), isolated from rabbit bone marrow, to adhere, proliferate and differentiate into osteoblast (OBs) with or without 55S41C4P-1300 was investigated. Two types of culture medium, i.e. growth medium (GM) and osteogenic medium (OM), were evaluated. The bioactive 55S41C4P-1300, containing pseudowollastonite, wollastonite, tricalcium phosphate and crystoballite as crystalline phases, was obtained by heat treatment of a sol-gel glass (55SiO(2), 41CaO, 4P(2)O(5) (mol.%)) at 1300 degrees C. The results showed that the MSCs adhered, spread, proliferated and produced mineralized extracellular matrix on 55S41C4P-1300 regardless of the culture medium used. As the same time, they showed an osteoblastic phenotype, and this phenomenon was accompanied by the gradual diminution of the marker CD90 expression. The 55S41C4P-1300 was able to induce the differentiation of MSCs into OBs in the same way as OM without glass ceramic. This effect increased with the combination of 55S41C4P-1300 with OM. The glass ceramic evaluated in this work is bioactive, cytocompatible and capable of promoting the differentiation of MSCs into OBs. For that reason, it could be regarded as a suitable matrix in tissue engineering for bone tissue regeneration.
Assuntos
Cerâmica/farmacologia , Vidro/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultura , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fluorescência , Células-Tronco Mesenquimais/ultraestrutura , Microscopia Eletrônica de Varredura , Osteocalcina/metabolismo , Coelhos , Análise Espectral , Antígenos Thy-1/metabolismoRESUMO
The effects of drying and pelletizing on the properties of broiler chicken litter, obtained from a farm in northwest Spain, were investigated. The drying and pelletizing process reduced among-batch variability in dry matter content, electrical conductivity, urea N, and K, S, Na, Fe, Cu and Cd contents, but increased among-batch variability in total N, ammonium N, nitrate N, total P and pH. N form contents in the pelletized product could be estimated with reasonable accuracy on the basis of dry matter content. Cr, Cu and Cd contents were all significantly lower in the dried pelletized product than in fresh litter, whereas Pb content was significantly higher. The dried pelletized product is of course clearly preferable to the fresh product as regards storage and handling, however, our results suggest a need to optimize the production process with the aim of reducing possible contamination during manufacture, and of minimizing variability in N form contents, P content and pH.