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The goal of this study was to apply the principles of analytical quality by design (AQbD) to the analytical method for determining the radiochemical purity (PQR) of the radiopharmaceutical sodium iodide 131I oral solution, utilizing thin-layer chromatography (TLC) with a radio-TLC scanner, which also enables the evaluation of product quality. For AQbD, the analytical target profile (ATP), critical quality attributes (CQA), risk management, and the method operable design region (MODR) were defined through response surface methodology to optimize the method using MINITAB® 19 software. This study encompassed the establishment of a control strategy and the validation of the method, including the assessment of selectivity, linearity, precision, robustness, detection limit, quantification limit, range, and the stability of the sample solution. Under the experimental conditions, the method parameters of the TLC scanner were experimentally demonstrated and optimized with an injection volume of 3 µL, a radioactive concentration of 10 mCi/mL, and a carrier volume of 40 µL. Statistical analysis confirmed the method's selectivity for the 131I iodide band Rf of 0.8, a radiochemical impurity IO3- Rf of 0.6, a linearity from 6.0 to 22.0 mCi/mL, and an intermediate precision with a global relative standard deviation (RSD) of 0.624%. The method also exhibited robustness, with a global RSD of 0.101%, a detection limit of 0.09 mCi/mL, and a quantification limit of 0.53 Ci/mL, meeting the prescribed range and displaying stability over time (at 0, 2, and 20 h) with a global RSD of 0.362%, resulting in consistent outcomes. The development of a method based on AQbD facilitated the creation of a design space and an operational space, with comprehensive knowledge of the method's characteristics and limitations. Additionally, throughout all operations, compliance with the acceptance criteria was verified. The method's validity was confirmed under the established conditions, making it suitable for use in the manufacturing process of sodium iodide 131I and application in nuclear medicine services.
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Radioisótopos de Yodo , Radiofármacos , Yoduro de Sodio , Cromatografía en Capa Delgada/métodos , Radiofármacos/química , Radiofármacos/análisis , Radioisótopos de Yodo/análisis , Yoduro de Sodio/química , Administración Oral , Reproducibilidad de los ResultadosRESUMEN
Previous research suggests that the Ages and Stages Questionnaire-3rd ed. (ASQ) fine motor domain (FMD) may not be culturally relevant for developmental screening in a rural Guatemalan community, as the FMD accounts for 40% of all abnormal screenings after a needs assessment in this community. We hypothesize this is due to a lack of exposure to objects assessed in the questionnaire, such as blocks or light switches. The FMD scores of rural Guatemalan children (n = 56) participating in a child development program were compared with Spanish- and English-speaking Latinx-American children attending a US primary care clinic and screened at yearly well-child checks. Groups were matched for age gender, and socioeconomic status. Item-level analyses explored differences across the three groups. In the Guatemalan sample, the FMD abnormal score rates were 16%, 62%, and zero in the 12-, 24-, and 36-month-old children, respectively. Abnormal scores for the Guatemalan sample on the 24-month ASQ-3 significantly differed (p = .01) when compared to the Latinx-American groups. The 24-month questionnaire has more questions about objects than the 12- and 36-month questionnaires, which may explain the higher rates of abnormal scores. Developmental screening with ASQ-3 may not adequately capture the skills of children in similar communities.
La investigación previa ha sugerido que el dominio de motricidad fina (FMD) del Cuestionario de Edades y Etapas - Tercera edición (ASQ) pudiera no ser culturalmente relevante para examinar el desarrollo en una comunidad rural de Guatemala, ya que el FMD representa el 40% de todas las examinaciones anormales después de la evaluación de necesidades en esta comunidad. Nuestra hipótesis es que esto se debe a la falta de exposición a objetos evaluados en el cuestionario, tales como bloques o interruptores de luz. Se compararon los puntajes del FMD de niños de áreas rurales en Guatemala (n=56) que participan en un programa de desarrollo del niño con niños norteamericanos latin-x hablantes del español y del inglés, quienes asisten a una clínica de cuidado primario y son examinados en chequeos anuales de rutina para niños sanos. Se clasificaron los grupos según la edad, el género y la condición económica. Los análisis del nivel de cada punto exploraron las diferencias a lo largo de los 3 grupos. En el grupo muestra de Guatemala, los índices de puntajes anormales de FMD fueron 16%, 62% y cero en los niños de 12, 24 y 36 meses de edad, respectivamente. Los puntajes anormales para el grupo de Guatemala en el ASQ-3 a los 24 meses significativamente difirieron (p=0.01) cuando se les comparó con los grupos muestras norteamericanos latin-x. El cuestionario para la edad de 24 meses tiene más preguntas acerca de objetos que los cuestionarios para las edades de 12 y 36 meses, lo cual pudiera explicar los más altos índices de puntajes anormales. La examinación del desarrollo con ASQ-3 pudiera no captar adecuadamente las destrezas de niños en comunidades similares.
Les recherches précédentes suggèrent que le domaine de la motricité fine (FMD en anglais) du Questionnaire des Ages et des Etapes - 3e édition (ASQ en anglais) pourrait ne pas être pertinent sur le point culturel pour le dépistage développemental dans une communauté rurale du Guatémala puisque le FMD explique 40% de tous les dépistages anormaux après une évaluation des besoins dans cette communauté. Nous émettons l'hypothèse que cela est dû au manque d'exposition à des objets évalués dans le questionnaire, comme des blocs ou des interrupteurs (électricité). Les scores de FMD d'enfants de milieu rural au Guatémala (n=56) participant à un programme de développement de l'enfant ont été comparés à ceux d'enfants Latinx-Américains parlant espagnol et anglais, patients d'une clinique de soins primaires aux Etats-Unis d'Amérique et dépisté avec des contrôles de santé annuels. Les groupes ont été assortis par groupe de genre et de statut socioéconomique. Des analyses de précision ont exploré les différences entre les 3 groupes. Dans l'échantillon du Guatémala les taux de score anormal FMD étaient de 16%, 62% et zéro chez les enfants de 12, 24 et 36 mois, respectivement. Les scores anormaux pour l'échantillon du Guatémala pour le ASQ-3 à 24 moi a différé de manière importante (p=0.01) lors de la comparaison aux groupes Latinx-Américains. Le questionnaire de 24 mois a plus de questions sur les objets que les questionnaires de 12 mois et de 36 mois, ce qui peut expliquer les taux plus élevés de scores anormaux. Le dépistage développemental avec le ASQ-3 pourrait s'avérer ne pas capturer de manière adéquate les compétences des enfants dans des communautés similaires.
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Desarrollo Infantil , Discapacidades del Desarrollo , Humanos , Lactante , Preescolar , Niño , Guatemala , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Discapacidades del Desarrollo/diagnósticoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Myrcia multiflora (Lam) DC. is a medicinal plant used in folk medicine for diabetes control, mainly in the Brazilian Amazon. The leaves of this species has already demonstrated antidiabetic properties; however, in mice with type 2 diabetes (DM2), the cumulative effect of the consumption of the dry extract of M. multiflora leaves (Mm) has not yet been reported. AIM OF THE STUDY: To investigate the effect of the dry extract obtained from the infusion of the dried leaves of M. multiflora on the blood glucose levels of diabetic mice. MATERIALS AND METHODS: DM2 was induced in Swiss male mice by a single intraperitoneal injection of streptozotocin [150 mg/kg body weight (bw)]. The animals were divided into two control groups (healthy and diabetic without treatment) and three sample groups that received Mm (25 and 50 mg/kg bw) and acarbose (200 mg/kg bw) by gavage once daily for 28 days (D28). Additionally, biochemical parameters, thiobarbituric acid reactive species (TBARS) levels in the liver, and histopathological analyses of the kidneys and liver were performed. RESULTS: On the seventh day of treatment, a 74.7% reduction in glucose levels were observed in the group of diabetic animals treated with Mm (50 mg/kg bw) when compared to the beginning of the treatment. At D28, the hypoglycemic effect was maintained. The results of the biochemical and histopathological parameters and the TBARS levels suggest that this dry extract exerts nephro- and hepatoprotective effects. CONCLUSIONS: The findings demonstrate the potential that this extract has to inhibit the α-glucosidase enzyme, and it acts similarly to the positive control acarbose. Furthermore, this extract is nephro- and hepatoprotective. Therefore, this dry extract has the potential to be an adjuvant for DM2, which corroborates its use in folk medicine.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Myrtaceae , Ratones , Animales , Hipoglucemiantes/farmacología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estreptozocina/farmacología , Acarbosa/efectos adversos , Extractos Vegetales/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Sustancias Reactivas al Ácido Tiobarbitúrico , Glucemia , Hojas de la Planta/química , HígadoRESUMEN
ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.
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This paper explores the epistemological sources of C.G. Jung's psychology over the course of its historical evolution. It considers whether his model should be seen as a scientific-philosophical, artistic, or an ethical-mystical model, or a combination of these; whether epistemological knowledge can come from getting a 'vision of the whole' or 'grasping the particulars thoroughly' (Jung 1939, para. 1012); as well as exploring the philosophers of science with whom Jung's epistemological model best coheres. The paper calls on the work of Joseph Henderson and his concept of the cultural unconscious, as well as exploring the contribution of Brazilian and Latin American civilization to the evolution of analytical psychology.
Cet article explore les sources épistémologiques de la psychologie de C.G. Jung au long de son évolution historique. L'article examine si son modèle devrait être considéré comme scientifique-philosophique, artistique, ou comme un modèle éthique-mystique, ou encore une combinaison de plusieurs de ces éléments. L'article s'intéresse également à la question suivante: le savoir épistémologique provient-il de l'obtention d'une « vision du tout ¼ ou bien « d'appréhender les details avec précision¼ (Jung 1939, para. 1012)? Il explore aussi l'apport des philosophes de la science avec lesquels le modèle épistémologique de Jung s'accorde le mieux. L'article s'appuie sur le travail de Joseph Henderson et son concept d'inconscient culturel, et étudie aussi l'apport des civilisations Brésilienne et d'Amérique Latine dans l'évolution de la psychologie analytique.
El presente trabajo explora las fuentes epistemológicas de la psicología de C.G. Jung a través de su evolución histórica. Considera si su modelo debiera ser visto como científico-filosófico, artístico, o como un modelo ético-místico, o una combinación de ambos; si el conocimiento epistemológico puede venir a través de 'una visión de la totalidad' o de 'aprehender las particularidades minuciosamente' (Jung 1939, para. 1012), También se exploran aquellos filósofos de la ciencia con quienes el modelo epistemológico de Jung coincide mejor. El escrito invoca el trabajo de Joseph Henderson y su concepto de inconsciente cultural, así como también explora la contribución de la civilización Brasilera y Latinoamericana a la evolución de la psicología analítica.
Este artigo explora as fontes epistemológicas de C.G. Jung. A psicologia de Jung ao longo de sua evolução histórica. Considera se seu modelo deve ser visto como um modelo científico-filosófico, artístico ou ético-místico, ou uma combinação destes; se o conhecimento epistemológico pode advir de obter uma "visão do todo" ou de "agarrar os detalhes completamente" (Jung 1939, parágrafo 1,012); bem como explorar os filósofos da ciência com quem o modelo epistemológico de Jung combina melhor. O artigo recorre ao trabalho de Joseph Henderson e seu conceito de inconsciente cultural, além de explorar a contribuição da civilização brasileira e latino-americana para a evolução da psicologia analítica.
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Teoría Junguiana , Psicoterapia , Civilización , Humanos , ConocimientoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Eugenia biflora (Myrtaceae) are traditionally used by Amazonian populations for the control of diabetes. However, their chemical composition has not yet been described and pharmacological evidence has not been reported. OBJECTIVE: This study aimed to identify the chemical constituents and evaluate the hypoglycemic and toxic effect of the dry extract of the E. biflora leaves (DEEB). MATERIALS AND METHODS: DEEB, obtained by infusion, was analyzed using LC-HRMS and NMR, whose the catechin flavonoid was quantified using NMR. The antidiabetic effect of DEEB was evaluated according to its inhibition of the enzymes α-amylase and α-glucosidase, as well as the content of total phenols, free radical scavengingand antiglycation activities, and its in vitro cell viability. Oral maltose tolerance and chronic multiple dose tests (28 days) in streptozotocin-induced diabetic mice (STZ) were performed. The hypoglycemic effect and toxicity of this extract were evaluated in the multiple dose assay. Biochemical parameters, hemolysis, and levels of the thiobarbituric acid reactive species in the liver were investigated and histopathological analyses of the kidneys and liver were performed. RESULTS: Eight phenolic compounds were identified, with catechin (15.5 ± 1.7 mg g-1) being the majority compound and a possible chemical marker of DEEB. The extract showed inhibition activity of the enzyme α-glucosidase. Chronic administration of DEEB (50 mg/kg of body weight) reduced glucose levels in diabetic animals, similar to acarbose; however, DEEB (100 and 200 mg/kg bw) caused premature death of mice by D22 of the treatment. Our data indicate that one of the mechanisms of toxicity in DEEB may be related to the aggravation of oxidative stress in the liver. This histopathological study indicated that DEEB failed to minimize the progression of the toxicity of diabetes caused by STZ. CONCLUSIONS: This study demonstrated the hypoglycemic potential of E. biflora leaves. However, the prolonged use of this tea can be harmful to its users due to its considerable toxicity, which needs to be better investigated.
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Diabetes Mellitus Experimental , Eugenia , Hipoglucemiantes , Animales , Antioxidantes/farmacología , Glucemia , Catequina , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Eugenia/química , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/toxicidad , Ratones , Extractos Vegetales/uso terapéutico , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Estreptozocina , alfa-Glucosidasas/metabolismoRESUMEN
Leaf extracts from Eugenia punicifolia are rich in pentacyclic triterpenic acids (PTAs), especially barbinervic acid (BA), which is an important biomarker of the species. Dichloromethane extracts of E. punicifolia leaf samples harvested in Amazonian summer and winter seasons were analysed by infrared spectroscopy using ATR-FTIR technique aiming to evaluate barbinervic acid (BA) and its PTAs equivalent contents. A validated HPLC-DAD quantification method was also performed to compare the relationship between BA and PTAs contents in E. punicifolia extracts with ATR-FTIR technique. The use of ATR-FTIR allowed a rapid, efficient and environment-friendly quantification method for total PTAs equivalent content, showing a significant statistical difference (p< 0.05) in the production of these metabolites (38.66 µg/mL, summer; 13.62 µg/mL, winter). A mathematical correction factor between the HPLC-DAD and ATR-FTIR quantification methods was established.
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Eugenia , Triterpenos Pentacíclicos/química , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Triterpenos Pentacíclicos/análisis , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Amyloid Protein Precursor gene duplication is a rare cause of early-onset Alzheimer's disease that can be associated with Cerebral Amyloid Angiopathy. This condition predisposes cerebrovascular events, specifically, intracerebral hemorrhagic stroke. This report describes a case of first-time intracerebral hemorrhage in a patient with APP gene duplication during SARS-CoV-2 infection, a typically pro-thrombotic and pro-inflammatory condition, as a possible trigger for this condition.
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Like soil-transmitted helminth infections, schistosomiasis is an important neglected tropical disease (NTD) related to poverty with a major impact on public health in developing countries. Diagnosis of active infection is crucial for surveillance of controlled or post-elimination schistosomiasis areas. In addition, the use of conventional diagnostic tools in non-exposed populations (such as travelers) results in misdiagnoses in the prepatent period of infection. Also, the accuracy of standard tests applied in low-endemicity areas (LEAs) decreases after several rounds of treatment. We aimed to determine whether it would be necessary to replace schistosomiasis conventional diagnostic tests such as parasitological methods in LEAs. Also, we evaluate the use of new tools in non-endemic areas. Reliable, cheap and easy-to-use diagnostic tools are needed to respond to the demands of a new era of elimination and eradication of schistosomiasis. To this end, molecular diagnosis-including nucleic acid-based assays (loop-mediated isothermal amplification, polymerase chain reaction) and circulating cathodic and anodic antigen detection tests have become promising strategies. In this review, we attempt to address the use of alternative diagnostic tests for active infection detection and drug-monitoring after specific schistosomiasis treatment.
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Enfermedades Desatendidas/diagnóstico , Esquistosomiasis/diagnóstico , Antihelmínticos/uso terapéutico , Antígenos Helmínticos/análisis , Humanos , Sistemas de Atención de Punto , Praziquantel/uso terapéutico , Esquistosomiasis/tratamiento farmacológico , Esquistosomiasis/inmunologíaRESUMEN
Techniques with high sensitivity and specificity are required for an accurate diagnosis in low-transmission settings, where the conventional parasitological methods are insensitive. We determined the accuracy of an up-converting phosphor-lateral flow circulating anodic antigen (UCP-LF CAA) assay in urine and serum for Schistosoma mansoni diagnosis in low-prevalence settings in Ceará, Brazil, before and after praziquantel treatment. Clinical samples of a total of 258 individuals were investigated by UCP-LF CAA, point-of-care-circulating cathodic antigen (POC-CCA), soluble worm antigen preparation (SWAP)-ELISA and Kato-Katz (KK); a selection of 128 stools by real-time PCR technique. Three and 6-weeks after treatment, samples were collected and evaluated by detection Schistosoma circulating antigens (CAA and CCA). The UCP-LF CAA assays detected 80 positives (31%) with urine and 82 positives (31.8%) with serum. The urine POC-CCA and serum SWAP-ELISA assays detected 30 (11.6%) and 107 (40.7%) positives, respectively. The Kato-Katz technique revealed only 4 positive stool samples (1.6%). Among the 128 individuals with complete data records, 19 cases were identified by PCR (14.8%); Sensitivities and specificities of the UCP-LF CAA assays, determined versus a combined reference standard based on CCA/KK/PCR positivity, ranged from 60-68% to 68-77%, respectively. In addition only for comparative purposes, sensitivities of the different assays were determined vs. a comparative reference based on CAA/KK/PCR positivity, showing the highest sensitivity for the urine CAA assay (80%), followed by the serum CAA (70.9%), SWAP-ELISA (43.6%), PCR (34.5%), POC-CCA (29.1%), whilst triplicate Kato-Katz thick smears had a very low sensitivity (3.6%). CAA concentrations were higher in serum than in urine and were significantly correlated. There was a significant decrease in urine and serum CAA levels 3 and 6-weeks after treatment. The UCP-LF CAA assays revealed 33 and 28 S. mansoni-infected patients at the 3- and 6-week post-treatment follow-up, respectively. The UCP-LF CAA assays show high sensitivity for the diagnosis of S. mansoni in low-endemicity settings. It detects a considerably higher number of infections than microscopy, POC-CCA or PCR. Also it shows to be very useful for evaluating cure rates after treatment. Hence, the UCP-LF CAA assay is a robust and promising diagnostic approach in low-transmission settings.
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Antígenos Helmínticos/inmunología , Pruebas Inmunológicas , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/diagnóstico , Esquistosomiasis mansoni/inmunología , Adolescente , Adulto , Anciano , Animales , Antígenos Helmínticos/sangre , Brasil/epidemiología , Niño , Preescolar , Humanos , Pruebas Inmunológicas/métodos , Pruebas Inmunológicas/normas , Estudios Longitudinales , Persona de Mediana Edad , Vigilancia de la Población , Prevalencia , Reproducibilidad de los Resultados , Schistosoma mansoni/genética , Esquistosomiasis mansoni/epidemiología , Esquistosomiasis mansoni/parasitología , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: ß-amyloid (Aß) can accumulate in the brain of aged dogs, and within vessels walls, the disease is called cerebral amyloid angiopathy (CAA). In humans, Alzheimer's disease and CAA are strongly correlated with cerebrovascular disease. However, in dogs, this association has not been extensively studied yet. The present report highlights the pathological and clinical features of a concomitant cerebrovascular disease and amyloid precursor protein (APP) accumulation in the brain of a dog. CASE PRESENTATION: A female, 16-year-old, Standard Poodle with a one-year history of cognitive deficits presented with an acute onset of right-sided postural reaction deficit and circling, left-sided head tilt, positional nystagmus, and ataxia. Due to poor prognosis the dog was euthanized, and pathological examination of the brain revealed an acute lacunar infarction within the thalamus extending to rostral colliculus. Additional findings included subacute and chronic areas of ischemia throughout the brain and areas of hemorrhage within the medulla. Immunolabeling revealed APP deposition within intraparenchymal vessels of frontal, temporal and occipital cortex, hippocampus, diencephalon, mesencephalon and myelencephalon, besides meningeal vessels walls. Glial fibrillary acidic protein (GFAP) immunolabeling showed marked astrocytosis around the acute area of infarction and within chronic areas of ischemia. Histological examination of the brain along with immunohistochemistry results showed a concomitant APP, which is an Aß precursor, accumulation within the neuroparenchyma and vessels (CAA) with histological evidences of a cerebrovascular disease in an aged dog. CONCLUSIONS: This report shows that APP accumulation in the brain can occur concomitantly to a severe cerebrovascular disease in a dog. Further studies are necessary to elucidate if cerebrovascular disease is associated with Aß accumulation in the brain of dogs.
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Precursor de Proteína beta-Amiloide/metabolismo , Infarto Encefálico/veterinaria , Encéfalo/metabolismo , Angiopatía Amiloide Cerebral/veterinaria , Enfermedades de los Perros/fisiopatología , Animales , Infarto Encefálico/etiología , Infarto Encefálico/metabolismo , Angiopatía Amiloide Cerebral/metabolismo , Angiopatía Amiloide Cerebral/fisiopatología , Enfermedades de los Perros/metabolismo , Perros , FemeninoRESUMEN
Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disorder caused by the unstable expansion of a cytosine-adenine-guanine (CAG)/cytosine-adenine-adenine (CAA) repeat in the ATXN2 gene, which normally encodes 22 glutamines (Q22). A large study was conducted to characterize the CAG/CAA repeat intergenerational instability in SCA2 families. Large normal alleles (Q24-31) were significantly more unstable upon maternal transmissions. In contrast, expanded alleles (Q32-750) were significantly more unstable during paternal transmissions, in correlation with repeat length. Significant correlations were found between the instability and the age at conception in paternal transmissions. In conclusion, intergenerational instability at ATXN2 locus is influenced by the sex, repeat length and age at conception of the transmitting parent. These results have profound implications for genetic counseling services.
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Factores de Edad , Ataxina-2/genética , Impresión Genómica , Inestabilidad Genómica , Ataxias Espinocerebelosas/genética , Repeticiones de Trinucleótidos , Adulto , Alelos , Femenino , Humanos , MasculinoRESUMEN
Sporadic cerebral amyloid angiopathy (CAA) is a very common small vessel disease of the brain, showing preferential and progressive amyloid-ßdeposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex. CAA now encompasses not only a specific cerebrovascular pathological trait, but also different clinical syndromes - including spontaneous lobar intracerebral haemorrhage (ICH), dementia and 'amyloid spells' - an expanding spectrum of brain parenchymal MRI lesions and a set of diagnostic criteria - the Boston criteria, which have resulted in increasingly detecting CAA during life. Although currently available validated diagnostic criteria perform well in multiple lobar ICH, a formal diagnosis is currently lacking unless a brain biopsy is performed. This is partly because in practice CAA MRI biomarkers provide only indirect evidence for the disease. An accurate diagnosis of CAA in different clinical settings would have substantial impact for ICH risk stratification and antithrombotic drug use in elderly people, but also for sample homogeneity in drug trials. It has recently been demonstrated that vascular (in addition to parenchymal) amyloid-ßdeposition can be detected and quantified in vivo by positron emission tomography (PET) amyloid tracers. This non-invasive approach has the potential to provide a molecular signature of CAA, and could in turn have major clinical impact. However, several issues around amyloid-PET in CAA remain unsettled and hence its diagnostic utility is limited. In this article we systematically review and critically appraise the published literature on amyloid-PET (PiB and other tracers) in sporadic CAA. We focus on two key areas: (a) the diagnostic utility of amyloid-PET in CAA and (b) the use of amyloid-PET as a window to understand pathophysiological mechanism of the disease. Key issues around amyloid-PET imaging in CAA, including relevant technical aspects are also covered in depth. A total of six small-scale studies have addressed (or reported data useful to address) the diagnostic utility of late-phase amyloid PET imaging in CAA, and one additional study dealt with early PiB images as a proxy of brain perfusion. Across these studies, amyloid PET imaging has definite diagnostic utility (currently tested only in probable CAA): it helps rule out CAA if negative, whether compared to healthy controls or to hypertensive deep ICH controls. If positive, however, differentiation from underlying incipient Alzheimer's disease (AD) can be challenging and so far, no approach (regional values, ratios, visual assessment) seems sufficient and specific enough, although early PiB data seem to hold promise. Based on the available evidence reviewed, we suggest a tentative diagnostic flow algorithm for amyloid-PET use in the clinical setting of suspected CAA, combining early- and late-phase PiB-PET images. We also identified ten mechanistic amyloid-PET studies providing early but promising proof-of-concept data on CAA pathophysiology and its various manifestations including key MRI lesions, cognitive impairment and large scale brain alterations. Key open questions that should be addressed in future studies of amyloid-PET imaging in CAA are identified and highlighted.
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Amiloide/metabolismo , Angiopatía Amiloide Cerebral/diagnóstico por imagen , Angiopatía Amiloide Cerebral/metabolismo , Tomografía de Emisión de Positrones/normas , Humanos , Tomografía de Emisión de Positrones/métodosRESUMEN
Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be linked to the etiology of many diseases, including neurodegenerative diseases (NDDs) such as Alzheimer diseases, Amyotrophic lateral sclerosis, Friedreich's ataxia, Huntington's disease, Multiple sclerosis, and Parkinson's diseases. In addition, oxidative stress causing protein misfold may turn to other NDDs include Creutzfeldt-Jakob disease, Bovine Spongiform Encephalopathy, Kuru, Gerstmann-Straussler-Scheinker syndrome, and Fatal Familial Insomnia. An overview of the oxidative stress and mitochondrial dysfunction-linked NDDs has been summarized in this review.
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Enfermedades Mitocondriales/etiología , Enfermedades Neurodegenerativas/complicaciones , Estrés Oxidativo/fisiología , Animales , HumanosRESUMEN
Coronary artery anomalies (CAA) are congenital changes in their origin, course, and/or structure. Intercoronary communication (ICC) is a very rare subset with uni- or bidirectional blood flow between two or more coronary arteries. We present the case of a 58-year-old man with an acute coronary syndrome whose coronary angiography incidentally showed a surprising and very rare communication between the right coronary and left circumflex arteries.
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Spinocerebellar ataxia type 7 (SCA7) is a genetic disorder characterized by degeneration of the cerebellum, brainstem, and retina that is caused by abnormal expansion of a CAG repeat located in the ATXN7 gene encoding sequence on chromosome 3p21.1. Although SCA7 is an uncommon autosomal dominant ataxia, we previously found increased prevalence of the disease in a Southeastern Mexican population. In this study, we described to our knowledge for the first time a marriage of consanguineous SCA7 mutation carriers and their offspring effect. We characterized a severely affected infantile-onset female patient whose parents and two siblings exhibited no symptoms of the disease at time of diagnosis. A comprehensive clinical analysis of the proband showed a progressive cerebellar syndrome, including gait ataxia, movement disorders, and saccadic movements, as well as hyperreflexia, visual deterioration, urinary and cardiovascular dysfunction, and impaired nerve conduction. The SCA7 mutation was detected in the proband patient. Subsequently, genetic examination using four ATXN7 gene-linked markers (three centromeric microsatellite markers [D3S1228, D3S1287, and D3S3635] and an intragenic Single Nucleotide Polymorphism [SNP-3145G/A]) revealed that the proband descends from a couple of consanguineous SCA7 mutation carriers. Genotyping analysis demonstrated that all offspring inherited only one mutant allele, and that the severe infantile-onset phenotype is caused by germinal expansion (from 37 to 72 CAG repeats) of the paternal mutant allele. Interestingly, the couple also referred a miscarriage. Finally, we found no CAA interruptions in the ATXN7 gene CAG repeats tract in this family, which might explain, at least in part, the triplet instability in the proband.
RESUMEN
Aluminum is one of the most abundant elements in nature and is used in diverse industrial processes. As a result, it contaminates aquatic ecosystems, inducing damage on associated biota. In fish, it has been observed to induce hypoxia, hypercapnia, metabolic acidosis and respiratory arrest. Although there is little information on Al-induced cytotoxicity and DNA damage, this type of studies are essential in order to identify the mechanisms of action of this metal. The cytotoxic and genotoxic effects induced by Al on common carp (Cyprinus carpio) erythrocytes were determined in specimens exposed to 0.05, 120 and 239mgAlL(-1) in static exposure systems. Blood samples were taken at 12, 24, 48, 72 and 96h, erythrocytes were separated, and the following were evaluated: frequency of micronuclei and frequency of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, blood Al levels, lipid peroxidation, protein carbonyl content, and activity of the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase. The results show that tested aluminum concentrations produces oxidative stress (increase in lipid peroxidation degree and oxidized proteins content, as well as decrease in antioxidant enzymes activity) and induced higher frequencies of micronuclei and TUNEL-positive cells, so this metal can be considered as a cytotoxic and genotoxic agent for erythrocytes of common carp.
Asunto(s)
Aluminio/toxicidad , Carpas/fisiología , Eritrocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/farmacología , Carpas/metabolismo , Catalasa/metabolismo , Daño del ADN/efectos de los fármacos , Eritrocitos/química , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Pruebas de Mutagenicidad , Carbonilación Proteica/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factores de Tiempo , Contaminantes Químicos del Agua/toxicidadRESUMEN
OBJECTIVE: To determine the association between Kawasaki disease (KD) and atopic diathesis (atopic dermatitis [AD], allergic rhinitis, and asthma) in children younger than 5 years of age. STUDY DESIGN: In this nationwide study, we aimed to analyze the association and temporal relationship between KD and atopic diathesis. Data were obtained from the National Health Insurance Research Database of Taiwan from 1997 to 2010. In total, 200 patients with KD younger than 5 years of age and 800 age- and sex-matched control subjects were enrolled. RESULTS: In the whole study population, an increased risk of any concomitant atopic diseases was observed in patients with KD (OR 1.61, 95% CI 1.15-2.26). The risk of AD was increased in male patients between 1 and 5 years of age (OR 3.02, 95% CI 1.22-7.50). More than 60% of the patients developed atopic diseases after the diagnosis of KD. CONCLUSION: There appears to be an association between KD and risk of AD. Most of the atopic diseases occurred after the episode of KD.
Asunto(s)
Hipersensibilidad Inmediata/etiología , Síndrome Mucocutáneo Linfonodular/complicaciones , Asma/epidemiología , Asma/etiología , Estudios de Casos y Controles , Preescolar , Bases de Datos Factuales , Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Femenino , Humanos , Hipersensibilidad Inmediata/epidemiología , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Análisis Multivariante , Prevalencia , Rinitis Alérgica Perenne/epidemiología , Rinitis Alérgica Perenne/etiología , Rinitis Alérgica Estacional/epidemiología , Rinitis Alérgica Estacional/etiología , Factores de Riesgo , TaiwánRESUMEN
OBJECTIVES: To determine the most effective first-line rescue therapy for intravenous immunoglobulin (IVIG) nonresponders, using IVIG, prednisolone, or both, to prevent coronary artery abnormalities (CAAs). STUDY DESIGN: We retrospectively reviewed the clinical records of 359 consecutive patients with Kawasaki disease who failed to respond to initial IVIG. RESULTS: CAAs up to 1 month after treatment were less common in the IVIG+prednisolone group (15.9%) than in the IVIG group (28.7%, P = .005) and the prednisolone group (30.6%, P = .01). The IVIG+prednisolone group had significantly lower risks of failing to respond to first-line rescue therapy (aOR 0.16, 95% CI 0.09-0.31), CAAs up to 1 month (aOR 0.46, 95% CI 0.27-0.90), and CAAs at 1 month (aOR 0.40, 95% CI 0.18-0.91) than the IVIG group. In the prednisolone and IVIG+prednisolone groups, risk score, day of illness at first-line rescue therapy, prednisolone monotherapy, and resistance to first-line rescue therapy were independent risk factors for CAA. Sex and resistance to first-line rescue therapy were independent risk factors in the IVIG group. CONCLUSIONS: IVIG+prednisolone may be superior to IVIG or prednisolone as first-line rescue therapy in the treatment of IVIG nonresponders. To establish the efficacy of rescue therapy with IVIG+prednisolone following nonresponse to initial IVIG, a prospective randomized trial is warranted.
Asunto(s)
Glucocorticoides/administración & dosificación , Inmunoglobulinas Intravenosas/administración & dosificación , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Prednisolona/administración & dosificación , Enfermedad Aguda , Preescolar , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
Myrcia uniflora Barb. Rodr., Myrtaceae, popularly known as "pedra-hume-caá" in Brazil, is sold as dry extracts in capsules or as tinctures for the treatment of diabetes mellitus. Previous phytochemical studies on this species described the occurrence of the flavonoids mearnsitrin and myricitrin. In the present study, the chromatographic profiles of M. uniflora leaves and commercial extracts were determined using HPLC-PAD. Myricitrin was used as an external standard in the development and validation of the HPLC method. The proposed method is simple, rapid and reliable and can be successfully applied in industry for standardization of herbs and phytomedicines commercialised in Brazil as "pedra-hume-caá".