RESUMEN
Cryptococcosis is the second most common invasive fungal infection reported in renal transplant recipients. Tissue granulomatous inflammation is necessary to contain Cryptococcus infection. This study aims to analyze the granuloma patterns and in situ expression of regulatory T (Treg) immune response in tissue samples from 12 renal transplant recipients with cryptococcosis. Fungal isolates were molecularly identified as Cryptococcus neoformans species complex. A detailed characterization of granulomas in tissue samples from 12 kidney transplant recipients with cryptococcosis was described by checking six lung and six skin biopsies by conventional histology and for immunohistochemical detection of CD4 and Treg markers: forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming-growth factor (TGF)-ß. Granulomas were classified as compact, loose or mixed. Patients with mixed (n = 4) and compact (n = 3) granulomatous inflammation patterns were associated with a better prognosis and presented a higher number of CD4+FoxP3+T cells compared to the group of patients with loose granulomas. In counterpart, three out of five patients with loose granulomas died with cryptococcosis. We suggest that Treg may have a protective role in the tissue response to Cryptococcus infection given its association with compact and mixed granulomas in patients with better clinical outcomes.
Asunto(s)
Criptococosis/etiología , Criptococosis/mortalidad , Trasplante de Riñón/efectos adversos , Criptococosis/diagnóstico , Criptococosis/epidemiología , Cryptococcus , Cryptococcus neoformans/inmunología , Susceptibilidad a Enfermedades/inmunología , Humanos , Huésped Inmunocomprometido , Trasplante de Riñón/métodos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismoRESUMEN
Nicotinamide adenine dinucleotide (NAD+ ) is an essential coenzyme required for all living organisms. In eukaryotic cells, the final step of NAD+ biosynthesis is exclusively cytosolic. Hence, NAD+ must be imported into organelles to support their metabolic functions. Three NAD+ transporters belonging to the mitochondrial carrier family (MCF) have been biochemically characterized in plants. AtNDT1 (At2g47490), focus of the current study, AtNDT2 (At1g25380), targeted to the inner mitochondrial membrane, and AtPXN (At2g39970), located in the peroxisomal membrane. Although AtNDT1 was presumed to reside in the chloroplast membrane, subcellular localization experiments with green fluorescent protein (GFP) fusions revealed that AtNDT1 locates exclusively in the mitochondrial membrane in stably transformed Arabidopsis plants. To understand the biological function of AtNDT1 in Arabidopsis, three transgenic lines containing an antisense construct of AtNDT1 under the control of the 35S promoter alongside a T-DNA insertional line were evaluated. Plants with reduced AtNDT1 expression displayed lower pollen viability, silique length, and higher rate of seed abortion. Furthermore, these plants also exhibited an increased leaf number and leaf area concomitant with higher photosynthetic rates and higher levels of sucrose and starch. Therefore, lower expression of AtNDT1 was associated with enhanced vegetative growth but severe impairment of the reproductive stage. These results are discussed in the context of the mitochondrial localization of AtNDT1 and its important role in the cellular NAD+ homeostasis for both metabolic and developmental processes in plants.
Asunto(s)
Antiportadores/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , NAD/metabolismo , Antiportadores/genética , Arabidopsis/crecimiento & desarrollo , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Transporte Biológico , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Cloroplastos/metabolismo , Citosol/metabolismo , Proteínas Fluorescentes Verdes , Homeostasis , Mitocondrias/metabolismo , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Mutagénesis Insercional , Proteínas de Transporte de Nucleótidos , Peroxisomas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/fisiología , Polen/genética , Polen/crecimiento & desarrollo , Polen/fisiología , Almidón/metabolismoRESUMEN
Approximately 255 million people consume illicit drugs every year, among which 18 million use cocaine. A portion of this drug is represented by crack, but it is difficult to estimate the number of users since most are marginalized. However, there are no recognized efficacious pharmacotherapies for crack-cocaine dependence. Inflammation and infection in cocaine users may be due to behavior adopted in conjunction with drug-related changes in the brain. To understand the metabolic changes associated with the drug abuse disorder and identify biomarkers, we performed a 1H NMR-based metabonomic analysis of 44 crack users' and 44 healthy volunteers' blood serum. The LDA model achieved 98% of accuracy. From the water suppressed 1H NMR spectra analyses, it was observed that the relative concentration of lactate was higher in the crack group, while long chain fatty acid acylated carnitines were decreased, which was associated with their nutritional behavior. Analyses of the aromatic region of CPMG 1H NMR spectra demonstrated histidine and tyrosine levels increased in the blood serum of crack users. The reduction of carnitine and acylcarnitines and the accumulation of histidine in the serum of the crack users suggest that histamine biosynthesis is compromised. The tyrosine level points to altered dopamine concentration.
Asunto(s)
Trastornos Relacionados con Cocaína , Cocaína Crack/farmacología , Espectroscopía de Resonancia Magnética/métodos , Metaboloma/efectos de los fármacos , Recolección de Muestras de Sangre , Carnitina/sangre , Estudios de Casos y Controles , Histidina/sangre , Humanos , Ácido Láctico/sangre , Tirosina/sangreAsunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Ketamina/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/fisiopatología , Adulto , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Femenino , Humanos , Ketamina/administración & dosificación , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Hemifacial spasm is a disorder of the seventh cranial nerve, which is characterized by irregular, involuntary and recurrent tonic and clonic contractions of the ipsilateral facial expression muscles. This disorder affects mainly adults, and there are few cases reported in childhood. The main etiologies are vascular problems, although tumors are an important cause of hemifacial spasm via a direct or an indirect mass effect. We report a 6-year-old girl who presented with right hemifacial spasm. Magnetic resonance imaging showed a lesion in the cerebellopontine angle, extending from the midbrain to the pons with a slight mass effect on the fourth ventricle. The histological examination revealed a pilocytic astrocytoma.
RESUMEN
A radiofrequência é um tipo de corrente de alta frequência que gera calor por conversão, atingindo profundamente as camadas tissulares promovendo a oxigenação, nutrição e vasodilatação dos tecidos. Este estudo teve como objetivo avaliar os efeitos da radiofrequência no tecido colágeno de ratos. Trata-se de uma pesquisa experimental, tendo como amostra 20 ratos pesando entre 250 g e 300 g, de ambos os sexos, da linhagem Wistar (Rattos norvegicos albinus). Os animais foram divididos em cinco grupos com três aplicações de radiofrequência em dias alternados e sacrifício em períodos distintos a contar após a última aplicação de cada grupo, da seguinte forma: grupo-controle (n=4) não sofreu aplicação de radiofrequência e teve sacrifício em 21 dias grupo II (n=4), com sacrifício em 24 horas grupo III (n=4) com sacrifício em sete dias grupo IV (n=4) com sacrifício em 15 dias e grupo V (n=4) com sacrifício em 21 dias. Utilizou-se a radiofrequência com frequência de 0,5 MHz em uma área de 5cm² do dorso do animal por um tempo de dois minutos após atingir a temperatura superficial da pele de 37ºC. Os dados demonstraram que até sete dias após as aplicações o colágeno sofreu modificações tornando-se mais denso, com presença de neocolagêneses, porém após 15 dias não ocorreram mais evidências importantes na formação neocolágena, mas foi detectada a neoelastogêneses, que também esteve presente na análise de 21 dias. A quantidade de novas fibras elásticas foi maior significativamente (p=0,0002) após análise estatística quando comparada ao grupo-controle. Sugere-se uma frequência de tratamento de no mínimo sete dias e que há permanência de efeitos da radiofrequência no tecido colágeno até 15 dias.
RESUMEN
BACKGROUND: Li-Fraumeni and Li-Fraumeni-like syndromes (LFS/LFL), characterised by the development of multiple early onset cancers with heterogeneous tumour patterns, are associated with germline TP53 mutations. Polymorphisms in the TP53 pathway (TP53 PEX4 at codon 72, rs1042522; MDM2 SNP309, rs2279744) have modifier effects on germline TP53 mutations that may account for the individual and familial diversity of tumour patterns. METHODS AND RESULTS: Four polymorphisms were analysed in a series of 135 Brazilian LFS/LFL cancer patients (32 TP53 mutation carriers and 103 wild-type subjects). We report for the first time that another polymorphism in the TP53 gene, TP53 PIN3 (rs17878362), has a strong modifier effect on germline TP53 mutations. This polymorphism, which consists of a 16 bp duplication in intron 3 (A1, non-duplicated allele; A2, duplicated allele), is associated with a difference of 19.0 years in the mean age at the first diagnosis in TP53 mutation carriers (n = 25, A1A1: 28.0 years; n = 7, A1A2: 47.0 years; p = 0.01). In addition, cancer occurrence before the age of 35 years is exclusively observed in A1A1 homozygotes. In this series, the effect of TP53 PEX4 and MDM2 SNP309 on age at diagnosis was similar to the one reported in other series and was smaller than the one of TP53 PIN3 (TP53 PIN3: difference of 19.0 years; TP53 PEX4: 8.3 years; MDM2 SNP309: 12.5 years). CONCLUSION: These results suggest that TP53 PIN3 is another polymorphism in the TP53 pathway that may have a modifier effect on germline TP53 mutations and may contribute to the phenotypic diversity of germline TP53 mutations associated with LFS/LFL patients.
Asunto(s)
Síndrome de Li-Fraumeni/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteína p53 Supresora de Tumor/genética , Adulto , Edad de Inicio , Brasil/epidemiología , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/epidemiología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estadísticas no ParamétricasRESUMEN
Fundamento e objetivo: O ecocardiograma tridimensional (ECO 3D) e a tomografia computadorizada ultra-rápida (CT) constituem 2 novos métodos de análise da fração de ejeção e dos volumes do ventrículo esquerdo (VE). Existem poucos estudos dirigidos à comparação da análise da fração de ejeção do VE aferidos por ambos os métodos. O objetivo deste estudo foi comparar as medidas da FEVE e dos volumes do VE ECO 3D em tempo real e pela CT ultra rápida. Método: Foram estudados pelo ECO 3D e pela CT ultra rápida de 64 cortes, 41 pacientes (29 homens, média etária de 58 + - 111 anos). Foram analisados com ambas as técnicas: FEVE, volumes sistólico final e diastólico final do VE. Os parâmetros aferidos com o ECO3D e com a CT foram comparados com o emprego do coeficiente de determinação (r:Pearson), do teste de Bland & Altman e do teste de regressão linear, 95 por cento IC, p<0,05. Resultados: Medidas do ECO 3D: a FEVE variou de 56,7 a 78,9 (65,3 + - 5,7) por cento; volume diastólico final variou de 49,6 a 178,2 (88+ - 27,5) mL; volume sistólico final variou de 11,4 a 78 (33,9 + - 13,7) mL. Medidas da CT: a FEVE variou de 7 a 72 (35,1 + - 13,8) mL. As correlações entre ECO 3D e CT foram: FEVE (r: 0,7877, p>0,0001, 95 por cento IC 0,6327 a 0,8853); volume diastólico final (r:0,7671, p< 0,0001, 95 por cento IC 0,5974 a 0,8745); volume sistólico final (r: 0,8121, p< 0,0001, 95 por cento IC 0,6659 a 0,8957). Conclusão: Foi evidenciada boa correlação entre as medidas da FEVE e entre os volumes ventriculares aferidos pelo ECO3D em tempo real e pela CT ultra rápida de 64 cortes.