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1.
J Am Soc Nephrol ; 32(9): 2362-2374, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34155059

RESUMEN

BACKGROUND: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail. METHODS: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value. RESULTS: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival (P=0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status (P=0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype. CONCLUSIONS: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Arteritis/complicaciones , Arteritis/diagnóstico , Fallo Renal Crónico/epidemiología , Arteria Renal , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Arteritis/mortalidad , Supervivencia sin Enfermedad , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
2.
An Acad Bras Cienc ; 94(4): e20201914, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36102391

RESUMEN

Fibrinolytic enzymes are considered promising alternative in the treatment of cardiovascular diseases by preventing fibrin clots. A protease from Mucor subtilissimus UCP 1262 was obtained by solid state fermentation and purified by ion exchange chromatography. The purified extract was administered at an acute dose of 2000 mg/mL to evaluate its toxic effects to the lungs of mice. After 14 days of treatment, a histomorphometric study was performed by the type 1 and 2 pneumocyte count and the evaluation of the lung area. As result, the experimental group showed a significant decrease of type 2 pneumocyte and although a decrease in the alveolar area was observed in relation to the control group, no significant pulmonary toxicity, emphysema, and fibrosis characteristics were detected. The in vitro tests suggest possible clinical applications for the enzyme.


Asunto(s)
Pulmón , Péptido Hidrolasas , Animales , Ratones , Péptido Hidrolasas/química
3.
Am J Transplant ; 19(10): 2910-2925, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31165546

RESUMEN

Molecular mismatch load analysis was recently introduced as a means for performing risk stratification following organ transplantation. However, although good correlation was demonstrated between molecular mismatch load and generation of de novo donor-specific HLA antibody (DSA), quite a few exceptions exist, and the underlying factors that define HLA immunogenicity remain unclear. Herein, we present a new paradigm to interrogate differences between molecular mismatches that lead to the generation of de novo DSA and those that do not (the 2MM1DSA cohort). Specifically, patients transplanted across 2 HLA-DQ mismatches, who formed de novo DSA only to one mismatch (foe) but not the other (friend), provide a unique environment in which patient-specific factors that affect the immune response other than immunogenicity, such as infection and immunosuppression, can be controlled for. It further permits focusing on mismatches uniquely exhibited by the de novo DSA allele, rather than mismatches shared by both DSA and non-DSA alleles. This concept paper illustrates several examples, highlights the need for center-specific or population-specific cutoff values for posttransplant risk stratification, and mostly argues that if there is no direct correlation between molecular mismatch load and immunogenicity, then molecular mismatch load must not be adopted as an approach for equitable organ allocation.


Asunto(s)
Rechazo de Injerto/diagnóstico , Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Histocompatibilidad/inmunología , Isoanticuerpos/efectos adversos , Fallo Renal Crónico/inmunología , Trasplante de Riñón/efectos adversos , Secuencia de Aminoácidos , Mapeo Epitopo , Epítopos/inmunología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Antígenos HLA/química , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Modelos Moleculares , Pronóstico , Conformación Proteica , Factores de Riesgo , Homología de Secuencia
4.
Curr Opin Rheumatol ; 31(1): 3-8, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30461541

RESUMEN

PURPOSE OF REVIEW: To provide a comprehensive overview of the current insight into the role of complement activation in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). In addition, the therapeutic options targeting the complement system in AAV are discussed. RECENT FINDINGS: It has become increasingly clear that complement, and more specifically signalling through the C5a receptor, contributes to the immunopathology of AAV. This has led to the design of clinical trials with a C5a receptor blocker. The first results show a reduction in tissue damage and a favourable safety profile, as other parts of the complement defence system are left intact. SUMMARY: Although AAV was initially regarded as a pauci-immune disease, it is now well established that, in addition to autoantibodies, complement plays an essential role in the disease process. Animal models delivered the first insight, but the effective therapeutic interventions using complement inhibitors provided the proof that indeed complement activation contributes to disease activity and tissue damage in human AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Proteínas del Sistema Complemento/inmunología , Animales , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Autoanticuerpos , Activación de Complemento , Inactivadores del Complemento/uso terapéutico , Humanos
5.
Rheumatology (Oxford) ; 58(1): 103-109, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30551161

RESUMEN

Objectives: To determine predictors of renal relapse and end-stage renal failure (ESRF) in patients with ANCA-associated vasculitis. Methods: Data from four European Vasculitis Society randomized controlled trials, conducted roughly simultaneously between 15 March 1995 and 30 September 2002, was pooled to determine predictors of long-term renal outcome. The respective trial inclusion criteria covered the entire spectrum of disease severity. Baseline predictors of time to first renal relapse and time to ESRF were assessed by competing events analysis and Cox proportional hazards regression. The effect of renal relapse on time to ESRF was assessed by adding renal relapses to the competing events analysis as a time-varying covariate. Results: The number of patients participating was 535; mean serum creatinine (±s.d.) at entry was 341 ± 321 µmol/l and 19.7% developed ESRF. One or more renal relapse(s) was experienced by 101 patients. Multivariable regression analysis demonstrated that, in addition to impaired baseline renal function, developing ⩾1 renal relapse was an independent risk factor for ESRF (subhazard ratio 9; 95% CI 4, 19; P < 0.001). No predictive factors for renal relapse were found. Conclusion: In addition to baseline renal function, the occurrence of renal relapses is an important determinant of ESRF in patients with ANCA-associated vasculitis. We did not find any clinical predictors for renal relapse itself, including disease activity elsewhere. In light of the silent nature of renal relapse in ANCA-associated vasculitis, we stress the need for long-term vigilant monitoring for early signs of renal relapse and propose performing 3-monthly urinalysis. This will enable timely treatment and help further improve renal outcome.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Fallo Renal Crónico/fisiopatología , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Creatinina/sangre , Femenino , Humanos , Inmunosupresores/uso terapéutico , Riñón/inmunología , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etiología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Recurrencia , Análisis de Regresión , Factores de Riesgo , Resultado del Tratamiento
6.
J Insect Sci ; 19(1)2019 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-30715436

RESUMEN

Studies investigating oviposition preference of Ceratitis capitata (Wiedemann, 1824) in table grapes (Vitis vinifera L.) cultivated in the São Francisco River Valley can provide important information to guide control measures, therefore minimizing damage caused by this species in the region. The aim of this study was to evaluate the oviposition preference of C. capitata females for berries cv. 'Italia' collected at five different times (60, 70, 80, 90, and 100 d after production pruning [DAPP]), representing five grapevine growth stages. We also assessed the performance of immature stages of C. capitata regarding the physiological development of the berry. The total soluble solid content was significantly higher in berries at more advanced physiological developmental stages (90 and 100 DAPP). Conversely, these berries showed the lowest values of firmness and titratable acidity. With the onset of physiological development, the average number of punctures per berry increased and reached 5.2 per berry in 100 DAPP berries. The infestation level and pupal weight showed a positive correlation with the growth stage. The highest recovery of pupae was observed in 100 DAPP berries (1.54). Pupal viability values ranged from 50.9 to 64.7% independent of berry maturity stage. The physiological developmental stage of the berry did not affect offspring sex ratio. Results obtained suggest that regardless of the female preference for laying eggs on berries in a more advanced physiological developmental stage, females can initiate the attack to bunches of this cultivar at 60 DAPP, even if the berries have unfavorable physicochemical parameters for oviposition and development of larvae.


Asunto(s)
Ceratitis capitata/fisiología , Producción de Cultivos , Oviposición , Vitis , Animales , Brasil , Ceratitis capitata/crecimiento & desarrollo , Larva/crecimiento & desarrollo , Larva/fisiología , Pupa/crecimiento & desarrollo , Pupa/fisiología , Vitis/crecimiento & desarrollo
7.
Curr Opin Rheumatol ; 30(1): 44-49, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28957961

RESUMEN

PURPOSE OF REVIEW: Patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have an increased malignancy risk compared with the general population. This review aims to evaluate recent evidence for changes in the incidence of malignancy in patients with AAV and to examine explanations for the association between AAV and malignancy. RECENT FINDINGS: The overall malignancy risk in patients with AAV has decreased, most likely as a result of recent changes in therapeutic regimen, that is, a decrease in the exposure to cyclophosphamide. The risk of nonmelanoma skin cancer (NMSC), however, remains increased, which is probably attributable to treatment with azathioprine. Malignancy risk in patients with AAV treated with rituximab was found to be lower than in cyclophosphamide-treated patients. The incidence of malignancy prior to AAV is not increased compared with the general population. SUMMARY: Continuing efforts to reduce the exposure to cyclophosphamide have led to a decrease in malignancy risk in patients with AAV, except for NMSC. Rituximab could be a well tolerated alternative for cyclophosphamide regarding the development of malignancies.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Neoplasias/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Azatioprina/uso terapéutico , Ciclofosfamida/uso terapéutico , Humanos , Incidencia , Factores de Riesgo , Rituximab/uso terapéutico , Neoplasias Cutáneas/epidemiología
8.
BMC Nephrol ; 18(1): 64, 2017 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-28202003

RESUMEN

BACKGROUND: Infection with the human T-cell lymphotropic virus type 1 (HTLV-1), although asymptomatic in most cases, can lead to potentially grave consequences, such as adult T-cell leukemia-lymphoma and HTLV-1-associated myelopathy / tropical spastic paraparesis. Its prevalence varies widely across different populations and geographic regions. A population-based study in the city of Salvador, located in the Northeast region of Brazil, showed an overall prevalence of HTLV-1 seropositivity of 1.7%. Blood borne virus infections are recognized as important hazards for patients and staff in maintenance hemodialysis (MHD) units but most studies focus on hepatitis B, hepatitis C and human immunodeficiency viruses. There are scarce data about HTLV-1 infection in the MHD population. We aimed to determine the prevalence and risk factors for HTLV-1 infection among MHD patients in the city of Salvador-Bahia, Brazil. METHODS: We conducted a multi-center, cross-sectional study nested in a prospective cohort of MHD patients enrolled from four outpatient clinics. HTLV-1 screening was performed with ELISA and positive cases were confirmed by Western Blot. Factors associated with HTLV-1 seropositivity were identified by multivariable logistic regression. RESULTS: 605 patients were included in the study. The overall prevalence of HTLV-1 infection was 2.48% (15/605), which was similar to that of hepatitis B [1.98% (12/605)] and C [3.14% (19/605)] viruses in our sample. HTLV-1 seropositivity was positively associated with age [prevalence odds ratio (POR) 1.04; 95% confidence interval (CI) 1.01-1.08], unmarried status (POR 3.65; 95% CI 1.13-11.65), and history of blood transfusion (POR 3.35; 95% CI 1.01-11.13). CONCLUSIONS: The overall prevalence of HTLV-1 infection in a sample of MHD patients was similar to that of other viral infections, such as hepatitis B and C. Our data revealed that MHD patients who are older, unmarried or who have received blood transfusions are at higher risk for HTLV-1 infection.


Asunto(s)
Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Fallo Renal Crónico/virología , Diálisis Renal/estadística & datos numéricos , Adulto , Anciano , Brasil/epidemiología , Causalidad , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Resultado del Tratamiento
9.
Lasers Med Sci ; 32(4): 921-930, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28349345

RESUMEN

The antifungal drug therapy often employed to treat paracoccidiodomycosis (PCM), an important neglected fungal systemic infection, leads to offensive adverse effects, besides being very long-lasting. In addition, PCM compromises the oral health of patients by leading to oral lesions that are very painful and disabling. In that way, photodynamic therapy (PDT) arises as a new promising adjuvant treatment for inactivating Paracoccidioides brasiliensis (Pb), the responsible fungus for PCM, and also for helping the patients to deal with such debilitating oral lesions. PDT has been linked to an improved microbial killing, also presenting the advantage of not inducing immediate microbial resistance such as drugs. For the present study, we investigated the generation of reactive oxygen species (ROS) by using the fluorescent probes hydroxyphenyl fluorescein (HPF) and aminophenyl fluorescein (APF) after toluidine blue (TBO-37.5 mg/L)-mediated PDT (660 nm, 40 mW, and 0.04 cm2 spot area) and the action of TBO-PDT upon Pb cultures grown for 7 or 15 days in semisolid Fava Netto's culture medium; we also targeted oral PCM manifestations by reporting the first clinical cases (three patients) to receive topic PDT for such purpose. We were able to show a significant generation of hydroxyl radicals and hypochlorite after TBO-PDT with doses around 90 J/cm2; such ROS generation was particularly useful to attack and inactivate Pb colonies at 7 and 15 days. All three patients reported herein related an immediate relief when it came to pain, mouth opening, and also the ability to chew and swallow. As extracted from our clinical results, which are in fact based on in vitro outcomes, TBO-PDT is a very safe, inexpensive, and promising therapy for the oral manifestations of PCM.


Asunto(s)
Viabilidad Microbiana/efectos de los fármacos , Enfermedades de la Boca/tratamiento farmacológico , Enfermedades de la Boca/microbiología , Paracoccidioides/efectos de la radiación , Paracoccidioidomicosis/tratamiento farmacológico , Paracoccidioidomicosis/microbiología , Fotoquimioterapia , Cloruro de Tolonio/uso terapéutico , Adulto , Antifúngicos/farmacología , Colorantes Fluorescentes/química , Humanos , Cinética , Masculino , Persona de Mediana Edad , Enfermedades de la Boca/patología , Paracoccidioides/crecimiento & desarrollo , Especies Reactivas de Oxígeno/metabolismo , Cloruro de Tolonio/farmacología
10.
Int J Mol Sci ; 18(9)2017 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-28906474

RESUMEN

Compound 8-C-rhamnosyl apigenin (8CR) induced a moderate reduction in the enzymatic activity of secretory phospholipase A2 (sPLA2) from Crotalus durissus terrificus and cytosolic phospholipase A2 (cPLA2), but the compound also significantly inhibited the enzymatic activity of the enzyme cyclooxygenase. In vitro assays showed that the compound induced a slight change in the secondary structure of sPLA2 from Crotalus durissus terrificus snake venom. In vivo assays were divided into two steps. In the first step, the 8CR compound was administered by intraperitoneal injections 30 min prior to administration of sPLA2. In this condition, 8CR inhibited edema and myonecrosis induced by the sPLA2 activity of Crotalus durissus terrificus in a dose-dependent manner by decreasing interleukin-1ß (IL-1ß), tumor necrosis factor α (TNF-α), prostaglandin E2 (PGE2), and lipid peroxidation. This has been demonstrated by monitoring the levels of malondialdehyde (MDA) in rat paws after the course of edema induced by sPLA2. These results, for the first time, show that sPLA2 of Crotalus durissus terrificus venom induces massive muscle damage, as well as significant edema by mobilization of cyclooxygenase enzymes. Additionally, its pharmacological activity involves increased lipid peroxidation as well as TNF-α and IL-1ß production. Previous administration by the peritoneal route has shown that dose-dependent 8CR significantly decreases the enzymatic activity of cyclooxygenase enzymes. This resulted in a decrease of the amount of bioactive lipids involved in inflammation; it also promoted a significant cellular protection against lipid peroxidation. In vivo experiments performed with 8CR at a concentration adjusted to 200 µg (8 mg/kg) of intraperitoneal injection 15 min after sPLA2 injection significantly reduced sPLA2 edema and the myotoxic effect induced by sPLA2 through the decrease in the enzymatic activity of cPLA2, cyclooxygenase, and a massive reduction of lipid peroxidation. These results clearly show that 8CR is a potent anti-inflammatory that inhibits cyclooxygenase-2 (COX-2), and it may modulate the enzymatic activity of sPLA2 and cPLA2. In addition, it was shown that Crotalus durissus terrificus sPLA2 increases cell oxidative stress during edema and myonecrosis, and the antioxidant properties of the polyphenolic compound may be significant in mitigating the pharmacological effect induced by sPLA2 and other snake venom toxins.


Asunto(s)
Apigenina/farmacología , Edema/tratamiento farmacológico , Peperomia/química , Extractos Vegetales/farmacología , Enfermedad Aguda , Animales , Apigenina/química , Biomarcadores , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Edema/etiología , Edema/metabolismo , Edema/patología , Mediadores de Inflamación/metabolismo , Estructura Molecular , Fosfolipasas A2 Secretoras/metabolismo , Extractos Vegetales/química , Ratas
11.
Tumour Biol ; 37(8): 11375-84, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26960831

RESUMEN

This study aimed to establish and characterize primary cell cultures and xenografts derived from penile carcinoma (PeCa) in order to provide experimental models for cellular processes and efficacy of new treatments. A verrucous squamous cell carcinoma (VSCC) was macrodissected, dissociated, and cultivated in KSFM/DF12 medium. Cell cultures were evaluated at passage 5 (P5) using migration and invasion assays and were serially propagated, in vivo, in BALB/c nude mice until passage 3 (X1-X3). Immunophenotypic characterization of cultures and xenografts was performed. Genomic (CytoScan HD, Affymetrix) and transcriptomic profiles (HTA 2.0 platform, Affymetrix) for VSCC, cell cultures, and xenografts were assessed. P5 cells were able to migrate, invade the Matrigel, and produce tumors in immunodeficient mice, demonstrating their malignant potential. The xenografts unexpectedly presented a sarcomatoid-like carcinoma phenotype. Genomic analysis revealed a high similarity between the VSCC and tumor-derived xenograft, confirming its xenograft origin. Interestingly, a subpopulation of P5 cells presented stem cell-related markers (CD44(+)CD24(-) and ALDH1(high)) and sphere-forming capacity, suggesting their potential xenograft origin. Cell cultures and xenografts retained the genomic alterations present in the parental tumor. Compared to VSCC, differentially expressed transcripts detected in all experimental conditions were associated with cellular morphology, movement, and metabolism and organization pathways. Malignant cell cultures and xenografts derived from a verrucous penile carcinoma were established and fully characterized. Nevertheless, xenograft PeCa models must be used with caution, taking into consideration the selection of specific cell populations and anatomical sites for cell/tumor implantation.


Asunto(s)
Carcinoma Verrugoso/patología , Modelos Animales de Enfermedad , Xenoinjertos , Neoplasias del Pene/patología , Células Tumorales Cultivadas , Anciano , Animales , Carcinoma Verrugoso/genética , Citometría de Flujo , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Análisis de Secuencia por Matrices de Oligonucleótidos , Neoplasias del Pene/genética
12.
Tumour Biol ; 37(10): 13855-13870, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27485113

RESUMEN

Breast carcinoma (BC) corresponds to 23 % of all cancers in women, with 1.38 million new cases and 460,000 deaths worldwide annually. Despite the significant advances in the identification of molecular markers and different modalities of treatment for primary BC, the ability to predict its metastatic behavior is still limited. The purpose of this study was to identify novel molecular markers associated with distinct clinical outcomes in a Brazilian cohort of BC patients. We generated global gene expression profiles using tumor samples from 24 patients with invasive ductal BC who were followed for at least 5 years, including a group of 15 patients with favorable outcomes and another with nine patients who developed metastasis. We identified a set of 58 differentially expressed genes (p ≤ 0.01) between the two groups. The prognostic value of this metastasis signature was corroborated by its ability to stratify independent BC patient datasets according to disease-free survival and overall survival. The upregulation of B3GNT7, PPM1D, TNKS2, PHB, and GTSE1 in patients with poor outcomes was confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in an independent sample of patients with BC (47 with good outcomes and eight that presented metastasis). The expression of BCL2-associated agonist of cell death (BAD) protein was determined in 1276 BC tissue samples by immunohistochemistry and was consistent with the reduced BAD mRNA expression levels in metastatic cases, as observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinomas with metastatic potential from those with favorable outcomes.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/secundario , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/metabolismo , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Prohibitinas , Proteína Fosfatasa 2C/genética , Proteína Fosfatasa 2C/metabolismo , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Tanquirasas/genética , Tanquirasas/metabolismo , Adulto Joven
13.
Tumour Biol ; 37(3): 3145-53, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26427657

RESUMEN

Despite one third of breast (BC) and colorectal cancer (CRC) cases having a hereditary component, only a small proportion can be explained by germline mutations. The aim of this study was to identify potential genomic alterations related to cancer predisposition. Copy number variations (CNVs) were interrogated in 113 unrelated cases fulfilling the criteria for hereditary BC/CRC and presenting non-pathogenic mutations in BRCA1, BRCA2, MLH1, MSH2, TP53, and CHEK2 genes. An identical germline deep intronic deletion of ROBO1 was identified in three index patients using two microarray platforms (Agilent 4x180K and Affymetrix CytoScan HD). The ROBO1 deletion was confirmed by quantitative PCR (qPCR). Six relatives were also evaluated by CytoScan HD Array. Genomic analysis confirmed a co-segregation of the ROBO1 deletion with the occurrence of cancer in two families. Direct sequencing revealed no pathogenic ROBO1 point mutations. Transcriptomic analysis (HTA 2.0, Affymetrix) in two breast carcinomas from a single patient revealed ROBO1 down-expression with no splicing events near the intronic deletion. Deeper in silico analysis showed several enhancer regions and a histone methylation mark in the deleted region. The ROBO1 deletion in a putative transcriptional regulatory region, its down-expression in tumor samples, and the results of the co-segregation analysis revealing the presence of the alteration in affected individuals suggest a pathogenic effect of the ROBO1 in cancer predisposition.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias Colorrectales/genética , Eliminación de Gen , Proteínas del Tejido Nervioso/genética , Receptores Inmunológicos/genética , Adulto , Anciano , Neoplasias Colorrectales/etiología , Variaciones en el Número de Copia de ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas Roundabout
14.
Exp Appl Acarol ; 69(3): 311-21, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27085718

RESUMEN

The effect of aromatic plants on number of twospotted spider mite (TSSM), Tetranychus urticae Koch, when intercropped with strawberry were assessed in the field. During the first year, chives (Allium schoenoprasum L.), coriander (Coriandrum sativum L.), fennel (Foeniculum vulgare Mill.), garlic (Allium sativum L.), oregano (Origanum vulgare L.), or sweet marjoram (Origanum majorana L.) were intercropped with strawberry. Assessments were performed on TSSM populations by taking six samples from July 20 to September 20, 2012. During the second year, garlic plants were intercropped between rows of strawberry at three densities in greenhouse and field. Mobile forms and eggs numbers (only in field) of TSSM were evaluated from April 18 to June 05 (greenhouse) and June 06 to August 14, 2013 (field). It was found that intercropping with garlic caused a greater reduction of TSSM (up to 52 %) in strawberry plants when higher populations of TSSM occurred in the field. TSSM reduction was found in one sample when fennel and chives were intercropped with strawberries (42 and 50 % reduction, respectively); this also occurred when populations of TSSM were higher. The three densities of garlic plants (one, two and three rows among the strawberry rows) reduced TSSM mobile forms by 49, 53 and 60 % (greenhouse) and 44, 51 and 65 % (field), and eggs by 38, 43 and 64 % (field), respectively. The results suggest that intercropping garlic plants between strawberry rows is a promising strategy to reduce TSSM populations.


Asunto(s)
Agricultura/métodos , Control Biológico de Vectores/métodos , Tetranychidae/fisiología , Animales , Brasil , Fragaria
15.
Exp Cell Res ; 326(1): 103-11, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24929113

RESUMEN

Clinical experience for peripheral arterial disease treatment shows poor results when synthetic grafts are used to approach infrapopliteal arterial segments. However, tissue engineering may be an option to yield surrogate biocompatible neovessels. Thus, biological decellularized scaffolds could provide natural tissue architecture to use in tissue engineering, when the absence of ideal autologous veins reduces surgical options. The goal of this study was to evaluate different chemical induced decellularization protocols of the inferior vena cava of rabbits. They were decellularized with Triton X100 (TX100), sodium dodecyl sulfate (SDS) or sodium deoxycholate (DS). Afterwards, we assessed the remaining extracellular matrix (ECM) integrity, residual toxicity and the biomechanical resistance of the scaffolds. Our results showed that TX100 was not effective to remove the cells, while protocols using SDS 1% for 2h and DS 2% for 1h, efficiently removed the cells and were better characterized. These scaffolds preserved the original organization of ECM. In addition, the residual toxicity assessment did not reveal statistically significant changes while decellularized scaffolds retained the equivalent biomechanical properties when compared with the control. Our results concluded that protocols using SDS and DS were effective at obtaining decellularized scaffolds, which may be useful for blood vessel tissue engineering.


Asunto(s)
Tensoactivos/farmacología , Ingeniería de Tejidos , Andamios del Tejido , Trasplante de Tejidos , Vena Cava Inferior/citología , Vena Cava Inferior/fisiología , Tejido Adiposo/citología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Fenómenos Biomecánicos , Diferenciación Celular , Células Cultivadas , Matriz Extracelular/química , Femenino , Técnicas para Inmunoenzimas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Conejos , Vena Cava Inferior/efectos de los fármacos
16.
J Stroke Cerebrovasc Dis ; 24(9): 2088-94, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26187787

RESUMEN

BACKGROUND: The present study aimed to evaluate the relation between the National Institutes of Health Stroke Scale (NIHSS) score and the presence of laryngeal penetration and/or laryngotracheal aspiration in ischemic stroke patients and to verify what factors are predictors of the occurrence of pneumonia in the evaluated patients. METHODS: This was an observational study of ischemic stroke in the acute or subacute phases. Neurologic examination included anamnesis, Bamford classification, and application of the NIHSS. Speech therapy evaluation was carried out after clinical stabilization of the patient, and all individuals who were considered dysphagic were sent for examination by means of videofluoroscopic recordings. The parameters observed in the objective examination were the presence of laryngeal penetration and/or laryngotracheal aspiration. The pneumonia data were obtained in accordance with local protocols, which were based on international guidelines. The relation of laryngeal penetration and laryngotracheal aspiration with the NIHSS score was assessed by the Mann-Whitney U test, and predictors for the occurrence of pneumonia were analyzed by multiple logistic regression using semiautomatic backward selection. Significance was set at P less than .05. RESULTS: The relations between laryngeal penetration and the NIHSS score and between laryngotracheal aspiration and the NIHSS score were not statistically significant. The predictors for pneumonia occurrence in the ischemic stroke patients with a clinical diagnosis of dysphagia were age (P = .002; odds ratio [OR], 1.12) and NIHSS score (P = .04; OR, 1.17), whereas laryngeal penetration of liquid (P = .065; OR, 3.70) tended to correlate with pneumonia but not significantly. CONCLUSIONS: There was no relation between the NIHSS score and laryngeal penetration or laryngotracheal aspiration, and the principal predictors of pneumonia in dysphagic patients after ischemic stroke were advanced age and neurologic severity.


Asunto(s)
Trastornos de Deglución/etiología , Neumonía/diagnóstico , Neumonía/etiología , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Trastornos de Deglución/rehabilitación , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , National Institutes of Health (U.S.)/normas , Examen Neurológico , Neumonía/epidemiología , Valor Predictivo de las Pruebas , Logopedia , Estadísticas no Paramétricas , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Estados Unidos
18.
J Nat Prod ; 77(8): 1881-6, 2014 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-25051336

RESUMEN

To determine the absolute configuration of 3-ishwarone, the experimental electronic circular dichroism (ECD), electronic dissymmetry factor (EDF), optical rotatory dispersion (ORD), vibrational circular dichroism (VCD), and vibrational dissymmetry factor (VDF) spectra of (+)-3-ishwarone are analyzed with the corresponding density functional theoretical predictions for different diastereomers. ECD and ORD spectra by themselves could not facilitate the determination of the absolute configuration of this molecule. However, the magnitude of the experimental EDF of (+)-3-ishwarone is found to match better with that predicted for the (1R,2S,4S,5R,9R,11R) diastereomer. The analyses of similarity measures between experimental and predicted spectra for VCD and VDF clearly suggested that the absolute configuration of (+)-3-ishwarone is (1R,2S,4S,5R,9R,11R).


Asunto(s)
Sesquiterpenos/química , Algoritmos , Brasil , Dicroismo Circular , Estructura Molecular , Dispersión Óptica Rotatoria , Peperomia/química , Componentes Aéreos de las Plantas/química , Estereoisomerismo
19.
BMC Med Educ ; 14: 51, 2014 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-24636494

RESUMEN

BACKGROUND: Medical students engage in curricular and extracurricular activities, including undergraduate research (UR). The advantages, difficulties and motivations for medical students pursuing research activities during their studies have rarely been addressed. In Brazil, some medical schools have included undergraduate research into their curriculum. The present study aimed to understand the reality of scientific practice among medical students at a well-established Brazilian medical school, analyzing this context from the students' viewpoint. METHODS: A cross-sectional survey based on a questionnaire applied to students from years one to six enrolled in an established Brazilian medical school that currently has no curricular UR program. RESULTS: The questionnaire was answered by 415 students, 47.2% of whom were involved in research activities, with greater participation in UR in the second half of the course. Independent of student involvement in research activities, time constraints were cited as the main obstacle to participation. Among students not involved in UR, 91.1% said they favored its inclusion in the curriculum, since this would facilitate the development of such activity. This approach could signify an approximation between the axes of teaching and research. Among students who had completed at least one UR project, 87.7% said they would recommend the activity to students entering the course. CONCLUSION: Even without an undergraduate research program, students of this medical school report strong involvement in research activities, but discussion of the difficulties inherent in its practice is important to future developments.


Asunto(s)
Investigación Biomédica , Educación Médica/métodos , Estudiantes de Medicina/psicología , Investigación Biomédica/organización & administración , Brasil , Estudios Transversales , Curriculum , Femenino , Humanos , Masculino
20.
J Stroke Cerebrovasc Dis ; 23(6): 1524-8, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24582786

RESUMEN

BACKGROUND: The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. METHODS: Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann-Whitney test and considered significant if P is less than .05. RESULTS: The moderate and severe degrees of dysphagia were more frequent (P=.013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P=.045). CONCLUSIONS: We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy.


Asunto(s)
Isquemia Encefálica/terapia , Trastornos de Deglución/epidemiología , Neumonía/epidemiología , Reperfusión , Accidente Cerebrovascular/terapia , Anciano , Isquemia Encefálica/complicaciones , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Femenino , Humanos , Incidencia , Masculino , Neumonía/diagnóstico , Neumonía/etiología , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones
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