Evaluation of serum levels of C-reactive protein, D-Dimer and Autologous Serum Skin Test in patients with Chronic Spontaneous Urticaria in a Brazilian tertiary center: a cross-sectional study

Abstract Background: The pathophysiology of urticaria is still poorly understood. Recent studies demonstrate that the activation of coagulation is correlated with the clinical activity of Chronic Spontaneous Urticaria. Coagulation and inflammation are strongly linked. Objectives: To correlate the severity and activity of Chronic Spontaneous Urticaria with the levels of D-dimer, C-reactive protein, and autologous serum test in patients with Chronic Spontaneous Urticaria. Methods: The study included 55 patients diagnosed with chronic spontaneous urticaria. D-dimer levels were measured using enzyme-linked fluorescent assay and C-reactive protein levels were measured using the nephelometric method; autologous serum testing was performed on patients who discontinued antihistamine therapy. The severity of the disease was assessed using the urticaria activity score. Results: patients with severe, spontaneous, and difficult-to-control chronic urticaria had elevated serum levels of D-dimer, as well as a positive autologous serum test. Little correlation was demonstrated between the severity of chronic spontaneous urticaria and the levels of C-reactive protein. Conclusion: The authors concluded that patients with severe Chronic Spontaneous Urticaria showed signs of activated fibrinolysis. Most patients with high clinical scores had high D-dimer values. Patients with positive results for the autologous serum test also had more severe Chronic Spontaneous Urticaria and needed more drugs to control the disease. Finally, little correlation was found between C-reactive protein levels and disease severity. Study limitations: The main limitation was the small sample of patients. In the present patients, it was demonstrated that serum D-dimer levels and the autologous serum test can act as predictive markers of severity and activity of Chronic Spontaneous Urticaria.

Immunohistochemical analysis of apoptosis and cell proliferation in lungs of premature infants with chronic lung disease (bronchopulmonary dysplasia) / Análise imuno-histoquímica da apoptose e proliferação celular em pulmões de prematuros com doença pulmonar crônica (displasia broncopulmonar)

ABSTRACT Introduction: The pathophisiology of chronic lung disease (CLD), clinically known as bronchopulmonary dysplasia is not clear. It is believed that protective mechanisms, such as the release of inflammatory mediators and the activation of apoptotic and/or proliferative processes are activated in the lung tissue of premature infants in an attempt to repair tissue injury caused by exposure to oxygen and mechanical ventilation. Objective: Assess the presence of apoptosis and cell proliferation in the lungs of premature infants with CLD, exposed to oxygen and/or mechanical ventilation, by analyzing the proteins expression: proliferating cell nuclear antigen (PCNA), phosphatase and tensin homolog (PTEN), B-cell lymphoma 2 (Bcl-2), tumor necrosis factor receptor family member (Fas), fas-associated protein with death domain (FADD), tumor necrosis factor receptor type 1-associated death domain protein (TRADD), Caspase 3 and Caspase 8. Material and methods: We analyzed 32 infants autopsies at gestational age of less than 34 weeks exposed to oxygen therapy. The study was divided into three groups: "classic" CLD, "new" CLD and "without" CLD. Immunohistochemical analysis was performed. Results and discussion: A higher proliferation rate was observed in infants with CLD suggesting that longer exposure to mechanical ventilation may stimulates cell proliferation. The PTEN and Caspase 8 expressions were higher in the "new" CLD group, compared to the "without" CLD group, indicating that the "new" CLD form is more susceptible to apoptosis. Conclusion: Apoptosis and cell proliferation are involved in the pathophisiology of CLD. The "new" CLD form is more susceptible to apoptosis, while cell proliferation is more evident in the groups with CLD.

RESUMO Introdução: A fisiopatologia da doença pulmonar crônica, clinicamente conhecida como displasia broncopulmonar (DBP), ainda é incerta. Acredita-se que mecanismos de proteção, como liberação de mediadores inflamatórios e ativação de processos apoptóticos e/ou proliferativos, são acionados no tecido pulmonar de prematuros na tentativa de reparar os danos teciduais causados pela exposição ao oxigênio e à ventilação mecânica. Objetivo: Avaliar a existência de apoptose e proliferação celular em pulmões de neonatos prematuros com DBP, expostos ao oxigênio e/ou à ventilação mecânica, por meio do estudo da expressão das proteínas: antígeno nuclear de proliferação celular (PCNA), homólogo da fosfatase e tensina (PTEN), linfoma de células B 2 (Bcl-2), membro da família de receptor do fator de necrose tumoral (Fas), proteína de domínio de morte associada ao Fas (FADD), proteína do domínio de morte associada ao receptor do fator de necrose tumoral (TRADD), Caspase 3 e Caspase 8. Material e método: Foram analisadas 32 autópsias de recém-nascidos, com idade gestacional inferior a 34 semanas, expostos ao oxigênio. O estudo foi dividido em três grupos: DBP "clássica", DBP "nova" e "sem" DBP; realizou-se estudo imuno-histoquímico. Resultados e discussão: Um índice de proliferação mais elevado foi observado nos recém-nascidos com DBP, sugerindo que o maior tempo de exposição à ventilação mecânica pode estimular a proliferação celular. A expressão das proteínas PTEN e Caspase 8 foram maiores no grupo da DBP "nova" em relação ao grupo sem DBP, indicando que a DBP "nova" é mais suscetível à apoptose. Conclusão: A apoptose e a proliferação celular estão envolvidas na fisiopatologia da DBP, sendo a apoptose mais evidente no grupo com DBP "nova".

Efeito nefroprotetor do α bisabolol na lesão renal aguda em modelos de isquemia reperfusão

A Isquemia/Reperfusão (I/R)é um fenômeno complexo, que contribui para a mortalidade e morbidade e é um fator predisponente para o estabelecimento da Lesão Renal Aguda (LRA). Várias estratégias e recursos são utilizados pelascélulas para prevenir ou diminuir a injúria celular causada pelo estresse oxidativo. Dessa forma, ressalta-se a importância do estudo utilizando substâncias como o (-)-α-Bisabolol, o qual apresenta um potencial antioxidante. Ademais, o estudo de ferramentaspara diagnóstico precoce do desenvolvimento da lesão renal utilizando biomarcadores cada vez mais sensíveis e específicos, como ressaltado neste trabalho o KIM-1, pode auxiliar na detecção da injúria e acompanhamento da progressão do processo de melhorae cura. Logo, o presente trabalho tem como objetivo estudar os possíveis efeitos nefroprotetores do (-)-α-Bisabolol na Lesão Renal Aguda (LRA) em modelos de Isquemia/Reperfusão (I/R), bem como estudar obiomarcador KIM-1 como preditor precoce da injúria renal. Ratos Wistar machos foram submetidos aoprocedimento cirúrgico de nefrectomia direita e clampeamento da artéria renal esquerda. Amostras de urina, sangue e tecido renal foram coletadas para avaliações adicionais. Um modelo in vitro de I/R foi realizado em cultura de linhagens de células tubulares renais LLC-MK2 para avaliar a viabilidade celular pelo ensaio de redução do MTT...

Ischemia / reperfusion (IR) isa complex phenomenon that contributes to mortality and morbidity and is a predisposing factor for the establishment of acute kidney injury (AKI). Various strategies and resources are used by cells to prevent or decrease the cellular injury caused by oxidative stress. Thus, it emphasizes the importance of studying using substances such as (-)-α-Bisabolol, which has an antioxidant potential. Furthermore, the study of strategies for early detection of developing kidney damage using increasingly sensitive and specific biomarkers, as pointed out in this paper the KIM-1, can aid in the detection of injury and follow the progression of improvement and healing process. Thus, this paper aims to study the possible nephroprotectiveseffects of (-)-α-Bisabolol in AcuteKidney Injury (AKI) in models of ischemia/reperfusion (I/R), as well as study the KIM-1 biomarker as a predictor early renal injury. Male Wistar rats underwent surgical procedure right nephrectomy and clamping of the left renal artery. Samples of urine, blood and kidney tissue were collected for further evaluation. An in vitro model of I/R was performed in a culture of renal tubular cell lines, LLC-MK2 to assess cell viability by the MTT reduction assay...

Análise dos níveis séricos do biomarcador CTX-II em atletas profissionais de futebol de salão durante uma temporada / Analysis on the serum levels of the biomarker CTX-II in professional indoor soccer players over the course of one season

OBJETIVO: Analisar os níveis séricos sanguíneos de CTX-II em atletas profissionais de futebol de salão, em três momentos distintos durante uma temporada: no início da pré-temporada, quatro meses após (período que marca o meio da temporada) e no fim da temporada. MÉTODOS: Foram incluídos 14 atletas do gênero masculino e média de idade de 19 anos. Foram coletados 3 mL de sangue de cada indivíduo. As amostras foram analisadas pelo teste do tipo Elisa. RESULTADOS: Houve aumento significativo dos níveis séricos de CTX-II nos atletas de futebol de salão, comparando-se o início e o fim de uma temporada (p < 0,01). CONCLUSÃO: Esses dados sugerem a ocorrência de degradação articular nos atletas, ao término desse período. Fica evidente a necessidade de futuros estudos, com rigor metodológico, que possam contribuir efetivamente para a elucidação precisa da etiologia da OA e sua relação com os biomarcadores como instrumento de diagnóstico precoce.

OBJECTIVE:The aim of this study was to analyze the blood serum levels of CTX-II in professional indoor soccer players, at three different times during one season: at the start of the pre-season, four months later (a time that marks the middle of the season) and at the end of the season.METHODS:Fourteen male soccer players of mean age 19 years were included. Blood samples of 3 mL were collected from each individual. The samples were analyzed by means of Elisa tests.RESULTS:There was a significant increase in the serum level of CTX-II in the indoor soccer players, from the beginning to the end of the season (p< 0.01).CONCLUSION:These data suggest that joint degradation had occurred in these soccer players, by the end of this period. It is evident that further studies are needed, with methodological rigor, so as to make an effective contribution toward precise elucidation of the etiology of this osteoarthritis and its relationship with the biomarkers, as a tool fr early diagnosis.

Drug Similarity Search Based on Combined Signatures in Gene Expression Profiles / 대한의료정보학회지

OBJECTIVES: Recently, comparison of drug responses on gene expression has been a major approach to identifying the functional similarity of drugs. Previous studies have mostly focused on a single feature, the expression differences of individual genes. We provide a more robust and accurate method to compare the functional similarity of drugs by diversifying the features of comparison in gene expression and considering the sample dependent variations. METHODS: For differentially expressed gene measurement, we modified the conventional t-test to normalize variations in diverse experimental conditions of individual samples. To extract significant differentially co-expressed gene modules, we searched maximal cliques among the co-expressed gene network. Finally, we calculated a combined similarity score by averaging the two scaled scores from the above two measurements. RESULTS: This method shows significant performance improvement in comparison to other approaches in the test with Connectivity Map data. In the test to find the drugs based on their own expression profiles with leave-one-out cross validation, the proposed method showed an area under the curve (AUC) score of 0.99, which is much higher than scores obtained with previous methods, ranging from 0.71 to 0.93. In the drug networks, we could find well clustered drugs having the same target proteins and novel relations among drugs implying the possibility of drug repurposing. CONCLUSIONS: Inclusion of the features of a co-expressed module provides more implications to infer drug action. We propose that this method be used to find collaborative cellular mechanisms associated with drug action and to simply identify drugs having similar responses.

Endophenotypes and biomarkers: an approach to molecular genetic studies of mental disorders / Endofenotipos y biomarcadores: un enfoque hacia el estudio genético molecular de los trastornos mentales

Many precise aspects of the etiology and pathophysiology of mental disorders are still unknown. Susceptibility to these disorders depends in part on variability in the genome sequence among individuals. The genotype, a given environment, a specific epigenetic profile and stochastic factors affect the phenotype, which includes body structures, physiological processes, and behavior. Since the access to the Central Nervous System is generally difficult and in most cases there are still no biological tests that necessarily contribute to diagnosis, psychiatric phenotypes are usually limited to clinical symptoms and functioning. Therefore, researchers are currently seeking alternatives to facilitate the identification of genetic risk factors. One strategy is to identify measurable biological, cognitive, and behavioral markers, intermediate phenotypes, or endophenotypes, which in the best case may be simpler than general psychiatric diagnoses, ideally with a precise biological meaning and a more direct relationship with the action of specific genes. Endophenotypes have been very useful in other fields of medicine. Currently, there are several proposed criteria and specifications for endophenotypes. Examples of possible types of endophenotypes or biomarkers, as well as treatment response phenotypes in some psychiatric disorders will be discussed in this review.

Aún se desconocen diversos aspectos de la etiología y fisiopatología de los trastornos mentales. La susceptibilidad a éstos depende en parte de la variabilidad en la secuencia genómica en las personas. El genotipo, un ambiente dado, un perfil epigenético específico y factores estocásticos afectan el fenotipo, el cual incluye estructuras corporales, procesos fisiológicos y conducta. Los fenotipos psiquiátricos generalmente se limitan al funcionamiento y a los síntomas clínicos, debido a que el acceso al Sistema Nervioso Central es complicado y en la mayoría de los casos no hay pruebas biológicas que necesariamente contribuyan al diagnóstico. Por esta razón, en la actualidad se buscan alternativas para facilitar la identificación de factores de riesgo de tipo genético. La identificación de marcadores biológicos, cognitivos o conductuales medibles, fenotipos intermedios o endofenotipos podría ser una de estas nuevas opciones. Estos marcadores podrían ser más simples que el diagnóstico psiquiátrico general, y de manera ideal tendrían un significado biológico preciso y una acción más directa en los genes. El empleo de endofenotipos ha sido útil en otras ramas de la medicina. Hasta ahora se han propuesto diversos criterios y especificaciones para los endofenotipos. En esta revisión se describirán posibles tipos de endofenotipos o biomarcadores, así como fenotipos relacionados con la respuesta farmacológica en algunos trastornos psiquiátricos.

Characterization of biological responses of colorectal cancer cells to anticancer regimens / 대한외과학회지

PURPOSE: Identification of subgroups of patients who differ in their response to treatment could help to establish which of the best available chemotherapeutic options are best, based on biological activity. In metastatic colorectal cancer (CRC), novel molecular-targeted agents that act on pathways that regulate cell growth, the cell cycle, apoptosis, angiogenesis, and invasion are being developed. Here, we employed an in vitro chemosensitivity assay to evaluate the biological efficacy of conventional monotherapies and combination chemotherapy with targeted drugs. METHODS: The chemosensitivities of 12 CRC cell lines to the established regimens FOLFOX (5-fluorouracil [5-FU] + leucovorin + oxaliplatin) and FOLFIRI (5-FU + leucovorin + irinotecan) and to therapy with these regimens in combination with the biologically targeted drugs bevacizumab or cetuximab were comparatively evaluated for their effects on apoptotic and autophagic cell death processes, angiogenesis, and invasion. RESULTS: Each of the chemotherapeutic regimens promoted apoptotic cell death and invasion. All drug regimens caused significantly greater apoptotic cell death with activation of caspase-3 in SW480 cells compared to other cells, effects that were associated with a remarkable reduction in matrix metalloproteinase-9 activity. The FOLFOX regimen more effectively promoted apoptotic cell death, angiogenesis, and invasion than the FOLFIRI regimen. Combination therapy with FOLFOX/FOLFIRI regimen and bevacizumab produced a moderate angiogenesis-blocking effect in most cell lines. CONCLUSION: The results validate our in vitro chemosensitivity assay, and suggest that it may be applied to help determine adequate regimens in individual CRC patients based on the biological characteristics of their tumors.