RESUMO
SUMMARY: Apocrine glands are sweat glands that are located in the skin of the dog. Anal sac apocrine, circunanal apocrine, and mammary glands are considered modified apocrine structures, and there are about nine possible types of neoplasms and other tumors in the apocrine glands of the dog and cat, including cysts, adenoma, carcinoma, and adenocarcinoma. Thus, it is important to provide new markers to characterize these glands to improve the histopathological diagnosis. In this article, we describe the distribution of kallikrein- related peptidases 5, 7, 8, and 10 in the normal apocrine glands of the dog's skin. These proteases have been shown to play a fundamental role in the homeostasis of the human skin barrier but have been scarcely studied in canine skin.
Las glándulas apocrinas son glándulas sudoríparas que se encuentran en la piel del perro. Las glándulas apocrinas del saco anal, apocrinas circunanales y mamarias se consideran estructuras apocrinas modificadas, y existen alrededor de nueve tipos posibles de neoplasias y otros tumores en las glándulas apocrinas del perro y el gato, incluidos quistes, adenoma, carcinoma y adenocarcinoma. Por lo tanto, es importante proporcionar nuevos marcadores para caracterizar estas glándulas para mejorar el diagnóstico histopatológico. En este artículo, describimos la distribución de las peptidasas 5, 7, 8 y 10 relacionadas con la calicreína en las glándulas apocrinas normales de la piel del perro. Se ha demostrado que estas proteasas desempeñan un papel fundamental en la homeostasis de la barrera de la piel humana, pero apenas se han estudiado en la piel canina.
Assuntos
Animais , Cães , Glândulas Apócrinas/metabolismo , Glândulas Apócrinas/química , Calicreínas/análise , Calicreínas/metabolismo , Pele , Imuno-HistoquímicaRESUMO
O tratamento do angioedema hereditário tem início com a educação dos pacientes e familiares sobre a doença, pois é fundamental o conhecimento da imprevisibilidade das crises, assim como os seus fatores desencadeantes. O tratamento medicamentoso se divide em terapia das crises e profilaxia das manifestações clínicas. As crises devem ser tratadas o mais precocemente possível com o uso do antagonista do receptor de bradicinina, o icatibanto ou o concentrado de C1-inibidor. É necessário estabeler um plano de ação em caso de crises para todos os pacientes. A profilaxia de longo prazo dos sintomas deve ser realizada preferencialmente com medicamentos de primeira linha, como concentrado do C1-inibidor ou o anticorpo monoclonal anti-calicreína, lanadelumabe. Como segunda linha de tratamento temos os andrógenos atenuados. Na profilaxia de curto prazo, antes de procedimentos que podem desencadear crises, o uso do concentrado de C1-inibidor é preconizado. Existem algumas restrições para uso desses tratamentos em crianças e gestantes que devem ser consideradas. Novos medicamentos baseados nos avanços do conhecimento da fisiopatologia do angioedema hereditário estão em desenvolvimento, devendo melhorar a qualidade de vida dos pacientes. O uso de ferramentas padronizadas para monitorização da qualidade de vida, do controle e da atividade da doença são fundamentais no acompanhamento destes pacientes. A criação de associações de pacientes e familiares de pacientes com angioedema hereditário tem desempenhado um papel muito importante no cuidado destes pacientes no nosso país.
The treatment of hereditary angioedema begins with the education of patients and their families about the disease, as it is essential to know the unpredictability of attacks as well as their triggering factors. Drug treatment is divided into attack therapy and prophylaxis of clinical manifestations. Attacks should be treated as early as possible with the bradykinin receptor antagonist icatibant or C1-inhibitor concentrate. An action plan needs to be established for all patients with attacks. Long-term prophylaxis of symptoms should preferably be performed with first-line drugs such as C1-inhibitor concentrate or the anti-kallikrein monoclonal antibody lanadelumab. Attenuated androgens are the second line of treatment. In short-term prophylaxis, before procedures that can trigger attacks, the use of C1-inhibitor concentrate is recommended. There are some restrictions for the use of these treatments in children and pregnant women that should be considered. New drugs based on advances in knowledge of the pathophysiology of hereditary angioedema are under development and are expected to improve patient quality of life. The use of standardized tools for monitoring quality of life and controlling disease activity is essential in the follow-up of these patients. The creation of associations of patients and families of patients with hereditary angioedema has played a very important role in the care of these patients in Brazil.
Assuntos
Humanos , Tratamento Farmacológico , Angioedemas Hereditários , Anticorpos Monoclonais Humanizados , Antagonistas dos Receptores da Bradicinina , Pacientes , Qualidade de Vida , Terapêutica , Bradicinina , Preparações Farmacêuticas , Calicreínas , Medicamentos de ReferênciaRESUMO
SUMMARY: Dental caries corresponds to an ecological and non-contagious, dynamic and chronic disease of multifactorial origin; currently there is evidence of how genetic factors could be included as predisposing agents to suffer it, however this evidence is diverse and incipient. a cross-sectional study was p erformed to investigate the possible associations of DSPP (rs36094464), RUNX2 (rs566712) and KLK4 (rs198968) polymorphisms in early childhood caries. Saliva samples of children (2-11years old) were collected and genotyped for DSPP (rs36094464), RUNX2 (rs566712) and KLK4 (rs198968) polymorphisms. Through the ceft index their caries history was determined and the gene variants were students through molecular biology techniques. polymorphisms of the DSSP (rs36094464) and RUNX2 (rs566712) are associated and contribute to the susceptibility of dental caries disease in early childhood, as they are related to their history of caries. KLK4 (rs198968) polymorphisms are not associated. In conclusions, the studied polymorphisms on DSSP and RUNX2 genes are associated with changes in the tooth microarchitecture, favoring the appearance of microlesions that would contribute to dental caries disease susceptibility in early childhood. Also, no association was found for the studied polymorphism of the KLK4 gene with dental caries disease susceptibility.
RESUMEN: La caries dental corresponde a una enfermedad crónica, no contagiosa, dinámica y de origen multifactorial. Actualmente existe evidencia de cómo los factores genéticos podrían incluirse como agentes predisponentes, sin embargo, esta evidencia es diversa e incipiente. Se realizó un estudio transversal para investigar las posibles asociaciones entre los polimorfismos DSPP (rs36094464), RUNX2 (rs566712) y KLK4 (rs198968) y la caries en la infancia. Se colectaron muestras de saliva de niños (de 2 a 11 años de edad) y se genotipificaron para los polimorfismos DSPP (rs36094464), RUNX2 (rs566712) y KLK4 (rs198968). Mediante el índice ceft se determinó su historial de caries y se estudiaron las variantes genéticas mediante técnicas de biología molecular. Los datos obtenidos indican que los polimorfismos del DSSP (rs36094464) y RUNX2 (rs566712) están asociados y contribuyen a la susceptibilidad de la enfermedad de caries dental en la infancia, ya que están - además - relacionados con el historial de caries. En conclusión, los polimorfismos estudiados en los genes DSSP y RUNX2 se asocian a la aparición de microlesiones que contribuirían a la susceptibilidad a la enfermedad de caries dental en la infancia. Creemos que este estudio es importante para la odontopediatría porque destaca el papel de DSSP (rs36094464) y RUNX2 (rs566712) y la susceptibilidad a la caries dental durante la infancia, además resalta la utilidad de la evaluación genética para la predicción y prevención de la caries dental y porque aporta evidencia que indica que los factores genéticos están implicados en la etiología de la caries.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Cárie Dentária/genética , Cárie Dentária/epidemiologia , Fosfoproteínas/genética , Polimorfismo Genético , Saliva/química , Sialoglicoproteínas/genética , Calicreínas/genética , Estudos Transversais , Suscetibilidade à Cárie Dentária/genética , Dentina , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Genótipo , Biologia MolecularRESUMO
Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.(AU)
Assuntos
Virulência , Angiotensinas , Calicreínas , Coronavirus , Aldosterona , SARS-CoV-2 , InflamaçãoRESUMO
Prostate cancer is the most common tumor of the urinary system, and its mortality rate is second only to lung cancer. With the specific and high expression on the surface of prostate cancer cells, prostate-specific membrane antigen (PSMA) has been an ideal theranostic target of prostate cancer with great clinical significance and research value. Positron emission tomography/computed tomography (PET/CT), a new modality of molecular imaging combining functional metabolic information and anatomical structure, provides high diagnostic performance for cancer detection. This paper mainly reviewed recent progress of PSMA inhibitors labeled by positron-emitting radionuclides for early diagnosis, preoperative staging, response assessment, restaging and metastasis detection of prostate cancer.
Assuntos
Humanos , Masculino , Elétrons , Calicreínas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico , Neoplasias da Próstata , Diagnóstico por Imagem , Radioisótopos , QuímicaRESUMO
Lachesis muta rhombeata is one of the venomous snakes of medical importance in Brazil whose envenoming is characterized by local and systemic effects which may produce even shock and death. Its venom is mainly comprised of serine and metalloproteinases, phospholipases A2 and bradykinin-potentiating peptides. Based on a previously reported fractionation of L. m. rhombeata venom (LmrV), we decided to perform a subproteome analysis of its major fraction and investigated a novel component present in this venom. Methods: LmrV was fractionated through molecular exclusion chromatography and the main fraction (S5) was submitted to fibrinogenolytic activity assay and fractionated by reversed-phase chromatography. The N-terminal sequences of the subfractions eluted from reversed-phase chromatography were determined by automated Edman degradation. Enzyme activity of LmrSP-4 was evaluated upon chromogenic substrates for thrombin (S-2238), plasma kallikrein (S-2302), plasmin and streptokinase-activated plasminogen (S-2251) and Factor Xa (S-2222) and upon fibrinogen. All assays were carried out in the presence or absence of possible inhibitors. The fluorescence resonance energy transfer substrate Abz-KLRSSKQ-EDDnp was used to determine the optimal conditions for LmrSP-4 activity. Molecular mass of LmrSP-4 was determined by MALDI-TOF and digested peptides after trypsin and Glu-C treatments were analyzed by high resolution MS/MS using different fragmentation modes. Results: Fraction S5 showed strong proteolytic activity upon fibrinogen. Its fractionation by reversed-phase chromatography gave rise to 6 main fractions (S5C1-S5C6). S5C1-S5C5 fractions correspond to serine proteinases whereas S5C6 represents a C-type lectin. S5C4 (named LmrSP-4) had its N-terminal determined by Edman degradation up to the 53rd amino acid residue and was chosen for characterization studies. LmrSP-4 is a fibrinogenolytic serine proteinase with high activity against S-2302, being inhibited by PMSF and benzamidine, but not by 1,10-phenantroline. In addition, this enzyme exhibited maximum activity within the pH range from neutral to basic and between 40 and 50 °C. About 68% of the LmrSP-4 primary structure was covered, and its molecular mass is 28,190 Da. Conclusions: Novel serine proteinase isoforms and a lectin were identified in LmrV. Additionally, a kallikrein-like serine proteinase that might be useful as molecular tool for investigating bradykinin-involving process was isolated and partially characterized.(AU)
Assuntos
Plasminogênio , Venenos de Serpentes , Lachesis muta , Serina Proteases , Calicreínas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Fosfolipases A2RESUMO
PURPOSE: Increased apoptosis was recently found in the hypertrophied left ventricle of spontaneously hypertensive rats (SHRs). Although the available evidence suggests that apoptosis can be induced in cardiac cells by various insults including pressure overload, cardiac apoptosis appears to result from an exaggerated local production of angiotensin in adult SHRs. Altered expressions of Bcl associated X (Bax), Bcl-2, chemokine receptor (CCR)-2, monocyte chemoattractant protein (MCP)-1, transforming growth factor (TGF)-β1, phosphorylated extracellular signal-regulated kinases (PERK), and connexin 43 proteins, and kallikrein mRNA were investigated to explore the effects of losartan on the SHR model. METHODS: Twelve-week-old male rats were grouped as follows: control (C), SHR (hypertension: H), and losartan (L; SHRs were treated with losartan [10 mg/kg/day] for 5 weeks). Western blot and reverse transcription polymerase chain reaction assays were performed. RESULTS: Expression of Bax, CCR-2, MCP-1, TGF-β1, PERK, and connexin 43 proteins, and kallikrein mRNA was significantly increased in the H group compared to that in the C group at weeks 3 and 5. Expression of Bax, CCR-2, MCP-1, TGF-β1, and connexin 43 proteins and kallikrein mRNA was significantly decreased after losartan treatment at week 5. PERK protein expression was significantly decreased after losartan treatment at weeks 3 and 5. Bcl-2 protein expression was significantly decreased in the H group compared to that in the C group at weeks 3 and 5. CONCLUSION: Losartan treatment reduced expression of Bax, CCR-2, MCP-1, TGF-β1, PERK, and connexin 43 proteins, and kallikrein mRNA in SHRs, along with decreased inflammation and apoptosis.
Assuntos
Adulto , Animais , Humanos , Masculino , Ratos , Angiotensinas , Apoptose , Western Blotting , Conexina 43 , MAP Quinases Reguladas por Sinal Extracelular , Expressão Gênica , Ventrículos do Coração , Inflamação , Calicreínas , Losartan , Monócitos , Reação em Cadeia da Polimerase , Ratos Endogâmicos SHR , Transcrição Reversa , RNA Mensageiro , Fatores de Crescimento TransformadoresRESUMO
Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA. TTN was defined as the time from start of chemotherapy to the nadir of PSA level during the treatment. Multivariable Cox regression models and Kaplan-Meier analysis were used to predict overall survival (OS). In these patients, the median of TTN was 17 weeks. Patients with TTN ≥17 weeks had a longer response time to chemotherapy compared to TTN <17 weeks (42.83 vs 21.50 weeks, P < 0.001). The time to PSA progression in patients with TTN ≥17 weeks was 11.44 weeks compared to 5.63 weeks when TTN was <17 weeks. We found several factors to be associated with OS, including TTN (hazard ratio [HR]: 3.937, 95% confidence interval [CI]: 1.502-10.309, P = 0.005), PSA level at the diagnosis of cancer (HR: 4.337, 95% CI: 1.616-11.645, P = 0.004), duration of initial androgen deprivation therapy (HR: 2.982, 95% CI: 1.104-8.045, P = 0.031), neutrophil-to-lymphocyte ratio (HR: 3.963, 95% CI: 1.380-11.384, P = 0.011), and total PSA response (Class 1 [<0 response] compared to Class 2 [0-50% response], HR: 3.978, 95% CI: 1.278-12.387, P = 0.017). In conclusion, TTN of PSA remains an important prognostic marker in predicting therapeutic outcome in Chinese population who receive chemotherapy for mCRPC and have >50% PSA remission.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos/uso terapêutico , China , Docetaxel/uso terapêutico , Calicreínas/sangue , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Contagem de Linfócitos , Metástase Neoplásica , Neutrófilos , Prognóstico , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Erectile dysfunction (ED) associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase (PK) has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate (cGMP) levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.
Assuntos
Animais , Masculino , Ratos , GMP Cíclico/metabolismo , Diabetes Mellitus Experimental/fisiopatologia , Disfunção Erétil/fisiopatologia , Calicreínas/uso terapêutico , Músculo Liso Vascular/fisiopatologia , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ereção Peniana/fisiologia , Pênis/metabolismo , Ratos Sprague-Dawley , Citrato de Sildenafila/uso terapêutico , Resultado do Tratamento , Agentes Urológicos/uso terapêuticoRESUMO
BACKGROUND: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. OBJECTIVE: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. METHODS: Normal human epidermal keratinocytes (NHEKs) were stimulated with 1α, 25-dihydroxyvitamin D3 (VD3) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. RESULTS: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by VD3 were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. CONCLUSION: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.
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Humanos , Ácido Ascórbico , Ensaio de Imunoadsorção Enzimática , Flavonoides , Técnicas In Vitro , Interleucina-33 , Calicreínas , Queratinócitos , Limoninas , Óleos Voláteis , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase em Tempo Real , RNA Mensageiro , Rosácea , Fator A de Crescimento do Endotélio VascularRESUMO
PURPOSE: Kallikrein (KLK) proteases are hormone-like signaling molecules with critical functions in different cancers. This study investigated the expression of KLK6 in gastric cancer and its potential role in the growth, migration, and invasion of gastric cancer cells. MATERIALS AND METHODS: In this study, we compared protein levels of KLK6, vascular endothelial growth factor (VEGF), and matrix metallopeptidase (MMP) 9 in normal gastric epithelial and gastric cancer cell lines by western blot. Fluorescence-activated cell sorting was employed to sort 2 clones of SGC-7901 cells with distinct KLK6 expression, namely, KLK6-high (KLK6high) and KLK6-low (KLK6low), which were then expanded. Lastly, immunohistochemical analysis was performed to investigate KLK6 expression in gastric cancer patients. RESULTS: The expression levels of KLK6, VEGF, and MMP 9, were significantly higher in the gastric cancer cell lines SGC-7901, BGC-823, MKN-28, and MGC-803 than in the normal gastric epithelial cell line GES-1. Compared to KLK6low cells, KLK6high cells showed enhanced viability, colony-forming ability, migration, and invasion potential in vitro. Importantly, immunohistochemical analysis of a human gastric cancer tissue cohort revealed that the staining for KLK6, VEGF, and MMP9 was markedly stronger in the cancerous tissues than in the adjacent normal tissues. KLK6 expression also correlated with that of VEGF and MMP9 expression, as well as several key clinicopathological parameters. CONCLUSIONS: Together, these results suggest an important role for KLK6 in human gastric cancer progression.
Assuntos
Humanos , Western Blotting , Linhagem Celular , Células Clonais , Estudos de Coortes , Células Epiteliais , Citometria de Fluxo , Técnicas In Vitro , Calicreínas , Peptídeo Hidrolases , Neoplasias Gástricas , Fator A de Crescimento do Endotélio VascularRESUMO
Objective@#To investigate the safety and efficacy of pancreatic kininogenase combined with sildenafil in the treatment of erectile dysfunction(ED) in type 2 diabetes mellitus (DM) patients in the high-altitude area.@*METHODS@#This study included 93 ED patients with type 2 DM, all residents of the Xining area 1500 meters above sea level. We randomly divided them into an experimental group (n = 48) and a control group (n = 45), the former treated with pancreatic kininogenase(120 u, tid) and sildenafil (25 mg, qd at bedtime), while the latter with sildenafil only (25 mg, qd at bedtime).After 4 and 8 weeks of medication, we obtained the penile hemodynamic parameters,IIEF-5 scores, and sexual intercourse satisfaction(SIS) scores and compared them between the two groups of patients.@*RESULTS@#There were no statistically significant differences in age or DM course between the two groups of patients (P >0.05).Compared with the baseline, both the experimental and control groups showed remarkably improvement inthe IIEF-5 score (8.81 ± 2.06 vs 11.54 ± 7.72 and 8.29 ± 1.91 vs 9.37± 1.65, P 0.05). Even more remarkable improvement was observed at 8 weeks in the experimental and control groups in the IIEF-5 score (19.29± 1.85 and 15.43± 1.74)(P <0.05), SIS score (11.73 ± 2.57 and 6.55± 2.71) (P <0.05), and penile hemodynamic parameters(P <0.05), all with significant differences between the two groups (P <0.05).@*CONCLUSIONS@#Pancreatic kininogenase combined with sildenafil has a better clinical effect than sildenafil alone on ED in type 2 DM patientsin the high-altitude area.
Assuntos
Idoso , Humanos , Masculino , Altitude , Coito , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Disfunção Erétil , Terapêutica , Calicreínas , Usos Terapêuticos , Pâncreas , Ereção Peniana , Fisiologia , Pênis , Fisiologia , Inibidores da Fosfodiesterase 5 , Usos Terapêuticos , Citrato de Sildenafila , Usos Terapêuticos , Resultado do TratamentoRESUMO
X-linked ichthyosis (XLI) is a recessively inherited ichthyosis. Skin barrier function of XLI patients reported in Western countries presented minimally abnormal or normal. Here, we evaluated the skin barrier properties and a skin barrier-related gene mutation in 16 Korean XLI patients who were diagnosed by fluorescence in situ hybridization and array comparative genomic hybridization analysis. Skin barrier properties were measured, cytokine expression levels in the stratum corneum (SC) were evaluated with the tape stripped specimen from skin surface, and a genetic test was done on blood. XLI patients showed significantly lower SC hydration, but normal basal trans-epidermal water loss and skin surface pH as compared to a healthy control group. Histopathology of ichthyosis epidermis showed no acanthosis, and levels of the pro-inflammatory cytokines in the corneal layer did not differ between control and lesional/non-lesional skin of XLI patients. Among the mutations in filaggrin (FLG), kallikrein 7 (KLK7), and SPINK5 genes, the prevalence of KLK7 gene mutations was significantly higher in XLI patients (50%) than in controls (0%), whereas FLG and SPINK5 prevalence was comparable. Korean XLI patients exhibited unimpaired skin barrier function and frequent association with the KLK7 gene polymorphism, which may differentiate them from Western XLI patients.
Assuntos
Adolescente , Adulto , Criança , Humanos , Masculino , Adulto Jovem , Povo Asiático/genética , Cromossomos Humanos X , Hibridização Genômica Comparativa , Citocinas/metabolismo , Concentração de Íons de Hidrogênio , Ictiose/diagnóstico , Hibridização in Situ Fluorescente , Proteínas de Filamentos Intermediários/genética , Calicreínas/genética , Polimorfismo de Nucleotídeo Único , Proteínas Secretadas Inibidoras de Proteinases/genética , República da Coreia , Pele/metabolismoRESUMO
X-linked ichthyosis (XLI) is a recessively inherited ichthyosis. Skin barrier function of XLI patients reported in Western countries presented minimally abnormal or normal. Here, we evaluated the skin barrier properties and a skin barrier-related gene mutation in 16 Korean XLI patients who were diagnosed by fluorescence in situ hybridization and array comparative genomic hybridization analysis. Skin barrier properties were measured, cytokine expression levels in the stratum corneum (SC) were evaluated with the tape stripped specimen from skin surface, and a genetic test was done on blood. XLI patients showed significantly lower SC hydration, but normal basal trans-epidermal water loss and skin surface pH as compared to a healthy control group. Histopathology of ichthyosis epidermis showed no acanthosis, and levels of the pro-inflammatory cytokines in the corneal layer did not differ between control and lesional/non-lesional skin of XLI patients. Among the mutations in filaggrin (FLG), kallikrein 7 (KLK7), and SPINK5 genes, the prevalence of KLK7 gene mutations was significantly higher in XLI patients (50%) than in controls (0%), whereas FLG and SPINK5 prevalence was comparable. Korean XLI patients exhibited unimpaired skin barrier function and frequent association with the KLK7 gene polymorphism, which may differentiate them from Western XLI patients.
Assuntos
Adolescente , Adulto , Criança , Humanos , Masculino , Adulto Jovem , Povo Asiático/genética , Cromossomos Humanos X , Hibridização Genômica Comparativa , Citocinas/metabolismo , Concentração de Íons de Hidrogênio , Ictiose/diagnóstico , Hibridização in Situ Fluorescente , Proteínas de Filamentos Intermediários/genética , Calicreínas/genética , Polimorfismo de Nucleotídeo Único , Proteínas Secretadas Inibidoras de Proteinases/genética , República da Coreia , Pele/metabolismoRESUMO
PURPOSE: Involvement of human kallikreins (hKs) in human cancers has been reported and several hKs are promising biomarkers of various cancers. The aim of this study was to evaluate the prognostic significance of hK11 expression in patients with non-metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The study included 44 patients with NSCLC. hK11 expression was determined by immunohistochemical staining. RESULTS: The estimation of disease-free and overall survival by Kaplan-Meier was 11 months and 17 months, respectively. The estimation of overall survival by Kaplan-Meier was significantly higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (20 months vs. 11 months, p=0.032). Although not statistically different, the estimation of disease-free survival by Kaplan-Meier was higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (12 months vs. 9 months, p=0.113). Multivariate Cox regression analysis showed that the overall survival rates were significantly associated with response to chemoradiotherapy and the degree of staining with hK11. CONCLUSION: The stronger hK11 expression in NSCLC appears to be associated with better survival rates. hK11 may be a prognostic biomarker of NSCLC.
Assuntos
Humanos , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas , Quimiorradioterapia , Intervalo Livre de Doença , Calicreínas , Neoplasias Pulmonares , Taxa de SobrevidaRESUMO
PURPOSE: To evaluate the effects of the dipeptide L-alanyl-glutamine (L-Ala-Gln) as a preconditioning agent to potentially promote reduction in the intensity of lesion or induction of resilience in rats subjected to global cerebral ischemia/reperfusion (I/R) injury. METHODS: Thirty-six male Wistar rats weighing 280-300g were randomly assigned to six groups (n=6). Groups Sham 1h and 24h were treated with saline and spared of further interventions. The remaining groups were submitted to clamping of the common carotid arteries for 30 minutes (ischemia) and treated with saline (SS) or L-Ala-Gln. Brain reperfusion was allowed for 1or 24 h. L-Ala-Gln was administered intravenously (0.75g/kg) 30 minutes before sham procedure or induction of global brain I/R injury. Brain edema and red neuron counting were determined. Results were expressed as Mean±SD for normal results and Median±Percentile for non parametric data. Significance was established at p<0.05. RESULTS: Global I/R injury promoted an increase in brain edema at 24 h after reperfusion, whereas preconditioning with L-Ala-Gln induced no change in edema. On the other hand, L-Ala-Gln preconditioning decreased significantly red neurons counting both at 1h and 24h post reperfusion (p<0.05). CONCLUSION: There was a significant preconditioning effect with L-Ala-Gln decreasing cell death (red neurons counting) at early (1h) and late reperfusion (24h) in the cerebral tissue. .
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Calicreínas/sangue , Imageamento por Ressonância Magnética/estatística & dados numéricos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais/sangue , Reações Falso-Negativas , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To analyze the association between the length of napping during the night shift and the recovery after work among nurses. METHOD: Cross-sectional epidemiological study involving 1940 nurses from 18 public hospitals in the City of Rio de Janeiro. A multidimensional and self-applied questionnaire was used with information about health, sociodemographic and occupational characteristics, health-related behaviors and housework. Multiple logistic regression was applied to identify the association, adjusted for confounding variables. RESULTS: The gross analyses showed 44%, 127% and 66% higher chances of a high level of recovery after work for nurses who sleep up to two hours, between 2.1 and 3 hours and 3.1 hours or more, respectively, when compared to the nurses who do not sleep. After adjusting for confounding variables, the association only continues significant for the group that sleeps 2.1 to 3 hours during the night shift (OR=1.79; 95%CI=1.33-2.41). CONCLUSION: The association between the length of napping and the high level of recovery after work, confirmed in the present results, can be included in the studies that aim to support more appropriate policies aimed at improving the workers' work, life and health conditions, not only in nursing, but night-shift workers in general. .
OBJETIVO: analisar a associação entre duração do cochilo durante o plantão noturno e recuperação após o trabalho, entre enfermeiros. MÉTODO: estudo epidemiológico seccional com 1940 enfermeiros, de 18 hospitais públicos, do Município do Rio de Janeiro. Utilizou-se questionário multidimensional e autopreenchível com informações sobre saúde, características sociodemográficas, ocupacionais, comportamentos relacionados à saúde e trabalho doméstico. Utilizou-se a regressão logística múltipla, buscando identificar a associação ajustada por variáveis de confundimento. RESULTADOS: as análises brutas mostraram chances 44%, 127% e 66% mais elevadas de alta recuperação após o trabalho, para aqueles que dormem até 2 horas, de 2,1 a 3 horas e de 3,1 horas ou mais, respectivamente, comparados aos que não dormem. Após o ajuste por variáveis de confundimento, a associação permanece significativa apenas para o grupo que dorme de 2,1 a 3 horas durante o plantão noturno (OR=1,79; IC95%=1,33-2,41). CONCLUSÃO: a associação entre tempo de cochilo e alta recuperação após o trabalho, confirmada nos resultados, pode compor os estudos que buscam subsidiar políticas mais adequadas voltadas à melhoria das condições de trabalho, de vida e saúde dos trabalhadores, não apenas da enfermagem, mas trabalhadores noturnos de forma geral. .
OBJETIVO: Analizar la asociación entre la duración de la siesta durante la guardia nocturna y la recuperación tras el trabajo entre enfermeros. MÉTODO: Estudio epidemiológico seccional con 1940 enfermeros de dieciocho hospitales públicos del Municipio de Rio de Janeiro. Fue utilizado cuestionario tipo multidimensional y autollenado con informaciones sobre salud, características sociodemográficas, ocupacionales, comportamientos relacionados a la salud y trabajo doméstico. Fue utilizada la regresión logística múltipla, buscando identificar la asociación ajustada por variables de confusión. RESULTADOS: Los análisis brutos mostraron posibilidades 44%, 127% y 66% más elevadas de alta recuperación tras el trabajo, para aquellos que duermen hasta 2 horas, de 2,1 a 3 horas y de 3,1 horas o más, respectivamente, comparados a aquellos que no duermen. Tras el ajuste por variables de confusión, la asociación sigue significativa solamente para el grupo que duerme de 2,1 a 3 horas durante la guardia nocturna (OR=1,79; IC95%=1,33-2,41). CONCLUSIÓN: La asociación entre el tiempo de siesta y la alta recuperación tras el trabajo, confirmada en nuestros resultados, puede componer los estudios con objeto de subsidiar políticas más adecuadas dirigidas a la mejora de las condiciones de trabajo, de vida y salud de los trabajadores, no solamente enfermeros, pero trabajadores nocturnos de manera general. .
Assuntos
Humanos , Masculino , Calicreínas/metabolismo , Neoplasias da Próstata/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Isoformas de Proteínas/metabolismo , Fatores de RiscoRESUMO
PURPOSE: Few data are available concerning the clinical outcome of abiraterone acetate treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) in terms of the duration of androgen deprivation therapy (ADT) before diagnosis of CRPC. We investigated the clinical efficacy of abiraterone acetate according to the duration of ADT. MATERIALS AND METHODS: We reviewed the medical records of 20 patients with mCRPC who received abiraterone acetate after failure of docetaxel chemotherapy from May 2012 to March 2014 at Seoul National University Bundang Hospital. Clinical factors including prostate-specific antigen (PSA) nadir level, time to PSA nadir, PSA doubling time, PSA response, and modes of progression (PSA, radiologic, clinical) were analyzed. Disease progression was classified according to the Prostate Cancer Working Group 2 criteria. RESULTS: The mean age and PSA value of the entire cohort were 76.0+/-7.2 years and 158.8+/-237.9 ng/mL, respectively. The median follow-up duration was 13.4+/-6.7 months. There were no statistically significant differences in clinical characteristics between patients who received abiraterone acetate with ADT duration or =35 months. There were also no significant differences in terms of PSA progression-free survival, radiologic progression-free survival, and clinical progression-free survival between patients with ADT duration or =35 months. CONCLUSIONS: Although this was a retrospective study with a small sample size, we did not observe any statistically significant differences in the clinical response to abiraterone acetate between mCRPC patients with long ADT duration and those with short ADT duration in terms of disease progression-free survival.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Acetato de Abiraterona/administração & dosagem , Antagonistas de Receptores de Andrógenos/administração & dosagem , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Esquema de Medicação , Calicreínas/sangue , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Estudos Retrospectivos , Taxoides/administração & dosagem , Resultado do TratamentoRESUMO
Mps one binder (MOB) proteins are integral components of signaling pathways that control important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation. However, the biochemical and cellular functions of the human MOB (hMOB) protein family remain largely unknown. The present study investigated the association between hMOB3B expression and clinicopathological characteristics of prostate cancer (PCa).Study subjects included 137 PCa patients and 137 age-matched benign prostatic hyperplasia (BPH) patients. hMOB3B expression was estimated using real-time PCR and compared with clinicopathological parameters of PCa. hMOB3B mRNA expression was significantly lower in PCa tissues than in BPH control tissues (P or =10 ng/mL), a Gleason score> or =8, and metastatic disease (any T, N+/M+) than in those with low PSA levels, a low Gleason score, and non-metastatic disease (each P<0.05). In conclusion, low levels of hMOB3B are closely associated with aggressive clinicopathologic features in patients with PCa. Our results suggest that hMOB3B may act as a tumor suppressor in human PCa.
Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Suscetibilidade a Doenças , Expressão Gênica , Calicreínas/sangue , Proteínas Associadas aos Microtúbulos/metabolismo , Gradação de Tumores , Reação em Cadeia da Polimerase , Próstata/patologia , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangueRESUMO
The purpose of this study was to determine whether contemporary active surveillance (AS) protocols could sufficiently discriminate significant from indolent tumors in men with low-risk prostate cancer. We retrospectively analyzed 312 patients with low-risk prostate cancer treated with radical prostatectomy. After exclusion of patients with fewer than 10 cores taken at biopsy and those who received neo-adjuvant treatment, 205 subjects satisfied the final inclusion criteria. Five widely accepted AS protocols were employed in this study. A total of 82.0% of the patients met the inclusion criteria of at least one protocol, and 18% did not meet any criteria of published AS protocols. A significant proportion of patients had non-organ-confined disease (8.6% to 10.6%) or a Gleason score of 7 or greater (18.6% to 23.9%) between the different AS criteria. Among patients who did not meet any AS criteria, 32.4% of patients had a pathologically insignificant cancer. Our results indicated a significant adverse pathology in patients who met the contemporary AS protocols. On the other hand, some patients in whom expectant management would be appropriate did not meet any criteria of published AS protocols. None of the clinical or histological criteria reported to date is able to sufficiently discriminate aggressive tumors from indolent ones.