RESUMO
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary disease of the heart muscle. Clinical challenges remain, however, in identifying patients with ARVC in the early or concealed stages with subtle clinical manifestations. Therefore, we wanted to identify potential targets by immunohistochemical (IHC) analysis in comparison with controls. Pathogenic mutations were identified in 11 of 37 autopsied patients with ARVC. As observed from IHC analysis of the RV, expression of αT-catenin and plakophilin-2 is significantly decreased in autopsied patients with ARVC as compared to controls, and the decreased expression is consistent in patients with and without pathogenic mutations. Furthermore, ARVC specimens demonstrated a reduced localization of αT-catenin, desmocollin-2, desmoglein-2, desmoplakin, and plakophilin-2 on intercalated discs. These findings have been validated by comparing RV specimens obtained via endomyocardial biopsy between patients with ARVC and those without. The pathogenic mutation was present in 3 of 5 clinical patients with ARVC. In HL-1 myocytes, siRNA was used to knockdown CTNNA3, and western blotting analysis demonstrated that the decline in αT-catenin expression was accompanied by a significant decline in the expression of plakophilin-2. The aforementioned effect was directed towards protein degradation rather than mRNA stability. Plakophilin-2 expression decreases concurrently with the decline in CTNNA3 expression. Therefore, the expression of αT-catenin and plakophilin-2 could be potential surrogates for the diagnosis of ARVC.
Assuntos
Displasia Arritmogênica Ventricular Direita , Cateninas , Placofilinas , Displasia Arritmogênica Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/metabolismo , Displasia Arritmogênica Ventricular Direita/patologia , Cateninas/metabolismo , Moléculas de Adesão Celular/metabolismo , Humanos , Imuno-Histoquímica , Mutação , Miocárdio/metabolismo , Miocárdio/patologia , Placofilinas/biossíntese , Placofilinas/genética , Placofilinas/metabolismoRESUMO
In Taiwan, the average prevalence of congenital heart disease (CHD) is 13.08/1000 live births. Most children with CHD die before the age of 5 years; therefore, identifying treatment methods to extend the life of CHD patients is an important issue in clinical practice. The objective of this study is to evaluate the roles of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelin-1 (ET-1), and CD34 in CHD autopsy cases in comparison with autopsy cases without CHD. The study included 19 autopsy cases, which were divided into the following four groups: acyanotic CHD (n = 11), cyanotic CHD (n = 3), CHD associated with chromosomal abnormalities (n = 3), and complex CHD (n = 2). Heart specimens obtained from 10 autopsy cases without CHD were included as controls. Our results indicated that high percentages of HIF-1α (100%), VEGF (89.5%), iNOS (78.9%), and ET-1 (84.2%) expressions were observed in CHD autopsy cases and this was found to be significant. HIF-1α induced by hypoxia could play a potential role in relating downstream gene expressions in CHD patients. Upregulation of VEGF by HIF-1α could play an important role in triggering angiogenesis to protect myocardial cell survival in a hypoxic microenvironment. Therefore, HIF-1α could be a significant prognosis marker in CHD and be a prospective candidate in the development of target therapy in cardiovascular diseases.
Assuntos
Endotelina-1/metabolismo , Cardiopatias Congênitas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo II/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Feminino , Cardiopatias Congênitas/patologia , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Microvasos/patologiaRESUMO
Facial reconstruction is a branch of forensic anthropology used to assist in the identification of skeletal remains. The majority of facial reconstruction techniques use facial soft tissue depth chart data to recreate facial tissue on a skull or a model of a skull through the use of modeling clay. This study relied on 193 subjects selected from the Taiwanese population on the basis of age and gender to determine the average values of 32 landmarks, include midline and bilateral measures, by means of CT scans. The mean age of the subjects was 46.9±16.4 years, with a mean age of 43.8±16.6 for males and 49.9±15.8 for females respectively. There were 16 landmarks with statistically significant differences between male and female subjects, namely S, G, N, Na, Ph, Sd and Id in the midline portion, FE, LO, ZA and Sub M2 in the bilateral-right and left portion, and IM point in the bilateral-left portion (abbreviations adapted from Karen T. Taylor's work). The mean soft tissue depth was greater in males than in females, and there was significant difference between the right and left sides of the face in Za point. This study's findings were compared with those of Bulut et al.
Assuntos
Povo Asiático , Face/anatomia & histologia , Face/diagnóstico por imagem , Adulto , Envelhecimento , Pontos de Referência Anatômicos , Bases de Dados Factuais , Feminino , Antropologia Forense , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Crânio/anatomia & histologia , Crânio/diagnóstico por imagem , Taiwan , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Intravenous amphetamine abuse may cause serious cardiopulmonary complications via unknown mechanisms. We investigated the role of free radicals in the amphetamine-induced lung injury using isolated rat lungs. Adding amphetamine into the perfusate caused dose-dependent increases in perfusion pressure and lung weight. Amphetamine increased the filtration coefficient (K(f)) by 90 +/- 20% and 210 +/- 10% at doses of 10 microM and 50 microM, respectively, as compared to the baseline level. Pretreatment with dimethylthiourea (DMTU), an oxygen radical scavenger, abolished the pulmonary hypertension, lung weight gain, and permeability changes. We also examined the effect of amphetamine on free radical generation in polymorphonuclear leukocytes (PMN). Adding phorbol myristate acetate (PMA, 1 nM) enhanced the chemiluminescence indicating the functional viability of the isolated PMN. Amphetamine (50 microM) significantly enhanced the chemiluminescence generation of PMN by 152 +/- 26% as compared with the baseline value. Combination of amphetamine and PMA increased free radical formation by 360 +/- 85%. In summary, our results showed that amphetamine may cause acute lung injury by overproduction of free radicals. Although amphetamine can activate PMN, the source of free radicals remains to be determined.
Assuntos
Dextroanfetamina/toxicidade , Radicais Livres/metabolismo , Pulmão/metabolismo , Edema Pulmonar/metabolismo , Tioureia/análogos & derivados , Doença Aguda , Animais , Vasos Sanguíneos/efeitos dos fármacos , Permeabilidade Capilar/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Técnicas In Vitro , Medições Luminescentes , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Masculino , Neutrófilos/metabolismo , Tamanho do Órgão , Circulação Pulmonar/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Tioureia/farmacologiaRESUMO
This study conducts an investigation of fatal falls from height, examines gender differences, and compares our findings with those of Western countries. We review deaths in Taiwan caused by falls from height that underwent forensic autopsy from 1994 to 2010. Among the examined cases, 182 were suicide, 156 were accidents, and 18 were homicides. Men who fell from greater heights had a lower probability of fatal head trauma (p = 0.045), and women exhibited a lower fatal head trauma rate when falling from heights of between 10 and 25 m in accident group (p = 0.003). There was no significant difference between cases of falling from greater and lower heights within the suicide group (p = 0.834). Psychiatric illness was only reported in 20.3% and 28.8% cases in suicide and accident groups. Only in male cases was the use of psychotropic substances higher in the suicide groups than in the accident groups (p = 0.047).
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Homicídio/estatística & dados numéricos , Suicídio/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Concentração Alcoólica no Sangue , Traumatismos Craniocerebrais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismo Múltiplo/mortalidade , Psicotrópicos/análise , Estudos Retrospectivos , Distribuição por Sexo , Transtornos Relacionados ao Uso de Substâncias/sangue , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Taiwan/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Sudden cardiac death (SCD) is the most catastrophic presentation in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). OBJECTIVES: To investigate the seasonal variations in the frequency of SCD and ventricular tachyarrhythmia in patients with AVRD/C and to elucidate the meteorological factors that trigger these events. METHODS: From 1998 to 2012, we enrolled 88 consecutive patients with ARVD/C from Taipei City. The cohort included 20 living patients who received implantable cardioverter-defibrillator (ICD) and 68 autopsied patients with SCD from the Taiwan National Forensic Institute registry. The baseline clinical characteristics, seasonal distribution, and associated meteorological factors were explored to predict the occurrences of events, which include appropriate ICD interventions and SCD. RESULTS: There were 106 events, including 38 (35.8%, 1.9 episodes per patient) appropriate ICD interventions in living patients with ARVD/C and 68 (64.2%) SCD events. The seasonal peak occurred predominantly in summer (P < .05) in both groups. For meteorological factors, the onset of event was associated with higher average daily temperature and longer sunshine duration. The variation in humidity within 3 days of events was significantly increased. After multivariate logistic regression analysis, higher average daily temperature and larger variation in humidity were associated with increase in events (odds ratio 1.23, 95% confidence interval 1.16-1.31, P < .001, and odds ratio 1.19, 95% confidence interval 1.15-1.23, P < .001, respectively). CONCLUSIONS: There was seasonal variation with a summer peak in the occurrence of ventricular arrhythmias and SCD in patients with ARVD/C. Meteorological factors including higher temperature and larger variation in humidity within 3 days of events were independently associated with the development of events.
Assuntos
Displasia Arritmogênica Ventricular Direita/complicações , Morte Súbita Cardíaca/epidemiologia , Estações do Ano , Taquicardia Ventricular/epidemiologia , Adulto , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Seguimentos , Humanos , Incidência , Masculino , Conceitos Meteorológicos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Taiwan/epidemiologia , Fatores de TempoRESUMO
The characteristics of knife tool marks retained on hard tissues can be used to outline the shape and angle of a knife. The purpose of this study was to describe such marks on bone tissues that had been chopped with knives. A chopping stage with a gravity accelerator and a fixed bone platform was designed to reconstruct the chopping action. A digital microscope was also used to measure the knife angle (θ) and retained V-shape tool mark angle (ψ) in a pig skull. The κ value (elasticity coefficient; θ/ψ) was derived and recorded after the knife angle (θ) and the accompanied velocity were compared with the proportional impulsive force of the knife and ψ on the bone. The constant impulsive force revealed a correlation between the V-shape tool mark angle (ψ) and the elasticity coefficient (κ). These results describe the tool marks--crucial in the medicolegal investigation--of a knife on hard tissues.