RESUMO
Thioredoxin-1 (Trx-1) is a potent therapeutic agent against a variety of diseases because of its actions as an antioxidant and regulator of apoptosis. N-acetyl-p-aminophenol (APAP), commonly known as acetaminophen, generates excessive oxidative stress and triggers hepatocyte cell death, exemplified by regulated necrosis. In the present study, we investigated whether APAP-induced liver injury in a mouse model is associated with "necroptosis," and if pretreatment with recombinant Trx-1 prevents the hepatic injury caused by APAP overdose. We also explored the mechanism underlying the preventive action of Trx-1 against APAP-induced hepatic injury. In a prevention study, C3H/he mice received different doses (0, 10, 50 or 100 mg kg-1 body weight) of recombinant human Trx-1 intraperitoneally, followed by a single oral dose of 300 mg kg-1 of APAP. In this experimental paradigm, liver injury and lethality were markedly decreased in rhTrx-1-pretreated mice. In survival experiments, mice received rhTrx-1 followed by oral administration of a lethal dose of APAP. APAP overdose caused a series of liver toxicity-associated events, beginning with overexpression of c-fos, excessive production of reactive oxygen species and reactive nitrogen species (RNS) and leading to decreased endogenous Trx-1 expression and activation of JNK signaling pathways. Pretreatment with rhTrx-1 inhibited all of these toxicological manifestations of APAP. In addition, rhTrx-1 significantly reduced the expression of RIP-3, a critical necrosome component. Taken together, our findings indicate that rhTrx-1 prevents APAP-induced liver injury through multiple action mechanisms, including scavenging reactive oxygen species and reactive nitrogen species, restoring endogenous Trx-1 levels and inhibiting RIP-3 overexpression.
Assuntos
Acetaminofen , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Tiorredoxinas/metabolismo , Tiorredoxinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citoproteção , Modelos Animais de Doenças , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C3H , Necrose , Estresse Nitrosativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
A new avian hepatitis E virus (HEV) GI-B was identified in broiler breeders with hematomas, liver rupture, and splenomegaly, along with excessive abdominal fat, in Korea. Previously, genotype 1 had been identified in avian HEV strains in Korea. Complete sequence analyses revealed that the new avian HEV clustered in genotype 2, which has been identified in the USA and Spain; the GI-B isolate was closely related to the USA prototype avian HEV isolated from a chicken with hepatitis-splenomegaly syndrome. Although some HEV genotypes show a geographical distribution pattern, the discovery of genotype 2 in addition to genotype 1 in Korea suggests that the geographical grouping might be reconsidered. These findings have important implications for understanding the global epidemiology and spread of avian HEV.
Assuntos
Galinhas/virologia , Hepatite E/virologia , Hepatite Viral Animal/virologia , Hepevirus/genética , Doenças das Aves Domésticas/virologia , Esplenomegalia/virologia , Sequência de Aminoácidos , Animais , Genótipo , Filogenia , República da Coreia , EspanhaRESUMO
A full-length infectious cDNA clone of the genotype 1 Korean avian hepatitis E virus (avian HEV) (pT11-aHEV-K) was constructed and its infectivity and pathogenicity were investigated in leghorn male hepatoma (LMH) chicken cells and broiler breeders. We demonstrated that capped RNA transcripts from the pT11-aHEV-K clone were translation competent when transfected into LMH cells and infectious when injected intrahepatically into the livers of chickens. Gross and microscopic pathological lesions underpinned the avian HEV infection and helped characterize its pathogenicity in broiler breeder chickens. The avian HEV genome contains a hypervariable region (HVR) in ORF1. To demonstrate the utility of the avian HEV infectious clone, several mutants with various deletions in and beyond the known HVR were derived from the pT11-aHEV-K clone. The HVR-deletion mutants were replication competent in LMH cells, although the deletion mutants extending beyond the known HVR were non-viable. By using the pT11-aHEV-K infectious clone as the backbone, an avian HEV luciferase reporter replicon and HVR-deletion mutant replicons were also generated. The luciferase assay results of the reporter replicon and its mutants support the data obtained from the infectious clone and its derived mutants. To further determine the effect of HVR deletion on virus replication, the capped RNA transcripts from the wild-type pT11-aHEV-K clone and its mutants were injected intrahepatically into chickens. The HVR-deletion mutants that were translation competent in LMH cells displayed in chickens an attenuation phenotype of avian HEV infectivity, suggesting that the avian HEV HVR is important in modulating the virus infectivity and pathogenicity.
Assuntos
DNA Complementar/genética , DNA Viral/genética , Hepatite Viral Animal/virologia , Hepevirus/genética , Hepevirus/fisiologia , Infecções por Vírus de RNA/veterinária , Replicação Viral , Experimentação Animal , Animais , Galinhas , Genótipo , Hepatite Viral Animal/patologia , Hepatócitos/virologia , Hepevirus/classificação , Masculino , Doenças das Aves Domésticas/patologia , Doenças das Aves Domésticas/virologia , Infecções por Vírus de RNA/patologia , Infecções por Vírus de RNA/virologiaRESUMO
Talc is a mineral that is widely used in cosmetic products, antiseptics, paints, and rubber manufacturing. Although the toxicological effects of talc have been studied extensively, until now no detailed inhalation study of talc focusing on oxidative stress has been done. This repeated 4 weeks whole-body inhalation toxicity study of talc involved Sprague-Dawley rats. Male and female groups of rats were exposed to inhaled talc at 0, 5, 50, and 100 mg/m(3) for 6 hours daily, 5 days/week for 4 weeks. The objective was to identify the 4-week inhalation toxicity of talc and investigate antioxidant activity after exposure to talc. There were no treatment-related symptoms or mortality in rats treated with talc. Glucose (GLU) was decreased significantly in male rats exposed to 50 and 100 mg/m(3) of talc. Histopathological examination revealed infiltration of macrophages on the alveolar walls and spaces near the terminal and respiratory bronchioles. In male and female rats exposed to 100 mg/m(3) talc, expression of superoxide dismutase 2, a typical biological indicator of oxidative damage, was significantly increased. Thus, inhalation of talc induces macrophage aggregations and oxidative damage in the lung.
Assuntos
Macrófagos/efeitos dos fármacos , Superóxido Dismutase/biossíntese , Talco/toxicidade , Administração por Inalação , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Bronquíolos/patologia , Feminino , Glutationa Peroxidase/metabolismo , Pulmão/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Alvéolos Pulmonares/patologia , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Talco/administração & dosagem , Regulação para CimaRESUMO
HemoHIM G is a functional food ingredient composed of a triple herbal combination of Angelica sinensis, Ligusticum chuanxiong, and Paeonia lactiflora, to improve impaired immune function. Considering the pharmacological benefits of its constituent herbal components, HemoHIM G is anticipated to have various health benefits; however, its toxicity has not been thoroughly evaluated. Here, we conducted a comprehensive study to assess the safety of HemoHIM G in terms of acute oral toxicity, 13-week repeat-dose toxicity, and genotoxicity. In the oral acute toxicity study, Sprague-Dawley rats were orally administered a single dose of HemoHIM G at 5000 mg/kg/day, the limit dose for the acute study. No abnormal findings or adverse effects were observed in this study, as confirmed by gross pathology. A 13-week repeated-dose toxicity study was conducted with HemoHIM G at doses of 1250, 2500, and 5000 mg/kg/day to examine the subchronic toxicity in both male and female rats after 28 days of dose-range finding study. No test substance-related clinical signs or mortality was observed at any of the tested doses. Gross pathology, hematology, blood chemistry, and histopathology were within normal ranges, further supporting the safety of HemoHIM G. Therefore, the NOAEL of HemoHIM G was considered to be at 5000 mg/kg/day for both sexes of rats. Bacterial reverse mutation tests, a chromosome aberration test in human peripheral blood lymphocytes, and a mouse micronuclei test were conducted to identify the potential genotoxicity of HemoHIM G. HemoHIM G is non-mutagenic and non-clastogenic. Collectively, these findings provide valuable evidence for the safe use of HemoHIM G as a functional food ingredient.
RESUMO
It is challenging to diagnose metastatic tumors whose cellular morphology is different from the primary. We characterized canine primary pulmonary adenocarcinoma (PAC) and its xenografted tumors by histological and immunohistochemical analyses for critical diagnostic and cancer stem cell (CSC) markers. To generate a tumor xenograft model, we subsequently transplanted the tissue pieces from the PAC into athymic nude mice. Immunohistochemical examination was performed for diagnostic (TTF-1, Napsin A, and SP-A) and CSC markers (CD44 and CD133). The use of CSC markers together with diagnostic markers can improve the detection and diagnosis of canine primary and metastatic adenocarcinomas.
Assuntos
Adenocarcinoma , Doenças do Cão , Doenças dos Roedores , Camundongos , Cães , Animais , Xenoenxertos , Camundongos Nus , Transplante Heterólogo/veterinária , Células-Tronco Neoplásicas , Biomarcadores , Adenocarcinoma/diagnóstico , Adenocarcinoma/veterinária , Doenças do Cão/diagnósticoRESUMO
Improvement of the quality and efficiency of health in medicine, both at home and the hospital, calls for improved sensors that might be included in a common carrier such as a wearable sensor device to measure various biosignals and provide healthcare services that use e-health technology. Designed to be user-friendly, smart clothes and gloves respond well to the end users for health monitoring. This study describes a wearable sensor glove that is equipped with an electrodermal activity (EDA) sensor, pulse-wave sensor, conducting fabric, and an embedded system. The EDA sensor utilizes the relationship between drowsiness and the EDA signal. The EDA sensors were made using a conducting fabric instead of silver chloride electrodes, as a more practical and practically wearable device. The pulse-wave sensor measurement system, which is widely applied in oriental medicinal practices, is also a strong element in e-health monitoring systems. The EDA and pulse-wave signal acquisition module was constructed by connecting the sensor to the glove via a conductive fabric. The signal acquisition module is then connected to a personal computer that displays the results of the EDA and pulse-wave signal processing analysis and gives accurate feedback to the user. This system is designed for a number of applications for the e-health services, including drowsiness detection and oriental medicine.
Assuntos
Vestuário , Fenômenos Eletrofisiológicos/fisiologia , Ergonomia/instrumentação , Eletrodos Seletivos de Íons , Fenômenos Fisiológicos da Pele , Telemedicina/instrumentação , Estudos de Viabilidade , Humanos , Microeletrodos , Monitorização Fisiológica , Medicina do TrabalhoRESUMO
Bone morphogenetic protein-2 (BMP-2) is commonly used to enhance bone regeneration. The potential of BMP-2 for bone regeneration varies according to the concentration and release kinetics on the implanted site. Therefore, it is important to determine appropriate carriers of BMP-2. However, no optimal delivery vehicles have been identified. In the present study, we used alginate microbeads as a delivery vehicle for BMP-2. Alginate microbeads can be implanted onto the disease site through surgery or injection. The objective of this study was to evaluate that the osteoinductive properties of BMP-2 are effective in alginate microbeads as a carrier. In this study, the release kinetics of BMP-2 in alginate microbeads was evaluated using an enzyme-linked immunosorbent assay. BMP-2 released from alginate microbeads induced high alkaline phosphatase activity in canine adipose tissue-derived mesenchymal stem cells. Injection of alginate microbeads with BMP-2 into mouse subcutaneous tissue, as well as surgical implantation into the 5-mm circular calvarial defects in rats, was conducted and the results showed extensive new bone formation. In conclusion, alginate microbeads can be utilized as an effective BMP-2 delivery vehicle for use in orthopedic surgery and as an injectable vehicle for a minimally invasive therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 286-294, 2019.
Assuntos
Alginatos , Proteína Morfogenética Óssea 2 , Regeneração Óssea/efeitos dos fármacos , Portadores de Fármacos , Microesferas , Crânio , Alginatos/química , Alginatos/farmacologia , Animais , Proteína Morfogenética Óssea 2/química , Proteína Morfogenética Óssea 2/farmacologia , Cães , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Gravidez , Ratos , Crânio/lesões , Crânio/metabolismo , Crânio/patologiaRESUMO
Nonunion of the scaphoid waist in skeletally immature patients is rarely diagnosed. We report 2 cases of scaphoid nonunion in skeletally immature patients who underwent percutaneous screw fixation without bone graft. In stable nonunions with minimal sclerosis, percutaneous screw fixation without bone graft can be an alternative to the conventional open procedure in skeletally immature patients, with successful union and clinical outcome.
Assuntos
Fraturas não Consolidadas/cirurgia , Osso Escafoide/lesões , Osso Escafoide/cirurgia , Acidentes por Quedas , Adolescente , Parafusos Ósseos , Fios Ortopédicos , Fraturas não Consolidadas/diagnóstico por imagem , Força da Mão , Humanos , Masculino , Amplitude de Movimento Articular , Osso Escafoide/diagnóstico por imagem , Contenções , Tomografia Computadorizada por Raios XRESUMO
Cysticercus fasciolaris, the larval form of Taenia taeniaeformis, is commonly encountered in rodents. In our study, 287 wild rats (Rattus norvegicus) in South Korea were examined in 2010 and 2011. Of 287 rats, 97 (33.8%) were infected with C. fasciolaris A strong positive correlation was found between the host body weight and prevalence in both sexes, regardless of the year of collection. The liver was the most common habitat of the parasite, and the lung was the most frequent ectopic region, followed by mesentery, pleura, abdominal wall, and kidney. The lesions of the affected organs were generally characterized by well-developed cysts, each containing a larva. However, the cysts within kidney and abdominal wall were poorly organized, filled with abscess, and lacked larvae. Collagen types I and III, but not type IV, played significant roles in constructing the cysts at differential stages, addressed by immunohistochemistry. During cyst wall development, both collagen types contributed equally to cyst formation at the early stage, whereas collagen type I was the major component at the late stage (p < 0.05). In early-stage cysts, distribution of collagens was interestingly differential depending on the development stage, as collagen type I was localized in the outer layer and type III was located in the inner layer. Our results suggest that an appropriate remodeling process of collagen fibers is necessary for C. fasciolaris to build the well-conditioned cysts in the target organs for survival.
Assuntos
Cisticercose/veterinária , Cysticercus/isolamento & purificação , Doenças dos Roedores/epidemiologia , Animais , Animais Selvagens , Cisticercose/epidemiologia , Cistos/epidemiologia , Cistos/veterinária , Feminino , Imuno-Histoquímica/veterinária , Fígado/parasitologia , Fígado/patologia , Masculino , Prevalência , Ratos , República da Coreia/epidemiologia , Doenças dos Roedores/patologiaRESUMO
Uterine smooth muscle tumor is very rare in laboratory rats and, there has been no report in the wild rodents. Among a total of 400 wild rats captured in Gyeonggi, Gangwon, and Chungbuk provinces of Korea in 2007, 2010, and 2011, we found a uterine spindle cell tumor, diagnosed as smooth muscle cell origin based on differential features of histology and immunohistochemistry. Its incidence was very low, like in the laboratory rats, as under 0.5% for female. Considering generally applied histological and cellular criteria, this case was difficult in differential diagnosis between benign and malignant. Ki-67 labeling index was therefore further investigated, and it ranged from 26.4 to 37.6% in the 10 different areas, representing an average of 32.9±0.05%. The Ki-67 labeling index of neoplastic cells near the necrotic area was recorded as 83.5%. According to such high Ki-67 labeling index, it was more likely a malignant leiomyosarcoma, assenting to the previous proposal that Ki-67 labeling index is a significant criterion to differentiate between malignant and benign in the smooth muscle tumors.
RESUMO
Aluminum nanoparticles (Al-NPs) are one of the most widely used nanomaterial in cosmetics and medical materials. For this reason, Al-NP exposure is very likely to occur via inhalation in the environment and the workplace. Nevertheless, little is known about the mechanism of Al-NP neurotoxicity via inhalation exposure. In this study, we investigated the effect AL-NPs on the brain. Rats were exposed to Al-NPs by nasal instillation at 1 mg/kg body weight (low exposure group), 20 mg/kg body weight (moderate exposure group), and 40 mg/kg body weight (high exposure group), for a total of 3 times, with a 24-hr interval after each exposure. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that the presence of aluminum was increased in a dose-dependent manner in the olfactory bulb (OFB) and the brain. In microarray analysis, the regulation of mitogen-activated protein kinases (MAPK) activity (GO: 0043405), including Ptprc, P2rx7, Map2k4, Trib3, Trib1, and Fgd4 was significantly over-expressed in the treated mice than in the controls (p = 0.0027). Moreover, Al-NPs induced the activation of ERK1 and p38 MAPK protein expression in the brain, but did not alter the protein expression of JNK, when compared to the control. These data demonstrate that the nasal exposure of Al-NPs can permeate the brain via the olfactory bulb and modulate the gene and protein expression of MAPK and its activity.
RESUMO
Chloramine T has been widely used as a disinfectant in many areas such as kitchens, laboratories and hospitals. It has been also used as a biocide in air fresheners and deodorants which are consumer products; however, little is known about its toxic effects by inhalation route. This study was performed to identify the subacute inhalation toxicity of chloramine T under whole-body inhalation exposure conditions. Male and female groups of rats were exposed to chloramine T at concentrations of 0.2, 0.9 and 4.0 mg/m³ for 6 hr/day, 5 days/week during 4 weeks. After 28-day repeated inhalation of chloramine T, there were dose-dependently significant DNA damage in the rat tissues evaluated and inflammation was histopathologically noted around the terminal airways of the lung in both genders. As a result of the expression of three types of antioxidant enzymes (SOD-2, GPx-1, PRX-1) in rat's lung after exposure, there was no significant change of all antioxidant enzymes in the male and female rats. The results showed that no observed adverse effect level (NOAEL) was 0.2 mg/m³ in male rats and 0.9 mg/m³ in female rats under the present experimental condition.
Assuntos
Cloraminas/toxicidade , Dano ao DNA/efeitos dos fármacos , Desinfetantes/toxicidade , Exposição por Inalação/efeitos adversos , Pneumonia/induzido quimicamente , Compostos de Tosil/toxicidade , Administração por Inalação , Animais , Cloraminas/administração & dosagem , Cloraminas/efeitos adversos , Desinfetantes/administração & dosagem , Desinfetantes/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Glutationa Peroxidase/metabolismo , Proteínas de Homeodomínio/metabolismo , Pulmão/enzimologia , Masculino , Nível de Efeito Adverso não Observado , Pneumonia/enzimologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Fatores de Tempo , Compostos de Tosil/administração & dosagem , Compostos de Tosil/efeitos adversos , Glutationa Peroxidase GPX1RESUMO
Cubital tunnel syndrome is one of the most frequently occurring compression neuropathy in the upper limb next to carpal tunnel syndrome. Recent minimal invasive technique has prompted us to gain clinical experience with simple in situ decompression with minimal skin incision for idiopathic cubital tunnel syndrome. Sixty six consecutive patients with cubital tunnel syndrome were treated using minimal skin incision technique. The mean age of the patients was 49.7 (range: 15-77) years and average follow up period was 23.9 months (range: 12-60 months). The severity of ulnar neuropathy was classified according to the McGowan classification: there were 17 in grade I, 47 in grade II and 2 in grade III. A preoperative nerve conduction study was done by inching method, which revealed motor conduction delay around the medial epicondyle. All operations were carried out in a day surgery unit under local anesthetics. The postoperative outcome was evaluated by Messina classification. The mean duration of the operation was 12 minutes. The technique was highly satisfactorily esthetic for all. Over 80% of the patients were completely satisfied with the procedure taking into consideration their symptoms. Postoperative outcome measures and patient satisfactions (pain, return to normal activities and work, scar and pillar tenderness) were comparable with published series of anterior transposition. The overall satisfactory results were recorded 81% in the patients of McGowan stage I and II. There were 2 cases of hematoma as a postoperative complication. This procedure is comparably effective alternative which involves less surgical trauma, morbidity and rehabilitation time with good surgical outcomes especially in mild and moderate degrees. Minimal skin incision is a simple, safe and effective method to treat patients with idiopathic cubital tunnel syndrome.
Assuntos
Síndrome do Túnel Ulnar/cirurgia , Descompressão Cirúrgica/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Complicações Pós-Operatórias , Adulto JovemRESUMO
A PrP gene, from a Korean bovine, exhibiting a nonsense and a missense polymorphism respectively at nucleotides 576 and 652 has been cloned. The latter resulted in Glu to Lys substitution at amino acid residue 218. After expression and purification of the recombinant bovine PrP (recBoPrP) with Glu218Lys substitution, a polyclonal antibody against this protein was raised. ELISA and Western blot analysis suggested that the recBoPrP obtained in this study had a unique conformation not presented in native PrP(C), and the polyclonal antibody recognized PrP in a conformation dependent manner. These reagents will be valuable tools for studying PrP conformation.
Assuntos
Príons/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Western Blotting , Bovinos , Clonagem Molecular , Primers do DNA , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Dados de Sequência Molecular , Príons/química , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Homologia de Sequência de AminoácidosRESUMO
Although distraction osteogenesis has solved limb length discrepancies, many complications are inevitable from long duration of external fixation. Use of intramedullary nails for early removal of fixators has its own challenges especially in pediatric age group. To facilitate early removal of external fixators in children, we tried a novel method of submuscular plating over the distraction callus, which is described, and the results and complications of this technique are presented. In eight children (four girls and four boys), of limb lengthening (four cases) and bone transport (four cases) done in three femurs and five tibiae with external fixators (five Ilizarov ring fixators and three monofixators), submuscular plating was done over the distraction callus. The causes of limb length discrepancy included traumatic and septic growth arrest, congenital pseudoarthrosis of tibia, fibular hemimelia, tumor salvage, and Perthes' disease. The purpose of plating was to remove the external fixator earlier after achieving the target length. Mean age of plating procedure was 11.62 years, and mean amount of distraction was 5.47 cm. In all patients, the distraction callus healed on maintaining its length or correcting into the original alignment. The mean external fixation index was 26.93 days/cm and healing index was 52.01 days/cm. One complication of superficial pin-track infection occurred, which resolved completely with conservative treatment. None of the patients developed deep infection or implant failures. The mean follow-up after plating was 28 months (range, 18-62 months). Submuscular plating over the distraction callus may be a successful method that permits early removal of fixator with fewer complications. This method can be a useful alternative in children or when nailing is difficult.