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1.
Can Vet J ; 65(3): 227-233, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38434166

RESUMO

A stray cat, an intact female Japanese domestic shorthair cat of unknown age (suspected to be a young adult), was rescued. The cat was lethargic and thin and had marked skin fragility, delayed wound healing without skin hyperextensibility, and hind limb proprioceptive ataxia and paresis. Survey radiography, computed tomography, and magnetic resonance imaging revealed congenital vertebral anomalies, including thoracolumbar transitional vertebrae, scoliosis resulting from a thoracic lateral wedge-shaped vertebra, and a kinked tail, and a dilated spinal cord central canal. Through nutritional support, the cat's general condition normalized, followed by a gradual and complete improvement of skin features. Whole-genome sequencing was completed; however, no pathogenic genetic variant was identified that could have caused this phenotype, including congenital scoliosis. A skin biopsy obtained 7 y after the rescue revealed no remarkable findings on histopathology or transmission electron microscopy. Based on clinical course and microscopic findings, malnutrition-induced reversible feline skin fragility syndrome (FSFS) was suspected, and nutritional support was considered to have improved the skin condition. Key clinical message: This is the second reported case of presumed malnutrition-induced reversible FSFS and was accompanied by long-term follow-up.


Syndrome de fragilité cutanée réversible induit par la malnutrition soupçonné chez un chat avec des difformités axiales congénitales. Un chat errant, une femelle intacte de race japonaise à poil court et d'âge inconnu (suspecté être une jeune adulte), a été secourue. La chatte était léthargique et maigre, et avait une fragilité marquée de la peau, un retard dans la guérison de plaies sans hyperextensibilité de la peau, et une ataxie proprioceptive et parésie des membres postérieurs. Des radiographies, un examen par tomodensitométrie, et de l'imagerie par résonnance magnétique ont révélé des anomalies congénitales des vertèbres, incluant des vertèbres transitionnelles thoraco-lombaires, une scoliose résultant d'une vertèbre thoracique en forme de coin, une queue pliée, et un canal central de la moelle épinière dilaté. Grâce à un soutien nutritionnel, la condition générale du chat s'est stabilisée, suivi d'une amélioration graduelle et complète des caractéristiques de la peau. Le séquençage du génome complet a été effectué; toutefois, aucune variation génétique pathogénique n'a été identifiée qui aurait pu causer ce phénotype, incluant la scoliose congénitale. Une biopsie cutanée obtenue 7 j après le sauvetage n'a révélé aucune trouvaille spéciale à l'histopathologie ou par microscopie électronique à transmission. Basé sur le déroulement clinique et l'examen microscopique, le syndrome de fragilité cutanée réversible félin induit par la malnutrition (FSFS) était suspecté, et le soutien nutritionnel a été considéré comme ayant amélioré la condition cutanée.Message clinique clé :Ce cas est le deuxième cas rapporté de FSFS induit par la malnutrition soupçonné et a fait l'objet d'un suivi à long terme.(Traduit par Dr Serge Messier).


Assuntos
Doenças do Gato , Desnutrição , Escoliose , Feminino , Gatos , Animais , Escoliose/veterinária , Desnutrição/veterinária , Ataxia/veterinária , Biópsia/veterinária , Doenças do Gato/diagnóstico , Doenças do Gato/etiologia
2.
J Cardiol Cases ; 26(5): 329-332, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36312775

RESUMO

Advances in radiation therapy (RT) have dramatically improved the survival rates of patients with cancer, but radiation-induced heart disease (RIHD) has become an emerging problem, which is complex and multifaceted.A 65-year-old man with a medical history of chemoradiotherapy for esophageal cancer, who had multiple admissions for acute heart failure (AHF), was readmitted to our hospital. Transthoracic echocardiography at rest revealed left ventricular diastolic dysfunction, moderate aortic stenosis with mild aortic regurgitation, and mild mitral regurgitation (MR). A diagnosis of RIHD was obtained, however, the main cause of the AHF was not clearly understood. Exercise echocardiography (ExE) revealed an exacerbation of the MR and exercise-induced pulmonary hypertension (EIPH), and the severe dynamic MR was considered to be the main cause of the AHF. A transcatheter edge-to-edge repair (TEER) with a MitraClip (Abbott Vascular, Menlo Park, CA, USA) was performed, and the post-procedural ExE showed the mitigation of the dynamic MR and EIPH. He had no further heart failure admissions for more than one year.Our case showed that ExE may be useful in the management of patients with RIHD, and a TEER with a MitraClip may be an effective treatment for RT-related dynamic MR. Learning objective: Radiation therapy (RT) has improved the survival rates of patients with cancer, but which involves radiation-induced heart disease (RIHD). RIHD is complex and multifaceted, and RT-related valvular disease may be underestimated with transthoracic echocardiography at rest alone. Then exercise echocardiography may be useful in the management. It is important to perform an individualized approach including medical therapy, surgery, and percutaneous intervention by a heart team.

3.
BMC Infect Dis ; 21(1): 1077, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663259

RESUMO

BACKGROUND: Taenia solium, present in most developing countries, infects many individuals and may result in their death. Neurocysticercosis (NCC) develops after invasion of the brain by parasitic larvae. It is the most common parasitic disease of the human central nervous system. On imaging scans it can be similar to brain tumors. We report a patient with a metastatic brain tumor and NCC. The co-presence of NCC was diagnosed based on specific neuroimaging- and epidemiologic findings. CASE PRESENTATION: A 36-year-old non-smoking Japanese woman with a history of non-small-cell lung cancer had undergone resection of the lower lobe followed by cytotoxic chemotherapy 2 years before apparently suffering recurrence. A positron emission computed tomography (PET) scan incidentally revealed multiple intracranial cold spots exhibiting differences in their shape and size. On brain magnetic resonance imaging (MRI) scans we observed many different patterns of peripheral edema and gadolinium-enhancing effects. As she had often visited Latin America and Southeast Asia and had eaten raw pork and Kimchi, we suspected that the brain lesions were due to NCC rather than metastatic brain tumors. However, serum immunoblotting assay and DNA analysis were negative for T. solium. Rather than performing resection, we administered albendazole (ABZ) and dexamethasone because her earlier cytotoxic chemotherapy had elicited severe pancytopenia. Except for a single large lesion in the left frontal lobe, this treatment resulted in a significant reduction in the size of these lesions and a decrease in perilesional edema. She underwent resection of the residual lesion 10 months later. Histology revealed it to be a metastatic tumor. Polymerase chain reaction (PCR) assay for NCC was negative. In the course of 11-months follow-up there has been no recurrence. CONCLUSION: This is the first presentation of NCC in a Japanese woman with a metastatic brain tumor. NCC was incidentally discovered on PET scans and, based on her travel history and epidemiological findings; it was diagnosed and successfully treated with ABZ. NCC is endemic in most developing countries and as visits to such countries have increased, NCC must be ruled out in patients with multiple cystic nodular brain lesions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neurocisticercose , Adulto , Feminino , Humanos , Japão , Recidiva Local de Neoplasia , Neurocisticercose/diagnóstico por imagem , Neurocisticercose/tratamento farmacológico
4.
Asia Ocean J Nucl Med Biol ; 9(1): 71-75, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33392354

RESUMO

A 73-year-old man with lung cancer underwent bone scintigraphy for disease staging. Diffuse myocardial technetium hydroxymethylene diphosphonate (99mTc-HMDP) uptake was incidentally found. A diagnosis of amyloid transthyretin (ATTR) cardiac amyloidosis was suspected, although the patient had no symptoms at this time. Single-photon emission computed tomography (SPECT) showed particularly strong uptake in the ventricular septum. Cardiac magnetic resonance imaging (CMR) showed widespread subendocardial and partly transmural enhancement of the left ventricular myocardium on delayed postcontrast T1-weighted images. These findings were consistent with ATTR cardiac amyloidosis. 18F-FDG uptake in the left ventricle wall was observed on PET/CT. He was finally diagnosed with ATTR by endomyocardial biopsy. There are two major subtypes of cardiac amyloidosis: ATTR amyloidosis and amyloid light-chain (AL) amyloidosis. Endomyocardial biopsy is the gold standard for diagnosis. Recently, however, several reports have shown that bone scintigraphy using a 99mTc-labelled bone-seeking agent can detect ATTR cardiac amyloidosis and differentiate it from AL amyloidosis. Bone scintigraphy may play an important role in the detection and differentiation of ATTR cardiac amyloidosis.

5.
Eur Heart J Case Rep ; 4(3): 1-7, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32617472

RESUMO

BACKGROUND: About 7% of amyloid A (AA) amyloidosis cases are accompanied by heart disease. Although several studies have recently reported that specific biologicals improved renal function in AA amyloidosis, little evidence is available regarding heart disease in AA amyloidosis. CASE SUMMARY: A 57-year-old woman with rheumatoid arthritis presented with sudden worsening of renal function. Echocardiography revealed granular sparkling appearance in the ventricular septum and posterior wall (PW). Echocardiography indicated left ventricular (LV) diastolic dysfunction. Global longitudinal strain (GLS) exhibited an apical sparing pattern. Cardiac biopsy demonstrated amyloid A deposition on immunostaining. Soluble tumour necrosis factor-alpha receptor etanercept therapy was initiated. Four years later, echocardiography showed improved diastolic function, including E/A and E/e', and decreased wall thickness in both the interventricular septum and PW of the left ventricle. Granular sparkling appearance had diminished. Moreover, the LV dysfunction improved on GLS. Five years later, the medication was gradually losing effect and the patient had worsening pain in the joints; moreover, articular destruction was observed on radiography. The patient was switched to abatacept therapy. Echocardiography showed recurrence of LV hypertrophy and electrocardiogram showed down-sloped ST depression in V4-6 leads. DISCUSSION: This case indicates that etanercept can be effective for heart disease in AA amyloidosis. Of particular, interest is the improvement of granular sparkling appearance in addition to cardiac function improvement noted in this case.

7.
Gen Thorac Cardiovasc Surg ; 68(8): 851-854, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31625083

RESUMO

We report a case of an 84-year-old Japanese female patient with transcatheter valve embolization treated with thoracic endovascular stenting. She was diagnosed with severe aortic stenosis and referred to our hospital. Transapical transcatheter aortic valve implantation (TA-TAVI) was selected because she had multiple comorbidities and peripheral vascular disease. During TA-TAVI, the transcatheter valve (TV) came loose and lodged in the distal aortic arch. The TV was floating and unstable, thereby affecting her hemodynamics. After a second TV was placed in the appropriate position with no trouble, we tried fixing the TV using a thoracic endovascular stent-graft. The procedure was successful, and the patient recovered well. The cause of embolization seemed to be associated with a relatively mild calcification of the native aortic valve. Although this complication is rare, several recovery procedures should be prepared.


Assuntos
Aorta Torácica/cirurgia , Estenose da Valva Aórtica/cirurgia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Próteses Valvulares Cardíacas/efeitos adversos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Idoso de 80 Anos ou mais , Valva Aórtica/cirurgia , Feminino , Hemodinâmica , Humanos , Stents , Resultado do Tratamento
8.
J Orthop Sci ; 23(5): 739-743, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29909125

RESUMO

BACKGROUND: Long-term exposure to radiation can lead to gene mutations and increase the risk of cancer. Low rate fluoroscopy has the potential to reduce the radiation exposure for both the examiner and the patient during various fluoroscopic procedures. The purpose of this study was to evaluate the impact of low rate fluoroscopy on reducing an examiner's radiation dose during nerve root block. METHODS: A total of 101 lumbar nerve root block examinations were performed at our institute during a 6-month period. During the first 3 months, low rate fluoroscopy was performed at 7.5 frames/s (FPS) in 54 examinations, while 47 were performed at 15 FPS during the last 3 months. The examiner wore a torso protector, a neck protector, radiation protection gloves, and radiation protection glasses. Optically stimulated luminescence (OSL) dosimeter badges were placed on both the inside and the outside of each protector. The dosimeters were exchanged every month. Radiation doses (mSv) were measured as the integrated radiation quantity every month from the OSL dosimeters. The effective and equivalent doses for the hands, skin, and eyes were investigated. RESULTS: The mean monthly equivalent doses were significantly lower both inside and outside the hand protector for the 7.5 FPS versus 15 FPS (inside; P = 0.021, outside; P = 0.024). There were no significant differences between the two groups for the mean monthly calculated effective dose for each protector's condition. CONCLUSIONS: Radiation exposure was significantly reduced for the skin on the examiner's hand when using low rate fluoroscopy at 7.5 FPS, with no noticeable decrease in image quality or prolonged fluoroscopy time.


Assuntos
Fluoroscopia/métodos , Bloqueio Nervoso , Exposição à Radiação/prevenção & controle , Idoso , Feminino , Fluoroscopia/efeitos adversos , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Dosímetros de Radiação , Proteção Radiológica , Raízes Nervosas Espinhais
9.
J Infect Chemother ; 23(9): 655-657, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28408304

RESUMO

IMP-1 type metallo-ß-lactamase-producing (MBL-producing) Acinetobacter radioresistens was isolated from a dog with cystitis and a cat with conjunctivitis. The MBL-producing A. radioresistens isolates were resistant to all of the ß-lactam antibiotics used in the sensitivity tests, but were susceptible to gentamicin, amikacin, and minocycline. Also, one of the two strains of A. radioresistens was susceptible to ciprofloxacin and levofloxacin. These two cases were cured by administration of tetracyclines and fluoroquinolones, which elicited a positive result in the sensitivity tests. This report of the isolation of MBL-producing A. radioresistens in companion animals is the first in the world. To prevent the proliferation of MBL-producing bacteria, veterinary hospitals need to be aware of the behavior of MBL-producing organisms.


Assuntos
Acinetobacter/isolamento & purificação , Doenças do Gato/microbiologia , Conjuntivite Bacteriana/veterinária , Cistite/veterinária , Doenças do Cão/microbiologia , Animais de Estimação/microbiologia , beta-Lactamases/biossíntese , Acinetobacter/enzimologia , Animais , Gatos , Conjuntivite Bacteriana/microbiologia , Cistite/microbiologia , Cães , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/veterinária , Masculino
10.
Neuropathology ; 37(1): 52-57, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27297614

RESUMO

Atypical teratoid/rhabdoid tumors (AT/RTs) are rare malignant neoplasms of the CNS that preferentially affect young children. We herein report an adult case of AT/RT surviving for more than 5 years with the residual tumor. The patient, a 24-year-old man at onset, presented with a contrast-enhancing mass lesion in the left occipital lobe, and underwent partial tumor resection. Histologically, the tumor was predominantly composed of long spindle cells exhibiting nuclear palisading and perivascular pseudorosettes, which appeared to mimic mesenchymal, ependymal and Schwann cell tumors. A small number of isolated rhabdoid cells did not initially attract attention, and a tentative pathological diagnosis of a malignant mesenchymal tumor was made. In a later examination focusing on the small areas of rhabdoid cells, the extensive loss of the nuclear expression of INI1 was detected in all areas. Diffuse staining with vimentin and focal immunoreactivity for epithelial membrane antigen and alpha smooth muscle actin were observed not only in AT/RT foci, but also in spindle cell areas. Thus, polyphenotypic immunoreactivity was evident. Fluorescence in situ hybridization revealed a homozygous deletion of chromosome 22q covering the INI1 locus. Histopathological differences between infant and adult AT/RTs currently remain unclear. In the case of a malignant adult brain tumor showing a hardly classifiable morphology and immunophenotypic diversity, an analysis of the INI1 status may contribute to an accurate diagnosis.


Assuntos
Neoplasias Encefálicas/patologia , Lobo Occipital/patologia , Tumor Rabdoide/patologia , Teratoma/patologia , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Terapia Combinada , Irradiação Craniana , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Lobo Occipital/diagnóstico por imagem , Lobo Occipital/cirurgia , Tumor Rabdoide/diagnóstico por imagem , Tumor Rabdoide/terapia , Temozolomida , Teratoma/diagnóstico por imagem , Teratoma/terapia , Resultado do Tratamento , Adulto Jovem
11.
J Orthop Sci ; 22(2): 243-247, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27998661

RESUMO

BACKGROUND: Exposure to radiation over many years prompts concerns regarding potential health-related effects, particularly the incidence of cataracts and the development of cancer. The purpose of this study was to examine and compare the exposure of the examiner to radiation during myelography versus radiculography and root block. METHODS: A total of 114 examinations were performed in our institute in the 6 months. Sixty-two examinations were performed during myelography in the first 3 months (MG group), while 52 were performed during radiculography and root block in the last 3 months (RB group). The examiner wore a torso protector, a neck protector, radiation protection gloves, and radiation protection glasses. Optically stimulated luminescence (OSL) dosimeter badges were placed on both the inside and the outside of each protector. The dosimeters were exchanged every month. Radiation doses (mSv) were measured as the integrated radiation quantity every month from the OSL dosimeters. The effective dose and the equivalent doses of hand, skin, and eyes were investigated. RESULTS: The mean equivalent doses were significantly lower outside the neck, torso, eye protectors, and inside the torso protector in the RB group than in the MG group. Conversely, the mean equivalent dose was significantly lower outside the hand protector in the MG group than in the RB group. The use of a neck protector significantly decreased the effective dose compared to the non-use of a neck protector in the RB group. CONCLUSIONS: The present study showed the standard radiation exposure to the examiner during myelography, radiculography, and root block. Receiving full protection including a neck protector and protection gloves is an easy and reliable means to reduce radiation exposure.


Assuntos
Mielografia/efeitos adversos , Exposição à Radiação/efeitos adversos , Proteção Radiológica/métodos , Radiografia Intervencionista/efeitos adversos , Doenças da Coluna Vertebral/diagnóstico por imagem , Estudos de Coortes , Feminino , Humanos , Masculino , Mielografia/métodos , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Roupa de Proteção , Doses de Radiação , Radiografia Intervencionista/métodos , Estudos Retrospectivos , Medição de Risco
12.
Nucleic Acids Res ; 39(12): 5067-81, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21345933

RESUMO

Lens epithelium-derived growth factor (LEDGF) or p75 is a co-activator of general transcription and also involved in insertion of human immunodeficiency virus type I (HIV-1) cDNA into host cell genome, which occurs preferentially to active transcription units. These phenomena may share an underlying molecular mechanism in common. We report here that LEDGF/p75 binds negatively supercoiled DNA selectively over unconstrained DNA. We identified a novel DNA-binding domain in the protein and termed it 'supercoiled DNA-recognition domain' (SRD). Recombinant protein fragments containing SRD showed a preferential binding to supercoiled DNA in vitro. SRD harbors a characteristic cluster of lysine and glutamic/aspartic acid residues. A polypeptide mimicking the cluster (K(9)E(9)K(9)) also showed this specificity, suggesting that the cluster is an essential element for the supercoil recognition. eGFP-tagged LEDGF/p75 expressed in the nucleus distributed partially in transcriptionally active regions that were identified by immunostaining of methylated histone H3 (H3K4me3) or incorporation of Br-UTP. This pattern of localization was observed with SRD alone but abolished if the protein lacked SRD. Thus, these results imply that LEDGF/p75 guides its binding partners, including HIV-1 integrase, to the active transcription site through recognition of negative supercoils generated around it.


Assuntos
DNA Super-Helicoidal/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/química , Proteínas Nucleares/química , Animais , Sequência de Bases , Núcleo Celular/genética , Células HeLa , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Dados de Sequência Molecular , Proteínas Nucleares/análise , Proteínas Nucleares/metabolismo , Estrutura Terciária de Proteína , Ratos , Ratos Sprague-Dawley , Transcrição Gênica
13.
Int J Cardiol ; 126(2): 171-6, 2008 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-18063145

RESUMO

During the progression of heart failure (HF), phases of chronic compensation and acute decompensation alternate and the clinical status worsens during the acute phase. At the present time, few studies have focused their attention on the cycles of compensated and decompensated phases from the perspective of myocyte injury. We hypothesize that persistently increased serum cTn concentrations during chronic compensated HF identify patients likely to need multiple admissions to the hospital for management of acute cardiac decompensation, worsening their long-term prognosis by causing further myocyte injury during the acute phase. In patients with acute cardiac decompensation, myocyte injury observed within hours or days has a long-term predictive value, and the acute surge of myocyte injury occurring in the acutely decompensated phase might be an important therapeutic target from the perspective of myocyte preservation. Clinical trials that limit myocyte injury during acutely decompensated as well as during chronic compensated HF are warranted.


Assuntos
Insuficiência Cardíaca/sangue , Troponina T/sangue , Doença Aguda , Biomarcadores/sangue , Doença Crônica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/terapia , Humanos , Admissão do Paciente , Recidiva
14.
Tohoku J Exp Med ; 208(2): 163-7, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16434840

RESUMO

The most common cause of death of patients suffering from amyloidosis is heart failure and sudden death, and cardiac troponin T (cTnT), a highly specific and sensitive biomarker of myocardial injury, has been reported to be a prognostic marker at presentation. But the relationship between serial measurements of serum cTnT and clinical course of the disease has not been described. An illustrative case was a 55-year-old man with normal renal function presenting with congestive heart failure (CHF), whose initial concentration of cTnT was 0.72 ng/ml. Eight samples of initial endomyocardial biopsy specimens showed the presence of myocyte degeneration and interstitial fibrosis with a small amount of amyloid infiltration. However, the cTnT values remained at 0.69 ng/ml after successful management of CHF, and four months later, a second endomyocardial biopsy revealed diffuse massive amyloid protein deposition. He died of CHF, 9 months after initial presentation. In addition, we present 4 cases of amyloidosis with increased serum cTnT levels. We therefore propose that serial measurements of serum cTnT might be helpful for early diagnosis and prediction of prognosis of patients with amyloidosis.


Assuntos
Amiloidose/sangue , Cardiomiopatias/sangue , Troponina T/sangue , Idoso , Amiloidose/complicações , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
15.
Eur J Heart Fail ; 6(2): 137-44, 2004 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-14984720

RESUMO

BACKGROUND: Nuclear factor kappa B (NF-kappaB) is activated by several factors, which increase the inflammatory response, and this activation, in turn, leads to the expression of several genes such as cytokines, and may play an important role in cardiovascular diseases. AIMS: The aim of the study is to examine the effect of SUN C8079, a newly synthesized NF-kappaB inhibitor in vitro and in vivo. METHODS: We examined the effects of SUN C8079 on the transcriptional responses of NF-kappaB, on activation of NF-kappaB in electrophoretic mobility shift assay, and on the gene expressions of tumor necrosis factor (TNF)-alpha and iNOS. We also studied effects of SUN C8079 on lethal endotoxemia and viral myocarditis in mice. RESULTS: SUN C8079 inhibited the lipopolysaccharide (LPS)-induced expression of the genes of TNF-alpha and iNOS by inhibiting the activation of NF-kappaB in vitro. SUN C8079 inhibited the systemic release of TNF-alpha and improved mortality in LPS-treated mice. In addition to protecting mice against lethal endotoxemia, SUN C8079 prevented the development of myocarditis due to the encephalomyocarditis virus (EMCV), and inhibited the expressions of proinflammatory cytokines and the iNOS gene in cardiac tissues. CONCLUSION: These findings suggest that the activation of NF-kappaB plays an important role in the pathogenesis of endotoxemia and viral myocarditis, and that the NF-kappaB inhibitor, SUN C8079, may be therapeutic in these disorders.


Assuntos
Endotoxemia/prevenção & controle , Miocardite/prevenção & controle , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase/genética , Piperidinas/farmacologia , Fator de Necrose Tumoral alfa/genética , Animais , Infecções por Cardiovirus/tratamento farmacológico , Infecções por Cardiovirus/prevenção & controle , Infecções por Cardiovirus/virologia , Núcleo Celular/metabolismo , Células Cultivadas , DNA Complementar/metabolismo , Vírus da Encefalomiocardite , Endotoxemia/tratamento farmacológico , Endotoxemia/etiologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Interleucina-1/biossíntese , Interleucina-1/genética , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Miocardite/tratamento farmacológico , Miocardite/virologia , NF-kappa B/metabolismo , Óxido Nítrico Sintase/biossíntese , Óxido Nítrico Sintase Tipo II , Piperidinas/uso terapêutico , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/biossíntese
16.
J Am Coll Cardiol ; 42(11): 2000-6, 2003 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-14662266

RESUMO

OBJECTIVES: This study examined the role of angiotensin II (Ang-II) in a murine model of viral myocarditis. BACKGROUND: Ang-II plays an important role in the pathophysiology of various cardiovascular disorders. However, the role of Ang-II in inflammatory heart diseases is not known. METHODS: Four-week-old wild-type (WT) and Ang-II type 1 receptor (AT(1)R) knockout (KO) mice were inoculated with the encephalomyocarditis virus (EMCV). Survival, histopathology, expression of proinflammatory cytokines, and activity of nuclear factor-kappa B (NF-kB) in the heart were examined. RESULTS: The 14-day survival was significantly increased in KO compared with WT mice. Histopathologic scores for myocardial necrosis (0.86 +/- 0.69 vs. 2.44 +/- 0.88, p < 0.01) and cellular infiltration (0.86 +/- 0.38 vs. 2.33 +/- 0.50, p < 0.01) were lower in KO than in WT mice. The expression of tumor necrosis factor-alpha (TNF-alpha) was increased 43.2-fold, that of interleukin-1-beta (IL-1-beta) 45.8-fold, and the activity of NF-kB 2.24-fold by EMCV inoculation in WT mice (each p < 0.01), but not in KO mice (5.9-fold, 6.3-fold, and 1.12-fold, respectively, each p = NS). The AT(1)R blocker also significantly attenuated the expression of proinflammatory cytokines and the activation of NF-kB in virus-inoculated WT mice. Intravenous Ang-II injection enhanced the activation of NF-kB (2.28-fold, p < 0.01) and increased the expression of TNF-alpha (2.31-fold, p < 0.01) and IL-1-beta (2.45-fold, p < 0.01) in heart tissue of WT but not KO mice. CONCLUSIONS: These results indicate that the AT(1)R signal is obligatory for the development of virus-induced myocardial injury through the proinflammatory action of Ang-II via the NF-kB/cytokine pathway.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II , Angiotensina II/fisiologia , Infecções por Cardiovirus/etiologia , Vírus da Encefalomiocardite , Miocardite/etiologia , NF-kappa B/análise , Receptor Tipo 1 de Angiotensina/fisiologia , Tetrazóis , Angiotensina II/farmacologia , Animais , Benzimidazóis/farmacologia , Compostos de Bifenilo/farmacologia , Infecções por Cardiovirus/patologia , Vírus da Encefalomiocardite/isolamento & purificação , Coração/virologia , Interleucina-1/análise , Interleucina-6/análise , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocardite/patologia , Miocárdio/metabolismo , RNA Mensageiro/análise , Fator de Necrose Tumoral alfa/análise
17.
Circulation ; 106(24): 3133-8, 2002 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-12473563

RESUMO

BACKGROUND: Plasma concentrations of hepatocyte growth factor (HGF), a powerful angiogenic growth factor inducible by heparin, increase in thrombus-associated disorders such as myocardial infarction and unstable angina. The mechanism of this thrombus-associated HGF release, however, is unknown. METHODS AND RESULTS: Wistar rats received through the tail vein (1) normal saline (NS), (2) 50 micro g of the mast cell-degranulating agent CP48/80, or (3) 1000 U/kg heparin. Blood samples were collected at 10 minutes or 30 minutes after the injections, or from untreated rats, for measurements of HGF. The same experiments were performed in mast cell-deficient white spotting (Ws) rats. Ws rats have a small deletion of the c-kit gene and are deficient in mast cells. Intravenous heparin immediately increased plasma HGF in both Wistar (38.02+/-2.08 ng/mL versus 1.11+/-0.70 ng/mL in untreated rats, P<0.0001) and Ws rats (36.39+/-4.15 ng/mL versus 0.66+/-0.18 ng/mL in NS-treated rats, P<0.0001). Injection of CP48/80 also increased plasma HGF in Wistar rats (9.12+/-1.11 ng/mL versus 0.65+/-0.24 ng/mL in NS group, P=0.004) but not in Ws rats (0.67+/-0.27 ng/mL versus 0.66+/-0.18 ng/mL in NS group, P=0.997). In a rat carotid artery microthrombus model, intra-arterial thrombus formation increased circulating HGF in Wistar rats (2.12+/-0.70 ng/mL versus sham 0.61+/-0.15 ng/mL in sham-operated Wistar rats, P=0.0064) but not in Ws rats (0.76+/-0.33 ng/mL versus 0.21+/-0.04 ng/mL in sham-operated Ws rats, P=0.29). In addition, in vitro stimulation of rat peritoneal mast cells with thrombin rapidly induced degranulation in a dose-dependent manner. CONCLUSIONS: These observations indicate that mast cell degranulation stimulated by thrombin is necessary for the rapid induction of plasma HGF in intravascular thrombus-associated disorders.


Assuntos
Trombose das Artérias Carótidas/fisiopatologia , Degranulação Celular , Fator de Crescimento de Hepatócito/sangue , Mastócitos , Animais , Anticoagulantes/farmacologia , Arginina/análogos & derivados , Trombose das Artérias Carótidas/induzido quimicamente , Trombose das Artérias Carótidas/patologia , Degranulação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Progressão da Doença , Histamina/sangue , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Mastócitos/fisiologia , Ácidos Pipecólicos/farmacologia , Proteínas Proto-Oncogênicas c-kit/genética , Ratos , Ratos Endogâmicos , Ratos Wistar , Reperfusão , Sulfonamidas , Trombina/antagonistas & inibidores , p-Metoxi-N-metilfenetilamina/farmacologia
18.
Vet Immunol Immunopathol ; 88(1-2): 49-56, 2002 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-12088644

RESUMO

The chicken IL-15 gene was recently cloned and shown to encode a polypeptide with T cell growth factor activity similar to IL-2. To further characterize the chemical and biological properties of chicken IL-15, we generated a panel of monoclonal antibodies against bacterially expressed protein and characterized their binding specificities. All antibodies were reactive by ELISA with recombinant IL-15, but not IL-2, and identified a 15kDa recombinant chicken IL-15 by Western blot analysis. Two antibodies inhibited IL-15-induced proliferation of splenic lymphoblast cells. These monoclonal antibodies will be useful for further structural and immunological studies of chicken IL-15.


Assuntos
Anticorpos Monoclonais/imunologia , Galinhas/imunologia , Interleucina-15/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Especificidade de Anticorpos/imunologia , Western Blotting/veterinária , Células COS , Divisão Celular/imunologia , Chlorocebus aethiops , Clonagem Molecular , Escherichia coli/genética , Feminino , Interleucina-15/genética , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase/veterinária , Proteínas Recombinantes , Organismos Livres de Patógenos Específicos
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