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Malignant pleural mesothelioma (MPM) is a rare but aggressive tumor originating from pleural mesothelial cells. Distant skeletal muscle metastasis is rare in MPM. A 54-year-old woman was diagnosed with epithelioid MPM and treated with surgery, chemotherapy, and radiotherapy 2 years ago. During follow-up, diffuse irregular pleural thickening with focal chest wall invasion in the right hemithorax and two small pleural thickenings in the left hemithorax were seen on control diagnostic contrast-enhanced computed tomography (CECT). Fluorine-18 fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) imaging was performed as part of restaging. PET showed diffusely increased FDG uptake in the recurrent right pleural tumor, and two hypermetabolic small metastatic foci in the contralateral pleura. In addition, multiple hypermetabolic areas of various sizes in various skeletal muscle localizations, suggestive of extensive muscle metastases were noted. Histopathologic study confirmed metastatic epithelioid MPM. FDG PET/CT revealed multiple muscle metastases which were not observed on earlier CECT and contributed to the visualization of more extensive metastatic involvements in the presented case with MPM. FDG PET/CT can detect rarely seen skeletal muscle metastases that are not visualized on diagnostic CT, and provides more accurate restaging of MPM.
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BACKGROUND: This experimental study was conducted to investigate the effect of dexpanthenol (converted in the body to pantothenic acid) and Y-27632 (a selective Rho-kinase inhibitor) on stricture formation after caustic (alkaline) esophageal injury in rats. MATERIALS AND METHODS: Sixty male Wistar albino rats were randomly allocated into six groups. In group 1 (sham) the distal esophagus was isolated and cannulated but no caustic injury was induced. In all remaining groups, a caustic esophageal burn was induced with 50% sodium hydroxide solution for 90 s and drug treatment was given by daily intraperitoneal injection, beginning 24 h after injury and continuing for 21 d. In group 2 (controls), animals were treated with 0.9% saline; in groups 3 and 4, with 50 and 500 mg/kg/d of dexpanthenol, respectively; and in groups 5 and 6, with 0.3 and 3 mg/kg/d of Y-27632, respectively. Rats were sacrificed 22 d after caustic injury and the distal esophagus was isolated for histopathology and biochemical investigation. RESULTS: Stenosis index and collagen deposition scores were significantly lower in both the dexpanthenol and Y-27632 treated groups (P<0.05). Dexpanthenol and Y-27632 treatment markedly depressed esophageal tissue malondialdehyde and hydroxyproline levels. CONCLUSION: In this experimental model of caustic esophageal stricture, dexpanthenol and Y-27632 significantly attenuated esophageal stricture formation. These findings indicate that inhibition of Rho-kinase or dexpanthenol administration may offer novel therapeutic approaches in the treatment of caustic esophageal injury.
Assuntos
Amidas/farmacologia , Estenose Esofágica/induzido quimicamente , Estenose Esofágica/prevenção & controle , Ácido Pantotênico/análogos & derivados , Piridinas/farmacologia , Hidróxido de Sódio/toxicidade , Animais , Cáusticos/toxicidade , Colágeno/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Estenose Esofágica/patologia , Esôfago/efeitos dos fármacos , Esôfago/metabolismo , Esôfago/patologia , Hidroxiprolina/metabolismo , Masculino , Malondialdeído/metabolismo , Ácido Pantotênico/farmacologia , Ratos , Ratos Wistar , Complexo Vitamínico B/farmacologia , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
We herein report a case of 32-year-old woman who developed erythematous, indurated plaques, nodules on her lower back, hips and inguinal areas which had started after immunotherapy on the injection sites. She had a history of recurrent oral aphthous-like ulcers for 2 years and also had abdominal pain for 2 months. Colonoscopy revealed multiple aphthous ulcers on intestine. Diagnosis of lobular panniculitis was confirmed by histopathological finding of the skin biopsy and she was diagnosed as Behcet's disease. Eruptions due to mesotherapy accepted as hypersensitivity reaction. Before employing this technique, patients should be carefully examined for Behcet's pathognomonic clinical findings.
Assuntos
Síndrome de Behçet/diagnóstico , Imunoterapia/efeitos adversos , Mesoterapia/efeitos adversos , Paniculite/diagnóstico , Tecido Adiposo/efeitos dos fármacos , Adulto , Azatioprina/uso terapêutico , Síndrome de Behçet/complicações , Síndrome de Behçet/tratamento farmacológico , Colchicina/uso terapêutico , Técnicas Cosméticas , Feminino , Humanos , Injeções Intradérmicas , Paniculite/tratamento farmacológico , Paniculite/etiologia , Prednisolona/uso terapêutico , Pele , Resultado do TratamentoRESUMO
In this study we aim to demonstrate the value of monoclonal Caveolin 1 expression in distinguishing between malignant pleural mesothelioma and pulmonary adenocarcinoma. Total of 129 cases, consisting of 68 cases of malignant pleural mesothelioma (51 epitheloid, 12 biphasic, and 5 sarcomatoid type) and 61 cases of pulmonary adenocarcinoma were examined and stained with monoclonal Caveolin-1. Caveolin 1 expression with a membranous and /or cytoplasmic pattern was detected only in 32.35% (n:22/68) of malignant pleural mesothelioma and 6.5% (n:4/61) of pulmonary adenocarcinoma cases. This finding suggests that the choice of poly/monoclonal antibody for Caveolin 1 in the differential diagnosis of malignant pleural mesothelioma and pulmonary adenocarcinoma is important.
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Adenocarcinoma de Pulmão/diagnóstico , Biomarcadores Tumorais/análise , Caveolina 1/biossíntese , Neoplasias Pulmonares/diagnóstico , Mesotelioma Maligno/diagnóstico , Neoplasias Pleurais/diagnóstico , Idoso , Anticorpos Monoclonais , Caveolina 1/análise , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
The original version of this article unfortunately contained an error in Fig. 1. Cav-1 expression in MPM and PA cases failed to show the histopathological details in Fig. 1 due to technical problem. The figure with the proper sharpness and clarity is shown in the next page.
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In this paper, we report a rare case of a 29-year-old boy who presented with papillary meningioma originating from the posterior fossa meninges. After a long, disease-free period, however, spinal drop metastases occurred 32 months after resection of the primary tumor. The primary and metastatic lesions had a similar histological appearance, meaning that multiple spinal metastatic lesions occurred through CSF route even after a gross total resection of the tumor. Tumor seeding during surgery is the evident reason for spinal metastasis, although we strictly adhered to the standard precautions for operations for malignant tumors such as obstruction of the cisterna magna with cotton paddies, and changing surgical gloves and instruments during the operation. In this report, we briefly discuss an exceedingly rare variant of meningioma, the papillary variant, and suggest a new approach, a CSF sampling, in the management of both malignant and benign meningiomas. CSF sampling allows for the early detection of metastasis and of tumor cells before metastasis has occurred, thus allowing treatment to begin as soon as possible. This early detection and management is possibly associated with longer survival. Furthermore, we discussed that meningiomas are tumors that are not as benign as initially thought.
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Neoplasias Meníngeas/patologia , Meningioma/secundário , Neoplasias da Medula Espinal/secundário , Adulto , Líquido Cefalorraquidiano/citologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/líquido cefalorraquidiano , Meningioma/líquido cefalorraquidiano , Meningioma/patologia , Neoplasias da Medula Espinal/líquido cefalorraquidiano , Neoplasias da Medula Espinal/patologiaRESUMO
Glomus tumours around the shoulder are very rare. To the best of our knowledge, seven cases have been reported to date. We present a case with special emphasis on its localization and time of appearance. Contrary to the related reports in the literature, the lesion was of short duration and it became symptomatic just 6 months before referral. Complete pain relief was achieved with surgical treatment.
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Tumor Glômico , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/cirurgia , Idoso , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Musculares/patologiaRESUMO
AIM: To investigate the relationship of fragile histidine triad (FHIT) and Ki-67 expression with clinicopathological variables of patients with malignant pleural mesothelioma (MPM). METHODS: Formalin-fixed, paraffin-embedded tissue sections of 30 asbestos induced MPM (epithelial and biphasic) patients were examined for FHIT and Ki-67 expression using immunohistochemical techniques and results were compared with clinicopathological variables. RESULTS: Immunohistochemical study results were as follows: 12 (40%) cases showed low FHIT expression and 18 (60%) showed high expression. There was no significant relationship between FHIT and age, gender or histological subtypes (p > 0.05). Ki-67 expression was 'low' in 13 (43.3%) cases and 'high' in 17 (56.7%) cases. No correlation could be demonstrated between Ki-67 expression and age, gender or histological subtypes (p > 0.05). No significant association was observed between FHIT and Ki-67 expression in MPM. CONCLUSION: The results support the role of FHIT as a tumour suppressor gene in asbestos induced MPM. There is no significant correlation between FHIT and cell proliferation marker expressions in malignant pleural mesothelioma. Therefore, it can be concluded that loss of FHIT does not interfere with tumour proliferation. This can be accepted as evidence for an early role of FHIT loss in carcinogenesis; however, it needs to be strengthened by further studies.
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Hidrolases Anidrido Ácido/metabolismo , Mesotelioma/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias Pleurais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Amianto , Carcinógenos , Proliferação de Células , Feminino , Humanos , Antígeno Ki-67/metabolismo , Masculino , Mesotelioma/induzido quimicamente , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/induzido quimicamente , Neoplasias Pleurais/patologiaRESUMO
Amyloid tumors of the breast are extremely rare. Few isolated cases have been reported to date. Amyloid involvement of the breast has no specific diagnostic features on mammography; on occasion, this causes diagnostic challenges. In this paper, the case of a 58-year-old woman with an amyloid tumor of the breast, which developed secondary to long-standing rheumatoid arthritis, is presented. She presented with a palpable mass in her right breast, which led to an erroneous clinical diagnosis of breast cancer. The unusual mammography findings are demonstrated and the differential diagnosis, in light of the radiological images and the clinical and pathologic features, is discussed.
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Amiloidose/diagnóstico , Doenças Mamárias/diagnóstico , Neoplasias da Mama/diagnóstico , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Mamografia , Pessoa de Meia-IdadeRESUMO
We present a case of synchronous bilateral carotid body tumor and vagal paraganglioma in a 49-year-old man who presented with 3 months history of tenderness and palpable neck masses bilaterally. An encapsulated mass which was thought to be a carotid body tumor and an incidental 3 cm x 2 cm, 5 cm x 1 cm, 5 cm mass which seemed to be originated from vagus nerve were dissected from the left side. Pathology revealed carotid body tumor and vagal paraganglioma. Six months after the first operation, the carotid body tumor on the right side was totally excised. A discussion of this case is followed by a review of the literature surrounding this rare clinic and pathological entity.
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Tumor do Corpo Carotídeo/diagnóstico , Neoplasias dos Nervos Cranianos/diagnóstico , Imageamento por Ressonância Magnética , Neoplasias Primárias Múltiplas/diagnóstico , Paraganglioma/diagnóstico , Ultrassonografia Doppler em Cores , Doenças do Nervo Vago/diagnóstico , Angiografia , Tumor do Corpo Carotídeo/irrigação sanguínea , Tumor do Corpo Carotídeo/patologia , Tumor do Corpo Carotídeo/cirurgia , Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Embolização Terapêutica , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Paraganglioma/patologia , Paraganglioma/cirurgia , Reoperação , Nervo Vago/patologia , Nervo Vago/cirurgia , Doenças do Nervo Vago/patologia , Doenças do Nervo Vago/cirurgiaRESUMO
Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal malignancy of the gastrointestinal (GI) tract. In neurofibromatosis (NF), the increased incidence of tumor needs to be considered even in non-symptomatic individuals. Patients with neurofibromatosis NF type 1 have an increased risk of developing GI tumors including rare types such as GIST. We report a case of GIST in a 53-year-old male patient with neurofibromatosis. The patient was diagnosed with NF four years ago and his medical history revealed that he was hospitalized 5 times with a provisional diagnosis of massive lower gastrointestinal bleeding. GIST was diagnosed at explorative laparotomy and the tumor was 21 cm multiply 13 cm multiply 7 cm in size. Immunohistochemical examination showed that vimentin, actin and CD117 were positive. Computerized tomography showed peritoneal implants three months later. Imatinib mesylate (600 mg/d) was initiated. However, control computerized tomography revealed liver and omental metastasis. The dosage was elevated to 800 mg/d. Despite high dosage, the progression of the metastatic lesions continued in the liver and omentum. The patient started oral sunitinib malate (Sutent) Pfizer Inc, New York, NY, USA) 50 mg per day for 4 consecutive weeks, followed by 2 wk off per treatment cycle. The metastatic lesions in the liver and omentum were decreased in size after four courses, suggesting that sunitinib is also an effective treatment modality for metastatic GIST in NF patients.
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Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neurofibromatose 1/complicações , Pirróis/uso terapêutico , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/secundário , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Omento/patologia , SunitinibeRESUMO
INTRODUCTION: A higher frequency of second malignancies is observed in patients with prostate cancer. We report a case of indolent non-Hodgkin's lymphoma diagnosed 2 years after prostate carcinoma. CASE REPORT: A 65-year-old man with diagnosis of localized prostate adenocarcinoma was presented with fatigue 2 years after prostatectomy operation. Abdominal ultrasonography showed hepatomegaly and paraaortocaval, parailiac, and perivascular multiple lymph nodes. The complete blood count revealed anemia and thrombocytopenia. Bone marrow biopsy demonstrated small lymphocytic lymphoma. CONCLUSION: Lymphoma should be suspected in cases with newly appeared adenopathy and/or cytopenias during follow-up. In patients with clinically organ-confined prostate cancer, indolent lymphoma should be in the differential diagnosis of newly appeared lymphadenopathy.
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Linfoma não Hodgkin/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Neoplasias da Próstata/patologia , Idoso , Diagnóstico Diferencial , Evolução Fatal , Humanos , Linfoma não Hodgkin/patologia , Masculino , Segunda Neoplasia Primária/patologia , Neoplasias da Próstata/cirurgiaRESUMO
The present case report defines a rare case of a liposarcoma with bone metastasis resulting in a complete remission (CR) following trabectedin treatment. The patient was referred with abdominal swelling and pain. A retroperitoneal mass was detected and described as dedifferentiated liposarcoma (DDLS). The mass was surgically removed and consequently adjuvant chemotherapy was administered. Three months after the completion of chemotherapy, patient presented with bone metastasis in thoracic and lumbar vertebrae. Vertebroplasty and radiotherapy (RT) was performed. After these therapies, bone pain persisted and bone scintigraphy showed increased activity in L4, T11, and T12 vertebrae. Zoledronic acid was added to trabectedin treatment. CR has been detected on bone scintigraphy and positron emission tomography-computed tomography (PET-CT) after 18 weeks. Previous cases about liposarcoma treated with trabectedin were mostly about the myxoid/round cell type (former name, currently known as myxoid liposarcoma (MLS)) and mostly reported partial responses. In this study, trabectedin was used for the treatment of a metastatic retroperitoneal DDLS and a CR was achieved.
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Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Dioxóis/uso terapêutico , Lipossarcoma Mixoide/tratamento farmacológico , Lipossarcoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Retroperitoneais/tratamento farmacológico , Tetra-Hidroisoquinolinas/uso terapêutico , Adulto , Neoplasias Ósseas/secundário , Feminino , Humanos , Lipossarcoma/patologia , Lipossarcoma Mixoide/patologia , Recidiva Local de Neoplasia/patologia , Tomografia por Emissão de Pósitrons , Prognóstico , Neoplasias Retroperitoneais/patologia , Tomografia Computadorizada por Raios X , TrabectedinaAssuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/análise , Neoplasias Pulmonares/diagnóstico , Mesotelioma/diagnóstico , Adenocarcinoma/metabolismo , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Queratina-5/biossíntese , Queratina-6/biossíntese , Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Vimentina/biossínteseRESUMO
BACKGROUNDS/AIMS: Drugs can cause several complications in the esophagus and lead to pill esophagitis. In this paper, our purpose is to share our clinical experience in light of the literature and put forward the general characteristics of pill esophagitis. MATERIALS AND METHODS: In our clinic, between January 2008 and June 2012, by excluding other factors, 48 patients were included in the study, diagnosed as drug-induced esophagitis with their history, endoscopic view, and histopathologic evaluation. RESULTS: There were 34 (70.9%) female and 14 (29.1%) male patients in the study, and their average ages were 35.1 and 32.4, respectively. Clinical symptoms were odynophagia (79.1%), retrosternal pain (62.5%), and dysphagia (47.9%). The reason for these symptoms for 85.5% of the patients was related to insufficient water consumption while taking the pill, taking the pill in recumbent position, or both. Tetracycline and its variant, doxycycline, were responsible for 52% of the patients, and 62.5% of the drugs were in capsule form. Ulcers were at the proximal and middle third of the esophagus in 79.2% of the patients. In the histopathologic evaluation, nonspecific acute inflammatory changes were found in 29.1% of the cases. Various proton pump inhibitors and sucralfate were used in the treatment. While no perforation and structure were detected, 1 patient died because of repetitive arterial bleeding. CONCLUSION: Almost every kind of drug, particularly doxycycline, can cause ulcer in the esophagus. Pill esophagitis can be prevented by warning patients about drinking water sufficiently and sitting up while taking the pill.
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Antibacterianos/efeitos adversos , Esofagite/induzido quimicamente , Úlcera/induzido quimicamente , Administração Oral , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Cápsulas , Dor no Peito/etiologia , Transtornos de Deglutição/etiologia , Doxiciclina/administração & dosagem , Doxiciclina/efeitos adversos , Esofagite/tratamento farmacológico , Esofagite/patologia , Esofagoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera/tratamento farmacológico , Úlcera/patologia , Água/administração & dosagem , Adulto JovemRESUMO
Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder that any valuable advance in the management of diseases has crucial importance. The present study aimed to compare the Endothelin1 (ET1) inhibitor bosentan which is regarded as standard therapy with different dose regimens of palosuran which is urotensin-II (UII) inhibitor and explore the discrepancy for mean pulmonary arterial pressure (mPAP), UII, ET1 levels, and pulmonary vascular pathology. Seventy rats were randomly divided into seven groups of ten animals each: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran 30 mg) received subcutaneous MCT and palosuran. Other groups consist of group 4 (MCT + palosuran 100 mg), group 5 (MCT + bosentan 30 mg), group 6 (MCT + bosentan 100 mg), and group 7 (combination therapy). Serum ET1, UII, mPAP levels, and pulmonary arteriolar pathology of different diameter vessels of all groups have been measured and recorded. The ET1 and UII levels of untreated rats (group 2) were significantly higher than the other groups (p < 0.05). Moreover, mPAP levels of group 2 were significantly higher than the other groups (p = 0.001). Finally, 50-125-µm diameter of arteriole wall thickness was found to be significantly thicker in monocrotaline group compared to groups 4 and 6 (p < 0.001). Statistical differences of wall thickness/diameter ratios of arteries and arterioles larger than 125 was found to be significant between group 5, group 6, and the control group (p < 0.001). UII inhibitor is at least as effective as standard therapy bosentan. Findings of this study consolidate that palosuran could be a new future promising therapeutic option in PAH.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Quinolinas/uso terapêutico , Sulfonamidas/uso terapêutico , Ureia/análogos & derivados , Animais , Pressão Arterial , Bosentana , Modelos Animais de Doenças , Antagonistas dos Receptores de Endotelina/uso terapêutico , Endotelina-1/metabolismo , Hemodinâmica , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Monocrotalina/administração & dosagem , Artéria Pulmonar/patologia , Ratos , Ratos Wistar , Ureia/uso terapêutico , Urotensinas/antagonistas & inibidoresRESUMO
Granulomatosis with polyangiitis (Wegener's) (GPA) is a chronic disease of unknown aetiology that leads to necrotising vasculitis in small and medium-sized vessels characterised by respiratory system and kidney involvement. Intestinal involvement is rare and perforation is even rarer in GPA. In this study, we are presenting a literature review of related cases, and a 29-year-old man referred from the emergency department with a multiple distal ileal perforation that was diagnosed with GPA, and successfully treated with rituximab.
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Anticorpos Monoclonais Murinos/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Doenças do Íleo/etiologia , Perfuração Intestinal/etiologia , Vasculite Sistêmica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Murinos/administração & dosagem , Colonoscopia , Diagnóstico Diferencial , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/diagnóstico , Humanos , Doenças do Íleo/diagnóstico , Doenças do Íleo/terapia , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Injeções Intravenosas , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/tratamento farmacológico , Masculino , Rituximab , Vasculite Sistêmica/complicações , Vasculite Sistêmica/diagnósticoRESUMO
Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-ß1 (TGF-ß1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups--group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-ß1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-ß1 levels (p < 0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-ß1 levels (p > 0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.
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Quinolinas/uso terapêutico , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/metabolismo , Ureia/análogos & derivados , Urotensinas/antagonistas & inibidores , Animais , Bleomicina , Endotelina-1/análise , Matriz Extracelular/metabolismo , Fibrose/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Escleroderma Sistêmico/induzido quimicamente , Pele/efeitos dos fármacos , Pele/patologia , Fator de Crescimento Transformador beta1/análise , Ureia/uso terapêuticoRESUMO
Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-ß1 (TGF-ß1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-ß1, and UII levels were significantly diminished in the treatment group, similar to the controls (p < 0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p = 0.001). Finally, in the 50-125-µm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p < 0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-µm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.