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1.
Front Vet Sci ; 11: 1400139, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840642

RESUMO

Introduction: Intramedullary cord tumors present diagnostic and therapeutic challenges. Furthermore, spinal cord tumors can move across compartments, making antemortem diagnosis difficult, even with advanced imaging. This report presents a rare case of a cranial cervical spinal glioma, confirmed by surgical histopathology, with postoperative improvement in a dog. Case description: A 9-year-old female Maltese dog presented with kyphotic posture, progressive left hemiparesis, and decreased appetite. Neurological examination revealed neck pain and decreased proprioception in the left limbs along with intact deep pain perception. Two days later, the patient developed non-ambulatory tetraparesis. Magnetic resonance imaging (MRI) revealed an ovoid, well-defined mass with homogeneously marked contrast enhancement in the second cervical spinal cord that severely compressed the spinal cord. This mass was heterogeneously hyperintense on T2-weighted images and iso-to-hypointense on T1-weighted images, showing an appearance resembling the "golf-tee" and "dural tail" signs. The MRI findings suggested an intradural extramedullary tumor. Intraoperatively, a well-demarcated mass which was locally adherent to the spinal meninges was removed. Both histopathological and genomic tumor tests were indicative of a glioma. Approximately 2 weeks postoperatively, the patient's neurological signs returned to normal. Conclusion: This case report describes an atypical cervical glioma with complicated MR characteristics in a dog, where MRI helped guide surgical intervention.

2.
Biomed Pharmacother ; 161: 114467, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36871538

RESUMO

Cancer cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, and there are currently no FDA-approved medications. In the present study, upregulation of six cytokines was observed in serum samples from patients with colorectal cancer (CRC) and in mouse models. A negative correlation between the levels of the six cytokines and body mass index in CRC patients was seen. Gene Ontology analysis revealed that these cytokines were involved in regulating T cell proliferation. The infiltration of CD8+ T cells was found to be associated with muscle atrophy in mice with CRC. Adoptive transfer of CD8+ T cells isolated from CRC mice resulted in muscle wasting in recipients. The Genotype-Tissue Expression database showed that negative correlations between the expression of cachexia markers and cannabinoid receptor 2 (CB2) in human skeletal muscle tissues. Pharmacological treatment with Δ9-tetrahydrocannabinol (Δ9-THC), a selective CB2 agonist or overexpression of CB2 attenuated CRC-associated muscle atrophy. In contrast, knockout of CB2 with a CRISPR/Cas9-based strategy or depletion of CD8+ T cells in CRC mice abolished the Δ9-THC-mediated effects. This study demonstrates that cannabinoids ameliorate CD8+ T cell infiltration in CRC-associated skeletal muscle atrophy via a CB2-mediated pathway. Serum levels of the six-cytokine signature might serve as a potential biomarker to detect the therapeutic effects of cannabinoids in CRC-associated cachexia.


Assuntos
Canabinoides , Neoplasias Colorretais , Humanos , Camundongos , Animais , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Dronabinol/farmacologia , Dronabinol/uso terapêutico , Caquexia/tratamento farmacológico , Caquexia/etiologia , Caquexia/prevenção & controle , Linfócitos T CD8-Positivos , Citocinas , Inflamação , Imunidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Atrofia Muscular
3.
J Aerosol Med Pulm Drug Deliv ; 36(2): 55-64, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36827329

RESUMO

Background: Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by lung scarring, which results in breathing difficulty. Currently, patients with IPF exhibit a poor survival rate and have access to very limited therapeutic options. Interferon beta (IFN-ß) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis, and it has also been shown to exhibit therapeutic potential in IPF. However, clinical use of IFN-ß did not lead to improved overall survival in IPF patients in existing studies. One possibility is the limited efficiency of IFN-ß delivery through intravenous or subcutaneous injection. Materials and Methods: The aerosol particle size distribution was determined with a laser diffraction particle size analyzer to characterize the droplet size and fine particle fraction generated by three types of nebulizers: jet, ultrasonic, and mesh. A breathing simulator was used to assess the delivery efficiency of IFN-ß, and the temperature in the medication reservoirs was monitored with a thermocouple during nebulization. To further evaluate the antifibrotic activity of IFN-ß pre- and postnebulization, bleomycin (BLM)- or transforming growth factor-beta (TGF-ß)-treated human lung fibroblast (HLF) cells were used. Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Transwell migration assay and Q-PCR analysis were used to evaluate cell migration and the myofibroblast differentiation ability, respectively. IFN-ß protein samples were prepared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample loading buffer, and the expression of IFN-ß was assessed by western blotting. Results: Among the current drug delivery systems, aerosolized medication has shown increased efficacy of drug delivery for treating respiratory diseases when compared with parenteral drugs. It was found that neither the structural integrity nor the biological function of nebulized IFN-ß was compromised by the nebulization process of the mesh nebulizer. In addition, in BLM dose-response or TGF-ß-induced lung fibroblast proliferation assays, these effects could be reversed by both parenteral and inhaled IFN-ß nebulized with the mesh nebulizer. Nebulized IFN-ß with the mesh nebulizer also significantly inhibited the migration and myofibroblast differentiation ability of TGF-ß-treated HLF cells. Conclusions: The investigations revealed the potential efficacy of IFN-ß in the treatment of IPF with the mesh nebulizer, demonstrating the higher efficiency of IFN-ß delivered through the mesh nebulizer.


Assuntos
Fibrose Pulmonar Idiopática , Interferon beta , Humanos , Administração por Inalação , Interferon beta/farmacologia , Interferon beta/uso terapêutico , Aerossóis e Gotículas Respiratórios , Nebulizadores e Vaporizadores , Sistemas de Liberação de Medicamentos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fator de Crescimento Transformador beta/uso terapêutico , Tamanho da Partícula
4.
Food Funct ; 11(10): 8602-8611, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084700

RESUMO

Nelumbo nucifera leaf water extract (NLE) attenuates high-fat diet (HFD)-induced rabbit atherosclerosis, but its mechanism of action and the relevant compounds remain unclear. Modulating the proliferation and migration of vascular smooth muscle cells (VSMCs) may be an enforceable strategy for atherosclerosis prevention. Therefore, we investigated the potential mechanisms of N. nucifera leaf polyphenol extract (NLPE) and its active ingredient gallic acid (GA) in VSMC proliferation and migration. A7r5 rat aortic VSMCs were provoked using 50 ng mL-1 tumor necrosis factor (TNF)-α; the NLPE or GA reduced the TNF-α-induced migration by inhibiting the transforming protein RhoA/cell division cycle protein 42 pathway. The NLPE or GA suppressed the TNF-α-induced VSMC proliferation by inhibiting the Ras pathway and increasing the expression of phosphatase and tensin homolog (PTEN), kinase suppressor of Ras 2, and inducible nitric oxide synthase. The NLPE or GA increased PTEN expression by downregulating microRNA (miR)-21 expression and reduced Ras and RhoA expression by upregulating miR-143 and miR-145 expression. The NLPE and GA use potentially prevents atherosclerosis by inhibiting the VSMC migration and proliferation. The mechanisms involve the regulation of the miRNA in PTEN, the Ras/extracellular-signal-regulated kinase pathway, and Rho family proteins.


Assuntos
Ácido Gálico/farmacologia , MicroRNAs/genética , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Nelumbo/química , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Folhas de Planta , Polifenóis , Ratos , Transdução de Sinais , Proteínas ras/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
5.
Food Funct ; 11(1): 483-492, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31833514

RESUMO

Obesity, being overweight and deposition of body fat are critically associated with metabolic disorders. The number of adipocytes and their lipid content, and the molecules involved in lipid metabolism are involved in obesity comorbidity. The food, Solanum nigrum L. (SN), has medical benefits in many aspects. In our recent report, SN was shown to reduce hepatic fat accumulation and oxidative stress, thus attenuating liver damage. However, it has not yet been explored whether SN is effective for weight loss and body fat reduction. Hence, we aimed to investigate if SN water extract (SWE) and the derived polyphenols (SNPE) are able to prevent obesity. Mice fed a high fat diet (HFD) and 3T3L1 cells model were used. The in vivo experiments showed SWE decreased serum triacylglyceride, cholesterol, and low-density lipoprotein (LDL)-cholesterol induced by a HFD. SWE promoted hepatic lipolysis by increasing PPARα and CPT-1, and inhibited lipogenesis by decreasing FaS and HMG-CoR. The expression of AMPK was enhanced, but sterol regulatory element binding proteins (SREBPs) were reduced by SWE, especially at 5%. In vitro analysis revealed that SNPE decreased the amount and lipid content of adipocytes. SNPE, especially at 0.5 mg mL-1, promoted lipolysis while inhibiting lipogenesis. In comparison with the doses applied in vivo and in vitro, the effect of SN could be attributed to the composition of the polyphenols. The results showed that SNPE is suggested to be an anti-obesity agent that is able to reduce body weight and body fat, by decreasing the amount and lipid content of adipocytes, and regulating lipid metabolism.


Assuntos
Tecido Adiposo/metabolismo , Fármacos Antiobesidade/administração & dosagem , Peso Corporal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Solanum nigrum/química , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Obesidade/fisiopatologia , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
6.
J Agric Food Chem ; 66(26): 6708-6716, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29877083

RESUMO

Tricin, a natural flavonoid present in large amounts in rice bran, was investigated for the mechanisms by which it exhibited antiproliferation and anti-invasion in C6 glioma cells. The results indicated that treatment with 5, 10, 25, and 50 µM tricin for 48 h significantly ( p < 0.05) inhibited cell numbers and colony numbers with values of 134.3 ± 5.5, 114.6 ± 2.5, 106.3 ± 3.2, and 57.3 ± 10.2, respectively. Tricin also inhibited C6-cell motility, migration, and invasion. Tricin changed the cytoskeletal organization, reduced matrix-metalloproteinase (MMP) expression, and upregulated E-cadherin. Tricin decreased FAK protein levels and suppressed focal-adhesion-kinase (FAK)-downstream-signal activation. Most importantly, tricin dose-dependently upregulated microRNA-7 (miR-7). Transfection with an miR-7 inhibitor suppressed miR-7 expression, increased FAK expression, and promoted the proliferation and invasion in C6 cells. The data support a novel anticancer mechanism of tricin that involves upregulation of FAK-targeting miR-7 in C6 glioma cells.


Assuntos
Antineoplásicos/farmacologia , Flavonoides/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/genética , Glioma/fisiopatologia , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/tratamento farmacológico , Glioma/enzimologia , Glioma/genética , Humanos , MicroRNAs/genética , Invasividade Neoplásica
7.
J Food Drug Anal ; 26(2): 778-787, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29567249

RESUMO

Mulberry (Morus alba) leaf has been used in Chinese medicine as the remedy for hyperlipidemia and metabolic disorders. Recent report indicated Mulberry leaf extract (MLE) attenuated dyslipidemia and lipid accumulation in high fat diet (HFD)-fed mice. Non-alcoholic fatty liver (NAFLD) is generally considered as the liver component of metabolic syndrome. The hepatic lipid infiltration induces oxidative stress, and is associated with interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) which are regulated by the leptin and adiponectin. MLE could prevent obesity-related NAFLD via downregulating the lipogenesis enzymes while upregulating the lipolysis markers. Treatment of MLE, especially at 2%, enhanced the expression of superoxide dismutase (SOD) and clenched the oxidative stress of liver. MLE decreased the plasma level of leptin but increased adiponectin. The advantage of MLE is supposed mainly attributed to chlorogenic acid derivative. We suggest MLE, with promising outcome of research, could be nutraceutical to prevent obesity and related NAFLD.


Assuntos
Adipocinas/metabolismo , Morus/química , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Obesidade/complicações , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Dieta Hiperlipídica , Humanos , Interleucina-6/genética , Interleucina-6/imunologia , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Folhas de Planta/química , Ratos Wistar , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
8.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-713442

RESUMO

Hypothalamic obesity is often complicated in patients with craniopharyngioma due to hypothalamic damage by the tumor itself, treatment modalities, and associated multiple pituitary hormone deficiency. Hypothalamic obesity causes secondary diseases such as nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM). We report a 19-year-old female who was diagnosed with craniopharyngioma, developed hypothalamic obesity after tumor resection, and progressed to hepatopulmonary syndrome. She manifested NAFLD 1 year after tumor resection. Two years later, the craniopharyngioma recurred, and she underwent a second resection. Three years after her second operation, she was diagnosed with type 2 DM, after which she did not visit the outpatient clinic for 2 years and then suddenly reappeared with a weight loss of 25.8 kg that had occurred over 21 months. One month later, she presented to the Emergency Department with dyspnea. Laboratory findings revealed liver dysfunction and hypoxia with increased alveolar artery oxygen gradient. Liver biopsy showed portal hypertension and micronodular cirrhosis. Echocardiography and a lung perfusion scan demonstrated a right to left shunt. She was finally diagnosed with hepatopulmonary syndrome and is currently awaiting a donor for liver transplantation. Patients surviving craniopharyngioma need to be followed up carefully to detect signs of hypothalamic obesity and monitored for the development of other comorbidities such as DM, NAFLD, and hepatopulmonary syndrome.


Assuntos
Feminino , Humanos , Adulto Jovem , Instituições de Assistência Ambulatorial , Hipóxia , Artérias , Biópsia , Comorbidade , Craniofaringioma , Diabetes Mellitus , Dispneia , Ecocardiografia , Serviço Hospitalar de Emergência , Fibrose , Síndrome Hepatopulmonar , Hipertensão Portal , Hipotálamo , Fígado , Hepatopatias , Transplante de Fígado , Pulmão , Hepatopatia Gordurosa não Alcoólica , Obesidade , Oxigênio , Perfusão , Doadores de Tecidos , Redução de Peso
9.
J Agric Food Chem ; 65(42): 9255-9265, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-28982243

RESUMO

Patients with diabetes, obesity, and hyperlipidemia are all high-risk groups for fatty liver; however, the mechanism of fatty liver formation is not completely understood. Studies have indicated that abnormal fat metabolism, oxidative stress, and insulin resistance are positively correlated with peroxidation and abnormal cytokine production. Recent studies have revealed that Solanum nigrum extracts (SNE) possess anti-inflammatory, antioxidation, antihyperlipidemia, and liver protection abilities. Therefore, the present study investigated the in vivo and in vitro effects of an SNE on nonalcoholic fatty liver (NAFL)-induced hepatitis. In vivo data demonstrated that the SNE reduced blood triglyceride, sugar, and cholesterol levels, as well as fat accumulation, oxidative stress, and lipid peroxidation in high-fat-diet-treated mice. The results indicated that the SNE downregulated the expression of fatty acid synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), and sterol regulatory element-binding proteins (SREBPs) through the AMP-activated protein kinase (AMPK) pathway and upregulated the expression of carnitine palmitoyltransferase 1 (CPT1) and peroxisome proliferator-activated receptor alpha. Furthermore, we prepared a Solanum nigrum polyphenol extract (SNPE) from the SNE; the SNPE reduced hepatic lipid (oleic acid) accumulation. Therefore, SNE have the potential to alleviate NAFL-induced hepatitis, and polyphenolic compounds are the main components of SNE. Moreover, SNE can be used to develop health-food products for preventing NAFL disease.


Assuntos
Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Solanum nigrum/química , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Acil Coenzima A/genética , Acil Coenzima A/metabolismo , Animais , Carnitina O-Palmitoiltransferase/genética , Carnitina O-Palmitoiltransferase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
10.
J Vet Med Sci ; 79(1): 192-196, 2017 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-27746404

RESUMO

A 12-year-old, spayed female Schnauzer presented with constipation. A mass was observed in the pelvic cavity, and metastasis was not identified. Mass resection was performed through celiotomy with pubic osteotomy, and hemangiosarcoma was diagnosed. At 10 weeks post-operatively, the patient died of multiple metastasis. Primary intrapelvic hemangiosarcoma is rare in dogs.


Assuntos
Doenças do Cão/cirurgia , Hemangiossarcoma/veterinária , Neoplasias Pélvicas/veterinária , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Cães , Evolução Fatal , Feminino , Hemangiossarcoma/diagnóstico , Hemangiossarcoma/patologia , Hemangiossarcoma/cirurgia , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/patologia , Neoplasias Pélvicas/cirurgia
11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-129016

RESUMO

PURPOSE: Studies on the efficacy of infliximab (IFX) in a large population of pediatric patients with Crohn's disease (CD) are limited, and prognostic factors are not well-known. The aim of this study was to evaluate outcomes of IFX in pediatric patients with CD and to identify factors associated with poor prognosis. METHODS: We retrospectively analyzed medical data of 594 pediatric patients with CD between 1987 and 2013 in a tertiary center. Of these, 156 children treated with IFX were enrolled and were followed up for at least a year with intact data. Outcomes of induction and maintenance, classified as failure or clinical response, were evaluated on the tenth and 54th week of IFX therapy. RESULTS: We treated 156 pediatric patients with CD with IFX, and the median duration of IFX therapy was 47 months. For IFX induction therapy, 134 (85.9%) patients experienced clinical response on the 10th week. Among the 134 patients who showed response to induction, 111 (82.8%) patients maintained the clinical response on the 54th week. In multivariate analysis, low hematocrit (p=0.046) at the time of IFX initiation was associated with the failure of IFX induction. For IFX maintenance therapy, longer duration from the initial diagnosis to IFX therapy (p=0.017) was associated with maintenance failure on the 54th week. CONCLUSION: We have shown the acceptable outcomes of IFX in a large cohort of pediatric CD patients in Korea. Hematocrit and early introduction of IFX may be prognostic factors for the outcomes of IFX.


Assuntos
Criança , Humanos , Estudos de Coortes , Doença de Crohn , Diagnóstico , Hematócrito , Infliximab , Coreia (Geográfico) , Análise Multivariada , Prognóstico , Estudos Retrospectivos
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-129001

RESUMO

PURPOSE: Studies on the efficacy of infliximab (IFX) in a large population of pediatric patients with Crohn's disease (CD) are limited, and prognostic factors are not well-known. The aim of this study was to evaluate outcomes of IFX in pediatric patients with CD and to identify factors associated with poor prognosis. METHODS: We retrospectively analyzed medical data of 594 pediatric patients with CD between 1987 and 2013 in a tertiary center. Of these, 156 children treated with IFX were enrolled and were followed up for at least a year with intact data. Outcomes of induction and maintenance, classified as failure or clinical response, were evaluated on the tenth and 54th week of IFX therapy. RESULTS: We treated 156 pediatric patients with CD with IFX, and the median duration of IFX therapy was 47 months. For IFX induction therapy, 134 (85.9%) patients experienced clinical response on the 10th week. Among the 134 patients who showed response to induction, 111 (82.8%) patients maintained the clinical response on the 54th week. In multivariate analysis, low hematocrit (p=0.046) at the time of IFX initiation was associated with the failure of IFX induction. For IFX maintenance therapy, longer duration from the initial diagnosis to IFX therapy (p=0.017) was associated with maintenance failure on the 54th week. CONCLUSION: We have shown the acceptable outcomes of IFX in a large cohort of pediatric CD patients in Korea. Hematocrit and early introduction of IFX may be prognostic factors for the outcomes of IFX.


Assuntos
Criança , Humanos , Estudos de Coortes , Doença de Crohn , Diagnóstico , Hematócrito , Infliximab , Coreia (Geográfico) , Análise Multivariada , Prognóstico , Estudos Retrospectivos
13.
Sci Rep ; 6: 38642, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27924924

RESUMO

Acarbose, an α-glucosidase inhibitor, is reported to reduce the incidence of silent myocardial infarction and slow the progression of intima-media thickening in patients with glucose intolerance. Here we investigate other impacts of acarbose on atherosclerosis development and the underlying mechanisms of atherosclerosis initiation and progression in vivo and in vitro. Rabbits fed a high cholesterol diet (HCD) were treated with acarbose (2.5-5.0 mg kg-1). Immunohistochemistry was used to assess the expression of inducible nitric oxide synthase (iNOS), Ras, proliferating cell nuclear antigen (PCNA), IL-6, ß-galactosidase, and p-AMPK in atherosclerotic lesions. Treatment with acarbose in HCD-fed rabbits was found to significantly reduce the severity of aortic atheroma and neointimal expression of α-actin, PCNA, IL-6, TNF-α, Ras, and ß-galactosidase; to significantly increase expression of iNOS and p-AMPK, but not to affect serum levels of glucose, total cholesterol, and LDL. Western blot analysis showed acarbose dose-dependently decreased ß-galactosidase and Ras expression and increased p-AMPK expression in TNF-α-treated A7r5 cells. In addition, acarbose restored p-AMPK and iNOS levels in AMPK inhibitor- and iNOS inhibitor-treated A7r5 cells, respectively. In conclusion, acarbose can pleiotropically inhibit rabbit atherosclerosis by reducing inflammation, senescence, and VSMCs proliferation/migration via upregulating AMPK signals.


Assuntos
Acarbose/efeitos adversos , Aterosclerose/etiologia , Aterosclerose/metabolismo , Inibidores de Glicosídeo Hidrolases/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Aterosclerose/patologia , Biomarcadores , Peso Corporal/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Imuno-Histoquímica , Lipídeos/sangue , Masculino , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Coelhos
14.
J Vet Sci ; 17(1): 97-102, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27051345

RESUMO

We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Regulação da Expressão Gênica , Traumatismos da Medula Espinal/terapia , Animais , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Humanos , Locomoção , Fator de Crescimento Neural/genética , Ratos
15.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-110760

RESUMO

We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.


Assuntos
Animais , Humanos , Ratos , Fator Neurotrófico Derivado do Encéfalo/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Ensaio de Imunoadsorção Enzimática , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Locomoção , Fator de Crescimento Neural/genética , Traumatismos da Medula Espinal/terapia
16.
Can Vet J ; 56(10): 1025-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26483575

RESUMO

A 10-year-old Maltese dog was presented with a firm mass on the left side of his neck. Physical examination confirmed a firm mass in the left and a submandibular swelling in the right cervical region. Sialolithiasis and associated sialocele in both mandibular salivary glands were suspected and bilateral sialoadenectomy was performed. The stones were identified as non-mineral sialoliths.


Changements anormaux dans les deux glandes salivaires mandibulaires chez un chien : sialolithes radiopaques non minéraux. Un chien Maltais âgé de 10 ans a été présenté avec une masse ferme du côté droit du cou. L'examen physique a confirmé une masse ferme dans l'enflure gauche et sous-mandibulaire dans la région cervicale droite. La sialolithiase et une sialocèle connexe dans les deux glandes salivaires mandibulaires ont été suspectées et une sialoadénectomie bilatérale a été réalisée. Les pierres ont été identifiées comme des sialolithes non minéraux.(Traduit par Isabelle Vallières).


Assuntos
Doenças do Cão/diagnóstico , Cálculos das Glândulas Salivares/veterinária , Animais , Doenças do Cão/cirurgia , Cães , Masculino , Cálculos das Glândulas Salivares/diagnóstico , Cálculos das Glândulas Salivares/cirurgia
17.
Cytotherapy ; 15(12): 1498-510, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23992828

RESUMO

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been extensively studied as a cellular therapeutic for various pathologic conditions. However, there remains a paucity of data regarding regional and systemic safety of MSC transplantations, particularly with multiple deliveries of allogeneic cells. The purpose of this study was to investigate the safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs into the region of the lacrimal gland, the gland of the third eyelid and the knee joint in dogs. METHODS: Allogeneic adipose tissue-derived canine MSCs were delivered to the regions of the lacrimal gland and the third eyelid gland as well as in the knee joints of six healthy laboratory beagles as follows: six times with 1-week intervals for delivery to the lacrimal gland and the third eyelid gland regions and three to four times with 1- to 2-week intervals for intra-articular transplantations. Dogs were sequentially evaluated by clinical examination. At the conclusion of the study, dogs were humanely euthanized, and a complete gross and histopathologic examination of all organ systems was performed. Mixed leukocyte reactions were also performed before the first transplantation and after the final transplantation. RESULTS: Clinical and pathologic examinations found no severe consequences after repeated MSC transplantations. Results of mixed leukocyte reactions demonstrated suppression of T-cell proliferation after MSC transplantations. CONCLUSIONS: This is the first study to demonstrate regional and systemic safety and systemic immunomodulatory effects of repeated local delivery of allogeneic MSCs in vivo.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Proliferação de Células , Cães , Humanos , Articulação do Joelho/patologia , Aparelho Lacrimal/patologia , Aparelho Lacrimal/transplante , Teste de Cultura Mista de Linfócitos , Masculino , Membrana Nictitante/patologia , Membrana Nictitante/transplante
18.
Cytotherapy ; 15(9): 1136-47, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23831362

RESUMO

BACKGROUND AIMS: Delivery of bone marrow-derived stem and progenitor cells to the site of injury is an effective strategy to enhance bone healing. An alternate approach is to mobilize endogenous, heterogeneous stem cells that will home to the site of injury. AMD3100 is an antagonist of the chemokine receptor 4 (CXCR4) that rapidly mobilizes stem cell populations into peripheral blood. Our hypothesis was that increasing circulating numbers of stem and progenitor cells using AMD3100 will improve bone fracture healing. METHODS: A transverse femoral fracture was induced in C57BL/6 mice, after which they were subcutaneously injected for 3 d with AMD3100 or saline control. Mesenchymal stromal cells, hematopoietic stem and progenitor cells and endothelial progenitor cells in the peripheral blood and bone marrow were evaluated by means of flow cytometry, automated hematology analysis and cell culture 24 h after injection and/or fracture. Healing was assessed up to 84 d after fracture by histomorphometry and micro-computed tomography. RESULTS: AMD3100 injection resulted in higher numbers of circulating mesenchymal stromal cells, hematopoietic stem cells and endothelial progenitor cells. Micro-computed tomography data demonstrated that the fracture callus was significantly larger compared with the saline controls at day 21 and significantly smaller (remodeled) at day 84. AMD3100-treated mice have a significantly higher bone mineral density than do saline-treated counterparts at day 84. CONCLUSIONS: Our data demonstrate that early cell mobilization had significant positive effects on healing throughout the regenerative process. Rapid mobilization of endogenous stem cells could provide an effective alternative strategy to cell transplantation for enhancing tissue regeneration.


Assuntos
Técnicas de Cultura de Células/métodos , Fraturas do Fêmur/terapia , Consolidação da Fratura/fisiologia , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas/fisiologia , Células-Tronco/fisiologia , Animais , Benzilaminas , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/fisiologia , Células Cultivadas , Ciclamos , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Fraturas do Fêmur/tratamento farmacológico , Fraturas do Fêmur/fisiopatologia , Consolidação da Fratura/efeitos dos fármacos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Compostos Heterocíclicos/uso terapêutico , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco/efeitos dos fármacos
19.
J Vet Sci ; 14(3): 329-35, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23820159

RESUMO

Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10 min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 µL (n = 18), 50 µL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 µL was used, but not after 50 µL was applied. In the 50 µL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo.


Assuntos
Embolectomia com Balão/métodos , Compressão da Medula Espinal/terapia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
20.
J Vet Sci ; 14(4): 495-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23820160

RESUMO

The use of human umbilical cord blood-derived mesenchymal stem cells for cell transplantation therapy holds great promise for repairing spinal cord injury. Here we report the first clinical trial transplantation of human umbilical cord (hUCB)-derived mesenchymal stem cells (MSCs) into the spinal cord of a dog suspected to have fibrocartilaginous embolic myelopathy (FCEM) and that experienced a loss of deep pain sensation. Locomotor functions improved following transplantation in a dog. Based on our findings, we suggest that transplantation of hUCB-derived MSCs will have beneficial therapeutic effects on FCEM patients lacking deep pain sensation.


Assuntos
Doenças das Cartilagens/veterinária , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doenças do Cão/terapia , Embolia/veterinária , Células-Tronco Mesenquimais/metabolismo , Doenças da Medula Espinal/veterinária , Animais , Doenças das Cartilagens/etiologia , Doenças das Cartilagens/terapia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/veterinária , Doenças do Cão/etiologia , Cães , Embolia/etiologia , Embolia/terapia , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/terapia , Resultado do Tratamento
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