RESUMO
Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder associated with skin barrier dysfunction. The lesional skin of AD exhibits T helper 2 (TH 2)-deviated immune reactions. Interleukin-31 (IL-31), preferentially produced from TH 2 cells, is a potent pruritogenic cytokine, and its systemic and local administration induces scratching behavior in rodents, dogs and monkeys. Recent clinical trials have revealed that administration of an anti-IL-31 receptor antibody significantly alleviates pruritus in patients with AD. In this review, we summarize recent topics related to IL-31 and its receptor with special references to atopic itch.
Assuntos
Dermatite Atópica/etiologia , Dermatite Atópica/metabolismo , Interleucinas/metabolismo , Prurido/etiologia , Prurido/metabolismo , Receptores de Interleucina/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores , Citocinas/metabolismo , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Gerenciamento Clínico , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/metabolismo , Interleucinas/química , Interleucinas/genética , Prurido/complicações , Prurido/diagnóstico , Receptores de Interleucina/química , Receptores de Interleucina/genética , Relação Estrutura-AtividadeRESUMO
Endothelin-1 (ET-1) is associated with skin diseases such as atopic dermatitis (AD) and psoriasis. ET-1 is enhanced in the skin of patients AD and psoriasis. In addition, plasma levels of ET-1 are elevated in AD and psoriasis. Although both AD and psoriasis are T-cell-mediated skin diseases, the association between ET-1 and the T-cell immune response has not been clarified. To evaluate the role of ET-1 in inflammatory skin disease, we sought to investigate the effects of ET-1 on the functions of dendritic cells (DCs) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET-1 in the epidermis of patients with AD or psoriasis. ET-1 directly induced phenotypic maturation of bone marrow-derived DCs (BMDCs). In addition, ET-1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDCs. Interestingly, ET-1-activated BMDCs primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET-1 polarizes the DC-T-cell response toward Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.
Assuntos
Células Dendríticas/imunologia , Dermatite Atópica/imunologia , Endotelina-1/imunologia , Psoríase/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Diferenciação Celular/imunologia , Ensaio de Imunoadsorção Enzimática , Epiderme/imunologia , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Endothelin-1 (ET-1) has been reported to evoke histamine-independent pruritus in mammals. However, its association with pruritus or inflammation of atopic dermatitis (AD) has not been clarified. We sought to investigate the role of ET-1 in the skin inflammation of AD. METHODS: To examine the role of ET-1 in AD, we investigated the expression of ET-1 and IL-25 in the skin of an AD mouse model and patients with AD and examined the mutual regulatory relationship between ET-1 and IL-25, one of the important cytokines in AD, using the human HaCaT keratinocyte cell line. RESULTS: We immunohistochemically confirmed the upregulation of ET-1 and IL-25 expression in the epidermis of both the AD mouse model and patients with AD. In vitro, IL-25 upregulated ET-1 mRNA and protein expression in a concentration- and time-dependent fashion in HaCaT cells. This IL-25-induced ET-1 expression was inhibited by ERK1/2 or JNK inhibitor. In a reciprocal manner, ET-1 also induced IL-25 upregulation. The enhancing effect of ET-1 on IL-25 was inhibited by an endothelin A receptor antagonist, ERK1/2 inhibitor, or p38 inhibitor, but not by an endothelin B receptor antagonist or JNK inhibitor. CONCLUSION: These findings suggest that mutual upregulation of ET-1 and IL-25 takes place in the epidermis of AD, which may be a future target for antipruritic agents.
Assuntos
Dermatite Atópica/metabolismo , Endotelina-1/metabolismo , Interleucina-17/metabolismo , Animais , Dermatite Atópica/genética , Dermatite Atópica/patologia , Modelos Animais de Doenças , Endotelina-1/genética , Expressão Gênica , Humanos , Interleucina-17/genética , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor de Endotelina A/genética , Receptor de Endotelina A/metabolismo , Regulação para CimaRESUMO
Major histocompatibility complex (MHC) class I-restricted T cell epitopes are generated mainly by the immunoproteasome in antigen-presenting cells. Therefore, inhibition of activity of this proteolytic complex molecule is thought to be a potential treatment for cell-mediated autoimmune diseases. We therefore studied the efficacy of an immunoproteasome inhibitor, ONX 0914 (formerly PR-957), for the treatment of autoimmune thyroid diseases, including cell-mediated Hashimoto's thyroiditis and autoantibody-mediated Graves' hyperthyroidism using mouse models. Our data show that ONX 0914 was effective prophylactically and therapeutically at suppressing the degree of intrathyroidal lymphocyte infiltration and, to a lesser degree, the titres of anti-thyroglobulin autoantibodies in non-obese diabetic (NOD)-H2(h4) mice, an iodine-induced autoimmune thyroiditis model. It also inhibited differentiation of T cells to T helper type 1 (Th1) and Th17 cells, effector T cell subsets critical for development of thyroiditis in this mouse strain. In contrast, its effect on the Graves' model was negligible. Although ONX 0914 exerts its immune-suppressive effect through not only suppression of immune proteasome but also other mechanism(s), such as inhibition of T cell differentiation, the present results suggest that the immunoproteasome is a novel drug target in treatment of Hashimoto's thyroiditis in particular and cell-mediated autoimmune diseases in general.
Assuntos
Inibidores de Cisteína Proteinase/uso terapêutico , Doença de Graves/tratamento farmacológico , Doença de Hashimoto/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Inibidores de Proteassoma , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Animais , Formação de Anticorpos/efeitos dos fármacos , Autoanticorpos/sangue , Células Cultivadas , Inibidores de Cisteína Proteinase/administração & dosagem , Inibidores de Cisteína Proteinase/efeitos adversos , Modelos Animais de Doenças , Doença de Graves/imunologia , Doença de Hashimoto/induzido quimicamente , Doença de Hashimoto/imunologia , Humanos , Imunidade Celular/efeitos dos fármacos , Iodo/administração & dosagem , Camundongos , Camundongos Endogâmicos NOD , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologia , Tireoglobulina/imunologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologiaAssuntos
Encéfalo/irrigação sanguínea , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Circulação Cerebrovascular , Transtornos Cognitivos/etiologia , Complicações Pós-Operatórias/etiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Humanos , Monitorização Fisiológica , Testes Neuropsicológicos , Consumo de OxigênioRESUMO
Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD20/imunologia , Linfócitos B/efeitos dos fármacos , Doença de Graves/imunologia , Doença de Graves/prevenção & controle , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Linfócitos B/citologia , Linfócitos B/imunologia , Contagem de Células , Modelos Animais de Doenças , Feminino , Doença de Graves/sangue , Doença de Graves/terapia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Interferon gama/metabolismo , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Depleção Linfocítica/métodos , Camundongos , Camundongos Endogâmicos BALB C , Cavidade Peritoneal/citologia , Receptores da Tireotropina/genética , Receptores da Tireotropina/imunologia , Baço/citologia , Baço/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Tiroxina/sangue , Vacinas de DNA/genética , Vacinas de DNA/imunologiaRESUMO
A 52-year-old woman underwent the surgical treatment for osteosarcoma of the left mandible in 2003 and was followed up afterward. She suffered from dry cough and bloody sputum, and was admitted to our hospital in April 2007. Computed tomography (CT) revealed several nodules in bilateral lung, and bronchofiberscopy showed the endobronchial tumor obstructing in the right main bronchus. The metastatic tumor progressed in the right main bronchus from the right S6 lung segment. The tumor rapidly progressed in the right bronchus in comparison with the CT findings in about 2 weeks, and the possibility of the tracheal obstruction was considered. She underwent the right middle and lower lobectomy, and the endobronchial tumor was pulled through the right main bronchus. The postoperative course was uneventful, the patient was discharged on 14th postoperative day, and the chemotherapy using cisplatin (CDDP) and adriamycin (ADR) is on-going.
Assuntos
Neoplasias Pulmonares/secundário , Neoplasias Mandibulares/patologia , Osteossarcoma/patologia , Osteossarcoma/secundário , Traqueia/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica/patologiaRESUMO
Adenocarcinoma of the thymus is a very rare malignant tumor. The standard treatment for advanced thymic carcinoma has not yet been established, and the prognosis is poor. We report a case of thymic carcinoma that involving the aortic arch and the innominate vein. A 78-year-old woman was admitted to our hospital complaining of hoarseness in April 2007. The computed tomography (CT) scan showed an anterior mediastinal tumor contiguous to the aortic arch and the innominate vein with swelling lymphnodes. Microspcopic examinations of specimens obtained by CT-guided needle biopsy revealed poorly differenciated adenocarcinoma. The carcinoembryonic antigen (CEA) level of serum elevated at 54.9 ng/ml. Thymic carcinoma was diagnosed. The chemoradiotherapy [concurrent, carboplatin (CBDCA) + paclitaxel(TXL)-->vinorelbine (NVB), 60 Gy] was performed, but the effect of the therapy was limited. The resection of the tumor with a part of aortic arch and other peripheral tissues was performed in Augast 2007. The postoperative course was uneventful and the CEA level of serum lowered to the normal. She was discharged 30 days after surgery.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Aorta Torácica/patologia , Neoplasias do Timo/patologia , Neoplasias do Timo/cirurgia , Adenocarcinoma/terapia , Idoso , Terapia Combinada , Feminino , Humanos , Invasividade Neoplásica , Neoplasias do Timo/terapiaRESUMO
An abnormal shadow was detected on chest X-ray mass screening in an asymptomatic 63-year-old man. The further examinations revealed the shadow to be primary lung cancer (Rt. S6. adenocarcinoma, cT2N0M0, c-stage IB) with right aortic arch. We used 3 dimentional-computed tomography (3D-CT) to assess an anatomical feature of vessels in detail. The right lower lobectomy and the dissection of medi astinal lymph nodes was performed. We confirmed no abnormal anatomy of pulmonary artery and vein at surgery, and it was possible to perform right lower lobectomy with the common procedure. Since lymph node was found by intraopetrative pathological examination, since no metastasis from interlobar to subcarinal lymph node was found, we did not perform dissection of upper mediastinal dissection, which was equivalent to ND2a lymph nodes dissection of the left lung cancer in General Rule for Clinical and Pathological Record of Lung Cancer. The patient with right aortic arch is known to have variant anatomy of other intrathoracic vessels occasionally. 3D-CT was quite useful in assessing anatomical feature, and enabled us to perform safe operation.
Assuntos
Adenocarcinoma/cirurgia , Aorta Torácica/anormalidades , Neoplasias Pulmonares/cirurgia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/diagnóstico por imagem , Angiografia , Aorta Torácica/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Pulmão/irrigação sanguínea , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Mediastino/irrigação sanguínea , Pessoa de Meia-Idade , Pneumonectomia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Neurogenesis in the adult hippocampal dentate gyrus is promoted by transient forebrain ischemia. The mechanism responsible for this ischemia-induced neurogenesis, however, remains to be determined. It has been suggested that there may be a close relationship between neurogenesis and the expression of vascular endothelial growth factor, an angiogenic factor. The purpose of the present study was to examine the relationship between vascular endothelial growth factor and cell proliferation in the dentate gyrus after transient forebrain ischemia. The mRNA expression of vascular endothelial growth factor was increased in the dentate gyrus on day 1 after ischemia. Immunohistochemical analysis on day 9 after ischemia, when a significant increase in cell proliferation was seen, showed that the cerebral vessel space in the subgranular zone of the dentate gyrus had not been affected by the ischemia. Neither were the vascular densities on days 1 and 3 after ischemia altered compared with those of non-operated naïve control rats. Furthermore, the distance from the center of the proliferative cells to the nearest cerebral vessel of ischemic rats was comparable to that of the sham-operated rats. We demonstrated that transient forebrain ischemia-induced cell proliferation and differentiation to mature neurons in the hippocampal dentate gyrus was attenuated by the i.c.v. administration of a vascular endothelial growth factor receptor tyrosine kinase inhibitor. These results suggest that vascular endothelial growth factor receptor at the early period of reperfusion may contribute to neurogenesis rather than to angiogenesis in the hippocampal dentate gyrus.
Assuntos
Proliferação de Células/efeitos dos fármacos , Giro Denteado/patologia , Inibidores Enzimáticos/farmacologia , Ataque Isquêmico Transitório , Neurônios/efeitos dos fármacos , Quinazolinas/farmacologia , Animais , Antígenos de Superfície/metabolismo , Bromodesoxiuridina/metabolismo , Giro Denteado/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica/métodos , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/fisiopatologia , Masculino , Glicoproteínas de Membrana/metabolismo , Fosfopiruvato Hidratase/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reperfusão/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: Superficial zone protein (SZP) has been shown to function in the boundary lubrication of articular cartilages of the extremities. However, the expression of SZP has not been clarified in mandibular cartilage which is a tissue that includes a thick fibrous layer on the surface. This study was conducted to clarify the distribution of SZP on the mandibular condyle and the regulatory effects of humoral factors on the expression in both explants and fibroblasts derived from mandibular condyle. METHODS: The distribution of SZP was determined in bovine mandibular condyle cartilage, and the effects of interleukin-1beta (IL-1beta) and transforming growth factor-beta (TGF-beta) on SZP expression were examined in condyle explants and fibroblasts derived from the fibrous zone of condyle cartilage. RESULTS: SZP was highly distributed in the superficial zone of intact condyle cartilage. The SZP expression was up-regulated by TGF-beta in both explants and cultured fibroblasts, whereas the expression was slightly down-regulated by IL-1beta. A significant increase in accumulation of SZP protein was also observed in the culture medium of the fibroblasts treated with TGF-beta. CONCLUSIONS: These results suggest that SZP plays an important role in boundary lubrication of mandible condylar cartilage, is synthesized locally within the condyle itself, and exhibits differential regulation by cell mediators relevant to mandibular condyle repairing and pathologies.
Assuntos
Cartilagem Articular/metabolismo , Côndilo Mandibular , Proteoglicanas/análise , Animais , Bovinos , Ensaio de Imunoadsorção Enzimática/métodos , Imuno-Histoquímica/métodos , Interleucina-1beta/farmacologia , Masculino , Proteoglicanas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Articulação Temporomandibular , Fator de Crescimento Transformador beta/farmacologiaRESUMO
BACKGROUND: Transanal intersphincteric resection (ISR) was introduced and has been increasingly performed as an ultimate surgical treatment for extremely low rectal cancer. We considered that high quality and less invasive surgery could be achieved if ISR and laparoscopic surgery were combined. METHODS: Between December 2003 and June 2004, we performed laparoscope-assisted ISR for two patients with very low rectal cancer and total colectomy for two patients with ulcerative colitis complicated by colorectal cancer. In all patients, the transanal procedure was preceded by trans-abdominal laparoscopic rectal excision. RESULTS: Preceding transanal dissection facilitated muscle layer-oriented curative dissection, and more importantly, made subsequent laparoscopic rectal excision effortless as a result of penetrating to the dissected pelvic cavity. All patients showed favorable recovery including postoperative anal function with no complication or recurrent disease. CONCLUSIONS: This procedure is feasible and has favorable short-term results for radical treatment of very low rectal disease, while preserving anal function.
Assuntos
Canal Anal/cirurgia , Proctoscopia , Neoplasias Retais/cirurgia , Canal Anal/fisiopatologia , Anastomose Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Neoplasias Retais/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Metastasis to regional lymph nodes (LNs) through lymphatic vessels is common in cancer progression and is an important prognostic factor in many cancers. Recent evidence suggests that tumour lymphangiogenesis promotes lymphatic metastasis. AIMS: To study the role of lymph vessel density (LVD) in gastric cancer and investigate whether LVD is associated with LN metastasis/prognosis. METHODS: Lymphatics of 117 primary human gastric cancer cases were investigated by quantitative immunohistochemical staining for podoplanin. The relation between LVD and LN metastasis and other established clinicopathological parameters was analysed. The relation between LVD and prognosis was also studied. RESULTS: Mean LVD of "hot spots" was 11.6/case. LVD significantly correlated with LN and podoplanin positive lymphatic invasion. High LVD was associated with worse overall survival. In multivariate analysis, positive LVD was a significant independent predictor of overall survival, depth of invasion, and TNM stage. LVD significantly correlated with LN metastasis at surgery and podoplanin positive lymphatic invasion. In multivariate analysis, positive LVD was an independent significant predictor of LN metastasis. CONCLUSIONS: Increased podoplanin expression is significantly associated with LN metastasis, and may play an important role in detecting LN metastasis in gastric cancer. Furthermore, LVD may be a significant prognostic factor in gastric cancer at any stage. In addition, LVD and lymph vessel invasion detected by podoplanin immunohistochemistry are associated with LN metastasis in T1 early gastric cancer. LVD assessment by podoplanin immunohistochemistry may become a useful predictor of LN metastasis in T1 early gastric cancer and may influence the decision making process for additional surgery.
Assuntos
Linfangiogênese , Vasos Linfáticos/patologia , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Metástase Linfática , Vasos Linfáticos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Estadiamento de Neoplasias , Prognóstico , Neoplasias Gástricas/metabolismo , Análise de SobrevidaRESUMO
Low-molecular-weight hyaluronan (LMW-HA) is often increased in osteoarthritic joints; however, its biological function in cartilage has not been clarified. We hypothesize that LMW-HA causes the catabolic activation of chondrocytes through its interaction with CD44. Cartilage explants and chondrocytes, derived from bovine temporomandibular joints (TMJ), were examined for matrix loss and the expression of matrix metalloproteinase-3 (MMP-3) following treatment with hyaluronan oligosaccharides (HA(oligos)). Hyaluronan and CD44 were uniformly distributed throughout the fibrous and cartilaginous zones of the TMJ condyle. Treatment of cartilage explants with HA(oligos) resulted in cartilage matrix loss with increased secreted caseinolytic activity. HA(oligos) treatment of TMJ chondrocytes resulted in enhanced MMP-3 expression, whereas wash-out of the HA(oligos) in the middle of the experimental period reduced this induction. These results suggest that HA(oligos) activate chondrocytes, resulting in a substantial enhancement of proteinase expression, and the removal of HA(oligos) by wash-out reverses this catabolic activation.
Assuntos
Condrócitos/enzimologia , Ácido Hialurônico/fisiologia , Metaloproteinase 3 da Matriz/biossíntese , Oligossacarídeos/fisiologia , Articulação Temporomandibular/citologia , Animais , Cartilagem Articular/citologia , Cartilagem Articular/enzimologia , Caseínas/análise , Caseínas/metabolismo , Bovinos , Células Cultivadas , Condrócitos/citologia , Indução Enzimática , Receptores de Hialuronatos/análise , Receptores de Hialuronatos/fisiologia , Masculino , Côndilo Mandibular/citologia , Côndilo Mandibular/enzimologia , Metaloproteinase 3 da Matriz/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Articulação Temporomandibular/enzimologiaRESUMO
Hyaluronan (HA) is one of the major extracellular matrix components in cartilage. In addition to the biomechanical functions, HA has various important roles in the differentiation of chondrocytes. The purpose of this study was to clarify the nature of HA synthesis during chondrocyte differentiation. Growth plate chondrocytes were isolated from rabbit ribs and cultured in chondrocyte differentiation medium. The amount of HA and HA synthase (HAS) mRNA levels were analyzed for each stage of chondrocyte differentiation by means of high-performance liquid chromatography (HPLC) and real-time PCR, respectively. The distribution of HA in cultured chondrocytes was observed by histochemical staining. The amount of HA, ranging widely in size, was increased substantially during the hypertrophic stage. The expression levels of HAS2 and HAS3 mRNAs were low during the matrix-forming stage. HAS2 mRNA level was substantially enhanced at the pre-hypertrophic stage, whereas HAS3 mRNA level exhibited a slight increase. HAS1 mRNA was not detected. The intensity of HA staining was high around the hypertrophic chondrocytes. These results suggest that HA metabolism in chondrocyte differentiation is regulated by the selective expression of HASs, and HAS2 and the related large size-HA may have a certain association with the hypertrophic changes of chondrocytes.
Assuntos
Condrócitos/metabolismo , Lâmina de Crescimento/citologia , Ácido Hialurônico/metabolismo , Animais , Diferenciação Celular , Proliferação de Células , Condrócitos/citologia , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Colágeno Tipo II/metabolismo , Colágeno Tipo X/metabolismo , Matriz Extracelular/metabolismo , Glucuronosiltransferase/metabolismo , Hialuronan Sintases , Imuno-Histoquímica , RNA Mensageiro/metabolismo , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
AIM: To evaluate the efficacy of topical aldose reductase inhibitor CT-112 (5-[3-ethoxy-4-pentyloxyphenyl]-2,4-thiazolidinedione) on corneal epithelial barrier function in diabetic patients. METHODS: This was a prospective, randomised, double masked placebo controlled study. 34 eyes of 34 diabetic patients were randomly assigned treatment with 0.25% eye drops of CT-112 (n = 22) or a placebo (n = 12) four times a day for 8 weeks. Corneal fluorescein staining and corneal sensation were examined before treatment as well as 4 and 8 weeks after administration. Corneal epithelial permeability to fluorescence was measured with an anterior fluorophotometer. RESULTS: Average scores of superficial punctate keratopathy and corneal sensitivity did not differ significantly between the two groups at any time. Whereas average fluorescein concentrations did not differ significantly for the CT-112 and placebo groups before treatment, they did differ significantly 4 and 8 weeks after treatment (4 weeks, p = 0.0327; 8 weeks, p = 0.0143). CONCLUSION: The topical aldose reductase inhibitor, CT-112 improves the corneal epithelial barrier function in diabetic patients.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Úlcera da Córnea/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Tiazolidinedionas/administração & dosagem , Idoso , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/etiologia , Método Duplo-Cego , Epitélio Corneano/metabolismo , Epitélio Corneano/fisiopatologia , Fluoresceína , Fluorofotometria , Humanos , Pessoa de Meia-Idade , Soluções Oftálmicas , Permeabilidade , Estudos Prospectivos , Limiar Sensorial , Estatísticas não Paramétricas , Tiazolidinedionas/uso terapêutico , Fatores de TempoRESUMO
The association between mechanical stimulation and chondrocyte homeostasis has been reported. However, the participation of PTHrP (parathyroid-hormone-related protein) in the mechano-regulation of chondrocyte metabolism remains unclear. We determined whether mechanical stimulation of chondrocytes induces the expression of PTHrP and, further, whether the mechano-modulation of PTHrP is dependent on the maturational status of chondrocytes. Cyclic mechanical strain was applied to rat growth plate chondrocytes at the proliferating, matrix-forming, and hypertrophic stages at 30 cycles/min. Cyclic mechanical strain significantly increased PTHrP mRNA levels in chondrocytes at the proliferating and matrix-forming stages only. The induction of PTHrP was dependent on loading magnitude at the proliferating stage. Using specific ion channel blockers, we determined that mechano-induction of PTHrP was inhibited by nifedipine, a Ca2+ channel blocker. These results suggest that mechanical induction of PTHrP possibly provides the environment for greater chondrocyte replication and matrix formation that would subsequently affect cartilage formation.
Assuntos
Canais de Cálcio/metabolismo , Condrócitos/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/biossíntese , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Sinalização do Cálcio , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Proteínas da Matriz Extracelular/biossíntese , Lâmina de Crescimento/citologia , Masculino , Nifedipino/farmacologia , Estimulação Física , Reação em Cadeia da Polimerase , RNA Mensageiro/biossíntese , Ratos , Ratos Wistar , Estresse MecânicoRESUMO
The work describes the uptake, retention/biological elimination and organ/tissue distribution of 137Cs by freshwater Japanese catfish (Silurus asotus Linnaeus) under laboratory conditions. The fish were divided into three groups based on their size and age and reared in 137Cs-spiked water. The concentration of 137Cs in the whole body of the live fish was measured at regular intervals up to 60 days. A significant accumulation of 137Cs was found, but a steady state condition was not achieved by the end of the experiment. The bioaccumulation factors at steady state and the required time to reach steady state were estimated to be 1.55 and 255 days, 1.76 and 180 days and 1.99 and 160 days for large, medium and small size fish, respectively. To determine the effective half-life of 137Cs, the fish were transferred and reared in the non-contaminated host water. The concentration of the remaining 137Cs in the whole body of the live fish was measured up to 66 days. The average effective half-life of 137Cs in the fish species was found to be approximately 142 days for fish of all sizes. The distribution of 137Cs in different organs/tissues of the fish was determined. Accumulation of 137Cs in muscle/flesh of the fish was found to be approximately 75% of whole body accumulation. The uptake rate and the retention capability of juvenile fish were found to be higher and therefore, these were more susceptible to 137Cs than adult and old fish, and could be an important source of 137Cs in the human food chain.