Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
Pathol Res Pract ; 216(9): 153071, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32825944

RESUMO

INTRODUCTION: Malignant melanomas (MM) are often connected with the expression of PD-L1 protein and the presence of tumor-infiltrating lymphocytes (TILs), however, their impact on prognosis remains controversial. Due to their supposed clinical significance and lack of convincing data, we decided to establish the relationships between CD8 + TIL count, PD-L1 level and certain clinical and histopathological parameters in patients with malignant melanoma, especially those associated with unfavorable prognosis. MATERIALS AND METHODS: We performed immunohistochemistry for PD-L1 and CD8 on 56 formalin-fixed paraffin-embedded specimens from patients with cutaneous and metastatic malignant melanomas. PD-L1 expression levels were determined by immunohistochemistry (clone 28-8) and subsequently the tumor proportion scores (TPS) were evaluated. CD8 + TIL expressions were classified as either grade 0, 1+, 2+ or 3+, based on the density and distribution of the infiltrating lymphocytes. RESULTS: The PD-L1 expression was detected in 20 out of 56 cases (35,71 %). The expression of PD-L1 on tumor cells was significantly increased with higher TILs infiltration in the tumor microenvironment (p = 0,038). Lower TIL score corresponds with poor prognostic clinicopathological parameters such as higher number of mitotic figures (p = 0,005), Clark's level (p = 0,007) and Breslow's depth (p = 0,010). CONCLUSIONS: Our results suggest a favorable prognostic value for CD8 + TIL infiltration. Moreover, TIL density was strongly correlated and geographically associated to PD-L1 expression. This analysis provides more insight into the role of TIL count and PD-L1 level in MM and their relationship with each other and association with other prognostic indicators.


Assuntos
Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos do Interstício Tumoral/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/imunologia , Linfócitos T CD8-Positivos/microbiologia , Feminino , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Melanoma/metabolismo , Pessoa de Meia-Idade , Microambiente Tumoral/imunologia , Melanoma Maligno Cutâneo
2.
Physiol Res ; 69(3): 389-404, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32469226

RESUMO

Experimental studies in animals provide relevant knowledge about pathogenesis of radiation-induced injury to the central nervous system. Radiation-induced injury can alter neuronal, glial cell population, brain vasculature and may lead to molecular, cellular and functional consequences. Regarding to its fundamental role in the formation of new memories, spatial navigation and adult neurogenesis, the majority of studies have focused on the hippocampus. Most recent findings in cranial radiotherapy revealed that hippocampal avoidance prevents radiation-induced cognitive impairment of patients with brain primary tumors and metastases. However, numerous preclinical studies have shown that this problem is more complex. Regarding the fact, that the radiation-induced cognitive impairment reflects hippocampal and non-hippocampal compartments, it is highly important to investigate molecular, cellular and functional changes in different brain regions and their integration at clinically relevant doses and schedules. Here, we provide a literature review in order support the translation of preclinical findings to clinical practice and improve the physical and mental status of patients with brain tumors.


Assuntos
Encefalopatias/etiologia , Sistema Nervoso Central/efeitos da radiação , Transtornos Cognitivos/etiologia , Lesões por Radiação/etiologia , Animais , Encefalopatias/patologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Sistema Nervoso Central/patologia , Transtornos Cognitivos/patologia , Humanos , Segunda Neoplasia Primária/etiologia , Segunda Neoplasia Primária/patologia , Lesões por Radiação/patologia , Radiação Ionizante
3.
Physiol Res ; 69(Suppl 3): S421-S432, 2020 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-33471542

RESUMO

Acute respiratory distress syndrome (ARDS) is characterized by diffuse lung damage, inflammation, oedema formation, and surfactant dysfunction leading to hypoxemia. Severe ARDS can accelerate the injury of other organs, worsening the patient´s status. There is an evidence that the lung tissue injury affects the right heart function causing cor pulmonale. However, heart tissue changes associated with ARDS are still poorly known. Therefore, this study evaluated oxidative and inflammatory modifications of the heart tissue in two experimental models of ARDS induced in New Zealand rabbits by intratracheal instillation of neonatal meconium (100 mg/kg) or by repetitive lung lavages with saline (30 ml/kg). Since induction of the respiratory insufficiency, all animals were oxygen-ventilated for next 5 h. Total and differential counts of leukocytes were measured in the arterial blood, markers of myocardial injury [(troponin, creatine kinase - myocardial band (CK-MB), lactate dehydrogenase (LD)] in the plasma, and markers of inflammation [tumour necrosis factor (TNF)alpha, interleukin (IL)-6], cardiovascular risk [galectin-3 (Gal-3)], oxidative changes [thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine (3NT)], and vascular damage [receptor for advanced glycation end products (RAGE)] in the heart tissue. Apoptosis of heart cells was investigated immunohistochemically. In both ARDS models, counts of total leukocytes and neutrophils in the blood, markers of myocardial injury, inflammation, oxidative and vascular damage in the plasma and heart tissue, and heart cell apoptosis increased compared to controls. This study indicates that changes associated with ARDS may contribute to early heart damage what can potentially deteriorate the cardiac function and contribute to its failure.


Assuntos
Traumatismos Cardíacos/patologia , Inflamação/patologia , Lesão Pulmonar/patologia , Síndrome do Desconforto Respiratório/patologia , Animais , Apoptose/fisiologia , Biomarcadores/metabolismo , Modelos Animais de Doenças , Feminino , Traumatismos Cardíacos/metabolismo , Inflamação/metabolismo , Lesão Pulmonar/metabolismo , Masculino , Síndrome de Aspiração de Mecônio/metabolismo , Síndrome de Aspiração de Mecônio/patologia , Estresse Oxidativo/fisiologia , Coelhos , Síndrome do Desconforto Respiratório/metabolismo
4.
Physiol Res ; 68(Suppl 3): S265-S273, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31928044

RESUMO

Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia, neutrophil-mediated inflammation, and lung edema formation. Whereas lung damage might be alleviated by nitric oxide (NO), goal of this study was to evaluate if intratracheal NO donor S-nitroso-N-acetylpenicillamine (SNAP) can positively influence the lung functions in experimental model of ARDS. New Zealand rabbits with respiratory failure induced by saline lavage (30 ml/kg, 9+/-3 times) were divided into: ARDS group without therapy, ARDS group treated with SNAP (7 mg/kg i.t.), and healthy Control group. During 5 h of ventilation, respiratory parameters (blood gases, ventilatory pressures) were estimated. After anesthetics overdosing, left lung was saline-lavaged and cell count, cell viability and protein content in bronchoalveolar lavage fluid (BALF) were measured. Right lung tissue was used for estimation of wet/dry weight ratio, concentration of NO metabolites, and histomorphological investigation. Repetitive lung lavage induced lung injury, worsened gas exchange, and damaged alveolar-capillary membrane. Administration of SNAP reduced cell count in BALF, lung edema formation, NO metabolites, and histopathological signs of injury, and improved respiratory parameters. Treatment with intratracheal SNAP alleviated lung injury and edema and improved lung functions in a saline-lavaged model of ARDS suggesting a potential of NO donors also for patients with ARDS.


Assuntos
Pulmão/efeitos dos fármacos , Doadores de Óxido Nítrico/uso terapêutico , Síndrome do Desconforto Respiratório/tratamento farmacológico , S-Nitroso-N-Acetilpenicilamina/uso terapêutico , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Pulmão/metabolismo , Pulmão/patologia , Masculino , Nitratos/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitritos/metabolismo , Coelhos , Síndrome do Desconforto Respiratório/patologia , S-Nitroso-N-Acetilpenicilamina/farmacologia
5.
Physiol Res ; 67(Suppl 4): S645-S654, 2018 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-30607971

RESUMO

Damage of alveolar-capillary barrier, inflammation, oxidative injury, and lung cell apoptosis represent the key features of acute lung injury (ALI). This study evaluated if selective phosphodiesterase (PDE)-4 inhibitor roflumilast can reduce the mentioned changes in lavage-induced model of ALI. Rabbits with ALI were divided into 2 groups: ALI without therapy (A group) and ALI treated with roflumilast i.v. (1 mg/kg; A+R group). One group of healthy animals without ALI served as ventilated controls (C group). All animals were oxygen-ventilated for further 4 h. At the end of experiment, total and differential counts of cells in bronchoalveolar lavage fluid (BALF) and total and differential counts of white blood cells were estimated. Lung edema formation was assessed from determination of protein content in BALF. Pro-inflammatory cytokines (TNFalpha, IL-6 and IL-8) and markers of oxidation (3-nitrotyrosine, thiobarbituric-acid reactive substances) were detected in the lung tissue and plasma. Apoptosis of lung cells was investigated immunohistochemically. Treatment with roflumilast reduced leak of cells, particularly of neutrophils, into the lung, decreased concentrations of cytokines and oxidative products in the lung and plasma, and reduced lung cell apoptosis and edema formation. Concluding, PDE4 inhibitor roflumilast showed potent anti-inflammatory actions in this model of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Aminopiridinas/uso terapêutico , Apoptose/efeitos dos fármacos , Benzamidas/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Fosfodiesterase 4/uso terapêutico , Pneumonia/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Aminopiridinas/farmacologia , Animais , Apoptose/fisiologia , Benzamidas/farmacologia , Líquido da Lavagem Broncoalveolar , Ciclopropanos/farmacologia , Ciclopropanos/uso terapêutico , Modelos Animais de Doenças , Feminino , Masculino , Estresse Oxidativo/fisiologia , Inibidores da Fosfodiesterase 4/farmacologia , Pneumonia/metabolismo , Coelhos
6.
J Physiol Pharmacol ; 69(5)2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30683832

RESUMO

Acute lung injury (ALI) is associated with deterioration of alveolar-capillary lining and transmigration and activation of inflammatory cells. Sildenafil, phosphodiesterase 5 (PDE5) inhibitor, inhibits degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. Positive effects of sildenafil treatment result from influencing proliferation of regulatory T cells and production of proinflammatory cytokines and autoantibodies as well as from modulation of platelet activation, angiogenesis, and pulmonary vasoreactivity. This study evaluated if intravenous sildenafil can influence inflammation, edema formation, apoptosis, and respiratory parameters in rabbits with a model of ALI induced by repetitive lung lavage by saline (30 ml/kg). animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with sildenafil intravenously (1 mg/kg; ALI + Sil), and healthy ventilated controls (Control) which were oxygen-ventilated for 4 hours following treatment administration. during this period, respiratory parameters (ventilator pressures, lung compliance, blood gases, oxygenation indexes etc.) were regularly measured. at the end of experiment, animals were overdosed by anesthetics. The left lung was saline-lavaged and total and differential cell counts and protein content in the bronchoalveolar lavage fluid (BAL) were estimated. The right lung was used for determination of lung edema formation expressed as wet/dry lung weight ratio, for detection of inflammation and oxidative stress markers by ELISA methods, and for detection of lung epithelial cells apoptosis by TUNEL methods and level of caspase-3. Sildenafil treatment reduced leak of cells (P < 0.05), particularly of neutrophils (P < 0.001) into the lung, release of pro-inflammatory mediators (TNF-α, P < 0.001; IL-8 and IL-6, P < 0.01), level of nitrite/nitrate (P < 0.001), markers of oxidative damage (3-nitrotyrosine and malondialdehyde, both P < 0.01), lung edema formation (P < 0.01), protein content in BAL (P < 0.001), and apoptosis of epithelial cells (P < 0.01), and improved respiratory parameters. Concluding, the results indicate a future potential of PDE5 inhibitors also for the therapy of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/uso terapêutico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/fisiopatologia , Animais , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Lavagem Broncoalveolar , Citocinas/imunologia , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Nitratos/imunologia , Nitritos/imunologia , Inibidores da Fosfodiesterase 5/farmacologia , Ventilação Pulmonar/efeitos dos fármacos , Coelhos , Solução Salina , Citrato de Sildenafila/farmacologia
7.
Physiol Res ; 65(Suppl 5): S663-S672, 2016 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-28006948

RESUMO

Acute lung injury (ALI) is characterized by diffuse alveolar damage, inflammation, and transmigration and activation of inflammatory cells. This study evaluated if intravenous dexamethasone can influence lung inflammation and apoptosis in lavage-induced ALI. ALI was induced in rabbits by repetitive saline lung lavage (30 ml/kg, 9+/-3-times). Animals were divided into 3 groups: ALI without therapy (ALI), ALI treated with dexamethasone i.v. (0.5 mg/kg, Dexamed; ALI+DEX), and healthy non-ventilated controls (Control). After following 5 h of ventilation, ALI animals were overdosed by anesthetics. Total and differential counts of cells in bronchoalveolar lavage fluid (BAL) were estimated. Lung edema was expressed as wet/dry weight ratio. Concentrations of IL-1beta, IL-8, esRAGE, S1PR3 in the lung were analyzed by ELISA methods. In right lung, apoptotic cells were evaluated by TUNEL assay and caspase-3 immunohistochemically. Dexamethasone showed a trend to improve lung functions and histopathological changes, reduced leak of neutrophils (P<0.001) into the lung, decreased concentrations of pro-inflammatory IL-1beta (P<0.05) and marker of lung injury esRAGE (P<0.05), lung edema formation (P<0.05), and lung apoptotic index (P<0.01), but increased immunoreactivity of caspase-3 in the lung (P<0.001). Considering the action of dexamethasone on respiratory parameters and lung injury, the results indicate potential of this therapy in ALI.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Dexametasona/administração & dosagem , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/administração & dosagem , Apoptose/fisiologia , Mediadores da Inflamação/antagonistas & inibidores , Infusões Intravenosas , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Coelhos
8.
Pathol Res Pract ; 212(8): 667-71, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27083240

RESUMO

The World Health Organization (WHO) defines PEComas as mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular cells. Uterus is the most common site of a subgroup of PEComas not otherwise specified(NOS). PEComas of the uterine cervix are extremely rare, and only thirteen cases have been described in the English literature to date. In this review, we summarize the available data concerning diagnostics, immunohistochemical analysis, genetics and treatment of cervical PEComas. Radical hysterectomy with bilateral salpingooophorectomy is the best surgical approach available. Adjuvant therapy in its present form is not efficient. Therefore, further studies are needed to evaluate the newest treatment strategies.


Assuntos
Colo do Útero/patologia , Neoplasias de Células Epitelioides Perivasculares/patologia , Neoplasias do Colo do Útero/patologia , Biomarcadores Tumorais/metabolismo , Colo do Útero/metabolismo , Colo do Útero/cirurgia , Feminino , Humanos , Histerectomia , Ovariectomia , Neoplasias de Células Epitelioides Perivasculares/metabolismo , Neoplasias de Células Epitelioides Perivasculares/cirurgia , Prognóstico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/cirurgia
9.
J Physiol Pharmacol ; 67(6): 919-932, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28195073

RESUMO

Diffuse alveolar injury, edema, and inflammation are fundamental signs of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Whereas the systemic administration of corticosteroids previously led to controversial results, this study evaluated if corticosteroids given intratracheally may improve lung functions and reduce edema formation, migration of cells into the lung and their activation in experimentally-induced ALI. In oxygen-ventilated rabbits, ALI was induced by repetitive saline lung lavage, until PaO2 decreased to < 26.7 kPa in FiO2 1.0. Then, one group of animals was treated with corticosteroid budesonide (Pulmicort susp inh, AstraZeneca; 0.25 mg/kg) given intratracheally by means of inpulsion regime of high-frequency jet ventilation, while another group was non-treated, and both groups were oxygen-ventilated for following 5 hours. Another group of animals served as healthy controls. After sacrifice of animals, left lung was saline-lavaged and protein content was measured and cells in the lavage fluid were determined microscopically. Right lung tissue was used for estimation of edema formation (expressed as wet/dry weight ratio), for histomorphological investigation, immunohistochemical determination of apoptosis of lung cells, and for determination of markers of inflammation and lung injury (IL-1ß, IL-6, IL-8, TNF-α, IFNγ, esRAGE, caspase-3) by ELISA methods. Levels of several cytokines were estimated also in plasma. Repetitive lung lavage worsened gas exchange, induced lung injury, inflammation and lung edema and increased apoptosis of lung epithelial cells. Budesonide reduced lung edema, cell infiltration into the lung and apoptosis of epithelial cells and decreased concentrations of proinflammatory markers in the lung and blood. These changes resulted in improved ventilation. Concluding, curative intratracheal treatment with budesonide alleviated lung injury, inflammation, apoptosis of lung epithelial cells and lung edema and improved lung functions in a lavage model of ALI. These findings suggest a potential of therapy with inhaled budesonide also for patients with ARDS.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Apoptose/efeitos dos fármacos , Budesonida/farmacologia , Inflamação/tratamento farmacológico , Pulmão/efeitos dos fármacos , Lesão Pulmonar Aguda/metabolismo , Corticosteroides/farmacologia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Caspase 3/metabolismo , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxigênio/metabolismo , Coelhos , Fator de Necrose Tumoral alfa/metabolismo , Ventilação/métodos
10.
Clin Otolaryngol ; 41(3): 249-58, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26220138

RESUMO

BACKGROUND: Surfactant proteins (SP) A and D play a critical role in the innate defence of respiratory mucosa. Although numerous studies have focused on the importance of surfactant in the lower airways, relatively little is known about its role in the upper respiratory system. METHODS: The prospective study was conducted with 61 subjects divided into patients with chronic rhinosinusitis with nasal polyps (CRSwNP), with chronic rhinosinusitis without nasal polyps (CRSsNP) and healthy controls. SP-A and SP-D were detected in nasal lavage fluid (NALF) by ELISA and in nasal mucosa by immunohistochemical staining. Severity of the diseases assessed by preoperative CT score, presence of comorbidity (allergy and bronchial asthma) and bacterial culture from the middle nasal meatus was evaluated. RESULTS: In nasal mucosa, SPs were localised in ciliated cells of the surface epithelium and serous acini of the submucosal glands. Stronger expression of SPs in submucosal glands was observed in CRSwNP and CRSsNP groups in comparison with controls. In patients with CRSsNP and more severe form of the disease, higher levels of SP-A and SP-D in NALF and stronger immunoreactivity of these proteins in nasal mucosa were detected. Identification of pathogenic bacteria was associated with higher levels of SP-A and SP-D in NALF and nasal mucosa in patients with CRSsNP and control group. Presence of allergy was associated with stronger expression of SP-A in submucosal glands in all CRS patients and with decreased levels of both SPs in NALF in CRSsNP patients. CONCLUSIONS: Surfactant proteins A and D play an important role in innate host defence of upper respiratory tract. Different expression of these proteins in patients with chronic rhinosinusitis indicates possible novel target of therapy in these patients.


Assuntos
Pólipos Nasais/metabolismo , Proteína A Associada a Surfactante Pulmonar/metabolismo , Proteína D Associada a Surfactante Pulmonar/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Biomarcadores/metabolismo , Doença Crônica , Comorbidade , Endoscopia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal , Pólipos Nasais/complicações , Pólipos Nasais/microbiologia , Pólipos Nasais/terapia , Estudos Prospectivos , Rinite/complicações , Rinite/microbiologia , Rinite/terapia , Índice de Gravidade de Doença , Sinusite/complicações , Sinusite/microbiologia , Sinusite/terapia
11.
Clin Otolaryngol ; 40(5): 429-36, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25688693

RESUMO

OBJECTIVE: The study was designed to determine whether there is an association between the comorbidity as atopy, bronchial asthma, aspirin intolerance and eosinophil infiltration of the upper airways, severity of the sinonasal disease and rate of revision sinus surgery in patients with nasal polyps. MATERIAL AND METHODS: One hundred and fifty patients were enrolled in the prospective study. Differences in CT score, rate of revision surgery, concentration of eotaxin and eosinophil cationic protein in nasal lavage fluid (NALF) and distribution of eosinophils in NALF and nasal tissue in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), chronic rhinosinusitis without nasal polyps (CRSsNP) and control group were investigated. We focused on the relationship between presence of comorbidity (atopy, bronchial asthma and aspirin intolerance) and severity of the disease, the need of revision surgery and markers of eosinophil inflammation in upper airways in patients with CRSwNP. RESULTS: Patients with CRSwNP had more severe form of the sinonasal disease, higher rate of revision FESS and significant higher presence of markers of eosinophil inflammation in NALF and nasal tissue than patients with CRSsNP (P < 0.05). Atopic and non-atopic asthma as well as aspirin sensitivity significantly more often coexisted with CRSwNP. Comorbidity did not influence eosinophil infiltration or severity of the disease in patients with CRSwNP. CONCLUSION: Presence of comorbidity (atopy, bronchial asthma and aspirin intolerance) has no impact on severity of the disease or eosinophil content in the upper airways in patients with CRSwNP.


Assuntos
Asma/complicações , Eosinofilia/etiologia , Rinite/complicações , Sinusite/complicações , Adulto , Comorbidade , Eosinófilos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/imunologia , Mucosa Nasal/imunologia , Pólipos Nasais , Estudos Prospectivos , Rinite/imunologia , Sinusite/imunologia
12.
Neoplasma ; 62(1): 88-97, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25563371

RESUMO

UNLABELLED: The hypoxia-inducible protein carbonic anhydrase IX is widely expressed in most human cancers, including breast carcinomas. CA IX attracts significant interest due to its strong association with neoplasms and its absence from corresponding normal tissues, suggesting its potential to serve as a promising diagnostic biomarker. This protein comes into the limelight also as a valuable prognostic and predictive parameter. Immunohistochemically, we examined the expression of this protein in 84 cases of invasive breast carcinoma to determinate the association with clinico-morphological and biological parameters such as age of patients, grade, stage and size of primary tumor, lymph node metastasis, vascular invasion as well as hormone receptor status and HER-2 expression. In each case, the subcellular localization of CA IX antigen, the intensity of staining and the percentage of labeled cells were assessed. Overall, CA IX was expressed in 34 cases (40.5%). The statistical analysis revealed a significant correlation between subcellular localization of CA IX and the age of patients. Furthermore, significant correlations were also found between the grade, estrogen and progesterone status and all immunohistochemical characteristics of CA IX expression (the subcellular localization of CA IX antigen, the intensity of staining and the percentage of labeled cells). We point out that mostly membrane or combined membrane and cytoplasmic positivity together with a higher intensity of CA IX immunoreactivity are associated with poor prognostic parameters, such as tumor grade 3 and also with negative estrogen and progesterone receptor status which may influence therapeutic approach. However, no significant correlations were shown with remaining clinico-morphological and biological parameters. We next investigate the relationship between CA IX expression in the group of invasive ductal carcinomas and the group of invasive lobular carcinomas and other less frequent types of breast carcinoma. There was, however, no significant difference. Our results suggest that moderate to strong membrane and combined membrane and cytoplasmic localization of CA IX may represent a valuable tumor biomarker as well as a promising prognostic and predictive parameter in invasive breast cancer. KEYWORDS: breast carcinoma, carbonic anhydrase IX, immunohistochemistry, clinico-morphological and biological parameters.

13.
Adv Exp Med Biol ; 838: 35-45, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25315623

RESUMO

High-conductive calcium-sensitive potassium channels (BK+Ca) and ATP-sensitive potassium (K+ATP) channels play a significant role in the airway smooth muscle cell and goblet cell function, and cytokine production. The present study evaluated the therapeutic potential of BK+Ca and K+ATP openers, NS 1619 and pinacidil, respectively, in an experimental model of allergic inflammation. Airway allergic inflammation was induced with ovalbumine in guinea pigs during 21 days, which was followed by a 14-day treatment with BK+Ca and K+ATP openers. The outcome measures were airway smooth muscle cells reactivity in vivo and in vitro, cilia beating frequency and the level of exhaled NO (ENO), and the level of pro-inflammatory cytokines in the plasma and bronchoalveolar lavage fluid. The openers of both channels decreased airway smooth muscle cells reactivity, cilia beating frequency, and cytokine levels in the serum. Furthermore, NS1619 reduced ENO and inflammatory cells infiltration. The findings confirmed the presence of beneficial effects of BK+Ca and K+ATP openers on airway defence mechanisms. Although both openers dampened pro-inflammatory cytokines and mast cells infiltration, an evident anti-inflammatory effect was provided only by NS1619. Therefore, we conclude that particularly BK+Ca channels represent a promising new drug target in treatment of airway's allergic inflammation.


Assuntos
Resistência das Vias Respiratórias/efeitos dos fármacos , Benzimidazóis/farmacologia , Hiper-Reatividade Brônquica/tratamento farmacológico , Canais KATP/agonistas , Canais de Potássio Ativados por Cálcio de Condutância Alta/agonistas , Moduladores de Transporte de Membrana/farmacologia , Administração por Inalação , Animais , Hiper-Reatividade Brônquica/induzido quimicamente , Hiper-Reatividade Brônquica/metabolismo , Hiper-Reatividade Brônquica/fisiopatologia , Líquido da Lavagem Broncoalveolar/química , Cílios/efeitos dos fármacos , Citocinas/biossíntese , Citocinas/metabolismo , Expiração , Cobaias , Canais KATP/metabolismo , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/fisiopatologia , Masculino , Músculo Liso/efeitos dos fármacos , Óxido Nítrico/biossíntese , Ovalbumina , Pinacidil/farmacologia , Pletismografia Total , Técnicas de Cultura de Tecidos
14.
J Physiol Pharmacol ; 66(6): 887-97, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26769838

RESUMO

Epidemiological studies show positive relationship between mild-to-moderate hyperhomocysteinemia (hHcy) and the risk of cerebrovascular diseases. The study determines whether hyperhomocysteinemia (risk factor of brain ischemia) alone or in combination with the ischemic preconditioning (IPC) affects the ischemia-induced neurodegenerative changes and imbalance in MAPK/p-ERK1/2 and MAPK/p-p38 expression in the rat brains. hHcy was induced by subcutaneous administration of homocysteine (0.45 µmol/g body weight) twice a day at 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia and 2 days later, 15 min of global forebrain ischemia was induced by four vessel occlusion. We observed that hHcy alone significantly increased neurodegeneration by Fluoro-Jade C and TUNEL possitive cells in hippocampus as well as in cortex. We found elevated level of MAPK/p-ERK and decreased level of MAPK/p-p38 after pre-ischemic challenge by Western blot and fluorescent immunohistochemistry. In conclusion, preconditioning even if combined with hHcy could preserve the neuronal tissue from lethal ischemic effect. This study provides evidence for the interplay and tight integration between ERK and p38 MAPKs signalling mechanisms in response to the hHcy and also if in association with brain ischemia/IPC challenge in the rat brain.


Assuntos
Isquemia Encefálica/metabolismo , Hiper-Homocisteinemia/metabolismo , Precondicionamento Isquêmico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Animais , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Modelos Animais de Doenças , Homocisteína/sangue , Masculino , Ratos Wistar
15.
J Physiol Pharmacol ; 65(6): 767-76, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25554980

RESUMO

Global brain ischemia-reperfusion causes delayed cell death in hippocampal CA1 (cornus ammonis 1) pyramidal neurons after reperfusion. Ischemic tolerance evoked by preconditioning (IPC) represents a phenomenon of CNS adaptation to any subsequent ischemia. This paper was designed to describe changes in the mitogen-activated protein kinases (MAPK) protein pathways of the hippocampal area following by IPC. Ischemia was induced by a 4-vessels occlusion (4VO) and the rats were preconditioned by a non-injurious ischemia. Apoptotic markers were used to follow the degeneration process. Western blot and immunohistochemistry identified p-ERK (phosphorylated extracellular signal-regulated protein kinase) and p38 proteins in injured hippocampal areas. P-ERK quantification increased after IPC and reached the highest level at 24 hours after ischemia. Interestingly, neuroprotection induced by IPC lead to the opposite effect on MAPK/p38, where the level was lowest at 24 hours after ischemia. Taken together, the present study clearly demonstrates that p-ERK takes part in complex cascades triggered by IPC in the selectively vulnerable hippocampal region. In addition, paper describes a crosstalk between p-ERK and p-p38 which occurs after preconditioning maneuver in 4VO model of global ischemia.


Assuntos
Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/metabolismo , Precondicionamento Isquêmico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Traumatismo por Reperfusão/metabolismo , Animais , Isquemia Encefálica/patologia , Região CA1 Hipocampal/patologia , Masculino , Células Piramidais/metabolismo , Células Piramidais/patologia , Ratos Wistar , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle
16.
Klin Onkol ; 26(5): 331-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24107155

RESUMO

BACKGROUND: The aim of our study was to investigate radiationinduced shortterm effects on the rat forebrain. MATERIAL AND METHODS: Adult male Wistar rats received whole body exposure with fractionated doses of gamma rays (a total dose of 3 Gy) and were investigated seven and 14 days later. Immunohistochemistry and confocal microscopy were used to determine proliferating cells derived from anterior subventricular zone (SVZa) and distributed along the subventricular zone olfactory bulb axis (SVZ OB axis). Cell counting was performed in four anatomical parts along the welldefined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm. RESULTS: Different rate of cell overdistribution was found in all counted parts through the entire experiment, mostly detectable in the elbow and horizontal arm. CONCLUSION: Results suggested that radiation response of proliferating cells resides the SVZa may a play contributory role in the development of more adverse radiationinduced: late effects.


Assuntos
Proliferação de Células , Prosencéfalo/efeitos da radiação , Radiação Ionizante , Animais , Astrócitos/efeitos da radiação , Movimento Celular/efeitos da radiação , Modelos Animais de Doenças , Relação Dose-Resposta à Radiação , Raios gama , Humanos , Imuno-Histoquímica , Masculino , Prosencéfalo/citologia , Prosencéfalo/patologia , Ratos , Ratos Wistar , Irradiação Corporal Total
17.
Bratisl Lek Listy ; 114(8): 431-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23944616

RESUMO

From the archive of BB Biocyt company, 32 urinary bladder carcinomas (urothelium carcinomas, UC) and 7 cases of chronic cystitis were selected and examined in semiserial sections for the following antigens: 1) cell proliferation marker Ki-67 (expressed in the nuclei), 2) cell cycle regulator p16/INK4a polypeptide (expressed in the cytoplasm and nuclei), 3) urothelium marker p63 (expressed in the nuclei), 4) cytokeratin 7 (CK7). 5) cytokeratin 20 (CK20) and 6) high molecular weight cytokeratin (HMWCK). Invasive urothelium carcinomas showing a high grade dysplasia (invasive HG UC) comprised over the half (20 out of 32) of the investigated tumours. Microinvasion to lamina propria (seen in three HG papillary carcinomas) was regarded as an early infiltration even when the position of muscular layer could not be determined. Classical invasion across the urinary bladder wall and/or to surrounding tissues was found in 17 cases of low-differentiated HG UCs. The rest (9 out of 32 neoplasms) were either non-invasive papillary carcinomas of high (non-invasive HG UC, 5 cases) or low malignant potential (noninvasive LG UC, 4 cases). Finally, 3 cases were papillary urothelium neoplasms of low malignant potential (PUNLMP). HMWCK was present in all invasive tumours, whereas the frequency of other urothelium markers ranged from 65 to 88 %. Nevertheless, at least two markers were expressed in each invasive tumour. Staining for Ki-67 antigen was positive in over 50 % of the nuclei of HG UCs, while in the LG UCs, the frequency of positive Ki-67 staining did not exceed 25 %. In PUNLMP, the positive rate of Ki-67 stained dysplastic cells was below 10 %. The staining for p16 antigen did not correlate with the degree of dysplasia within urothelium tumours. For routine diagnostic, we recommend to combine the Ki-67 staining with detection of HMWCK. In cases of chronic cystitis, which developed urothelial hyperplasia and/or squamous metaplasia, the presence of p63 antigen was a relevant marker confirming the urothelial origin of the altered transitional cells (Tab. 6, Fig. 4, Ref. 69).


Assuntos
Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/patologia , Humanos , Imuno-Histoquímica
18.
Adv Exp Med Biol ; 756: 15-21, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22836614

RESUMO

Apoptosis is the fundamental process necessary for eliminating damaged or mutated cells. Alterations in the apoptotic pathway appear to be key events in cancer development and progression. Bcl-2 is the key member of the Bcl-2 family of apoptosis regulator proteins with anti-apoptotic effects. Survivin acts as an inhibitor of apoptosis as well and has been implicated in both inhibition of apoptosis and mitosis regulation. p53 is one of the tumor suppressor proteins, prevents tumor formation through cell cycle blocking and eliminates damaged cells via the activation of apoptosis. The Ki-67 protein is a cellular marker for proliferation. To investigate the possible interactions of the aforementioned proteins, we examined their expression in 76 patients with diagnosed lung cancer using immunohistochemical visualisation. Ki-67 protein was expressed in the cancer cells of all patients with small cell lung cancer (SCLC). We found a negative correlation between survivin and p53 expression. A decreased intensity of survivin expression and fewer cells positive for survivin (66.7%) in SCLC in comparison with other lung cancer types (98.0%) was detected. Reversely, expression of Bcl-2 was found in more than 90% of cases with SCLC. We hypothesize that high expression and intensity of Bcl-2 protein could be a factor behind a bad prognosis in SCLC.


Assuntos
Proteínas Inibidoras de Apoptose/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Humanos , Neoplasias Pulmonares/patologia , Prognóstico , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Survivina
19.
Adv Exp Med Biol ; 756: 39-48, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22836617

RESUMO

Calcium release-activated calcium channels (CRAC) play unambiguous role in secretory functions of mast cells, T cells, and eosinophils. Less knowledge exists about the role of CRAC, widely distributed in airway smooth muscle (ASM) cells, in airway contractility. The presented study seeks to determine the possible participation of CRAC in ASM-based inflammatory airway disorders in guinea pigs. The acute and long-term administration (14 days) of the CRAC antagonist 3-fluoropyridine-4-carboxylic acid was used to examine the ASM contractility and associated reflexes in the guinea pig model of allergic airway inflammation by the following methods: (i) evaluation of specific airway resistance in vivo; (ii) evaluation of the contractile response of isolated ASM strips in vitro; and (iii) citric acid-induced cough reflex; (iv) measurement of exhaled NO levels (E(NO)). Allergic airway inflammation was induced by repetitive exposure of guinea pigs to ovalbumin (10(-6) M). The CRAC antagonist administered in a single dose to guinea pigs with confirmed allergic inflammation significantly reduced the cough response and the airway resistance, which corresponded with the findings in vitro. Long-term application of the CRAC antagonist had more strongly expressed effects. The results confirm the role of CRAC in the pathophysiology of experimental animal asthma and have a potential meaning for anti-asthma therapy.


Assuntos
Asma/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Hipersensibilidade/tratamento farmacológico , Ácidos Isonicotínicos/farmacologia , Contração Muscular , Miócitos de Músculo Liso/fisiologia , Animais , Antiasmáticos/farmacologia , Cálcio/metabolismo , Tosse , Retículo Endoplasmático/metabolismo , Eosinófilos/metabolismo , Cobaias , Humanos , Masculino , Mastócitos/metabolismo , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Óxido Nítrico/análise , Ovalbumina/administração & dosagem , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/imunologia , Linfócitos T/metabolismo
20.
Klin Onkol ; 25(2): 110-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22533885

RESUMO

BACKGROUNDS: The aim of the present study was to investigate the effect of ionizing radiation on the cell population that co-forms hippocampal formation in an adult rat brain. MATERIALS AND METHODS: Adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Thirty, 60 and 90 days after irradiation the cell-specific types housed in the CA1, CA3 subregions and adjacent layers were labelled using immunohistochemistry for specific cell phenotypes; Ki-67 marker was used for proliferating cells and GFAP for detection of astrocytes. RESULTS: During the 30th day post-exposure, a considerable increase in the numbers of Ki-67-positive cells was seen. Moreover, significant decline in the density of neurons, mostly in the CA1 subregion, was observed on the 60th day. Slight overaccumulation of Ki-67-positive cells was seen in CA1 area 90 days after radiation treatment. Temporary decrease of GFAP-positive astrocytes was seen thirty days after irradiation, followed by their subsequent increase 60 days after exposure. Secondary decrease of GFAP-positive cells in both of regions was found in the group surviving 90 days post-irradiation. CONCLUSION: Results showed that radiation response of neurons and astrocytes that form the adult hippocampus may play contributory role in the development of prognostically unfavourable adverse radiation-induced late effect.


Assuntos
Hipocampo/efeitos da radiação , Animais , Astrócitos/patologia , Raios gama , Proteína Glial Fibrilar Ácida/análise , Hipocampo/metabolismo , Hipocampo/patologia , Imuno-Histoquímica , Antígeno Ki-67/análise , Masculino , Doses de Radiação , Ratos , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...