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AIMS: Allergic asthma is a chronic inflammatory lung disease characterized by a Th2-type immune response pattern. The development of nonspecific immunotherapy is one of the primary goals for the control of this disease. METHODS AND RESULTS: In this study, we evaluated the therapeutic effects of Lactococcus lactis-producing mycobacterial heat shock protein 65 (LLHsp65) in an ovalbumin (OVA)-induced allergic asthma model. OVA-challenged BALB/c mice were orally administrated with LLHsp65 for 10 consecutive days. The results demonstrate that LLhsp65 attenuates critical features of allergic inflammation, like airway hyperresponsiveness and mucus production. Likewise, the treatment decreases the pulmonary eosinophilia and the serum level of OVA-specific IgE. In addition to deviating immune responses towards Th1-cytokine profile, increase regulatory T cells, and cytokine levels, such as IL-6 and IL-10. CONCLUSIONS: Our results reveal that the mucosal immunotherapy of LLHsp65 significantly reduces the overall burden of airway allergic inflammation, suggesting a promising therapeutic strategy for allergic asthma treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This research reveals new perspectives on nonspecific immunotherapy based on the delivery of recombinant proteins by lactic acid bacteria to treat of allergic disorders.
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Asma/tratamiento farmacológico , Proteínas Bacterianas/farmacología , Chaperonina 60/farmacología , Inflamación/tratamiento farmacológico , Lactococcus lactis/inmunología , Administración Oral , Animales , Asma/inmunología , Líquido del Lavado Bronquioalveolar/citología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Hipersensibilidad/tratamiento farmacológico , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Inmunoterapia , Lactococcus lactis/metabolismo , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Linfocitos T Reguladores/inmunologíaRESUMEN
AIM: To correlate solitary dilated ducts (SDDs) detected by mammography with ultrasound and histopathological findings of intraductal lesions and evaluate the association with invasive or in situ breast carcinoma. The secondary goal was to evaluate the prevalence of SDDs in screening and diagnostic mammography. MATERIALS AND METHODS: This prospective study of consecutive screening and diagnostic mammograms from March 2016 to March 2017 at a referral centre for the diagnosis and treatment of breast cancer was registered at clinicatrials.gov (NCT03161392). SDDs were recorded prospectively on mammography, and regardless of the findings' stability, the participants were recalled for targeted ultrasound to evaluate the intraductal content, which was submitted to histopathological analysis when heterogeneous content or masses were found. SDD stability was evaluated for 2 years. The categorical data are shown as frequency and percentage, and the comparisons were conducted using the chi-squared test. RESULTS: A total of 9,035 mammograms were evaluated. SDDs were identified in 130 (1.43%) mammograms and 94 targeted ultrasound were conducted. In 22 cases, histological analysis were performed, and the main findings were fibrocystic changes (n = 14) and papilloma (n = 8). The main clinical and imaging characteristics associated with statistical significance (p < 0.05) were the presence of nipple discharge, intraductal masses, and calcifications on mammography. CONCLUSION: SDDs visualised using mammography and without other associated findings should be complemented with targeted ultrasound to evaluate the intraductal content that shows benign histopathological results when papilloma is the most relevant finding. No cases of invasive or in situ breast carcinoma were found in this study.
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Neoplasias de la Mama/diagnóstico por imagen , Carcinoma in Situ/diagnóstico por imagen , Carcinoma Ductal de Mama/diagnóstico por imagen , Mamografía , Ultrasonografía Mamaria , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/patología , Calcinosis/diagnóstico por imagen , Calcinosis/patología , Carcinoma in Situ/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The aim of this study was to evaluate the effects of oral creatine supplementation on the athletic performance of equines used for barrel racing. Ten healthy Quarter Horses, or Quarter Horse crossbred, weighing 429.7 ± 25.3 kg and with mean age of 3.8 ± 1.2 years, were used. Animals were evaluated in four different moments (M1, M2, M3, M4), and between M3 and M4, they were supplemented with 28 g of creatine/100 kg of body weight, orally, for 45 days. Although significant alterations for LDH activity, plasma glucose and packed cell volume were observed, it was possible to conclude that there was no improvement in the athletic performance for the animals used on the experiment, as there were no changes in time scores, heart rate and plasma lactate, variables considered as performance indicators, before and after supplementation.
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Creatina/farmacología , Caballos/fisiología , Condicionamiento Físico Animal/fisiología , Deportes , Administración Oral , Animales , Creatina/administración & dosificación , Femenino , MasculinoRESUMEN
AIM: The aim of this paper was to compare the dentin-pulp complex response to cavity preparation in human teeth using ultrasonic chemical vapor deposition (CVD) diamond tip and high-speed diamond bur. METHODS: Class V buccal cavities were randomly prepared in 40 premolars from 14 patients aged 11 to 15 years. The cutting time was recorded and the cavities had the axial walls protected with gutta-percha and were filled with glass ionomer cement. The teeth were extracted at intervals of 0, 5, 10 and 20 days, and were decalcified, sectioned and stained by Hematoxylin & Eosin, Masson's Trichrome and Brown & Brenn techniques. The inflammatory response and cell disorganization were blindly evaluated by two examiners. The remaining dentin thickness (RDT) was measured by a linear scale using computer software. Statistical analysis by one-way ANOVA showed no statistically significant difference (P≤0.05) among the cavities prepared with either type of instrument, with mean RDT of 1132.50 mm. Cutting time and the pulp-dentin complex responses were analyzed statistically by Kruskal-Wallis and Dunn tests (P≤0.05). RESULTS: The ultrasonic CVD diamond tip took 5 times longer to prepare the cavities and there were no typical inflammatory pulp responses in cavities prepared with either type of cutting instrument, only mild to moderate cell disorganization was present. CONCLUSION: Even taking longer to cut the dental substrate, the ultrasonic CVD diamond tip produced similar pulp response compared to the conventional high-speed diamond bur.
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Diente Premolar/ultraestructura , Preparación de la Cavidad Dental/efectos adversos , Equipo Dental de Alta Velocidad , Cavidad Pulpar/ultraestructura , Dentina/ultraestructura , Adolescente , Diente Premolar/cirugía , Niño , Preparación de la Cavidad Dental/instrumentación , Diamante , Cementos de Ionómero Vítreo , Gutapercha , Humanos , Inflamación/etiología , Odontometría , Método Simple Ciego , Coloración y Etiquetado , Factores de Tiempo , Extracción Dental , UltrasonidoRESUMEN
BACKGROUND AND PURPOSE: Spinal cord damage is a hallmark of hereditary spastic paraplegias, but it is still not clear whether specific subtypes of the disease have distinctive patterns of spinal cord gray (GM) and white (WM) matter involvement. We compared cervical cross-sectional GM and WM areas in patients with distinct hereditary spastic paraplegia subtypes. We also assessed whether these metrics correlated with clinical parameters. MATERIALS AND METHODS: We analyzed 37 patients (17 men; mean age, 47.3 [SD, 16.5] years) and 21 healthy controls (7 men; mean age, 42.3 [SD, 13.2] years). There were 7 patients with spastic paraplegia type 3A (SPG3A), 12 with SPG4, 10 with SPG7, and 8 with SPG11. Image acquisition was performed on a 3T MR imaging scanner, and T2*-weighted 2D images were assessed by the Spinal Cord Toolbox. Statistical analyses were performed in SPSS using nonparametric tests and false discovery rate-corrected P values < .05. RESULTS: The mean disease duration for the hereditary spastic paraplegia group was 22.4 [SD, 13.8] years and the mean Spastic Paraplegia Rating Scale score was 22.8 [SD, 11.0]. We failed to identify spinal cord atrophy in SPG3A and SPG7. In contrast, we found abnormalities in patients with SPG4 and SPG11. Both subtypes had spinal cord GM and WM atrophy. SPG4 showed a strong inverse correlation between GM area and disease duration (ρ = -0.903, P < .001). CONCLUSIONS: Cervical spinal cord atrophy is found in some but not all hereditary spastic paraplegia subtypes. Spinal cord damage in SPG4 and 11 involves both GM and WM.
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Sustancia Gris/patología , Paraplejía Espástica Hereditaria/patología , Médula Espinal/patología , Sustancia Blanca/patología , Adulto , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
In transplant centers, few topics are more controversial than communication between organ donor families (ODF) and recipients (RE). The Organ Procurement Organizations and transplant centers have felt obliged to protect the confidentiality and interests of ODF and RE. However, some authors have reported favorable effects of contact between ODF and RE. This study sought to investigate the current situation of the communication between ODF and RE from the viewpoint of transplanted patients (n = 50) and waiting transplant patients (n = 50) at a Brazilian University Hospital, ODF (n = 10), physicians from transplant centers (n = 50), as well as the opinion of the general population of a Brazilian city (n = 100). This work was developed as a survey whose questions related to the issue of communication between ODF and RE. The results showed that the majority of transplanted patients (82%) and patients awaiting transplant (60%) wanted to meet ODF to express their gratitude for receiving the organ. Likewise, ODF (67%) wanted to have a meeting with recipients, which allowed them to confirm the benefit of their donation. The general population was also favorable (66%) to ODF and RE communication. In contrast, the physicians (74%) were opposed to the ODF and RE contact. They affirmed that direct contact could lead to serious emotional conflicts or attempts of material involvement. One believes that decisions concerning the contact between ODF and RE would have to be determined by the involved parties. The transplant team could analyze the requests case by case, but ODF and RE must have the right to make the final decision.
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Familia , Relaciones Interpersonales , Trasplante de Riñón/psicología , Donantes de Tejidos/psicología , Adulto , Anciano , Comunicación , Femenino , Humanos , Renta , Masculino , Persona de Mediana Edad , Listas de EsperaRESUMEN
The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAP. Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5% among FAP and Child A patients (P < .05) and 16.6% for period B among 11.1% Child B patients and 5.5% FAP patients; 3.3% of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.
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Trasplante de Hígado/fisiología , Adolescente , Adulto , Anciano , Brasil , Hepatitis Viral Humana/cirugía , Hospitales Universitarios , Humanos , Cirrosis Hepática/cirugía , Hepatopatías/clasificación , Hepatopatías/cirugía , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
This study was directed towards investigating suitable compounds to be used as stable isotope reference materials for gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) calibration. Several compounds were selected from those used in the 'Grob-test' mixture. Oxygen- and nitrogen-containing substances were added to these compounds to allow the mixture to be used as a possible multi-isotopic calibration tool for 2H/1H, 13C/12C, 15N/14N and 18O/16O ratio determinations. In this paper we present the results of delta13C measurements performed by the consortium of the five laboratories taking part in this inter-calibration exercise. All the compounds were individually assessed for homogeneity, short-term stability and long-term stability by means of EA-IRMS, as required by the bureau communitaire de reference (BCR) Guide for Production of Certified Reference Materials. The results were compared then with the GC-C-IRMS measurements using both polar and non-polar columns, and the final mixture of selected compounds underwent a further certification exercise assessing limits of accuracy and reproducibility under specified GC-C-IRMS conditions.
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Isótopos de Carbono/química , Isótopos de Carbono/normas , Análisis de los Alimentos/normas , Cromatografía de Gases y Espectrometría de Masas/normas , Laboratorios/normas , Europa (Continente) , Valores de ReferenciaRESUMEN
OBJECTIVE: Shift workers have metabolic changes more often than day workers. It is also known that night workers prefer foods high in saturated fat. Such data suggest that shift workers are prone to cardiovascular disease. Therefore, the objective of this study was to propose an animal model to test the effect of high-fat diet (HFD) based on shift workers' diet. METHODS: This is an experimental study with 20 Wistar rats. Ten rats were allocated to the control group (CG) and were fed standard diet. Ten rats were allocated to the experimental group (EG) and were fed HFD (45% fat). Serum triglycerides (TG), glucose and high-density lipoprotein-cholesterol (HDL-cho) were measured 5, 10 and 15 weeks after the beginning of the study. The amount of visceral adipose tissue (VAT) was determined. Body weight was assessed weekly, and food and water intake were measured daily. Student's t-test was used for independent samples, and P<0.05 was considered significant. RESULTS: After 15 weeks of intervention, the EG showed increased serum levels of TG (P=0.001) and glucose (P<0.001) and decreased HDL-cho (P<0.001) when compared with the CG. The EG showed increased VAT (P=0.005) and liver weight (P=0.01). Food intake and water intake were higher in the CG (P<0.001 and P<0.001, respectively), whereas energy intake showed no difference (P=0.48). No difference was found in the weight of adrenal glands (P=0.07) and body weight (P=0.63). CONCLUSIONS: The experimental diet was effective to show changes in the serum levels of glucose, TG and HDL-cho and visceral fat in spite of no change in body weight in 15 weeks.
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Glucemia/análisis , Peso Corporal/fisiología , HDL-Colesterol/sangre , Dieta Alta en Grasa , Triglicéridos/sangre , Animales , Modelos Animales de Enfermedad , Ingestión de Líquidos/fisiología , Ingestión de Alimentos/fisiología , Resistencia a la Insulina , Grasa Intraabdominal , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is highly associated with metabolic syndrome, a major cause of morbidity in the globalized society. The renin-angiotensin system (RAS) influences hepatic fatty acid metabolism, inflammation and fibrosis. Thus, in the present study, we aimed to evaluate the effect of aliskiren, a direct renin inhibitor, on metabolic syndrome-related NASH. METHODS: C57BL/6 male mice (n = 45) were divided into three groups: controls; animals inoculated with streptozotocin (STZ) (40 mg/kg/day) for 5 days and fed with high fat diet (HFD) for 8 weeks; and animals inoculated with STZ for 5 days, fed with HFD for 8 weeks and treated with aliskiren (100 mg/kg/day) for the final 2 weeks. Glycemic and insulin levels, hepatic lipid profile, histological parameters and inflammatory protein expression were analyzed. RESULTS: Aliskiren normalized plasma glucose and insulin levels, reduced cholesterol, triglycerides and total fat accumulation in liver and diminished hepatic injury, steatosis and fibrosis. These results could be explained by the ability of aliskiren to block angiotensin-II, lowering oxidative stress and inflammation in liver. Also, it exhibited a beneficial effect in increasing insulin sensitivity. CONCLUSION: These findings support the use of aliskiren in the treatment of metabolic syndrome underlying conditions. However, clinical studies are indispensable to test its effectiveness in the treatment of patients with metabolic syndrome.
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Gestational trophoblastic diseases are a group of interrelated diseases of trophoblastic tissue that include partial hydatidiform mole, complete hydatidiform mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. P63 is a p53 homologue that, in normal placentas, is expressed in the cytotrophoblast cells. The role of p63 in gestational trophoblastic diseases, however, merits further investigation. Immunohistochemistry with the p63 antibody (clone 4A4) was performed in formalin-fixed paraffin-embedded samples of hydropic abortion (n=10), partial hydatidiform mole (n=12), complete hydatidiform mole (n=12) and choriocarcinoma (n=5). P63 expression was quantitatively assessed as 0 (no stained cells), + (less than 10% positive cells), ++ (10-50% positive cells), and +++ (more than 50% positive cells). The intensity was scored as 0 (absence), + (weak), ++ (moderate), or +++ (strong). Statistical analysis was carried out by the Fisher test. In contrast to the other diagnoses, none of the choriocarcinomas analyzed exhibited p63-positive cells. There was no difference in distribution of p63 positive cells between hydropic abortion, partial hydatidiform mole, and complete hydatidiform mole. Concerning the intensity of immunostaining, there was difference only between partial hydatidiform mole and complete hydatidiform mole. According to our results, p63 might be useful to differentiate a choriocarcinoma from other gestational trophoblastic diseases. Besides, since the intensity of p63 expression was much stronger in partial hydatidiform mole and complete hydatidiform mole than in hydropic abortion, this feature may be helpful in distinguishing these two diagnoses in challenging cases.
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Aborto Espontáneo/metabolismo , Coriocarcinoma/metabolismo , Mola Hidatiforme/metabolismo , Proteínas de la Membrana/metabolismo , Trofoblastos/metabolismo , Neoplasias Uterinas/metabolismo , Aborto Espontáneo/patología , Adulto , Biomarcadores/metabolismo , Recuento de Células , Coriocarcinoma/patología , Femenino , Edad Gestacional , Humanos , Mola Hidatiforme/patología , Embarazo , Coloración y Etiquetado , Trofoblastos/patología , Neoplasias Uterinas/patologíaRESUMEN
Among the postoperative complications, hepatic artery thrombosis can occur in up to 10% of adult orthotopic liver transplants and intervention is indicated when this occurs within 30 days by retransplantation. Primary graft dysfunction, which can occur in up to 30% of the cases and is another potential complication, although reversible, has a relatively high mortality rate. Hyperbaric therapy, an efficient mode of tissue oxygenation, is being used in an increasing number of clinical situations. We report here two cases where hyperbaric oxygen therapy greatly benefited patients with complications after orthotopic liver transplantation: one with hepatic artery thrombosis and the other with primary graft dysfunction. Both patients showed rapid clinical recovery with gradual reduction of liver and canalicular enzymes soon after commencing hyperbaric oxygen therapy.
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Arteria Hepática , Oxigenoterapia Hiperbárica/métodos , Trasplante de Hígado/efectos adversos , Complicaciones Posoperatorias/terapia , Trombosis/etiología , Trombosis/terapia , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Humanos , Lactante , Masculino , Resultado del TratamientoRESUMEN
Subjects with chronic liver disease are susceptible to hypovitaminosis A due to several factors. Therefore, identifying patients with vitamin deficiency and a requirement for vitamin supplementation is important. Most studies assessing vitamin A in the context of hepatic disorders are conducted using cirrhotic patients. A cross-sectional study was conducted in 43 non-cirrhotic patients with chronic hepatitis C to evaluate markers of vitamin A status represented by serum retinol, liver retinol, and serum retinol-binding protein levels. We also performed the relative dose-response test, which provides an indirect estimate of hepatic vitamin A reserves. These vitamin A indicators were assessed according to the stage of liver fibrosis using the METAVIR score and the body mass index. The sample study was predominantly composed of male subjects (63%) with mild liver fibrosis (F1). The relative dose-response test was <20% in all subjects, indicating vitamin A sufficiency. Overweight or obese patients had higher serum retinol levels than those with a normal body mass index (2.6 and 1.9 µmol/L, respectively; P<0.01). Subjects with moderate liver fibrosis (F2) showed lower levels of serum retinol (1.9 vs 2.5 µmol/L, P=0.01) and retinol-binding protein levels compared with those with mild fibrosis (F1) (46.3 vs 67.7 µg/mL, P<0.01). These results suggested an effect of being overweight on serum retinol levels. Furthermore, more advanced stages of liver fibrosis were related to a decrease in serum vitamin A levels.
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Hepatitis C Crónica/complicaciones , Deficiencia de Vitamina A/diagnóstico , Vitamina A/análisis , Adulto , Anciano , Biomarcadores/análisis , Biopsia , Índice de Masa Corporal , Estudios Transversales , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hígado/química , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Sobrepeso/sangre , Proteínas de Unión al Retinol/análisis , Deficiencia de Vitamina A/complicaciones , Adulto JovenRESUMEN
Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention.
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Interacciones Huésped-Patógeno , Estomatitis/microbiología , Humanos , Microbiota , Boca/microbiología , Boca/patología , Estomatitis/patologíaRESUMEN
Renin-angiotensin system (RAS) is an important factor in the pathophysiology of hypertension. Mas receptor, Angiotensin-(1-7) [Ang-(1-7)]-activated receptor, is an important RAS component and exerts protective effects in the vasculature. Ang-(1-7) vascular effects and Mas receptor expression in carotid from renovascular hypertensive (2K-1C) rats is not clear. In the present study we investigated Mas receptor vasodilator response activated by Ang-(1-7) in the carotid rings from sham and 2K-1C rats. Changes in isometric tension were recorded on organ chamber. Mas receptors expression was investigated in carotid by Western blot. Nitric oxide production was evaluated by 2,3-diaminonaphthalene (DAN) and eNOS expression and activity by immunofluoresce and western blot, respectively. Ang-(1-7) induced concentration-dependent vasodilator effect in carotid rings from sham and 2K-1C, which the hypertension increased vasodilatation response. In the 2K-1C carotid rings, A-779 (Mas receptor antagonist) reduced but not abolish the vasodilator effect of Ang-(1-7). Corroborating, Mas receptor protein expression was significantly increased in the 2K-1C rats. L-NAME and ibuprofen decreased Ang-(1-7) vasodilator response and L-NAME plus ibuprofen practically abolish the remaining vasodilatation response. Nitric oxide production is increased due increased of eNOS expression and pSer(1177) activity. Our results demonstrated that renovascular hypertension increased Mas receptors expression and nitric oxide production in the rats carotid which, consequently increased Ang-(1-7)-vasorelaxant response.
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Angiotensina I/metabolismo , Arterias Carótidas/metabolismo , Regulación de la Expresión Génica , Hipertensión/metabolismo , Fragmentos de Péptidos/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sistema Renina-Angiotensina , Vasodilatación , Animales , Arterias Carótidas/patología , Arterias Carótidas/fisiopatología , Hipertensión/patología , Hipertensión/fisiopatología , Ibuprofeno/farmacología , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Proto-Oncogenes Mas , Ratas , Ratas WistarRESUMEN
Nitric oxide (NO) levels increase considerably after 24h of exposure of skin to ultraviolet B (UVB) radiation, which leads to nitrosative skin injury. In addition, increased NO levels after exposure to UVB radiation are associated with inhibition of cell proliferation. Compared to the UV-control group, UV-genistein at 10 mg/kg (UV-GEN10) group showed tissue protection, decreased lipid peroxide and nitrotyrosine formation, and low CAT activity. Furthermore, NO levels and iNOS labeling remained high. In this group, the reduction in lipid peroxides and nitrotyrosine was accompanied by upregulation of cell proliferation factors (Ki67 and PCNA), which indicated that prevention of nitrosative skin injury promoted cell proliferation and DNA repair. Genistein also prevented nitrosative events, inhibited ONOO(-) formation, which leads to tissue protection and cell proliferation. The UV-GEN15 group did not result in a greater protective effect compared to that with UV-GEN10 group. In the UV-GEN15 group, histological examination of the epidermis showed morphological alterations without efficient protection against lipid peroxide formation, as well as inhibition of Ki67 and PCNA, and VEGF labeling, which suggested inhibition of cell proliferation. These results help to elucidate the mechanisms underlying the photoprotective effect of genistein and reveal the importance of UVB radiation-induced nitrosative damage.
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Genisteína/farmacología , Protectores contra Radiación/farmacología , Piel/efectos de los fármacos , Piel/lesiones , Rayos Ultravioleta/efectos adversos , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Antígeno Ki-67/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Ratones , Antígeno Nuclear de Célula en Proliferación/metabolismo , Piel/metabolismo , Piel/efectos de la radiación , Proteína p53 Supresora de Tumor/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The effects of benzalkonium chloride (BAC) on the number of myenteric neurons after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied with time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase.
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Compuestos de Benzalconio/farmacología , Yeyuno/inervación , Plexo Mientérico/citología , Neuronas/fisiología , Animales , Desnervación , Yeyuno/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Bradykinin has been reported to act as a growth factor for fibroblasts, mesangial cells and keratinocytes. Recently, we reported that bradykinin augments liver regeneration after partial hepatectomy in rats. Angiotensin-converting enzyme (ACE) is also a powerful bradykinin-degrading enzyme. We have investigated the effect of ACE inhibition by lisinopril on liver regeneration after partial hepatectomy. Adult male Wistar rats underwent 70% partial hepatectomy (PH). The animals received lisinopril at a dose of 1 mg kg body weight(-1) day(-1), or saline solution, intraperitoneally, for 5 days before hepatectomy, and daily after surgery. Four to six animals from the lisinopril and saline groups were sacrificed at 12, 24, 36, 48, 72, and 120 h after PH. Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen using the PC-10 monoclonal antibody. The value for the lisinopril-treated group was three-fold above the corresponding control at 12 h after PH (P<0.001), remaining elevated at approximately two-fold above control values at 24, 36, 48 (P<0.001), and at 72 h (P<0.01) after PH, but values did not reach statistical difference at 120 h after PH. Plasma ACE activity measured by radioenzymatic assay was significantly higher in the saline group than in the lisinopril-treated group (P<0.001), with 81% ACE inhibition. The present study shows that plasma ACE inhibition enhances liver regeneration after PH in rats. Since it was reported that bradykinin also augments liver regeneration after PH, this may explain the liver growth stimulating effect of ACE inhibitors.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Lisinopril/farmacología , Regeneración Hepática/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/sangre , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Animales , Bradiquinina/farmacología , División Celular , Inmunoquímica , Lisinopril/sangre , Lisinopril/metabolismo , Hígado/citología , Regeneración Hepática/fisiología , Masculino , Antígeno Nuclear de Célula en Proliferación/análisis , Ratas , Ratas Wistar , Sistema Renina-Angiotensina/efectos de los fármacosRESUMEN
Several investigators have identified Epstein-Barr virus (EBV) particles in breast carcinomas, a fact that supports a role for EBV in mammary tumorigenesis. The possible mechanism involved in this process is not clear. The present study was carried out in an attempt to determine whether there is a relationship between latent infection with EBV and p53 and p63 expression in breast carcinomas. Immunohistochemistry developed with 3.3-diaminobenzidine tetrahydrochloride was performed in 85 formalin-fixed paraffin-embedded breast carcinomas using anti-EBV EBNA-1, anti-p63, anti-p53, anti-estrogen receptor (ER) and anti-progesterone receptor (PR) antibodies. The cases were selected to represent each of the various histologic types: intraductal carcinoma (N=12), grade I invasive ductal carcinoma (N=15), grade II invasive ductal carcinoma (N=15), grade III invasive ductal carcinoma (N=15), tubular carcinoma (N=8), lobular carcinoma (N=10), and medullary carcinoma (N=10). The ductal breast carcinomas were graded I, II and III based on the Scarff-Bloom and Richardson grading system modified by Elston and Ellis. One slide containing at least 1000 neoplastic cells was examined in each case. ER, PR, p63, p53 and EBNA-1 were positive in 60, 40, 11.8, 21.2 and 37.6% of carcinomas, respectively. There was a correlation between EBNA-1 and p63 expression (P<0.001), but not between EBNA-1 and p53 (P=0.10). These data suggest a possible role for p63 in the mammary tumorigenesis associated with Epstein-Barr virus infection.