RESUMO
Urinary tract tumors are tenth in frequency, and many environmental carcinogens are excreted by urine. Interplay between chronic inflammatory urolithiasis and urothelial carcinogenesis is not well understood. Experimental evidences show that dietary melamine induce these events even at low concentrations. This is important because thousands of children were exposed to melamine through intentionally contaminated milk formula worldwide. We propose that an increased risk for urinary tumors in adult life may occur and screenings for early urinary signs may be necessary. Therefore, urothelial biology, melamine carcinogenic potential, and related epidemiology are discussed, recommending a preventive dietary polyunsaturated fatty acid-based supplementation, since they modulate such interplay in rodents.
Assuntos
Ácidos Graxos Insaturados/uso terapêutico , Contaminação de Alimentos , Fórmulas Infantis/química , Triazinas/toxicidade , Urolitíase/induzido quimicamente , Neoplasias Urológicas/induzido quimicamente , Neoplasias Urológicas/dietoterapia , Adulto , Animais , Testes de Carcinogenicidade , Carcinógenos/toxicidade , Bovinos , Causalidade , Comorbidade , Suplementos Nutricionais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Ratos , Medição de Risco , Triazinas/análise , Urolitíase/dietoterapia , Urolitíase/epidemiologia , Neoplasias Urológicas/epidemiologiaRESUMO
High salt intake (HS) is a risk factor for cardiovascular and kidney disease. Indeed, HS may promote blood-pressure-independent tissue injury via inflammatory factors. The lipid-lowering 3-hydroxy 3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors exert beneficial lipid-independent effects, reducing the expression and synthesis of inflammatory factors. We hypothesized that HS impairs kidney structure and function in the absence of hypertension, and these changes are reversed by atorvastatin. Four groups of rats were treated for 6 wk in metabolic cages with their diets: normal salt (NS); HS, NS plus atorvastatin and HS plus atorvastatin. We measured basal and final body weight, urinary sodium and protein excretion (U(Prot)V), and systolic blood pressure (SBP). At the end of the experimental period, cholesterolemia, creatinine clearance, renal vascular reactivity, glomerular volume, cortical and glomerular endothelial nitric oxide synthase (eNOS), and transforming growth factor (TGF)-ß1 expression were measured. We found no differences in SBP, body weight, and cholesterolemia. HS rats had increased creatinine clearence, U(Prot)V, and glomerular volume at the end of the study. Acetylcholine-induced vasodilatation decreased by 40.4% in HS rats (P < 0.05). HS decreased cortical and glomerular eNOS and caused mild glomerular sclerosis, interstitial mononuclear cell infiltration, and increased cortical expression of TGF-ß1. All of these salt-induced changes were reversed by atorvastatin. We conclude that long-term HS induces inflammatory and hemodynamic changes in the kidney that are independent of SBP. Atorvastatin corrected all, suggesting that the nitric oxide-oxidative stress balance plays a significant role in the earlier stages of salt induced kidney damage.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Ácidos Heptanoicos/farmacologia , Rim/efeitos dos fármacos , Pirróis/farmacologia , Cloreto de Sódio na Dieta/efeitos adversos , Vasodilatação/efeitos dos fármacos , Animais , Atorvastatina , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Masculino , Ratos , Ratos WistarRESUMO
In this investigation, we study the relation between chronic inflammation of the tonsils, clinical features, and the presence of biofilms in the crypts in patients presenting with obstructive hypertrophy and recurrent upper airway pathology. Thirty-six patients who needed to undergo a tonsillectomy for obstructive reasons (aged 1 to 6 years), among which none of them had taken any antibiotics 30 days prior to surgery, were included. Samples were examined with hematoxylin-eosin and Gram staining, fluorescent microscopy, and confocal laser microscopy. The predominance of symptoms were those related to obstructive pathology rather than infection (p < 0.01). All patients had tonsillar hypertrophy (grade III or IV), but an association with adenoids hypertrophy was detected in 66.66% of cases (p < 0.05). 77.28% of tonsils presented biofilms in their crypts, but hypertrophy and tonsillar follicle number were not related to the presence or absence of biofilms. Here, we demonstrated that symptoms like harsh raucous sound, tonsillar and adenoids hypertrophy, apnea, and cervical adenopathies are clearly related to the presence of biofilm in tonsils. Our results allow us to propose that biofilms are involved in the pathogenesis of tonsils and adenoids hypertrophy. The prevention of biofilms formation should be focused in the early stages, attempting to restrain bacterial attachment to the respiratory mucosa.
Assuntos
Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Biofilmes/crescimento & desenvolvimento , Tonsilite/microbiologia , Tonsilite/patologia , Obstrução das Vias Respiratórias/patologia , Infecções Bacterianas/complicações , Pré-Escolar , Doença Crônica , Feminino , Humanos , Hipertrofia/patologia , Lactente , Masculino , Tonsila Palatina/patologia , Tonsilite/complicaçõesRESUMO
Dietary arachidonic acid (AA) and eicosanoids influence neoplastic cell (NC) growth, differentiation and apoptosis. Plasma membrane fatty acid and cyclooxygenase (COX) and lipoxygenase (LOX) products were investigated in lung alveolar carcinoma cells from mice fed on different diets. Two groups were fed on a basic diet plus 6% of: corn oil (rich in 18:2n-6; CO) and on olein oil (rich in 18:1n-9; O), respectively. Control group (C) received commercial diet. NC fatty acids were analyzed by GLC, and apoptosis by flow cytometry and microscopy. In NC from CO group AA levels and LOX metabolites were increased, whereas COX metabolites decreased. NC from CO compared to O group diet showed a higher count of apoptosis and increased LOX:COX ratio. High levels of AA and decreased COX eicosanoids has been involved in anti-tumoral mechanisms by increasing tumor cell apoptosis. Present data emphasizes the implications of the dietary fatty acids on the neoplastic process in this tumoral model.
Assuntos
Adenocarcinoma Bronquioloalveolar/metabolismo , Adenocarcinoma Bronquioloalveolar/patologia , Apoptose/efeitos dos fármacos , Gorduras na Dieta/farmacologia , Eicosanoides/metabolismo , Adenocarcinoma Bronquioloalveolar/enzimologia , Animais , Membrana Celular/metabolismo , Ácidos Graxos/metabolismo , Feminino , Lipoxigenase/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Prostaglandina-Endoperóxido Sintases/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The modulatory effects of polyunsaturated fatty acids (PUFA) on urinary tract tumorigenesis of 275 Wistar rats were evaluated by treating animals with the tumorigenic agent melamine. Rats were fed with formulae containing 6% of 4 varieties of fats: fish oil enriched in n-3 PUFA (FO), corn oil enriched in n-6 (CO), olein containing mainly n-9 oleic acid (O), and 98% stearic acid (SA), the latter two being essential (EFA)-deficient inducers. Two commercially fed control groups with (CM) and without (C) melamine were used. Animals were autopsied at 22-25 and at 36-40 weeks. Hepatic fatty acids showed that O and SA groups were EFA-deficient. Simple well differentiated hyperplasias were significantly higher in the FO lot, whereas dysplasia was increased in the CO, O and SA lots. Most of the animals fed for 36-40 weeks with the three latter formulae developed the more severe lesions. Increased urothelial proliferation was more frequent in EFA-deficient rats. The apoptosis/mitosis ratio was higher in O, SA and CO fed animals with respect to FO and chow ones. Results show that dietary PUFA modulate differentially both normal and pre-neoplastic urothelial proliferation induced by melamine. FO, rich in n-3 fatty acids, showed a strong protective effect.
Assuntos
Carcinógenos , Dieta , Ácidos Graxos Insaturados/farmacologia , Lesões Pré-Cancerosas/prevenção & controle , Triazinas/toxicidade , Neoplasias Urológicas/prevenção & controle , Urotélio/patologia , Animais , Apoptose/efeitos dos fármacos , Testes de Carcinogenicidade , Cromatografia Gasosa , Feminino , Rim/patologia , Masculino , Mitose/efeitos dos fármacos , Índice Mitótico , Região Organizadora do Nucléolo/efeitos dos fármacos , Região Organizadora do Nucléolo/fisiologia , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Wistar , Bexiga Urinária/patologia , Neoplasias Urológicas/induzido quimicamente , Neoplasias Urológicas/patologiaRESUMO
INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.(AU)
Introducción: Según el concepto de cancerización de campo, existría alteración en la proliferación epitelial en áreas cercanas a tumores. Dicha proliferación podría ser modificada por lípidos dietarios. Objetivos: este estudio fue diseñado para analizar proliferación y apoptosis en epitelio lingual de ratones portadores de tumores salivalesinducidos por DMBA y alimentados con dietas a base de diferentes lípidos. Materiales y Métodos: Cuarenta y cinco días posteriores al destete, diez ratones BALB/c fueron asignados a dos dietas: maíz(M) y bacalao (B). Dos semanas después se inyectó DMBA en la zona submandibular. Los animales fueron sacrificados a ala 13º semana post-inyección. Muestras de lengua fueron fijadas en formal-etanl y procesadas inmunohistoquímicamente con marcadores de proliferación (Ki-67) y apoptosis. Mediante microscopia óptica, se efectuó un conteo de núcleos positivos a ambos marcadosres en un total de trecientas células en interfase, tanto en cara dorsal como ventral de lengua. Los resultados fueron analizados mediante Anális de Varianza y Test t. Resultados: La proliferación celular fue mayor en cara dorsal que en ventral (p> 0.001), sin diferencias por dieta. La apoptosis fue significativamentes mayor en ratones alimentados con B que M, en particular en cara dorsal (p<0.018). Conclusiones: Este estudio demuestra que la dieta B induce mayor apoptosis en ela epitelio lingua, sgiriendo un mecanismo defensivo de los tejidos ante el agente cancerígeno-tumoral. (AU)
Assuntos
Animais , Camundongos , Apoptose/efeitos dos fármacos , Carcinoma/patologia , Gorduras na Dieta/administração & dosagem , Neoplasias das Glândulas Salivares/patologia , 9,10-Dimetil-1,2-benzantraceno , Carcinógenos , Carcinoma/induzido quimicamente , Carcinoma/dietoterapia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Lesões Pré-Cancerosas/patologia , Neoplasias das Glândulas Salivares/induzido quimicamente , Neoplasias das Glândulas Salivares/dietoterapiaRESUMO
INTRODUCTION: According to the concept of field defects during the carcinogenesis process, excessive epithelial proliferation/apoptosis may exist in areas near tumors. Proliferation or apoptosis could be modified by dietary lipids. PURPOSE: The present study was designed to analyze proliferation and apoptosis in tongue epithelium of mice fed diets based on different lipids followed by induction of salivary tumors with DMBA. MATERIALS AND METHODS: Forty-five days after weaning, ten BALB/c mice were assigned to two diets: corn oil (CO) and fish oil (cod liver, FO). Two weeks later, DMBA was injected in the submandibular area. Animals were sacrificed at the 13th post-injection week. Samples of tongue were fixed in formalin-ethanol and immunohistochemically stained for proliferation (Ki-67) and apoptosis (Bax). By light microscopy, the number of nuclei positive for these markers were counted out of three-hundred total interphase cells both in dorsal and in ventral tongue surfaces. Results were analyzed through Analysis of Variance and t Test. RESULTS: Cell proliferation was greater in dorsal than in ventral tongue surfaces (p < 0.0001) with no diet difference. Apoptosis was significantly greater in mice fed FO than CO, particularly in tongue dorsal epithelia (p < 0.018). CONCLUSIONS: This study shows that FO diet induces higher levels of apoptosis in tongue epithelia suggesting a tissue defensive mechanism when exposed to a carcinogenic-tumoral agent.
Introducción: Según el concepto de cancerización de campo, existría alteración en la proliferación epitelial en áreas cercanas a tumores. Dicha proliferación podría ser modificada por lípidos dietarios. Objetivos: este estudio fue diseñado para analizar proliferación y apoptosis en epitelio lingual de ratones portadores de tumores salivalesinducidos por DMBA y alimentados con dietas a base de diferentes lípidos. Materiales y Métodos: Cuarenta y cinco días posteriores al destete, diez ratones BALB/c fueron asignados a dos dietas: maíz(M) y bacalao (B). Dos semanas después se inyectó DMBA en la zona submandibular. Los animales fueron sacrificados a ala 13º semana post-inyección. Muestras de lengua fueron fijadas en formal-etanl y procesadas inmunohistoquímicamente con marcadores de proliferación (Ki-67) y apoptosis. Mediante microscopia óptica, se efectuó un conteo de núcleos positivos a ambos marcadosres en un total de trecientas células en interfase, tanto en cara dorsal como ventral de lengua. Los resultados fueron analizados mediante Anális de Varianza y Test t. Resultados: La proliferación celular fue mayor en cara dorsal que en ventral (p> 0.001), sin diferencias por dieta. La apoptosis fue significativamentes mayor en ratones alimentados con B que M, en particular en cara dorsal (p<0.018). Conclusiones: Este estudio demuestra que la dieta B induce mayor apoptosis en ela epitelio lingua, sgiriendo un mecanismo defensivo de los tejidos ante el agente cancerígeno-tumoral.
Assuntos
Animais , Camundongos , Apoptose/efeitos dos fármacos , Carcinoma/patologia , Gorduras na Dieta/administração & dosagem , Neoplasias das Glândulas Salivares/patologia , Carcinógenos , Carcinoma/induzido quimicamente , Carcinoma/dietoterapia , Lesões Pré-Cancerosas/patologia , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Neoplasias das Glândulas Salivares/induzido quimicamente , Neoplasias das Glândulas Salivares/dietoterapia , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: The lack of certain essential polyunsaturated fatty acids (PUFAs) induces perturbation in cell proliferation, apoptosis and dedifferentiation that could be linked to an increased protumorigenic trend. Contrarily, n-3 essential fatty acids (EFAs) arrest cell proliferation in several tumor models. According to the concept of field cancerization, multiple patches of abnormal epithelial proliferation may coexist in the vicinity of oropharyngeal neoplasms. The purpose of the present study is to determine whether certain dietary PUFAs differentially modulate the patterns of cell proliferation and apoptosis at non-tumoral sites of the oral mucosa in mice bearing DMBA induced salivary tumors. After weaning, BALB/c mice were assigned to four diets: Control (C), Corn Oil (CO), Fish (FO) and Olein (O). Two weeks later, DMBA was injected into the submandibular area. The animals were sacrificed between 94 and 184 days at 4-6 PM. Fixed samples of lip, tongue and palate were stained using H-E and a silver technique. A quantification of AgNORs in the basal (BS) and suprabasal stratum (SBS) of the covering squamous epithelia as well as of mitosis and apoptosis was performed. RESULTS: Analysis of Variance showed greater proliferation in tongue than in palate or lip. According to the diet, a significant difference was found in the Fish Oil, in which palate exhibited fewer AgNOR particles than that of the control group, both for BS and SBS (p < 0.05 and 0.152, respectively), indicating a reduced cell proliferation. CONCLUSIONS: These results corroborate and reaffirm that the patterns of cell proliferation, apoptosis and differentiation of the oral stratified squamous epithelium may be differentially modulated by dietary lipids, and arrested by n-3 fatty acids, as shown in several other cell populations.