RESUMEN
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
AIM: To evaluate the potential biostimulatory effects of grape seed extract (GSE) on a primary culture of human pulp cells. METHODOLOGY: Human molars were used to obtain the primary pulp cell culture and 0.5-mm dentine discs. For GSE direct exposure, dose-response (0.0065-6.5%) and time response (1-60 min of contact) were examined. For transdentinal exposure, 0.65% of GSE was tested for 24 h. Cellular metabolism, nitric oxide and collagen production, and cell morphology alterations were assessed at periods of 24 and 72 h. After cell differentiation and direct exposure to GSE, the total protein production (TP), alkaline phosphatase activity (ALP) and formation of mineralization nodules (MN) were assessed. The results were analysed by parametric tests or non-parametric tests (α = 0.05). RESULTS: The lower concentration of GSE tested (0.0065%) was associated with an increase in cellular metabolism, a reduction in the production of nitric oxide and an increase in extracellular matrix synthesis (collagen). Distinct behaviours were observed for the different concentrations, without a reduction of cellular metabolism >10% compared with the control, either when applied directly or transdentinally. SEM revealed no significant change in cell morphology, except for the positive control (H2 O2 ). There was no difference in TP, ALP or MN between the control group and the group exposed to GSE. CONCLUSIONS: Treatment with grape seed extract, even at the highest concentration and longest period, caused neither direct nor transdentinal cytotoxic effects on human pulp cells. Grape seed extract components may play a biostimulatory role and protect dental pulp cells when in direct contact.
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Extracto de Semillas de Uva , Proantocianidinas , Diferenciación Celular , Pulpa Dental , Dentina , HumanosRESUMEN
There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aß) and Tau) and exacerbates AD pathology. Neuroinflammation can also be induced by systemic influences (factors from outside the central nervous system). However, the role of systemic inflammation in AD pathophysiology is much less understood. Thus, our main objective in this study was to verify whether the presence of serum cytokines (IL-1ß, IL-6, IL-10, IL-12, and TNF-α) affects different AD biomarkers: Aß1-42 and Tau protein levels, hippocampal volumes (HV), and default mode network functional connectivity (DMN FC) in healthy elderly controls, amnestic mild cognitive impairment (aMCI) patients due to AD, and mild AD patients. To accomplish this, we acquired 3-T MRI, blood, and cerebrospinal fluid (CSF) samples from 42 healthy controls, 55 aMCI patients due to AD, and 33 mild AD patients. Comparing the groups, we found that the mild AD patients presented smaller HV, disrupted DMN FC, and proportionally less IL-1ß than the controls. The aMCI patients only differed from the controls in DMN FC. In intra-group comparison, aMCI and mild AD with detectable levels of cytokines (TNF-α, IL-1ß, IL-10, and IL-12) had decreased DMN FC. On the other hand, patients with detectable levels of IL-10 and IL-12 presented a more favorable AD biomarkers profile (larger HV, more CSF Aß1-42, and less p-Tau), indicating a possible protective role of these ILs. Our findings indicate a possible relationship between systemic inflammation with DMN FC disruption, hippocampal atrophy, and CSF protein levels in the subjects with mild AD and aMCI.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/complicaciones , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/complicaciones , Inflamación/líquido cefalorraquídeo , Inflamación/complicaciones , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Estudios de Casos y Controles , Disfunción Cognitiva/diagnóstico por imagen , Citocinas/líquido cefalorraquídeo , Femenino , Humanos , Inflamación/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
Antibiotic-resistant infections are predicted to kill 10 million people per year by 2050, costing the global economy $100 trillion. Therefore, there is an urgent need to develop alternative technologies. We have engineered a synthetic peptide called clavanin-MO, derived from a marine tunicate antimicrobial peptide, which exhibits potent antimicrobial and immunomodulatory properties both in vitro and in vivo. The peptide effectively killed a panel of representative bacterial strains, including multidrug-resistant hospital isolates. Antimicrobial activity of the peptide was demonstrated in animal models, reducing bacterial counts by six orders of magnitude, and contributing to infection clearance. In addition, clavanin-MO was capable of modulating innate immunity by stimulating leukocyte recruitment to the site of infection, and production of immune mediators GM-CSF, IFN-γ and MCP-1, while suppressing an excessive and potentially harmful inflammatory response by increasing synthesis of anti-inflammatory cytokines such as IL-10 and repressing the levels of pro-inflammatory cytokines IL-12 and TNF-α. Finally, treatment with the peptide protected mice against otherwise lethal infections caused by both Gram-negative and -positive drug-resistant strains. The peptide presented here directly kills bacteria and further helps resolve infections through its immune modulatory properties. Peptide anti-infective therapeutics with combined antimicrobial and immunomodulatory properties represent a new approach to treat antibiotic-resistant infections.
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Antibacterianos/farmacología , Factores Inmunológicos/farmacología , Péptidos/farmacología , Animales , Infecciones Bacterianas/tratamiento farmacológico , Proteínas Sanguíneas/farmacología , Modelos Animales de Enfermedad , Femenino , Células HEK293 , Humanos , Inmunidad Innata/efectos de los fármacos , Inmunomodulación/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , Péptidos/química , Péptidos/uso terapéutico , Péptidos/toxicidad , Células RAW 264.7RESUMEN
BACKGROUND AND PURPOSE: Machado-Joseph disease (MJD/SCA3) is the most frequent spinocerebellar ataxia, characterized by brainstem, basal ganglia and cerebellar damage. Few magnetic resonance imaging based studies have investigated damage in the cerebral cortex. The objective was to determine whether patients with MJD/SCA3 have cerebral cortex atrophy, to identify regions more susceptible to damage and to look for the clinical and neuropsychological correlates of such lesions. METHODS: Forty-nine patients with MJD/SCA3 (mean age 47.7 ± 13.0 years, 27 men) and 49 matched healthy controls were enrolled. All subjects underwent magnetic resonance imaging scans in a 3 T device, and three-dimensional T1 images were used for volumetric analyses. Measurement of cortical thickness and volume was performed using the FreeSurfer software. Groups were compared using ancova with age, gender and estimated intracranial volume as covariates, and a general linear model was used to assess correlations between atrophy and clinical variables. RESULTS: Mean CAG expansion, Scale for Assessment and Rating of Ataxia (SARA) score and age at onset were 72.1 ± 4.2, 14.7 ± 7.3 and 37.5 ± 12.5 years, respectively. The main findings were (i) bilateral paracentral cortex atrophy, as well as the caudal middle frontal gyrus, superior and transverse temporal gyri, and lateral occipital cortex in the left hemisphere and supramarginal gyrus in the right hemisphere; (ii) volumetric reduction of basal ganglia and hippocampi; (iii) a significant correlation between SARA and brainstem and precentral gyrus atrophy. Furthermore, some of the affected cortical regions showed significant correlations with neuropsychological data. CONCLUSIONS: Patients with MJD/SCA3 have widespread cortical and subcortical atrophy. These structural findings correlate with clinical manifestations of the disease, which support the concept that cognitive/motor impairment and cerebral damage are related in disease.
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Ganglios Basales/patología , Tronco Encefálico/patología , Corteza Cerebral/patología , Enfermedad de Machado-Joseph/patología , Adulto , Atrofia/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
Rickettsia rickettsii infection is being increasingly recognized as an important cause of fatal acute illness in Brazil, where this tick-borne disease is designated Brazilian spotted fever (BSF). In this study we report five fatal cases of BSF in employees of an animal shelter in an urban area in the municipality of Rio de Janeiro in southeast Brazil after a natural disaster on 11 January 2011. Four of the cases occurred from 27 January to 11 April 2011, while the fifth fatal case was identified in April 2012. Three cases were confirmed by molecular analysis and two by epidemiological linkage. An investigation of BSF was performed in the animal shelter, and blood samples were collected from 115 employees and 117 randomly selected dogs. The presence of high levels (1024-4096) of antibodies against spotted fever group rickettsiae was found in three (2·6%) employees and 114 (97·5%) dogs. These findings emphasize the need to consider BSF as a possible cause of undifferentiated febrile illness, especially dengue and leptospirosis, in patients occupationally exposed to dogs heavily infested by ticks, mainly working at kennels and animal shelters that have inadequate space for the animals housed and frequently providing an environment conducive to exposure to pathogens such as R. rickettsii.
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Anticuerpos Antibacterianos/inmunología , Enfermedades de los Perros/diagnóstico , Vivienda para Animales , Enfermedades Profesionales/diagnóstico , Rickettsia rickettsii/inmunología , Fiebre Maculosa de las Montañas Rocosas/veterinaria , Garrapatas , Adulto , Animales , Brasil , Dengue/diagnóstico , Diagnóstico Diferencial , Perros , Resultado Fatal , Femenino , Humanos , Leptospirosis/diagnóstico , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inmunología , Fiebre Maculosa de las Montañas Rocosas/diagnóstico , Fiebre Maculosa de las Montañas Rocosas/inmunología , Población UrbanaRESUMEN
Diabetes mellitus (DM) is one of the most common metabolic disorders. DM is characterized by hyperglycaemia, resulting in wound healing difficulties and systemic and oral manifestations, which have a direct effect on dental pulp integrity. Experimental and clinical studies have demonstrated a higher prevalence of periapical lesions in patients with uncontrolled diabetes. The influence of DM on periapical bone resorption and its impact on dental intervention of such patients are reviewed, and its aetiology and pathogenesis are analysed at molecular level. Pulps from patients with diabetes have the tendency to present limited dental collateral circulation, impaired immune response, increased risk of acquiring pulp infection (especially anaerobic ones) or necrosis, besides toothache and occasional tendency towards pulp necrosis caused by ischaemia. In regard to molecular pathology, hyperglycaemia is a stimulus for bone resorption, inhibiting osteoblastic differentiation and reducing bone recovery. The relationship between poorly controlled diabetes and bone metabolism is not clearly understood. Molecular knowledge about pulp alterations in patients with diabetes could offer new therapeutic directions. Knowledge about how diabetes affects systemic and oral health has an enduring importance, because it may imply not only systemic complications but also a higher risk of oral diseases with a significant effect on pulp and periapical tissue.
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Complicaciones de la Diabetes , Periodontitis Periapical/complicaciones , Pulpitis/complicaciones , Pérdida de Hueso Alveolar/complicaciones , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/fisiopatología , Humanos , Hiperglucemia/complicaciones , Factores de Riesgo , Tratamiento del Conducto RadicularRESUMEN
AIM: To assess the influence of co-culture with mineral trioxide aggregate (MTA) on phagocytosis and the production of reactive oxygen intermediates (ROI) and nitrogen (NO) species and the arginase activity by M1 and M2 peritoneal macrophages. METHODOLOGY: Cellular viability, adherence and phagocytosis of Saccharomyces boulardii were assayed in the presence of MTA. Macrophages were stimulated with zymosan for ROI assays and with Fusobacterium nucleatum and Peptostreptococcus anaerobius and IFN-gamma for NO production and arginase activity, when in contact with capillaries containing MTA. Data were analysed by T, anova, Kruskall-Wallis and Mann-Whitney tests. RESULTS: M2 macrophages displayed greater cellular viability in polypropylene tubes, greater ability to ingest yeast and smaller production of ROI and higher arginase activity when compared with M1 macrophages. Both macrophages, M1 and M2, presented similar cell adherence and NO production. The addition of bacterial preparations to macrophages interfered with NO and arginase productions. MTA did not interfere with any of the parameters measured. CONCLUSIONS: Phagocytosis and the ability of the two macrophage subtypes to eliminate microbes were not affected by MTA.
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Compuestos de Aluminio/farmacología , Compuestos de Calcio/farmacología , Óxidos/farmacología , Fagocitosis/efectos de los fármacos , Materiales de Obturación del Conducto Radicular/farmacología , Silicatos/farmacología , Animales , Arginasa/efectos de los fármacos , Combinación de Medicamentos , Femenino , Macrófagos/citología , Macrófagos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Especies de Nitrógeno Reactivo/análisis , Especies Reactivas de Oxígeno/análisisRESUMEN
AIM: To test the effect of two commercial brands of grey mineral trioxide aggregate (ProRoot and MTA-Angelus) on cytokine production by M1 and M2 inflammatory macrophages. METHODOLOGY: M1 (from C57BL/6 mice) and M2 peritoneal inflammatory macrophages (from C57BL/6 IL12p40-/- mice) were obtained and cultured in vitro in the presence of MTA. The cellular viability and the production of tumour necrosis factor-alpha, interleukin (IL)-12 and IL-10 in response to stimulation with interferon-gamma and Fusobacterium nucleatum or Peptostreptococcus anaerobius were evaluated. Data were analysed by Mann-Whitney, Kruskal-Wallis and anova tests. RESULTS: The cements did not interfere with cellular viability or with cytokine production by either type of macrophage. However, M2 macrophages produced higher levels of IL-10 when stimulated with F. nucleatum than M1 macrophages (P < 0.05). CONCLUSIONS: The brands of MTA evaluated did not interfere in the cytokine response by M1 or M2 macrophages to the two bacteria tested. However, a difference in cytokine production between the two types of macrophages was found.
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Compuestos de Aluminio/farmacología , Compuestos de Calcio/farmacología , Interleucina-10/análisis , Interleucina-12/análisis , Macrófagos Peritoneales/efectos de los fármacos , Óxidos/farmacología , Materiales de Obturación del Conducto Radicular/farmacología , Silicatos/farmacología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Combinación de Medicamentos , Femenino , Fusobacterium nucleatum/fisiología , Interferón gamma/farmacología , Subunidad p40 de la Interleucina-12 , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Peptostreptococcus/fisiología , Subunidades de Proteína/efectos de los fármacosRESUMEN
The purpose of this study was to determine the rate of whole-body protein turnover in moderately and severely alcoholic, malnourished, cirrhotic patients fed with different amounts of protein or energy. Six male patients (Child classes B and C) and four age- and sex-matched healthy control subjects were studied for 18 d in fasting and feeding states; a single oral dose of [(15)N]glycine was used as a tracer and urinary ammonia was the end product. The kinetic study showed that patients had higher protein catabolism while fasting (patients: 3.14 +/- 1.2 g of lean body mass/9 h; controls: 1.8 +/- 0.3 g of lean body mass/9 h; P < 0.02). Although not statistically significant, protein catabolism (grams of lean body mass/9 h) was lower with the hyperproteic/hyperenergetic diet when compared with fasting. Nitrogen retention was consistent with the lower protein-catabolism rate; a statistically significant increase in nitrogen balance was observed when patients were fed with the hyperproteic/hyperenergetic diet compared with fasting (4.3 +/- 3.2 g of nitrogen/d and -2.2 +/- 1.9 g of nitrogen/d, respectively; P < 0.01). These data indicate that Child class B and C cirrhotic patients are hypercatabolic and that long-term nutritional intervention with a hyperproteic/hyperenergetic diet is likely needed to improve their clinical and nutritional status.
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Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Cirrosis Hepática Alcohólica/metabolismo , Trastornos Nutricionales/metabolismo , Proteínas/metabolismo , Adulto , Amoníaco/orina , Estudios de Casos y Controles , Ayuno , Glicina , Humanos , Cirrosis Hepática Alcohólica/complicaciones , Masculino , Persona de Mediana Edad , Nitrógeno/metabolismo , Isótopos de Nitrógeno , Trastornos Nutricionales/complicacionesRESUMEN
In five male cirrhotic patients (Child A) and in four age- and sex-matched healthy control subjects, whole-body protein turnover was measured using a single oral dose of 15N-glycine as a tracer and urinary ammonia as end product. Subjects were studied in the fasting and feeding state, with different levels of protein and energy intake. The patients were underweight and presented lower plasma transthyretin and retinol-binding protein levels. When compared with controls, the kinetic studies showed patients to be hypometabolic in the fasting (D0) state and with the control diet [D1 = (0.85 g of protein/ 154 kJ) x kg-1.day-1]. However, when corrected by body weight, the kinetic differences between groups disappeared, whereas the N-retention in the feeding state showed better results for the patients due mainly to their efficient breakdown decrease. When fed high-level protein or energy diets [D1 = (0.9 g protein/195 kJ) and D3 = (1.56 g protein/158 kJ) x kg-1.day-1], the patients showed D0 = D1 = D2 < D3 for N-flux and (D0 = D1) < D3 (D2 is intermediary) for protein synthesis. Thus, the present data suggest that the remaining mass of the undernourished mild cirrhotic patients has fairly good protein synthesis activity and also that protein, rather than energy intake, would be the limiting factor for increasing their whole-body protein synthesis.
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Proteínas en la Dieta/administración & dosificación , Ingestión de Energía , Glicina , Cirrosis Hepática Alcohólica/complicaciones , Desnutrición Proteico-Calórica/metabolismo , Proteínas/metabolismo , Adulto , Amoníaco/orina , Proteínas Sanguíneas/metabolismo , Ayuno , Alimentos , Humanos , Cirrosis Hepática Alcohólica/sangre , Masculino , Persona de Mediana Edad , Nitrógeno/metabolismo , Isótopos de Nitrógeno , Prealbúmina/metabolismo , Desnutrición Proteico-Calórica/etiología , Proteínas de Unión al Retinol/metabolismo , Proteínas Plasmáticas de Unión al RetinolRESUMEN
The dietary protein assimilation by cirrhotic undernourished patients (lower lean body mass and plasma TBPA and RBP levels) was investigated in five-adult male subjects suffering from histologically diagnosed liver cirrhosis, in its clinically mild stage (Child-Turcotte-Pugh grade A). During the 9 day-dietary study the patients received orally a sequence of complete-regional diets containing different protein-energy compositions identified as (g prot/Cal/kg/day): D0 = 0.42/20.9; D1 = 0.91/37.5; D2 = 0.99/47.9 and D3 = 1.60/40.5. The respective N-balance values (g/day) found were (mean +/- SD): low protein calorie (D0) = -4.24 +/- 2.46; normal protein calorie (D1) = 0.66 +/- 1.99; normal protein-high calorie (D2) = 1.14 +/- 2.54; high protein normal calorie (D3) = 5.12 +/- 2.48. The correspondent urea-N output (g/kg/day) were D0 = 0.22 +/- 0.100; D1 = 0.238 +/- 0.099; D = 0.20 +/- 0.063 and D3 = 0.310 +/- 0.121. The present data thus suggest that protein rather than energy intake would be the limited factor for increasing the N-retention in (mild) cirrhotic patients whom tolerate well dietary protein at either normal or elevated levels.
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Proteínas en la Dieta/metabolismo , Cirrosis Hepática/metabolismo , Nitrógeno/metabolismo , Estado Nutricional , Adulto , Índice de Masa Corporal , Proteínas en la Dieta/administración & dosificación , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/dietoterapia , Masculino , Persona de Mediana Edad , MuestreoRESUMEN
A retrospective study of the HBsAg was done in 56 liver biopsies of children less than 12 year-old and 78 biopsies of adults. The study was performed by orcein stain and indirect immunofluorescent method. In 23 of the adults patients, the serological detection of HBsAg and antibodies (HbsAb) was determined by reverse passive haemagglutination technique. The adults patients' histological dianosis were variable and included acute or chronic hepatitis (20.5%) and cirrhosis (24.4%). Orcein was positive in 7 and IFI in 6 cases; 5 biopsies were positive by both methods. The highest incidence of HBsAg was seen in active cirrhosis (75%), including two cases of alcoholic cirrhosis. In the 23 serologically studied patients, 15 cases were HBsAg negative and 3 were HBsAg positive both in the liver and serum; only 2 cases showed discrepancy between these results. Three patients were HBsAb positive and HBsAg negative both in the liver and serum. All children biopsies were HBsAg negative. Among these patients, 26.8% had acute or chronic hepatitis and 10.7% cirrhosis. Serological and tissue techniques for HBsAg and HbsAb detection have different sensitivity. This should be kept in mind when studying the incidence of hepatitis B virus related to liver diseases.
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Antígenos de Superficie de la Hepatitis B/análisis , Hepatitis B/inmunología , Adulto , Niño , Preescolar , Femenino , Técnica del Anticuerpo Fluorescente , Pruebas de Inhibición de Hemaglutinación , Humanos , Lactante , Masculino , Oxazinas , Estudios Retrospectivos , Coloración y EtiquetadoRESUMEN
The experiment was performed in order to evaluate the beta-glucuronidase activity in gastric juice and gastric mucosa of rats submitted to protein-free diet. A group of 36 young adult male wistar rats was fed a protein-free diet ad libitum for five weeks; a second group of 36 wistar rats ingested a purified isocaloric 12,5% casein diet for the same period. The concentration of proteins in plasma, gastric juice and gastric glandular mucosa and the beta-glucuronidase activity in the gastric juice and gastric glandular mucosa were determined. Protein deficient rats had lower plasma protein concentration and also a lower protein concentration in gastric juice and gastric mucosa. In these animals there was no significant change of beta-glucuronidase activity in the gastric juice, but there was a significant increase of the specific enzimatic activity in the gastric mucosa. The results suggest that protein restriction in young adult rats affects the gastric mucosa. The increase of the specific beta-glucuronidase activity might be due to heightened local catabolism or to a comparatively more severe protein depletion.