Efeito do consumo de farinha de linhaça (Linum usitatissimum) no crescimento de ratos Wistar e relação com a digestibilidade de globulinas e fatores antinutricionais protéicos

Linseed is an important oilseed consumed raw as nutritional supplement, that although represents a rich source of nutrients, its nutritional value could be impaired due to the presence of antinutritional factors. In this study, protein fractions from raw linseed flour were extracted and isolated being obtained 12% of albumins, 82% of globulins, 5% of glutelins and 1% of prolamins. These proteins were visualized by SDS-PAGE and albumins showed low molecular mass protein bands around 21 kDa and minor bands, similar to that of trypsin inhibitor; Globulins presented protein bands with high molecular masses, which possibly are constituents of multimeric proteins, such as legumins. After determination of the centesimal composition of raw linseed, it was used as exclusive protein source for young rats to evaluate its effect on animal growth. The results showed negative effects on rat growth (weight gain 73% less than the control group) and reduction of intestinal villus (35%), that could be related with in vitro and in vivo globulin digestibility and proteinaceous antinutritional factors (mammalian digestive enzymes inhibitors and lectins) in albumin fraction. Native globulins showed, by SDS-PAGE, low susceptibility in vitro to trypsin and chymotrypsin, however presented high degradation by pancreatin. Thermal treatment of globulins for 5 and 15 minutes at 100ºC improved considerably its digestibility by trypsin and pancreatin. Globulins presented 93.2% in vivo digestibility, similar to the control protein. Albumin fraction had high trypsin inhibition activity (100%) and chymotrypsin inhibition of 28.3%; haemagglutinating activity was not detected. The results of this study indicate the negative action of trypsin inhibitors on animal growth, but can not be discarded its combined action with other antinutritional factors, which could compromise the raw linseed utilization as an alternative food

Efeito de glucanas do fungo Caripia montagnei em modelo de inflamação intestinal induzida por tnbs em ratos Wistar e em células de carcinoma de cólon humano HT-29

Compounds derived from fungi has been the subject of many studies in order to broaden the knowledge of their bioactive potential. Polysaccharides from Caripia montagnei have been described to possess anti-inflammatory and antioxidant properties. In this study, glucans extracted from Caripia montagnei mushroom were chemically characterized and their effects evaluated at different doses and intervals of treatment. It was also described their action on colonic injury in the model of colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS), and its action on cells of the human colon carcinoma (HT-29). Compounds extracted of C. montagnei contain high level of carbohydrates (96%), low content of phenolic compounds (1.5%) and low contamination with proteins (2.5%). The (FT-IR) and (NMR) analysis showed that polysaccharides from this species of mushroom are composed of α- and β-glucans. The colonic damage was evaluated by macroscopic, histological, biochemical and immunologic analyses. The results showed a reduction of colonic lesions in all groups treated with the glucans of Caripia montagnei (GCM). GCM significantly reduced the levels of IL-6 (50 and 75 mg/kg, p < 0.05), a major inflammatory cytokine. Biochemical analyses showed that such glucans acted on reducing levels of alkaline phosphatase (75 mg/kg, p < 0.01), nitric oxide (p < 0.001), and myeloperoxidase (p < 0.001). These results were confirmed microscopically by the reduction of cellular infiltration. The increase of catalase activity suggest a protective effect of GCM on colonic tissue, confirming their anti-inflammatory potential. GCM displayed cytostatic activity against HT-29 cells, causing accumulation of cells in G1 phase, blocking the cycle cell progression. Those glucans also showed ability to modulate the adhesion of HT-29 cells to Matrigel® and reduced the oxidative stress. The antiproliferative activity against HT-29 cells displayed by GCM (p <0.001) can be attributed to its cytostatic activity and induction of apoptosis by GCM

Estudo comparativo de carragenanas comerciais Kappa, Iota e Lambda no processo inflamatório em ratos :edema intraplantar e pleurisia

The Iota, Kappa and Lambda commercial carrageenans are rarely pure and normally contain varying amounts of the other types of carrageenans. The exact amount of impurity depends on the seaweed source and extraction procedure. Then, different analysis methods have been applied for determination of the main constituents of carrageenans because these three carrageenans are extensively used in food, cosmetic and pharmaceutical industry. The electrophoresis of these compounds proved that the carrageenans are constituted by sulfated polysaccharides. These compounds were characterized by colorimetric methods and was observed that the Lambda carrageenan shown the greater value (33.38%) of sulfate. These polymers were examined by means of 13C NMR spectroscopy and infrared spectra. The polysaccharides consisted mainly of units alternating of sulfated galactoses and anhydrogalactoses. The aim of the study was also to test the inflammatory action of these different polysaccharides. A suitable model of inflammation is acute sterile inflammation of the rat hind limb induced by carrageenan. Paw edema was induced by injecting carrageenans (κ, ι and λ) in saline into the hind paw of a male Wistar rats (175–200 g). The pathway to acute inflammation by carrageenan (kappa, iota and lambda) were expressed as time-edema dependence and measured by paw edema volume. For this purpose, was used an apparatus (pakymeter), which makes it possible to measure the inflammation (swelling of the rat foot) with sufficient accuracy. The results showed that κ-carrageenan (1%) have an edema of 3.7 mm and the paw edema increase was time and dose dependent; the ι-carrageenan (0.2%) caused an edema of 4 mm and the λ-carrageenan (1%) caused an edema of 3.6 mm. Other model was used in this study based in the inflammation of pleura for comparatives studies. Injection of carrageenans into the pleural cavity of rat induced an acute inflammatory response characterized by fluid accumulation in the pleural cavity, a large number of neutrophils and raised NO production. The levels of NO were measured by Griess reactive. The ι-carrageenan caused the greater inflammation, because it has high concentration of nitrite/nitrate (63.478 nmoles/rat), exudato volume (1.52 ml) and PMNs (4902 x 103 cells). Quantitative evaluation of inflammations of rats is a useful and important parameter for the evaluation of the efficacy of anti-inflammatory drugs

Efeitos da dieta hipoprotéica na formação e composição de estruturas dentárias. Estudo Experimental em ratos wistar

Protein and caloric malnutrition has been considered one of the most concerned endemic diseases in Brazil and in the world. It has been known that depletion or reduction of proteins as far as meals are concerned can steer irreversible damages upon several organic systems. This study had as aim evaluate the effects the low-protein diet had over the formation and composition of the teeth components. 18 females and 6 males were used for the experiment. 12 from the 18 females had undertaken the low-protein diet (DH) for 03 weeks and the other 6, which remained, and those males had undertaken a controlled diet (DC) for the same period. All animals had the diets during their mating, pregnancy and lactation cycle. As soon as the offsprings had been born, 10 young males and females of each group faced a disease hood analysis to check the teeth germs of their lower fore teeth. The rest of the group had their lactation cycle normally 60 days. Then they were put to death and had their lower fore teeth removed both to be analyzed through a scanning electronic microscopy (SEM) of the structure alterations and to have their calcium checked by an atomic absorption of the phosphorus vanadate-molibdate method and by other minerals EDX method. The animals livers were removed to have their hepatic proteins analyzed as well. The histopatologic study showed that at first day of birth, all animals had their lower fore teeth come out. It was verified that 90% of the animals teeth were in an apposition and calcification period and it was possible to observe the dentin formation from 60% of the 90% already mentioned. Through the SEM method it could be realized that 90% of the animals of the DH group had their lower fore teeth easily broken and no definite shape. In this same group itself, it was also observed long micro fissures 369,66 nm ± 3,45 while the DC group had fissures of 174 nm ± 5,72. Now regarding the calcium and phosphorus concentration, it could be noticed that there was a great reduction of these components and other minerals in the DH group. Almost all minerals, except for the Cl and K, presented higher levels in the DC group enamel.The reduction of the protein input greatly influenced the offsprings´ weight and height. However the hepatic proteins had no important difference between the groups what can make one believe that those animals suffered from protein malnutrition of marasmic kind

Efeito de preparações de produtos naturais (cravo da índia e tomate) e de um produto sintético na marcação de constituintes sangüineos com tecnécio-99m e na morfologia de hemácias isoladas de sangue de ratos wistar

There are strong interests in the evaluation of the biological effects of natural and synthetic products. Blood constituents labeled with technetium-99m (99mTc) are used in nuclear medicine. The aim of this work was to study the effects of Clove (Caryophyllus aromaticas L.) and OZE (preparation used in the Health Sciences) on the labeling blood constituents with 99mTc and on the morphologic red blood cells (RBC) and the action of an extract of tomato (TO) on the labeling of blood constituents Blood samples were incubated with clove or OZE or TO, stannous chloride and 99mTc. Plasma (P), blood cells (BC), insoluble fractions (IF) of plasma and blood cells were separated. The radioactivity was counted and percentage of radioactivity (%ATI) to each blood fraction was calculated. The shape and morphometric parameter (perimeter/area ratio) were evaluated in the studies with clove and OZE. Clove extract and OZE altered significantly (p<0.05) the %ATI of blood constituents and the shape of red blood cells. However, clove extract not altered the red blood cells perimeter/area ratio. The tomato extract used at the highest concentrations reduced significantly (p<0.05) the %ATI in IF-P, although this extract did not modify the radiolabeling on BC, neither the radioactivity fixation on IFBC. The results indicate that these chemical compounds would have oxidative/chelating actions

Efeitos de um extrato aquoso de buzhong yi qi wan (fórmula magistral chinesa) na marcação de constituintes sanguíneos com tecnécio-99m, na morfologia e na fragilidade osmótica de hemácias de ratos Wistar

Technetium-99m (99mTc) has been used to obtain several radiobiocomplexes utilized to aid in the diagnosis of diseases. Blood constituents, as red blood cells (RBC) and plasma proteins, have been labeled with 99mTc. Natural and synthetic drugs can alter the labeling of these constituents. The aim of this work was to investigate the possibility of a Buzhong YiQi Wan extract to alter (i) the labeling of blood constituents with 99mTc, (ii) the RBC morphology, and (iii) osmotic fragility of RBC withdrawn from Wistar rats. The data showed that the BYQW extract (i) could affect labeling of blood constituintes with 99mTc, (ii) could affect the membrane integrity decreasing the osmotic resistance and (iii) could not alter the shape of RBC. Probably, these findings would be associated with properties of the substances present in the aqueous extract of BYQW. This study has multiple disciplinary aspects in knowledge areas: Radiobiology, Botanic, Phytotherapy and Haematology

Biodistribuição de samário -153- EDTMP em ratos TRATADOS com docetaxel

A dor óssea decorrente das metástases é um sintoma comum nos tumores avançados de mama e próstata. Nenhuma opção terapêutica isolada é completamente eficaz, e uma série de modalidades costuma ser empregada, entre eles a terapia com radiofármacos, como o samário153-etilenodiaminatetrametileno fosfonato (EDTMP-153Sm). O docetaxel, um taxano com ação sobre tumores avançados de mama e próstata, tem-se apresentado como uma nova opção de tratamento quimioterápico. Muitos pacientes fazem uso simultâneo de EDTMP-153Sm e docetaxel. Este estudo procurou avaliar a influência do docetaxel na biodisponibilidade de EDTMP-153Sm em ratos Wistar, aleatoriamente alocados em 2 grupos de 6 animais cada. O grupo DS (docetaxel/samário) recebeu docetaxel (15 mg/kg) intraperitoneal em dois ciclos com 11 dias de intervalo. Os ratos do grupo S (samário/controle) não foram tratados com docetaxel. Nove dias após a quimioterapia, todos os animais receberam 0.1ml de EDTMP-153Sm via plexo orbital (25μCi). Após 2 horas, os animais foram mortos, e realizaram-se análises de amostras de cérebro, tireóide, pulmão, coração, estômago, cólon, fígado, rim e fêmures. O percentual de radioatividade por grama (%ATI/g) de tecido de cada biópsia foi determinado em contador gama automático (Wizard-1470, Perkin-Elmer, Finland). No 9º dia após 2º ciclo de docetaxel, os ratos tiveram perda de peso significante, passando de 353.66± 22.8g (controle/pré-tratamento) para 314,50±22,09g (p<0.5). Os %ATI/g nos órgãos dos ratos tratados com EDTMP- 153Sm e docetaxel tiveram redução significante nos fêmures direito e esquerdo, rim, fígado e pulmão, quando comparados aos animais não tratados com docetaxel. Em conclusão, a combinação de docetaxel com EDTMP-153Sm foi associada à menor concentração do radiofármaco em órgãos alvo. Futuras investigações sobre o impacto do docetaxel na biodisponibilidade do EDTMP- 153Sm poderão complementar estes achados. Deve-se ressaltar o caráter multidisciplinar deste estudo, que contou com a participação ativa e com a troca constante de conhecimentos entre profissionais das áreas de Medicina Nuclear, Cirurgia, Oncologia, Biologia e Estatística

Avaliação de efeitos de um extrato aquoso de cinnamomum zeylanicum L. na marcação de constituintes sanguíneos com tecnécio-99m e na morfologia das hemácias de ratos wistar

Radiobiocomplexes are used to obtain images in nuclear medicine and employed in basic research. Blood constituents labeled with technetium-99m (99mTc) have also been employed as radiobiocomplexes and used also experimental model for evaluation of the biological effects of natural or synthetic drugs. The analysis of the morphology and the morphometrics parameters (perimeter/área ratio) can be used to evaluate the effects of drugs upon the structure of the membrane of red blood cells. Cinnamomum zeylanicum (cinnamon) is a spice used as herbal medicine to treat diseases. The aim of this study was to evaluate the effect of in vitro and in vivo treatment with an aqueous cinnamon extract on the labeling of blood constituents with 99mTc and on the morphology of red blood cells from Wistar rats. In the in vitro treatment, isolated blood sample from animals were incubated with cinnamon extract. In the in vivo treatment, blood samples were also withdrawn from animals treated with cinnamon extract. In both cases, the radiolabeling of blood constituents was done. The morphological analysis of red blood cells was also done. As control, blood or animals treated with NaCl 0.9%. The data obtained on the labeling of blood constituents with 99mTc experiments indicated that the in vitro treatment with cinnamon extract was capable to decrease signiicantly (p<0.05) the percentage of radioactivity in cellular compartments and on the fixation of cellular and plasma proteins. These effects were not observed on the in vivo treatment. The results obtained for the morphology of red blood cells suggest that the in vitro and in vivo treatments did not alter the morphology and the perimeter/area ratio. The in vitro treatment with aqueous cinnamon extract could affect the membrane structures related with the oxidation status of the stannous ion pertechnetate ion, altering the labeling of blood constituentes with 99mTc. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade do Estado do Rio de Janeiro

Efeitos de um extrato aquoso de lantana camara (Cambará de espinho) na marcação de constituintes sanguíneos com técnecio-99m e na morfologia de hemácias de ratos-wistar

Medicinal plants have been studied and used in the world. Lantana camara has medicinal properties and it has been used in folk medicine. The aim was to verify the effect of a lantana extract on the labeling of blood constituents with 99mTc, and to evaluate the effect of an aqueous extract of Lantana camara on the morphology of RBC withdrawn from Wistar rats. The results showed that lantana extract has decreased the fixation of radioactivity on the IF-P. This effect was not observed in the BC compartment and in IF-BC. The BC-%ATI was decreased in all concentrations tested when the BC was washed. The osmotic fragility assay and morphological analysis were carried out. In presence of the extract, the data obtained indicated that (i) an increase of the hemolysis and (ii) modifications on the morphology of RBC. These effects of the Lantana camara could be associated with some pharmacological properties of the chemical compounds of this studied extract

Efeito do sildenafil na lesão renal por isquemia-reperfusão em ratos

A lesão renal causada pelo processo isquemia-reperfusão ocorre em várias intervenções cirúrgicas, como transplantes de rins, cirurgias vasculares renais e na nefrectomia parcial. Devido ao processo isquêmico, ocorre disfunção do órgão e morte celular. Com o objetivo de avaliar o efeito do sildenafil, em ratos, administrado previamente à isquemia renal e reperfusão, em avaliações cintilográficas e histopatológicas, foram utilizados vinte e quatro ratos Wistar, aleatoriamente distribuídos em dois grupos. Os animais receberam 0,1 ml IV 99mTecnécio-Etilenodicisteína, realizando-se a cintilografia renal inicial e, em seguida, foram submetidos à laparotomia, provocando-se isquemia no rim esquerdo, com oclusão da artéria renal, durante 1 hora, com posterior reperfusão. Os animais do grupo sildenafil receberam previamente 1mg/kg de sildenafil via oral, 60 minutos antes da isquemia. O grupo controle recebeu somente solução salina. Após a isquemia e reperfusão, metade dos animais de cada grupo foi avaliada com 24 horas e a outra metade, com sete dias, com nova cintilografia renal. Após eutanásia, com superdose de anestésico, os rins foram retirados e submetidos a exame histopatológico. Empregou-se avaliação estatística com o teste t de Student e com teste não-paramétrico de Mann-Whitney. Foi observado no rim esquerdo do grupo controle um déficit funcional nas imagens cintilográficas, após sete dias, comparativamente ao respectivo estudo cintilográfico inicial (p<0,05). Nos rins esquerdos dos animais do grupo controle (24 horas pós-isquemia), ocorreu um maior grau de necrose celular quando comparados ao grupo tratado com o sildenafil (p<0,05). A cintilografia e a histopatologia demonstraram que o sildenafil exerceu ação protetora dos rins, após episódio de isquemia-reperfusão renal normotérmica. Deve ressaltar-se o x caráter interdisciplinar desta tese, que contou com a participação ativa de profissionais das áreas de cirurgia, medicina nuclear, urologia, patologia e estatística

Estudo de efeitos de um extrato de Arctium lappa (Bardana) na marcação dos constituintes sangüíneos com Tecnécio-99m, na biodisponibilidade do radiofármaco pertecnatato de sódio e na morfologia de hemácias de ratos Wistar

Radionuclides have been used in Nuclear Medicine for diagnostic and treatment. In basic research, cellular and molecular structures are labeled with technetium-99m (99mTc) and used as radiobiocomplexes. Some natural or synthetic drugs are capable to alter the labeling of blood constituents with 99mTc, as well as in the biodistribution of radiobiocomplexes. Arctium lappa (Bardana) has been used to treat inflammatory processes. The aim of this work was to evaluate the effects of an extract of Bardana on the labeling of blood constituents with 99mTc, on the morphology of red blood cells, on the perimeter/area ratio of red blood cells and on the biodistribution of radiophamaceutical sodium pertechnetate in Wistar rats. Extract of Bardana was capable to alter the labeling of cellular compartment with 99mTc. Plasma and cellular proteins did not present alteration on the percentage of radioactivity (%ATI). Extract of Bardana was also capable to alter the morphology and the perimeter/area ratio of red blood cells. On the biodistribution of sodium pertechnetate in animals treated with the extract of Bardana, it was observed a small and significant uptake in liver, tooth and tongue, and a high and a significant uptake in stomach, lung and testis (p<0.05). In conclusion, these findings could be justified due to the effects of some chemical compounds in the Bardana extract. This study was a multidisciplinary experimental research. It was developed with the contribution of the different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade Estadual do Rio de Janeiro

Estudo de efeitos de um extrato aquoso de farinha de casca de maracujá (Passiflora edulis f. flavicarpa) na marcação de constituintes sangüíneos com Tecnécio 99m, na morfometria das hemácias e na biodisponibilidade do radiofármaco Pertecnetato de Sódio em ratos Wistar

Blood constituents labelled with technetium-99m (99mTc) has been used with radiobiocomplexes in several procedures in nuclear medicine. Some natural and sintetic drugs are capable to interfere on the labeling of blood constituents with 99mTc, on the morphology of red blood cells (RBC) and on the biodistribution of radiobiocomplexes. The aim of this study was evaluate the effect of an extract of Passiflora edulis f. flavicarpa on the labeling of blood constituints with 99mTc, on the morphology of RBC and on the biodistribution of the radiopharmaceutical sodium perthecnetate in Wistar rats. On the in vitro studies the Passiflora edulis f. flavicarpa decreased significantly (p<0.05) the %ATI on plasma proteins and on the in vitro morhology of RBC, the passion fruit peel flour altered the shape and the perimeter/área ratio. On the in vivo estudies the extract did not altered the %ATI in blood constituents, and did not altered the shape of RBC. Although, on the biodistribution of the radiobiocomplex sodium perthecnetate (Na99mTcO4) this extract decreased significantly (p<0.05) the uptake in duodenum, spleen, pâncreas and blood, and increased the uptake in stomach. It can be suggested that the effects presented by this extract could be a result of some substances contained in this extract that could alter the binding of 99mTc to plasma proteins, the morphology of RBC and the biodistribution of the radiobiocomplex sodium perthecnetate. This study was multidisciplinary experimental research. It was developed with the contribution of different Departments and Services of the Hospital Universitário Pedro Ernesto of the Universidade Estadual do Rio de Janeiro

Avaliação do efeito de um adoçante comercial com sucralose na marcação de constituintes sanguíneos com tecnécio-99m, na morfologia das hemácias e na biodisponibilidade dos radiofármacos pertecnetato de sódio e ácido dietilenotriaminopentacético-tecnécio-99m em ratos Wistar.

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Efeito de um extrato de Artemísia Vulgaris L. marcação in vitro de constituintes sanguíneos com tecnécio-99m em ratos wistar

Artemisia vulgaris L..is used in folk medicine and in Traditional Chinese Medicine (TCM). This medicinal plant has been utilized as anticonvulsive, analgesic, antispasmodic effect, rheumatic pains, menstrual dyspepsia, asthenia, epilepsy, hepatitis, fevers, anemia and to expel parasites. In nuclear medicine, blood constituents are labeled with technetium-99m (99mTc) and used as radiopharmaceuticals (radiobiocomplexes). Authors have been described that synthetic and/or natural drugs could modify the labeling of blood constituents with 99mTc. The aim of this work was to evaluate the effects of an aqueous extract of Artemisia vulgaris L. on the labeling of blood constituents with 99mTc. Blood samples withdrawn of Wistar rats were incubated with Artemisia vulgaris L, stannous chloride and 99mTc, as pertechnetate ion. Aliquots of plasma (P) and blood cells (BC) were isolated. Aliquots of P and BC were also precipitated with trichloroacetic acid and soluble (SF) and insoluble (IF) fractions were separated. The radioactivity in each fraction was counted and the percentages of radioactivity (%ATI) were calculated. Artemisia vulgaris L. extract decreased significantly (p<0.05) the %ATI on BC and on IF-BC. The analysis of the results indicates that the extract could have substances that could interfere on the transport of stannous through the erythrocyte membrane altering the labeling of blood cells with 99mTc. Working in this study was a multidisciplinary group, with Phisical therapists, Biomedicals, Physicals, Pharmacists, Biologists, Statistics and Physicians.

Emprego dos ácidos graxos de cadeia curta na colite de derivação fecal : estudo em ratos Wistar

Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, after a colostomy. It is postulated that nutritional deficiency of the colonic epithelium by the absence of short-chain fatty acids (SCFA) is one of the factors responsible for the appearance of DC and that their employment could reverse the morphological changes of the mucosa. The treatment of choice for fecal diversion colitis (DC) is the reconstruction of the intestinal tract, although they suggested therapeutic options using enemas. This study evaluates the effect of SCFA in atrophy and inflammation in excluded colonic segments before and after the installation DC. Forty Wistar rats were divided into four groups (n = 10 for each group), submitted colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after postoperative day 40), for 07 days. Histological sections stained with HE were used for histological analysis of the thickness of the colonic mucosa excluded (t- Student p ≤0.05). Inflammatory reaction of the lamina propria and mucosa were measured with scores previously established (Mann Whitney p ≤ 0.05). There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 did not prevent the mucosal atrophy and significant increases in the numbers of lymphocytes (p=0.0006) and 50 eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy