Offspring of streptozotocin diabetic rats: size changes in Langerhans islets with time after birth.

It has been demonstrated that, in the diabetic rat, pregnancy and lactation are severely altered: in this study, we have measured the size of Langerhans islets of rat pups, the offspring of experimental diabetic mothers and nondiabetic controls. Diabetes was induced through streptozotocin administration (dose, 60 mg/kg body wt.). This drug was injected in every animal; their blood sugar was measured 1 week later (Haemo-Glukotest, Boehringer Mannheim), and they were then separated into three groups according to their fasting blood sugar levels: (a) severe diabetics (above 16.5 mM/l); (b) mild diabetics (6.5-16.5 mM/l); and (c) nondiabetic normals. They received insulin therapy (2-4 I.U./day) as the mild diabetics exhibited a slightly higher than normal fasting blood sugar, and the diabetic ones, above 15 mM/l. The areas of Langerhans islets of pups were measured 1 and 5 days after parturition; pancreas sections were dyed (haematoxylin-eosin) and morphometry was then performed using a digitalized magnetic tabloid connected to a Zeiss Morphomat 30 (Kontron). On the first day after parturition, the pancreas section areas in pups from mildly and severely diabetic mothers were smaller than those in neonates from nondiabetic controls (P < 0.001). The areas in neonates from severely diabetic mothers showed a more intense decrease than those from mildly diabetic animals (P < 0.01). On day 5 after delivery, the areas of Langerhans islets in offspring from normal mothers decreased and those in pups from diabetic mothers tended to normalize (P < 0.01), particularly those from the severely sick group (P < 0.01). We conclude that after parturition the offspring is no longer exposed to the high blood sugar levels found in both diabetic groups of mothers, thereby no hyperinsulinemia is needed; as time elapses, then, the area of their Langerhans islets tends to normalization.

Influence of pirenzepine on colonic serotonin changes induced by short chain fatty acid.

In this work we have demonstrated the influence of a short chain fatty acid (acetate) on the number of enterochromaffin (EC) cells containing serotonin (5HT), at two different pH (pH 6.9 absorptive stimuli, and pH 2.9 secretory stimuli), infused into the colon during one hour. The number of EC cells decrease significatively, specially in the cecum with a solution of low pH (2.9). The action of piprenzepine in preventing this reduction demonstrated that was partly mediated by a cholinergic receptor mechanism. On the other hand, a decrease on the release of 5HT to the lumen was a observed under the influence of pirenzepine. We conclude that the short chain fatty acid acetate, at a low pH induces the release of serotonin through a cholinergic mechanisms indicated by the inhibition observed with antimuscarinic drug.

Influence of pirenzepine on colonic serotonin changes induced by short chaim fatty acid

En este trabajo hemos la influencia de un ácido graso de cadena corta (acetato) sobre el número de células enterocromafines (EC) conteniendo serotonina (5HT) a dos diferentes pH (pH 6.9, estímulo absortivo y pH 2.9 estímulo secretor) infundido durante una hora en el colon. El número de células EC disminuye significativament con una solución infundida a pH 2.9, especialmente en el ciego. La acción de la pirencepina en prevenir esta reducción demuestra que el mecanismo se efectúa parcialmente a través de receptores colinérgicos. Por parte, se observa una disminución de la liberación de 5HT, a través de un mecanismo colinérgico, como lo indica la inhibición observada con la droga antimuscarínica

Influence of pirenzepine on colonic serotonin changes induced by short chain fatty acid.

In this work we have demonstrated the influence of a short chain fatty acid (acetate) on the number of enterochromaffin (EC) cells containing serotonin (5HT), at two different pH (pH 6.9 absorptive stimuli, and pH 2.9 secretory stimuli), infused into the colon during one hour. The number of EC cells decrease significatively, specially in the cecum with a solution of low pH (2.9). The action of piprenzepine in preventing this reduction demonstrated that was partly mediated by a cholinergic receptor mechanism. On the other hand, a decrease on the release of 5HT to the lumen was a observed under the influence of pirenzepine. We conclude that the short chain fatty acid acetate, at a low pH induces the release of serotonin through a cholinergic mechanisms indicated by the inhibition observed with antimuscarinic drug.

Influence of pirenzepine on colonic serotonin changes induced by short chaim fatty acid

En este trabajo hemos la influencia de un ácido graso de cadena corta (acetato) sobre el número de células enterocromafines (EC) conteniendo serotonina (5HT) a dos diferentes pH (pH 6.9, estímulo absortivo y pH 2.9 estímulo secretor) infundido durante una hora en el colon. El número de células EC disminuye significativament con una solución infundida a pH 2.9, especialmente en el ciego. La acción de la pirencepina en prevenir esta reducción demuestra que el mecanismo se efectúa parcialmente a través de receptores colinérgicos. Por parte, se observa una disminución de la liberación de 5HT, a través de un mecanismo colinérgico, como lo indica la inhibición observada con la droga antimuscarínica (AU)

Action of cisapride on rat colonic secretion.

The stimulating effect of cisapride on the motility of the digestive tract is well known. However, there are only a few studies on the influence of this drug on the absorptive or secretory activity of the colonic mucosa. In the present study, the ability of cisapride to alter the mural transport of water and electrolytes in the colon and its effects on mucus secretion and albumin permeation were studied. The effects of cisapride on the rat colon in vivo were studied under different conditions, by means of an instillation of sodium acetate solution at pH 6.9, which induced absorption of water and electrolytes, and in two models of colonic secretion, one employing the instillation of an acetic acid solution at pH 2.9 and the other, an intravenous infusion of 5-hydroxytryptamine (serotonin) 45 micrograms.kg-1.min-1 together with intracolonic instillation of sodium acetate. Cisapride (i.v.), at a dose of 0.32 mg.kg-1, in rats whose colon was instilled with sodium acetate (pH 6.9) induced an increase in sodium absorption and a reduction in water absorption. Cisapride (i.v.), at doses of 0.32, 0.64 and 1.0 mg.kg-1, inhibited the secretion of water, Na+, Cl-, and mucus and the permeation of albumin induced by acetic acid instillation or by serotonin infusion. It is concluded that the effect of cisapride on the colonic mucosa varies in accordance with the functional mucosal conditions and that this action may be of clinical importance.

Ulex europeus agglutinin I binding pattern during chemical carcinogenesis in the rat gastrointestinal tract.

BACKGROUND: Fluorescein isothiocyanate-Ulex europeus agglutinin I stain (UEA1) was postulated as a prominent histochemical marker for premalignant mucosa in dimethylhydrazine (DMH)-treated animals. UEA1 (evaluated by two scanning methods) and high iron diamine Alcian blue (HIDAB) stain were used in attempt to detect premalignant colonic mucosa in this animal model. The authors also examined the influence of the duodenal medium on colonic segments transposed to the upper gastrointestinal tract. METHODS: Rats were placed into three groups: those with interposed intestine, those receiving the sham operation, and controls. Half of the animals received DMH, and surviving rats were killed at 2, 4, and 8 months. RESULTS: The authors found no differences in tumor development in the transposed and nontransposed colons of animals treated with DMH. Several transposed segments of animals without carcinogen induction showed dysplastic areas. These findings suggest a trophic role of certain duodenal factors in the epithelial kinetics of the transposed colons. The authors did not find HIDAB stain useful in the identification of premalignant colonic mucosa. The quantitative evaluation method of UEA1 binding was more reliable. Fifteen percent of all the colon specimens of animals without chemical induction were stained with UEA1 with this form of evaluation. Positive staining of the interposed colon samples was the most important factor for these findings. CONCLUSIONS: In this animal model, UEA1 staining is a potentially useful marker of premalignant mucosa, particularly when the nontransposed distal colon of animals treated with DMH is considered.

Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina / Influence of sodium butyrate intake on murine colonic carcinogenesis

El papel de los ácidos grasos de cadena corta (AGCC) en la carcinogénesis colónica murina (CCM) no fue aclarado. Evaluamos el efecto de la hemicolectomía derecha (HCD) (colon derecho, fuente de AGCC) y de la ingesta en agua de bebida de butirato de sodio (Buti.Na) al 2 por ciento a pH 7 o de cloruro de sodio (CINa) 4g/l, en la CCM. Formamos 7 grupos de 12 ratas Wistar macho de 150 g: HCD, Buti. Na, CINa, control (C). La mitad recibió dimetilhidrazina (DMH) 20 mg/Kg subucutánea semanal durante 12 semanas. La necropsia fue realizada a los 6 meses. Determinamos el contenido de AGCC en materia fecal por cromatografía gaseosa. El 70 por ciento de las ratas con DMH desarrolló tumor. El nº de animales con tumor, por grupo fue: HCD 4/6, Buti.Na 4/6, CINa 3/5, C 6/6. El nº de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 3/5, C 6/6. El nº de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 1,50 ñ 0,76, ClNa 1,20 ñ 0,49, C 1,50 ñ 0,22. El grupo Buti.Na (DMH) presentó una concentración significativamente menor de butirato (p < 0,05) en relación a los demás grupos. En conclusión, el suplemento en agua de bebida de Buti.Na, CINa y la HCD redujeron en forma no significativa la CCM, con este número de animales (AU)

Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina / Influence of sodium butyrate intake on murine colonic carcinogenesis

El papel de los ácidos grasos de cadena corta (AGCC) en la carcinogénesis colónica murina (CCM) no fue aclarado. Evaluamos el efecto de la hemicolectomía derecha (HCD) (colon derecho, fuente de AGCC) y de la ingesta en agua de bebida de butirato de sodio (Buti.Na) al 2 por ciento a pH 7 o de cloruro de sodio (CINa) 4g/l, en la CCM. Formamos 7 grupos de 12 ratas Wistar macho de 150 g: HCD, Buti. Na, CINa, control (C). La mitad recibió dimetilhidrazina (DMH) 20 mg/Kg subucutánea semanal durante 12 semanas. La necropsia fue realizada a los 6 meses. Determinamos el contenido de AGCC en materia fecal por cromatografía gaseosa. El 70 por ciento de las ratas con DMH desarrolló tumor. El n§ de animales con tumor, por grupo fue: HCD 4/6, Buti.Na 4/6, CINa 3/5, C 6/6. El n§ de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 3/5, C 6/6. El n§ de tumores promedio por animal, por grupo fue: HCD 1,17 ñ 0,48, Buti.Na 1,50 ñ 0,76, ClNa 1,20 ñ 0,49, C 1,50 ñ 0,22. El grupo Buti.Na (DMH) presentó una concentración significativamente menor de butirato (p < 0,05) en relación a los demás grupos. En conclusión, el suplemento en agua de bebida de Buti.Na, CINa y la HCD redujeron en forma no significativa la CCM, con este número de animales

[Influence of sodium butyrate intake on murine colonic carcinogenesis]. / Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina.

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2%-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70% of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of different lactic acid isomers in the colon of rats]. / La acción de los diferentes isómeros del acido láctico en el colón de la rata.

Depending on quantity and/or quality, the presence of lactic acid in the colonic lumen may be associated with metabolic damage of the colon. The influence exerted on the rat colon by the different isomers and racemic of the lactic acid, used at two extreme dilutions (20 and 100 mEq/l), has been the subject of study in this paper. The modifications on pH, water and electrolytes are associated with the absorptive/secretory action of the colonic wall. In addition, a study has been made on the influence of lactic acid on the colonic mucus and albumin permeation. Histopathologic studies of the caecum and left colon have been performed. There is a different colonic wall behaviour for each of the different isomers of the lactic and its racemic; a larger absorption of water, Na+ and Cl- for the D (-) isomer at a low concentration; its behaviour is completely opposite at high concentration. The final pH is higher when the D (-) isomer takes part; comparing the different isomers, there are small variations as far as albumin permeation is concerned. At high concentration there is a decline in Cl- absorption. The high percentage of erosions that take place especially in the caecum, where L (+) isomer can be found at high concentration, it is remarkable. The present observations suggest that the presence of lactic acid in (the) ulcerative colitis deserves great attention, especially in about the quantity and quality in which the acid can be found.

La acción de los diferentes isómeros del acido láctico en el colón de la rata / The action of different lactic acid isomers in the colon of rats

La presencia de ácido láctico en la luz colónica según su calidad y/o cantidad, puede asociarse con un daño metabólico del colonocito. En este trabajo se estudio la influencia de los diferentes isómeros del ácido lático y su recêmico en dos concentraciones extremas (20 y 100 mEq/l) en la luz colônica de la rata. Las modificaciones sobre el pH, el agua y los electrólitos se asociaron con la acción absortivo secretora de la pared colónica. Por otro lado se determinó la influencia del ácido láctico sobre el mucus colônico y la permeación de albúmina. Se efectuó el estudio histopatológico del ciego y del colon izquierdo. Se demuestra que existen diferencias en el comportamiento de la pared colónica frente a los distintos isómeros y al recémico del ácido láctico; (una) mayor absorción de agua, Na+ y Cl- para el isómero D(-) a baja concentración; comportándose en forma opuesta a altas concentraciones. El pH final es más alto con la forma D(-), no habiendo grandes variaciones en la permeación de albunina entre los diferentes isómeros. A altas concentraciones se frena la absorción de Cl-. Llama la atención el porcentaje alto de erosiones especialmente en el ciego dondo se halla el isómero (+) a alta concentración. Las presentes observaciones sugieren que la presencia de ácido láctico en la colitis ulcerosa merece mayor atención sobretudo en determinar la cantidad y calidad del mismo

La acción de los diferentes isómeros del acido láctico en el colón de la rata / The action of different lactic acid isomers in the colon of rats

La presencia de ácido láctico en la luz colónica según su calidad y/o cantidad, puede asociarse con un daño metabólico del colonocito. En este trabajo se estudio la influencia de los diferentes isómeros del ácido lático y su recÛmico en dos concentraciones extremas (20 y 100 mEq/l) en la luz col¶nica de la rata. Las modificaciones sobre el pH, el agua y los electrólitos se asociaron con la acción absortivo secretora de la pared colónica. Por otro lado se determinó la influencia del ácido láctico sobre el mucus col¶nico y la permeación de albúmina. Se efectuó el estudio histopatológico del ciego y del colon izquierdo. Se demuestra que existen diferencias en el comportamiento de la pared colónica frente a los distintos isómeros y al recémico del ácido láctico; (una) mayor absorción de agua, Na+ y Cl- para el isómero D(-) a baja concentración; comportándose en forma opuesta a altas concentraciones. El pH final es más alto con la forma D(-), no habiendo grandes variaciones en la permeación de albunina entre los diferentes isómeros. A altas concentraciones se frena la absorción de Cl-. Llama la atención el porcentaje alto de erosiones especialmente en el ciego dondo se halla el isómero (+) a alta concentración. Las presentes observaciones sugieren que la presencia de ácido láctico en la colitis ulcerosa merece mayor atención sobretudo en determinar la cantidad y calidad del mismo (AU)

Influencia de la ingesta de butirato de sodio en la carcinogénesis colónica murina. / [Influence of sodium butyrate intake on murine colonic carcinogenesis]

The role of short chain fatty acids (SCFA) in murine colonic carcinogenesis (MCC) has not yet been clarified. In rats, Freeman et al have reported an increased number of colonic tumors induced with dimethylhydrazine (DMH) and sodium butyrate in drinking water. On the other hand, Deschner et al showed that tributyrin intake did not increase MCC induced with azoxymethane. Both of them have reported high levels of fecal butyric acid with sodium butyrate and tributyrin intake. Although salt intake has been positively associated with colorectal cancer some authors do not support this association. We have evaluated the influence of right hemicolectomy (RH) (right colon as main source of SCFA) and the intake of 2

-pH 7 sodium butyrate (S.BUT) and 4 g/l sodium chloride (S.CHL) in drinking water, in MCC. Forty eight male Wistar rats weighing 150 g were divided into 4 groups: RH, S.BUT, S.CHL, control (C). Half of the animals received weekly DMH 20 mg/kg subcutaneously for 12 weeks. Necropsy was performed after 6 months. We have determined fecal SCFA content by gas chromatography. Neoplasm was present in 70

of rats treated with DMH. The number of animals with tumors was: RH 4/6, S.BUT 4/6, S.CHL 3/5, C 6/6. Tumor frequency was: RH 1.17 +/- 0.48, S.BUT 1.50 +/- 0.76, S.CHL 1.20 +/- 0.49, C 1.50 +/- 0.22. S.BUT group, treated with DMH, presented a lower butyric acid concentration (p < 0.05) in comparison with other groups. We have no explanation for this finding; gastric absorption of sodium butyrate may be an important factor.(ABSTRACT TRUNCATED AT 250 WORDS)

La acción de los diferentes isómeros del acido láctico en el colón de la rata. / [The effect of different lactic acid isomers in the colon of rats]

Depending on quantity and/or quality, the presence of lactic acid in the colonic lumen may be associated with metabolic damage of the colon. The influence exerted on the rat colon by the different isomers and racemic of the lactic acid, used at two extreme dilutions (20 and 100 mEq/l), has been the subject of study in this paper. The modifications on pH, water and electrolytes are associated with the absorptive/secretory action of the colonic wall. In addition, a study has been made on the influence of lactic acid on the colonic mucus and albumin permeation. Histopathologic studies of the caecum and left colon have been performed. There is a different colonic wall behaviour for each of the different isomers of the lactic and its racemic; a larger absorption of water, Na+ and Cl- for the D (-) isomer at a low concentration; its behaviour is completely opposite at high concentration. The final pH is higher when the D (-) isomer takes part; comparing the different isomers, there are small variations as far as albumin permeation is concerned. At high concentration there is a decline in Cl- absorption. The high percentage of erosions that take place especially in the caecum, where L (+) isomer can be found at high concentration, it is remarkable. The present observations suggest that the presence of lactic acid in (the) ulcerative colitis deserves great attention, especially in about the quantity and quality in which the acid can be found.

Effect of ethanol intake on pancreatic exocrine secretion in mice.

Swiss mice were fed conventional lab chow and 10% ethanol or water as drinking fluid for 2 weeks. Pancreatic juice was obtained by cannulation of the bile pancreatic common duct of mice anesthetized with urethane. Isolated pancreatic lobules were also obtained. The flow rate and the amylase output were determined in pure pancreatic juice. The release of amylase was measured in pancreatic lobule preparations. The basal pancreatic juice flow rate and the amylase output were significantly increased by ethanol consumption. The magnitude of the pancreatic juice flow rate and the amylase output responses to increasing doses of bethanechol, a cholinergic agent, was significantly decreased in ethanol-fed mice. The amount of spontaneously released amylase was higher in pancreatic lobule preparations from ethanol-fed animals than that from control mice, and the difference was abolished by addition of atropine to the incubation media. The amylase release rate in response to increasing doses of bethanechol was significantly reduced in lobule preparations from the ethanol-fed group. These data indicate that ethanol intake in mice has a stimulating effect on the spontaneous pancreatic secretion and lends support to the hypothesis that ethanol consumption increases the intrapancreatic cholinergic tone.

Influence of VIP on the number of enterochromaffin and mucosal mast cells in the colon of the rat.

The possibility that VIP (Vasoactive intestinal peptide) could influence the enterochromaffin (EC) cell secretion of serotonin (5HT) and the action of VIP on the mast cell population of lamina propria were investigated in Wistar rat colon infused with a short chain fatty acid solution (sodium acetate), during a 1 h period. Under the action of an intravenous injection of synthetic porcine VIP, 14 micrograms/kg/h), the number of EC cells diminished significantly in the cecum and left colon, when compared to non-injected animals, both infused with a sodium acetate solution. At the same time, the number of mucosal mast cells in the crypts and lamina propria decreased significantly in the cecum. The postulate we put forward is that these VIP-induced changes are exerted through the stimulation of 5HT released from EC cells not only under normal physiological conditions but probably also under pathological conditions.