A potyclonal antibody against rat intestinal‐type alkaline phosphatase (I‐ALP) was generated and proven to be applicable immunohistochemically to paraffin‐embedded sections. Expression of I‐ALP in normal tissues, intestinal metaplasia and stomach tumors induced by N‐methyl‐N′‐nitro‐N‐nitroso‐guanidine (MNNG) was then investigated in five different strains of rats. Male SD (Crj:CD), Lewis (LEW/Crj), WKY (WKY/NCrj), Wistar (CrjrWistar) and F344 (F344/DuCrj) animals were given drinking water containing 100/μ/ml of MNNG for 30 weeks and were killed at week 50. Among the 5 strains, stomach adenocarcinomas were found most frequently in the SD case. The susceptibility of rats to induction of stomach carcinoma did not correlate with the development of intestinal metaplasias in each strain. Histochemical staining for mucin demonstrated all stomach tumors (adeno‐matous hyperplasias and well‐differentiated adenocarcinomas) to consist mainly of gastric type cells (pyloric gland cell and surface mucous cell types), with intestinal‐type tumor cells (goblet cell and intestinal absorptive cell types) being only occasional findings. Immunohistochemically, I‐ALP was strongly positive on the striated cell borders of small intestinal absorptive cells of the villus and on brush borders of epithelial cells of kidney proximal tubules. I‐ALP was also detected in the normal stomach, limited to the striated cell borders of absorptive cells of the upper one‐fourth of intestinal metaplastic glands. I‐ALP may thus be a useful marker for stomach tumor cells of intestinal absorptive cell type, indicative of maturation and differentiation. No stomach tumors consisting mainly of intestinal‐type cells were found, and therefore there was no suggestion of any derivation from intestinal metaplasias.
: After the intravenous administration of '4C-D=aspartic acid (Asp) into Sprague-Dawley rats (male, 7-week-old), the distribution and elimination of radioactivity was investigated by the whole body autoradiography. High radioactivities were detected in pineal gland, pituitary gland and salivary gland at 30 min after administration. The other tissues detected were liver, lung, adrenal gland, pancreas and spleen where DAsp was reported to occur naturally. After 24 hr, the radioactivities were still detected at high levels in the pineal, pituitary and salivary glands. The data suggested the natural occurrence of D-Asp in salivary gland. After careful examination utilizing fluorescent derivatization and chiral separation by high-performance liquid chromatography, the presence of D-Asp was, for the first time, demonstrated in salivary gland in situ, the concentration of which was 7.85 ± 1.0 nmol/g. The administration of 14C-L-Asp was also carried out. The data suggested that D-Asp in the circulating blood is one of the sources of the tissue D-Asp.
In the present study, we investigated the potential toxic effects of 2-week oral treatment with T-0126, a novel microsomal triglyceride transfer protein (MTP) inhibitor, on the liver and intestine in male and female rats. Administration of T-0126 decreased serum lipids and resulted in fat accumulation in the liver and the small intestine. In addition, slight changes in the liver, including an increase in serum aminotransferase (AST and ALT) activity, presence of focal inflammatory lesions, and prolongation of PT and APTT were observed after treatment with T-0126. These changes may be related to a mechanism based on malabsorption of fat, fat-soluble antioxidants, and vitamin K, although we cannot exclude other potential mechanisms such as direct cytotoxicity of T-0126.
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