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During chemo-and radiation therapy, the balance between epithelial cell proliferation, differentiation, and cell death at the villus tip is disrupted by premature death of dividing epithelial cells. This will subsequently lead to the onset of mucosal barrier injury in the whole gastrointestinal tract. Up till now there is no validated method to treat side effects occurring due to therapy. An approach to manage this side effect might be to reversibly arrest growth of epithelial stem cells during therapy using Transforming Growth Factor-b2. A Transforming Growth Factor-b2 enriched fraction prepared from bovine milk was shown to protect small intestinal epithelial cells against cell cycle specific chemotherapeutic agents by arresting the cells in G1-phase. Secondly, in a rat model for induced small intestinal damage, oral supplementation of rats exposed to methotrexate with the Transforming Growth Factor-b2 enriched fraction significantly reduced the chemotherapy-associated weight loss and ileal villus atrophy by reducing cell proliferation in the normal stem cell population. Thus oral supplementation with a bovine milk fraction enriched for Transforming Growth Factor-b2 attenuated the side effects of chemotherapy in the small intestine in rats.

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Francisco(2) ; the Drpurtiiient of P d h O l O g y ( 3 ) and the Radioisotope U n i t ( 4 ) of the Veterans AdministrationHospital, Sun Francisco, Calif.During the course of the evaluation of other drugs upon the thyroidal accumulation of iodine in patients, it was observed that a patient being given butazolidin' had a very 1011-P1 thyroid uptake. In this study rats were used in order to measure more completely the effect of this drug upon iodine metabolism.Young albino rats were given butazolidine" by subcutaneous injection a t dosage levels ranging from 8 to 200 mg/kg body weight. In some groups of animals this 11-as followed immediately by a tracer dose of 5 pc of I1;I intraperitoneally. N o additional iodide was added in these studies; thus the administration of the served only to label the iodide pool of the body. The total amount of iodide present in 5 pc of 11"1 is calculated to be less than 1 x 10" pg. As will be noted in Table 1: the uptake of P1 by control animals varied as much as 100%. Although the experimental and control animals for each group are of the same lot and origin, both Sprague Dawley and Slonaker strains of rats were employed in the several experiments combined in Table I. In our hands, SpragueDawley rats recently received from Wisconsin have much higher thyroid uptake of than that observed in rats bred locally. We believe that this merely represents a smaller iodide pool in rats imported from the Midwest since this higher uptake is reduced to that seen in local rats after a period of several weeks in their new environment. These animals were sacrificed 2 0 hours following 1ls1 administra-* ButazolidinR is 3,5-dioso-l.2-diphenyl-?-n butyl-ButazolidinR was synlthesized and sup--l / e f / i o d~. -~-_ _ _ _ _~ pyrazolidin. plied bj-Geigy Co., New York.tion. Other groups of rats were given the drug daily for periods of 10 to 16 days in which the last injection of the drug was followed by 5 pc of P I . After sacrifice selected organs of all of the rats were measured for 1131 with a scintillation counter in which the error in measurement was less than t4%. The geometry of the scintillation counter was such that 8% of all of the Y disintegrations occurring in the sample was observed as counts. The beta particles associated with 1131 decay were completely absorbed with a 200 mg cm--" aluminum filter and were not seen by the counter. Because of this, the wet tissues were counted directly for 1131 by placing them in metal dishes 5 cm from the crystal of the counter. Corrections for mass absorption or small differences in geometry were not necessary when the samples were counted in this manner. The tissues of animals which were given butazolidineR for longer periods of time were also examined for pathological changes and compared to the controls.Results. The data as summarized in Table I show that the administration of butazolidineR once to rats will reduce the amount of a test dose of P1 accumulated by the thyroid. The degree of reduction is directly related to the quantity of the drug given. Mor...

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