Long-term effects of dietary calcium on risk markers for colon cancer in patients with familial polyposis.

There is conflicting evidence regarding the benefit of calcium in prevention of colon cancer. Patients who have undergone ileorectal operations for familial polyposis can be useful to study hypotheses on prevention of colon cancer. In this study we evaluated the effect of long-term calcium supplementation on risk markers of colon cancer. Thirty-one patients with familial polyposis, after subtotal colectomy, were randomized to group A, which received placebo, and group B, which received 1200 mg of calcium daily. Intervention lasted 9 months, in which they underwent four 3-monthly evaluations that included food records, fecal pH, calcium and bile acids, and rectal biopsy for thymidine labeling. Age, height, weight, macronutrients, and dietary fiber were comparable in both groups. More women were in the group that received placebo. Fecal pH, weight, and bile acid levels were similar before intervention and remained unchanged. Fecal calcium levels were similar before intervention and increased in the calcium group throughout the study (p less than 0.05). Labeling index of placebo and calcium groups was similar before intervention (4.8 and 6.1, respectively). After 3 months it was reduced in both groups (3.1 and 4.4, respectively; p less than 0.05). After 6 months it was reduced only in the calcium group (3.4; p less than 0.05). After 9 months it did not differ from the starting point (3.4 and 4.0, respectively). In a long-term intervention study with a homogenous group of patients with familial polyposis, supplemental dietary calcium did not affect mucosal risk factors for colon cancer.

Therapy for shigellosis. II. Randomized, double-blind comparison of ciprofloxacin and ampicillin.

Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin-treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis.

Inhibition of the promotional phase of azoxymethane-induced colon carcinogenesis in the F344 rat by calcium lactate: effect of simulating two human nutrient density levels.

The effects of 2 levels of dietary calcium and 2 types of dietary fat on the promotional phase phase of azoxymethane-induced colon cancer in the F344 rat were investigated. During the initiation phase of carcinogenesis all animals were fed a 5% corn oil AIN-76A diet containing 0.32% Ca in the form of calcium lactate. Rats were then injected with azoxymethane (AOM) weekly for 8 weeks. Thereafter, the rats were fed 1 of 3 diet formulations: a 5% corn oil diet or a 20% corn oil or 20% American Blend oil fat diet, with the level of Ca set at either 0.32% of the diet, a nutrient density simulating a daily human intake of approximately 1700 mg Ca/day, or at 0.04% of the diet, reflecting a human daily intake of approximately 200-250 mg of Ca/day, thus modeling 2 human nutrient density levels for calcium. Measurements of fecal pH during the experiment indicated an acidic adaptation of the large bowel to the lactate anion. Analysis of collected fecal samples showed more total fatty acids to be present in the colon when higher amounts of calcium were consumed. However, results of the tumorigenesis study indicated that calcium lactate fed at the 0.32% level significantly inhibited the development of colonic adenocarcinoma in all dietary groups. Taken together, this investigation supports the hypothesis that calcium supplementation can inhibit colon neoplasia in rats fed a high fat diet; however, under the conditions of this study, the 20% fat level did not significantly promote colon cancer as compared to a 5% fat level.

Site and extent of apparent magnesium absorption by lambs fed different sources of magnesium.

Ten abomasally cannulated crossbred wether lambs (avg wt, 33 kg) were used in a replicated 5 x 5 latin square design to determine the site and extent of apparent absorption of Mg when fed different sources of Mg. Lambs were fed twice daily 220 g of chopped mixed grass hay and 180 g of a corn-based supplement (control; .13% mg, DM basis), or the control diet supplemented with Mg (.26% Mg, DM basis) from MgO, magnesium citrate (MgC), smectite-vermiculite (Mg-Mica) or MgOH. Lambs were maintained in metabolism stalls during each of the five experimental periods. Each period consisted of a 7-d dietary adjustment followed by a 3-d collection of abomasal samples, feces and urine. Abomasal contents were sampled four times daily during the 3-d collection period. The diet contained .5% chromium oxide as a digestion marker. Apparent absorption of Mg was .17, .55, .85, .78 and .82 g/d for lambs fed the control, MgO, MgC, Mg-Mica and MgOH diets, respectively. Apparent absorption of Mg (g/d) was similar (P greater than .05) in the lambs fed the supplemented diets and greater (P less than .05) than in those fed the control diet. Preintestinal absorption of Mg was .21, .57, 1.08, .14 and .92 g/d when the control, MgO, MgC, Mg-Mica and MgOH diets were fed. Lambs fed the control and Mg-Mica diets absorbed similar (P greater than .05) quantities of Mg in the preintestinal region and less (P less than .05) than lambs fed the MgO, MgC and MgOH diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of extrusion on the ileal and fecal digestibilities of lysine in yellow corn in diets for young pigs.

Forty crossbred barrows (initial avg BW of 20 kg) were fitted with T-cannulas to determine the effects of extrusion of yellow corn on lysine digestibility. A basal corn-cornstarch-soybean meal diet was formulated to contain .55% lysine. Extruded corn (EC), non-extruded corn (C) and L-Lysine-HCl (LLH) replaced cornstarch in the basal diet to provide total dietary lysine levels of .60, .65 and .70% lysine for each lysine source. Diet intake was 5.5% of BW. Treatments were arranged as a 3 x 3 factorial with the basal diet as an extra dietary treatment. Apparent ileal digestibilities of lysine, threonine, methionine and isoleucine were greater (P less than .05) for diets with added LLH than for diets containing EC or C, which were similar (P greater than .05). Apparent ileal and fecal digestibilities and retention of nitrogen (N) as a percentage of N absorbed or consumed were greater (P less than .05) for diets containing LLH than for those containing EC or C, which were not different (P greater than .05). Plasma urea N levels were also lower (P less than .05) for pigs fed diets containing LLH than for pigs fed EC or C. Fecal DE and ME as a percentage of GE were greater (P less than .05) in diets containing EC than in those containing C. In summary, extrusion improved (P less than .05) energy utilization but did not affect the utilization of lysine or N in corn by pigs. However, lysine and N utilization were greater (P less than .05) in diets supplemented with LLH compared with EC or C.

The effect of variation in dietary protein or mineral supply on calcium and phosphorus metabolism in lactating ewes.

Two experiments are described in which changes in both nitrogen and mineral balance were monitored in ewes during lactation. In Expt 1, two groups (n 6) of ewes were fed on diets that were either high (15 g crude protein (N X 6.25; CP)/MJ metabolizable energy (ME)) or low (10 g CP/MJ ME) in protein content, and concurrent N and mineral balance studies were made at intervals during lactation with 45Ca and 32P being used to monitor faecal endogenous calcium and phosphorus losses. Ewes fed on the high-protein diet maintained a positive N balance during early lactation, whereas those fed on the low-protein diet were in negative N balance. Both groups, however, showed the same degree of negative Ca and P balance, with the amounts lost being directly related to milk yield. This indicates that loss of mineral from the skeleton at this time is not secondary to a loss of bone matrix due to a shortfall in dietary protein supply. In Expt 2, two groups of ewes (n 4) were fed on diets in late pregnancy that were either just adequate or generous in Ca and P supply relative to requirement (TCORN, 1990). After parturition both groups were fed on a diet which was formulated to meet their estimated Ca and P requirements for lactation. As in the previous experiment both groups were in negative Ca and P balance in early lactation and variation in dietary Ca and P supply during pregnancy had no effect on the extent of this loss. Alternative explanations for the cause of this loss of mineral from the skeleton are discussed.

Dietary fiber: in vitro methods that anticipate nutrition and metabolic activity in humans.

Gravimetric measurement of dietary fiber (DF) gives no indication of the biological function of any particular fiber. This study describes simple methods based on dialysis and fermentation that enable a hierarchy of fibers to be described for each of the major actions of fiber along the gastro-intestinal tract: nutrient absorption, sterol metabolism, cecal fermentation, and fecal bulking. These results were compared with previous metabolic studies with the same fiber isolates in humans. DF that modifies nutrient absorption can be identified by using dialysis studies, whereas identifying DF that modifies sterol metabolism, cecal fermentation, and fecal weight requires formulas that incorporate dialysis and fermentation results. Results from dialysis and fermentation predicted the action of wheat bran, pectin, guar, gum arabic, carboxymethylcellulose, gellan, tragacanth, xanthan, and karaya in humans and generated anomalous results for karaya and tragacanth. These methods could form the basis of techniques that would enable a screening of novel and processed fibers before studies in animals, including humans.

Selenium utilization in humans--a long-term, self-labeling experiment with stable isotopes.

A stable (nonradioactive) isotope of selenium in a chemical form common in foods (selenomethionine) or inorganic selenite was taken orally (200 micrograms/d) for 3 wk to label deep body pools. By deep body pools we mean selenium compartments that are large and/or have a slow turnover (exchange) rate. Blood plasma was removed, stored for 11 mo, and later reinfused as a labeled tracer dose with the selenium label in all of the biologically significant chemical forms. Accessible tissues such as red blood cells were highly labeled (20-25%) in the subjects receiving selenomethionine. Selenium from deep body pools is excreted primarily via the urine (80%). Reexcretion of previously absorbed selenium back into the gastrointestinal tract can be measured, avoiding a major source of error in conventional balance studies used to estimate nutrient absorption.

Dietary butyrate (tributyrin) does not enhance AOM-induced colon tumorigenesis.

Butyrate has induced differentiation in neoplastic cells grown in vitro, among them being colon cancer cell lines. In vivo, only one major study used sodium butyrate in the drinking water and showed an elevation in 1,2-dimethylhydrazine induced colon cancer in rats. Seeking to show that it was the sodium and not the butyrate which was responsible for the enhancement, we fed tributyrin at a 5% level to mice for 48 weeks. Mice experienced normal growth and development at this dose. Analysis of short chain fatty acids in the feces after 6 months in tributyrin feeding showed a 10-fold increase in butyric acid. However no difference in AOM induced focal areas of dysplasia or colonic tumor incidence was observed between tributyrin fed and control mice. At least two conclusions have been reached by this study, (1) that the dietary use of a sodium salt can contribute to the enhancement of chemically induced colon neoplasia and (2) butyrate may be discounted as providing any major therapeutic benefit against colonic tumorigenesis.

Oral copper supplementation: effect on copper and zinc balance during acute gastroenteritis in infants.

To evaluate the effect of copper supplementation during recovery from acute diarrhea, we randomly assigned 14 hospitalized infants to receive either 80 micrograms copper sulfate.kg body wt-1.d-1 or a placebo. Metabolic balance and plasma copper and zinc concentrations were measured before randomization (period 1) and 6 d after admission (period 2). Fifteen control subjects were studied after respiratory illness. Fecal copper was not affected by supplementation; fecal zinc during period 2 rose significantly only in the copper-supplemented group. Copper retention was significantly higher in the supplemented infants; plasma concentrations increased for period 2 but were similar to those in the placebo group. Zinc concentrations improved over time in both groups but zinc retention was higher in the placebo group for period 2. A significant interference by copper supplementation on zinc absorption was noted. Copper supplementation during the early phase of recovery from diarrhea is not recommended.

Nitrogen metabolism and somatotropin secretion in beef heifers receiving abomasal arginine infusions.

Twelve Angus x Hereford heifer calves (233 kg) were fitted with abomasal infusion cannulas and used to study N and endocrine responses to abomasally infused arginine (Arg). Heifers were allotted randomly to three treatment groups and received continuous abomasal infusions (2 liters/d) of water (CON) or Arg solutions providing .33 g Arg.HCl/kg BW (LOW) or .50 g Arg.HCl/kg BW (HIGH) each day. A 12-d dietary adjustment period preceded a 7-d infusion and collection period. Each calf received 4,544 g DM/d of a basal diet in equal portions at 0600, 1200, 1800 and 2400. Calves were housed in individual metabolism crates and fitted with urinary bladder catheters for total excreta collection. On d 1 and 5, blood samples were collected at 15-min intervals for 8 h between 1200 and 2000. Single samples were obtained at 1400 on remaining days. The infusion of Arg increased the quantity of N retained by heifers (P less than .01) and the percentage of total N retained (P less than .10); however, no differences were observed between LOW and HIGH heifers. Increased (P less than .01) urinary N excretion by Arg heifers was associated with greater (P less than .05) quantities of urinary urea N and ammonia N. Blood urea N and serum Arg concentrations were highest (P less than .05) in Arg heifers, whereas total serum AA concentrations were lower (P less than .05) in Arg heifers than in CON heifers. Serum glucose and insulin concentrations were not affected (P greater than .10) by treatment. Characterization of somatotropin (STH) profiles revealed that amplitude and frequency of STH pulses were not affected (P greater than .10) by treatment, whereas mean (P less than .10) and basal (P less than .05) STH concentrations were elevated in HIGH compared to LOW heifers on d 1 and 5. The similar N retention responses of LOW and HIGH heifers and similar STH profiles of CON and LOW heifers suggest that the stimulatory effect of the HIGH dose on STH secretion occurred only after tissue N requirements had been satisfied.

Studies of an oral iron chelator: 1,2-dimethyl-3-hydroxy-pyrid-4-one. I. Iron excretion in rats: development of a new rapid microwave method for iron analysis in faeces.

We have developed a simple, rapid method for analysing faecal iron using a microwave oven for digestion followed by atomic absorption spectrometry. The chelating effect of 1,2-dimethyl-3-hydroxy-pyrid-4-one (DMHP) has been tested in rats with experimental iron overloading and three routes of DHMP administration, oral, subcutaneous, and intraperitoneal, have been compared. Regardless of the route of administration, we have found that DMHP promotes iron excretion via the urine. We have not observed a difference in the amount of iron excreted in the faeces before and after DMHP administration by any route. The subcutaneous route of administration is the most effective in promoting iron excretion, followed by the intraperitoneal route. Although most convenient for clinical use, oral administration promotes the excretion of only a small fraction of that by the subcutaneous route.

Dietary modification of potential vitamin K supply from enteric bacterial menaquinones in rats.

Rats given a low-fibre diet based on boiled white rice developed symptoms of severe vitamin K deficiency within 23 d. Inclusion of autoclaved black-eye beans (Vigna unguiculata) in the diet prevented the bleeding syndrome. To test the hypothesis that deficiency resulted from low phylloquinone intake exacerbated by inadequate production of menaquinones by the enteric bacteria, a follow-up experiment was carried out in which groups of rats were given an all-rice diet, a rice + beans diet or a stock diet. Rats on the all-rice diet had significantly lower faecal concentrations of the main menaquinone-producing bacterial species (Bacteroides fragilis and Bacteroides vulgatus) than animals on either of the other two diets. This coupled with the much lower faecal output on this diet suggests that total menaquinone production was low for the all-rice diet. The alterations in faecal flora were associated with several significant changes in caecal metabolism. Rats given the stock diet had much shorter caecal transit times and a considerably greater proportion of butyric acid in volatile fatty acid end-products than did rats on either of the other two diets.

Chelating agents in the treatment of acute vanadyl sulphate intoxication in mice.

Eighteen chelating or reducing agents were tested to determine their relative efficacy as antagonists in acute intramuscular vanadyl sulphate intoxication in mice. The chelating or reducing agents were administered intraperitoneally to male Swiss mice at doses equal to one-fourth of their respective LD50. Therapeutic effectiveness (TEF) was calculated. In a subsequent experiment, the effect of EDTA, glutathione, DFOA, ascorbic acid, succinic acid, monosodium phosphate, Tiron, DTPA, and 2-mercaptosuccinic acid on the excretion, and distribution of vanadium was determined. Of the compounds examined, Tiron followed by ascorbic acid, and 2-mercaptosuccinic acid were effective in increasing the urinary excretion of vanadium. Tiron, and 2-mercaptosuccinic acid were also effective in reducing the concentration of vanadium found in kidney, the main target organ of vanadium accumulation. Tiron appears to be the most effective agent of those tested in the prevention of acute vanadium (IV) intoxication in mice.

Effects of foods rich in polyphenols on nitrogen excretion in rats.

The extent to which tea, cocoa and carob (foods rich in polyphenols) influence fecal nitrogen (N) excretion was investigated in rats. The studies took into account the methylxanthine contents of tea and cocoa as well as the poor digestibility of cocoa nitrogen. Balance measurements indicated that all three food sources significantly increased fecal nitrogen excretion relative to methylxanthine-matched control diets (p less than 0.01). In the case of cocoa, virtually all the increase could be attributed to the poor digestibility of cocoa protein itself (estimated to be only 28-30% of total N in cocoa powder). There appeared to be no other effects. With extracts of tea and carob, however, the increased excretion of N in feces resulted either from a decreased digestibility of other dietary protein, through interaction with their polyphenols, or from a stimulation of the excretion of endogenous (body) nitrogen. With respect to the latter possibility, a preliminary investigation with the stable isotope of nitrogen (15N) showed that tea produced a marked increase in the excretion of endogenous nitrogen. These studies, therefore, indicate that foods rich in polyphenols have varying effects on N excretion in feces and that, in the case of tea at least, the loss of endogenous nitrogen may be a major contributing factor.

Effect of cholestyramine in early weaning on later response to serum and fecal steroid levels and cholesterol 7 alpha-hydroxylase activity to high-cholesterol diet in ExHC rats.

Male ExHC (exogenous hypercholesterolemic) rats were either prematurely weaned at 17 days of age or allowed to nurse until 35 days of age. The prematurely weaned rats were either fed a diet containing cholestyramine or cholestyramine-free diet until 35 days of age. Cholestyramine supplementation markedly increased fecal bile acid excretion and modified the composition. After giving a stock diet for 7 weeks, all rats received a cholesterol-enriched diet for 9 weeks. The serum cholesterol level in later time was not affected by early dietary manipulation. The activity of hepatic cholesterol 7 alpha-hydroxylase and fecal bile acid excretion at the end of the cholesterol challenge decreased in the cholestyramine-pretreated group, when compared to the normally weaned group. Fecal excretion and the ratio of the secondary (deoxycholic and lithocholic acids) to the primary (cholic and chenodeoxycholic acids) bile acids significantly decreased in the early cholestyramine-treated group. These results suggest that a modification of bile acid metabolism in early life may strongly influence the hepatic and possibly colonic bile acid metabolism in later life, when challenged with a high-cholesterol diet.

Urinary calcium and calcium balance in young women affected by high protein diet of soy protein isolate and adding sulfur-containing amino acids and/or potassium.

The effects of sulfur-containing amino acids (SAA) and potassium (K) on urinary excretion and retention of calcium (Ca) of 27 young Japanese women were studied. A basal diet low in protein level (50 g per day) was fortified by meat or soy protein isolate (SPI) to a protein level of 100 g per day, and effects of addition of apple to these high protein diets, and addition of SAA and/or potassium (K) to the high SPI diet, especially on urinary Ca excretion, were studied. The addition of meat which increased protein intake to 100 g caused the increase in apparent absorption and urinary excretion of Ca with increased excretion of urinary sulfur (S), phosphate, ammonia, and titratable acids (TA), whereas addition of SPI did not. The addition of apple to high meat diet decreased absorption and urinary excretion of Ca. Urinary Ca, S, K, ammonia, and TA excretion increased by the addition of SAA to high SPI diet in a manner similar to the meat diet. Consequently, SAA-supplemented diet had a significantly negative effect on Ca retention. In SPI+SAA,K diet period, urinary K excretion markedly increased, and increments in urinary Ca, ammonia, and TA excretion were reversed. These changes observed in SPI+SAA, K diet period were similar to those by adding apple to meat diet without any effect on Ca absorption. The results suggest that the hypercalciuria induced by high meat diet is mainly caused by high content of SAA and may be reversed by the ingestion of K-rich foodstuffs, and soy protein does not induce hypercalciuria because of it contains less SAA than animal protein.

Identification of human urinary stains by the quotient uric acid/urea nitrogen.

Uric acid (UA) and urea nitrogen (UN) were determined in urinary stains and the UA/UN x 20 values were calculated. The values in human urinary stains were 1.11-4.21, while those in other mammals except some of chimpanzees, were under 0.7, and those in fecal stains of birds were over 80. Most of the stains of other human body fluids or plant juices tested contained neither UA nor UN, and some contained one, but never the other. Ascorbic acid (AS) of up to 100 mg/dl in urine did not interfere with UA determination when dried human urinary stains were analyzed. It was also found that the contents of UA were very low at the peripheral parts of urinary stains. The present results indicate that the quotient UA/UN is useful for identification of human urinary stains in forensic practice provided that the peripheral part of the stain is not used.

Calcium and magnesium utilization in rats: effect of dietary butterfat and calcium and of age.

This factorial study was designed to examine the effect of short- and long-term ingestion of dietary calcium (0.25% and 1.0%) and butterfat (5% and 20%) and treatment with dimethylhydrazine (DMH) in rats. Calcium, magnesium and phosphorus absorption and, to a lesser extent, total diet digestibility decreased as the rats aged from 2 to 8 mo. Increased ingestion of butterfat had no effect on apparent absorption of calcium among young rats but tended to decrease calcium absorption in mature rats. The weak effect (P less than 0.05) of butterfat on calcium absorption reflected the small amount of calcium (less than 2% of fecal calcium) associated with lipids in feces. Ingestion of 10 vs. 2.5 mg Ca/g diet reduced the efficiency of apparent absorption of calcium, magnesium and phosphorus of young and mature rats and resulted in slightly, but significantly, greater retention of calcium in bone after 27 wk. The total amounts of calcium retained in tibias were correlated with the amounts of calcium absorbed by rats after 4, but not after 27, wk of dietary treatments. Rats dosed with DMH exhibited improved efficiency of calcium absorption, but the incidence of intestinal tumors did not affect mineral utilization.