PubMed Health⌕ Search

Biomedical subjects

N F Adham

Publications and source records attributed to N F Adham.

At least 19 recordsLinked to original sources
PubMed1995

Metabolic alterations of zinc and prostaglandins in both human and animal colonic tumor cells.

OBJECTIVE: To understand the relationship between zinc and prostaglandin (PG) metabolisms in inducing colon cancer incidence in human and animals. METHODS: Human colonic tumor and normal cells were obtained from Departments of Surgery and Pathology at the Kaiser Permanente Medical Center, Los Angeles, CA and US VA Medical Center, North Hills, CA. Rat colonic tumor and normal cells were isolated from the rats that received two injections of 50 mg/kg of Azoxymethan (AOM) in 2 weeks and then kept 30 weeks in the animal facility. Then, the effects of zinc on the PGE2 synthesis and PGE2 on zinc metabolism in tumor and normal cells were determined. RESULTS: PGE2 concentrations in both human and AOM-induced rat colonic tumor cells increased compared to those in adjacent normal colonocytes, whereas PGF2 alpha concentrations did not change. Gene expression of inducible form of prostaglandin synthase (PGS-2) is stimulated in rat colonocytes by epidermal growth factor and by tetradecanoyl 13-phorbol acetate (a tumor promoter and mitogen) only in the presence of zinc. PGE2 binding activity of rat enterocytes was maximum at 15 microM of zinc (normal plasma zinc concentration), but PGE2 synthesis activity increased for the first 15 minutes when extracellular zinc concentrations were either higher or lower than the normal extracellular zinc concentration. However, variations in extracellular zinc concentrations did not change the rate of PGF2 alpha synthesis in the normal rat enterocytes. PGE2 significantly increased zinc uptake rates of colonic tumor cells but PGF2 alpha showed only moderate effect. CONCLUSIONS: These results suggest that zinc is required for PGS-2 gene expression, that maintaining an optimal zinc nutriture is important for normal PG synthesis of intestinal cells, and that only PGE2 synthesis mechanisms rather than PGS-2 gene expression are altered in colonic tumor cells resulting in the abnormal zinc nutriture of these cells.

Animals↗
PubMed1992

Prostaglandin interacts with steroid sex hormones in the regulation of intestinal zinc transport.

1. The effects of prostaglandins (PGs) E1 and E2, testosterone, 17 beta-estradiol and indomethacin on the intestinal zinc transport rates of male and female rats were compared. 2. PGE1 stimulated Jms (the zinc flux rate from mucosa-to-serosa) of jejunal segments from male rats but inhibited Jms of those from female rats in Ussing chamber experiments. 3. 17 beta-Estradiol inhibited Jms of jejunal segments from male rats, while testosterone stimulated it in those from female rats. However, testosterone inhibited Jms of segments isolated from male rats and 17 beta-estradiol that of those from female rats, while in segments from ovariectomized rats, both of these steroid hormones stimulated Jms. 4. When PGE2 was added to an indomethacin containing medium, Jms significantly increased whereas Jsm (the zinc flux rate from serosa-to-mucosa) decreased further.

Alprostadil↗
PubMed1989

Role of zinc in treatment of experimental acute pancreatitis in mice.

A study on the effect of zinc feeding on the survival rate as well as the levels of trypsinogen, alpha 2-macroglobulin, zinc, calcium, and magnesium in the plasma, pancreata, and livers of BALB/c mice fed a choline-deficient diet supplemented with 0.5% DL-ethionine (CDE diet) was undertaken. Feeding them a zinc-excess diet significantly increased the survival rate of mice with pancreatitis induced by CDE diet feeding. Trypsinogen concentrations in plasma and pancreas increased in mice fed a CDE diet and further increased in mice fed a zinc-deficient diet. The plasma alpha 2-macroglobulin levels in mice fed a zinc-deficient diet decreased compared to those fed a zinc-adequate or a zinc-excess diet. In mice with pancreatitis, zinc and calcium concentrations of pancreata increased and magnesium concentrations decreased compared to those of normal controls. The calcium concentrations in both livers and pancreata increased, but magnesium concentrations in these tissues decreased. These results suggest that altered mineral metabolism in the pancreas may have contributed to the pathophysiology of the mice with acute pancreatitis and that zinc supplementation in the diet may be therapeutic for pancreatitis.

Acute Disease↗
PubMed1989

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice.

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.

Animals↗
PubMed1988

Influence of prostaglandins on unidirectional zinc fluxes across the small intestine of the rat.

1. The regulatory role of prostaglandins (PGs) E2 and F2 alpha on the zinc transport rate across the jejunal segments of rats was examined by employing the Ussing chamber technique. The Zn flux rate from mucosa to serosa across jejunal segments (Jms) was 5.24 (SE 1.54) nmol/h per cm2 (n 48) and that from serosa to mucosa (Jsm) was 15.16 (SE 2.38) nmol/h per cm2 (n 48) when both sides of the segment were bathed with Ringer's bicarbonate solution containing 0.5 mM-zinc chloride and 3 mM-L-histidine. 2. When 5.0 or 50 microM of either PGE2 or PGF2 alpha were added to the serosal side of the tissue, Jsm generally decreased and Jms generally increased, compared with controls. On the other hand, when PGE2 or PGF2 alpha was added to the mucosal side of the tissue, Jms either did not change or increased while Jsm had a tendency to decrease. 3. The Zn uptake capacity of tissue increased significantly when PG was added to the serosal side of the tissue-bathing medium, but not when PG was added to the mucosal side. The uptake capacity of mucosal Zn by jejunal segments was approximately twice that of serosal Zn. 4. When PG was included in the tissue-bathing medium, the short-circuit current, potential difference and conductance between the mucosa- and serosa-bathing media generally decreased. 5. These results suggest that (a) PGs influence Zn flux rate not by chelating Zn and carrying it across the mucosal cell membrane but by interacting with the cytosolic components, (b) it is the serosal PGs which control the Zn flux rate and (c) PGs play a part in triggering a transduction mechanism in the intestinal Zn transport process.

Animals↗
PubMed1986

Relative zinc-binding activities of ligands in the cytosol of rat small intestine.

Relative zinc-binding activities of high-molecular-weight zinc-binding ligand (HMW-ZBL), metallothionein (MT) and low-molecular-weight zinc-binding ligand (LMW-ZBL) in the cytosols of rat small intestines under various experimental conditions were examined. Zinc-binding activities of MT decreased and those of LMW-ZBL increased in the intestinal cytosols from most of the experimental rat groups after incubating at 37 degrees C for 2 hr. The relative zinc-binding activity of MT increased with increasing doses of injected zinc and decreased with orally-administered zinc. Isolated MT did not lose zinc-binding activity during incubation at 37 degrees C for 48 hr, but moved from the MT eluting peak to the LMW-ZBL eluting peak after 1 week.

Animals↗
PubMed1985

Effect of oral administration of arachidonic acid on prostaglandin and zinc metabolism in plasma and small intestine of the rat.

The effect of different doses of arachidonic acid (AA) on the intestinal zinc transport rate and on the plasma and intestinal PGE2, PGF2 alpha and 6-keto-PGF1 alpha levels in rats were measured to determine whether the metabolism of AA is involved in the zinc transport mechanism. Twenty-four rats were divided into 4 groups of 6 rats. Each rat received either 1.0 ml of distilled water, 0.5 mg, 1.0 mg or 1.5 mg/ml of AA intraduodenally at 24 and 4 hours before sacrifice. One hour before sacrifice, each rat also received 10 micrograms of 65Zn intraduodenally. The zinc transport rate decreased in comparison to controls when 0.5 mg of AA was given to the rats, but increased when 1.0 mg or 1.5 mg of AA was given. The levels of PGE2, PGF2 alpha and 6-keto-PGF1 alpha (PGI2 metabolite) in the intestinal mucosa all decreased in proportion to the amount of AA given. However, in the plasma, only PGF2 alpha levels decreased while PGE2 and 6-keto-PGF1 alpha levels showed no change compared to controls. When rats were given 1.5 mg of AA without oral administration of 65Zn, plasma PGE2 levels increased while PGF2 alpha levels decreased. The results suggest that AA metabolism influences the zinc transport mechanism by modulating the relative levels of PGE2, PGF2 alpha and PGI2 in plasma and small intestine.

Animals↗
PubMed1985

Relationship between zinc and prostaglandin metabolisms in plasma and small intestine of rats.

The effect of zinc nutriture on levels of prostaglandin (PG) E2, F2 alpha and 6-keto-PGF1 alpha in the plasma and small intestine of rats, and that of PGE2 and PGF2 alpha on unidirectional uptake of 65Zn by everted gut sac of rats was determined. When zinc was given intraperitoneally, plasma PGE2 and intestinal PGF2 alpha levels increased, while the intestinal PGE2 and the plasma PGF2 alpha and 6-keto-PGF1 alpha levels decreased in accordance with the amount of zinc given. Oral administration of excess zinc increased intestinal PGE2, PGF2 alpha and 6-keto-PGF1 alpha levels and the plasma 6-keto-PGF1 alpha levels. The intestinal levels of PGE2 increased significantly only in rats on zinc excess diet, and of PGF2 alpha only in rats on a zinc deficient diet. The plasma PGE2 levels in rats on both zinc deficient and zinc excess diets increased but PGF2 alpha levels in zinc deficient rats were greatly reduced compared to controls. Unidirectional zinc uptake by everted gut sac of the rat is also enhanced by PG metabolites. These results are consistent with the view that PGs participate in regulating the zinc transport mechanism in small intestine.

Administration, Oral↗
PubMed1985

Factors that modify the effects of prostaglandin on diet-induced acute pancreatitis in mice.

Considerable disagreement exists as to whether prostaglandins improve survival in animals with experimental pancreatitis. In prior studies we have demonstrated a beneficial effect of prostaglandin in the choline deficient, ethionine supplemented diet model of acute hemorrhagic pancreatitis. In the present study we have examined the effects of 1) delaying treatment with 16,-16-dimethyl prostaglandin E2 (PGE2) till 24 h after introduction of the diet and 2) exposing animals to the test diet for 3 days instead of 2. Following delayed treatment mortality in the saline control group (57%) was significantly higher on the fourth day compared to the PGE2 treatment group (3%). However, the overall mortality on day 7 was not significantly different from that seen in the control group (43% versus 60%). In the second series of experiments, PGE2 no longer had a beneficial effect if animals were fed the CDE diet for 3 days. We would conclude from this study and others that the ability to demonstrate a protective effect of PGE2 on the pancreas is dependent upon the experimental protocol employed. Thus, the ability to demonstrate this effect is dependent upon the dose and type of prostaglandins employed, the length of exposure to the test diet, and the time at which treatment is started relative to the induction of the pancreatitis.

Acute Disease↗
PubMed1984

Effect of different levels of dietary zinc on longevity of BALB/c mice inoculated with plasmacytoma MOPC 104E.

The effect of different levels of Zn intake on survival was studied in 6 groups of 4-week-old BALB/c mice inoculated with MOPC 104E tumor cells. The first 3 groups received either a Zn-deficient (0.5 microgram Zn/g), a Zn-supplemented (1 mg Zn/g), or a control diet (37.5 micrograms Zn/g) starting 11 days after tumor inoculation (T11). The remaining 3 groups received the same diets starting the day the tumor was implanted (T0). The mean survival of rats beginning the Zn-deficient diet at T11 was significantly increased compared with that of the control group. However, when the same diet was begun at T0, the mean survival of the Zn-deficient group was significantly reduced; for this group the results probably related to the combined adverse effects from prolonged Zn deficiency and to those effects of the tumor itself. Similarly, excess Zn intake significantly prolonged the mean survival when given at T11. However, excess Zn intake at T0 produced no significant effect on survival, probably because of the elevation of plasma Zn level following oral Zn intake that occurred before the establishment of the tumor or possibly because of the inability of the small intestine to absorb excess Zn at T11 when the tumor was fully developed.

Animals↗
PubMed1983

Relationship between the functional status of the reticuloendothelial system and the outcome of experimentally induced pancreatitis in young mice.

Physiologically, the main function of alpha 2-macroglobulin is the binding of active endopeptidases rather than their inhibition. The interaction results in a conformational change in the alpha 2-macroglobulin that leads to its rapid elimination by the reticuloendothelial system. In this way, the reticuloendothelial system may help in the regulation of extracellular proteolytic activity resulting from the release of proteinases from injured pancreatic acinar cells in acute pancreatitis. To evaluate this concept, the effect of feeding a choline-deficient diet supplemented with 0.5% DL-ethionine was determined in 4 and 6-wk-old mice in which the reticuloendothelial system was normal, stimulated, or depressed. Stimulating the reticuloendothelial system in 4-wk-old mice significantly (a) decreased the mortality rate; (b) lessened the drop in the plasma content of both alpha 2-macroglobulin and alpha 1-antitrypsin; and (c) decreased the severity of pancreatitis noted microscopically. In contrast, reticuloendothelial suppression in this group of mice had no demonstrable effect. However, when similar studies were done in 6-wk-old mice, in which this diet induces a milder disease, reticuloendothelial suppression significantly increased the mortality rate as compared with normal mice, whereas reticuloendothelial stimulation significantly decreased it. The possible mechanism for the salutory effect of stimulating the reticuloendothelial system on the outcome of diet-induced pancreatitis in mice is discussed.

Age Factors↗
PubMed1980

Effect of calcium and copper on zinc absorption in the rat.

The effect of cupric and calcium ions on zinc absorption was examined in Sprague-Dawley rats. In in vivo studies test solutions containing 7.5 mM 65ZnCl2 alone or in combination with 500 mM of either CuSO4 or CaCl2 were administered intraduodenally to three groups of rats. 2 h later the animals were sacrificed and their organ 65Zn content was determined. The results of these studies revealed that excess cupric ions had no effect on the 65Zn content of rat internal organs, whereas excess calcium ions decreased organs 65Zn content to 40%. Similar results were obtained in in vitro studies using three sets of rat jejunal sacs each filled with one of the above test solutions and incubated in oxygenated Eagle's medium. To investigate the reason(s) for the observed decreased rate of zinc absorption in the presence of excess luminal calcium, we examined zinc transport in 6 sets of jejunal sacs using six test solutions, each containing 7.5 mM 65ZnCl2 with 0, 12.5, 25, 37.5, 50, or 62.5 mM CaCl2. These experiments showed that 65Zn transport from mucosa to serosa was decreased by 40% in the presence of 25.0 mM CaCl2 but lower calcium concentrations had no effect on zinc transport. Increasing the luminal calcium concentration from 25 to 62.5 mM did not cause a further significant decrease in the rate of zinc transport. These results strongly suggest that zinc absorption in the rat is mediated by a transcellular transport process different from that which mediates copper and calcium absorption. The fact that calcium has been shown to reduce passive cation movements via shunt pathways in the gallbladder mucosa suggests the possibility that calcium in high luminal concentration may depress zinc absorption by reducing the passive component of jejunal zinc absorption.

Animals↗
PubMed1978

Enteropeptidase levels in duodenal juice of normal subjects and patients with gastrointestinal disease.

Enteropeptidase, trypsin, and chymotrypsin activity in basal and secretin-stimulated duodenal juice of 20 normal adult volunteers and 15 patients with gastrotestinal disease were determined. All enzyme concentrations showed skew distributions, but fluctuations in the secretin-stimulated juices were less pronouced than in the basal secretions. Secretin administration had no influence on the release of enteropeptidase from human duodenal mucosa, but resulted in a very small increase in secretion of pancreatic enzymes. Six out of seven patients with chronic alcoholic pancreatitis or cancer of the pancreas exhibited highly significant elevations of enteropeptidase in their basal as well as secretin-stimulated duodenal juice. It is suggested that raised luminal enteropeptidase activity may be the result of pancreatic insufficiency or elevated blood glucagon concentrations.

Adult↗
PubMed1978

Effect of bile acids and pH on the release of enteropeptidase in man.

Bile acids increase the release of human enteropeptidase as well as other brush-border enzymes (alkaline phosphatase, leucine aminopeptidase) from duodenal mucosa, as had been shown earlier in experimental animals. The action of bile acids is independent of their known enhancing effect on enteropeptidase activity. The pH of duodenal juice is an important, hitherto unrecognized, factor in the release mechanism of brush-border enzymes. All of the above enzymes tested were released to a markedly greater extent at pH 8.2 than 6.3, regardless of the presence or absence of bile acid. Contrary to some results obtained with animal tissue, by other investigators, our experiments with human duodenal mucosa indicate that enteropeptidase, under all conditions tested, is released at a rate considerably greater than that for alkaline phosphatase or leucine aminopeptidase. The looser association of enteropeptidase with cellular components relative to that of other brush-border enzymes, as indicated by our observations, may be related to the unique function of enteropeptidase as the trigger enzyme of protein digestion.

Alkaline Phosphatase↗
PubMed1978

Role of prostaglandin E2 in zinc absorption in the rat.

The supernatant of cytoplasmic extract of rat small intestine was mixed with 65Zn and subjected to Sephadex G-75 column chromatography. The activity of 65Zn was detected in four peaks with estimated 800, 10,000, 50,000-75,000 mol wt, and larger than 100,000 daltons. The zinc-binding ligand from the 800 mol wt peak was prostaglandin or prostaglandin-like as indicated by ultra-violet absorption spectrum, by absorption spectrum shift in alcoholic potassium hydroxide, by its effects on pulmonary vascular resistance, and by radioimmunoassay. Addition of prostaglandin E2 or prostaglandin extracted from rat small intestine with ethyl acetate into the lumen of intestinal sacs resulted in a two to threefold increase in the activity of 65Zn in the external medium after 15-20 min incubation. The absorption and tissue distribution of orally administered 65Zn were decreased by 60% in indomethacin-treated rats and increased 70% when ethyl acetate-extracted prostaglandin and radioactive zinc were given simultaneously. These data suggest that prostaglandin not only binds zinc, but also facilitates its transport across the intestinal mucosa.

Animals↗
PubMed1978

Hyper-alpha-2-macroglobulinemia in narcotic addicts.

Significant increases of serum alpha-2-macroglobulin (alpha-2-M) were detected in narcotic addicts presenting at a methadone treatment center. The mean alpha-2-M level was 341 +/- 14 mg/dl compared with 231 +/- 8 mg/dl in normal persons (p less than 0.01). In a comparable group of alcoholics with laboratory evidence of hepatic dysfunction the mean alpha-2-M level was 208 +/- 10 mg/dl. Although the serum immunoglobulin M content was also substantially elevated in the narcotic-addict group, no correlation was obtained between the serum content of this protein and alpha-2-M. Similarly, no correlation between alpha-2-M level and serum zinc content was observed. When the values of the trypsin-binding activity of serum measured in 13 addicts, 15 alcoholics with laboratory evidence of hepatic dysfunction, and 16 normal subjects were plotted against the amount of alpha-2-M measured in the same subjects, a linear correlation was obtained between trypsin-binding activity and alpha-2-M. Thus, the significantly increased serum trypsin-binding activity observed in the addicts is that which might be expected if normal alpha-2-M is being accumulated in large amounts as a result of increased macroglobulin synthesis.

Blood Proteins↗