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Metabolic acidosis enhances 1,25(OH)2D3-induced intestinal absorption of calcium and phosphorus in rats.

The effect of metabolic acidosis on the intestinal absorption of calcium (Ca) and phosphorus (P), plasma vitamin D metabolites and urinary excretion of Ca in adult rats treated with a small dose of 1,25(OH)2D3 were investigated. The rats in the experimental group received 1.8% ammonium chloride (NH4Cl) and a commercial chow, and their pair-fed controls received 0.45% NaCl. Both groups were given subcutaneously 1,25(OH)2D3. Intestinal absorption of Ca and P was measured by gut sac uptake of 45Ca and 32P. In the acidotic rats, duodenal, jejunal and ileal 45Ca uptake as well as jejunal and ileal 32P uptake were significantly increased. Plasma 1,25(OH)2D, 25(OH)D and 24,25(OH)2D were similar in both groups. 1,25(OH)2D3 treatment induced a greater calciuria in acidotic rats and increased their fractional excretion (FE) of Ca. An additional experiment showed increased 45Ca uptake by duodenum at a pH of 7.0 compared to pH 7.4. The present study suggests that NH4Cl-induced metabolic acidosis may enhance the effect of 1,25(OH)2D3 on intestinal absorption of Ca and P in the rat. However, the data from the study cannot exclude the possibility that acidosis may have a direct, vitamin D-independent effect on the intestine.

Acidosis

[Displacing effect of serum protein binding on intestinal absorption of sulfadimethoxine].

The displacing effect of serum protein binding on the intestinal absorption of sulfadimethoxine (SDM) in rabbits was examined by using N4-acetylsulfadimethoxine (N4-AcSDM), a major metabolite of SDM, as a displacing drug. N4-AcSDM markedly decreased the in vitro serum protein binding of SDM, while many drugs including phenylbutazone and salicylic acid did not display such a marked decreasing-effect. The intravenous administration of N4-AcSDM clearly decreased the in situ intestinal absorption of SDM. As expected, the intravenously administered N4-AcSDM enhanced the serum concentration of unbound SDM in the common jejunal vein. However, the intravenously administered N4-AcSDM caused no change in the transfer of SDM across the intestinal membrane. These results indicate that the displacement of serum protein binding can become one of factors decreasing the intestinal absorption of SDM.

Animals

Neuropeptide Y-induced intestinal absorption: mediation by alpha 2-adrenergic receptors.

In the intestine neuropeptide Y (NPY) is contained in sympathetic nerves, in neuroendocrine cells of the mucosa, and in neurons of the enteric plexuses. After a meal is ingested the concentration of NPY in the blood rises, and intestinal absorption of water and ions increases. We have recently demonstrated a proabsorptive effect of NPY on water and ion transport in the small intestine. The current experiments tested the hypothesis that the alpha 2-adrenergic receptor mediates NPY-induced intestinal absorption. Rabbit ileal segments (n = 35) were harvested and arterially perfused ex vivo. The intestinal lumen was perfused with an isotonic solution containing carbon 14-labeled polyethylene glycol. Net fluxes of H2O, Na+, and Cl- were calculated for three 20-minute periods: basal, drug infusion, and recovery. Five groups were randomly studied: (1) NPY (500 pmol/min); (2) terazosin (1 microgram/min, alpha 1-adrenergic receptor antagonist); (3) NPY + terazosin; (4) yohimbine (1 microgram/min, alpha 2-adrenergic receptor antagonist); and (5) NPY + yohimbine. The infusion of NPY alone caused a significant (p less than 0.05) proabsorptive response for H2O, Na+, and Cl-. Neither terazosin nor yohimbine alone had a significant effect on the transport state of the intestine. Yohimbine, but not terazosin, completely prevented the NPY-induced proabsorptive response. These data support the hypothesis that the proabsorptive effect of NPY is mediated by the alpha 2-adrenergic receptor system.

Adrenergic alpha-Antagonists

Intestinal absorption studies in Fasciolopsis buski infection.

The intestinal absorption of carbohydrate, fat, protein and vitamin B12, serum vitamin B12, serum and red cell folate levels were performed in 10 patients harbouring F. buski. No disturbance of carbohydrate, fat and protein absorption was observed but vitamin B12 absorption was found to be slightly lower than normal in 8 out of 10 patients, and serum vitamin B12 was also lower than normal in 4 out of 9 patients. Red cell and serum flolate levels were within the normal limits. Histological study of jejunal biopsy was normal in 7 out of 8 patients.

Adolescent

Inhibitory effect of bile salts on the enterohepatic circulation of methotrexate in the unanesthetized rat: inhibition of methotrexate intestinal absorption.

The effect of conjugated and unconjugated bile salts on the intestinal absorption of methotrexate (MTX) in the unanesthetized rat was investigated using a recycling perfusion technique. We initially determined the general characteristics of MTX absorption in vivo. Absorption of low (0.5 microM) and high (6 microM) concentrations of MTX was linear with time for 60 min perfusion and occurred at rates of 0.2 and 1.65 nmol/100 cm dry length/min, respectively. Absorption of 0.5 microM MTX was pH-dependent and increased with decreasing perfusate pH. Absorption of MTX involves two processes: (1) a saturable process with a Kt of 0.98 microM, and (2) a nonsaturable diffusion process. The unconjugated deoxycholate and the conjugated taurocholate inhibited the intestinal absorption of 1 microM MTX in a concentration-dependent manner. The inhibitory effect of bile salts was reversible, and was not due to damage to the intestinal mucosa. The structural analogues folic acid and 5-methyltetrahydrofolate and the organic anions rose bengal and sulfobormophthalein were also inhibitory to MTX absorption. This study demonstrates that a variety of organic anions inhibit MTX intestinal absorption. The possible therapeutic importance of this observation is discussed.

Animals

Age influences on intestinal sugar absorption.

Intestinal absorption of sugars show differences depending on animals age. This is demonstrated using in vivo and in vitro techniques. The age dependence relationship is present in animals of different species such as avian, rodents and ruminants. In chicken the intestinal sugar transport increases after hatching and attains its maximum capacity by the first week of life. The D-glucose and D-galactose uptake is greater in young rats, maximum at 21 days, while it decreases thereafter. The total capacity of the small intestine of adult sheep for sugar absorption was approx. 25% of that for lambs less than 1 week of age. The differences observed in intestinal absorption of sugars at different ages could be attributed to differences in sodium and calcium transport. Other authors assume that it is induced by morphological differentiation during intestinal development.

Aging

[Mucus models for investigation of intestinal absorption mechanisms. 2. Mechanisms of drug interactions with intestinal mucus].

Using in vitro models previously described [1] mucus retention and mucus diffusion of polar and non-polar drugs were measured. It could be shown that drug interaction with pig intestinal mucus was based on non-specific binding. The pH-dependence of retention by mucus does not confirm electrostatic interaction of drugs with mucus but favour drug distribution to hydrophobic areas within the mucus. High lipophilicity and retention by mucus correlate with low diffusion of drugs through mucus.

Chemical Phenomena

[The role of aluminum-induced inhibition of the intestinal absorption of calcium in the pathogenesis of aluminum osteopathy].

The aim of the study was to investigate the effect of aluminium on duodenal calcium absorption, the impairment of which can represent a pathogenic factor in the development of aluminium bone lesions. The authors investigated in the chick the effect of Al(OH)3 administered orally and of AlCl3 administered subcutaneously on the duodenal absorption of 47Ca, on serum concentration of calcium, phosphorous, aluminium and 1,25-dihydroxycholecalciferol and on bone morphology. Oral administration of Al(OH)3 for 8, 15, and 22 days was without any significant change. Subcutaneous administration of Al/Cl/3 for 8 day was associated with a significant increase in serum aluminium and 1,25-dihydroxycholecalciferol levels and with a significant decrease of the duodenal absorption of 47Ca. Decreased intestinal absorption of calcium may play a pathogenic role in the development of aluminium osteopathy. Increased serum 1,25-dihydroxycholecalciferol reflects presumably a compensatory mechanism of the lowered calcium absorption.

Aluminum

Improvement of large intestinal absorption of insulin by chemical modification with palmitic acid in rats.

The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 greater than Palins-1 greater than native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.

Animals

Effect of low calcium and low phosphorus diets on the intestinal absorption of phosphate in intact and parathyroidectomized pigs.

The intestinal absorption of phosphate has been studied in conscious pigs, each prepared with a Thiry-Vella loop of jejunum. The feeding of diets low in either calcium or phosphorus caused a significant increase in the efficiency of absorption of phosphate from the solution used to perfuse the jejunal loop in both intact and parathyroidectomized (PTX) pigs. An intravenous infusion of parathyroid hormone (0.22 u. kg-1 h-1) into a PTX pig also enhanced the absorption of phosphate. The increase in the absorption of phosphate when the low phosphorus diet was fed was not caused by an increase in the concentration gradient of phosphate ions between the jejunal lumen and blood. It is concluded that the intestinal absorption of phosphate shows similar changes to those of calcium when diets low in calcium or phosphorus are fed and that parathyroid hormone, although capable of stimulating the absorption of phosphate, is not essential for this adaptation. These effects are probably brought about by changes in the renal production and mucosal uptake of 1,25-dihydroxycholecalciferol, the active metabolite of vitamin D3.

Animals

Non-linear intestinal absorption kinetics of cefadroxil in the rat.

Absorption of cefadroxil in a selective intestinal absorption area (the proximal third of the small intestine) of the anaesthetized rat, at seven initial perfusion concentrations, ranging from 0.01 to 10.0 mg mL-1, is shown to be a non-linear transport mechanism. With the aid of computer-fitting procedures based on differential and integrated forms of Michaelis-Menten equation, Vm and Km values of 36.7-37.3 mg h-1 and 12.0-13.0 mg, respectively, were found. The statistical parameters were better than those obtained both for first-order and for combined Michaelis-Menten and first-order kinetics. There is no evidence for substantial passive diffusion processes. The results reported here, together with allometric considerations and literature data analysis, may help to explain some particular non-linear features of plasma level curves associated with the administration of fairly high oral doses of cefadroxil to humans.

Animals

Intestinal absorption of arsenate in the chick.

The intestinal absorption of arsenate(As(V)) has been investigated in the chick by means of the in situ ligated duodenal loop technique. By this procedure, it was observed that arsenate is rapidly and essentially completely absorbed (80-95%) from the lumen at As(V) concentrations up to 5 mM, declining to about 50% absorption at 50 mM. Transfer from the intestinal lumen to the mucosal cells at low As(V) concentration (0.1 mM) is rapid, while transfer from the mucosal cells to the body occurs more slowly. At stable As(V) concentrations greater than 1 mM, fractional mucosal cell accumulation of As(V) remains constant, while fractional transfer to the body declines. However, total mucosal accumulation of As(V) and that transferred to the body increase in a linear logarithmic fashion from 0.05 to 5 mm As(V). The results indicate that As(V) readily penetrates both the mucosal and serosal surfaces of the epithelial membrane. Furthermore, arsenate and phosphate do not appear to share a common transport pathway in the duodenum and no evidence was obtained for any interaction between the two at this level. Vitamin D3 administration to rachitic chicks was effective in significantly elevating duodenal arsenate absorption, acting primarily to enhance serosal transport.

Administration, Oral

[Intestinal absorption of calcium gluconate and oseine-mineral complex: an evaluation by conventional analyses].

Calcium (Ca) preparations are widely used in the treatment of osteoporosis, usually as soluble salts. Tolerance might be improved by prescription of slowly dissolved Ca preparations, since Ca is also absorbed distally, even in the colon. In this regard the use of natural forms of Ca might be advantageous, but natural products cannot be labeled reliably for easy evaluation of their absorption. To study the intestinal absorption of an osseino-mineral complex (Ossopan) in comparison with Ca-gluconate, healthy males were investigated by means of conventional blood and urinary measurements before and after ingestion of either substance containing 1.58 g Ca. All subjects were placed on a standard diet 2 days before and during test day. Ca-gluconate (n = 7) evoked a marked and transient rise in plasma ionized calcium; total plasma calcium and urinary calcium followed a parallel course, while plasma and urinary phosphate decreased. After administration of osseino-mineral complex (n = 6), a slow but sustained elevation of plasma ionized calcium was observed while total calcium remained unchanged when corrected by the plasma proteins. Plasma phosphate and proteins increased, as did urinary phosphate. Comparing the 24-hour urine of the test day with that of the previous day, the rise in calcium excretion was slightly greater in the subjects treated by osseino-mineral complex than in those who were given Ca-gluconate, while phosphate excretion increased in the first group and decreased in the second. It is concluded that the bioavailability of Ca in osseino-mineral complex is as good as, if not better than, that of Ca-gluconate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improvement of intestinal absorption of thyrotropin-releasing hormone by chemical modification with lauric acid.

Intestinal absorption of 125I-labelled lauryl thyrotropin-releasing hormone (Lau-TRH), a novel lipophilic derivative of TRH, was examined by rat in-situ closed intestinal loops. At a dose of 1 mumol per rat into the small intestine, a significant increase in percent of dose in plasma radioactivity of Lau-TRH was observed in comparison with that of TRH. A dose-dependent decrease in percent of dose in plasma radioactivity of TRH was noted, suggesting a saturable process of TRH transport. In contrast, the percent of dose in plasma radioactivity of Lau-TRH increased with increasing dose of Lau-TRH. The stability of TRH and Lau-TRH was studied in plasma and rat small intestinal homogenates. Lau-TRH was more stable than TRH in rat plasma. These results suggest that chemical modification of TRH with lauric acid may not only increase the lipophilicity of TRH but also reduce the degradation of TRH, resulting in the increased plasma radioactivity of TRH. On the other hand, Lau-TRH was gradually converted to TRH in the intestinal mucosal homogenate. These findings indicate that chemical modification of TRH with lauric acid might be a useful approach for improving the intestinal absorption of this peptide.

Animals