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Association between HCO3(-) absorption and K+ uptake by Amphiuma jejunum: relations among HCO3(-) absorption, luminal K+, and intracellular K+ activity.

Titration techniques and K+- sensitive microelectrodes have been used to investigate the relations among HCO3(-) absorption, luminal K+, and intracellular K+ activity in in vitro Amphiuma jejunum. The HCO3(-) absorptive flux (JHCO3(-] measured by pH-stat under short circuit was reduced by removal of K+ from the medium but not by replacement of Na+ with choline. JHCO3(-) exhibited a seasonal variation when K+ was absent from the media and was increased to a maximum when K+ equaled 5 mM. Addition of K+ to a K+-free luminal medium stimulated JHCO3(-) much more than addition to the serosal medium. Acetazolamide (10(-4) M) blocked K+-stimulated HCO3(-) absorption while benzolamide reduced the short-circuit current associated with HCO3(-) absorption much more rapidly when added to the mucosal bathing medium. Intracellular K+ activity (aik) and mucosal membrane potential (psi m) of jejunal villus cells were measured with double-barreled microelectrodes. When bathed bilaterally with HCO3(-)-containing media, K+ was actively accumulated for many hours (aik = 58.5 mM) but in the presence of ouabain fell to equilibrium (16 mM) after 2 h. In contrast, when HCO3(-) absorption was induced by removal of serosal HCO3(-), aik was elevated to 83.6 mM and, after 4-h exposure to ouabain cell K+, remained far above electrochemical equilibrium at 33 mM. Tissues bathed in Na+-free (Tris) media containing ouabain retained cell K+ after 4 h at even higher levels (46 mM). Cell K+ activity was reduced by removal of K+ from either the mucosal or serosal medium. Acetazolamide reduced aik over 2 h in Na+-free media from 66 to 42 mM. The decline in aik was associated with a concomitant decline in the HCO3(-) absorptive current. It is concluded that K+ is actively accumulated across both luminal and serosal membranes of the jejunal absorptive cell and that the luminal uptake mechanism is linked to HCO3(-) absorption or an equivalent process.

Absorption

Food iron absorption in man. Applications of the two-pool extrinsic tag method to measure heme and nonheme iron absorption from the whole diet.

A new radioisotope method to measure iron absorption from the whole diet was used in this study. The method is based on the concept that food iron is absorbed from two pools, the heme iron pool and the nonheme iron pool, which can be especially labeled with two radioiron isotopes given as hemoglobin and as an iron salt. The purpose of this study was to test the accuracy of this two-pool extrinsic tag method. The meals served were composed as an average of 6 wk consumption in the present material of 32 young enlisted men. The mean and total heme and nonheme iron absorption in all the 32 young men was 1.01+/-0.11. This figure agrees well with the mean daily losses expected for this group of subjects (1.0 mg). The conclusion can therefore be made that there are no major systematic errors of the present method to measure the total iron absorption from a mixed diet. In one series a comparison was made of the absorption of heme and nonheme iron from the meals. A significant correlation between the absorption of the two kinds of iron was found. However, a much greater fraction of the heme iron was absorbed (37%) than of the nonheme iron (5%). The absorption both from breakfast and lunch was in two series found to give a good prediction of the total daily nonheme iron absorption. One series was designed to compare the effect of two levels of iron fortification. There was a significant increase in iron absorption when the level of iron fortification of the meals was increased.

Absorption

Intestinal absorption of several beta-lactam antibiotics. V. Effect of amino beta-lactam analogues and dipeptides on the absorption of amino beta-lactam antibiotics.

The absorption mechanism of amino beta-lactam antibiotics was investigated by using the whole small intestine of a rat. Mutual inhibition among amino beta-lactam analogues and the effects of dipeptides were studied. The influences of glycylglycine on the absorption of cephradine at the four different parts of intestine were also studied. Similarly to the case of cephalexin and cephradine, the absorption of amoxicillin was significantly inhibited by cyclacillin, cephradine, and cephalexin, but the absorption of ampicillin was not reduced by all tested antibiotics. In the experiments using dipeptides (6.0 mM), the absorption of cyclacillin was reduced significantly by glycylglycine, not by L-carnosine. And cephalexin absorption was influenced by L-carnosine (6.0, 10 mM), not by glycylglycine (6 mM). On the contrary, the absorption of cephradine was not reduced at all by these dipeptides. And from the experiment using the four different parts of intestine, it was shown that the transport interaction of glycylglycine with cephradine was observed in only one segment (the upper part of jejunum). These result suggest that the carrier-mediated transport system correlated to dipeptides participates only to a small degree in the common absorption mechanisms of these amino beta-lactam antibiotics.

Amoxicillin

Immunological control of drug absorption from the gastrointestinal tract: effect of local anaphylaxis on the intestinal absorption of low molecular weight drugs in the rat.

Intestinal absorption of various drugs was examined by means of in situ recirculation technique during local anaphylaxis. The antibody was determined by passive cutaneous anaphylaxis technique in rats immunized once or three times. The optimal condition of local anaphylaxis was determined by the leakage of Evans Blue. The most significant increase in leaks of the dye was observed by the intraluminal challenge with 400 mg of ovalbumin for 10 min in ovalbumin-immunized rats, and this condition was chosen as the optimal condition of local anaphylaxis. Under this condition, intestinal absorption of caffeine, phenylbutazone, and bromthymol blue (BTB) significantly decreased in ovalbumin-immunized rats compared with the control, whereas no significant effect was noted in the intestinal absorption of salicylic acid, quinine, pralidoxime iodide (2-PAM), tetracycline, and phenol red. In normal rats, no significant decrease was obtained in the intestinal absorption of caffeine, phenylbutazone, and BTB. On the other hand, the decreased absorption of BTB was not found in ovalbumin-immunized rats by the intraluminal challenge with bovine gamma-globulin. Furthermore, there was no significant change in the decreased absorption of BTB between rats immunized once and three times. The most effective condition for decreased BTB absorption was observed by the intraluminal challenge with 200 mg of ovalbumin for 10 min in ovalbumin-immunized rats, which almost correlated with the data of Evans Blue leakage. From these observations, it appears that the mucosal immune responses affect the intestinal absorption of low molecular weight drugs.

Anaphylaxis

Iron absorption in early pregnancy - a study of the absorption of non-haeme iron and ferrous iron in early pregnancy.

The absorption of non-haeme iron in the food and from a 3 mg reference dose of ferrous iron in solution was measured in 17 healthy women before the 12th week of gestation and in 13 of the women two months after legal abortion. The absorption of ferrous iron in solution was calculated from determinations of the 55Fe activity in blood samples. The food iron absorption was measured from 59Fe-labelled test meals using a highly sensitive whole-body counter. In addition bone-marrow smears and other haematological parameters were studied. The median value of the absorption from the non-haeme food iron was 2.5% and from the ferrous iron salt 10.0 % in early pregnancy in women with storage iron. Two months after abortion the absorption increased to 12.6 and 42.6 % respectively. In early pregnancy the absorption of iron was higher in women without stainable iron in bone-marrow smears. The present results confirm previous observations that the absorption of food iron in early pregnancy is lower than the basal daily requirements. The low absorption is only partly explained by the reduced requirements of iron in early pregnancy. Some other factors related to pregnancy seem also to be involved.

Abortion, Induced

Experimental studies on absorption, distribution and excretion of a new antibiotic, fosfomycin. II. Absorption of oral preparations of fosfomycin calcium salt in dogs (author's transl).

To establish the best usage and dosage of fosfomycin granule and capsules which had been prepared based on our fundamental experiences as described in the first report, absorption of calcium salt contained in both preparations was evaluated using dogs as test animals. (1) Granule containing the calcium salt equivalent to 200 mg of fosfomycin free acid per g showed almost the same absorption as the bulk (fosfomycin calcium), having no disadvantage due to processing. (2) Capsules containing the calcium salt equivalent to 250 mg and 500 mg of the free acid per capsule showed slightly more retarded absorption than the bulk, probably due to some inevitable factors such as disintegration rate of capsules and dispersion rate of the calcium salt. But, once dispersed, the calcium salt in capsules was well absorbed as well as the bulk material. (3) Gastrointestinal absorption of granule and the capsule contents was almost the same. (4) Simultaneous administration of capsules and water improved the absorption efficiency. Though administration after feeding caused somewhat retarded absorption of the drug, the serum levels were rather well sustained with a slight drop but sufficiency of absorption, suggesting better clinical advantages than in the fasted animals. (5) Fosfomycin calcium salt in both preparations was well absorbed in the test animals through gastrointestinal tract as well as the bulk calcium salt, without any possible disadvantage caused by processing. In addition, the absorption efficiency was improved by giving with water or meal to the animals.

Administration, Oral

Drug absorption VII: influence of mesenteric blood flow on intestinal drug absorption in dogs.

Intestinal absorption of sulfaethidole and haloperidol was determined using an in situ canine intestinal preparation. Intestinal absorption of sulfaethidole was determined at three or four mesenteric blood flow rates in each dog, ranging from unaltered flow (100%) to no flow (0%). A relatively small change in absorption rate occurred when the splanchnic blood flow rate was decreased about 35%. Further reductions in mesenteric blood flow resulted in progressive impairment of sulfaethidole absorption. The simultaneous measurement of sulfaethidole intestinal disappearance and appearance in blood indicates that sulfaethidole disappearance is equivalent to absorption. Haloperidol absorption also decreased with decreased intestinal perfusion but differed from sulfaethidole in that membrane storage of haloperidol appeared to take place during its absorption.

Animals

Lateral hypothalamic responses to pre-absorptive and post-absorptive signals related to amino acid ingestion.

This paper reports an investigation of the comparative effects of pre-absorptive and post-absorptive stimuli associated with amino acid ingestion on cat and rat lateral hypothalamic neuronal activity. Pre-absorptive signals, conveyed by the vagus nerve and originating from the small intestine while the amino acids are about to be absorbed, have been previously identified electrophysiologically in our laboratory [3]. They were found to selectively modulate the neuronal activity of some lateral hypothalamic (LHA) cells [4]. The effects of both pre-absorptive and post-absorptive signals associated with amino acid ingestion were analyzed with regard to their degree of convergence at the lateral hypothalamic level. The pre-absorptive signals consisted of either chemospecific information arising from intestinal chemoreceptors and related to the chemical nature of the ingested nutrient, or mechanical information arising from intestinal mechanoreceptors and related to distension. The post-absorptive signal consisted of a microiontophoretic application of amino acids known to selectively affect the neuronal activity of LHA amino acid-sensitive cells [15]. The convergence on these cells of the intestinal afferent amino acid-sensitive units was postulated in this study.

Amino Acids

Age-dependent alterations of intestinal absorption. II. A clinical study using a modified D-xylose absorption test.

With advancing age functional and morphological changes take place within the intestinal tract. The age-dependency of intestinal absorption has been studied using a D-xylose absorption test. The absorption rate (constant k12), the time of appearance of the relative maximum of the D-xylose concentrations in the blood serum after oral administration (time tm), and the extent of the relative absorption in the small intestine as a function of time RA(t) were determined by graphic-mathematical evaluation of the blood level kinetics of D-xylose after oral and intravenous administration. Within the age range of 3 to 96 yr, it has been proven that a slowing down of intestinal absorption occurs with advancing age. By prolonging the period during which the food components are absorbed in the small intestine (shift of tm towards the absorption processes take place at a slower rate. Absorption disorders in old age are due to morbidity and not, sui generis, to involution.

Adolescent

Food iron absorption. I. Use of semisynthetic diet to study absorption of nonheme iron.

Recent studies have established the validity of employing an extrinsic radioiron tag to measure the absorption of nonheme iron from a complex meal. In the present study, extrinsic tagging was used to measure absorption of nonheme iron from a standard meal chosen as representative of a typical American meal, and from a semisynthetic meal having the same total chemical composition. The latter was designed so that the major dietary components could be systematically altered to determine their separate effects on food iron absorption. Absorption from the standard meal in 32 healthy women averaged 10.0% as compared with a mean absorption of 1.8% from semisynthetic meal. Most but not all of this fivefold difference in absorption could be explained by the enhancing effect of meat in the standard meal. The low availability of iron from the semisynthetic meal will be of particular value in studying factors which enhance food iron absorption, whereas the standard meal is suitable for studying factors which reduce availability of food iron.

Absorption

Mechanisms of absorption of inorganic mercury from rat small intestine. I. Solvent drag effect on absorption of inorganic mercury.

A correlation of mercury absorption with water absorption was investigated by using the perfusion of rat small intestine with buffers containing 10(-4) M HgCl2. With a decrease in the osmolarity of the buffers or with increases in the sodium ion and urea concentrations in the buffers, absorption of water and mercury and accumulation of mercury in the intestinal tissue increased, and the increases in mercury absorption and accumulation were found to correlate with the increase in water absorption. Both the decrease in osmolarity and the increase in sodium ion concentration increased mercury accumulation in the epithelial cell after the perfusion. But these changes did not alter the mercury distribution in subcellular fractions. The results suggest that the increase in water absorption due to the hyptonicity or the increase in concentration of sodium ion or urea increases the mercury absorption and accumulation in the epithelial cell without change in the distributional pattern of mercury in the cell.

Adenosine Triphosphate

The role of the pancreas in vitamin B 12 absorption: studies of vitamin B 12 absorption in partially pancreatectomized rats.

The effect of partial pancreatectomy (80-90%) on vitamin B(12) absorption was studied in the rat. The absorption of 5 ng of (57)Co-labeled vitamin B(12) was significantly reduced from 70 +/-2.5% (mean +/-SE) in control and sham-operated rats to 32 +/-2.6% in partially pancreatectomized rats. Hog pancreatic extract (0.17 g/kg) improved vitamin B(12) absorption from 30.0 to 61.0% in partially pancreatectomized rats but did not alter vitamin B(12) absorption in control rats. Chloramphenicol did not enhance vitamin B(12) absorption in partially pancreatectomized rats with pancreatic extract-improved vitamin B(12) malabsorption. The partially pancreatectomized rats with pancreatic extract-improved vitamin B(12) malabsorption were sacrificed and the stomach and small bowel studied in vitro to further define the pathogenesis of the vitamin B(12) malabsorption. Rat gastric intrinsic factor stimulated vitamin B(12) uptake by intestinal sacs prepared from partially pancreatectomized rats 3.1-fold. Gastric intrinsic factor prepared from partially pancreatectomized rats was as effective in promoting vitamin B(12) uptake by rat intestinal sacs as intrinsic factor prepared from control rats. These data indicate that partially pancreatectomized rats develop an abnormality in the absorption of labeled vitamin B(12) which can be corrected by pancreatic extract. The vitamin B(12) malabsorption is due to neither an alteration in gastric intrinsic factor activity nor an impairment of the intrinsic factor-vitamin B(12) receptor in the intestine. It is suggested that in the partially pancreatectomized rats the intrinsic factor-vitamin B(12) complex exists in a form which is not available for absorption.

Animals

Dietary iron absorption in pregnancy - a longitudinal study with repeated measurements of non-haeme iron absorption from whole diet.

In 22 healthy women the non-haeme iron absorption (bone-marrow smears and haematological parameters) was studied at the 12th, the 24th and the 36th week of gestation and two months after delivery. In eight non-pregnant women and in seven pregnant women (at the 36th week of gestation) the absorption of food iron was measured from different types of meals. The iron absorption was measured from radioiron-labelled test meals using a whole-body counter with a very high sensitivity. During pregnancy the non-haeme iron absorption increased continuously from less than 1 % in early pregnancy to almost 15 % in late pregnancy. Calculations indicated that the amount of iron absorbed from the diet covered only about half of the demands. The increasing absorption of food iron during pregnancy seems to be related to the still more increasing demands. However, the very low absorption values in early pregnancy was quite unexpected. The amount of iron absorbed was actually below the basal demands, which means that even in early pregnancy, for reasons unknown, there is a negative iron balance. Further studies are necessary to elucidate the significance of this finding. Two months after delivery the absorption of iron from the diet was increased compared to in non-pregnant women and exceeded the demands at that phase thus indicating that a positive iron balance was achieved.

Adult

Oral magnesium load test for the assessment of intestinal magnesium absorption. Application in control subjects, absorptive hypercalciuria, primary hyperparathyroidism, and hypoparathyroidism.

The intestinal absorption of magnesium (Mg) was estimated from the increment in urinary Mg following oral administration of 25 mmol of Mg. Fasting urinary Mg did not differ between the control group and patient groups (absorptive hypercalciuria, primary hyperparathyroidism, and hypoparathyroidism). As compared to the value in the control group, the increment in urinary Mg above the fasting value was not significantly different in absorptive hypercalciuria. However, it was significantly increased in primary hyperparathyroidism and significantly reduced in hypoparathyroidism. In control subjects, the increment in urinary Mg was much higher during a low than during a high calcium diet. The results suggest that 1,25-(OH)2-vitamin D stimulates Mg absorption, since Mg absorption was elevated in situations associated with stimulated 1,25-(OH)2-vitamin D synthesis (primary hyperparathyroidism and low calcium diet) and reduced in a condition characterized by low 1,25-(OH)2-vitamin D production (hypoparathyroidism). Moreover, the data indicate that 1,25-(OH)2-vitamin D may not be pathogenetically important in absorptive hypercalciuria, since Mg absorption was normal.

Adult

On the absorption probabilities and absorption times of finite homogeneous birth-death processes.

This paper provides some formulas for the absorption probabilities, the mean absorption times and the variances of first absorption times in finite homogeneous absorbing birth-death processes. The results are then applied to a genetic model of Moran [1958] for computing the absorption probability densities, the mean absorption times and the variances of first absorption times. Specifically, it is shown that the probability distribution of the first absorption time is the matrix analog of exponential distribution or a mixture of exponential distributions if the transition matrix is diagonable.

Alleles

Gastric absorption of D-xylose in the rat: its influence on the D-xylose absorption test.

Relatively high incidences of false-positive results of D-xylose absorption tests have been reported. Delayed gastric emptying is invariably listed as one important cause for such tests. However, this conclusion assumes that gastric absorption from the relatively concentrated D-xylose solutions used clinically is negligible. In our study, D-xylose was injected (0.5 gm/kg) into either the stomach or duodenum of rats that had undergone pyloric ligation. Blood xylose levels 30 minutes later were almost as high after intragastric administration (0.61 +/- 0.22 mmol/L) as they were after intraduodenal injection (0.65 +/- 0.16 mmol/L). A chymotrypsin-labile peptide (N-benzoyl-L-tyrosyl-p-aminobenzoate), given at the same time, was poorly absorbed from the stomach, as shown by the low plasma p-aminobenzoic acid levels (14 +/- 2 mumol/L vs. 158 +/- 22 mumol/L after intraduodenal injection). Intragastric absorption of xylose, therefore, did not appear to result from the surgical trauma of pyloric ligation. In rats given doses orally of the D-xylose, the peptide, and a nonabsorbable marker (phenol red), epinephrine and atropine both showed gastric emptying without any surgical trauma, decreased digestion and absorption of the peptide as expected, but did not significantly decrease xylose absorption. These results indicate that, at least in rats, D-xylose is absorbed from relatively concentrated solutions within the stomach. Consequently, circumstances that delay gastric emptying should not markedly decrease xylose absorption. Bacterial overgrowth and altered blood flow seem more likely causes for false-positive D-xylose absorption test results.

4-Aminobenzoic Acid

Absorption of polyethylene glycols 600 through 2000: the molecular weight dependence of gastrointestinal and nasal absorption.

Polyethylene glycols (PEGs) 600, 1000, and 2000 were used to study the molecular weight permeability dependence in the rat nasal and gastrointestinal mucosa. Absorption of the PEGs was measured by following their urinary excretion over a 6-hr collection period. HPLC methods were used to separate and quantitate the individual oligomeric species present in the PEG samples. The permeabilities of both the gastrointestinal and the nasal mucosae exhibited similar molecular weight dependencies. The steepest absorption dependence for both mucosae occurs with the oligomers of PEG 600, where the extent of absorption decreases from approximately 60% to near 30% over a molecular weight range of less than 300 daltons. Differences in the absorption characteristics between the two sites appear in the molecular weight range spanned by PEG 1000. For these oligomers, the mean absorption from the nasal cavity is approximately 14%, while that from the gastrointestinal tract is only 9%. For PEG 2000, mean absorption decreases to 4% following intranasal application and below 2% following gastrointestinal administration. Within the PEG 1000 and 2000 samples, however, very little molecular weight dependency is seen among the oligomers. In the range studied, a distinct molecular weight cutoff was not apparent at either site.

Absorption

Studies on the absorption of sodium guaiazulene-3-sulfonate. II. Absorption mechanism from nasal and intestinal membrane.

To examine the absorption mechanism of sodium guaiazulene-3-sulfonate (GAS) through the nasal and the intestinal membrane, the apparent absorption rate under the various experimental conditions was measured with the in situ perfusion method in rats, and the apparent partition coefficient of GAS was also determined. The absorption rate of GAS changed biphasically depending on the initial GAS concentration in the perfusate. At the lower concentration range (less than 1 mg/ml), the absorption rate of GAS decreased with the increased in the concentration, and the absorption was inhibited by HgCl2 and ouabain. However, at the higher concentration range (greater than 1 mg/ml), the absorption rate from the nasal mucosa increased markedly with the increase in the concentration, and ouabain had no effect. The apparent partition coefficient of GAS increased with the increase in the concentration of GAS, and GAS was found to be readily transferred to the organic phase by forming ion-pair complexes with the cation such as NH4+ ion. These results suggested that GAS is absorbed through the nasal membrane by at least two kinds of mechanisms: one is a carrier mediated system and the other is a hydrophobic interaction with the nasal mucosa which is increased by forming an ion-pair complex of GAS with cation.

Absorption