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Biomedical subjects

R C Rose

Publications and source records attributed to R C Rose.

At least 91 records · Page 5Linked to original sources

Glucose-independent transport of dehydroascorbic acid in human erythrocytes.

It has been previously reported that glucose and its structural analogs inhibit dehydroascorbic acid (DHA) transport across the membranes of nonpolar cells, which led to the suggestion that the hexose transporter mediates dehydroascorbic acid transport. The present study examines the role of the erythrocyte hexose transport system in dehydroascorbic acid uptake. We have confirmed that dehydroascorbic acid may be a ligand of the hexose transport system under certain experimental conditions. However, there is an additional pathway of dehydroascorbic acid transport that is uninfluenced by external glucose. This pathway is one of facilitated diffusion, demonstrating saturation kinetics of transport, cis-inhibition, and trans-stimulation. The Km for the system is 412 microM. It is suggested that this previously undescribed sugar-independent transporter is the physiologically important route of DHA uptake in erythrocytes.

Adult↗

Transport and metabolism of vitamins.

Although the biochemical roles of most vitamins in the body are reasonably well understood, our knowledge of how the body transports and metabolizes the vitamins is incomplete. This paper summarizes the information available on riboflavin, vitamin B-6, biotin, vitamin D, vitamin C, and pantothenic acid. As might be expected on the basis of the diverse chemistry and biology of these substrates, the body has quite unique mechanisms for handling each of them.

Animals↗

Effective use of renal cortical slices in transport and metabolic studies.

The uptake and metabolism of two water-soluble vitamins were measured in rat renal cortical slices, isolated tubules, and vesicles of the brush-border and basolateral cell membranes to determine (a) whether it is possible to produce slices that have open tubules and, (b) whether slices and tubules metabolize vitamins similarly. Transport of ascorbic acid is sodium-dependent in slices and in brush-border vesicles but is sodium-independent in basolateral vesicles, suggesting that the brush-border membrane of slices is accessible to components of the bathing solution. Nicotinic acid was metabolized similarly (97-98%) in both slices and isolated tubules. Oxygen consumption by slices maintained in a closed chamber was constant as pO2 decreased from 88% to 58%. Slices are concluded to be a suitable model for transport and metabolic studies providing that care is taken in their preparation and use.

Animals↗

Transport of L-ascorbic acid and dehydro-L-ascorbic acid across renal cortical basolateral membrane vesicles.

The uptake of L-ascorbic acid and dehydro-L-ascorbic acid into renal cortical basolateral membrane vesicles has been characterized. The uptake systems for both solutes demonstrate saturation kinetics. The presence of structural analogs of L-ascorbic acid and dehydro-L-ascorbic acid results in cis-inhibition and trans-stimulation. Uptake of each substrate is Na+-independent, proceeding to an endpoint of substrate equilibrium across the vesicular membrane. The transport mechanism(s) for L-ascorbic acid and dehydro-L-ascorbic acid appears to be facilitated diffusion.

Animals↗

Na+-independent dehydro-L-ascorbic acid uptake in renal brush-border membrane vesicles.

A membrane preparation enriched in the brush-border component of the plasma membrane was isolated from rat renal superficial cortex by a divalent cation precipitation procedure. Uptake of dehydro-L-ascorbic acid, the oxidized form of L-ascorbic acid, by the brush-border membrane vesicles was studied. The uptake mechanism was found to be sodium-independent and insensitive to the trans-membrane electrical potential difference. Uptake was saturable and subject to cis-inhibition. Concentrative uptake was demonstrated only under conditions of trans-stimulation by structural analogs. The results suggest a mechanism of facilitated diffusion for the uptake of dehydro-L-ascorbic acid in renal brush-border membranes.

Animals↗

Intestinal transport of vitamins.

Animals rely on acquiring through their diet, certain micronutrients required to support metabolism that we refer to as vitamins. The water-soluble vitamins are absorbed in the intestine only slowly by simple diffusion; specific mechanisms of transport have evolved that normally insure complete availability of each substrate to the organism. Secondary genetic errors that result in the impairment of an intestinal transport mechanism may become debilitating.

Animals↗

Liquid chromatographic behavior of ascorbate on amine columns.

Quantitation of ascorbate at concentrations normally found in biological samples and foods has previously been shown to be possible by HPLC analysis. Prefilled amine columns from three manufacturers were presently used to evaluate their potential for separating low concentrations of [14C]ascorbic acid from its degradation products, [14C]dehydroascorbic acid and [14C]diketogulonic acid. A successful separation was achieved on some columns with as little as 200 cpm (30 pmol) of total ascorbate injected. On other columns, injection of 30-500 pmol of ascorbate resulted in as much as 80% of [14C]ascorbic acid eluting with an unpredictable retention time. In these instances the inclusion of nonlabeled ascorbic acid (0.5 mg/ml) to the sample resulted in most of the [14C]ascorbic acid activity eluting at the expected retention time of ascorbic acid. The inclusion of ascorbic acid in samples injected onto the column also resulted in a more discrete peak in the elution of dehydroascorbic acid, and more complete recovery of the total [14C]activity (ascorbic acid, dehydroascorbic acid, and diketogulonic acid) injected onto the column.

Amines↗

Norepinephrine stimulates amylase release from pancreatic acini.

alpha-Adrenergic blockade decreases food-stimulated amylase secretion in dogs, suggesting that physiologic sympathetic nerve discharge of norepinephrine enhances pancreatic enzyme secretion. Previous studies have not separated direct effects of adrenergic agonists on pancreatic exocrine cells from effects on blood flow. An in vitro preparation of dispersed acini from guinea pig pancreas was modified and amylase release in response to common pancreatic stimulants was measured. It was demonstrated that physiologic concentrations of norepinephrine enhance amylase release from dispersed pancreatic acini evoked by supramaximal concentrations of cholecystokinin. These observations suggest that the sympathetic nervous system plays a role in modulating pancreatic enzyme secretion independent of effects on blood flow.

Amylases↗

Herpes simplex virus type II meningoencephalitis in an immunocompromised adult.

A 35-year-old man with chronic granulocytic leukemia had disseminated herpes simplex virus type II. Cerebrospinal fluid pleocytosis, aphasia, and an abnormal electroencephalogram suggested the diagnosis of meningoencephalitis. He was treated with adenosine arabinoside and recovered without clinically evident sequelae.

Adult↗

Nicotinamide uptake and metabolism by chick intestine.

Intestinal uptake and metabolism of nicotinamide (NAm) were studied in isolated epithelial cells and in isolated segments in situ at a physiological concentration of [14C]NAm (11.7 microM). [14C]NAm was rapidly taken up from the bathing medium and largely metabolized to [14C]NAD by the isolated cells. Total accumulation of 14C label was energy dependent and saturable at higher concentrations of NAm (148 and 351 microM). In contrast, the tissue content of NAm was unaffected by metabolic inhibitors, and the bathing media NAm rapidly equilibrated with intracellular space at all levels of NAm. NAm was converted directly to NAD via the intermediate nicotinamide mononucleotide (NMN); nicotinic acid was not an intermediate in this conversion and was a less efficient precursor of NAD. NAm absorption in vivo was substantial, 30.6% of dose after 10 min. Also, data on NAm entry into the mucosa and subsequent metabolism in vivo supported the in vitro observations. Exogenous NMN reduced NAm entry into the mucosal cells both in vivo and in vitro; the effect was specific to NAm. This is the only suggestion to date that NAm entry might proceed by some form of specialized transport process.

Adenosine Triphosphate↗

Ascorbic acid uptake in guinea pig intestinal mucosa.

Cellular accumulation of ascorbic acid was investigated in vitro in distal intestinal mucosa of guinea pig. With 14C-ascorbic acid present at 8 microM/L in the bathing media, tissue/media (T/M) concentration ratios of at least 5 were routinely achieved. Recently absorbed ascorbic acid appeared to be free in solution in the cellular fluid in that it diffused from tissue exposed to poisons with a disappearance half-time of approximately 10 minutes. Ascorbic acid uptake was highly dependent on the presence of sodium in the bathing media; total Tris substitution resulted in a 97% decrease in uptake. Also, metabolically depleted tissue did not accumulate ascorbic acid against a concentration gradient. Uptake of 14C-ascorbic acid from a bathing solution concentration of 8 microM/L was reduced 67% in the presence of 0.8 mM/L nonlabeled ascorbic acid. Recently absorbed 14C-ascorbic acid moved more rapidly back into the lumen when the luminal solution contained nonlabeled ascorbic acid (5 mM) than when it contained mannitol (5 mM). This demonstration of counter transport substantiates a carrier mechanism in the brush border.

Animals↗

Ions and water in the epithelial cells of rabbit descending colon.

1. Isolated sheets of rabbit descending colon epithelial cells stripped from their underlying muscle coats were incubated in chambers at 37 degrees C with oxygenated media, and their non-inulin space water, sodium, potassium and chloride contents were subsequently determined. 2. With sodium Ringer bathing both surfaces, amiloride, 10(-4) M, decreased non-inulin space sodium content by 76 mmol/kg dry wt. Ouabain, 10(-3) M, caused loss of non-inulin space potassium which was not completely compensated for by uptake of sodium over 30 min incubation. Chloride and water, therefore, decreased. Amiloride, 10(-4) M, inhibited but did not prevent this uptake of sodium after ouabain. 3. Tissues exposed to sodium-free choline Ringer rapidly exchanged non-inulin space sodium for choline and, more slowly, lost potassium, chloride and water. The equilibration of sodium in the non-inulin space when sodium Ringer was restored to the mucosal medium alone was largely amiloride-insensitive. For restoration of non-inulin space potassium to normal levels, sodium was required in the serosal but not the mucosal medium. 4. Neither the absence of glucose nor the absence of chloride from the mucosal medium affected the non-inulin space sodium content when sodium was restored to the mucosal medium bathing sodium-depleted tissues. 5. It is argued that, whereas non-inulin space potassium and water contents are synonymous with their cellular values, only about one third of non-inulin space sodium is cellular when sodium Ringer bathes both surfaces, and the concentration of the sodium within the cellular transport pool approximated 20 mmol/kg H2O, consistent with estimates obtained from other techniques.

Amiloride↗

Bile acids: effects on absorption of 1,2-dimethylhydrazine and 7,12-dimethylbenz[a]anthracene in the colon of the rat and guinea pig.

The specific effects of bile acids as cocarcinogens were investigated. Absorptions of [14C]7,12-dimethylbenz[a]anthracene, [14C]dimethylhydrazine ([14C]DMH), and [3H]inulin from loops of colons from outbred Sprague-Dawley rats and Hartley guinea pigs were determined. In each animal absorption of one carcinogen and inulin was studied in one control loop and in an experimental loop containing either deoxycholic acid (DOC) or chenodeoxycholic acid (CDOC). DOC had a more pronounced effect on increasing loss of carcinogen from the intestinal lumen than did CDOC. This role of bile acids was consistent with their known effect of increasing intestinal permeability. Less carcinogen remained in the colon mucosa when DOC was present in the intestinal lumen. Although [14C]DMH was absorbed more rapidly from the intestinal lumina of guinea pigs than from those of rats, the rat accumulated more of the carcinogen in the intestinal mucosa and liver.

1,2-Dimethylhydrazine↗

Transport and metabolism of water-soluble vitamins in intestine.

An overview of intestinal absorption of water-soluble vitamins is presented. Evidence relating to absorption of ascorbic acid by the "sodium-gradient" hypothesis and folic acid by the "acidic microclimate" hypothesis is discussed. Over the last decade, vitamin absorption by the intestine has been attributed in large part to simple diffusion. Recently, however, this view has been changing as information continues to be gathered which suggests the participation of membrane-bound "carriers" in transport and the involvement of cellular enzymes in metabolism of the vitamins during absorption. The circumstances that make vitamin absorption difficult to investigate are described. A brief look toward the future stresses the types of information that will be helpful to acquire, identifies some technological advances that will promote progress, and discusses potential application of the results to health care. Some reasons are given for confusion that has prevailed in descriptions of vitamin absorption during the last decade; suggestions are made that might help investigators to correct this situation.

Animals↗