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PubMed1981

Role of platelets in vasogenic brain edema. II. Contribution of platelet serotonin in brain edema.

In this study of the function of platelets after CNS injury, platelets were treated with serotonin labeled with radioactive carbon (14C) in animals subjected to a freezing lesion of the cerebrum. The distribution of platelet serotonin was measured by counting the specific activity of 14C-labeled serotonin in tissue and by autoradiography. Some of the animals were treated with RA-233, which inhibits the formation of platelet plugs after endothelial damage and the release of serotonin from platelets. Platelet serotonin accumulated near the surface of the cortex at the site of injury in all animals. More cerebral edema developed in animals treated with the platelet inhibitor than in untreated animals, probably because platelet aggregates were inhibited from forming and were not available to plug leaks in the traumatized vessels. Serotonin did not appear to facilitate the spread of edema.

Animals↗

PubMed1983

Penetration of topical indomethacin into phakic and aphakic rabbit eyes.

The penetration of indomethacin labeled with radioactive carbon (14C) into all ocular tissues and fluids was determined at various intervals in both phakic and aphakic rabbit eyes after either single or multiple (every 12 hours for three days) topical application (50 microL) regimens. More indomethacin was found in the vitreous of aphakic eyes compared with phakic eyes after single- or multiple-drop administration. Retinal and choroidal indomethacin concentrations were equal in both phakic and aphakic eyes after either drug regimen and are much greater than those of the vitreous. A pathway other than diffusion through the vitreous exists for the drug to reach these tissues. The concentration of indomethacin reaching the retina and choroid is not sufficient to inhibit prostaglandin formation locally. The concentrations of indomethacin are high enough to inhibit the biotransformation of prostaglandin precursor only in the anterior segment.

Administration, Topical↗

PubMed1983

Radial keratotomy. Effect on cornea and aqueous humor physiology in the rabbit.

Radial keratotomy may cause anatomical damage to the rabbit corneal endothelium. To determine if physiological and functional alterations occur, radial keratotomy was performed on rabbit corneas using eight incisions with sparing of a 3.5-mm central pupillary area. Cornea endothelial membrane permeabilities were determined at various times up to ten weeks following the procedure using simultaneous flux determinations of tritiated inulin and dextran labeled with radioactive carbon on isolated corneas. At all times after radial keratotomy, there was no probable physiologically important change in corneal endothelial permeability to either of the labeled compounds. Fluorophotometry performed in a second group of animals at varying intervals following radial keratotomy showed no probable physiologically important change in endothelial fluorescein permeability. Aqueous humor turnover rate was reduced 16% and 29% at one week and nine to ten weeks, respectively, following radial keratotomy.

Animals↗

PubMed2006

Gene variants of brain dopamine pathways and smoking-induced dopamine release in the ventral caudate/nucleus accumbens.

CONTEXT: Preclinical studies demonstrate that nicotine administration leads to dopamine release in the ventral striatum. However, human studies reveal considerable interindividual variability in the extent of smoking-induced dopamine release. OBJECTIVE: To determine whether common gene variants of the brain dopamine pathway explain this observed phenotypic variability in humans. DESIGN: Blood samples were drawn to determine gene variants of dopamine system components, and positron emission tomography scanning with the radiotracer raclopride labeled with radioactive carbon (11C) was performed to measure smoking-induced dopamine release. SETTING: Academic brain imaging center. PARTICIPANTS: Forty-five tobacco-dependent smokers. INTERVENTIONS: Subjects either smoked a cigarette (n = 35) or did not smoke (n = 10) during positron emission tomography scanning. MAIN OUTCOME MEASURES: Gene variants of dopamine system components (the dopamine transporter variable nucleotide tandem repeat, D2 receptor Taq A1/A2, D4 receptor variable nucleotide tandem repeat, and catechol-O-methyltransferase Val158Met polymorphisms) and change in [11C]raclopride binding potential in the ventral caudate/nucleus accumbens on positron emission tomography scans. RESULTS: For subjects who smoked during scanning, those with at least one 9 allele of the dopamine transporter variable nucleotide tandem repeat, fewer than 7 repeats of the D4 variable nucleotide tandem repeat, and the Val/Val catechol-O-methyltransferase genotype had greater decreases in binding potential (an indirect measure of dopamine release) with smoking than those with the alternate genotypes. An overall decrease in ventral caudate/nucleus accumbens binding potential in those who smoked compared with those who did not smoke was also found but was smaller in magnitude than previously reported. CONCLUSIONS: Smokers with genes associated with low resting dopamine tone have greater smoking-induced (phasic) dopamine release than those with alternate genotypes. These findings suggest that dopamine system genotype variabilities explain a significant proportion of the interindividual variability in smoking-induced dopamine release and indicate that smoking-induced dopamine release has a genetic predisposition.

Adult↗

PubMed1994

The primary site of bacterial translocation.

OBJECTIVE: To establish the primary anatomic site of bacterial translocation in the intestinal tract. DESIGN: Prospective randomized experimental trials. SETTING: Laboratory. MATERIALS: Hartley guinea pigs. INTERVENTIONS: In guinea pigs, 10-cm closed loops of upper jejunum, distal ileum, or proximal colon were created. The animals then received intraluminal injections of Escherichia coli labeled with radioactive carbon (14C) before a 50% full-thickness burn was inflicted. Four hours after the burn injury, the animals were killed, and the intestinal loops, mesenteric lymph nodes, spleen, liver, and lung were harvested. Intestinal loops were irrigated and then treated with ethylenedinitroilotetraacetic acid to separate the enterocytes and colonocytes from the lamina propria. Radionuclide counts were determined in the effluents, the enterocytes (or colonocytes), lamina propria, and other organs. Colony-forming units of E coli were also determined in mesenteric lymph nodes, spleen, liver, and lung. MEASUREMENTS AND MAIN RESULTS: No significant differences were noted in the radionuclide counts in the lamina propria and epithelial cell fraction related to the type of loop. In addition, no significant differences were noted in the radionuclide counts in the mesenteric lymph nodes, liver, spleen, and lung related to the type of loop, but more viable bacteria were recovered when bacteria were injected into the jejunal loop. CONCLUSIONS: Translocation of bacteria occurred with similar intensity throughout the gut, but more bacteria were killed in the process of translocation across the lower part of the intestinal tract.

Animals↗

PubMed1980

An autoradiographic, biochemical, and morphological study of the harderian gland of the mouse.

Biochemical and morphological properties of the Harderian gland of the mouse were examined by combining autoradiographic, biochemical, and electron microscopic techniques. Autoradiographs show that the radioactive carbon from [U-14C]glucose injected to the abdominal cavity is completely incorporated into the acid-insoluble substances within 30 minutes. The results of chemical analysis show that the main components of this gland are glyceryl ether diesters and phospholipids. Scanning electron microscopy shows numerous lipid droplets in the secretory cells and alveolar lumina. Myoepithelial cells lie between the secretory cell base and the basement membrane and have a basket-like distribution of processes as confirmed by hydrochloric acid and collagenase digestions. Myofilaments are demonstrated in the cytoplasm. Two types of secretory cells (A and B) comprise the alveolar epithelium and can be differentiated under the electron microscope. The cytoplasm of both contains numerous vacuoles. The vacuoles are almost empty in A cells, which are more numerous constituent of the alveolar epithelium than B cells. However, the vacuoles of the B cells contain densely osmiophilic material. In both, cell types show a merocrine mode of secretion. Unmyelinated nerve cell endings occur in the interstices of the connective tissue, and contain clear or cored vesicles.

Animals↗

PubMed1982

Studies on regional blood flow of the mouse using whole-body autoradiography of 14C-iodoantipyrine.

In order to visualize regional blood flow in various tissues of the mouse at the same time, the distribution of radioactive carbon from 14C-iodoantipyrine was studied by whole-body autoradiography. The mice were frozen with Dry-Ice-hexane at 1, 10, 30 min, and 1 h and 3 h after intravenous injection of 14C-iodoantipyrine. Whole-sagittal sections of the frozen mouse, obtained by using a cryostat microtome, were dried in a cryostat and subjected to autoradiograhy. The resulting dry autoradiographs are called untreated autoradiographs in the present work. The sections were then fixed in cold 6% (w/v) HClO4, dried at room temperature and again subjected to autoradiography. Autoradiographs thus obtained are referred to as treated autoradiographs. It was found that the method could be suitable for the estimation of regional blood flow of the renal cortex, spleen, lung, skeletal muscle, bone marrow, thymus, testes, and brain.

Animals↗

PubMed1982

Microbial degradation of thidiazuron and its photoproduct.

Degradation of the cotton defoliant thidiazuron and its photoproduct photothidiazuron by soil and thirteen species of microorganisms was examined. Aspergillus versicolor, Torula rosea, and Flavobacter sp. were most active in degrading thidiazuron. Unknown water-soluble metabolites and phenylurea were the major products. A. versicolor and Penicillium cyclopium were most active in degrading photothidiazuron. 4-Hydroxyphenylphotothidiazuron was the major organosoluble product formed by A. versicolor; phenylurea and an unidentified metabolite constituted the major organosoluble products from P. cyclopium. Both microbes also formed appreciable water-soluble metabolites. Radioactive carbon dioxide was formed from thidiazuron-aniline-14C by Oscillatoria sp. but not by Chlorella sp., suggesting that the former algal species utilized the defoliant as an energy source.

Bacteria↗

PubMed1979

Laboratory simulations of the Viking labeled release experiment: kinetics following second nutrient injection and the nature of the gaseous end product.

Injection of 14C-labeled nutrient onto Mars soil produced an evolution of 14C gas in the Viking Labeled Release (LR) experiment. However, a second injection of nutrient seven days later was followed by an abrupt diminution of the amount of radioactive gas in the test cell. Simulation experiments performed in the LR Test Standards Module (TSM) have yielded a plausible explanation for this diminution. Radioactive carbon gases were injected into the TSM test cell in the presence and absence of two Mars analog soils. After equilibration, water was injected and its effect observed. The results indicate that the flight data following second nutrient injection can be explained on a physico-chemical basis involving a carbon dioxide/water/soil equilibrium in the test cell. The results also suggest that the gaseous end product of the Labeled Release reaction on Mars is more likely carbon dioxide than carbon monoxide.

Carbon Radioisotopes↗

PubMed1984

Mineralization of 2,4-dichlorophenoxyacetic acid in soil simultaneously enriched with saccharides.

Detoxication of 2,4-dichlorophenoxyacetic acid (2,4-D) in samples of chernozem soil was determined by a biological test and the time course of production of 14CO2, a product of microbial degradation of 2-14C-2-4-D, was measured during 38-d incubation at 28 degrees C in the dark. Enrichment of the soil with glucose (1000 ppm), two exocellular bacterial glucan and glucomannan polysaccharides (750 ppm), or a mixture of glucose with (NH4)2SO4 (C : N = 5 : 1) brought about acceleration of both detoxication and mineralization of 2,4-D (50 ppm) added simultaneously with the saccharides. Mineralization of the saccharides always preceded the degradation of the herbicide. The lag phase of 2,4-D mineralization did not exceed 3 d. In samples with saccharides the doubling time of the mineralization activity in the exponential phase of the process was substantially shortened and the mineralization of 2,4-D was accelerated even when the soil was inoculated with a suspension of soil in which microbial 2,4-D decomposers had accumulated. The extent of mineralization was not affected by the presence of saccharides (about 1/3 of the introduced radioactive carbon was transformed into 14CO2). All saccharides had a similar effect which reflected an increase in the overall bacterial count and in the relative abundance of bacterial 2,4-D decomposers . The role of other mechanisms such as co-metabolism in the stimulation of the degradation process is discussed.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1984

Mineralization of 2,4-dichlorophenoxyacetic acid in soil previously enriched with organic substrates.

Samples of chernozem soil were enriched with vanillic acid, protocatechuic acid glucose, a mixture of glucose and (NH4)2SO4 (C : N = 5 : 1), ethanol and 2,4-dichlorophenoxyacetic acid (2,4-D). After a 6-d (with 2,4-D 35-d) incubation during which primary oxidation of the introduced substrates occurred, the soil was supplied with a solution of 2-14C-2,4-D (50 ppm; 6.7 kBq) and production of 14CO2 (product of microbial degradation of 2,4-D) was measured. Previously enriched samples exhibited a higher degradation rate; both the lag phase and doubling time of mineralization activity in the exponential phase of the process were markedly higher. This reflected an overall proliferation of bacteria and the increased relative proportion of bacterial strains capable of mineralizing 2,4-D in enriched samples. The stimulation of 2,4-D degradation may involve specific adaptation and selection mechanisms (as in the case with samples previously enriched with 2,4-D or its structural analogues--aromatic monomers, ethanol) as well as non-specific mechanisms. The extent of mineralization of 2,4-D was not affected by soil pretreatment, about 1/3 of introduced radioactive carbon being invariably transformed to 14CO2.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1975

Comparative distribution of pilocarpine in ocular tissues of the rabbit during administration by eyedrop or by membrane-controlled delivery systems.

We compared the patterns of pilocarpine distribution in the rabbit eye during two regimens that were comparably efficacious in human clinical use: an administration of 2% pilocarpine nitrate eyedrops, every six hours, for four and eight days, and a continuous delivery of pilocarpine for as long as eight days, at 20 mug/hr, from a membrane-controlled delivery system in the inferior cul-de-sac. Pilocarpine labeled with radioactive carbon (14C) was used as a tracer. With administration of eyedrops, 14C levels in ocular tissues rose and fell within each six-hour interval between eyedrops, but with the delivery system, 14C levels remained constant over the two- to eight-day period. In each tissue, the 14C level within the first hour after the most recently administered eyedrop always exceeded the constant level maintained by the delivery system. Three to six hours after eyedrop administration, the 14C levels in cornea, iris, and sclera were approximately equal to those maintained by the delivery system. However, in lens, vitreous humor, and conjunctiva, the 14C levels were always two to five times higher with eyedrop administration than with the delivery system. Only aqueous humor showed a significantly lower 14C level with eyedrops than with the delivery system, occurring late in the interval between eyedrops. Compared to eyedrop administration, the membrane-controlled delivery system produced drug levels in ocular tissues that were constant rather than variable with time, and appreciably lower in tissues where the drug made no known contribution to the reduction of pressure.

Administration, Topical↗

PubMed1976

Glucose concentrations and glycogen levels in the aqueous humor of fresh and refrigereated bovine eyes.

Glucose concentrations in the aqueous humor and its incorporation into epithelial glycogen were measured by adding glucose uniformly labeled with radioactive carbon to the anterior chamber of both fresh and stored bovine eyes (24 hours at 5 degrees C). Concentrations of exogenous glucose in the aqueous humor were higher in refrigerated eyes but declined as rapidly as those in fresh eyes. Furthermore, the epithelium retained the ability to incorporate the exogenous glucose into glycogen after 24 hours of storage at 5 degrees C. Addition of glucose to the aqueous humor of human eyes after refrigeration may increase epithelial retention on donor corneal buttons.

Animals↗

PubMed1977

Experimental intraocular penetration of dacarbazine.

Radioactive carbon (14C)-labeled dacarbazine was used to trace penetration of the drug to the eye after intravenous and subtenon-retrobulbar injection on experimental animals. After subtenonretrobulbar injection of 1 or 2.5 mg of commercial dacarbazine twice daily for two weeks, there were no clinical changes. However, doses of 5 to 7.5 mg per injection produced destructive chorioretinitis, and a proliferative type of retinopathy was confirmed histopathologically.

Animals↗

PubMed1977

Regional differences in ocular concentration of gentamicin after subconjunctival and retrobulbar injection in the rabbit.

We compared the penetration of radioactive carbon (14C) labeled-gentamicin into ocular tissues and fluids of albino rabbit eyes after subconjunctival (anterior subtenon's) and retrobulbar (posterior subtenon's) injections. In both normal and infected (Staphylococcus aureus endophthalmitis) eyes, higher levels of drug were produced with subconjunctival rather than with retrobullar admininistration in cornea, sclera, choroid and retina (as a unit), and iris; levels in the aqueous and vitreous humors of infected eyes were similar with the two routes of injection. Marked regional variations in the concentrations of gentamicin were noted in cornea, sclera, and choroid-retina after subconjunctival therapy. The pattern of these variations suggests that subconjunctival antibiotic penetrates the eye by direct diffusion. The low levels of drug after retrobulblar injection may be due to systemic absorption through the highly vascular orbital plexus of the rabbit.

Absorption↗

PubMed1982

The effect of intraocular irrigating solutions on lens clarity in normal and diabetic rabbits.

We conducted a series of experiments on normal and diabetic rabbits to evaluate the effect of intraocular irrigating solutions on the lens. Lenticular clarity was studied in vivo in eyes undergoing vitreous cavity perfusions with various irrigating solutions. The clarity of isolated lenses incubated in these same solutions was also evaluated. In order to quantitate the cataractous changes observed, we measured the uptake of inulin (tagged with radioactive carbon) by isolated lenses. We found that balanced salt solution (BSS) and BSS Plus maintain excellent lens clarity in normal rabbits; that diabetic lenses are more likely to develop opacification than normal lenses, becoming cataractous when exposed to BSS Plus; and that adding supplemental glucose to BSS Plus allows this solution to maintain excellent lens clarity in diabetic rabbits.

Animals↗

PubMed1983

Glucocorticoid induction of tryptophan oxygenase. Attenuation by intragastrically administered carbohydrates and metabolites.

In vivo tryptophan 2,3-dioxygenase (TPO) activity in male rats was estimated from the rate of production of 14CO2 after intragastric administration of [14C-2]tryptophan. The synthetic glucocorticoids hydrocortisone-21-sodium succinate or Triamcinolone acetonide were injected to elevate hepatic TPO activity on an acute (1-6 hr) or chronic (24 hr) basis. Glucose, fructose, or glycerol was intragastrically intubated in doses ranging from 4 to 16 mmoles to assess their abilities to attenuate acute or chronic increases of TPO activity by these glucocorticoids. Hydrocortisone-21-sodium succinate at doses of 0, 25, and 50 mg/kg produced dose-dependent elevations of TPO. A 50 mg/kg dose produced a 3-fold elevation of enzyme activity when measured in vitro as product produced by liver homogenates and a 2-fold elevation when assessed from expired radioactive carbon dioxide from radiolabeled tryptophan in vivo. Enzyme activity measured by 14CO2 production reached peak values in 2-3 hr and returned to baseline in 5 hr. Glucose, fructose or glycerol completely prevented the rise in conversion of [14C-2]tryptophan produced by hydrocortisone hemisuccinate when administered at doses of 12 or 16 mmoles 0.5 hr before the steroid. Lower doses had less effect. The potencies of the compounds in inhibiting acute increases in TPO activity produced by hydrocortisone hemisuccinate were in the order glycerol greater than fructose greater than glucose. Chronic Triamcinolone treatment elevated in vivo TPO activity by 2.5-fold and in vitro TPO activity by 5-fold. The chronic elevation of in vivo TPO by Triamcinolone could be arrested within 1 hr by an intragastric fructose load. The present finding, that acute or chronic glucocorticoid-induced increases in in vivo TPO activity were rapidly blocked by intragastric carbohydrate loads, is consistent with the view that dietary carbohydrates modulate hepatic TPO activity via feedback repression and not by a cessation of TPO enzyme synthesis.

Animals↗

PubMed1980

Putrescine catabolism in rats given heparin or aminoguanidine.

Rats treated acutely with aminoguanidine, a potent inhibitor of diamine oxidase, or with heparin display reduced ability to metabolize 14C-putrescine to radioactive carbon dioxide. After either drug rats recover 50% of the ability to catabolize putrescine in 15--18 h. This is in close agreement with the half-time for recovery of diamine exidase activity, and indicates that putrecine-catabolizing ability of the rat reflects in a physiologically significant way the function of diamine oxidase in vivo.

Amine Oxidase (Copper-Containing)↗