Search PubMed⌕ Search

Biomedical subjects

A Vinegar

Publications and source records attributed to A Vinegar.

At least 19 recordsLinked to original sources
PubMed1992

Polychlorotrifluoroethylene (PCTFE) oligomer pharmacokinetics in Fischer 344 rats: development of a physiologically based model.

The hydraulic fluid oil polychlorotrifluoroethylene (PCTFE) is hepato- and nephrotoxic in the rat. Male Fischer 344 rats were exposed to PCTFE either for a single 6-hr exposure (0.5 or 0.25 mg/liter) or daily 5 days/week, 6 hr/day, for 13 weeks (0.5, 0.25, or 0.01 mg/liter). Blood, tissue, and urinary PCTFE concentrations measured postexposure were used to develop a physiologically based pharmacokinetic (PB-PK) model. The PCTFE hydraulic fluid used was a mixture of trimeric and tetrameric oligomers with minor amounts of other chain lengths. The PB-PK model was designed to describe the behavior, not of individual oligomers, but of total mass for the trimer and tetramer in each tissue. Partition coefficients were estimated using the model to optimize tissue/blood concentration ratios measured at the end of the 13-week exposure. First-order metabolic rate constants for both trimeric (2.0 hr-1) and tetrameric (1.0 hr-1) portions were estimated by optimization against urinary fluoride data assuming release of 0.77 mole fluoride per mole trimer and 0.844 mole fluoride per mole tetramer metabolized. To obtain accurate simulation of pharmacokinetic data it was necessary to hypothesize two fat compartments with diffusion-limited exchange of PCTFE oligomer with the blood. Relative concentrations of trimer and tetramer in venous blood, liver, and fat after a single 6-hr exposure were proportional to inhaled concentrations. Tetramer accumulated preferentially with multiple exposure. Components of PCTFE were metabolized to carboxylic acids with release of fluoride. Due to their persistence tetrameric oligomers appear to be more important than trimeric oligomers as causative agents of PCTFE hepato- and nephrotoxicity in the rat.

Administration, Inhalation↗
PubMed1991

Effects of short-term oral dosing of polychlorotrifluoroethylene (polyCTFE) on the rhesus monkey.

Polychlorotrifluoroethylene (polyCTFE--primarily oligomers with 3-4 monomer units), a non-flammable hydraulic fluid for aircraft, was given daily for 15 days by oral gavage to four Rhesus monkeys at a concentration of 0.725 g kg-1. The administered dose was at a level that had caused toxicity in rats. Steady-state blood and liver concentrations reached were the same in both species. In monkeys, polyCTFE did not cause the electrolyte, serum protein, liver enzyme and anemic disturbances previously seen in rats. Liver sections taken at 15 days, analyzed for palmitoyl Co-A beta-oxidation rates or by electron microscopy, showed no significant indication of peroxisomal proliferation. An increased blood urea nitrogen (BUN) at 15 days was the only clinical pathological abnormality seen in both monkeys and rats. Previously unobserved effects were increased triglycerides and glycogen depletion.

Administration, Oral↗
PubMed1990

Action by the lungs on circulating xenobiotic agents, with a case study of physiologically based pharmacokinetic modeling of benzo(a)pyrene disposition.

The lungs contain enzyme systems that metabolize xenobiotic agents, and the structure and position in the circulation render this organ potentially important in the metabolic removal of substances from the blood. Pulmonary enzyme systems that oxidize xenobiotic agents include cytochrome P450- or flavin-containing monooxygenases. In addition, the lungs accumulate certain agents, notably basic amines, without substantially metabolizing them. Benzo(a)pyrene (B(a)P) is one example of a xenobiotic agents that is eliminated from the circulation largely by oxidative metabolism. We have described the metabolic elimination of B(a)P using a physiologically based pharmacokinetic model applied retrospectively to existing data sets of B(a)P metabolism and disposition in rats. The result suggests that the lungs may, under certain conditions, contribute significantly to xenobiotic disposition and that this contribution is greater than that predicted by the activity of dispositional enzyme in this organ. Thus, the lungs may play a significant role in the metabolic elimination of some xenobiotic agents under certain circumstances.

Animals↗
PubMed1990

Chloropentafluorobenzene: short-term inhalation toxicity, genotoxicity and physiologically-based pharmacokinetic model development.

Ten Fischer 344 rats and six B6C3F1 mice of each sex were exposed to air, 0.25, 0.80, or 2.50 mg chloropentafluorobenzene (CPFB)/liter of air for three weeks, excluding weekends. Exposure to 2.50 mg/liter caused a reduction in the growth rate of rats but did not affect the growth rate of mice. Following the exposure there was reduced SGOT activity in the blood serum of exposed rats and a dose related increase in liver weights. Increased liver weights were observed in mice as well; the response in the female groups was clearly dose dependent. Histologically the livers of both rats and mice presented single cell necrosis. In exposed mice hepatocytes exhibited mild hepatocytomegaly with increased granular eosinophilic cytoplasm. In evaluations for its potential to induce chromosomal damage following this exposure regimen, CPFB did not alter the rate of bone marrow cellular proliferation. Assessment of the micronucleated polychromatic erythrocytes and normochromatic erythrocyte populations during the inhalation exposures indicated a general absence of genotoxic activity.

Administration, Inhalation↗
PubMed1987

Use of a modified Swan-Ganz pacing catheter for measuring Pdi and diaphragmatic EMG.

Measurements of pressures across the diaphragm (Pdi) and diaphragmatic electromyogram (EMG) have become an integral tool to study respiratory muscle fatigue. To measure Pdi and diaphragmatic EMG, three balloon catheter systems have to be swallowed; two of these measure esophageal and gastric pressures and the third one, usually a Swan-Ganz catheter records diaphragmatic EMG. In the present study we describe how a thermodilution Swan-Ganz pacing catheter can be very simply modified to measure both Pdi and diaphragm EMG. Because only one catheter has to be swallowed, subject's acceptability improves, particularly for repeated measurements in the same subject. We have used such a catheter system for more than 18 months to study respiratory muscle fatigue in man. The measurements of Pdi by the modified Swan-Ganz catheter compare well with those recorded simultaneously with conventional balloons, and in vitro frequency response measurements showed that amplitude responses differed by 2% at 2 1/2 Hz. Phase responses of the esophageal and gastric balloons were linear over the range of frequencies tested.

Catheterization↗
PubMed1986

Toluene diisocyanate-induced airway hyperreactivity and pathology in the guinea pig.

We assessed the nature and progression of airway mucosal disease and histaminic reactivity in English short-haired guinea pigs at 2, 24, 72, 168, and 504 hours after toluene diisocyanate (TDI) exposure (4 hours of 3 ppm of TDI for 5 consecutive days). To also determine whether TDI-specific, IgE-like antibodies developed in TDI-exposed animals, passive cutaneous anaphylaxis testing was done 28 days after TDI. Bronchial reactivity was determined serially by measuring specific airway conductance as a function of increasing doses of aerosolized histamine in six exposed and three control animals studied intact and unanesthetized. The remaining 10 exposed and 10 control guinea pigs were sacrificed in groups of two at each time point to obtain airway tissue for light microscopic examination. We found that airway hyperreactivity to histamine occurred after TDI in all animals tested. It was maximal 2 hours after the 5-day exposure and remitted by 72 hours. In addition, marked airway obstruction occurred after TDI that persisted for at least 168 hours. There were dramatic signs of airway mucosal damage associated with the bronchial hyperreactivity that included substantial decreases in epithelial cilia, mucin content, and mast cells, as well as squamous metaplasia, numerous mitotic figures, and a prominent polymorphonuclear leukocytic infiltrate. Passive cutaneous anaphylaxis tests in exposed animals were negative. Our results suggest that TDI-induced bronchial hyperreactivity may be related to airway mucosal injury and inflammation.

Airway Resistance↗
PubMed1986

The pathogenesis of experimental pulmonary histoplasmosis. Correlative studies of histopathology, bronchoalveolar lavage, and respiratory function.

A murine model of acute pulmonary histoplasmosis was employed to study the pathogenesis of the disease process by means of histopathology, bronchoalveolar lavage, and respiratory function tests. These studies were performed on C57BL/6 mice from 8 h to 8 wk after intranasal inoculation of 10(5) yeast forms of Histoplasma capsulatum and on age-matched control animals that received saline only. At Week 1, the histopathology was characterized by subacute inflammation consisting of polymorphonuclear leukocytes (PMN), lymphocytes, and macrophages that infiltrated the interstitium around small bronchioles and adjacent alveoli. At Weeks 2 and 4, the infiltrates were comprised predominantly of lymphocytes and macrophages; noncaseating granulomas were present at Week 2. Aggregates of lymphoid cells were prominent along the bronchial tree and in perivascular distribution. Those in close contact with bronchiolar epithelium resembled hyperplastic bronchus associated lymphoid tissue. Quantitative studies of cells in the BAL fluid revealed a large influx of PMN at Week 1 with return to normal range by Week 2. At this time there was a significant (p less than 0.02) increase in lymphocytes that persisted through Week 8, although histopathologic changes were minimal in lung at this time. A significant decrease in the DLCO/TLC at Week 2 in association with a normal vital capacity indicated impairment of respiratory function secondary to the alveolitis induced by H. capsulatum infection rather than a reduction of lung volume. This model offers promise for additional correlative studies of lymphocyte subsets in lung tissue and alveolar spaces as well as of the functions subserved by these respective populations.

Animals↗
PubMed1986

Morphology of tracheal and bronchial epithelium and type II cells of the peripheral lung of the guinea pig after inhalation of toluene diisocyanate vapors.

Toluene diisocyanate (TDI), a polymerizing agent used in production of plastics, can cause airways disease in some exposed individuals. Using guinea pigs as a model, the response of the airways and the type II cells of the peripheral lung was monitored morphologically and morphometrically after exposure to TDI vapors at 30 ppb, 260 ppb, and 3100 ppb. The two low doses of TDI caused little change in airways epithelium. There was no gross inflammatory cell infiltrate, however, surface infoldings and intracellular ciliated cysts increased in numbers. Animals exposed to 3100 ppb TDI 4 h/day for 5 days, sustained considerable damage to the epithelium, and stratified nonkeratinizing cells lined the airways until one week after exposure. Polymorphonuclear leukocytes were present in the early period after exposure. Increased numbers of eosinophils were present between one and two weeks following exposure. Mitoses in the epithelium were common during recovery. In the peripheral lung, though a modest subjective increase in the number of type II cells was seen after 3100 ppb TDI, the volume density of type II cells, and organellar components (lamellar bodies, mitochondria, cisternal bodies) did not change significantly after any exposure level of TDI.

Animals↗
PubMed1985

Effect of exposure to 500 ppm sulfur dioxide on the lungs of the ferret.

Male ferrets (Mustela putorius furo) were exposed 3 h/day, 3 days/week for 12 weeks to 500 ppm SO2. Determinations were made of airway responsiveness by producing histamine dose-effect curves. Lung tissues were fixed and studied by light and electron microscopy. Epithelial cells of the trachea and bronchus were most affected. Lesions observed included changes in ciliated cells, edema and cell infiltration. The most responsive animals to histamine were 2 from the exposed group. Nasal discharge and dried mucus were observed after 3 days of exposure. Coughing was first noted after 2 weeks. Results favor further pursuit of the use of the ferret as a model for human airways disease.

Animals↗
PubMed1985

Pulmonary physiology of the ferret and its potential as a model for inhalation toxicology.

Physiological measurements were made from anesthetized, tracheotomized, supine male ferrets. Six animals weighing 576 +/- 12 g, had tidal volumes (Vt) of 6.06 +/- 0.30 ml, respiratory frequencies (f) of 26.7 +/- 3.9 min(-1), dynamic lung compliance (CDYN) of 2.48 +/- 0.21 ml cmH2O(-1), pulmonary resistance (RL) of 22.56 +/- 1.61 cmH2O L(-1) sec. Pressure-volume curves from nine ferrets (including the above six) revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC) (89 +/- 5 ml) and functional residual capacity (FRC) (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets was about the same as in 2.5 kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) sec(-1) at 75% VC and flows of 8.4 and 5.4 VC sec(-1) at 50% and 25% VC. No particular problems were encountered in making these measurements using conventional techniques available in laboratories capable of making pulmonary function measurements on rats and guinea pigs. Preliminary studies of airways reactivity showed equal increases in pulmonary resistance in response to equivalent challenges of aerosolized carbachol and histamine. Light and electron microscopic studies showed that the airways of ferrets are even more like those of humans than are the dog's. The ease with which physiological measurements can be made and the favorable aspects of the lung anatomy indicate the ferret may be more useful, as well as less expensive, than the dog for use in studies of pulmonary physiology and inhalation toxicology.

Aerosols↗
PubMed1982

Respiratory mechanics of a small carnivore: the ferret.

The ferret, Mustela putorius furo, is a small relatively inexpensive carnivore with minimal housing requirements. Measurements were made from anesthetized tracheotomized supine males. Values obtained during tidal breathing for six animals (576 +/- 12 g) were as follows: tidal volume, 6.06 +/- 0.30 ml; respiratory frequency, 26.7 +/- 3.9 breaths min-1; dynamic lung compliance, 2.48 +/- 0.21 ml cmH2O-1; pulmonary resistance, 22.56 +/- 1.61 cmH2O . l-1 . s. Pressure-volume curves from nine ferrets revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC, 89 +/- 5 ml) and functional residual capacity (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets is about the same as in 2.5-kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) . s-1 at 75% VC and flows of 8.4 and 5.4 VC . s-1 at 50 and 25% VC.

Animals↗
PubMed1981

Pulmonary defense mechanisms in Boa constrictor.

We studied aerosol deposition and the response to inhaled particles and irritants in lungs of Boa constrictor. Snakes which breathed submicrometric particles radiolabeled with 99mTc retained 41.4 +/- 9.9% of the aerosol in the trachea, 42.5 +/- 8.8% in the anterior faveolar regions, and 8.7 +/- 4.1% in the posterior saccular regions of the lungs. Low activity recovered in the gastrointestinal tract over a 5-h period following aerosol exposure indicated slow clearance of inhaled particles. In contrast to mammalian lungs, there are no macrophages resident on the surface of boa lungs, and uningested particles persist for up to 4 days without being phagocytized. Particles and irritant stimuli (Fe2O3, endotoxin, and N-formylmethionylphenylalanine) elicited only eosinophilic granulocytes that were not phagocytic. The numbers of these cells peaked at 24 h following exposure and declined gradually over the next 7 days. Lavage fluid from stimulated snake lungs contained many large lamellar figures continuous with tubular myelin, a form of surfactant. Very little of this material was recovered from control lungs. Response to inhaled particles and lung injury in boas increased surfactant release, elicited eosinophilic granulocytes, but did not recruit phagocytic mononuclear cells.

Animals↗
PubMed1979

Dynamic mechanisms determine functional residual capacity in mice, Mus musculus.

Awake mice (22.6--32.6 g) were anesthetized intravenously during head-out body plethysmography. One minute after pentobarbital sodium anesthesia, tidal volume had fallen from 0.28 +/- 0.04 to 0.14 +/- 0.02 ml and frequency from 181 +/- 20 to 142 +/- 8. Functional residual capacity (FRC) decreased by 0.10 +/- 0.02 ml. Expiratory flow-volume curves were linear, highly repeatable, and submaximal over substantial portions of expiration in awake and anesthetized mice; and expiration was interrupted at substantial flows that abruptly fell to and crossed zero as inspiration interrupted relaxed expiration. FRC is maintained at a higher level in awake mice due to a higher tidal volume and frequency coupled with expiratory braking (persistent inspiratory muscle activity or increased glottal resistance). In anesthetized mice, the absence of braking, coupled with reductions in tidal volume and frequency and a prolonged expiratory period, leads to FRCs that approach relaxation volume (Vr). An equation in derived to express the difference between FRC and Vr in terms of the portion of tidal volume expired without braking, the slope of the linear portion of the expiratory flow-volume curve expressed as V/V, the time fraction of one respiratory cycle spent in unbraked expiration, and respiratory frequency.

Anesthesia↗
PubMed1979

A technique for measuring frequency response of pressure, volume, and flow transducers.

A device and methodology is presented for testing the frequency response of pressure, volume, or flow transducers. Also reported are responses of selected transducers of all three types over the range of 2--120 Hz. Several pressure transducers tested had good frequency response when connected to the test system with a minimum of interconnecting fittings; others did not. Use of additional connectors degraded the response as did the addition of air-filled catheters. The frequency response of the pneumotachometers tested were influenced largely by the response characteristics of the associated pressure transducer and interconnecting fittings. These results emphasize the need to test the response characteristics of any transducer with specific connectors and fittings that are to be used to make the actual measurements of pressure, volume, or flow.

Mathematics↗
PubMed1978

Biochemical and physiologic changes in lungs of rats exposed to a cadmium chloride aerosol.

The purpose of this study was to examine the in vivo effects of acute exposure to a cadmium chloride aerosol on the activity of pulmonary enzymes and selected physiologic parameters that are altered by exposure to oxidant agents. Male rats were exposed for 1 hour to 0.5 per cent aerosol of cadmium chloride. At 1,5, and 11 days after exposure to cadmium chloride, exposed rats compared to control rats (data expressed as per cent of control values) had lung-to-body weight ratios of 192, 174, and 140 per cent; lung glucose-6-phosphate dehydrogenase activities of 90, 107, and 135 per cent; lung superoxide dismutase activities of 96, 101, and 132 per cent; tidal volumes of 62, 63, and 89 per cent; respiratory frequencies of 170, 145, and 108 per cent; and lung weight-specific static deflation volumes at 30 cm water of 30, 13, and 31 per cent. A zero-order clearance of cadmium from whole lung was observed, with a half-time of 27.4 days. Light microscopic examination of lung tissue revealed initial pulmonary edema on day 1 that progressed to interstitial pneumonitis on day 5, with some recovery by 11 days after exposure. The cadmium induced biochemical, physiologic, and pathologic alterations were similar to the responses observed in lungs of rats exposed to a wide variety of pulmonary irritants; thus, the changes observed may represent a nonspecific response to tissue injury.

Aerosols↗