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[Oxidative and anti-oxidative effects of ambroxol on acute hydrochloric acid-induced lung injury in rats].

OBJECTIVE: To evaluate the protective effect of ambroxol on acute hydrochloric acid-induced lung injury in rats. METHODS: Thirty pathogen-free SD rats were randomly divided into 3 groups: Group A (n=10) served as control group, and received intracheal instillation of normal saline (NS, pH5.3, 1.2 ml/kg) with pre-treatment of intraperitoneal NS; Group B (n=10) received intracheal instillation of hydrochloric acid /NS (pH1.25, 1.2 ml/kg) with pre-treatment of intraperitoneal NS; and Group C received intracheal instillation of hydrochloric acid /NS (pH1.25, 1.2 ml/kg) with pre-treatment of intraperitoneal ambroxol (50 mg/kg/d, 3 days). Five hours after the instillation of the injury vehicle, the arterial gas was examined, the levels of superoxide dismutase (SOD), malondialdehyde (MDA) in the blood and homogenate of harvested lung were assayed respectively. RESULTS: PaO2 in Group B was significantly lower than that in Group A and C (P < 0.01), and pH and PaCO2 in the 3 groups had little difference (P > 0.05). MDA in the lungs of Group B increased obviously, and levels of SOD in the lung and blood decreased significantly in Group B (Group B vs Group A, P < 0.01). Levels of SOD of Group C in the lung and blood were markedly higher than those of Group B (P < 0.01), MDA of Group C was obviously lower than that of Group B (P < 0.01), and MDA of blood in the 3 groups had no significant difference (P > 0.05). CONCLUSION: Ambroxol can inhibit lipid peroxidation and increase antioxidant activity, which may be one of the mechanisms in protecting lung tissue from hydrochloric acid-induced injury.

Ambroxol↗

Bile-induced adenosine triphosphate depletion and mucosal damage during reflux esophagitis.

BACKGROUND: This study was designed to investigate the role of bile in a large animal model of acute esophageal reflux disease. METHODS: An agar electrode was used to measure the transmucosal potential difference of the esophagus in anaesthetized dogs. The vascular permeability index and the epithelial permeability index of the mucosa were evaluated by means of the Evans blue and the sodium-fluorescein clearance method, respectively. The tissue adenosine triphosphate (ATP) level and the myeloperoxidase activity were determined from tissue biopsies, while the degree of mucosal damage was evaluated histologically on a grade 0-100 scale. Group 1 (n = 8) served as saline-treated control; groups 2 (n = 8), 3 (n = 5) and 4 (n = 5) were exposed for 4 h to canine bile alone, to hydrochloric acid + bile, or to hydrochloric acid alone, respectively. RESULTS: In Groups 2, 3 and 4 the degree of mucosal damage was significantly increased, and a 4-fold elevation in myeloperoxidase activity was observed. The transmucosal potential difference was decreased significantly below the control level, while the vascular and epithelial permeability indices were significantly increased compared with the control values. Bile, but not hydrochloric acid, evoked a significant (40%) decrease in the ATP level of the esophageal tissue. CONCLUSIONS: We propose that mucosal dysfunction, structural damage and leukocyte invasion during hydrochloric acid-induced esophageal injury are exacerbated by bile-induced changes in tissue ATP concentrations during experimental esophageal reflux disease.

Acute Disease↗

Skin reactions to irritants assessed by non-invasive bioengineering methods.

Pathophysiological components of irritant contact dermatitis caused by 3 chemically-different irritants were investigated. 20 healthy volunteers were patch tested with sodium lauryl sulphate, nonanoic acid and hydrochloric acid on the flexor side of the upper arm. The skin response was evaluated after 24, 48 and 96 h by visual scoring and measured by the following bioengineering methods: transepidermal water loss measurement, electrical conductance for measurement of skin hydration, laser Doppler flowmetry for measurement of cutaneous blood flow and 20 MHz ultrasound A-scan for measurement of skin thickness. In spite of homogeneous inflammatory responses, significant differences in the severity of the injury to the skin barrier function caused by the different irritants were found. Also significant differences between irritants were found in the time course of development of maximum irritant reactions. Bioengineering methods indicating inflammatory responses (measurement of blood flow and skin thickness) were helpful in quantifying the irritant response in general, while bioengineering methods indicating epidermal damage (measurement of TEWL and electrical conductance) were helpful in classifying the individual irritants.

Adult↗

The use of capillary gas chromatography-mass spectrometry for identification of radiation-induced DNA base damage and DNA base-amino acid cross-links.

Application of capillary gas chromatography-mass spectrometry (GC-MS) to isolation and identification of radiation-induced DNA base damage including DNA base-amino acid crosslinks is reported. gamma-Irradiated samples of thymine (thy), thymidine (dT), thymidine-5'-monophosphate (pdT), cytosine(cyt),2'-deoxycytidine (dC), 2'-deoxycytidine-5'-monophosphate (pdC), and mixtures of thy, dT and pdT with tyrosine were used as model systems. Trimethylsilylation was used as the derivatization method. Samples containing nucleosides and nucleotides were first subjected to hydrolysis with formic acid or hydrochloric acid to remove sugar or sugar-phosphate moieties, then trimethylsilylated and analyzed by GC-MS. Trimethylsilyl derivatives of radiation-induced monomeric and dimeric products of the model systems mentioned above were shown to have excellent GC properties and easily interpretable mass spectra. The presence of the molecular ion (M+.) and a characteristic (M-CH3)+ ion in the mass spectra facilitated structural elucidation. The complementary use of tert.-butyldimethylsilyl derivatives was also demonstrated. These derivatives provided an intense characteristic (M-57)+ ion in their mass spectra, which may be used to corroborate the molecular weight and to monitor the corresponding compounds in a complex mixture by means of selected-ion monitoring. All gas chromatograms and mass spectra obtained are discussed in detail.

Amino Acids↗

Effect of intraesophageal acid instillation on airway reactivity in patients with asthma.

OBJECTIVE: To study the change in airway reactivity due to presence of acid in lower esophagus and its reversibility by antacid. METHOD: In this double blind study 12 subjects with asthma and gastroesophageal reflux received acid (N/10 hydrochloric acid) and antacid (mixture of magnesium trisilicate and aluminum hydroxide) perfusion in lower esophagus via a nasogastric tube. The four combinations were antacid-antacid (control), antacid-acid, acid-antacid and acid-acid. Airway reactivity (Histamine PD20) was recorded after each perfusion. RESULTS: Histamine PD20 significantly decreased (airway reactivity increased) (p < 0.05) with all three combinations containing acid as compared to control. No significant difference in airway reactivity was observed if the antacid was given before or after the acid. CONCLUSION: Presence of acid in lower esophagus can increase airway reactivity. This effect lasts longer than the presence of acid in esophagus itself.

Adolescent↗

Sucralfate does not reduce the risk of acid aspiration pneumonitis.

OBJECTIVE: To study the pulmonary effects of aspirating a mixture of sucralfate in water and sucralfate in hydrochloric acid in an animal model of aspiration pneumonia. DESIGN: Prospective, randomized, controlled study with repeated measures. SETTING: University research laboratory. SUBJECTS: Thirty-two in situ, isolated, blood perfused porcine lung preparations. INTERVENTIONS: Five control preparations received no aspiration. Twenty-seven preparations received a standard aspiration of 1.5 mL/kg body of a) distilled water (n = 5), b) sucralfate in distilled water (n = 8), c) 1/10 normal hydrochloric acid (n = 6), and d) mixture of sucralfate in distilled water and hydrochloric acid (n = 8). MEASUREMENTS: The pH measurements were made of all aspirates. Lung weight, airway pressures, and pulmonary artery pressures were continuously monitored before and for 4 hrs after aspiration. Lung wet/dry weight ratio was measured at the completion of the study. RESULTS: The pH of sucralfate mixed with distilled water was 4.9, pH of 1/10 normal hydrochloric acid was 1.0, and pH of equal volumes of a sucralfate-water suspension mixed with hydrochloric acid was 1.5. Airway pressures and pulmonary arterial pressures increased in all aspirate groups over time compared with those values of control lungs. Control lungs gained 18 +/- 3 (SEM) g over 4 hrs and the wet/dry ratio was 4.951 +/- 0.310. Lungs aspirating distilled water gained 147 +/- 49 g and the wet/dry ratio was 5.198 +/- 0.120. Lungs aspirating sucralfate and distilled water increased their weight by 109 +/- 30 g and the wet/dry ratio was 5.380 +/- 0.076. Lungs aspirating a suspension of sucralfate and water and hydrochloric acid were similar to lungs aspirating hydrochloric acid alone with weight increases of 265 +/- 30 g and 346 +/- 81 g, and the wet/dry ratio of 7.011 +/- 0.273 and 7.230 +/- 0.390, respectively. CONCLUSIONS: Sucralfate has minimal acid buffering effect. Aspiration of sucralfate mixed with distilled water causes lung edema similar to aspiration of water alone. Aspiration of a sucralfate-water suspension mixed with hydrochloric acid causes severe lung edema. These results suggest that patients given sucralfate prophylaxis for stress ulceration are at risk for acid aspiration.

Airway Resistance↗

Somatic antigens of Streptococcus group E. I. Comparison of extraction techniques.

Eleven Streptococcus group E strains, representing serotypes I, II, III, IV, V, and "untypable" isolates, were extracted by formamide, trichloroacetic acid, and hydrochloric acid under various conditions in an effort to determine the best method for recovering maximum amounts of group and type antigens. The group antigen was found to be relatively stable, and adequate amounts for identification purposes were recovered by a wide spectrum of conditions. Type-specific antigens were relatively labile, and were destroyed at low pH in acid hydrolysis or by prolonged heating in formamide hydrolysis. The best single procedure for recovering both type and group antigens from Streptococcus group E was formamide hydrolysis for 30 min at 180 C.

Animals↗

Role of leukotrienes in hydrochloric acid-induced gastric lesions in rats.

This study was designed to clarify the role of leukotrienes (LTs) in 0.6 N hydrochloric acid (HCl)-induced gastric lesions. In rats given 1 ml of 0.6 N HCl intragastrically, severe hemorrhagic lesions were observed in the gastric corpus mucosa 15 min, and 1, 3, and 5 hr after HCl administration. In the control rats treated with physiological saline, LTs in gastric mucosa were not observed throughout the experiments. Peptide LT contents (sum of LTC4 and LTD4) after 1 or 3 hr were increased to 13.2 +/- 2.9 ng/g tissue and 6.3 +/- 1.9, respectively, although peptide-LTs were not observed 15 min and 5 hr after HCl administration. Premedication with AA-861, a lipoxygenase inhibitor, decreased dose-dependently peptide LT contents 1 hr after HCl administration. Furthermore, gastric lesions caused by 0.6 N HCl were significantly prevented by 300 mg/kg of AA-861 3 hr after HCl administration, although the dose of AA-861 did not significantly prevent gastric lesions 1 hr after HCl administration. Administration of YM-638, a peptide LT antagonist, showed similar protective effects to AA-861 except inhibition of increase in LT levels after HCl administration. These results suggest that peptide LTs contribute to persistence of gastric lesions, although they might not participate in the onset of 0.6 N HCl-induced gastric lesions.

Animals↗

Sulfur influences on rumen microorganisms in vitro and in sheep and calves.

When continuously cultured ruminal microbes were given orchardgrass hay and sufficient sulfuric acid or hydrochloric acid to maintain a pH of 5.5, fermentation and numbers of protozoa were reduced compared with cultures whose pH was controlled with phosphoric acid. Likewise, when sulfur-deficient, purified diets were supplied to cultures, less methane (mmol X liter-1 X d-1), 3.2 vs 32.6, was produced and fewer cellulolytic bacteria (log10/ml), 5.8 vs 7.2 were present than when cultures were given the same diet supplemented with .3% elemental sulfur. The rumen of sheep fed the .04% sulfur diet had reduced digesta weights (1.69 vs 3.2 kg) compared with sheep fed the diet with .34% sulfur at the same intake. There also was reduced methanogenesis 12.3 vs 25.8 mmol X liter-1 X d-1) and reduced numbers of cellulolytic bacteria (7.4 vs 8.4 log10/ml) in sulfur-deficient sheep in comparison to sulfur-supplemented sheep. In growing calves, the same types of bacteria predominated in the rumen, but more facultative anaerobic bacteria were isolated from calves fed .04% sulfur than from calves fed diets with .34 to 1.72% sulfur. None of the dietary levels of sulfur appeared toxic. Regardless of treatment, volatile fatty acids were more predominant than lactic acid as end-products of fermentation of ruminal microbes in fermenters, sheep and calves. The greater methanogenesis and the greater cellulolytic bacterial numbers of sulfur-supplemented sheep compared with sulfur-deficient in vitro cultures, is interpreted to be the result of recycling of sulfur to the rumen in sheep where it is efficiently scavengered by ruminal bacteria.

Animal Feed↗

[The area around the wound in experimental chemical injuries to the skin].

This is an experimental assessment of the morphological patterns of skin in the area surrounding wounds, produced by exposure to sodium base, sulfuric acid and hydrochloric acid. The changes are followed up from 6th hour to 28th post-injury day, and compared with those in the skin surrounding thermal burns using the same experimental setup. The differences in healing processes, both by comparison with the control group, and between the individual chemical agents, are insignificant. Following chemical injury as well, nonspecific tissue healing processes develop in the area around the wound. The diagnostic and therapeutic problems faced, and the potentials in the wound area after chemical lesions are similar to those following other types of skin damage.

Animals↗

Reaction-frequencymetric method: a new analytical technique for determination of submicromolar concentration levels of vitamin C.

A new analytical technique for the assay of pharmaceutical substances at low concentration levels has been proposed and applied to the determination of vitamin C as an example of its application. It is based on the chemical reaction of vitamin C with iodine in a sodium citrate-hydrochloric acid medium, followed by measurement of the frequency change of a silver-plated piezoelectric quartz crystal. The frequency change is proportional to the vitamin C concentration from 2 x 10(-7) to 4 x 10(-6) M. The method was applied to the assay of vitamin C in pharmaceutical preparations.

Ascorbic Acid↗

Button battery ingestion: assessment of therapeutic modalities and battery discharge state.

Button batteries immersed in a simulated gastric environment (0.1N hydrochloric acid) demonstrated less crimp dissolution (corrosion of the metal can) after the addition of neutralizing doses of eight of nine antacids tested. Of 64 ingestion episodes in dogs, clinical manifestations of button battery-induced injury were limited to a single animal developing guaiac-positive stools. Endoscopic lesions included only mild gastritis, occurring with a frequency comparable to that observed in dogs prior to battery ingestion. After ingestion blood mercury levels were not significantly elevated. Crimp dissolution was absent in discharged cells, implying a decreased risk of electrolyte leakage or subsequent tissue injury in patients who ingest spent cells. No protective effect of metoclopramide, cimetidine, or magnesium citrate could be demonstrated in the canine model.

Animals↗

Stability of esomeprazole capsule contents after in vitro suspension in common soft foods and beverages.

STUDY OBJECTIVE: To determine the in vitro stability of esomeprazole pellets from an opened capsule after suspension in various common soft foods and beverages. DESIGN: In vitro study. SETTING: Pharmaceutical company research laboratory. MEASUREMENTS AND MAIN RESULTS: Pellets from opened esomeprazole 20-mg capsules were suspended in 100 ml of tap water, milk (1.5% fat), orange juice, apple juice, yogurt, or cultured milk for 30 minutes, then added to 500 ml of hydrochloric acid to simulate gastric acid exposure. After a 2-hour incubation, the mixture was filtered through a sieve, and the collected pellets were dissolved in an alkaline solution. Esomeprazole concentrations were measured using reverse-phase liquid chromatography The stability of the esomeprazole pellets exceeded 98% in all beverages and soft foods except milk. CONCLUSION: Administration of the pellets from an opened esomeprazole capsule shortly after suspending them in tap water, yogurt, cultured milk, orange juice, or apple juice may be a practical alternative for patients who cannot swallow an intact capsule. Bioavailability studies comparing esomeprazole administered as an intact capsule to that of the pellets from an opened capsule suspended in these beverages or soft foods are recommended to confirm these findings.

Animals↗

Modification of collagen film by certain chemical agents.

Morphological changes and the content of free carboxyl groups in bovine collagen (type I) film under the influence of trypsin, hydrochloric acid (HCl) and ethylenediaminetetraacetic acid (EDTA) were studied. Incubation with trypsin and HCl was found to cause some delamination of the film and the appearance of some low-density spots. Incubation with EDTA did not cause any morphological changes. A high concentration of free carboxyl groups (10-fold higher than in control) was seen after incubation with trypsin.

Animals↗

Technical notes for age estimation using the femur: influence of various analytical conditions on D-aspartic acid contents.

In order to make a better estimate of the individual age using bone samples, we evaluated the effects of various criteria on the analytical measurement of D-aspartic acid contents. Using compact bone from a male femur, we varied six analytical conditions (sample volume, sample particle size, hydrolysis temperature, hydrolysis time, hydrochloric acid volume during hydrolysis, and hydrochloric acid concentration during hydrolysis). D-form/L-form ratios were affected most by hydrolysis temperature (estimated age differences were 3.03 years/ degrees C), followed in order by hydrochloric acid volume (1.44 years/ml) and hydrochloric acid concentration (0.69 years/0.1 M). Larger sample particle sizes and hydrochloric acid volumes during hydrolysis tended to result in lower racemization rates. Nonetheless, within a range of 5-50 mg, sampling volume did not affect the detected D-aspartic acid contents. Since the racemization reaction rate in femur compact bone is slower than in dentin, bone samples seem to be more greatly influenced by analytic conditions than dentin. Tests must therefore be performed with caution, especially with regard to the hydrolysis temperature, hydrochloric acid volume and concentration when estimating age using femur samples.

D-Aspartic Acid↗

Acid secretion and suppression.

Hydrochloric acid is involved in the causation of peptic ulcer, but the exact role has not been defined. Suppression of acid secretion is associated with ulcer healing. The acid secreting cell is the parietal cell, which possesses a proton pump in the secretory membrane; morphologic changes accompany and facilitate the active secretion of hydrochloric acid. Stimulation of acid secretion occurs by three major pathways, which utilize acetylcholine, histamine, and gastrin. The predominant effects of histamine are mediated by adenylate cyclase, whereas those of gastrin and acetylcholine involve cytosolic calcium. There is a complicated arrangement of receptors and pathways that culminate in the activation of the proton pump. The parietal cell is influenced by neurocrine, hormonal, and paracrine mechanisms. Peptides join the more familiar neurotransmitters in affecting the parietal cell. Somatostatin is present in the gut and acts to decrease acid secretion. The hormone gastrin is released, in a feedback fashion, when the antrum is alkalinized. Most stimuli of acid secretion are blocked by H2-antagonists. Inhibitory hormones are released when acid arrives in the intestine. Inhibition of acid secretion can be achieved by influencing the parietal cell at the level of histamine, gastrin, and muscarinic receptors. The proton pump itself can be blocked by drugs that inhibit the final phase of acid secretion.

Central Nervous System↗