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Lateral positioning with differential lung ventilation and unilateral PEEP following unilateral acid aspiration in the dog.

Body position can significantly alter the efficiency of gas exchange following unilateral lung injury. We systematically examined three positions during differential lung ventilation with unilateral positive end-expiratory pressure (PEEP) following unilateral hydrochloric acid aspiration in the dog. Twelve mongrel dogs were intubated with a double-lumen endobronchial tube and mechanically ventilated with a microcomputer-controlled pair of ventilators. A tidal volume of 7.5 ml/kg was delivered to each lung. The PaCO2 was maintained at 4.67 kPa. A unilateral injury was induced with an injection of 0.1 N hydrochloric acid (2.5 ml/kg) into one lumen of the endobronchial tube. 0.984 kPa PEEP was applied to the injured lung and the dogs were placed sequentially in one of three positions (supine, lateral decubitus with injured lung non-dependent, and lateral decubitus with injured lung dependent) for 1 h apiece. There was no significant difference between the three positions with regard to PaO2 (F (2, 10) = 1.60, P = 0.25) of venous admixture (F (2, 10) = 0.49, P = 0.63). Our data indicated that position did not alter oxygenation. This was probably due to the use of differential ventilation with unilateral PEEP which eliminated redistribution of ventilation between the two lungs and minimized position-dependent changes in pulmonary blood flow.

Animals↗

Influence of achlorhydria on aspirin-induced occult gastrointestinal blood loss: studies in Addisonian pernicious anaemia.

The effect of aspirin (acetylsalicylic acid) ingestion on occult gastrointestinal blood loss has been studied in patients with treated Addisonian pernicious anaemia and proved achlorhydria and in control patients able to secrete hydrochloric acid. A highly significant increase in gastrointestinal blood loss (1.9 ml./day of treatment) occurred with aspirin ingestion in the achlorhydric patients. The control group had a significantly greater increase in blood loss (4.29 ml./day of treatment). Thus aspirin can produce occult gastrointestinal blood loss by a mechanism unrelated to hydrochloric acid. Half of the control patients had losses of similar magnitude to those in the pernicious anaemia group, and the degree of blood loss in individual control patients appeared unrelated to gastric acidity. Differences in gastric mucosal characteristics, in the rate of gastric emptying, or in systemic effects of aspirin may explain the variation between individuals in the degree of occult gastrointestinal blood loss after aspirin.

Achlorhydria↗

Progressive, severe lung injury secondary to the interaction of insults in gastric aspiration.

This study examines lung injury and inflammation over 24 hours following intratracheal instillation of hydrochloric acid (acid), small nonacidic gastric particles (SNAP), or combined acid and small particles (CASP) in adult rats. The severity and duration of injury was significantly greater for CASP compared to acid or SNAP based on PaO2/FiO2, bronchoalveolar lavage (BAL) albumin, and BAL cell numbers. The inflammatory response associated with aspiration injury from CASP was distinct in several respects. Tumor necrosis factor (TNF)-alpha was greatly reduced in CASP compared to SNAP or acid, whereas interleukin (IL)-1beta was increased. Levels of cytokine-induced neutrophil chemoattractant (CINC)-1, monocyte chemoattractant protein (MCP)-1, and IL-10 in lavage were also significantly increased in animals injured with CASP compared to other forms of aspiration. Statistical analysis showed that BAL levels of IL-10 correlated most strongly with albumin leakage in aspiration-injured animals at 6 and 24 hours, followed by BAL levels of MCP-1. Additional cytokine cluster analyses indicated that levels of MCP-1 and CINC-1 in BAL from all injured animals were strongly correlated with inflammatory neutrophil numbers at 6 and 24 hours post aspiration, and that IL-10 levels in BAL were strongly correlated with inflammatory cell numbers at 24 hours. Preliminary blocking experiments showed that administration of anti-IL-10 antibody increased the albumin permeability index at 6 hours in SNAP and CASP animals, but anti-MCP-1 antibody did not affect the severity of injury. The results of this study support the possibility that different forms of aspiration are associated with identifiable cytokine profiles, and that specific cytokines, including IL-10 and MCP-1, may have utility as diagnostic or prognostic markers in clinical applications.

Animals↗

Adaptive cytoprotection by 0.25 M HCl is truly "cytoprotective" and may not depend upon elevated levels of prostaglandin synthesis.

The ability of a mild irritant to reduce ethanol-induced damage to the rat gastric mucosa was investigated using an ex vivo gastric chamber preparation. Exposure to 0.25 M hydrochloric acid (HCl) did not cause significant damage to the surface epithelium, but did reduce both the lesion area and the extent of superficial epithelial damage caused by subsequent exposure to 40% ethanol (EtOH). "Adaptive cytoprotection" was also demonstrated by the reduction of ethanol-induced changes in transmural potential difference and net K+ efflux, and by rapid recovery of these physiological parameters following the removal of ethanol from the chamber. Pretreatment of rats with indomethacin at a dose that has been shown to significantly inhibit gastric cyclooxygenase activity did not significantly affect the ability of 0.25 M HCl to reduce the effects of ethanol on lesion area, epithelial damage, potential difference, and net K+ efflux.

Animals↗

Laboratory diagnosis of zinc phosphide poisoning.

Zinc phosphide, a readily-available rodenticide, poses a significant risk for intoxication in animals. Animals have been poisoned by ingesting treated bait or the carcasses of poisoned rodents. Toxicity is due to the liberation of phosphine gas in the stomach. Clinical signs include central nervous system excitation, depression and vomition. Similarities of clinical signs with other central nervous system toxicants make the diagnosis difficult without a specific diagnostic test. The procedure outlined in this paper detects phosphine liberated from zinc phosphide by the addition of hydrochloric acid as well as the phosphine previously generated by contact with stomach acid.

Animals↗

Antiulcer activity of the calcium antagonist propyl-methylenedioxyindene--II. Effects on acid secretion and gastric emptying in rats.

1. Propyl-methylenedioxyindene (pr-MDI) is an intracellularly acting calcium antagonist which protects against cold/restraint-induced stress ulcers in rats. The doses of pr-MDI which produce antiulcer activity (10-30 mg/kg i.p.) are significantly lower than those which exhibit cardiovascular effects. 2. Two potential mechanisms for the antiulcer action of pr-MDI were investigated in this study: the effects on hydrochloric acid secretion and on gastric motility (gastric emptying). 3. Bethanechol-induced hydrochloric acid secretion in acutely pylorus-ligated rats was significantly obtunded by pr-MDI (30 mg/kg i.p.), but the effect was significantly weaker than that produced by verapamil (16 mg/kg i.p.) or cimetidine (10 mg/kg i.p.). Since 30 mg/kg pr-MDI produces greater antiulcer activity than the very high dose of 16 mg/kg verapamil, it is unlikely that inhibition of acid secretion plays more than a contributory role in the antiulcer mechanism of action of pr-MDI. 4. pr-MDI (10-30 mg/kg i.p.) produced a dose-dependent slowing of gastric emptying in rats fed a methylcellulose/Phenol Red test meal, and this effect correlated well with the antiulcer action. Verapamil (16 mg/kg i.p.) did not affect gastric emptying. 5. The results indicate that a reduction of gastric motility plays a major role in the mechanism of the antiulcer action of pr-MDI.

Animals↗

Extraction and measurement of pamidronate from bone samples using automated pre-column derivatization, high-performance liquid chromatography and fluorescence detection.

A method for the determination of 3-amino-1-hydroxylpropylidene-1, 1-bisphosphonic acid (pamidronate) in bone samples is described. This method combines and modifies parts of previous procedures. Pamidronate is extracted from finely ground bone with dilute hydrochloric acid. Amine-containing contaminants are removed by co-precipitation of pamidronate with calcium. Excess calcium is removed with EDTA and an ion-exchange resin. Pamidronate is automatically derivatized at the primary amine and quantified by high-performance liquid chromatography with fluorescence detection. The method assay was linear in the concentration range 7.5-600 ng/mg bone (20-100 pmol/mg). The imprecision for repeat analyses were 16.5 and 7.8%, at pamidronate levels of 7.5 and 600 ng/mg bone, respectively. The method has been used to analyze bone samples from pharmacokinetic animal studies involving both acute and chronic dosages.

Animals↗

Tissue fibrinolysis in experimental gastric ulcer: a study in the rat.

Gastric mucosal lesions were induced in rats by pyloric ligature and intragastric instillation of hydrochloric acid. Within 4 h all rats developed focal mucosal lesions. Early regeneration was observed 72 h after release of the pyloric ligature and replacement of the hydrochloric acid by a phosphate buffer. A significantly increased gastric mucosal fibrinolytic activity was found 4 h after pylorus ligation. The submucosal vascular fibrinolysis remained unchanged. Following release of the pyloric ligature the increased mucosal fibrinolysis returned to normal values after 72 h. Intravenous administration of tranexamic acid significantly decreased the mucosal and vascular fibrinolytic activity without influencing the formation of induced gastric lesions. Increased mucosal fibrinolysis is probably not involved in the development of mucosal lesions.

Animals↗

Staining of minerals and solubility of iron in tissues.

Iron deposits in ethionine induced aortic siderosis of rats, in splenic deposits in sickle cell anemia and siderocalcific vessels in cerebral arteriosclerosis were completely removed by exposure to 20 percent hydrochloric acid for 30 min. This contrasted with idiopathic hemochromatosis and idiopathic pulmonary hemosiderosis in which the iron containing organs had to be exposed to 40 percent hydrochloric acid for two hours. The more soluble iron appeared colorless in unstained tissues, purplish blue with hematoxylin and eosin, turquoise blue with Perls' stain, violet blue with gallocyanin and dark-drown with sodium rhodizonate. The less soluble iron was golden yellow in unstained tissues. It appeared golden yellow with hematoxylin and eosin and sodium rhodizonate, but it stained greenish blue with Perls' method and dark brown with gallocyanin. Lead and copper were capable of deposition in some tissues in vitro in the presence of iron and/or calcium but not when these minerals were removed. This phenomenon may be of importance in certain pathological conditions, e.g. hemochromatosis, where on preexisting tissue-iron-complexes there is a secondary deposition of copper.

Anemia, Sickle Cell↗

Phosphoric acid-its use in the extraction of RNA: staining of DNA in mammalian tissue sections.

This communication presents highly satisfactory methods for the demonstration of DNA in animal materials. The method involves selective extraction of RNA with concentrated, 90% or 75% phosphoric acid of 5 degrees C for 20, 40 and 120 min, respectively, followed by staining with aqueous solutions of basic dyes, such as setoglaucine, setocyanine, pinakryptol green 2) and alcoholic aniline blue without SO2. Perfect blue nuclei were seen when staining was performed with aqueous solutions of setoglaucine and setocyanine at pHs 3.5 and 4.0 to 4.5, respectively. Sections of tissues from which RNA has been extracted and then hydrolysed in 6 N HCl at 28 degrees C for 15 min followed by staining with these dyes also revealed perfect colouration of the nuclei. Acid-hydrolysed sections when stained with alcoholic aniline blue-SW2 prepared with N HCl and sodium thiosulphate revealed nuclei of magenta colour, and sections from whcih RNA has been extracted and then hydrolysed in hydrochloric acid and stained with this dye-reagent revealed nuclei of purplish colour. Sections of tissues fixed in Carnoy, 10% buffered neutral formalin as well as paraformaldehyde were found to be most suitable for staining with these dyes. The in situ absorption spectra of nuclei stained with aqueous solutions of setoglaucine, setocyanine and alcoholic aniline blue without SO2, after extraction of RNA as well as those of nuclei in tissue sections from which RNA has been extracted and then acid-hydrolysed and stained with alcoholic aniline blue-SO2 have been presented. Also presented herein are absorption data of nuclei in tissue sections which wee hydrolysed in hydrochloric acid and then stained with alcoholic aniline blue-SO2. Some implications of these findings have been discussed.

Aniline Compounds↗

Diphosphoinositide and triphosphoinositide in animal tissues. Extraction, estimation and changes post mortem.

1. A method is presented for the determination of the di- and tri-phosphoinositide in animal tissues. 2. The polyphosphoinositides are quantitatively extracted into chloroform-methanol-hydrochloric acid solvent after a preliminary chloroform-methanol (1:1, v/v) extraction to remove the bulk of the other phospholipids. On washing this extract with n-hydrochloric acid the polyphosphoinositides pass completely into the lower chloroform-rich phase. Their concentrations in the lower phase are determined by chromatography on formaldehyde-treated paper or chromatography and ionophoresis of the acid hydrolysis products. 3. When guinea-pig brain is extracted by the method of Folch (1942), considerable hydrolysis of the triphosphoinositide and accumulation of diphosphoinositide occurs during the initial acetone extraction. 4. The tri- and di-phosphoinositide contents of rat and guinea-pig brain decline substantially within a few minutes after death. 5. The concentrations of tri- and di-phosphoinositide in rat brain are not changed by insulin-hypoglycaemia or electrical stimulation. 6. Examination of frozen rat tissues showed that the brain contained the highest concentration of polyphosphoinositides. Much smaller amounts are present in kidney, and only trace quantities in liver and lung. None could be detected in spleen, heart and skeletal muscle.

Animals↗

Faulty healing in the lower extremities; vascular deficiency as a complication in industrial injuries.

The failure of injuries of the lower extremities to heal properly can often be traced in older persons to arteriosclerosis obliterans. In industry this condition presents a serious problem to older workers, to employers and to insurance carriers. In persons with severe varicosis or those who have had extensive thrombophlebitis, ulcers of the leg may develop following bruising of the skin in the region of the ankle.A third and little recognized condition is edema with or without induration of the skin and subcutaneous structures of the leg, with or without the existence of varicose veins and without evidence of cardiac or renal disorders. This condition is often associated with the absence of or marked diminution of the production of hydrochloric acid by the stomach. An accompanying diminution in or absence of pepsin may occur. It is corrected slowly by taking with each meal small amounts of dilute hydrochloric acid. When pepsin is deficient, the enzyme papain is given.

Arteriosclerosis Obliterans↗

The role of gastric acid in preventing foodborne disease and how bacteria overcome acid conditions.

The secretion of hydrochloric acid by the stomach plays an important role in protecting the body against pathogens ingested with food or water. A gastric fluid pH of 1 to 2 is deleterious to many microbial pathogens; however, the neutralization of gastric acid by antacids or the inhibition of acid secretion by various drugs may increase the risk of food- or waterborne illnesses. Peptic ulcer disease is often treated by decreasing or eliminating gastric acid secretion, and such treatment blocks the protective antibacterial action of gastric fluid. The majority of peptic ulcer disease cases originate from Helicobacter pylori infections. Treatment of H. pylori-induced peptic ulcers with antibiotics reduces the need for drugs that inhibit gastric acid secretion and thereby diminishes the risk of food- and waterborne illness for peptic ulcer disease patients. Many bacterial pathogens, such as Escherichia coli, Salmonella Typhimurium, and H. pylori, can circumvent the acid conditions of the stomach by developing adaptive mechanisms that allow these bacteria to survive in acid environments. As a consequence, these bacteria can survive acidic stomach conditions and pass into the intestinal tract, where they can induce gastroenteritis.

Antacids↗

[Immunoglobulins in the gastric juice in some stomach and duodenal diseases].

IgA, IgM and IgC content in blood serum and gastric juice were determined in 89 patients with different gastric and duodenal diseases (57 with duodenal ulcers, 13 with gastric ulcers 8 with chronic atrophic gastritis, 9 with superficial chronic gastritis and gastroduodenitis and two with gastric cancer). Immunoglobulin was established in gastric juice (over 0,3 mg/100 ml) in 49 per cent of all the patients examined with gastric and duodenal diseases. No correlation was found between serum immunoglobulin level and their presence in the gastric juice. No correlation exists between the volume of the basal secretion and the presence or absence of immunoglobulins in the gastric juice. Immunoglobulins were established more often in the gastric juice with lower secretion of hydrochloric acid (in chronic atrophic gastritis and gastric ulcer), while in cases of higher secretion they are more frequently absent. A certain parallelism was established between the changes of hydrochloric acid output and JgA secretion in the gastric juice after stimulation of gastric secretion by Pentagastrin or histamine.

Chronic Disease↗

Formate buffer as preservative for urinary free catecholamine measurement.

BACKGROUND: Strong mineral acid is the most commonly used preservative for measuring urinary free catecholamines. Leakage of corrosive acid is a safety hazard. The use of formate buffer as a safer alternative was studied. METHODS: Twenty-two urine specimens from post-operative patients were collected and preserved in 0.5 M hydrochloric acid or 0.75 M formate buffer. The specimens were stored at 4 degrees C or -70 degrees C, respectively. The free catecholamine content was measured at regular intervals by high-performance liquid chromatography for 6 months. RESULTS: The preservation capability of formate buffer was equivalent to that of hydrochloric acid. Deep-freeze storage offered additional protection independent of the preservative used. CONCLUSION: The results of this study demonstrate that formate buffer, compared to the most popularly used strong mineral acid solution, is an equally effective preservation for urinary free catecholamines. The less acidic nature of formate should invite fewer unpleasant incidents and safety hazards.

Buffers↗

[Spectrophotofluorimetric determination of trace nitrite with safranine T].

A new fluorescence quenching method has been developed to determine nitrite in water samples. The method is based on the diazo-reaction between nitrite ion and safranine T in hydrochloric acid medium. The fluorescence intensity was measured at excitation and emission wavelengths of 525.0 and 556.0 nm, respectively. The optimum experimental conditions have been confirmed and the concentration of hydrochloric acid was 0.096 mol.L-1; the reaction time was 10 min. Under the selected conditions, the relationship was obtained between the fluorescence intensity and nitrite concentration in the range 4-200 x 10(-9) g.mL-1 NO2-. The detection limit was 4 x 10(-9) g.mL-1 NO2-. The method was applied to determine trace nitrite in water samples. The mechanism involved in the reaction was discussed.

Nitrites↗

Effect of the hydrolysis method on the determination of the amino acid composition of proteins.

Fast and reproducible separation and determination of amino acids serves the economical and reliable characterization and quantification of peptides and proteins as well as the identification of proteins by amino acid composition analysis on a large-scale. A prerequisite of a successful compositional analysis is a complete hydrolysis of the peptides and proteins and a quantitative recovery of the residues in the hydrolyzate. We investigated the effect of different acid-hydrolysis methods on the compositional analysis of known proteins in solution and after blotting onto polyvinylidene difluoride membranes and worked out the conditions for the processing of large numbers of samples. The reliability of each method was studied by introducing the analysis data into the AACompIdent software and deducing the protein identification scores. All acid-hydrolysis methods delivered reliable analysis data. The most accurate data were provided by conventional, thermal hydrolysis of proteins in solution in the presence of methanesulfonic acid, closely followed by hydrolysis with hydrochloric acid and microwave radiation-dependent hydrolysis with hydrochloric or methanesulfonic acid, respectively. For blotted proteins, conventional hydrolysis delivered more accurate analysis data in comparison with the microwave radiation-induced hydrolysis. The extraction of the residues from the membrane hydrolyzate was a critical step for unambiguous protein identification. Microwave radiation-induced hydrolysis was responsible for a higher degree of racemization of the residues.

Amino Acids↗

Lateral hypothalamic lesions cause gastric injury by stimulating gastric contractility.

Changes in gastric contractility following lateral hypothalamic (LH) lesions with and without bilateral cervical vagotomy were measured in urethan-anesthetized rats. LH lesions were induced with direct current passed through stereotaxically placed electrodes. Gastric contractility was recorded continuously for 4 h with acutely implanted strain gauge force transducers and analyzed by computer. LH lesions consistently stimulated gastric contractility and caused more gastric mucosal injury than control conditions. Vagotomy blocked both gastric mucosal injury and high-amplitude gastric contractions. In rats with LH lesions and exogenously infused intragastric hydrochloric acid, atropine methyl nitrate inhibited high-amplitude gastric contractions and gastric erosions. These findings indicate that LH lesions stimulate vagally mediated high-amplitude gastric contractions, which, in the presence of hydrochloric acid, cause gastric mucosal erosions.

Animals↗