Effects of stress on amino acids and related compounds in various tissues of fasted rats.

The purpose of this study was to examine the effect of stress on the free amino acid pattern of plasma and various organs. Two groups of rats were deprived of food, for 24 hrs. One group was sacrificed after this time (fasting control representing mostly free endogenous amino acids) and the second group was first restrained in wire cages for 120 min before being sacrificed (fasting stress representing mostly the effects of stress on endogenous free amino acids). A third group had free access to food and was sacrificed at the same time (fed control representing mostly free amino acids absorbed from the gut and endogenous free amino acid metabolism). Fasting (as compared to fed controls) reduced alanine and arginine but increased ethanolamine, glutamic acid and glutamine in the plasma; increased ethanolamine, phosphoethanolamine and glutamic acid in the liver; increased carnosine, glutamic acid, phosphoethanolamine and glutamine in the ventricle; increased oxidized glutathione in the aorta; decreased alanine, aspartic acid, glutamic acid, leucine and methionine and increased glutamine in the pancreas; and decreased arginine in skeletal muscle. Fasting plus stress (as compared to fasting controls) reduced alanine and glutamine in the plasma; increased methionine in the liver; increased ethanolamine, GABA, and glutamic acid in the aorta; reduced arginine, glutamic acid, glutamine, leucine and methionine but increased ethanolamine in the ventricle; reduced ammonia and ethanolamine but increased histidine, isoleucine, leucine, lysine, phenylalanine, tyrosine and valine in the pancreas; and reduced ammonia in skeletal muscle. Fasting plus stress affects the amino acid composition of plasma and various of tissues but effects seen were individually different and strongly substance and tissue specific. Plasma changes did not coincide with tissue changes. Changes in the endogenous pattern of amino acids and related compounds in response to stress could be first indications of stress induced organ pathology.

Effects of L-DOPA/carbidopa administration on the levels of L-DOPA, other amino acids and related compounds in the plasma, brain and heart of the rat.

Rats were treated intraperitoneally with a mixture of 250 mg/kg L-DOPA and 40 mg/kg carbidopa or with vehicle and sacrificed 30 min later. Plasma, heart and cortex, midbrain, brainstem and cerebellum were removed from each animal and assayed by HPLC for L-DOPA and a large number of amino acids and related amino compounds. L-DOPA levels increased from undetectable (<0.2 nmol/ml or g) to 1,146, 1,007, 399, 376, 368 and 850 nmol/ml or g in the above tissues. In addition, several amino compounds were significantly affected by L-DOPA/carbidopa (p < or = 0.01). Plasma concentrations of phosphoserine, oxidized glutathione, citrulline, phenylalanine, tyrosine and 1-methylhistidine increased and arginine, glutamic acid and lysine decreased. In the heart, concentrations of phosphoserine, taurine, reduced glutathione, threonine, serine, glutamine, glycine, alanine, valine, GABA, ethanolamine, ammonia and arginine decreased. In the cortex, camosine and homocarnosine increased. In the midbrain, valine increased and leucine, ornithine and oxidized glutathione decreased. In the cerebellum, citrulline increased. In the brainstem, threonine, serine, asparagine, glutamine, oxidized glutathione, alanine, and leucine decreased. In the brainstem, arginine was slightly decreased with a concomitant increase in citrulline (p < 0.05), indicative of nitrous oxide formation. These results show that administration of L-DOPA/ carbidopa not only raises dopamine levels but can also affect other biochemicals and that the observed changes in amino acids and related compounds can perhaps contribute to the beneficial and/or adverse effects of L-DOPA/carbidopa therapy of Parkinson's disease.

Levels of amino acids and related compounds in bronchoalveolar lavage fluids of asthmatic patients.

The constituents of bronchoalveolar lavage (BAL) fluid have been shown to reflect the presence and possible etiology of several pulmonary diseases. Presently, although research studies have reported the concentrations of cytokines and compounds such as major basic protein in BAL fluids, only the cellular elements, total protein, albumin, and immunoglobulins have been well defined. We hypothesize that amino acids and related amino compounds, well known participants in physiologic and biochemical processes, are present in BAL fluid and may have involvement in asthma. Our objective was to extend knowledge of the total chemical profile and clinical value of BAL fluids in humans by measuring these amino compounds in normal control subjects and asthmatic patients. Analysis by high-pressure liquid chromatography revealed the presence of 25 compounds. A few compounds in control subjects and patients were found to have values > 1.0 nmol/ml, while the majority were present in comparatively low concentrations < 1.0 nmol/ml. Asparagine, phosphoethanolamine, and taurine were significantly increased in the asthmatic patients. We conclude that the present profile of amino acids and related amino compounds in BAL fluid serves as a potential diagnostic tool in the study of various pulmonary disorders. The significance of increased asparagine, phosphoethanolamine, and taurine in the asthmatic patients is discussed and deserves further study.

A profile of amino acid and catecholamine levels during endotoxin-induced acute lung injury in sheep: searching for potential markers of the acute respiratory distress syndrome.

The identification of plasma markers of the course of the acute respiratory distress syndrome (ARDS) is needed to improve its treatment and to further advance the development of new therapeutic agents. The status of markers of lung injury in ARDS is reviewed and some new potential markers are proposed. This study focused on plasma amino acids, related amino compounds, and catecholamine levels during the acute phase of endotoxin-induced lung injury in 8 sheep characterized by the onset of pulmonary edema caused by increased microvascular permeability. A number of significant changes from baseline values were found. During the sixth hour of a 12-hour period of endotoxin infusion, norepinephrine, epinephrine, and alanine levels increased whereas the isoleucine level decreased. During the sixth hour of the immediate postendotoxin period, the taurine level increased while the levels of arginine, citrulline, glycine, isoleucine, methionine, ornithine, serine, threonine, and tryptophan decreased. These findings are compared with prior studies in human subjects detailing the amino acid profile characteristic of advanced sepsis. We conclude that the present profile of catecholamine and amino acid changes during endotoxemia in sheep deserves further study in human subjects to determine its significance as a marker of the early stage of ARDS.

Effect of arginine administration on plasma and brain levels of arginine and various related amino compounds in the rat.

Arginine (ARG) was injected (0.8 g/kg, i.p.) into rats and levels of ARG were determined in plasma and four brain areas in the morning and afternoon. In control rats, brain values for ARG and some amino compounds are lower in the afternoon than in the morning. After ARG administration, ARG levels increase about 10-fold in the plasma and 2- to 3-fold in the brain areas. Brain ARG levels follow plasma levels. Elevated ARG levels affect a number of related amino compounds both in the plasma and all brain areas most notably ornithine, phosphoserine, glycine, GABA and ammonia. An increase of citrulline after ARG administration suggests the possibility of ARG-stimulated nitric oxide formation in the midbrain. Thus, ARG shows a daily rhythm in the plasma and brain and its administration increases ARG brain levels which seem to follow plasma levels. In addition, ARG alters a number of other amino compounds most notably GABA, glycine, ornithine and ammonia, indicating that some pharmacological effects seen after ARG administration might be caused by elevated levels of ARG and/or changes in other amino compounds.

Levels of taurine, amino acids and related compounds in plasma, vena cava, aorta and heart of rats after taurine administration.

A pharmacokinetic study on the fate of administered taurine in blood and some tissues and the effects on other amino compounds is presented. Injection of taurine (0.8 g/kg i.p.) causes markedly elevated plasma levels (70-fold at 15 min) which decrease later and approach baseline values after about 4 h. Concomitantly, other plasma amino compounds such as ornithine, threonine, asparagine, glutamine, alanine, citrulline, tyrosine, tryptophan, glycine, ammonia and arginine are reduced, whereas beta-alanine and phosphoserine are increased. At 30 min, tissue levels of taurine are roughly doubled in the vena cava and heart and tripled in the aorta. Other amino compounds affected are aspartic acid, serine, valine, methionine, tyrosine, ammonia, lysine, histidine, and arginine in the vena cava; aspartic acid, reduced glutathione, serine, and ammonia in the aorta; and reduced glutathione, alanine, citrulline and methionine in the heart. In most of these cases, plasma changes do not predict tissue changes which are generally substance- and tissue-specific. Thus, pharmacological effects seen after taurine administration could be caused by elevated taurine levels per se and/or taurine-induced changes in some of the amino acids and related compounds.

Effect of ethanol on amino acids and related compounds in rat plasma, heart, aorta, bronchus, and pancreas.

The composition of 36 amino acids and related amino compounds is presented for plasma, aorta, heart, pancreas, and bronchi. The distribution pattern of these biochemicals is similar but not identical among the tissues. The effect of an acute dose of ethanol (2 g/kg, i.p.) on these amino acids and related compounds was then studied. In the plasma, alanine, arginine, aspartic acid, beta-alanine, glycine, phenylalanine, and serine are decreased. In the aorta, ammonia and taurine are decreased. In the heart, aspartic acid and leucine are decreased, and carnosine, GABA, glutamic acid, and ornithine are increased. In the pancreas, asparagine and taurine are decreased, and citrulline, cysteine, histidine, and isoleucine are increased. In the bronchi, GABA, ethanolamine, histidine, taurine, and isoleucine are decreased. A number of correlations of some compounds in plasma or tissues were found but differed often between control and ethanol-treated animals. Ethanol-induced tissue changes generally do not correlate with plasma changes and are mostly specific for a given tissue.

The effects of arginine administration on the levels of arginine, other amino acids and related amino compounds in the plasma, heart, aorta, vena cava, bronchi and pancreas of the rat.

Arginine (0.8g/kg, ip) or a vehicle was administered to rats and the levels of arginine and a large number of related amino compounds++ were measured in plasma, heart, aorta, vena cava, pancreas and bronchi at specified time intervals. Arginine levels (nmol/ml) increased in the plasma from 237 to 3172 at 15 min, 1236 at 30 min and 509 at 120 min. Peak concentrations (nmol/g) of arginine are reached in the tissues at 15 or 30 minutes with control and postinjection values of 500 and 1769 in the heart, 314 and 1563 in the aorta, 575 and 2976 in the vena cava, 760 and 1943 in the bronchi, and 234 and 3638 in the pancreas. Arginine injection also affects a number of amino acids and related compounds in the plasma and tissues most notably ornithine, isoleucine, phosphoserine, leucine and ethanolamine. However, plasma level changes do not predict tissue level changes which are highly specific for an individual compound and tissue. There was no general indication that arginine injection stimulates nitric oxide (NO) formation in any tissue. Thus, arginine is rapidly absorbed from the abdominal cavity into the blood stream, is quickly taken up by the tissues studied and disappears after about 2 to 3 hours. The effects seen after arginine administration could be caused by arginine per se and/or changes in one or more of the related amino compounds but not by NO.

Effect of stress on amino acids and related compounds in various tissues of the rat.

The composition of various amino acids and related compounds in the aorta, ventricle, atria, liver, kidney, pancreas, bronchi and adrenals of rats is presented. These patterns are qualitatively similar, but quantitatively different. Stress changed these patterns. In the aorta, alpha-aminobutyric acid and ammonia are decreased. In the ventricle, phosphoserine and red. Glutathione are increased; and ammonia, arginine, asparagine, carnosine, ethanolamine, glutamic acid, glutamine, lysine, phosphoethanolamine and taurine are decreased. In the atria, alpha-aminobutyric acid, aspartic acid, ethanolamine and red. glutathione are increased; and ammonia is decreased. In the liver, alpha-aminobutyric acid, cystine, isoleucine, red. glutathione, methionine and phenylalanine are increased. In the kidney, ethanolamine is increased; and beta - aminobutyric acid, citrulline, cystathionine, glutamic acid, glycine and tryptophan are decreased. In the pancreas, alpha-aminoadipic acid, ox. glutathione, leucine, glutamine, 1-methylhistidine, phenylalanine, phosphoserine, tryptophan and valine are increased; and ammonia, cystine and aspartic acid are decreased. In the adrenal glands, anserine, glutamic acid, glutamine and ox. glutathione are increased; and arginine is decreased. In the bronchi, ethanolamine and beta-alanine are increased and alpha-aminobutyric acid and ox. glutathione are decreased. Thus, stress affects certain amino compounds but changes are substance and tissue specific and independent of changes seen in the plasma.

Metered dose inhaler therapy for asthma, bronchitis, and emphysema.

This review addresses the use of the metered dose inhaler (MDI) to administer aerosol therapy in the treatment of asthma, bronchitis, and emphysema. Studies have shown that physicians' prescribing patterns for use of the inhaler have been inconsistent with optimal therapy. Furthermore, the medical literature suggests that the metered dose inhaler should replace the jet nebulizer in hospital and outpatient settings as a more efficient and cost-effective treatment method. All classes of aerosol drugs are now available for administration by the MDI. Reports suggest that patients whose conditions do not respond to treatment administered by the MDI may improve following instruction in the proper method of using the inhaler or by increasing the recommended dosage of medication for those receiving beta-adrenergic, anticholinergic, and glucocorticoid drugs. A consensus now recommends that aerosol glucocorticoids be considered the primary method of therapy for asthma; however, the effectiveness of glucocorticoids in the treatment of bronchitis and emphysema has not been determined. Although available data do not prove that drugs used in the treatment of asthma increase mortality, further study is recommended in view of the potential toxicity of these drugs.

The nutritional status in advanced emphysema associated with chronic bronchitis. A study of amino acid and catecholamine levels.

Advanced emphysema with bronchitis is associated with significant weight loss and malnutrition, the true cause of which has not been clearly identified. The purpose of this exploratory study was to compare plasma amino acids and related compounds and catecholamines in a group of patients with advanced end-stage emphysema with a control group of similar age and sex in an effort to further understand this malnourished state. Fasting blood samples were obtained by venipuncture after a rest period. Plasma amino acid levels were determined by ion exchange high pressure liquid chromatography with fluorometric detection. Plasma catecholamines were determined by radioenzymatic analysis. Anthropometric measurements, the usually accepted biochemical markers of nutrition, dietary analysis, pulmonary function tests, and a historical analysis of the state of health including drug use and smoking history in each subject were analyzed. Ages and heights were comparable, whereas weights were significantly decreased in the patients with emphysema. Total serum protein and serum albumin values were significantly lower in the patient group. Significant respiratory muscle weakness was indicated by reduced negative inspiratory force in these end-stage patients, contrasting with well-preserved muscle strength usually found in obstructive lung disease. The dietary caloric intake of the patients was comparable to that of the control subjects. We conclude that the fine balance of the amino acid pool in patients with bronchitis and emphysema is well preserved, except for significant elevations of aspartic acid, glutamine, and cystine, and a decreased level of leucine. In addition, norepinephrine levels were significantly increased. Weight loss in patients with emphysema and bronchitis is likely due to increased energy demands related to hypermetabolism.