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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.

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.

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.

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.

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.

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.