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.

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.

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.

Self-administration of either nicotine (NIC) or ethanol (ETH) has been extensively studied. This study addressed for the first time the self-administration of both substances when offered together. Male and female rats of different ages were offered NIC and ETH using the two- or three-bottle free-choice method. When NIC and ETH were offered together at different concentrations to young male rats (about 45 days old), intake of NIC increased with increasing NIC concentrations, and intake of ETH increased with decreasing ETH concentrations, but these effects were independent of the presence of the second drug. These rats also consumed the same amounts of NIC or ETH regardless of whether offered individually or together. A prior choice of only NIC or ETH did not affect a subsequent intake of both drugs offered together. A choice of both drugs for 24 h for several days followed by a choice for only 2 h for several days showed the same intake of NIC but a decreased intake of ETH for the shorter period. Young female rats (about 45 days old) and older male rats (about 75 days old) consumed the same amounts of NIC but less ETH than did the young male rats. These results show that young male rats voluntarily consume NIC and ETH independently of each other and that preexposure to one drug does not affect the subsequent intake of both drugs in combination. The data also suggest that these drugs act on different reward centers which have to be ‘satisfied’ independently of each other.

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