Plasma amino acid concentrations in elderly patients with protein energy malnutrition.

OBJECTIVE: to compare amino acid concentrations in healthy and malnourished elderly patients. METHOD: plasma amino acid concentrations were examined in 24 men and women (80-100 years of age) with protein energy malnutrition (PEM) and compared with those of 44 healthy, similarly-aged controls. Plasma samples were determined by using cation exchange columns with ninhydrin detection in an high performance liquid chromatography system. RESULTS: essential amino acid and non-essential amino acid plasma concentrations were significantly decreased in PEM (0.01 < P < 0.0001). Branched-chain amino acids and urea cycle amino acid plasma concentrations fell significantly (P < 0.0001). Plasma concentrations of alanine and glutamic acid + glutamine were also significantly reduced (P < 0.0001). CONCLUSIONS: in underweight elderly patients, the plasma amino acid pattern reflects the severity of the metabolic disturbance.

Pepstatin analogues as novel renin inhibitors.

Pepstatin analogues corresponding to the general formula A-X-Y-Sta-Ala-Sta-R were synthesized in solution phase. Various changes in the nature of the A, X, and Y groups were made to improve the inhibitory potency against human plasma renin activity. The results were interpreted by use of the active-site model based on the sequence of human angiotensinogen. The tert-butyloxycarbonyl group and the isovaleryl group were found to be the most effective acyl groups (A). The analogues having a Phe residue in place of Val1 (X) and His or amino acid with an aliphatic side chain such as norleucine or norvaline in the Y position showed the highest inhibition of human plasma renin activity with IC50 values of about 10(-8)M. Esterification or amidification of the carboxyl group of the C-terminal statine did not change the inhibitory potency. The selectivity for rat, dog, pig, and monkey plasma renin of the most interesting compounds was studied.

[Hypotensive effect of a human anti-renin monoclonal antibody (4G1D8) in the sodium-depleted alert marmoset]. / Effet hypotenseur d'un anticorps monoclonal anti-rénine humaine (4G1D8) chez le marmouset vigile désodé.

A dose-response relationship was involved after an intravenous bolus of a human antirenin monoclonal antibody (4G1D8), in sodium depleted marmosets. The sodium depletion (furosemide: 30 mg/kg/d for 2 days) was used to potentiate the contribution of the renin-angiotensin system in the blood pressure (BP) control. To record BP and inject the antibody, 2 catheters were implanted the day before the experiment. The plasma renin activity (PRA) was measured by the RIA of angiotensin I after an incubation of plasmas for 1 hour at pH 7.4. The sodium depletion induced a dramatic increase of PRA (63.68 +/- 20.03 ng/ml/h of angiotensin I compared to 2.96 +/- 1.03; p less than or equal to 0.01; n = 13). The basal BP was 102.6 +/- 2.4 mmHg (n = 17). The maximal fall in BP was noted at about 30 min for the three groups of animals treated by 4G1D8; it was -7.5 +/- 4.3 mmHg at the dose of 0.01 mg/kg (n = 4), -21.3 +/- 3.8 mmHg (p less than or equal to 0.01) at 0.10 mg/kg (n = 4), and -27.5 +/- 1.4 mmHg (p = 0.10) at 0.24 mg/kg (n = 4). At the 0.10 and 0.24 mg/kg doses, the hypotension was lasting (greater than 3 h). PRA was strongly inhibited and HR was little modified. A dose-response relationship with a human antirenin monoclonal antibody, 4G1D8, provides a very interesting pharmacological model for a comparative study of renin inhibitors.