L-alanyl-L-glutamine-supplemented parenteral nutrition improves infectious morbidity in secondary peritonitis.

BACKGROUND & AIMS: A growing number of randomized clinical trials suggest that glutamine (Gln) supplementation may be beneficial in a selected group of patients and conditions. However, the effects of Gln-enriched total parenteral nutrition (TPN) on recovery from acute intra-abdominal infection have not been thoroughly investigated. Therefore, the aim of this study was to investigate whether the provision of Gln-enriched TPN after surgical and medical treatment of secondary peritonitis improves infectious morbidity. METHODS: Thirty-three patients with secondary peritonitis were randomly assigned to receive either standard (n=16) TPN or L-alanyl-L-glutamine-supplemented (n=17) TPN, after medical and surgical treatment of the infectious focus. The two TPN formulae were isonitrogenous and isocaloric, which commenced the morning after surgery and ran continuously for 10 consecutive days. The control group received standard TPN, while the treatment group was given L-alanyl-L-glutamine, 0.40 g/kg/d (Dipeptiven, Fresenius Kabi, Bad Homburg, Germany). Infectious morbidity, nitrogen balance, leukocytes, lymphocytes, subpopulations CD(4) and CD(8), Immunoglobulin A (IgA), total proteins, albumin, hospital and intensive care unit (ICU) stays, and mortality were evaluated. Statistical analysis included one-way ANOVA, the unpaired Student's t-test, the Mann-Whitney U-test, chi(2) test, or Fisher's exact test. RESULTS: Patients in both groups were comparable prior to the operation. Nitrogen balance and the levels of albumin and IgA were significantly better than those in the control group. Also, a significant reduction in the infectious morbidity was found in the Gln-treated group. Lymphocyte counts as well as subpopulations CD(4) and CD(8), and proteins showed a propensity to improvement and a tendency to reduced rates of mortality were observed when comparing the groups. Hospital and ICU stays were similar. CONCLUSION: L-alanyl-L-glutamine-supplemented TPN improved the infectious morbidity of patients with secondary peritonitis. Gln supplementation to parenteral nutrition may be an alternative for enhancing host defenses and improving infectious morbidity.

The effect of amino acid spacers on the antigenicity of dimeric peptide--inducing cross-reacting antibodies to a cell surface protein antigen of Streptococcus mutans.

In the course of developing a synthetic peptide vaccine for dental caries, we identified a unique 13-mer peptide named PAc(365-377), TYEAALKQYEADL, as a minimum peptide inducing cross-inhibiting antibodies to a cell surface protein antigen (PAc) of Streptococcus mutans. However, the peptide could hardly induce the production of antibody in the absence of adjuvant. Thus using this peptide as a unit peptide, tandem constructs of dimeric unit peptide with or without spacer amino acid residues were synthesized, and their antigenicities were examined in B10.D2 mice. Significant augmentation of antigenicity was obtained in all of the dimeric unit peptides with spacers, especially for lysine spacers. In addition, analysis for cross-reactivity of anti-construct antibodies against a set of double valine-substituted analogues of the unit peptide revealed that the di-lysine spacer might be more effective in inducing the cross-reacting antibodies to rPAc.

Stimulation of the in vivo dinitrophenyl antibody response to the DNP conjugate of L-glutamic acid60-L-alanine30-L-Tyrosine10 (GAT) polymer by a synthetic adjuvant, muramyl dipeptide (MDP): target cells for adjuvant activity and isotypic pattern of MDP-stimulated response.

Specific anti-dinitrophenyl (DNP) response to DNP-conjugated L-glutamine60-L-alanine30-L-tyrosine10 (DNP-GAT) was obtained in GAT-responder mice by using synthetic N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) as adjuvant. Significant levels of anti-DNP antibodies were observed during a secondary response to DNP-GAT, when both antigen and MDP were used for priming. In this system, MDP was able to prime the carrier-specific T cells but not the hapten specific B cells. The study of the isotypic pattern of the anti-DNP response shows that MDP stimulates only the appearance of specific anti-DNP IgG1 plaque-forming cells. Anti-DNP plaque-forming cells were stimulated in animals primed with DNP-GAT in Freund's complete adjuvant or in Maalox-pertussis and used as control IgG1, IgG2a, and IgG2b.

Genetic control of the immune response in rats to the known sequential polypeptide (Tyr-Glu-Ala-Gly)n. I. Antibody responses.

In inbred rats, the antibody response to the known sequential polypeptide (Tyr-Glu-Ala-Gly)n (T-G-A-Gly)n is under the control of two independently assorting loci; (co) dominant, Ag-B-linked Ir-(T-G-A-Gly) I, controlling qualitative responsivenss, and a non-Ag-B-linked modifier locus termed Ir-(T-G-A-Gly) II, controlling the level of antibody produced. The antibody response to (T-G-A-Gly)n was solely IgG and the level of antibody produced was dependent upon Ir-(T-G-A-Gly) II for phenotypic response type.