N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) and certain derivatives that are structural analogs of part of the bacterial peptidoglycan monomer have been shown to be adjuvant active ...and to enhance the nonspecific immunity of adult mice infected by Klebsiella pneumoniae. In the present study muramyl dipeptide and two other synthetic analogs were found to be active in newborn mice. This activity could be demonstrated after administration by subcutaneous or even by oral route. In contrast to what was observed after treatment by lipopolysaccharide, 8-day-old mice were definitively protected against bacterial challenge by these glycopeptides. Therefore such molecules could have a great value in view of studying and correcting the neonate's unresponsiveness.
This study was conducted to compare the cross-reactivity of two commercially available carbamazepine (CBZ) immunoassays (PETINIA and EMIT 2000) with carbamazepine-10,11-epoxide (CBZ-E), the active ...metabolite of CBZ. Oxcarbazepine (OCBZ) and its main metabolite 10-hydroxy-carbazepine (HCBZ) have a chemical structure closely related to that of CBZ. The cross-reactivities of these two drugs were also investigated. In the first part of the study, Lyphocheck blank human serum and Chemonitor quality controls (containing CBZ without CBZ-E) were spiked with variable amounts of CBZ-E. The apparent CBZ levels were measured by PETINIA and EMIT 2000 methods. The interference from OCBZ and HCBZ was directly assessed by measuring the apparent CBZ levels in Chromsystems Trileptal quality controls (containing OCBZ and HCBZ). In the second part of the study, the CBZ levels of serum samples from 49 patients, including 2 patients with massive CBZ ingestion, were measured by immunoassays and compared with a high-pressure liquid chromatography (HPLC) reference technique allowing the simultaneous measurement of CBZ and CBZ-E. The antibody used in the PETINIA assay cross-reacts (about 90%) with CBZ-E. In one case of CBZ poisoning (CBZ and CBZ-E levels measured by HPLC were 26.2 and 18.2 mg/L, respectively), CBZ level measured by PETINIA was falsely elevated (42.5 mg/L). In contrast, the specificity of EMIT 2000 was satisfactory (29.5 mg/L). The two immunoassays tested showed low cross-reactivity with OCBZ and HCBZ. In conclusion, it appears that the CBZ-E metabolite present in samples can falsely increase CBZ levels measured by the PETINIA assay.
N-Acetylmuramyl-L-Ala-D-Glu-NH$_{2}$ (muramyl dipeptide) and several of its derivatives are effective immunoactivators that can enhance nonspecific resistance to infection but can also elicit fever. ...In contrast, one of its stereoisomers, N-acetylmuramyl-D-Ala-D-Glu-NH$_{2}$, is devoid of both these activities. Our present report demonstrates that macromolecularization of muramyl dipeptide by attachment of several units to a multi-poly(DL-Ala)- -poly(L-Lys) carrier potentiates both its pyrogenic and its immunostimulant activity. This branched polymer has been extensively used as carrier to various haptens. Surprisingly, inactive N-acetylmuramyl-D-Ala-D-Glu-NH$_{2}$, after conjugation under the same conditions, becomes capable of increasing nonspecific immunity although its lack of pyrogenicity is not greatly modified. Moreover, the N-acetylmuramyl-D-Ala-D-Glu-NH$_{2}$ conjugate remains devoid of adjuvant, sensitizing, or eliciting activity.
N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP), is a synthetic immunoadjuvant analogue of a bacterial peptidoglycan subunit that has a definite pyrogenic effect in the rabbit. ...Some adjuvant-active derivatives such as murabutide MDP(Gln)-OnBu or murametide MDP(Gln)-OMe are not pyrogenic. Murabutide did not stimulate human or rabbit cells to release endogenous pyrogen (EP), but murametide induced EP production at the same dosage levels as MDP. Moreover, plasma from rabbits treated with murametide transferred into untreated recipients elicited a febrile response typical of EP fever and comparable with that induced by plasma from MDP-treated animals. Murametide not only inhibited the central effect of EP that is generated but also the effect of an extra dose of EP administered later by the intravenous route. Moreover, pretreatment of rabbits with murametide decreased fever responses induced by certain high-molecular-weight exogenous pyrogens as mediated through the production of EP.
A fall in plasma iron level and an increase in copper level were observed in rabbits subsequent with the febrile response induced by an intravenous administration of muramyl dipeptide, ...AcMur-L-Ala-D-isoGln (MDP). The pyrogenic activity of MDP was due partly to the induction of circulating endogenous pyrogen (EP). EP produced in vitro by activated macrophages also elicited changes in iron and copper levels in rabbits. Nonpyrogenic MDP derivatives murabutide MDP(Gln)-OnBu and the stereoisomer of MDP MDP(D,D) did not cause any change in blood metal levels. Another adjuvant and nonpyrogenic analogue, murametide MDP(Gln)-OMe, elicited hypoferremia and hypercupremia. Murametide, which has been previously shown to induce secretion of circulating EP but prevents in vivo fever response, was unable to prevent an EP-induced effect on plasma metal concentrations. Injection of supernatant fluids of macrophages incubated with these different glycopeptides showed that only compounds able to induce EP release were capable of evoking hypoferremia and hypercupremia. The EP-containing fluid was 10-fold more active on change in temperature and in plasma metal levels when it was given intracerebroventricularly compared with intravenously. In contrast, a pyrogenic dose of MDP that can act directly on the central thermoregulatory structures did not modify iron and copper levels when it was injected intracerebroventricularly.
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