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The objective of the present study was to evaluate the pharmacokinetic parameters for both S- and R-ibuprofen enantiomers in very premature neonates (gestational age strictly inferior to 28 weeks) and possible relationships between the pharmacokinetic parameters and various covariates. Newborns were randomized to receive ibuprofen or placebo for the prophylactic treatment of patent ductus arteriosus (PDA) at an initial dose of 10 mg/kg ibuprofen within 6 hours after birth, followed by two 5-mg/kg doses at 24-hour intervals (n = 52). If a PDA was still present afterwards, a curative course of ibuprofen using the same dosage regimen was administered (n = 10). A sparse sampling strategy was used because only 2 samples were collected after the third prophylactic injection and 1 after the third curative injection. A model including the chiral transformation of R- to S-ibuprofen was fitted to the concentration-time data using a population approach (NONMEM). R- and S-ibuprofen t(1/2) were about 10 hours and 25.5 hours, respectively. After prophylactic treatment, the mean clearance of R-ibuprofen (CLR = 12.7 mL/h) was about 2.5-fold higher than for S-ibuprofen (CLS = 5.0 mL/h). In addition, clearance of R- and S-ibuprofen increased significantly with gestational age. The mean estimation of R-ibuprofen clearance was found to be higher than for S-ibuprofen, and the clearance of both enantiomers increased with gestational age. This should be considered to assess pharmacokinetic-pharmacodynamic relationships of ibuprofen in premature neonates and subsequently to understand and refine the use of ibuprofen in managing PDA either as a prophylactic or curative treatment. [ABSTRACT FROM AUTHOR]

A spleen-derived immunosuppressive peptide (SDIP) has been purified to homogeneity. Its physicochemical properties (electrophoretic mobility, u.v. spectra, absence of dansyl derivative) and its enzymatic susceptibilities (proteolytic enzymes, RNase, and DNase) were similar to those of the thymic hormone 'FTS'. SDIP and FTS were eluted with identical retention times in high performance liquid chromatography analysis in three different systems. When tested in sheep cell rosettes, and in the FTS radioimmunoassay in J.F. Bach's laboratory, SDIP presented an activity similar to FTS. In order to compare the thymic hormone to SDIP the biological activity of FTS was determined in in vivo and in in vitro humoral immunity reactions to a T- dependent antigen. As SDIP, FTS inhibited in vivo and in vitro the 19S-bearing cell formation during the last step of the differentiation of the lymphocytes, in the same range of concentration. The two factors appeared to stimulate the incorporation of [³H]-thymidine into the DNA of short-term cultures of thymocytes. The similarity of biological properties of SDIP and FTS together with the similarity observed in the physico-chemical and biochemical properties led to the conclusion that bovine spleen contains a factor similar to FTS. [ABSTRACT FROM AUTHOR]

Some biological properties of a highly-purified non-cytotoxic spleen-derived immunosuppressive peptide (SDIP) have been investigated. SDIP was shown to inhibit the primary anti-sheep red blood cell (SRBC) response at the last step of differentiation of the lymphocyte. In the present study we demonstrated that this response seemed to be T- and adherent spleen-cell dependent as no inhibition was noticed either in the response to TNP-LPS, a T-independent antigen, or in the response to SRBC in adherent spleen cell-depleted cultures. SDIP activity did not occur through an inhibition of sptenocytes DNA synthesis since [3H]-thymidine ([3H]-TdR) incorporation was not modified in mitogen or allogenic stimulated cultures. Conversely, SDIP could act through a stimulation of a T-cell subset as a low specific increase of [3H]-TdR was noticed in cultured thymocytes. [ABSTRACT FROM AUTHOR]