[Comparative study of two antitussive drugs in the treatment of acute dry cough of infectious origin (prospective, randomized, single blind study)]. / Etude comparative de deux antitussifs dans le traitement des toux aiguës sèches d'origine infectieuse (étude prospective, randomisée, en simple aveugle).

The objective was to compare, during a 5-day therapy, the efficacy and tolerability of an antihistaminic antitussive syrup, oxomemazine, combining a small quantity of guaifenesine (T), with a centrally acting antitussive, clobutinol (S), in adult patients aged from 18 to 70 years and presenting with a dry cough of infectious origin. This study was performed by 22 general practitioners and 130 ambulatory patients were enrolled. The primary criterion of this multicenter, randomized, single blind study was to compare the evolution of cough intensity using a Visual Analog Squale (VAS) graduated from 0 to 10 cm. Nine secondary criteria including tolerability were also assessed. With regard to cough intensity, the treatments were not equivalent. A greater reduction was observed with T (-5.2 +/- 2.3 versus -4.3 +/- 2.3). This result was confirmed by a further reduction in cough intensity at days: 2 (p = 0.04), 4 (p = 0.05), and 5 (p = 0.02). The frequency of cough disappearance before the end of the study was significantly greater for T than for S: 46% versus 29% (p = 0.05). The time before disappearance of the cough was 4.0 + 1.1 days for both medicines. Induction of sleep and the frequency of nocturnal wakening were significantly better for T from day 4 (p = 0.02). The drowsiness induced by T meant that diurnal quality of life was better with S on days 1 (p = 0.002) and 2 (p = 0.01). Tolerability was similar for both medicines. In conclusion, as a symptomatic treatment of dry cough, T is efficient and well tolerated. Moreover, we have observed a tendency towards superior efficacy of T than S. T is therefore a useful alternative in the therapeutic armamentarium available to the general practitioner.

Decreased erythrocyte deformability in glycogen storage disease.

Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations and possibly reduced cell deformability. Since decreased erythrocyte deformability is known to disturb blood flow in capillaries and may promote ischaemic diseases, this study was designed to investigate erythrocyte deformability using a new filtration system, the Cell Transit Analyser (CTA), and to examine lipid compounds in the blood of 23 patients affected with GSD, aged from 1 to 20 years and 18 controls aged from 1 to 17 years. The patients showed a mixed hyperlipidaemia with predominant hypertriglyceridaemia and an increase in erythrocytes mean transit times (TT) due to the presence of more rigid erythrocytes subpopulations when compared to controls. Thus the erythrocyte rigidity, in addition to the lipid abnormalities must be taken into account for long-term evolution of GSD patients. Moreover this cellular alteration may contribute to shortened erythrocyte survival.

Blood lipids and rheological modifications in glycogen storage disease.

OBJECTIVES: Hyperlipidemia is a feature of liver glycogen storage disease (GSD). Recent studies have suggested that rheological mechanisms such as elevated erythrocyte aggregation may be involved in the pathogenesis of ischemic syndromes associated with hyperlipidemia. DESIGN AND METHODS: We investigated erythrocyte aggregation, lipids, and circulatory proteins in the blood of 24 patients affected with GSD, aged from 1 to 23 years (mean = 8) and 26 controls aged from 1 to 28 years (mean = 9). RESULTS: The aggregation results were much higher in patients than controls. The lipid data showed a mixed hyperlipidemia with predominant hypertriglyceridemia, low HDL-C, apoA-I and LpA-I/A-II, and high apoB as compared with controls. However, the LpA-I was not significantly different from controls. CONCLUSIONS: In conclusion, patients with GSD presented hyperlipidemia and elevated erythrocyte aggregation such that they are at long-term risk of ischemic complications.

Alterations in erythrocyte membrane fluidity and fatty acid composition in glycogen storage disease.

Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations. Reduced erythrocyte membrane fluidity has been associated with ischaemic cardiovascular disease. Our study has been designed to investigate membrane erythrocyte fluidity, and to determine its lipid composition and peroxidation parameters. Membrane erythrocyte fluidity has been studied by electron spin resonance (ESR) with two fatty acid nitroxide probes (5NS and 16NS). Twenty-five GSD cases aged 1-27 years and 15 controls aged 1-28 years were included. The erythrocyte membrane of GSD patients appeared less fluid with the two probes (P < 0.001). The membrane fatty acid pattern explained this reduced fluidity. Patients showed a relative saturated fatty acid (SFA) increase and polyunsaturated fatty acid (PUFA) decrease which induced lower PUFA/SFA ratio than in controls. We have provided evidence that the PUFA decrease was independent of the oxidative process. These findings should be taken into account for the management of the dietary treatment of GSD patients.

Discrepancies between lipoprotein(a) concentrations in icteric sera measured by immunonephelometry and electroimmunodiffusion.

We compared the lipoprotein(a) [Lp(a)] levels in 32 icteric sera determined both by an electroimmunodiffusion assay (EIA), using the Hydragel Lp(a) kit (Sebia, France) and by two immunonephelometric assays, one on a Behring Nephelometer Analyzer (BNA), using antiserum from immunofrance, and the other on a Beckman analyzer (Array), using antiserum from Dako (Denmark). With the EIA assay, the Lp(a) level was 0.09 +/- 0.09 (mean +/- SD in g/L), with the BNA assay, 1.01 +/- 1.51 and with the Array assay, 0.05 +/- 0.05. Sample blanks values (0.76 +/- 1.28 g/L) demonstrated that the high Lp(a) levels obtained in the BNA assay are caused by nonspecific precipitation. Analysis of the precipitate indicated the presence of Lipoprotein X, an abnormal lipoprotein that appears in the serum of patients with obstructive jaundice or with lecithin-cholesterol acyltransferase deficiency. The precipitant seems to be polyethyleneglycol (PEG) that was added to the reaction medium in both the BNA and the Array assays to stabilize the Lp(a)-anti Lp(a) immune complex. In the Array assay, interference by this nonspecific precipitation is eliminated by preliminary centrifugation of the diluted sample. However, coprecipitation of Lp(a) could occur during this step. Consequently, the results of Lp(a) measurement in serum from patients with hepatobiliary diseases should be interpreted with caution when immunonephelometric assays are used with a medium containing PEG.

Specific binding sites on human phagocytic blood cells for Gly-Leu-Phe and Val-Glu-Pro-Ile-Pro-Tyr, immunostimulating peptides from human milk proteins.

Two immunostimulating peptides were isolated from human milk proteins by enzymatic digestion, the tripeptide GLF and the hexapeptide VEPIPY. These peptides increased the phagocytosis of human and murine macrophages and protected mice against Klebsiella pneumoniae infection. The present study showed that this activity may be correlated to the presence of specific binding sites on human blood phagocytic cells. The receptor molecules implicated were different for the two peptides. [3H]GLF specifically bound to PMNL and monocytes, whereas [3H]VEPIPY only bound to monocytes. The leukemic promyelocytic cell line HL-60 differentiated into granulocytes or into macrophages (depending on inducer used) coroborated these results. Specific binding of [3H]GLF on plasma membrane preparations of human PMNL (20 degrees C) was saturable and Scatchard analysis indicated two classes of binding sites: high-affinity sites of Kd 2.3 +/- 1.0 nM and Bm 60 +/- 9 fmol/mg protein and low-affinity sites of Kd 26.0 +/- 3.5 nM and Bm 208 +/- 45 fmol/mg protein. [3H]GLF binding was inhibited in a concentration-dependent manner by various analogous peptides, such as LLF, GLY, LLY and RGDGLF, but not by RGD, RGDS, VEPIPY and the chemotactic peptide f-Met-Leu-Phe (f-MLF). Only at high concentrations the direct analog MLF competed with labeled GLF. An important inhibitory effect was also observed with C1q component of the complement whereas C3 and BSA were uneffective. Specific binding of [3H]VEPIPY on monocyte membranes (20 degrees C) was saturable and Scatchard analysis was consistent with one class of binding sites of Kd 3.7 +/- 0.3 nM and Bm 150 +/- 6 fmol/mg protein.

Effects of tripeptides derived from milk proteins on polymorphonuclear oxidative and phosphoinositide metabolisms.

The tripeptide GLF (glycyl-leucyl-phenylalanine) was isolated from human milk proteins. This peptide increased phagocytosis by human and murine macrophages and protected mice against Klebsiella pneumoniae infection. Specific binding sites on human polymorphonuclear leukocytes (PMNs) have been demonstrated recently. The aim of the present research was to study the action of this peptide on rat and human PMN oxidative burst and to investigate the consequences of cell stimulation on polyphosphoinositide hydrolysis. A biphasic stimulating concentration-dependent effect of GLF on PMN chemiluminescence and superoxide anion generation was demonstrated. One of the peaks of the oxidative response occurred around 10(-9) M, which correlates with the Kd of high affinity receptors of GLF. The other maximum, around 10(-4) M, might be due to the hydrophobic nature of the tripeptide. O2- generation mimicked the phorbol myristate acetate response: after a lag period of 2-5 min, O2- release gradually increased for 10-15 min until a plateau was reached. Furthermore, GLF enhanced phosphoinositide breakdown with maximal IP3 production at 10(-7) M. Various analogs of GLF were synthesized in order to define the relative importance of the different amino acids and their position in the tripeptide molecule: glycyl-phenylalanine-leucine was devoid of biological properties but enhanced the activity of GLF on the metabolic burst at high concentrations; peptides leucyl-leucyl-phenylalanine and leucyl-leucyl-tyrosine, which displaced GLF from its specific membrane receptors, exerted stimulating effects on PMN oxidative and phosphoinositide metabolisms. It is quite conceivable that these short peptides, which may be generated in the newborn during digestion and which are able to stimulate phagocytic cells, are implicated in the defense of the neonate immature organism against infection.