Benefits, limits and danger of ephedrine and pseudoephedrine as nasal decongestants.

Due to their vasoconstrictive action on the nasal mucosa, ephedrine and pseudoephedrine are highly efficient amines for relief of nasal congestion. As with any vasoconstrictor and as underscored by the French Society of Otorhinolaryngology in its 2011 guideline, these molecules should not be used in patients under the age of 15. Furthermore, due to unpredictable severe cardiovascular and neurological adverse events that may occur even at low dose and in the absence of any pre-existing pathology, they should not be prescribed for the common cold, and ENT physicians must carefully weigh the risk/benefit ratio in patients with allergic rhinitis. Distribution should be regulated and over-the-counter sales banned.

Piracetam en el tratamiento de un paciente con mioclonía cortical idiopática / Pirazetam in the treatment of an idiopathic cortical myoclonus patient

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The role of airway stents in the management of pediatric tracheal, carinal, and bronchial disease.

OBJECTIVE: A variety of stents are available to aid in the management of complex tracheal, carinal and bronchial stenoses. We reviewed our multi-institutional experience with airway stents in children. METHODS: Thirty-three children (age, 13 days-18 years) from four institutions have had a total of 40 stents placed to aid in the management of complex airway stenoses. Three stent types were utilized: 29 silastic stents, five expandable metal stents and six customized carinal stents (four patients had two stents and one patient had four stents). Thirty children had tracheal stents, six children had bronchial stents, and two infants had carinal stents (three children had stenting of more than one area and two had stenting of all three locations). Twenty-eight patients (age, 5 months-18 years; mean, 8.06 years; SEM, 1.13 years) had stents placed after a variety of airway reconstructive procedures. Four underwent stenting in a non-operative setting and one as preoperative stabilization. RESULTS: Twenty-seven patients survived. One patient died early due to bleeding. Five patients died late: two due to bleeding, one from mediastinitis, and two patients with functional airways died late from unrelated problems. Complications are related to stent type and location. Carinal stents can migrate; several techniques are available to help manage this problem. Wire stents are essentially non-removable requiring periodic dilation. Silastic stents stimulate granulation tissue formation requiring periodic bronchoscopic removal. CONCLUSION: Tracheal stenting can aid in the management of pediatric airway problems. Complications are common, but can be managed with appropriate intervention.

Mioclonía cortical idiopática. A propósito de un caso / Idiopathic cortical myoclonia. A case report

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[Pharmacology of recombinant cytokines]. / Pharmacologie clinique des cytokines recombinantes.

The explosive growth in cytokines has been followed by many attempts to bring them into clinical use. Immediate applications are already recognized in cancer and infectious diseases. Future applications are foreseeable in inflammatory and auto-immune diseases. The use of accurate and sensitive methods for cytokine measurements in body fluids is an absolute prerequisite to define the pharmacological effect of parenterally administered recombinant cytokines. Enzyme-linked immunosorbent assay (ELISA) has become the most convenient method but there is an urgent need for a real standardization of this technique. Moreover, ELISA may be susceptible to cross-reactivity due to the high percentage of amino-acid homology between the various cytokines. The pharmacokinetic profile of recombinant cytokines may be influenced by endogenous production, receptor binding effect, receptor antagonists and soluble receptors. Cytokines elicit an immunogenic response and anticytokine antibodies should be monitored. Serum half-life of elimination is about 4 h after subcutaneous administration. In contrast with conventional drugs, pharmacokinetic data do not provide useful information for the design of a clinical protocol, and the rational choice of the unit dose and dosing schedule should be based on biological considerations. In vitro studies on the duration of receptor occupancy required for effector augmentation provide one of the bases for the choice of therapeutic protocol. Recombinant cytokines share biological activities and synergize with or antagonize one another so that it is difficult to evaluate their effects in clinical studies. Thus, pharmacological results do not always correlate with therapeutic effect. There is no direct relationship between dose and activity. One must determine the optimum biological dose (OBD), which is the minimal dose resulting in a significant augmentation of effector cell activity correlating with the therapeutic response. Surrogate markers may help to assess the clinical response such as 2',5'-oligo(A) synthetase or neopterin following interferon administration. Cytokines' adverse effects are difficult to foresee in the human because studies in rodents and dogs cannot fully predict them because of their species specificity. New relevant animal models are needed such as transgenic animals and parallel animal models. Pro-inflammatory cytokines inhibit cytochrome P-450 and have the potential to cause drug-cytokine interactions.

[Antibacterial activity of urine after administration of ofloxacin for 5 days]. / Activité antibactérienne des urines après administration d'ofloxacine pendant 5 jours.

The antibacterial activity of ofloxacin was evaluated in urine over a period of 96 h after oral administration for 5 days of 200 mg twice a day in 12 healthy female volunteers. Bacteriostatic and bactericidal activity of urines were studied for five strains of enterobacterias recovered from urinary infections: two strains of Escherichia Coli Nal-S and Nal-R, two strains of Proteus mirabilis Nal-S and Nal-R, and one strain of Klebsiella pneumoniae Nal-S. Mean urinary concentrations of ofloxacin were very high during the first 12 h following last intake. They were still above 7 mg/l till the 48th hour and above 1.6 mg/l till the 72nd hour. Bactericidal activity of urine was present for 72 h in respect of four strains studied at that time; urine was not bactericidal as regards E. coli Nal-R. After 5 days of oral treatment with ofloxacin (200 mg b.i.d.), urine retains a bactericidal activity for at least 72 h against bacterial strains of urinary tract infections.

Contribution of mitogen-activated protein kinase to stimulation of phospholipase D by the chemotactic peptide fMet-Leu-Phe in human neutrophils.

Phospholipase D (PLD) plays an important role in signaling through phosphatidylcholine (PC) and in the production of superoxide (respiratory burst) by polymorphonuclear leukocytes (PMN) stimulated by the chemoattractant fMet-Leu-Phe (fMLP). However, the regulation of PLD activity by protein kinases is not fully understood. In the present study, we have used a mitogen-activated protein (MAP) kinase inhibitor (PD 98059) to investigate a possible connection between extracellular signal-regulated kinase (ERK) and PLD activity and respiratory burst. Using a range of concentrations (3-20 microM) which inhibit ERK activity, PD 98059 inhibited PLD activity induced by fMLP in cytochalasin B-primed PMN, as assessed by production-tritiated phosphatidylethanol (PEt), phosphatidic acid (PA), and hydrolysis of PC. However, the inhibition was partial (approximately 50%), while inhibition of PC hydrolysis was almost complete, suggesting a concomitant inhibition of PLA2 activity. In addition, PD 98059 reduced fMLP-induced respiratory burst by 50%, an effect which was correlated with PLD inhibition of PLD (r = 0.981, P < 0.01), and neither did PD 98059 inhibit the PLD activity and respiratory burst induced by PKC upon its direct activation by phorbol myristate acetate. These data provide the first evidence for implication of the ERK cascade in the stimulation of PLD through Gi signaling. They further indicate that PLD stimulation by fMLP receptors occurs through two pathways, dependent and independent on MAP kinase, the former pathway being linked to superoxide production.

[Treatment of different types of pain]. / Traitement des différents types de douleurs.

Accurate assessment of pain is the key to appropriate analgesia. This necessitates not only an understanding of the organic component, but also a comprehension of the role played by the mental, social and spiritual dimensions in the individual patient's suffering. It implies that the entire care team must be involved in pain management. The nature of a patient's pain is one predictor of the response to treatment. It is mainly characterized by its location, intensity, extent, timing and type (excessive nociception, neurogenic, or mixed), the circumstances in which it appears, and any accompanying signs. The choice of analgesic for treating pain due to excessive nociception was greatly facilitated by the introduction of the WHO three-step approach. Better knowledge of the pharmacological and pharmacokinetic properties of the different analgesics has contributed to increase their efficacy and tolerability. Certain types of pain of neurogenic origin respond poorly to both opiate and non opiate analgesics. They can be treated with other drugs whose mechanisms of action in pain relief are not fully understood. They include the following; antidepressants (amitriptyline, nortriptyline, desipramine and doxepine); anticonvulsants (carbamazepine, phenytoin, valporic acid and clonazepam); antiarrhythmic agents (lidocaine, mexiletine, flecainide and tocainide). The unwanted effects of these different treatments, together with psychological disturbances induced by the underlying disease, can call for the use of antiemetics, laxatives, spasmolytics, glucocorticoids and psychotropic agents (anxiolytics, neuroleptics and antidepressants). Finally, in many cases, better pain relief is obtained by combining drug-based therapy with other interventions such as radiation therapy, neurosurgery, and psychological/behavioral approaches. All these means must be chosen and used according to each individual patient's needs. Pain must be considered as a disease that can and must be eliminated or at least attenuated.

Copper-indomethacinate associated with zwitterionic phospholipids prevents enteropathy in rats: effect on inducible NO synthase.

Intestinal toxicity exerted by indomethacin was compared to that induced by copper-indomethacinate, free or associated to zwitterionic phospholipids. A single high dose of indomethacin (15 or 20 mg/kg), copper-indomethacinate (15 or 20 mg/kg), or copper-indomethacinate liposomes or nanocapsules (15 mg/kg) was orally administered. Then 24 hr later jejunoileal tissue was taken for macroscopic observation, ex vivo nitrite production, and determination of myeloperoxydase and iNOS activities. Antiinflammatory activity of the drugs was investigated using the carrageenan-induced paw edema model. Indomethacin induced penetrating ulcerations of the intestine that were maximal at hour 24. Copper-indomethacinate induced significantly less ulceration than indomethacin with no significant difference in MPO and iNOS activities. The injurious action of indomethacin on the small intestine was further reduced when copper-indomethacinate was administered as the phospholipid-associated state while similar anti-inflammatory action was observed on rat paw edema. The antiulcerogen effect of copper-indomethacinate seems to be linked to its free radical scavenging effect without any modification of nitric oxide release.

Effect of piracetam on polyphosphoinositide metabolism, cytosolic calcium release, and oxidative burst in human polymorphonuclear cells: interaction with fMLP-induced stimulation.

We investigated the action of piracetam on human polymorphonuclear leukocyte (PMN) responsiveness in vitro. We first studied phosphoinositide metabolism and calcium release with and without fMLP (formyl-methionyl-leucyl-phenylalanine) stimulation. Piracetam at concentrations from 10(-4) to 10(-2) M induced a slight increase in inositol 1,4,5-trisphosphate (IP3) release and phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown. At concentrations above 10(-3) M, piracetam sensitized PMNs to subsequent stimulation by fMLP used at subliminal concentrations (10(-9) and 10(-8) M), inducing a significant increase in IP3 release and PIP2 breakdown similar to that obtained with cells stimulated by the highest effective concentrations of fMLP (10(-7) and 10(-6) M). In the same way, piracetam greatly enhanced calcium release induced by weak concentrations of fMLP. However, piracetam had no effect on oxidative metabolism. We then studied the binding of (3H)fMLP to the PMN membrane in the presence of various concentrations of piracetam. We were not able to demonstrate an obvious action of piracetam either on receptor recruitment or on receptor affinity to fMLP. The difference between the actions of piracetam on phosphoinositide metabolism and calcium release on the one hand and oxidative burst on the other could be explained by an uncoupling of the triggering and activating effects of piracetam on PMNs. The enhancement by piracetam of intracellular cyclic AMP levels rapidly induced termination of the PMN response and accounted for the lack of effect on superoxide production. Thus, piracetam was able to modulate human PMN reactivity and in particular to exert a "priming effect" (rather due to structural modifications of the membrane), which might be of importance in infectious episodes given the absence of deleterious actions such as oxygen free radical production leading to tissue injury.

[Drugs for respiratory tropism and pregnancy]. / Médicaments à tropisme respiratoire et grossesse.

The pharmokinetics of drugs used to treat lung disease in pregnant women undergo changes due to the physiological variations induced by pregnancy. Dosage must therefore be adapted; increased doses are often required for the treatment of severe lung infections. Most drugs used for lung disease have a teratogenic potential and thus carry a risk for the fetus. Drugs used for asthma usually present little risk for the fetus. Administration by inhalation is particularly well adapted as it limits systemic diffusion. Excessively high doses can however lead to neonatal toxicity. Penicillins, cephalosporins and erythromycin have been shown to be well tolerated and are the choice antibiotics. Aminoglycosides require careful monitoring due to the risk of renal and auditory toxicity. Fluoroquinolones, sulfamides and tetracyclines should be avoided. Available data on recent compounds such as the new macrolides (azithromycin, clarithromycin) are too limited for recommending their use during pregnancy. In case of resistant tuberculosis, it is sometimes necessary to prescribe a second choice anti-tuberculosis drug with known or suspected fetal toxicity.

Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis.

OBJECTIVE: The inflammatory component of most human inflammatory chronic diseases implicates the production of proinflammatory cytokines. Tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta) seem to play an important role in ulcerative colitis (UC) in relevant experimental models. Moreover, antiTNF therapy seems promising experimentally and clinically. However, these cytokines, and TNFalpha more particularly, are hardly seen in vivo in such patients. The mediators of choice, correlated with disease activities or drug efficacy, remain unclear. To characterize in vivo the network of colonic cytokines in patients with UC, and the contribution of the various cytokines to disease activity we performed this study, using the colonic perfusion method. METHODS: A 20-cm colon length was perfused. Perfusate samples were collected for cytokine determination by enzyme-linked immnoassays. Nineteen perfusions were performed in mild to moderate UC, including two successive perfusions in four patients. Six healthy control patients and four having Crohn's disease (CD) with rectal involvement were studied. Endoscopic score, leukocyte scintigraphy, and systemic markers of inflammation were simultaneously quantified. RESULTS: Large amounts of IL1beta, TNFalpha, IL6, and IL8 were produced in UC patients with a highly significant correlation between TNFalpha, IL1beta and IL8 two by two. Multivariate factorial analysis indicated that IL1beta showed the best correlation with disease activity. Locally produced IL6 was strongly associated with circulating platelet counts. Moreover, production of inflammatory cytokines was associated with similar variations of disease activity in the four patients with two successive perfusions performed. The level of inflammatory cytokines in CD was lower than in UC; TNFalpha, IL1beta, and IL6 were not found in any control patients. CONCLUSION: UC appears to be a chronic inflammatory disease characterized by high production of all four proinflammatory cytokines (IL1beta, TNFalpha, IL6, and IL8). These results suggest that colonic perfusion may be a suitable method to evaluate the local anticytokine properties of new drugs, in correlation with disease activity and systemic markers of inflammation.

Analysis of choline and phosphorylcholine content in human neutrophils stimulated by f-Met-Leu-Phe and phorbol myristate acetate: contribution of phospholipase D and C.

ABSTRACT. We analysed changes in choline (CHO) and phosphorylcholine (PCHO) content of stimulated human polymorphonuclear leukocytes (PMNs) by a chemiluminescence assay to further examine the relative contributions of phospholipase D (PLD) and PLC to phosphatidylcholine (PC) breakdown. PLD activation was also analysed by measuring tritiated phosphatidic acid (PA) and diglycerides (GDs) in PMNs labelled with tritiated alkyl-lyso PC. Stimulation of PMNs with formyl-methionyl-leucyl-phenylalanine fMLP; 0.1 microM induced a weak elevation of mass choline (+25% of basal level) that was strongly potentiated in PMNs primed with cytochalasin B (+350% relative to the control value of 657+/-53 pmol/10(7) cells). CHO production was rapid and transient, peaking within 1 min, and ran parallel to that of tritiated PA. Thereafter, the amount of tritiated PA declined strongly (40% of maximum by 3 min), whereas the elevated choline content induced by fMLP plateaued for at least 5 min. Phorbol myristate acetate (PMA) sustained the formation of CHO for as long as 20 min, which correlated with that of [3H]PA in a time- and concentration-dependent manner. PCHO content of resting PMN leukocytes (1560 +/- 56 pmol/10(7) cells) was not modified after stimulation of PMNs with fMLP or PMA for at least 10 min, which argues against breakdown of phosphatidylcholine by PLC. For longer treatment (10-20 min), fMLP stimulated a significant enhancement of PCHO level, which occurred concomitantly with a decrease in CHO level, suggesting that choline kinase rather than PLC may be activated. Unlike fMLP, PMA stimulated a fall in PCHO between 10 and 15 min after PMN stimulation, pointing to different regulatory mechanisms of PCHO level. These data indicate that DG formation from PC in PMNs is mediated by PLD but not by PLC and show that chemiluminescence measurement of choline is a reliable index of PLD activation.

Role of tumour necrosis factor-alpha and inducible nitric oxide synthase in the prevention of nitro-flurbiprofen small intestine toxicity.

The present study compares the intestinal toxicity of nitro-flurbiprofen and flurbiprofen in order to determine their differential properties on tumour necrosis factor-alpha production and inducible nitric oxide synthase induction. Rats received one s.c. injection of flurbiprofen, nitro-flurbiprofen at equimolar dose of solvent. Twenty-four hours later, the rats were sacrificed and small intestine tissue was taken up for macroscopical quantification of ulceration, ex vivo production of tumour necrosis factor-alpha and nitrites, and determination of tissue inducible nitric oxide synthase and myeloperoxidase activities. Anti-inflammatory activity was examined in the carrageenan-induced paw edema model. We demonstrated that flurbiprofen induced dose-dependently small intestine production of tumour necrosis factor-alpha, nitrites, myeloperoxidase and inducible nitric oxide synthase activities. On the other hand, nitro-flurbiprofen did neither induce tumour necrosis factor-alpha nor nitrite production. Concurrently, no small intestine ulceration was observed with nitro-flurbiprofen whereas flurbiprofen induced dose-dependent ulceration. Nitro-flurbiprofen is devoid of intestinal toxicity despite inhibiting cyclooxygenase activity. This is associated with the absence of tumour necrosis factor-alpha and inducible nitric oxide synthase induction in normal rats. Nitro-flurbiprofen is an anti-inflammatory drug with a much more favorable gastro-intestinal toxicity profile than flurbiprofen.

Increase in tumor necrosis factor-alpha production linked to the toxicity of indomethacin for the rat small intestine.

1. The toxic effects of nonsteroidal anti-inflammatory drugs for the lower gastrointestinal tract share certain features with inflammatory processes, suggesting that the release of inflammation cytokines such as TNF-alpha may damage the intestine. 2. Rats received a s.c. injection of indomethacin. Then, jejunum-ileum was taken up for the quantification of ulcerations, production of TNF-alpha, nitrites and PGE2 ex vivo and activity of calcium-independent NO synthase and myeloperoxydase. Activation of NO metabolism and myeloperoxydase were measured as potential effectors of TNF-alpha. 3. Jejunum-ileum from rats having received indomethacin (10 mg kg(-1)) produced TNF-alpha ex vivo. Cytokine production was associated with the onset of macroscopic ulcerations of the small intestine, and preceded nitrite production and tissue activity of myeloperoxidase. 4. Similar intestinal ulcerations and upregulation of TNF-alpha were obtained with flurbiprofen (30 mg kg(-1)), chemically unrelated to indomethacin. 5. TNF-alpha production was proportional to the indomethacin dose (from 3-20 mg kg(-1)) and correlated with the surface area of ulcerations and nitrite production, 24 h after indomethacin administration. 6. Pretreatment of rats with RO 20-1724, a type-IV phosphodiesterase inhibitor which inhibits TNF-alpha synthesis, substantially reduced jejunum-ileum ulcerations, TNF-alpha and nitrite production and tissue enzyme activities. 7. These findings provide evidence that TNF-alpha is increased in indomethacin-induced intestinal ulcerations and support suggestions that TNF-alpha is involved at an early stage of nonsteroidal anti-inflammatory drug toxicity for the small intestine.

Effects of murine recombinant interleukin-10 on the inflammatory disease of rats transgenic for HLA-B27 and human beta 2-microglobulin.

Rats transgenic for HLA-B27 and human beta 2-microglobulin develop a spontaneous, multisystem, inflammatory disease that resembles human B27-associated disease and that involves the gut mucosa. This model predominantly affects the colon and is characterized by an extensive infiltration of the mucosa by inflammatory cells, largely composed of mononuclear cells. In addition, an increased plasma level of nitric oxide (NO)-derived metabolites was described in this model. Deficiency in the anti-inflammatory cytokine, interleukin-10 (IL-10), leads to the development of colitis in IL-10 knockout mice, suggesting that IL-10 plays a major role in the control of gut inflammation. The objectives of this work were to study the mechanisms of the inflammatory bowel disease (IBD) in HLA-B27 rats and to determine the effects of treatment with IL-10. The 33-3 line of HLA-B27 recombinant rats with established disease was treated in two consecutive experiments with murine recombinant IL-10 for five weeks. Assessment of the effect of this treatment was performed, based on clinical, histological and biological (myeloperoxidase and inducible NO synthase activities; tumor necrosis factor-alpha, interferon-delta, CD3, iNOS and beta-actin mRNA expression. In 33-3 rats with established disease, mesenteric lymph nodes were hyperplastic, and colonic cellularity and MPO and iNOS activities in the colonic mucosa were increased without any detectable effects of IL-10 administration. IFN-gamma and iNOS mRNA were only detected in the colon of transgenic rats. Despite a lack of effect on disease expression, IL-10 strikingly reduced the level of IFN-gamma mRNA in gut mucosa. Up-regulation of IFN-gamma mRNA suggests that the IBD of HLA-B27 rats is mediated by T-helper 1 lymphocytes. Sustained administration of IL-10, in HLA-B27 rats with established disease, efficiently inhibited IFN-gamma mRNA expression but did not influence disease expression: these results indicate that IFN-gamma may exert a critical role at an earlier stage of the disease rather in the maintenance of the lesions.

Crystal structure of 180 degree K of bis-3, 5-diisopropylsalicylatobisdimethylsulfoxidozinc(II) and the inhibition of seizures and polymorphonuclear leukocyte chemiluminescence.

Dimethylsulfoxide (DMSO) formed a ternary complex when mixed with a Zn-3, 5-diisopropylsalicylate complex of unknown structure. The structure of this new ternary complex was characterized in an initial effort to understand the nature of this compound. Since the original complex is known to have anticonvulsant activity, the new ternary complex was also examined for anticonvulsant activity. The original complex was examined for inhibition of the polymorphonuclear leukocyte (PMNL) respiratory burst in an effort to mechanistically account for zinc complex mediated anticonvulsant activity. Dissolving the structurally unknown complex in DMSO gave crystals of a characterizable complex with an empirical formula C30H46O8S2Zn. Crystallographic data: P 1, Z = 2, a = 8.06(1), b = 12.452(2), c = 17.951(2) A, alpha = 74.42(l), beta = 77.07(1), gamma = 89.50(1) degree. The structure was refined to R = 0.03, RW = 0.04 for 3815 independent reflections with I > 2 sigma(I). This complex is mononuclear, with two 3,5-diisopropylsalicylate ligands and two bonded DMSO ligands, Zn(II)(3,5-DIPS)2(DMSO)2, Zn(II) is coordinate covalently bonded to four O atoms in a strongly distorted tetrahedral arrangement. Each DMSO ligates via its sulfoxide O atom while each 3,5-diisopropylsalicylate ligand is monodentate The non-ligating carbonyl O atom of each 3,5-DIPS is free except for an intramolecular hydrogen bond from the hydroxy group of the same ligand. Both 3,5-DIPS acid and Zn(II)(3,5-DIPS)2(DMSO)2 were examined for anticonvulsant activity in the Maximal Electroshock (MES) and Metrazol (MET) models of seizures and found to prevent both types of seizures. The Zn complex was qualitatively and quantitatively more effective than treatment with the free ligand. The influence of a Zn 3,5-DIPS complex and of the ligand 3,5-DIPS on PMNL oxidative metabolism was also studied to help understand the mechanism of anticonvulsant activity of these compounds. A dose-related and significant decrease in chemiluminescent (CL) response to opsonized Zymosan was observed, and the Zn complex was significantly more effective than the free ligand. It is concluded that mononuclear Zn complexes have anticonvulsant activity in Grand Mal and Petit Mal models of seizure possibly due to inhibition of the synthesis of superoxide or down-regulation of Nitric Oxide Synthase in activated phagocytic cells of the central nervous system.

Dermaseptin, a peptide antibiotic, stimulates microbicidal activities of polymorphonuclear leukocytes.

Dermaseptin (DRs S1), a 34-amino acid residue cationic antimicrobial peptide was studied for its effects on the production of reactive oxygen species (respiratory burst) and exocytosis of polymorphonuclear leukocytes (PMN). Treatment of PMN with DRs S1 (10-100 nM) stimulated significant production of reactive oxygen species (approximately a 2-fold increase relative to control) and release of myeloperoxidase. In addition, low DRs S1 concentrations (1-10 nM) primed the stimulation of respiratory burst induced by zymosan particles. In contrast to the native peptide, a dermaseptin fragment without either the COOH-terminal (DRs 1-10) or NH2 terminal (DRs 16-34) portion was inactive. The DRs S1-induced respiratory burst was inhibited by a selective protein kinase C inhibitor, GF 109203X, and was associated with early signalling events such as a rapid and transient elevation of cytosolic-free calcium concentration and phospholipase D activity. These data provide the first evidence of stimulating and priming properties of a peptide antibiotic on microbicidal activities of neutrophils, suggesting a potential role of dermaseptin in modulating host-defense mechanisms.