Biomedical subjects

I M Garrelds

Publications and source records attributed to I M Garrelds.

At least 19 recordsLinked to original sources

PubMed2002

Interleukin-2-Deficient mice: effect on cytokines and inflammatory cells in chronic colonic disease.

Mice deficient in interleukin-2 (IL-2-/-) develop inflammatory bowel disease resembling human ulcerative colitis. After death, macroscopic and microscopic scores were used to determine colonic inflammation. Both scores were significantly increased in the colon of IL-2-/- mice as compared to wild types mice. The level of IL-1beta 24-week-old was increased in IL-2-/- mice produced by the colon as compared with IL-2+/+ controls. However, the concentrations of IL-6 and IL-10 were not changed. The spleen weight of IL-2-/- mice was significantly increased compared with IL-2+/+ controls. We used immunochemical techniques in low-temperature paraffin-embedded spleen of IL-2-/- mice to examine pathological changes of CD4+ T cells, CD8' T cells, and CD11b+ cells. The tissue was successfully stained and was well preserved. The percentage CD4+ T cells was not significantly changed, while the percentage CD8+ T cells was significantly decreased in IL-2-/- mice compared with IL-2+/+ controls. On the other hand, the percentage CD11b+ cells was significantly increased in the spleen of IL-2-/- mice compared with IL-2+/- controls. As well as the marked difference in CD8+ and CD11b+ cells in the spleen, the increased level of IL-1beta in colonic tissue might indicate that cytotoxic T cells as well as macrophages are involved in the development and/or perpetuation of the inflammatory reactions in IL-2-/- mice.

Animals↗

PubMed2001

Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease.

BACKGROUND: In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone. AIMS: To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo. METHODS: A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyper-responsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4, LTC4/D4/E4, PGE2, 6kPGF1alpha, PGF2alpha and TxB2. A control group consisted of asymptomatic smokers (n=6). RESULTS: Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1alpha (41%) and PGF2alpha (54%). CONCLUSIONS: In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.

Adult↗

PubMed2000

Intranasal capsaicin is lacking therapeutic effect in perennial allergic rhinitis to house dust mite. A placebo-controlled study.

In a recent placebo-controlled study we demonstrated that capsaicin is an efficacious substance in the treatment of non-allergic non-infectious rhinitis. In this study the therapeutic effect lasted more than 9 months. This effect was not based on modulation of inflammation. To evaluate the effect of repeated application of capsaicin to patients with a nasal allergy to house dust mites (HDM), using the same treatment protocol as recently introduced in the treatment of non-allergic patients. Twenty-six patients with rhinitis, 15 females and 11 males (range: 20-46 years; mean 30.5), allergic to HDM were treated with either capsaicin or placebo in a double-blind, placebo-controlled, parallel group design. Nasal reactivity to HDM expressed as nasal symptoms, albumin and leukotriene levels in nasal lavage fluid and responsiveness to histamine, assessed as symptoms before and 6 weeks after treatment, were used to compare both treatment groups. In addition, visual analogue scales and rhinitis quality of life (RQL) assessment before, 6 weeks after and 3 months after treatment were used as outcome variables. No significant effect of capsaicin on nasal challenge tests with HDM (nasal symptoms, albumin and leukotriene levels), on VAS or RQL outcome 6 weeks or 3 month's after treatment, was demonstrated. Capsaicin did have a small effect on the area of the curve (AUC) of histamine dose response curves (P = 0.03). Desensitization with capsaicin in doses sufficient to control symptoms in patients with severe non-allergic rhinitis is lacking therapeutic effect in perennial allergic rhinitis.

Administration, Inhalation↗

PubMed1999

Time dependent production of cytokines and eicosanoids by human monocytic leukaemia U937 cells; effects of glucocorticosteroids.

In the present study the human monoblast cell line U937 has been used as a model to study the function of human mononuclear phagocytes in asthma. The kinetics of the production of eicosanoids and cytokines, which are thought to play a role in the pathogenesis of asthma, were studied. In addition, the effects of glucocorticosteroids were investigated, as these drugs are of great importance for the treatment of asthmatic patients. After stimulation with phorbol-12 myristate acetate (PMA) for 24 h, U937 cells were cultured in the absence or presence of lipopolysaccharide (LPS: 1 and 5 microg ml(-1)) and glucocorticosteroids (budesonide, fluticasone propionate and prednisolone: 10(-11), 10(-9) and 10(-7) M) for 96 h. The production of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) gradually increased in time after stimulation with LPS, whereas the transient production of tumor necrosis factor alpha (TNF-alpha) reached its maximum between 6 and 12 h. Interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and leukotriene B4 (LTB4) were not detectable. All three glucocorticosteroids (budesonide, fluticasone propionate and prednisolone) completely inhibited the production of both eicosanoids and cytokines. The production of eicosanoids was more sensitive to these glucocorticoids than the production of cytokines. The observed differences in the kinetics of the production of eicosanoids and cytokines stress the importance of time course experiments in studies on the effect of drugs on mononuclear cells.

Administration, Topical↗

PubMed1999

Nasal hyperreactivity.

Nasal hyperreactivity is an important feature of allergic and non-allergic rhinitis. This paper reviews the possible mechanisms behind hyperreactivity. Distinct mechanisms may play a role in allergic rhinitis--an inflammatory disease--and non-allergic rhinitis, mainly a non-inflammatory disease. In allergic rhinitis, particularly in perennial allergic rhinitis, there is a close connection between allergic response and non-specific hyperreactivity. In non-allergic rhinitis, a pathological entity comprising a heterogeneous series of diseases, understanding and measuring nasal hyperreactivity is much more difficult. A variety of methods to assess nasal hyperreactivity are available. Given the heterogeneity of mechanisms, the various patients groups and the lack of standardization in tests, it is not surprising that measurement of nasal hyperreactivity is not included in the diagnostic arsenal of the clinician.

Allergens↗

PubMed1997

Response to intranasal fluticasone propionate in perennial allergic rhinitis not associated with glucocorticoid receptor characteristics.

BACKGROUND: The reduction of symptoms due to treatment with corticosteroids varies among patients with perennial rhinitis. Most patients will respond but a few patients respond less to these drugs. OBJECTIVE: To investigate the association in reduction of symptoms due to glucocorticoids and glucocorticoid receptor characteristics in patients with perennial allergic rhinitis, in vitro glucocorticoid receptor binding studies were performed with peripheral blood mononuclear cells using dexamethasone and in vitro production of mediators were measured. METHODS: During a double-blind placebo-controlled crossover study, 200 micrograms fluticasone propionate aqueous nasal spray (in the active treatment period) and placebo (in the placebo treatment period) were administered twice daily for 2 weeks to 22 patients allergic to house dust mite. At the end of both treatment periods symptoms were scored after allergen provocation (100, 1000, 10000 BU/mL) and during the 9.5 hours after this challenge. Receptor binding studies with dexamethasone were performed with peripheral blood mononuclear cells. Leukotriene B4 produced by monocytes in vitro and soluble interleukin-2 receptor released by lymphocytes in vitro and cortisol levels in plasma were determined. RESULTS: No significant partial correlations of the number of the peripheral blood mononuclear cell glucocorticoid receptors (6821 +/- 5669 binding sites per cell) and the affinity (Kd: 16.5 +/- 13.51 nmol/L) for the glucocorticoid receptors with the symptom score (placebo: 4.3 +/- 2.45 pts; fluticasone: 2.4 +/- 1.55 pts) after active treatment were found. Also no significant partial correlations of the levels of leukotriene B4 (45.6 +/- 105.3 ng/10(6) cells) produced by monocytes in vitro, soluble interleukin-2 receptor (734 +/- 237 ng/10(6) cells) released by lymphocytes in vitro and cortisol levels (571 +/- 236 ng/mL) in plasma with the symptom score after active treatment were found. CONCLUSIONS: The reduction of symptoms due to topical fluticasone propionate in patients with rhinitis and allergy to house dust mite is not correlated with the characteristics of the glucocorticoid receptor.

Administration, Intranasal↗

PubMed1997

Intranasal capsaicin is efficacious in non-allergic, non-infectious perennial rhinitis. A placebo-controlled study.

BACKGROUND: Several authors described capsaicin, the pungent substance in red pepper, as an efficacious therapy for non-allergic non-infectious perennial rhinitis (NANIPER). Repeated capsaicin application induces peptide depletion and specific degeneration of the unmyelinated sensory C-fibres in the nasal mucosa. METHODS: We performed a placebo-controlled (NaCl 0.9%) study with 25 NANIPER patients. Daily record charts and visual analogue scales (VAS) were used for clinical evaluation. Nasal lavages were obtained before, during, and after treatment. RESULTS: There was a significant and long-term reduction in the VAS scores in the capsaicin group. No significant difference was found between the placebo and capsaicin treated groups for the mean group concentrations of leukotriene (LT) C4/D4/E4, prostaglandin D2 (PGD2), and tryptase. The levels of mast cell mediators, tryptase and PGD2, and leukotrienes, mediators derived from a variety of inflammatory cells, were low at baseline and comparable with levels observed in nasal lavages obtained from normals. CONCLUSION: As involvement of inflammation could not be demonstrated, it is not surprising that capsaicin has no effect on inflammatory mediators. This suggests that inflammatory cells do not play a major part in the pathogenesis of NANIPER.

Adolescent↗

PubMed1997

Nasal responsiveness to allergen and histamine in patients with perennial rhinitis with and without a late phase response.

BACKGROUND: In the lower airways an association has been found between early phase reaction (EPR), late phase reaction (LPR), and bronchial hyperreactivity. However, this association has not been shown for the upper airways in nasal pollen challenge studies. A study was undertaken to determine whether the EPR, LPR, and nasal hyperreactivity are related in perennial allergic rhinitis. METHODS: Twenty four patients with rhinitis who were allergic to house dust mite (HDM) were challenged with HDM extract. The nasal response was monitored by symptom scores and nasal lavages for up to 9.5 hours after challenge and concentrations of albumin, tryptase, and eosinophil cationic protein (ECP) in the lavage fluid were measured. Thirteen patients (defined as dual responders) had increased symptom scores between 3.5 and 9.5 hours compared with the baseline score. The other 11 patients (defined as early responders) showed an isolated EPR only. Nasal hyperreactivity was determined by nasal histamine challenge 24 hours later. RESULTS: Dual responders showed a significantly higher symptom score, albumin influx, and tryptase release during the EPR. During the late phase (3.5-9.5 hours) albumin influx was significantly increased at most time points and ECP release was significantly higher at 9.5 hours in the dual responder group. Dual responders showed a significantly stronger response to all doses of histamine. The area under the curve (AUC) of symptom scores during EPR and LPR and the AUC of the histamine dose response were significantly correlated (EPR-LPR: r = 0.49, p < 0.01; EPR-histamine: r = 0.75, p < 0.001; LPR-histamine: r = 0.66, p < 0.001). CONCLUSIONS: In patients with perennial allergic rhinitis the nasal responses to allergen and histamine are associated. Dual responders have an increased EPR, increased levels of mediators, and increased allergen-induced hyperreactivity.

Adult↗

PubMed1996

Nitric oxide plays a role as a mediator of conjunctival edema in experimental allergic conjunctivitis.

The role of nitric oxide in allergic conjunctivitis was studied in a guinea pig model. The eyes of sensitized guinea pigs were challenged with ovalbumin (20 micrograms per eye) or histamine (20 micrograms per eye). Synthesis of nitric oxide (NO) was inhibited using L-NAME (200 micrograms per eye) or aminoguanidine (200 micrograms per eye). The formation of conjunctival edema was graded and levels of nitrite, a breakdown product of nitric oxide were measured in lavage fluid. Conjunctival vasopermeability was determined by measuring the albumin concentration in the fluid on the surface of the eye (lavage fluid). Animals were treated with sodium nitroprusside (SNP) or phenylephrine after which histamine induced conjunctival vasopermeability changes were measured. Drugs were administered topically with the other eye serving as a control. Both ovalbumin and histamine produced a marked inflammatory response including hyperaemia and edema. At the top of the inflammatory response occurring 30 min after challenge, increased levels of nitrite, a breakdown product of NO, were measured in lavage fluid. Prophylactic treatment with L-NAME or aminoguanidine resulted in a significant inhibition of the NO synthesis. Both L-NAME and aminoguanidine decreased conjunctival vascular permeability and edema formation significantly. Administration of SNP resulted in a marked dilatation of conjunctival blood vessels and produced a dose-dependent increase of vascular permeability. Addition of SNP to histamine significantly enhanced conjunctival edema and potentiated vascular permeability. These results indicate that NO is produced in the acute phase of allergic conjunctivitis and mediates vasodilatation after topical provocation with ovalbumin or histamine in sensitized guinea pigs. The resulting increase of the conjunctival blood flow subsequently increases the vascular permeability and enhances conjunctival edema formation. Inhibition of NO synthesis leads to a reduction of conjunctival hyperaemia and subsequently reduces the formation of edema.

Animals↗

PubMed1996

The relationships between nasal hyperreactivity, quality of life, and nasal symptoms in patients with perennial allergic rhinitis.

BACKGROUND: A clinical test that could inform the clinician about the severity of a patient's nasal symptoms and health-related quality of life (QOL) would be very useful. OBJECTIVE: We attempted to determine whether, in patients with perennial allergic rhinitis, nasal challenge with histamine could be used to estimate daily symptoms and QOL. METHODS: Forty-eight patients with perennial allergic rhinitis were challenged with histamine to determine nasal hyperreactivity. Nasal response was monitored by the number of sneezes, the amount of secretion, and a symptom score. Daily nasal symptoms were recorded during the 2 preceding weeks. Patients also completed a rhinitis QOL questionnaire. RESULTS: Responsiveness to histamine and total daily nasal symptoms were moderately correlated (r = 0.51, p = 0.001). Comparison of total daily nasal symptoms with the overall QOL score showed a moderate correlation (r = 0.59, p < 0.001). Nasal response to histamine and overall QOL score were also correlated (r = 0.43, p = 0.002). However, overall QOL and daily nasal symptoms could be predicted by wide 95% confidence intervals only for each decade of nasal responsiveness to histamine (expressed as a composite symptom score). CONCLUSION: In patients with perennial allergic rhinitis nasal hyperreactivity as determined by histamine challenge, QOL, and daily nasal symptoms are moderately correlated. Therefore nasal histamine challenge can be used as a tool for estimating the severity of daily nasal symptoms and QOL, although it cannot predict nasal symptoms and QOL very accurately.

Adult↗

PubMed1996

Selective effect of levocabastine on histamine receptor and histamine release from human leukocytes and guinea pig isolated tissue.

BACKGROUND: Levocabastine is a potent histamine H1 receptor antagonist used topically in the treatment of patients with allergic rhinitis. It has been suggested that antihistamines also have anti-inflammatory properties. OBJECTIVE: The present study was performed to investigate whether levocabastine, in addition to the anti-H1 receptor activity, has anti-inflammatory properties and thus is able to modulate the release of histamine and cytokines, such as interleukin 5 from human leukocytes and isolated tissues. METHODS: Leukocytes suspensions were prepared by dextran sedimentation of peripheral venous blood drawn from allergic and healthy volunteers. Leukocytes obtained from allergic volunteers were preincubated for 30 minutes with levocabastine (doses 10(-8) M to 10(-6) M) and thereafter incubated with allergen. Leukocytes obtained from healthy volunteers were incubated for zero to three hours with levocabastine (doses 10(-14) M to 10(-3) M). Histamine release was measured by an automated fluorometric method. Interleukin-5 release was measured by enzyme linked immunoassay. Contractile responses to histamine on guinea pig trachea and lung parenchyma as well as the release of histamine and interleukin-5 by the tissues were investigated in the absence or presence of levocabastine and/or the histamine H2 receptor antagonist cimetidine. RESULTS: Levocabastine did not influence allergen-induced histamine release from leukocytes obtained from allergic volunteers. High concentrations (10(-4)and 10(-3) M) of levocabastine, however, caused release of histamine from leukocytes obtained from healthy volunteers as well as guinea pig airway smooth muscle tissues. Pretreatment with levocabastine dose-dependently decreased the contractile response to histamine, showing an irreversible competitive mechanism. Interleukin 5 release from human leukocytes and by guinea pig airway smooth muscle was not detectable. CONCLUSIONS: These findings indicate that the H1 receptor blocker, levocabastine, has probably no anti-inflammatory properties, measured as histamine release, and that the histamine release from both human leukocytes and guinea pig trachea and lung parenchyma is significantly increased by the drug only at high concentrations.

Adult↗

PubMed1996

Relationship between nasal hyperreactivity, mediators and eosinophils in patients with perennial allergic rhinitis and controls.

BACKGROUND: In perennial allergic rhinitis, patients are almost daily exposed to aeroallergens. This ongoing allergic reaction results in increased sensitivity to allergens and non-specific stimuli. It is generally known that inflammatory cells and mediators are involved in the pathogenesis of the allergic reaction. OBJECTIVES: To study the relationship between nasal hyperreactivity and nasal inflammation during natural allergen exposure. METHODS: In 48 patients with perennial allergic rhinitis and in 11 volunteers a nasal brush, a nasal lavage and a histamine challenge were performed. Nasal inflammation was estimated by the number of eosinophils, levels of albumin, tryptase, prostaglandin D2 (PGD2), eosinophil cationic protein (ECP) and leukotriene C4/D4/E4 (LTC4/D4/E4). RESULTS: In contrast to PGD2 and tryptase, eosinophils (1.9 vs 0%, P = 0.0023), LTC4/ D4/E4 (17.51 vs 1.43 pg/mL, P < 0.0001) and albumin (8.61 vs 2.37 mg/mL, P = 0.0008) were significantly increased in rhinitis patients as compared with controls. Patients also showed increased responses to nasal histamine challenge assessed using a composite symptom score (21.5 vs 4 points, P < 0.0001). The nasal response to histamine was weakly correlated with the total number of eosinophils in the cytospin (correlation coefficient r = 0.38, P = 0.009). CONCLUSION: Nasal hyperreactivity is correlated with the percentage of eosinophils in patients with perennial rhinitis. The patients' mediator profiles suggest that eosinophils are important in the ongoing allergic reaction and nasal hyperreactivity.

Adult↗

PubMed1995

Interleukin-5 and eosinophil cationic protein in nasal lavages of rhinitis patients.

The production of interleukin-5 and eosinophil cationic protein (ECP) in the nasal cavity was examined in 24 patients with rhinitis who were allergic to the house dust mite. During a double-blind placebo-controlled cross-over study, fluticasone propionate aqueous nasal spray (200 micrograms) was administered twice daily for 2 weeks. After four basal nasal lavages provocation with house dust mite extract was performed and nasal lavages were collected every hour for 9.5 h. Interleukin-5 was present in detectable amounts in nasal lavages from patients allergic to house dust mite. Nasal challenge with house dust mite extract caused immediate nasal symptoms and increased levels of interleukin-5. Between 3.5 and 8.5 h after the challenge symptoms recurred and interleukin-5 levels increased, reflecting a late phase reaction. Eosinophil cationic protein, a marker of activated eosinophils, was released between 6.5 and 9.5 h after challenge. Treatment with fluticasone propionate (as an aqueous nasal spray) significantly decreased the evoked interleukin-5 and ECP levels in the late phase reaction. This response was correlated with an improved symptom score. This could indicate that the number and activity of eosinophils are increased during the late phase allergic reaction, a response that is inhibited by corticosteroids.

Adult↗

PubMed1995

Levels of soluble intercellular adhesion molecule 1, eicosanoids and cytokines in ascites of patients with liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis.

The levels of the eicosanoids leukotriene B4, prostaglandin E2, prostacycline and thromboxane B2, the cytokines interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha and soluble intercellular adhesion molecule 1 were measured in ascites and plasma samples of patients with liver cirrhosis (53), peritoneal cancer (26) and spontaneous bacterial peritonitis (10) to assess their value as a possible diagnostic and prognostic parameter in the course of the disease. Soluble intercellular adhesion molecule 1, of the eicosanoids prostaglandin E2 and leukotriene B4, and the protein concentration in ascites were all significantly elevated in ascites of patients with peritoneal cancer in comparison to ascites of patients with liver cirrhosis. In ascites of patients with spontaneous bacterial infection interleukin-6 concentration was significantly elevated and the protein concentration was significantly lower in comparison to the other two groups. None of these parameters, however, seems to be of practical use as a diagnostic parameter, as there is an overlap between all the levels of these mediators in ascites of liver cirrhosis, peritoneal cancer and spontaneous bacterial peritonitis group. Soluble intercellular adhesion molecule 1 levels were much higher in plasma than in ascites, in contrast to interleukin-6 levels which were much higher in ascites than in plasma. Soluble intercellular adhesion molecule 1 in ascites correlated with soluble intercellular adhesion molecule 1 in plasma (r = 0.6926, P = 0.0001). Soluble intercellular adhesion molecule 1, interleukin-6 and the number of polymorphonuclear cells in peritoneal fluid correlated during episodes of infection in patients with a peritonitis. For this reason soluble intercellular adhesion molecule 1 and interleukin-6 could be of prognostic value for patients with peritonitis.

Adult↗

PubMed1995

Effect of intranasal fluticasone proprionate on the immediate and late allergic reaction and nasal hyperreactivity in patients with a house dust mite allergy.

BACKGROUND: Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. OBJECTIVE: To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. METHODS: Twenty-four rhinitis patients allergic to house dust mite (HDM), participated in a double-blind, placebo-controlled crossover study. After 2 week's treatment with placebo or 200 micrograms FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreactivity was determined by histamine challenge 24 h later. RESULTS: Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%, 69% and 63% after 100, 1000 and 10,000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU/mL (P = 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32% and sneezes with 41%. CONCLUSION: FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.

Administration, Intranasal↗

PubMed1995

Nitric oxide metabolites in nasal lavage fluid of patients with house dust mite allergy.

BACKGROUND: The role of nitric oxide in the early and late phase of the allergic process was investigated in patients with allergic rhinitis against house dust mite and the effect of fluticasone propionate aqueous nasal spray was determined. METHODS: Production of nitric oxide (measured as nitrite+nitrate) in vivo in nasal mucosa was examined in 24 patients with rhinitis allergic to the house dust mite. In a double blind placebo controlled crossover study fluticasone propionate 200 micrograms aqueous nasal spray was administered twice daily for two weeks. In response to provocation with house dust mite extract (after four basal nasal lavages) nasal lavages were performed every hour for 9.5 hours by washing the nose with saline. In addition, a similar lavage protocol was performed in healthy volunteers with or without challenge with phosphate buffered saline. RESULTS: Nitric oxide is present in nasal lavage fluid in detectable amounts (range 10-50 microM), the level gradually increasing with time in both patients and controls after a decrease during the four basal lavages. Treatment with fluticasone propionate aqueous nasal spray did not affect initial basal production of nitric oxide nor production following provocation with house dust mite extract. CONCLUSIONS: Production of nitric oxide in nasal mucosa determined in sequential nasal washings is not affected by therapeutic doses of intranasal steroids.

Administration, Intranasal↗

PubMed1995

Effect of topical levocabastine on nasal response to allergen challenge and nasal hyperreactivity in perennial rhinitis.

BACKGROUND: It has been demonstrated that some oral antihistamines reduce nasal nonspecific reactivity and that topical levocabastine reduces cellular influx after nasal allergen challenge. This suggests that antihistamines possess other properties besides classical H1-receptor antagonism. OBJECTIVE: To evaluate the effect of 1 week's treatment with topical levocabastine on the nasal clinical response, inflammatory mediators, and nasal hyperreactivity. METHODS: In a double-blind, placebo-controlled, 2-period, 2-treatment, crossover study, 21 rhinitic patients allergic to house dust mite participated. After each treatment period patients were challenged with house dust mite extract. Symptom scores and nasal lavages were collected for nine and one-half hours after challenge. Allergen-induced nasal hyperreactivity was determined by nasal methacholine challenge 24 hours after allergen challenge. A nasal histamine challenge was performed as well. RESULTS: Patients showed only an immediate nasal response. Levocabastine significantly reduced the symptom score after 100 (P = .0063), 1000 (P = .0035), and 10,000 biological units (BU)/mL (P = .0013) of house dust mite extract. Albumin influx and tryptase release were not significantly reduced by levocabastine. No release of histamine and eosinophil cationic protein was seen. Levocabastine did not reduce nasal response to methacholine. Active treatment significantly reduced histamine-induced nasal secretion (P = .0009) and the number of sneezes (P = .0001). CONCLUSION: A significant effect of levocabastine was shown on the immediate clinical response to house dust mite and to histamine challenge only. Our findings suggest that levocabastine is an effective H1-receptor antagonist without anti-inflammatory properties.

Administration, Topical↗

PubMed1994

Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes.

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number of cells was isolated from the peritonea of treated than control young rats after 4 d feeding, but after 60 d no differences were observed. A similar reduction in cell number was found when old animals were given L-acetyl carnitine or L-propionyl carnitine (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine levels were higher in young rats given carnitine both chronically and acutely. Carnitine derivatives were without effect. In contrast, levels of total carnitine in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60 d were higher than in controls. There was no correlation between total plasma carnitine level and effects on prostaglandin, thromboxane and leukotriene B4 (LTB4) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI2), measured as 6 keto-prostaglandin F1 alpha. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1 alpha: thromboxane B2 and the 6-keto-prostaglandin F1 alpha: LTB4 ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗