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PubMed1990

The effect of indomethacin on the kinetics of histamine, 48/80 and antigen wealing.

1. The kinetics of weal formation and disappearance following intradermal injection of histamine, compound 48/80 and antigen were measured in indomethacin and inert geltreated human forearm skin. 2. Rates of formation went in descending order for histamine, 48/80 and antigen; rate constants of disappearance for equal sized weals were the same for histamine and 48/80 but were much less for antigen. The corresponding half-lives were 77, 73 and 160 min for histamine, 48/80 and antigen weal disappearance respectively. 3. Cyclo-oxygenase inhibition by topical indomethacin had no effect either on the immediate weal and flare responses or on the rates of formation and disappearance of the weals. 4. These findings together with previous studies using H1-receptor antagonists indicate that 48/80 acts by histamine release but that antigen releases both histamine and an additional material or materials which are not related to cyclo-oxygenase activity. 5. Exacerbation of chronic idiopathic urticaria by cyclo-oxygenase inhibitors is therefore likely to be part of the urticarial disease process.

Adult↗
PubMed1994

Clinical response to non-steroidal anti-inflammatory drugs in urate-crystal induced inflammation: a simultaneous study of intersubject and intrasubject variability.

1. It is well known that an individual subject often responds preferentially to a particular nonsteroidal anti-inflammatory drug (NSAID) and clinical response to these drugs is characterised by considerable variability between individuals. Variability in response has often been attributed to the episodic nature of musculoskeletal disease. Few studies have studied intrasubject variability in response to these drugs using a multiple crossover design. A major difficulty has been the lack of objective, validated measures of inflammation sensitive to NSAIDs. The primary aim of the present study was to test the utility of urate-crystal induced inflammation as a tool to predict NSAID response in humans. 2. An inflammatory reaction was established in twenty-five healthy subjects with intradermal injection of urate crystals on four separate occasions separated by 1 week. Each subject was randomly assigned to receive either ibuprofen on two of these occasions (800 mg four times over 36 h) or matched placebo on the other two occasions using a double-blind, cross-over design. Decrease in the area under the wheal size-time curve was used to indicate anti-inflammatory response. 3. Peak inflammatory response was observed at about 32 h and had dissipated by 56 h post-urate injection. The logarithmic mean wheal area was significantly lower after ibuprofen (mean +/- s.e. mean; 6.74 +/- 0.09) compared with placebo (6.96 +/- 0.07 mm h); a difference of 20% (95% confidence interval for difference: 1 to 35%; P < 0.05). 4. There was marked intra- and intersubject variability in response to ibuprofen over the four treatment periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Degradation of porcine dermal connective tissue by collagenase and hyaluronidase.

Selective destruction of connective tissue may be a useful therapeutic tool in conditions associated with abnormal deposition of scar tissue. We have investigated intradermal injections of clostridial collagenase and bovine testicular hyaluronidase alone and in combination in Yucatan miniature hairless pigs. Collagenase in combination with hyaluronidase was quite efficient at destroying the connective tissue matrix, although elastic tissue appeared to be completely spared. Collagenase alone at higher doses degraded collagen, but hyaluronidase had little effect on connective tissue architecture.

Animals↗
PubMed1977

Neutrophil accumulation in vivo following the administration of chemotactic factors.

Intravenously administered 51Cr-labelled homologous neutrophils accumulated at guinea-pig skin sites prepared by intradermal injection of factors derived from complement-activated serum, possessing in vitro chemotactic activity. There was a strong correlation between the in vitro potency of Sephadex G-100 fractions of the activated serum and their ability to evoke neutrophil accumulation in vivo. These experiments suggest that agents which are chemotactic for neutrophils in vitro also induce the localization of this cell in vivo.

Animals↗
PubMed2006

Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy.

BACKGROUND: Allergen-derived (T cell epitope) peptides may be safer for immunotherapy than native allergen, as they do not cross-link immunoglobulin (Ig)E. However, HLA polymorphism results in multiple potential epitopes. Synthetic peptides of phospholipase (PL) A(2) were selected for a peptide vaccine, on the basis of binding affinity for commonly expressed HLA-DR molecules. OBJECTIVE: To evaluate treatment with an HLA-DR-based PLA(2) peptide vaccine in subjects with mild honeybee allergy in an open, controlled study. METHODS: Twelve volunteers with allergy to bee venom received nine intradermal injections of PLA(2) peptides, with six untreated subjects serving as controls. Outcome was assessed by the size of the late-phase cutaneous reaction to allergen, peripheral blood mononuclear cell (PBMC) proliferation, cytokine release, and expression of genes associated with immune regulation. RESULTS: Subjects receiving peptides showed a decrease in the magnitude of the late-phase cutaneous reaction to bee venom compared with controls (P=0.03). The proliferation of venom-stimulated PBMCs decreased in treated subjects compared with controls (P=0.01). Peptide treatment reduced the production of IL-13 by PLA(2)-stimulated PBMCs (P<0.01) and IFN-gamma (P<0.01), and increased the production of IL-10 (P=0.02). Transcription of the suppressor of cytokine signalling (Socs)3 gene was significantly increased following therapy. A transient, but modest, increase in allergen-specific IgG was also observed. CONCLUSION: HLA-DR-based T cell epitopes modify surrogate markers associated with successful immunotherapy and induction of immune regulation, supporting the concept that this form of treatment may be efficacious in human allergic disease.

Adult↗
PubMed2006

Killed Mycobacterium vaccae suspension in children with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: The hygiene hypothesis is often proposed to explain the high prevalence of atopy in the western world. Dysregulation of the immune system may result from inadequate exposure to micro-organisms such as mycobacteria. A small trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic dermatitis (AD). OBJECTIVES: To confirm in a large clinical trial whether killed M. vaccae ameliorates AD in 5-16-year-old children. METHODS: This was a randomized, placebo-controlled, double-blind, multi-centre study of the effect of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16, with moderate-to-severe AD. Patients were followed up for 24 weeks. The primary end point was the change in severity of AD at 12 weeks, assessed using the six area, six-sign, atopic dermatitis (SASSAD) score. Secondary end points included changes in disease extent, patient's global assessment and children's dermatology life quality index. RESULTS: There were 166 patients randomized. The mean SASSAD score fell to a similar degree at week 12 in all treatment arms: from 33 to 24, (26%) in the high-dose group, from 30 to 23 (25%) in the low-dose group and from 36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the same trend. Adverse events were generally those expected to occur in this population. Injection site reactions occurred in 32 patients at week 4. CONCLUSIONS: M. vaccae was no more effective than the placebo in ameliorating the severity of AD.

Adolescent↗
PubMed2004

Protection against systemic candidiasis in mice immunized with secreted aspartic proteinase 2.

Secreted aspartic proteinases (Sap) have been described as virulence factors implicated in the mechanisms of host colonization by the yeast Candida albicans in different types of candidiasis. Intraperitoneal inoculation of C. albicans into BALB/c mice rapidly leads to systemic candidiasis, with significant colonization of the kidneys measurable in the following week. In this study we assessed the potential of vaccination with C. albicans secreted aspartic proteinase 2 (Sap2) in preventing systemic candidiasis in BALB/c mice. Intradermal injection of highly purified native Sap2 protein incorporated in alum adjuvant provided efficient immune protection, as indicated by a 20-fold decrease in the colonization of kidneys. The protective effect of Sap2 immunization with alum adjuvant was also observed in mice infected with a lethal inoculum of C. albicans. Immunization with the native Sap2 alone, as well as with a denatured recombinant form of the protein, also conferred protection, albeit to a lesser level. In all cases, protection correlated with an increase in serum antibodies to Sap2. Moreover, passive transfer of anti-Sap2 immunoglobulin G (IgG) significantly decreased the yeast burden in kidneys of C. albicans-infected mice. This result shows that immune protection against systemic candidiasis in mice immunized with Sap2 is antibody-mediated. Taken together, these analyses demonstrate that Sap2 can be successfully used as a vaccination target in systemic candidiasis and reveals the potential immunomodulatory role of Sap2 on C. albicans infection.

Adjuvants, Immunologic↗
PubMed1989

Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus.

Secondary hyperparathyroidism has been suggested as a cause of itching in chronic renal failure. The aim of the present study was to evaluate the possible role of parathyroid hormone (PTH) in pruritus affecting patients undergoing maintenance haemodialysis. In agreement with our previous findings, patients with pruritus had significantly (P less than 0.01) higher serum levels of PTH fragment 53-68 (m-PTH53-68) than patients without pruritus, 47.7 +/- 40.0 and 23.4 +/- 17.1 micrograms l-1 respectively. Serum concentrations of other substances including calcium, phosphate and magnesium did not differ between the two groups of patients. Intradermal injections of human PTH1-34 and PTH44-68 failed to evoke any acute or delayed cutaneous reactions in either patients or controls. Immunohistochemical investigations of skin biopsies from uraemic patients using several different antibodies against PTH were negative. Thus, the present results do not support PTH as a peripheral mediator of uraemic itching.

Adult↗
PubMed1980

Effect of leucocyte interferon on natural killer cells in healthy volunteers.

The effect of partially purified human leucocyte interferon on natural killer activity (NK activity) of peripheral blood in six healthy volunteers was tested in this study. After 4 h of intradermal injection of interferon, a rapid transient decline in NK activity and in the number of NK cells (large granular lymphocytes) in peripheral blood was observed. The decline was most distinct at 20 h and recovered at 72 h. Since no clear activation of Nk cells in peripheral blood was detected, the results suggest an extravasation of NK cells as a result of interferon injection. NK cells did not accumulate at the injection site on the skin, because the suction blister fluids over the injection sites did not contain increased numbers of NK cells.

Adult↗
PubMed1983

Potentiation by acetylsalicylic acid of skin weal response to compound 48/80 in ASA-sensitive asthmatics.

The influence of acetylsalicylic acid (ASA) on skin response to intradermal injection of compound 48/80 and histamine was studied in order to determine whether ASA elicits any abnormalities also in the skin of asthmatics reacting with bronchoconstriction to ingestion of this drug. The applied ASA dose (mean dose 150 mg) elicited bronchoconstriction in all 16 patients with asthma and ASA sensitivity (mean fall of FEV1 34%) and increased the weal response to compound 48/80 to about 51% (P less than 0.05) as compared with the response before the ASA-challenge. In asthmatic persons without ASA sensitivity a 150 mg ASA dose did not influence the skin response to any of the reagents. On the other hand, a 600 mg dose decreased skin response to histamine and compound 48/80 in persons without ASA intolerance, although the decrease was statistically significant only in the flare after compound 48/80 (P less than 0.05). The authors believe that additional local defect is needed to reveal sensitivity to ASA in the skin of ASA-sensitive asthmatics, just as bronchial hyperreactivity is indispensible for revealing the action of ASA in the bronchi.

Adult↗
PubMed1983

Reaction to intradermally applied phytohaemagglutinin in asthma patients in relation to corticosteroid therapy.

Phytohaemagglutinin (PHA) skin test (diameter of induration 24 h following intradermal injection of 1.0 microgram purified PHA) was carried out on 23 patients with exacerbated atopic asthma and 28 patients with exacerbated non-atopic asthma. Preselected adult patients had either not previously been treated with systemic corticosteroids or steroid therapy had been suspended for at least 3 months. Nearly all non-atopic asthma patients and patients with atopic asthma previously treated with corticosteroids showed increased reactions to PHA. Patients with atopic asthma not earlier treated with corticosteroids demonstrated normal responses. None of the asthmatics showed a negative PHA reaction. Administration of single depot doses of corticosteroids produced decreased reactivity to PHA in nearly all patients. These results suggest that neither atopic nor non-atopic asthma is in itself associated with impaired PHA skin reactivity but that changes in this reactivity are largely due to the corticosteroid therapy administered to these patients. In relation to PHA reactivity certain effects of this therapy may persist for as long as 3 months after its cessation.

Adrenal Cortex Hormones↗
PubMed1990

Inhibition of anti-IgE induced skin response in normals by formoterol, a new beta 2-adrenoceptor agonist, and terbutaline. 2. Effect on the late phase reaction.

Formoterol, a new beta 2-selective long-acting bronchodilator, was compared with terbutaline in terms of ability to inhibit dual phase skin reactions to anti-human IgE in volunteers. Anti-IgE induced an early wheal and flare reaction (WFR) followed by a progressively increasing induration, the late phase reaction (LCR), lasting greater than or equal to 24 h. Intradermal injection of formoterol 20 ng or terbutaline 500 ng 5 min before challenge gave equal inhibition of the WFR. The subsequent LCR was suppressed by formoterol (30%) for the whole 24 h period, while terbutaline only attenuated the first 4 h period. Increasing the dose range of both drugs 25-fold, caused a further analogous reduction of the WFR to anti-IgE. In this higher dose range formoterol (0.5 micrograms) antagonized the following 1-24 h LCR by 50%, while terbutaline (25 micrograms) only attenuated the LCR by an average of 20%, with higher effect in the first 6 h period. The anti-LCR capacity of formoterol was highly superior to that of terbutaline (P less than 0.001). The histamine-elicited wheal response was attenuated by both drugs, but they had no effect on the flare response, favouring an anti-permeability action of both compounds. The data support the concept that terbutaline, given locally in a single dose shortly before challenge, inhibits the mast cell mediator release reaction with limited consequences for the following LCR. In contrast to terbutaline, formoterol exerted a substantial anti-LCR action, probably by interfering with inflammatory mechanisms after the initial mast cell mediator release.

Adult↗
PubMed1995

Methacholine induces wheal-and-flare reactions in human skin but does not release histamine in vivo as assessed by the skin microdialysis technique.

A number of investigations have indicated that cholinergic agonists release histamine from isolated mast cells and suggested that cholinergic stimulation releases histamine in vivo. The purpose of this study was to investigate whether the cutaneous wheal-and-flare reaction induced by methacholine challenge in human skin involves histamine release as measured by the skin microdialysis technique. Five hollow dialysis fibers were inserted intradermally in forearm skin in eight healthy subjects. Each fiber was perfused with Kreb's-Ringer bicarbonate at a rate of 3 microliters/min. Dialysates were collected in 2-min fractions before skin challenge and for 20 min after intradermal injection of methacholine 10(-3)-10(-1) M, the vehicle, and a positive control, codeine phosphate 0.3 mg/ml. Histamine was assayed spectrofluorometrically. Methacholine caused a statistically significant dose-related wheal-and-flare reaction, the flare reaction to methacholine 10(-1) M being comparable with that seen with codeine 0.3 mg/ml. No significant histamine release was observed with methacholine, cumulative histamine release of 16 +/- 8 nM by methacholine 10(-1) M being similar to vehicle responses of 15 +/- 9 nM. Histamine release by codeine was 2524 +/- 435 nM. In conclusion, methacholine-induced wheal-and-flare reactions in human skin appeared not to involve histamine release from skin mast cells.

Adult↗
PubMed1995

The influence of patent blue V on pulse oximetry and haemoximetry.

Patent Blue V (PBV) is a blue dye solution which is used to visualize lymphatic vessels for surgical procedures. There has been some conflicting reports about the influence of this dye solution on pulse oximetry and haemoximetry, why we decided to: 1) produce a spectrum of PBV in plasma, 2) measure absorbances of full blood before and after addition of PBV and 3) to record the effect on the pulse oximeter and haemoximeter of an intradermal injection of PBV to a patient. Computer analysis of the blood gas measurements were carried out by the Oxygen Status Algorithm (OSA). The spectrum of PBV demonstrated a peak absorption at 640 nm and correspondingly the absorbances of the haemoximeter increased most significantly at 622 and 636 nm. These changes invalidated the determination of haemoglobin pigments, and the results should not be used. Computer analysis interpreted the measurements as a shift of the haemoglobin oxygen binding curve.

Absorption↗
PubMed1997

Cutaneous vascular response to calcitonin gene-related peptide in psoriasis and normal subjects.

To determine whether cutaneous blood vessels in subjects with psoriasis possess a generalized inherently abnormal response to neuropeptides, the effect of three doses of intradermally injected calcitonin gene-related peptide (CGRP) on skin blood flow in normal subjects (n = 10), and on clinically normal skin (greater than 5 cm from psoriatic lesions) in subjects with psoriasis (n = 9) was measured using a laser Doppler technique. Calcitonin gene-related peptide caused a dose-dependent increase in local blood flow in both psoriatic and normal subjects, which was not statistically different between the two groups. This study has shown that the cutaneous vasculature at sites distant from lesions of psoriasis (> 5 cm) is not inherently different from normal skin in its response to CGRP.

Adult↗
PubMed1999

Role of nitric oxide in the regulation of microvascular perfusion in human skin in vivo.

1. Nitric oxide (NO) concentrations were measured in dialysate from healthy human skin, in vivo, both at rest and during the inflammatory response to intradermal histamine or bradykinin. Changes in dialysate NO concentration, measured by electrochemical detection, were related to changes in dermal vascular perfusion, measured using scanning laser Doppler imaging. 2. Basal NO concentration in dermal microdialysate was 0.60 +/- 0.14 microM (mean +/- s.e.m.). Following the intradermal injection of histamine, a transient, time-dependent increase in NO concentration was measured in areas of skin incorporating the weal and in others incorporating the flare. The increase in NO concentration was associated with an increase in dialysate cGMP concentration in both the weal and flare areas. 3. Addition of N G-nitro-l-arginine-methyl ester (L-NAME, 5 mM) to the probe perfusate resulted in an inhibition of the histamine-induced increase in NO and cGMP. Moreover, the reduction in dialysate NO concentration was associated with a reduction in dermal vascular flux, both under basal conditions and within the weal and flare response. 4. These results demonstrate, by the use of microdialysis, that vasoactive mediators can be measured in healthy human skin in vivo. They provide direct evidence that endogenous concentration of NO increases during the inflammatory weal and flare response to histamine and that the increase in dermal NO concentration is associated with increases in cGMP concentration and dermal vascular perfusion, thus confirming a role for NO in vasoregulation in human skin.

Adult↗
PubMed1957

A comparative study of kinin, kallidin, and bradykinin.

Partially purified kinin, a polypeptide in wasp venom, has been found to be a potent smooth-muscle stimulating and hypotensive agent. Such a preparation was 10 to 100 times more effective than histamine in enhancing capillary permeability on intradermal injection, and 10 times more effective than acetylcholine in evoking pain on a cutaneous blister base. Some differences between the actions of salivary kallikrein and trypsin in releasing kallidin or bradykinin have been observed, and some modifications of previous methods of preparing crude kallidin and bradykinin are suggested. Kallidin and bradykinin are effective enhancers of capillary permeability in the guinea-pig and rabbit. Chemical and pharmacological tests failed to differentiate between kallidin and bradykinin which must be, therefore, closely similar compounds. The possible role of kallidin and bradykinin in physiological or pathological conditions is discussed.

Acetylcholine↗
PubMed1971

Interaction between prostaglandins E and F given intradermally in the rat.

1. Increases in permeability observed after intradermal injection of prostaglandins PGE(1) or PGE(2) (0.1 mug) into rats were greatly reduced when they were given in admixture with PGF(2alpha). This effect was not seen with PGF(1alpha) at doses of 0.5-1 mug.2. Effects of the histamine releasing agent compound 48/80 (25 ng) were inhibited by PGF(2alpha) (0.5 mug) but not by PGF(1alpha) (0.5 mug).3. Responses to histamine (1 mug), 5-hydroxytryptamine (0.1 mug) and bradykinin (1 mug), which have a direct action on the microvasculature, were not significantly altered by PGF(2alpha) (0.5 mug).4. It is concluded that PGF(2alpha) probably acts by interfering with the release of mast cell histamine by PGE(1), PGE(2) and compound 48/80.

Animals↗