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Biomedical subjects

M Schmelz

Publications and source records attributed to M Schmelz.

At least 37 records · Page 2Linked to original sources
PubMed2003

Different lipid profiles as constituencies of liquid formula diets do not influence pain perception and the efficacy of opioids in a human model of acute pain and hyperalgesia.

Nutritional support and pain control by medication are often used concomitantly, but interactions are hardly investigated. A randomised, double-blind, cross-over study in ten right-handed volunteers was performed evaluating the influence of cholecystokinin (CCK)-excretion on the perception of pain in a standardised model. CCK-excretion was induced by a liquid formula diet with either long- or medium-chain triglycerides (LCT, MCT). Plasma samples were drawn over a 60 min period in 15-min intervals and CCK and somatostatin (SMS) were measured by radioimmunoassay (RIA). Gastric emptying was evaluated by C-13-breath testing. Transcutaneous electrical stimulation at a high current density (5 Hz, 70.1+/-5.8 mA) was used to provoke acute pain and stable areas of secondary mechanical hyperalgesia and pinprick allodynia for 2 h. Ongoing pain ratings as well as extension of pinprick-hyperalgesia and allodynia were compared between both liquid formula diets. In a second series of experiments, alfentanil (4.1+/-0.5 mg) was administered for 90 min using target-controlled infusions and measurements were performed as stated above. Oral administration of LCT as well as MCT may lead to different CCK blood levels, but we found no evidence for CCK-induced effects on pain sensation, touch-evoked allodynia, secondary hyperalgesia or morphine-induced anti-nociception in humans. In our studies, liquid formula diets did not influence acute pain perception or the efficacy of opioids in a human model of pain.

Acute Disease↗
PubMed2003

Injection pain of rocuronium and vecuronium is evoked by direct activation of nociceptive nerve endings.

BACKGROUND AND OBJECTIVE: Rocuronium and, to a lesser extent, vecuronium can induce burning sensations associated with withdrawal reactions during administration. Dermal microdialysis in human and electrophysiological recordings of nociceptors in mouse skin were used to elucidate the underlying mechanisms of pain induction. METHODS: Microdialysis catheters were inserted intradermally into the forearm of 10 volunteers and were perfused with two different concentrations of rocuronium and vecuronium (1 and 10 mg mL(-1)) or a control. Dialysis samples were taken every 15 min and analysed for protein, histamine, tryptase and bradykinin content. Pain intensity was rated on a numerical scale of 0-10. In a parallel design, activation of cutaneous nociceptors was assessed directly in a skin-nerve in vitro preparation of the mouse hind paw. The receptive fields of identified single C-nociceptors (n = 12) were superfused with rocuronium or vecuronium solutions (10 mg mL(-1)) at physiological pH. RESULTS: In accordance with clinical observations, microdialysis of rocuronium (10 mg mL(-1)) induced sharp burning pain (NRS 4.1 +/- 1.8), whereas vecuronium given in the usual clinical concentration (1 mg mL(-1)) induced only minor pain sensations (NRS 0.6 +/- 1.3). At equimolar concentrations, pain sensation and concomitant mediator release evoked by both drugs were similar. No correlations were found between pain rating and mediator release. In the in vitro preparation, C-fibres showed a consistent excitatory response with rapid onset after stimulation with vecuronium as well as rocuronium (differences not significant). CONCLUSIONS: The algogenic effect of aminosteroidal neuromuscular blocking drugs can be attributed to a direct activation of C-nociceptors.

Adult↗
PubMed2002

Assessment of the neurogenic flare reaction in small-fiber neuropathies.

To improve sensitivity of the analysis of axon reflex flare reaction, the authors used a laser Doppler scanner and analyzed flare intensity and size induced by histamine iontophoresis simultaneously at the foot and thigh in patients with small-fiber neuropathy (n = 10) and controls (n = 9). Flare size, but not laser Doppler flux, clearly distinguished patients from controls at both locations (p < 0.01) and may be useful for evaluation of small-fiber neuropathies.

Aged↗
PubMed2002

Influence of vagus nerve stimulation on histamine-induced itching.

OBJECTIVE: To investigate whether vagus nerve stimulation (VNS) reduces pruritus in humans. BACKGROUND: Recently, it has been shown that VNS has antinociceptive and antidepressant effects in humans. METHODS: Eleven patients were investigated before (baseline) and during chronic VNS treatment. The experiments were performed at two different stimulation intensities: 2 to 5 days after implantation at a low stimulation intensity (mean intensity 0.7 +/- 0.2 mA, second session) and after 8 to 14 weeks of VNS therapy (mean intensity 1.4 +/- 0.3 mA, third session). Twelve healthy age- and sex-matched subjects were investigated using the same experimental protocol. Itch was induced by histamine-iontophoresis and quantified on a visual analogue scale (VAS). Histamine-induced flare was quantified using laser-Doppler flowmetry. RESULTS: Itch was reduced by VNS from 24 +/- 8% VAS at baseline to 15 +/- 5% VAS at second session, and 19 +/- 8% VAS at third session (p < 0.05 multivariate analysis of variance). In the control group, itch remained unaltered in all three sessions (26 +/- 5% at baseline, 23 +/- 5% in the second session, and 25 +/- 5% in the third session, not significant). The flare was unaltered in both patients and control subjects. CONCLUSIONS: VNS may suppress pruritus in humans.

Adult↗
PubMed2002

Itch--mediators and mechanisms.

A specialized subpopulation of unmyelinated chemonociceptors and dedicated spinal neurons which are responsible for the itch sensation have been identified recently. Under physiological conditions, painful stimuli such as activation of conventional mechano-heat-sensitive ('polymodal') nociceptors (scratching) inhibit the itch sensation via central mechanisms. Conversely, centrally acting pain-inhibiting opioids enhance itch by disinhibition. These mechanisms might well explain the itch in diseases characterized by histamine release like urticaria, and might provide evidence for the role of endogenous opioids as central itch promotors in cholestasis or nephropathy. After the discovery of itch-specific neurons has dramatically improved our understanding of itch mechanisms under experimental conditions, the present task is to correlate these new findings to the clinical situation of itch patients.

Antipruritics↗
PubMed2002

Dermal microdialysis provides evidence for hypersensitivity to noradrenaline in patients with familial dysautonomia.

OBJECTIVES: To use the technique of dermal microdialysis to examine sensitivity of skin vessels to noradrenaline (NA) in patients with familial dysautonomia (FD) and in healthy controls. METHODS: In 14 patients with FD and 12 healthy controls, plasma extravasation, local laser Doppler blood flow, and skin blanching were observed before, during, and after application of 10(-6) M NA through a microdialysis membrane, located intradermally in the skin of the lower leg. RESULTS: Maximum local vasoconstriction measured by laser Doppler blood flow did not differ between patients with FD and controls. In contrast, patients with FD had an earlier onset of vasoconstriction (p = 0.02). Moreover, reaction to NA was more prominent and prolonged in FD, shown by a larger zone of skin blanching around the microdialysis membrane (p < 0.001) and delayed reduction of the protein content in the dialysate after termination of NA application (p = 0.03). CONCLUSION: These data support the hypothesis that peripheral blood vessels of patients with FD show a denervation hypersensitivity to catecholamines. This may be one mechanism contributing to the major hypertension that frequently occurs during "dysautonomic crises" in FD.

Administration, Cutaneous↗
PubMed2002

Innervation territories of mechano-insensitive C nociceptors in human skin.

Microneurographic recordings were obtained in the peroneal nerve from 20 mechano-insensitive units (CMi) and six mechano-heat responsive C units (CMH) in healthy human subjects. Their innervation territories in the skin of the leg or foot were assessed by transcutaneous electrical stimulation with a pointed probe at intensities of 10 to 100 mA (0.2 ms) and, when applicable, by mechanical von Frey hair stimulation. Electro-receptive fields (eRFs) of CMH units had a median area of 1.95 cm(2) when mapped with 10 mA that coincided approximately with mechano-receptive fields (mRFs) as mapped with a 750-mN von Frey hair. Fifty-milliampere stimuli increased the eRFs to 3.08 cm(2) in a concentric manner. This was probably due to current spread since these units are known to have low electrical thresholds. Further increase of the stimulus strength to 70 or 100 mA increased the eRFs only marginally. Mechano-insensitive units had much smaller eRFs (median: 0.35 cm(2)) than CMH units when mapped with the same pointed probe at 10 mA (n = 13). The receptive territories consisted of one distinct spot or of several spots separated by distances of more than 1 cm. However, when mapping stimuli of 50 mA were applied, eRFs became continuous and grew to a median area of 5.34 cm(2), i.e., larger than those of CMHs. The borders of eRFs of CMi units were significantly more irregular compared with CMH units. A further increase of the stimulus intensity to a maximum of 100 mA only marginally enlarged the eRFs. The CMi units could be activated by heat or chemical substances applied inside the 50-mA eRF, indicating that receptive nerve endings were mapped. Responsiveness to these stimuli was inhomogeneous within the eRFs. It was concluded that innervation territories of CMi units in human skin exceed those of CMH units in size by a factor of approximately 3. The widely branched terminals underlying the large fields are consistent with a role of this nociceptor class in axon reflex flare and preclude a role in exact spatial discrimination of noxious stimuli.

Adult↗
PubMed2001

The important role of neuropeptides in complex regional pain syndrome.

OBJECTIVE: To test the contribution of neurogenic inflammation and neuropeptide release to the pathophysiology of complex regional pain syndrome (CRPS). BACKGROUND: CRPS is characterized by edema and increased skin temperature, sympathetic dysfunction and pain, or hyperalgesia. This investigation was prompted by a recent study by the authors that suggested a facilitated neurogenic inflammation in CRPS. METHODS: In addition to physical examination, calcitonin gene-related peptide (CGRP) serum concentrations were measured using a radioimmunoassay (RIA) for human CGRP in 19 patients with acute CRPS, on the affected and unaffected sides (n = 13), before and 9 months after therapy (n = 9). In addition, an age- and sex-matched group of 16 healthy controls was investigated. RESULTS: In blood from the cubital vein, CGRP levels in patients with CRPS (122.2 +/- 14.6 pmol/L) were increased (controls 83.8 +/- 6.7 pmol/L, p < 0.03). There was no difference between the affected and unaffected sides. There was, however, a reduction of serum CGRP after therapy (acute disease: 141.2 +/- 18.5 pmol/L, after therapy 106.7 +/- 11.3 pmol/L, p < 0.005); absolute CGRP levels then no longer differed from controls. Increased serum CGRP was correlated to the incidence of nerve lesions (p < 0.02) and hyperhidrosis (p < 0.04). There was no correlation to other clinical symptoms, duration of CRPS, or pain. However, normalization of CGRP after therapy was accompanied by clinical improvement of local inflammatory signs, but not by pain reduction. CONCLUSIONS: Increased systemic CGRP levels in patients with acute CRPS suggest neurogenic inflammation as a pathophysiologic mechanism contributing to vasodilation, edema, and increased sweating. However, pain and hyperalgesia, in particular in chronic stages, were independent of increased neuropeptide concentration.

Adult↗
PubMed2001

In vitro dorsal root ganglia and human prostate cell line interaction: redefining perineural invasion in prostate cancer.

BACKGROUND: Little is understood regarding mechanisms of perineural invasion in prostate cancer progression. We present a novel model system and data that indicate perineural invasion is an active, specific, and reciprocal interaction between nerves and prostate cancer cells. METHODS: Mouse dorsal root ganglia (DRG) and human prostate cancer cells (Du-145, LNCaP, PC3) and stromal cells (HTS-40F) were co-cultured in Matrigel matrix. Control cultures consisted of prostate cancer and stromal cells only and DRG only. Neurite outgrowth, cell colony growth, neurite-colony contact, and retrograde extension were quantitated with dark phase microscopy and image analysis (Optimas 6.1). RESULTS: Directional outgrowth of neurites was observed projecting into DU-145 colonies within 24 hr of co-culture. Cultures with the greatest number of DU-145 cells recruited significantly more neurites and established contact earlier, indicating this process was cell-seeding density dependent. Once neurite/DU-145 cell contact was established neurite growth diminished, suggesting an active neurite recruitment by DU-145 cells. Subsequent to neurite contact, DU-145 cells migrated along neurites in a retrograde fashion into the nerve/ganglion of origin (retrograde extension) establishing perineural invasion. In addition to perineural invasion, DU-145 colony growth was elevated in DRG co-cultures relative to DU-145-only control cell cultures. Similarly, the degree of neurite outgrowth was elevated in DRG-cell co-cultures relative to DRG-only control cultures. The same observations were made with LNCaP and PC3 cells, but interactions between stromal cells and nerves were not found. CONCLUSIONS: This study shows the utility of the prostate cancer/DRG in vitro system to study specific mechanism of prostate cancer cell-nerve interaction. Moreover, these data suggest that perineural invasion mechanisms involve active and reciprocal interactions between carcinoma cells and adjacent nerve/ganglions in prostate cancer progression.

Animals↗
PubMed2001

PEAZ-1: a new human prostate neoplastic epithelial cell line.

BACKGROUND: The generation of prostatic cell lines provides in vitro models for experimental studies of the pathogenesis of prostate carcinoma. Therefore, we established and characterized a new human prostate epithelial cell line, PEAZ-1 (prostate epithelial Arizona-1). METHODS: The PEAZ-1 cells were grown from a primary human prostate carcinoma specimen obtained from radical prostatectomy. The isolated cells were characterized by immunobiochemistry, immunohistochemistry, and tumorigenicity studies. RESULTS: PEAZ-1 cells are near diploid, tumorigenic, and androgen independent for cell growth. PEAZ-1 cells express N-cadherin, alpha- and beta-catenins, and p120 at cell-cell contacts, cytoplasmic laminin 5, vinculin, paxillin, and phosphotyrosine at focal adhesions, vimentin, and cytokeratins 8 and 18. They do not express plakoglobin, E-cadherin, and PSA, and do not form desmosomes and hemidesomomes. PEAZ-1 respond to ocadaic acid, a pro-apoptotic agent, by expression of p53. CONCLUSIONS: PEAZ-1 cells is a human prostate cancer cell line that has a number of mesenchymal characteristics.

Androgens↗
PubMed2001

Laminin-5-mediated gene expression in human prostate carcinoma cells.

Interactions between extracellular matrix (ECM) proteins and prostate carcinoma cells provide a dynamic model of prostate tumor progression. Previous work in our laboratory showed that laminin-5, an important member of a family of ECM glycoproteins expressed in the basal lamina, is lost in prostate carcinoma. Moreover, we showed that the receptor for laminin-5, the alpha6beta4 integrin, is altered in prostate tumors. However, the genes that laminin-5 potentially regulates and the significance of its loss of expression in prostate cancer are not known. We selected cDNA microarray as a comprehensive and systematic method for surveying and examining gene expression induced by laminin-5. To establish a definitive role for laminin-5 in prostate tumor progression and understand the significance of its loss of expression, we used a cDNA microarray containing 5289 human genes to detect perturbations of gene expression when DU145 prostate carcinoma cells interacted with purified laminin-5 after 0.5, 6, and 24 h. Triplicate experiments showed modulations of four, 61, and 14 genes at 0.5, 6, and 24 h, respectively. Genes associated with signal transduction, cell adhesion, the cell cycle, and cell structure were identified and validated by northern blot analysis. Protein expression was further assessed by immunohistochemistry. Mol. Carcinog. 30:119-129, 2001.

Blotting, Northern↗
PubMed2001

Facilitated neurogenic inflammation in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is characterized by a variety of clinical features including spontaneous pain and hyperalgesia. Increased neuropeptide release from peripheral nociceptors has been suggested as a possible pathophysiologic mechanism triggering the combination of trophic changes, edema, vasodilatation and pain. In order to verify the increased neuropeptide release in CRPS, electrically induced neurogenic vasodilatation and protein extravasation were evaluated in patients and controls. We performed a prospective study on 10 patients with acute and untreated CRPS and 10 matched healthy controls. Neurogenic inflammation was elicited by strong transcutaneous electrical stimulation via intradermal microdialysis capillaries which simultaneously enabled measurement of protein extravasation. Laser-Doppler scanning was used to assess axon reflex vasodilatation. Axon reflex vasodilatation was significantly increased in CRPS patients (438 +/- 68% of baseline vs. 306 +/- 52%; P < 0.05) and transcutaneous electrical stimulation provoked protein extravasation only in the patients (before, 0.28 +/- 0.03 mg/ml; during stimulation, 0.34 +/- 0.04 mg/ml), whereas protein concentration steadily declined during stimulation in the healthy controls (before, 0.23 +/- 0.04 mg/ml; during stimulation, 0.18 +/- 0.04; P < 0.001). The time course of electrically induced protein extravasation in the patients resembled the one observed following application of exogenous substance P (SP). We conclude that neurogenic inflammation is facilitated in CRPS. Our results suggest an increased releasability of neuropeptides in CRPS.

Adult↗
PubMed2001

Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study.

BACKGROUND: Recent reports have indicated cetirizine, a potent H(1)-receptor antagonist, to possess a number of anti-inflammatory effects, e.g. inhibition of mast cell degranulation and inhibition of leucocyte migration and activation. OBJECTIVE: The aim of this study was to compare the effects of cetirizine on skin responses and mediator release in intact skin in immediate and developing late-phase allergic reactions by microdialysis technique. METHODS: Cetirizine 10 mg once daily or matching placebo were administered to 10 atopic subjects for 6 days followed by a 2-week washout in a randomized, double-blind, placebo-controlled, cross-over trial. Immediate skin test responses to allergen, codeine, and histamine and late-phase reactions to allergen were assessed. The time course of extracellular levels of inflammatory mediators in intact skin were monitored by microdialysis techniques using 2 kDa and 3 MDa cut-off fibers, respectively. RESULTS: Cetirizine significantly reduced immediate weal and flare reactions to allergen, codeine, and histamine. Injection of allergen, but not buffer controls, induced a significant release of histamine, tryptase, prostaglandin D(2), total protein, and eosinophilic cationic protein. No significant increase of leukotriene B(4) and myeloperoxidase was observed. Cetirizine inhibited early total protein extravasation by 40%, but this did not reach a significant level. None of the inflammatory mediators were significantly inhibited by cetirizine. Cetirizine significantly reduced the late-phase skin induration to allergen by approximately 30%. CONCLUSION: Cetirizine potently reduced skin responses in immediate allergic reactions without inhibition of early mediators. These data indicate cetirizine to be a potent H1-receptor antagonist with no effect on mast cell activation. It did not inhibit any of the late-phase mediators, but it reduced the late skin reaction. These data suggest that mediators other than those actually measured may play a significant role in the clinical late-phase reaction.

Administration, Cutaneous↗
PubMed2001

Nociceptor activation and protein extravasation induced by inflammatory mediators in human skin.

Protein extravasation (PE) is known to play an important role in inflammatory conditions. In this study we used dermal microdialysis to apply inflammatory mediators (histamine, bradykinin, serotonin) to human skin. Locally induced PE was compared to pain ratings and axon reflex erythema measured simultaneously. Linear microdialysis capillaries (outer diameter 0.4 mm; cut-off 3000 kDa) were inserted intracutaneously at a length of 1.5 cm in the volar forearm of healthy volunteers. The capillaries were perfused with Ringer's solution at a constant flow rate of 4 microl/min. The perfusate was sampled at 15-min intervals and was analysed for total protein concentration. After a baseline of 60 min, the perfusion was switched to inflammatory mediators for 30 min and then back to vehicle again. Sensations evoked by the stimulation were assessed on a visual analogue scale and visible axon reflex erythema was measured planimetrically.Dose-dependent increases in PE could be assessed for all inflammatory mediators tested. Bradykinin (10(-7)M) induced a significant PE, whereas serotonin was effective only at a concentration of 10(-3)M. While serotonin in lower concentrations induced moderate burning pain and an axon reflex flare but no PE, bradykinin provoked PE without pain or axon reflex flare at a concentration of 10(-7)M. Application of histamine similarly evoked PE at lower concentrations as compared to the induction of itch sensation and axon reflex flare. It is concluded that there is no link between nociceptor activation and protein extravasation induced by inflammatory mediators in healthy human skin.

Adult↗
PubMed2001

Selective disruption of cadherin/catenin complexes by oxidative stress in precision-cut mouse liver slices.

Previous work has shown that chemically induced oxidative stress disrupts the protein interactions of the E-cadherin/beta-catenin/alpha-catenin complex in precision-cut mouse liver slices (Parrish et al., 1999, Toxicol. Sci. 51, 80-86). Although these data suggest a role for oxidative stress in disruption of hepatic cadherin/catenin complexes, multiple complexes are co-expressed in the liver. Both E- and N- cadherin are co-expressed in hepatocytes, as well as beta-catenin and gamma-catenin; thus four distinct complexes mediate cell-cell adhesion in the liver: E-cadherin/beta-catenin/alpha-catenin, E-cadherin/gamma-catenin/alpha-catenin, N-cadherin/beta-catenin/alpha-catenin, and N-cadherin/gamma-catenin/alpha-catenin. Taking advantage of the retention of normal organ architecture and cellular heterogeneity offered by precision-cut mouse liver slices, the current study was designed to examine the impact of chemically induced oxidative stress on cadherin/catenin complexes. Precision-cut mouse liver slices were challenged with diamide (25-250 microM; 6 h) or tert-butylhydroperoxide (5-50 microM; 6 h). A polyclonal antibody against beta- or gamma-catenin was used to immunoprecipitate proteins prior to Western-blot analysis with monoclonal antibodies to E- or N-cadherin. Although a decrease in E-cadherin:beta-catenin co-immunoprecipitation was seen, interactions between beta-catenin and N-cadherin were not disrupted by chemical challenge. In addition, no effect on protein interactions of gamma-catenin with either cadherin was observed. Indirect immunofluorescence was used to co-localize catenins and cadherins following chemical challenge. Consistent with the biochemical observations, a heterogeneous reduction in co-localization of E-cadherin and beta-catenin was seen in precision-cut liver slices, but not other cadherin/catenin complexes. Taken together, these data suggest that oxidative stress selectively disrupts E-cadherin/beta-catenin complexes in the liver. This response is dictated, in part, by the protein composition of the cell-adhesion complex.

Animals↗
PubMed2001

A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine.

BACKGROUND: The authors used the analgesics alfentanil, S(+)-ketamine, and systemic lidocaine to examine a new human model of experimental pain and hyperalgesia. METHODS: Transcutaneous electrical stimulation at a high current density (5 Hz, 67.5+/-6.6 mA) was used to provoke acute pain (numeric rating scale, 5 of 10), stable areas of secondary mechanical hyperalgesia to pin prick (43.6+/-32.1 cm2), and light touch (27.5+/-16.2 cm2) for 2 h. Alfentanil, S(+)-ketamine, and lidocaine were applied for 20 min in a double-blind, placebo-controlled, crossover design in 12 subjects using target controlled infusions. RESULTS: In the placebo session, pain ratings and areas of hyperalgesia were stable during the stimulation period, which facilitated the assessment of analgesic effects. Alfentanil effectively inhibited electrically evoked pain and reduced pin prick hyperalgesia and allodynia during its infusion. S(+)-ketamine-induced inhibition of secondary hyperalgesia was more pronounced and lasted for the whole experimental protocol. Therapeutic levels of systemic lidocaine showed only marginal analgesic effects, but lasting antihyperalgesic effects. CONCLUSIONS: A new model of electrically induced pain and hyperalgesia was established, which enabled assessment of the time course of analgesic and antihyperalgesic effects with high temporal resolution and minimum tissue damage and which was further validated by use of common intravenous anesthetics.

Adult↗
PubMed2001

Different patterns of mast cell activation by muscle relaxants in human skin.

BACKGROUND: Activation of mast cells and systemic release of histamine are major side effects of intravenously administered muscle relaxants. In the current study, dermal microdialysis was used for the investigation of mast cell activation by muscle relaxants. Dermal microdialysis enabled simultaneous assessment of mediator release, vascular reactions, and sensory effects induced by intradermal application of muscle relaxants without systemic side effects. METHODS: Succinylcholine, the isoquinolines cisatracurium, atracurium, and mivacurium, and the steroids pancuronium, vecuronium, rocuronium, and rapacuronium were tested in human volunteers (n = 6 each). After intradermal insertion of microdialysis capillaries (0.4 mm diameter, cutoff 3,000 kd) and a 60-min equilibration period, the muscle relaxants were delivered via the capillaries for 30 min, followed by a 30-min washout period. Dialysate was sampled at 15-min intervals, and histamine, mast cell tryptase, and protein extravasation were determined. Changes in skin blood flow were measured using a laser Doppler imager. Potency and efficacy were derived from nonlinear fittings of the dose-response curves. RESULTS: For succinylcholine and the isoquinolines, dose-response curves for the vascular and sensory effects paralleled the histamine and tryptase release. In contrast, aminosteroids evoked a rapid histamine release that was accompanied by a delayed increase in tryptase. CONCLUSIONS: Dermal microdialysis has been successfully used to simultaneously assess mediator release, vascular reactions, and sensory effects. The different pattern of tryptase release by isoquinolines and aminosteroids suggests different mechanisms of mast cell activation.

Adult↗