Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Injections, Intradermal”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 829 records · Page 46Linked to original sources
PubMed2004

Differential role of neutrophils and monocytes during subcutaneous plasma extravasation.

We examined the behavior of polymorphonuclear leukocytes (PMNs) and monocytes during subcutaneous plasma extravasation in guinea-pigs. Plasma extravasation was induced by intradermal injection of zymosan-activated plasma (ZAP). The degree of extravasation correlated logarithmically with the concentration of injected ZAP, and was composed of PMN-dependent and -independent components. The latter was mediated primarily by histamine. The former accounted for 40-50% of the total plasma extravasation, peaked within 15 min, and then rectilinearly decreased with a half-life between 30 and 40 min. Histological examination of skin at 15 min after ZAP injection demonstrated PMN attachment to the luminal surface of venule endothelial cells, without evidence of PMN extravasation. We next examined whether monocyte infiltration of subcutaneous tissue played a causal role in plasma extravasation. Monocyte-predominant infiltration was initially caused by an intradermal injection of a monocyte-specific chemotactic factor, the S19 ribosomal protein (RP S19) dimer. Monocyte infiltration did not induce plasma extravasation even in guinea-pigs with elevated peripheral blood monocyte levels following administration of a macrophage-colony stimulating factor. A simultaneous injection of prostaglandin E2, a vasodilating agent, with RP S19 dimer also did not induce plasma extravasation. In contrast, a simultaneous injection of RP S19 dimer with ZAP changed the leukocyte infiltration pattern from PMN-predominant to monocyte-predominant, and almost completely suppressed the PMN-dependent component of the ZAP-induced plasma extravasation. The lack of plasma extravasation in the monocyte-predominant pattern was reproduced when a strong monocyte infiltration was induced by an intradermal injection of apoptotic cells. We conclude that leukocyte-induced plasma extravasation is specific for PMN, and is not due to a physical leakage of plasma during leukocyte emigration. Rather, plasma extravasation is probably caused by a cognate interaction between PMNs and postcapillary venule endothelial cells.

Animals↗
PubMed1998

Priming and induction of eosinophil trafficking in guinea-pig cutaneous inflammation by tumour necrosis factor alpha.

Tissue eosinophilia is a hallmark of allergic and parasitic diseases. Priming mechanisms may play an important role in mediating the process of eosinophil accumulation in these conditions. We have previously shown that blockade of tumour necrosis factor alpha (TNFalpha) inhibited the capacity of lipopolysaccharide to prime skin sites for chemoattractant-induced eosinophil recruitment. The present study was carried out to investigate the capacity of TNFalpha to prime an inflammatory site for enhanced eosinophil accumulation. Initial experiments investigated the capacity of TNFalpha itself to induce eosinophil accumulation. Intradermal injection of murine TNFalpha (10-300 ng per site) in the guinea-pig induced significant accumulation of 111In-eosinophils. Kinetic studies showed the response to be delayed in onset and inhibited by cycloheximide, consistent with a dependency on protein synthesis. Trafficking of 111In-eosinophils to sites treated for 2 h with TNFalpha (10-100 ng per site) was inhibited by monoclonal antibodies (mAbs) against beta2 or alpha4 integrins. Intradermal injection of a low dose (3 ng) of TNFalpha (which by itself had no significant effect on eosinophil trafficking) prior to chemoattractants or antigen in sensitized skin sites, induced significant priming of eosinophil accumulation. Recruitment of both 111In-eosinophils and endogenous eosinophils was enhanced. Trafficking to TNFalpha-primed responses was dependent on protein synthesis and beta2 integrins. In contrast, the alpha4 integrin mAb failed to inhibit the TNFalpha primed response. Thus, TNFalpha can induce and also prime eosinophil recruitment in guinea-pig skin. Our results provide further evidence that this cytokine may be an important mediator of allergic- or parasite-induced eosinophilic inflammation.

Animals↗
PubMed2006

Contribution of xanthoma tissue-derived LDL density substances in the transformation of macrophages to foam cells.

BACKGROUND: The source of accumulated lipids in the foam cells of xanthoma is primarily the lipoproteins existing in the lesional dermis. OBJECTIVE: This study was designated to clarify the contribution of low density lipoprotein (LDL) density substances existing in xanthoma tissue to foam cell formation. METHODS: An LDL density fraction was obtained from homogenized rabbit experimental xanthoma tissue. Biochemical and functional characteristics of xanthoma-extracted LDL density substance were examined. The in vivo foam cell-inducing ability of xanthoma-extracted LDL density substance was examined microscopically at the intradermal injection site. RESULTS: Xanthoma-extracted LDL density substance showed more negatively charged mobility on agarose gel electrophoresis than plasma native LDL. A small amount of aggregated material remained at the origin on agarose gel electrophoresis. Xanthoma-extracted LDL density substance contained much higher level of lipid peroxides than native LDL. Mouse peritoneal macrophages internalized xanthoma-extracted LDL density substance extensively and transformed into foam cells by incubation with xanthoma-extracted LDL density substance. Intradermal injection of the xanthoma-extracted LDL density substance induced foam cell infiltration in the skin of a normolipemic rabbit. CONCLUSION: LDL density substances prepared ex vivo from experimental xanthoma tissue contained lipid-protein complexes that have physiochemical properties of oxidized LDL. The lipid-protein complexes were incorporated into foam cells. The substances were considered to contribute to foam cell recruitment during the persistence of xanthoma lesions.

Animals↗
PubMed1998

Cutaneous responses to endothelin-1 and histamine in patients with vibration white finger.

Vibration white finger (VWF) is the episodic blanching of the fingers that occurs in response to cold in those who work with hand-held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent pain and paresthesia are common in the hands and arms and occur independently of the "white attacks." We have previously reported a decrease in protein gene product 9.5 and calcitonin gene-related peptide-immunoreactive nerve fibers in the digital skin of individuals with VWF. In this study, we have sought to determine whether this deficit of immunoreactive sensory-motor nerves has a functional counterpart in vivo. Histamine produces a rapid wheal and flare response following intradermal injection, whereas endothelin-1 (ET-1) produces a central area of pallor with a surrounding neurogenic flare. In contrast, calcitonin gene-related peptide produces a non-neurogenic erythema. In this study, histamine and ET-1 were injected into the dorsum of the middle phalanx and the local neurovascular response was assessed by measuring the area of the visible flare or pallor. Basal finger blood flow was also measured by laser Doppler flowmetry in each of the digits prior to intradermal injection. The experiments were performed at 21 degrees C and 4 degrees C. Patients with VWF and asymptomatic vibration-exposed workers had significantly lower resting skin blood flow at both 21 degrees C and 4 degrees C than heavy manual workers with no vibration exposure. The size of the histamine- and ET-1-induced flares at both 21 degrees C and 4 degrees C was significantly smaller in patients with VWF when compared with the asymptomatic vibration-exposed workers and heavy manual workers. The size of the ET-1-induced pallor was smaller in patients with VWF when compared with the heavy manual workers at both 21 degrees C and 4 degrees C. In contrast, the area of erythema induced by intradermal injection of calcitonin gene-related peptide at both 21 degrees C and 4 degrees C was of a similar size in patients with VWF and in heavy manual workers. These results indicate that the neuroneal deficit identified by immunohistochemistry in the digital skin of patients with VWF has a functional counterpart in vivo and is evident as a reduced ability to propagate an axon-reflex vasodilator response when challenged with histamine and ET-1. Furthermore, these results enable patients with VWF to be differentiated from both asymptomatic vibration-exposed workers, in whom the histamine- and ET-1-induced flares are normal, and those with primary Raynaud's disease, in whom the ET-1 flare is reduced and the histamine-induced flare is normal.

Adult↗
PubMed2003

Acute stress results in skin corticotropin-releasing hormone secretion, mast cell activation and vascular permeability, an effect mimicked by intradermal corticotropin-releasing hormone and inhibited by histamine-1 receptor antagonists.

BACKGROUND: Mast cells play an important role in allergic inflammation by releasing vasoactive molecules, proteases and cytokines. Corticotropin-releasing hormone (CRH) and its structural analogue urocortin (Ucn) were shown to trigger skin mast cell activation and vascular permeability. We investigated the effect of acute stress on rat skin vascular permeability and CRH secretion, as well as the effect of intradermal CRH, and that of two histamine-1 receptor antagonists, azelastine and olopatadine, on vascular permeability. METHODS: Rats were stressed by restraint and vascular permeability was assessed by extravasation of (99)Tc-gluceptate, while mast cell activation was determined by skin rat mast cell protease-1 (RMCP-1) content. Skin CRH content was evaluated by ELISA. The effect of intradermal injection of CRH and Ucn, as well as that of two histamine-1 receptor antagonists, azelastine and olopatadine, was assessed by Evan's blue extravasation. Purified rat peritoneal mast cells (RPMCs) were also pretreated with azelastine (24 microM) or olopatadine (133 microM) for 5 min before challenge with compound 48/80 (0.5 microg/ml) for 30 min. Histamine secretion was measured fluorometrically. Intracellular Ca(2+) ions were evaluated in RPMCs loaded with calcium crimson and stimulated with compound 48/80. RESULTS: Acute stress increased skin vascular permeability and CRH content, while it decreased RMCP-1. Intradermal injection of CRH or Ucn induced substantial Evan's blue extravasation that was inhibited by pretreatment with azelastine (24 microM) and olopatadine (133 microM). Both antihistamines also inhibited histamine release and intracellular increase of Ca(2+) ions from RPMCs stimulated by compound 48/80. CONCLUSIONS: These results indicate that acute stress increases skin CRH that can trigger mast cell-dependent vascular permeability, effects inhibited by certain histamine-1 receptor antagonists, possibly acting to reduce intracellular Ca(2+) ion levels.

Acute Disease↗
PubMed2005

Use of immunostimulatory liposome-nucleic acid complexes in allergen-specific immunotherapy of dogs with refractory atopic dermatitis - a pilot study.

This pilot study evaluated the effects of immunostimulatory liposome-plasmid-DNA complexes combined with specific allergens for immunotherapy of refractory canine atopic dermatitis. Seven dogs with previously diagnosed atopic dermatitis and unsatisfactory response to at least 12 months of conventional allergen-specific immunotherapy underwent a series of six intradermal injections (weeks 0, 2, 4, 6, 10 and 14), with patient-specific allergen extracts contained in cationic liposome-DNA complexes. Degree of pruritus was assessed on a visual analogue scale. Lesion scores were determined using the Canine Atopic Dermatitis Extent and Severity Index (CADESI) and medication usage was recorded at weeks 0 and 14. Canine cytokine mRNA expression in peripheral blood mononuclear cells collected prior to treatment and at the completion of the study was determined for IFN-gamma, IL-4, TNF and IL-10 genes using quantitative reverse transcription competitive polymerase chain reaction. Repeated intradermal injections of specific allergens incorporated into liposome-nucleic acid complexes were well tolerated in all seven dogs. There was a significant improvement in pruritus scores (P = 0.0277) and concurrent significant decrease in IL-4 production (P = 0.0428) at the completion of the trial compared to pretreatment values. Medication scores, CADESI and production of other cytokines did not change significantly with treatment. These early results suggest that antigen-specific immunotherapy using a novel liposome-nucleic acid complex vaccine may be beneficial for treatment of established atopic dermatitis in dogs using lower antigen doses. Further investigations in larger numbers of dogs with earlier stages of disease are warranted.

Adjuvants, Immunologic↗
PubMed2003

A double-blind, randomized, comparative study of Dysport vs. Botox in primary palmar hyperhidrosis.

BACKGROUND: Intradermal injections of type A botulinum toxin have been reported to reduce excessive sweating in patients with primary palmar hyperhidrosis. Two preparations are commercially available in Europe: Botox (Allergan; 100 U per vial) and Dysport (Beaufour Ipsen Biotech; 500 U per vial), which are not bioequivalent. A few studies have tried to find an appropriate conversion factor between the two preparations in dystonic patients but results remain controversial. OBJECTIVES: To compare the efficacy of Botox and Dysport in palmar hyperhidrosis using a conversion factor of 1 : 4. METHODS: In a double-blind, randomized study, eight patients with severe primary palmar hyperhidrosis received in the same session intradermal injections of Dysport in one palm and Botox in the other, after regional median and ulnar nerve blocks. Quantification of sweat production was performed by Minor's iodine starch test at baseline, 1, 3 and 6 months after the treatment. Subjective assessment of sweat production was performed using a visual analogue scale. RESULTS: The mean +/- SD number of injection sites (28 +/- 1), mean volume of reconstituted solution injected (2.8 mL) and mean sweating area at baseline (BSA) were similar in each palm group. The mean +/- SD dose injected was 69.3 +/- 3.1 U for the Botox-treated palms and 283.7 +/- 11.3 U for the Dysport-treated palms (1 : 4). At 1 month, Minor's test revealed significant decreases in mean sweating area for each preparation (Dysport palms: -78.6% vs. BSA, P = 0.0002; Botox palms: -56.6% vs. BSA, P = 0.003). The percentage of decrease was more pronounced in Dysport palms compared with Botox palms but the difference did not reach statistical significance. At 3 months, the decrease in sweating area remained significant for Dysport palms (-69.4% vs. BSA, P = 0.008) but not for Botox palms (-48.8% vs. BSA). Self-evaluation showed a similar amount of improvement in both palm groups at 1 and 3 months (77% and 75% for Dysport; 68% and 72% for Botox). Local side-effects were more frequent in Dysport palms (weakness of thumb-index pinch in four cases, lasting 8-30 days) than in Botox palms (weakness of thumb-index pinch in two cases, lasting 15-21 days). The mean duration of positive effect was similar: 17 weeks in Dysport (range 8-32) and 18 weeks in Botox palms (range 8-32). CONCLUSIONS: Using a conversion factor of 1 : 4, the efficacy of Botox and Dysport injections was similar. However, there was a trend towards a larger improvement after Dysport treatment but with a higher incidence of adverse effects.

Adult↗
PubMed1991

Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia.

1. A local cutaneous injury can produce primary hyperalgesia within the injured area and secondary hyperalgesia in the normal surrounding skin. An intradermal injection of capsaicin in humans causes intense pain and hyperalgesia to heat and to mechanical stimuli in the surrounding skin. Psychophysical studies in humans supported the conclusions that the hyperalgesia was predominantly the secondary type and depended on one set of neurons sensitizing another ("neurogenic hyperalgesia") and that the latter set of neurons is located in the central and not the peripheral nervous system. To further test this hypothesis and to search for peripheral neural mechanisms contributing to the pain and neurogenic hyperalgesia from a local injury, we performed neurophysiological experiments in the monkey (Macaca fascicularis) and recorded the responses of cutaneous primary afferent fibers to an intradermal injection of capsaicin and to mechanical and heat stimuli delivered before and after the injection. 2. Most C- and A-fiber mechanoheat-sensitive nociceptive afferent fibers (CMHs and AMHs, respectively) responded too weakly or transiently to capsaicin to account quantitatively for the magnitude of capsaicin pain. Of the known primary afferents tested with capsaicin injections, only the responses of heat-selective nociceptors could potentially account for the pain measured psychophysically in the human. In addition, a novel type of primary afferent--tentatively termed "chemonociceptive"--may have contributed as well. 3. Nociceptive fibers did not become sensitized to either mechanical or heat stimulation after an injection of capsaicin either outside, adjacent to, or inside the receptive field (RF); any changes that occurred could not explain the hyperalgesia to mechanical or heat stimuli observed in humans. 4. The depressed responsiveness ("desensitization") of both myelinated and unmyelinated nociceptive fibers in the monkey to heat and/or mechanical stimulation of the injection site after capsaicin was injected inside their RFs correlated with the analgesia observed at the capsaicin injection site in the human. 5. Capsaicin, topically applied to the RF in a vehicle of dimethyl sulfoxide or alcohol, excited CMHs and AMHs and enhanced the responses of some of these fibers to heat and/or to stroking the skin. In some cases, similar results were produced by the vehicle alone. However, capsaicin and not the vehicle lowered the thresholds of some CMHs to heat. Thus the sensitization of CMHs contributes to the primary hyperalgesia known to occur within the area of skin directly exposed to topically applied capsaicin.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1995

Preliminary studies on the inflammatory actions of the venoms of some Australian spiders.

Experiments were performed using an anaesthetised rat model to investigate the local inflammatory responses produced by intradermal injections of crude venom gland extracts from a number of Australian spiders, namely, Phonognatha graeffei, Delena cancerides, Isopeda montana, Badumna insignis, Lampona cylindrata, Steatoda grossa, S. capensis Hann. All of the venom gland extracts tested, with the exception of that from S. capensis, produced increases in vascular permeability consistent with acute inflammatory responses. The responses primarily involved the activation of 5-HT receptors, since they were markedly reduced by the nonselective 5-HT1/5-HT2-receptor antagonist methiothepin. Some of the venoms caused liberation of endogenous mediators of inflammation, and some had components that acted directly on the vasculature to increase vascular permeability. Histamine appeared to have little if any role in the observed increases in vascular permeability following intradermal injection of the spider venoms.

Anesthesia↗
PubMed1994

Contact sensitivity of and cross-sensitivity between 2-(2'-hydroxy-5'-methylphenyl)benzotriazole (Tinuvin P) and 2-(2'-hydroxy-3'-tert-butyl-5'-methylphenyl)-5-chlorobenzotriazole (Tinuvin 326) evaluated by lymph node cell proliferation and ear swelling response in mice.

Contact sensitivity of and cross-sensitivity between 2-(2'-hydroxy-5'-methylphenyl)benzotriazole (Tinuvin P, TP) and 2-(2'-hydroxy-3'-tert-butyl-5'-methylphenyl)-5-chlorobenzotriazole (Tinuvin 326, T326) were investigated in BALB/c mice. Mice received an intradermal injection and subsequent topical application of the test chemical. Following final application, auricular lymph node cell (LNC) proliferation was measured. In another experiment, the appearance of contact sensitivity was assessed by increases in ear thickness following challenge of the test chemical. Application of TP to mice caused a significant increase in LNC proliferation. Challenge of these mice with TP resulted in an increase in ear thickness. However, TP-sensitized mice did not show an increase in ear thickness by challenge with T326. Under the same conditions, application of T326 failed to induce either LNC proliferation or ear swelling response. The induction of LNC proliferative response was closely related to the ear swelling response by challenge. Following intradermal injection of TP, topical application of T326 to mice did not induce LNC proliferation. A significant ear swelling response was not induced by first challenge with TP or T326 but induced by rechallenge with TP. Topical exposure of mice to TP following injection of T326 failed to induce LNC proliferation or any ear responses by challenge with T326 and TP. These data suggest that TP is a sensitizer, while T326 is not a sensitizer, and these chemicals do not cross-sensitize.

Administration, Topical↗
PubMed1993

Delayed type hypersensitivity to human cytomegalovirus.

A skin test for immunity to human cytomegalovirus (HCMV) is described in which skin induration is measured after intradermal injection of antigen derived from heat-inactivated Towne strain HCMV or of envelope prepared from the virus. Randomly selected healthy young adult males and females were prescreened for evidence of past infection with HCMV using serologic tests. Each individual was inoculated with heat inactivated whole virion HCMV antigen prepared from serum-free supernatants of HCMV-infected MRC-5 cells, non-infected MRC-5 cell lysates, and Candida extract. HCMV seropositive individuals developed positive skin reactions to both the Candida extract and the HCMV test antigen. No response was observed at the MRC-5 cell lysate inoculation site. The envelope antigen also elicited a response in seropositive individuals. Seronegative individuals who were negative to the HCMV intradermal antigen at the start of the study developed a positive response 1 week after subcutaneous immunization with live attenuated Towne strain HCMV. This response also correlated with the onset of in vitro proliferation responses to HCMV antigens by peripheral blood lymphocytes obtained from the immunized individuals. Furthermore, skin test and lymphocyte proliferation responses remained positive when tested up to 93 days post-immunization. In guinea pig experiments with HCMV, those animals immunized with purified HCMV or a virus envelope preparation developed strong skin reactions to intradermal injection of each of those antigens. In contrast, no reaction was observed in immune animals, either to viral capsid antigen or uninfected cell-lysate antigen, and no reactions were observed to any HCMV antigen in non-immune animals.

Animals↗
PubMed2002

Suppression of cutaneous inflammation by intradermal gene delivery.

Biological effects of in vivo transfection of a potential anti-inflammatory gene, designated Sm16, cloned from the human parasite Schistosoma mansoni were analyzed in these studies. A single intradermal injection of a full-length cDNA of Sm16 resulted in the expression of Sm16 in the epidermis, dermis, skin migratory cells and skin-draining lymph nodes of mice for up to 7 days. Subsequently the anti-inflammatory effect of this gene expression was evaluated by inducing an inflammatory response in the skin of mice. These studies showed that Sm16 gene delivery resulted in a significant suppression of cutaneous inflammation as shown by a reduction in cutaneous edema, decrease in neutrophil infiltration, suppression of pro-inflammatory cytokine expression and down-regulation of ICAM-1 expression in the skin inflammatory site. Cells collected from the skin-draining lymph nodes showed reduced proliferation to mitogen. Multiple intradermal injection of Sm16 cDNA failed to induce any antibody response in mice for up to 8 weeks after initial injection. These findings suggest a potential for developing Sm16 gene delivery as a therapeutic agent for treating inflammatory skin disorders.

Animals↗
PubMed1979

Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation.

1. Plasma exudation and blood flow changes induced by intradermal injection of prostaglandins E2 (PGE2), I2 (PG12), D2 (PGD2) and F2 alpha (PGF2 alpha) were measured in rabbit dorsal skin by the use of [131I]-albumin and 133Xe. 2. Little plasma exudation was produced by any of the prostaglandins when injected alone. 3. Both PGE2 and PGI2 were potent at increasing blood flow, whereas PGF2 alpha and PGD2 produced an increase only at high doses. 4. All of the prostaglandins studied potentiated the plasma exudation induced by bradykinin. PGE2 and PGI2 had similar potent potentiating activity, whereas PGD2 and PGF2 alpha had activity at doses too high to be of biological significance. 5. Intradermal injections of arachidonate alone resulted in little plasma exudation but produced an increase in blood flow. Arachidonate potentiated bradykinin-induced plasma exudation. 6. Locally-injected indomethacin had no effect on basal blood flow and little effect on the exudation produced by bradykinin, but indomethacin did inhibit the vasodilatation and exudation potentiation produced by arachidonate. 7. PGE2 and PGI2 had similar potency in producing marked potentiation of plasma exudation induced by intradermal injection of zymosan. 8. In the reaction to zymosan, it is concluded that vasodilatation is the result of the release of arachidonate, which is subsequently coverted to either PGE2 or PGI2. These substances regulate the plasma exudation induced by independently-released vascular permeability-increasing mediators.

Animals↗
PubMed1992

Effect of topical application with capsaicin on skin responses to bradykinin and histamine in man.

Pre-treatment with topical capsaicin is known to induce neuropeptide depletion from sensory nerve endings and it is a useful pharmacological tool to evaluate the contribution of these nerves to skin injury and inflammation. To investigate the relative contribution of sensory neural stimulation to the action of bradykinin and histamine, a randomized, double-blind study has been undertaken evaluating the effect of topical capsaicin pre-treatment on the responses to intradermal injections of both agonists in 12 healthy volunteers. Capsaicin pre-treatment caused significant inhibition of the immediate mean flare responses (95% CI) to both bradykinin (from 51.5 [39.7-63.3] mm2 to 16.2 [8.0-24.5] mm2) (P < 0.01) and histamine (from 108.4 [80.4-136.4] mm2 to 52.3 [37.1-67.1] mm2) (P < 0.01). Topical capsaicin elicited a significant inhibition of the weal response induced by histamine, the mean weal area being reduced from 14.8 (12.6-17.0) mm2 to 12.1 (10.1-14.1) mm2 (P < 0.05). In addition, the effect of topical capsaicin was to completely inhibit the bradykinin induced weal response compared to control, the mean weal area (95% CI) being reduced from 13.4 (11.4-15.4) mm2 to 8.2 (5.3-11.0) mm2 (P < 0.01). Our findings show that repeated topical application with capsaicin led to a significant reduction of the skin responses to intradermal injections with both agonists, and particularly with bradykinin. The weal responsiveness to bradykinin may entirely follow neuropeptide release from sensory nerves within the skin and the same applies to the flare response, although this is not completely inhibited by topical application with capsaicin.

Administration, Cutaneous↗
PubMed2006

The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin.

In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenous neuropeptides calcitonin gene-related peptide (CGRP) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection of the peptides. The mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar to the transient response induced by substance P. PAMP (10(-6)-10(-5) M) caused distinct itch sensation and local erythema. This effect could be abolished when combining the histamine H1-receptor antagonist mepyramin and PAMP. Real-time PCR data showed a higher level of mRNA for RAMP2 than CL-R, RAMP1 and RAMP3 in the tissue. Though the PCR data demonstrated the presence of mRNA for both CGRP1 and adrenomedullin receptors the rank order of potency (CGRP>adrenomedullin>amylin) for the blood flow increase indicated vasodilatation for these peptides was induced by activation of CGRP1 receptors. Intradermal injection of CGRP, adrenomedullin and amylin induces long lasting dilatation of human skin vasculature by activation of CGRP1 receptors. PAMP induces transient vasodilatation. PAMP but not CGRP, adrenomedullin and amylin causes itch sensation and local erythema. The transient effect on vasodilatation as response to PAMP is discussed.

Adrenomedullin↗
PubMed1988

Electrically-induced collagen calcification in pig skin. A histopathologic and histochemical study.

Deposition of calcium salts on collagen fibres in skin of fully anaesthetized pigs was induced by exposure to direct current (d.c.). In biopsies obtained from cathode areas successively from day 1 to day 7 after exposure the histopathologic and histochemical changes before and after the initial deposition of calcium salts have been examined. For comparison skin sites with intradermal injected calcium hydroxyapatite crystals were studied in addition. Small areas of calcified collagen and elastic fibres were noted in viable tissue 2 days after d.c. exposure. In succeeding days the calcified areas enlarged with new deposits always more superficial and closer to the epidermis than the original calcium deposits. Preconditions for calcification appear to be (1) a pH change in basic direction and/or the electrochemical processes specific to the cathode area and (2) a viable tissue. Elastic fibres appear to have a lower calcification threshold than collagen fibres. A positive staining for glycoproteins (PAS) and glycosaminoglycans (alcian blue pH 2.5) was noted in the calcified collagen fibres simultaneously with the calcification. In succeeding days the intensity of the staining reactions increased. Whether changes in the glycoproteins, collagen and its intimately bound glycosaminoglycans precede the calcification or the staining reactions develop secondarily to this deposition is not known. However, seven days after intradermal injections of Ca-apatite crystals in pig skin small and large crystals were observed ultrastructurally without any relation to collagen fibrils, but the calcified tissue presented a positive PAS and alcian blue reaction from day 2. Thus the PAS and alcian blue stainings in this model develop secondary to the deposition of calcium salts.

Animals↗
PubMed2005

Activation of protein kinase B/Akt signaling pathway contributes to mechanical hypersensitivity induced by capsaicin.

We investigated the involvement of the protein kinase B/Akt (PKB/Akt) signaling pathway in the mechanical hypersensitivity induced in rats by capsaicin. Intradermal injection of capsaicin results in activation of PKB/Akt in the lumbar spinal cord, most prominently in the dorsal horn, starting by 5 min after capsaicin injection and lasting at least 1h. The activated PKB/Akt in the spinal cord is in neurons, since phospho-PKB/Akt (p-PKB/Akt) colocalizes with the neuronal marker, neuronal-specific nuclear protein (NeuN). The mechanical hypersensitivity is shown by the enhanced paw withdrawal frequency to applications of von Frey filaments with different bending forces (30, 100, 200 mN) on the rat paw. Pre-treatment with several different PKB/Akt inhibitors, including SH-6, Akt inhibitor IV, and Akt inhibitor V, blocked the mechanical hypersensitivity induced by intradermal injection of capsaicin, a measure of spinal cord central sensitization. Two structurally unrelated phosphoinositide 3-Kinase (PI3K, upstream of PKB/Akt) inhibitors, Wortmannin and LY294002, also prevented the mechanical hypersensitivity induced by intradermal injection of capsaicin. Furthermore, post-treatment with the PI3K inhibitor, Wortmannin, or PKB/Akt inhibitors, such as NL-71-101, SH-6, Akt inhibitor IV, and inhibitor V significantly reduced the established mechanical hypersensitivity induced by capsaicin. The PKB/Akt signaling pathway in the spinal cord is therefore involved in pain hypersensitivity.

Animals↗
PubMed1986

Isolation, purification, and partial characterization of a lipopolysaccharide from Haemophilus pleuropneumoniae.

Lipopolysaccharide (LPS) from Haemophilus pleuropneumoniae 1536, serotype 2, was isolated and purified by a procedure designed to be equally satisfactory for both smooth- and rough-type LPS. The LPS yield was 53%. Analysis of the preparations revealed that protein, nucleic acid, and cellular phospholipid contamination was negligible (less than 0.1%). Analysis of the sugar content of the LPS by gas-liquid chromatography and colorimetric analysis revealed the presence of rhamnose, mannose, galactose, glucose, heptose, glucosamine, galactosamine, and 3-deoxy-D-manno-2-octulosonic acid. The heptose and glucose contents appeared to be unusually high. The fatty acids of the LPS consisted of a mixture of C14:0 and C16:0 in a ratio of about 4.5:1 (50% of the total) and 3-hydroxy C14:0. When used as a preparatory dose for the dermal Shwartzman reaction, as little as 10 micrograms of the LPS injected intradermally in rabbits produced reddening and swelling. After intravenous injection of a 100-micrograms LPS provoking dose, necrosis was observed at all intradermal injection sites. Limulus amebocyte lysate gelation was observed with an LPS concentration as low as 0.5 ng/ml. A typical biphasic fever response was noted in rabbits injected with as little as 0.25 ng of LPS per kg of body weight.

Animals↗