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Intradermal Injection (intradermal + injection)
Selected AbstractsPain Sensation during Intradermal Injections of Three Different Botulinum Toxin Preparations in Different Doses and DilutionsDERMATOLOGIC SURGERY, Issue 7 2006GOTTFRIED KRANZ MD BACKGROUND Pain sensation associated with injections of botulinum neurotoxin (BoNT) is commonly reported. To date differences in pain sensation between the commercially available products containing BoNT have not been quantified. OBJECTIVES The pain sensations during injection of Dysport, Botox, Neurobloc, and pure saline (control) were compared. In addition, the nociceptive effect of different volumes used for the dilution of the same BoNT dose was investigated. METHODS In a prospective, double-blind, controlled trial, 10 healthy subjects were injected intradermally with Dysport (12 U), Botox (3 and 4 U), Neurobloc (150 and 300 U) reconstituted in 0.9% saline, and pure saline. Pain sensation was quantified during injections. RESULTS Neurobloc injections caused significantly more injection pain than Botox, Dysport, and saline. No significant differences between Dysport, Botox, and saline were found, although there was a trend toward less pain with pure saline injections. Higher pain levels with higher volumes could not be demonstrated significantly. CONCLUSION Our data demonstrate that BoNT type B injections are associated with substantial pain. There is a considerable difference between the commercially available BoNT type B compared to the two BoNT type A preparations. Therefore, considering mitigation of injection pain seems necessary when using BoNT type B. [source] Attenuation of Flightless I, an actin-remodelling protein, improves burn injury repair via modulation of transforming growth factor (TGF)-,1 and TGF-,3BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2009D.H. Adams Summary Background, The pathophysiological mechanisms involved in burn injury repair are still not fully understood but include processes involving cellular proliferation, migration and adhesion. The actin cytoskeleton is intricately involved in these key wound repair processes. Flightless I (Flii), an actin-remodelling protein and transcriptional regulator, is an important regulator of wound healing. Objectives, To investigate the function of Flii gene expression in burn injury repair. Methods, Partial-thickness scald wounds were created on Flii heterozygous (Flii+/,), wild-type (WT) and Flii transgenic (FliiTg/+) mice. Burns were assessed using histology and immunohistochemistry, real-time quantitative polymerase chain reaction and biochemical analysis. Results, Flii expression, while upregulated in burn injuries, was significantly lower in the wounds of Flii+/, vs. WT vs. FliiTg/+ mice and healing was improved in Flii+/, mice with their burns healing faster than WT and FliiTg/+. Pro-scarring transforming growth factor (TGF)-,1 protein and gene expression were reduced in Flii+/, burns while antiscarring TGF-,3 was significantly elevated. Anti-,-smooth muscle actin (,-SMA) was decreased in Flii+/, burns suggesting a decrease in contractile myofibroblasts in the developing scars. Although Flii is primarily a nuclear and cytoplasmic protein it is also released by wounded cells. Intradermal injection of Flii-neutralizing antibodies (FliAbs) to WT burn wounds significantly improved their healing, indicating a potential novel approach for treating burns. Decreased TGF-,1 and elevated TGF-,3 expression were observed in FliAb-treated burns, which may contribute to their observed improvement in healing. Conclusions, Strategies aimed at reducing Flii expression, for example using neutralizing antibodies, may lead to improved burn outcomes. [source] Inhibitory effect of the polyinosinic-polycytidylic acid/cationic liposome on the progression of murine B16F10 melanomaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2006Taku Fujimura Abstract Cellular proteins, retinoic acid inducible gene-I and Toll-like receptor 3, sense dsRNA including polyinosinic-polycytidylic acid (PIC) to stimulate innate immune response. The local administration of PIC has been demonstrated to be effective in anti-tumor immunotherapy. However, the effects of PIC delivered cross the cell membrane have not yet been examined. To address this issue, we used a complex of PIC and cationic liposome (PIC liposome) and examined its anti-tumor effects in vitro and in vivo. PIC liposome could directly suppress the growth of B16F10 melanoma in vitro and repeated peritumoral injections of PIC liposome inhibited melanoma growth in a dose-dependent manner. This treatment induced tyrosinase-related protein-2 (TRP-2)-tetramer+ CD8+ cells in the lymph nodes. As the mechanism for its anti-tumor immune response, we showed that the intradermal injection of PIC liposome induced the maturation of dendritic cells (DC). Moreover, the intratumoral injection of immature DC after treatment with PIC liposome significantly increased the number of TRP-2-specific IFN-,-producing cells in the lymph nodes as well as spleen, which resulted in an augmentation of the anti-tumor immune response. These studies demonstrate the potential of peritumoral injection of PIC liposome as immunotherapy for malignant melanoma. [source] Peripheral T,cell tolerance occurs early during spontaneous prostate cancer development and can be rescued by dendritic cell immunizationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2005Elena Degl'Innocenti Abstract In the tumor-prone transgenic adenocarcinoma mouse prostate (TRAMP) mouse model we followed the fate of the immune response against the SV40 large T,antigen (Tag) selectively expressed in the prostate epithelium during the endogenous transformation from normal cells to tumors. Young (5,7-week-old) male TRAMP mice, despite a dim and patchy expression of Tag overlapping foci of mouse prostate intraepithelial neoplasia, displayed a strong Tag-specific cytotoxic T,lymphocyte (CTL) response after an intradermal injection of peptide-pulsed dendritic cells (DC). This response was weaker than the one found in vaccinated wild-type littermates, and was characterized by a reduced frequency and avidity of Tag-specific CTL. Early DC vaccination also subverted the profound state of peripheral tolerance typically found in TRAMP mice older than 9,10,weeks. The DC-induced CTL response indeed was still detectable in TRAMP mice of 16,weeks, and was associated with histology evidence of reduced disease progression. Our findings suggest that tumor antigens are handled as self antigens, and peripheral tolerance is associated with in situ antigen overexpression and cancer progression. Our data also support a relevant role for DC-based vaccines in controlling the induction of peripheral tolerance to tumor antigens. [source] Infiltrating cells and related cytokines in lesional skin of patients with chronic idiopathic urticaria and positive autologous serum skin testEXPERIMENTAL DERMATOLOGY, Issue 5 2003M. Caproni Abstract:, In approximately one-third of patients with chronic idiopathic urticaria (CIU), autoantibodies against the high-affinity IgE receptor and/or against IgE can be detected and a wheal-and-flare response can be provoked by the intradermal injection of autologous serum (ASST). In this study we aimed to further characterize the inflammatory response observed in the subgroup of CIU patients with positive ASST and serum-evoked histamine-release in vitro from basophils in comparison with unaffected skin and healthy donors. An immunohistochemical analysis of infiltrating cells (CD4, MPO, EG1, EG2, tryptase), cytokines (IL-4, IL-5, IFN-,), chemokines and chemokine receptors (IL-8, CCR3, CXCR3), and adhesion molecules (ICAM-1, VCAM-1, ELAM-1) was performed on seven selected patients (four males and three females; median age: 45 years; range: 22,57) and five healthy donors. Cytokine evaluation was also performed in five psoriatic patients to obtain an additional control. In spontaneous wheals we observed an increased number of CD4+ T lymphocytes when compared with the controls, and an increased number of neutrophils and eosinophils, whereas mast cells did not show a significant variation. A significant expression for IL-4 and IL-5 could only be observed in lesional skin, while IFN-, showed a slight expression in the same site. Chemokine receptors CCR3 and CXCR3 did not show a defined polarized response in either lesional or unaffected skin. An increased expression of all cellular adhesion molecules (CAMs) studied was detected in spontaneous wheals. The lack of a significant difference in the expression of tryptase + mast cells, T lymphocytes, IL-8, CXCR3 and CCR3, a few CAMs between the lesional and unaffected skin of CIU patients suggests a wide immunological activation that involves not only lesional tissues, but possibly extends to the whole of the skin's immune system. [source] The Neurogenic Vasodilator Response to Endothelin-1: A Study in Human Skin In VivoEXPERIMENTAL PHYSIOLOGY, Issue 6 2000Ruwani Katugampola We have investigated the mediators and mechanisms underlying the vasodilator effects of the potent vasoactive peptide, endothelin-1 (ET-1) and its isomers ET-2 and ET-3 in human skin, in vivo, using cutaneous microdialysis to quantify the release of mediators within the dermal response and scanning laser Doppler imaging to measure changes in blood flux. The effects of local anaesthesia, inhibition of nitric oxide synthase (NOS) by L-NAME and ET receptor blockade on the ET-induced vascular response were also investigated. ET-1, -2 and -3 all caused a dose-dependent area of pallor surrounded by a long-lasting flare which was accompanied by a short-lived burning pruritus. The concentration of nitric oxide (NO) in dialysate collected within the pallor response to 5 ,M ET-1 (1.43 ± 0.64 ,M, n = 5) was not significantly different from baseline levels collected prior to injection (0.86 ± 0.38 ,M) whilst that in the flare increased to reach a peak value of 2.28 ± 0.61 ,M at between 4 and 10 min after intradermal injection (P < 0.004). Pretreatment with local anaesthetic slowed the development of the flare and significantly reduced its size by up to 52% at 20 min after injection (P < 0.05) but had no significant effect on the central pallor. L-NAME, delivered by dialysis also caused a significant reduction in the ET-1-induced flare (P < 0.005). Bosentan, the non-selective ETA/ETB antagonist, when given by dialysis at the site of injection, reduced the area of both the ET-1-induced pallor and surrounding flare by 41 and 26%, respectively. No significant increase in tissue histamine was measured within either the pallor or flare response to ET-1, -2 or -3. Together these data confirm that the vasodilator response to endothelin-1 in human skin is neurogenic in origin and that it is in part mediated by the local release of nitric oxide. There appears to be little evidence for the involvement of mast cell-derived histamine in the initiation or modulation of ET-induced vasodilatation, in vivo. [source] Efficiency of combined methotrexate/chloroquine therapy in adjuvant-induced arthritisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2005M.A.R.C.P. Silva Abstract The present study evaluates the effects of methotrexate (MTX) and chloroquine (CQ), and of combined MTX + CQ treatment, on the inflammatory response and on plasma and liver phosphatase and transaminase activities, employing an adjuvant-induced arthritis model in rats. Arthritis was induced by the intradermal injection of a suspension of Mycobacterium tuberculosis in mineral oil into the plantar surface of the hind paws. Development of the inflammatory response was assessed over a 21-day period. Animal groups received either: (i) MTX, administered i.p., weekly, in 0.15, 1.5, 3, 6 or 12 mg/kg doses; (ii) CQ, given intragastrically, in daily 25 or 50 mg/kg doses; or (iii) MTX + CQ, administered in two combinations (MTX1.5 mg/kg + CQ50 mg/kg, or MTX6 mg/kg + CQ50 mg/kg). At the end of the experimental period, the animals were anesthetized and killed, blood and liver samples were collected and prepared for measurement of acid and alkaline phosphatase (AP, ALP), and aspartate (AST) and alanine aminotransferase (ALT) activities. MTX at 6 and 12 mg/kg reduced the inflammatory response while CQ had no effect. MTX6 mg/kg + CQ50 mg/kg reduced the inflammatory response similar to MTX12 mg/kg, without affecting the bone marrow. Plasma AP and liver ALP activities were very elevated in the arthritic rats. While MTX treatment partially reduced both plasma AP and liver ALP activities at all doses used in the arthritic rats, CQ treatment reduced plasma AP, but increased liver AP activity. MTX + CQ treatment decreased plasma AP and liver ALP activities in the arthritic rats to control values. Plasma and liver AST activities were unaltered in the arthritic rats, and were unaffected by treatment. However, plasma and liver ALT activities were significantly reduced in the arthritic rats. While MTX or CQ treatment did not alter plasma transaminase activity in the arthritic rats, after MTX + CQ treatment, plasma ALT activity returned to normal values. In conclusion, the present data suggest that MTX + CQ treatment provides more effective anti-inflammatory protection against adjuvant-induced arthritis than does MTX alone, reverting the alterations in enzyme activities induced by this inflammatory disease in rats. [source] Tuberculosis verrucosa cutis: antitubercular therapy, a well-conceived diagnostic criterionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2005Virendra N. Sehgal MD A 39-year-old housewife sustained inadvertent trauma to the right index finger about 6 years ago, whilst stitching clothes. A couple of weeks later, the site of trauma became hard and gritty. Ever since, it has progressed slowly, without any appreciable outward sign. It was not associated with any discomfort/pain. Consequent on an opinion from a surgeon, it was decided to operate on the right index finger. During the operation, under local anesthesia, a hard and gritty material was removed. The material was subjected to histopathologic study. Several stitches were applied to the wound. It failed to respond to antimicrobial therapy over a 4-week period, prompting the patient to seek another opinion. Examination of the skin surface revealed a plaque with an irregular configuration on and around the distal interphalangeal joint of the right index finger. It was erythematous and pigmented. The top of the plaque was irregular and had alternating elevations and depressions (Fig. 1). Diascopy was negative for apple jelly nodule. A bacillus Calmette,Guérin (BCG) vaccination scar was identified on the left deltoid. There was no regional lymphadenopathy or systemic abnormality. Mantoux test with intradermal injection of 0.1 mL SPAN's tuberculin (purified protein derivative/5 tuberculin units/0.1 mL) (Span Diagnostic Ltd., Murat, India) was negative after 72 h. Investigations, including total and differential leukocyte count, erythrocyte sedimentation rate, serum biochemistry, and renal and liver function tests, were within the normal range, as was a chest X-ray. Figure 1. Tuberculosis verrucosa cutis before (a) and after (b) antitubercular therapy (ATT) Hematoxylin and eosin-stained sections prepared from the biopsy taken from the lesion revealed noteworthy changes in the epidermis and the dermis. The former was marked by the presence of hyperkeratosis, acanthosis, and papillomatosis, whilst the latter contained tubercle granulomas. Each of the granulomas was well formed and consisted of large numbers of lymphocytes, histiocytes, and foreign body (Langerhans') giant cells (Fig. 2). Caseation necrosis and acid-fast bacilli could not be demonstrated. The preceding revelations were fairly conducive to the diagnosis. Accordingly, antitubercular therapy (ATT), comprising 450 mg of rifampicin, 300 mg of isonicotinic acid hydrazide, and 800 mg of ethambutol, was recommended for oral administration each day for 60 days. The outcome of the treatment was satisfactory, resulting in perceptible regression of the skin lesion (Fig. 1b). The patient was advised to continue the treatment for another 30 days, after which 450 mg of rifampicin and 300 mg of isonicotinic acid hydrazide were to be continued for another 6 months. Figure 2. Tuberculosis verrucosa cutis depicting well-formed tubercle(s) comprising lymphocytes, histiocytes, neutrophils, and a few giant cells (hematoxylin and eosin, × 100) [source] Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experienceINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2002Takeshi Azuma Abstract Background : Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. Methods : Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte,macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. Results : Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. Conclusion : Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy. [source] Intraoperative labeling of sentinel lymph nodes with a combination of vital dye and radionuclide tracer , results in sentinel lymph node-positive patientsJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 3 2006Wolfgang Pfützner Sentinel-Lymphknoten; Melanom; Metastasierung; Diagnostik Summary Background: Sentinel lymph node biopsy enhances the accuracy of tumor staging in patients with malignant melanoma and can help select candidates for regional lymphadenectomy. There are two techniques for identifying the sentinel lymph node: intradermal injection of a radionuclide tracer or of a blue dye. We evaluated both methods to determine how they can be best utilized to locate a sentinel lymph node. Patients and methods: In a retrospective study, 323 patients with melanoma (tumor thickness , 0.75 mm) who underwent sentinel lymph node biopsy after both radionuclide and blue dye injection were evaluated. The labeling of lymph nodes showing micrometastasis by histopathological examination was determined. Results: 63 patients showed sentinel lymph nodes with micrometastasis. All of these nodes (100 %) were labeled with radionuclide tracer, but only 90 % with blue dye. In 5 patients, only radionuclide labeling identified the histopathologically-positive lymph node. In 36 patients, several sentinel lymph nodes were identified, with the histopathologically-positive nodes usually showing a higher radioactive signal intensity than the negative ones. Conclusion: Since in some patients histopathologically-positive lymph nodes are only labeled by radionuclide tracer, radionuclide labeling is indispensable for locating sentinel lymph nodes. In contrast, labeling with blue dye represents a supplementary method, which can simplify the recognition of the sentinel lymph node during surgery. Zusammenfassung Hintergrund: Die Entnahme des Sentinel-Lymphknotens erlaubt eine genauere Aussage über das Tumorstadium bei Patienten mit malignem Melanom und eine Auswahl der Patienten, bei denen eine therapeutische Dissektion der regionären Lymphknoten indiziert ist. Es existieren zwei Methoden,den Sentinel-Lymphknoten zu lokalisieren: Intradermale Injektion eines Radionuklidtracers oder eines blauen Farbstoffes. Wir prüften die Wertigkeit beider Methoden und stellten die Frage, welche Empfehlungen zum Einsatz dieser Verfahren beim Auffinden des Sentinel-Lymphknotens gegeben werden können. Patienten und Methodik: In eine retrospektiven Studie wurden 323 Patienten mit einem Melanom (Tumordicke , 0,75 mm) evaluiert, bei denen zur Entfernung des Sentinel-Lymphknotens sowohl eine Radionuklid- als auch eine Farb-stoffmarkierung erfolgte. Es wurde untersucht, welche Markierung die Lymph-knoten aufwiesen, bei denen sich in der histopathologischen Begutachtung Mikrometastasen fanden. Ergebnisse: 63 Patienten zeigten Sentinel-Lymphknoten mit Mikrometastasen, von denen alle (100 %) radionuklidmarkiert waren, jedoch nur 90 % auch eine Farbstoffmarkierung aufwiesen. Bei 5 Patienten wurde der histopathologisch positive Lymphknoten nur durch die Radionuklidmarkierung entdeckt. Mehrere Sentinel-Lymphknoten fanden sich bei 36 Patienten,wobei die histopatho-logisch positiven zumeist eine höhere radioaktive Impulsrate aufwiesen als die negativen Lymphknoten. Schlussfolgerung: Da bei bestimmten Personen histologisch positive Lymph-knoten ausschliesslich radioaktiv markiert sind, ist die Radionuklidmarkierung bei der Lokalisation des Sentinel-Lymphknoten unverzichtbar. Die Farbstofffärbung dagegen stellt eine ergänzende Methode dar, die das intraoperative Auffinden des Sentinel-Lymphknotens erleichtern kann. [source] Efficacy of in-feed probiotics against Aeromonas bestiarum and Ichthyophthirius multifiliis skin infections in rainbow trout (Oncorhynchus mykiss, Walbaum)JOURNAL OF APPLIED MICROBIOLOGY, Issue 3 2008N. Pieters Abstract Aims:, The aim of this study was to assess the efficacy of in-feed probiotics as a preventive measure against skin infections caused by Aeromonas bestiarum and Ichthyophthirius multifiliis (Ich) in rainbow trout. Methods and Results:, Fin rot was induced in fish by intradermal injection with 0·1 ml volumes containing 105 cells per ml A. bestiarum at the base of the dorsal fin. Ich infections resulted from immersion in Ich-contaminated water. Each probiotic was administered orally [108 cells per g feed for GC2 (Aeromonas sobria) and 1010 cells per g feed for BA211 (Brochothrix thermosphacta)] for 14 days. Results showed that, after challenge with A. bestiarum, probiotics GC2 and BA211 led to 76% and 88% survival, respectively, in contrast to 22% survival for controls. Fish fed with probiotic GC2 had 100% survival after challenge with Ich compared with 2% for probiotic BA211 and 0% for controls. Analysis of innate immune responses revealed that probiotic GC2 promoted higher phagocytic activity, whereas probiotic BA211 led to enhanced respiratory burst activity. Conclusion:, Of the two probiotics examined, GC2 was more effective in protecting against both fin rot and Ich. Each probiotic appeared to stimulate different pathways within the innate immune system. Significance and Impact of the Study:, This is the first demonstration that probiotics can protect fish against surface infections. Furthermore, this is the first time a probiotic has been shown to protect against a eucaryotic pathogen, namely I. multifiliis. [source] Intradermal radioisotope injection is superior to subdermal injection for the identification of the sentinel node in breast cancer patientsJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2003Kazuyoshi Motomura MD Abstract Background and Objectives The purpose of the present study was to evaluate whether the intradermal injection of radiocolloids would improve the identification rate of sentinel nodes over the subdermal injection in breast cancer patients. Methods Sentinel node biopsy was performed in T2 breast cancer patients with clinically negative nodes, using subdermal or intradermal injection of radioisotopes with the peritumoral dye injection. We used Tc-99m tin colloid, with a larger particle size (0.4,5 ,m), rather than sulfur colloid and colloidal albumin. Results The initial 55 patients underwent subdermal injection of radiocolloids; the next 61 patients underwent intradermal injection of radiocolloids for sentinel node biopsy. The detection rate of sentinel nodes was significantly (P,=,0.048) higher in the intradermal injection group (61/61, 100%) than in the subdermal injection group (51/55, 92.7%). False-negative rates were comparable between the two groups. Lymphoscintigraphy visualized the sentinel nodes significantly (P,<,0.0001) more often in the intradermal injection group (59/61, 96.7%) than in the subdermal injection group (20/54, 37.0%). Conclusions A significantly higher identification rate of sentinel node biopsy and lymphoscintigraphy can be achieved by intradermal injection of Tc-99m tin colloid with a large particle size than by subdermal injection. J. Surg. Oncol. 2003;82:91,97. © 2003 Wiley-Liss, Inc. [source] Lichen planus and leukocytoclastic vasculitis induced by interferon alpha-2b in a subject with HCV-related chronic active hepatitisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2003JM De Sousa Pinto ABSTRACT Lichen planus (LP) has been reported in association with chronic active hepatitis, primary biliary cirrhosis and other chronic liver diseases. The occurrence of LP in persons with hepatitis C virus (HCV) was reported by Robert et al., and the possible relationship between LP and hepatitis virus has also been supported by cases of LP following hepatitis B vaccination. Exacerbation or appearance of LP during the treatment of chronic hepatitis C, lymphoproliferative diseases and melanoma with alpha-interferon (IFN-,) and improvement of these diseases after discontinuation of this drug indicate that IFN-, may possibly induce LP. We present a case of cutaneo-mucous LP in a woman with chronic active hepatitis treated with IFN-, and in whom local leukocytoclastic vasculitis was induced by the intradermal injection of a very low dose of IFN-,. [source] Gender-medicine aspects in allergologyALLERGY, Issue 5 2008E. Jensen-Jarolim Despite the identical immunological mechanisms activating the release of mediators and consecutive symptoms in immediate-type allergy, there is still a clear clinical difference between female and male allergic patients. Even though the risk of being allergic is greater for boys in childhood, almost from adolescence onwards it seems to be a clear disadvantage to be a woman as far as atopic disorders are concerned. Asthma, food allergies and anaphylaxis are more frequently diagnosed in females. In turn, asthma and hay fever are associated with irregular menstruation. Pointing towards a role of sex hormones, an association of asthma and intake of contraceptives, and a risk for asthma exacerbations during pregnancy have been observed. Moreover, peri- and postmenopausal women were reported to increasingly suffer from asthma, wheeze and hay fever, being even enhanced by hormone replacement therapy. This may be on account of the recently identified oestradiol-receptor-dependent mast-cell activation. As a paradox of nature, women may even become hypersensitive against their own sex hormones, resulting in positive reactivity upon intradermal injection of oestrogen or progesterone. More importantly, this specific hypersensitivity is associated with recurrent miscarriages. Even though there is a striking gender-specific bias in IgE-mediated allergic diseases, public awareness of this fact still remains minimal today. [source] Evidence that the human cutaneous venoarteriolar response is not mediated by adrenergic mechanismsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2002C. G. Crandall The venoarteriolar response causes vasoconstriction to skin and muscle via local mechanisms secondary to venous congestion. The purpose of this project was to investigate whether this response occurs through ,-adrenergic mechanisms. In supine individuals, forearm skin blood flow was monitored via laser-Doppler flowmetry over sites following local administration of terazosin (,1 -antagonist), yohimbine (,2 -antagonist), phentolamine (non-selective ,-antagonist) and bretylium tosylate (inhibits neurotransmission of adrenergic nerves) via intradermal microdialysis or intradermal injection. In addition, skin blood flow was monitored over an area of forearm skin that was locally anaesthetized via application of EMLA (2.5 % lidocaine (lignocaine) and 2.5 % prilocaine) cream. Skin blood flow was also monitored over adjacent sites that received the vehicle for the specified drug. Each trial was performed on a minimum of seven subjects and on separate days. The venoarteriolar response was engaged by lowering the subject's arm from heart level such that the sites of skin blood flow measurement were 34 ± 1 cm below the heart. The arm remained in this position for 2 min. Selective and non-selective ,-adrenoceptor antagonism and presynaptic inhibition of adrenergic neurotransmission did not abolish the venoarteriolar response. However, local anaesthesia blocked the venoarteriolar response without altering ,-adrenergic mediated vasoconstriction. These data suggest that the venoarteriolar response does not occur through adrenergic mechanisms as previously reported. Rather, the venoarteriolar response may due to myogenic mechanisms associated with changes in vascular pressure or is mediated by a non-adrenergic, but neurally mediated, local mechanism. [source] Skin Testing in Predicting Response to Nasal Provocation with Alternaria,THE LARYNGOSCOPE, Issue 8 2004John H. Krouse MD Abstract Objective: Examine the efficacy of epicutaneous and intradermal testing in predicting response to nasal provocation with Alternaria antigen. Study Design and Setting: Prospective study. Subjects were tested with the Multi-Test II (MT) epicutaneous testing device. Subjects with negative wheals were then tested with a 1:500 weight:volume intradermal injection of Alternaria. They had baseline assessment of nasal cross-sectional area (CSA) using acoustic rhinometry and underwent nasal provocation with increasing Alternaria concentrations. CSA was assessed at each concentration. A nasal allergen provocation score (NAP) of nasal symptoms as well as a nasal visual analogue scale (VAS) were also completed with each concentration. Results: Sensitivity and specificity of MT in predicting nasal response to Alternaria were poor at 42% and 44%, respectively. The addition of intradermal testing increased sensitivity only modestly to 58%. hierarchical linear modeling analysis demonstrated that subjects positive to Alternaria on skin testing did not show a significant reduction in nasal CSA on acoustic rhinometry or significant elevations in two nasal symptom scores with direct nasal provocation. Conclusion and Significance: Skin testing with either epicutaneous or intradermal testing may not be an accurate or sufficient technique in the assessment of Alternaria reactivity. These results suggest that mold allergies may involve more complex immune mechanisms than simply an immunoglobulin (Ig)E mediated type I immediate hypersensitivity response alone. An alternate model for mold sensitivity, as well as modifications in testing methods, may be required in the evaluation of mold allergy. [source] Mechanisms influencing the vasoactive effects of lidocaine in human skin,ANAESTHESIA, Issue 2 2007D. J. Newton Summary The vasodilator properties of lidocaine are believed to be due mainly to the inhibition of action potentials via sodium channel blocking in vasoconstrictor sympathetic nerves. However, mechanisms involving the vascular endothelium may also play a role, and in this study we investigated the potential influences of nitric oxide release, the cyclo-oxygenase pathway and the ,-adrenoceptors of vascular smooth muscle. Laser Doppler imaging was used to measure microvascular blood flow responses to intradermal injection of lidocaine 2%, with or without the addition of preservatives, in eight healthy, male volunteers. Co-injection of the nitric-oxide,synthase inhibitor N,-nitro- l -arginine methyl ester caused a 60% reduction in the response after about 20 min, and this reduction was enhanced with the lidocaine solution containing the preservatives methylhydroxybenzoate and propylhydroxybenzoate. No reduction in response was seen after blocking the cyclo-oxygenase or ,-adrenoceptor pathways. Nitric oxide release contributes to the vasoactivity of lidocaine in human skin. [source] Optimization of pulsed electromagnetic field therapy for management of arthritis in ratsBIOELECTROMAGNETICS, Issue 6 2005Venkatachalam Senthil Kumar Abstract Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 ,g/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and ,-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau,Braunbeck coil system. A magnetic field of 5 Hz,×,4 ,T,×,90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of ,-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans. Bioelectromagnetics 26:431,439, 2005. © 2005 Wiley-Liss, Inc. [source] Granulocyte/macrophage colony-stimulating factor treatment of human chronic ulcers promotes angiogenesis associated with de novo vascular endothelial growth factor transcription in the ulcer bedBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006F. Cianfarani Summary Background, Granulocyte/macrophage colony-stimulating factor (GM-CSF), a cytokine with pleiotropic functions, has been successfully employed in the treatment of chronic skin ulcers. The biological effects underlying GM-CSF action in impaired wound healing have been only partly clarified. Objectives, To investigate the effects of GM-CSF treatment of chronic venous ulcers on lesion vascularization and on the local synthesis of the angiogenic factors vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF). Methods, Patients with nonhealing venous leg ulcers were treated with intradermal injection of recombinant human GM-CSF, and biopsies were taken at the ulcer margin before and 5 days after administration. Wound vascularization was analysed by immunohistochemistry using antiplatelet endothelial cell adhesion molecule-1/CD31 and anti-,-smooth muscle actin antibodies. VEGF and PlGF transcription was assessed by in situ hybridization. To identify the cell populations transcribing VEGF within the ulcer bed, the VEGF hybridization signal was correlated with the immunostaining for different cell type markers on serial sections. Direct induction of VEGF transcription by GM-CSF was investigated in GM-CSF-treated cultured macrophages and keratinocytes. Results, Blood vessel density was significantly increased in the ulcer bed following GM-CSF treatment. VEGF transcripts were localized in keratinocytes at the ulcer margin both before and after GM-CSF treatment, whereas a VEGF hybridization signal was evident within the ulcer bed only following administration. PlGF mRNA was barely detectable in keratinocytes at the ulcer margin and was not visibly increased after treatment. Unlike VEGF, a specific PlGF hybridization signal could not be detected in cells within the ulcer following GM-CSF administration. Monocytes/macrophages were the main cell population transcribing VEGF after GM-CSF treatment. In vitro analysis demonstrated that VEGF transcription can be directly stimulated by GM-CSF in a differentiated monocytic cell line, but not in keratinocytes. Conclusions, Our data show that increased vascularization is associated with GM-CSF treatment of chronic venous ulcers and indicate that inflammatory cell-derived VEGF may act as an angiogenic mediator of the healing effect of GM-CSF in chronic ulcers. [source] Cloricromene, a coumarine derivative, protects against collagen-induced arthritis in Lewis ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2000Salvatore Cuzzocrea The aim of the present study was to investigate the effects of cloricromene, a coumarine derivative, in rats subjected to collagen-induced arthritis. Collagen-induced arthritis (CIA) was induced in Lewis rats by an intradermal injection of 100 ,l of the emulsion (containing 100 ,g of bovine type II collagen) (CII) and complete Freund's adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Lewis rats developed an erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as peri-articular erythema and oedema in the hind paws. The incidence of CIA was 100% by day 27 in the CII challenged rats and the severity of CIA progressed over a 35-day period with radiographic evaluation revealing focal resorption of bone together with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathology of CIA included erosion of the cartilage at the joint margins. Treatment of rats with cloricromene (10 mg kg,1 i.p. daily) starting at the onset of arthritis (day 23), delayed the development of the clinical signs at days 24,35 and improved histological status in the knee and paw. Immunohistochemical analysis for iNOS, COX-2, nitrotyrosine and for poly (ADP-ribose) synthetase (PARS) revealed a positive staining in inflamed joints from collagen-treated rats. The degree of staining for iNOS, COX-2, nitrotyrosine and PARS were markedly reduced in tissue sections obtained from collagen-treated rats, which had received cloricromene. Radiographic signs of protection against bone resorption and osteophyte formation were present in the joints of cloricromene-treated rat. This study provides the first evidence that cloricromene, a coumarine derivative, attenuates the degree of chronic inflammation and tissue damage associated with collagen-induced arthritis in the rat. British Journal of Pharmacology (2000) 131, 1399,1407; doi:10.1038/sj.bjp.0703695 [source] The effects of T cell peptides in patients sensitive to catsCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004Mark Larché Summary Synthetic peptides representing T cell epitopes of the major cat allergen Fel d 1 were administered by intradermal injection or inhalation to cat allergic asthmatic volunteers. Both routes of administration were associated with the induction of IgE-independent, MHC-restricted isolated late asthmatic reactions (LAR; prolonged bronchoconstriction initiating 2,4 hours after peptide challenge) in a proportion of individuals. Administration via the intradermal, but not the inhaled route, was associated with the induction of antigen-specific hyporesponsiveness or "tolerance", both in vivo and in vitro. Following intradermal peptide administration, the magnitude of both the early- and late-phase skin reaction to intradermal challenge with whole allergen extract were significantly reduced. In vitro, proliferative responses of peripheral blood mononuclear cells (PBMC) were reduced together with both Th1 and Th2 cytokines. Production of IL-10 was increased. LAR were not a pre-requisite for the induction of tolerance. Hyporesponsiveness was transient but several months were required to return to basal reactivity. [source] Allergen dose dependency of the early- and late-phase cutaneous response in the cynomolgus monkeyCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009A. Tomkinson Summary Background Cutaneous administration of allergen provides a means to confirm an allergic status, investigate the pathogenesis of allergic diseases, and/or provide a mechanism to evaluate the benefit of new potential therapeutics. Objective Studies were performed to characterize the allergen-induced cutaneous early- and late-phase response (EPR and LPR) in the cynomolgus monkey. Methods Following intradermal injections of Ascaris suum allergen, the cutaneous weal and flare EPR was measured 15 min post-injection, and skin biopsies were collected at 8,24 h to determine the optimal time of LPR occurrence. Biopsies were analysed for epidermal and dermal inflammatory changes. Results The EPR was dose related with a reproducible, measurable response at 1 : 10 000 and maximal at a 1 : 100 allergen dilution. In contrast, the threshold dose required for a reproducible LPR was much greater requiring a dilution of 6 : 100, suggesting independent mechanisms for the EPR and LPR. The LPR 20 h post-allergen injection induced an inflammatory response in the upper and deep dermis. The response was characterized by a moderate perivascular to diffuse inflammation consisting of mononuclear cells, neutrophils and eosinophils. Dexamethasone, while having no effect on the EPR, reduced dermal inflammation (upper dermis, P=0.004; deep dermis, P=0.03). Similarly, dermal eosinophilia was also reduced (upper dermis, P<0.001; deep dermis, P=0.02). Conclusion Collectively, the results indicate the dose dependency of the EPR and LPR. Furthermore, our observations indicate the value of the LPR response in the cynomolgus monkey to evaluate new therapeutics for the treatment of allergic diseases such as atopic dermatitis. [source] | ||||||||||||||||||||||||||||