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Intratumoral injection of IL-2-activated NK cells enhances the antitumor effect of intradermally injected paraformaldehyde-fixed tumor vaccine in a rat intracranial brain tumor model.
Combined therapy with a fixed-tumor cell vaccine and intratumoral injection of NK cells induced strong tumor regression of rat glioma. Rat 9L glioma cells were inoculated into syngeneic male rats at the flank (subcutaneous tumor model) or at the basal ganglia of the right hemisphere (intracranial tumor model). Rats were intradermally injected three times with vaccine comprising fixed 9L cells, IL-2- and GMCSF-microparticles, and tuberculin prior to (protective studies) or after (therapeutic studies) challenge with live 9L cells. In the protective studies, the vaccine alone achieved significant tumor growth inhibition and elongation of mean life span in both the subcutaneous and intracranial tumor models. No therapeutic effect was observed in the intracranial tumor model with the vaccine alone. However, intratumoral injection of rat NK cells strongly assisted the therapeutic effect of the vaccine in the brain tumor model and resulted in a statistically significant elongation of life span. We propose that intratumoral injection of NK cells may not only kill brain tumor cells directly, but also trigger a strong immune response in the focal lesion of the brain after vaccination.
Responses of human skin to intradermal injection of leukotrienes C4, D4 and B4.
The ability of intradermally injected leukotrienes C4 (LTC4), LTD4 and LTB4 to produce inflammatory changes in human skin alone and in combination with prostaglandin E2 (PGE2) has been investigated. LTC4 and D4 (0.012-0.38 nmol) caused dose-related erythema and wealing. No evidence of synergism between PGE2 and LTC4 or LTD4 was detected, although only single dose combinations were studied. LTB4 (0.15-1.5 nmol) caused areas of induration which persisted for more than 4 h and which showed perivascular neutrophil infiltrates on histological examination. Only slight synergism between PGE2 and LTB4 was found. It was concluded that these pro-inflammatory properties of LTC4, LTD4 and LTB4 are consistent with their proposed roles as mediators of inflammation in the skin and other tissues.
Enhanced phosphorylation of NMDA receptor 1 subunits in spinal cord dorsal horn and spinothalamic tract neurons after intradermal injection of capsaicin in rats.
The functional enhancement of NMDA receptors after peripheral tissue injury is proposed to contribute to the sensitization of spinothalamic tract (STT) cells and hyperalgesia. Protein phosphorylation is a major mechanism for the regulation of NMDA receptor function. In this study, Western blots, immunofluorescence double labeling, and the retrograde tracing method were used to examine whether phosphorylation of NMDA receptor 1 (NR1) subunits increases in spinal cord tissue and spinal dorsal horn neurons, especially in STT cells, after injection of capsaicin (CAP) into the glabrous skin of one hindpaw of anesthetized rats. Western blots showed that phosphorylated NR1 protein in spinal cord tissue was increased 30 min after CAP injection. Immunofluorescence double-labeling staining showed no significant difference in the number of the NR1-like immunoreactive neurons in laminae I-VII in the lumbosacral segments (L(4)-S(1)) on the ipsilateral and the contralateral sides 30 min after CAP or vehicle injection. However, the numbers of phospho-NR1-like immunoreactive neurons were significantly increased on the ipsilateral side compared with the vehicle injection group. STT cells were labeled by bilateral microinjections of the retrograde tracer fluorogold into the lateral thalamus, including the ventral-posterior lateral nucleus. Immunofluorescence staining was performed at 30, 60, and 120 min after CAP injection or at 30 min after vehicle injection. There was a significant increase in the proportion of STT cells with phosphorylated NR1 subunits compared either with the contralateral side 30 and 60 min after CAP injection or either side of animals after intradermal injection of vehicle. These results provide direct evidence that NMDA receptors in STT cells are phosphorylated after CAP injection.
The inhibition spectrum of solar urticaria suppresses the wheal-flare response following intradermal injection with photo-activated autologous serum but not with compound 48/80.
BACKGROUND: The inhibition spectrum (IS) in solar urticaria was identified mainly in Japanese patients with solar urticaria, although the mechanism of action of the IS has not been elucidated. METHODS: Because an intradermal injection of action spectrum (AS)-irradiated serum in a case of solar urticaria induced a wheal response, we studied the responsiveness of the intradermal injection after an IS irradiation. RESULTS: An AS in this patient was composed of visible light shorter than 500 nm, while an IS was composed of visible light longer than 530 nm. When the IS was exposed immediately after the AS irradiation, the wheal response was inhibited. However, when the IS was exposed before the AS irradiation, the wheal response was not inhibited. An intradermal injection of her serum produced no reaction, whereas an intradermal injection of her serum pre-irradiated with visible light induced a wheal flare response. Further examination revealed that the in vivo wheal-inducing activity of her serum irradiated with visible light could be attenuated by post-IS irradiation at the injection site, while the wheal-inducing activity of her visible light-irradiated serum was not inhibited by irradiation of the activated serum with the IS. The wheal-flare response induced by compound 48/80 and histamine was not altered by IS irradiation at the site of skin tests. CONCLUSION: These findings indicate that photoallergens in the patient's serum that are activated by visible light irradiation are responsible for the development of her symptoms and that the IS may suppress the wheal response by inhibiting the binding of the photoallergens to mast cells, not by inactivating the photoallergens and stabilizing mast cells.
[Is the skin a passive organ of absorption of drugs? III. The number of leukocytes after intradermal injections of various drugs].
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Cushing's syndrome associated with the intradermal injection of triamcinolone diacetate.
A case of long-term Cushing's syndrome after intradermal injection of 160 mg of triamcinolone diacetate has been presented. The evidence of whether this decrease occurred secondary to the intradermal injections of triamcinolone diacetate or to exogenous abuse is not clear. However, because of the extensive use of intradermal steroids in the treatment of keloids as well as other lesions, this case is significant, whatever the cause. Further study is being accomplished and the final results will be reported by the endocrinology service, Wilford Hall Medical Center, in a follow-up article.
Intradermal injection of lentiviral vectors corrects regenerated human dystrophic epidermolysis bullosa skin tissue in vivo.
Dystrophic epidermolysis bullosa (DEB) is a family of inherited mechanobullous disorders caused by mutations in the gene, COL7A1, that codes for type VII, (anchoring fibril), collagen, which is critical for epidermal-dermal adherence. Most gene therapy approaches have been ex vivo, involving cell culture and culture graft transplantation, which is logistically difficult. To develop a more simplified approach, we engineered a self-inactivating lentiviral vector expressing human type VII collagen and injected this vector intradermally into hairless, immunodeficient mice and into a human DEB composite skin equivalent grafted onto immunodeficient mice. In both situations, the vector transduced dermal cells, which in turn synthesized and exported type VII collagen into the extracellular space. Remarkably, the type VII collagen selectively adhered to and incorporated into the basement membrane zone (BMZ) between the dermis and the epidermis, where it formed anchoring fibril structures. In the case of the DEB skin equivalent, the newly expressed type VII collagen reversed the DEB phenotype characterized by poor epidermal-dermal adherence and anchoring fibril defects. A single lentiviral vector injection provided stable type VII collagen at the BMZ for at least 3 months. These data demonstrate efficient and long-term type VII collagen gene transfer in vivo using direct intradermal injection of an engineered lentiviral vector.
Sentinel lymph node mapping and biopsy for breast cancer at a rural-based university medical center: initial experience with intraparenchymal and intradermal injection routes.
BACKGROUND: Recent data suggests that intradermal (ID) injection for sentinel lymph node (SLN) mapping and biopsy in breast cancer is as effective and reproducible as intraparenchymal (IP) injection. The aim of this study was to review our initial experience with IP and ID injection for SLN mapping and biopsy at our rural-based university medical center. METHODS: From January 4, 1999 to January 5, 2001, 113 of 165 patients with breast cancer underwent attempted SLN mapping and biopsy by either IP (n=63) or ID (n=50) injection. Selection of the IP versus ID injection route was non-randomized and based on surgeon preference. Success of SLN localization was examined. RESULTS: SLN localization was successful in 82% of IP and 100% of ID for radioisotope (p=0.001), 69% of IP and 92% of ID for blue dye (p=0.002), and 90% of IP and 100% of ID (p=0.024) for radioisotope and blue dye. Identical comparisons made after excluding the first 10 cases, 20 cases, and 30 cases from each injection group showed that the percentage of cases in each group in which the SLN localized changed minimally; however, some of the resultant p values eventually lost statistical significance. CONCLUSIONS: SLN localization was more successful by ID injection than by IP injection, thus favoring utilization of the ID injection route. The eventual loss of statistical power in some of the comparisons with increasing numbers of initial cases excluded may reflect differential learning curves of the two injection techniques; however, this may simply be a reflection of decreasing sample size used in each subsequent analysis. A prospective randomized trial comparing the IP and ID injection route may be warranted.
Spinal opioid receptor like1 receptor agonist, but not N-methyl-D-aspartic acid antagonist, reverses the secondary mechanical allodynia induced by intradermal injection of capsaicin in rats.
Secondary mechanical allodynia induced by intradermal injection of capsaicin has been widely used to search for the underlying mechanisms of tissue injury induced mechanical allodynia. However, the capsaicin concentration dependency of the development of secondary mechanical allodynia and the underlying mechanisms of development and maintenance of capsaicin-induced mechanical allodynia are not fully understood. In the present study, we clarify the capsaicin concentration dependency for development and maintenance of secondary mechanical allodynia and the role of spinal opioid receptor like1 (ORL1) receptor and N-methyl-D-aspartate receptor in the development and maintenance of secondary mechanical allodynia induced by an intradermal capsaicin injection. Capsaicin 50 microL of 0.03% induced the most intense secondary mechanical allodynia. Intrathecal injection of nociceptin, an ORL1 receptor agonist, attenuated the maintenance of secondary mechanical allodynia but had no effect on the development of secondary mechanical allodynia. An intrathecal injection of MK801, an N-methyl-D-aspartate receptor antagonist, had no effect on the development and maintenance of secondary mechanical allodynia. These findings suggest that spinal ORL1 receptor should be the target of study for the treatment of secondary mechanical allodynia induced by tissue injury.
[The effect of intradermal injection of collagenase in implanted hypertrophic scar in nude mice].
OBJECTIVE: Effects of collagen degradation in hypertrophic scar by intradermal injection of collagenase were observed. METHODS: Hypertrophic scar was implanted into nude mice and collagenase was injected locally. Light and electron microscopic observations were carried out. RESULTS: Collagen degradation in hypertrophic scar by intradermal injection of collagenase was observed. The implanted scars became soft, thin and small. CONCLUSION: These results suggested that local injection of collagenase may be a useful therapeutic tool for hypertrophic scar.
Enhanced cutaneous gene delivery following intradermal injection of naked DNA in a high ionic strength solution.
Intradermal injection of naked DNA results in gene transfer to skin cells, but the efficiency of this gene transfer method is relatively low and variable. We have systematically optimized several parameters to obtain reproducible, high-level gene transfer to the mouse skin. Older mice (approximately 7 weeks) showed a significant decrease in gene expression compared with younger mice (4-5 weeks old). The composition of the solvent vehicle (electrolyte versus nonelectrolyte) strongly affected gene expression in the skin. A higher level of gene expression was achieved when naked DNA was dissolved in isotonic phosphate buffered saline solution compared with isotonic dextrose solution. Finally, transfection efficiency in older mice was greatly improved by increasing the ionic strength of the solvent vehicle. The improved transfection efficiency was due to an enhanced DNA uptake by the skin cells. Gene transfer was most evident in the subdermal smooth muscle cells and epidermal cells. With the optimized conditions, gene transfer mediated by intradermal injection of naked DNA was comparable in efficiency to electroporation. However, cellular distributions of the gene transfer of the two methods were different.
Cutaneous blood flow responses in the forearms of Raynaud's patients induced by local cooling and intradermal injections of CGRP and histamine.
1. The cutaneous responses of the forearm to local cold exposure and intradermal injection of CGRP and other vasoactive mediators were compared in primary Raynaud's sufferers and normal volunteers. 2. Skin responses in the forearm were measured in terms of erythema reddening and skin blood flow. Visual responses were recorded by tracing and then area calculated by computerised planimetry. Skin blood flow was measured using a laser Doppler blood flow meter. 3. Cooling (5-6 degrees C for 2 min) of a 1 cm2 area of the forearm caused a localised reactive hyperaemia response in normal volunteers, measured using the last Doppler blood flow meter. The peak response in Raynaud's patients was significantly smaller than that of normal volunteers. 4. The cutaneous responses of Raynaud's patients and normal volunteers to intradermal injections of CGRP, histamine and PGE2 were not significantly different. 5. The results suggest that Raynaud's sufferers do not exhibit a diminished response to CGRP in the cutaneous microvasculature and can respond normally to histamine with an axon reflex mediated flare.
Granulomatous reaction after intradermal injections of hyaluronic acid gel.
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Physiologic studies in atopic dermatitis (disseminated neurodermatitis). I. The local cutaneous response to intradermally injected acetylcholine and epinephrine.
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Effects of intradermal injection of vasopressors in normal and diseased human skin.
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Monoamine oxidase and catechol O-methyl transferase inhibitors. Effect of intradermal injection on exogenous and endogenous norepinephrine.
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The eosinophilic response in the horse to intramedullary and intradermal injections of histamine, ACTH, and cortisone.
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