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1.
Artigo em Inglês | MEDLINE | ID: mdl-31131754

RESUMO

BACKGROUND: Fentanyl is primarily an opioid agonist. It is frequently used in general anesthesia as a potent analgesic. It can be administered either orally, transdermally or systemically. Adverse effects due to opium alkaloids are usually because of a non-specific histamine release. Only in a few cases, a true allergy mechanism could be involved. Immediate reactions to opioids are most frequent than delayed reactions. In the past years, delayed reactions have increased in frequency because of the wide use of Transdermal Therapeutic System (TTS) with several opioids for its potent analgesic properties. OBJECTIVE: The objective was to study delayed reaction to fentanyl TTS and cross-reactivity with other opioids. METHODS: A 52-year-old man with a diagnosis of pancreatic cancer who began treatment for a bone metastases pain with fentanyl TTS, at a dose of 50 micrograms per hour (mcg/h) is the subject of the study. After 10-15 days of treatment, he developed an itchy papulovesicular rash in the application site of the fentanyl TTS. Afterward, eczema and superficial desquamation just on the application site of the patch were observed. He changed several times the site of application, but always developing the same symptoms in every single application. Later on, he tolerated other opioids such as oral morphine or tramadol. An allergy workout was performed. We performed Patch Tests (PT) with fentanyl at a concentration of 10% in aqua (aq) and with buprenorphine 10% aq., in order to investigate probable crossreactivity among other topical opioids. RESULTS: Readings were recorded at day 2 (D2) and day 4 (D4), with positive PT only with fentanyl at D2 (+++) and D4 (+++). We decided to perform a single-blind challenge test with buprenorphine 35 mcg/h in TTS, with a negative result. At this moment, fentanyl TTS was replaced by buprenorphine TTS, with good tolerance. CONCLUSION: We present the case of Allergic Contact Dermatitis (ACD) due to hypersensitivity to fentanyl with good tolerance to buprenorphine. Positive PT in this patient suggests a type IV hypersensitivity mechanism. Allergic reactions to opioids are frequently immediate, but delayed reactions could appear, especially when the drug is administered topically.


Assuntos
Dermatite Alérgica de Contato/diagnóstico , Hipersensibilidade a Drogas/diagnóstico , Fentanila/efeitos adversos , Hipersensibilidade Tardia/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Administração Cutânea , Buprenorfina/uso terapêutico , Dermatite Alérgica de Contato/tratamento farmacológico , Hipersensibilidade a Drogas/tratamento farmacológico , Substituição de Medicamentos , Tolerância a Medicamentos , Exantema , Fentanila/uso terapêutico , Humanos , Hipersensibilidade Tardia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Neoplasias Pancreáticas/complicações , Testes Cutâneos
2.
Bull Exp Biol Med ; 166(6): 754-758, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31028579

RESUMO

We studied immunocorrecting effects of Semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the model of "social" stress caused by sensory contact and intermale confrontation. Functional activity of the immune system of laboratory animals was evaluated in standard immunopharmacological tests: delayed-type hypersensitivity reaction, direct agglutination test, latex test for studying phagocytic activity of peripheral blood neutrophils, changes in differential leukocyte count, and weight of immunocompetent organs. It was found that changes in the immune response caused by "social" stress are multidirectional, which confirms the theory of stress-induced "immune imbalance". Semax acted as effective immune corrector restoring cellular and humoral immunogenesis reactions and phagocytic activity of neutrophils. This attested to the presence of immunomodulating properties in Semax and necessitates further studies in this field.


Assuntos
Hormônio Adrenocorticotrópico/análogos & derivados , Fatores Imunológicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Fragmentos de Peptídeos/farmacologia , Estresse Psicológico/tratamento farmacológico , Hormônio Adrenocorticotrópico/farmacologia , Agressão , Animais , Animais não Endogâmicos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , Imunidade Inata/efeitos dos fármacos , Testes de Fixação do Látex , Contagem de Leucócitos , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Fagocitose/efeitos dos fármacos , Estresse Psicológico/imunologia , Estresse Psicológico/fisiopatologia
5.
Ann Vasc Surg ; 55: 239-245, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30217712

RESUMO

BACKGROUND: Cyanoacrylate closure for the treatment of incompetent saphenous veins does not cause thermal damage and demonstrates satisfactory outcomes with rapid recovery. However, the characteristics of phlebitis-like abnormal reaction (PLAR), the most common adverse event after cyanoacrylate closure, have not been clarified. Moreover, it differs from typical phlebitis after thermal ablation. The objective of our study is to investigate the clinical features of PLAR after cyanoacrylate closure and to report its management. METHODS: A total of 160 patients with 271 incompetent saphenous veins (great saphenous veins, 201; small saphenous veins, 70) underwent cyanoacrylate closure with the VenaSeal™ system. We defined PLAR as any unusual skin condition that develops suddenly, such as erythema, itching, swelling, and pain/tenderness, over the treated veins several days after cyanoacrylate closure. Oral antihistamines and intravenous dexamethasone were administered to manage PLAR. RESULTS: Of the 271 treated veins, 69 experienced PLAR (25.4%). The mean time of occurrence was 13.6 ± 4.6 days after treatment. The rate of occurrence of erythema, itching, swelling, and pain/tenderness were 92.2%, 91.2%, 66.2%, and 48.5%, respectively. The occurrence of PLAR was significantly higher for great saphenous veins than for small saphenous veins (P < 0.001). Occurrences were more frequent in cases with a suprafascial great saphenous vein of length >10 cm than in cases with a subfascial great saphenous vein (P = 0.001). The proportion of patients who reported swelling decreased by more than half after the administration of oral antihistamine. The pain score on the 10th day also decreased significantly after the administration of antihistamine (P = 0.006). CONCLUSIONS: PLAR must be distinguished from classic phlebitis. We believe that PLAR is a type IV hypersensitivity reaction due to a foreign body, and in our experience, antihistamines or steroids are effective for the prevention and management of PLAR.


Assuntos
Cianoacrilatos/efeitos adversos , Reação a Corpo Estranho/induzido quimicamente , Hipersensibilidade Tardia/induzido quimicamente , Flebite/induzido quimicamente , Veia Safena , Adesivos Teciduais/efeitos adversos , Insuficiência Venosa/terapia , Administração Intravenosa , Administração Oral , Adulto , Idoso , Dexametasona/administração & dosagem , Feminino , Reação a Corpo Estranho/diagnóstico por imagem , Reação a Corpo Estranho/tratamento farmacológico , Reação a Corpo Estranho/fisiopatologia , Glucocorticoides/administração & dosagem , Antagonistas dos Receptores Histamínicos/administração & dosagem , Humanos , Hipersensibilidade Tardia/diagnóstico por imagem , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Flebite/diagnóstico por imagem , Flebite/tratamento farmacológico , Flebite/fisiopatologia , Estudos Prospectivos , Fatores de Risco , Veia Safena/diagnóstico por imagem , Veia Safena/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/fisiopatologia , Adulto Jovem
6.
Int Immunopharmacol ; 65: 108-118, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30312879

RESUMO

Immunosuppressive drugs are widely used for the treatment of immune-mediated diseases and inflammation, but the toxicity and side effects of the available immunosuppressors make the search of new agents of great relevance. Here, we evaluated the immunomodulatory activity of an N-acylhydrazone derivative, (E)-N'-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), a phosphodiesterase-4 (PDE-4) inhibitor. LASSBio-1386 inhibited lymphocyte activation in a concentration-dependent fashion, decreasing lymphoproliferation and IFN-γ and IL-2 production stimulated by anti-CD3/CD28 mAbs or concanavalin A (Con A) and inducing cell-cycle arrest in the G0/G1 phase. These effects were not blocked by RU486, a glucocorticoid receptor (GR) antagonist, indicating an effect independent of glucocorticoid receptor activation. Combination index-isobologram analysis indicates a synergistic effect between LASSBio-1386 and dexamethasone in lymphoproliferation inhibition. LASSBio-1386 presented immunomodulatory action in macrophage cultures, as observed by a significant and concentration-dependent decrease in NO and TNF-α production, an effect achieved by reducing IĸB expression and NF-κB activation. In the mouse model of endotoxic shock, LASSBio-1386 at 50 and 100 mg/kg protected 50 and 85% of mice against LPS-induced lethality, respectively. In agreement to its in vitro action, treatment with 100 mg/kg of LASSBio-1386 reduced TNF-α and IL-1ß serum levels, while increased IL-6 and IL-10. Finally, LASSBio-1386 reduced the paw edema in a BSA-induced delayed-type hypersensitivity model. These findings demonstrate the immunomodulatory and immunosuppressant effects of LASSBio-1386 and indicate this molecule is a promising pharmacologic agent for immune-mediated diseases.


Assuntos
Hidrazonas/farmacologia , Hipersensibilidade Tardia/tratamento farmacológico , Imunossupressores/farmacologia , Lipopolissacarídeos/toxicidade , Inibidores da Fosfodiesterase 4/farmacologia , Choque/tratamento farmacológico , Animais , Benzamidas , Citocinas/genética , Citocinas/metabolismo , Dexametasona/farmacologia , Antagonistas de Hormônios/farmacologia , Hidrazonas/química , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mifepristona/farmacologia , Estrutura Molecular , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Células RAW 264.7
7.
Pharmacol Res ; 137: 76-88, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30227260

RESUMO

T lymphocytes produced by the thymus are essential mediators of immunity. Accelerated thymic atrophy appears in the patients with administration of glucocorticoids (GCs) which are commonly-used drugs to treat autoimmune and infectious diseases, leading to dysregulation of immunity with manifestation of progressive diminution of new T cell production. However, there is no ideal method to overcome such side effects of GCs. In the current study, we proposed a composition of dexamethasone (DEX) and dihydromyricetin (DMY) derived from a medicinal plant, which could protect from DEX-induced thymus damage and simultaneously enhance the anti-inflammatory effect of DEX. In the current study, we found that DEX-damaged thymic cellularity and architecture, reduced thymocyte numbers, induced thymocyte apoptosis and dropped CD4+ and CD8+ double positive T cell numbers in thymus which was effectively improved by co-treatment with DMY. Quantification of signal joint TCR delta excision circles (TRECs) and Vß TCR spectratyping analysis were employed to determine the thymus function with indicated treatments. The results showed that DEX-impaired thymus output and decreased TCR cell diversity which was ameliorated by co-treatment with DMY. iTRAQ 2D LC-MS/MS was applied to analyze the proteomic profiling of thymus of mice treated with or without indicated agents, followed by informatics analysis to identify the correlated signaling pathway. After validated by Western blotting and Real-time PCR, we found that PPARγ-associated fatty acid metabolism was increased in the thymic tissues of the animals treated with DMY plus DEX than the animals treated with DEX alone. The agonist and antagonist of PPARγ were further employed to verify the role of PPARγ in the present study. Furthermore, DMY demonstrated a synergistic effect with co-administration of DEX on suppressing inflammation in vivo. Collectively, DMY relieved thymus function damaged by DEX via regulation of PPARγ-associated fatty acid metabolism. Our findings may provide a new strategy on protection of thymus from damage caused by GCs by using appropriate adjuvant natural agents through up-regulation of PPARγ-associated fatty acid metabolism.


Assuntos
Anti-Inflamatórios/farmacologia , Dexametasona/farmacologia , Ácidos Graxos/metabolismo , Flavonóis/farmacologia , Glucocorticoides/farmacologia , PPAR gama/metabolismo , Timo/efeitos dos fármacos , Animais , Anti-Inflamatórios/uso terapêutico , Dexametasona/uso terapêutico , Quimioterapia Combinada , Flavonóis/uso terapêutico , Glucocorticoides/uso terapêutico , Hipersensibilidade Tardia/tratamento farmacológico , Camundongos , Timo/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Molecules ; 23(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071672

RESUMO

Background: Allergic disease is a common clinical disease. Natural products provide an important source for a wide range of potential anti-allergic agents. This study was designed to evaluate the anti-allergic activities of the water-soluble polysaccharides extracted and purified from Saposhnikoviae Radix (SRPS). The composition and content of monosaccharides were determined to provide a material basis. Methods: An ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established to determine the composition and content of SRPS. 2,4-dinitrofluorobenzene (DNFB) induced a delayed-type hypersensitivity (DTH) mouse model orally administrated SRPS for seven consecutive days. Ear swelling, organ index, and serum IgE levels were observed to evaluate the anti-allergic activities. Results: The UPLC-MS/MS analysis showed that SRPS was consisted of eight monosaccharides including galacturonic acid, mannose, glucose, galactose, rhamnose, fucose, ribose, and arabinose with a relative molar ratio of 4.42%, 7.86%, 23.69%, 12.06%, 3.10%, 0.45%, 0.71%, and 47.70%, respectively. SRPS could effectively reduce ear swelling, a thymus index, and a serum IgE levels. Conclusions: The method was simple, rapid, sensitive, and reproducible, which could be used to analyze and determine the monosaccharide composition of SRPS. The vivo experiments demonstrated that SRPS may effectively inhibit development of DNFB-induced DTH. SRPS is a novel potential resource for natural anti-allergic drugs.


Assuntos
Apiaceae/química , Cromatografia Líquida de Alta Pressão/métodos , Monossacarídeos/análise , Espectrometria de Massas em Tandem/métodos , Animais , Antialérgicos/análise , Antialérgicos/uso terapêutico , Anti-Inflamatórios/análise , Anti-Inflamatórios/uso terapêutico , Dinitrofluorbenzeno/toxicidade , Modelos Animais de Doenças , Feminino , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/tratamento farmacológico , Camundongos , Monossacarídeos/uso terapêutico , Polissacarídeos/análise , Polissacarídeos/uso terapêutico
9.
Int Immunopharmacol ; 58: 32-39, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29549717

RESUMO

Iron oxide nanoparticles (IONPs) have been shown to attenuate T helper (Th)1 and Th2 cell-mediated immunity in ovalbumin (OVA)-sensitized mice. The objective of this study is to investigate the effects of IONPs on the immune responses of Th17 cells, a subset of T cells involved in various inflammatory pathologies. For in vivo study, a murine model of delayed-type hypersensitivity (DTH) was employed. BALB/c mice received a single dose of IONPs (0.2-10 mg iron/kg) via the tail vein 1 h prior to ovalbumin (OVA) sensitization. Their footpads were subcutaneously challenged with OVA to induce DTH reactions. The expression of Th17 cell-related molecules in inflamed footpads were examined by immunohistochemistry. For in vitro study, OVA-primed splenocytes were directly exposed to IONPs (1-100 µg iron/mL), and then re-stimulated with OVA in culture. The expression of Th17 cell-related molecules were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. IONP administration attenuated the number of interleukin (IL)-6, IL-17, the transcription factor ROR-γ, and chemokine receptor 6 positive cells in OVA-challenged footpads, whereas the number of transforming growth factor-ß, IL-23 and chemokine (C-C motif) ligand 20 positive cells was not altered. Direct exposure of OVA-primed splenocytes to IONPs suppressed the production of IL-6 and IL-17, and the mRNA expression of IL-17 and ROR-γt. These data indicate that exposure to IONPs attenuates Th17 cell responses in vivo and in vitro.


Assuntos
Compostos Férricos/uso terapêutico , Hipersensibilidade Tardia/tratamento farmacológico , Imunossupressores/uso terapêutico , Subpopulações de Linfócitos T/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Alérgenos/imunologia , Animais , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ovalbumina/imunologia , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologia
10.
Vet Dermatol ; 29(3): 250-e93, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29512229

RESUMO

BACKGROUND: Topical Janus kinase (JAK) inhibition is a promising therapeutic target for several inflammatory skin diseases of humans. OBJECTIVES: To evaluate the anti-inflammatory effect of tofacitinib, a JAK 1/3 inhibitor, on immediate and late-phase skin reactions in dogs. ANIMALS: Five healthy laboratory beagle dogs. METHODS: Topical tofacitinib (total daily dosage: 0.5 mg/cm2 ) or its gel vehicle were applied on either the left or right lateral thorax of each dog for eight days. Three days before application and after eight days of topical treatment, intradermal injections of histamine and anticanine-IgE antibodies were performed on both sides; they were evaluated by an investigator blinded to the interventions. RESULTS: The tofacitinib gel was well-tolerated; one dog developed mild erythema at Day 5 that resolved by the next application. Treatment with tofacitinib reduced histamine and anticanine-IgE global wheal scores (one-way ANOVA, P ≤ 0.005 for both) compared to baseline; there was no significant difference for the vehicle placebo (histamine; P = 0.163; IgE, P = 0.223). Late-phase reactions (LPRs) were markedly, but not significantly reduced after tofacitinib treatment (P = 0.071). A blinded histological evaluation of 6 h-anti-IgE-associated LPRs revealed a significant reduction in the total leucocyte superficial dermal cellularity (P = 0.022), as well as eosinophil (P = 0.022) and mast cell (P = 0.022) counts at tofacitinib-treated sides compared with pretreatment values. Post-treatment complete blood counts and serum chemistry profiles did not show relevant tofacitinib-induced changes. CONCLUSIONS: Our observations suggest that topical tofacitinib exerts an inhibitory effect on activated canine skin-emigrating immune cells; this drug should be investigated further as a topical immunosuppressive drug in dogs.


Assuntos
Dermatite Atópica/veterinária , Doenças do Cão/tratamento farmacológico , Hipersensibilidade Tardia/veterinária , Hipersensibilidade Imediata/veterinária , Piperidinas/farmacologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Cães , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Imediata/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/veterinária , Projetos Piloto
11.
Pediatr Dermatol ; 35(2): 234-236, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29314223

RESUMO

A 3-year-old girl presented with a 7-month history of a waxing and waning left thigh mass associated with pruritus and erythema at the site of two previous DTaP-HepB-IPV vaccinations. Patch testing was positive to aluminum chloride, supporting a diagnosis of vaccine granuloma secondary to aluminum allergy; her symptoms had been well controlled with antihistamines and topical steroids. Injection site granulomas are a benign but potentially bothersome reaction to aluminum-containing immunizations that can be supportively managed, and we encourage strict adherence to the recommended vaccine schedule in this setting. Patch testing is a sensitive, noninvasive diagnostic tool for patients presenting with this clinical finding, and dermatologist awareness can prevent unnecessary medical examination and provide reassurance.


Assuntos
Compostos de Alumínio/efeitos adversos , Cloretos/efeitos adversos , Granuloma/etiologia , Hipersensibilidade Tardia/diagnóstico , Urticária/diagnóstico , Vacinação/efeitos adversos , Cloreto de Alumínio , Compostos de Alumínio/imunologia , Pré-Escolar , Cloretos/imunologia , Feminino , Glucocorticoides/uso terapêutico , Granuloma/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/etiologia , Perna (Membro)/patologia , Testes do Emplastro/métodos , Urticária/tratamento farmacológico , Urticária/etiologia
12.
Allergy ; 73(1): 221-229, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28658503

RESUMO

BACKGROUND: Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. METHODS: We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. RESULTS: There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. CONCLUSIONS: PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.


Assuntos
Hipersensibilidade a Drogas/imunologia , Hipersensibilidade Tardia/imunologia , Inibidores da Bomba de Prótons/efeitos adversos , Reações Cruzadas/imunologia , Citocinas/metabolismo , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade a Drogas/mortalidade , Feminino , Humanos , Hipersensibilidade Tardia/diagnóstico , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/mortalidade , Tolerância Imunológica , Ativação Linfocitária/imunologia , Masculino , Inibidores da Bomba de Prótons/química , Testes Cutâneos , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Avaliação de Sintomas , Linfócitos T/imunologia , Linfócitos T/metabolismo
13.
J Pharm Pharmacol ; 70(1): 101-110, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29057517

RESUMO

OBJECTIVES: Compounds PH2 and PH5 are distereoisomers of novel indane compounds, synthesised as analogues of secondary metabolites of the fern, Onychium. In this study, we compare their effects on a variety of inflammatory models. METHODS: In an effort to extend our knowledge of their anti-inflammatory profile, we have investigated their activity in two models of delayed-type hypersensitivity (DTH); the methylated bovine serum albumin model (mBSA) and the oxazolone contact hypersensitivity (CHS) model, on IL2 release from Jurkat cells and in the dextran sulphate sodium (DSS) murine model of inflammatory bowel disease. KEY FINDINGS: Both diastereoisomers are equipotent in reducing paw swelling in the mBSA model and in inhibiting interleukin (IL) 2 release from Jurkat cells. They are equally ineffective in the oxazolone contact hypersensitivity model (CHS). Only the diastereoisomer, PH5, protects against DSS-induced colitis and of its two enantiomers, only the S,S-enantiomer, PH22, possesses this activity. PH2 is ineffective in the DSS model. CONCLUSIONS: The results suggest that the beneficial effect of PH5, and its enantiomer PH22, in the DSS model is a consequence of an action on a target specific to the colitis model. The implications of such data suggest an unknown target in this disease model that may be exploited to therapeutic advantage.


Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Hipersensibilidade Tardia/tratamento farmacológico , Indanos/farmacologia , Animais , Anti-Inflamatórios/química , Colite/patologia , Dermatite de Contato/tratamento farmacológico , Sulfato de Dextrana , Modelos Animais de Doenças , Feminino , Humanos , Indanos/química , Inflamação/tratamento farmacológico , Inflamação/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Células Jurkat , Camundongos , Camundongos Endogâmicos BALB C , Estereoisomerismo
14.
Int Immunopharmacol ; 54: 261-266, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29172063

RESUMO

The present study was focused on examining the effect of catechin on the cellular and humoral immunity in rat model. Immunomodulatory effect of catechin was determined by delayed-type hypersensitivity (DTH) response, carbon clearance assay, leucocyte mobilization test and cyclophosphamide-induced myelosuppression and hemagglutinating antibody (HA) titer assay. Catechin in experimental dose (25, 50 and 100mg/kg, p.o.) elevated a significant increase in antibody titer in the hemagglutination test with increased levels of immunoglobulin. There was an enhancement in the delayed-type hypersensitivity reaction produced by sheep red blood cells. There was also restoration in the functioning of leucocytes in cyclophosphamide-treated rats with an increased clearance of carbon particles. The results of the present study signify that catechin possesses sufficient potential for modulating immune activity by cellular and humoral mechanisms.


Assuntos
Carbono/metabolismo , Catequina/uso terapêutico , Hipersensibilidade Tardia/tratamento farmacológico , Animais , Carbono/imunologia , Bovinos , Modelos Animais de Doenças , Eritrócitos/imunologia , Feminino , Humanos , Hipersensibilidade Tardia/imunologia , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Imunomodulação , Masculino , Ratos , Ratos Wistar
15.
Clin Rev Allergy Immunol ; 54(1): 147-176, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29188475

RESUMO

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered a delayed-type hypersensitivity reaction to drugs. They represent true medical emergencies and an early recognition and appropriate management is decisive for the survival. SJS/TEN manifest with an "influenza-like" prodromal phase (malaise, fever), followed by painful cutaneous and mucous membrane (ocular, oral, and genital) lesions, and other systemic symptoms. The difference between SJS, SJS/TEN overlap, and TEN is defined by the degree of skin detachment: SJS is defined as skin involvement of < 10%, TEN is defined as skin involvement of > 30%, and SJS/TEN overlap as 10-30% skin involvement. The diagnosis of different degrees of epidermal necrolysis is based on the clinical assessment in conjunction with the corresponding histopathology. The mortality rates for SJS and TEN have decreased in the last decades. Today, the severity-of-illness score for toxic epidermal necrolysis (SCORTEN) is available for SJS/TEN severity assessment. Drugs with a high risk of causing SJS/TEN are anti-infective sulfonamides, anti-epileptic drugs, non-steroidal anti-inflammatory drugs of the oxicam type, allopurinol, nevirapine, and chlormezanone. Besides conventional drugs, herbal remedies and new biologicals should be considered as causative agents. The increased risk of hypersensitivity reactions to certain drugs may be linked to specific HLA antigens. Our understanding of the pathogenesis of SJS/TEN has improved: drug-specific T cell-mediated cytotoxicity, genetic linkage with HLA- and non-HLA-genes, TCR restriction, and cytotoxicity mechanisms were clarified. However, many factors contributing to epidermal necrolysis still have to be identified, especially in virus-induced and autoimmune forms of epidermal necrolysis not related to drugs. In SJS/TEN, the most common complications are ocular, cutaneous, or renal. Nasopharyngeal, esophageal, and genital mucosal involvement with blisters, erosions as well as secondary development of strictures also play a role. However, in the acute phase, septicemia is a leading cause of morbidity and fatality. Pulmonary and hepatic involvement is frequent. The acute management of SJS/TEN requires a multidisciplinary approach. Immediate withdrawal of potentially causative drugs is mandatory. Prompt referral to an appropriate medical center for specific supportive treatment is of utmost importance. The most frequently used treatments for SJS/TEN are systemic corticosteroids, immunoglobulins, and cyclosporine A.


Assuntos
Corticosteroides/uso terapêutico , Ciclosporina/uso terapêutico , Hipersensibilidade Tardia/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Pele/patologia , Síndrome de Stevens-Johnson/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticonvulsivantes/efeitos adversos , Humanos , Hipersensibilidade Tardia/etiologia , Síndrome de Stevens-Johnson/etiologia , Sulfonamidas/efeitos adversos
16.
J Dtsch Dermatol Ges ; 15(11): 1111-1132, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29106000

RESUMO

Adverse drug reactions of the delayed type rank among the most common dermatoses and are predominantly characterized by exanthematous macular or maculopapular eruptions. However, approximately 2 % of affected individuals develop severe or even life-threatening systemic immune reactions associated with organ involvement, requiring immediate diagnosis and treatment. Numerous drugs are capable of eliciting delayed-type hypersensitivity reactions, with antibiotics, anticonvulsant drugs, and the xanthine oxidase inhibitor allopurinol being the most common. Apart from genetic susceptibility, predisposing factors for the development of drug hypersensitivity reactions include high drug doses, polypharmacy, long treatment duration, female gender, as well as acute or chronic infections.


Assuntos
Erupção por Droga/diagnóstico , Hipersensibilidade Tardia/induzido quimicamente , Medicamentos sob Prescrição/efeitos adversos , Administração Oral , Administração Tópica , Corticosteroides/uso terapêutico , Erupção por Droga/tratamento farmacológico , Erupção por Droga/imunologia , Humanos , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , Hipersensibilidade Imediata/induzido quimicamente , Hipersensibilidade Imediata/tratamento farmacológico , Hipersensibilidade Imediata/imunologia , Infusões Parenterais , Testes Intradérmicos , Testes do Emplastro , Medicamentos sob Prescrição/administração & dosagem , Fatores de Risco , Viroses/complicações , Viroses/imunologia
17.
Mol Med Rep ; 16(5): 6248-6254, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901381

RESUMO

Allergy is an acquired hypersensitivity reaction of the immune system mediated by IgE­induced mast cell degranulation. In China, bacillus Calmette­Guerin extract (BCGE) has been shown to be clinically effective for regulating immunity, which enhances the resistance of the body to anaphylactic disease, infectious diseases and cancer. However, the mechanisms remain to be fully elucidated. The present study investigated the potential anti­allergic effects of BCGE in animal models of mast cell­dependent anaphylaxis and mechanisms of BCGE in mast cells. Anti­allergic actions of BCGE were evaluated in passive cutaneous anaphylaxis, dextran T40­induced scratching behavior mouse models, and in ovalbumin (OVA)­induced contraction of intestinal tube isolated from OVA­sensitized guinea pigs. Direct mast cell­stabilizing effects of BCGE were examined in mast cells from the abdominal cavity of OVA­sensitized rats. Anti­allergic signaling mechanisms of BCGE in mast cells were investigated by detection of cyclic adenosine monophosphate levels and protein kinase A expression in mast cells. It was observed that BCGE prevented OVA­induced cutaneous vascular hyperpermeability, skin itching, elevation in plasma histamine levels and abdominal cavity fluid mast cell degranulation in animal models, in a dose­dependent manner. BCGE also suppressed OVA­mediated guinea pig intestinal tube contraction in vitro. In addition, BCGE was found to increase the levels of interferon­Î³, and reduce the levels of interleukin­4 and OVA­sIg E levels in OVA­sensitized rats. BCGE also increased levels of cyclic adenosine monophosphate and the expression of protein kinase A in mast cells separated from the abdominal cavity fluid of OVA­sensitized rats. In conclusion, the results suggested that BCGE possesses anti­allergic activity by inhibiting IgE­induced mast cell degranulation, providing a foundation for the development of BCGE for the treatment of mast cell­mediated allergic disorders.


Assuntos
Antialérgicos/farmacologia , Bacillus/metabolismo , Hipersensibilidade/tratamento farmacológico , Mastócitos/efeitos dos fármacos , Anafilaxia Cutânea Passiva/efeitos dos fármacos , Animais , Antiasmáticos/farmacologia , Degranulação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Cobaias , Histamina/metabolismo , Hipersensibilidade Tardia/tratamento farmacológico , Imunoglobulina E/metabolismo , Camundongos , Ovalbumina/farmacologia , Ratos , Ratos Wistar
18.
Eur J Pharmacol ; 815: 156-165, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28899698

RESUMO

Betulinic acid (BA) is a naturally occurring triterpenoid with several biological properties already described, including immunomodulatory activity. Here we investigated the immunomodulatory activity of eight semi-synthetic amide derivatives of betulinic acid. Screening of derivatives BA1-BA8 led to the identification of compounds with superior immunomodulatory activity than BA on activated macrophages and lymphocytes. BA5, the most potent derivative, inhibited nitric oxide and TNFα production in a concentration-dependent manner, and decreased NF-κB activation in Raw 264.7 cells. Additionally, BA5 inhibited the proliferation of activated lymphocytes and the secretion of IL-2, IL-4 IL-6, IL-10, IL-17A and IFNÉ£, in a concentration-dependent manner. Flow cytometry analysis in lymphocyte cultures showed that treatment with BA5 induces cell cycle arrest in pre-G1 phase followed by cell death by apoptosis. Moreover, BA5 also inhibited the activity of calcineurin, an enzyme that plays a critical role in the progression of cell cycle and T lymphocyte activation. BA5 has a synergistic inhibitory effect with dexamethasone on lymphoproliferation, showing a promising profile for drug combination. Finally, we observed immunosuppressive effects of BA5 in vivo in mouse models of lethal endotoxemia and delayed type hypersensitivity. Our results reinforce the potential use of betulinic acid and its derivatives in the search for potent immunomodulatory drugs.


Assuntos
Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/imunologia , NF-kappa B/antagonistas & inibidores , Choque Séptico/tratamento farmacológico , Choque Séptico/imunologia , Triterpenos/química , Triterpenos/farmacologia , Amidas/química , Animais , Inibidores de Calcineurina/química , Inibidores de Calcineurina/farmacologia , Inibidores de Calcineurina/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hipersensibilidade Tardia/induzido quimicamente , Hipersensibilidade Tardia/metabolismo , Imunomodulação/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Células RAW 264.7 , Choque Séptico/induzido quimicamente , Choque Séptico/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Triterpenos/uso terapêutico
19.
Int J Mol Sci ; 18(7)2017 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-28672829

RESUMO

Palladium is frequently used in dental materials, and sometimes causes metal allergy. It has been suggested that the immune response by palladium-specific T cells may be responsible for the pathogenesis of delayed-type hypersensitivity in study of palladium allergic model mice. In the clinical setting, glucocorticoids and antihistamine drugs are commonly used for treatment of contact dermatitis. However, the precise mechanism of immune suppression in palladium allergy remains unknown. We investigated inhibition of the immune response in palladium allergic mice by administration of prednisolone as a glucocorticoid and fexofenadine hydrochloride as an antihistamine. Compared with glucocorticoids, fexofenadine hydrochloride significantly suppressed the number of T cells by interfering with the development of antigen-presenting cells from the sensitization phase. Our results suggest that antihistamine has a beneficial effect on the treatment of palladium allergy compared to glucocorticoids.


Assuntos
Alérgenos/imunologia , Antialérgicos/farmacologia , Antagonistas dos Receptores Histamínicos H1 não Sedativos/farmacologia , Hipersensibilidade Tardia/imunologia , Paládio/efeitos adversos , Terfenadina/análogos & derivados , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/imunologia , Edema/patologia , Feminino , Hipersensibilidade Tardia/tratamento farmacológico , Hipersensibilidade Tardia/patologia , Camundongos , Prednisolona/farmacologia , Transdução de Sinais , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Terfenadina/farmacologia
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