BACKGROUND: Currently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs.
OBJECTIVE: To determine and compare the effects oral of DPH and cetirizine on the immediate- and late-phase cutaneous allergic reactions in healthy dogs.
METHODS: Twelve healthy laboratory beagle dogs.
METHODS: The study was designed as a randomized, double-blinded crossover study in which each dog served as its own control; twice-daily oral DPH (2.2 mg/kg) or cetirizine (2 mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10 days before drug administration (baseline), during oral antihistamine administration on Day 6 and 10 days after last medication dosage. Global wheal scores (GWS) at 20 min and late-phase reactions (LPR) at 6 h post-injection were evaluated by an investigator blinded to the drug and the interventions.
RESULTS: Treatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. In all dogs, oral DPH and cetirizine reached plasma concentrations considered therapeutic in people. No adverse effect or behavioural changes were observed during the study.
UNASSIGNED: In conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.
UNASSIGNED: A ce jour, il n\'existe pas assez de preuve pour confirmer l\'efficacité de la diphenhydramine (DPH) orale pour prévenir la dégranulation mastocytaire et le relargage d\'histamine chez le chien. HYPOTHÈSES/OBJECTIFS: Déterminer et comparer les effets oraux de la DPH et de la cétirizine sur les réactions cutanées allergiques immédiates et retardées chez les chiens sains.
UNASSIGNED: Douze chiens beagle sains, de laboratoire. MATÉRIELS ET MÉTHODES: Cette étude est randomisée, croisée en double aveugle et chaque chien a servi comme son propre contrôle ; deux fois par jour, par voie orale, de la DPH (2,2 mg/kg) ou de la cétirizine (2 mg/kg) ont été administrées pendant six jours avec deux semaines de blanc thérapeutique. Les injections intradermiques d\'histamine, composé 48/80 (contrôle positif) et de solution saline (contrôle négatif) ont été réalisées sur le thorax droit 10 jours avant le traitement, au cours de l\'administration d\'antihistaminique au jour 6 et 10 jours après la dernière dose de traitement. Les scores globaux (GWS) à 20 min et les réactions retardées (LPR) à 6h après injection ont été évalués par un investigateur en aveugle pour la molécule et les interventions. RÉSULTATS: Le traitement avec la cétirizine réduit significativement les GWS et LRP de l\'histamine et du composé 48/80 comparé aux valeurs de base ; il n\'y avait pas de différence significative pour DPH. La DPH et la cétirizine orale ont atteints les concentrations plasmatiques considérées comme thérapeutiques chez l\'homme chez tous les chiens. Aucun effet secondaire ou de changement de comportement n\'a été observé au cours de l’étude.
UNASSIGNED: En conclusion, la cétirizine orale a été efficace pour prévenir les réactions allergiques cutanées sans effet secondaire chez le chien. La DPH orale n\'a pas montré d\'effet inhibiteur malgré les concentrations plasmatiques atteintes considérées comme efficaces chez l\'homme.
INTRODUCCIÓN: actualmente, no hay pruebas suficientes para confirmar la eficacia de la difenhidramina oral (DPH) para prevenir la degranulación de los mastocitos y la liberación de histamina en los perros. HIPÓTESIS/OBJETIVO: determinar y comparar los efectos orales de DPH y cetirizina en las reacciones alérgicas cutáneas inmediatas y tardías en perros sanos. ANIMALES: doce perros Beagle de laboratorio sanos. MÉTODOS Y MATERIALES: el estudio se diseñó como un estudio cruzado al azar, doble ciego, en el que cada perro sirvió como su propio control; se administró DPH oral dos veces al día (2,2 mg/kg) o cetirizina (2 mg/kg) durante seis días con un período de lavado de dos semanas. Las inyecciones intradérmicas de histamina, compuesto 48/80 (control positivo) y solución salina (control negativo) se realizaron en el tórax derecho 10 días antes de la administración del fármaco (línea basal), durante la administración de antihistamínico oral en el día 6 y 10 días después de la última dosis del medicamento. Los valores globales de la formación de pápula (GWS) a los 20 min y las reacciones de fase tardía (LPR) a las 6 h después de la inyección fueron evaluados por un investigador desconocedor de los fármacos y las intervenciones. RESULTADOS: el tratamiento con cetirizina redujo significativamente la histamina y GWS de el compuesto 48/80 y LPR en comparación con el valor inicial; no hubo diferencia significativa para DPH. La DPH oral y la cetirizina alcanzaron concentraciones plasmáticas consideradas terapéuticas en personas en todos los perros. No se observaron efectos adversos o cambios de comportamiento durante el estudio. CONCLUSIÓN E IMPORTANCIA CLÍNICA: en conclusión, la cetirizina oral fue efectiva para prevenir reacciones alérgicas cutáneas sin efectos adversos obvios en los perros. La DPH oral no mostró un efecto inhibidor a pesar de alcanzar concentraciones plasmáticas de fármacos que se consideran efectivas en las personas.
UNASSIGNED: Zurzeit gibt es nicht genug Evidenz, um die Wirkung von Diphenhydramin (DPH) per os auf eine Verhinderung der Mastzelldegranulation und den Histaminausstoss von Hunden zu bestätigen.
UNASSIGNED: Eine Bestimmung und der Vergleich der Wirksamkeit von DPH und Cetirizin per os auf die unmittelbare Spätphasenreaktion der allergischen Hautreaktionen bei gesunden Hunden.
UNASSIGNED: Zwölf gesunde Labor Beagles.
UNASSIGNED: Diese Studie wurde als randomisierte, doppel-blinde Crossover Studie designed, in der jeder Hund als seine eigene Kontrolle diente; zweimal täglich wurde DPH (2,2 mg/kg) oder Cetirizin (2 mg/kg) sechs Tage lang mit einer zwei-wöchigen Auswaschphase verabreicht. Es wurden intradermale Injektionen von Histamin, Compound 48/80 (Positivkontrolle) und Kochsalzlösung (Negativkontrolle) an der rechten Thoraxseite durchgeführt, bevor die Wirkstoffe verabreicht wurden (Nullpunkt), sowie während der Verabreichung von Antihistaminen per os am Tag 6 und 10 nach der letzten Wirkstoffdosis. Gesamtwerte der Quaddeln (GWS) nach 20 Minuten und nach den Spätphasereaktionen (LPR) 6h nach der Injektion wurden durch eine/n gegenüber Wirkstoffen und dem Ablauf geblindeten UntersucherIn evaluiert.
UNASSIGNED: Die Behandlung mit Cetirizin reduzierte die Histamin und Compound 48/80 GWS und LPR im Vergleich zum Nullpunkt signifikant; es bestand ein signifikanter Unterschied für DPH. Bei allen Hunden erreichten DPH per os und Cetirizin Plasmakonzentrationen, die beim Menschen als therapeutisch betrachtet werden. Es wurden keine Nebenwirkungen oder Verhaltensänderungen während dieser Studie beobachtet.
UNASSIGNED: Zusammenfassend war Cetirizin per os wirksam bei der Vermeidung von kutanen allergischen Reaktionen ohne offensichtliche Nebenwirkungen für die Hunde. DPH per os zeigte keine inhibitorische Wirkung, obwohl es Plasmawirkstoffkonzentrationen erreicht, die beim Menschen als wirksam betrachtet werden.
背景: 現在、犬の肥満細胞の脱顆粒とヒスタミン放出を防ぐためのジフェンヒドラミン(DPH)経口投与による有効性を確認する証拠は不十分である。 仮説/目的: 本研究の目的は、健常犬の即時型および遅発型皮膚アレルギー反応に対するDPHおよびセチリジンの経口投与による効果を決定し、比較することである。 被験動物: 実験用健常ビーグル犬12頭。 材料と方法: 本研究では、各犬を各々の対照として機能させるランダム化二重盲検クロスオーバー試験として設計した。 1日2回経口DPH(2.2 mg / kg)またはセチリジン(2 mg / kg)を6日間投与し、2週間のウォッシュアウト期間を設けた。ヒスタミン、化合物48/80(陽性対照群)および生理食塩水(院生対照群)の皮内注射は、薬物投与の10日前(ベースライン)、経口抗ヒスタミン薬投与中の6日目および最後の薬物投与10日後に右胸部で実施された。注射後20分後の全体膨疹スコア(GWS)および注射後6時間後の後期相反応(LPR)を、薬物および介入について知らされていない研究者が評価した。 結果: セチリジンによる治療は、ベースラインと比較してヒスタミンおよび化合物48/80におけるGWSおよびLPRを有意に減少させた。 DPHにおいて有意差は認めなかった。経口DPHおよびセチリジンは、すべての犬において、人で薬効があると考えられる血漿濃度に達していた。研究中に有害事象や行動の変化は観察されなかった。 結論と臨床的意義: 結論として、経口セチリジンは、犬に明らかな有害事象を与えることなく皮膚アレルギー反応を予防するのに効果的であった。経口DPHは、人に効果があると考えられる血漿中薬物濃度に達したにもかかわらず、抑制効果を示すことができなかった。.
背景: 目前,没有足够的证据证实口服苯海拉明 (DPH) 能预防犬肥大细胞脱颗粒和组胺释放。 假设/目的: 确定并比较 DPH 和西替利嗪经口给药,对健康犬速发型和迟发型皮肤过敏反应的影响。 动物: 实验室12只健康比格犬。 方法和材料: 本研究设计为随机、双盲交叉试验,每只犬作为自身对照;每日两次经口给予 DPH (2.2mg/kg) 或西替利嗪 (2mg/kg),持续6天,洗脱期为2周。给药前10天(基线)、第6天口服抗组胺药期间和末次给药后10天,在右侧胸部皮内注射组胺、化合物 48/80(阳性对照)和生理盐水(阴性对照)。不告知研究者药物和干预情况,使其盲评注射后20min的整体风疹评分 (GWS)和6h迟发反应 (LPR) 。 结果: 与基线相比,西替利嗪治疗显著降低了组胺和化合物 48/80的GWS和LPR;DPH无显著差异。在所有犬中,口服 DPH 和西替利嗪均达到了人体治疗血浆浓度。研究期间未观察到不良反应或行为变化。 结论和临床意义: 总之,口服西替利嗪可有效预防犬皮肤过敏反应,且无任何明显不良反应。尽管达到了在人体中有效的血浆药物浓度,但口服DPH未能显示抑制作用。.
UNASSIGNED: Atualmente, há evidencias insuficientes que confirmem a eficácia do uso de difenidramina (DPH) por via oral para prevenir a degranulação de mastócitos e a liberação de histamina em cães. HIPÓTESE/OBJETIVO: Determinar e comparar os efeitos de DPH e cetirizina por via oral nas fases imediatas e tardias das reações alérgicas cutâneas em cães saudáveis.
UNASSIGNED: Doze cães de laboratório da raça beagle saudáveis. MÉTODOS E MATERIAIS: Este estudo foi delineado como um estudo cruzado, duplo-cego e randomizado em que cada cão serviu de controle de si mesmo; cetirizina (2 mg/kg) ou DPH (2,2 mg/kg) foram administrados duas vezes ao dia por seis dias com um período de eliminação de duas semanas entre os tratamentos. Injeções intradérmicas de histamina, composto 48/80 (controle positivo) e salina (controle negativo) foram realizadas no tórax direito 10 dias antes da administração dos fármacos (tempo zero), durante a administração de anti-histamínico no Dia 6 e 10 dias após a última dose de medicamento. Escores globais de pápulas (GWS) em 20 minutos e reações tardias (LPR) em 6 h após foram avaliados por um investigador cego para a droga e para as intervenções.
UNASSIGNED: O tratamento com cetirizina reduziu significativamente os GWS de histamina e composto 48/80 e LPR comparado com o tempo zero e LPR comparado ao tempo zero; não houve diferença significativa para o DPH. Cetirizina e DPH atingiram, em todos os cães, concentrações plasmáticas consideradas terapêuticas em humanos. Não foram observados efeitos adversos e alterações comportamentais durante o período do estudo. CONCLUSÃO E SIGNIFICÂNCIA CLÍNICA: Em conclusão, a cetirizina oral foi eficaz na prevenção de reações alérgicas cutâneas sem nenhum efeito adverso óbvio nos cães. A DPH por via oral não demonstrou efeitos inibitórios apesar de ter atingido concentrações plasmáticas consideradas terapêuticas em humanos.

BACKGROUND: Mikania glomerata Spreng. (MG) and Mikania laevigata Sch. Bip. ex Baker (ML), popularly known as guaco, are medicinal plants similar in morphology, chemical composition and medicinal uses. Both species are often used and sold without distinction; however, it is believed that their chemical composition is different.
OBJECTIVE: Thus, the aim of this study is to investigate if the aqueous extract of MG and ML present similar anti-inflammatory activity to the point of being used interchangeably.
METHODS: Different doses of both extracts and coumarin were given to rats in different experimental models to assess the anti-inflammatory activity between these two species. For this, the animals were submitted to paw edema, pleurisy and degranulation of peritoneal mast cell and the extracts were also characterized by Ultra High Efficiency Liquid Chromatography coupled to Mass Spectrometry (UHPLC-MS).
RESULTS: The chromatographic method showed that ML presents ten times more coumarin than MG. Oral administration of MG, ML and coumarin inhibited paw edema induced by carrageenan (400 mg/kg, 55% inhibition; 400 mg/kg, 57% inhibition; 75 mg/kg, 38% inhibition; p < 0.05, respectively). MG, ML and coumarin treatment also inhibited the edema induced by compound 48/80 (400 mg/kg, 56% inhibition; 400 mg/kg, 69% inhibition; 75 mg/kg, 40% inhibition; p < 0.05, respectively). MG, ML and coumarin did not prevent mast cell degranulation and the consequent histamine release in Wistar rat peritoneal mast cells induced by compound 48/80. MG did not inhibit cell infiltration in pleurisy nor the highest dose tested, while ML decreased the leukocyte migration (200 and 400 mg/kg, 23% and 30% inhibition; p < 0.001, respectively) and, to a lesser extent, coumarin also reduced cell infiltration (10, 50 and 75 mg/kg; 15%, 16% and 17% inhibition; p < 0.001, respectively).
CONCLUSIONS: The variation of the results of the anti-inflammatory activity found in M. glomerata and M. laevigata demonstrates that these two species should not be used interchangeably. Coumarin, as already proven, has anti-inflammatory action however, we have suggested that it probably is not the only component responsible for this therapeutic effect in the extracts.

Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound 48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14 and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral hind paw scratching was determined using an automated recording device. The effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human and murine mast cells and the presence of SNAREs was determined using qPCR, immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced 48/80 and CQ induced scratching behavior starting on day 2 with reversal by day 21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells, however, Western blots did not. This study demonstrates the long-lasting anti-pruritic effects of two BoNT serotypes, in a murine pruritus model using two different mechanistically driven pruritogens. These data also indicate that BoNTs may have a direct effect upon mast cell degranulation.

Nonallergic hypersensitivity reaction (NHR) accounts for more than 77% of all immune-mediated immediate hypersensitivity reactions and has become a serious threat to public health. Here, proteomics was used to study the NHR mechanism of two typical substances, the compound 4880 and ovalbumin. Twelve different proteins were suggested as potential biomarkers for examining the NHR mechanism, and our results revealed that the mechanism mainly encompassed 2 processes, i.e., generation and effect processes. The generation process could be classified as direct stimulation, complement (classical and alternative), coagulation, kallikrein-kinin, and integrated pathways. Thus glutathione peroxidase 1, terminal complement complex (complement factor 4d and Bb), coagulation 13, kininogen-1, and IgE could be used as candidate biomarkers for the indication of the corresponding pathways respectively, the proteins were further confirmed by ELISA. And the effect process was mainly composed of histamine as well as proteins such as DCD and MYLPF, which could be used as important indices for the symptoms of NHR. Our study differs from previous studies in that C4880 was found to not only be involved in the direct stimulation pathway, but also in the activated complement and kallikrein-kinin pathways through the coagulation pathway. We also report for the first time that ovalbumin-induced NHR could be a combination of the coagulation, classical complement, and integrated pathways.

OBJECTIVE: To verify if the methylene blue (MB) administration prevents and/or reverses the compound 48/80 (C48/80)-induced anaphylactic shock in pigs.
METHODS: Female Dalland pigs were anesthetized and had the hemodynamic parameters recorded during the necessary time to administer some drugs and observe their effect. The animals were randomly assigned to one of the five groups: 1) control; 2) MB: the animals received a bolus injection of MB (2 mg/kg) followed by continuous infusion of MB (2.66 mg/Kg/h delivered by syringe infusion pump); 3) C48/80: the animals received a bolus injection of C48/80 (4 mg/kg); 4) C48/80+MB: the animals received a bolus injection of C48/80 (4 mg/kg) and 10 minutes after the C48/80 administration the animals received a bolus injection of MB (2 mg/kg) followed by continuous infusion of MB (2.66 mg/Kg/h delivered by syringe infusion pump); 5) MB+C48/80: the animals received a bolus injection of MB (2 mg/kg) and 3 minutes later they received a bolus injection of C48/80 (4 mg/kg).
RESULTS: The intravenous infusion of MB alone caused no changes in the mean arterial pressure (MAP) showing that the administered MB dose was safe in this experimental model. The C48/80 was effective in producing experimental anaphylactic shock since it was observed a decrease in both MAP and cardiac output (CO) after its administration. The MB did not prevent or reverse the C48/80-induced anaphylactic shock in this model. In fact, the MAP of the animals with anaphylactic shock treated with MB decreased even more than the MAP of the animals from the C48/80 group. On the other hand, the C48/80-induced epidermal alterations disappeared after the MB infusion.
CONCLUSIONS: Despite our data, the clinical manifestations improvement brings some optimism and does not allow excluding the MB as a possible therapeutic option in the anaphylactic shock.

We performed this study to demonstrate the applicability of the microelectrode array (MEA) to study electrophysiological changes of rat peritoneal mast cells in the presence of compound 48/80 under normal, Ca(2+)-free, Ca(2+)-free with EDTA, and Cl(-)-free conditions. The use of high extracellular K(+) (KCl, 150 mM), charybdotoxin (ChTX, 100 nM), and Cl(-)-free containing ChTX buffers verified that the hyperpolarizing signal was due to the activation of mainly K(+) and, to a lesser extent, Cl(-) channels. Compound 48/80 concentration-dependently shortened the latent periods (the onset of response) and increased both the spatial (the K(+) and Cl(-) hyperpolarizing field potentials, HFP) and temporal measurements (the duration of response). Ca(2+)-free buffer had no effect on the latent period of compound 48/80 but increased the HFP at high concentrations. The latent period increased while the HFP diminished when cells were equilibrated in Ca(2+)-free buffer containing EDTA. Durations of the HFP were generally longer when cells were in either Ca(2+)-free or Ca(2+)-free containing EDTA buffers than when cells were in normal buffer. The EC(50) values confirmed that effects were only affected in Ca(2+)-free buffer containing EDTA but not in Ca(2+)-free or Cl(-)-free buffers, further reinforcing the hypothesis that the presence of Ca(2+) is not essential to the action of compound 48/80. The present study is the first application of MEA to study rat peritoneal mast cells, and our results indicate that it could be of value in future pharmacological research on other non-excitable cells.

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