Histamine iontophoresis on the viability of random skin flap in rats / Iontoforese de histamina na viabilidade do retalho cutâneo randômico em ratos

PURPOSE: To evaluate the effects of the histamine iontophoresis on the random skin flap viability in rats. METHODS: Sixty adult male Wistar rats were used. A cranially-based dorsal skin flap measuring 10 x 4 cm was raised and a plastic barrier was placed between the flap and its bed. After the surgical procedure, the animals were randomized into four groups (G1-G4) (n=15 each group) as follows: G1 (control) - sham electrical stimulation, G2 (electrical stimulation) - direct current electrical stimulation, G3 (histamine) - histamine and sham electrical stimulation and G4 (histamine iontophoresis) - transdermal iontophoresis of histamine. In all groups the procedures were performed immediately after the surgery and on the two subsequent days. The percentage of flap necrosis was measured on the seventh postoperative day. RESULTS: The mean and the respective standard deviation of the percentage of flap necrosis areas were as follows: G1 (control) - 47.87 ± 9.13 percent, G2 - 51.49 ± 8.19 percent, G3 - 46.33 ± 8.32 percent and G4 - 30.82 ± 11.25 percent. The G4 group presented a significantly smaller amount of flap necrosis when compared to the other groups (p<0.001). CONCLUSION: The topical administration of the histamine by iontophoresis was effective to increase the viability of the random skin flaps in rats.

OBJETIVO: Avaliar o efeito da iontoforese de histamina na viabilidade do retalho cutâneo randômico em ratos. MÉTODOS: Foram utilizados 60 ratos adultos e machos da linhagem Wistar. O retalho cutâneo de base cranial, medindo 10x4 cm, foi elevado no dorso dos animais e uma barreira plástica foi interposta entre o retalho e a área doadora. Após o procedimento operatório, os animais foram distribuídos aleatoriamente em 4 grupos (G1-G4) (n=15 em cada grupo) a saber: G1 (controle) - simulação da estimulação elétrica, G2 (estimulação elétrica) - estimulação elétrica com corrente direta, G3 (histamina) - histamina e simulação da estimulação elétrica e G4 (iontoforese de histamina) - iontoforese transdérmica de histamina. Em todos os grupos os procedimentos foram realizados imediatamente após a operação e nos 2 dias subseqüentes. A porcentagem de área de necrose foi avaliada no 7º dia pós-operatório. RESULTADOS: As médias e respectivos desvios-padrão das porcentagens de área de necrose foram: G1 (controle) - 47,87 ± 9,13 por cento, G2 - 51,49 ± 8,19 por cento, G3 - 46,33 ± 8,32 por cento and G4 - 30,82 ± 11,25 por cento. O grupo G4 apresentou menor média de área de necrose quando comparado aos demais grupos (p<0,001). CONCLUSÃO: A administração tópica de histamina por iontoforese aumentou a viabilidade do retalho cutâneo randômico em ratos.

Comparative efficacy of levocetirizine, desloratidine and fexofenadine by histamine wheal suppression test.

BACKGROUND: Histamine is the major mediator of allergic reactions. Newer H1 antihistaminics like levocetirizine, fexofenadine, and desloratadine are used in the treatment of seasonal and perennial allergic rhinitis and urticaria. The ability to block the cutaneous response to intradermal histamine is used to evaluate the potential of antihistamines. AIMS: To compare the potency, onset, and duration of action of the commonly used antihistamines-levocetirizine, fexofenadine, and desloratadine. METHODS: Thirty volunteers were given three single doses of levocetirizine, fexofenadine and desloratadine at weekly intervals. A pretest was performed by using the intradermal histamine prick test. After administration of the drugs, the intradermal test was repeated at (1/2), 1, 2, 3, 6 and 24 h, and the sizes of the wheal were measured. The mean values were taken and were compared by using Levene's t-test. RESULTS: At 30 min, fexofenadine showed a statistically significant suppression of wheal size compared to levocetirizine and desloratadine. Two and three hours after administration, levocetirizine and fexofenadine showed statistically significant inhibition of wheal size while only levocetirizine had this effect after six hours when compared to desloratadine. Desloratadine showed greater inhibition of wheal size at the end of 24 h when compared to levocetirizine and fexofenadine but this was not statistically significant. CONCLUSIONS: Fexofenadine had the earliest onset of action while levocetirizine showed maximum inhibition of wheal response after three and six hours.

Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats

OBJETIVO: Avaliar o potencial benéfico da histamina combinada ao melfalano, na perfusão de membro isolado (PMI), como alternativa à combinacão TNF-alfa mais melfalano, no tratamento de sarcomas de partes moles irressecaveis em extremidades, em ratos de linhagem Brown Norway (BN). MÉTODOS: 20 ratos BN foram submetidos a implantacão de fragmentos de fibrosarcoma singênico BN-175 na pata traseira direita. Em cerca de 7-10 dias o tumor atingiu um diâmetro médio de 12-15 mm e foram aleatóriamente divididos em quatro grupos (controle, melfalano,histamina em doses progessivas combinada ao melfalano e histamina) sendo submetidos a PMI experimental por 30 minutos. Os tumores foram então medidos diariamente com o uso de paquímetro e o volume tumoral calculado. RESULTADOS: As curvas de resposta mostram um efeito significativo da combinacão de Histamina na concentracão de 200 mg/mL ao melfalano, com 66% de resposta global incluindo 33% de respostas completas (p < 0.01). Não houve efeitos colaterais sistêmicos e localmente apenas edema leve e transitório nos animais tratados com histamine. CONCLUSAO: A histamina em combinacão com o melfalano apresenta um efeito promissor na PMI garantindo maiores investigacões do seu mecanismo de acão e do seu potencial uso na perfusão de órgãos.

Oropharyngeal Angioedema Induced by Inhaled Histamine

Inhaled histamine used to measure airway responsiveness produces some side effects more frequently than does methacholine. It is possible that the inhaled histamine induces the side effects in asthmatics with increased end organ responsiveness to histamine. A 56-yr-old woman with chronic idiopathic angioedema presented with asthma-like symptoms. Methacholine challenge test was performed, with a negative result. Five days later, histamine inhalation test was done. FEV1 fell by 37% after inhalation of histamine concentration of 8 mg/mL. Immediately thereafter, severe angioedema on face, lips, and oropharyngeal area, foreign body sensation at throat, and hoarseness occurred. To assess end organ responsiveness to histamine, skin prick tests with doubling concentrations of histamine (0.03-16 mg/mL) were carried out on the forearm of the patient and six age- and sex-matched asthmatic controls. The wheal areas were measured. The patient showed greater skin responses than the controls. Regression analysis showed that the intercept and slope were greater than cut-off levels determined from six controls. The patient showed an increased skin wheal response to histamine, indicating the enhanced end organ responsiveness to histamine, which is likely to contribute to the development of the oropharyngeal angioedema by inhaled histamine.

Efecto del Bromuro de ipratropio sobre la broncoconstriccion por histamina en sujetos con obstruccion cronica al flujo aereo / Effect of ipratropium bromide on histamine-induced bronchoconstriction in subjects with chronic airway obstruction

El bromuro de ipratropio (B I) es un agente anticolinérgico muy recomendado para el tratamiento de la obstrucción crónica al flujo aéreo (EPOC). No obstante, no hay definición respecto a la existencia de efectos preventivos (no broncodilatadores) del BI. Con el fin de evaluar la acción del BI (80 µg en aerosol) ante una prueba de histamina se estudiaron 9 sujetos (hombres) con EPOC moderada, mediante un diseño doble ciego, aleatorio, controlado y cruzado entre placebo y BI. Tenían una edad promedio (ñ error standard de media) = 57,9 ñ 2,4 años con antecedentes de tabaquismo de 54,6 ñ 5,1 paquete-años y un FEV1 basal = 1,36 ñ 0,08 litros (47,2 ñ 3,8 percent del teórico).La hiperreactividad bronquial a la histamina en el día control fue logPC20 =-0,54 ñ 0,24 mg/ml (media geométrica: 0,27 mg/ml). El BI produjo un aumento significativo en el FEV1 basal; aunque no hubo correlación entre la obstrucción basal (FEV1, FEV1/FVC percent) y la broncodilatación con la hiperreactividad (logPC20). El BI redujo la broncoconstricción por histamina (logPC20 BI = -0,15 ñ 0,17 mg/ml; media geométrica [MG] = 0,70 mg/ml) en comparación con placebo (logPC20 post placebo = -0,76 ñ 0,22 mg/ml [MG = 0,17 mg/ml]; P = 0,018) y la dosis doble fue para BI = 2,02 ñ 0,68 vs placebo = -0,62 ñ 0,79; p: 0,024. Tanto el fenoterol como el BI revirtieron totalmente la caída del FEV1 al final de la prueba de histamina. Se concluye que el BI mostró un efecto protector ante la histamina en estos sujetos con diagnóstico de EPOC moderada

Histamine induced decrease of lecithin levels in broncho-alveolar lavage fluid of rats is mediated by H2 receptor.

Lecithin, a major surface active substance of the surfactant system of the lung, was estimated in broncho-alveolar lavage (BAL) fluid in four groups of healthy adult male albino rats. Rats from group I were not administered any drug and acted as controls. Group II were administered histamine diphosphate. Group III were given H1 blocker (pyrilamine maleate) followed by histamine diphosphate. Group IV received H2 blocker (ranitidine hydrochloride) followed by histamine diphosphate. Lecithin content of BAL fluid in the control group was compared with that in the other three groups. A significant decrease in lecithin content was observed in the rats that received either histamine diphosphate or H1 blocker followed by histamine diphosphate. However, compared to control rats no significant difference in lecithin content was seen in rats that received H2 blocker followed by histamine diphosphate. The results clearly indicate that the decrease in surface active lecithin content in BAL fluid following administration of histamine diphosphate was unaffected by prior administration of H1 blocker, but was blocked by prior administration of H2 blocker. It was concluded that histamine induced decrease in lecithin content of BAL fluid is mediated through H2 receptors. Since the predominant source of intra-alveolar lecithin are Type II cells of the alveolar epithelium, It is possible that Type II cells have H2 receptors, stimulation of which resulted in decreased intraalveolar lecithin.

Ranitidina, inhibidor de la permeabilidad vascular en la rata / Inhibitory effects of ranitidine on the vascular permeability in rat

La alta afinidad de la ranitidina hacia el receptor histaminérgico H2 y la sospecha de su participación en cambios de permeabilidad vascular, nos motivo a investigar si la ranitidina tiene efectos inhibitorios sobre los cambios en la permeabilidad provocados por la histamina. Para lograr este objetivo, se utilizaron 3 lotes de ratas variedad Wistar: Lote control, lote histamina y lote ranitidina + histamina. Se determinaron las concentraciones de proteínas totales, albúmina, sodio y cloro como indicadores de cambios en la permeabilidad vascular. Nuestros resultados demuestran parcialmente, que la ranitidina inhibe los incrementos de permeabilidad provocados por la histamina. Aunque clásicamente se ha atribuido al receptor H1, la regulación de la permeabilidad inducida por histamina, es probable que el receptor H2 también este involucrado tal como se demostró en este trabajo al bloquear su activación con ranitidina

Effect of histamine on lecithin content in broncho-alveolar lavage fluid of rat.

Deficiency of surfactant in alveoli leads to increased resistance to breathing. Histamine is a mediator in allergic respiratory diseases. Though the bronchoconstrictor effect of histamine is well recognised, histamine may have additional actions that contribute to pathogenesis in these diseases. The present study aimed to observe the effect of histamine on lecithin, a major component of alveolar surfactant. Lecithin content in broncho-alveolar lavage (BAL) fluid of healthy adult male rats was estimated by enzymatic method using Boehringer-Mannheim kits. Lecithin content in these control animals was compared with that in three groups of healthy adult male rats following subcutaneous administration of 0.06 mg of histamine diphosphate at 10 minutes, 30 minutes and 60 minutes intervals, respectively. A significant reduction in lecithin levels in BAL fluid was observed up to one hour after administration of histamine. The results indicate a possible additional action of histamine in the pathogenesis of allergic respiratory diseases.

Evaluation of threshold criteria for the nasal histamine challenge test in perennial allergic rhinitis.

Nasal reactivity to histamine was determined in patients with perennial allergic rhinitis and in control subjects. A histamine titration method delivered by a metered dose pump was used. Stuffiness, itching, and the number of sneezes were recorded, nasal secretions measured, and nasal airway resistance was recorded by active anterior rhinomanometry. Increased nasal reactivity to histamine was observed among rhinitic patients and inversely correlated with the severity of nasal symptoms. A 3-fold increase of post-saline nasal airway resistance (NAR) best differentiated the nasal responses to histamine in rhinitic patients from those in control subjects. A histamine dose of < or = 2.5 microg provoked a 3-fold increase in NAR, strongly suggesting moderate or severe symptomatic rhinitis in most cases. Nasal provocation techniques might be a useful tool for objectively assessing disease severity and response to treatment in perennial allergic rhinitis.

Alteraciones electrolíticas inducidas por histamina exógena en ratas / Electrolytic alterations induced by exogen histamine in rats

La liberación de histamina desde diversos tipos celulares promueve la dilatación vascular, incrementa la frecuencia cardiaca y la permeabilidad vascular. Debido a que la permeabilidad vascular ha sido poco considerada como factor inductor de varias alteraciones fisiológicas, en este artículo se evalúan las alteraciones a nivel de las concentraciones de electrólitos séricos en ratas albinas. Para lograr esto, se formaron tres grupos de organismos; el control y dos experimentales denominados A y B. Al grupo A se le inyectó 1 µg de histamina / kg de peso corporal, en tanto que al grupo B se le inyectaron 10 µg de histamina / kg de peso. El Na+ y el C1- mostraron incrementos significativos en el grupo B. El K+ sufrió incrementos significativos en ambos grupos. El Ca++ no experimentó ningún cambio. Estos resultados muestran una probable movilización de Na+ y C1- desde el espacio intersticial. El origen del incremento de K+ es incierto, sin embargo, quizás proceda desde las células sanguíneas, vasculares o cardiacas. La histamina liberada provoca alteraciones homeostáticas a nivel de los electrólitos séricos pero han sido poco valoradas en la práctica clínica

Central serotonergic and histaminergic modulation of peripheral inflammation and nociception in rats.

Possible central serotonergic and histaminergic modulation of acute peripheral inflammation was investigated in rats, adopting the formaldehyde-induced acute pedal inflammation as an experimental model. Intracerebroventricular (icv) administration of central inhibitory neurotransmitter, serotonin and its precursor, 5-hydroxytryptophan (5-HTP) attenuated the oedema volume and exudate protein content alongwith augmentation in pain threshold. On the contrary, cyproheptadine, a 5-HT-receptor antagonist and selective serotonin synthesis inhibitor, parachlorophenylalanine (PCPA) produced oedema augmenting and pro-nociceptive effects besides elevating the protein content of the exudate. Centrally administered histamine attenuated pedal oedema, nociception as well as protein concentration in oedema fluid. Cimetidine, an H2 histaminergic receptor blocker did not produce any significant effect on inflammation.

Comparación de la potencia de drogas conveniencia de expresar la dosificación en molaridad / Comparison of durg potency. Convinience of expressing the dosification in moles

Se comparó la potencia del diclorhidrato de histamina en relación con su sal de fostatocido mediante el método de Litchfield y Wilcoxon de determinación de dosis letales en el ratón, y el método de "los cuatro puntos" en tiras de fleon aislado de cobayo. Se encontr'o que tanto in vivo como in vitro la potencia relativa difiri'o significativamente, al efectuar los c'alculos tomando las dosis o concentraciones en unidades que no reflejan la masa activa de la droga (g ó mg/kg y g ó mg/L), pero no hubo diferencias significativa cuando dichas dosificaciones se expresaron en moles/kg o moles/L según el tipo de experimento. Se concluyó que para obtener la verdadera relación de potencia entre drogas la comparación debe realizarse mol a mol tanto in vivo como in vitro, siendo lo más adecuado utilizar las dosis o concentraciones moleculares de las drogas que se comparan

Antihistaminic efficacy of Ranitidine with & without Dimethendine maleate on histamine-induced cutaneous reactions.

The effect of Ranitidine, the H2-receptor antagonist, was investigated on cutaneous response to intradermal injection of histamine in healthy volunteers in a controlled, randomized, cross over study. The response was compared with that of the H1-receptor blocker; Dimethendine maleate used alone and in combination with the two antagonists. Reduction in the wheal area was significant in subjects pretreated with Ranitidine alone (P less than 0.05), and Dimethendine maleate alone (P less than 0.05); the combination of the two antagonists, did not produce additional reduction. Reduction in erythema area was not significant with Dimethendine maleate alone, but significant with Ranitidine alone (P less than 0.01). With the combination of the two antagonists the reduction was not more significant than with Ranitidine alone. The flare response scoring on visual analogue scale was not reduced significantly by Dimethendine maleate alone but reduced significantly by Ranitidine alone (P less than 0.10), and by combination of Ranitidine and Dimethendine maleate (P less than 0.05). Thus, Ranitidine appears to be more effective than Dimethendine maleate in reducing the erythema area and intensity of flare response and equieffective in reducing wheal response to histamine injection.

Broncoprovocaçäo com histamina e metacolina em crianças com asma brónquica e em controles normais / Bronchoprovocation with histmine and methacholine in Brazilian asthmatic and normal children

Submetemos 31 crianças asmáticas e 20 crianças controles "normais" a testes de broncoprovocaçäo com histamina e metacolina. A histamina e a metacolina foram diluídas em soluçäo salina e administradas por via inalatória, através de um nebulizador de De Vilbiss 645, com obturador nasal. Foram usadas concentraçöes crescentes de ambas as drogas: 0,025; 0,125; 0,25; 1,0; 2,0; 8,0; 16,0; 32,0 e 64,0 mg/ml para histamina e 0,025; 0,25; 1,0; 2,5; 10,0; 25,0 e 50,0 mg/ml para metacolina. Medidas do VEF1 foram realizadas um e dois minutos após inalaçäo da soluçäo salina e após inalaçäo de cada uma das concentraçöes em ambas as provas. Queda do VEF1 em 20% ou mais em relaçäo ao VEF1 basal (após soluçäo salina) interrompeu a prova. Com os dados obtidos foi construída uma curva log dose-resposta e por interpolaçäo linear dos dois últimos pontos desta curva foi encontrada a concentraçäo cumulativa capaz de produzir queda de 20% do VEF1 (PC20VEF1). A média da PC20 VEF1 obtida para crianças asmáticas foi significantemente menor que a média do grupo controle, tanto para a histamina como para a metacolina. Näo houve diferença estadística entre os tempos estudados (um a dois minutos). Para a metacolina houve uma evidente diferenciaçäo nas doses capazes de induzir a PC20VEF1 entre asmáticos e controles, ou seja, todos os asmáticos apresentaram uma PC20VEF1 com concentraçäo de metacolina igual ou inferior a 2 mg/ml. Com a histamina, houve certa interposiçäo entre os grupos. O TBP com histamina apresentou especificidade de 100% e sensibilidade de 80%, enquanto a metacolina apresentou especificidade e sensibilidade de 100%

Histamine bronchoprovocation tests in subjects with gastro-oesophageal reflux disease.

The relationship of gastro oesophageal reflux (GER) with bronchial asthma has already been well documented in asthmatic subjects and it has been postulated that their asthma might have been caused by GER disease. Thus, it was planned to establish an association, if any, between GER and increased bronchial reactivity by histamine broncho provocation. The study was done in 25 GER disease patients and 15 controls. The difference in bronchial reactivity between the two groups was found to be significant (p less than 0.01). It was concluded that GER subjects expressed greater bronchial reactivity and it has been discussed that at a later stage of life they may be more prone to develop asthma.

Inhibition of gastric acid secretion by cholinergic stimulation of the lateral hypopthalamic area

Cholinergic stimulation of the lateral hypothalamic area with carbachol (1 microng in 1 micronl) markedly inhibited gastric acid secretion in the anesthetized rat. Inhibition was bloced by prior microinjection of atropine (4 microng/micronl) into the same brain area and was accompanied by an increased soldium content in the stomach. Muscarinic receptor mediated cholinergic inhibitory influence of the hypothalamus on gastric acid secretion is suggested by these results

Funçäo tireoideana do rato tratado com dieta aterogênica e cimetidina / Thyroid gland function of rats treated with atherogenic diet and cimetidine

Determinou-se, em ratos Sprague-Dowley machos e jovens, o efeito de dietas com conteúdo lipídico variável e de tratamento com cimetidina na funçäo da glândula tireóide, durante o período de 70 dias. Avaliando a funçäo tireoideana através de vários parâmetros, determinou-se que estes variam de forma diferente de acordo com a estimativa do nível funcional sob controle do pesquisador, contudo, determinou-se que as dietas ricas em banha e óleo de oliva, além de colesterol e sais biliares, determinam diminuiçäo da capacidade de concentrar iodeto da glândula tireóide, avaliado pela relaçäo T/P, enquanto que a dieta enriquecida em óleo de soja incrementa a relaçäo T/P. O tratamento com cimetidina permite detectar significâncias objetivas apenas no índice de conversäo (PBI/I 131), porque esta aumenta em condiçöes de tratamento com cimetidina, particularmente em condiçöes de dieta rica em banha ou óleo de oliva. Postula-se que a cimetidina poderia interferir a dois níveis diferentes como bloqueador ou antagonista dos receptores H2 da histamina: a nível hipotalâmico (diminuindo a secreçäo de TRH e consequentemente de TSH) e a nível tireoideano (facilitando a secreçäo dos hormônios tireoideanos, talvez por mecanismo H1)

Thermoregulatory response in rats following administration of histamine in different CSF compartments.

Recently histamine is being considered as an important neurotransmitter/neuromodulator in the central nervous system. This has been supported from the present observations with regard to thermoregulatory responses elicited following histamine administration into different CSF compartments. Administration of histamine into the right lateral cerebral ventricle of rats showed a dose dependent fall in rectal temperature. This hypothermic response was evident only at moderately low or at thermoneutral ambient temperature. Administration of histamine into fourth ventricle produced hypothermic response at low ambient temperature and hyperthermia at thermoneutral ambient temperature, which was no longer observed when the ambient temperature remained above the thermoneutral zone. Infusion of histamine into spinal subarachnoid space produced hyperthermia which developed very slowly. However, the infusion of histamine into the subarachnoid space around the brain stem did not exhibit any change in rectal temperature. The significance of these observations has been discussed.