Application of capillary zone electrophoresis to determine second-generation H1 antihistaminic drugs, loratadine and rupatadine

Abstract The second generation of H1 antihistamines from the piperidine group are often used for treating allergic diseases due to their action on histaminic receptors, the primary mediator of allergy. Moreover, the antihistamines have anti-inflammatory action, mediated through platelet-activating factor blocking activity. A simple and rapid capillary zone electrophoresis method was developed and validated for the determination of loratadine (LOR) and rupatadine (RUP) in tablets. The analyses were carried out using a fused silica capillary of 50.2 cm (40 cm effective length), 75 µm i.d. The background electrolyte was composed of boric acid 35 mmol/L, pH 2.5. Voltage of 20 kV, hydrodynamic injection of 3447.3 Pa for 3s, temperature at 25 ºC, and UV detection at 205 nm were applied. Electrophoretic separation was achieved at 1.8 and 2.8 min for RUP and LOR, respectively. The method was linear for both drugs in a range of 50.0 to 400.0 µg/mL (r>0.99). The limits of detection and quantification were 46.37 and 140.52 µg/mL, for LOR and 29.60 and 89.69 µg/mL for RUP respectively. The precision was less than 5.0 % for both drugs. The average recovery was approximately 100 %. The proposed novel method can significantly contribute to the rapid detection of counterfeit products and in quality control of drug products containing antihistamines

Effect of ketotifen fumarate on experimental autoimmune orchitis and torsion of the spermatic cord / 亚洲男科学杂志(英文版)

The aim of this work was to study effects of ketotifen fumarate (KF) on prevention of tissue damage in testes of rats with experimental autoimmune orchitis (EAO) and on the contralateral testis in a model of prolonged testicular cord torsion (TCT). Rats with EAO or TCT were injected intraperitoneally once daily with KF or saline solution (vehicle group). Incidence and severity of testicular damage were evaluated by histopathology using an EAO score or a Johnsen score. Mast cells (MC) were identified by histochemistry and quantified. In EAO model, KF significantly reduced severity of histopathological testicular damage compared to rats in the vehicle group. KF also reduced the number of testicular MC compared to vehicle group. Similarly, in TCT model, multifocal damage of the contralateral testis was observed 30 days after testicular torsion characterized by sloughing of the germinal epithelium, seminiferous tubule atrophy, and interstitial edema. Focal signs of inflammation and fibrosis of seminiferous tubular walls were also observed. In contrast, sections of contralateral testis of rats injected with KF and killed 30 days after surgery showed normal histological features. A significant decrease in the number of MC was observed in rats treated with KF compared to untreated animals. In conclusion, we demonstrated that treatment with KF reduced testicular inflammatory process and MC infiltrates in both EAO and TCT models. The results suggest a promising treatment for infertile male patients with testicular pathologies associated with inflammation and germ cell loss.

Suppression of wheal and flare in histamine test by the main H1 antihistamines commercialized in Brazil

Abstract: Background: Several dermatoses are mediated by histamine, such as urticaria, angioedema, and papular urticaria. There are no Brazilian studies comparing the potency of antihistamines. Objectives: To evaluate the tolerability and efficacy of the main commercial brand and generic H1 antihistamines, regarding the suppression of the wheal and flare to the histamine test. Methods: A quasi-experimental, open study with 10 healthy adults submitted to the histamine test on the ventral aspect of the forearms. After 20 minutes, wheal and flares were measured. The tests were performed after two hours of intake of dexchlorpheniramine, hydroxyzine, levocetirizine, fexofenadine, cetirizine, loratadine, ebastine, desloratadine, epinastine and rupatadine, as well as generics of loratadine, cetirizine and fexofenadine. Results: All antihistamines presented a reduction in the wheal compared to the control (p <0.02), as well as in the flare, except for rupatadine (p = 0.70). In the internal comparison, cetirizine, fexofenadine, epinastine, levocetirizine, dexchlorpheniramine and hydroxyzine were the most potent, with no difference between them (p > 0.1). As for halo, cetirizine, epinastine, hydroxyzine and fexofenadine were the most potent, with no difference between them (p > 0.1). The most common adverse effect was drowsiness, which was more prevalent among first-generation drugs (p < 0.01). Generic loratadine, fexofenadine and cetirizine halos were higher than their controls (p <0.03).. Study limitations: A single-center study evaluating only aspects related to histamine. Conclusions: Brazilian commercial antihistamines presented different profiles of inhibition of wheal and flares in the histamine test, as well as adverse effects. Generic loratadine, fexofenadine and cetirizine presented larger flares than brand drugs.

Investigation of the antioxidant effects of pheniramine maleate and nebivolol on testicular damage in rats with experimentally induced testis torsion

Abstract Purpose: To investigate the biochemical, histopathologic, and spermatogenetic changes in the detorsionated testicle after experimental torsion and to study the antioxidant effects of pheniramine maleate and nebivolol. Methods: Twenty-four Sprague-Dawley male rats were divided into 4 groups: Group 1: Sham; Group 2: Torsion/Detorsion (T/D); Group 3: T/D + Pheniramine maleate (PM); Group 4: T/D + Nebivolol (NB) group. Paroxanase (PON), total antioxidant status (TAS), total oxidant status (TOS), and oxidative stres index (OSI) were measured, and spermatogenetic and histopathologic evaluation was performed in tissue and blood samples. Results: The evaluation of tissue TAS indicated no statistically significant difference in Group 3 compared to Group 2. A statistically significant increase was detected in Group 4 compared to Group 2. Serum PON levels revealed a statistically significant increase in Groups 3 and 4 compared to Groups 1 and 2. The Johnsen testicular biopsy score decreased in Groups 3 and 4, but the decrease was not statistically significant. Conclusions: Pheniramine maleate and nebivolol have antioxidant effects against ischemia-reperfusion damage. They also support tissue recovery, which is more significantly observed by nebivolol.

The effect of pheniramine on fentanyl-induced cough: a randomized, double blinded, placebo controlled clinical study / Efeito de feniramina sobre a tosse induzida por fentanil: estudo clínico, randômico, duplo-cego e controlado com placebo

Abstract Background and objectives: There are many studies conducted on reducing the frequency and severity of fentayl-induced cough during anesthesia induction. We propose that pheniramine maleate, an antihistaminic, may suppress this cough. We aim to observe the effect of pheniramine on fentanyl-induced cough during anesthesia induction. Methods: This is a double-blinded, prospective, three-arm parallel, randomized clinical trial of 120 patients with ASA (American Society of Anesthesiologists) physical status III and IV who aged ≥18 and scheduled for elective open heart surgery during general anesthesia. Patients were randomly assigned to three groups of 40 patients, using computer-generated random numbers: placebo group, pheniramine group, and lidocaine group. Results: Cough incidence differed significantly between groups. In the placebo group, 37.5% of patients had cough, whereas the frequency was significantly decreased in pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p = 0.0007 and p = 0.0188, respectively). There was no significant change in cough incidence between pheniramine group (5%) and lidocaine group (15%) (Fischer exact test, p = 0.4325). Cough severity did also change between groups. Post Hoc tests with Bonferroni showed that mean cough severity in placebo differed significantly than that of pheniramine group and lidocaine group (p < 0.0001 and p = 0.009, respectively). There was no significant change in cough severity between pheniramine group and lidocaine group (p = 0.856). Conclusion: Intravenous pheniramine is as effective as lidocaine in preventing fentayl-induced cough. Our results emphasize that pheniramine is a convenient drug to decrease this cough.

Resumo Justificativa e objetivos: Há muitos estudos sobre a redução da frequência e da gravidade da tosse induzida por fentanil durante a indução da anestesia. Propomos que maleato de feniramina, um anti-histamínico, pode suprimir essa tosse. Nosso objetivo foi observar o efeito de feniramina sobre a tosse induzida por fentanil durante a indução da anestesia. Métodos: Este é um estudo clínico prospectivo, de três braços paralelos, randômico e duplo-cego, de 120 pacientes com estado físico ASA III e IV (de acordo com a Sociedade Americana de Anestesiologistas), ≥ 18 anos e programados para cirurgia cardíaca aberta eletiva sob anestesia geral. Os pacientes foram divididos aleatoriamente em três grupos de 40 pacientes cada, com números aleatórios gerados por computador: grupo placebo, grupo feniramina e grupo lidocaína. Resultados: A incidência de tosse diferiu significativamente entre os grupos. No grupo placebo, 37,5% dos pacientes apresentaram tosse, enquanto que a frequência foi significativamente reduzida no grupo feniramina (5%) e no grupo lidocaína (15%) (teste exato de Fischer, p = 0,0007 e p = 0,0188, respectivamente). Não houve alteração significativa na incidência de tosse entre os grupos feniramina (5%) e lidocaína (15%) (teste exato de Fischer, p = 0,4325). A gravidade da tosse também alterou entre os grupos. Testes post hoc com Bonferroni mostraram que a média da gravidade da tosse no grupo placebo diferiu significativamente das médias dos grupos feniramina e lidocaína (p < 0,0001 e p = 0,009, respectivamente). Não houve alteração significativa na gravidade da tosse entre o grupo feniramina e grupo lidocaína (p = 0,856). Conclusão: Feniramina por via intravenosa tem a mesma eficácia que lidocaína na prevenção da tosse induzida por fentanil. Os resultados enfatizam que feniramina é um medicamento conveniente para diminuir essa tosse.

Modulatory effects of taurine on jejunal contractility

Taurine (2-aminoethanesulfonic acid) is widely distributed in animal tissues and has diverse pharmacological effects. However, the role of taurine in modulating smooth muscle contractility is still controversial. We propose that taurine (5-80 mM) can exert bidirectional modulation on the contractility of isolated rat jejunal segments. Different low and high contractile states were induced in isolated jejunal segments of rats to observe the effects of taurine and the associated mechanisms. Taurine induced stimulatory effects on the contractility of isolated rat jejunal segments at 3 different low contractile states, and inhibitory effects at 3 different high contractile states. Bidirectional modulation was not observed in the presence of verapamil or tetrodotoxin, suggesting that taurine-induced bidirectional modulation is Ca2+ dependent and requires the presence of the enteric nervous system. The stimulatory effects of taurine on the contractility of isolated jejunal segments was blocked by atropine but not by diphenhydramine or by cimetidine, suggesting that muscarinic-linked activation was involved in the stimulatory effects when isolated jejunal segments were in a low contractile state. The inhibitory effects of taurine on the contractility of isolated jejunal segments were blocked by propranolol and L-NG-nitroarginine but not by phentolamine, suggesting that adrenergic β receptors and a nitric oxide relaxing mechanism were involved when isolated jejunal segments were in high contractile states. No bidirectional effects of taurine on myosin phosphorylation were observed. The contractile states of jejunal segments determine taurine-induced stimulatory or inhibitory effects, which are associated with muscarinic receptors and adrenergic β receptors, and a nitric oxide associated relaxing mechanism.

Effect of histamine H1 and H2 receptor antagonists, microinjected into cerebellar vermis, on emotional memory consolidation in mice

This study investigated the effects of histamine H1 or H2 receptor antagonists on emotional memory consolidation in mice submitted to the elevated plus maze (EPM). The cerebellar vermis of male mice (Swiss albino) was implanted using a cannula guide. Three days after recovery, behavioral tests were performed in the EPM on 2 consecutive days (T1 and T2). Immediately after exposure to the EPM (T1), animals received a microinjection of saline (SAL) or the H1 antagonist chlorpheniramine (CPA; 0.016, 0.052, or 0.16 nmol/0.1 µL) in Experiment 1, and SAL or the H2 antagonist ranitidine (RA; 0.57, 2.85, or 5.7 nmol/0.1 µL) in Experiment 2. Twenty-four hours later, mice were reexposed to the EPM (T2) under the same experimental conditions but they did not receive any injection. Data were analyzed using one-way ANOVA and the Duncan test. In Experiment 1, mice microinjected with SAL and with CPA entered the open arms less often (%OAE) and spent less time in the open arms (%OAT) in T2, and there was no difference among groups. The results of Experiment 2 demonstrated that the values of %OAE and %OAT in T2 were lower compared to T1 for the groups that were microinjected with SAL and 2.85 nmol/0.1 µL RA. However, when animals were microinjected with 5.7 nmol/0.1 µL RA, they did not show a reduction in %OAE and %OAT. These results demonstrate that CPA did not affect behavior at the doses used in this study, while 5.7 nmol/0.1 µL RA induced impairment of memory consolidation in the EPM.

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

In vitro antibacterial activity of some antihistaminics belonging to different groups against multi-drug resistant clinical isolates

Antihistaminics are widely used for various indications during microbial infection. Hence, this paper investigates the antimicrobial activities of 10 antihistaminics belonging to both old and new generations using multiresistant Gram-positive and Gram-negative clinical isolates. The bacteriostatic activity of antihistaminics was investigated by determining their MIC both by broth and agar dilution techniques against 29 bacterial strains. Azelastine, cyproheptadine, mequitazine and promethazine were the most active among the tested drugs. Diphenhydramine and cetirizine possessed weaker activity whereas doxylamine, fexofenadine and loratadine were inactive even at the highest tested concentration (1 mg/ml). The MIC of meclozine could not be determined as it precipitated with the used culture media. The MBC values of antihistaminics were almost identical to the corresponding MIC values. The bactericidal activity of antihistaminics was also studied by the viable count technique in sterile saline solution. Evident killing effects were exerted by mequitazine, meclozine, azelastine and cyproheptadine. Moreover, the dynamics of bactericidal activity of azelastine were studied by the viable count technique in nutrient broth. This activity was found to be concentration-dependant. This effect was reduced on increasing the inoculum size while it was increased on raising the pH. The post-antimicrobial effect of 100 fg/ml azelastine was also determined and reached up to 3.36 h.

Chlorpheniramine impairs functional recovery in Carassius auratus after telencephalic ablation

We determined the effect of an H1 receptor antagonist on the functional recovery of Carassius auratus submitted to telencephalic ablation. Five days after surgery the fish underwent a spatial-choice learning paradigm test. The fish, weighing 6-12 g, were divided into four groups: telencephalic ablation (A) or sham lesion (S) and saline (SAL) or chlorpheniramine (CPA, ip, 16 mg/kg). For eight consecutive days each animal was trained individually in sessions separated by 24 h (alternate days). Training trials (T1-T8) consisted of finding the food in one of the feeders, which were randomly blocked for each subject. Animals received an intraperitoneal injection of SAL or CPA 10 min after the training trials. The time spent by the animals in each group to find the food (latency) was analyzed separately at T1 and T8 by the Kruskal-Wallis test, followed by the Student Newman-Keuls test. At T1 the latencies (mean ± SEM) of the A-SAL (586.3 ± 13.6) and A-CPA (600 ± 0) groups were significantly longer than those of the S-SAL (226.14 ± 61.15) and S-CPA (356.33 ± 68.8) groups. At T8, the latencies of the A-CPA group (510.11 ± 62.2) remained higher than those of the other groups, all of which showed significantly shorter latencies (A-SAL = 301.91 ± 78.32; S-CPA = 191.58 ± 73.03; S-SAL = 90.28 ± 41) compared with T1. These results support evidence that training can lead to functional recovery of spatial-choice learning in telencephalonless fish and also that the antagonist of the H1 receptor impairs it.

Antihistamine Pretreatment to Reduce Incidence of Withdrawal Movement After Rocuronium Injection

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection.

Chlorpheniramine facilitates inhibitory avoidance in teleosts submitted to telencephalic ablation

The present study investigated the involvement of H(1) histaminegic receptor on the acquisition of inhibitory avoidance in Carassius auratus submitted to telencephalic ablation. The fish were submitted to telencephalic ablation 5 days before the experiment. The inhibitory avoidance procedure included 1 day for habituation, 3 days for training composed of 3 trials each (1st day: T1, T2, T3; 2nd day: 2T1, 2T2, 2T3; 3rd day: 3T1, 3T2, 3T3) and 1 day for test. On training days, the fish were placed in a white compartment, after 30 s the door was opened. When the fish crossed to a black compartment, a weight was dropped (aversive stimuli). Immediately after the third trial, on training days, the fish received, intraperitoneally, one of the pharmacological treatments (saline (N = 20), 8 (N = 12) or 16 (N = 13) µg/g chlorpheniramine, CPA). On the test day, the time to cross to the black compartment was determined. The latency of the saline group increased significantly only on the 3rd trial of the 2nd training day (mean ± SEM, T1 (50.40 ± 11.69), 2T3 (226.05 ± 25.01); ANOVA: P = 0.0249, Dunn test: P < 0.05). The group that received 8 µg/g CPA showed increased latencies from the 2nd training day until the test day (T1 (53.08 ± 17.17), 2T2 (197.75 ± 35.02), test (220.08 ± 30.98); ANOVA: P = 0.0022, Dunn test: P < 0.05)). These results indicate that CPA had a facilitating effect on memory. We suggest that the fish submitted to telencephalic ablation were able to learn due to the local circuits of the mesencephalon and/or diencephalon and that CPA interferes in these circuits, probably due an anxiolytic-like effect.

Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish

This work investigated the effect of the Hj receptor blockade in the forebrain of ablated Carassius auratus in a simple stimulus-response learning task using a T-maze test with positive reinforcement. The goldfish were submitted to surgery for removal of both telencephalic lobes five days before beginning the experiment. A T-shaped glass aquarium was employed, with two feeders located at the extremities of the long arm. One of the two feeders was blocked. The experimental triáis were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for food for ten minutes (máximum period). Time to find food was analysed in seconds. Animáis were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after being placed back in the home aquarium. The results show that all the training latencies of the A-SAL group were higher than the latencies of the S-SAL group. The S-SAL group had decreased latencies from the second trial on, while the S-CPA group showed decreased latencies after the fourth trial. The A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group mainteined the latencies throughout the experiment. This suggests that CPA impairs the consolidation of learning both on telencephalon ablated animáis and in sham-operated ones through its action on mesencephalic structures of the brain and/or on the cerebellum in teleost fish.

Demonstration of antihistamine properties with AST-1: a bioactive extract from garden slugs (Diplosolenodes occidentalis) / Demostración de las propiedades antihestamínicas con ast-1, un extracto bioactivo de las babosas de jardín (diplosolenodes occidentalis)

Parched and ground whole garden slugs are claimed in rural Jamaican folklore practices to have useful effects in the treatment of bronchial asthma. Since this claim may be associated with respiratory dysfunction due to histamine from allergic sensitization, the authors investigated the effects of a semi-pure alcoholic extract (AST-1) on histamine-induced contraction of the guinea pig in vitro tracheal muscle preparation and cutaneous allergic responses in ovalbumin sensitized guinea pigs. Chemical analysis of AST-1 by column chromatography and thin layer chromatography indicated two compounds in the composition, but the molecular structures were not determined Pharmacological evaluation of AST-1 produced a concentration-dependent inhibition of histamine-induced contraction of the guinea pig tracheal muscle preparation. AST-1 also inhibited contraction of the tracheal muscle produced by selective H1 receptor stimulation with HTMT dimaleate. H2 receptors were not involved, as indicated by the absence of contraction with dimaprit hydrochloride, a selective H2 agonist. Also, in ovalbumin sensitized guinea pigs, AST-1 and diphenhydramine, a selective H1 antagonist, inhibited the cutaneous responses due to intradermal injection of histamine and ovalbumin. These results suggest that AST-1 has H1 anti-histamine properties which can inhibit histamine-induced tracheobronchial muscle contraction and cutaneous responses due to allergy.

En el contexto de las prácticas folclóricas de la Jamaica rural, se afirma que las babosas de jardín tostadas y molidas, tienen efectos útiles en el tratamiento del asma bronquial. Como que esta afirmación puede estar asociada con una disfunción respiratoria debida a la histamina de la sensibilización alérgica, los autores se dieron a la tarea de investigar los efectos de un extracto alcohólico semi-puro (AST-1) sobre la contracción inducida por histamina de un preparado in vitro de músculo de tráquea de cobayo, y las respuestas cutáneas alérgicas en cobayos sensibilizados con ovalbúmina. El análisis químico de AST-1 mediante cromatografía en columna y cromatografía en capa fina, indicaron dos compuestos en la composición, pero no se determinaron las estructuras moleculares. La evaluación farmacológica de AST-1 produjo una inhibición ­ dependiente de la concentración ­ de la contracción, inducida por histamina, del preparado de músculo de tráquea de cobayo. El AST-1 también inhibió la contracción del músculo traqueal producida por la estimulación de receptor selectivo H1 con dimaleato de HTMT. No se involucraron receptores H2, como lo indicó la ausencia de contracción con hidrocloruro de dimaprit ­ un agonista selectivo H2. Asimismo, en cobayos sensibilizados con ovalbúmina, el AST-1 y la difenidramina ­ un antagonista selectivo H1 ­ inhibieron las respuestas cutáneas debido a la inyección intradérmica de histamina y ovalbúmina. Estos resultados sugieren que el AST-1 tiene propiedades antihestamínicas H1, las cuales pueden inhibir la contracción muscular traqueobronquial inducida por la histamina y las reacciones cutáneas debido a la alergia

Inhibition of tryptase release from human colon mast cells by histamine receptor antagonists.

The main objective of this study was to investigate the ability of histamine receptor antagonists to modulate tryptase release from human colon mast cells induced by histamine. Enzymatically dispersed cells from human colon were challenged with histamine in the absence or presence of the histamine receptor antagonists, and the tryptase release was determined. It was found that histamine induced tryptase release from colon mast cells was inhibited by up to approximately 61.5% and 24% by the H1 histamine receptor antagonist terfenadine and the H2 histamine receptor antagonist cimetidine, respectively, when histamine and its antagonists were added to cells at the same time. The H3 histamine receptor antagonist clobenpropit had no effect on histamine induced tryptase release from colon mast cells at all concentrations tested. Preincubation of terfenadine, cimetidine or clobenpropit with cells for 20 minutes before challenging with histamine did not enhance the ability of these antihistamines to inhibit histamine induced tryptase release. Apart from terfenadine at 100 microg/ml, the antagonists themselves did not stimulate tryptase release from colon mast cells following both 15 minutes and 35 minutes incubation periods. It was concluded that H1 and H2 histamine receptor antagonists were able to inhibit histamine induced tryptase release from colon mast cells. This not only added some new data to our hypothesis of self-amplification mechanisms of mast cell degranulation, but also suggested that combining these two types of antihistamine drugs could be useful for the treatment of inflammatory bowel disease (IBD).

Influence of histamine and H1-receptor antagonists on ejaculated human spermatozoa: role of intrasperm Ca2+.

Histamine reduced sperm viability in a dose- and time-dependent manner, accompanied by rise in intrasperm Ca2+. Further, 2',4'-dichlorobenzamil hydrochloride (DBZ), a Na+-Ca2+ exchange inhibitor, known to elevate intrasperm Ca2+, potentiated both, elevation of intrasperm Ca2+ and spermicidal action of histamine. Pretreatment of sperm with very low doses of H1-receptor antagonists (chlorpheniramine, promethazine or diphenhydramine) prevented the histamine-induced elevation of intrasperm Ca2+ as well as its spermicidal action. However, pretreatment with famotidine, a H2-receptor antagonist did not produce such a protective action. The results strongly suggest that histamine elicits its spermicidal action via H1-receptors present on sperm cells.

Effects of anti-allergic drugs on intestinal mastocytosis and worm expulsion of rats infected with Neodiplostomum seoulense

The effects of anti-allergic drugs on intestinal mastocytosis and the expulsion of Neodiplostomum seoulense were observed in Sprague-Dawley rats, after oral infection with 500 metacercariae. The drugs used were hydroxyzine (a histamine receptor H1 blocker), cimetidine (a H2 blocker), cyclosporin-A (a helper T-cell suppressant), and prednisolone (a T- and B-cell suppressant). Infected, but untreated controls, and uninfected controls, were prepared. Worm recovery rate and intestinal mastocytosis were measured on weeks 1, 2, 3, 5, and 7 post-infection. Compared with the infected controls, worm expulsion was significantly (P < 0.05) delayed in hydroxyzine- and cimetidine-treated rats, despite mastocytosis being equally marked in the duodenum of all three groups. In the cyclosporin-A- and prednisolone-treated groups, mastocytosis was suppressed, but worm expulsion was only slightly delayed, without statistical significance. Our results suggest that binding of histamine to its receptors on intestinal smooth muscles is more important in terms of the expulsion of N. seoulense from rats than the levels of histamine alone, or mastocytosis.

Responses of isolated scale melanophores of a fresh water carp, Cirrhinus mrigala (Ham.) to zidovudine.

Zidovudine (AZT) induced concentration related aggregation in C. mrigala melanophores. Denervated melanophores failed to respond to AZT. Specific and nonspecific alpha adrenoceptor antagonists completely blocked the responses of fish melanophores to AZT. Histamine and prostaglandin antagonists also inhibited aggregation of the melanophores induced by AZT. The results suggest that AZT may release a mixture of neurotransmitter like substances, which cause the aggregation of this fish melanophores.

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.

Revisión de los medicamentos antivertiginosos / a review of antivertigo medication

Objetivo. Valorar la información existente sobre los efectos de las sustancias antivertiginosas, basados en la bibliografía asequible. Información. Se localizaron artículos pertinentes en Medline y en revistas obtenidas en la ciudad de México. Selección del material. Los artículos se seleccionaron en base a su aparente consistencia interna y su relación con el propósito de la revisión. Conclusión. Se evaluaron 22 substancias pertenecientes a 8 grupos farmacológicos (colinérgicos, antihistamínicos, GABAérgicos, bloqueadores de canales de calcio, serotoninérgicos, hemorreológicos, antiagregantes plaquetarios y diuréticos) útiles en diversos padecimientos vertiginosos. Se advirtió la necesidad de un método objetivo y cuantitativo para valorar resultados de ensayos clínicos en humanos. Mientra esto no ocurra, tendremos que usar los medicamentos en base de una información veraz, confiable y basada sólidamente en la farmacología estudiada en experimentos con animales y en la valoración cuidadosa de los efectos -buenos y malos- observados en nuestros pacientes.