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.

Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models.

The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs.

Eficácia clínica do cetotifeno e seu papel na hiperreatividade brônquica e fase tardia da asma infantil / Ketotifen in the late asthmatic response

Objetivo: Avaliar o efeito do cetotifeno na fase tardia da asma e seu papel na hiperreatividade brônquica.Métodos: Estudo duplo-cego, randomizado, paralelo, comparativo entre três grupos, controlado por placebo. Foram estudadas 39 crianças, maiores de seis anos, com asma leve a moderada segundo os critérios da ATS, com episódios mensais nos últimos três meses. Todas eram alérgicas ao D. pteronyssinus e tinham teste de broncoprovocaçäo para D. pteronyssinus, com presença de fase tardia. As crianças foram randomizadas para receber durante seis meses cetotifeno (C) na dose de 1mg (12 em 12 horas), ou C na dose de 2mg (12 em 2 horas) (CDD)ou placebo (P). Resultados: Os três grupos eram homogêneos quanto à idade (p=0,805), ao sexo (p=0,209), ao peso (p=0,584), à estatura (p-0,506), ao intervalo entre as crises (p=0,825) e PD20 para metacolina (M;p=0,106) e antígeno (Ag;p=0,330). Näo houve diferença sigficativa entre os grupos em relaçäo aos dias assintomáticos (p=0,226) ao PD20 para M (p=0,705) e ao PD20 para Ag (p=0,928). Da mesma forma, os valores de funçäo pulmonar mantiveram-se estáveis durante o tempo de estudo. Conclusöes: O presente estudo näo demonstrou diferenças estatisticamente significativas em relaçäo à eficácia clínica do C e do P em crianças com asma brônquica moderada, independente da dose empregada, portanto, o C näo se mostrou eficaz na profilaxia da asma na faixa etária estudada

Ketotifen inhibits allergen-specific T lymphocytes' responses by suppressing antigen presentation with concomitant decrease of HLA-DQ antigen on macrophages.

Allergen activates T lymphocytes responsive to interleukin 2 (IL-2) in allergic patients but not in normal individuals. This response was suppressed by anti-allergic agent, Ketotifen (4-(1-methyl-4-piperidylidene)-4H-benzo [4, 5] cyclohepta [1, 2-b] thiophen-10 (9H)-one hydrogen (fumarate). Prolonged culture of antigen-presenting adherent cells impaired the ability to present Dermatophagoides farinae (Df) antigen to T cells, whereas stimulation of adherent cells with recombinant interferon-gamma (IFN-gamma) restored the antigen-presenting capability. The maintained antigen presenting ability of adherent cells treated with IFN-gamma was also suppressed by Ketotifen. Fluorescence activated cell sorter (FACS) analysis disclosed that Ketotifen selectively reduced the expression of HLA-DQ antigen, crucial restriction elements in Df antigen-related responses, on macrophages but not on B cells, even in the presence of IFN-gamma. Collectively, Ketotifen prevented macrophages from inducing allergen-activated T lymphocytes' responsiveness to IL-2 at least in part by decreasing the expression of HLA-DQ antigen.

Prevención de las crisis de asma con ketotifeno / Prevention of asthma crisis with ketotifen

En su estudio clínico retrospectivo, se valoraron los expedientes de 70 niños de ambos sexos que fueron tratados con ketotifeno para prevenir las crisis de broncoespasmo por asma de citología diversa. Se valoró la respuesta al tratamientos a los 3 y 6 meses y al año y dos años. Los resultados fueron buenos y muy buenos, lográndose la disminución de las crisis en más del 50% o su desaparición, en el 92.86% de los casos a los 3 meses, en el 87.69% a los 6 meses, en el 80.95% al año y en el 77.78% a los 2 años de tratamientos. En el 77.15% de los casos se logró el control de las crisis con ketotifeno solo y en el 11.43% asociado a inmunoterapia. Los efectos secundarios, sedación principalmente, fueron mínimos. Como conclusión se comprueba una vez más la eficacia del ketotifeno para prevenir y controlar las crisis de asma bronquial en el niño, eficacia que se mantiene en tratamientos prolongados hasta 2 años y que se acompaña de una excelente tolerancia

Childhood asthma, response to oral prophylaxis

The value and efficacy of ketotifen as a prophylactic drug for childhood asthma was assessed for 1 year in 45 children. Sixty seven percent showed good response, 15.5% moderate and 17.7% poor response to ketotifen therapy. The side effects [sedation, dizziness, headache] were seen in 20% children which resolved without interruption of therapy. Ketotifen appeared to be an effective and safe oral prophylactic drug for childhood asthma