Fatal myelotoxicity after azathioprine treatment.

Azathioprine and 6-mercaptopurine have been used for many years in the treatment of inflammatory bowel disease. Approximately 0.3% of the population are homozygous for variant alleles associated with extremely low thiopurine S-methyltransferase enzyme activity. We describe the case of a young patient with ulcerative colitis, homozygous for TPMT*3A alleles, who suffered fatal azathioprine-induced myelotoxicity after standard dosing with azathioprine. Screening for decreased activity of TPMT in patients prior to azathioprine treatment is advised to minimize the risk of drug-induced toxicity.

Intratracheal and intranasal immunization with ovalbumin conjugated with Bacillus firmus as a carrier in mice.

Inactivated Bacillus firmus (BF), G+ nonpathogenic bacterium of the external environment, was coupled to ovalbumin (OVA) and used in immunization experiments as antigen carrier. Balb/c mice were immunized thrice intra-tracheally and intra-nasally with conjugates of OVA and BF. Surprisingly, administration of OVA-BF conjugates inhibited anti-OVA IgG response in both sera and mucosal secretions if compared to an exposure to OVA alone. The suppression of antigen-specific antibody production was accompanied by promotion of TH1 phenotype.

Role of T cells in the adjuvant effect of Bacillus firmus on the immune system of mice: intranasal and intratracheal immunization study with ovalbumin.

Functions of T cells were determined after intranasal and intratracheal immunization of mice with ovalbumin (Ova) and Bacillus firmus (Bf), a Gram-positive nonpathogenic bacterium of the external environment, or delipidated Bf (dBf) as adjuvants, with the aim to elucidate the mechanism of support of Ova-specific antibody production caused by Bf that had been observed in an identical experiment. Neither Bf nor dBf in a mixture with Ova stimulated Ova-specific T-cell response tested as antigen-specific blast transformation. By contrast, a mild polyclonal stimulation was observed in splenocytes from mice given dBf. In vitro incubation of splenocytes with 100 micrograms (but not 10 micrograms) of Bf or dBf led to a highly significant inhibition of proliferation below the control level in all groups of animals. Supernatants of splenocyte cultures were further tested for cytokine production. IL-10 and IFN-gamma were released after in vitro challenge with dBf and in some cases also with Bf. Analysis of sera demonstrated that administration of Ova + adjuvant brought about an increase in anti-Ova IgG1, IgG2a and IgG2b whereas treatment with Ova alone caused a rise in IgG1 only. The role of Bf or dBf in the enhancement of antigen-specific antibody production could be in influencing macrophages and inducing cytokine milieu composed of IL-10, IFN-gamma and other factors that leads to a bystander stimulation of specifically activated Ova-B cell receptor (Ova-BCR)-bearing cells.

Immunostimulatory effect of Bacillus firmus on mouse lymphocytes.

Bacillus firmus (a Gram-positive nonpathogenic and harmless bacterium), was shown to be a strong polyclonal activator of mouse B lymphocytes as estimated by ELISA testing of Ig concentrations in culture supernatants after incubation of BALB/c mouse splenocytes with inactivated bacillus. Synthesis of all main Ig classes and all IgG subclasses was stimulated in vitro, the considerable effect on IgA formation being the most interesting feature. B cell stimulation was T cell dependent, as was demonstrated by the effect of B. firmus on all Ig isotypes and by comparison of lymphocyte response of nu/nu mice and heterozygous nu/+ mice. The effect of B. firmus on splenocyte proliferation was stimulatory or suppressive depending on the dose of the bacterium. Increased synthesis of IFN-gamma and IL-10 (detected by ELISA in splenocyte culture supernatants) showed probable stimulation of Th1 and Th2 subpopulations. Considering the stimulatory effect on IgA formation and macrophage stimulation, B. firmus seems to be a prospective mucosal adjuvant and/or probiotic.

[Adverse effects of nonsteroidal antirheumatic agents on the digestive tract]. / Nezádoucí úcinky nesteroidních antirevmatik na trávicí trakt.

In this review the authors focus on the adverse GIT events during long-term treatment with non-steroid anti-inflammatory drugs, and explain pathogenesis of the NSA induced gastropathy and enteropathy. The risk groups of patients and prophylactic and therapeutic modalities are discussed. There are indices that most of the NSA gastric ulcers don't induce clinical symptoms, and massive bleeding may be the first clinical manifestation. This is why the clinical symptoms cannot be used as predictors of NSA gastropathy. It seems, on the author's clinical experience, that more than half cases of massive non-variceal bleeding from upper GIT is induced by non-steroid anti-inflammatory drugs and acetylsalicylic acid. NSA-gastropathy often presents with multifocal ulcers and erosions in the antrum of the stomach. The course of massive bleeding induced by NSA is associated with high rate of lethality.

[Cutaneous complications in idiopathic inflammatory bowel disease]. / Kozní komplikace idiopatického strevního zánetu.

A 29-year-old male patient with the anamnesis of inflammatory bowel disease and Grave-Basedowov disease was hospitalized because of rapidly spreading skin defect with affected muscle on the left shin. This skin defect appeared after the significant decreasing of corticoids. The small skin trauma preceded the pyoderma gangrenosum. First the skin disease was not right diagnosed and patient was cured by the excision of the defect. It caused tissue disintegration, muscle necrosis and extension of the defect. The whole leg was endangered. Patient was cured with corticoids and cyclosporin A after the right diagnosis. The defect healed and laboratory inflammatory markers decreased. The immunosuppresive therapy was changed to azathioprin, the corticoid therapy was interrupted. After three months the defect was healed.

Enhanced systemic and mucosal antibody responses to a model protein antigen after intranasal and intratracheal immunisation using Bacillus firmus as an adjuvant.

Bacillus firmus, a non-pathogenic Gram positive (G+) bacterium of the external environment was investigated for immunomodulatory properties. It stimulated an increase in anti-ovalbumin IgG in sera, bronchoalveolar lavages and intestinal washings after both intranasal (i.n.) and intratracheal (i.t.) immunisation, and enhanced anti-ovalbumin IgA in intestinal secretions and in bronchoalveolar lavage fluid after i.n. or i.t. immunisation, respectively. The immunomodulatory effect of B. firmus on antibody formation was antigen specific.

Effect of Bacillus firmus on antibody formation after mucosal and parenteral immunization in mice.

Immunostimulatory properties of B. firmus, a nontoxic, nonpathogenic G + bacterium of external environment, were described previously. Antiinfectious and antitumor activity, macrophage activation and strong polyclonal stimulation of B lymphocytes were proved in human, mice and rats. The adjuvant effect of B. firmus on specific antibody response to ovalbumin in BALB/c mice is the topic of the present study. Against our expectation, B. firmus exerts more suppressive than stimulatory effect on specific antibody response. Formolized B. firmus decreased anti-ovalbumin response after subcutaneous immunization and only slightly increased serum antibodies after intraperitoneal immunization. After mucosal immunization, both oral and rectal, ovalbumin itself did not cause a significant systemic response but induced IgA anti-ovalbumin response in the intestine. B. firmus applied together with ovalbumin increased systemic serum response but absolutely eliminated intestinal response. The rectal route of antigen administration has been found less convenient because of less precise dosing of antigen in this mode of immunization.