Toxic oxygen products alter calcium homeostasis in an asthma model

After anaphylactic or synthetic leukotriene C4 contractions in guinea pig trachealis muscle, an accelerated initial rate and greater total myorelaxation are induced in these muscle preparations when they are immersed in calcium-free medium, O(Ca++)E. Inhibition of the late phase of anaphylaxis (ANA) by FPL 55712 (10(-5) mol/L) eliminated the post-ANA O(Ca++)E-augmented myorelaxation, suggesting a causal role for SRS-A products. Hypoxia or superoxide dismutase/catalase pretreatment also abolished the post-ANA or leukotriene C4 O(Ca++)E-augmented myorelaxation. The data support the hypothesis that toxic oxygen products generated with SRS-A and/or LTC4 induce an alteration in Ca++ homeostasis in airway smooth muscle. In this model of allergic asthma, airway smooth muscle alteration after ANA may contribute to the pathogenesis of asthma and/or airway hypersensitivity associated with allergic asthma.     

Response to RIT 4237 Oral Rotavirus Vaccine in Human Milk, Adapted- and Soy-Formula Fed Infants

ABSTRACT. During the first month of life 28 full-term newborns were breast-fed (18 males and 11 females). Thereafter 8 infants continued breast-feeding while the remainder were randomly fed on either an adapted milk formula ( n =13) or a soy-formula ( n =7). At five months, after an oral dose of RIT 4237 rotavirus vaccine of bovine origin was given, growth and IgM/IgG type antibodies against rotavirus were measured. Weight gain was similar in all infants. There were 2 IgM and 1 IgG responders out of 7 soy fed infants, compared with 4 out of 8 human milk fed (both IgM and IgG) and 7 out of 13 IgM and 6/12 IgG formula fed infants responding to vaccination. This observation confirms previous results obtained with polio, diphtheria tetanus and pertussis vaccines indicating that soy-protein formulas may interfere with immunization processes.     

Minimally invasive local ablative therapies in combination with radioiodine therapy in benign thyroid disease: preparation,feasibility and efficiency – preliminary results

Abstract

Purpose: Initial studies of combinations of radioiodine therapy (RIT) and local ablative procedures for the treatment of thyroid nodules have shown promising results. The goal of this study was to evaluate the effectiveness of RIT combined with radiofrequency ablation (RFA) in patients with goitres and to determine which ablative procedure is the most suitable for a combined therapy.

Methods: Thirty patients with goitres were divided into two subgroups. A test group of 15 patients received combined therapy (RIT?+?RFA) and a control group of 15 patients received RIT mono therapy. All patients underwent assessments including ultrasound, laboratory evaluation (T3, T4, TSH, TG, TPOAb, TgAbTRAb) and scintigraphic imaging with Tc-99m-Pertechnetate. The 3-month volume reduction was used to evaluate therapy effectiveness.

Results: Combined therapy (subgroup 1) resulted in a significant (p?<?0.05) thyroid volume reduction (22.3?±?54?ml/32.2?±?58.2%) with better performance (p?>?0.05) than the control group (20.2?±?32.2?ml/29.6?±?42.1%). All patients became euthyroid after treatment. No major discomfort or complications occurred. A review of the literature investigating combinations of other local ablative procedures with RIT was performed to determine the most promising combination.

Conclusions: The present study confirms the positive experiences with the combined therapy of RIT and local ablative procedures shown in the current literature and approves this approach for the treatment of goitres with RFA?+?RIT. These findings, when confirmed by further studies, should expand the indication of combined therapy as a minimally invasive alternative to surgery.     

Radioimmunotherapy of solid tumors targeting a cell-surface protein, FZD10: therapeutic efficacy largely depends on radiosensitivity

Objective  Frizzled homolog 10 (FZD10) is expressed at high levels on the cell surface of almost all synovial sarcoma tissues, but is absent in most normal organs. In a previous study, yttrium-90 (⁹⁰Y)-labeled anti-FZD10 antibody (MAb 92-13) showed considerable therapeutic efficacy in synovial sarcoma cell-bearing mice. The purpose of the present study was to elucidate the factors associated with this therapeutic efficacy of ⁹⁰Y-MAb 92-13. Methods  FZD10 expression levels of SYO-1 (FZD10-overexpressing synovial sarcoma cell line) and DLD-1/FZD10 (FZD10-transfected DLD-1 cell) were determined by the cell binding assay, and their radiosensitivity was evaluated by incubation with ⁹⁰Y-MAb 92-13 in vitro. Biodistribution study of indium-111 (¹¹¹In)-MAb 92-13 was performed in SYO-1 and DLD-1/FZD10 tumor-bearing mice. For therapeutic studies, SYO-1 and DLD-1/FZD10 tumor-bearing mice were treated with ⁹⁰Y-MAb 92-13 (100, 150, and 200 μCi), after which the change in tumor volume was measured. Immunohistochemical staining was performed on the excised tumor. Results  Expression level of FZD10 on DLD-1/FZD10 was much greater than that on SYO-1. The accumulation of ¹¹¹In-MAb 92-13 was much higher in DLD-1/FZD10 tumor-bearing mice than in SYO-1 tumor-bearing mice (49.0 ± 4.2 and 22.0 ± 4.5% ID/g, respectively, at 48 h after administration). In SYO-1 tumor, substantial tumor size reduction was observed in all mice treated with ⁹⁰Y-MAb 92-13 (tumor volume decreased to less than 0.1 cm³ at 11 days after treatment) and tumor regrowth was not observed in most of them. In contrast, only slow progression was observed in DLD-1/FZD10 tumor. When incubated with ⁹⁰Y-MAb 92-13, high radioactivity was needed to damage DLD-1/FZD10. Immunohistochemical study indicated apoptosis of SYO-1 tumor. Conclusions  The therapeutic efficacy of RIT seems to largely depend on the tumor radiosensitivity.