The immunomodulatory role of esmolol in patients undergoing laparoscopic gastrectomy due to gastric cancer.

Esmolol has a beneficial effect on the T helper 1/T helper 2 balance in patients with heart failure. The aim of this study was to investigate the immunomodulatory role of esmolol during and after surgery. Patients undergoing laparoscopic gastrectomy due to gastric cancer were enrolled. Patients in the esmolol group (n = 15) received esmolol during surgery, and a saline-treated group (n = 14) served as a control. Cytokines were quantified by sandwich enzyme-linked immunoassays before, during and after surgery. The esmolol group was associated with higher ratios of interferon-γ/interleukin-4 (T helper 1/T helper 2 signature cytokines) than the saline group during (2.36 vs 0.57, respectively, p = 0.041) and after (5.79 vs 0.69, respectively, p = 0.033) surgery. The postoperative increase in interleukin-6 was attenuated in the esmolol group, and the C-reactive protein level on postoperative day 1 was significantly lower in the esmolol group than in the saline group (mean (SD) 26.2 (18.3) mmol.l(-1) vs 56.8 (44.3) mmol.l(-1), p = 0.021). Our findings suggest that esmolol played an immunomodulatory role and mitigated the postoperative inflammatory response in patients under surgical and anaesthetic stress.

Adrenergic modulation of dendritic cell cancer vaccine in a mouse model: role of dendritic cell maturation.

The aim of the present study was to evaluate the role of beta2-adrenergic receptors (beta2-ARs) in the outcome of a dendritic cell (DC)-based cancer vaccine in the murine E.G7-ovalbumin (OVA) model. We found that unlike the beta2-AR expressed on antigen loaded DCs, beta2-ARs expressed in the site of DCs inoculation may influence the efficacy of the antitumor response. Intradermal injection of Staphylococcus aureus peptidoglycan along with the beta2-AR-specific antagonist ICI 118,551 increased the local innate cytokine response in tumor-bearing mice. When the adoptive transfer of immature DCs loaded with OVA followed this skin preconditioning, the antitumor response was increased and tumor growth was significantly reduced. Surprisingly, when OVA-loaded mature DCs were used, the effect of the skin preconditioning was the opposite and tumor growth was similar to that observed in control, nonimmunized mice. The extent of the antitumor response on transfer of immature or mature DCs was mediated by a different migration in the draining lymph nodes and by a distinct recruitment of endogenous DCs that resulted in a modulation of the OVA-specific cytotoxic T lymphocyte response. The unexpected tolerogenic effect exerted by mature DCs on skin preconditioning was apparently mediated by the expression of a distinctive pattern of cytokines and of the suppressive enzyme indoleamine 2, 3-dioxygenase in draining lymph nodes. In conclusion, we found that beta2-ARs inhibition along with toll-like receptor2 activation at the site of cancer vaccination may either enhance the resulting antitumor response or be tolerogenic in dependence of the maturation state of the transferred DCs.

Iosimenol, a new non-ionic dimeric contrast medium, does not induce immunoreactivity in the popliteal lymph node assay.

Animal studies in mice were conducted to determine the potential immunoreactivity of the new non-ionic dimeric contrast medium (CM) iosimenol using the PLNA and flow cytometric analyses. Comparative studies were performed with iodixanol. The known immune-reactive substance strepozotocin (STZ) and vehicle injections served as positive and negative controls, respectively. Our experiments did not show any immunological effect of iosimenol, concluding that the new CM iosimenol may be beneficial for use in high-risk patients.

Iosimenol, a low-viscosity nonionic dimer: preclinical physicochemistry, pharmacology, and pharmacokinetics.

RATIONALE AND OBJECTIVES: Newer radiologic techniques require fast bolus injections and thus low-viscosity, high-concentration, well-tolerated contrast media (CM), especially in vulnerable patients. To this end, we designed and developed iosimenol, a novel isotonic nonionic dimer, and have conducted tests to enable its clinical evaluation. METHODS: Standard physicochemical methods were used. Effects on erythrocyte morphology and coagulation were investigated in human and rat blood. Neural tolerance was assessed by behavioral tests in rats after intracisternal injection. Immunosensitizing potential was evaluated by the skin sensitization test in guinea pigs and by the popliteal lymph node assay in rats. Pharmacokinetics and biotransformation were investigated in rats and dogs. RESULTS: Iosimenol is extremely hydrophilic, it is less viscous than any other isotonic CM, has little effect on erythrocytes and blood coagulation, and has good neural tolerance. No immunosensitizing effect was found in validated animal models. Pharmacokinetics are identical with other angio- and urographic CM. CONCLUSIONS: Iosimenol is the only CM which, although isotonic, affords, unlike current nonionic dimers, at the same iodine concentration the low viscosity of monomeric, nonionic agents, which are all hypertonic. Iosimenol's pharmacologic characteristics closely resemble those of iotrolan and iodixanol.

[Levels of antiphospholipid antibodies in the serum and aqueous humor of glaucoma patients]. / Poziom przeciwcial antyfosfolipidowych w surowicy i cieczy wodnistej pacjentów z jaskra.

PURPOSE: Evaluation of antiphospholipid antibodies in the serum and aqueous humor in patients with glaucoma. MATERIAL AND METHODS: 48 persons (38 women and 17 men), aged 30-86 (mean age 70), suffering from glaucoma was examined. There were 19 with POAG, 18 with PACG and 11 with PEXG. All patients have undergone trabeculectomia. The group of 20 operated, because of age-related cataracta patients (7 men and 13 women), aged 47-82 (mean age 65) constituted a control group. All patients agreed to samples collection. In plasma and anterior chamber fluid the level of antiphospholipids antibodies classes IgM and IgG were measured, using ELISA method (commercial kits produced by Euroimmun) according to producent's instruction. Statistical analysis was performed using U Mann-Whitney test. RESULTS: The mean values of antiphospholipids in both group are put in the table. The significant differences between glaucoma and no-glaucoma patients were observed in levels of IgG in serum (p=0.014) and in levels of IgM antibodies in aqueous humor (p=0.013). CONCLUSIONS: The presence of elevated levels of antiphospholipid antibodies in aqueous humor and serum may be a risk factor in progression of glaucomatous neuropathy.

Antibody against a novel, myriocin (ISP-I)-based immunosuppressant, FTY720.

An antibody was prepared by immunizing rabbits with an ovalbumin conjugate of 2-amino-2-(2-(4-(4-mercaptobutyl)phenyl)ethyl)propane-1,3-diol HCl (AMPD-4), which contains the essential structure of the novel immunosuppressant FTY720. As the antibody reacted to not only AMPD-4, but also FTY720, it should be useful for immunoassay of FTY720 in body fluids, tissues and cells.

[Antigenicity of suloctidil].

Studies on antigenicity of suloctidil were performed on ASA, Schultz-Dale reaction, PCA and PHA in guinea pigs. Two sensitizing procedures were enforced. One was performed by means of treatment of suloctidil (p. o. and i. p.) and the other was done by means of injection of suloctidil, suloctidil-BSA-mixture and suloctidil-BSA-conjugate emulsified with FCA. Guinea pigs treated with suloctidil by oral or intraperitoneal administration showed no ASA, Schultz-Dale reaction, PCA and PHA by the challenge of suloctidil. The animals treated with suloctidil-BSA-conjugate only evoked severe anaphylactic reaction to challenge of suloctidil-OVA-conjugate. Guinea pigs treated with suloctidil and suloctidil-BSA-mixture showed no anaphylactic reaction to challenge of suloctidil, suloctidil-OVA-mixture and suloctidil-OVA-conjugate. The animals sensitized with suloctidil-BSA-conjugate showed no anaphylactic reaction to challenge of suloctidil and suloctidil-OVA-mixture. Therefore, it is concluded that suloctidil does not have any antigenicity.

[Toxicological properties of a cephedrine preparation]. / Toksikologicheskie svoistva preparata tsefedrina.

The antidepressant drug cephedrine experimentally displays a little acute and chronic toxicity, does not influence the development of allergic reaction in guinea pigs, changes but little the ECG and does not possess teratogenic and embryotoxic properties. When used in a subtoxic dose it is capable of causing dystrophic changes in individual neurons in the cortex and subcortical formations of the central nervous system, to delay the growth of fetuses, especially when administered during the second half of gestation.