Inhibition of methylprednisolone elimination in the presence of clarithromycin therapy

BACKGROUND: Macrolide antibiotics have long been used as steroid-sparing agents in patients with severe steroid-dependent asthma. Their efficacy and their propensity to potentiate glucocorticoid adverse effects have been attributed in part to their ability to delay glucocorticoid clearance. OBJECTIVE: We sought to determine whether clarithromycin, a newer macrolide antibiotic, can alter the pharmacokinetic profile of oral glucocorticoids and thereby increase the risk of steroid-induced adverse effects. METHODS: An open-label study in a paired design (before and after treatment) was conducted in a hospital-based outpatient clinic. Participants were 6 adult patients (mean age, 30 years) with mild-to-moderate asthma. Prednisone (40 mg/1.73 m2) and methylprednisolone (40 mg/1.73 m2) were given as single randomized doses on consecutive study days before and on days 8 and 9 of a clarithromycin (500 mg twice daily) course. Twelve-hour pharmacokinetic profiles with measurement of plasma methylprednisolone and prednisolone levels were taken before and after clarithromycin therapy. RESULTS: Clarithromycin therapy resulted in a 65% reduction of methylprednisolone clearance and significantly higher mean plasma methylprednisolone concentrations compared with preclarithromycin concentrations but had no significant effect on prednisolone clearance or mean prednisolone plasma concentrations. CONCLUSIONS: Clinicians must be aware of potential drug interactions that could place patients at increased risk for steroid-induced adverse effects. Such an effect has been demonstrated between clarithromycin and methylprednisolone, two drugs that may be administered concomitantly in asthma. To avoid potential steroid-enhancing effects, prednisone should be substituted for methylprednisolone during prolonged courses of clarithromycin therapy.     

Role of Thy 1.2+ cells in hemopoietic regulation in cytostatic-induced hemosuppression

Effect of Thy 1.2⁺ cells (direct and mediated by stromal elements) on the growth of granulomonocyte and erythroid colonies in the bone marrow is studied on CBA mice with cytostatic disease induced by single injection of adriamycin, cyclophosphamide, and 5-fluorouracil in maximum permissible doses. It is shown that Thy 1.2⁺ cells stimulate colony formation in regenerating bone marrow, the effect depending on functional activity of hemopoiesis-inducing microenvironment. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol 125, No. 5, pp. 509–513, May, 1998     

Increased expression of the CD80 accessory molecule by alveolar macrophages in asthmatic subjects and its functional involvement in allergen presentation to autologous TH2 lymphocytes

Background: Alveolar macrophages (AMs) are more efficient antigen-presenting cells in allergic individuals than in nonatopic subjects. Objective: We studied whether this difference may be correlated to increased expression of membrane costimulatory molecules, such as the B7 molecules (CD80 and CD86). Methods: Eleven subjects with allergic asthma sensitized to Dermatophagoides pteronyssinus and 5 healthy nonatopic volunteers underwent bronchoalveolar lavage, and the costimulatory molecule expression on AMs was evaluated. Peripheral blood T cells, either freshly isolated or as established D pteronyssinus -specific cell lines, were cultured with autologous monocytes or AMs as antigen-presenting cells. In vitro allergen-induced proliferation and cytokine production were evaluated in the presence of B7-blocking reagents. Results: Allergic individuals had a significantly higher proportion of AMs expressing the CD80 molecule than control subjects (28.5% ± 14.8% vs 1.4% ± 1.2%; P < .001), whereas no difference was observed in CD86 expression (2.0% ± 2.3% vs 1.1% ± 0.6; P > .1). In a large proportion of the asthmatic subjects we studied, AMs were presenting soluble antigens (tetanus toxoid and streptolysin-O) to freshly isolated T cells more efficiently than AMs from nonatopic control subjects. Finally, both T-cell proliferation and cytokine production of D pteronyssinus- specific established T-cell lines were inhibited by a CD80-blocking antibody in a dose-dependent manner. Conclusion: Costimulation by means of CD80 expressed by AMs is probably involved in the amplification of the allergen-specific T-lymphocyte response in the airways of asthmatic subjects. (J Allergy Clin Immunol 1999;103:1136-42.)     

Changes in state of the surfactant in experimental pneumonia

The state of the lung surfactant in rabbits at different stages of development of experimental pneumonia (3–60 days) was compared with the dynamics of oxidoreductases in the alveolar epithelium and cells of the inflammatory focus of infiltration. In the initial stage (3–7 days) of activation of cell metabolism there was a brief increase in, the intensity of surfactant lipid synthesis, accompanied by relative inhibition of phospholipid synthesis. Later, development of degenerative changes and sclerosis of the parenchyma was accompanied by inhibition of synthesis of all components of the surfactant. The surface activity of the surfactant became stabilized at a low level.Laboratory Division, I. M. Sechenov Research Institute of Medical Climatology and Physical Methods of Treatment, Yalta. Department of Pathological Anatomy, Faculty of Internal Medicine, and Department of Organic Chemistry, Crimean Medical Institute, Simferopol'. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 84, No. 9, pp. 286–288, September 1977.     

Effect of glucocorticoids and gestagens on glutathione redox-system in rat skin involved in dermatitis

In the model of experimental dermatitis the effect of hydrocortisone and two gestagens (endogenous progesterone and synthetic mecygestone) on the level of glutathione redox-system components (reduced glutathione, glutathione reductase, and glutathione peroxidase) in rat dermis and epidermis is characterized by different degree of activation of this system.     

Specific IgE to cross-reactive carbohydrate determinants strongly affect the in vitro diagnosis of allergic diseases

BACKGROUND: Cross-reacting carbohydrate determinants (CCDs) are antigenic structures shared by allergenic components from taxonomically distant sources. The case history of a patient with a great discrepancy between skin test and specific IgE results led us to investigate the role of these determinants in his specific case and in an allergic population. OBJECTIVE: We sought to determine the role of CCDs in causing false-positive and clinically irrelevant results in in vitro tests. METHODS: The involvement of CCDs was studied by specific IgE inhibition by using glycoproteins with a known carbohydrate structure. Direct and inhibition assays were performed by commercially available systems, in-house ELISA, and the immunoblotting technique. The binding to the periodate-oxidated carbohydrate structure of glycoproteins and allergenic extracts was also evaluated. A comparative study between skin test and specific IgE responses to the antigens studied was carried out in 428 consecutive allergic subjects. RESULTS: All the tests performed suggested that cross-reacting carbohydrate epitopes were the cause of false-positive specific IgE results in one of the commercial systems and the high reactivity in all the solid-phase in vitro tests. None of the cross-reacting carbohydrate allergens yielded a positive skin test response. Periodate treatment caused variable degrees of reduction of IgE binding to the different antigens studied, indicating that CCDs played a different role in each of them. About 41% of patients allergic to pollen had specific IgE for a glycoprotein, without a positive skin test response to the same molecule. CONCLUSIONS: CCDs must be taken into account when evaluating the clinical relevance of positive results in in vitro specific IgE assays, at least in the diagnosis of patients with pollen allergy. Commercial systems should be carefully assessed for the ability to detect specific IgE for carbohydrate determinants to avoid false-positive or clinically irrelevant results.     

Role of the hormonal status of the father in involution of the thymus in the progeny

This study was aimed at assessing the consequences of the influence of exogenous androgens on the epididymal sperm of fathers for their progeny. A single injection of testosterone or dihydrotestosterone to adult rats caused a transient increase of the level of the corresponding androgen, later leading to augmentation of the androgen-dependent organs and loss of thymus weight. Hyperandrogeny and earlier age-associated involution of the thymus were observed in the male progeny of androgenized males of reproductive age. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 562–564, May, 1996     

Role of the interaction between different types of serotonin and α2-adrenergic receptors in the regulation of audiogenic seizures in DBA/2 micereceptors in the regulation of audiogenic seizures in DBA/2 mice

It is shown that the serotonin receptors 5-HT_1c, 5-HT₃, and 5-HT₄ and α₂-adrenergic receptors are involved in the regulation of audiogenic seizures in DBA/2 mice, and that the effects of these serotonin receptors on the duration and magnitude of convulsive activity are the opoosite of those produced by α₂-adrenergic receptors. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 4, pp. 381–383, April, 1995     

Changes in thermonociceptive thresholds and the role of enkephalinase A in homeostasis in morphine-tolerant rat offspring

The dynamics of thermonociceptive thresholds as a marker of the state of the endogenous opioid system was studied in the offspring of morphine-tolerant rats. Significant, age-dependent increase in thermonociceptive thresholds and higher levels of enkephalinase A in structures of the endogenous antinociceptive system were observed in the offspring compared with the control. These findings attest to disturbances of the opioid system in the progeny of morphine-tolerant rats and confirm the key role of enkephalinase A in the maintenance of homeostasis disturbed by chronic prenatal morphine treatment. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 129, No. 5, pp. 560–562, May, 2000     

Serotonin-producing cells in the duodenum of hibernants during periods of hypothermia in midwinter and before awakening in the spring

Ultrastructural differences are demonstrated between the duodenal serotonin-producing cells of ground squirrel during periods of hypothermia in winter and before awakening in the spring. In spring, the free ribosomes/polysomes ratio changes in these cells, and serotonin is actively released from secretory granules. These changes are associated with the preparation of the digestive system to functioning after hibernation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 346–348, March, 1997     

Participation of cholesterol in hypochlorite-induced oxidation of cholesterol-phosphatidylcholine liposomes

The effect of cholesterol on hypochlorite-induced lipid peroxidation is studied in cholesterol-phosphatidylcholine liposomes. Cholesterol is shown to promote the accumulation of lipid peroxidation products in the presence of 0.1–3 mM hypochlorite anion in the incubation medium. The content of 2-thiobarbituric acid-reactive products is maximal at a cholesterol: phosphatidylcholine molar ratio of 1∶1. On the other hand, in the presence of low hypochlorite concentrations (10–100 μM) cholesterol is found to inhibit lipid peroxidation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, No. 5, pp. 516–519, May, 1996     

Role of Corticosterone in realization of immunosuppressive effects in acute poisoning with toxic chemicals

Experiments on random-bred male rats shows that acute poisoning with metaphos and acrylonitrile inhibites mainly the thymus-dependent humoral immune response, delayed type hypersensitivity reaction, and activities of natural killers and K cells. The increase in plasma corticosterone under the effect of metaphos ensures the participation of this hormone in the realization of suppression of natural killers and thymus-dependent humoral immune response (production of IgG), the contribution of the hormone to this suppression being 35.6 and 35.1%, respectively. Suppression of immune reactions by acrylonitrile is not associated with corticosterone effect. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 5, pp. 552–555, May, 2000     

Mechanisms of modulation of GABA-induced currents in isolated cerebellar cells by tacrine

Tacrine, when applied by the concentration clamp technique to isolated Purkinje cells from rat cerebellum, dose-dependently reduced the amplitude of GABA-activated chloride currents recorded by the patch clamp technique. Half-maximal inhibition (IC₅₀) of currents activated by 2 μM GABA was observed at a tacrine concentration of 107 μM. Tacrine produced a right shift of the dose-response curves for GABA-induced currents without affecting their peak amplitudes. It is suggested that suppression of GABA-induced currents caused by tacrine can not be attributed to its interaction with the benzodiazepine site of the GABA_A receptor. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 5, pp. 539–542, May, 1999     

Ultradian rhythms in cells and their role in stimulation of regeneration

Protein concentration in a cell increases during stimulation of ultradian rhythms by multifrequency irritation corresponding to the hierarchy of cell biorhythms. Physiotherapy synchronous with patient's pulse and respiratory rhythms accelerates regeneration of postoperative wounds and trophic ulcers. Rhythms of physiological regeneration stimulate the repair regeneration. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 7, pp. 93–96, July, 1999     

Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: Effect of topical corticosteroids

BACKGROUND: Human allergen-induced rhinitis is associated with the recruitment and activation of inflammatory cells, particularly eosinophils and CD4(+) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCPs), a subfamily of CC chemokines, have been shown to induce chemotactic activity particularly in eosinophils, T cells, and monocytes under in vitro assay conditions. OBJECTIVE: To assess the contribution of MCPs in the recruitment of inflammatory cells in vivo, we investigated the allergen-induced late response in subjects with allergic rhinitis. METHODS: Patients were randomized to receive a 6-week treatment with either topical corticosteroid (n = 6) or a matched placebo (n = 6). Nasal inferior turbinate biopsy specimens were obtained from all subjects before and during allergen-induced late responses. By using immunocytochemistry, tissue sections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for the phenotype of infiltrating cells within the nasal mucosa. In addition, double sequential immunocytochemistry was used to confirm the phenotype of MCP-immunoreactive positive cells. Furthermore, the effect of topical corticosteroids on the expression of MCPs and on the cellular infiltrate was also examined. RESULTS: MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples, with prominent staining observed within the nasal epithelium. Biopsy specimens taken after challenge exhibited significant upregulation in the expression of MCP-3 and MCP-4 (P <.001). On the other hand, this increase in response to allergen was reduced in patients pretreated with topical corticosteroids. Colocalization experiments revealed that the majority of MCP+ cells in the subepithelium were macrophages, followed by T cells and eosinophils. CONCLUSION: Our results demonstrate that allergen-induced rhinitis is associated with an increased expression of MCP-3 and MCP-4, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis.     

Excretion of catecholestrogens in women receiving estrogen-substitution therapy

We compared excretion of classical estrogens and catecholestrogens in smoker and nonsmoker postmenopausal women receiving estrogen-substitution therapy. Combined effect of substitution therapy and smoking, but not smoking along increased production of catecholestrogens, which could enhance the risk of genotoxic (clinically more severe) variant of hormone-induced carcinogenesis. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 11, pp. 575–577, November, 1999     

Asymmetry during regeneration of microvessels in rabbit ear

General principle of development, the left-to-right gradient of maturation, is valid for the regeneration of microvessels in rabbit ear. This manifests itself in a more rapid regeneration of microvessels of the left ear. The right ear is characterized by excessive regeneration which then decreases to the normal. Dalargin has different effects on microvessels in different ears: in the left ear the peptide inhibits revascularization, while in the right ear it accelerates the process of revascularization. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 3, pp. 343–345, March, 1997