ABSTRACT
Local application of the Dorogov's antiseptic-stimulant onto the skin of 2-month-old male Sprague-Dawley rats in a low dose (0.5 g/kg/day) for 1 week increased motor and ultrasonic activity of experimental animals and the content of activated c-Fos+ neurons on the cingular, motor, insular, and pyriform cortex and in the striatum.
Subject(s)
Anti-Infective Agents, Local/pharmacology , Animals , Central Nervous System Stimulants/pharmacology , Cerebral Cortex/drug effects , Corpus Striatum/drug effects , Male , Motor Activity/drug effects , Neurons/drug effects , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-DawleyABSTRACT
The review represents a modern concept about cells-molecular basis of mechanisms of neuro-immune interactions, the data on the effects of destabilizing factors (electric pain stimulation, rotation, cold and psychoemotional stress) on the functioning of neurons and immune cells. It must be underlined, that under the stress conditions take place the alterations of ligand-receptors interactions on the membrane of lymphocyte. In particular the reaction of these cells to regulating signal - application of Interleikin-1 grow up after mild stress, but it falls down after an influence of severe stress factors. Special attention is paid to the role of the orexinergic system in mechanism of realization of CNS reactions to application of antigens. In the present work the possible methods of correction of imbalance in functional interactions between nervous and immune systems, caused by different destabilizing factors, are reviewed.
Subject(s)
Central Nervous System/immunology , Immune System/metabolism , Neuroimmunomodulation/genetics , Signal Transduction/immunology , Stress, Psychological/immunology , Animals , Cell Differentiation/drug effects , Central Nervous System/metabolism , Central Nervous System/physiopathology , Corticosterone/blood , Corticosterone/immunology , DNA/pharmacology , Gene Expression Regulation , Humans , Immune System/physiopathology , Immunologic Factors/pharmacology , Interleukin-1alpha/blood , Interleukin-1alpha/immunology , Interleukin-1beta/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Neuroimmunomodulation/drug effects , Neurons/immunology , Neurons/metabolism , Orexin Receptors/genetics , Orexin Receptors/immunology , Orexins/genetics , Orexins/immunology , Signal Transduction/genetics , Stress, Psychological/genetics , Stress, Psychological/physiopathology , Stress, Psychological/prevention & control , Thymocytes/cytology , Thymocytes/drug effects , Thymocytes/immunologyABSTRACT
The synthesis and biological activities of acidic, basic and neutral types of butyric acid (BA) prodrugs possessing increased aqueous solubility are described. The compounds are butyroyloxyalkyl derivatives of carboxylic acids, which possess functionalities suitable for aqueous solubilization. The anticancer activity of the prodrugs in vitro was evaluated by examining their effect on the growth of human colon, breast and pancreatic carcinoma cell lines, and their solubility in aqueous media was determined. The most promising compounds, with respect to activity and solubility, were found to be the butyroyloxymethyl esters of glutaric 2a and nicotinic acids 4a and phosphoric acid as its diethyl ester 10a, which displayed IC(50) values of 100 microM or lower. These prodrugs are expected to release formaldehyde upon metabolic hydrolysis. The corresponding butyroyloxyethyl esters (2b, 4b and 10b) that release acetaldehyde upon metabolism were significantly less potent. A similar correlation was observed for growth inhibition of the human prostate carcinoma cell lines PC-3 and LnCap and for induction of differentiation and apoptosis in the human myeloid leukemia cell line HL-60. The higher biological activity of the formaldehyde-releasing prodrugs 2a and 10a was further confirmed when induction of hemoglobin (Hb) synthesis in the human erythroleukemic cell line K562 was measured. Moreover, a therapeutic index (IC(50)/ED(50)) of ca. 5 was observed. The acute i.p. toxicity LD(50) in mice for 2a, 2b, 10a and 10b was similar and in the range of 400-600 mg kg(-1). The results obtained support the potential use of the butyric acid prodrugs for the treatment of neoplastic diseases and beta-globin disorders.
Subject(s)
Butyric Acid/chemistry , Butyric Acid/pharmacology , Neoplasms/drug therapy , Prodrugs/chemical synthesis , Prodrugs/pharmacology , Animals , Apoptosis , Cell Division/drug effects , Female , HL-60 Cells/drug effects , Hemoglobins/biosynthesis , Hemoglobins/drug effects , Humans , Lethal Dose 50 , Male , Mice , Mice, Inbred BALB C , Neoplasms/pathology , Prodrugs/chemistry , Solubility , Tumor Cells, CulturedSubject(s)
Hospitals, District , Surgical Procedures, Operative , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Reoperation/statistics & numerical data , Surgical Procedures, Operative/statistics & numerical data , Treatment Outcome , Ukraine/epidemiologyABSTRACT
Clinical signs of chronic nonspecific diseases of the lung and their frequency in patients with and without tuberculosis and in those with nonspecific processes are described. The treatment results in the patients with nonspecific diseases of the lung and tuberculosis are presented.
