ABSTRACT
Novel continuous-flow cascade reactions are developed for producing 1,4-diaryl-disubstituted dipolar γ-carbolines 2 that contain a carboxylate group and their two pentacyclic precursors 6, 7 from hemiindigos 1. The nucleophilic and pro-electrophilic chemistry described is new to the hemiindigos 1, and it led to the discovery of antimycobacterial scaffold characteristic of rimino-type pentacycles 6, 7 and potent drug clofazimine. The new scaffold like clofazimine appears to be useful in developing lead agents active against drug-resistant/dormant TB.
ABSTRACT
Biologic scaffold materials composed of the extracellular matrix (ECM) are typically derived by processes that involve decellularization of tissues or organs. All decellularization methods result in the ECM architecture disruption and a potential loss of surface structure and composition. Freeze-thaw processing effectively lyses cells and permits to diminish amounts of chemical lysing agents henceforth. However, it also causes certain disruptions of the ECM ultrastructure. In order to diminish these adverse effects we suggested using extracellular cryoprotectants (namely 5 % trehalose) to preserve the ECM molecular network without impeding the cell lysis. The original optimization of the perfusion-mediated decellularization method to comprise the single freeze-thaw processing cycle and subsequent perfusion with chemical agents' solution is presented here.
Subject(s)
Cryopreservation , Cryoprotective Agents/metabolism , Extracellular Matrix/ultrastructure , Glycerol/metabolism , Liver/ultrastructure , Trehalose/metabolism , Animals , Cryopreservation/methods , Extracellular Matrix/chemistry , Extracellular Matrix/drug effects , Freezing , Liver/chemistry , Liver/cytology , Liver/drug effects , Rats , Tissue Engineering , Tissue Scaffolds/chemistryABSTRACT
We studied high-resolution (1)H nuclear magnetic resonance spectra of the serum and serum albumin from patients with the first episode of schizophrenia and healthy individuals. A relative increase in signal intensities of CH(2) protons in serum LDL and VLDL in schizophrenia was demonstrated. Higher intensities of CH(2) and CH(3) protons of non-esterified fatty acids were found in (1)H nuclear magnetic resonance spectra of serum albumin. These data attest to an essential role of changes in lipid metabolism and changed ligand load of albumin in schizophrenia.
Subject(s)
Protons , Schizophrenia/diagnosis , Serum Albumin/chemistry , Adolescent , Adult , Female , Humans , Lipid Metabolism , Lipoproteins, LDL/chemistry , Lipoproteins, LDL/metabolism , Lipoproteins, VLDL/chemistry , Lipoproteins, VLDL/metabolism , Male , Nuclear Magnetic Resonance, Biomolecular , Protein Conformation , Schizophrenia/metabolism , Serum Albumin/metabolismABSTRACT
Ethyl 4,4-difluoro-4-phenoxyacetoacetate was obtained and studied as a precursor to new heterocyclic compounds. 6-Hydroxypyrimidine, 1,3-dihydro-1,5- benzodiazepin-2-one, quinolin-2-one and 6-hydroxypyrazolo[3,4-b]pyridine derivatives containing phenoxydifluoromethyl groups were synthesized. These results make it possible to introduce aryloxydifluoromethyl substituents for the design of biologically active heterocycles.
Subject(s)
Acetoacetates/chemical synthesis , Heterocyclic Compounds/chemistry , Acetoacetates/chemistry , Cyclization , Heterocyclic Compounds/chemical synthesis , Nitrogen/chemistryABSTRACT
The Expanded Programme on Immunization (EPI) whose goal is to reduce morbidity and mortality by providing children with immunizations against diphtheria, pertussis, tetanus, poliomyelitis, measles, and tuberculosis continually faces the problem of documenting immunization coverage rates. Therefore the EPI seeks simple, effective, and inexpensive methods of evaluation which could be implemented in different countries. An example of such a method is a simplified cluster sampling technique of estimation of immunization coverage through the examination of 210 children, selected randomly as 30 groups of 7 children each. In 1978-1984 more than 1000 immunization coverage surveys were performed all over the world, mainly in developing countries. In a modified way this method is also used to collect data on morbidity and mortality of certain EPI target diseases as well as diarrhoeal diseases.
Subject(s)
Epidemiologic Methods , Statistics as Topic , Child , Communicable Disease Control/methods , Communicable Diseases/epidemiology , Global Health , Humans , Immunization , Research Design , World Health OrganizationABSTRACT
The state of the parodontium was studied clinically and morphologically in 70 patients suffering from diabetes mellitus. Blood histamine and serotonin level was determined fluorometrically. Gingivitis was revealed in diabetic patients; the severity of inflammatory changes in the gingiva proved to depend on the duration and the severity of diabetes mellitus. Changes pointing to increase of the vaso-tissue permeability were revealed histologically. At the same time there was an increase in the blood histamine level and a tendency to reduction of serotonin level. This can serve as one of the factors causing an increase of the vascular permeability and a disturbance of microcirculation in the gingiva.
