Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents

The chemical structure of phenothiazine provides a most valuable molecular template for the development of agents able to interact with a wide variety of biological processes. Synthetic phenothiazines (with aliphatic, methylpiperazine, piperazine-ethanol, piperazine-ethyl, or piperidine side-chain) and/or phenothiazine-derived agents e.g., thioxanthenes, benzepines, imonostilbenes, tricyclic antidepressants, dimetothiazine, and cyproheptadine have been effective in the treatment of a number of medical conditions with widely different etiology. These include various currently clinically used drugs for their significant antihistamic, antipsychotic, anticholinergic (antiparkinson), antipruritic, and/or antiemetic properties. They are also employed, although to a minor extent, as antidepressants, antispasmodics, analgesics, and antiarrhythemics. Some of these agents are also useful as anti-inflammatory, coronary vasodilator, radioprotective, sedative, antitussive, and skeletal muscle-rela

Trophic factors in cerebrospinal fluid and spinal cord of patients with tropical spastic paraparesis, HIV, and Creutzfeldt-Jakob disease

HTLV-1-associated myelopathy/tropical spastic paraparesis (TSP/HAM) is a chronic CNS disease characterized by axomyelinic degeneration of the long axons of corticospinal tracts. Levels of NGF, NT-3, NT-4/5, BDNF, GDNF, CNTF, and FGF-2 were measured in the cerebrospinal fluid (CSF) of 21 TSP/HAM patients and 20 controls. NGF, BDNF, and FGF-2 levels were also determined in 19 patients with HIV motor cognitive motor syndrome, and in 21 subjects diagnosed with Creutzfeldt Jakob disease (CJD). No significant differences were detected in the concentrations of NGF, BDNF, NT-3, NT-4/5, GDNF, and CNTF in the CSF between TSP/HAM patients and controls. FGF-2 was significantly lower in the CSF of the three groups of patients compared with controls; the HIV group exhibited the lowest values. HIV patients differed from TSP/HAM in their significantly higher levels of NGF and lower levels of BDNF and FGF-2, whereas CJD patients differed only in their higher levels of NGF. Immunohistochemical studies

Maximization of the docosahexaenoic and eicosapentaenoic acids content in concentrates obtained from a by-product of rainbow trout (Oncorhynchus mykiss) processing

This study was focused on a by-product (i.e., belly muscle) resulting from the commercial processing of rainbow trout (Oncorhynchus mykiss). In it, n-3 long-chain polyunsaturated fatty acid (LCPUFA) concentrates were obtained from the belly oil by optimization of the urea-complexation process variables. Thus, the effect of urea:fatty acids (FA) ratio (0-6, w/w), crystallization temperature (- 30 to 30 degrees C), crystallization time (3.0-48.0 h) and stirring speed (0-1000 rpm) on the eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) contents in concentrates was analyzed by response surface methodology. As a result, high values were obtained for total FA yield recovered, and contents on LCPUFA, EPA and DHA in the non-urea complexing fraction, as well as a great retention of saturated and monounsaturated FA in the urea-crystal adducts. After validation of the model obtained, the combination of process variables levels that maximizes the desirability function (0.91 score) for response variables was 4.21, -15 degrees C, 24 h and 1000 rpm, respectively. In agreement with the great significance and availability of farmed rainbow trout, belly muscle by-product confirmed to be a profitable source of n-3 LCPUFA to be commercialized as an added-value component.FONDECYT-CONICYT (Fondo Nacional de Desarrollo Cientifico y Tecnologico-Comision Nacional de Investigacion Cientifica y Tecnologica) program 112062

Properties of two apyrases from Solanum tuberosum

Two homogeneous isoenzymes of apyrase from Pimpernel and Desirée varieties of Solanum tuberosum were obtained by affinity chromatography on agarose-Cibacron Blue or agarose-ATP-phosphonate columns. Both enzymes split POP bonds of organic and inorganic di- and triphosphates. The ratio of ATPase/ADPase is different for the two apyrases: 10 for Pimpernel and 1 for Desirée. All these activities require bivalent metals. Both isoapyrases have the same MW (49 000) but differ in their pI (8.74 for Pimpernel and 6.69 for Desirée). The optimum pH of hydrolysis of organic di- and triphosphates is 6 (except for Pimpernel ADPase) and 5 for inorganic substrates. Chemical modification of tryptophan, tyrosine, arginine and carboxylic residues decreased all enzymic activities of both enzymes. Protection by substrates and inactivation rates of the individual activities are different for each isoenzyme. © 1982

Gelatinase activitiy of matrix metalloproteinases in the cerebrospinal fluid of various patient populations

Artículo de publicación ISIWe have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis

Stimulatory response of neutrophils from periodontitis patients with periodontal pathogens

Publicación ISIOBJECTIVE: Neutrophils play a crucial role in the defense of invading bacteria by releasing biologically active molecules. The response of peripheral blood neutrophils was studied in periodontitis-affected patients and in healthy controls towards stimulation to Porphyromonas gingivalis (Pg) and Actinobacillus actinomycetemcomitans (Aa) extracts. MATERIALS AND METHODS: Peripheral venous blood was drawn from 23 adult patients with moderate to advanced chronic periodontitis (probing depth >= 5 mm, attachment loss >= 3 mm), and 30 healthy volunteers. Neutrophil response followed by metalloproteinase-9 (MMP-9) and interleukin-8 (IL-8) secretion was assayed by zymography and enzyme-linked immunosorbent assay, respectively, on both whole blood and purified neutrophils. In addition to periodontal pathogen extracts, known stimulating agents were tested, such as Escherichia coli-lipopolysaccharide (LPS), phytohemagglutinin, and zymosan A. RESULTS: Neutrophil response, expressed as a secretion ratio under stimulated and non-stimulated conditions, measured in whole blood, showed no differences between periodontitis and healthy controls. Instead, in purified neutrophils from patients, MMP-9 exhibited a significantly higher secretion ratio with LPS and Pg (1.5- to 2-fold), whereas IL-8 showed a larger increase in secretion ratio (3- to 7-fold) in the presence of Pg, Aa, LPS, and zymosan A. CONCLUSION: Peripheral neutrophils of periodontitis-affected patients are more reactive as suggested by their significantly higher response toward periodontal pathogen extracts and other stimulating agents