ETHNOPHARMACOLOGICAL RELEVANCE: The development of selective inhibitors of monoamine oxidase B (MAO-B) has been essential in treating Parkinson's disease. However, the apparent hepatotoxicity and drug-drug interactions of current inhibitors accentuate the need for the development of novel pharmacotherapies. Crossyne guttata (L.) D. & U. Müll-Doblies is used frequently by Rastafarian bush doctors to treat alcoholism, a disorder which is also accentuated by MAO. OBJECTIVE: The study sought to isolate, identify and characterise the biologically active constituents of C. guttata based on their ability to inhibit the MAO enzymes. MATERIALS AND METHODS: Column chromatography was used to isolate the biologically active alkaloids of C. guttata. The ability of the alkaloids to inhibit the biotransformation of 4-aminoantipyrine by the MAO enzymes was evaluated in vitro. In silico docking was conducted using AutoDock Vina server while the pharmacokinetic properties of the compounds were evaluated using SwissADME. RESULTS: Chromatographic separation of an ethanolic fraction of C. guttata yielded the alkaloids crinamine 1 and epibuphanisine 2. 1 and 2 along with structurally related alkaloids haemanthamine 3 and haemanthidine 4 were evaluated for their ability to inhibit the action of isozymes of MAO in vitro. Alkaloids effected submicromolar IC50 values against MAO-B, the most potent of which being crinamine 1 (0.014 μM) > haemanthidine 4 (0.017 μM) > epibuphanisine 2 (0.039 μM) > haemanthamine 3 (0.112 μM). Binding energies of the alkaloids correlated well with their inhibitory potential with crinamine displaying the best binding efficacy and binding energy score with MAO-B. DISCUSSION AND CONCLUSION: Crinamine and epibuphanisine exhibited potent and selective inhibitory activity towards MAO-B. After comprehensive in silico investigations encompassing robust molecular docking analysis, the drug-like attributes and safety of the alkaloids suggest the crinamine is a potentially safe drug for human application.
- MeSH
- alkaloidy amarylkovitých chemie farmakokinetika farmakologie toxicita MeSH
- bezpečnost pacientů MeSH
- biologické modely * MeSH
- Cercopithecus aethiops MeSH
- hodnocení rizik MeSH
- inhibitory MAO chemie farmakokinetika farmakologie toxicita MeSH
- konformace proteinů MeSH
- lidé MeSH
- monoaminoxidasa chemie metabolismus MeSH
- mutace MeSH
- Salmonella typhimurium účinky léků genetika MeSH
- simulace molekulového dockingu * MeSH
- Vero buňky MeSH
- viabilita buněk účinky léků MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
8. vydání 266 stran : ilustrace, tabulky ; 23 cm
- MeSH
- klasifikace MeSH
- nádory klasifikace MeSH
- staging nádorů MeSH
- Publikační typ
- přehledy MeSH
- příručky MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- onkologie
- Publikační typ
- abstrakt z konference MeSH
Fourteen blue-green and green algae survived for widely different time periods ranging between 22-102 d in control culture medium. Irrespective of their long or short survival period in control cultures, their pro- or eukaryotic nature, their different morphological types or natural habitats, they all survived for a short time period ranging between 3-8 d in sewage water, 5-10 d in fertilizer factory effluent, (1/4)-2 d in brassica oil, (1/2)-2 d in phenol, 1-3 d in toluene, and 1-4 d in benzene (showing the relative toxicity of different chemicals to different algae, and the antialgal nature of brassica oil). Dilution decreased the toxicity of these agents very little, indicating that they all were very toxic to algae. None of the agent induced the formation of any reproductive or dormant cells. Sewage water, fertilizer factory effluent, brassica oil and/or benzene favored the formation of necridia cells in Phormidium bohneri, P. foveolarum, Microcoleus chthonoplastes, Lyngbya birgei, and L. major filaments. Scenedesmus quadricauda shed off all spines earlier, Hormidium flaccidum fragmented less or not at all, Scytonema millei formed no false branch and heterocyst, Aphanothece pallida and Gloeocapsa atrata cells did not divide, Cosmarium granatum cells did not form any zygospore and Oedogonium sp. not any oogonia-like cells under all or most of treatments with 25-100 % sewage water, 1-100 % fertilizer factory effluent, 1-100 % brassica oil, 25-100 % phenol, toluene and benzene.
- MeSH
- benzen farmakologie MeSH
- chemické látky znečišťující vodu farmakologie MeSH
- Chlorophyta fyziologie účinky léků MeSH
- fenol farmakologie MeSH
- odpadní vody analýza MeSH
- organické látky farmakologie MeSH
- průmyslový odpad analýza MeSH
- rozmnožování účinky léků MeSH
- spory fyziologie účinky léků MeSH
- toluen farmakologie MeSH
Lyngbya major (a wall alga), survived throughout year, maximally to >80 % at atmospheric temperature (AT) of 17-36 degrees C and relative humidity (RH) 60-100 % in rainy and spring seasons, but the survival was 43-64 % in winter when AT decreased to 5 degrees C and RH was 65-98 %, and 15-23 % in summer when AT reached 48 degrees C and RH was 23-60 %. All soil algae (Lyngbya birgei, Aphanothece pallida, Gloeocapsa atrata, Oscillatoria subbrevis, O. animalis) survived >90 % in rainy season when soil moisture content (SMC) was 89-100 %. Lowering of SMC to a minimum of 55 % in spring and 39 % in winter led L. birgei, O. subbrevis and O. animalis to survive from 75, 66, and 65 %, respectively, in spring and 12, 14, and 20 % in winter, and A. pallida and G. atrata not at all in both seasons. All soil algae did not survive in summer when SMC was 12-30 %. Myxosarcina burmensis survived only in rainy and spring seasons when pond water temperature (PWT) was 19-25 degrees C and 18-26 degrees C, respectively, and not in winter and summer when PWT was 2-14 degrees C and 25-36 degrees C, respectively. L. major and A. pallida survived almost equally well under both submerged and air-exposed conditions for 15 d but less if submerged for more time than air-exposed on moist soil surface, while L. birgei, G. atrata, O. subbrevis, and O. animalis survived submergence in liquid medium better and longer than air-exposure on moist soil surface. Pond alga M. burmensis survived submergence better than air-exposure, true to its aquatic habitat. All algae survived less and died without forming any resistant cells when exposed to physical and physiological water stress (imposed by growing them on highly agarized media or in salinized liquid media), light stress (at 0, 2 and 10 micromol m(-2) s(-1) light intensity) or following UV shock (0.96-3.84 kJ/m(2)). A. pallida and G. atrata cells did not divide on 8 % agarized solid media, in > or =0.3 mol/L salinized liquid media, and in darkness. The presence of sheath over L. major and L. birgei filament cells and mucilage cover over A. pallida and G. atrata cells protect them against physical desiccation to some extent but not against UV shock.
Pithophora oedogonia and Cladophora glomerata survived lowest 60 and 58%, respectively, in June when the pond diurnal water temperature (PDWT) increased to a maximum of 28 degrees C. The lowering of PDWT only by 1 degrees C in July improved survivability of both algae to their almost maximum level of 100 and 96%, respectively. Further lowering of PDWT to 17-22 degrees C in November initiated akinete formation in P. oedogonia. The process of akinete initiation, maturation and germination continued till April when PDWT increased to 20-24 degrees C, but not beyond that in May when PDWT was 21-26 degrees C. By this time, probably all akinetes have germinated in situ, and the alga was entirely vegetative. P. oedogonia population is not synchronous in nature, since during the 5-6-month reproductive season, some filaments were in active vegetative stage, some had akinete initiation, some had completed akinete formation, and some had akinetes germinating. C. glomerata grew dense vegetative in November and initiated (zoo)sporangial primordia formation (to some extent) in February (when PDWT was lowest, viz. 10-14 degrees C) till April. Meanwhile, no (zoo)-sporangial primordia either produced any zoospore or germinated into a germ tube; and all released their cytoplasmic content and died (along with some vegetative cells) with an increase in PDWT to 21-26 degrees C in May. Vaucheria geminata vegetative patches appeared on the soil surface, 2nd week of January by lowering of atmospheric diurnal temperature (ADT) to 9-16 degrees C in the 1st week. The alga started sexual reproduction by the 2nd week of March (when ADT increased to 20-23 degrees C) and completed the process of reproduction by the 1st week of April (when ADT increased to 24-26 degrees C) and died thereafter. P. oedogonia, C. glomerata and V. geminata survived better and longer in submerged conditions than air-exposed (which was true for P. oedogonia and C. glomerata aquatic habitat and also indicated that the soil alga V. geminata could survive to some extent if submerged in rain water). P. oedogonia formed akinetes and C. glomerata (zoo)sporangial primordia only in submerged condition and not when air-exposed on moist soil surface. V. geminata did not complete the life cycle both under submerged and air-exposed conditions. Vegetative survival in P. oedogonia, C. glomerata, V. geminata, Aphanothece pallida, Gloeocapsa atrata, Scytonema millei, Myxosarcina burmensis, Phormidium bohneri, Oscillatoria animalis, O. subbrevis, Lyngbya birgei, L. major, Microcoleus chthonoplastes and Rhizoclonium crassipellitum, reproduction in P. oedogonia, C. glomerata and V. geminata, cell division in A. pallida and G. atrata, heterocyst and false branch formation in S. millei, all, were adversely affected at approximately 28.5 degrees C for t12 h at light intensity of approximately 160 micromol m(-2) s(-1); high intensity does not ameliorate high temperature damage to any algae. The presence of liquid water, than its absence, outside the different algae moderated the severity of heat to some extent but not when the heat was severe.
Navicula grimmei and Nitzschia palea occurring almost equally in a mixed population on department moist garden soil surface when maintained in fresh supernatant (of soil-water medium) at pH 7.0, temperature of 26 +/- 1 degree C and under continuous light (intensity of approximately equal to 30 micromol m(-2) s(-1)) in a culture chamber exhibited a similar cell survival period (of 28 d) and percentage (at the beginning 100 % and mid of survival period 65 %) and stop gliding 11 d prior to cell death (with gliding speed reduced in both from 204-330 microm/min at the beginning to 82.5-99 microm/min at the mid of gliding period) irrespective of their size differences. However, a sharp fall in the cell gliding period, gliding cell percentage and speed occurred at various levels (different from cell survival period and percentage) in both diatoms in a similar extent under water stress (2, 4 and 6 % agarized supernatant, liquid supernatant with 0.2-1.0 mol/L NaCl, blot-dryness of cells for 5-15 min), pH extreme of liquid supernatant (< or =5.0, > or =9.0), temperature extremes in liquid supernatant (< or =15, > or =40 degrees C), UV exposure (0.96-5.76 kJ/m2), lack of all nutrients from the medium (double distilled water), darkness or low light intensities (2 and 10 micromol m(-2) s(-1)), presence of 'heavy' metals (Ni, Cu, Zn, Co, Fe, Hg; 1-200 ppm), organic substances in liquid supernatant (DDT, captan, urea, 2,4-D, 100-2000 ppm; thiourea, 50-1000 ppm). N. palea sway (turn around at either ends) or not only when gliding but independent of cell gliding speed, which decreased continuously under all conditions.
- MeSH
- Eukaryota cytologie klasifikace růst a vývoj MeSH
- močovina chemie škodlivé účinky MeSH
- organické látky chemie škodlivé účinky MeSH
- pohyb buněk fyziologie účinky léků MeSH
- rozsivky fyziologie chemie růst a vývoj MeSH
- těžké kovy chemie škodlivé účinky MeSH
- thiomočovina chemie škodlivé účinky MeSH
- ultrafialové záření škodlivé účinky MeSH
- viabilita buněk fyziologie účinky léků MeSH
Population and evolutionary analyses of pathogenic bacteria are frequently hindered by sampling strategies that concentrate on isolates from patients with invasive disease. This is especially so for the gram-negative diplococcus Neisseria meningitidis, a cause of septicemia and meningitis worldwide. Meningococcal isolate collections almost exclusively comprise organisms originating from patients with invasive meningococcal disease, although this bacterium is a commensal inhabitant of the human nasopharynx and very rarely causes pathological effects. In the present study, molecular biology-based techniques were used to establish the genetic relationships of 156 meningococci isolated from healthy young adults in the Czech Republic during 1993. None of the individuals sampled had known links to patients with invasive disease. Multilocus sequence typing (MLST) showed that the bacterial population was highly diverse, comprising 71 different sequence types (STs) which were assigned to 34 distinct complexes or lineages. Three previously identified hyperinvasive lineages were present: 26 isolates (17%) belonged to the ST-41 complex (lineage 3); 4 (2.6%) belonged to the ST-11 (electrophoretic type [ET-37]) complex, and 1 (0.6%) belonged to the ST-32 (ET-5) complex. The data were consistent with the view that most nucleotide sequence diversity resulted from the reassortment of alleles by horizontal genetic exchange.
- MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Neisseria meningitidis klasifikace genetika MeSH
- přenašečství mikrobiologie MeSH
- sérotypizace MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
