BACKGROUND: Venotonics are a class of therapeutically active molecules that have vaso-protective effects. They are used to alleviate venous diseases and disorders, particularly venous insufficiency. We compared the composition of prescription versus over-the-counter (OTC) venotonics using high-performance liquid chromatography with UV detection (HPLC-DAD) and simulating their digestion using a static digestive model. METHODS: From each drug, five tablets were weighed. A homogenate was prepared, and 25 mg of crushed homogenized tablets were weighed into 25 ml volumetric flasks. Dissolved in MeOH and added two drops of saturated NaOH solution. The samples were filtered into vials (Teflon, 0.45 μm) and used for analysis. An Ultimate 3000 HPLC system (Thermo Fisher Scientific, Waltham, MA, USA) consisting of a quaternization pump, autosampler, column thermostat and DAD (UV/VIS detector) was used. The composition of the mobile phase proceeded in a linear gradient from 30% methanol and 70% phosphoric acid (0.15%) in water at time t=0 min. to 80% methanol and 20% phosphoric acid (0.15%) at time t=15 min., at a constant mobile phase flow rate of 1.2 mL/min. Detection was performed using a DAD detector in the 190-450 nm wavelength range. The content of monitored flavonoids was calculated from peaks at a wavelength of 277 nm, in which both flavonoids have their absorption maxima. The static digestive model was used to simulate the digestive phase from the oral cavity to the corresponding intestinal phase. RESULTS: The content of diosmin and hesperidin (mg per table) for a prescription drug: Detralex: 480 mg, 26 mg. The content of diosmin and hesperidin (mg per tablet) for OTC drugs: Venostop: 502 mg, 48 mg, Diosminol: 520 mg, 50 mg, Devenal: 496 mg, 49 mg, Diohes: 493 mg, 46 mg. Digestion did not affect the solubility of all tested drugs. The active substances could not be determined in the non-alkalized sample. After alkalization, part of the insoluble matter was visibly dissolved and converted to a yellow flavonoid complex. Neither diosmin nor hesperidin could be identified afterwards. CONCLUSIONS: Our experimental results show that the contents of both listed active substances, diosmin and hesperidin, met the declared amounts in all tested medicaments. Digestion simulation showed identical behaviour in prescription and OTC venotonics. The active substances could not be determined in the non-alkalized sample. Digestion did not affect the solubility of the tested drugs.
- MeSH
- Models, Biological MeSH
- Diosmin analysis MeSH
- Hesperidin analysis MeSH
- Nonprescription Drugs * chemistry MeSH
- Prescription Drugs analysis chemistry MeSH
- Humans MeSH
- Tablets MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Comparative Study MeSH
Lysosomes, now known to take part in multiple cellular functions, also respond to various stress stimuli. These include biogenesis in response to nanomolar concentrations of hydrophobic weak-base anticancer drugs. However, since lysosomal stress mediated by accumulation of weak-base drugs at such concentrations has never been proven and these drugs have diverse effects on malignant cells, we investigated whether the interpretation of the data was true. We found that lysosomal accumulation of the drugs daunorubicin, doxorubicin, mitoxantrone, symadex, chloroquine, clomipramine and sunitinib alone, was insufficient to induce lysosomal alkalization i.e., lysosomal stress-mediated biogenesis at nanomolar concentrations. Instead, we found that some of the drugs used induced G2 phase arrest and lysosomal biogenesis that is associated with activation of transcription factor EB (TFEB). Similarly, cantharidin, a control compound that does not belong to the weak base drugs, induced cell cycle arrest in the G2 phase associated with TFEB-driven lysosomal biogenesis. Overall none of the tested drugs caused stress-induced lysosomal biogenesis at nanomolar concentrations. However, daunorubicin, doxorubicin, mitoxantrone, symadex and cantharidin induced a massive block in the G2 phase of the cell cycle which is naturally associated with TFEB-driven lysosomal biogenesis.
- MeSH
- Autophagy MeSH
- Cell Cycle MeSH
- Doxorubicin metabolism pharmacology MeSH
- Cantharidin * MeSH
- Lysosomes metabolism MeSH
- Mitoxantrone * pharmacology MeSH
- Publication type
- Journal Article MeSH
The genus Pseudogymnoascus encompasses soil psychrophilic fungi living also in caves. Some are opportunistic pathogens; nevertheless, they do not cause outbreaks. Pseudogymnoascus destructans is the causative agent of the white-nose syndrome, which is decimating cave-hibernating bats. We used comparative eco-physiology to contrast the enzymatic potential and conidial resilience of P. destructans with that of phylogenetically diverse cave fungi, including Pseudogymnoascus spp., dermatophytes and outdoor saprotrophs. Enzymatic potential was assessed by Biolog MicroArray and by growth on labelled substrates and conidial viability was detected by flow cytometry. Pseudogymnoascus destructans was specific by extensive losses of metabolic variability and by ability of lipid degradation. We suppose that lipases are important enzymes allowing fungal hyphae to digest and invade the skin. Pseudogymnoascus destructans prefers nitrogenous substrates occurring in bat skin and lipids. Additionally, P. destructans alkalizes growth medium, which points to another possible virulence mechanism. Temperature above 30 °C substantially decreases conidial viability of cave fungi including P. destructans. Nevertheless, survival of P. destructans conidia prolongs by the temperature regime simulating beginning of the flight season, what suggests that conidia could persist on the body surface of bats and contribute to disease spreading during bats active season.
- MeSH
- Ascomycota enzymology metabolism physiology MeSH
- Chiroptera microbiology physiology MeSH
- Phylogeny MeSH
- Caves MeSH
- Lipase MeSH
- Mycoses physiopathology MeSH
- Nose microbiology MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
This study analysed the effect of three alkalizing soil amendments (limestone, dolomite chalcedonite) on aided phytostabilization with Festuca rubra L. depending on the hexavalent chromium (Cr(VI)) level in contaminated soil. Four different levels of Cr(VI) were added to the soil (0, 50, 100 and 150 mg/kg). The Cr contents in the plant roots and above-ground parts and the soil (total and extracted Cr by 0.01 M CaCl2) were determined with flame atomic absorption spectrometry. The phytotoxicity of the soil was also determined. Soil amended with chalcedonite significantly increased F. rubra biomass. Chalcedonite and limestone favored a considerable accumulation of Cr in the roots. The application of dolomite and limestone to soil contaminated with Cr(VI) contributed to a significant increase in pH values and was found to be the most effective in reducing total Cr and CaCl2-extracted Cr contents from the soil. F. rubra in combination with a chalcedonite amendment appears to be a promising solution for phytostabilization of Cr(VI)-contaminated areas. The use of this model can contribute to reducing human exposure to Cr(VI) and its associated health risks.
- MeSH
- Kidney Failure, Chronic diagnosis therapy MeSH
- Renal Dialysis adverse effects methods MeSH
- Hemodialysis Solutions adverse effects chemistry MeSH
- Bicarbonates blood MeSH
- Humans MeSH
- Parathyroid Hormone blood MeSH
- Hyperparathyroidism, Secondary etiology physiopathology MeSH
- Sensitivity and Specificity MeSH
- Calcium blood MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Letter MeSH
Cíl: Popsat nález neobvyklého močového konkrementu u pětiletého pacienta s kongenitální hypofosfatázií. Typ studie: Kazuistika se zhodnocením laboratorních nálezů. Název a sídlo pracoviště: Ústav lékařské chemie a klinické biochemie 2. lékařské fakulty Univerzity Karlovy a Fakultní nemocnice Motol, Pediatrická klinika 2. lékařské fakulty Univerzity Karlovy a Fakultní nemocnice Motol, V Úvalu 84, 150 06 Praha 5 Materiál a metody: Popis kazuistiky se zaměřením se především na analýzy močových konkrementů pomocí polarizační mikroskopie a infračervené spektrometrie. Výsledky: U pětiletého pacienta s kongenitální hypofosfatázií efektivně léčeného rekombinantní alkalickou fosfatázou (jejíž hodnota v séru představovala desetinásobek horní hranice referenčního rozmezí) byl prokázán raritní pyrofosfátový močový konkrement s příměsí sulfátu. K jeho tvorbě došlo v období, kdy byla u pacienta terapeuticky alkalizována moč (jejímž důvodem byla metafylaxe urátové urolitiázy), a pacient užíval profylakticky sulfonamidy před plánovanou litotrypsí. Závěr: Ačkoliv sérová koncentrace alkalické fosfatázy, jejíž funkcí je přeměna pyrofosfátu na fosfát, byla vysoká, byl u pacienta s kongenitální hypofosfatázií identifikován pyrofosfátový močový konkrement. Sulfátová složka konkrementu vznikla pravděpodobně na podkladě profylaktického podávání sulfonamidů.
Objectives: Identification of unusual renal pyrophosphate stone in 5 years old patient with congenital hypophosphatasia. Design: Case report and evaluation of laboratory results. Settings: Department of Medical Chemistry and Clinical Biochemistry, University Hospital Motol, Charles University, Second Faculty of Medicine, Department of Paediatrics, University Hospital Motol, Charles University, Second Faculty of Medicine, V Úvalu 84, 150 06 Prague 5 (Czech Republic). Material and methods: Case report focusing on determination of urinary stone composition by polarized light microscopy and infra-red spectrometry. Results: In 5 years old patient with effectively treated congenital hypophosphatasia by recombinant alkaline phosphatase (the serum value of which was ten times the upper limit of the reference range), rare pyrophosphate renal stone with addition of sulphate was demonstrated. The formation of the stone occurred in the period when the patient´s urine was therapeutically alkalized (due to the history of urate stones) and the patient used prophylactically sulfonamides prior to planned lithotripsy. Conclusion: Despite the high serum alkaline phosphatase concentration, the function of which is the conversion of pyrophosphate to phosphate, pyrophosphate renal stone was identified in a patient with congenital hypophosphatasia. The sulphate component of the stone is probably due to the prophylactic administration of sulfonamides.
- Keywords
- infračervená spektrometrie,
- MeSH
- Urinalysis methods MeSH
- Chemistry Techniques, Analytical methods MeSH
- Diphosphates analysis MeSH
- Hypophosphatasia * complications pathology MeSH
- Clinical Laboratory Techniques methods MeSH
- Kidney Calculi * etiology chemistry therapy MeSH
- Humans MeSH
- Lithotripsy methods MeSH
- Child, Preschool MeSH
- Sulfonamides therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Publication type
- Case Reports MeSH
Hydroxychlorochin primárně sloužil k léčbě a prevenci malárie, postupem doby byl zjištěn jeho terapeutický účinek i na autoimunitní zánětlivé revmatické onemocnění. Hydroxychlorochin má schopnost alkalizace kyselého prostředí lyzosomů, kdy prostřednictvím zvýšení pH dochází k ovlivnění celé řady důležitých dějů, které ve svém důsledku vedou k zásahu do mechanismů buněčné i humorální imunitní odpovědi. Podávání hydroxychlorochinu je u systémového lupus erythematodes doporučováno u všech nemocných, pokud nejsou přítomny kontraindikace. Hydroxychlorochin u těchto pacientů redukuje riziko vzplanutí (tzv. flare) orgánového postižení, má účinky šetřící kortikosteroidy a snižuje riziko tromboembolických příhod. Hydroxychlorochin lze podávat v těhotenství i v laktaci. Jedná se o relativně dobře tolerovaný lék. Mezi nežádoucí účinky patří potenciální rozvoj očních komplikací, obzvláště retinopatie. Tato práce se zabývá mechanismem účinku a bezpečností léčby u systémového lupus erythematodes.
Hydroxychloroquine was primarily used for the treatment and prevention of malaria, and its therapeutic effect on autoimmune inflammatory rheumatic disease has been reported over time. Hydroxychloroquine has the ability to alkalize the acidic environment of lysosomes, whereby a number of important events are influenced by an increase in pH, leading to an intervention in the mechanisms of both cellular and humoral immune responses. Hydroxychloroquine is recommended for systemic lupus erythematosus in all patients unless contraindications are present. Hydroxychloroquine reduces the risk of flare, organ involvement, has corticoid-sparing effects and reduces the risk of thromboembolic events in systemic lupus erythematosus. Hydroxychloroquine can be used during pregnancy and lactation. It is a relatively well tolerated drug. Side effects include the potential development of ocular side effects, especially retinopathy. This paper deals with the mechanism of action and safety of treatment in systemic lupus erythematosus.
- MeSH
- Antimalarials history therapeutic use MeSH
- Antirheumatic Agents therapeutic use MeSH
- Hydroxychloroquine * pharmacokinetics adverse effects therapeutic use MeSH
- Cardiovascular Diseases prevention & control MeSH
- Humans MeSH
- Lupus Erythematosus, Systemic drug therapy immunology complications MeSH
- Toll-Like Receptors drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Though bivalve mollusks are keystone species and major species groups in aquaculture production worldwide, gamete biology is still largely unknown. This review aims to provide a synthesis of current knowledge in the field of sperm biology, including spermatozoa motility, flagellar beating, and energy metabolism; and to illustrate cellular signaling controlling spermatozoa motility initiation in bivalves. Serotonin (5-HT) induces hyper-motility in spermatozoa via a 5-HT receptor, suggesting a serotoninergic system in the male reproductive tract that might regulate sperm physiology. Acidic pH and high concentration of K+ are inhibitory factors of spermatozoa motility in the testis. Motility is initiated at spawning by a Na+-dependent alkalization of intracellular pH mediated by a Na+/H+ exchanger. Increase of 5-HT in the testis and decrease of extracellular K+ when sperm is released in seawater induce hyperpolarization of spermatozoa membrane potential mediated by K+ efflux and associated with an increase in intracellular Ca2+ via opening of voltage-dependent Ca2+ channels under alkaline conditions. These events activate dynein ATPases and Ca2+/calmodulin-dependent proteins resulting in flagellar beating. It may be possible that 5-HT is also involved in intracellular cAMP rise controlling cAMP-dependent protein kinase phosphorylation in the flagellum. Once motility is triggered, flagellum beats in asymmetric wave pattern leading to circular trajectories of spermatozoa. Three different flagellar wave characteristics are reported, including "full", "twitching", and "declining" propagation of wave, which are described and illustrated in the present review. Mitochondrial respiration, ATP content, and metabolic pathways producing ATP in bivalve spermatozoa are discussed. Energy metabolism of Pacific oyster spermatozoa differs from previously studied marine species since oxidative phosphorylation synthetizes a stable level of ATP throughout 24-h motility period and the end of movement is not explained by a low intracellular ATP content, revealing different strategy to improve oocyte fertilization success. Finally, our review highlights physiological mechanisms that require further researches and points out some advantages of bivalve spermatozoa to extend knowledge on mechanisms of motility.
- MeSH
- Species Specificity MeSH
- Energy Metabolism MeSH
- Flagella physiology MeSH
- Bivalvia physiology MeSH
- Sperm Motility physiology MeSH
- Spermatozoa cytology physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
A novel method for assessing the disintegration degree (DD) of waste activated sludge (WAS) with the use of differential centrifugal sedimentation method (DCS) was shown herein. The method was validated for a WAS sample at four levels of disintegration in the range of 14.4-82.6% corresponding to the median particle size range of 8.5-1.6 µm. From the several sludge disintegration methods used (i.e. microwave, alkalization, ultrasounds and peroxydisulfate activated by ultrasounds), the activated peroxydisulfate disintegration resulted in the greatest DD 83% and the smallest median particle size of WAS. Particle size distribution of pretreated sludge, measured by DCS, was in a negative correlation with the DD, determined from soluble chemical oxygen demand (SCOD; determination coefficient of 0.995). Based on the obtained results, it may be concluded that the DCS analysis can approximate the WAS disintegration degree.
- MeSH
- Biological Oxygen Demand Analysis MeSH
- Microwaves MeSH
- Waste Disposal, Fluid * MeSH
- Sewage * MeSH
- Particle Size MeSH
- Publication type
- Journal Article MeSH
The main aim of this study was to investigate the impact of a hybrid disintegration process with the use of alkalization and freezing by dry ice on waste activated sludge (WAS) and on the course of the process of mesophilic methane fermentation. In order to achieve the mentioned goal, various analytical techniques were used for assessment of the sludge disintegration and its influence on the further biogas production. As a result of the investigation, it was found that the chemical-thermal process of destruction of WAS results in an increased concentration of organic compounds in the supernatant (expressed as a change in the value of the soluble chemical oxygen demand - SCOD). The use of disintegrated WAS and feeding of the material into the fermentation digester influences, depending on its proportion by volume, the production of biogas and the biogas yield (higher biogas production by ca. 39% in comparison to blank sample was achieved with the appropriately disintegrated sludge). The hybrid process is simple and easy to implement in the full technical scale and does not influence or change the pH value of the sludge feed into the fermentation chambers (the dry ice neutralizes the high pH of the sludge). Additionally, it was determined that the herein developed process, can improve hygienization of the digested sludge.
- MeSH
- Anaerobiosis MeSH
- Biofuels analysis MeSH
- Bioreactors microbiology MeSH
- Water Purification methods MeSH
- Hydrolysis MeSH
- Hydrogen-Ion Concentration MeSH
- Biological Oxygen Demand Analysis MeSH
- Methane biosynthesis MeSH
- Waste Disposal, Fluid methods MeSH
- Sewage chemistry microbiology MeSH
- Sanitation methods MeSH
- Publication type
- Journal Article MeSH
