Injekční aplikace výplňového materiálu zejména do oblasti obličeje jsou populární estetickou procedurou, která se využívá k obnovení objemu, zlepšení kontur a vyhlazení vrásek. Za nejbezpečnější je považována kyselina hyaluronová, ale i ta nese riziko vzniku vaskulárních komplikací. Tyto komplikace mohou být závažné a vést k ischemii, nekróze tkání nebo dokonce slepotě či centrální mozkové příhodě. Tento článek se zaměřuje na identifikaci rizik spojených s vaskulárními komplikacemi při aplikaci dermálních výplní a na strategie pro jejich prevenci a řešení.
The application of filler material, particularly in the facial area, is a popular aesthetic procedure used to restore volume, improve contours and smooth wrinkles. Hyaluronic acid is considered the safest option, but it too carries the risk of vascular complications. These complications can be severe and lead to ischemia, tissue necrosis, or even blindness or stroke. This article focuses on identifying the risks associated with vascular complications associated with dermal filler application and strategies for prevention and management.
- MeSH
- arteria centralis retinae patologie MeSH
- dermální výplně škodlivé účinky MeSH
- hyaluronoglukosaminidasa * farmakologie škodlivé účinky MeSH
- injekce subkutánní škodlivé účinky MeSH
- kyselina hyaluronová škodlivé účinky MeSH
- lidé MeSH
- nemoci cév * chemicky indukované patologie prevence a kontrola terapie MeSH
- nežádoucí účinky léčiv patologie prevence a kontrola terapie MeSH
- oční symptomy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Endothelial glycocalyx (EG) plays a crucial role in maintaining the plasma proteins within the intravascular space. OBJECTIVE: We studied whether exogenous albumin protects the EG in an experimental model of EG enzymatic damage in rats. METHODS: Rats were divided into three groups of 10 animals that received (1) Evans blue (2) Evans blue + hyaluronidase, or (3) Evans blue + hyaluronidase + 20% human albumin via the tail vein. Spectrophotometric analysis was performed 2 h later to quantify the leakage of Evans blue-labeled albumin into the heart, lungs, brain, kidneys, liver, small intestine, spleen, and skeletal muscle. RESULTS: Administration of hyaluronidase numerically increased the capillary leakage of Evans blue in all examined tissues. Co-administration of albumin decreased the leakage of albumin in all tissues except the heart. In the lungs, the ratio between the absorbance and dry organ weight decreased from 5.3 ± 2.4 to 1.7 ± 0.5 (mean ± SD) (P < 0.002), and in the liver, the absorbance decreased from 2.2 ± 0.7 to 1.5 ± 0.4 (P < 0.011). CONCLUSION: Exogenous albumin decreased the capillary leakage of albumin which was interpreted as a sign of maintained EG integrity.
- MeSH
- albuminy * metabolismus MeSH
- cévní endotel účinky léků metabolismus MeSH
- Evansova modř MeSH
- glykokalyx * metabolismus účinky léků MeSH
- hyaluronoglukosaminidasa farmakologie MeSH
- kapilární permeabilita * účinky léků MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Hyaluronan, a linear glycosaminoglycan comprising D-N-acetylglucosamine and D-glucuronic acid, is the main component of the extracellular matrix. Its influence on cell proliferation, migration, inflammation, signalling, and other functions, depends heavily on its molecular weight and chemical modification. Unsaturated HA oligosaccharides are available in defined length and purity. Their potential therapeutic utility can be further improved by chemical modification, e. g., reduction. No synthesis of such modified oligosaccharides, either stepwise or by hyaluronan cleavage, has been reported yet. Here we show a three-step synthesis (esterification, depolymerization and reduction) of unsaturated even numbered hyaluronan oligosaccharides with carboxylates and the reducing terminus reduced to an alcohol. Particular oligosaccharides were synthesised. The modified oligosaccharides are not cleaved by mammalian or bacterial hyaluronidase and do not affect the growth of mouse and human fibroblasts. Further, MTT and NRU viability tests showed that they inhibit the growth of human colon carcinoma cells HT-29 by 20-50 % in concentrations 500-1000 μg/mL. Interestingly, this effect takes place regardless of CD44 receptor expression and was not observed with unmodified HA oligosaccharides. These compounds could serve as enzymatically stable building blocks for biologically active substances.
- MeSH
- antigeny CD44 metabolismus MeSH
- buňky HT-29 MeSH
- cytostatické látky * farmakologie chemie chemická syntéza MeSH
- fibroblasty účinky léků MeSH
- hyaluronoglukosaminidasa * metabolismus antagonisté a inhibitory MeSH
- kyselina hyaluronová * chemie farmakologie MeSH
- lidé MeSH
- myši MeSH
- oligosacharidy * chemie farmakologie MeSH
- proliferace buněk * účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Alginate lyases have countless potential for application in industries and medicine particularly as an appealing biocatalyst for the production of biofuels and bioactive oligosaccharides. Solid-state fermentation (SSF) allows improved production of enzymes and consumes less energy compared to submerged fermentation. Seaweeds can serve as the most promising biomass for the production of biochemicals. Alginate present in the seaweed can be used by alginate lyase-producing bacteria to support growth and can secrete alginate lyase. In this perspective, the current study was directed on the bioprocessing of brown seaweeds for the production of alginate lyase using marine bacterial isolate. A novel alginate-degrading marine bacterium Enterobacter tabaci RAU2C which was previously isolated in the laboratory was used for the production of alginate lyase using Sargassum swartzii as a low-cost solid substrate. Process parameters such as inoculum incubation period and moisture content were optimized for alginate lyase production. SSF resulted in 33.56 U/mL of alginate lyase under the static condition maintained with 75% moisture after 4 days. Further, the effect of different buffers, pH, and temperature on alginate lyase activity was also analyzed. An increase in alginate lyase activity was observed with an increase in moisture content from 60 to 75%. Maximum enzyme activity was perceived with phosphate buffer at pH 7 and 37 °C. Further, the residual biomass after SSF could be employed as biofertilizer for plant growth promotion based on the preliminary analysis. To our knowledge, this is the first report stating the usage of seaweed biomass as a substrate for the production of alginate lyase using solid-state fermentation.
- MeSH
- algináty * metabolismus MeSH
- biomasa MeSH
- Enterobacter * metabolismus enzymologie izolace a purifikace růst a vývoj MeSH
- fermentace * MeSH
- koncentrace vodíkových iontů MeSH
- kyselina glukuronová metabolismus MeSH
- mořské řasy * mikrobiologie MeSH
- Phaeophyceae mikrobiologie MeSH
- polysacharid-lyasy * metabolismus MeSH
- Sargassum * mikrobiologie metabolismus MeSH
- teplota MeSH
- Publikační typ
- časopisecké články MeSH
Spinal cord injuries (SCI), for which there are limited effective treatments, result in enduring paralysis and hypoesthesia, in part because of the inhibitory microenvironment that develops and limits regeneration/sprouting, especially during chronic stages. Recently, we discovered that targeted enzymatic removal of the inhibitory chondroitin sulfate proteoglycan (CSPG) component of the extracellular and perineuronal net (PNN) matrix via Chondroitinase ABC (ChABC) rapidly restored robust respiratory function to the previously paralyzed hemi-diaphragm after remarkably long times post-injury (up to 1.5 years) following a cervical level 2 lateral hemi-transection. Importantly, ChABC treatment at cervical level 4 in this chronic model also elicited improvements in gross upper arm function. In the present study, we focused on arm and hand function, seeking to highlight and optimize crude as well as fine motor control of the forearm and digits at lengthy chronic stages post-injury. However, instead of using ChABC, we utilized a novel and more clinically relevant systemic combinatorial treatment strategy designed to simultaneously reduce and overcome inhibitory CSPGs. Following a 3-month upper cervical spinal hemi-lesion using adult female Sprague Dawley rats, we show that the combined treatment had a profound effect on functional recovery of the chronically paralyzed forelimb and paw, as well as on precision movements of the digits. The regenerative and immune system related events that we describe deepen our basic understanding of the crucial role of CSPG-mediated inhibition via the PTPσ receptor in constraining functional synaptic plasticity at lengthy time points following SCI, hopefully leading to clinically relevant translational benefits.
- MeSH
- chondroitinasa ABC farmakologie MeSH
- chondroitinsulfát proteoglykany * farmakologie MeSH
- krysa rodu rattus MeSH
- mícha MeSH
- poranění míchy * MeSH
- potkani Sprague-Dawley MeSH
- přední končetina MeSH
- regenerace nervu fyziologie MeSH
- tyrosinfosfatasy receptorového typu, třída 2 MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.
- MeSH
- chronická zánětlivá demyelinizační polyneuropatie * farmakoterapie MeSH
- dospělí MeSH
- hyaluronoglukosaminidasa terapeutické užití MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru chemicky indukované farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
Aging is a complex physiological process that can be accelerated by chemical (high blood glucose levels) or physical (solar exposure) factors. It is accompanied by the accumulation of altered molecules in the human body. The accumulation of oxidatively modified and glycated proteins is associated with inflammation and the progression of chronic diseases (aging). The use of antiglycating agents is one of the recent approaches in the preventive strategy of aging and natural compounds seem to be promising candidates. Our study focused on the anti-aging effect of the flavonoid hesperetin, its glycoside hesperidin and its carbohydrate moieties rutinose and rhamnose on young and physiologically aged normal human dermal fibroblasts (NHDFs). The anti-aging activity of the test compounds was evaluated by measuring matrix metalloproteinases (MMPs) and inflammatory interleukins by ELISA. The modulation of elastase, hyaluronidase, and collagenase activity by the tested substances was evaluated spectrophotometrically by tube tests. Rutinose and rhamnose inhibited the activity of pure elastase, hyaluronidase, and collagenase. Hesperidin and hesperetin inhibited elastase and hyaluronidase activity. In skin aging models, MMP-1 and MMP-2 levels were reduced after application of all tested substances. Collagen I production was increased after the application of rhamnose and rutinose.
- MeSH
- hesperidin * farmakologie MeSH
- hyaluronoglukosaminidasa MeSH
- kolagenasy metabolismus MeSH
- lidé MeSH
- pankreatická elastasa MeSH
- rhamnosa * farmakologie MeSH
- stárnutí kůže * účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- dimethylsulfoxid aplikace a dávkování terapeutické užití MeSH
- hojení ran * MeSH
- hyaluronoglukosaminidasa aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- nádory * komplikace ošetřování MeSH
- onkologické ošetřovatelství * metody MeSH
- protinádorové látky škodlivé účinky MeSH
- radiodermatitida ošetřování MeSH
- radioterapie škodlivé účinky MeSH
- rány a poranění etiologie ošetřování MeSH
- týmová péče o pacienty MeSH
- Check Tag
- lidé MeSH
Preparáty pro imunoglobulinovou substituční léčbu slouží k náhradě nedostatečné tvorby opsonizačních a neutralizačních protilátek proti široké škále patogenů u pacientů s vrozenými nebo získanými poruchami tvorby protilátek. Mezi základní způsoby aplikace patří intravenózní, konvenční subkutánní a nejnověji také subkutánní podání facilitované hyaluronidázou (fSCIG). Podkožní aplikace tohoto enzymu v úvodu léčby umožní dočasně rozmělnit extracelulární matrix, a tím pádem aplikovat objem normálního lidského imunoglobulinu v dávce a intervalu podání jako při intravenózní aplikaci (0,4-0,8 g/kg/měsíc jednou za 2-4 týdny). Biologická dostupnost fSCIG léčby se pohybuje kolem 93 % a je vyšší než při konvenčním subkutánním podávání. Většinou dochází k aplikaci do 1-2 míst. Maximální doporučená rychlost podávání je 300 ml/h. Mezi nejčastější nežádoucí účinky léčby patří lokální reakce charakteru bolesti či dyskomfortu v místě vpichu, svědění, zarudnutí nebo otok. Specifickým problémem fSCIG léčby je možná tvorba protilátek proti hyaluronidáze, které však nejsou neutralizační a jejich přítomnost nekoreluje s výskytem nežádoucích reakcí. Základní výhodou fSCIG léčby je subkutánní podávání v delším časovém intervalu v domácím prostředí.
The immunoglobulin replacement therapy serves to compensate for the insufficient production of opsonizing and neutralizing antibodies against a wide range of pathogens in patients with congenital or acquired antibody production disorders. The basic routes of administration include intravenous, conventional subcutaneous and subcutaneous administration facilitated by hyaluronidase (fSCIG). Subcutaneous administration of this enzyme at the beginning of the treatment allows to temporarily grind the extracellular matrix and thus use the volume of normal human immunoglobulin in the dose and interval of administration as in intravenous route of administration (0.4-0.8 g/kg/month once every 2-4 weeks). The bioavailability of fSCIG treatment is around 93 % and is higher than with conventional subcutaneous administration. It is usually applied to 1-2 sites. The maximum recommended infusion rate is 300ml/h. The most common side effects of treatment include local reactions of pain or discomfort at the injection site, itchy, redness or swelling. The formation of antibodies against hyaluronidase is possible, however they are not neutralizing and their presence does not correlate with the occurrence of adverse reactions. The main advantage of fSCIG treatment is subcutaneous administration over a longer period of time in the home environment.
- Klíčová slova
- facilitované subkutánní podávání,
- MeSH
- hyaluronoglukosaminidasa aplikace a dávkování terapeutické užití MeSH
- imunoglobuliny * aplikace a dávkování terapeutické užití MeSH
- injekce subkutánní MeSH
- lidé MeSH
- syndromy imunologické nedostatečnosti * farmakoterapie MeSH
- způsoby aplikace léků MeSH
- Check Tag
- lidé MeSH
Osteoarthritis (OA) is one of the most common musculoskeletal disorders in the world. OA is often associated with the loss of viscoelastic and tribological properties of synovial fluid (SF) due to degradation of hyaluronic acid (HA) by reactive oxygen species (ROS) and hyaluronidases. Viscosupplementation is one of the ways how to effectively restore SF functions. However, current viscosupplementation products provide only temporal therapeutic effect because of short biological half-life. In this article we describe a novel device for viscosupplementation (NV) based on the cross-linked tyramine derivative of HA, chondroitin sulfate (CS), and high molecular weight HA by online determination of viscoelastic properties loss during degradation by ROS and hyaluronidase. Rheological and tribological properties of developed viscosupplement were compared with HA solutions with different molecular weights in the range 500-2000 kDa, which are currently commonly used as medical devices for viscosupplementation treatment. Moreover, based on clinical practice and scientific literature all samples were also diluted by model OA SF in the ratio 1:1 (vol/vol) to better predict final properties after injection to the joint. The observed results confirmed that NV exhibits appropriate rheological properties (viscosity, elastic, and viscous moduli) comparable with healthy SF and maintain them during degradation for a significantly longer time than HA solutions with molecular weight in the range 500-2000 kDa and cross-linked material without CS.
- MeSH
- artróza kolenních kloubů * MeSH
- chondroitinsulfáty farmakologie MeSH
- hyaluronoglukosaminidasa terapeutické užití MeSH
- injekce intraartikulární MeSH
- kyselina hyaluronová farmakologie MeSH
- lidé MeSH
- osteoartróza * farmakoterapie MeSH
- reaktivní formy kyslíku MeSH
- tyramin terapeutické užití MeSH
- viskosuplementace * metody MeSH
- viskosuplementy terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
