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1
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EN
Objective. To explore the effect of dexamethasone (DEX) on monocyte adhesion function and its underlying mechanism. Methods. The effects of DEX and fasudil on adhesion of cultured U937 monocytes to human umbilical vein endothelial cells (HUVEC) following stimulation with phorbol myristate acetate (PMA) were studied; Changes in the Rho-associated coiled-coil protein kinase 1 (ROCK1) protein content and activity were evaluated. Results. DEX and fasudil significantly inhibited U937 cell adhesion rates under PMA stimulation and inhibited ROCK1 activity. Mifepristone (RU-486) and cycloheximide (CHX) did not alter these effects of DEX. Conclusions. DEX interferes with the adhesion function of U937 cells through the inhibition of ROCK1 activity.
EN
A fast reliable micellar electrokinetic methodology was investigated for the concurrent quantitation of six antimicrobial and anti-inflammatory drugs, namely, ciprofloxacin, dexamethasone, metronidazole, ornidazole, spiramycin and tinidazole. The method has the merits of rapidity, precision, and sensitivity. The separation was carried out in less than 7 min by applying a basic background electrolyte consisting of 25 mM disodium tetraborate buffer, pH 9 containing 50 mM SDS at 25 kV using photodiode array detector at 230 and 315 nm. The internal standard used during analysis was cromolyn sodium and validation was carried out following ICH guidelines. The proposed method showed linear response over the range from 0.5 to 10.0 μg mL⁻¹ reaching limits of detection and limits of quantitation in the ranges of 0.09–0.2 μg mL⁻¹ and 0.27–0.6 respectively. The method's greenness was estimated using the GAPI tool where excellent greenness was concluded. Co-formulated or single-ingredient commercial preparations were investigated and the results were statistically evaluated.
EN
Reversed phase high-performance liquid chromatography (RP-HPLC) and thin-layer chromatography (TLC)-spectrodensitometric methods have been developed and validated for the separation and quantitation of two binary mixtures: Ofloxacin (OFX) and dexamethasone (DXM) in eye preparation; ciprofloxacin hydrochloride (CIP) and hydrocortisone (HYD) in ear preparation. The linearity ranges of RP-HPLC methods were found to be (2.5–45 μg mL-1) for OFX, (2.5–50 μg mL-1) for DXM and (1–8 μg mL-1) for both CIP and HYD. The percentage recoveries/relative standard deviation (RSD) were found to be 100.36/1.38, 100.13/1.49, 99.98/0.61 and 100.28/1.27, respectively. The linearity ranges of TLC-spectrodensitometric methods were found to be (0.5–2 μg band-1), (0.5–3.5 μg band-1), (0.2–1.6 μg band-1), and (0.6–2 μg band-1 for OFX, DXM, CIP, and HYD, respectively. The percentage recoveries/RSD were found to be 99.98/1.06, 99.93/1.18, 99.74/1.27, and 99.94/1.54, respectively. A comparative study was conducted to show the advantages of the proposed methods which showed that the TLC-spectrodensitometric methods were simpler, more sensitive, and economic, while RP-HPLC methods were more precise and robust. The methods were validated in compliance with the ICH guidelines and were successfully applied for determination of the selected drugs in their laboratory-prepared mixtures and commercial dosage forms.
PL
Spektroskopię elektronowego rezonansu paramagnetycznego (EPR) zastosowano do oceny optymalnych warunków sterylizacji deksametazonu. Sterylizację sproszkowanego leku wykonano w suchym powietrzu w temperaturze 180°C w czasie wynoszącym 30 minut. Celem pracy jest określenie właściwości wolnorodnikowych sterylizowanego deksametazonu. Optymalnym warunkom sterylizacji powinno towarzyszyć powstawanie niewielkiej ilości wolnych rodników w substancji leczniczej, które mogą powodować szereg efektów ubocznych podczas farmakoterapii. Deksametazon jest syntetycznym glikokortykosteroidem z grupy hormonów steroidowych. Wykazuje silne działanie przeciwzapalne i immunosresyjne. Jest silniejszy ok. 20-30 -krotnie przewyższając hydrokortyzon i 4-5 krotnie niż prednizolon. Deksametazon hamuje zapalenie i obrzęk tkanki, dlatego jest używany do leczenia zapaleń o szerokim zakresie chorób auto-immunologicznych takich zapalenie stawów itp. Jest również aplikowany małych ilościach przed lub po zabiegach dentystycznych. W onkologii deksametazon jest podawany w trakcie chemioterapii [1,2]. Strukturę chemiczną deksametazonu przedstawiono na RYSUNKU 1. Pomiary widm wykonano za pomocą spektrometru EPR Firmy RADIOPAN (Poznań) przy modulacji pola magnetycznego wynoszącej 100kHz. Częstotliwość promieniowania mikrofalowego wynosiła 9.3GHz. Widma EPR w postaci pierwszej pochodnej rejestrowano w szerokim zakresie mocy mikrofalowej 0.7- 70mW. Analizowano parametry widm EPR oraz koncentrację wolnych rodników w sterylizowanym leku. Zbadano zmiany koncentracji i parametrów widm EPR wraz ze wzrostem czasu przechowywania leku sterylizowanego w 180°C przez 30 minut. Wyznaczono zależność amplitudy i szerokości linii EPR od mocy mikrofalowej. Analizowano wpływ mocy mikrofalowej na kształt i asymetrię widm EPR. Próbki deksametazonu nie poddane działaniu wysokiej temperatury nie dawały sygnału EPR. Widma EPR deksametazonu sterylizowanego w 180°C przez 30 minut wykazywały złożony charakter (RYS.2). Wskazuje to, że w sterylizowanym deksametazonie występuje kilka rodzajów wolnych rodników. Rejestrowane widma EPR stanowią superpozycję linii składowych pochodzących od poszczególnych typów wolnych rodników. Zbadano wpływ mocy mikrofalowej na amplitudę i szerokość linii EPR termicznie sterylizowanego deksametazonu. Zaobserwowano zmianę kształtu widm EPR wraz z mocą mikrofalową. Wraz ze wzrostem mocy mikrofalowej rośnie amplituda linii EPR deksametazonu. Podobną zależność zarejestrowano dla szerokości linii EPR. Taki charakter zamian wskazuje na jednorodne rozmieszczenie centrów paramagnetycznych w termicznie sterylizowanym deksametazonie (RYS. 3 i 4). Linie EPR różnych grup wolnych rodników nasycają się przy innej mocy mikrofalowej. Wolne rodniki w sterylizowanym deksametazonie są stabilne. Nie obserwowano szybkiego zaniku wolnych rodników z czasem przechowywania próbki. Badania EPR wskazują na niewielką zależność asymetrii linii EPR od mocy mikrofalowej. Moc mikrofalowa nieznacznie wpływa na wszystkie analizowane parametry IA1-A2I, IA1/A2I, IB1-B2I, IB1/B2I wyznaczone w pracy w celu oceny asymetrii linii EPR.
EN
Electron paramagnetic resonance (EPR) spectroscopy was applied to examine optimal sterilization conditions of dexamethasone. Sterilization of powdered dexamethasone was done in dry air at temperature 180°C during the time of 30 minutes. The aim of this work was to determine free radical properties of sterilized dexamethasone. It is expected that optima conditions of sterilization is accompanied by formation of low amount of free radicals in drug which can cause many side effects during pharmacotherapy. Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid hormones. It acts as an anti-inflammatory and immunosuppressant. Its potency is about 20-30 times that of hydrocortisone and 4-5 times of prednisone. Dexamethasone inhibit the inflammatory and the edema of the tissue, so its making useful for the treatment of a wide range of inflammatory and auto-immune conditions such as rheumatoid arthritis ect. It is also given in small amounts before and/or after some forms of dental surgery. In oncology dexamethasone, it is given to cancer patients undergoing chemotherapy [1,2]. Chemical structure of dexamethasone is presented in FIGURE 1. Measurements of spectra were done by the use of EPR spectrometer produced by RADIOPAN Firm (Poznań) with modulation of magnetic field of 100 kHz. Microwave frequency of 9.3GHz was applied. The first-derivative EPR spectra were recorded with microwave power of the wide range of 0.7-70mW. Parameters of EPR spectra and free radical concentration in the sterilized drug were analyzed. Changes of free radical concentration and EPR parameters with increasing of storage time after heating of the drug at 180°C were evaluated. Changes of amplitud es and linewidths of EPR spectra with microwave power were determined. The influence of microwave power on lineshape of EPR spectra and line asymmetry was analyzed. Samples of dexamethasone not heated with high temperature gave no EPR signals. EPR spectra of dexamethasone sterilized in 180°C during 30 minutes reveal complex structure (FIG. 2). It was stated that several types of free radicals exist in the sterilized drug. Its EPR spectra reveal multi-component structure. The recorded EPR spectra are superposition of component lines of the individual types of free radicals. Influence of microwave power on amplitude and linewidths thermally sterilized dexamethasone was tested. Changes of EPR lineshapes with microwave power were observed. Amplitude of EPR line increase with microwave power increasing. Similar relationship for linewidths of EPR lines was recorded. This kind of relationship evidence on homogenous location of paramagnetic centers in thermally sterilized dexam-ethasone (FIG. 3 and 4). EPR lines of the individual groups of free radicals saturate at different microwave powers. Free radicals in sterilized dexamethasone are stabile. EPR studies indicate on small influence of microwave power on line asymmetry. Microwave power only slightly affects on all analyzed parameters IA1-A2I, IA1/A2I, IB1-B2I, IB1/B2I determined to evaluate line asymmetry.
EN
The case of preterm, male infant (27 Hbd) with extremely low birth weight (868 g) and Respiratory Distress Syndrom is presented. Despite prolonged artifi cial ventilation (with High Frequency Oscillation Ventilation and FiO2 =100%), dopamine continuous iv infusion) on 30th day of life he started to deteriorate dramatically and the risk of chronic lung disease appeared. On the 32nd day of life Dexamethasone therapy was started. Post initial therapy his condition began improving clearly. This resulted in a successful extubation on the seventh day of Dexamethasone treatment. Breathing with C-PAP (FiO2=34%, Sa02 = 100%) was started. Dexamethasone was gradually reduced, its total cumulative dose was 4.52 mg/kg. The revision of bibliography related with corticosteroids application in preterm infants with chronic lung disease is presented.
PL
Zaprezentowano przypadek wcześniaka płci męskiej (Hbd 27) z niską masą urodzeniową (868 g), u którego wystąpiły objawy zespołu zaburzeń oddechowych. Stosowano przedłużoną wentylację mechaniczną ( również z zastosowaniem High Frequency Oscillation Ventilation z FiO2100%, ciągłą dożylną infuzją dopaminy), w 30 dniu życia jego stan zaczął się dramatycznie pogarszać i pojawiło się podejrzenie przewlekłej choroby płuc. W 32 dniu życia rozpoczęto stosowanie Dexametazonu. Już po rozpoczęciu leczenia zaobserwowano bardzo istotną poprawę w stanie zdrowia dziecka, co umożliwiło jego ekstubację w 7-mym dniu terapii i zastosowanie CPAP z FiO2 =34% uzyskując SaO2=100%. Dexametazon stopniowo odstawiono a jego całkowita dawka wyniosła 4,52 mg/kg. W pracy przedstawiono przegląd piśmiennictwa dotyczący zastosowania sterydoterapii u wcześniaków z przewlekłą chorobą płuc.
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EN
Myostatin (MSTN) and transforming growth factor-ß1 (TGF-ß1) belong to the same TGF-ß superfamily of proteins. They are involved in regulation of skeletal muscle growth and development as well as muscle catabolism. The aim of the present study was to investigate the relationship between mstn and TGF-ß1 expression in proliferating and differentiating mouse C2C12 myoblasts cultured in normal and catabolic conditions and to evaluate the effect of exogenous TGF-ß1 as well as "knock down" of TGF-ß1 receptor type II on mstn expression in proliferating and differentiating myogenic cells. The direct effect of TGF-ß1 on myostatin was also examined. Myostatin expression increased gradually with cell confluency in proliferating cultures, while the level of TGF-ß1, detected in the form of a 100 kDa small latent complex diminished. Myostatin expression was accompanied by a partial cell cycle arrest. Three forms of myostatin were found: a 52 kDa precursor, a 40 kDa latency associated propeptide, and a 26 kDa active peptide. A decrease in myostatin and TGF-ß1 levels was observed during the first three days of differentiation, which was subsequently followed by significant increase of their expression during next three to four days of differentiation. Catabolic state induced by dexamethasone significantly increased the level of all forms of myostatin as well as latent (100 kDa) and active (25 kDa) forms of TGF-ß1 in differentiating myoblasts in a dose dependent manner. Exogenous TGF-ß1 (2 ng/ml) significantly increased myostatin levels both in proliferating and differentiating C2C12 myoblasts, whereas silencing of the TGF-ß1 receptor II gene significantly lowered myostatin level in examined cells. The presented results indicate that TGF-ß1 may control myostatin-related regulation of myogenesis through up-regulation of myostatin, predominantly in the course of terminal differentiation and glucocorticoid-dependent catabolic stimulation.
EN
Sustainable chemistry established one of kind standards to maintain protection of environment through using safer mobile phase composition and/or lower solvent consumption. A fast green micellar HPLC method was developed and applied for the first time aiming at simultaneous determination of chlorpheniramine maleate, one of the most widely used antihistamine in combination with levochlopersatine fenodizoate or dextromethorphan hydrobromide or dexamethasone, in their pure forms, laboratory prepared mixtures and pharmaceutical dosage forms used in alleviating the symptoms of cough resulting from common colds and allergy. The separation was achieved on Kinetex C18 column (100 mm34.6 mm i.d., 2.6-mm particle size) using micellar aqueous mobile phase consisting of (30 mM sodium dodecyl sulfate and 50 mM sodium dihydrogen phosphate, pH 5) and ethanol (85:15) with UV detection at 230 nm. The four drugs were successfully separated using isocratic elution in a single run not exceeding 7 min. According to ICH guidelines, the method was confirmed to be linear, accurate and precise over the concentration ranges of 5–60 mg mL1 for chlorpheniramine maleate, 10–100 mg mL1 for levocloperastine fenodizoate and dextromethorphan hydrobromide and 5–30 mg mL1 for dexamethasone. In addition, the greenness of the developed method was assessed using two different tools indicating their least hazardous effect on the environment.
10
Content available remote Badanie kinetyki uwalniania deksametazonu z emulsji wielokrotnych
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PL
Przedstawiono wyniki badań doświadczalnych dotyczących otrzymania emulsji podwójnych za pomocą klasycznej metody dwustopniowej. Do otrzymania emulsji zastosowano skwalan z oliwek jako fazę olejową. Rolę emulgatora hydrofilowego pełnił Phytocream 2000, a emulgatora lipofilowego Cithrol PG3PR. Jako nośnik substancji aktywnej wybrano emulsję podwójną zawierającą 80% emulsji pierwotnej, 5% emulgatora W/O oraz 15% skwalanu z oliwek. Na podstawie testu uwalniania leku z preparatu przez membrany dializacyjne do roztworu akceptorowego stwierdzono, że stężenie deksametazonu uwolnionego z emulsji podwójnej wynosiło 15% i było niższe niż uzyskane dla prób odniesienia, czyli emulsji prostych O/W i W/O. Profil uwalniania deksametazonu wskazuje jednak na potencjał zastosowania tego typu układów jako preparatów o kontrolowanym dozowaniu substancji aktywnej.
EN
Four oil-in-water (O/W), 8 water-in-oil (W/O) and 5 oil-in-water-in-oil (O/W/O) emulsions were prepd. by a conventional 2-stage method. Olive squalane was used as the oil of the emulsions. The Phytocream 2000 played the role in a hydrophilic emulsifier, while the Cithrol PG3PR was the lipophilic emulsifier. The multiple emulsions were composed of 80% primary emulsion, 5% W/O emulsifier and 15% squalene. They were used as an active substance carrier. The drug release test was used for evaluation of the formulations. The released amt. of dexamethasone through dialysis membranes from o/w/o emulsion was 15%. This value was lower than that obtained in a ref. tests (O/W and W/O simple emulsions). The release profile of dexamethasone from o/w/o emulsion confirmed that this system can play a role as a carrier with delayed release of the active substance.
EN
The aim of the study was to examine the changes in the density of VAChT (marker of acetylcholine present)-, NPY-, VIP-, SOM-, SP- and nNOS-immunoreactive (IR) nerve terminals and co-localization of VAChT with the above-mentioned neurotransmitters after the occurrence of dexamethasone (DXM)-induced ovarian cysts in gilts. DXM administration led to an increase in the density of VAChT/SP-, VAChT/nNOS- and NPY-IR nerve terminals around the cystic walls. In DXM-treated animals an elevated number of VAChT- and SP-IR nerve endings was found close to the tertiary follicles. Moreover, in the gilts receiving DXM the density of NPY-IR nerve endings (that simultaneously co-localized VAChT) was high near the interstitial gland. An increase in the number of VAChT/SP- and VIP-IR nerve fibers around the medullar arteries (A) was observed in cystic ovaries, while the number of VAChT-IR nerve endings near the cortical A was lowered after DXM application. Furthermore, nerve fibers containing VAChT were absent around veins in the whole ovary of DXM-treated animals. After DXM injections, an increase in the number of VAChT/SP- and VAChT/nNOS-IR nerve endings in the cortical, as well as VIP- and nNOS-IR (co-existing with VAChT), nerve terminals in the medullar part of the autonomic ground plexus (GP) was present. However, the administration of DXM led to a drop in the density of SOM-positive nerve endings (also VAChT-IR) in the medullar subdivision of the GP. The present study shows that in the porcine ovaries with DXM induced cysts the pattern of cholinergic innervation, as well as the co-localization of VAChT and NPY, VIP, SOM, SP or nNOS, were changed. Data obtained also suggest that acetylcholine and the above-mentioned neurotransmitters effecting the functioning (steroidogenic activity, blood flow) of the polycystic ovaries may have a significant influence on the course of this pathological status.
EN
The therapeutic effect of 1 mg/kg of dexamethasone on lung oedema and respiratory distress induced by 0.08 mg/kg of oleic acid (OA) in dogs was investigated into 8 dogs. One hour after OA injection, blood pH, HCO₃, pO₂, O₂Hb, and heart rate decreased, whereas COHb, pCO₂, temperature, and respiration rate increased. Lung oedema was confirmed histopathologically in a dog from the control group who died. Blood pH, COHb, temperature, and respiration rate returned to normal values after administration of dexamethasone. It has been determined that respiratory distress and lung oedema cause important changes in blood gases and the administration of a single dose of 1 mg/kg of dexamethasone is effective in the treatment of lung oedema and respiratory distress induced in dogs by OA.
EN
Multiple myeloma is a neoplastic disease which is characterised by proliferation of monoclonal plasmocytes in the bone marrow. It is the second most common hematologic cancer and it represents 1% of all cancer deaths. Despite enormous development in multiple myeloma biology and treatment over the last 30 years - it is still incurable disease with a median survival of 50 – 55 months. Currently, one of the most important goals in the treatment of multiple myeloma is to achieve long-term control of the disease, without negative impact on the patient’s quality of life. Thanks to therapeutic regimens based on new immunomodulatory drugs, this aim seems to be achievable. In this paper we present the case of a female patient living with multiple myeloma for 14 years. Initially patient was treated with standard VAD (vincristine, doxorubicin, dexamethasone) chemotherapy regimen. After a nearly complete remission of the disease, autotransplantation of hematopoietic cells was performed. One year after transplantation there was a relapse of the disease. In the treatment of relapse it was decided to use scheme based on lenalidomide and dexamethasone. After 4th cycle of treatment, a complete remission was achieved. So far, the patient received 149 cycles. In the evaluation of minimal residual disease still maintains a state of complete remission maintains. During over 12 years of treatment no complications in grade 3 and 4 of the CTCAE v.4 was observed. Currently the patient is 58 years old, she still receives lenalidomide and leads moderately active life.
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