Salbutamol Ameliorates the Phenotype of the Skin Inflammatory Disease Psoriasis According to Skin Spheroid Models

DergiPark: 878417trkjnatSedef hastalığı; genetik, bağışıklık sistemi ve çevrenin karşılıklı etkileşiminden kaynaklanan, çok faktörlü kronik inflamatuar bir hastalıktır. Epitel hücrelerinin hiperproliferasyonu ile karakterizedir ve hastaların yaşamında büyük olumsuz etkileri olan kırmızı, pullu psoriatik plaklar oluşturur. Kortikosteroidler veya D vitamini analogları iyileşmeye bir dereceye kadar yardımcı olabilse de hastalığın henüz tam bir tedavisi yoktur. Bu çalışmada, ?2-adrenerjik reseptör agonisti salbutamol'ün potansiyel etkinliğinin taranması için üç boyutlu (3D) stresle ilişkili psoriatik deri sferoidleri oluşturulması amaçlanmıştır. İnsan dermal fibroblast (HDF), İnsan epidermal keratinosit (HEK) ve İnsan monosit hücreleri (THP-1) ile 3D kültür modelleri oluşturulmuş ve buna göre stres kökenli psoriatik model protokolü uygulanmıştır. İlacın etkinliği, gen ve protein ekspresyon seviyelerindeki değişiklikler ve çeşitli metabolik deneylerle değerlendirilmiştir. Sedef hastalığının sferoid modellerini in vitro olarak büyütebilmek için optimize bir yöntem geliştirilmiştir. Salbutamol'ün sedef sferoidleri üzerindeki potansiyel terapatik etkileri test edilmiştir. Salbutamol ile tedavi edilen sferoidler, tedavinin etkinliğini kanıtlayan literatürle paralel sonuçlar göstermiştir. 3D sferoroid sistemimiz, in vitro olarak sedef hastalığının fizyolojik özelliklerini taklit etmede kısmen etkili bulunmuştur. Çalışmamız, stresle ilişkili bir psoriatik model oluşturduğu ve potansiyel bir tedavi seçeneği olarak bir ?2 agonistini deneyen ilk çalışma olduğu için bir başlangıç noktası olabilir. Salbutamol'ün etkileri ve uygunluğu göz önünde bulundurulduğunda etkinliği küçümsenmemeli ve gelecekte klinikte kullanım potansiyeli göz önünde bulundurulmalıdır. Psoriasis is a multifactorial chronic inflammatory disorder resulting by the interplay of genetics, the immune system and the environment. It is characterized by the hyperproliferation of epithelial cells, generating red, itchy psoriatic plaques which have no cure but have great negative impact in patients’ life. Although corticosteroids or vitamin D analogs might help recovery to some extent, there is yet no total cure for the disease. In this study, we sought to generate three-dimensional (3D) stress-related psoriatic skin spheroids with the screening of the potential efficacy of a ?2-adrenergic receptor agonist, salbutamol. 3D Culture spheroids with human dermal fibroblasts (HDF), human epithelial keratinocytes (HEK) and human monocytic cell line (THP-1) were generated as a representative model of skin and the protocol of stress-related modelling was conducted. The efficacy of the drug salbutamol was evaluated by the changes in mRNA and protein expression levels of selected genes, as well as by several metabolic assays. We developed a method for culturing spherical organoid models of psoriasis in vitro. We tested the potential theurapetic effects of salbutamol on psoriasis spheroids. Spheroids treated with salbutamol indicated the effictiveness of the treatment. 3D spheroid system was found partially efficient for mimicking the physiological features of psoriasis in vitro. This present work may be a starting point for future investigation as it is the first to generate a stress-related psoriatic model and first to try a ?2 agonist as a potential treatment option. Considering the effects and suitability of topical application of salbutamol, its efficacy should not be underestimated and should be investigated further for translating this knowledge into clinics

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results

Učinak formulacijskih parametara na oslobađanje lijeka i svojstva dvoslojnih tableta koje plutaju u želucu

Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanism.U radu su opisane plutajuće tablete acetilsalicilne kiseline za antikoagulacijsku upotrebu s produljenim zadržavanjem u želucu i većom bioraspoloživošću. Plutajući dio tih dvoslojnih tableta sadržavao je hidroksipropil metilcelulozu (HPMC) visoke viskoznosti i efervescentnu smjesu limunske kiseline i natrijevog hidrogenkarbonata. Drugi sloj sadržavao je ljekovitu tvar, sredstvo za izravno tabletiranje i različite vrste matriksnog polimera poput HPMC niske viskoznosti, natrij-karboksimetilceluloze i kitozana. Tablete su pripravljene metodom izravne kompresije. Ispitivan je utjecaj formulacijskih varijabli na fizikokemijska i plutajuća svojstva, te oslobađanje ljekovite tvari. Plutajuća svojstva ovise o količini efervescentnih tvari i gelirajućeg polimera u plutajućem sloju. Promjenom vrste i viskoznosti polimera u matriksnom sloju s lijekom produljeno je oslobađanje ljekovite tvari na 8 sati. Iz svih formulacija ljekovita tvar oslobađala se difuzijom

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results

Ectopic High Origin of a Coronary Artery from the Aorta – A Possible Cause of Sudden Death

Congenital anomalies originating it the coronary arteries are of special interest for forensic specialists. The presented case is a man found dead on the Coast of Marmara Sea. The death was considered to be suspicious and an autopsy was performed. On the macroscopic autopsy, the ostium of the right coronary artery was hole-like, located in a normal position, but the ostium of the left coronary artery was pocket-shaped and located in the left wall of the ascending aorta and above the rim of the sinotubular junction. We describe an asymptomatic, but didactic case with ectopic high origin of the left coronary artery