622 research outputs found
Asher Lev at the Israel Museum: Stereotyping art and craft
Jesper Svartvik and Jakob Wirén (Eds.), Religious stereotyping and interreligious relations. New York: Palgrave Macmillan, 2013, reproduced with permission of Palgrave Macmillan. This extract is taken from the author's original manuscript and has not been edited. The definitive, published version of record is available here: http://www.palgrave.com/page/detail/religious-stereotyping-and-interreligious-relations-jesper-svartvik/?K=9781137344601 and http://www.palgraveconnect.com/pc/doifinder/10.1057/978113734267
Razvoj i vrednovanje plutajućih tableta norfloksacina s produljenim zadržavanjem u želucu
Floating matrix tablets of norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using polymers such as hydroxy propyl methylcellulose (HPMCK4M, HPMCK100M) and xanthan gum. Tablets were evaluated for their physical characteristics viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets, indicating that water diffusion and the polymer rearrangement played an essential role in drug release. The best formulation (F4) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 180 ± 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for absorption window drugs.Razvijene su plutajuće tablete norfloksacina koje se produljeno zadržavaju u želucu i time povećavaju bioraspoloživost. Tablete su pripravljene metodom vlažne granulacije, koristeći hidroksipropil metilcelulozu (HPMCK4M, HPMCK100M) i ksantan gumu. Tabletama su određena fizikalna svojstva (čvrstoća, debljina, lomljivost i varijacija mase) te sadržaj ljekovite tvari i plutajuća svojstva. Nadalje, praćeno je oslobađanje ljekovite tvari in vitro tijekom 9 h. Uočeno je da je oslobađanje kontrolirano i produljeno te da tablete plutaju u ispitivanom mediju. Mehanizam oslobađanja nije slijedio Fickov zakon, što ukazuje da difuzija vode i promjene u strukturi polimera imaju bitnu ulogu u oslobađanju ljekovite tvari. Najbolja formulacija (F4) in vitro uporabljena je s dodatkom barijevog sulfata za radiografska ispitivanja in vivo. Ispitivanja na volonterima koji su apstinirali od hrane pokazala su da primjena plutajućih tableta produljuje vrijeme zadržavanja u želucu na 180 ± 30 min
Termoreverzibilni mukoadhezivni in situ hidrogel za oftalmičku primjenu: dizajniranje i optimizacija koristeći kombinaciju polimera
The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 32 full factorial design was employed with two polymers Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 3336 ºC. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.Cilj rada bio je razvoj i optimizacija termoreverzibilnog sustava za isporuku lijekova koji gelira in situ. Sustav je napravljen na bazi Pluronic F 127, a sadrži moksifloksacin hidroklorid kao modelni lijek. U radu je primjenjeno 32 potpuno faktorijsko dizajniranje s dva polimera, Pluronic F 68 i Gelrite kao nezavisnim varijablama koji su kombinirani s Pluronic F 127. Kao zavisne varijable odabrane su temperatura geliranja, čvrstoća gela, jačina bioadhezije, viskoznost i in vitro oslobađanje lijeka nakon 1 i 10 h. Pronađeno je da Pluronic F 68 u kombinaciji s Pluronic F 127 ima značajan učinak na temperaturu geliranja u rasponu od 33 do 36 C. S druge strane, Gelrite ima povoljan učinak na jačinu bioadhezije, čvrstoću gela i oslobađanje lijeka. Razvijen je kvadratni matematički model pomoću kojeg se može predvidjeti temperatura geliranja, čvrstoća gela, jačina bioadhezije i oslobađanje ljekovite tvari
Expression of interleukin 2 receptors on activated human B cells.
Using anti-Tac, a monoclonal anti-interleukin 2 (IL-2) receptor antibody, we have explored the possibility that certain activated B cells display receptors for IL-2. Resting normal B cells and unselected B cell lines established from normal individuals were Tac antigen negative. In contrast, the cell surface Tac antigen expression was demonstrable on 6 of 10 B cell lines from patients with Burkitt's lymphoma, 5 of 6 B cell lines derived from patients with HTLV-I-associated adult T cell leukemia (including all four that had integrated HTLV-I into their genome), and on certain normal B cells activated with pokeweed mitogen. Furthermore, cloned Epstein-Barr virus-transformed B cell lines derived from Tac-positive normal B cells continued to express the Tac antigen in long-term cultures and manifested high affinity IL-2 receptors identified in binding studies with purified radiolabeled IL-2. The line 5B4 developed in the present study could be induced with purified JURKAT-derived or recombinant IL-2 to express a larger number of IL-2 receptors. Furthermore, the addition of IL-2 to the 5B4 B cell line augmented IgM synthesis, which could be blocked by the addition of anti-Tac. The size of the IL-2 receptors expressed on the cloned normal B cell lines was similar (53,000-57,000 daltons) to that of receptors on phytohemagglutinin-stimulated T cell lymphoblasts. Thus, certain malignant and activated normal B cells display the Tac antigen and manifest high affinity receptors for IL-2. These data suggest that IL-2 may play a role in the differentiation of activated B cells into immunoglobulin-synthesizing and -secreting cells
Izrada i karakterizacija IPN alginatnih i želatinskih mikrogelova s tramadolom: Optimiranje pomoću metode odzivnih površina
Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X1) and glutaraldehyde (X2) on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Qe) and 50 % drug release time (t50). Microgels with average particle size in the range of 44.31102.41 m were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of crosslinking and amount of gelatin used in preparing IPNs. The release rates were fitted to power law equation and Higuchi’s model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition.Interpenetrirajući umreženi polimerni (IPN) alginatno-želatinski (AG) mikrogelovi (MG) tramadola pripravljeni su metodom umrežavanja koristeći glutaraldehid kao sredstvo za umrežavanje. Pripravci su optimirani pomoću odzivnih površina. Kompozitini dizajn s dva faktora na tri nivoa upotrijebljen je za procjenu kritičnih formulacijskih varijabli: praćen je utjecaj količine želatine (X1) i glutaraldehida (X2) na prosječnu veličinu čestica, sposobnost kapsuliranja, koeficijent difuzije (D), količinu adsorbiranog mucina po jedinici mase (Qe) i vrijeme potrebno za oslobađanje 50 % lijeka (t50). Dobiveni su mikrogelovi prosječne veličine čestica od 44,31 do 102,41 m, a maksimalno postignuto vezanje lijeka bilo je 86,5 %. Mikrogelovi su karakterizirani FT-IR spektroskopijom i diferencijalnom pretražnom kalorimetrijom (DSC). Ravnotežne i dinamičke studije bubrenja provedene su u fosfatnom puferu pH 7,4. Koeficijenti difuzije i eksponenti za transport vode određeni su pomoću empirijske jednadžbe. Mukoadhezivna svojstva MGs evaluirana su u vodenoj otopini mjerenjem adsorpcije mucina na mikrogelove. Konstruirane su adsorpcijske izoterme i uspoređene s Freudlichovim i Langmuirovim jednadžbama. Pokusi in vitro pokazuju da oslobađanje ljekovite tvari ovisi o stupnju umreženja i količini želatine upotrijebljene u pripravi IPN. Vrijednosti oslobađanja uvrštene su u jednadžbu zakona potencije i u Higuchijev model kako bi se izračunali razni parametri prijenosa lijeka; n vrijednosti bile su između 0,4055 i 0,5754, što ukazuje na to da oslobađanje varira od Fickovog do kvazi-Fickovog, ovisno o sastavu pripravka
Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis
Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions
A methoxy derivative of resveratrol analogue selectively induced activation of the mitochondrial apoptotic pathway in transformed fibroblasts
Resveratrol (R-3), a trihydroxy trans-stilbene from grape, inhibits multistage carcinogenesis in animal models. A resveratrol derivative 3,4,5,4′-tetrahydroxystilbene (R-4) exhibits potent growth inhibitory effect against transformed human cells. Here we report that 3,4,5,4′-tetramethoxystilbene (MR-4), converted from R-4, was more potent against cancer cell lines (WI38VA, IMR-90SV, HeLa, LNCaP, HT-29, and HepG2), but had almost no inhibitory effect on the growth of normal cells (WI38, IMR-90, BJ-T) at the concentrations tested. The IC50 value of MR-4 on the growth inhibition of transformed WI38VA human cells was 0.5 μM, as compared to the value of greater than 50 μM for the normal WI38 cells. Resveratrol, however, did not exhibit such clear differential effect and the IC50 value of R-3 for WI38VA cells was about 50 μM. The growth inhibitory effect of MR-4 correlated with the induction of apoptosis in the transformed cells. When normal WI38 cells and transformed WI38VA cells were compared, MR-4 induced increases of the Bax/Bcl-2 mRNA ratio, p53 and Bax protein level, activation of caspases, and DNA fragmentation in transformed, but not in normal cells. Further analysis revealed that MR-4 caused a rapid appearance of perinuclear aggregation of mitochondria in WI38VA but not in WI38 cells, suggesting that the mitochondria could serve as an early target of MR-4. R-3 also induced apoptosis and mitochondrial clustering but only at a much higher concentration, close to 500 μM. Taken together, the specific activation of the mitochondria-mediated apoptotic pathway could be a major reason for the striking differential growth inhibitory effect of MR-4
Computational Prototyping Tools and Techniques
Contains reports on five research projects.Industry Consortium (Mobil, Statoil, DNV Software, Shell, OTRC, Petrobras, NorskHydro, Exxon, Chevron, SAGA, NSWC)U.S. Navy - Office of Naval ResearchAnalog DevicesDefense Advanced Research Projects Agency Contract J-FBI-95-215Cadence Design SystemsHarris SemiconductorMAFET ConsortiumMotorola SemiconductorDefense Advanced Research Projects AgencyMultiuniversity Research InitiativeSemiconductor Research CorporationIBM Corporatio
Priprava i vrednovanje šumećih plutajućih tableta tizanidin hidroklorida
Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility throughout the length of the gastrointestinal tract. The objective of the present investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (3440 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.Tizanidin hidroklorid je prokinetički agens za peroralnu primjenu koji olakšava ili obnavlja mobilnost kroz gastrointestinalni trakt. Cilj rada bio je razvoj šumećih plutajućih matriksnih tableta tizanidin hidroklorida za produljenje zadržavanja u želucu u svrhu poboljšanja niske bioraspoloživosti (3440 %) i produljenja vremena poluživota (4,2 h). Tablete su pripravljene metodom izravne kompresije, koristeći hidroksipropil metilcelulozu različite viskoznosti (HPMCK4M, K15M i K100M). Određeni su različiti fizikalni parametri. Oslobađanje ljekovite tvari in vitro bilo je polagano tijekom 12 sati, a tablete su imale svojstvo plutanja. Prema DSC ispitivanja nema interakcije s pomoćnim tvarima. Kinetička ispitivanja pokazuju da oslobađanje iz svih pripravaka slijedi Higuchijev model, kinetiku prvog reda i ne-Fickov zakon. Na temelju faktora sličnosti (f2) (74,2), oslobađanja ljekovite tvari nakon 2, 6 i 8 h, te vremena poluživota t50 (5,4 h) izabrana je optimirana formulacija (F9) i upotrebljena u radiografičkim ispitivanjima koja uključuju BaSO4. In vivo ispitivanja rendgenskim zrakama na dobrovoljcima pokazala su da je srednje vrijeme zadržavanja u želucu bilo 6,2 ± 0,2 h
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