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

Alkaline activation of ceramic waste materials

Ceramic materials represent around 45 % of construction and demolition waste, and originate not only from the building process, but also as rejected bricks and tiles from industry. Despite the fact that these wastes are mostly used as road sub-base or construction backfill materials, they can also be employed as supplementary cementitious materials, or even as raw material for alkali-activated binders This research aimed to investigate the properties and microstructure of alkali-activated cement pastes and mortars produced from ceramic waste materials of various origins. Sodium hydroxide and sodium silicate were used to prepare the activating solution. The compressive strength of the developed mortars ranged between 22 and 41 MPa after 7 days of curing at 65 C, depending on the sodium concentration in the solution and the water/binder ratio. These results demonstrate the possibility of using alkaliactivated ceramic materials in building applications.The authors are grateful to the Spanish Ministry of Science and Innovation for supporting this study through Project GEOCEDEM BIA 2011-26947, and also to FEDER funding. They also thank Universitat Jaume I for supporting this research through Lucia Reig's granted research stay.Reig Cerdá, L.; Mitsuuchi Tashima, M.; Soriano, L.; Borrachero Rosado, MV.; Monzó Balbuena, JM.; Paya Bernabeu, JJ. (2013). Alkaline activation of ceramic waste materials. Waste and Biomass Valorization. 4:729-736. https://doi.org/10.1007/s12649-013-9197-zS7297364Puertas, F., García-Díaz, I., Barba, A., Gazulla, M.F., Palacios, M., Gómez, M.P., Martínez-Ramírez, S.: Ceramic wastes as alternative raw materials for Portland cement clinker production. 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Wnt signalling in human breast cancer: expression of the putative Wnt inhibitor Dickkopf-3 (DKK3) is frequently suppressed by promoter hypermethylation in mammary tumours

INTRODUCTION: Expression of the putative Wnt signalling inhibitor Dickkopf-3 (DKK3) is frequently lost in human cancer tissues because of aberrant 5'-cytosine methylation within the DKK3 gene promoter. Since other Wnt signalling inhibitors have been reported to be targets of epigenetic inactivation in human breast cancer, we questioned if DKK3 expression is also epigenetically silenced during breast carcinogenesis and therefore might contribute to oncogenic Wnt signalling commonly found in this disease. METHODS: DKK3 mRNA expression and DKK3 promoter methylation were determined by RT-PCR, realtime PCR and methylation-specific PCR in breast cell lines (n = 9), normal breast tissues (n = 19) and primary breast carcinomas (n = 150), respectively. In vitro DNA demethylation was performed by incubating breast cell lines with 5-aza-2'-deoxycytidine and trichostatin A. DKK3 protein expression was analysed by immunohistochemistry in breast carcinomas (n = 16) and normal breast tissues (n = 8). Methylation data were statistically correlated with clinical patient characteristics. All statistical evaluations were performed with SPSS 14.0 software. RESULTS: DKK3 mRNA was downregulated in 71% (five of seven) of breast cancer cell lines and in 68% of primary breast carcinomas (27 of 40) compared with benign cell lines and normal breast tissues, respectively. A DNA demethylating treatment of breast cell lines resulted in strong induction of DKK3 mRNA expression. In tumourous breast tissues, DKK3 mRNA downregulation was significantly associated with DKK3 promoter methylation (p < 0.001). Of the breast carcinomas, 61% (92 of 150) revealed a methylated DKK3 promoter, whereas 39% (58 of 150) retained an unmethylated promoter. Loss of DKK3 expression in association with DKK3 promoter methylation (p = 0.001) was also confirmed at the protein level (p < 0.001). In bivariate analysis, DKK3 promoter methylation was not associated with investigated clinicopathological parameters except patient age (p = 0.007). CONCLUSIONS: DKK3 mRNA expression and consequently DKK3 protein expression become frequently downregulated during human breast cancer development due to aberrant methylation of the DKK3 promoter. Since DKK3 is thought to negatively regulate oncogenic Wnt signalling, DKK3 may be a potential tumour suppressor gene in normal breast tissue

The ubiquitin-like molecule interferon-stimulated gene 15 (ISG15) is a potential prognostic marker in human breast cancer

INTRODUCTION: ISG15 is an ubiquitin-like molecule that is strongly upregulated by type I interferons as a primary response to diverse microbial and cellular stress stimuli. However, alterations in the ISG15 signalling pathway have also been found in several human tumour entities. To the best of our knowledge, in the current study we present for the first time a systematic characterisation of ISG15 expression in human breast cancer and normal breast tissue both at the mRNA and protein level. METHOD: Using semiquantitative real-time PCR, cDNA dot-blot hybridisation and immunohistochemistry, we systematically analysed ISG15 expression in invasive breast carcinomas (n = 910) and normal breast tissues (n = 135). ISG15 protein expression was analysed in two independent cohorts on tissue microarrays; in an initial evaluation set of 179 breast carcinomas and 51 normal breast tissues; and in a second large validation set of 646 breast carcinomas and 10 normal breast tissues. In addition, a collection of benign and malignant mammary cell lines (n = 9) were investigated for ISG15 expression. RESULTS: ISG15 was overexpressed in breast carcinoma cells compared with normal breast tissue, both at the RNA and protein level. Recurrence-free (p = 0.030), event-free (p = 0.001) and overall (p = 0.001) survival analyses showed a significant correlation between ISG15 overexpression and unfavourable prognosis. CONCLUSION: Therefore, ISG15 may represent a novel breast tumour marker with prognostic significance and may be helpful in selecting patients for and predicting response to the treatment of human breast cancer

Synthesis of an ordered mesoporous carbon with graphitic characteristics and its application for dye adsorption

An ordered mesoporous carbon (OMC) was prepared by a chemical vapor deposition technique using liquid petroleum gas (LPG) as the carbon source. During synthesis, LPG was effectively adsorbed in the ordered mesopores of SBA-15 silica and converted to a graphitic carbon at 800 °C. X-ray diffraction and nitrogen adsorption/desorption data and high-resolution transmission electron microscopy (HRTEM) of the OMC confirmed its ordered mesoporous structure. The OMC was utilized as an adsorbent in the removal of dyes from aqueous solution. A commercial powder activated carbon (AC) was also investigated to obtain comparative data. The efficiency of the OMC for dye adsorption was tested using acidic dye acid orange 8 (AO8) and basic dyes methylene blue (MB) and rhodamine B (RB). The results show that adsorption was affected by the molecular size of the dye, the textural properties of carbon adsorbent and surface-dye interactions. The adsorption capacities of the OMC for acid orange 8 (AO8), methylene blue (MB) and rhodamine B (RB) were determined to be 222, 833, and 233 mg/g, respectively. The adsorption capacities of the AC for AO8, MB, and RB were determined to be 141, 313, and 185 mg/ g, respectively. The OMC demonstrated to be an excellent adsorbent for the removal of MB from wastewater.Web of Scienc

Changes in leptin, plasminogen activator factor and oxidative stress in morbidly obese patients following open and laparoscopic Swedish adjustable gastric banding

Background: Oxidative stress is increased in obesity, leading to endothelial dysfunction, atherogenesis, and platelet aggregation. The purpose of this study was to determine the effects of weight loss after bariatric surgery on serum lipids, malondialdehyde (MDA, a marker of oxidative stress), oxidized low-density lipoprotein (oxLDL, which is increased in obesity and causes endothelial dysfunction), paraoxonase (PON-1, which inhibits lipid peroxidation), leptin and plasminogen activator inhibitor type-1 (PAI-1, which contributes to a thrombotic state)

The efficacy of chloroquine treatment of Giardia duodenalis infection in calves

The purpose of the present study was to evaluate the effect of chloroquine treatment on cyst excretion in calves naturally infected with Giardia duodenalis. The calves were randomly assigned into two groups based on placebo (group I, n=7 untreated control calves) or treatment (group II, n=7 calves treated orally with 2.5 mg/kg chloroquine twice daily for five consecutive days). The G. duodenalis isolates were identified by molecular characterization with beta-giardin nested PCR and gene sequence analysis as assemblage A3. Cyst excretion was determined on days 0, 3, 7 and 10, before and after treatment. Geometric means of the number of excreted cysts did not change significantly in the control group during the trial. The reduction in cyst excretion after chloroquine treatment was 99% on day 3 and 100% on days 7 and 10. Chloroquine treatment is most probatly practically applicable, relatively inexpensive and highly effective against giardiosis in calves