Produs original pentru tratamentul hiperplaziei de prostată; mecanisme de acţiune preclinică

NEWTONE Laboratories, Bucharest, Romania, S.C. Biotehnos S.A., Ilfov, Romania, The Academy of Romanian Scientists, Bucureşti, Romania, Al VI-lea Congres de Urologie, Dializă şi Transplant Renal din Republica Moldova cu participare internaţională (21-23 octombrie 2015)Adenoprosin product is based on the exploitation of certain entomological resources, whose biological systems are analogs with the human ones in a higher percent than other natural sources. This compatibility is concretized in a higher responsiveness of cellular structures to the action of the entomological biocomplex with an optimized design towards a particular therapeutical target. Adenoprosin is involved in inflammatory processes associated with static and dynamic mechanisms of prostate hyperplasia. The „in vitro” specific action was investigated using standardized cell lines (PWR-1E - androgenresponsive and DU-145 - prostate adenocarcinoma metastasis; hormone independent cells) and experimental positive controls (dutasteride - drug involved in hormone -dependent aberrant proliferative mechanisms induced by testosterone; methotrexate - cell division inhibitor; dexamethasone - anti by its anti-apoptotic, anti-proliferative and anti-inflammatory biological activity, proved by methods of performant cellular and molecular multi-parametric analysis. It was highlighted the stop of IL6 and IL8 cytokines extracellular release in stimulating conditions with pro-inflammatory agents (phorbol-myristateacetate- PMA and tumor necrosis factor - TNFa). As well as, Adenoprosin shows significant action on extracellular signaling pathways of tumor progression and invasion, inhibiting IL6 cytokine - morbidity mediator in prostate cancer and VEGF - responsible of the onset of angiogenesis in metastatic -process, ffie preclinical studies revealed an optimum efficacy / toxicity profile, remarkable in the actual tendencies of therapeutical capitalization of natural raw materials with significant biological efficiency and minimal side effects. In recent years, the pathologies resulted from prostate disorders had a rising incidence, Adenoprosin covering an important therapeutical niche on the pharmaceutical market. The research was conducted as part of the project ENTOMED / Ctr DPST 26/2013.Produsul Adenoprosin se bazeaza pe exploatarea unor anumite resurse entomologice ale căror sisteme biologice sunt analoge celor umane intr-un procent ridicat fata de alte surse naturale. Aceasta compatibilitate este concretizata printr-o responsivitate superioara a structurilor celulare la acţiunea biocomplexului entomologie cu design optimizat către o anumita tinta terapeutica. Adenoprosin intervine in procese inflamatorii asociate cu mecanisme statice si dinamice implicate in hiperplazia de prostata. Acţiunea specifica in vitro a fost investigata utilizând linii celulare standardizate (PWR-1E - androgen-responsiva si DU-145 - metastaza de adenocarcinom de prostata, hormon independenta) si martori pozitivi experimentali (dutasterid - medicament ce intervine in mecanismele aberant proliferative hormon-dependente induse de testosteron, metrotrexat - inhibitor diviziune celulara, dexametazona - agent antiinflamator) .Efectul produsului Adenoprosin este susţinut de activitatea biologica antiapoptotica, antiproliferativa si antiinflamatoare demonstrate in vitro prin metode performante de analiza multiparametrica celulara si moleculara. S-a evidenţiat stoparea eliberării de citokine IL6 si IL8 in condiţii de stimulare cu agenţi pro-inflamatorii (forbol miristat acetat-PMA si factor necrotic tumoral-TNFa). De asemenea, Adenoprosin manifesta acţiune semnificativa pe caile de semnalizare extracelulara a progresiei si invaziei tumorale inhibând citokina IL6 - mediator al morbidităţii in cancerul de prostata si VEGF - factor declanşator al angiogenezei in metastazare. Studiile preclinice au evidenţiat de asemenea, un profil eficacitate / toxicitate optim, remarcabil in tendinţele actuale de valorificare terapeutica a materiilor prime naturale cu activitate biologica eficienta si efecte secundare minime. In ultimii ani, patologiile rezultate din disfunctiile prostatei au o incidenţa crescută, produsul Adenoprosin acoperind o nisa terapeutica importanta in piaţa farmaceuticelor. Cercetările s-au realizat in cadrul proiectului ENTOMED / Ctr26 DPST/2013

A new approach to balance dental fear and anxiety by using BachTM Flower Therapy

Treatments in dentistry currently consist of an interdisciplinary approach, including (but not necessarily limited to) the holistic perspective. The different fields of allopathic and complementary medicine are used together to ensure not only a high-quality restorative treatment, but also to provide patients with psychological and emotional support. This perspective also applies to dental anxiety, which consists of complex (emotional, vegetative and psychomotor) manifestations. One of the most well-known complementary therapies for reducing dental fear and anxiety is BachTM Flower Therapy. Even if the mechanism of action of this therapy is not yet scientifically documented, notable results have been and continue to be reported in the literature in several clinical studies on patients with dental diseases. It is indicated for both adults and children, in the latter when they go through major biological changes, such as primary and permanent dentition. As a conclusion, BachTM flower therapy is effective and complementary to dental treatments applied to patients, by reducing stress, anxiety, as well as creating a climate of peace, trust and confidence, both for the patient and the doctor. In addition, it is a relatively accessible and cheap form of care, with no significant adverse effects noted so far

Antifungal effect of some steroidal glycoalkaloids on monilinia fructigena (ADERH. & RUHL.) honey fungus

Monilinia fructigena is the pathogen responsible for the appearance of brown rot and mummification of apple fruit present anywhere this species is grown. In Romania, the fungus attack is frequently in the apple orchards every year, depending on the environmental conditions, variety resistance, pathogen control management. The antifungal activity aainst this pathogen of steroidal glycoalcaloids extracted from Solanum species was tested in vitro. The steroidal glycoalkaloids considered were: solanine, solanidine, tomatine, solamargine, chaconine. Of these, a structural group, encoded GLY, was selected as one of the active components of a patented biofungicide. It was tested in concentrations of 0.1%, 0.5% and 1% and compared with the control. The biological material was represented by the isolated Monilinia fructigena (Mf 7), collected on apple fruit, the Idared variety, originated from RIFG Maracineni. The fungus did not develop in the first 3 days of incubation in any of the experimental variants. After 6 days of observation, the fungus developed at variants of GLY 0.1%, GLY 0.5% and control. The maximum mycelial diameter was determined in the control variant with 73.3 mm after 12 days of observation. In the GLY0.1% variant the diameter of the colony was 50 mm and in the GLY 0.5% variant the diameter of the fungus colony reached 8.2 mm, after 12 days of observation. In GLY 1% variant fungus did not develop throughout the observation period. Efficacy was maximal (E = 100%) in the GLY1% variant, followed by the GLY0.5% variant, with the efficacy of 88.8%. The EC 50 and EC 90 values were 0. 21% and 0.75% for the data obtained after 12 days of observation

Hydrogenation of unsaturated carbonyl compounds on non-calcined LDHs. I. Synthesis and characterization of ZnNiCuAl hydrotalcite-like materials

International audienceSeveral Zn/Ni/Cu/Al layered double hydroxides (LDH) with variable Ni/Cu ratios but constant Zn/Al, as well as M2+/M3+ ratios, were synthesized by coprecipitation method with CO3 2– as compensating anion. The main goal of the study was to investigate the influence of the catalysts composition, especially Ni/Cu ratio, on the physical and catalytic properties of these materials. The XRD results show that all the LDHs samples are well crystallized and contain only pure phases. Moreover, the spectral techniques (FT-IR and DR-UV-VIS) indicated that both Ni and Cu species are present in the brucite-like layers of LDHs. The shape of the nitrogen physisorption isotherms obtained at –196 °C indicates a predominantly mesoporous materials; the surface areas and pore volumes are in the specific ranges between 37–86 m2.g–1 and 0.31–0.75 cm3.g–1, respectively. Three characteristic weight losses between 30 and 400 °C are identified by TG analysis for the hydrotalcite-like materials synthesized in this study. Moreover, an influence of the Ni/Cu ratios on the amount of the physisorbed water was noticed. The preliminary catalytic test revealed unusual catalytic properties of the non-calcined samples in the liquid phase hydrogenation of trans-cinnamaldehyde

CELLULAR AND MOLECULAR ACTIVITY OF A STANDARDIZED SMALL SEA FISH EXTRACT IN AN EXPERIMENTAL MODEL OF PRIMARY HUMAN CARTILAGE CELLS

The inflammatory, degenerative and rheumatic diseases are triggered and evolving at osteoarticular level due to the disruption of functionality of constitutive cells and extracellular microenvironment correlated with systemic responses as synthesis of progressively degradative cytokines. Objectives. The in vitro bioactive efficacy of standardized small sea fish extract has therapeutic relevance on the strength of optimal physiological and structural biologic system rendered by primary cells isolated from human cartilage (HCH, PromoCell) unlike standardized cell lines that may have genetic and functional changes and beside the primary cells directly isolated from animal tissue that do not reproduce an authentic biological response because of metabolic stress adaptation to growing conditions in vitro. The main therapeutic targets in osteoarticular disorders are regeneration of affected cartilage and attenuation of local inflammatory processes. Materials and methods. The in vitro articular matrix reconstruction action was evaluated by molecular tests with relative quantification of gene expression (qPCR) for aggrecan, the predominant component of human cartilage, and for the enzyme responsible for degradation of aggrecan, aggrecanase (ADAMTS4) whose activities were phenotypically measured by ELISA (enzyme-linked immunosorbent assay) test. The anti-inflammatory profile was proved by techniques of quantitative evaluation of mRNA level and detection of extracellular soluble proteins by flow-cytometry (BD™ Cytometric Bead Array) for pro-inflammatory cytokines IL-6, IL-8 and gene expression for nuclear factor NF-κB. Results and discussion. The results prove the matrix regenerator effect of standardized small fish extract by stimulation at gene expression level of aggrecan synthesis in early stages of chondrocytes differentiation, directing cells to a mature functional status, as well as by inhibition of aggrecan degradation by action on gene expression and extracellular activity of ADAMTS4. The standardized small sea fish extract has an anti-inflammatory effect proven by extracellular and transcriptional inhibition of pro-inflammatory cytokines, IL-6, IL-8 and the nuclear factor NF-κB gene. Conclusions. The in vitro anti-inflammatory and regenerative action of standardized small fish extract reflects a significant therapeutic potential for osteoarticular disease sustained both through the effects at gene and phenotypic expression levels and through the reproducible characteristics of dynamics of in vivo chondrocytes evolution evidenced by primary cell lines

Effect of aluminium incorporation by the ''pH-adjusting'' method on the structural, acidic and catalytic properties of mesoporous SBA-15

International audienceA series of Al-SBA-15 catalysts in a wide compositional range (Si/Al = 130-5.2) was prepared by ''pHadjusting'' aiming to evaluate the effect of aluminium incorporation on their structural, acidic and catalytic properties. The calcined materials were characterized by ICP, XRD, N2 adsorption/desorption, TEM, 27Al MAS NMR, microcalorimetry of ammonia adsorption and FTIR of adsorbed pyridine. It was found that the progressive incorporation of aluminium in SBA-15 has a positive effect on the structural and textural characteristics of catalysts as well as on the number of Brönsted and Lewis acid sites, whereas no net effect was observed on the relative distribution of acid sites according to their nature or strength. The catalytic properties of mesoporous SBA-15 aluminosilicates were finally evaluated by test-reactions in the liquid phase tert-butylation of phenol and isomerization of styrene oxide, under mild conditions. The catalytic results showed that the progressive incorporation of aluminium results in higher reaction rates in the O- and C-alkylation of phenol as well as isomerization of styrene oxide, providing evidence that the number of acid sites controls the catalytic activity of Al-SBA-15. On the other hand, the incorporation of aluminium had no effect on the selectivity to the reaction products, indicating that selectivity levels are controlled by the relative distribution of acid sites. It was also reported that Al-SBA-15 prepared by ''pH-adjusting'' are highly active catalysts in the isomerization of styrene oxide and very selective to phenylacetaldehyde

Selective conversion of styrene oxide to 2-phenylethanol in cascade reactions over non-noble metal catalysts

International audienceThe catalytic hydrogenation of styrene oxide (SO) and phenylacetaldehyde (PAA) to 2-phenylethanol(2-PEA), with H2 in a tri-phase system, was investigated under various reaction conditions using supportedCo and Ni metal catalysts. The catalysts were produced from tri-component layered double hydroxides(i.e., hydrotalcite-like compounds (Ni)CoMgAl with 1 : 1 : 1 molar ratios), after calcination and reduction of thelayered double hydroxides precursors. Among the tested solids, the metallic Co-based catalyst has provento be an efficient material for the selective hydrogenation of PAA towards 2-PEA. Taking into account thehigh activity and selectivity of Al-SBA-15 for SO isomerization to PAA, a two-step process was proposed asan original and highly selective route for producing 2-PEA from SO. This process involves cheap catalystsand it includes a first step of SO isomerization reaction over a mild acid strength mesoporous solidfollowed by hydrogenation of the resulted PAA over a redox metallic catalyst

Enhancing the performance of SBA-15-supported copper catalysts by chromium addition for the chemoselective hydrogenation of transcinnamaldehyde

International audienceSBA-15-supported copper-chromium mixed oxide nanoparticles (CuCr/SBA-15) were prepared by incipient wetness impregnation followed by mild drying at 25 1C and calcination. The Cu : Cr weight ratios were 1 : 1, 5 : 1, and 10 : 1, at a constant total loading of 5 wt%. Monocomponent SBA-15-supported Cu-oxide (Cu/SBA-15) and Cr-oxide (Cr/SBA-15) were prepared as reference samples. The materials were systematically characterized by XRD at low and high angles, N2 physisorption, DR UV-vis, FT-IR, and XPS spectroscopies, and TPR. XRD at low angles and N2 physisorption confirmed the preservation of the mesoporous structure of the SBA-15 support after impregnation and calcination. In the case of monocomponent samples, CuO appeared poorly dispersed, while the Cr species (Cr2O3, mono- and polychromates) appeared highly dispersed on the surface of the SBA-15 support. The progressive addition of chromium to copper had positive effects on the average crystallite size of CuO, which decreased from B28 nm (Cu/SBA-15) to B3 nm (CuCr/SBA-15; Cu : Cr = 1 : 1), and on reducibility, as well. Metallic active phases were obtained by reducing of the oxide phases under a hydrogen flow at 350 1C. By comparison to the monometallic catalysts, the reduced CuCr/SBA-15 materials were active in the hydrogenation of cinnamaldehyde and chemoselective towards cinnammyl alcohol (450 mol%). The activity can be correlated with the particle size of copper, whereas the high selectivity to unsaturated alcohol can be associated with the presence of dual Cu0-Crn+ sites

Controlling the distribution of cobalt (oxide) nanoparticles in the dual pore system of SBA-15 scaffolds

International audienc

Playing on 3D spatial distribution of Cu-Co (oxide) nanoparticles in inorganic mesoporous sieves: Impact on catalytic performance toward the cinnamaldehyde hydrogenation

International audienceThe preparation of supported bimetallic materials based on transition metals has attracted much interest since their use as catalysts towards hydrogenation processes for the production of fine chemicals or environmental depollution processes. The synthesis procedure proposed in this study allows to obtain bimetallic materials with high dispersion of the active sites, control of the chemical composition and localization as well as good thermal resistance against sintering. In this line, a series of materials based on Cu and Co supported on SBA-15 were prepared by the optimization of the drying step during incipient wetness impregnation, the ratio of Cu-Co was studied and the monometallic materials were used for comparison. The physico-chemical properties of freshly calcined and reduced materials were investigated by ICP-EOS, nitrogen physisorption, ex-situ and in-situ XRD, TEM-EDX, TPR and XPS. The materials showed improved dispersion at low copper ratio, due to the stabilization of CuxCo(1-x)Co2O4 spinel phase, promoting a high dispersion of confined NPs of 9 nm within the large pores of the SBA-15. Subsequent stabilization of the Cu and Co NPs is observed by in situ-XRD, and the collected HAADF micrographs clearly evidence a high dispersion of the copper within the bimetallic NPs. However, when copper is exceeding the CuCo ratio of 4:1, larger NPs of CuO located outside the silica mesopores are observed. Subsequent catalytic performances were investigated in the hydrogenation reaction of cinnamaldehyde (CNA), in two different pressure regimes (1 bar and 10 bars). For the reaction under pressure, CuCo1:4 showed the highest conversion with 67 mol % after 150 min of reaction, while the selectivity to the cinnamyl alcohol (CNOL) was of 47 mol %. The same catalyst showed a conversion of 99 mol % in atmospheric pressure after 24 h of reaction and the selectivity to CNOL reached 72 mol %. Such results confirm that our modified IWI protocol using mild drying step is valuable towards the preparation of confined bimetallic nanoparticles within mesoporous sieves. High stability of such confined nanoparticles allow reduction of the active elements up to the metallic state, which strongly promotes the catalytic performance towards CNA hydrogenation reaction