The role of Olea Europaea L. Fruit on A2780, A172 and HFFF2 proliferation

Olea europaea L. commonly known as olive has been traditionally used for the prevention and treatment of many diseases since ancient times. Olive has been reported to possess a broad spectrum of pharmacological properties. In the present study, we investigated the activity of aqueous extract of Olea europaea L. fruit at various concentrations on A2780, A172, and HFFF2 cell lines proliferation by MTT assay. Aqueous extract of olive significantly increased cell proliferation in a dose dependent manner in the cell lines. It has been previously reported that olive has chemoproventive and anti-tumor effects. These disagreements can be explained by differences in cell line properties, type of olive and different solvents in the extracts. However, further investigation is needed to clarify the exact role of olive in cell proliferation and cancer. In this study fruit extract of Olea europaea L. showed more activatory effects on A2780 cell line in comparison with A172 and HFFF2. These differences in the activatory effects may be related to the activation of different signaling pathways in different cell lines. © 2016, Iranian Association of Pharmaceutical Scientists. All rights reserved

Determination of mebudipine in human plasma by liquid chromatography�tandem mass spectrometry

In previous studies, mebudipine, a dihydropyridine calcium channel blocker, showed a considerable potential to be used in cardiovascular diseases. The aim of the current study was to develop a valid method using reversed-phase high performance liquid chromatography coupled with electrospray ionization mass spectrometry to assay mebudipine in the human plasma. Separation was achieved on a Zorbax Eclipse® C18 analytical column using a mobile phase consisted of methanol/water (90:10, v/v). The flow rate was 0.6 mL/min and carbamazepine was used as an internal standard (IS). This method involved the use of M +Na+ ions of mebudipine and IS at m/z 411 and 259, respectively with the selected ion monitoring (SIM) mode. There were no interfering peaks from endogenous components in blank plasma chromatograms. Standard curves were linear (r2>0.99) between 5 to 100 ng/mL. The mean extraction efficiency was about 84% and the limit of quantification for mebudipine was 5 ng/mL in plasma. The coefficient of variation and error at all of the intra-day and inter-day assessments were less than 11%. The results indicated that this method is a fast, accurate, sensitive, selective and reliable method for the determination of mebudipine in the human plasma. The assay method has been successfully used to estimate plasma concentration of mebudipine after the oral administration of 2.5 mg tablet in healthy adults. © 2015 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services

Improved HPLC method for determination of four PPis, omeprazole, pantoprazole, lansoprazole and rabeprazole in human plasma

PURPOSE: To develop a simple and rapid HPLC method for measuring of four proton-pump inhibitors (PPIs), omeprazole (OPZ), pantoprazole (PPZ), lansoprazole (LPZ) and rabeprazole (RPZ) concentrations in human plasma. METHODS: Following a single step liquid-liquid extraction analytes along with an internal standard (IS) were separated using an isocratic mobile phase of phosphate buffer (10 mM)/acetonitrile (53/47, v/v adjusted pH to 7.3 with triethylamine) at flow rate of 1 mL/min on reverse phase TRACER EXCEL 120 ODS-A column at room temperature. RESULTS: Total analytical run time for selected PPIs was 10 min. The assays exhibited good linearity (r2>0.99) over the studied range of 20 to 2500 ng/mL for OPZ, 20 to 4000 ng/mL for PPZ, 20 to 3000 ng/mL for LPZ and 20 to 1500 ng/mL for RPZ. The recovery of method was equal or greater than 80 and lower limit of quantification (LLOQ) was 20 ng/mL for four PPIs. Coefficient of variation and error at all of the intra-day and inter-day assessment were less than 9.2 for all compounds. CONCLUSIONS: The results indicated that this method is a simple, rapid, precise and accurate assay for determination of four PPIs concentrations in human plasma. This validated method is sensitive and reproducible enough to be used in pharmacokinetic studies and also is time- and cost-benefit when selected PPIs are desired to be analyzed

Design and evaluation of a novel nanodrug delivery system for reducing the side effects of clomiphene citrate on endometrium

Background: Stimulation of ovulation with clomiphene citrate can cause side effects on endometrial receptivity. Formulation with nano-size may be an alternative therapy for women with ovulatory disorders. In this study, we investigated sustained-release clomiphene citrate by using Phosal-based formulation (PBF) and evaluate its decreased side effect on the endometrial receptivity. Methods: In the in-vitro study, CC loaded PBF was analyzed using Zetasizer, Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM). In the in-vivo study, 24 female mice were randomly divided into three groups: CC (5 mg/kg), CC/PBF (5 mg/kg) and SS (1 ml) daily administered and injected with 5 IU HCG and mated after two days. At day 4.5, pregnant mice were euthanized and endometrial tissue was extracted for quantitative polymerase chain reaction (Q-PCR) analysis. Results: The optimized PBF contained Phosal 50PG/glycerol in a 2:8 ratios (w/w) and the particle size of optimum formulation was 67 ± 0.30551 nm and the release of CC from CC-containing PBF was slightly faster in the first 24 h; wherein, 29 of CC was released, and 76 of CC was released up to 120 h. The mRNA levels of leukemia inhibitory factor (LIF), leukemia inhibitory factor receptor alpha (LIFR), HOXA10, Heparin-binding epidermal growth factor (HB-EGF), and epidermal growth factor (EGF) were significantly upregulated and MUC1 and PGR mRNA levels were significantly downregulated in the CC-containing PBF-treated animals compared with only CC group (P < 0.05). Conclusion: Sustained release formulation of clomiphene citrate increased its targeting efficiency and improved the impact of the CC on implantation. Figure not available: see fulltext. © 2019, Springer Nature Switzerland AG

The Insulin-Like Growth Factor System in the Long-Lived Naked Mole-Rat.

Naked mole-rats (Heterocephalus glaber) (NMRs) are the longest living rodents known. They show negligible senescence, and are resistant to cancers and certain damaging effects associated with aging. The insulin-like growth factors (IGFs) have pluripotent actions, influencing growth processes in virtually every system of the body. They are established contributors to the aging process, confirmed by the demonstration that decreased IGF signaling results in life-extending effects in a variety of species. The IGFs are likewise involved in progression of cancers by mediating survival signals in malignant cells. This report presents a full characterization of the IGF system in the NMR: ligands, receptors, IGF binding proteins (IGFBPs), and IGFBP proteases. A particular emphasis was placed on the IGFBP protease, pregnancy-associated plasma protein-A (PAPP-A), shown to be an important lifespan modulator in mice. Comparisons of IGF-related genes in the NMR with human and murine sequences indicated no major differences in essential parts of the IGF system, including PAPP-A. The protease was shown to possess an intact active site despite the report of a contradictory genome sequence. Furthermore, PAPP-A was expressed and translated in NMRs cells and retained IGF-dependent proteolytic activity towards IGFBP-4 and IGF-independent activity towards IGFBP-5. However, experimental data suggest differential regulatory mechanisms for PAPP-A expression in NMRs than those described in humans and mice. This overall description of the IGF system in the NMR represents an initial step towards elucidating the complex molecular mechanisms underlying longevity, and how these animals have evolved to ensure a delayed and healthy aging process

Chimeric Vitronectin : Insulin-like Growth Factor Proteins Enhance Cell Growth and Migration through Co-Activation of Receptors

Complexes comprised of IGF-I, IGF-binding proteins and the ECM protein vitronectin (VN) stimulate cell migration and growth and can replace the requirement for serum for the ex vivo expansion of cells, as well as promote wound healing in vivo. Moreover, the activity of the complexes is dependent on co-activation of the IGF-I receptor and VN-binding integrins. In view of this we sought to develop chimeric proteins able to recapitulate the action of the multiprotein complex within a single molecular species. We report here the production of two recombinant chimeric proteins, incorporating domains of VN linked to IGF-I, which mimic the functions of the complex. Further, the activity of the chimeric proteins is dependent on co-activation of the IGF-I- and VN-binding cell surface receptors. Clearly the use of chimeras that mimic the activity of growth factor:ECM complexes, such as these, offer manufacturing advantages that ultimately will facilitate translation to cost-effective therapies

A comparative study of stability, antioxidant, DNA cleavage and antibacterial activities of green and chemically synthesized silver nanoparticles.

Silver nanoparticles have a wide range of research, industrial and biomedical applications that make it essential to develop a low cost and eco-friendly approach with scaling up potential. Green synthesis of nanoparticles through bio-reactions leads to a reduction of silver ions to particles could be an acceptable selection using no additional reducing chemicals. Moreover, the simplicity of scale-up processes of the method makes it more efficient than chemical and physical synthesis methods. In this study, Datura stramonium leaf extract and sodium citrate were used as biological and chemical reducing and stabilizing agents to make silver nanoparticles. The main goal is to comprise properties and evaluate antibacterial activity of nanoparticles synthesized through two approaches. Size and morphology compared between the two types of the synthesized nanoparticle by UV-Visible spectroscopy, DLS, AFM, TEM and their antibacterial effects were evaluated through growth inhibition MIC and MBC methods. The results showed narrow size range, spherical shape, high anti-oxidant, antibacterial and DNA cleavage activities of green synthesized silver nanoparticles comparing to less average size, wider range of nanoparticle size, no anti-oxidant activity and less antibacterial and DNA cleavage activities of chemically synthesized nanoparticles. The green synthesized silver nanoparticles had more desirable characteristics and biological activities compared to chemically synthesized nanoparticles. For instance, the green nanoparticles showed narrow size range, spherical shape, high anti-oxidant, antibacterial and DNA cleavage activities versus the chemically synthesized which had less average size, higher range of nanoparticles size, no anti-oxidant activity and less antibacterial and DNA cleavage activities

Antibodies to insulin-like growth factor I receptor

International Application No.: PCT/AU2007/000168The present invention relates to an antibody to insulin-like growth factor I receptor, or an antigen-binding portion of the antibody. The antibody, or the antigen-binding portion, bind to an epitope located in the cysteine-rich domain of the alpha-subunit of the insulin-like growth factor I receptor, and the antibody or the antigen-binding portion modulates IGF-I mediated proliferation of an IGF-I dependent cell.http://www.wipo.int/patentscopedb/en/fetch.jsp?LANG=ENG&DBSELECT=PCT&SERVER_TYPE=19&SORT=1209482-SCORE&TYPE_FIELD=256&IDB=0&IDOC=1479628&C=00&ELEMENT_SET=BASICHTML-ENG&RESULT=3&TOTAL=3&START=1&DISP=25&FORM=SEP-0/HITNUM,B-ENG,DP,MC,PA,ABSUM-ENG,SCORE&SEARCH_IA=AU2007000168&QUERY=%22booker%2c+grant%2