301 research outputs found

    Antidiarrheal action of Zataria multiflora hydroalcoholic and hexane extracts in mice

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    Introduction: Zataria multiflora Boiss. is an indigenous herbal plant found in many parts of Iran. This herb is traditionally used as a remedy for treating gastrointestinal disorders including diarrhea. Despite the existence of few pharmacological evidences which support the antispasmodic action of Z. multiflora in vitro, there is no scientific report about therapeutic efficacy of Z. multiflora in animal models. The objective of this research was to investigate the antispasmodic activity of hydroalcoholic and hexane extracts of Z. multiflora on intestinal peristaltic movement as well as assessment of its antidiarrheal action in mice. Methods: Dried leafy branches of Z. multiflora were coarsely powdered and subjected to extraction by ethanol or hexane in a percolator apparatus. Antispasmodic activity of Z. multiflora in vivo was assessed by investigating effect of the extracts on intestinal charcoal meal transit. The antidiarrheal activity of Z. multiflora extracts was evaluated by castor oil and magnesium sulfate-induced diarrhea. The inhibitory effects of the extracts were compared with the standard drug loperamide. Results: The antispasmodic activity of Z. multiflora (20 & 40 mg/kg) hydroalcoholic and hexane extracts was confirmed by a reduction in the distance traveled by charcoal meal alongside the small intestine. Z. multiflora extracts (20 & 40 mg/kg) also significantly attenuated the castor oil and magnesium sulfate-induced diarrhea. Loperamide was more efficacious in reducing number of total stools in both models of diarrhea. Conclusion: The obtained results have established a pharmacological evidence for the folkloric use of the Z. multiflora as an antidiarrhoeal and spasmodic agent

    A FBWM-PROMETHEE approach for industrial robot selection

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    Industrial engineering; Multidisciplinary design optimization; Manufacturing engineering; Technology management; Operations management; Industry management; Business management; Industrialization; Industrial robots; Fuzzy best-worst method; PROMETHEE; MCDM; Robot selection; Criteria.publishersversionpublishe

    Inhibitory effect of Ketotifen on rat isolated uterus contraction in compare with a β2-adrenoceptor agonist and an ATP-dependent K channel activator

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    Ketotifen is a Benzocycloheptathiophene with a range of pharmacological activities, including inhibitory effect on ileum and bladder smooth muscle contraction. However, effect of Ketotifen on uterus contraction has not been investigated. The present study was carried out to look for action of Ketotifen on rat isolated uterus contractions, induced by KCL and Acetylcholine, compared with effects of other drugs. Ketotifen inhibited the response to 80 mM KCL in a concentration-dependent manner (pD2=6.2±0.13) and shifted Acetylcholine concentration-response curve by 25 folds to the right at 5 µM bath concentration. Effect of Ketotifen on KCL concentration-response curve was similar to that of metaproterenol, inhibiting the response to all concentration of KCL and attenuating the maximum response. Diazoxide only at very high concentrations (50 and 500 µM) inhibited the induced contractions. This study showed that Ketotifen is a relaxant of rat isolated uterus. As the inhibition of contractile over-activity of the uterus is the base of the treatment of pre-term labor, provided that similar effect will be seen in vivo, then Ketotifen may have clinical benefits for treatment of this condition

    Prolonged Response to Anti–PD-1 Antibody Therapy in Chemotherapy-Refractory Cholangiocarcinoma With High Tumor Mutational Burden

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    Management of advanced intrahepatic cholangiocarcinoma (iCCA) is challenging and overall survival is poor. Progress in the development of new therapeutic options for metastatic cholangiocarcinoma (CCA) has been slow; hence, to date, there are no approved second-line agents in this setting. Although the development of immune checkpoint inhibitors has significantly improved overall survival in a variety of malignancies, there has not been a clinically important impact in CCA. This report presents a 66-year-old patient with chemotherapy-refractory iCCA who experienced a prolonged response to immunotherapy. Tumor genome profiling revealed a high tumor mutation burden of 17 mutations per megabase in the absence of microsatellite instability. He was started on immunotherapy with nivolumab and has experienced an ongoing response for 16 months without clinical symptoms and only minimal radiologic disease

    Driving Simulator Motion Cueing Assessment: A Platform Design Perspective

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    The overall aim of this thesis was to study the effects of a simulator’s motion system on vestibular motion cueing fidelity in different contexts, evaluated in terms of drivers’ perception and behaviour, in low and high road friction conditions. The effects of manipulating the motion cueing algorithm (MCA), was found to be a function of the vehicle motion in a manoeuvre, and significant effects were observed. The applicability of simulators for the assessment of vehicle driven attribute qualities such as ride, steering and handling were studied by manipulating vehicle ride height (RH). The differences between the RHs were subjectively distinguishable by the drivers in the simulator. Incongruities between the subjective preferences and objective performances were observed in both of the independent comparisons of the MCAs and RHs. The effects of motion platform (MP) workspace size were found to be dependent on the manoeuvres and road friction level. In the low-friction condition, with the increase of MP size, two opposite effects were observed on drivers’ preferences and their performances, depending on the manoeuvre. In high-friction, in most of the handling and steering qualities, a direct relation was found between the MP size and appropriate vehicle RH. Furthermore, the optimal tuning of the MCAs and optimisation of the MP workspace size was introduced. A conservative motion cueing fidelity criteria was defined. A multi-layered optimisation method was developed that uses the optimal setting of the MCA, to address the MP translational workspace size, and to meet the fidelity criteria; applicable for different manoeuvres. This method was tested on the drivers’ performance data collected from the experiments in the simulator

    Antispasmodic activity of apigenin and luteolin, two components of Dracocephalum kotschyi extract, on rat ileum contractions

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    Introduction: Aerial parts of Dracocephalum kotschyi have been used as antispasmodic agents in Iranian traditional medicine. Recent pharmacological studies confirmed antispasmodic activity of D. kotschyi extract. The objective of this research was to investigate antispasmodic activities of apigenin and luteolin to find out if they are responsible for the spasmolytic activity of hydroalcoholic extract of D. kotschyi. Methods: Aerial parts of D. kotschyi were extracted with ethanol. Antispasmodic effect of hydroalcoholic extract of D. kotschyi, apigenin and luteolin were examined on KCl and/or acetylcholine (ACh)-induced contractions in rat isolated ileum. Results: Hydroalcoholic extract of D. kotschyi concentrations-dependently inhibited KCl and ACh induced contractions with IC50 values of 41±10 µg/mL and 133±19 μg/mL, respectively. Apigenin concentrations-dependently inhibited KCl and ACh induced contractions with IC50 values of 57±12 μM and 80±18 µM, respectively. Luteolin concentrations-dependently inhibited KCl induced contractions with IC50 values of 68±14 μM. Loperamide reduced both KCl and ACh induced contraction with IC50 values of 189±44 nM and 82±20 μM, respectively. Conclusion: In this study apigenin and luteolin were identified as two active ingredients responsible for antispasmodic activities of D. kotschyi extract

    Progress towards the Synthesis of Carbohydrate-Based Biomedical and Material-Science Relevant Molecules

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    Cancer cells express unique carbohydrate signatures on their surfaces known as tumour-associated carbohydrate antigens (TACAs). These antigens are not typically found on healthy cells and therefore are promising targets for immunotherapy using adap-tive immune response tools. If the immune system could theoretically be “trained” to tar-get this molecule, then the immune system could be used to help eradicate any cancer cells from the host. A problem with carbohydrate-based targets is they are not stable in the body because of their inherent acetal functionality: the glycosidic bond. This research aims to remove the unstable acetal functionality in carbohydrates by replacing the exocy-clic anomeric oxygen with a methylene group (C-glycoside) to make new N-Fmoc pro-tected acetal-free C-glycoside analogues of the Tn antigen, a TACA found on many tu-mor cells. Removing the labile functionality should result in a greatly enhanced lifetime and bioavailability relative to the native system with no likely loss in recognition specifici-ty as the exocyclic oxygen is not generally involved in molecular recognition events. The Thomsen-Friedenreich antigen is another tumour-associated carbohydrate, which is found on specific types of cancer cells, such as CD34+ T-cells in leukemia and sarcoma, as well as CD 44+-cells in colon and breast cancers. The application of this anti-gen confronts the same limitation as to the Tn antigen. In order to be more effective, it has to be modified to increase its stability and have a higher chance of getting to the tar-get and inducing the required immune response. The synthesis of a fully acetal-free TF is challenging because of the unique 1,3-β one carbon linkage between the galactose and N-acetyl galactosamine moieties. Through the removal of both the exocyclic oxygens in the anomeric position and the linkage between the two sugar moieties, and replacing them with methylene groups, the stability of this antigen under biological conditions in the body greatly increases, and as a result, can better activate the immune system. This type of double C-glycoside-amino acid conjugate has never been reported in the literature for any carbohydrate. This thesis will discuss significant progress towards the synthesis of this promising, but challenging, fully acetal-free TF antigen. The next portion of the thesis expresses the synthesis of two glycolipids isolated from S. pneumoniae, the leading cause of neonatal sepsis and meningitis. Two main frac-tions of antigenic S. pneumoniae glycolipids were identified. One contains a monosaccha-ride, and the second fraction contains a disaccharide. Both the monosaccharide and the disaccharide appear capable of activating invariant natural killer T cells (iNKT), a subclass of white blood cells that produce non-specific cytokines whose activation can lead to a systemic uncontrolled immune response. The total synthesis of both the mono- and the disaccharide will be discussed in this thesis and the biological activity of these synthe-sized saccharides will be measured in order to confirm their structures, which have never been examined. The next part of the thesis reports the efforts toward the study of the limitations of the selective removal of acetates in the presence of long-chain esters. This area of re-search remains under development as selective deprotection of the acetyl group, especial-ly in the pyranose sugar moiety is largely unexplored. The final section of the thesis outlines the synthesis of an acetylated lactose bear-ing free hydroxyl groups at the C-6 and C-6΄ for attachment to conjugated polymers, with applications in electronic devices
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