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In-vivo Activity (in-vivo + activity)
Selected AbstractsPharmacokinetic/pharmacodynamic assessment of the in-vivo efficacy of imipenem alone or in combination with amikacin for the treatment of experimental multiresistant Acinetobacter baumannii pneumoniaCLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2005M. Bernabeu-Wittel Abstract A guinea-pig pneumonia model involving imipenem-susceptible and imipenem-resistant strains of Acinetobacter baumannii was developed to assess the in-vitro and in-vivo activities of imipenem, alone or in combination with amikacin, and the pharmacokinetic and pharmacodynamic parameters. Serum levels were measured by bioassay (imipenem) or immunoassay (amikacin), followed by calculation of pharmacokinetic and pharmacodynamic parameters (Cmax, AUC, t1/2, Cmax/MIC, AUC/MIC, and ,t/MIC). In-vivo efficacy was evaluated by comparing bacterial counts in the lungs of treatment groups with end-of-therapy controls by anova and post-hoc tests. Decreases in the Cmax (13.4%), AUC (13%), t1/2 (25%) and ,t/MIC (11.8,32.2%) of imipenem were observed when it was administered with amikacin, compared with administration of imipenem alone. Similarly, decreases in the Cmax (34.5%), AUC (11.6%), Cmax/MIC (34.5%) and AUC/MIC (11.7%) of amikacin were observed when it was administered with imipenem. Bacterial counts in lungs were reduced by imipenem (p 0.004) with the imipenem-susceptible strain, and by amikacin (p 0.001) with the imipenem-resistant strain. The combination of imipenem plus amikacin was inferior to imipenem alone with the imipenem-susceptible strain (p 0.01), despite their in-vitro synergy, and was inferior to amikacin alone with the imipenem-resistant strain (p < 0.0001). In summary, combined use of imipenem with amikacin was less efficacious than monotherapy, probably because of a drug,drug interaction that resulted in decreased pharmacokinetic and pharmacodynamic parameters for both antimicrobial agents. [source] Design, synthesis, characterization and in-vivo activity of a novel salmon calcitonin conjugate containing a novel PEG-lipid moietyJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2010Weiqiang Cheng Abstract Objectives The aim of the study was to explore (1) the synthesis of a novel poly(ethylene glycol) modified lipid (PEG-lipid, PL) containing a chemically active tri-block linker, ,-maleimido lysine (Mal), and its conjugation with salmon calcitonin (sCT), and (2) the biophysical properties and activity of the resulting conjugate, Mal-PL-sCT, relative to the control, 2PEG-Mal-sCT, which comprises sCT conjugated with ,-palmitoyl- N -,-maleimido- l -lysine at cysteine 1 and cysteine 7, and PEG moieties at lysine 11 and lysine 18 via a conventional stepwise method. Methods The PEG-lipid was obtained by condensing palmitic acid derivative of ,-maleimido lysine with methoxy poly(ethylene glycol) amine. Under reductive conditions, the PEG-lipid readily reacted with sCT to yield the resultant compound, Mal-PL-sCT. Key findings Dynamic light scattering analyses suggested that Mal-PL-sCT and 2PEG-Mal-sCT exhibited robust helical structures with a high tendency to aggregate in water. Both compounds were more stable against intestinal degradation than sCT, although Mal-PL-sCT was less stable than 2PEG-Mal-sCT. However, 2PEG-Mal-sCT did not possess hypocalcaemic activity while Mal-PL-sCT retained the hypocalcaemic activity of sCT when it was subcutaneously injected in the rat model. Multiple functional groups may be conjugated to a peptide via a tri-block linker without the risk of obliterating the intrinsic bioactivity of the peptide. Conclusions The resultant novel PEG-lipid has a potential role to optimize protein and peptide delivery. [source] In-vitro and in-vivo immunomodulatory effects of syringinJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2001Jae Youl Cho Syringin was found to possess immunomodulatory activity by which it inhibited the in-vitro immunohaemolysis of antibody-coated sheep erythrocytes by guinea-pig serum through suppression of C3-convertase of the classical complement. In this study, we examined its in-vitro and in-vivo activity on tumour necrosis factor (TNF)-, and nitric oxide (NO) production, CD4 + T cell and CD8+ cytotoxic T cell (CTLL-2) proliferation, and croton oil-, arachidonic acid- and fluorescein-isothiocynate (FITC)-induced mouse ear oedema model. Syringin significantly inhibited both TNF-, production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells and CD8+ T cell (CTLL-2) proliferation in a dose-dependent manner, whereas neither NO production nor CD4+ T cell proliferation were blocked even by high concentrations of syringin. In the in-vivo experiments, syringin also significantly suppressed FITC-induced ear oedema in mice but not the ear oedema induced by croton or arachidonic acid. These results suggest that syringin may be implicated as an immunomodulator having an anti-allergic effect rather than an antiinflammatory effect. The anti-allergic effect of syringin seems to be due, in part, to inhibition of TNF-, production and cytotoxic T cell proliferation. [source] Recombinant Human Lactoferrin is Effective in the Treatment of Helicobacter felis -infected MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2000E. J. DIAL Recombinant human lactoferrin possesses in-vitro antibiotic and anti-inflammatory activity similar to the native form. It was tested for in-vivo activity in mice infected with the gastritis-inducing bacterium Helicobacter felis. A two-week course of treatment with lactoferrin was sufficient to partially reverse both infection-induced gastritis and the infection rate, and fully reverse gastric surface hydro-phobicity changes. A comparison of lactoferrin with amoxicillin and standard triple therapy revealed no differences in infection rate. These results show that recombinant human lactoferrin is effective in a mouse model of Helicobacter infection, and support further testing of this promising agent for this application. [source] Dreaming as a ,curtain of illusion': Revisiting the ,royal road' with Bion as our guideTHE INTERNATIONAL JOURNAL OF PSYCHOANALYSIS, Issue 4 2009James S. Grotstein One of Bion's most unique contributions to psychoanalysis is his conception of dreaming in which he elaborates, modifies, and extends Freud,'s ideas. While Freud dealt extensively with dream-work, he showed more interest in dreams themselves and their latent meaning and theorized that dreams ultimately constituted wish-fulfillments originating from the activity of the pleasure principle. Bion, on the other hand, focuses more on the process of dreaming itself and believes that dreaming occurs throughout the day as well as the night and serves the reality principle as well as the pleasure principle. In order for wakeful consciousness to occur, dreaming must absorb (contain) the day residue, and transfer it to System Ucs. from System Cs. for it to be processed (transformed) and then returned to System Cs. through the selectively-permeable contact-barrier. Dreaming, consequently, allows the subject to remain awake by day and asleep by night by its processing of the day's residue. Bion seems to conceive of dreaming as an ever-present invisible filter that overlays much of our mental life, including perception, as well as attention itself. He further believes that dreaming is a form of thinking that normally involves the collaborative yet oppositional (not conflictual) activity of the reality and pleasure principles as well as the primary and secondary processes. He also conflates Freud,'s primary and secondary processes into a single ,binary,oppositional' structure (Lévi-Strauss, 1958, 1970) that he terms ,alpha-function', which constitutes a virtual model that corresponds to the in-vivo activity of dreaming. He further believes that the analyst dreams as he or she listens and interprets and that the analysand likewise dreams while he or she freely associates. [source] | ||||||||||