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Feline Interstitial Cystitis Enhances Mucosa-Dependent Contractile Responses to Serotonin
Youko Ikeda,Amanda Wolf-Johnston,James R. Roppolo,Charles A. T. Buffington,Lori Birder 대한배뇨장애요실금학회 2018 International Neurourology Journal Vol.22 No.4
Purpose: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). Methods: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response (0.01–10μM) was determined for each strip with the mucosa intact or denuded. Results: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by 1μM atropine in both control and FIC bladder strips. Conclusions: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.
A Molecular Mucosal Adjuvant To Enhance Immunity Against Pneumococcal Infection In The Elderly
Fukuyama, Yoshiko,Ikeda, Yorihiko,Ohori, Junichiro,Sugita, Gen,Aso, Kazuyoshi,Fujihashi, Keiko,Briles, David E.,McGhee, Jerry R.,Fujihashi, Kohtaro The Korean Association of Immunobiologists 2015 Immune Network Vol.15 No.1
Streptococcus pneumoniae (the pneumococcus) causes a major upper respiratory tract infection often leading to severe illness and death in the elderly. Thus, it is important to induce safe and effective mucosal immunity against this pathogen in order to prevent pnuemocaccal infection. However, this is a very difficult task to elicit protective mucosal IgA antibody responses in older individuals. A combind nasal adjuvant consisting of a plasmid encoding the Flt3 ligand cDNA (pFL) and CpG oligonucleotide (CpG ODN) successfully enhanced S. pneumoniae-specific mucosal immunity in aged mice. In particular, a pneumococcal surface protein A-based nasal vaccine given with pFL and CpG ODN induced complete protection from S. pneumoniae infection. These results show that nasal delivery of a combined DNA adjuvant offers an attractive potential for protection against the pneumococcus in the elderly.
Wu, Huali,Infante, Jeffrey R,Keedy, Vicki L,Jones, Suzanne F,Chan, Emily,Bendell, Johanna C,Lee, Wooin,Kirschbrown, Whitney P,Zamboni, Beth A,Ikeda, Satoshi,Kodaira, Hiroshi,Rothenberg, Mace L,Burris Dove Medical Press 2015 International journal of nanomedicine Vol.10 No.-
<P>IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11). The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW]) were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time curve (AUC) to sum total CPT-11 AUC. Patients aged <60 years had a 1.3-fold higher ratio of percent decrease in monocytes at nadir to percent decrease in absolute neutrophil count at nadir as compared with patients aged ≥60 years. There was an inverse relationship between patient age and percent decrease in monocytes at nadir, ie, younger patients have a higher percent decrease in monocytes. Patients with a higher percent decrease in monocytes at nadir have a decreased plasma exposure of sum total CPT-11. The pharmacokinetics and pharmacodynamics of IHL-305 are consistent with those of other PEGylated liposomal carriers. Interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 was associated with age, body composition, and monocytes.</P>
A Molecular Mucosal Adjuvant To Enhance Immunity Against Pneumococcal Infection In The Elderly
Yoshiko Fukuyama,Yorihiko Ikeda,Junichiro Ohori,Gen Sugita,Kazuyoshi Aso,Keiko Fujihashi,David E. Briles,Jerry R. McGhee,Kohtaro Fujihashi 대한면역학회 2015 Immune Network Vol.15 No.1
Streptococcus pneumoniae (the pneumococcus) causes amajor upper respiratory tract infection often leading to severeillness and death in the elderly. Thus, it is important toinduce safe and effective mucosal immunity against thispathogen in order to prevent pnuemocaccal infection. However, this is a very difficult task to elicit protective mucosalIgA antibody responses in older individuals. A combindnasal adjuvant consisting of a plasmid encoding the Flt3 ligandcDNA (pFL) and CpG oligonucleotide (CpG ODN) successfullyenhanced S. pneumoniae-specific mucosal immunityin aged mice. In particular, a pneumococcal surfaceprotein A-based nasal vaccine given with pFL and CpG ODNinduced complete protection from S. pneumoniae infection. These results show that nasal delivery of a combined DNAadjuvant offers an attractive potential for protection againstthe pneumococcus in the elderly.
Y. Sabi,Y. Yamada,T. Tanaka,F. Ikeda,M. Okamoto,S. R. Lee 전력전자학회 2023 ICPE(ISPE)논문집 Vol.2023 No.-
This study proposes a new direct individual-phase reactive current control method that can suppress the neutral-line current for an active power-line conditioner in three-phase four-wire low-voltage distribution feeders. When the reactive currents are individually controlled with harmonics compensation, the sinusoidal and unbalanced source currents are obtained. This results in a large neutral-line current on the source side. This paper suggests the redistribution of the active components on the source side to suppress the large neutral-line current. The basic principle of the proposed active-component redistribution is discussed in detail and was confirmed by digital computer simulation. A laboratory-scale experimental setup was built and verified. Simulation and experimental results prove that the proposed direct individual-phase reactive current control method achieves sinusoidal and unbalanced source currents with the suppressed neutral-line current.