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991.
Diabetic kidney disease(DKD) is the most common cause of chronic kidney disease, leading to end-stage renal disease and cardiovascular disease. The overall number of patients with DKD will continue to increase in parallel with the increasing global pandemic of type 2 diabetes. Based on landmark clinical trials, DKD has become preventable by controlling conventional factors, including hyperglycemia and hypertension, with multifactorial therapy; however, the remaining risk of DKD progression is still high. In this review, we show the importance of targeting remission/regression of microalbuminuria in type 2 diabetic patients, which may protect against the progression of DKD and cardiovascular events. To achieve remission/regression of microalbuminuria, several steps are important, including the early detection of microalbuminuria with continuousscreening, targeting HbA1c 7.0% for glucose control, the use of renin angiotensin system inhibitors to control blood pressure, the use of statins or fibrates to control dyslipidemia, and multifactorial treatment. Reducing microalbuminuria is therefore an important therapeutic goal, and the absence of microalbuminuria could be a pivotal biomarker of therapeutic success in diabetic patients. Other therapies, including vitamin D receptor activation, uric acid-lowering drugs, and incretin-related drugs, may also be promising for the prevention of DKD progression. 相似文献
992.
993.
Takahashi T Kawakami K Mishima S Akimoto M Takenaga K Suzumiya J Honma Y 《Leukemia research》2011,35(5):638-645
Cyclopamine, a plant-derived steroidal alkaloid, inhibits the hedgehog (Hh) signaling pathway by antagonizing Smoothened. This drug can induce the differentiation of myeloid leukemia cell lines and acute myeloid leukemia (AML) cells in primary culture. The treated cells were stained with Luxol-fast-blue, which is specific for eosinophilic granules. Ligation of CD44 with some specific monoclonal antibodies can reverse the differentiation of AML cells. Combined treatment with cyclopamine and a monoclonal antibody to ligate CD44 more than additively induced the differentiation of HL-60 cells. These results may provide useful information for the development of a CD44-targeted therapy in AML. 相似文献
994.
Maeda A Shinoda T Ito N Baba K Oku N Mizumoto T 《International journal of pharmaceutics》2011,406(1-2):84-90
The purpose of the present study was to prepare matrix extended release pellets of diclofenac potassium using low amount of release-modifying agents and, to compare its performance in vivo with coated pellets and matrix tablets. Coated pellets were prepared by extrusion-spheronization, followed by double layer coating using different polymers separately. Matrix pellets with different release rate in vitro were prepared by extrusion-spheronization with different kinds of retarding materials. Bioavailability study of different coated pellets revealed that the drug concentration in plasma of beagle dogs was too low to be detected and, implied that the drug was nearly not released from the preparations before reaching colon due to the appearance of lag time in the dissolution process. The phenomenon indicated that slow-release pellets of diclofenac potassium perhaps should not be developed as double membrane-controlled type. The AUC((0 → 24)) of the immediate release pellets, the two matrix pellets and the reference were 304.4, 87.7, 204.1 and 179.1 μg h/ml, respectively. The C(max) of the formulations mentioned above were 46.3, 13.0, 33.6 and 32.1 μg/ml, respectively. All the matrix formulations, including the reference, exhibited incomplete absorption due to the short small intestine transit time and termination of the drug release in the colon because of its limited solubility. The matrix pellets were bioequivalent with the commercially available tablet (Voltaren(?)) although the drug release in vitro of the former was much faster, while the bioavailability of the matrix pellets with similar in vitro drug release to the reference (Voltaren(?)) was much lower than the latter. The results perhaps was caused by lacking of physical robustness in the waxy tablet formulation, resulted in low wet strength and easily destroyed by the mechanical destructive forces and finally introduced faster drug release rate in vivo. It is apparent that preparations with similar performance in vitro may differ a lot in vivo because of the differences in drug release rate in vivo owing to various wet strengths of excipients contained, especially for sustained release products. 相似文献
995.
Hirayama F Koshio H Ishihara T Hachiya S Sugasawa K Koga Y Seki N Shiraki R Shigenaga T Iwatsuki Y Moritani Y Mori K Kadokura T Kawasaki T Matsumoto Y Sakamoto S Tsukamoto S 《Journal of medicinal chemistry》2011,54(23):8051-8065
Inhibitors of factor Xa (FXa), a crucial serine protease in the coagulation cascade, have attracted a great deal of attention as a target for developing antithrombotic agents. We previously reported findings from our optimization study of a high-throughput screening (HTS) derived lead compound 1a that resulted in the discovery of potent amidine-containing FXa inhibitors represented by compound 2. We also conducted an alternative optimization study of 1a without incorporating a strong basic amidine group, which generally has an adverse effect on the pharmacokinetic profile after oral administration. Replacement of 4-methoxybenzene with a 1,4-benzodiazepine structure and introduction of a hydroxy group at the central benzene led to the discovery of the potent and orally effective factor Xa inhibitor 14i (darexaban, YM150). Subsequent extensive study revealed a unique aspect to the pharmacokinetic profile of this compound, wherein the hydroxy moiety of 14i is rapidly transformed into its glucuronide conjugate 16 (YM-222714) as an active metabolite after oral administration and it plays a major role in expression of potent anticoagulant activity in plasma. The distinctive, potent activity of inhibitor 14i after oral dosing was explained by this unique pharmacokinetic profile and its favorable membrane permeability. Compound 14i is currently undergoing clinical development for prevention and treatment of thromboembolic diseases. 相似文献
996.
Tokunaga J Takamura N Ogata K Setoguchi N Matsuoka T Sato K 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》2011,131(4):655-659
Vital-sign checks and physical assessment have been performed by physicians and nurses among medical staff in particular. However, pharmacists must also have basic skills of vital-sign checking and physical assessment to evaluate the patient condition/drug efficacy or prevent adverse reactions to drugs. To promote the acquisition of these skills, we prepared simulation programs with an emergency-care simulator, which facilitate the reproduction of excess-dose drug administration/condition changes. We used an emergency-care simulator equipped with a personal computer. General condition was established using the blinking velocity, cardiac/respiratory sounds and blood pH as parameters. As a results, concerning drug administration, the simulation programs facilitated the reproduction of symptoms related to the excess-dose insulin administration. With respect to changes in the condition, it facilitated the reproduction of asthma, hyperglycemia, and hemorrhage. This facilitated the palpation-, visual perception-, and auditory perception-mediated understanding of changes in the patient condition through fingertips and warnings/alarms on the monitor. Evaluation of the student for these program contents increased significantly (p<0.01). These programs can be downloaded via the Internet. Experience regarding excess-dose drug administration/condition changes with an emergency-care simulator is useful for checking patients' vital signs, evaluating the drug efficacy, and confirming adverse reactions to drugs. By the practice of these programs, we can teach pharmacy students how to check for vital signs (pulse palpation, auscultation, blood pressure measurement, and electrocardiography) in a school setting, not a hospital setting. Mastering these techniques may allow pharmacy students to determine the efficacy of a drug and adverse reactions. 相似文献
997.
Two-Layered Dissolving Microneedles for Percutaneous Delivery of Peptide/Protein Drugs in Rats 总被引:1,自引:0,他引:1
Keizo Fukushima Ayaka Ise Hiromi Morita Ryo Hasegawa Yukako Ito Nobuyuki Sugioka Kanji Takada 《Pharmaceutical research》2011,28(1):7-21
Purpose
Feasibility study of two-layered dissolving microneedles for percutaneous delivery of peptide/proteins using recombinant human growth hormone (rhGH) and desmopressin (DDAVP). 相似文献998.
Masaki Wakutsu Nobuyo Tsunoda Sachiko Shiba Etsuko Muraki Keizo Kasono 《Lipids in health and disease》2010,9(1):101
Background
Fish oil is known to improve lifestyle-related diseases. These effects occur partly via activation of PPARs by the n-3 polyunsaturated fatty acids included abundantly in fish oil. We investigated fish oil functions on glucose and lipid metabolism that are both dependent on and independent of PPARs pathway. 相似文献999.
A case report--transarterial embolization for advanced gallbladder carcinoma with hepatic metastasis
Yanagawa T Shimizu J Dono K Yasumoto T Hata T Fujino S Kitahara T Munakata K Watanabe N Takamoto K Nagai K Miyake M Hata T Kawanishi K Ikeda K Fujita J Akagi K Iwasawa T Kitada M Shimano T 《Gan to kagaku ryoho. Cancer & chemotherapy》2010,37(12):2711-2713
A 75-year-old female presented with appetite and weight loss and epigastralgia. CT revealed a primary gallbladder carcinoma Stage IVb with multiple hepatic metastases. Gastrofiberscopy revealed an invasion to duodenal and bleeding from the tumor. For her poor performance status, it seems to be too difficult to undergo a general chemotherapy. So after gastrojejunostomy, transarterial embolization (TAE) was performed. She underwent 2 times TAE. There was a notable reduction in tumor size. But pulmonary metastases were found in bilateral lung. She died after 8 months. TAE may be useful for advanced gallbladder carcinoma with tumor vascularity. 相似文献
1000.
Whole‐exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia 下载免费PDF全文
Norio Shiba Kenichi Yoshida Yuichi Shiraishi Yusuke Okuno Genki Yamato Yusuke Hara Yasunobu Nagata Kenichi Chiba Hiroko Tanaka Kiminori Terui Motohiro Kato Myoung‐ja Park Kentaro Ohki Akira Shimada Junko Takita Daisuke Tomizawa Kazuko Kudo Hirokazu Arakawa Souichi Adachi Takashi Taga Akio Tawa Etsuro Ito Keizo Horibe Masashi Sanada Satoru Miyano Seishi Ogawa Yasuhide Hayashi 《British journal of haematology》2016,175(3):476-489
Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole‐exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations. We also revealed intratumoural heterogeneities in many patients, implicating multiple clonal evolution events in the development of AML. Furthermore, targeted deep sequencing in 182 paediatric AML patients identified three major categories of recurrently mutated genes: cohesion complex genes [STAG2, RAD21 and SMC3 in 17 patients (8·3%)], epigenetic regulators [ASXL1/ASXL2 in 17 patients (8·3%), BCOR/BCORL1 in 7 patients (3·4%)] and signalling molecules. We also performed WES in four patients with relapsed AML. Relapsed AML evolved from one of the subclones at the initial phase and was accompanied by many additional mutations, including common driver mutations that were absent or existed only with lower allele frequency in the diagnostic samples, indicating a multistep process causing leukaemia recurrence. 相似文献