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Purpose To analyze and characterize data regarding the prevalence and types of outpatient drug-related problems (DRPs) found by clinical pharmacists after implementation of the Virtual Medicine Record in Cloud System (VMRCS). Methods A cross-sectional study regarding outpatient pharmaceutical care was conducted at a medical center in Taiwan. Patients aged >20 years old with multiple chronic diseases and polypharmacy were enrolled. In Stage I (1 October–31 December 2014), patients received pharmaceutical care according to prescription data accessed online in the VMRCS. In Stage II (1 June–31 August 2015), the VMRCS were pre-download and arranged to the institute's required format, facilitated DRP detection. Clinical pharmacists then reviewed and evaluated the prescription data through pre-downloaded VMRCS. Overall, 1539 and 1600 prescriptions were evaluated in these two stages, respectively. DRPs were recorded using the Pharmaceutical Care Network Europe (PCNE)-DRP. Results DRPs were found for 50.2% of patients in Stage I and 55.2% in Stage II (p

For clinical application, there is a great need for small-molecule inhibitors (SMIs) that could control pathogenic effects of transforming growth factor (TGF-β) and/or modulate effects of TGF-β in normal responses. Selective SMIs of the TGF-β signaling pathway developed for therapeutics will also be powerful tools in experimentally dissecting this complex pathway, especially its cross-talk with other signaling pathways. In this study, we characterized (1'R,5'S,6'S)-2-(3',5'-dibromo-1',6'-dihydroxy-4'-oxocyclohex-2'-enyl) acetonitrile (DT), a member of a new class of small-molecule inhibitors related to bromotyrosine derivate from Pseudoceratina sp., which inhibits the TGF-β type I receptor serine/threonine kinase known as activin receptor-like kinase (ALK) 5. The inhibitory effects of DT on TGF-β-induced Smad signaling and epithelial-to-mesenchymal transition (EMT) were investigated in epithelial cells using in vitro kinase assay, luciferase reporter assays, immunoblotting, confocal microscopy, and wound healing assays. The novel ALK5 inhibitor, DT, inhibited the TGF-β-stimulated transcriptional activations of 3TP-Lux. In addition, DT decreased phosphorylated Smad2/3 levels and the nuclear translocation of Smad2/3 increased by TGF-β. In addition, DT inhibited TGF-β-induced EMT and wound healing of A549 cells. Our results suggest that DT is a potential therapeutic agent for fibrotic disease and cancer treatment. J. Cell. Biochem. 117: 2800-2814, 2016. © 2016 Wiley Periodicals, Inc.

Reorganization of the actin cytoskeleton is essential for cell motility and chemotaxis. Actin-binding proteins (ABPs) and membrane lipids, especially phosphoinositides PI(4,5)P2 and PI(3,4,5)P3 are involved in the regulation of this reorganization. At least 15 ABPs have been reported to interact with, or regulated by phosphoinositides (PIPs) whose synthesis is regulated by extracellular signals. Recent studies have uncovered several parallel intracellular signalling pathways that crosstalk in chemotaxing cells. Here, we review the roles of ABPs and phosphoinositides in chemotaxis and cell migration. Linked Articles This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24

Objectives To evaluate the anti-oxidant activity of the flavonoid compound, kaempferol, and to examine its role in the suppression of oxidative stress and attenuation of bladder hyperactivity in a rat model of bladder injury. Methods The anti-oxidative activity of kaempferol was examined in lipopolysaccharide-treated RAW264.7 macrophages by using flow cytometry. For in vivo studies, rats were pretreated with kaempferol or vehicle for 24 h. The rat urothelium was injured by the administration of protamine sulfate for 1.5 h and irritated by the subsequent infusion of potassium chloride for 4 h. Oxidative stress in the bladder tissue was assessed using chemiluminescence assay, and the bladder pressure was determination by cystomertrogram. Results Kaempferol significantly suppressed lipopolysaccharide-induced reactive oxygen species production in RAW264.7 rat macrophages. Exposure of the rat bladder to sequential infusion of protamine sulfate and potassium chloride induced bladder hyperactivity. Pretreatment with kaempferol, prevented the formation of reactive oxygen species and prolonged the intercontraction interval. Conclusion Kaempferol suppresses oxidative stress and attenuates bladder hyperactivity caused by potassium chloride after protamine sulfate-induced bladder injury.

Background Data are limited on antiplatelet therapy for ischemic stroke prevention in liver cirrhosis patients.Methods ThisretrospectivestudyidentifiedcasesoflivercirrhosisfromtheNationalHealthInsuranceResearchDatabase.Antiplatelettherapywasadministeredfor2yearstopatientswhohadexperiencedafirstischemicstrokebetween1997and2006.Primaryoutcomes,includingdeathand readmission to hospital for stroke, and secondary outcomes, including death, stroke, or gastrointestinal bleeding, were examined.Results One thousand one hundred eighty patients experienced a first stroke. According to time-dependent analysis, the hazard ratio forprimary outcomes in patients treated with aspirin was 0.915 (95%CI: 0.872–0.960). In secondary outcomes, hazard ratio for readmissionfor stroke was 0.904 (95%CI: 0.836–0.978) and that for gastrointestinal bleeding was 0.998 (95%CI: 0.946–1.052) in patients treated withaspirin. Subgroup analysis showed that aspirin was more effective in patients with non-alcoholic cirrhosis than in those with other types ofliver cirrhosis. Moreover, hyperlipidemia and statins may have decreased the efficacy of antiplatelet therapy in cirrhosis patients.Conclusions This study includes the largest sample for evaluating outcomes of antiplatelet therapy in liver cirrhosis patients for preventingrecurrent stroke. The study results show that antiplatelet therapy still offers safe and effective treatment for ischemic stroke prevention inpatients with cirrhosis. Copyright © 2012 John Wiley & Sons, Ltd.key words—liver cirrhosis; antiplatelet; clinical efficacy; safety; pharmacoepidemiologyReceived 25May 2012; Revised 30August2012; Accepted 24September 2012

A simple and reliable high-performance liquid chromatographic method with ultraviolet detection (280 nm) has been developed for the simultaneous analysis of 12 bioactive components in San-huang-xie-xin-tang (SHXXT), a traditional Chinese medicine containing Rhei rhizome, Coptidis rhizome and Scutellariae radix. A relatively simple extraction procedure was employed and optimised, and separation of the components was obtained within 1 h using a reversed-phase column under gradient elution with acetonitrile and a buffer containing 0.01 M sodium 1-pentanesulphonate (pH 3). The lower limit of detection for the analytes ranged from 25 to 75 ng/mL. The correlation coefficients associated with each calibration curve were greater than 0.99. The precision and accuracy of the method ranged from 1.0 to 10.5% at low concentration levels, 0.8 to 8.7% at medium levels and 1.2 to 5.8% at high levels. In commercial products of SHXXT, baicalin and berberine were present in the highest amounts with levels up to 4.0 and 3.3%, respectively, in one sample. The HPLC method was able rapidly and efficiently to analyse constituents in crude herb and traditional Chinese medicinal preparations containing Rhei rhizome, Coptidis rhizome and Scutellariae radix.

The influences of some formulation variables and manufacturing processes of the release rates of propranolol from gelation of hydroxypropylmethylcellulose (HPMC) matrices tablets were investigated. The amount of propranolol was determined by UV–Vis spectroscopy at 290 nm. The effects of extended release of matrices tablets were evaluated by the in vitro dissolution test and were compared to the United States Pharmacopoeia (USP) monograph specifications. The results showed that the lowest viscosity grade of HPMC (Metolose 4000) used gave the least burst effect in the earlier stage. The drug/Metolose ratio was an important influence on the drug release; increasing the polymer content decreased the dissolution rate of the drug. The release rate was increased with increase in the tablet content of avicel. The release curve of experimental formulation with 17% avicel was optimal compared with the USP monograph specification; there was no burst effect in the earlier stage (the release percent at 1.5 h was 26.6%) and almost total drug was released from matrices tablet after 24 h (97.4%). The other factors such as lubricant level (0.5 to 2.0%), compaction pressure (100 to 200 kPa), brand of HPMC (HPMC 4000 from Shin Etsu or Methocel K4MP from Dow Chemical Co.), and manufacturing process (tabletted from wet-massed granules or by direct compression) appeared not to modify release rates. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 1886–1890, 2004

Transforming growth factor-β (TGF-β) is correlated with poorer prognosis in gastric cancer. Therefore, inhibition of the TGF-β pathway is an attractive strategy for the treatment of cancer. In this...

By using an intradermal microdialysis technique 22 h after the transdermal iontophoretic delivery of sodium nonivamide acetate (SNA), a synthetic derivative of capsaicin, the amount of SNA in the extracellular space was measured. Transdermal iontophoresis is a process that enhances skin permeation of ionized species by using an electric field as a driving force. Iontophoresis increased the amount of SNA in dialysate compared with passive diffusion in this study. By using various polymers incorporated in formulations, indicated hydrogels showed higher capacity for SNA delivery than solution formulations. This result was possibly attributable to the antinucleant ability of polymers resulting in the increase of thermodynamic activity of SNA in formulations. Pretreatment with isopropyl myristate, a lipophilic penetration enhancer, on rat skin enhanced transdermal delivery of SNA both for passive and iontophoretic penetration, indicating the possibility of reducing the surface area of the administrations site in clinical use. Microscopic examination revealed no or slight changes in the skin after iontophoretic treatment compared with penetration enhancer pretreatment. The histologic results also suggested iontophoretic treatment with 0.5 mA/cm2 current density of not more than 7-h application duration may be acceptable clinically. Drug Dev. Res. 46:87–95, 1999. © 1999 Wiley-Liss, Inc.

Nonivamide (NVA) and sodium nonivamide acetate (SNA) are synthetic derivatives of capsaicin. In this study, the cationic surfactant benzalkonium chloride was incorporated into the Carbopol 940® gel bases of capsaicin and its synthetic derivatives to evaluate the in vitro percutaneous absorption capacity. Afterwards, the optimal gel formulation selected from the in vitro study was used in a series of in vivo non-invasive bioengineering methods. To quantify the skin erythema and irritation caused by capsaicin, NVA, and SNA, laser Doppler flowmetry (LDF), transepidermal water loss (TEWL), and colorimetry were utilized for determining the cutaneous blood flow and skin barrier impairment to assess the level of irritant reaction. In the in vitro transdermal study, the gel base with 0.05% benzalkonium chloride possessed the highest penetration capacity: this was chosen for the in vivo study. After quantification of skin erythema by LDF, capsaicin developed more severe irritation than NVA, and SNA showed no skin irritation or pungent sensation in volunteers. The result of the TEWL experiment suggested that 0.05% benzalkonium chloride did not cause any skin impairment. Moreover, the Carbopol 940® gel base itself offered a moderate penetration capacity for drugs and avoided any skin irritation. The result of colorimetry confirmed that both Δa* and ΔE* parameters correlated well with the data of LDF and that they are good indicators of skin erythema response. After a series of in vivo applications, SNA was shown to be a potent analogue of capsaicin with a marked pharmacological effect and moderate percutaneous capacity and reduced skin erythema and painful sensation. Drug Dev. Res. 40:56–67, 1997. © 1997 Wiley-Liss, Inc.