Effects of Berberine and Hwangryunhaedok-Tang on Oral Bioavailability and Pharmacokinetics of Ciprofloxacin in Rats

Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat bacterial infection and inflammatory diseases in eastern Asia. The combination of berberine-containing herbal medicines and ciprofloxacin can be an excellent antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the pretreatment effect of berberine and HR, vehicle, berberine (25 and 50 mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20 mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were coadministered by single oral gavage. Pharmacokinetic data were estimated by noncompartmental model. Compared with ciprofloxacin alone (control group), coadministration of berberine (50 mg/kg) and ciprofloxacin significantly decreased Cmax of ciprofloxacin (P<0.05). In addition, the pretreatment of berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreased Cmax and AUC0→∞, compared with control group (P<0.05). The oral bioavailability of ciprofloxacin was reduced by cotreatment of berberine and pretreatment of berberine and HR. Our results suggest that the expression of P-glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR

Doxorubicin-incorporated polymeric micelles composed of dextran-b-poly(DL-lactide-co-glycolide) copolymer

Young-Il Jeong1,*, Do Hyung Kim1,2,*, Chung-Wook Chung1, Jin-Ju Yoo1, Kyung Ha Choi1, Cy Hyun Kim1,2, Seung Hee Ha1, Dae Hwan Kang1,2 1National Research and Development Center for Hepatobiliary Cancer, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, Research Institute for Convergence of Biomedical Science and Technology, 2School of Medicine, Pusan National University, Yangsan, Republic of Korea*These authors contributed equally to this work.Background: Polymeric micelles using amphiphilic macromolecules are promising vehicles for antitumor targeting. In this study, we prepared anticancer agent-incorporated polymeric micelles using novel block copolymer.Methods: We synthesized a block copolymer composed of dextran and poly (DL-lactide-co-glycolide) (DexbLG) for antitumor drug delivery. Doxorubicin was selected as the anticancer drug, and was incorporated into polymeric micelles by dialysis. Polymeric micelles were observed by transmission electron microscopy to be spherical and smaller than 100 nm, with a narrow size distribution. The particle size of doxorubicin-incorporated polymeric micelles increased with increasing drug content. Higher initial drug feeding also increased the drug content. Results: During the drug-release study, an initial burst release of doxorubicin was observed for 10 hours, and doxorubicin was continuously released over 4 days. To investigate the in vitro anticancer effects of the polymeric micelles, doxorubicin-resistant HuCC-T1 cells were treated with a very high concentration of doxorubicin. In an antiproliferation study, the polymeric micelles showed higher cytotoxicity to doxorubicin-resistant HuCC-T1 cells than free doxorubicin, indicating that the polymeric micelles were effectively engulfed by tumor cells, while free doxorubicin hardly penetrated the tumor cell membrane. On confocal laser scanning microscopy, free doxorubicin expressed very weak fluorescence intensity, while the polymeric micelles expressed strong red fluorescence. Furthermore, in flow cytometric analysis, fluorescence intensity of polymeric micelles was almost twice as high than with free doxorubicin.Conclusion: DexbLG polymeric micelles incorporating doxorubicin are promising vehicles for antitumor drug targeting.Keywords: dextran, polymeric micelle, block copolymer, poly(DL-lactide-co-glycolide

Effect of 5-aminolevulinic acid-based photodynamic therapy via reactive oxygen species in human cholangiocarcinoma cells

Cancer cells have been reported to exhibit an enhanced capacity for protoporphyrin IX (PpIX) synthesis facilitated by the administration of 5-aminolevulinic acid (ALA). We investigated the effect of ALA-based photodynamic therapy (PDT) on human cholangiocarcinoma cells (HuCC-T1). Since protoporphyrin IX (PpIX), a metabolite of ALA, can produce reactive oxygen species (ROS) under irradiation and then induce phototoxicity, ALA-based PDT is a promising candidate for the treatment of cholangiocarcinoma. When various concentrations of ALA (0.05–2 mM) were used to treat HuCC-T1 cells for 6 or 24 hours, the intracellular PpIX level increased according to the ALA concentration and treatment time. Furthermore, an increased amount of PpIX in HuCC-T1 cells induced increased production of ROS by irradiation, resulting in increased phototoxicity

Surgical management of giant adrenal myelolipoma using a modified Makuuchi incision: a case report

Giant adrenal myelolipomas are rare, benign, and hormonally inactive tumors. We present the case of a 53-year-old man with a 19-cm retroperitoneal mass, initially suspected to be a retroperitoneal liposarcoma, angiomyolipoma, or adrenal myelolipoma. After conducting endocrine assessments, which were within normal ranges, we decided to perform surgical excision using a modified Makuuchi incision. The tumor was successfully removed, and the final pathological examination confirmed the diagnosis of adrenal myelolipoma. The patient was discharged with no complications and remained without disease recurrence or distant metastasis as of 1 year postoperatively. In conclusion, giant myelolipomas are rare and cause symptoms owing to their large size. Surgical removal is recommended for large or symptomatic myelolipomas. The modified Makuuchi incision allows efficient and safe tumor removal in open surgery for giant myelolipomas

Robot-Assisted Radical Prostatectomy in a Patient with a Preexisting Three-Piece Inflatable Penile Prosthesis

We report a rare case of robot-assisted laparoscopic radical prostatectomy (RARP) in a patient with a preexisting penile prosthesis. In this case, we completed RARP without removing the reservoir by using a deflation-inflation technique, and there were no complications related to the prosthesis. The patient had a negative surgical margin. The preserved three-piece inflatable penile prosthesis continued to function properly in 1 month. Reservoir-preserving RARP is technically feasible and safe. However, it is important to be aware of device-related complications. Long-term studies on the mechanical survival rate and patient satisfaction should be also performed

Development of a dual optical fiber probe for the hydrodynamic investigation of a horizontal annular drive gas/liquid ejector

A dual-channel optical fiber probe was developed to quantify the bubble characteristics (void fraction, velocity, and bubble size) in a gas–liquid annular ejector system. Water is pumped upstream of the ejector contraction. Since a low pressure region exists downstream in the ejector diffuser, this permits air to be sucked into the flowing liquid by jet pump action and the inlet air volumetric flow rate is measured by a flow meter. Verification of the void fraction (range 0.15–0.5) measured by the optical fiber probe was then possible and deviations were generally around ± 5%. Also, bubble velocity was measured using the optical probe by cross-correlating signals from the two fibers whose tips are separated by a known distance. Alternatively measuring bubble velocity using a particle image velocimetry method provided validation for the optical fiber probe system where a high speed camera was used to capture instantaneous bubble images at time intervals of 0.125 ms. Excellent agreement between the velocities using both methods is reported. For bubble size measurements, analyzing the temporal signals from a single probe enabled estimation of the size of a bubble. Bubble sizes measured ranged between 1.5 and 6.0 mm and size distributions were constructed for different ejector water volumetric flow rates ranging from 0.0022 to 0.0063 m3/s. LabVIEW provided a convenient platform for coding the algorithms for estimating the void fraction, bubble velocity and bubble size. For further comparison, a CFD study of the ejector system was done, and the vertical radial profiles of the void fraction were compared with those obtained by the optical fiber system and these showed good agreement

Could Fractional Exhaled Nitric Oxide Test be Useful in Predicting Inhaled Corticosteroid Responsiveness in Chronic Cough? A Systematic Review

© 2016 Background Fractional exhaled nitric oxide (FENO) is a safe and convenient test for assessing T H 2 airway inflammation, which is potentially useful in the management of patients with chronic cough. Objective To summarize the current evidence on the diagnostic usefulness of FENO for predicting inhaled corticosteroid (ICS) responsiveness in patients with chronic cough. Methods A systematic literature review was conducted to identify articles published in peer-reviewed journals up to February 2015, without language restriction. We included studies that reported the usefulness of FENO (index test) for predicting ICS responsiveness (reference standard) in patients with chronic cough (target condition). The data were extracted to construct a 2 × 2 accuracy table. Study quality was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Results We identified 5 original studies (2 prospective and 3 retrospective studies). We identified considerable heterogeneities in study design and outcome definitions, and thus were unable to perform a meta-analysis. The proportion of ICS responders ranged from 44% to 59%. Sensitivity and specificity ranged from 53% to 90%, and from 63% to 97%, respectively. The reported area under the curve ranged from abou t 0.60 to 0.87; however, studies with a prospective design and a lower prevalence of asthma had lower area under the curve values. None measured placebo effects or objective cough frequency. Conclusions We did not find strong evidence to support the use of FENO tests for predicting ICS responsiveness in chronic cough. Further studies need to have a randomized, placebo-controlled design, and should use validated measurement tools for cough. Standardization would facilitate the development of clinical evidence

Identification of Recently Selected Mutations Driven by Artificial Selection in Hanwoo (Korean Cattle)

Hanwoo have been subjected over the last seventy years to intensive artificial selection with the aim of improving meat production traits such as marbling and carcass weight. In this study, we performed a signature of selection analysis to identify recent positive selected regions driven by a long-term artificial selection process called a breeding program using whole genome SNP data. In order to investigate homozygous regions across the genome, we estimated iES (integrated Extended Haplotype Homozygosity SNP) for the each SNPs. As a result, we identified two highly homozygous regions that seem to be strong and/or recent positive selection. Five genes (DPH5, OLFM3, S1PR1, LRRN1 and CRBN) were included in this region. To go further in the interpretation of the observed signatures of selection, we subsequently concentrated on the annotation of differentiated genes defined according to the iES value of SNPs localized close or within them. We also described the detection of the adaptive evolution at the molecular level for the genes of interest. As a result, this analysis also led to the identification of OLFM3 as having a strong signal of selection in bovine lineage. The results of this study indicate that artificial selection which might have targeted most of these genes was mainly oriented towards improvement of meat production

Agreement on the Level Selection in Laminoplasty among Experienced Surgeons: A Survey-Based Study

Study DesignSurvey based study.PurposeTo assess the degree of agreement in level selection of laminoplasty (LP) for the selected cervical myeloradiculopathy cases between experienced spine surgeons.Overview of LiteratureAlthough, cervical LP is a widely used surgical technique for multi-level spinal cord compression, until now there is no consensus about how many segments or which segments should be opened to achieve a satisfactory decompression.MethodsThorough clinical and radiographic data (plain X-ray, computed tomography, and magnetic resonance imaging) of 30 patients who had cervical myelopathy were prepared. The data were provided to three independent spine surgeons with over 10 years experience in operation of their own practices. They were questioned about the most preferable surgical method and suitable decompression levels. The second survey was carried out after 6 months with the same cases. If the level difference between respondents was a half level or below, agreement was considered acceptable. The intraobserver and interobserver agreements in level selection were assessed by kappa statistics.ResultsThree respondents selected LP as an option for 6, 8, and 22 cases in the first survey and 10, 21, and 24 cases in the second survey. The reasons for selection of LP were levels of ossification of the posterior longitudinal ligament (p=0.004), segmental kyphotic deformity (p=0.036) and mean compression score (p=0.041). Intraobserver agreement showed variable results. Interobserver agreement was poor to fair by perfect matching (kappa=0.111–0.304) and fair to moderate by acceptable matching (kappa=0.308–0.625).ConclusionsThe degree of agreement for level selection of LP was not high even though experienced surgeons would choose the opening segments on the basis of same criteria. These results suggest that more specific guidelines in determination of levels for LP should be required to decrease unnecessary wide decompression according to individual variance