Development of alternative gene transfer techniques for and gene therapy in a canine model.

Introduction: Gene therapy have recently attracted much attention as a curative therapeutic option for inherited single gene disorders such as hemophilia. Hemophilia is a hereditary bleeding disorder caused by the deficiency of clotting activity of factor VIII (FVIII) or factor IX (FIX), and gene therapy for hemophilia using viral vector have been vigorously investigated worldwide. Toward further advancement of gene therapy for hemophilia, we have previously developed and validated the efficacy of novel two types of gene transfer technologies using a mouse model of hemophilia A.

Useful Parameters in Dynamic Contrast-enhanced Ultrasonography for Identifying Early Response to Chemotherapy in a Rat Liver Tumor Model.

Objectives: The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether the parameter could correlate with the early response to irinotecan in a rat liver tumor model.

Material And Methods: Twenty rats with tumors were evaluated (control: Saline, = 6; treatment: Irinotecan, = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP). Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were evaluated.

A Rat Model of Frozen Shoulder Demonstrating the Effect of Transcatheter Arterial Embolization on Angiography, Histopathology, and Physical Activity.

Purpose: To assess the angiographic findings and the effects of transcatheter arterial embolization on physical activity and histopathology using a frozen shoulder rat model.

Materials And Methods: First, the angiographic and histopathologic findings of rats in which the shoulder was immobilized with molding plaster for 6 weeks (n = 4) were compared to control rats with normal non-immobilized shoulders (n = 4). Next, a total of 16 frozen shoulder rats were divided into 2 groups.

Comparison of embolic effect between water-in-oil emulsion and microspheres in transarterial embolization for rat hepatocellular carcinoma model.

Aim: To compare two different embolic materials, water-in-oil (W/O) emulsion followed by gelatin particles and microspheres in transarterial embolization (TAE), using a rat hepatocellular carcinoma model.

Methods: Twenty rats bearing N1S1 cells were divided into the W/O emulsion group and Microsphere group. Water-in-oil emulsion was created by a glass membrane emulsification device.

Use of a Glass Membrane Pumping Emulsification Device Improves Systemic and Tumor Pharmacokinetics in Rabbit VX2 Liver Tumor in Transarterial Chemoembolization.

Purpose: To evaluate the phamacokinetics of epirubicin in conventional transarterial chemoembolization using a developed pumping emulsification device with a microporous glass membrane in VX2 rabbits.

Materials And Methods: Epirubicin solution (10 mg/mL) was mixed with ethiodized oil (1:2 ratio) using the device or 3-way stopcock. Forty-eight rabbits with VX2 liver tumor implanted 2 weeks prior to transarterial chemoembolization were divided into 2 groups: a device group (n = 24) and a 3-way-stopcock group (n = 24).

Development of Repeatable Microcatheter Access Port for Intra-arterial Therapy of Liver Cancer.

Purpose: To develop an implantable port in which a microcatheter can be inserted for a combination therapy of repeated transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for advanced liver cancer.

Materials And Methods: The design of a currently used implantable port was modified. A funnel part was constructed in the port.

Superabsorbent Polymer Microspheres Prepared with Hypertonic Saline to Reduce Microsphere Expansion.

Purpose: To analyze size changes of superabsorbent polymer (SAP) microspheres with the reduced expansion technique, and to evaluate pharmacological advantages of transarterial chemoembolization using cisplatin-loaded SAP microspheres with the reduced expansion technique.

Materials And Methods: In an in vitro study, diluted contrast materials containing different concentrations of sodium ions were examined to expand SAP microspheres and determined the reduced expansion technique. Size distributions of cisplatin-loaded SAP microspheres were analyzed.

Development of pumping emulsification device with glass membrane to form ideal lipiodol emulsion in transarterial chemoembolization.

Purpose: To evaluate a pumping emulsification device that can improve the physiochemical properties and stability of lipiodol emulsion for conventional transarterial chemoembolization.

Materials And Methods: A pumping emulsification device constructed of a glass membrane with a hydrophobic surface with pore size of 50 μm in diameter was placed between two syringe adaptors. Epirubicin solutions were mixed with lipiodol with pumping exchanges using the emulsification device or a three-way cock.

Techniques to Form a Suitable Lipiodol-Epirubicin Emulsion by Using 3-Way Stopcock Methods in Transarterial Chemoembolization for Liver Tumor.

Purpose: To compare physicochemical properties of emulsions of ethiodized oil (Lipiodol; Guerbet, Villepinte, France) and epirubicin prepared using different techniques for conventional transarterial chemoembolization.

Materials And Methods: Lipiodol was mixed with epirubicin solution (8.33 mg/mL) by using a 3-way stopcock.

Intraarterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rabbit Liver Tumor Model.

Purpose: To evaluate the pharmacokinetics of intraarterial (IA) administration of micellar nanoparticles incorporating SN-38 injection compared with intravenous (IV) administration in a rabbit liver tumor model.

Materials And Methods: In this animal care committee-approved study, 18 rabbits (mean weight, 3.89 kg; range, 3.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model.

Purpose: The purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).

Materials And Methods: Eighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved.

Compatibility of an Ultraselective Microcatheter and Epirubicin Loaded 300-500-μm DC Bead in Ex Vivo Study.

Purpose: The purpose of this study is to examine whether epirubicin loaded DC Bead 300-500 μm in size can pass through a 1.8-Fr ultraselective microcatheter in ex vivo study.

Methods: Epirubicin (25 mg/1 mL) loaded 100-300 and 300-500 μm DC Bead were tested.

Evaluation of a noise reduction procedure for chest radiography.

Background: The aim of this study was to evaluate the usefulness of noise reduction procedure (NRP), a function in the new image processing for chest radiography.

Methods: A CXDI-50G Portable Digital Radiography System (Canon) was used for X-ray detection. Image noise was analyzed with a noise power spectrum (NPS) and a burger phantom was used for evaluation of density resolution.

Dihydropyrimidine dehydrogenase (DPD) expression is negatively regulated by certain microRNAs in human lung tissues.

Dihydropyrimidine dehydrogenase (DPD) is important to the antitumor effect of 5-fluorouracil (5-FU). DPD gene (DPYD) expression in tumors is correlated with sensitivity to 5-FU. Because the 5-FU accumulated in cancer cells is also rapidly converted into inactivated metabolites through catabolic pathways mediated by DPD, high DPD activity in cancer cells is an important determinant of the response to 5-FU.

Pollen augments the influence of desert dust on symptoms of adult asthma patients.

Background: East Asian desert dust storms that occur during mainly spring are called Asian dust storms (ADS). Our objective was to study the association of pollen and ADS with symptoms of adult asthma patients in Japan.

Methods: We designed a telephone survey to investigate the upper and lower respiratory, ocular, and skin symptoms of asthma patients during ADS in February, March, and December on 2009.

[Clinical evaluation of an oxygen concentrator and humidifier that does not require additional reservoir water].

A conventional humidifier with a reservoir of water for humidification can produce micro-aerosols contaminated with bacteria. The present study was undertaken to determine the clinical efficiency of a membrane humidifier that does not require additional reservoir water. We analyzed relative room air humidity and oxygen levels obtained from 2 pressure-swing adsorption (PSA)-type oxygen concentrators with membrane humidifiers.

Correlation between Asian dust storms and worsening asthma in Western Japan.

Background: Severe wind storms during spring in East Asia, called Asian dust storms (ADS), have been assessed in the past for their effect on health in Asian countries. Our objective was to study the ADS association with asthma symptoms in adult patients in Japan.

Methods: We designed a telephone survey to assess ADS influence on upper and lower respiratory, ocular and cutaneous symptoms in 98 patients with adult asthma from April to May 2007.

Asthma: Chronopharmacotherapy and the molecular clock.

Bronchial asthma is characterized by chronic airways inflammation and reversible airflow limitation. In patients with asthma, symptoms generally worsen during the early hours of the morning, and pulmonary function often deteriorates at the same time, suggesting a role for chronopharmacotherapy. Several drugs for asthma have been developed based on chronopharmacology.

Influence of intermittent hypoxia on the signal transduction pathways to inflammatory response and circadian clock regulation.

Aims: Obstructive sleep apnea syndrome (OSAS), characterized by intermittent hypoxia/reoxygenation (IHR), is often associated with changing levels of circulating inflammatory cytokines and causes excessive daytime sleepiness, mood disturbances, and cardiovascular disease. An abnormal rhythm in the expression of circadian clock genes is observed in OSAS patients, and is also implicated in OSAS-related clinical symptoms. IHR-induced signal transduction is thought to underlie OSAS-associated complications.

Day-night variations of serum interleukin-6 in patients with severe obstructive sleep apnea syndrome before and after continuous positive airway pressure (CPAP).

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin-6 (IL-6) is one of the important proinflammatory cytokines. We examined the levels of serum IL-6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy.

Severe toxicities after irinotecan-based chemotherapy in a patient with lung cancer: a homozygote for the SLCO1B1*15 allele.

Irinotecan is used widely in the treatment of several malignancies, but unpredictable severe toxicities such as myelosuppression and delayed-type diarrhea are sometimes experienced. Polymorphism of the UGT1A1 gene is one of the likely reasons for interindividual differences in irinotecan pharmacokinetics and severe toxicity. Also, polymorphic organic anion-transporting polypeptide 1B1 (OATP1B1, SLCO1B1) is reported to be involved in the hepatocellular uptake of SN-38.

Treatment with beta2-adrenoceptor agonist in vivo induces human clock gene, Per1, mRNA expression in peripheral blood.

This study examined whether in vivo exposure to a beta2-adrenoceptor agonist, tulobuterol, induces human Period1 (hPer1) mRNA expression in cells from peripheral whole blood. In one experiment, oral tulobuterol was administered to five healthy volunteers at 22:00 h, while in another, a transdermally tulobuterol patch was applied to the same five subjects at 20:00 h. In each experiment, serum tulobuterol concentrations were measured at four time points, and total RNA was isolated from peripheral blood cells for determinations of hPer1 mRNA expression by real-time polymerase chain reaction.

Circadian rhythms in the CNS and peripheral clock disorders: function of clock genes: influence of medication for bronchial asthma on circadian gene.

Bronchial asthma is a chronic inflammatory disorder of the airways, in which inflammation causes bronchial hyper-responsiveness and flow limitation in the presence of various stimuli. Pulmonary function in asthmatic patients frequently deteriorates between midnight and early morning, which has suggested a role for chronotherapy. Although relationships between bronchial asthma and the function of clock genes remain unclear, some medications given for asthma such as glucocorticoids or beta(2)-adrenoceptor agonists may influence clock genes in vivo.

[A case of small-cell lung cancer effectively treated by bi-weekly administration of amrubicin].

The patient was a 62-year-old man with small-cell lung cancer (limited disease). He was treated with cisplatin (CDDP) plus etoposide(ETP) and concurrent radiotherapy as first-line treatment. Although a complete response was achieved, his pro-GRP elevated 10 months later.