Search

We investigated whether treatments with beta-blockers or other administrations that have similar actions to beta-blockers, such as Chinese herbs or needling, were effective in treating osteoporosis induced by ovariectomy (OVX). Female Wister rats were divided into five groups: a sham-operated control group treated with vehicle (Sham, n = 8), an ovariectomized (OVX) group treated with vehicle (Model, n = 8), an OVX group administered with propranolol (Pro, n = 10), an OVX group administered an ethanol extract of Fructus Citri Sarcodactylis (Fcs, n = 9), and an OVX punctured at Sanyinjiao (SP-6) and Neiguan (PC-6) (Needling, n = 8). The treatment started when rats were 12 weeks old and continued for 24 weeks. Serum osteocalcin and urinary deoxypyridinoline (Dpd) levels were upregulated in rats in response to OVX, together with a significantly decreased BMD and trabecular bone area. The Pro, Fcs and Needling treatment improved the decreased BMD and the trabecular area, increased the trabecular number, lowered the trabecular separation to some extent as well as significantly depressed the urinary Dpd levels (p < 0.05). The bone formation markers, such as the mineralizing surface, mineral apposition rate and bone formation rate were not significantly changed, along with a slightly higher trend of osteocalcin levels when compared with the Model rats. The slower heart rate and lower plasma NE levels in these therapeutic groups were also found. Our results suggested that propranolol, Fcs and needling on Sanyinjiao (SP-6) and Neiguan (PC-6) may improve the bone mass of OVX rats, and it provides an alternative and potential therapy for the prevention of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To clarify whether the acupoints of Zusanli (ST36) and Sanyinjiao (SP6) have specific actions other than non-acupoints to bone. METHODS: Forty Sprague-Dawley female rats were divided into five groups: Sham operated (sham) group; Ovariectomized (OVX, model) group; non-acupuncture group; OVX, needling on Zusanli and Sanyinjiao (Acp-A) group; OVX, needling on the reverse sides of Zusanli and Sanyinjiao (Acp-B) group; OVX, periostineal stimulation on the same height as points of Zusanli and Sanyinjiao (Acp-C) group. The experiment was continued for 23 weeks and then all animals were sacrificed. RESULTS: OVX had a significantly higher body weight and lower bone mineral density (BMD) on the lumbar vertebrae, total femora and tibiae than sham rats, however, Acp-A showed a higher BMD compared with the other OVX groups. On the other hand, bone weights, bone strength and bone morphometry such as trabecular volume, trabecular separation, labeled width and bone formation rate also showed the same improvements in Acp-A as compared to the other OVX rats. CONCLUSION: The stimulation on Zusanli and Sanyinjiao specifically prevented the development of osteopenic rats compared with non-acupoints. [ABSTRACT FROM AUTHOR]

Background: Anterior cruciate ligament injuries are commonly treated with ligament reconstruction surgery, but post-operative joint contracture is a major complication. The optimal timing for anterior cruciate ligament reconstruction remains controversial, with some clinical studies suggesting that early surgery may increase the risk of joint contractures, while others have found no such association. To clarify this, we investigated the effects of the timing of reconstruction surgery on contracture formation using a rat model., Methods: Anterior cruciate ligament-transected rats were divided into groups based on the timing of reconstruction: immediate, early, and delayed (1, 14, and 28 days after transection, respectively). Some anterior cruciate ligament-transected rats did not receive reconstruction surgery. Untreated rats served as controls. At 56 days after ligament transection, we assessed knee extension range of motion before (including both myogenic and arthrogenic factors) and after myotomy (arthrogenic factor only), as well as fibrotic changes in the joint capsule., Finding: Anterior cruciate ligament transection alone significantly decreased range of motion before myotomy, but not after myotomy. In all reconstructed groups, both range of motions before and after myotomy were significantly reduced compared to the control, indicating the induction of arthrogenic contracture by reconstruction surgery. Fibrotic changes in the joint capsule were observed in all reconstructed groups, contributing to arthrogenic contracture formation. However, the timing of reconstruction had no effect on range of motions and fibrotic changes in the joint capsule., Interpretation: Our findings may help guide clinical decision-making regarding the timing of anterior cruciate ligament reconstruction surgery., Competing Interests: Declaration of competing interest The authors report no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Abnormal hip bone morphologies are associated with various diseases of the hip joint. Weight bearing, especially during growth, may be important to achieve normal acetabulum development. This study aimed to investigate whether hip bone morphologies were affected by hindlimb suspension (HS) in 4 week-old rats. In HS groups, tail suspension was applied for 0, 2, 4, and 8 weeks. Age-matched rats were used as controls. The complex of hip bones with lumbar and sacral vertebrae were assessed based on morphological indexes using three-dimensional reconstructed images from X-ray computed tomography. Acetabular widths (measured from cranial to caudal) unchanged and depths became larger in both groups with age. Acetabular lengths (from the ventral side to the dorsal side) became larger in control groups but unchanged in HS groups with age. In HS groups, acetabular width, length, and depths were smaller than the control groups at 4 and/or 8 weeks. Acetabular versions became enlarged (rotated inwards) with age in both groups, although this was particularly pronounced in HS groups. Histologically, triradiate cartilage layers in the acetabulum were thinner with age and almost disappeared at 8 weeks in both groups. However, HS decreased Safranin O staining and prolonged the presence of hypertrophic chondrocyte indicating alterations in the chondral ossification processes. Iliac wing angles remained unchanged and anterior superior iliac crest (ASIC) distances increased with age in controls. In contrast, HS groups showed narrowed iliac wing angles with small ASIC distances. These results suggest that reduced mechanical loading during growth can interfere with hip joint formation. Keywords Hindlimb suspension, Hip joint, Acetabular morphology, Triradiate cartilage.

Knee malalignment is a risk factor for patellar instability and patellofemoral osteoarthritis (PFOA), but etiologies remain unknown. We investigated the potential effects of decreased weight loading during growth on knee alignments and patellofemoral (PF) joint pathology. Hindlimb suspension (HS) was performed in 4-week-old female rats for 2, 4, and 8 weeks (HS groups). Age-matched rats were used as controls. Three-dimensional reconstructed images of the knee were obtained using X-ray computed tomography. Tibial tubercle-trochlear groove (TT-TG) distance, patellar tilt angle, and bisect offset were measured as indices of knee alignment. Histological analysis was also performed to evaluate the changes in cartilage and synovium in the PF joints. At Week 8, TT-TG distance, patella tilt angle, and bisect offset were significantly larger in the HS group than in the control group, respectively, indicating tibial external rotation, outward patellar tilt, and external displacement of the patella. Lateral patellar dislocation was frequently found in the HS group at Week 8 (five of eight knee joints, p < 0.05). Degenerative changes in the cartilage of the trochlear groove were observed at Week 8, and synovial changes such as hypertrophy and synovitis were observed at Weeks 4 and 8. Correlation analyses revealed significant relationships between the Mankin score and bisect offset, and between the OARSI synovitis score and all knee alignments indices. These results suggest that decreased weight loading on the lower extremities in growing rats resulted in knee malalignments characterized by external rotation of tibia and high incidence of lateral patellar dislocation with concomitant PFOA., (© 2024 Orthopaedic Research Society.)

The prevalence of primary osteoarthritis is higher in females than males. However, it remains unclear if there are sex differences in the incidence of post-traumatic osteoarthritis after anterior cruciate ligament (ACL) reconstruction. In this study, we aimed to investigate the effects of sex on osteoarthritic changes after ACL reconstruction using an animal model. Rats were divided into the following four groups: male control, male ACL reconstruction, female control, and female ACL reconstruction. ACL reconstruction surgery was performed on the right knees of rats in the ACL reconstruction groups, while rats in the control groups did not undergo knee surgery. At 1, 4, and 12 weeks after surgery, cartilage degeneration in the medial tibial plateau and osteophyte formation in the proximal tibia were histologically assessed. After ACL reconstruction, an increase in the Mankin score, cartilage fissures, and osteophyte formation were detected within 12 weeks in both male and female rats, with similar degrees of these changes between males and females. However, changes in cartilage thickness and chondrocyte density after ACL reconstruction differed between males and females. Cartilage thickening was observed in male rats but not in female rats. The increase in chondrocyte density in the anterior region was detected in both males and females but was more pronounced in female rats. In conclusion, osteoarthritic changes were observed after ACL reconstruction in both male and female rats, but differences in changes in cartilage thickness and chondrocyte density were observed between males and females., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Cost-effective copper conductive inks are considered as the most promising alternative to expensive silver conductive inks for use in printed electronics. However, the low stability and high sintering temperature of copper inks hinder their practical application. Herein, we develop rapidly customizable and stable copper-nickel complex inks that can be transformed in situ into uniform copper@nickel core-shell nanostructures by a self-organized process during low-temperature annealing and immediately sintered under photon irradiation to form copper-nickel alloy patterns on flexible substrates. The complex inks are synthesized within 15 min via a simple mixing process and are particle-free, air-stable, and compatible with large-area screen printing. The manufactured patterns exhibit a high conductivity of 19-67 μΩ·cm, with the value depending on the nickel content, and can maintain high oxidation resistance at 180 °C even when the nickel content is as low as 6 wt %. In addition, the printed copper-nickel alloy patterns exhibit high flexibility as a consequence of the local softening and mechanical anchoring effect between the metal pattern and the flexible substrate, showing strong potential in the additive manufacturing of highly reliable flexible electronics, such as flexible radio-frequency identification (RFID) tags and various wearable sensors.

Additive printing techniques have been widely investigated for fabricating multilayered electronic devices. In this work, a layer-by-layer printing strategy is developed to fabricate multilayered electronics including 3D conductive circuits and thin-film transistors (TFTs) with low-temperature catalyzed, solution-processed SiO 2 (LCSS) as the dielectric. Ultrafine, ultrasmooth LCSS films can be facilely formed at 90 °C on a wide variety of organic and inorganic substrates, offering a versatile platform to construct complex heterojunction structures with layer-by-layer fashion at microscale. The high-resolution 3D conductive circuits formed with gold nanoparticles inside the LCSS dielectric demonstrate a high-speed response to the transient voltage in less than 1 µs. The TFTs with semiconducting single-wall carbon nanotubes can be operated with the accumulation mode at a low voltage of 1 V and exhibit average field-effect mobility of 70 cm 2  V -1  s -1 , on/off ratio of 10 7 , small average hysteresis of 0.1 V, and high yield up to 100% as well as long-term stability, high negative-gate bias stability, and good mechanical stability. Therefore, the layer-by-layer printing strategy with the LCSS film is promising to assemble large-scale, high-resolution, and high-performance flexible electronics and to provide a fundamental understanding for correlating dielectric properties with device performance., (© 2021 Wiley-VCH GmbH.)

The directed self-assembly of electronic circuits using functional metallic inks has attracted intensive attention because of its high compatibility with extensive applications ranging from soft printed circuits to wearable devices. However, the typical resolution of conventional self-assembly technologies is not sufficient for practical applications in the rapidly evolving additively manufactured electronics (AMEs) market. Herein, an ultrahigh-resolution self-assembly strategy is reported based on a dual-surface-architectonics (DSA) process. Inspired by the Tokay gecko, the approach is to endow submicrometer-scale surface regions with strong adhesion force toward metallic inks via a series of photoirradiation and chemical polarization treatments. The prepared DSA surface enables the directed self-assembly of electronic circuits with unprecedented 600 nm resolution, suppresses the coffee-ring effect, and results in a reliable conductivity of 14.1 ± 0.6 µΩ cm. Furthermore, the DSA process enables the layer-by-layer fabrication of fully printed organic thin-film transistors with a short channel length of 1 µm, which results in a large on-off ratio of 10 6 and a high field-effect mobility of 0.5 cm 2  V -1  s -1 ., (© 2021 Wiley-VCH GmbH.)

Background: The current randomized, double-blind, phase 2 study assessed the efficacy and safety profile of a single intravenous administration of fosnetupitant, a neurokinin 1 receptor antagonist prodrug, for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving cisplatin-based chemotherapy., Methods: Patients scheduled to receive cisplatin (at a dose of ≥70 mg/m 2 )-based regimens were randomly assigned to receive fosnetupitant at a dose of 81 mg or 235 mg or placebo in combination with palonosetron at a dose of 0.75 mg and dexamethasone. The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase (0-120 hours). The overall CR rate was compared between each dose of fosnetupitant and the placebo group adjusting for the stratification factors of sex and age class (age <55 years vs age ≥55 years). Safety was assessed, with special attention given to events that potentially were suggestive of infusion site reactions., Results: A total of 594 patients were randomized. Of these, 194 patients, 195 patients, and 195 patients, respectively, in the placebo and fosnetupitant 81-mg and 235-mg dose groups were evaluable for efficacy. The overall CR rate was 54.7% for the placebo group, 63.8% for the fosnetupitant 81-mg dose group (adjusted difference, 9.1%; 95% CI, -0.4% to 18.6% [P = .061]), and 76.8% for the fosnetupitant 235-mg dose group (adjusted difference, 22.0%; 97.5% CI, 11.7% to 32.3% [P < .001]). Safety profiles were comparable between the 3 groups. The incidence of infusion site reactions related to fosnetupitant was ≤1% in each dose group., Conclusions: Fosnetupitant at a dose of 235 mg provided superior prevention of chemotherapy-induced nausea and vomiting among patients receiving cisplatin-based chemotherapy compared with the control group, and with a satisfactory safety profile., (© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.)

We developed a facile method for fabricating large-area, two-dimensional (2D), organic, highly crystalline films and extended it to organic thin-film transistor arrays. Tilted spinning provided oriented flow at the three-phase contact line, and a 2D crystalline film that consisted of layer-by-layer stacked 2,7-diocty[1]benzothieno[3,2- b]benzothiophene (C 8 -BTBT) was obtained facilely for organic thin-film transistors (OTFTs). The extracted field-effect mobility is 4.6 cm 2 V -1 s -1 , but with nonideal features. By applying this method to microdroplet arrays, an oriented crystal was fabricated, and the channel region for OTFTs was covered by adjusting the spinning speed. By tuning the tilt angle (θ) of the revolving substrate, we fabricated high-performance OTFT arrays with average and maximum mobilities of 7.5 and 10.1 cm 2 V -1 s -1 , respectively, which exhibited high reliability factors of over 90% and were close to that of ideal transistors. These results suggest that high-quality crystalline films can be obtained via a facile tilted-spinning method.

The Asian cultivated rice, Oryza sativa, is one of the most important crops feeding more than a third of global population. In spite of the studies for several decades, the origin and domestication history of rice varietal groups, japonica and indica, have not been fully unveiled. Genetic information of ancient rice remains is essential for direct and exclusive insight into the domestication history of rice. We performed ancient DNA analysis of 950- to 2,800-year-old rice remains excavated from Japan and Korea. We found the presence of both japonica- and indica-type varieties in the Yayoi period and the middle ages of Japan and the middle part of Korea Peninsula 2,000 years ago. It is popularly considered that japonica has been exclusively cultivated in northern part of East Asia including Japan and Korea. Our result disclosed unexpectedly wide diversity of rice varieties in archaic East Asia. The present results from ancient rice DNA reveal an exclusive insight for the domestication history of rice which is not provided as far as contemporary rice., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The epidermal growth factor receptor (EGFR) tyrosine kinase has been an important target for non-small-cell lung cancer. Several EGFR tyrosine kinase inhibitors (TKIs) are currently approved, and both gefitinib and erlotinib are the most well-known first-generation EGFR-TKIs. This randomized phase III study was conducted to investigate the difference between these two EGFR-TKIs., Patients and Methods: Previously treated patients with lung adenocarcinoma were randomly assigned to receive gefitinib or erlotinib. This study aimed to investigate the noninferiority of gefitinib compared with erlotinib. The primary end point was progression-free survival (PFS)., Results: Five hundred sixty-one patients were randomly assigned, including 401 patients (71.7%) with EGFR mutation. All baseline factors (except performance status) were balanced between the arms. Median PFS and overall survival times for gefitinib and erlotinib were 6.5 and 7.5 months (hazard ratio [HR], 1.125; 95% CI, 0.940 to 1.347; P = .257) and 22.8 and 24.5 months (HR, 1.038; 95% CI, 0.833 to 1.294; P = .768), respectively. The response rates for gefitinib and erlotinib were 45.9% and 44.1%, respectively. Median PFS times in EGFR mutation-positive patients receiving gefitinib versus erlotinib were 8.3 and 10.0 months, respectively (HR, 1.093; 95% CI, 0.879 to 1.358; P = .424). The primary grade 3 or 4 toxicities were rash (2.2% for gefitinib v 18.1% for erlotinib) and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) elevation (6.1%/13.0% for gefitinib v 2.2%/3.3% for erlotinib)., Conclusion: The study did not demonstrate noninferiority of gefitinib compared with erlotinib in terms of PFS in patients with lung adenocarcinoma according to the predefined criteria., (© 2016 by American Society of Clinical Oncology.)

On page 6568, T. Minari and co-workers describe spontaneous patterning based on the parallel vacuum ultraviolet (PVUV) technique, enabling the homogeneous integration of complex, high-resolution electronic circuits, even on large-scale, flexible, transparent substrates. Irradiation of PVUV to the hydrophobic polymer surface precisely renders the selected surface into highly wettable regions with sharply defined boundaries, which spontaneously guides a metal nanoparticle ink into a series of circuit lines and gaps with the widths down to a resolution of 1 μm., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A spontaneous patterning technique via parallel vacuum ultraviolet is developed for fabricating large-scale, complex electronic circuits with 1 μm resolution. The prepared organic thin-film transistors exhibit a low contact resistance of 1.5 kΩ cm, and high mobilities of 0.3 and 1.5 cm(2) V(-1) s(-1) in the devices with channel lengths of 1 and 5 μm, respectively., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Monodisperse cadmium sulphide (CdS) quantum dots (QDs) with a tunable size from 1.4 to 4.3 nm were synthesized by a non-injection method, and their surface states were characterized by photoluminescence spectroscopy and X-ray Photoelectron Spectroscopy (XPS). The steady state photoluminescence study identified that the proportion of the trap state emission increased with the QD size decrease, while from the photoluminescence decay study, it appeared that the trap state emission results from the emission via a surface deep trap state. The XPS measurements revealed the existence of surface Cd with sulfur vacancy sites which act as electron trap sites, and the population of these sites increases with the QD size decrease. These results are consistent to conclude that the trap state emission mainly originates from the surface deep trapped electrons at the surface Cd with sulfur vacancy sites.

Pemetrexedis a key drug in the first and second -line therapy for non-small-cell lung cancer. It exhibits an increased area under the plasma drug concentration-time curve, and it has a prolonged half -life when administered to patients with reduced renal function, resulting in a high frequency of neutropenia. Accordingly, pemetrexed is administered to these patients with caution. Herein, we retrospectively investigated the background characteristics of patients with a creatinine clearance rate (Ccr) of<45 mL/min, who experienced severe adverse events due to pemetrexed. Thirty-eight patients with a Ccr of <45 mL/min were administered pemetrexed. Of these patients, 13 (34%) developed severe adverse events (≥Grade 3) such as neutropenia, thrombocytopenia, and nausea. Multiple logistic regression analysis revealed that a Ccr of <30 mL/min (p= 0.033) and the concomitant use of non-steroidal anti-inflammatory drugs (p=0.012) were significant risk factors for adverse events. Therefore, whenever possible, pemetrexed administration should be avoided in patients with a Ccr of <30 mL/ min and in those receiving concomitant non-steroidal anti-inflammatory drugs.

Various factors, including renal function and the combination of nonsteroidal anti-inflammatory drugs, influence the pharmacokinetics of pemetrexed. In this study, we aimed to determine the risk factors for severe adverse events associated with pemetrexed administration. We retrospectively examined the medical records of 82 patients who received pemetrexed. Multiple logistic regression analysis indicated that a creatinine clearance (CCr) of less than 45 mL/min and administration of pemetrexed as early-line treatment were significant risk factors. We then retrospectively compared the adverse events associated with pemetrexed between patients with normal renal function (CCr≥45 mL/min) and those with impaired renal function (CCr<45 mL/min). With regard to hematological toxicity, the frequency of occurrence of grade 3 neutropenia was significantly higher among patients with a CCr of <45 mL/min. With regard to non-hematological toxicity, the frequency of occurrence of grade 2 or higher nausea was significantly higher among patients with a CCr of <45 mL/min. However, the efficacy of pemetrexed did not differ significantly between the 2 groups. Our findings suggest that, for patients with a decline in renal function (CCr <45 mL/min), attention must be paid to the possibility of serious adverse events such as neutropenia and nausea when considering the administration of pemetrexed.

Synthesis of ω-alkenyl-terminated silver nanoparticles (AgNPs) and then their immobilization on a hydrogen-terminated silicon surface in two-dimensional arrangement through covalent interaction are demonstrated. The thermal-induced hydrosilylation at mild conditions facilitate nanoparticles assembly through interaction between terminal alkenyl (CH(2)=CH-) groups of AgNPs and hydrogen-terminated silicon surface. The assembly of AgNPs on a silicon surface is characterized by FESEM and XPS. Adequate coating of 10-undecene-1-thiol (UDT) on AgNPs and mild temperature hydrosilylation impede the fusion or aggregation of nanoparticles, while they immobilized on a silicon surface, which is very crucial to preserve the discrete entities of nanoparticles. This elegant and facile approach provides stable monolayer of AgNPs with very good coverage area and promises potential to fabricate electronic devices and solar cells, where nanoparticles needs to be directly attached to the silicon surface without an interfacial oxide thin film., (Copyright © 2012 Elsevier Inc. All rights reserved.)

High-quality CdS and Cu(7)S(4) quantum dots (QDs) were synthesized with N,N-dibutylthiourea (DBTU) as an organic sulfur source. In this method, nucleation and growth reactions were controlled simply by the heating rate of the reaction. The mild oxidation conditions gave monodisperse CdS QDs exhibiting pure band-edge emission with relatively high photoluminescence quantum yield. During the synthesis of Cu(7)S(4) QDs, the addition of dodecanethiol to the reaction system controlled the reaction rate to give monodisperse spherical or disk-shaped QDs. A hundred-gram scale of copper precursor could be used to generate the high-quality Cu(7)S(4) QDs, indicating that an industrial-scale reaction is achievable with our method. As observed in anisotropic noble-metal nanocrystals, larger disk-shaped Cu(7)S(4) QDs showed lower localized-surface-plasmon resonance energy in the near-infrared region. The disk-shaped Cu(7)S(4) QDs could be used effectively as templates to form cation-exchanged monodisperse disk-shaped CdS QDs., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Pemetrexed, a folate metabolic antagonist, is considered to be effective against plural mesotheliomas, non-small cell lung cancer, and especially for non-squamous cell cancer. However, it has been reported to have adverse interactions with nonsteroid anti-inflammatory drugs(NSAIDs). In the present study, we compared the incidence of adverse events between patients receiving pemetrexed therapy with and without concomitant NSAID administration. No significant difference in the incidence of hematotoxic events of Grade 3 or worse was observed. As for the incidence of non-hematotoxic events, the increase in the amount of creatinine, namely a severe adverse effect of Grade 2 or more, was significantly higher in the combined therapy group (p=0.018). No other significant differences were noted for other adverse events. A creatinine increase to Grade 2 or greater developed significantly earlier in the combined group(median value, 12.7 courses; p=0.0063). Our results suggest that renal dysfunction may easily develop as a result of continued pemetrexed administration combined with NSAID therapy. Therefore, it is necessary to take precautions against adverse side effects such as renal dysfunction when combining pemetrexed with NSAID therapy, by conducting periodic examinations.

An enhancing factor: the enhancement of the electric properties of a dye molecule (IR26) by indium-tin oxide nanoparticles (ITO NPs, see picture) has been shown by measuring the near-infrared two-photon-excited transient absorption spectra. The dye molecule was excited much more efficiently in the presence of an ITO NP layer., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-β levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.

Purpose: We have treated patients with non-small-cell lung cancer (NSCLC) who developed leptomeningeal metastases (LM) during gefitinib therapy, and then found symptomatic improvement following treatment change to erlotinib. Based on this experience, we wondered whether erlotinib could be detected in cerebrospinal fluid (CSF) when it was used for NSCLC patients with LM. This study was conducted to determine erlotinib concentrations in CSF and assess responses to erlotinib in patients with NSCLC developing LM during gefitinib therapy., Methods: Three advanced NSCLC patients with LM that developed during gefitinib therapy were treated with erlotinib. On day 28 after the initiation of erlotinib treatment, plasma and CSF were obtained and the concentrations of erlotinib in these samples were measured. Eastern Cooperative Oncology Group (ECOG) performance status (PS) and neurologic symptoms were determined., Results: Erlotinib CSF penetration was 6.3% ± 6.1% (mean ± SD). In cases 1 and 2, we observed improvements in ECOG PS and neurologic symptoms. In case 3, cytological improvement was seen in the CSF. In each patient, deletion of exon 19 or exon 21 L858R mutation of the epidermal growth factor receptor (EGFR) gene was detected in carcinoma cells from the CSF., Conclusions: We report on 3 patients with NSCLC who had developed LM during gefitinib treatment and showed clinical improvements following change to erlotinib therapy. In all cases, small but measurable penetration of erlotinib into CSF was observed. Because EGFR mutations were detected in all cases, we suggest that erlotinib is a therapeutic option for LM carcinoma cells with EGFR mutations.

Bisphosphonates are widely used for the treatment of metastatic skeletal tumors and hypercalcemia resulting from malignant tumors. Zoledronic acid (ZOL), a third-generation bisphosphonate agent, was recently demonstrated to show synergistic antitumor activity of ZOL when combined with chemotherapy in lung cancer patients. However, whether ZOL exerts direct antitumor activity on lung cancer remains unclear. Here, we report an atypical case encountered while treating a 57-year-old woman with pulmonary adenocarcinoma and multiple metastases of the liver, left adrenal gland, and bone. The nonskeletal lesions, consisting of the primary lesion and hepatic metastasis, regressed after treatment with ZOL alone. We believe this case demonstrates a possible antitumor effect of ZOL against lung cancer.

S-1 is a novel oral fluorouracil prodrug that plays a role in non-small cell lung cancer (NSCLC). Docetaxel (DTX) is one of the standard agents for relapsed NSCLC. We performed a phase I study of DTX plus S-1 combination therapy as second-line treatment for NSCLC to determine the maximum tolerated dose (MTD) and recommended dose (RD). Patients with recurrent NSCLC, aged 20-74 years with an Eastern Cooperative Oncology Group performance status of 0-1 and measurable lesions, were enrolled. The treatment consisted of four dose levels. The patients received DTX (40-60 mg/m(2) intravenously on day 1) and S-1 (65-80 mg/m(2) orally, daily on days 1-14) for each 21-day cycle. Three to six patients were treated at each dose level with the two drugs, with MTD defined as the dose level at which dose-limiting toxicity (DLT) occurred in 33% of the patients. A total of 17 patients were enrolled. At dose level 4 (DTX, 60 mg/m(2); S-1, 80 mg/m(2)) 3 of 5 patients experienced DLT and this level was regarded as the MTD. Therefore, dose level 3 (DTX, 60 mg/m(2); S-1, 65 mg/m(2)) was selected as the RD for subsequent studies. The DLTs were neutropenia (grade 4) and mucositis (grade 3). The response rate was 5.9% (1 of 17 patients achieved a partial response) and 14 of 17 patients achieved stable disease. This combination regimen showed a tolerable and manageable profile in recurrent NSCLC and therefore warrants further evaluation.

Core-shell-structured nanoparticles, consisting of a noble metal or metal oxide core and a chromia (Cr(2)O(3)) shell, were studied as promoters for photocatalytic water splitting under visible light. Core nanoparticles were loaded by impregnation, adsorption or photodeposition onto a solid solution of gallium nitride and zinc oxide (abbreviated GaN:ZnO), which is a particulate semiconductor photocatalyst with a band gap of approximately 2.7 eV, and a Cr(2)O(3) shell was formed by photodeposition using a K(2)CrO(4) precursor. Photodeposition of Cr(2)O(3) on GaN:ZnO modified with a noble metal (Rh, Pd and Pt) or metal oxide (NiO(x), RuO(2) and Rh(2)O(3)) co-catalyst resulted in enhanced photocatalytic activity for overall water splitting under visible light (lambda>400 nm). This enhancement in activity was primarily due to the suppression of undesirable reverse reactions (H(2)-O(2) recombination and/or O(2) photoreduction) and/or protection of the core component from chemical corrosion, depending on the core type. Among the core materials examined, Rh species exhibited relatively high performance for this application. The activity for visible-light water splitting on GaN:ZnO modified with an Rh/Cr(2)O(3) core-shell configuration was dependent on both the dispersion of Rh nanoparticles and the valence state. In addition, the morphology of the Cr(2)O(3) photodeposits was significantly affected by the valence state of Rh and the pH at which the photoreduction of K(2)CrO(4) was conducted. When a sufficient amount of K(2)CrO(4) was used as the precursor and the solution pH ranged from 3 to 7.5, Cr(2)O(3) was successfully formed with a constant shell thickness (approximately 2 nm) on metallic Rh nanoparticles, which resulted in an effective promoter for overall water splitting.

In the present work, we studied a unique and facile method for the drastic structural transformation of hydrophobic small CdE (E = S, Se, Te) nanoparticles into large, high-quality pencil-shaped nanoparticles through an Ostwald ripening process induced by Cl(-) and surfactants (oleic acid and oleylamine). This study revealed that Cl(-) is the effective anion for the controlled structural transformation of CdE nanoparticles. This transformation reaction can be readily extended to the formation of various functional materials.