[Show abstract][Hide abstract] ABSTRACT: To prepare orally available oxaliplatin (OXA), nanocomplexes were formed by ionic conjugation of OXA with the deoxycholic acid derivative, N α -deoxycholyl-L-lysyl-methylester (DCK), as an oral absorption enhancer. We characterized the DCK-conjugated OXA nanocomplexes by differential scanning calorimetry, particle size determination, and morphological analysis. To evaluate the effects of DCK on the intestinal permeability of OXA, we assessed the solubilities and partition coefficients of OXA and the OXA/DCK nanocomplex, and then conducted in vitro artificial intestinal membrane and Caco-2 cell permeability studies. Finally, bioavailability in rats and tumor growth inhibition in the squamous cell carcinoma (SCC7) model after oral administration of the OXA/DCK nanocomplex were investigated compared to pure OXA. Analysis of the ionic complex formation of OXA with DCK revealed that OXA existed in an amorphous form within the complex, resulting in formation of nanocomplexes (35.05±4.48 nm in diameter). The solubility of OXA in water was approximately 7.07 mg/mL, whereas the water solubility of OXA/DCK was approximately 2.04 mg/mL and its partition coefficient was approximately 1.2-fold higher than that of OXA. The in vitro intestinal membrane permeability of OXA was significantly enhanced by complex formation with DCK. An In Vivo pharmacokinetic study revealed that the C max value of the OXA/DCK nanocomplex was 3.18-fold higher than that of OXA (32.22±10.24 ng/mL), and the resulting oral bioavailability of the OXA/DCK nanocomplex was 39.3-fold more than that of OXA. Furthermore, the oral administration of OXA/DCK significantly inhibited tumor growth in SCC7-bearing mice, and maximally inhibited tumor volume by 54% compared to the control. These findings demonstrate the therapeutic potential of the OXA/DCK nanocomplex as an oral anti-cancer therapy because it improves the oral absorption of OXA, which may improve patient compliance and expand the therapeutic applications of OXA to the prevention of recurrence and metastasis.
Full-text · Article · Feb 2016 · Journal of Nanoscience and Nanotechnology
[Show abstract][Hide abstract] ABSTRACT: In this paper, the effect of polyimide surface modification – using near-atmospheric pressure plasmas – on the line width and adhesion of inkjet-printed Ag was investigated by texturing and modifying the chemical composition of the polyimide surface. The polyimide surface was textured with He/O2, to increase the surface area of the polyimide substrate and it increased the water contact angle from 57 to 137°, when the textured polyimide surface was treated with a SF6 plasma after the texturing process. The textured polyimide surface also exhibited the increased adhesion strength of Ag film (by about two times), due to the increase in the contact area, as expected, according to the Wenzel model. The linewidth of the inkjet-printed Ag line decreased by about ten times from 330 µm (for the flat polyimide surface) to 23 µm (for the textured polyimide surface) in addition to having smoother line edges.
No preview · Article · Feb 2016 · Plasma Processes and Polymers
[Show abstract][Hide abstract] ABSTRACT: Histone H3S10 phosphorylation has been known as a cell cycle-specific marker and has a role in transcriptional activation. Various kinases phosphorylate H3S10 in different species, however, the role of the mitotic serine/threonine protein kinase Aurora A (AURKA) is largely unknown. Here we present evidence that AURKA phosphorylates H3S10 and activates target gene transcription. We show that down-regulation of AURKA level during leukemia cell differentiation results in decreased H3S10 phosphorylation level. We further show that AURKA is recruited to target gene promoters and activates transcription via H3S10 phosphorylation. Furthermore, this recruitment can be disrupted by the AURKA inhibitor Alisertib and results in H3K9-me2 recruitment by G9a.
No preview · Article · Nov 2015 · Biochemical and Biophysical Research Communications
[Show abstract][Hide abstract] ABSTRACT: We assessed the possibility of changing the route of administration of zoledronic acid to an oral dosage form and its therapeutic efficacy in an estrogen-deficient osteoporosis rat model. To enhance oral bioavailability, we formed an ionic complex by electrostatic conjugation of zoledronic acid with lysine-linked deoxycholic acid (Lys-DOCA, an oral absorption enhancer). After forming the complex, the characteristic crystalline features of pure zoledronic acid disappeared completely in the powder X-ray diffractogram and differential scanning calorimetry thermogram, indicating that zoledronic acid existed in an amorphous form in the complex. In vitro permeabilities of zoledronic acid/Lys-DOCA (1:1) (ZD1) and zoledronic acid/Lys-DOCA (1:2) (ZD2) complex across Caco-2 cell monolayers were 2.47- and 4.74-fold higher than that of zoledronic acid, respectively. Upon intra-jejunal administration to rats, the intestinal absorption of zoledronic acid was increased significantly and the resulting oral bioavailability of the ZD2 complex was determined to be 6.76±2.59% (0.548±0.161% for zoledronic acid). Ovariectomized (OVX) rats showed 122% increased bone mineral density versus the OVX control at 12weeks after treatment with once weekly oral administration of ZD2 complex (16μg/kg of zoledronic acid). Furthermore, rats treated with ZD2 complex orally showed significant improvement in the parameters of trabecular microarchitecture and bone strength: 149% higher bone volume fraction (BV/TV), 115% higher trabecular number (Tb.N), and 56% higher mean maximum load (Fmax) than in the OVX group. The trabecular microstructure and bone mechanical properties in the oral zoledronic acid group were not significantly changed compared with the OVX control. Thus, the oral ZD2 complex inhibited osteoporosis progression effectively by promoting osteogenesis and trabecular connectivity. The oral ZD2 complex would be expected to improve patient compliance by replacing the conventional injectable form and expand the indications, to include prophylaxis for osteoporosis and bone metastases.
Full-text · Article · Nov 2015 · European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences
[Show abstract][Hide abstract] ABSTRACT: Using a reactive ion beametching (RIBE) system, the possibility of removing the sidewall residues remaining on etched nanoscale CoFeB features and the W hard mask after using a conventional inductively coupled plasmaetching system was investigated. Upon increasing the ion energy of the Ar beam, a similar sputter yield increase was found for both CoFeB side wall residues and the W hard mask. Hence, increasing the ion beam energy to improve etch residue removal efficiency at the same time induces a degradation of the CoFeB profile because of the W hard mask erosion. However, when CO/NH3 was used as the RIBE gas mixture, at ion energy in the range of 90–110 eV, the effective residue removal from CoFeB etched features without etching the W hard mask. When the ion energy of the CO/NH3 RIBE exceeds 140 eV, again similar sputter yields are found for both CoFeB side wall residues and the W hard mask.
[Show abstract][Hide abstract] ABSTRACT: The amorphous carbon layer (ACL), used as the hardmask for the etching of nanoscale semiconductor materials, was etched using O2/CHF3 in addition to O2/N2 using pulsed dual-frequency capacitively coupled plasmas, and the effects of source power pulsing for different gas combinations on the characteristics of the plasmas and ACL etching were investigated. As the etch mask for ACL, a patterned SiON layer was used. The etch rates of ACL were decreased with the decrease of pulse duty percentage for both O2/N2 and O2/CHF3 due to decrease of the reactive radicals, such as F and O, with decreasing pulse duty percentage. In addition, at the same pulse duty percentage, the etch selectivity of ACL/SiON with O2/CHF3 was also significantly lower than that with O2/N2. However, the etch profiles of ACL with O2/CHF3 was more anisotropic and the etch profiles were further improved with decreasing the pulse duty percentage than those of ACL with O2/N2. The improved anisotropic etch profiles of ACL with decreasing pulse duty percentage for O2/CHF3 were believed to be related to the formation of a more effective passivation layer, such as a thick fluorocarbon layer, on the sidewall of the ACL during the etching with O2/CHF3, compared to the weak C–N passivation layer formed on the sidewall of ACL when using O2/N2.
No preview · Article · Nov 2015 · Journal of Nanoscience and Nanotechnology
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Deoxycholic acid (DOCA) is involved in many physiological functions and has been used in various fields of pharmaceutical formulations as a natural active solubilizing and permeation-enhancing agent. Although DOCA has been suggested to be a promoter of colon cancer, it has also been used extensively as a starting material to obtain new derivatives for potential therapeutic applications. Area covered: In this review, we focus on patents and research reports from 2011 to 2014 related to pharmaceutical formulations and therapeutic applications using DOCA and its derivatives as surfactants or absorption enhancers, drug delivery carriers, and anti-cancer agents. Expert opinion: In recent few years, DOCA and its derivatives have been used mostly as pharmaceutical excipients for solubilizing lipophilic compounds to improve their bioavailability. Other studies have expanded its applications to include enhanced drug permeability and have designed more effective drug carriers by conjugation with polymeric materials. Recently, a synthetic DOCA injection, ATX-101, has shown long-term efficacy in the non-surgical treatment of unwanted submental fat and acceptable tolerability in humans. Thus, it may be used for reducing specific localized fat accumulations. Additionally, DOCA has been a starting material for anti-cancer drugs, and some derivatives showed strong inhibitory activities against several carcinoma cells.
No preview · Article · Oct 2015 · Expert Opinion on Therapeutic Patents
[Show abstract][Hide abstract] ABSTRACT: Two key conditions are required for the application of fine-line inkjet printing onto a flexible substrate such as polyimide (PI): linewidth control during the inkjetting process, and a strong adhesion of the polyimide surface to the ink after the ink solidifies. In this study, the properties of a polyimide surface that was roughened through etching in a He/SF6 plasma, using a polystyrene nanosphere array as the etch mask, were investigated. The near-atmospheric-pressure plasma system of the He/SF6 plasma that was used exhibits two notable properties in this context: similar to an atmosphericpressure plasma system, it can easily handle inline substrate processing; and, similar to a vacuum system, it can control the process gas environment. Through the use of plasma etching, the polyimide surface masked the 120-nm-diameter polystyrene nanospheres, thereby forming a roughened nanoscale polyimide surface. This surface exhibited not only a greater hydrophobicity—with a contact angle of about 150° for water and about 30° for silver ink, indicating better silver linewidth control during the silver inkjetting process—but also a stronger adhesion to the silver ink sprayed onto it when compared with the flat polyimide surface.
No preview · Article · Oct 2015 · Journal of Nanoscience and Nanotechnology
[Show abstract][Hide abstract] ABSTRACT: A 4-year-old schizencephaly patient admitted to authors' institution with dysphagia caused by upper esophageal sphincter (UES) dysfunction. Videofluoroscopic swallowing study (VFSS) was done for the diagnosis and the botulinum toxin type A (BTX-A) was injected to the cricopharyngeal muscle. UES dysfunction improved and oral feeding was possible after the injection. This normal swallowing function remained for over 79 months which was confirmed by follow up VFSS. To the best of our knowledge, this is first case of schizencephaly patient to be treated by BTX-A for UES dysfunction and longest to maintain its effect with single session of injection.
No preview · Article · Sep 2015 · International journal of pediatric otorhinolaryngology
[Show abstract][Hide abstract] ABSTRACT: Detection and quantification of 8-oxo-7,8-dihydroguanine (8-oxoG) within cells are important for the study of the molecular mechanisms in cancer. Human ribosomal protein S3 (hRpS3), which involved in DNA repair, has high binding affinity to 8-oxoG. We developed an imaging probe to detect 8-oxoG using a specific peptide of hRpS3. Sequence analysis was conducted to elucidate the 8-oxoG-specific binding region of hRpS3, and three truncated mutants, D1 (amino acids 1–85), D2 (amino acids 86–159), and D3 (amino acids 160–242), were constructed. Both wild-type-hRpS3 and D2 were able to bind 8-oxoG, which is consistent with the results of a previous report on the role of K134 in Drosophila melanogaster RpS3. We synthesized a specific peptide and covalently linked with a fluorophore (FPR-552, similar to Cy3) to generate an 8-oxoG imaging probe. Our 8-oxoG S3-probe successfully detected the presence of 8-oxoG in damaged cells. Furthermore, this probe has threefold higher sensitivity than 8-oxoG DNA lesion antibody.
No preview · Article · Sep 2015 · Bulletin of the Korean Chemical Society
[Show abstract][Hide abstract] ABSTRACT: Aqueous precursor solutions prepared by water-soluble molecular precursors, CuCl2, InCl3, GaCl3, and SeC(NH2)2, have been successfully employed to deposit Cu(InGa)Se2 thin-film solar cell absorbers by spray-deposition
followed by selenization. The spray-deposition process was optimized by adjusting the spray operation parameters (e.g., spray flow rate, time, and spray distance from substrate) and the substrate conditions (e.g., rotational speed and substrate temperature). The selenization process was then
adjusted by changing the selenization temperature and Se flux. Here we report a cell efficiency of 4.7% obtained from spray-deposition of an aqueous precursor followed by selenization in a vacuum thermal evaporator.
No preview · Article · Aug 2015 · Journal of Nanoelectronics and Optoelectronics
[Show abstract][Hide abstract] ABSTRACT: Histone lysine methylation contributes to transcriptional regulation by serving as a platform for the recruitment of various cofactors. Intense studies have been conducted for elucidating the functional meaning of H3K79 methylation, and to date, the only known HMTase responsible for the modification was DOT1L. In this study, we report that the MMSET isoform RE-IIBP has HMTase activity for H3K79. It was uncovered that RE-IIBP up-regulates MEIS1 transcription through H3K79 methylation via recruitment to the MEIS1 promoter. By means of proteomic and biochemical analysis, association of RE-IIBP with the E3 ubiquitin ligase RNF20 was demonstrated for synergistic activation of MEIS1 transcription via H3K79 HMTase activity. Furthermore, It was observed that RE-IIBP induces MEIS1-mediated apoptosis, which was dependent on H2BK120 ubiquitination by RNF20. These findings suggest RE-IIBP as another candidate for further studies to elucidate the mechanism of H3K79 methylation and its biological functions.
[Show abstract][Hide abstract] ABSTRACT: In recent years, advances in biotechnology and protein engineering have enabled the production of large quantities of proteins and peptides as important therapeutic agents. Various researchers have used biocompatible functional polymers to prepare oral dosage forms of proteins and peptides for chronic use and for easier administration to enhance patient compliance. However, there is a need to enhance their safety and effectiveness further. Most macromolecules undergo severe denaturation at low pH and enzymatic degradation in the gastrointestinal tract. The macromolecules' large molecular size and low lipophilicity cause low permeation through the intestinal membrane. The major strategies that have been used to overcome these challenges (in oral drug carrier systems) can be classified as follows: enteric coating or encapsulation with pH-sensitive polymers or mucoadhesive polymers, co-administration of protease inhibitors, incorporation of absorption enhancers, modification of the physicochemical properties of the macromolecules, and site-specific delivery to the colon. This review attempts to summarize the various advanced oral delivery carriers, including nanoparticles, lipid carriers, such as liposomes, nano-aggregates using amphiphilic polymers, complex coacervation of oppositely charged polyelectrolytes, and inorganic porous particles. The particles were formulated and/or surface modified with functional polysaccharides or synthetic polymers to improve oral bioavailability of proteins and peptides. We also discuss formulation strategies to overcome barriers, therapeutic efficacies in vivo, and potential benefits and issues for successful oral dosage forms of the proteins and peptides.
No preview · Article · May 2015 · Current pharmaceutical design
[Show abstract][Hide abstract] ABSTRACT: We investigated whether leflunomide can be delivered topically and metabolized into teriflunomide through the skin, and evaluated the therapeutic effect of topical leflunomide.
Permeation of leflunomide across and formation of its active metabolite within the skin was examined ex vivo. Deposition of teriflunomide in micropig knee joints after applying topical and transdermal patches containing leflunomide was investigated by determining the plasma and joint tissue concentrations. Finally, the anti-inflammatory effects and inhibition of skin sensitization by topical leflunomide were evaluated in a rat adjuvant arthritis model and mice with delayed-type induced hypersensitivity.
We found that after topical application of leflunomide on freshly excised mouse, rat and guinea pig skin, ∼24% of the permeated drug existed as teriflunomide. In micropigs treated topically with leflunomide on the knee joint, significantly lower teriflunomide concentrations were found in plasma, but its concentrations in the knee joint were 3.4-fold to 54.6-fold higher than those after oral administration. In a rat arthritis model, the plasma concentration of teriflunomide after treatment with 10% leflunomide topical solution was 7.54-fold lower than that after 10 mg/kg oral leflunomide. However, topical leflunomide was nearly as effective as oral in inhibiting paw edema (37% versus 56%, respectively). The values for hypersensitized mouse ear weight after treatment with topical leflunomide decreased significantly by 26% compared to vehicle.
These results demonstrate that topically applied leflunomide can be delivered effectively and deposited as teriflunomide in an arthritic joint, possibly allowing better compliance in rheumatoid arthritis patients by avoiding leflunomide's side effects.
No preview · Article · May 2015 · Drug Development and Industrial Pharmacy
[Show abstract][Hide abstract] ABSTRACT: Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia.Neuropsychopharmacology accepted article preview online, 10 February 2015. doi:10.1038/npp.2015.41.
Preview · Article · Feb 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
[Show abstract][Hide abstract] ABSTRACT: Groin pain in athletes is a complex diagnostic and therapeutic challenge. Sports hernia is one of the common causes of groin pain. We report a case of sports hernia, initially presented as groin pain and aggravated by sports activity. A 19-year-old soccer player visited the outpatient department of general surgery and was referred to the rehabilitation center due to no abnormalities detected in the abdomen and pelvis by computed tomography. An incipient direct bulge of the posterior inguinal wall was detected with dynamic ultrasound when abdominal tension was induced by raising both legs during a full inhalation. Surgery was performed and preoperatively both groins showed the presence of inguinal hernia. Diagnosing sports hernia is very challenging. Through careful history documentation and physical examination followed by dynamic ultrasonography, we identified his posterior inguinal wall deficiency for early management.
Preview · Article · Jan 2015 · Annals of Rehabilitation Medicine
[Show abstract][Hide abstract] ABSTRACT: Piriformis syndrome (PS) is an uncommon neuromuscular disorder caused by the piriformis muscle (PM) compressing the sciatic nerve (SN). The main symptom of PS is sciatica, which worsens with certain triggering conditions. Because the pathophysiology is poorly understood, there are no definite diagnostic and therapeutic choices for PS. This case report presents a young woman who mainly complained of bilateral leg weakness. Electromyography revealed bilateral sciatic neuropathy and magnetic resonance imaging confirmed structural lesions causing entrapment of the bilateral SNs. After a laborious diagnosis of bilateral PS, she underwent PM releasing surgery. Few PS cases present with bilateral symptoms and leg weakness. Therefore, in such cases, a high level of suspicion is necessary for accurate and prompt diagnosis and treatment.
Preview · Article · Jan 2015 · Annals of Rehabilitation Medicine
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to identify the clinical characteristics of benign paroxysmal positional vertigo (BPPV) occurring after head trauma by comparing them to those of idiopathic BPPV (i-BPPV).
[Show abstract][Hide abstract] ABSTRACT: Benign paroxysmal positional vertigo (BPPV) generally involves a single semicircular canal (single canal BPPV) but it has been reported that more than one semicircular canal on either the same or the opposite side can be involved in 6.8-20% of the cases (multiple canal BPPV). In this study, the clinical characteristics of multiple canal BPPV were analyzed and compared to those of single canal BPPV.
Retrospective analysis was performed on 1054 consecutive patients diagnosed with BPPV. Multiple canal BPPV was diagnosed when the combination of typical nystagmus was provoked by the Dix-Hallpike and supine head roll tests. Canalith repositioning maneuver was performed sequentially starting with the semicircular canal causing more severe nystagmus or symptoms. Clinical characteristics and the treatment course were statistically compared between single canal BPPV and multiple canal BPPV.
Among the 1054 patients, single canal BPPV was diagnosed in 1005 patients (95.4%) while multiple canal BPPV was diagnosed in 49 patients (4.6%). BPPV involving semicircular canals on the same side was more common (79.6%) than BPPV with bilateral involvement. The most common combination of the involved canals was ipsilateral posterior and horizontal semicircular canals (63.3%). Multiple canal BPPV was significantly more associated with underlying otologic diseases, especially labyrinthitis. Multiple canal BPPV required more treatment sessions and longer duration of treatment to achieve resolution of nystagmus and symptoms.
As all cases of multiple canal BPPV were treated successfully although a longer duration of treatment and more treatment sessions were required compared to single canal BPPV, the results of our study could aid in making an accurate diagnosis and providing appropriate treatment of multiple canal BPPV.
Preview · Article · Dec 2014 · Korean Journal of Audiology