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Find video protocols related to scientific articles indexed in Pubmed.
Spontaneous bilateral rod fracture of malleable penile prosthesis.
Can Urol Assoc J
PUBLISHED: 11-20-2014
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Mechanical failure with a malleable penile prosthesis is very rare. To the best of our knowledge, this is the first case reporting on a bilateral AMS 650 rod mechanical failure. We present a 50-year-old man with organic erectile dysfunction who experienced bilateral AMS 650 rod fracture after 14 years. The rod fracture of the left side was confirmed via X-ray preoperatively. The surgical exploration revealed a fracture of both rods. After the removal of both rods, we implanted a new malleable device during the same session. At the 6-month follow-up, the patient was satisfied with his prosthesis.
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Myeloid-derived suppressor cells: Their role in the pathophysiology of hematologic malignancies and potential as therapeutic targets.
Leuk. Lymphoma
PUBLISHED: 11-20-2014
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ABSTRACT Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells at various stages of differentiation/maturation that have a role in cancer induction and progression. They function as vasculogenic and immunosuppressive cells, utilizing multiple mechanisms to block both innate and adaptive anti-tumor immunity. Recently, their mechanism of action and clinical importance has been defined, and the cross talk between myeloid cells and cancer cells has been shown to contribute to tumor induction, progression, metastasis, and tolerance. In this review, we focus on the role of MDSCs in hematologic malignancies and the therapeutic approaches targeting MDSCs that are currently in clinical studies.
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Correlation Between Static Radiographic Measurements and Intersegmental Angles Measurements During Gait Using a Multisegment Foot Model With a 15-Marker Set.
Foot Ankle Int
PUBLISHED: 11-19-2014
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Radiographic examination is a widely used evaluation method in the orthopedic clinic. However, conventional radiography alone does not reflect the dynamic changes between foot and ankle segments during gait. Multiple 3-dimensional multisegment foot models (3D MFMs) have been introduced to evaluate intersegmental motion of the foot. In this study, we evaluated the correlation between static radiographic indices and intersegmental foot motion indices.
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Formal protocol for emergency treatment of ruptured intracranial aneurysms to reduce in-hospital rebleeding and improve clinical outcomes.
J. Neurosurg.
PUBLISHED: 11-19-2014
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OBJECT While the incidence of a recurrent hemorrhage is highest within 24 hours of subarachnoid hemorrhage (SAH) and increases with the severity of the clinical grade, a recurrent hemorrhage can occur anytime after the initial SAH in patients with both good and poor clinical grades. Therefore, the authors adopted a 24-hour-a-day, formal protocol, emergency treatment strategy for patients with ruptured aneurysms to secure the aneurysms as early as possible. The incidences of in-hospital rebleeding and clinical outcomes were investigated and compared with those from previous years when broadly defined early treatment was used (< 3 days of SAH). METHODS During an 11-year period, a total of 1224 patients with a ruptured aneurysm were managed using a strategy of broadly defined early treatment between 2001 and 2004 (Period B, n = 423), a mixture of early or emergency treatment between 2005 and 2007, and a formal emergency treatment protocol between 2008 and 2011 (Period A, n = 442). Propensity score matching was used to adjust the differences in age, sex, modified Fisher grade, World Federation of Neurosurgical Societies (WFNS) clinical grade at admission, size and location of a ruptured aneurysm, treatment modality (clip placement vs coil embolization), and time interval from SAH to admission between the two time periods. The matched cases were allotted to Group A (n = 280) in Period A and Group B (n = 296) in Period B and then compared. RESULTS During Period A under the formal emergency treatment protocol strategy, the catheter angiogram, endovascular coiling, and surgical clip placement were started at a median time from admission of 2.0 hours, 2.9 hours, and 3.1 hours, respectively. After propensity score matching, Group A showed a significantly reduced incidence of in-hospital rebleeding (2.1% vs 7.4%, p = 0.003) and a higher proportion of patients with a favorable clinical outcome (modified Rankin Scale score 0-3) at 1 month (87.9% vs 79.7%, respectively; p = 0.008). In particular, the patients with good WFNS grades in Group A experienced significantly less in-hospital rebleeding (1.7% vs 5.7%, respectively; p = 0.018) and better clinical outcomes (1-month mRS score of 0-3: 93.8% vs 87.7%, respectively; p = 0.021) than the patients with good WFNS grades in Group B. CONCLUSIONS Patients with ruptured aneurysms may benefit from a strategy of emergency application of surgical clip placement or endovascular coiling due to the reduced incidence of recurrent bleeding and improved clinical outcomes.
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Can Pelvic Floor Muscle Training Improve Sexual Function in Women with Pelvic Organ Prolapse? A Randomized Controlled Trial.
J Sex Med
PUBLISHED: 11-18-2014
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Pelvic floor muscle training (PFMT) has level 1 evidence of reducing the size and symptoms associated with pelvic organ prolapse (POP). There is scant knowledge, however, regarding whether PFMT has an effect on sexual function.
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Evaluation of the Protective Effect of Silibinin in Rats with Liver Damage Caused by Itraconazole.
Cell Biochem. Biophys.
PUBLISHED: 11-15-2014
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Itraconazole (ITZ) belongs to the triazole group of antifungals with potent keratinophilic and lipophilic features. Hepatotoxicity is one of its most remarkable features. Silibinin (SIL) is a plant used worldwide which is used in the treatment of many liver diseases and it is especially very well known for its hepatoprotective-cytoprotective effect. The aim of our study was to research the protective effect of SIL in ITZ-induced hepatotoxicity using biochemical and pathological tests. Liver enzymes and antioxidant enzyme activities were measured spectrophotometrically by using commercial kits. ALT and AST levels in ITZ group were significantly increased compared to the group, while the activities of GSH-Px and SOD had decreased (p < 0.05). When ITZ group was compared to ITZ + SIL group, AST, ALT, and levels of NO and MPO were significantly decreased, while the activities of GSH-Px and SOD were increased (p < 0.05). Histopathological evaluation showed that SIL significantly decreased periportal inflammation and parenchymal hepatocyte apoptosis in ITZ and ITZ + SIL groups (p < 0.05). Eventhough not statistically significant, partial improvement with the use of SIL has been detected (p > 0.05) in hepatocyte degeneration and multinuclear giant cell formation. According to the evaluation performed with comet assay method, ITZ leads to DNA damage, and the use of SIL significantly decreases DNA damage (p < 0.05). We have detected that the use of ITZ increases oxidative stress (MPO, NO), decreases antioxidant activity (SOD and GSH-Px), and leads to DNA damage and histopathological liver damage, whereas the use of SIL has a cytoprotective effect on the liver by increasing the antioxidant effect (SOD, GSH-Px) and by decreasing the oxidative stress (NO, MPO). ITZ causes the generation of ROS and leads to DNA damage and liver damage. SIL has a cytoprotective effect on the liver by increasing antioxidant enzyme activities, preventing the formation of ROS.
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Should magnetic resonance imaging or computed tomography be the primary brain imaging modality in the transient ischemic attack clinic?
JRSM Open
PUBLISHED: 11-01-2014
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The Royal College of Physicians and National Institute of Clinical Excellence have recommended that magnetic resonance imaging should be the modality of choice for cerebral imaging in transient ischemic attack patients. However, implementation of this is often difficult. Therefore, it is important to know whether magnetic resonance imaging contributes significantly to early clinical management in transient ischemic attack patients.
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Activation of ACLY by mTOR Signal Induces Disturbed Lipid Metabolism in HBV Pre-S2 Mutant Tumorigenesis.
J. Virol.
PUBLISHED: 10-24-2014
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The development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) has been found to be associated with disturbed lipid metabolism. To elucidate the role of lipid metabolism in HBV tumorigenesis, we investigated the dynamic pattern of lipid metabolism in HBV pre-S2 mutant-induced tumorigenesis. Lipid and gene expression profiles were analyzed in an in vitro culture system and in transgenic mice livers harboring HBV pre-S2 mutant. The pre-S2 mutant transgenic livers showed a biphasic pattern of lipid accumulation, starting from mild fatty change in early (1 month) transgenic livers, which subsided and then remarkably increased in HCC tissues. This biphasic pattern was synchronized with ATP citrate lyase (ACLY) activation. Further analyses revealed that the pre-S2 mutant initiated an endoplasmic reticulum (ER) stress-dependent mammalian target of rapamycin (mTOR) signal cascade. The pre-S2 mutant-induced mTOR signal activated the sterol regulatory element binding transcription factor 1 (SREBF1) to upregulate ACLY, which then activated the fatty acid desaturase 2 (FADS2) mediated through ACLY-dependent histone acetylation. Such an ER stress-dependent mTOR signal cascade is also important for the proliferation of hepatocytes in vitro and is further validated in HBV-related HCC tissues.
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Primary fallopian tube carcinoma diagnosed with endoscopic ultrasound elastography with fine needle biopsy.
Clin Endosc
PUBLISHED: 09-30-2014
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Primary fallopian tube carcinoma (PFTC) is a rare gynecological cancer that is very difficult to diagnose preoperatively. Here, we report the case of a 66-year-old female patient with PFTC that was diagnosed preoperatively on the basis of the characteristic features on endoscopic ultrasound (EUS) elastography and fine needle biopsy (FNB). EUS showed a sausage-shaped hypoechoic mass, 8 cm in size, with irregular margins and heterogeneous internal echoes extending to both adnexa. EUS elastography revealed that the mass had a blue color pattern, representing hard stiffness, and a heterogeneous green/red color pattern distributed outside the tumor, representing intermediate stiffness. Histopathologic analysis of the FNB and operative specimens confirmed the diagnosis of fallopian tube carcinoma. This is the first reported case of a combined EUS elastography and FNB of an adnexal mass leading to a preoperative diagnosis of fallopian tube carcinoma.
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G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Increases A?42/A?40 Ratio and Elevates ER Ca(2+) Accumulation.
Mol. Neurobiol.
PUBLISHED: 09-24-2014
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Early-onset familial Alzheimer's disease (AD) is most commonly associated with the mutations in presenilin-1 (PS1). PS1 is the catalytic component of the ?-secretase complex, which cleaves amyloid precursor protein to produce amyloid-? (A?), the major cause of AD. Presenilin enhancer 2 (Pen2) is critical for activating ?-secretase and exporting PS1 from endoplasmic reticulum (ER). Among all the familial AD-linked PS1 mutations, mutations at the G206 amino acid are the most adjacent position to the Pen2 binding site. Here, we characterized the effect of a familial AD-linked PS1 G206D mutation on the PS1-Pen2 interaction and the accompanied alteration in ?-secretase-dependent and -independent functions. We found that the G206D mutation reduced PS1-Pen2 interaction, but did not abolish ?-secretase formation and PS1 endoproteolysis. For ?-secretase-dependent function, the G206D mutation increased A?42 production but not Notch cleavage. For ?-secretase-independent function, this mutation disrupted the ER calcium homeostasis but not lysosomal calcium homeostasis and autophagosome maturation. Impaired ER calcium homeostasis may due to the reduced mutant PS1 level in the ER. Although this mutation did not alter the cell survival under stress, both increased A?42 ratio and disturbed ER calcium regulation could be the mechanisms underlying the pathogenesis of the familial AD-linked PS1 G206D mutation.
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Primary epiphyseal osteomyelitis caused by mycobacterium species in otherwise healthy toddlers.
J Bone Joint Surg Am
PUBLISHED: 09-05-2014
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Mycobacterial osteomyelitis involving only the epiphysis of a long bone is extremely rare, and its clinical and radiographic features remain unclear. The purpose of this study was to characterize mycobacterial epiphyseal osteomyelitis and to identify differences between its features and those reported for epiphyseal osteomyelitis caused by bacteria or unidentified pathogens.
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Draft Genome Sequences of the Mycobacterium tuberculosis Clinical Strains A2 and A4, Isolated from a Relapse Patient in Taiwan.
Genome Announc
PUBLISHED: 09-04-2014
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The recurrence rate of Mycobacterium tuberculosis in Taiwan is 3%. Here, we present the draft genome sequences of M. tuberculosis strains A2 and A4 from a relapse patient. The draft genome sequences comprise 4,443,031 bp and 4,487,096 bp, revealing 4,220 and 4,143 coding sequences for A2 and A4, respectively, as well as 49 tRNA genes for the both isolates.
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Bone mineral density is not associated with musculoskeletal pain in postmenopausal Korean women aged ?50 years.
Clin. Rheumatol.
PUBLISHED: 09-03-2014
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Although many studies reported improvement of back pain after osteoporosis treatment, there is insufficient evidence to determine whether osteoporosis is painful. We investigated whether bone mineral density correlated with musculoskeletal pain in postmenopausal Korean women aged ?50 years. Data for postmenopausal women aged ?50 years were obtained from the fifth Korea National Health and Nutrition Examination Survey database. Demographics, Kellgren-Lawrence grade, and numeric rating scale for pain in the hip and knee joints, presence of back pain, and activity level were analyzed. Only subjects with dual-energy X-ray absorptiometry scans and hip and knee radiographs were included. Those with malignancy, pain medication use, or a history of fragility fractures were excluded. After univariate analysis, multiple linear regression analysis was performed to examine the significant factors correlated with the degree of hip and knee pain. Binary logistic regression analysis was performed to identify factors significantly associated with the presence of back pain. In total, 387 women were included in the data analysis. Age (p?=?0.005) was the only significant factor correlated with the intensity of hip pain, while Kellgren-Lawrence grade (p?
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Outcomes of two different incision techniques for surgical treatment of stress urinary incontinence with concomitant anterior vaginal wall prolapse.
World J Urol
PUBLISHED: 08-31-2014
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To assess the outcomes of two different incision techniques used in the surgical treatment of stress urinary incontinence (SUI) with concomitant anterior vaginal wall prolapse and to identify possible associated risk factors with a medium-term follow-up in patients who underwent TOT procedure.
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Dissolution and bioavailability of lercanidipine-hydroxypropylmethyl cellulose nanoparticles with surfactant.
Int. J. Biol. Macromol.
PUBLISHED: 08-23-2014
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The objective of this study was to develop lercanidipine-hydroxypropylmethyl cellulose (HPMC) nanoparticles with high oral bioavailability. The lercanidipine-HPMC nanoparticles with/without surfactants were manufactured using a supercritical antisolvent (SAS) process. Gelucire 44/14, poloxamer 407, and d-?-tocopheryl polyethylene glycol 1000 succinate (TPGS) were evaluated as surfactants. Spherical lercanidipine-HPMC nanoparticles with a mean particle size less than 400nm were successfully prepared using a SAS process. The dissolution and oral bioavailability of lercanidipine was significantly increased by addition of surfactants. Especially lercanidipine-HPMC nanoparticles with TPGS showed a 2.47-fold higher oral bioavailability than raw material. Furthermore, the dissolution efficiency was strongly correlated to the in vivo Cmax and AUC0?24h. Therefore, the preparation of HPMC nanoparticles with TPGS using a SAS process is a highly effective formulation strategy for enhanced oral bioavailability of lercanidipine.
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Initial experience of integrated PET/MR mammography in patients with invasive ductal carcinoma.
Hell J Nucl Med
PUBLISHED: 08-18-2014
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The purpose of this study was to evaluate the feasibility of integrated fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance ((18)F-FDG PET/MR) mammography in invasive ductal carcinoma (IDC) patients. From August 2012 to March 2013, we enrolled 42 consecutive breast cancer patients who received whole- body PET/MR and subsequent PET/MR mammography by an integrated PET/MR scanner and were scheduled for surgery within 2 weeks after the of scan. On the whole body PET/MR, 2-point Dixon VIBE, coronal T1w image, axial T2w image, and post-contrast T1 sequences were acquired with simultaneous PET acquisition. For PET/MR mammography, T1w, T2w, and dynamic contrast-enhancement (DCE) sequences were acquired using a breast coil during simultaneous PET acquisition. We compared the detectability of the lesions between whole-body PET/MR and PET/MR mammography. Forty-eight IDC (1.89±1.19cm of width) were diagnosed in 42 women. Lesion conspicuity in (18)F-FDG PET was equivalent between whole-body PET/MR and PET/MR mammography; both PET/MR images showed 38 hypermetabolic masses. In the analysis of 10 IDC with <1.0cm wide lesions, only 1 IDC showed (18)F-FDG uptake, and 4 IDC were noted on whole-body PET/MR; however, all 10 IDC showed a depictable mass on PET/MR mammography. In the analysis of 38 IDC >1.0cm wide, 37 IDC showed (18)F-FDG uptake, and 38 IDC were detected on both whole-body PET/MR and PET/MR mammography. The overall sensitivity was 79.2% (38/48) on PET, 87.5% (42/48) on whole-body PET/MR, and 100% on PET/MR mammography. The SUV between whole-body PET/MR and PET/MR mammography showed strong and highly significant correlation (r=0.987, P<0.001). In conclusion, our results, although in a limited number of cases show that integrated PET/MR mammography is feasible and has the advantage of combining high-resolution breast images with metabolic images. Furthermore, PET/MR mammography could provide an accurate diagnosis in case of IDC that are less than 1cm in size.
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Characteristics and osteogenic effect of zirconia porous scaffold coated with ?-TCP/HA.
J Adv Prosthodont
PUBLISHED: 08-14-2014
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The purpose of this study was to evaluate the properties of a porous zirconia scaffold coated with bioactive materials and compare the in vitro cellular behavior of MC3T3-E1 preosteoblastic cells to titanium and zirconia disks and porous zirconia scaffolds.
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Risk factors for postoperative infectious complications following percutaneous nephrolithotomy: a prospective clinical study.
Urolithiasis
PUBLISHED: 08-07-2014
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The aim of the study was to assess the preoperative and intraoperative potential risk factors for infectious complications after percutaneous nephrolithotomy (PCNL). A total of 303 patients who underwent PCNL for renal stones were included in the recent study. A detailed history including past renal surgery, nephrostomy insertion and recurrent urinary infection were obtained from all patients. Preoperative urine culture, renal pelvic urine culture and stone culture were obtained from all patients. The intraoperative data were prospectively noted. All patients were followed up postoperatively for signs of systemic inflammatory response syndrome (SIRS) and sepsis. In 83 (27.4 %) of the patients, SIRS was observed and of these patients 23 (7.6 %) were diagnosed as sepsis. Escherichia coli was the most common organism detected in cultures, followed by Pseudomonas aeruginosa, Enterococcus and Klebsiella spp. in all patients. By multivariate logistic regression analysis, presence of infection stone, stone burden and recurrent urinary tract infection were associated with both SIRS and sepsis development. Presence of infection stone, stone burden ?800 mm(2) and recurrent urinary tract infection can be identified as independent predictors for the development of SIRS and sepsis.
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Incidental findings on knee radiographs in children and adolescents.
Clin Orthop Surg
PUBLISHED: 08-05-2014
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Despite the wide use of knee radiography in children and adolescent patients visiting the outpatient clinic, there has been no analysis about the prevalence and type of incidental findings yet. This study was performed to investigate the incidental findings on knee radiographs in children and adolescents according to age.
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Early dexamethasone treatment exacerbates enterovirus 71 infection in mice.
Virology
PUBLISHED: 08-05-2014
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Enterovirus 71 (EV71) infection can induce encephalitis. Overt immune responses is suspected to cause severe symptoms, so anti-inflammatory agents, corticosteroids have been recommended for treatment. However, one clinical study reported that treatment with glucocorticoids, dexamethasone (Dex) exacerbates disease severity. Here we investigated Dex treatment on EV71 infection using the murine model and found that both long-term (14-day) and short-term (4-day) Dex treatment starting from 1 or 3 days postinfection increased the mortality and disease severity of infected mice. Dex treatment starting from 4 or 8 days postinfection did not affect mouse mortality and disease severity. Early Dex treatment starting from 1 day postinfection caused atrophy and enhanced apoptosis in lymphoid organs to decrease the numbers of lymphocytes (CD4(+) T cells, CD8(+) T cells, and CD19(+) B cells) and to increase viral loads in infected tissues of mice. Our results demonstrate that Dex treatment has no beneficial effect on EV71 infection.
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Recurrence of Equinus Foot Deformity After Tendo-Achilles Lengthening in Patients With Cerebral Palsy.
J Pediatr Orthop
PUBLISHED: 07-31-2014
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Recurrence of equinus deformity after surgery is common in patients with cerebral palsy. This retrospective study was undertaken to estimate the recurrence rate of the equinus deformity after tendo-Achilles lengthening (TAL) in patients with cerebral palsy and to investigate the risk factors associated with the recurrence.
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Development of a population pharmacokinetic model to describe olmesartan medoxomil/ hydrochlorothiazide (20/12.5 mg) FDC tablet in male healthy South Korean subjects.
Int J Clin Pharmacol Ther
PUBLISHED: 07-31-2014
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The objective of the present study was to develop population pharmacokinetic models for olmesartan medoxomil and hydrochlorothiazide and to investigate the influence of demographic factors on these population pharmacokinetics.
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Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis.
Autophagy
PUBLISHED: 07-25-2014
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Autophagy and microRNA (miRNA) are important regulators during cancer cell tumorigenesis. Impaired autophagy and high expression of the oncogenic microRNA MIR224 are prevalent in hepatocellular carcinoma (HCC); however, the relationship between the 2 phenomena remains elusive. In this study, we are the first to reveal that autophagy selectively regulates MIR224 expression through an autophagosome-mediated degradation system. Based on this finding, we further demonstrated that in hepatitis B virus (HBV)-related HCC, aberrant autophagy (low autophagic activity) results in accumulation of MIR224 and decreased expression of the target gene Smad4, which leads to increased cell migration and tumor formation. Preferential recruitment of MIR224 into the autophagosome was clearly demonstrated by a) miRNA in situ hybridization under confocal microscopy, and b) immunogold labeling of MIR224 under electron microscopy compared with a ubiquitously expressed microRNA MIRlet7e/let-7. Furthermore, we found that off-label use of amiodarone, an antiarrhythmic agent, effectively suppressed HCC tumorigenesis through autophagy-mediated MIR224 degradation both in vitro and in vivo. In summary, we identified amiodarone as a new autophagy inducer, which may provide an alternative approach in HCC therapy through a novel tumor suppression mechanism.
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Incidence and Risk Factors of Allograft Bone Failure After Calcaneal Lengthening.
Clin. Orthop. Relat. Res.
PUBLISHED: 07-13-2014
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Calcaneal lengthening with allograft is frequently used for the treatment of patients with symptomatic planovalgus deformity; however, the behavior of allograft bone after calcaneal lengthening and the risk factors for graft failure are not well documented.
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Percutaneous Epiphysiodesis Using Transphyseal Screws in the Management of Leg Length Discrepancy: Optimal Operation Timing and Techniques to Avoid Complications.
J Pediatr Orthop
PUBLISHED: 07-01-2014
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Percutaneous epiphysiodesis using transphyseal screws (PETS) has been used to manage leg length discrepancy (LLD) in growing children. The purposes of this study were to analyze effects of PETS on LLD, its associated complications, to determine optimal operation timing, and find ways of preventing complications.
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Proximal Migration of Femoral Telescopic Rod in Children With Osteogenesis Imperfecta.
J Pediatr Orthop
PUBLISHED: 06-12-2014
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Intramedullary telescopic rod fixation has been used for stabilization of the long bones in growing children who have osteogenesis imperfecta. Proximal migration of the rod is the most common complication of telescopic rodding in the femur. The purposes of this study were to evaluate incidence and temporal pattern of proximal migration of the femoral rod, and to investigate factors related to it.
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Determining the best treatment for coronal angular deformity of the knee joint in growing children: a decision analysis.
Biomed Res Int
PUBLISHED: 06-05-2014
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This study aimed to determine the best treatment modality for coronal angular deformity of the knee joint in growing children using decision analysis. A decision tree was created to evaluate 3 treatment modalities for coronal angular deformity in growing children: temporary hemiepiphysiodesis using staples, percutaneous screws, or a tension band plate. A decision analysis model was constructed containing the final outcome score, probability of metal failure, and incomplete correction of deformity. The final outcome was defined as health-related quality of life and was used as a utility in the decision tree. The probabilities associated with each case were obtained by literature review, and health-related quality of life was evaluated by a questionnaire completed by 25 pediatric orthopedic experts. Our decision analysis model favored temporary hemiepiphysiodesis using a tension band plate over temporary hemiepiphysiodesis using percutaneous screws or stapling, with utilities of 0.969, 0.957, and 0.962, respectively. One-way sensitivity analysis showed that hemiepiphysiodesis using a tension band plate was better than temporary hemiepiphysiodesis using percutaneous screws, when the overall complication rate of hemiepiphysiodesis using a tension band plate was lower than 15.7%. Two-way sensitivity analysis showed that hemiepiphysiodesis using a tension band plate was more beneficial than temporary hemiepiphysiodesis using percutaneous screws.
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A genetically attenuated malaria vaccine candidate based on P. falciparum b9/slarp gene-deficient sporozoites.
Elife
PUBLISHED: 06-04-2014
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A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can be achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated by radiation or under anti-malarial drug coverage. Immunization with genetically attenuated parasites (GAP) would be an attractive alternative approach. Here we present data on safety and protective efficacy using sporozoites with deletions of two genes i.e. the newly identified b9 and slarp, which govern independent and critical processes for successful liver-stage development. In the rodent malaria model, Pb?b9?slarpGAP was completely attenuated showing no breakthrough infections while efficiently inducing high level protection. The human Pf?b9?slarpGAP generated without drug-resistance markers were infective to human hepatocytes in vitro and to humanized mice engrafted with human hepatocytes in vivo but completely aborted development after infection. These findings support the clinical development of a Pf?b9?slarpSPZ vaccine.
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Preparation and evaluation of solid dispersion of atorvastatin calcium with Soluplus® by spray drying technique.
Chem. Pharm. Bull.
PUBLISHED: 06-03-2014
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The aim of the present study was to investigate the effect of Soluplus® on the solubility of atorvastatin calcium and to develop a solid dispersion formulation that can improve the oral bioavailability of atorvastatin calcium. We demonstrated that Soluplus® increases the aqueous solubility of atorvastatin calcium. Several solid dispersion formulations of atorvastatin calcium with Soluplus® were prepared at various drug?:?carrier ratios by spray drying. Physicochemical analysis demonstrated that atorvastatin calcium is amorphous in each solid dispersion, and the 2?:?8 drug?:?carrier ratio provided the highest degree of sustained atorvastatin supersaturation. Pharmacokinetic analysis in rats revealed that the 2?:?8 dispersion significantly improved the oral bioavailability of atorvastatin. This study demonstrates that spray-dried Soluplus® solid dispersions can be an effective method for achieving higher atorvastatin plasma levels.
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Development of a pharmacokinetic/pharmacodynamic/disease progression model in NC/Nga mice for development of novel anti-atopic dermatitis drugs.
Xenobiotica
PUBLISHED: 05-30-2014
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Abstract 1.?JHL45, a novel immune modulator against atopic dermatitis (AD), was synthesized from decursin isolated from Angelica gigas. The goal is to evaluate the lead compound using quantitative modeling approaches to novel anti-AD drug development. 2.?We tested the anti-inflammatory effect of JHL45 by in vitro screening, characterized its in vitro pharmacokinetic (PK) properties. The dose-dependent efficacy of JHL45 was developed using a pharmacokinetics/pharmacodynamics/disease progression (PK/PD/DIS) model in NC/Nga mice. 3.?JHL45 has drug-like properties and pharmacological effects when administered orally to treat atopic dermatitis. The developed PK/PD/DIS model described well the rapid metabolism of JHL45, double-peak phenomenon in the PK of decursinol and inhibition of IgE generation by compounds in NC/Nga mice. Also, a quantitative model was developed and used to elucidate the complex interactions between serum IgE concentration and atopic dermatitis symptoms. 4.?Our findings indicate that JHL45 has good physicochemical properties and powerful pharmacological effects when administered orally for treatment of AD in rodents.
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The emerging role of hepatitis B virus Pre-S2 deletion mutant proteins in HBV tumorigenesis.
J. Biomed. Sci.
PUBLISHED: 04-28-2014
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Chronic hepatitis B virus (HBV) infection can cause hepatocellular carcinoma (HCC). Several hypotheses have been proposed to explain the mechanisms of HBV tumorigenesis, including inflammation and liver regeneration associated with cytotoxic immune injuries and transcriptional activators of mutant HBV gene products. The mutant viral oncoprotein-driven tumorigenesis is prevailed at the advanced stage or anti-HBe-positive phase of chronic HBV infection. Besides HBx, the pre-S2 (deletion) mutant protein represents a newly recognized oncoprotein that is accumulated in the endoplasmic reticulum (ER) and manifests as type II ground glass hepatocytes (GGH). The retention of pre-S2 mutant protein in ER can induce ER stress and initiate an ER stress-dependent VEGF/Akt/mTOR and NF?B/COX-2 signal pathway. Additionally, the pre-S2 mutant large surface protein can induce an ER stress-independent pathway to transactivate JAB-1/p27/RB/cyclin A,D pathway, leading to growth advantage of type II GGH. The pre-S2 mutant protein-induced ER stress can also cause DNA damage, centrosome overduplication, and genomic instability. In 5-10% of type II GGHs, there is co-expression of pre-S2 mutant protein and HBx antigen which exhibited enhanced oncogenic effects in transgenic mice. The mTOR signal cascade is consistently activated throughout the course of pre-S2 mutant transgenic livers and in human HCC tissues, leading to metabolic disorders and HCC tumorigenesis. Clinically, the presence of pre-S2 deletion mutants in sera frequently develop resistance to nucleoside analogues anti-virals and predict HCC development. The pre-S2 deletion mutants and type II GGHs therefore represent novel biomarkers of HBV-related HCCs. A versatile DNA array chip has been developed to detect pre-S2 mutants in serum. Overall, the presence of pre-S2 mutants in serum has implications for anti-viral treatment and can predict HCC development. Targeting at pre-S2 mutant protein-induced, ER stress-dependent, mTOR signal cascade and metabolic disorders may offer potential strategy for chemoprevention or therapy in high risk chronic HBV carriers.
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Oral absorption of a valsartan-loaded spray-dried emulsion based on hydroxypropylmethyl cellulose.
Int. J. Biol. Macromol.
PUBLISHED: 04-18-2014
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The aim of this study was to develop a novel valsartan-loaded spray-dried emulsion based on hydroxypropylmethyl cellulose (HPMC) with enhanced oral absorption. The valsartan-loaded redispersible dry emulsion was prepared by using a high-pressure homogenization and spray-drying process with water, Capryol 90, HPMC, and different surfactants, based on the results of the solubility study. The spray-dried emulsions formed small and homogeneous emulsions with a mean droplet emulsion size ranging from 133.5 to 152.5nm at the dispersion state in water. The valsartan-loaded redispersible dry emulsion with HPMC/poloxamer 407 showed enhanced pH-independent valsartan release, resulting in a dramatically enhanced oral bioavailability of valsartan compared to the raw material and commercial product. Therefore, a formulation strategy using the redispersible dry emulsion with HPMC/poloxamer 407 is very effective for the development of a new dosage form containing valsartan.
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Neurofibromin Deficiency-Associated Transcriptional Dysregulation Suggests a Novel Therapy for Tibial Pseudoarthrosis in NF1.
J. Bone Miner. Res.
PUBLISHED: 04-11-2014
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Neurofibromatosis type 1 (NF1) is an autosomal dominant disease caused by mutations in NF1. Among the earliest manifestations is tibial pseudoarthrosis and persistent nonunion after fracture. To further understand the pathogenesis of pseudoarthrosis and the underlying bone remodeling defect, pseudoarthrosis tissue and cells cultured from surgically resected pseudoarthrosis tissue from NF1 individuals were analyzed using whole-exome and whole-transcriptome sequencing as well as genomewide microarray analysis. Genomewide analysis identified multiple genetic mechanisms resulting in somatic bi-allelic NF1 inactivation; no other genes with recurring somatic mutations were identified. Gene expression profiling identified dysregulated pathways associated with neurofibromin deficiency, including phosphoinosital-3-kinase (PI3K) and mitogenactivated protein kinase (MAPK) signaling pathways. Unlike aggressive NF1-associated malignancies, tibial pseudoarthrosis tissue does not harbor a high frequency of somatic mutations in oncogenes or other tumor-suppressor genes, such as p53. However, gene expression profiling indicates pseudoarthrosis tissue has a tumor-promoting transcriptional pattern, despite lacking tumorigenic somatic mutations. Significant overexpression of specific cancer-associated genes in pseudoarthrosis highlights a potential for receptor tyrosine kinase inhibitors to target neurofibromin-deficient pseudoarthrosis and promote proper bone remodeling and fracture healing. © 2014 American Society for Bone and Mineral Research.
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Fibular lengthening for the management of translational talus instability in hereditary multiple exostoses patients.
J Pediatr Orthop
PUBLISHED: 04-08-2014
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Hereditary multiple exostoses (HME) patients frequently present with ankle valgus deformity and marked fibular shortening. Loss of the lateral buttress may cause translational talus instability (TTI) that manifests as ankle pain after physical exercise, medial clear space widening on plain radiographs, and gross translational movement of the talus within the mortise. Among 123 HME patients examined and/or surgically treated, 10 patients (14 ankles) with symptomatic TTI underwent fibular lengthening with osteochondroma excision. Twelve ankles of 9 patients were followed for >1 year after surgery. Total fibular length gain averaged 15.3 mm and distal migration of the distal fibular fragment averaged 5.5 mm. The mean medial clear space decreased from preoperative 6.7 mm to postlengthening 3.5 mm. Gross instability of the talus within the ankle mortise disappeared in all cases. AOFAS ankle-hindfoot score improved from preoperative 80.3 to 97.3 at the latest follow-up. The current study showed the fibular lengthening improved lateral ankle stability by providing lateral buttress on the talus and providing favorable short-term result by ameliorating exercise-induced ankle pain in TTI of HME. The authors carefully conclude that TTI is a rare but potentially disabling condition in HME patients, requiring special attention during follow-up of HME patients.
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Induction of apurinic endonuclease 1 overexpression by endoplasmic reticulum stress in hepatoma cells.
Int J Mol Sci
PUBLISHED: 04-07-2014
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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Previous studies have noted the induction of endoplasmic reticulum stress or apurinic endonuclease 1 (APE1) expression in many tumors. Therefore, the aim of this study was to investigate the relationship between endoplasmic reticulum (ER stress) and APE1 in hepatocellular carcinoma. Here we investigate the expression of APE1 during ER stress in HepG2 and Huh-7 cell lines. Tunicamycin or brefeldin A, two ER stress inducers, increased APE1 and GRP78, an ER stress marker, expression in HepG2 and Huh-7 cells. Induction of APE1 expression was observed through transcription level in response to ER stress. APE1 nuclear localization during ER stress was determined using immunofluorescence assays in HepG2 cells. Furthermore, expression of Hepatitis B virus pre-S2? large mutant surface protein (pre-S2?), an ER stress-induced protein, also increased GRP78 and APE1 expression in the normal hepatocyte NeHepLxHT cell line. Similarly, tumor samples showed higher expression of APE1 in ER stress-correlated liver cancer tissue in vivo. Our results demonstrate that ER stress and HBV pre-S2? increased APE1 expression, which may play an important role in resistance to chemotherapeutic agents or tumor development. Therefore, these data provide an important chemotherapeutic strategy in ER stress and HBV pre-S2?-associated tumors.
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Comparison of orthopaedic manifestations of multiple epiphyseal dysplasia caused by MATN3 versus COMP mutations: a case control study.
BMC Musculoskelet Disord
PUBLISHED: 03-05-2014
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Multiple epiphyseal dysplasia (MED) is a relatively common skeletal dysplasia mainly involving the epiphyses of the long bones. However, it is a genetically heterogeneous group of diseases sharing certain aspects of the radiologic phenotype. In surveys conducted in East Asia, MATN3 was the most common causative gene, followed by COMP. In this study, the authors compared clinical manifestation of MED patients caused by MATN3 and COMP gene mutations, as well as subsequent orthopaedic interventions.
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Does concomitant vaginal prolapse repair affect the outcomes of the transobturator tape procedure in the long term?
Int Urogynecol J
PUBLISHED: 02-27-2014
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Little information is available on the effects of concomitant vaginal prolapse repair on the outcomes of the transobturator tape (TOT) procedure. The purpose of this study is to assess the results and complications of TOT when combined with vaginal prolapse repair with a long-term follow-up.
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Is endoscopic retrograde cholangiopancreatography safe in patients 90 years of age and older?
Gut Liver
PUBLISHED: 02-24-2014
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This case-control study evaluated the safety and efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in patients 90 years of age and older.
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Rectus femoris transfer in cerebral palsy patients with stiff knee gait.
Gait Posture
PUBLISHED: 02-19-2014
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Although several studies have reported on the outcomes of rectus femoris transfer (RFT), few have investigated the multiple factors that could affect the results. Therefore, we evaluated the outcomes of RFT and analyzed factors that influence improvement and annual change in knee motion after surgery in patients with cerebral palsy (CP).
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Determining the best treatment for simple bone cyst: a decision analysis.
Clin Orthop Surg
PUBLISHED: 02-14-2014
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The treatment of simple bone cysts (SBC) in children varies significantly among physicians. This study examined which procedure is better for the treatment of SBC, using a decision analysis based on current published evidence.
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A survey of the satisfaction of patients who have undergone implant surgery with and without employing a computer-guided implant surgical template.
J Adv Prosthodont
PUBLISHED: 02-12-2014
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This study aims to investigate the degree of subjective pain and the satisfaction of patients who have undergone an implant treatment using a computer-guided template.
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Dissolution and oral absorption of pranlukast nanosuspensions stabilized by hydroxypropylmethyl cellulose.
Int. J. Biol. Macromol.
PUBLISHED: 02-12-2014
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The objective of this study was to investigate the effect of particle size on the dissolution and oral absorption of pranlukast microsuspensions and nanosuspensions stabilized by hydroxypropylmethyl cellulose. Four pranlukast suspensions with different mean particle sizes (0.16, 0.89, 3.13, and 18.21?m) were prepared by various top-down processes such as jet milling, high pressure homogenization, and bead milling. The dissolution rate and oral absorption of pranlukast suspensions were significantly affected by the particle size. The in vivo pharmacokinetic parameters of pranlukast suspensions were increased with decreasing mean particle size of suspensions. Especially, the AUC0?24h and Cmax values of pranlukast nanosuspension with a particle size of 0.16?m were approximately 3.5- and 6.3-fold greater, respectively, than that of pranlukast microsuspension with a particle size of 18.21?m. Therefore, the preliminary results from our study suggest that a pranlukast nanosuspension with a mean particle size of about 0.16?m may have significant potential for clinical application.
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Minipigs as an animal model for dermal vaccine delivery.
Comp. Med.
PUBLISHED: 02-12-2014
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Appropriate animal models for intradermal vaccine delivery are scarce. Given the high similarity of their skin anatomy to that of humans, minipigs may be a suitable model for dermal vaccine delivery. Here we describe the immunization of Göttingen minipigs by using intradermal and intramuscular delivery of hepatitis B surface antigen (HBsAg). Intradermal vaccine delivery by needle and syringe and by needle-free jet injection induced humoral antiHBsAg responses. Priming immunization by using the disposable syringe jet injector (DSJI) resulted in a higher antibody titer than did conventional intradermal immunization and a titer comparable to that after intramuscular vaccination with HBsAg and Al(OH)3 adjuvant. This study highlights the utility of the minipig model in vaccine studies assessing the efficacy of conventional and novel methods of dermal delivery. Moreover, we include suggestions regarding working with minipigs during dermal vaccine delivery studies, thereby fostering future work in this area of vaccinology.
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Pleural mesothelioma: an institutional experience of 66 cases.
Korean J Pathol
PUBLISHED: 02-07-2014
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Malignant mesothelioma of the pleura is an aggressive tumor known to be associated with asbestos. Histological diagnosis of mesothelioma is challenging and is usually aided by immunohistochemical markers.
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Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development.
FASEB J.
PUBLISHED: 02-07-2014
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The 10 Plasmodium 6-Cys proteins have critical roles throughout parasite development and are targets for antimalaria vaccination strategies. We analyzed the conserved 6-cysteine domain of this family and show that only the last 4 positionally conserved cysteine residues are diagnostic for this domain and identified 4 additional "6-Cys family-related" proteins. Two of these, sequestrin and B9, are critical to Plasmodium liver-stage development. RT-PCR and immunofluorescence assays show that B9 is translationally repressed in sporozoites and is expressed after hepatocyte invasion where it localizes to the parasite plasma membrane. Mutants lacking B9 expression in the rodent malaria parasites P. berghei and P. yoelii and the human parasite P. falciparum developmentally arrest in hepatocytes. P. berghei mutants arrest in the livers of BALB/c (100%) and C57BL6 mice (>99.9%), and in cultures of Huh7 human-hepatoma cell line. Similarly, P. falciparum mutants while fully infectious to primary human hepatocytes abort development 3 d after infection. This growth arrest is associated with a compromised parasitophorous vacuole membrane a phenotype similar to, but distinct from, mutants lacking the 6-Cys sporozoite proteins P52 and P36. Our results show that 6-Cys proteins have critical but distinct roles in establishment and maintenance of a parasitophorous vacuole and subsequent liver-stage development.
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A Case Report of IgG4-Related Disease Clinically Mimicking Pleural Mesothelioma.
Tuberc Respir Dis (Seoul)
PUBLISHED: 01-29-2014
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An immunoglobulin G4 (IgG4)-related disease is a recently emerging entity, and a few cases of IgG4-related disease in lung and pleura have been reported. Herein, we report the case of a 74-year-old man with IgG4-related disease of lung and pleura, clinically suspicious of malignant mesothelioma. Chest computed tomography showed diffuse nodular pleural thickening, and microscopic finding disclosed diffuse thickening of visceral pleura with infiltrations of many lymphoplasma cells with increased number of IgG4-positive plasma cells and a few multinucleated giant cells. It is important for pathologists and clinicians to recognize this rare entity and its histologic finding, because it can be confused with malignant tumors on the radiologic examination although it can be treated with steroid therapy.
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Two cases of glomus tumor arising in large airway: well organized radiologic, macroscopic and microscopic findings.
Tuberc Respir Dis (Seoul)
PUBLISHED: 01-29-2014
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Glomus tumors of the lung are rare benign neoplasm, originating from modified smooth muscle cells. The patients are usually presented with no or non-specific symptoms such as cough, dyspnea or hemoptysis. Although surgical treatment is considered as the treatment of choice, the endobronchial therapy can be applied to the patients who are unfit for surgical excision. Herein, we describe two rare cases of glomus tumor originated at large airway (trachea and main bronchus) without respiratory symptoms and review their characteristic radiologic, macroscopic and pathological features.
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Residual bone height measured by panoramic radiography in older edentulous Korean patients.
J Adv Prosthodont
PUBLISHED: 01-24-2014
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The aim of this study was to obtain statistical data on the residual bone height at different natural tooth positions by panoramic radiography in edentulous Korean patients aged 60-90 years.
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Penile fracture with bilateral corporeal rupture without urethral involvement.
Can Urol Assoc J
PUBLISHED: 01-24-2014
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Concomitant urethral injury is rare in penile fracture. We report the case of a 34-year-old male who presented to the emergency department 12 hours after a blunt self-injury of the penis. Physical examination revealed a swollen, ecchymotic, and deviated circumcised penis without blood at the meatus. The fracture line extending along the bilateral corpora without urethral involvement was seen intraoperatively. The fracture side was repaired primarily. The patient healed and recovered without complication. To our knowledge, this is the second reported case of bilateral corporeal rupture without urethral involvement.
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Extrapulmonary lymphangioleiomyoma: clinicopathological analysis of 4 cases.
Korean J Pathol
PUBLISHED: 01-15-2014
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Lymphangioleiomyomatosis (LAM) is a slowly progressive neoplastic disease that predominantly affects females. Usually, LAM affects the lung; it can also affect extrapulmonary sites, such as the mediastinum, the retroperitoneum, or the lymph nodes, although these locations are rare. A localized form of LAM can manifest as extrapulmonary lesions; this form is referred to as extrapulmonary lymphangioleiomyoma (E-LAM). Due to the rare occurrence of E-LAM and its variable, atypical location, E-LAM is often difficult to diagnose. Herein, we report the clinicopathological information from four E-LAM cases, and also review previous articles investigating this disease.
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Incidence of pulmonary non-epithelial tumors: 18 years' experience at a single institute.
Pathol. Res. Pract.
PUBLISHED: 01-11-2014
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Primary and metastatic non-epithelial tumors of the lung and pleura (NETs-LP) are presumed to represent a small proportion of pulmonary neoplasm, and their epidemiologic characterization is lacking. Moreover, classification of pulmonary mesenchymal tumor according to 'WHO Classification of Tumors of Lung and Pleura' (2004) is simple and necessary to give a supplementation like new 'WHO Classification of Tumors of Soft Tissue and Bone' (2013). Non-epithelial tumors of the lung and pleura diagnosed from January 1995 to April 2013 were retrospectively reviewed and classified in accordance with 'WHO Classification of Tumors of Soft Tissue and Bone' (2013). Of 681 cases represented in the study, smooth muscle tumor (13.1%) was most common, and tumor of uncertain differentiation (10.5%) and fibroblastic/myofibroblastic tumor (5.7%) were followed. Smooth muscle tumor (12.6%) was the common primary tumor, whereas chondrogenic or osteogenic tumor (21.6%) was common in metastatic ones. Pulmonary vascular sarcoma (n=15) was the most frequent primary pulmonary sarcoma with following synovial sarcoma (n=9) and malignant type of solitary fibrous tumor (n=9). This study is the first trial of epidemiologic investigation in Korea about NETs-LP, indirectly representing their incidence in Korea and northeast Asia, and we hope that this presentation offers guidance in further study of NETs-LP.
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Usual interstitial pneumonia with lung cancer: clinicopathological analysis of 43 cases.
Korean J Pathol
PUBLISHED: 01-08-2014
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Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.
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Epithelial-myoepthelial carcinoma of the tracheobronchial tree: the prognostic role of myoepithelial cells.
Lung Cancer
PUBLISHED: 01-07-2014
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Epithelial myoepithelial carcinoma (EMC) of the lung is a very rare tumor that is characterized by biphasic differentiation of epithelial and myoepithelial cells. Current discussion about this entity focuses on the malignant potential of the tumor and the role of myoepithelial cells in diagnosis and patient prognosis. This study reports five EMC cases in the lung and discusses issues related to EMC prognosis.
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Pleural epithelioid hemangioendothelioma harboring CAMTA1 rearrangement.
Lung Cancer
PUBLISHED: 01-07-2014
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Pleural epithelioid hemangioendothelioma (EHE) is a very rare disease with adverse clinical outcomes. Recently, CAMTA1 rearrangement has been introduced as a consistent genetic abnormality in EHEs of different anatomical locations. We report a 71-year-old man with pleural EHE harboring CAMTA1 rearrangement confirmed by fluorescence in situ hybridization on paraffin embedded tissue.
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The role of the right inferior frontal gyrus in the pathogenesis of post-stroke psychosis.
J. Neurol.
PUBLISHED: 01-03-2014
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Psychotic symptoms have previously been reported following right hemisphere brain injury. We sought to identify the specific neuroanatomical basis of delusions following stroke by studying a series of patients with post-stroke psychosis. Lesion overlap analysis was conducted on three individuals with delusions following right hemisphere stroke. These cases were compared with a control group of patients with similar anatomical damage. The main outcome measures were presence of delusions and presence of behavioural susceptibility. The right inferior frontal gyrus and underlying white matter, including the superior longitudinal fasciculus and anterior corona radiata, were involved in all three cases. All three had a preexisting untreated psychiatric disorder. In contrast, only one of nine control cases with equivalent lesions had evidence of previous psychiatric disorder (p = 0.0182, Fisher's exact test), and this was being treated at the time of stroke. We provide clinical evidence from patients with structural brain lesions implicating damage to the right inferior frontal lobe in the generation of persistent psychosis following stroke. We suggest that preexisting psychiatric disease provided a behavioural susceptibility to develop delusions in these individuals.
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Are the outcomes of transobturator tape procedure for female stress urinary incontinence durable in long-term follow-up?
Int Urol Nephrol
PUBLISHED: 01-03-2014
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To evaluate long-term cure rates and late complication rates after treatment for female stress urinary incontinence (SUI) with transobturator tape (TOT) procedure and to compare the outcomes of 1st year versus 5th year.
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Fabrication and evaluation of valsartan-polymer- surfactant composite nanoparticles by using the supercritical antisolvent process.
Int J Nanomedicine
PUBLISHED: 01-01-2014
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The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan-hydroxypropyl methylcellulose-poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan-hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability.
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Distinct modes of transmission of tuberculosis in aboriginal and non-aboriginal populations in taiwan.
PLoS ONE
PUBLISHED: 01-01-2014
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Tuberculosis incidence among aborigines is significantly higher than for Han Chinese in Taiwan, but the extent to which Mycobacterium tuberculosis (MTB) strain characteristics contribute to this difference is not well understood. MTB isolates from aborigines and Han Chinese living in eastern and southern Taiwan, the major regions of aborigines, were analyzed by spoligotyping and 24-loci MIRU-VNTR. In eastern Taiwan, 60% of aboriginal patients were ?20 years old, significantly younger than the non-aboriginal patients there; aborigines were more likely to have clustered MTB isolates than Han Chinese (odds ratio (OR)?=?5.98, p<0.0001). MTB lineages with high clustering were EAI (54.9%) among southern people, and Beijing (62.5%) and Haarlem (52.9%) among eastern aborigines. Resistance to first-line drugs and multidrug resistance (MDR) were significantly higher among eastern aborigines (?15%) than in any other geographic and ethnic group (p<0.05); MDR was detected in 5 of 28 eastern aboriginal patients ?20 years old. Among patients from the eastern region, clustered strains (p?=?0.01) and aboriginal ethnicity (p?=?0.04) were independent risk factors for MDR. The lifestyles of aborigines in eastern Taiwan may explain why the percentage of infected aborigines is much higher than for their Han Chinese counterparts. The significantly higher percentage of the MDR-MTB strains in the aboriginal population warrants close attention to control policy and vaccination strategy.
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On the crucial cerebellar wound healing-related pathways and their cross-talks after traumatic brain injury in Danio rerio.
PLoS ONE
PUBLISHED: 01-01-2014
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Upon injury, the direct damage and the subsequent secondary injury in the brain often result in chronic neurological disorders. Due to multifactorial nature of secondary injury and subsequent complex cellular responses, much of the underlying mechanisms are unclear. This study used an adult zebrafish cerebellum injury model to investigate the phenotypes and the secondary injury responses for recovery mechanisms of injured brain. Using the time course microarray analysis, a candidate protein-protein interaction (PPI) network was refined as cerebellar wound healing PPI network by dynamic modeling and big data mining. Pathway enrichment and ontological analysis were incorporated into the refined network to highlight the main molecular scheme of cerebellar wound healing. Several significant pathways, including chemokine, Phosphatidylinositide 3-kinases, and axon guidance signaling pathway and their cross-talks through PI3K, PAK2, and PLXNA3 were identified to coordinate for neurogenesis and angiogenesis, which are essential for the restoration of the injured brain. Our finding provides an insight into the molecular restoration mechanisms after traumatic brain injury, and open up new opportunity to devise the treatment for traumatic brain injury in human.
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Repeatability of a multi-segment foot model with a 15-marker set in healthy adults.
J Foot Ankle Res
PUBLISHED: 01-01-2014
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Several 3D multi-segment foot models (MFMs) have been introduced for the in vivo analysis of dynamic foot kinematics. However, reproducibility of a model should be checked and ascertained before clinical utilization of a MFM. The purpose of this study was to determine the reliability of recently introduced MFM with a 15-marker set by assessing the participant's stride-to-stride (intra-session) and visit-to-revisit (inter-session) repeatability.
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Tibial hemimelia-polydactyly-five-fingered hand syndrome associated with a 404 G>A mutation in a distant sonic hedgehog cis-regulator (ZRS): a case report.
J Pediatr Orthop B
PUBLISHED: 10-18-2013
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Tibial hemimelia-polydactyly-triphalangeal thumb syndrome is a distinct congenital limb anomaly complex, whose association with the 404 G>A mutation in a distant sonic hedgehog cis-regulator (ZRS) was suggested. The authors report a sporadic case of bilateral tibial hemimelia-preaxial polydactyly-five-fingered hands harboring the same mutation. This case further supports a causal relationship between this mutation and the phenotype.
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Molecular epidemiology of Mycobacterium tuberculosis in aboriginal peoples of Taiwan, 2006-2011.
J. Infect.
PUBLISHED: 10-07-2013
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Previous research revealed a 6-fold higher incidence of tuberculosis (TB) amongst aborigines compared to Han Chinese in Taiwan. To investigate the reasons for this disparity, we genotyped Mycobacterium tuberculosis (MTB) strains obtained from members of different aboriginal tribes in different geographical regions of Taiwan by using molecular methods. In total, 177 isolates of MTB collected from patients at four hospitals in Taiwan from January 2006 to December 2011 were analysed by spoligotyping, mycobacterial interspersed repetitive unit-variable number tandem-repeat (MIRU-VNTR) typing. The most prevalent strains in the eastern and central regions of Taiwan were Beijing (45.7% in eastern) and Haarlem (39.1% in eastern, 37.1% in central) lineages, whereas in southern regions the most prevalent strains were EAI (47.7%) and Haarlem (20.5%) lineages. The high prevalence of EAI in southern Taiwan aborigines may be closely associated with Austronesian culture. This study provides a first overview of the M. tuberculosis strains circulating in aboriginal populations in Taiwan. The high prevalences of certain MTB lineages within aboriginal sub-populations suggest that transmission of MTB may have been restricted to close contacts.
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Slipped capital femoral epiphysis caused by neurogenic heterotopic ossification.
J Pediatr Orthop B
PUBLISHED: 08-24-2013
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Slipped capital femoral epiphysis (SCFE) is rare in nonambulatory patients, as mechanical factors play important roles in the development of the disease. We report a case of SCFE, which occurred in a 12-year-old girl with a nonambulatory status after cerebral infarction. SCFE occurred after she received passive range of motion exercise and extracorporeal shock wave treatment for neurogenic heterotopic ossification around the hip joint. The patient was successfully managed by a stepwise approach, with radiological and clinical improvements.
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Age-related changes in physical examination and gait parameters in normally developing children and adolescents.
J Pediatr Orthop B
PUBLISHED: 08-16-2013
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This study aimed to examine the correlations between physical examinations and gait kinematics, and age-related changes in 47 normally developing children. Physical examinations were not found to be significantly correlated with kinematics, except for Thomas and Staheli tests. Unilateral and bilateral popliteal angles decreased significantly by 2.2 and 1.6° per annum, and ankle dorsiflexion with knee extension and 90° flexion decreased significantly by 0.7 and 0.8°. Physical examinations and gait parameters might represent different dimensions of gait, and care should be taken when assessing gait problems. Age-related changes should be considered when interpreting physical examination and gait kinematics for surgery.
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Treadmill exercise represses neuronal cell death and inflammation during A?-induced ER stress by regulating unfolded protein response in aged presenilin 2 mutant mice.
Apoptosis
PUBLISHED: 08-03-2013
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Alzheimers disease (AD) is characterized by the deposition of aggregated amyloid-beta (A?), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of neuronal apoptosis and inflammation by A?-induced ER stress to exercise training are not fully understood. Here, we demonstrated that treadmill exercise (TE) prevented PS2 mutation-induced memory impairment and reduced A?-42 deposition through the inhibition of ?-secretase (BACE-1) and its product, C-99 in cortex and/or hippocampus of aged PS2 mutant mice. We also found that TE down-regulated the expression of GRP78/Bip and PDI proteins and inhibited activation of PERK, eIF2?, ATF6?, sXBP1 and JNK-p38 MAPK as well as activation of CHOP, caspase-12 and caspase-3. Moreover, TE up-regulated the expression of Bcl-2 and down-regulated the expressions of Bax in the hippocampus of aged PS2 mutant mice. Finally, the generation of TNF? and IL-1? and the number of TUNEL-positive cells in the hippocampus of aged PS2 mutant mice was also prevented or decreased by TE. These results showed that TE suppressed the activation of UPR signaling pathways as well as inhibited the apoptotic pathways of the UPR and inflammatory response following A?-induced ER stress. Thus, therapeutic strategies that modulate A?-induced ER stress through TE could represent a promising approach for the prevention or treatment of AD.
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A simple pharmacokinetic model of alendronate developed using plasma concentration and urine excretion data from healthy men.
Drug Dev Ind Pharm
PUBLISHED: 07-25-2013
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Abstract The study of pharmacokinetics of alendronate has been hampered by difficulties in accurately and reproducibly determining their concentrations in serum and urine. Thus, pharmacokinetic characteristics of alendronate have been described in many reports based on urinary excretion data; and plasma pharmacokinetics and the simultaneous pharmacokinetic models of alendronate in plasma and urine are not available. The aims of this study were to measure alendronate concentration in plasma and excretion in urine concurrently and to develop compartmental pharmacokinetic model using urine data. In open-label, single-dose pharmacokinetic study, 10 healthy male volunteers received oral dose of alendronate (70?mg tablet). Blood and urine alendronate concentrations were determined using validated high-performance liquid chromatography method. Non-compartmental analysis was performed using WinNonlin program (Pharsight Inc., Apex, NC). A one-compartment pharmacokinetic model was applied to describe pharmacokinetics of alendronate. A peak plasma alendronate concentration of 33.10?±?14.32?ng/mL was attained after 1.00?±?0.16?h. The cumulative amount of alendronate excreted in urine and peak excretion rate were 731.28?±?654.57??g and 314.68?±?395.43??g/h, respectively. The model, which included first-order absorption rate for oral dosing, showed good fit to alendronate data obtained from plasma and urine. The absorption rate constant was 2.68?±?0.95?h(-1). The elimination rate constants Kurine and Knon-ur were 0.005?±?0.004?h(-1) and 0.42?±?0.08?h(-1), respectively. The pharmacokinetics of alendronate in plasma and urine of healthy men can be predicted using one-compartment model, and thus the behavior of drug in plasma can be estimated from urinary excretion data.
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Genotoxicity of drinking water disinfection by-products (bromoform and chloroform) by using both Allium anaphase-telophase and comet tests.
Cytotechnology
PUBLISHED: 07-24-2013
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Genotoxic effects of bromoform and chloroform, disinfection by-products of the chlorination of drinking water, were examined by using mitotic index (MI), mitotic phase, chromosome aberrations (CAs) and comet assay on root meristematic cells of Allium cepa. Different concentrations of bromoform (25, 50, 75 and 100 ?g/mL) and chloroform (25, 50, 100 and 200 ?g/mL) were introduced to onion tuber roots. Distilled water was used as a negative control and methyl methansulfonate (MMS-10 ?g/mL) as positive control. All obtained data were subjected to statistical analyses by using SPSS 15.0 for Windows software. For comparison purposes, Duncan multiple range tests by using one-way analysis of variance were employed and p < 0.05 was accepted as significant value. Exposure of both chemicals (except 25 ?g/mL applications of bromoform) significantly decreased MI. Bromoform and chloroform (except 25 ?g/mL applications) increased total CAs in Allium anaphase-telophase test. A significant increase in DNA damage was also observed at all concentrations of both bromoform and chloroform examined by comet assay. The damages were higher than that of positive control especially at 75-100 ?g/mL for bromoform and 100-200 ?g/mL for chloroform.
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Genotoxicity of indium tin oxide by Allium and Comet tests.
Cytotechnology
PUBLISHED: 07-23-2013
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Genotoxic effects of indium tin oxide (ITO) were investigated on root cells of Allium cepa by employing both Allium and Comet assays. A. cepa roots were treated with the aqueous dispersions of ITO at 5 different concentrations (12.5, 25, 50, 75, and 100 ppm) for 4 h. Exposure of ITO significantly increased mitotic index, and total chromosomal aberrations by the Allium test. While chromosome laggards, stickiness, disturbed anaphase-telophase and anaphase bridges were observed in anaphase-telophase cells, c-metaphase and binuclear cells were observed in other cells. A significant increase in DNA damage was also observed at all concentrations of ITO by the Comet assay. These results indicate that ITO exhibits genotoxic activity in A. cepa root meristematic cells.
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Lessons we learn from hematopathology consultation in Taiwan.
J. Formos. Med. Assoc.
PUBLISHED: 07-21-2013
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The appropriate management of hematology patients depends first on correct diagnoses. Expert review is important in reaching accurate diagnoses. To improve diagnostic accuracy, the Taiwan Society of Pathology and the Taiwan Division of the International Academy of Pathology has been conducting an expert consultation program for general pathologists since 2001. As per this program, we have received a total of 395 cases (406 samples) for review. We found that meaningful diagnostic discrepancies occurred frequently in hematopathology reviews. Ambiguous or nondiagnostic original reports were the major causative factor for the major discrepancy cases, which demonstrates that diagnostic uncertainty is a big problem for referring pathologists. However, the World Health Organization lymphoma classification may be poorly reproducible in countries where extensive use of an ancillary technique is not used by general pathologists. This review is intended to report the misdiagnoses most commonly seen in the hematopathology practice in Taiwan. Awareness of the easily misinterpreted entities helps to achieve the right diagnosis and improve patient care.
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