Tri Service General Hospital and National Taiwan University | Date: 2012-12-28
Amiodarone inhibits the invagination during zebrafish heart development and makes the defect on valves development. The present invention demonstrates that Amiodarone inhibits cancer metastasis and provides a method for inhibiting cancer metastasis in a subject in need thereof comprising administering to the subject a pharmaceutically effective amount of an Amiodarone or its salt.
Lin S.-H.,Tri Service General Hospital |
Huang C.-L.,Southwestern Medical Center
Journal of the American Society of Nephrology | Year: 2012
The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increasedNa+-K + ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. This mechanism alone, however, cannot adequately explain how hypokalemia occurs during acute attacks or the associated paradoxical depolarization of the resting membrane potential. Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K + (Kir) channel, Kir2.6, associatewith thyrotoxicperiodicparalysisprovide newinsights intohowreduced outwardK + efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na + channels and causes muscle unexcitability and paralysis. Copyright © 2012 by the American Society of Nephrology.
Chang W.K.,Tri Service General Hospital
International journal of nanomedicine | Year: 2011
Fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA)-loaded polyethylene glycol (PEG)-modified liposomes and lipoparticles with high protein entrapment were developed. The lipid formula of the liposomes contained PEGylated lipids and unsaturated fatty acids for enhancing membrane fluidity and effective delivery into cells. The preparation techniques, lipid content, and PEG-modified lipoparticle ratios were evaluated. The PEG-modified lipoparticles prepared by ethanol injection extrusion (100 nm pore size) achieve a population of blank liposomes with a mean size of 125 ± 2.3 nm and a zeta potential of -12.4 ± 1.5 mV. The average particle size of the PEG-modified lipoparticles was 133.7 ± 8.6 nm with a zeta potential of +13.3 mV. Lipoparticle conformation was determined using transmission electron microscopy and field-emission scanning electron microscopy. The FITC-BSA encapsulation efficiency was dramatically increased from 19.0% for liposomes to 59.7% for lipoparticles. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results confirmed the preparation process, and an 8-hour leaching test did not harm the protein structure. Once prepared, the physical and chemical stability of the PEG-modified lipoparticle formulations was satisfactory over 90 days. In vitro retention tests indicated that the 50% retention time for the protein-containing lipoparticles was 7.9 hours, substantially longer than the liposomes at 3.3 hours. A Caco-2 cell model was used for evaluating the cytotoxicity and cell uptake efficiency of the PEG-modified lipoparticles. At a lipid content below 0.25 mM, neither the liposomes nor the lipoparticles caused significant cellular cytotoxicity (P < 0.01) and FITC-BSA was significantly taken up into cells within 60 minutes (P < 0.01).
Lin G.Y.,Tri Service General Hospital
The journal of headache and pain | Year: 2013
Multiple sclerosis (MS) is a chronic autoimmune disease that targets myelinated axons in the central nervous system. Headache has been reported as a subtle symptom of the onset of MS, with a variable frequency of 1.6-28.5%; however, it remains unclear whether headache is a true symptom of MS onset. Here, we report the case of a female patient who had a history of migraine without aura and experienced worsening of migraine-headache symptoms as the initial manifestation of MS. Three similar cases were reported previously; however, unlike this case, those cases had no history of migraine without aura. In our case, we excluded factors that could trigger migraine attacks, such as changes in weather, drugs, alcohol, caffeine withdrawal, stress, fatigue, lack of sleep, hormonal therapy, diet, and hunger. The patient had one episode of MS attack with the simultaneous presence of asymptomatic gadolinium-enhancing and non-enhancing lesions, including hyperintense lesions in the bilateral periventricular white matter, body of the corpus callosum, and periaqueductal grey matter, as observed on the T2-weighted images obtained at the first brain magnetic resonance imaging. In addition, after the injection of gadolinium contrast, ring enhancement over these lesions was noted in T1-weighted images, which was suggestive of active demyelination. MS was diagnosed according to the McDonald criteria (2010 revision). We conclude that MS with periaqueductal grey matter involvement may present with worsening migraine. It is important to be cautious if any secondary causes exist, especially when the patient has a history of migraine without aura. MS should be one of the differential diagnoses in young women showing a change in headache pattern or poor clinical drug response to migraine treatment accompanied by episodes of focal neurological deficit. Failure to recognize MS may lead to inappropriate treatment and worse prognosis; early diagnosis in patients with MS is essential to improve their clinical outcomes and quality of life.
Cheng C.-J.,University of Texas Southwestern Medical Center |
Cheng C.-J.,Tri Service General Hospital |
Huang C.-L.,University of Texas Southwestern Medical Center
Journal of the American Society of Nephrology | Year: 2011
WNK kinases stimulate endocytosis of ROMK channels to regulate renal K+ handling. Phosphatidylinositol 3-kinase (PI3K)-activating hormones, such as insulin and IGF 1, phosphorylate WNK1, but how this affects the regulation of ROMK abundance is unknown. Here, serum starvation of ROMK-transfected HEK cells led to an increase of ROMK current density; subsequent addition of insulin or IGF1 inhibited ROMK currents in a PI3K-dependent manner. Serum and insulin also increased phosphorylation of the downstream kinases Akt1 and SGK1 as well as WNK1. A biotinylation assay suggested that insulin and IGF1 inhibit ROMK by enhancing its endocytosis, a process that WNK1 may mediate. Knockdown of WNK1 with siRNA or expression of a phospho-deficient WNK1 mutant (T58A) both prevented insulin-induced inhibition of ROMK currents, suggesting that phosphorylation at Threonine-58 of WNK1 is important to mediate the inhibition of ROMK by PI3K-activating hormones or growth factors. In vitro and in vivo kinase assays supported the notion that Akt1 and SGK1 can phosphorylate WNK1 at this site, and we established that Akt1 and SGK1 synergistically inhibit ROMK through WNK1. We used dominant-negative intersectin and dynamin constructs to show that SGK1-mediated phosphorylation of WNK1 inhibits ROMK by promoting its endocytosis. Taken together, these results suggest that PI3K-activating hormones inhibit ROMK by enhancing its endocytosis via a mechanism that involves phosphorylation of WNK1 by Akt1 and SGK1. Copyright © 2011 by the American Society of Nephrology.
Feng H.M.,Tri Service General Hospital
The New England journal of medicine | Year: 2014
A 48-year-old woman presented to the emergency department with severe otalgia of 1 day's duration. Bloody otorrhea in the left ear was noted after her hearing aid was removed. A video shows findings in the auditory canal.
Yeh Y.-W.,Tri Service General Hospital
Clinical Neuropharmacology | Year: 2011
Antipsychotics are thought to be effective in the treatment of hiccups; however, they are rarely reported to induce hiccups. We report a case of persistent hiccups after administration of aripiprazole in a patient with concurrence of schizophrenia and cerebral palsy. Prior brain injury and switching antipsychotics may precipitate the development of hiccups in the present case. Aripiprazole with a partial agonist of dopamine D2 receptors and serotonin 1A receptors may play a crucial role in the pathophysiology of hiccups. © 2011 by Lippincott Williams & Wilkins.
Liu Y.C.,Tri Service General Hospital
World journal of surgical oncology | Year: 2014
Findings related to the influence of the -160C → A promoter polymorphism and haplotypes of the E-cadherin (CDH1) gene have not been consistent in previous studies regarding the risk for sporadic gastric cancer. Investigators in most previous studies detected those genotypes using restriction fragment length polymorphism analysis. Therefore, we conducted a case-control study to investigate the association of the CDH1 - 160C → A promoter polymorphism and haplotypes for cancer risk related to sporadic diffuse and intestinal gastric cancer by direct sequencing analysis. We included 107 diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134 controls. The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis. Genotype frequencies were compared. The CDH1 - 160C → A promoter polymorphism and four polymorphisms (48 + 6 T → C, 2076C → T, 2253C → T and 1937-13 T → C) were included in the haplotype analyses, which were estimated using the expectation-maximization algorithm. Compared to controls, the frequency of the -160A allele was significantly higher in diffuse gastric cancer cases (P = 0.005), but it was not significantly different in intestinal gastric cancer cases (P = 0.119). Two sets of three-marker haplotypes (-160C → A, 48 + 6 T → C, 2076C → T and -160C → A, 1937-13 T → C, 2253C → T) were associated with the risk of diffuse gastric cancer (P = 0.011 and P = 0.042, respectively). Based on direct sequencing analysis, our findings suggest that the CDH1 - 160C → A promoter polymorphism and haplotypes play significant roles in cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric cancer, in a Taiwanese population.
Chen Y.C.,Tri Service General Hospital
The Journal of bone and joint surgery. American volume | Year: 2013
Although shoulder problems frequently occur in patients with hemophilia, systematic evaluation of shoulder joint damage in these patients has only rarely been reported. The clinical, radiographic, and ultrasonographic characteristics of the shoulder joint were studied in a cohort of seventy consecutive patients with hemophilia. We collected information on age, disease severity, history of shoulder hemarthrosis, prophylaxis therapy, functional Oxford shoulder score, and crutch use. Both shoulders of each patient were evaluated with shoulder motion and visual analog pain scale scores as well as with radiography and ultrasonography. Sixty-six patients had hemophilia A, and four had hemophilia B. The median age was thirty-four years (range, ten to sixty-three years). Fifty-six shoulders in thirty-five patients had shoulder bleeds, and twenty-seven patients (38.6%) had shoulder pain or limited motion. As determined with radiographs, eighteen (25.7%) of the seventy patients had hemophilic shoulder arthropathy. A strong correlation between the functional Oxford shoulder score and the radiographic Pettersson score was also noted (r = 0.749, p < 0.001). The ultrasonographic abnormalities in the fifty-six hemarthrotic shoulders included chondromalacia (76.8%), osseous irregularity (60.7%), bicipital tenosynovitis (60%), partial-thickness rotator cuff tear (35.7%), and full-thickness rotator cuff tear (17.9%). Older age, the absence of any previous prophylaxis therapy, and higher frequency of crutch use were the most significant factors associated with shoulder bleeds. Shoulder arthropathy is relatively common in patients with hemophilia. Rotator cuff tears were common in the present study, and there was a strong correlation between shoulder function and the radiographic severity of the arthropathy. Ultrasonography was useful for the evaluation of disorders of the soft tissues of the hemophilic shoulder.
Tri Service General Hospital, National Taiwan University of Science and Technology | Date: 2011-12-22
The present invention discloses an approximately -shaped improved bone plate structure, fixed on a bone of an animal for maintaining the relative positions of different portions of the bone. One of the other features of the present invention is that bone plate structure comprises at least one contouring portion for allowing the surgeons to intra-operatively adjusting the shape in accordance with the shape of the bone. Furthermore, the present invention may fit the bone with multi-axis, decreasing stress concentration, preventing the opening portion from being unsuitably covered and preventing the wound deformation from being pressed.