Surface-modified poly(lactide- co -glycolide) nanospheres for targeted bone imaging with enhanced labeling and delivery of radioisotope

Surface-modified nanospheres can be utilized for targeting drugs and diagnostic agents to the bone and bone marrow while extending their circulation time in the blood stream. The surface modification of poly(lactide- co -glycolide) (PLGA) nanospheres by radioisotope carrying poly(ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) triblock copolymers (Poloxamer 407) has been assessed by in vitro characterization and in vivo biodistribution studies after intravenous administration of the nanospheres to the mouse. A hydroxyphenylpropionic acid, a ligand for 125 I and 131 I labeling, was conjugated to the hydroxyl group of the Poloxamer 407 by using dicyclohexyl carbodiimide. The ligand-conjugated Poloxamer 407 was adsorbed onto the surface of PLGA nanospheres. Surface coating was confirmed by measuring both size distribution and the surface charge of the nanospheres. Besides, 125 I-labeling efficiency, radiolabeling stability, whole body imaging, and biodistribution of the radioisotope-labeled nanospheres were examined. Ligand-labeled, surface-modified PLGA nanospheres were in 100-nm size ranges, which may be adequate for long-circulation and further bone imaging. 125 I-labeling efficiency was >90% and was more stable at human serum for 24 h. A noticeable decrease in liver or spleen uptake was obtained by the surface-modified nanospheres. 125 I-labeled nanospheres showed higher blood maintenance and bone uptake compared with stannous colloid with the same size distribution. Therefore, a fully biodegradable, radioisotope-carrying, surface-modified nanosphere system has been developed as a promising tool for targeting bone and bone marrows. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res 67A: 751–760, 2003Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34431/1/10167_ftp.pd

Infective endocarditis caused by methicillin-resistant Staphylococcus aureus in a young woman after ear piercing: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ear piercing is a common practice among Korean adolescents and young women and usually is performed by nonmedical personnel, sometimes under suboptimal hygienic conditions. Consequently, ear piercing has been associated with various infectious complications, including fatal infective endocarditis. We report a case of infective endocarditis that was caused by community-associated methicillin-resistant <it>Staphylococcus aureus </it>after ear piercing and that was accompanied by a noticeable facial rash.</p> <p>Case presentation</p> <p>A 29-year-old Korean woman underwent ear piercing six days before hospitalization. On admission, she had fever, erythematous maculopapular rashes on her face, signs of generalized emboli, vegetation in her mitral valve, and methicillin-resistant <it>S. aureus </it>bacteremia. On the basis of the blood culture results, she was treated with vancomycin in combination with gentamicin. On day six of hospitalization, a rupture of the papillary muscle of her mitral valve developed, and emergency cardiac surgery replacing her mitral valve with a prosthetic valve was performed. After eight weeks of antibiotic therapy, she was treated successfully and discharged without significant sequelae.</p> <p>Conclusions</p> <p>Numerable cases of body piercing-related infective endocarditis have been reported, and since ear piercing is commonplace nowadays, the importance of risk recognition cannot be overemphasized. In our report, a patient developed infective endocarditis that was caused by methicillin-resistant <it>S. aureus </it>after ear piercing and that was accompanied by an interesting feature, namely facial rash.</p

The secondary prophylactic efficacy of beta-blocker after endoscopic gastric variceal obturation for first acute episode of gastric variceal bleeding

Background/AimsThe most appropriate treatment for acute gastric variceal bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using Histoacryl®. However, the secondary prophylactic efficacy of beta-blocker (BB) after GVO for the first acute episode of GVB has not yet been established. The secondary prophylactic efficacy of BB after GVO for the first acute episode of GVB was evaluated in this study.MethodsNinety-three patients at Soonchunhyang University Hospital with acute GVB who received GVO using Histoacryl® were enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB group). This study was intended for patients in whom a desired heart rate was reached. The rates of rebleeding-free survival and overall survival were calculated for the two study groups using Kaplan-Meyer analysis and Cox's proportional-hazards model.ResultsThe follow-up period after the initial eradication of gastric varices was 18.14±25.22 months (mean±SD). During the follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16 (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months, respectively; P=0.774), whereas the mean overall survival time did differ (52.54 and 72.65 months, respectively; P=0.036).Conclusions Adjuvant BB therapy after GVO using Histoacryl® for the first acute episode of GVB could decrease the mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no benefit for the secondary prevention of rebleeding in GV

Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

Background Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone

Degradable Poly(ester amine) Based on Poly(ethylene glycol) Dimethacrylate and Polyethylenimine as a Gene Carrier

Degradable poly(ester amine) (PEA) based on poly(ethylene glycol) dimethacrylate (PMEG) and polyethylenimine (PEI) were synthesized by Michael addition reaction. The ratios of PEI to PMEG in PEAS were 0.99, 1.02, and 1.07 with corresponding number-average molecular weight of 1.3 x 10(4), 1.2 x 10(4), and 0.9 x 10(4), respectively. Degradation rate of PEA at pH 7.4 was higher than that at pH 5.6. Good plasmid condensation and protection ability was shown when N/P molar ratio of PEA to DNA was above 15 (N: nitrogen element in PEA, P: phosphate in DNA). PEA/DNA complexes had positive zeta potential, narrow size distribution, good dispersity, and spheric shape with size below 250 nm when N/P ratio was above 30, suggestion of their endocytosis potential. Compared with PEI 25 KDa, the PEAs showed essential nontoxic to HeLa, HepG2 and 293T cells. With an increase in the molecular weight of PMEG, the transfection efficiency of PEAS in HeLa, HepG2 and 293T showed a tendency to decrease as well as the percent decrease of gene transfection efficiency with serum. The mechanism of PEA-mediated gene transfection was attributed to "proton sponge effect" of PEI in the PEA. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 115: 1189-1198, 201

Comparison of the protective efficacy between single and combination of recombinant adenoviruses expressing complete and truncated glycoprotein, and nucleoprotein of the pathogenic street rabies virus in mice

Abstract Background Rabies is an important viral zoonosis that causes acute encephalitis and death in mammals. To date, several recombinant vaccines have been developed based on G protein, which is considered to be the main antigen, and these vaccines are used for rabies control in many countries. Most recombinant viruses expressing RABV G protein retain the G gene from attenuated RABV. Not enough is currently known about the protective effect against RABV of a combination of recombinant adenoviruses expressing the G and N proteins of pathogenic street RABV. Methods We constructed a recombinant adenovirus (Ad-0910Gsped) expressing the signal peptide and ectodomain (sped) of G protein of the Korean street strain, and evaluated the immunological protection conferred by a single and combination of three kinds of recombinant adenoviruses (Ad-0910Gsped and Ad-0910G with or without Ad-0910 N) in mice. Results A combination of Ad-0910G and Ad-0910 N conferred improved immunity against intracranial challenge compared to single administration of Ad-0910G. The Ad-0910G virus, expressing the complete G protein, was more immunogenic than Ad-0910Gsped, which expressed a truncated G protein with the transmembrane and cytoplasmic domains removed. Additionally, oral vaccination using a combination of viruses led to complete protection. Conclusions Our results suggest that this combination of viruses is a viable new intramuscular and oral vaccine candidate

The Effectiveness of Compartmentalized Bone Graft Sponges Made Using Complementary Bone Graft Materials and Succinylated Chitosan Hydrogels

Bone defects can occur from many causes, including disease or trauma. Bone graft materials (BGMs) have been used to fill damaged areas for the reconstruction of diseased bone tissues since they are cost effective and readily available. However, BGMs quickly disperse around the tissue area, which ultimately leads to it migrating away from the defect after transplantation. We tested chitosan hydrogels as a useful carrier to hold BGMs in the transplantation area. In this study, we synthesized succinylated chitosan (SCS)-based hydrogels with a high decomposition rate and excellent biocompatibility. We confirmed that BGMs were well distributed inside the SCS hydrogel. The SCS-B hydrogel showed a decrease in mechanical properties, such as compressive strength and Young&rsquo;s modulus, as the succinylation rate increased. SCS-B hydrogels also exhibited a high cell growth rate and bone differentiation rate. Moreover, the in vivo results showed that the SCS hydrogel resorbed into the surrounding tissues while maintaining the BGMs in the transplantation area for up to 6 weeks. These data support the idea that SCS hydrogel can be useful as a bioactive drug carrier for a broad range of biomedical applications