Preparation and characterization of intelligent core-shell nanoparticles based on poly(D,L-lactide)-g-poly(N-isopropyl acrylamide-co-methacrylic acid).

New thermo-responsive, pH-responsive, and biodegradable nanoparticles comprised of poly(D,L-lactide)-graft-poly(N-isopropyl acrylamide-co-methacrylic acid) (PLA-g-P(NIPAm-co-MAA)) were developed by grafting biodegradable poly(D,L-lactide) onto N-isopropyl acrylamide and methacrylic acid. A core-shell type nano-structure was formed with a hydrophilic outer shell and a hydrophobic inner core, which exhibited a phase transition temperature above 37 degrees C suitable for biomedical application. Upon heating above the phase transition temperature, PLA-g-P(NIPAm-co-MAA) nanoparticle showed a polarity increase of pyrene in either buffer solution or intra-hepato-carcinoma cells as determined by fluorescence measurement, indicating that the structure of nanoparticles caused leakages from outer shell copolymers aggregation and collapsed. The drug loading level of 5-fluorouracil (5-FU) encapsulated in the PLA-g-P(NIPAm-co-MAA) nanoparticles can be as high as 20%. The release of 5-FU from nanoparticles was strongly controlled by the pH in the aqueous solution. Based on these results, PLA-g-P(NIPAm-co-MAA) nanoparticles can be used as a drug carrier for intracellular delivery of anti-cancer drug.     

Gas permeation through two side-chain liquid-crystalline polyacrylate-based membranes containing 4-methoxyphenyl 4-hexyloxybenzoate or 4-cyanophenyl 4-hexyloxybenzoate mesogenic side groups

Two kinds of side-chain liquid-crystalline (LC) polymers with different side-chain mesogenic end groups were synthesized. The laminated membrane was prepared by sandwiching the side-chain LC polymer between two porous polypropene (Celgard) films. Permeation properties for O₂, N₂, CO₂ and CH₄ through the laminated side-chain LC polymer-based membranes were measured using a gas-chromatographic method at several temperatures corresponding to the stability range of the different phases of the side-chain LC polymers. The gas permeation behaviour depends strongly on the state of the side-chain LC polymer. The activation energy for permeation depends on the state, too. The plot of separation factor P/P versus P exhibits an unusual behaviour. P/P increases with P when the temperature rises and the phase of the side-chain LC Polymer changes from the glassy state to the liquid-crystalline state. The magnitude of gas permeability coefficients for the laminated membranes is rather low compared to those of some common polymers. The low gas permeability seems to originate from the low gas solubility rather than from the low gas diffusivity in the laminated side-chain LC polymer membrane.     

Synthesis and properties of thermotropic polyesters modified with a non-mesogenic rigid group

Four series of copolyesters, namely BB6-DMT, BB5-DMT, BB6-DMI and BB5-DMI series, were prepared by melt polycondensation of dimethyl 4,4′-bibenzoate (BB) with a dimethyl phthalate (DMT: dimethyl terephthalate or DMI: dimethyl isophthalate) and an alkanediol (1,6-hexanediol or 1,5-pentanediol). The homopolyesters poly(hexamethylene 4,4′-bibenzoate) (BB6) and poly(pentamethylene 4,4′-bibenzoate) (BB5) exhibit a smectic phase. The thermotropic liquid crystalline and crystalline properties of the copolyesters are significantly influenced by the presence of the non-mesogenic rigid phthalate unit. All BB6-DMT copolyesters remain crystalline. As x, the molar fraction of the phthalate units in the diacid units, ≧ 0.7 the mesophase of the BB6-DMT copolyesters is destroyed completely. For BB5-DMT copolyesters, the mesophase disappears as x ≧ 0.4, and the copolyesters become amorphous as 0.5 ≦ x ≦ 0.8. The mesophase and the crystallinity of the BB6-DMI copolyesters are destroyed completely as x > 0.5. The BB5-DMI copolyesters lose the mesophase as x ≧ 0.3, and become amorphous as x ≧ 0.4. The results indicate that the non-linear isophthalate unit destroys mesophase and crystallinity of the copolyesters to a greater extent than the para-linked terephthalate unit.     

The association between glutathione S-transferase P1, M1 polymorphisms and asthma in Taiwanese schoolchildren

STUDY OBJECTIVES: Genetic polymorphisms in the glutathione S-transferase P1 gene (GSTP1) and the glutathione S-transferase M1 gene (GSTM1) have been implicated as risk factors for asthma. However, their roles in asthma pathogenesis and the interaction between these two genes have not been extensively investigated. This study, therefore, examined the relationship among GSTP1 and GSTM1 genotypes and childhood asthma, and evaluated their gene-gene interactions. SETTING: The population from three southern Taiwan communities of a 2001 national survey. SUBJECTS AND METHODS: Two hundred sixty-six fourth-grade to ninth-grade schoolchildren were recruited for oral mucosa samplings based on questionnaire information. Polymerase chain reaction-based assays were performed to determine GSTP1 and GSTM1 genotypes among asthmatic subjects and nonasthmatic control subjects. Multiple logistic regression was used to adjust for potential confounding factors. RESULTS: All of the participants were homozygous at the GSTP1 Ala-114 locus. After controlling for age, sex, and atopic eczema, compared with participants carrying any Val-105 allele, children who were homozygotic for GSTP1 Ile-105 had a significantly increased risk of physician-diagnosed asthma (adjusted odds ratio [adjOR], 1.94; 95% confidence interval [CI], 1.08 to 3.59). A positive risk for childhood asthma was also noted on the GSTM1 null genotype but did not reach statistical significance (adjOR, 1.37; 95% CI, 0.80 to 2.38). Among children with GSTM1 present genotypes, GSTP1-105 polymorphisms were associated with the increased risk of asthma. However, the reduced and statistically insignificant asthma risk was observed among those with GSTM1 null genotype. CONCLUSIONS: We concluded that GSTP1-105 was a predictor for childhood asthma, whereas GSTM1 polymorphism might modify the risk. Our study also suggested a competitive effect for homozygous GSTP1 Ile-105 and GSTM1 null genotypes on childhood asthma.     

Impact of renal disease on elective shoulder arthroplasty outcomes for glenohumeral osteoarthritis

BackgroundRenal disease including chronic renal disease and end-stage renal disease has been associated with the development of primary glenohumeral osteoarthritis. However, little is known about how renal disease affects outcomes after shoulder arthroplasty. Thus, the purpose of this study was to evaluate the impact of renal disease on outcomes of shoulder arthroplasty for glenohumeral osteoarthritis.MethodsThis was a retrospective review using the Nationwide Readmissions Database. Using International Classification of Diseases, 9th Revision, codes, patients who underwent shoulder arthroplasty (including total shoulder arthroplasty and reverse total shoulder arthroplasty) for primary glenohumeral osteoarthritis were identified. These patients were divided into 3 groups: no renal disease, predialysis chronic renal disease (including stages 1-5), and end-stage renal disease. Primary outcomes of interest included the risk of complications during index hospitalization as well as within 90 days of index surgery. Secondary outcomes included index hospitalization length of stay, cost, and discharge location.ResultsFrom 2010 to 2014, a total of 29,336 patients underwent shoulder arthroplasty for glenohumeral osteoarthritis. Of these 29,336, 27,928 (95.2%) patients had no renal disease, 1355 (4.6%) had predialysis chronic renal disease, and 53 (0.2%) patients had end-stage renal disease. Compared with patients with no renal disease, both predialysis chronic renal disease and end-stage renal disease patients had an increased risk of receiving blood transfusions (odds ratio [OR] = 2.04, P < .0001, and 5.37, P = .04, respectively) and experiencing any postoperative complication during the index hospitalization (OR = 2.31, P < .0001, and 3.94, P = .003, respectively). Specifically, predialysis chronic renal disease patients were at an increased risk for cardiac (OR = 1.96, P < .0001) and respiratory (OR = 1.55, P < .0001) complications as well as acute renal failure (OR = 14.70, P < .0001) postoperatively. End-stage renal disease patients were at an increased risk for cardiac (OR = 3.87, P = .003) complications as well as acute renal failure (OR = 10.35, P = .002) postoperatively. Within 90 days, end-stage renal disease patients had an increased risk of hospital readmission (OR = 8.01, P < .0001), dislocation (OR = 8.70, P = .039), and surgical site infection (OR = 19.06, P = .001). Finally, compared with patients with no renal disease, predialysis chronic renal disease and end-stage renal disease patients both had increased hospital length of stay and cost; predialysis chronic renal disease patients had an increased risk of discharge to a skilled nursing facility (OR = 1.39, P = .039).Discussion and ConclusionThis retrospective cohort study demonstrates that even predialysis chronic renal disease patients have worse outcomes compared with patients with no renal disease after shoulder arthroplasty for glenohumeral osteoarthritis. These findings serve to highlight the importance of close perioperative monitoring to prevent complications in a potentially overlooked patient population.     

Macro- and micropulmonary hemodynamic changes to nitric oxide blockade in monocrotaline-induced pulmonary hypertension in rats--an in vivo approach.

BACKGROUND AND PURPOSE: Data on the role of nitric oxide (NO) in monocrotaline (MC)-induced pulmonary hypertension of rats have all been derived from in vitro measurements. In vivo pulmonary hemodynamics and microvascular responses to NO blockade in MC-treated rats have not been reported. The current study evaluated the role of NO in live MC-treated rats. METHODS: Male Sprague-Dawley rats (n = 29) were divided into saline control and MC-treated groups. Three to 4 weeks after either saline or MC injection, pulmonary hemodynamics were measured using pulmonary arterial catheter and thermodilution techniques. Pulmonary microvascular diameter changes were assessed using an intravital microscope. RESULTS: Three to 4 weeks after subcutaneous injection of MC (50 mg/kg), MC-treated rats showed elevated pulmonary arterial pressure compared to control rats (23.6 +/- 2.9 mm Hg vs 14.5 +/- 0.8 mm Hg). N(omega)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg, intravenously), an NO synthase inhibitor, produced significant increases in pulmonary arterial pressure and total pulmonary vascular resistance compared to control rats (12.3 +/- 2.5 mm Hg vs 1.0 +/- 0.9 mm Hg; 0.21 +/- 0.04 mm Hg/mL/min vs 0.05 +/- 0.02 mm Hg/mL/min, p < 0.05). Intravital microscopic observation of the subpleural vessels showed significant vasoconstriction in medium-sized (> 40 microm) pulmonary arterioles of MC-treated rats following L-NAME administration (58.4 +/- 3.6 microm vs 47.1 +/- 3.4 microm, p < 0.05) while no significant diameter changes were found in either the small-sized (< 40 microm) pulmonary arterioles or pulmonary venules. Diameters of pulmonary arterioles and venules in control rats were not affected by L-NAME administration. CONCLUSION: Pulmonary arterial pressure and pulmonary vascular resistance increased after NO blockade in live MC-treated rats. The site of vasoconstriction after NO blockade included medium-sized pulmonary arterioles but not small-sized pulmonary arterioles. This study has provided both macro- and microhemodynamic evidence of a modulatory role of NO in live MC-treated rats.