Molecular weights of poly(butyl cyanoacrylate) nanoparticles determined by mass spectrometry and size exclusion chromatography

Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and size exclusion chromatography (SEC) were employed to elucidate the chemical composition, mean number average molecular weight (M_n), mean weight average molecular weight (M_w), and polydispersity (PD) of poly(butyl cyanoacrylate) (PBCA) manufactured by emulsion polymerisation. Both methods gave similar results for M_n, but substantial differences were observed for M_w and PD, with MALDI producing consistently lower values which could not be improved by off-line coupling of SEC and MALDI. MALDI gave a more detailed view on the chemical composition of the cyanoacrylate and revealed the presence of two additional polymer series with different end groups besides the expected PBCA series, which showed different retention in SEC. Their formation is explained by the secession/addition of formaldehyde from/to the regular polymer via (reverse) Knoevenagel reaction. In additional experiments, the influence of different pH on PBCA-NP during polymerisation was examined by comparison of polymerisation yield and particle diameter to their chemical composition as revealed by the MALDI spectra. The most uniform nanoparticles, with the highest polymerisation yield, narrowest particle size, and mass distribution were produced at pH 1.     

PGD9 Outcomes and Cost-Benefit of Inhaled Corticosteroid Therapy Introduction in Medicaid-Enrolled Asthmatic Children

OBJECTIVE: The purpose of this study was to assess the clinical and economic impact of the introduction of inhaled corticosteroid therapy for asthma in a cohort of children 12 years and younger who were North Carolina Medicaid enrollees.
METHODS: The North Carolina Medicaid claims database was used to retrieve clinical and economic variables for the purpose of this study. The case group, which was comprised of 84 children who started corticosteroid inhaler therapy between March 1994 and March 1995, was followed up for 1 year before and 1 year after the start of the therapy. The control group was comprised of 72 children with similar severity of asthma who remained on any other therapy other than corticosteroids for a continuous 2-year period. Paired t-tests were used to compare differences, and multiple regression analysis was used to adjust for potential confounders.
RESULTS: There was a 58% reduction in hospital visits, and a 19% reduction in physician visits in the case group after initiation of inhaled corticosteroids. In the control group, an increase of 34% in the number of outpatient visits occurred in the second year. All the decreases and increases were statistically significant. Children with regular patterns of inhaled corticosteroid refills were found to be significantly lower costing for Medicaid. However, after adjusting for potential confounders, no significant change in health care costs per asthmatic child occurred as a result of the introduction of inhaled corticosteroid therapy.
CONCLUSION: Overall, the study found that introduction of inhaled corticosteroids in a cohort of asthmatic children enrolled in Medicaid was beneficial to Medicaid because it brought about dramatic decreases in health care utilization without additionally increasing costs.     

Mechanisms of hepatotoxicity.

This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.     

Mortality and failure among tuberculosis patients who did not complete treatment in Vietnam: a cohort study

Background  

Tuberculosis treatment failure and death rates are low in the Western Pacific Region, including Vietnam. However, failure or death may also occur among patients who did not complete treatment, i.e. reported as default or transfer-out. We aimed to assess the proportion failures and deaths among new smear-positive pulmonary tuberculosis patients with reported default or transfer-out.     

苄基四氢巴马汀对表达于非洲爪蟾卵母细胞及中华大蟾蜍卵母细胞的延迟整流钾电流的抑制作用

苄基四氢巴马汀对表达于非洲爪蟾卵母细胞及中华大蟾蜍卵母细胞的延迟整流钾电流的抑制作用童秋生，夏国瑾，姚伟星，江明性，白小川，包永德（同济医科大学基础医学院药理学教研室，武汉４３００３０；中国科学院上海生理学研究所，上海２０００３１）苄基四氢巴马汀（ｂ...     

Transient synovitis of the hip in children: role of US

Transient synovitis of the hip remains a common diagnostic problem for the clinician. The physical signs are not pathognomonic of the condition, and the classic technical examinations are of little help. Therefore, the authors retrospectively studied the value of hip arthrosonography in 46 children with clinical symptoms suggesting pathologic hip conditions. In 20 of the 21 patients with a final diagnosis of transient synovitis, articular effusion was detected on ultrasound (US). Conventional radiography showed an increased medial joint space in only eight of these patients. Increased echogenicity of the articular fluid was found in both transient synovitis and septic arthritis. The high sensitivity of US in detecting intraarticular fluid was demonstrated by cadaver studies.     

Clinical significance of anti-Yt(b). Report of a case using a 51chromium red cell survival study

Several published reports have documented the variable survival of Yt(a+) red cells (RBC) in patients with anti-Yt(a) as measured by 51Chromium (Cr)-labeled RBC survival studies. Similar studies with anti-Yt(b) have not been reported. A 51Cr-labeled RBC survival study was performed using Yt(b+) RBCs and a monocyte monolayer assay in a young hemodialysis patient who required chronic transfusion therapy and who had developed anti-Yt(b). The survival of the transfused RBCs was 100 and 93 percent at 1 and 24 hours, respectively, with a half life of 21 days at termination of the study (normal, 28 to 32 days). These results showed no evidence of rapid destruction of the Yt(b+) RBCs, indicating that this patient could be transfused safely with blood from Yt(b+) donors. Long-term survival of the 51Cr-labeled Yt(b+) RBCs was shortened moderately, however, a finding that correlated with a slightly abnormal monocyte monolayer assay test.     

自体与异体移植重建膝关节前交叉韧带的关键技术

目的:探索膝关节前交叉韧带重建术的各个关键技术环节,为提高前交叉韧带修复的临床效果提供理论和实践依据。方法:通过分析与总结与前交叉韧带重建相关的文献资料,包括其手术方式、移植物的选择、骨道定位、髁间窝成形、移植物预张与张力、移植物固定等,同时结合作者的工作经验旨在进一步提高前交叉韧带重建技术。结果:①手术方式选择:膝关节镜下生物材料移植重建前交叉韧带取得比以往优良的临床效果,已得到广泛认可。多数采用单束重建,部分学者正在尝试双束重建以改善移植物生物力学性能。②移植材料的选择:包括自体和同种异体材料,其中自体骨-髌腱-骨与腘绳肌腱最为常用。骨-髌腱-骨由于两端带有骨块,固定牢靠,允许早期重返运动场,颇受年轻运动员青睐。腘绳肌腱取材切口小,术后很少出现膝前痛,但其稳定性不如骨-髌腱-骨,且术后相对容易出现骨隧道扩大。异体移植物在体内结合、重塑速度较自体移植慢,但若经过严格的供体筛选、合理的组织取材、消毒和保存,而不减弱移植物强度,仍可取得与自体移植相当的效果。③骨道位置:正确的骨道定位非常重要,骨道位置太靠前会造成髁间窝撞击和伸直受限。研究表明,术中采用骨性标志定位法要比采用软组织标志定位法准确,术中摄片有助于骨道位置的正确定位。④髁间窝成形术:髁间窝成形的目的是为了便于更清楚的观察髁间窝后侧,同时也是为了避免髁间窝撞击综合征的发生,由于髁间窝过度成形会增加关节出血、疼痛、肿胀以及骨赘生长,所以一般不主张广泛的髁间窝成形,除非术中确有必要时才进行。⑤移植物预张与张力:移植物初始张力不够会导致膝关节持续松弛,而张力过高会限制关节活动并加速关节退变。目前对于最佳的初始张力尚无确切说法。⑥固定:现在已经研制出许多不同类型的固定材料。对于骨-髌腱-骨而言,界面挤压螺钉单切口重建前交叉韧带时,股骨侧靠近关节腔侧固定,胫骨侧远离关节腔侧固定,双切口技术时胫骨侧靠近关节腔侧固定,股骨侧远离关节腔侧固定。股骨侧固定完毕后,膝关节取何角度对胫骨侧进行固定尚存争议。膝关节稍屈曲状态下固定不容易发生松弛,但正常的膝关节在前后方向上是允许有一定松弛度的。有些学者认为在膝关节完全伸直状态下固定可以避免屈曲挛缩畸形的发生并允许前后方向有轻度松弛。而有些学者认为在膝关节稍微屈曲状态下固定会更紧。结论:要真正做到解剖、生物力学、生理功能全方位重建,前交叉韧带重建技术,仍需不断完善,分子生物学、基因工程和组织工程技术的发展以及计算机辅助机器人手术的开展会使前交叉韧带重建技术日臻完善。