Amniotic membrane, tear film, corneal, and aqueous levels of ofloxacin in rabbit eyes after amniotic membrane transplantation

PURPOSE: We evaluated ocular penetration and drug levels in tears after topical ofloxacin instillation in rabbit eyes with amniotic membrane transplantation (AMT). METHODS: Forty-eight New Zealand White rabbits were used. In the first set of experiments, 24 rabbits (24 eyes) were divided into four groups according to the epithelial removal or AMT. Topical ofloxacin was instilled four times every 15 minutes. One hour after the last eyedrop, the concentration of ofloxacin in the amniotic membrane, cornea, and aqueous humor was evaluated. In the second set of experiments, 24 rabbits were divided into six groups according to AMT (transplantation of lyophilized or fresh amniotic membrane) or duration of application. Ofloxacin ointment or two drops of ofloxacin were applied to the right eye, and then tear samples were collected after 0.5, 1, 2, 4, and 6 hours for the analysis of ofloxacin concentration. RESULTS: Mean ofloxacin concentrations in the cornea and aqueous humor were statistically higher in deepithelialized cornea regardless of AMT (p < 0.05). The mean tear levels of ofloxacin in the AMT groups were statistically higher than those in non-AMT groups (p < 0.05). There was no statistical significance in the tear level of ofloxacin between lyophilized amniotic membrane groups and fresh amniotic membrane groups nor between 1-hour amniotic membrane-attached groups and 6-hour amniotic membrane-attached groups. CONCLUSION: Amniotic membrane transplantation seems to interfere with the ocular penetration of topical ofloxacin in normal rabbit corneas but enhances ofloxacin penetration in corneas with epithelial defects. The ofloxacin level in tears was higher in eyes with AMT up to 1 hour after topical ofloxacin use. Therefore, it seems that amniotic membrane has some potential to act as an effective drug delivery system.     

Congenital infantile fibrosarcoma of the upper extremity

Congenital-infantile fibrosarcoma is an unusual childhood tumor that occurs mainly in children under 5 years of age. More than 300 cases have been reported in the literature so far, very few of them at birth. A distinction must be made between it and its adult counterpart because of differences in their clinical behaviour. We report here a case of congenital fibrosarcoma in a 4-day-old female infant.     

The preterm gut microbiota: changes associated with necrotizing enterocolitis and infection

Aim: To describe gut colonization in preterm infants using standard culture and 16S gene rRNA profiling, exploring differences in healthy infants and those who developed NEC/late onset sepsis (LOS). Methods: Ninety‐nine stools from 38 infants of median 27‐week gestation were cultured; 44 stools from 27 infants had their microbial profiles determined by 16S. Ordination analyses explored effects of patient variables on gut communities. Results: Standard microbiological culture identified a mean of two organisms (range 0–7), DGGE 12 (range 3–18) per patient. Enterococcus faecalis and coagulase negative staphylococci (CONS) were most common by culture (40% and 39% of specimens). Meconium was not sterile. No fungi were cultured. Bacterial community structures in infants with NEC and LOS differed from healthy infants. Infants who developed NEC carried more CONS (45% vs 30%) and less Enterococcus faecalis (31% vs 57%). 16S identified Enterobacter and Staphylococcus presence associated with NEC/LOS, respectively. Conclusions: Important differences were found in the gut microbiota of preterm infants who develop NEC/LOS. The relationship of these changes to current practices in neonatal intensive care requires further exploration.     

The Efficacy of Tranexamic Acid in Total Knee Arthroplasty: A Network Meta-Analysis

Background

A growing body of published research on tranexamic acid (TXA) suggests that it is effective in reducing blood loss and the risk for transfusion in total knee arthroplasty (TKA). The purpose of this network meta-analysis was to evaluate TXA in primary TKA as the basis for the efficacy recommendations of the combined clinical practice guidelines of the American Association of Hip and Knee Surgeons, American Academy of Orthopaedic Surgeons, Hip Society, Knee Society, and American Society of Regional Anesthesia and Pain Medicine on the use of TXA in primary total joint arthroplasty.

LC-MS/MS测定人血浆中对乙酰氨基酚及其人体药动学和生物等效性研究

目的 建立一种快速、灵敏的高效液相色谱-串联质谱（HPLC-MS/MS）方法以测定人血浆中对乙酰氨基酚浓度,并应用于两种对乙酰氨基酚制剂的人体药代动力学和生物等效性研究。方法 以替硝唑为内标,200μL血浆样品经5倍于其体积的乙酸乙酯液液萃取,再经Waters XBridge? C18柱等度洗脱分离后导入串联质谱,以正离子多反应监测模式进行定量分析,对乙酰氨基酚和内标的选择性反应离子对分别是m/z 152→110和248→121。方法经验证后应用于19名健康受试者单剂量空腹口服两种对乙酰氨基酚制剂500mg后药代动力学和生物等效性的研究。结果 血浆中对乙酰氨基酚在0.1～8.0 μg·mL-1范围内线性良好（r2 > 0.99）,最低检测限为 0.1 μg·mL-1,提取回收率为91.0%～98.7%,日内和日间准确度分别为98.8%～111.3% （精密度：CV ? 9.03%）和94.9%～102.6% （精密度：CV ? 10.68%）。生物等效性试验中,受试制剂与参比制剂的主要药代动力学参数Cmax、AUC0-t和AUC0-∞ 几何均值比的90%置信区间分别为83.50%～105.79%,94.25%～101.54%和93.24%～101.02%,均落在生物等效可接受标准80.00%～125.00%范围内。结论 所建立测定人血浆中对乙酰氨基酚浓度的HPLC-MS/MS法具有快速灵敏、回收率高、选择性好的特点,适用于对乙酰氨基酚片人体药代动力学和生物等效性研究。受试制剂与参比制剂在人体内吸收速度和程度相似,两种制剂生物等效。     

Novel method for the quantitative assessment of cell migration: a study on the motility of rabbit anterior cruciate (ACL) and medial collateral ligament (MCL) cells

A novel method of quantitating cell migration has been proposed for the potential utilization of tissue engineered scaffolds. Applying Alt's conservation law to describe the motion of first passage ACL and MCL cells, we have developed a quantitative method to assess innate differences in the motility of cells from these two ligamentous tissues. In this study, first passage ACL and MCL cells were cultured from four mature New Zealand white rabbits. One side of the cell monolayer was scraped completely away to create a wound model. The cell moved into the cell-free area, and cell density profiles were analyzed at 6 h and 12 h. Values of the random motility coefficient (mu) were then estimated by curve fitting the 6 h and 12 h data to a mathematical model, derived from the conservation law of cell flux. During 6 h of incubation in medium supplemented with 1% FBS, MCL cells (mu(MCL) = 4.63 +/- 0.65 X 10(-6) mm(2)/sec) were significantly (p < 0.05) more mobile than ACL cells (mu(ACL) = 2.51 +/- 0.31 X 10(-6) mm(2)/sec). At 12 h, the MCL cells also appeared to move faster (mu(ACL) = 4.39 +/- 0.63 X 10(-6) mm(2)/sec, mu(MCL) = 6.59 +/- 1.47 X 10(-6) mm(2)/sec), but the difference was not statistically significant (p = 0.18). Exposure of the cells to growth factors PDGF-BB or bFGF for 6 h had no significant effect on the migration of the ACL and MCL cells. However, exposure of the ACL cells (p < 0.05) and the MCL cells (p = 0.19) to 1 ng/mL of PDGFBB for 12 h enhanced their migration. Incubation with a high concentration (100 ng/mL) of PDGF-BB or bFGF at concentrations tested (1 or 100 ng/mL) for 12 h, produced little or no migratory stimulation on these ligament cells. Our findings support the previous qualitative observations made by numerous investigators. The novel methodology developed in this study may provide a basis for tissue engineering, and the results may be applied to tissue reconstruction techniques of the knee ligaments.     

Early repeat endoscopic retrograde cholangiopancreatography: Predictive factors and interventions required

Background/aims: Early repeat endoscopic retrograde cholangiopancreatography may be required due to various conditions in patients who underwent planned endoscopic retrograde cholangiopancreatography. We aimed to assess the factors leading to early repeat endoscopic retrograde cholangiopancreatography and to determine the patients who need closer follow-up. Materials and Methods: A total of 691 patients with a mean age of 60.3±16.4 years who had naive papilla on endoscopic retrograde cholangiopancreatography were involved in the study. The patients who required repeat endoscopic retrograde cholangiopancreatography were identified. Presentations, predictive factors, treatment modalities, and outcomes of the patients were investigated. Results: Early repeat endoscopic retrograde cholangiopancreatography was needed in 19 (2.7%) patients. The most common presentation was cholangitis in 10 (52.6%) and unresolved jaundice in 4 (21.1%). Multivariate analysis identified biliary stricture (p=0.024), stricture at the hilus (p=0.005) and unilateral drainage in the presence of hilar stricture (p=0.017) as the independent risk factors for early repeat endoscopic retrograde cholangiopancreatography. Stent migration or dysfunction was the most common underlying cause. Therapeutic interventions were nasobiliary drainage in 13, stent exchange in 4 and stone removal in 2. Additionally, percutaneous drainage in 4 patients, drainage of abscess in 2 patients and percutaneous drainage of gallbladder in 1 patient were performed. Three patients died due to their underlying illness. Conclusions: Unilateral stenting especially in hilar strictures is a predictive factor for early repeat endoscopic retrograde cholangiopancreatography with high mortality. These patients should be under close follow-up.     

Ca2+-activated K+ (BK) channel inactivation contributes to spike broadening during repetitive firing in the rat lateral amygdala

In many neurons, trains of action potentials show frequency-dependent broadening. This broadening results from the voltage-dependent inactivation of K⁺ currents that contribute to action potential repolarisation. In different neuronal cell types these K⁺ currents have been shown to be either slowly inactivating delayed rectifier type currents or rapidly inactivating A-type voltage-gated K⁺ currents. Recent findings show that inactivation of a Ca²⁺-dependent K⁺ current, mediated by large conductance BK-type channels, also contributes to spike broadening. Here, using whole-cell recordings in acute slices, we examine spike broadening in lateral amygdala projection neurons. Spike broadening is frequency dependent and is reversed by brief hyperpolarisations. This broadening is reduced by blockade of voltage-gated Ca²⁺ channels and BK channels. In contrast, broadening is not blocked by high concentrations of 4-aminopyridine (4-AP) or α-dendrotoxin. We conclude that while inactivation of BK-type Ca²⁺-activated K⁺ channels contributes to spike broadening in lateral amygdala neurons, inactivation of another as yet unidentified outward current also plays a role.