Sensory neuropeptides are not directly involved in bronchial hyperresponsiveness induced by interleukin-8 in guinea-pigs in vivo

Background Interleukin-8 (IL-8) hus been shown to be a chemotactic factor for netitrophils, T-lymphocytes and eosinophils. Repeated intranasal administration of IL-8 enhances bronchial responsiveness to inhaled histamine in guinea-pigs. Neuropeptides which arc released trotn C-fibre nerve-endings have been postulated to induce bronchial hyperresponsiveness through neurogenic inflammation. Objective This study was conducted to examine whether sensory neuropeptides are involved in the IL-8-induced bronchial hyperresponsiveness. Methods IL-8 at a dose of 5μg/kg was administered intranasally to guinea-pigs twice a week for 3 weeks. One day after the last administration, animals were anesthetized and artificially ventilaled through tracheal cannula, and lateral pressure at the tracheal cannula (Pao) was measured as an overall index of airway responses lo increasing concentrations of inhaled histamine (25, 50, 100, and 200 μg/mL). A NKI and NK2 dual antagonist FK224(10mg/kg), a selective NK1 antgonist FK888 (10mg/kg) or vehicle was intravenously administered 10min before measurement of bronchial responsiveness. Result The IL-8 treatment significantly enhanced bronchial responsiveness to histamine (ANOVA P < 0.01). FK224 or FK888 did not alter the IL-8-induced bronchial hyperresponsiveness. Conclusion We conclude that repeated intranasal administratioti of IL-8 causes bronchial hyperresponsiveness (BHR) and that neuropeptides such as neurokinin A and substance P do not directly contribute to the development of BHR induced by IL-8.     

Time-dependent Effects of Klebsiella pneumoniae Endotoxin on Hepatic Drug-metabolizing Enzyme Activity in Rats

The time-dependent effects of Klebsiella pneumoniae endotoxin on hepatic cytochrome P450-dependent drug-metabolizing capacity (cytochrome P450 and b₅ content, activity of aminopyrine N-demethylase, p-nitroanisole O-demethylase, aniline hydroxylase and benzphetamine N-demethylase) and on the pharmacokinetics of antipyrine have been determined in rats. Measurement of enzyme activity and antipyrine (after intravenous injection of 20 mgkg^?1) were performed 2, 24 and 96 h after a single intraperitoneal injection of endotoxin (1 mgkg^?1) and after repeated doses (once daily for 4 days). The contribution of tumour necrosis factor α (TNFα) to the endotoxin-induced changes was also examined in rats pretreated with granulocyte colony-stimulating factor (G-CSF). The systemic clearance of antipyrine and the activity of hepatic cytochrome P450-dependent drug-metabolizing enzymes were dramatically reduced 24 h after a single injection of endotoxin, but had returned to control levels by 96 h. The magnitudes of these decreases in these measurements after repeated doses of endotoxin were similar to those seen 24 h after the single dose. The systemic clearance of antipyrine correlated significantly with cytochrome P450 content and aminopyrine N-demethylase activity. In histopathological experiments, moderate hypertrophy of Kupffer cells was observed, with no evidence of severe liver-tissue damage. G-CSF pretreatment suppressed the increased plasma concentrations of TNFα produced 2 h after single endotoxin injection, but did not eliminate the endotoxin-induced decrease in the systemic clearance of antipyrine, suggesting that TNFα is not the sole component responsible for the reduction of cytochrome P450-mediated drug-metabolizing enzyme activity. These results provide evidence that a single intraperitoneal injection of 1·0 mgkg^?1 K. pneumoniae endotoxin in rats reduces hepatic P450 and b₅ levels, and reduces the activity of various cytochrome P450-mediated drug-metabolizing enzymes without causing severe liver-tissue damage. This suggests that the effect of endotoxin on hepatic cytochrome P450-mediated drug-metabolizing isozymes is non-selective.     

Development and Validation of Scoring Indication of Surgical Clipping and Endovascular Coiling for Aneurysmal Subarachnoid Hemorrhage from the Post Hoc Analysis of Japan Stroke Data Bank

There are no scoring methods for optimal treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). We developed a scoring model to predict clinical outcomes according to aSAH risk factors using data from the Japan Stroke Data Bank (JSDB). Of 5344 patients initially registered in the JSDB, 3547 met the inclusion criteria. Patients had been diagnosed with aSAH and treated with surgical clipping or endovascular coiling between 1998 and 2013. We performed multivariate logistic regression for poor outcomes at discharge, indicated by a modified Rankin Scale (mRS) score >2, and in-hospital mortality for both treatment methods. Based on each risk factor, we developed a scoring model assessing its validity using another dataset of our institution. In the surgical clipping group, scoring criteria for aSAH were age >72 years, history of more than once stroke, World Federation of Neurological Societies (WFNS) grades II–V, aneurysmal size >15 mm, and vertebrobasilar artery (VBA) aneurysm location. In the endovascular coiling group, scoring criteria were age >80 years, history of stroke, WFNS grades III–V, computed tomography (CT) Fisher group 4, and aneurysmal location in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). The rates of poor outcome of mRS score >2 in an isolated dataset using these scoring criteria were significantly correlated with our model’s scores, so this scoring model was validated. This scoring model can help in the more objective treatment selection in patients with aSAH.     

金钱草抗炎利胆有效部位研究

目的:寻找金钱草抗炎利胆有效部位。方法:采用二甲苯致小鼠耳廓肿胀实验和醋酸致小鼠腹腔毛细血管通透性增高实验对金钱草各提取部位进行了抗炎活性筛选,用小鼠及大鼠胆汁分泌实验进行利胆活性筛选。结果:金钱草醇提物和乙酸乙酯提取物能显著抑制二甲苯所致的小鼠耳廓肿胀和醋酸所致的小鼠腹腔毛细血管通透性亢进,明显促进小鼠和大鼠胆汁的分泌。结论:乙酸乙酯提取部分可能是金钱草抗炎利胆的有效部位。     

Three cases of pyogenic sacro-iliitis,and factors in the relapse of the disease

Pyogenic sacro-iliitis (PS) is a rare disease in childhood. Three cases of PS are reported that were difficult to diagnose. Scintigraphy and magnetic resonance imaging (MRI) were useful for diagnosis. One patient suffered from an episode of relapse. Seventeen other cases of PS were reviewed in the literature to investigate the incidence of abnormal imaging findings and various factors in disease relapse. It was found that the incidence of abnormal findings by scintigraphy was significantly higher than that by computed tomography (P = 0.0057). The duration of intravenous antibiotic administration of the relapse group (14.7 ± 4.7 days) was significantly shorter than that of the non-relapse group (24.3 ± 10.7 days; P = 0.0376). The statistical analysis suggested that intravenous antibiotic administration is necessary at least for 20 days to prevent a relapse of PS.     

Factors affecting the bond strength of denture base and reline acrylic resins to base metal materials

Objective

The shear bond strengths of two hard chairside reline resin materials and an auto-polymerizing denture base resin material to cast Ti and a Co-Cr alloy treated using four conditioning methods were investigated.

Material and Methods

Disk specimens (diameter 10 mm and thickness 2.5 mm) were cast from pure Ti and Co-Cr alloy. The specimens were wet-ground to a final surface finish of 600 grit, air-dried, and treated with the following bonding systems: 1) air-abraded with 50-70-µm grain alumina (CON); 2) 1) + conditioned with a primer, including an acidic phosphonoacetate monomer (MHPA); 3) 1) + conditioned with a primer including a diphosphate monomer (MDP); 4) treated with a tribochemical system. Three resin materials were applied to each metal specimen. Shear bond strengths were determined before and after 10,000 thermocycles.

Results

The strengths decreased after thermocycling for all combinations. Among the resin materials assessed, the denture base material showed significantly (p<0.05) greater shear bond strengths than the two reline materials, except for the CON condition. After 10,000 thermocycles, the bond strengths of two reline materials decreased to less than 10 MPa for both metals. The bond strengths of the denture base material with MDP were sufficient: 34.56 MPa for cast Ti and 38.30 for Co-Cr alloy.

Conclusion

Bonding of reline resin materials to metals assessed was clinically insufficient, regardless of metal type, surface treatment, and resin composition. For the relining of metal denture frameworks, a denture base material should be used.     

Vascular Endothelial Growth Factor–Bound Stents: Application of In Situ Capture Technology of Circulating Endothelial Progenitor Cells in Porcine Coronary Model

Objectives

We evaluated the in vivo performance of a newly devised vascular endothelial growth factor (VEGF)‐bound stent in a porcine coronary model.

Background

An anti‐CD34 antibody‐bound stent, which captures endothelial progenitor cells (EPCs) to accelerate tissue formation, did not reduce intimal hyperplasia. By targeting the VEGF receptor, which is expressed on endothelial‐lineage cells, we developed VEGF‐bound stents that may enable selective capture of EPCs followed by rapid endothelialization.

Methods

Metallic stents were first coated with poly‐(ethylene‐co‐vinyl alcohol), and then chemically bound with either VEGF or anti‐CD34 antibody. These stents were placed in porcine coronary arteries for up to 14 days. Stent surface was evaluated by immunohistochemistry and by scanning electron microscope (SEM).

Results

After 2‐day stenting with VEGF‐bound stents, small populations of KDR (VEGF receptor‐2)‐positive cells adhered to the stent struts. After 7‐ and 14‐day stenting, struts were fully covered with newly regenerated tissue. SEM images showed that the uniform tissue formed on struts was morphologically similar to native endothelium and was continuously connected with adjacent native endothelium. On the other hand, for the anti‐CD34 antibody‐bound stents, stent struts were rapidly covered by newly generated tissue that consisted of multicellular aggregates.

Conclusions

Compared with anti‐CD34 antibody‐bound stents, VEGF‐bound stents provide highly selective capture of EPCs, followed by rapid formation of intact endothelium tissue at an early period of stenting. These results suggest that VEGF‐bound stents could represent a promising therapeutic option for cardiovascular stenting, although further long‐term follow‐up experiment with double‐blinded fashion is needed prior to clinical application. (J Interven Cardiol 2014;27:63–72)

     

Fatal cytomegalovirus myocarditis in a seronegative ALL patient

Fatal cytomegalovirus (CMV) myocarditis occurred in a 2 year old boy with acute lymphoblastic leukemia (ALL) in remission. The patient showed mild hepatic dysfunction and a rapid progress of pancytopenia after complete remission had been achieved. At the fifth week of complete remission, he presented signs of heart failure such as tachycardia, S4 gallop on auscultation and decreased ejection fraction on echocardiography. However, no significant electrocardiographic changes were recognized. In addition to the cardiac dysfunction, the patient presented a marked tachypnea and dyspnea associated with hypoxemia. These were dramatically improved by methylprednisolone pulse therapy (30 mg/kg per day, for 3 days) and CMV high titer immunoglobulin (400 mg/kg per day, for 3 days). On the sixth day after signs of respiratory failure were improved, the patient suddenly presented a paroxysmal atrial tachycardia followed by a fatal ventricular fibrillation. Although we could detect neither a specific IgM antibody, a significant increase of IgG antibody, nor CMV genome by DNA hybridization techniques during the course of the illness, microscopic examination of necropsy specimens of the heart showed a marked disruption and disintegration of muscle bands associated with cytomegalic inclusion bodies. Polymerase chain reaction (PCR) yielded a 305 bp amplification product in the heart and lung tissues, supporting the view that myocarditis was caused by CMV.