Antibacterial activity of nadifloxacin against Staphylococcus and Propionibacterium isolated from patients with dermatological infections

Nadifloxacin (NDFX) is a fluoroquinolone antibiotic developed by Otsuka Pharmaceutical Co., Ltd. and is used as a topical drug for the treatment of infections in the field of dermatology. We investigated the susceptibility of a total of 575 strains (two kinds of Staphylococcus species and Propionibacterium species which were isolated from patients with dermatological infections for 3 periods, i.e., 1996, 2000 and 2005) to NDFX and other reference antibiotics. The minimum inhibitory concentration of the four antibiotics, NDFX, levofloxacin (LVFX), clindamycin (CLDM) and gentamicin (GM), against the test strains were determined by the agar dilution methods, in according with the Japan Society of Chemotherapy. The antibacterial activity of NDFX against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis and P. acnes was the most potent of all the antibiotics tested, and there were no test organisms which became resistant to NDFX with period. The MIC90 values of NDFX for the four test organisms isolated in 2005 were 0.05 microg/mL; MSSA, 1.56 microg/mL; MRSA, 0.78 microg/mL; S. epidermidis and 0.20 microg/mL; P. acnes, respectively. On the other hand, there were LVFX-, CLDM- and GM-resistant MRSA. The MIC50 values of CLDM and GM for MRSA were >100 and 25 microg/mL, respectively. The MIC50 value of GM for P acnes was 12.5 microg/mL, but NDFX was potently active against these organisms as compared with these two antibiotics and the MIC50 values of NDFX were 0.05 microg/mL for MRSA and 0.20 microg/mL for P. acnes. These results suggest that NDFX is even at present useful as an antibiotic for the treatment of infections in the field of dermatology though it is more than 12 years since the approval to manufacture and sell the drug was obtained in 1993.     

coagulation and D-dimer in 58 patients with Kawasaki disease

目的 探讨川崎病(KD)患儿治疗前后出凝血四项和D-二聚体的变化及其与冠状动脉损伤的关系.方法 测定58例KD患儿出凝血四项,包括凝血酶原时间(PT)、部分凝血酶原活化时间(APTT)、凝血时间(TT)、纤维蛋白原定量(FIB)和D-二聚体(D-D),以及血小板计数(PLT),根据心脏彩超结果分为非冠状动脉损伤组(nCAL)和冠状动脉损伤组(CAL),并进行分析与评价.结果 两组患儿治疗前PLT、FIB、D-D均高于正常,冠状动脉损伤组增高更明显,两组比较差异有统计学意义,治疗一周后PLT仍处于上升期,而FIB、D-D均较治疗前有所下降,但冠状动脉损伤组仍高于非冠状动脉损伤组,两组比较差异有统计学意义.结论 FIB、D-D是判断川崎病血液高凝状态及疗效的敏感指标.     

Trial of isolation of a virus from sera of patients with Kawasaki disease

We tried to isolate pathogenic viruses from specimens of patients with Kawasaki disease. Blood clots and sera, spinal fluid, throat swabs, stool and urine from 24 patients with Kawasaki disease were studied. The specimens were inoculated into HEL cells and Vero cells. The cells were observed for one month, but no cytopathic effect (CPE) occurred. Blind passage was performed, but no degeneration of the second series of cells was observed. Fluorescent antibody indirect methods to determine viral antigens in cells inoculated with patients' specimens was also negative.     

Protective effects of an acidic polysaccharide isolated from fruiting bodies of Ganoderma lucidum against murine hepatic injury induced by Propionibacterium acnes and lipopolysaccharide

Fruiting bodies of Ganoderma lucidum were extracted with chloroform followed by hot water, from which an acidic polysaccharide named GLAa was separated and purified using 10% CCl₃COOH followed by column chromatography on DE-52 cellulose and Toyopearl HW-65. Chemical and spectroscopic analyses showed that GLAa was composed of Glc, Gal, Man and Fuc (1:0.013:0.009:0.024), in which β-d-(1→6)-Glc, β-d-(1→3)-Glc and β-d-(1→4)-Glc linkages comprised 34.9, 33.9, and 28.7% of the total linkages, respectively. The average molecular weight of GLAa was 12.5×10⁵ Da and the optical rotation was [a]^{25° \textC}_\textD = - 9.1^° [\alpha ]^{{25^\circ {\text{C}}}}_{{\text{D}}} = - 9.1^\circ ; c =0.55, H₂O. Uronic (mannuronic) acid accounted for 14.8% of the molecule, protein, 0.14% and nitrogen, 0.75%. The hepatoprotective effect of GLAa was evaluated using a mouse model in which hepatic injury was induced with Propionibacterium acnes and lipopolysaccharide (LPS). GLAa (0.4 and 0.8 g kg⁻¹ day⁻¹, b.w., p.o.), significantly prevented increases in serum aspartate aminotransferase and alanine aminotransferase levels in mice exposed to P. acnes–LPS, indicating that GLAa has hepatoprotective activity in vivo.     

11味中药对痤疮丙酸杆菌的体外抑制作用研究

通过研究11味中药对痤疮丙酸杆菌的体外抑制作用,筛选出用于治疗痤疮的中药单方与复方。采用牛津杯法测定了11味中药的水提液与醇提液的抑菌圈直径,发现同种中药的水提液与醇提液的抑菌效果相近,且痤疮丙酸杆菌对黄连高敏,对黄柏、黄芩、丹参、半枝莲中敏,对其余6味中药耐药。将黄连分别与其它4味有效中药复配,所得复方水提液中,黄连丹参复方抑菌效果较好,当黄连∶丹参（w/w）=1.5∶8.5时,其抑菌圈直径较大,达23.5 mm。提示黄连以及黄连丹参复方对痤疮丙酸杆菌有较好的抑制作用,为研制治疗痤疮的新药提供了依据。     

Investigation of antibacterial activity of rosemary essential oil against Propionibacterium acnes with atomic force microscopy

In the present study, the antibacterial activity of rosemary (Rosmarinus officinalis L. Labiatae) essential oil against Propionibacterium acnes (P. acnes) was observed with atomic force microscopy (AFM). The MIC (minimal inhibitory concentration) value of rosemary essential oil against P.acnes was 0.56 mg/mL. Significant changes in morphology and size of P. acnes were observed by atomic force microscopy (AFM) in response to essential oil treatment. The essential oil first attached to the surface of P. acnes at low concentration, the width and height of the bacterial body became larger, whereas the length did not change considerably. With increasing concentration of the essential oil, the bacterial bodies were severely damaged. The length, width and height were all reduced, when the concentration was increased up to 64xMIC, the length, width and height were reduced by 42.56%, 92.00% and 41.58%, respectively. Furthermore, treated bacteria lost their native shape, the cell wall desquamated, and the cytoplasm leaked out of the bacterial body, finally leading to bacterial death. With the increasing time at MIC, the bacteria length was reduced at 8 h, the width and height gradually became smaller, the shape of the cell became distorted, and finally led to cell wall damage and bacterial death at 8 h. In conclusion, the AFM investigation of morphology and size of P. ACNES treated with rosemary essential oil represents a powerful technique, which can generally be applied to reveal the biological changing mechanisms of bacteria induced by antibacterial agents at the nanometer level.     

延迟使用静脉注射免疫球蛋白对川崎病的临床疗效观察

目的探讨延迟静脉注射免疫球蛋白IVIG治疗对川崎病（KD）的临床效果。方法选择2010年1月～2012年9月我院延迟使用IVIG治疗的KD患儿78例记为观察组,同时选择7d内接受IVIG治疗且在性别、年龄、体重与之匹配的患儿78例为对照组。比较两组治疗前后WBC、NEUT、HGb、PLT、AI用、AST、TB和CRP等,并计算改变分数（Fractionalchanges,FC）;同时比较两组治疗前、急性期及恢复期发生冠状动脉病变（CALs）的例数,CALs包括冠状动脉扩张（CAD）和冠状动脉瘤（CAA）。结果治疗前,与对照组比较,观察组不典型川崎病（IKD）的例数、发病至IVIG的时间、NEUT、ALT及CRP明显增高,PIJrr明显降低,差异有统计学意义（P〈0．05）;两组治疗后WBC、NEUT、ALT和CRP的FC差异无统计学意义（P〉O．05）;治疗前、急性期和恢复期,观察组CALs总例数（CAD与CAA之和）均明显高于对照组,差异有统计学意义（P〈0．01,P〈0．05）。结论延迟IVIG治疗与早期IVIG治疗对KD患者免疫系统的调节作用相当,但延迟IVIG治疗与CALs的发生率增高有关。     

Influence of histamine in a liver injury model induced by Propionibacterium acnes and lipopolysaccharide

In normal mice, plasma histamine levels were 29.4+/-10.1 pmol/ml. When 0.1 microg of lipopolysaccharide (LPS) was intravenously injected into Propionibacterium acnes (P. acnes)-primed ICR mice, histamine levels increased remarkably to 61.2+/-15.9 pmol/ml (p<0.001). An increase was also observed in liver tissues. Oral administration of histidine at 200 mg/kg once daily for 5 d before intravenous LPS injection increased the plasma alanine aminotransferase (ALT) activity to 2936.5+/-356.3 IU/l, a significant change compared with the controls (2244.8+/-425.5 IU/l, p<0.05). The 24 h survival rate after LPS injection was 72.7% in the mice treated with 50 mg/kg of ranitidine, in contrast with 50% in the control group although the treatment did not significantly decrease the plasma ALT activity. On the other hand, 50 mg/kg of pyrilamine significantly reduced plasma ALT activity (p<0.001). The results suggested that histamine levels are related to hepatic damage in the P. acnes plus LPS induction of liver injury.     

58例川崎病患儿出凝血四项和D-二聚体的检测及分析

目的探讨川崎病(KD)患儿治疗前后出凝血四项和D-二聚体的变化及其与冠状动脉损伤的关系。方法测定58例KD患儿出凝血四项,包括凝血酶原时间(PT)、部分凝血酶原活化时间(APTT)、凝血时间(TT)、纤维蛋白原定量(FIB)和D-二聚体(D-D),以及血小板计数(PLT),根据心脏彩超结果分为非冠状动脉损伤组(nCAL)和冠状动脉损伤组(CAL),并进行分析与评价。结果两组患儿治疗前PLT、FIB、D-D均高于正常,冠状动脉损伤组增高更明显,两组比较差异有统计学意义,治疗一周后PLT仍处于上升期,而FIB、D-D均较治疗前有所下降,但冠状动脉损伤组仍高于非冠状动脉损伤组,两组比较差异有统计学意义。结论 FIB、D-D是判断川崎病血液高凝状态及疗效的敏感指标。     

Chain terpenoids isolated from cultures of basidiomycete Phellinus sp.

Two new sesquiterpenoids (phellinuins H and I), together with five known compounds, were isolated from cultures of mushroom Phellinus sp. Their structures were elucidated based on comparison of nuclear magnetic resonance and MS data and those reported in the literature. All of these compounds were tested for cytotoxicity against five cancer cell lines (HL-60, SMMC-721, A-549, MCF-7, and SW-480).     

静脉丙种球蛋白治疗不完全川崎病与典型川崎病患儿的疗效

目的探究典型和不完全川崎病患者均行静脉丙种球蛋白治疗的效果差异性。方法选取2017年1～12月我院收治的60例川崎病患儿为研究对象,根据患儿病变情况进行分组,其中24例典型川崎病患儿为典型组,36例不完全川崎病患儿为不完全组,两组患者均行静脉丙种球蛋白治疗法,应用统计学软件对两组患儿临床症状改善及住院时间进行比较,对两组患儿治疗前后血液检测指标及冠状动脉病变情况进行比较。结果不完全组患儿发热、粘膜充血、皮疹、手足肿胀及淋巴结肿大等临床症状消退时间及住院时间相较于典型组患儿显著更少,数据经比较差异有统计学意义(P 0.05);治疗前两组患儿血小板、白细胞、血沉、C反应蛋白水平等血液检测指标,及冠状动脉病变发生率经比较差异无统计学意义(P 0.05),治疗后不完全组患儿4项血液检测指标及冠状动脉病变发生率相比典型组显著更低,数据经比较差异有统计学意义(P 0.05)。结论静脉丙种球蛋白对小儿不完全川崎病的疗效显著优于典型川崎病患儿,提示针对典型川崎病患儿需要加大给药剂量,延长给药时间以提升其临床疗效,同时针对不完全川崎病患儿的治疗可采取本次研究所用疗法,并可用于临床推广。     

C反应蛋白在静脉丙种球蛋白不敏感川崎病患儿中的临床意义

目的 分析川崎病患儿血清C反应蛋白（CRP）在静脉丙种球蛋白（IVIG）治疗过程中的变化,对血清CRP变化水平预测IVIG治疗不敏感患儿的疗效进行评价.方法 收集2009年1月至2012年12月在我院与广东省妇幼保健院住院的川崎病患儿;首剂IVIG（2g· kg-1·d-1）治疗后48 h退热为A组,未退热者再予相同剂量IVIG,次剂48 h退热为B组,继续/反复发热为C组.所有患儿均在首剂IVIG前、首剂48 h后（次剂IVIG前）抽取CRP.分析各组CRP变化情况及其与冠状动脉病变（CALs）的关系.结果 纳入病例146例,男性患儿84例,女性患儿62例,A组110例,B组26例,C组10例.发生CALs 20例,A、B、C组分别有8（7.3％）、5（19.2％）、7（70.0％）例.CALs阳性与阴性患儿首剂IVIG前CRP的差异无统计学意义（P＞0.05）,治疗48 h后差异具有统计学意义（P＜0.05）.A、B、C三组比较,首剂IVIG治疗前组间CRP水平、最终形成CALs的例数差异无统计学意义（P＞0.05）,48 h后差异有统计学意义（P＜0.05）,结果表明CRP水平的变化与CALs的发生有相关性.结论 对首剂IVIG不敏感的患儿更易患CALs,治疗48 h后CRP水平仍然较高者更易发生CALs;对首剂IVIG不敏感者在首剂IVIG治疗后48 h CRP仍然较高时,很可能对次剂IVIG仍然失败,应及早考虑对此类表现的患儿使用更强的抗炎手段.     

丙种球蛋白无反应性川崎病的治疗研究

目的探讨对大剂量静脉注射丙种球蛋白(IVIG)无反应性川崎病(KD)的临床特点,以及再治疗方案的选择。方法收集2007年1月至2009年12月入院的140例IVIG无反应性的KD患儿,将患儿随机分为4组对照组(单用阿司匹林),IVIG追加治疗组(阿司匹林基础上加2 g.kg-1.d-1IVIG),泼尼松组(阿司匹林基础上加甲泼尼龙20～30 mg.kg-1.d-1)及乌司他丁治疗组(阿司匹林基础上加乌司他丁5 000 U.kg-1),比较各组的临床特点及治疗效果。结果单用阿司匹林治疗的对照组患儿,心脏冠状动脉病变(CAD)并发率明显高于IVIG追加治疗组、泼尼松组及乌司他丁组。且恢复时间较长。IVIG追加治疗组、泼尼松组及乌司他丁组治疗有效率明显高于对照组,但3组之间无统计学差异,且3组患儿CAD并发率相似。结论 IVIG无反应性川崎病较IVIG敏感性川崎病更易发生CAD和严重并发症;对IVIG无反应性川崎病可以用IVIG追加治疗、糖皮质激素或合用乌司他丁,都可以取得较好的疗效。     

Impaired cholinergic dilator response of resistance arteries isolated from patients with Raynaud''s disease

AIMS: We examined the effect of cooling on the response to the endothelium-dependent and -independent dilators, acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in human microvessels in vitro, and compared the responses between Raynaud's disease (RD) patients and controls, in order to assess the pathogenic role of the endothelium in RD. METHODS: Subcutaneous resistance arteries were dissected from gluteal fat biopsies taken from patients with RD (n=18) and from age-and sex-matched control subjects (n=17). Vessels were cannulated in a small vessel arteriograph, in which a pressure of 50 mmHg was maintained across the vessel wall. Cumulative concentration-response curves for ACh (10-10-10-4 m ) and SNP (10-10-10-3 m ) were generated in vessels at either 37 degrees C or 24 degrees C, with endothelium intact for ACh and removed for SNP (n=6 per group). RESULTS: Neither dilator showed significant differences in sensitivity when comparing responses between vessels from RD patients and controls, at either temperature, but the maximal relaxation to ACh was depressed in vessels from RD patients compared with controls at 37 degrees C (Emax=45+/-13 in RD vs 89+/-4 in controls; P=0.004). CONCLUSIONS: These results support the hypothesis that impaired endothelium-dependent vasodilatation is involved in the pathophysiology of RD.     

云南省川崎病患病情况调查

目的　了解云南省川崎病的发病、分布和流行病学特征。方法　采用日本中国川崎病流行病调查表 ,对云南省 12 6家县级以上有儿科病床的医院、妇幼保健院进行填表调查。结果　 5年间共报告患儿 594例 ,发病率 4 45 10万 ;男女之比为 1 50∶1(3 56 2 3 8) ,发病年龄以 5岁以下为主 (86 2 % )。以城市患儿居多为 3 98例(67 0 % )。少数民族患儿 45例 (7 6% )。 3 99例中发生心脏后遗症者 114例 (2 8 6% )。无死亡病例。复发病例4例 (0 7% )。结论　云南省川崎病发病明显低于日本 ,而与国内部分省份相近。心脏后遗症者高于日本与国内一些省份。基层医院应提高对川崎病的认识和提高诊断治疗水平     

川崎病的静脉注射免疫球蛋白治疗

川崎病(Kawasaki disease,KD)的病因目前尚未完全明了,尽管许多证据表明其发病可能与感染有关,但是尚未被证实.     

Altered protein binding of disopyramide in plasma from patients with cancer and with inflammatory disease

Protein binding of disopyramide (D) was studied in eight patients with cancer, seven with inflammatory diseases, and seven healthy subjects. Plasma samples containing concentrations of 0.2-12.0 micrograms/ml were ultrafiltered, and the free fractions were measured with fluorescence polarization immunoassay. The mean free fractions at D concentrations ranging from 1.0 to 6.0 micrograms/ml were significantly less in patients with cancer (p less than 0.01) and those with inflammatory diseases (p less than 0.05) than in healthy subjects. Patients with cancer had a greater (p less than 0.05) D binding than those with inflammatory diseases. A multiple regression analysis revealed a significant contribution of plasma alpha 1-acid glycoprotein (AAG) (r = -0.79, p less than 0.01), but not of albumin (r = -0.096), to the overall variability in D binding at 3.0 micrograms/ml. The mean capacity constant in the two patient groups was similar, but significantly (p less than 0.01) greater than in the healthy group. Nonspecific D binding was greater in cancer patients (p less than 0.01) compared to the other two groups. Our results suggest that (a) therapeutic range of D measured as total drug concentration in patients with cancer and with inflammatory diseases would be greater than previously thought, and (b) unidentified component(s) (other than AAG and albumin) might contribute to the greater D binding in cancer patients compared to other study groups.     

Plasma protein binding of azapropazone in patients with kidney and liver disease.

1 The free fraction of azapropazone in the plasma of 37 healthy volunteers ranged from 0.0027 to 0.0070 (0.0044 +/- 0.0009, mean +/- s.d.). The principal binding protein was found to be albumin. 2 In 27 patients with various degrees of renal failure the free fraction values of azapropazone were markedly enhanced (0.0260 +/- 0.0239, mean +/- s.d.) and increased more than tenfold in some patients. There was a weak correlation (r = 0.46, P less than 0.05) between the free fraction and the clearance of endogenous creatinine. Such correlation was not found for serum creatinine, serum albumin, serum uric acid and serum urea nitrogen. 3 In 32 patients with chronic liver disease the free fraction values of azapropazone were also markedly higher (0.0210 +/- 0.0242, mean +/- s.d.) than in healthy subjects. There were statistical significant correlation between free fraction values and the prothrombin complex activity in the plasma (r = 0.40, P less than 0.05) and the total bilirubin concentration in the plasma (r = 0.90, P less than 0.001), respectively. Such correlation was not found for serum albumin, serum glutamic oxalacetic transaminase, serum gamma-glutamyl transpeptidase and serum alkaline phosphatase. 4 In patients with kidney and liver disease the free fraction values of azapropazone correlated well with those of the anticoagulant drug phenprocoumon (r = 0.93, P less than 0.001). However, the binding of the latter drug was less impaired. Bilirubin, when added in vitro, displaced both drugs from plasma proteins but this displacing effect was much smaller than the binding changes observed in patients with liver disease. 5 Kidney and liver disease caused a marked impairment of the plasma protein binding of azapropazone. In patients with kidney disease the degree of impairment of azapropazone binding cannot or only poorly (creatinine clearance) be predicted from the biochemical parameters of kidney function whereas in patients with chronic liver disease the total bilirubin concentration in the plasma may serve as an index of the binding defect.     

川崎病96例临床分析

目的比较不完全性川崎病与典型川崎病的临床特征,以期为川崎病的临床诊疗提供帮助。方法选择在我院住院部治疗过的96例川崎病患儿,分为不完全性川崎病组与典型川崎病组,比较两组的临床表现及治疗前的实验室指标。结果除肛周脱屑外,两组眼球结膜充血、口唇充血皲裂、皮疹、手足硬肿、指端脱皮,淋巴结肿大、草莓舌、冠状动脉病变的发生例数比较差异均有统计学意义（P〈0.05）。应用药物治疗前,除血红蛋白外,白细胞、血小板、血沉、C反应蛋白、白蛋白比较差异无统计学意义（P〉0.05）。结论对于不完全性川崎病,在排除其他疾病引起的发热后,参考血红蛋白下降及肛周脱屑可初步诊断为川崎病,以避免错过患儿的最佳治疗时机。     

40例川崎病合并重症感染患儿的病因及预后分析

目的 探讨川崎病合并重症感染的发病原因及治疗效果.方法 选择我院儿科2003年1月至2011年2月收治的川崎病患儿,40例重症感染者作为研究组,40例无感染或中轻度感染者作为对照组.对两组患儿进行治疗,对比治疗后、随访中冠状动脉扩张的例数;并对所有患儿的病例资料进行分析,总结川崎病合并重症感染的病因.结果 研究组出院时冠状动脉扩张29例,对照组26例,差异无显著性;出院后1、2年冠状动脉扩张例数较对照组明显减少.研究组红细胞压积、白蛋白均低于对照组,血沉及C反应蛋白高于对照组.结论 川崎病合并重症感染患儿预后不理想,容易遗留冠状动脉扩张;红细胞压积、白蛋白、血沉、C反应蛋白可作为判断川崎病预后情况的指标.