Coronary Angiography ; adverse effects ; Heart Atria ; Humans ; Male ; Middle Aged

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.
Animals ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; Antineoplastic Agents ; chemical synthesis ; chemistry ; Carboxylic Acids ; Carcinoma, Hepatocellular ; Cell Line ; Cell Proliferation ; Drug Design ; Escherichia coli ; drug effects ; Fluoroquinolones ; chemical synthesis ; chemistry ; HL-60 Cells ; Humans ; Leukemia L1210 ; Liver Neoplasms ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Naphthyridines ; Triazines

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.
Antineoplastic Agents ; chemical synthesis ; chemistry ; Cell Line, Tumor ; Fluoroquinolones ; chemistry ; Humans ; Oxadiazoles ; chemistry ; Structure-Activity Relationship

BACKGROUND:Extracorporeal membrane oxygenation(ECMO)adopts heparin-coated oxygenator as key membrane oxygenation,which is a covalent bonding of artificial material surface with mucopolysaccharide on one side of heparin.Thas artificial materials can stimulate human vascular endothelial function partly,leading to decrease production of lactic acid,increase biocompatibility of the matedals,prevent thrombogenesis and relieve inflammatory reaction after operation.OBJECTIVE:To discuss the relationship between the plasma lactic acid level and the prognosis of patients after ECMO applied with heparin-coated oxygenator.DESIGN:Self-controlled clinical study,grouping by age and survival prognosis.SETTING:Department of Cardiopuimonary Bypass,Fuwai Cardiovascular Hospital,Chinese Academy of Medical Sciences.PARTICIPANTS:Forty patients received ECMO in Fuwai Cardiovascular Hospital,Chinese Academy of Medical Sciences were selected from December 2004 to September 2006.They suffered from failing weaning of cardiopulmonary bypass postcardioctomy,cardiogenic shock based on dilated cardiomyopathy or cardiogenic shock based on coronary heart disease.All patients were divided into four groups according to age and survival prognosis:adult survival group,adult death group,infant survival group and infant death group.METHODS:All the patients received venoarterial ECMO support treatment.ECMO perfusion system consisted of centrifugal pump,water tank,heparin-coated membrane oxygenator(Jorstra Novalung,Germany)and corollary circuits (Bioline Coating,Germany,batch number:SFDA-I-20063450801).MAIN OUTCOME MEASURES:The concentrations of lactic acid were measured at the ECMO institution,6 hours later,the median time at ECMO support,6 hours before weaning off and at the time of weaning.RESULTS:①In 26 patients of adult groups,20 of them(76.9%)weaned from ECMO,16 of them(61.5%)survived and 10 of them died.In 14 patients of infant groups,7 of them weaned from ECMO(50%),5 of them(35.7%)survived and 9 of them died.②The concentrations of lactic acid in two survival groups were significantly lower than those in death groups(P＜0.05 or 0.001).The concentration decreased significantly at the time points of median time,6 hours before weaning off and at the weaning time,compared with the level at the time of ECMO institution(P＜0.01),indicating a decreasing concentration of lactic acid.CONCLUSION:①The concentration of lactic acid in patients after ECMO decreascs obviously.②Patients with high lactate level at the weaning time show unfavourable prognosis.

Objective To investigate the expression and distribution of the downstream substrate of extracellular regulated protein kinase(ERK1/2) pathway, ternary complex factor phospho-Elk-1, in rat brains with chronic fluorosis, and reveal the mechanism of the impaired learning and memory ability caused by chronic fluorosis. Methods Seventy-two SD rats, weighing 100 - 120 g, were randomly divided into 3 groups, 24 in each group (half male and half female). The rats in control group were fed with tap water (fluoride < 0.5 mg/L); low- and high-dose fluoride groups were fed with tap water with different concentrations of NaF(5.0,50.0 mg/L F-, respectively). After 6 months, body weight was weighed, dental fluorosis was determined by observation and urinary fluoride and bone fluoride were detected by fluorine ion-selective electrode; the learning ability of rats was measured by navigation test of Morris water maze, and memory ability by spatial probe test in Morris water maze; the expression and distribution of phospho-Elk-1 in different brain regions were detected by immunohistochemistry method. Results In low- and high-fluoride groups, the body weight of rat[(449.2 ± 77.1), (312.8 ± 89.7)g] was significantly decreased than that of control [(635.5 ± 76.2 )g, all P< 0.05], the varying degrees of dental fluorosis were observed(x2 = 7.83, P<0.05), urinary fluoride[(2.56 ±0.91),(5.73 ±3.14)mg/L] and bone fluoride[(709.2 ± 37.4) ,(1306.3 ± 102.4) mg/kg] were significantly higher than those in controls[(0.92 ± 0.30)mg/L,(348.5 ± 89.2)mg/kg, all P< 0.05]. The escape latency of low- and high-fluoride groups[ (7.4 ± 4.1), (12.2 ± 5.7)s] was longer than that of control [(4.8 ± 2.7 )s, all P < 0.05] and the escape latency in high-fluoride group was significantly longer than that in other groups (all P < 0.05); in spatial probe test, the time of first crossing platform was longer in rats with fluorosis [(4.18 ± 1.10),(5.89 ± 0.56)s] as compared to control[(1.17 ± 0.75)s, all P< 0.05]. Expressions of phospho-Elk-1 in the hippocampus CA1(167.4 ± 8.3,163.2 ± 9.4), CA2(175.7 ± 5.0,183.3 ± 4.2), CA3(165.2 ± 11.6,162.9 ± 4.4), CA4(168.7± 6.9,169.5 ±5.3), fascia dentate (185.2 ±4.0,193.1 ±6.1) and caudate putamen( 181.4 ± 3.8, 179.8 ± 5.5) in low- and high-fluoride groups were higher than those of controls(142.4 ± 8.1,144.9 ± 8.4,143.6 ± 5.8, 116.8 ± 9.1,140.2 ± 7.8,163.1 ± 13.1, all P< 0.05). Conclusion Chronic fluorosis can cause increased expression of phospho-Elk-1 in the hippocampus and caudate putamen region of rat brains, which might be related to the mechanisms of decreased learning and memory ability of rats overexposed to fluoride.

?AIM: To evaluate the effect for refractory glaucoma by using Ex - Press miniature implantation with deep sclerectomy.?METHODS: Thirty eyes in 24 patients with refractory glaucoma were treated by Ex- Press miniature ( P50 ) implantation with deep sclerectomy. The patients’ symptom, intraocular pressure ( IOP ) , visual acuity and complications were analyzed in a 12mo follow-up period.?RESULTS: During the follow-up period, all patients’ ocular pain was reduced. The mean IOP before operation and at the last follow-up time were 51. 15 ± 2. 60mmHg (1kPa=7. 5mmHg) and 15. 11 ± 2. 51mmHg, respectively, there was significant difference (P<0. 05). Postoperative visual acuity was improved in 8 eyes, had no significant change in 22 eyes. After operation, hyphema of anterior chamber appeared in 2 eye ( 7%) , which were obsorbed after 1wk.? CONCLUSION: Ex - Press miniature implantation combined with deep sclerectomy surgery is a relatively effective and safe treatment for the patients with refractory glaucoma. This method can significantly degrade the IOP, lessen ocular pain and reduce the complications risk.

Objective To evaluate the value of serum procalcitonin (PCT)on antibiotic use in treatment of community acquired pneumonia (CAP) in outpatient. Methods From November 2006 to February 2008, a total of 127 patients with CAP in outpatient were randomly assigned into two groups:PCT group(n=63)and control group(n =64). PCT levels of all patients were measured after study admission. On the base of similarly normal treatment, the control group received antibiotics according to the attending physicians and the PCT group were treated with antibiotics according to serum PCT levels: antibiotic treatment was applied with PCT level ≥ 0. 25 μg/L and was discouraged with PCT level < 0.25 μg/L. Clinical efficacy, rate of antibiotics use, duration courses and costs of antibiotics were observed. Results Clinical efficacy of the PCT group was similar with the control group (92.1% vs 87.5%, P >0.05) ;rate and costs of antibiotics use was lower, antibiotic duration of the PCT group was shorter than that ofthecontroigroup(P<0.05,P<0.001,P<0.001).Conclusion PCT could be used in treatment of CAP for antibiotic use in outpatient, which may reduce antibiotic use, shorten antibiotic duration and lower costs of antibiotic.

Objective To evaluate the predicting value of serum procaleitonin (PCT) in treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in elderly patients. Methods A total of 267 elderly patients requiring hospitalization for AECOPD were randomly assigned into 2 groups: standard therapy group (standard group, n= 135) and PCT-guided group(PCT group, n= 132). Standard group received antibiotics according to the guideline of attending physicians and PCT group were treated with antibiotics according to serum PCT levels.Length of hospitalization, clinical efficacy, costs of hospitalization and antibiotics, rate of antibiotics use, hospital mortality, rate of exacerbation and rehospitalization, frequency of exacerbation within 1 year were observed. Results Length of hospitalization, clinical efficacy, hospital mortality, rate of exacerbation and rehospitalization, frequency of exacerbation within 1 year were similar in 2 groups(all P＞0.05);costs of hospitalization and antibiotics, rate of antibiotics use of PCT group[10 882 (3808-16 651)yuan, 6934 (2390-10 660)yuan, 76.5%] were lower than those of standard group[13 637(4650-19 730)yuan, 8589(3144-12 117)yuan, 87.4%] (all P＜0.05). Conclusions PCT guidance offers an advantage over standard therapy in reducing antibiotic use and in lowering the costs of hospitalization in treatment of AECOPD in elderly patients.

Gymnastics ; physiology ; Humans ; Workload

OBJECTIVETo improve the X-ray diagnosis of cervical spondylosis of vertebral artery type (VCS).

METHODSA blinded design research. The X-ray signs both 60 patients with VCS and 60 patients with cervical spondylotic radiculopathy were collected from January 2011 to November 2012. There were 36 males and 84 females, aged from 25 to 65 years old with an average of (48.4 ± 12.3) years old. Cervical curvature, atlanto-occipital joint angle, atlanto-axial joint angle, C2/C3 joint angle and lower cervical instability condition and segmental distribution were measured and recorded by X-rays. These data were analyzed and compared between the two groups after unblended. Combined with clinical manifestations,the X-ray imaging features of VCS were further analyzed.

RESULTSThere was significant difference in cervical curvature between two groups in anteflexion X-ray films (P < 0.05). There was significant difference in extension degree of atlanto-occipital joint angle between two groups (P < 0.01). There was significant difference in atlanto-axial joint angle between two groups in lateral X-ray films (P< 0.05). There was significant.difference in anteflexion degree of atlanto-axial joint angle between two groups (P < 0.05). There was no significant difference in C2/C3 joint angle between two groups. There was no significant difference in the lower cervical instability condition and segmental distribution between two groups. In VCS group, the mild and moderate dizziness was main symptom, flexion and extension activities of neck was most common cause in the dizziness; and always accompanied with headache; tenderness mostly concentrated in the upper cervical area.

CONCLUSIONBoth X-ray signs and clinical manifestations can prompt the abnormalities of the upper cervical structure or function in patients with VCS. Anteflexion activities of neck observed by functional position of X-ray films should be emphasized in diagnosis of VCS.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Radiculopathy ; diagnostic imaging ; Radiography ; Spondylosis ; diagnostic imaging ; Vertebral Artery ; X-Rays