Humans ; Inflammation ; drug therapy ; metabolism ; MicroRNAs ; metabolism ; Stilbenes ; pharmacology ; therapeutic use

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

Background Vancomycin has been increasingly recommended for the management of endophthalmitis,but few research report has been published about the pharmacokinetics of intravitreal vancomycin up to now.It is necessary to have an exact method to measure the concentration of vancomyein in animal eyes after intravitreal injection.Objective This study was to observe and compare the phamacokinetical process of vancomycin in serum,vitreous and aqueous humor between normal and infected rabbit eyes.Methods Seventy-two healthy adult rabbits were randomly divided into normal group and infected group and 36 rabbits for each.The animal models of endophthalmitis were established by intravitreal inoculation of 2000 CFU/ml staphylococcus aureus in the right eyes of rabbits in the infected group.Once endophthalmitis developed,0.1 ml vancomycin ( 10 g/L) solution was injected into the vitreous of every rabbit.The peripheral blood,vitreous and aqueous humor samples were respectively collected in 4 rabbits for each group at 0.5,2,4,6,12,24,48,72 and 84 hours after injection for detection of vancomycin concentration by high performance liquid chromatography(HPLC-UV).3p97 software was used to create fit parameters of pharmacokinetics.This experiment followed the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission (Version 1988).Results The accuracy of HPLC fitted the detecting request of biological specimen.The concentration-time data of vancomycin in normal rabbit aqueous humor and vitreous was subject to two-compartment model.The pharmacokinetic parameters were separately as following:Cmax was 50.16 mg/L and 751.42 mg/L,t1/2was 51.04 hours and 53.21 hours.The concentration-time data of vancomycin in infected rabbit aqueous humor and vitreous was subject to one-compartment model.The pharmacokinetic parameters were separately as following:Cmaxwas 24.94 mg/L and 687.66 mg/L,t1/2was 11.42 hours and 12.91 hours.The concentration of vancomycin in serum was much lower and almost undectable.The concentration of vancomycin in vitreous was gradually reduced as the prolong of time after injection in both normal group and infected group,but a obvious decline after increased level was scen in aqueous humor.Compared with normal group,the concentrations of vancomycin in both vitreous and aqueous humor were reduced at various time points(P＜0.05,P＜0.01 ).Conclusions HPLC is simple,highly sensitive and specific for the pharmacokinetic analysis of vancomycon.These results indicate that pharmacokinetic parameters of vancomycin alter in pathological condition,which is helpful for us to establish the better treatment guidelines for endophthalmitis.

Background: Creatine transporter (CRTR) deficiency is the most common creatine deficiency syndrome, of which the final diagnosis relies on mutation in the X-linked CRTR gene. To date, more than 90 mutations in the SLC6A8 gene have been reported. This paper discusses a novel mutation detected via the thorough sequencing of all the X-chromosome-specific exons investigated in a four and a half year old boy with an intellectual disability, speech and language delay and motor disturbance. Methods: A brain magnetic resonance imaging (MRI) and a proton magnetic resonance spectroscopy (MRS) were carried out, the creatine and creatinine concentrations in the urine were checked and all exons were sequenced. Results: A detailed clinical investigation revealed a reduction in the cerebral creatine levels in the brain by the MRS, elevated creatine and creatinine concentrations in the urine and signal abnormalities in the left frontal cortex of the brain by the MRI. A novel change was identified in the heterozygosity of the exon 10: c.1395-c.1401 deletion. Conclusion: The use of a combination of powerful new technologies, such as thorough exome-nextgeneration sequencing and a brain MRS, should be considered, in order to determine any neurometabolic diseases, especially when the signal abnormalities in the brain MRI cannot be explained by any other factors. This mutation results most likely in a dysfunction of the creatine transport and synthesis, hence causing central nervous system symptoms.
Carrier Proteins

Anatomical features of the lamina and petiole of 11 species of Salvia had been compared. The microstructures of 11 species of Salvia were observed by paraffin method, and indexes such as the epidermis, xylems and phloems were measured. The data set was analyzed by principal components analysis method and cluster analysis method. The results indicated that the laminae of 11 species of Salvia were bifacial leaf, and the surface of laminae and petioles were covered with villous. The upper epidermis and lower epidermis of the laminae of 11 species of Salvia were constituted by a dense cuticular layer without stratum corneum. Differences existed in the structure of cross sectio mn of laminae and petioles of 11 species of Salvia. Among them, upper epidermal thickness of nine different micromorphological characters could serve as one of the criteria to identify species of taxonomic Salvia. The identification of genetic relationship of these characters in Salvia were discussed in the paper to provide an evidence of anatomy in Salvia.
Cluster Analysis ; Plant Leaves ; anatomy & histology ; Salvia ; anatomy & histology ; classification

Objective To evaluate the efficacy and safety of linezolid in the treatment of severe lung infections caused by methicillin-resistant Staphylococcus aureus (MRSA).Methods Fifteen patients admitted to ICU due to severe lung infection caused by MRSA received linezolid treatment. WBC, lactic acid (LAC), IL-1β, IL-6, and TNF-α levels were measured before and after treatment. Results Clinical efficacy rate was 73.3%. The level of WBC, LAC and inflammatory cytokines decreased significantly after linezolid treatment (P<0.01).Conclusions Linezolid shows good efficacy in the treatment of severe lung infections caused by MRSA.

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

Objective To explore the changes in cardiac index and oxygenation index in sepsis piglets after nitric oxide (NO) gas inhalation. Methods A piglet model of sepsis was induced by intravenous infusion of Gram-negative bacterial endotoxin (LPS), then the piglets were randomly divided into two groups. NO group (n=8) was administered with inhaled nitric oxide of 80ppm via volume control (VC) mechanical ventilation for one hour, while the control group (n = 4) received mechanical ventilation with VC and was observed for one hour to assess the stability of the model. The parameters of oxygenation and hemodynamics were measured by PICCO and arterial blood gas analysis every fifteen minutes for one hour. Results Injection of endotoxin induced a stable pig model of sepsis. PH, HCO3-, arterial oxygen pressure (PaO2), mean arterial pressure (MAP) and cardiac index in this model were significantly lower the baseline values (P < 0.01). Arterial oxygen pressure and cardiac index were significantly higher in N0 group than in the control group (P<0.01). Heart rate (HR), central venous pressure (CVP), global end-diastolic volume index (GEDI) and intrathoracic blood volume index (ITBI) did not significantly differ between NO group and the control group. Conclusions Inhalation of nitric oxide gas can significantly improve oxygenation and cardiac function in piglets with sepsis.

Objective To explore the change of plasma orexin A concentration and the correlation between plasma orexin A concentration and energy intake in obese children.Methods Fasting plasma orexin A concentrations,boaly mass index(BMI) and energy intake were measured in 48 obese children(obese group) and 48 healthy children(healthy control group),and these indexes were compared,the correlation between plasma orexin A concentration and BMI,energy intake were analyzed.Results 1.The plasma orexin A concentration in obese group was significantly lower than that in healthy control group(F=5.632 P=0.008).2.In obsess group,there were negative correlation between plasma orexin A concentration and BMI(r=-0.478 P=0.012),positive correlation between plasma orexin A concentration and total energy intake(r=0.503 P=0.007),fat intake(r=0.659 P=0.006) and protein intake(r=0.381 P=0.026),and there was negative correlation between plasma orexin A concentration and carbohydrate(r=-0.316 P=0.022).3.In healthy control group,there were negative correlation between plasma orexin A concentration and BMI(r=-0.491 P=0.018),positive correlation between plasma orexin A concentration and total energy intake(r=0.512 P=0.009),fat intake(r=0.406 P=0.005),protein intake(r=0.313 P=0.020),and carbohydrate(r=0.432 P=0.025).Conclusions Orexin A may be involved in regulation of energy metabolism in obese children,and the interaction between plasma orexin A and energy intake might be different in different nutritional status in children.