Angiogenesis Inducing Agents ; metabolism ; Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antibodies, Monoclonal ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents ; therapeutic use ; Bevacizumab ; Drug Delivery Systems ; Endostatins ; therapeutic use ; Humans ; Neoplasms ; drug therapy ; Neovascularization, Pathologic ; drug therapy ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; physiology ; Vascular Endothelial Growth Factors ; metabolism ; physiology

Child, Preschool ; Echocardiography, Transesophageal ; methods ; Heart Septal Defects, Ventricular ; diagnostic imaging ; therapy ; Humans ; Male

This study is to investigate the mechanism and action characteristics of 6-chloro-3-methyl-4-(2-methyoxycarbonylthiophene-3-sulfonyl)-3, 4-dihydroquinoxa-lin-2-(1 H)-one (XU07011) against HIV-1 replication. XU07011 anti-HIV activity was tested by using VSVG/HIV pseudotype viral system and confirmed by HIV-1 live viruses' infectious assay. Time of addition was used to test HIV-1 reverse transcription process. RNA-dependent DNA polymerase activity and RNase H activity were tested by using enzyme linked immunoabsorbent assay and fluorescence method. Wild type and nine NNRTIs-resistant reverse transcriptase enzymatic models and cell-based pharmacological models were used to evaluate XU07011 bio-characteristics. The results showed that XU07011 inhibited HIV-1 replication with IC50 of (0.057 +/- 0.01) micromol x L(-1) which was comparable to nevirapine [IC50: (0.046 +/- 0.01) micromol x L(-1)]. Mechanism study data indicated that XU07011 blocked HIV-1 reverse transcription process through acting on reverse transcriptase RNA-dependent DNA polymerase with IC 50 of (1.1 +/- 0.3) micromol x L(-1). The compound showed no effect on RNase H activity. XU07011 exhibited better activities comparing with nevirapine on K103N mutated NNRTIs-resistant HIV-1 strains. This study could provide a theoretical basis for novel anti-HIV reagents development.

Anemia, Dyserythropoietic, Congenital ; pathology ; Child ; Humans ; Male ; Siblings

This study is to establish a cell-based model targeting to neuraminidase (NA) of the 2009 H1N1 influenza A virus. NA is an influenza virus structural protein with enzymatic activity of the cleavage of HA-sialic acid interaction to release new viral particles from cells. A model of HIV-1 (pNL4-3.Luc.R(-)E(-)) based pseudovirions packed with HA [hemagglutinin, A/VietNam/1203/2004 (H5N1)] and NA [A/California/04/2009 (H1N1)] was established to evaluate compounds activities on NA function. The viral release can be blocked by neuraminidase inhibitors, oseltamivir and oseltamivir carboxylate, with IC50 of (61 +/- 31) nmol L(-1) and (5.5 +/- 2.9) nmol L(-1) respectively. A point mutation of H275Y on NA leads oseltamivir-resistance. This corresponding mutation was introduced into the system which was also confirmed by oseltamivir and oseltamivir carboxylate.

85 mL/min),CL=6.0?(WT/60)~(0.52).④The increased volume of peripheral distribution (V_2) was observed when norvancomycin was co-administered with diuretics;④Reduced drug clearance,prolonged t_(1/2),and increased values of AUC_(24) were found in elderly patients.Conclusions Renal function impairment and age have significant impact on PK parameters of norvancomycin.Dosing regimens of norvancomycin were finally established for different patients on the basis of important PPK parameters generated from different groups of patients.

Aged ; Humans ; Male ; Middle Aged ; Receptors, Interleukin-2 ; blood ; Silicosis ; blood ; classification ; T-Lymphocyte Subsets ; metabolism

The multidisciplinary synthetic therapy for the colorectal liver metastases has been a hot spot in clinical research,which includes operative therapy,tumor local therapy,conversion therapy,chemotherapy, molecular targeted therapy and so on. It is need to choose multiple therapies for the patients and make the whole treatment strategy in accordance with the condition of patients to maximize the survival benefit in clinical prac-tice. So,it is important to comprehend the newest research process of the clinical therapy to make a good choice for the colorectal liver metastases patients.

BACKGROUND: Researches suggest that transient ischemic attack (TIA)can induce cognitive dysfunction, and cerebral blood flow and its distribution are hypothesized to be closely related to cognitive activities.OBJECTIVE: To investigate the alteration of cognitive function and provide insights into its relations with cerebral perfusion in TIA patients.DESIGN: A case-control study.SETTING: Departments of Geriatrics, Electrophysiology and Magnetic Resonance of Urumqi General Hospital of Lanzhou Military Area Command of Chinese PLA.PARTICIPANTS: Totally 35 male right-handed TIA patients aged 45-78 years with an average of (68.1±8.4) years were selected from the inpatients and outpatients in the Department of Geriatrics, Urumqi General Hospital of Lanzhou Command of Chinese PLA between January 2002 and June 2003. Another 33 healthy right handed male subjects aged 45-77 years with an average of (67.8±8.6) years coming for physical examination were recruited to serve as the control group.METHODS: Patients and control subjects were tested with event-related potentials (ERPs) and the scale of elderly cognitive function (SECF) to examine the orientation, learning and memory, span, recall 1 (association),long-term memory, naming of animals, calculation, classification, copying,language and recall 2 (relation). According to the T score transformation table, the original scores were transformed into T scores relative to the age to eliminate the impact of age, and also into T'score to eliminate the interference by the patients'education, so that cognitive function of the patients could be evaluated with T'score, and the lower the score, the poorer the cognitive function. Cases in the two groups were all tested, and TIA patients were also examined with magnetic resonance angiography (MRA).MAIN OUTCOME MEASURES: Results of ERPs, SECF and MRA.RESULTS: Of the 35 TIA patients and 33 control subjects all completed the trial. Examination of ERPs reveled significantly prolonged latency of P300 components of ERP in the TIA group [(336.2±34.2) ms] than that in the control group [(311.3±44.2) ms, P ＜ 0.05]. The scores of span, recall 1,long-term memory, naming of animals, calculation, and recall 2 in SECF in TIA group were all lower than those in control group (39.7±11.9 vs 47.4±12.0; 54.5±14.8 vs 61.8±14.5; 61.1±7.8 vs 64.7±1.7; 59.4±11.0 vs 64.7±8.8; 50.0±14.7 vs 58.1±14.2; 44.6±15.4 vs 53.2±17.8, t=4.151 0-7.292 8, P ＜ 0.05-0.01). MRA identified abnormalities in 33 of the 35 TIA patients (94%), manifested mainly by stenosis and occlusion involving the vertebral artery (54%, 19/35), bilateral anterior, middle and posterior cerebral arteries (40% ,28/70;59% ,41/70;47% ,33/70), basilar artery (5.71%, 2/35) and bilateral internal carotid artery (5.71%, 4/70) respectively.CONCLUSION: TIA patients are characterized by prolonged P300 latency with multiple cognitive impairments especially in memory and cerebral artery stenosis and occlusion as shown by MRA, suggests that TIA patients have persistent low cerebral perfusion and frequently, cognitive dysfunction in the presence of local blood supply disorder in the hemispheres.

Objective To study the expressions of osteopontin (OPN),caspase-3 and mt-P53 proteins, and their relationship in gliomas. Methods Seventy gliomas specimens of patients (glioma group) were selected, and 10 samples of non-glioma brain tissue were used as control group. The SP method was used to detect the positive rates of protein expressions of OPN, caspase-3 and mt-P53 between two groups. The relationship between protein expressions of OPN, caspase-3 and mt-P53 in gliomas and grade of gliomas were detected by Western blot assay. Spearman rank correlation was compared between the positive expression of OPN, caspase-3 and rate mt-P53. Results The positive expression rates of OPN and mt-P53 were significantly higher in glioma group (64.29%and 60%) than those of control group (no positive expression), but the positive expression rate of caspase-3 was significantly lower than that of control group (47.14%vs. 90%, P<0.05). There were no significant differences in OPN, caspase-3 and mt-P53 expressions between different gender, age, tumor size and tumor position (P>0.05). The higher the WHO classification, the higher the positive expression rates of OPN and mt-P53 (P<0.001), and the lower the positive expression rate of caspase-3 (P<0.001). With the increased level of glioma grade, OPN and mt-P53 protein levels were increased, but caspase-3 protein expression level was decreased. There was a negatively correlation between OPN and the positive expression of caspase-3, but there was a positive correlation between OPN and the expression of mt-P53 (rs=-0.720 and 0.722, P<0.05). There was a negative correlation between caspase-3 and mt-P53 expressions (rs=-0.556, P<0.05). Conclusion The higher the WHO classification, the higher the positive expression rates of OPN and mt-P53, while the lower the positive expression rate of caspase-3. The study reveals that OPN, caspase-3 and mt-P53 expressions are associated with the occurrence and the progress of gliomas. The combined detection of them can contribute to the judgment of biological behavior of gliomas.