Objective: To evaluate color velocity imaging-quantitative method (CVI-Q) in estimating cerebral hemodynamic change in patients with cerebral infarction. Methods: The carotids of 60 normal people and 40 cerebral infarction patients were detected by CVI-Q. We observed endangium thickness and atheromatous plaques,and measured the diameter (d), peak velocity(Vmax), resistance index(RI) and blood flow volume(Q) of the common carotid arteries. Results: In cerebral infarction group there were 75% cases with endangium thickening to different degrees, 45% cases with atheromatous plaques and 71% plaques in carotid enlargement section or bifurcation. The data measured in 2 groups were compared: (1)The d value in cerebral infarction cases increased than that in normal（P<0.05 or P<0.01）; (2)The Vmax reduced in cerebral infarction cases(P<0.05); (3)The RI increased in cerebral infarction cases (P<0.05 or P< 0.01); (4) The Q value reduced in cerebral infarction cases (P<0.01). Conclusion: CVI-Q can be used for detecting cerebral hemodynamic changes and provide quantitative indexes for clinicians to estimate ischemia degree and treatment in cerebral infarction patients.

Estrogen receptor alpha (ERalpha) has been a primary target of treatment as well as a prognostic indicator for breast cancer. The level of human X-box binding protein 1 (XBP-1) mRNA was related with that of ERalpha in breast tumors and was over-expressed in some breast tumors. These previous studies suggested that XBP-1 may interact with ERalpha. XBP-1 has two isoforms, XBP-1S and XBP-1U, as the result of unique splicing. GST pull-down assay showed that both XBP-1S and XBP-1U bound to ERalpha in vitro. The binding of XBP-1S to ERalpha was stronger than that of XBP-1U to ERalpha. Co-immunoprecipitation revealed that the binding was in a ligand-independent manner. XBP-1S and XBP-1U interacted with the region of ERalpha that contains a DNA-binding domain. The ERalpha-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, the N-terminal basic region leucine zipper domain (bzip) and the C-terminal activation domain. These findings suggest that XBP-1S and XBP-1U may participate in ERalpha signaling pathway through the mediation of ERalpha.
Breast Neoplasms ; genetics ; metabolism ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; metabolism ; Estrogen Receptor alpha ; genetics ; metabolism ; Female ; Humans ; Protein Interaction Domains and Motifs ; physiology ; RNA, Messenger ; biosynthesis ; genetics ; Regulatory Factor X Transcription Factors ; Signal Transduction ; Transcription Factors ; genetics ; metabolism ; X-Box Binding Protein 1

OBJECTIVE: To detect the changes of mitochondrion DNA (mtDNA) sequence in articular chondrocytes of cartilage affected by osteoarthritis and to clarified the pathogenetic mechanism of osteoarthritis. METHODS: We analyzed the mtDNA 4,977 bp deletion mutations of articular chondrocytes in 10 patients with osteoarthritis and 3 normal cartilages using the gap-PCR amplification method. We designed a two round PCR detection method, in which total DNA was isolated from articular chondrocytes as the template of the first round PCR reaction and products from the first round were the template in the second round reaction. RESULTS: The results of the first rounds of PCR reaction showed the mtDNA 524 bp amplified products in the osteoarthritis group and in the corresponding peripheral blood samples were not detected, but the 533 bp products were detected. However,the results of the second round reaction revealed that the 524 bp zones were detected in 2 of the 10 osteoarthritis patients and the corresponding peripheral blood samples were not detected. The 533 bp products were detected in all specimens. The mtDNA 524 bp amplified products in all the normal articular chondrocytes and the corresponding peripheral white blood cells contrast were not detected in both rounds PCR. CONCLUSION This was the first study to evaluate the mtDNA 4799 bp large fragment deletion mutational accumulation between nt8,470 - nt13,447 of articular chondrocytes in osteoarthritic cartilage. Osteoarthritis may be related to mtDNA mutation of articular chondrocytes.
Adult ; Cartilage, Articular ; metabolism ; pathology ; Chondrocytes ; metabolism ; DNA, Mitochondrial ; genetics ; Female ; Gene Deletion ; Humans ; Male ; Middle Aged ; Osteoarthritis ; genetics ; Osteoarthritis, Hip ; genetics ; Osteoarthritis, Knee ; genetics ; Sequence Analysis, DNA

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.
Adenosine Triphosphate ; blood ; pharmacokinetics ; Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Biotransformation ; Cardiotonic Agents ; administration & dosage ; blood ; pharmacokinetics ; Creatine ; administration & dosage ; metabolism ; pharmacokinetics ; Erythrocytes ; metabolism ; Injections, Intravenous ; Male ; Phosphocreatine ; administration & dosage ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the feasibility and efficacy of Narcotrend (NT) monitor in monitoring the depth of anesthesia in severely burned patients with target-controlled infusion (TCI) of remifentanil hydrochloride and propofol during perioperative period.

METHODSEighty patients with severe burn hospitalized from February to November 2011, to whom eschar excision was performed within one week after injury, were enrolled. They were classified into II to III grade according to the American Society of Anesthetists classification, and their total burn area ranged from 31% to 50%TBSA, or full-thickness burn area from 11% to 20% TBSA. Patients were divided into trial group (monitoring depth of anesthesia with routine method and NT monitor) and control group (monitoring depth of anesthesia with routine method) according to the random number table, with 40 cases in each group. All patients received TCI of remifentanil hydrochloride and propofol to induce and maintain anesthesia. During the operation, the anesthesia level of NT monitor used in the trial group was maintained from grade D1 to E0, while the fluctuation of mean arterial pressure (MAP) and heart rate of patients in control group was maintained around the basic values within a range of 20%, and on the basis of which, concentrations of two narcotics were adjusted. Concentrations of remifentanil hydrochloride and propofol during maintenance of anesthesia were recorded. The duration from drug withdrawal to waking from anesthesia (including the duration from drug withdrawal to eye opening by calling and the duration from drug withdrawal to orientation recovery) of patients was recorded. Values of MAP and heart rate at admission into the operation room, loss of consciousness, 2 min after intubation, before operation, 2, 15, and 30 min after the beginning of operation, and the end of operation were recorded. The prediction probability (P(k)) of NT stage (NTS) and NT index (NTI) in trial group, and that of MAP and heart rate in control group for two durations from drug withdrawal to waking form anesthesia were recorded. The administration of vasoactive drugs and intraoperative awareness of patients in two groups were recorded. Data were processed with t test, analysis of variance, and chi-square test, and the relationship between NTS, NTI, MAP, heart rate and their corresponding P(k) for the duration from drug withdrawal to orientation recovery was processed with Spearman correlation analysis.

RESULTSMaintained target effect-site concentration of remifentanil hydrochloride and target plasma concentration of propofol of patients were obviously lower in trial group [(2.62 ± 0.35) ng/mL, (3.84 ± 0.22) µg/mL] than in control group [(2.95 ± 0.21) ng/mL, (4.16 ± 0.31) µg/mL, with t values respectively -5.113 and -5.324, P values all below 0.01]. The duration from drug withdrawal to eye opening by calling and the duration from drug withdrawal to orientation recovery were obviously shorter in trial group [(10.2 ± 0.7) min, (11.1 ± 1.0) min] than in control group [(11.3 ± 1.0) min, (13.1 ± 0.7) min, with t values respectively -5.740 and -10.806, P values all below 0.01]. The MAP (except for 2 min after intubation) and the heart rate of patients in both groups were lower at the time points from loss of consciousness to the end of operation than at the time of entering operation room (with F values respectively 12.074, 36.425, P values all below 0.01 in trial group and F values respectively 21.776, 35.759, P values all below 0.01 in control group). The statistically significant difference between two groups in MAP level was only observed at the time of loss of consciousness (t = 3.985, P < 0.01). MAP level was close in two groups at other time points. Heart rates of patients in two groups were close during perioperative period. P(k) values of NTS and NTI for the duration from drug withdrawal to eye opening by calling (0.937 ± 0.025, 0.899 ± 0.049) were obviously higher than those of MAP and heart rate for this duration (0.579 ± 0.057, 0.536 ± 0.039, F = 900.337, P < 0.01). P(k) values of NTS and NTI for the duration from drug withdrawal to the orientation recovery (0.901 ± 0.031, 0.868 ± 0.046) were significantly higher than those of MAP and heart rate for this duration (0.532 ± 0.060, 0.483 ± 0.044, F = 890.895, P < 0.01). NTS, NTI, MAP, and heart rate were respectively negative, positive, positive and positive in correlation with their P(k) values for the duration from drug withdrawal to the orientation recovery (with r values from -0.734 to 0.682, P values all below 0.01). There was no statistically significant difference between two groups in administration of vasoactive drugs. No intraoperative awareness occurred.

CONCLUSIONSApplication of Narcotrend monitor in monitoring the depth of anesthesia in severely burned patients during perioperative period with TCI of remifentanil hydrochloride and propofol is beneficial to reducing dosage of narcotics and shortening duration of recovery from anesthesia, and it can accurately predict the level of consciousness of patients at the time of withdrawal of anesthesia.

Adolescent ; Adult ; Aged ; Anesthesia, Intravenous ; Burns ; surgery ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Intraoperative ; instrumentation ; methods ; Piperidines ; Propofol ; Skin Transplantation ; methods ; Young Adult

Adult ; Aged ; Aged, 80 and over ; Fascia Lata ; surgery ; Female ; Humans ; Male ; Middle Aged ; Synovial Cyst ; surgery

OBJECTIVETo explore the relationship between hypoxia and the apoptosis of corpus cavernosum smooth muscle cells (CCSMC) in SD rats.

METHODSCCSMCs were cultured in vitro and identified by immunohistochemistry, and then underwent hypoxia interference at the concentration of 1% O2 for 12, 24, 48 and 72 hours, with normal oxygen concentration as the control. Flow cytometry was used to determine the cycles and apoptosis of the cells.

RESULTSThe cultured CCSMCs grew well, positive for anti-smooth muscle alpha-actin monoclonal antibody immunohistochemical staining. Flow cytometry showed that the number of CCSMCs in G0/G1 was gradually increased within 48 hours and then decreased, just opposite to the proportion of the S phase cells. But no regular change was found in the proportion of the cells in the G2/M phase.

CONCLUSIONHypoxia promotes the apoptosis of CCSMCs in a time-dependent manner, to the maximum at 48 hours, and then cell lysis may occur, but with no further apoptosis.

Animals ; Apoptosis ; Cell Hypoxia ; Cells, Cultured ; Male ; Muscle, Smooth, Vascular ; cytology ; Penis ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effects of microcystin-LR (MCLR) on the expression of base excision repair genes and genes related to apoptosis.

METHODSThe BRL-3A cells were exposed to different concentrations of MCLR for various periods of time and the cell viability was measured by MTT. The mRNA expression was determined with the quantitative real-time polymerase chain reaction (QRT-PCR).

RESULTSThe viability of BRL-3A cells significantly reduced in a concentration- and time-dependent manner. In 30 µg/ml group, the mRNA expression level (1.327 ± 0.028) of p53 increased significantly at 24 h after exposure, as compared with the other groups (1.005 ± 0.117, 0.862 ± 0.154, 1.028 ± 0.056 and 1.015 ± 0.091) (P < 0.05). The mRNA expression levels (5.080 ± 0.729, 5.820 ± 0.373, 6.018 ± 0.359 and 6.183 ± 0.515) of Bax in all exposure groups were significantly higher than that (1.024 ± 0.277) in control group at 24 h after exposure. However, the Bax mRNA expression level (0.604 ± 0.146) in the 30 µg/ml group at 72 h after exposure was significantly lower than those (1.004 ± 0.107, 0.811 ± 0.142, 0.855 ± 0.101 and 0.814 ± 0.056) in other groups (P < 0.05). When compared with control group (1.006 ± 0.132) and 1 µg/ml group (1.034 ± 0.241), the mRNA expression level (0.488 ± 0.147) of PARP1 in 30 µg/ml group at 48 h after exposure decreased significantly (P < 0.05). Furthermore, the mRNA expression levels (0.594 ± 0.180, 0.491 ± 0.015 and 0.305 ± 0.091) of JWA, XRCC1 and PARP1 in 30 µg/ml group at 72 h after exposure decreased significantly, as compared with the other groups (P < 0.05).

CONCLUSIONThe induction of gene expression is a transient phenomenon that occurred at different times of exposure for different genes. Inhibition of MCLR on the base excision repair gene expression may play important role in the course of MCLR promoting liver tumor.

Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; genetics ; Base Sequence ; Cell Line ; DNA Repair ; Gene Expression ; Microcystins ; toxicity ; RNA, Messenger ; genetics ; Rats

OBJECTIVETo study epidemiological characteristics and influential factors of in-hospital patients struck by the Wenchuan earthquake disaster.

METHODSThe clinical data of 196 cases were collected from 2 hospitals of Chongqing city, including age, sex, occupation, injury site, dwelling and injury severity score.

RESULTSIn this series, 31.63% victims'age was over 60 years, and 54.08% were farmers. Multiple trauma accounted for 35.71%, and lower limb injury for 33.67%. There was no significant difference on injury severity score between city dwellers and rural ones (P>0.05).

CONCLUSIONThe earthquake injury is influenced by many factors. More attention should be paid to the treatment at first 5 days after injury and high risk population.

Adult ; Aged ; China ; epidemiology ; Disasters ; statistics & numerical data ; Earthquakes ; statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Wounds and Injuries ; epidemiology

Amorphous is a special physical state of solid compounds that the positions of the molecules or atoms have no long-range order. Sometimes amorphous compounds have better bioavailability, or achieve ultra-fast absorption in situation of acute and intermittent symptoms than that of morphous compounds, thus change drug efficacy. Besides, different pharmaceutical preparing methods can lead to different characters. Research of amorphous compounds has been a hotspot, both in research field and industry world. However, there are challenges as amorphous compounds could be unstable; unexpected adverse drug reactions may also exist. In this review, recent progress in the research of amorphous pharmaceutical compounds both in the research field and the pharmaceutical industry is reviewed. Factors which can influence the efficacy of amorphous pharmaceuticals are summarized. The prospect of amorphous techniques is also discussed.
Absorption ; Animals ; Biological Availability ; Chemistry, Pharmaceutical ; Crystallization ; Drug Stability ; Humans ; Pharmaceutical Preparations ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods