In order to elucidate the mechanism underlying the attenuation of streptomycin ototoxicity by tetramethylpyrazine (TMP), the present study investigated the effect of TMP on the outward K(+) current in the outer hair cells of guinea pig cochlea. Sixty guinea pigs were divided into 6 groups randomly. Auditory brainstem response (ABR) was used to observe the change in thresholds and to evaluate ototoxicity induced by streptomycin. Whole-cell patch-clamp technique was used to observe the effect of TMP on outward K(+) current in isolated outer hair cells. The results showed that TMP attenuated the threshold shift caused by streptomycin and increased the amplitudes of Ca(2+)-sensitive K(+) current [I(K(Ca))] in the outer hair cells. The present data suggest that TMP displays anti-ototoxicity induced by streptomycin. The augmented amplitudes of I(K(Ca)) of the outer hair cells induced by TMP may be one of the mechanisms underlying its ototoxicity-attenuating effect.
Animals ; Auditory Threshold ; Cochlea ; cytology ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Hair Cells, Auditory, Outer ; drug effects ; Patch-Clamp Techniques ; Potassium Channels ; metabolism ; Pyrazines ; Streptomycin ; toxicity

OBJECTIVETo study the impacts of exposure to electromagnetic radiation (EMR) on liver function in rats.

METHODSTwenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/ d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and those of malondialdehyde (MDA) and glutathione (GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl- 2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling (TUNEL) method was used for analysis of apoptosis in liver.

RESULTSCompared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes (P>0.05), while the contents of MDA increased (P < 0.01) and those of GSH decreased (P < 0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group (all P < 0.01).

CONCLUSIONThe exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.

Animals ; Apoptosis ; Cell Phone ; Electromagnetic Radiation ; Liver ; pathology ; radiation effects ; Male ; Oxidative Stress ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Staining and Labeling

The paper is to report the pharmacokinetic character of a series of chemical compounds in vitro and in vivo. Metabolism stability of a series of chemical compounds was screened by using rat liver microsomes. The samples of different chemical compounds were combined and then simultaneously detected by LC-MS/MS. Compounds y13, y12 and y11 were screened out by microstability assay in vitro. The pharmacokinetics of compounds y11, y12 and y13 was evaluated by using SD rat. The plasma samples were pooled at the same time. The plasma concentrations were determined by LC-MS/MS. The pharmacokinetic character of two compounds y13, y11 was good by screening in vivo, so they were developed for further research. High-throughput screening of drug candidates in vitro and in vivo was effective, to provide information for the chemical structure information and lower the drug development risk.
Animals ; Chromatography, Liquid ; methods ; Drug Evaluation, Preclinical ; methods ; Female ; High-Throughput Screening Assays ; methods ; Male ; Microsomes, Liver ; metabolism ; Pharmaceutical Preparations ; administration & dosage ; blood ; metabolism ; Pharmacokinetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; methods

OBJECTIVETo probe into the relationship between hypertension and hemodynamic score of cerebral vascular accumulative function by though studying the history of hypertension and level of blood pressure.

METHODSThe database of blood pressure and cerebral vascular hemodynamic indexes (CVHI) were from baseline data and measurement in a cohort. 18,512 participants who met the included criteria were enlisted in the study. The function scores were estimated using uniform methods according to CVHI. Participants were grouped by age, years of having hypertension and level of blood pressure. Differences of the function score between different groups were compared.

RESULTSThe function score in hypertension group was significantly lower than that of normal tension group, which decreased by 13.3 points. Within 5 years of hypertension history, the function score decreased as course of hypertension prolonged. The same trend was found between the score and level of both systolic and diastolic blood pressure. When systolic blood pressure elevated to 140 mmHg or diastolic blood pressure elevated to 95 mmHg, the function score was below 75 points.

CONCLUSIONThere were significant relationship between decrease of the function scores and medical history, course of hypertension as well as level of blood pressure.

Adult ; Age of Onset ; Aged ; Blood Pressure ; physiology ; Cerebrovascular Circulation ; physiology ; China ; epidemiology ; Cohort Studies ; Female ; Hemodynamics ; physiology ; Humans ; Hypertension ; epidemiology ; physiopathology ; Male ; Middle Aged

The aim of the present study was to observe whether protein tyrosine kinase (PTK) within the nucleus tractus solitarius (NTS) was involved in the regulation of ventilatory responses of peripheral chemoreflex. The experiments were performed on anesthetized, immobilized and artificially ventilated rabbits. Peripheral chemoreflex was elicited by ventilating the animal with 10% O2-balance 90% N2. Changes in the peak amplitude and frequency of integrated phrenic nerve activity were observed. The ventilatory responses of peripheral chemoreflex following 0.1 microl microinjection within the NTS of either PTK inhibitor genistein (10 mol/L), AMPA glutamate receptor inhibitor CNQX (10 mol/L),or inactive PTK inhibitor daidzein (10 mol/L) were recorded. The results are as follows: Both genistein and CNQX attenuated the ventilatory responses of peripheral chemoreflex, while no changes occurred following daidzein. The amplitude of integrated phrenic nerve discharge and the phrenic burst frequency were decreased by (-21.77+/-6.93)% and (-24.70+/-7.61)% respectively after administration of genistein. CNQX resulted in similar decreases in the amplitude of phrenic nerve discharge (-27.13+/-7.63)% and the burst frequency (-21.34+/-4.88)%. In addition, the inhibitory effects of CNQX and genistein were the same whether they were applied alone or one after another, indicating that they had no cooperative effects. The results obtained suggest that PTK within the NTS regulates the peripheral chemoreflex control of respiration and that this regulation of PTK may be mediated through the phosphorylation of AMPA receptors in NTS neurons.
Animals ; Brain Stem ; enzymology ; physiology ; Chemoreceptor Cells ; physiology ; Female ; Male ; Protein-Tyrosine Kinases ; physiology ; Rabbits ; Receptors, AMPA ; physiology ; Respiration ; Solitary Nucleus ; enzymology

To detect the characteristics of "pre-ALIP" and to investigate their relevance with the development of acute myeloid leukemia (AML) by computer image procession technology, bone marrow (BM) was collected by aspiration/trephine biopsy from AML patients during the complete remission (CR). BM sections were stained by HGF (haematoxylin-Giemsa-acid fuchsin) and photographed by optical microscope imaging system. 4 kinds of computer image segmentation technologies were compared to select the best one for detecting the localization and quantitation of the precursor cells. Planimetry was combined with morphology to segment bone trabeculae. The number of single and double-cluster precursor cells and their distance from bone trabeculae was detected with Euclidean distance change method in BM images of AML patients, and compared with the normal controls. Moreover, the morphological characteristics of "pre-ALIP" were investigated, and the correlation with the development of AML was analyzed. The results showed that the computer image segmentation method based on morphology could identify the precursor cells and bone trabeculae more exactly in BM image, as compared with the methods of 8-Sobel operater. Canny operator and watershed algorithm. Bone trabeculae could be segmented with combinative methods of morphology and planimetry. The number of single precursor cells (19.27 ± 11.60)/mm(2) and double-cluster precursor cells (1.77 ± 1.76)/mm(2) in CR group were higher than that in normal controls (p < 0.05). The distance of single precursor cells from bone trabeculae in CR group were closer to bone trabeculae than that in controls [(230.12 ± 97.68) µm vs (260.92 ± 99.88 µm)] (p < 0.05), but the distance of double-cluster precursor cells from bone trabeculae in AML patients was (274.56 ± 139.48) µm, which showed no statistically significant different from controls (p > 0.05), while the double-cluster precursor cells showed the tendency of migrating to the intermediate zone of bone trabeculae compared with the single precursor cells in CR group (p < 0.05). It is concluded that the structure of "pre-ALIP" in BM tissue exists before the occurrence of ALIP. The characteristics of "pre-ALIP" are single and double-cluster precursor cells with abnormal localization or quantitation, which showed correlation with the development of AML.
Adolescent ; Adult ; Aged ; Bone Marrow Cells ; cytology ; pathology ; Female ; Humans ; Leukemia, Myeloid, Acute ; pathology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo describe the distribution of cerebral vascular hemodynamic indexes (CVHI).

METHODSA number of 25,355 age 35 and over were selected in the Northeast China by cluster sampling. CVHI were checked during baseline survey and were followed to see the occurrence of stroke. Distribution of CVHI among non-stroke population, individuals prior to the onset of stroke and patients with stroke were described.

RESULTSThe CVHI accumulative score, V(mean), V(max) and V(min) were dramatically decreasing, but RV, Zcv, WV and DR were significantly increasing as age increased. V(max), RV and CP were significantly higher in males but WV was lower than that of females. The CVHI accumulative score, V(min) and RV were 95.0, 10.23 and 75.8 in non-stroke population, 51.25, 6.71 and 122.72 pre stroke group, and 55.0, 6.78 and 115.89 in patients with stroke respectively. There were significant differences among three groups after controlling of age and sex (P < 0.01).

CONCLUSIONVariance of CVHI was closely related to age, and there appeared a significant abnormal of CVHI before and after stroke.

Age Factors ; Aged ; Cluster Analysis ; Female ; Hemodynamics ; Humans ; Male ; Middle Aged ; Risk Factors ; Sex Factors ; Stroke ; physiopathology

Objective To analyze the efficacy of bevacizumab combined with paclitaxel+carboplatin in the treatment of recurrent/metastatic cervical cancer,and to explore the influence on survival prognosis of patients.Methods Patients with recurrent/metastatic cervical cancer were divided into control group and treatment group according to different treatment methods.The control group received paclitaxel combined with carboplatin chemotherapy regimen(intravenous infusion of 170 mg·m-2 paclitaxel and carboplatin(AUC=5 mg·mL-1·min)for 3 weeks as a course of chemotherapy),and the treatment group was given bevacizumab on the basis of control group,intravenous infusion of 15 mg·kg-1 bevacizumab,once every 3 weeks.Both groups were treated for 3 cycles of treatment by taking 3 weeks as 1 treatment cycle.The clinical efficacy,levels of serum tumor markers,quality of life,survival prognosis and occurrence of drug-related adverse reactions during treatment were compared between the two groups.Results There were 41 cases in treatment group and 48 cases in control group.After treatment,the overall response rate(ORR)of treatment group and control group were 31.71％(13 cases/41 cases)and 14.58％(7 cases/48 cases),with no statistical significance(P＞0.05).After treatment,the disease control rate(DCR)in control group and treatment group were 62.50％(30 cases/48 cases)and 82.93％(34 cases/41 cases);the squamous cell carcinoma antigen(SCCA)levels were(3.58±0.73)and(2.52±0.57)ng·mL-1;carbohydrate antigen 19-9(CA19-9)levels were(23.60±4.29)and(19.19±3.72)U·mL-1;carbohydrate antigen 15-3(CA15-3)levels were(27.13±5.36)and(22.86±3.94)U·mL-1;carbohydrate antigen 125(CA125)levels were(39.24±6.88)and(26.47±5.09)U·mL-1;the overall improvement rates of quality of life were 41.67％(20 cases/48 cases)and 73.17％(30 cases/41 cases),the progression-free survival times were 8.67 months(95％CI:7.82-9.53)and 10.25 months(95％CI:9.68-10.81),the total survival times were 9.96 months(95％CI:9.13-10.79)and 11.47 months(95％CI:11.00-11.93),all with significant difference(all P＜0.05).There were no statistically significant differences in the incidence of nausea and vomiting,leukopenia,thrombocytopenia and liver-kidney function impairment between both groups(all P＞0.05).Conclusion Bevacizumab combined with chemotherapy has significant efficacy in the treatment of recurrent/metastatic cervical cancer,and it can reduce the levels of serum tumor markers,enhance the quality of life,and improve the survival prognosis,and it has good safety.

Objective The aim of this study was to investigate associations of overall obesity (OO) and abdominal obesity (AO) with brachial-ankle pulse wave velocity (baPWV) among type 2 diabetes(T2DM) patients. Methods A community-based study for T2DM patients was conducted in rural communities in Beijing．Every patient completed a questionnaire to collect demography, lifestyle and diseases history, and underwent physical examinations, baPWV assessments and blood biochemical tests. Multivariate linear regression was used to assess the relationship between obesity index and baPWV. Abnormal baPWV was defined as patients with baPWV≥1,700 cm/s. Logistic regression model was performed to explore the risk of abnormal baPWV after adjusting for poetential confounders step by step. Results A total of 2 048 T2DM patients were recruited. The average age was (59.2±8.3) years and total prevalence of abnormal baPWV was 49.7%. After multivariable adjustment, linear regression showed that there was a negative correlation between body mass index(BMI) and baPWV and a positive correlation between waist-to-hip ratio (WHR) and baPWV. Compared to normal weight group, those with BMI≥28 kg/m2 had lower risk of abnormal baPWV (OR=0.59, 95% CI: 0.44-0.78，P<0.001), but there was an increased risk of 46% among patients with obesity in WHR (OR=1.46, 95% CI:1.07-2.00，P=0.018). Compared to those without OO and AO, patients without OO but with AO had a 1.67-fold increasesd risk of abnormal baPWV (OR=1.67, 95% CI: 1.19-2.35，P=0.003). Conclusions Abdominal obesity is related with arterial stiffnening among T2DM patients, and it is critical to evaluate arterial stiffness of T2DM patients with abdmonal obesity and normal BMI in order to reduce future risk of cardiovascular diseases.

OBJECTIVETo explore the molecular mechanism and prevention of retinoic acid syndrome (RAS).

METHODSSDF-1 alpha mRNA from healthy adult lung tissue was measured by RT-PCR, CXCR4 protein expression on the cell membrane of APL cells induced by ATRA (APL-ATRA) was tested by FCM, and the rotary cell culture system (RCCS) was used to build a modal for in vitro stimulation of APL-ATRA infiltrating human lung tissue. The ability of APL-ATRA in adhesion, migration and infiltration was observed by interference from DEX, Ara-C and DNR.

RESULTSThe APL-ATRA cells could evidently infiltrate into normal lung tissue. Mean fluorescence intensity (MFI) of CXCR4 on the cell membrane of APL-ATRA cells was 30.6 +/- 1.8, which was much higher than that on unspecialized APL cells (9.8 +/- 4.2). SDF-1 alpha mRNA expression was detected positive in all 6 lung tissue. Contrary to the control groups, DEX could dramatically restrain the ability of APL-ATRA cells in adhesion and migration [(27.2 +/- 2.6)% vs. (46.0 +/- 3.0)%, (28.1 +/- 4.0)% vs. (48.2 +/- 3.0)%], while Ara-C and DNR could distinctly depress the ability in adhesion, migration and infiltration [(28.1 +/- 3.0)%, (30.2 +/- 3.2)% vs. (46.0 +/- 3.0)%; (29.0 +/- 4.0)%, (23.0 +/- 5.2)% vs. (48.2 +/- 3.0)%; (16.8 +/- 7.6)%, (17.1 +/- 6.0)% vs. (43.6 +/- 5.0)%].

CONCLUSIONIn vitro APL-ATRA cells can infiltrate into the human lung tissue. High expression of CXCR4 on APL-ATRA and SDF-1 alpha in the lung tissue may be one of the molecular mechanisms of the lung infiltration and RAS. DEX, Ara-C and DNR can dramatically restrain the ability of APL-ATRA cells in adhesion, migration and infiltration.

Adolescent ; Adult ; Cell Adhesion ; Cell Culture Techniques ; Cell Movement ; Chemokine CXCL12 ; genetics ; metabolism ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Receptors, CXCR4 ; genetics ; metabolism ; Tretinoin ; adverse effects ; Tumor Cells, Cultured