Objective To evaluate the role of cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) signal transduction pathway in lidocaine-induced up-regulation of the expression of surfactant protein-A (SP-A) in rat alveolar epithelial type Ⅱ cells (AEC Ⅱ).Methods Healthy male Sprague-Dawley rats were sacrificed and AEC Ⅱ were isolated,purified and incubated in 24-well culture plates (100μd/hole) with density of 1 × 106/ml.After being incubated for 2 h,the culture medium was replaced with serum-free medium DMEM.The cells were randomly divided into 4 groups (n =48 each):control group (group C),forskolin (adenylate cyclase agonist) group (group F),lidocaine 200 μg/ml group (group L),and PKA inhibitor H89 + L group (group P+ L).Forskolin 10 μmol/ml was added to DMEM in group F.Lidocaine 200 μg/ml was added to DMEM in group L.H89 10μnol/ ml was added to DMEM and AEC Ⅱ were incubated for 10 min,and then lidocaine 200 μg/ml was added in group P + L.At 6,12 and 24 h of incubation (T1-3),cAMP content and PKA activity (using ELISA),and expression of SP-A mRNA (by real-time fluorescent quantitative PCR) and SP-A (by Western blot) were measured.Results Compared with group C,the expression of SP-A mRNA and SP-A was significantly upregulated,and cAMP level and PKA activity were increased at T1-3 in group F and at T2,3 in group L.Compared with group L,the expression of SP-A and SP-A mRNA was down-regulated,PKA activity was decreased,and no significant change was found in cAMP level at T1-3 in group P + L.Conclusion Lidocaine can up-regulate the expression of SP-A in AEC Ⅱ of rats through activating cAMP-PKA signal transduction pathway.

Cephalosporins ; adverse effects ; therapeutic use ; Humans ; Infant, Newborn ; Penicillins ; adverse effects ; therapeutic use ; Skin Tests

Objective To explore the mechanism of neuropmtective effects of puerarin for the treatment of acute spinal ischenia-reperfusion injury in a rat model.Methods Acute spinal ischemia-reperfusion injury was induced via aortic occlusion in 28 male Sprague-Dawley rats.The animals were randomly divided into four groups,as follows:group negative contrast (NC sham operation),group positive control group (IR+ S ischemia/reperfusion + saline),group puerarin (IR+P ischemia/reperfusion + puerarin),group mscovitine (IR+R ischemia/reperfusion + roscovitine).The motor function,spinal infarction volume,apoptosis indices,and CDK5 and P25 activities were examined.Results Spinal ischemia-reperfusion caused the injury of the spines and was associated with motor deficit,elevation of CDK5 and P25 activities,and increase in the spinal apoptosis and spinal infarction volume.Puerarin improved motor function and decreased apoptosis,spinal infarction volume,and CDK5 and P25 activities.Conclusion The findings of the present study indicated that puerarin treatment-mediated reduction of spinal injury was associated with the inhibition of CDK5 and P25,and that the inhibition was one among the neuroprotective mechanisms of puerarin against acute ischemia/reperfusioninduced spinal injury in rats.

OBJECTIVE:To observe the efficacy and safety of eprosartan in the treatment of hypertensive patients with coro-nary heart disease. METHODS:160 hypertensive patients with coronary heart disease randomly divided into observation group and control group. All patients were given aspirin,nitroglycerin,low molecular weight heparin,statins and other conventional treat-ment;control group was additioanlly given 50 mg Losartan potassium tablet,orally,once a day. Observation group was additional-ly given 600 mg Eprosartan tablet,orally,once a day. The treatment course for both groups was 6 months. Clinical efficacy,sit-ting systolic blood pressure and diastolic blood pressure,alanine aminotransferase(ALT),aspartate aminotransferase(AST),urea (UREA),creatinine(Cr),uric acid(UA),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol (LDL-C),the Mini-Mental status (MMSE) scale and activities of daily living (ADL) scale scores before and after treatment and incidence of adverse reactions in 2 groups were observed. RESULTS:There was no signifi-cant difference in the total effective rate between 2 groups(P>0.05). After treatment,the sitting systolic blood pressure and diastol-ic blood pressure,MMSE and ADL scale scores in 2 groups were significantly lower than before,and sitting systolic blood pres-sure in observation group was lower than control group,the differences were statistically significant(P<0.05),and there were no significant differences in sitting diastolic blood pressure,MMSE and ADL scale scores between 2 groups(P>0.05),and no signifi-cant differences in ALT,AST,UREA,Cr,UA,TC,TG,HDL-C and LDL-C between 2 groups before and after treatment(P>0.05). There were no obvious adverse reactions during treatment. CONCLUSIONS:Eprosartan can effectively reduce sitting systol-ic blood pressure in hypertensive patients with coronary heart disease,and improve cognitive function,with good safety.

OBJECTIVE:To study the effects and mechanism of propranolol on the myocardial abnormal electrophysiology sta-tion in diabetic model rats. METHODS:SD rats were randomly divided into normal control(normal saline)group,diabetic(nor-mal saline)group,PD98059(ERK inhibitor,10 mg/kg)group and propranolol low-dose,medium-dose and high-dose(1,20,50 mg/kg)groups,with 8 rats in each group. Except for normal control group,rats were given alloxan(20 mg/kg)intravenously via tail vein to induce diabetic model. They were given relevant medicine intragastrically,once a day,for consecutive 42 days. The car-diac index,electrocardiogram and action potential durations (APD) of rats were analyzed;the expression of TNF-α,IL-2,IL-6 and IL-10 protein in serum were detected,and the expression of Ras,Raf,ERK kinase(MEK)and ERK1/2 in myocardial tissue were detected. RESULTS:Compared with normal control group,cardiac index increased in diabetes group;heart rate decreased;QT interval and APD were prolonged;the relative expression of TNF-α,IL-2,IL-6,IL-10,Ras,Raf,MEK and ERK1/2 protein increased (P<0.01). Compared with diabetes group,cardiac index decreased in propranolol medium-dose and high-dose groups and PD98059 group,heart rate increased,QT interval and APD were shortened;the relative expression of TNF-α,IL-2,IL-6, IL-10,Ras,Raf,MEK and ERK1/2 protein decreased(P<0.05 or P<0.01). CONCLUSIONS:Propranolol can improve myocar-dial abnormal electrophysiology station of diabetic model rats by down-regulating inflammatory reactions in serum and inhibiting the activation of MEK/ERK signaling pathway.

Functional targets are the objects that Chinese herbal medicines act directly upon. If the relationships between the properties of Chinese herbs and their functional targets were analyzed clearly, it would benefit the overall understanding of the holistic mechanisms of Chinese herbal treatments. In this paper, data regarding the properties of Chinese herbs and their functional targets were collected from the 2005 edition of The People's Republic of China Pharmacopoeia. After analyzing and assessing the data, the relationships were defined between the four qi, meridian entry and medicinal functional targets and between the four qi, five flavors and mode of function. Then the relationships between a single herbal medicine and a prescription were analyzed, and the results conformed with the traditional knowledge of Chinese herbal nature and efficacy. This demonstrated that the holistic mechanisms of the properties of Chinese herbs adhere to the findings, which may be beneficial for the development and compatibility of Chinese herbal medicines.

Objective To clarify great benefit to prevention of wound infection as well as reduction of economic expenditures by a new method of connecting latex gloves and cigarettes in peritoneal drainage. Methods We randomly selected 121 cases of patients with peritoneal pyogenic infection, divided them into the latex gloves group (64 eases)and the common dressing group (57 cases). The incision infection rate and eco-nomic cost in two groups were comparately studied. Results The latex gloves group's incision infection rate was 10.94% (7 / 64), the common dressing was 31.58% (18/57). Each patient of the latex gloves group spent less cost about 15.70 yuan,changed dressing 5.3 times less than the common dressing group. Conclusions Connecting latex gloves and cigarettes in peritoneal drainage is a new method of reducing economic expandi-tures and the chances of incision infection. Clinical application of this method should be fully prospected.

ObjectiveTo determine the cerebral protection effect and mechanism of propofol on global cerebral ischemia and reperfusion damage in rats.Methods19 adult male Wistar rats were randomly divided into 3 groups, ischemia group (n=7), propofol group (n=7), and sham injury group (n=5). Global cerebral ischemia and reperfusion model were made by means of Pulsinelli's method. Rats in propofol group were anesthesia with propofol at the dosage of 1.5 ml/h for 30 min at the beginning of reperfusion. Apoptosis and necrosis rate were detected by cytometry. In the same time, bcl-2, Bax and p53 protein expression in hippocampus neurons were detected. ResultsThe apoptosis and necrosis rate in propofol group were significantly decreased as compared with ischemia group ( P<0.05). Bax and p53 protein expression in hippocampus neurons were also significantly decreased as compared with ischemia group (P<0.05), however, no significant findings in bcl-2 protein expression (P>0.05).ConclusionPropofol can decrease apoptosis and necrosis rate in cerebral ischemia reperfusion injured neuron, and the mechanism maybe related to decreasing the expression of Bax, p53 protein.

Tumorous cells are characterized by distinctive metabolic reprogramming and living conditions. Understanding drug metabolizing features in tumor cells will not only favor the estimation of metabolic rate, elimination half life and the assessment of potency, but also facilitate the optimal design of anti-tumor drugs/prodrugs. This article reviewed the expression and activity features of major drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver, intestine, breast and lung, and the difference from the correspondingly normal tissues, exemplified by the metabolic properties of some classic antitumor-agents in tumorous tissues. In combination with the data retrieved in vitro tumor cell lines, we discussed the similarities and differences of DMEs expression and function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed the possible factors that cause the differences.
Antineoplastic Agents ; pharmacokinetics ; Cell Line, Tumor ; Humans ; Inactivation, Metabolic ; Liver ; metabolism ; Neoplasms ; enzymology ; Prodrugs ; pharmacokinetics

Objective To establish the methodology of uncertainty evaluation with reference measurement procedure by Monte Carlo method (MCM).Methods According to JCGM 101:2008,we established the methodology of uncertainty evaluation by MCM in the example of GGT reference measurement procedure.We could calculate an estimate of GGT concentration,the associated standard uncertainty and a coverage interval with a specified probability by MATLAB software,setting the uncertainty evaluation by GUM method as a control.Results When the uncertainty was evaluated by GUM method,the results of sample A and Sample B were (95.8 ±2.4) U/L (k =2) with coverage interval [93.4 U/L,98.2 U/L] and (180.0 ± 3.9) U/L (k =2) with coverage interval [176.1 U/L,183.9 U/L] respectively,while using MCM method,the uncertainty evaluation result of sample A and Sample B were (95.8 ± 2.4) U/L (k =2) with coverage interval [93.4 U/L,98.2 U/L] and (180.0 ± 3.9) U/L with symmetrical 95％ coverage interval [176.2 U/L,183.8 U/L].The output quantity simulated by MCM was normal distributed.Conclusions When the distribution of the output quantity is normal,the measurement uncertainty evaluated by both MCM and GUM method is nearly the same.When the distribution of the output quantity is unknown,MCM can be used as a verification of GUM method.