AIM: To explore the effects of cellular signal transduction pathways of heme oxygenase-1(HO-1)-carbon monoxide (CO)-cyclic GMP (cGMP) and nitric oxide synthase (NOS)-nitric oxide (NO)-cGMP on cholecystokinin octapeptide (CCK-8) reversed vascular hyporeactivity in endotoxemic rats. METHODS: According to the treatments given in vivo , rats were devided into four groups: control; lipopolysaccharide (LPS); CCK and CCK+LPS. Using isolated vascular ring tension detecting technique, thoracic aortic rings (TARs) were prepared and accumulation of contractive responses to phenylephrine (PE) were measured under which the TARs were incubated with Hemin (He, donor of CO), Zinc-protoporphyrin-IX (ZnPP-IX, selective inhibitor of HO-1), L-arginine (L-Arg, substrate of NOS), aminoguanidine (AG, selective inhibitor of iNOS), N ?-nitro-L-arginine (L-NNA, inhibitor of NOS) or methylene blue (MB, inhibitor of guanylyl cyclase), respectively. RESULTS: CCK-8 alone did not affect vascular tension. Injection of LPS induced the hyporeactivity of the TARs and was reversed by pretreatment of CCK-8. In LPS and CCK+LPS groups, the hyporeactivity was partly reversed by incubation of TARs with ZnPP-IX or AG, and restored to normal by incubation of TARs with L-NNA or MB. Incubation of TARs with He or L-Arg showed to make the vascular hyporeactivity worse in different degree. CONCLUSIONS: CCK-8 alone did not affect the activity of HO-1 and iNOS but influenced the activity of these enzymes induced by LPS, which lead to reduced CO/NO production, decreased the content of cGMP and plays its important role in reversing vascular hyporeactivity in endotoxemic rats.

BACKGROUND: Different processes of thinking may lead to the same results, which represent one of the forms of the complexity of the human brain.OBJECTIVE: To analyze the similarity in the results of thinking and difference in the thinking process by means of questionnaires.DESIGN: A comparative analysis of the answers in the final term examination with the difference in answers analyzed by x2 test with contingency table.SETTING: Department of Physiology, Medical College of Henan University of Science and Technology.PARTICIPANTS: This study was conducted between June and November,2004, involving totally 300 volunteered second-year medical students (150male and 150 female, aged 20-22 years) of the medical school of Henan Science and Technology University who took their final examination in physiology.METHODS: The first "question for thinking" in the final examination was taken as an example, and the papers with full score for this question (completely correct group, n=42) and zero score (totally wrong group, n=49)were chosen, from which one paper was randomly selected from each group. The first 10 words in the answer to the question was used as the control and compared with the answers of the other papers word by word.Each same word was given a score of 1 and otherwise a score of 0, and the number of the same words and different words were counted for comparison. Meanwhile the total words of the answer were also counted and compared. The difference in the answers was analyzed with x2 test with contingency table.MAIN OUTCOME MEASURES: The difference in the first 10 words between completely correct group and totally wrong group.RESULTS: Totally 42 students in the complete correct group and 49 in totally wrong group were included in the final result analysis. The number of the total words of the answer was different between the students in spite of the same scores. The first 10 words of the chosen paper in completely correct group was significantly different from those in the other 41 papers (x2=270.978, P ＜ 0.01); there was also significant difference in the first 10words between the chosen paper and the other 41 papers in totally wrong group (x2=285.153, P ＜ 0.01).CONCLUSION: Longitudinal thinking as well as lateral thinking processes are different between persons.

In order to investigate the possible role of ONOO- in regulatory disorder of pulmonary arterial tension in endotoxic shock, the responses of rabbit pulmonary arterial rings (PARs) preincubated with ONOO- to endothelial dependent and receptor dependent relaxants acetylcholine (ACh) and adenosine diphosphate (ADP), endothelial dependent and receptor independent relaxant A23187, endothelial independent relaxant sodium nitroprusside (SNP) and α1-adrenoceptor agonist phenylephrine (PE) were observed in vitro in accumulative manner. Results were as follow: (1) Relaxations of PARs to ACh, A23187 and ADP were markedly impaired with shift of accumulative dose response curve of each agonist to the right. Inhibition of endothelial dependent and receptor dependent or independent relaxation by ONOO- was dose dependent. (2) ONOO- incubation inhibited SNP-induced relaxation in a dose dependent manner. Accumulative dose response curve of SNP was right shift to some degree depending on the doses of ONOO-. (3) Contractile response of PARs to PE varied with the different doses of ONOO-. In PARs preincubated with 0.5 mmol/L ONOO-, contractile reponse was significantly enhanced with shift of PE accumulative dose response curve to the left, while in PARs preincubated with 1.0 mmol/L or 2.0 mmol/L ONOO-, it was markedly reduced with right shift of PE accumulative dose response curve. (4) Vehicle of ONOO- had no effect on responses to every agonist, whereas decomposed ONOO- had minimal effect on the response to PE and ADP. In contrast, relaxation of PARs to ACh, A23187 and SNP were enhanced. These results suggested that direct effect of ONOO- on pulmonary artery may be a key factor contributing to regulatory disorder of pulmonary arterial tension induced by LPS and pulmonary hypertension in the early stage of endotoxic shock.

This study was designed to invesigate vasodilatory action of exogenous peroxynitrite (ONOO-), and effect of endothelial cells on ONOO- -induced relaxation in isolated rabbit pulmonary arterial rings (PARs). Results were as follows: (1) In precontracted PARs, ONOO- could give rise to vasodilation in a dose-dependent manner. Relaxations of PARs to ONOO- at doses of 10-5 mol/L, 5×10-5 mmol/L and 10-4 mol/L were 11.09%±1.84%, 31.10%±3.53% and 64.35%±3.83%, respectively, all of which were significantly higher than those of decomposed ONOO- with 5.88%±1.27%、16.15%±1.82% and 34.44%±3.26% at same concentrations, respectively. (2) Compared with SNP and ACh, ONOO- had weak relaxant action. (3) ONOO- induced more significantly enhanced relaxation in denuded endothelial PARs than in intact endothelial PARs. (4) In this experimental condition, the relaxation of PARs to 10-6 mol/L ACh remained unchanged before and after observation of relaxation to ONOO-. (5) The relaxations of PARs to 5×10-5 mol/L ONOO- in repetitively administered manner appeared progressively decreased. These results suggested that ONOO- might be implicated in pulmonary hypertension in the early stage of endotoxic shock.

AIM: To verify the effect of cholecystokinin octapeptide(CCK-8) on cardiac function in endotoxin shock (ES) rats.METHODS: The rats were divided into four groups:control,lipopolysaccharide(LPS),CCK-8 and CCK-8+LPS.The left ventricle pressure(LVP),the maximal/minimum rate of LVP(?LVd p /d t max ),heart rate (HR) and mean arterial pressure (MAP) were measured.The activity of superoxide dismutase (SOD),the contents of malondialdehyde (MDA) and nitric oxide (NO) in both serum and myocardium were also measured,respectively.RESULTS: CCK-8 (40 ?g?kg -1 , iv) elicited bradycardia in short time and gently increase MAP,LVP and ?LV d p /d t max . Lipopolysaccharide(LPS, 8 mg?kg -1 , iv) caused a variation in heart rate (HR)(a bradycardia following a tachycardia) and rapid decreases in MAP,LVP and ?LVd p /d t max . The rapid variation of HR and the decline of MAP,LVP and ?LVd p /d t max were reversed by pretreatment with CCK-8 in ES rats, but didn't restore to normal.The activity of SOD was increased and the contents of MDA and NO were decreased by pretreatment with CCK-8 in ES rats.CONCLUSION: The decline of cardiac function in ES rats could be reversed by pre-administration of CCK-8 and the decrease in NO production may be one of the mechanisms.

AIM：The mechanism of tumor necrosis factor-alpha (TNF-α) induced pulmonary artery hypertension(PAH) in endotoxic shock (ES) is not clear. Cholecystokinin-octapeptide (CCK-8) had anti-ES and anti-PAH effects. The impact of CCK-8 on changes in vascular reactivity and endothelial ultrastructure induced by TNF-α was studied. The role of nitric oxide (NO) was preliminarily studied. METHODS：Rabbit pulmonary artery rings were divided into four groups: TNF-α, TNF-α+CCK-8, CCK-8 and Vehicle. The rings were incubated for 2 h, 7 h or 14 h. Relaxative responses to ACh(10-8-10-5 mol/L)， SNP (10-9-10-6 mol/L) and contractile responses to PE(10-8-10-5 mol/L) were generated seperately. The NOS activity of rings was detected and the ultrastructure of endothelium was observed in the groups that incubated for 7 h.RESULTS:The relaxative responses to ACh were not affected by TNF-α and CCK-8 after incubation for 2 h. TNF-α(7 h,14 h) significantly reduced ACh-induced endothelium-dependent relaxation response of pulmonary artery. CCK-8 reversed the effect. CCK-8 itself had no effect on responses of normal pulmonary artery. Contraction to PE and relaxation to SNP were unaffected by TNF-α, CCK-8. The NOS activity increased in the TNF-α and the TNF-α+CCK-8 groups. While no significant difference was obseved between the Vehicle and the CCK-8 groups. Endothelial injury in TNF-α group and alleviated changes in TNF-α+CCK-8 group were observed. CONCLUSION:TNF-α significantly inhibits endothelium-dependent relaxation, which be one of the mechanisms of PAH induced by TNF-α during ES. It was found for the first time that CCK-8 reversed TNF-α induced impairment of endothelium-dependent relaxation and alleviated structural injury of endothelium, which might be one of the mechanisms of anti-PAH effect by CCK-8 during ES. The effects of TNF-α and CCK-8 might be related to NO.

AIM and METHODS: To elucidate the mechanism of anti-endotoxic shock of cholecystokinin octapeptide(CCK-8), the effects of CCK-8 on changes in rabbit thoracic aortic reactivities induced by lipopolysaccharides(LPS) in vitro were studied, and the ultrastructure of the endothelial cells was observed under scanning electron microscope. RESULTS: Incubation of thoracic aortic rings(TARs) with LPS(100 mg/L) resulted in an time-dependent impairment of the endothelium-dependent relaxations to acetylcholine(incubation for 3, 7, 14 h), a reduction of contractive response to phenylphrine(incubation for 14 h) and ultrastructural injury in endothelial cells(incubation for 7 h), all of which were alleviated by concomitant incubation with CCK-8(1 mg/L). In contrast, neither the vascular contractions nor the relaxations were affected by CCK-8 (1 mg/L) alone. CONCLUSION: CCK-8 improved the vascular reactivities in the presence of LPS, which may be one of the anti-endotoxic shock mechanisms of CCK.

AIM: To investigate the effect of cholecystokinin octapeptide(CCK-8) on the L-arginine-nitric oxide(NO) pathway in rabbit thoracic aortae treated with lipopolysaccharide(LPS). METHODS: The isolated thoracic aortic rings(TARs) from rabbits were incubated with LPS, LPS+CCK or vehicle for 14 h. Then the contractility to phenylephrine(PE) by TARs and the response to L-arginine(L-Arg) by pre-contractile TARs were measured. In addition, we added NO synthase(NOS) inhibitors aminoguanidine(AG)and N ?-nitro-L-arginine(L-NNA) into organ baths to observe the changes of vascular contractility to PE. NOS activity in isolated TARs were also detected. RESULTS: Incubation of TARs with LPS for 14 h resulted in an increase of NOS activity and a reduction of contractility to PE. Treatment with CCK-8 significantly inhibited the increased NOS activity in thoracic aortae and improved the hypocontractility of TARs to the same degree as AG. CONCLUSION: CCK-8 may improve the hypocontractility of TARs induced by LPS by inhibiting the activity of NOS.

Objective: To investigate the antibiotic resistance status of Streptococcus pneumoniae isolates from hospitalized children in Shanxi Children′s Hospital. Method: E-test and Kirby-Bauer methods were applied to determine drug sensitivity of the isolates collected from the body fluid specimens of hospitalized children in Shanxi Children's Hospital from January 2012 to December 2014. The antimicrobial sensitivity and minimum inhibitory concentration (MIC) of Streptococcus pneumoniae to the conventional antibiotics were analyzed, in order to compare the annual trends of non-invasive isolates, while the differentiation of sensitivity from specimens. The comparison of rates was performed by Chi-squared test and Fisher's exact test. Result: A total of 671 isolates of streptococcus pneumoniae were obtained, which could be divided as non-invasive isolates(607), invasive isolates from non-cerebrospinal fluid(non-CSF)(40) and invasive isolates from cerebrospinal fluid(CSF)(24). The antimicrobial sensitivity(isolates(%)) of the 671 isolates were respectively vancomycin 671(100.0%), linezolid 671(100.0%), levofloxacin 665(99.1%), penicillin 595(88.7%), ceftriaxone 516(76.9%), cefotaxime 512(76.3%), sulfamethoxazole-trimethoprin(SMZ-TMP) 103(15.4%), clindamycin 28(4.2%), tetracycline 26(3.9%), erythromycin 12(1.8%). From 2012 to 2014, the susceptibility rates of non-invasive isolates to penicillin every year were 95.0%(96/101), 97.3%(110/113), 87.3%(343/393), respectively, and there was significant difference among the three years(χ²=13.266, P<0.05), and the values of MIC₅₀, MIC₉₀ and the maximum values of MIC(mg/L) of penicillin were 0.064, 2.000, 6.000 in 2012, which grew up to 1.000, 3.000, 16.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to ceftriaxone and cefotaxime during these three years, (χ²=1.172, 1.198, both P>0.05). On the other hand, the values of MIC₅₀, MIC₉₀ and the maximum value of MIC(mg/L) of ceftriaxone and cefotaxime both increased from 0.500, 2.000, 8.000 in 2012 to 0.750, 4.000, 32.000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to the rest antibiotic. Based on the same examining standard of CSF, the antimicrobial sensitivity(isolates(%)) of the non-invasive isolates to ceftriaxone, cefotaxime, SMZ-TMP were respectively 281(46.3%), 278(45.8%), 78(12.9%), were significantly lower than the susceptibility rate of the invasive isolates from non-CSF (28(70%), 28(70%), 14(35%), χ²=8.453, 8.817, 15.094, all P<0.012 5), and lower than the invasive isolates from CSF (18(75%), 18(75%), χ²=7.631, 7.905, P<0.012 5; 11(45.8%), P=0.001). The sensitivity of the isolates to the rest antibiotics were similar(P>0.05). Conclusion More than 95.0% strains of the streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children's Hospital were sensitive to vancomycin, linezolid, levofloxacin, and the susceptibility rate of penicillin, ceftriaxone, cefotaxime were 88.7%, 76.9%, 76.3%. However, less than 20.0% of streptococcus pneumoniae were sensitive to erythromycin, clindamycin, SMZ-TMP and tetracycline. The susceptibility rate of penicillin of non-invasive Streptococcus pneumoniae declined by these years, and the differences to ceftriaxone and cefotaxime can be neglected, but the values of MIC₅₀, MIC₉₀ and the maximum value of MIC of all were linearly rising. The susceptibility rate of antibiotics to ceftriaxone and cefotaxime of the non-invasive isolates was lower than the invasive isolates.

AIM: To investigate the binding characteristics of cholecystokinin receptors in rat pulmonary interstitial macrophages (PIMs). METHODS: The PIMs were isolated from rat lung tissues, purified using the collagenase digestion method combined with alveolar lavage and pulmonary vessel perfusion. The PIM membrane was obtained by supercentrifuge. Receptors for CCK in PIMs were examined using [~3H] labeled CCK-8S as ligand. The specificity of [~3H]-CCK-8S binding to PIMs membrane and the subtypes of CCK receptors were determined by competitive inhibition experiments with CCK-8S, CCK-A and CCK-B receptors selective antagonists (CR1409 and CR2945). The effects of time and incubation temperature on the specific binding were also observed. RESULTS: The specific binding of [~3H]-CCK-8S was not detected in normal rat PIMs, but was detected in the rat administrated with LPS for 48 h. The capacity of ligand-receptor binding was dependent on the incubation temperature and time. Scatchard analysis of the saturation curves suggested that the presence of CCK receptors with high affinity [Kd=(0.68?0.28)mmol/L] and low binding capacity [Bmax=(32.50?2.70) pmol?g~(-1) protein] in PIMs. By means of competitive inhibition studies, the specific binding of [~3H]-CCK-8S to rat PIMs was inhibited by unlabelled CCK-8S [IC_(50)=(3.20?1.13) nmol/L], CCK-AR specific antagonist CR 1 409 [IC_(50)=(0.19?0.06)?mol/L] and CCK-BR specific antagonist CR 2945[IC_(50)=(2.30?0.80)nmol/L]. CONCLUSION: These results suggest the presence of two subtypes of CCK-AR and CCK-BR and provide a structural basis for CCK to play a pivotal role in PIMs.