Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

PURPOSE: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. RESULTS: Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine. .

Inibição da corrente de cálcio tipo l por tramadol e enantiômeros em miócitos cardíacos de ratos / Inhibition of L-type calcium current by tramadol and enantiomers in cardiac myocytes from rats

FUNDAMENTO: O tramadol é um analgésico de ação central cujo mecanismo de ação envolve a ativação de um receptor opioide. Anteriormente, mostramos que o tramadol e seus enantiômeros apresentavam um efeito inotrópico negativo sobre o músculo papilar no qual o (+)-enantiômero era mais potente que (-)- e (±)-tramadol. OBJETIVO: No presente trabalho, investigamos os efeitos do tramadol e seus enantiômeros na corrente de cálcio tipo L (I Ca-L). MÉTODOS: Os experimentos foram realizados em miócitos ventriculares isolados de ratos Wistar utilizando a técnica de patch-clamp com configuração de célula inteira. RESULTADOS: O tramadol (200 µM) reduziu a amplitude de pico do I Ca-L em potenciais de 0 a +50 mV. Em 0 mV, a I Ca-L foi reduzida em 33,7 ± 7,2 por cento. (+)- e (-)-tramadol (200 µM) produziram uma inibição semelhante da I Ca-L, na qual a amplitude do pico foi reduzida em 64,4 ± 2,8 por cento e 68,9 ± 5,8 por cento, respectivamente a 0 mV (P > 0,05). O tramadol, (+)- e (-)-tramadol mudaram a inativação de estado estacionário de I Ca-L para potenciais de membrana mais negativos. Além disso, tramadol e (+)-tramadol alteraram significativamente a curva de recuperação dependente de tempo da I Ca-L para a direita e reduziram a recuperação de I Ca-L da inativação. A constante de tempo foi aumentada de 175,6 ± 18,6 a 305,0 ± 32,9 ms (P < 0,01) para o tramadol e de 248,1 ± 28,1 ms para 359,0 ± 23,8 ms (P < 0,05) para o (+)-tramadol. O agonista do receptor µ-opioide (DAMGO) não tem nenhum efeito na I Ca-L. CONCLUSÃO: A inibição da I Ca-L induzida por tramadol e seus enantiômeros não teve relação com a ativação de receptores opioides e poderia explicar, pelo menos em parte, seu efeito inotrópico negativo cardíaco.

BACKGROUND: Tramadol is a centrally acting analgesic, whose mechanism of action involves opioid-receptor activation. Previously, we have shown that tramadol and its enantiomers had a negative inotropic effect on the papillary muscle in which the (+)-enantiomer is more potent than (-)- and (±)-tramadol. OBJECTIVE: In this study, we investigated the effects of tramadol and its enantiomers on L-type calcium current (I Ca-L). RESULTS: Tramadol (200 µM) reduced the peak amplitude of I Ca-L at potentials from 0 to +50 mV. At 0 mV, I Ca-L was reduced by 33.7 ± 7.2 percent. (+)- and (-)-tramadol (200 µM) produced a similar inhibition of I Ca-L, in which the peak amplitude was reduced by 64.4 ± 2.8 percent and 68.9 ± 5.8 percent, respectively at 0 mV (p > 0.05). Tramadol, (+)- and (-)-tramadol shifted the steady-state inactivation of I Ca-L to more negative membrane potentials. Also, tramadol and (+)-tramadol markedly shifted the time-dependent recovery curve of I Ca-L to the right and slowed down the recovery of I Ca-L from inactivation. The time constant was increased from 175.6 ± 18.6 to 305.0 ± 32.9 ms (p < 0.01) for tramadol and from 248.1 ± 28.1 ms to 359.0 ± 23.8 ms (p < 0.05) for (+)-tramadol. The agonist of µ-opioid receptor DAMGO had no effect on the I Ca-L. CONCLUSION: The inhibition of I Ca-L induced by tramadol and its enantiomers was unrelated to the activation of opioid receptors and could explain, at least in part, their negative cardiac inotropic effect.

Modulação autonômica e atividade cronotrópica durante exercício aeróbio em pacientes que utilizam atenolol / Autonomic modulation and chronotropic activity during aerobic exercise in patients using atenolol

Introduction: The negative chronotropic effect of beta-blockers (BB) can modify itself according to its pharmacokinetics. Objective: To investigate the influence of pharmacokinetics of beta-blockers in heart rate (HR) and autonomic activity (AA) in response to the exercise. Methods: Three groups of hypertensive patients, users of atenolol (n=9), enalapril, (n=8), and a normotensive control group (n=8), performed two sessions of moderate exercise on a cycloergometer, during 40 minutes, whereby 2 hours (Session I), or 23 hours after drug administration (Session II). Records of electrocardiogram were made before, during and after the exercises. Results: The HR was lower in session I comparing with session II of the atenolol group during the exercise. There were no differences in the components of low and high frequency of AA between these sessions. Conclusions: These results confirm the negative chronotropic effect of BB. However, the absence of changes in AA suggests that other mechanisms may be contributing to this phenomenon.

Introdução: O efeito cronotrópico negativo dos betabloqueadores pode modificar-se de acordo com sua farmacocinética. Objetivo: Investigar a influência da farmacocinética dos betabloqueadores na frequência cardíaca (FC) e atividade autonômica (AA) em resposta ao exercício. Método: Três grupos de hipertensos, usuários de atenolol, n=9, enalapril, n=8 e um controle normotenso, n=8, realizaram duas sessões de exercício moderado em cicloergômetro, com duração de 40 minutos, sendo 2 horas (sessão I), ou 23 horas após administração do fármaco (sessão II). Registros de eletrocardiograma foram feitos antes, durante e após os exercícios. Resultados: A FC, durante o exercício, foi menor na sessão I, quando comparada com a sessão II do grupo atenolol. Não se observou diferenças nos componentes de baixa e alta frequência da AA entre essas sessões. Conclusão: Esses resultados confirmam o efeito cronotrópico negativo dos BB. No entanto, a ausência de alterações na AA sugere que outros mecanismos podem estar contribuindo para esse fenômeno.

Cardioprotection by the inhibitory effect of nitric oxide / 生理学报

Endothelial and neuronal nitric oxide synthases (eNOS and nNOS) are constitutively expressed in cardiomyocytes under the physiological condition, while inducible nitric oxide synthase (iNOS) is only expressed in cell stress. Nitric oxide (NO) derived from the constitutive isoforms of eNOS and nNOS plays four kinds of inhibitory effects on the myocardium: reducing the contractile frequency of cardiomyocyte, slightly attenuating cardiac contractility, accelerating relaxation and increasing distensibility of cardiomyocyte, and slightly inhibiting mitochondrial respiration and improving the efficiency of myocardial oxygen consumption. In conditions of enhanced cardiac reserve and cardiac hypertrophy, NO derived from eNOS, which forms a complex with a certain kind of receptor on the sarcolemma, modulates receptor-mediated signaling and generates an "accentuated antagonism" by moderate inhibition of cardiac contractility. NO derived from the complex of nNOS-ryanodine receptor (RyR) stabilizes RyR calcium release and increases the efficiency of Ca(2+) cycling in sarcoplasmic reticulum by the inhibitory effects. However, besides the above-mentioned inhibitions of NO derived from eNOS and nNOS, NO derived from iNOS generally prevents mitochondrial permeability transition pore opening by inhibiting mitochondrial respiration under the conditions of the myocardial ischemia-reperfusion injury and heart failure. Therefore, both in the physiological condition and in the pathological condition, NO exhibits a moderate inhibition in cardiac function, and eventually produces cardioprotection.

Inhibitory effect of hydrogen sulfide on cardiac fibroblast proliferation / 生理学报

The aim of the present study was to investigate the role of hydrogen sulfide (H(2)S) in the proliferation of neonatal rat cardiac fibroblasts (NRCFs). Proliferation of NRCFs was induced by the presence of fetal bovine serum (FBS) or angiotensin II (Ang II) at various concentrations. The concentration-dependent effect of NaHS (donor of H(2)S) on NRCFs proliferation was examined. NRCFs proliferation was assessed by 5'-bromo-2'-deoxyuridine (BrdU) incorporation method. Reactive oxygen species (ROS) level was measured using the dye probe, 2', 7'-dichlorofluorescein diacetate (DCFH-DA). The results showed that FBS- or Ang II-induced NRCFs proliferations were inhibited with the treatment of relatively high concentrations of NaHS (5 × 10(-5) mol/L, 1 × 10(-4) mol/L), but FBS-induced proliferation was increased by low concentration of NaHS (1 × 10(-5) mol/L). Two or 6 h of Ang II (1 × 10(-7) mol/L) treatment caused an increase of ROS level in NRCFs, while this increase was inhibited with NaHS (1 × 10(-4) mol/L) treatment. These results suggest that H(2)S is an inhibitor of cardiac fibroblast at a certain concentration range. This inhibitory effect may be mediated by a reduction in intracellular ROS production.

Suppressing poly(ADP-ribose)polymerase-1 inhibits tau phosphorylation in HEK293/tau441 cells / 生理学报

The study aimed to investigate the effect of inhibition of poly(ADP-ribose) polymerase-1 (PARP-1) activity on tau phosphorylation in HEK293/tau441 cells and its mechanism. HEK293/tau441 cells were treated with 3-aminobenzamide (3-AB), a PARP-1 inhibitor, at different doses (0.5, 1, 2, 4 mmol/L). After 24 h, the cell morphology was observed under phase contrast microscope, tau phosphorylation level in different sites (tau-1, tau-5, Thr231) and the activity of glycogen synthase kinase 3 (GSK-3) were detected by Western blotting. The results showed: (1) 3-AB at different doses failed to change the morphology of cells; (2) The 3-AB-induced decrease in activity of PARP-1 resulted in increase of unphosphorylation level in tau-1(Ser195/198/199/202) sites; (3) The phosphorylation of tau was decreased in Thr231 site, while the total tau was slightly changed after 3-AB treatment; (4) With the increased phosphorylation of GSK-3 at Ser9 site, the activity of GSK-3 was decreased after 3-AB treatment. The results suggest that the inhibition of PARP-1 by 3-AB could decrease tau phosphorylation in HEK293/tau441 cells probably through decreasing GSK-3 activity.

Mevastatin inhibits the differentiation of thyroid-associated ophthalmopathy derived orbital preadipocytes / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of mevastatin (Mev) on the expression of peroxisome-proliferator-activated receptor-gamma (PPAR-gamma) mRNA and differentiation of Thyroid-associated ophthalmopathy (TAO) derived orbital preadipocytes in vitro.@*METHODS@#Orbital adipose tissues were obtained from TAO patients undergoing orbital decompression surgery. The orbital preadipocytes cultured from the orbital adipose tissues were divided into Group A (a control group) and Group B (an intervention group). Group B was subdivided into Group B1-B5, all groups were stimulated to differentiate into mature adipocytes with cocktail differentiation medium.The entire course of differentiation was 10 d. The differentiation of orbital preadipocytes in Group A was induced with routine inducer,while at in Group B1,B2, and B3 was interfered with 5 micromol/L (B1), 10 micromol/L(B2),20 micromol/L (B3) mevastatin respectively during the whole process of differentiation. The differentiation of orbital preadipocytes in Group B4 and B5 was interfered with 10 micromol/L mevastatin day 4 (B4) or day 8 (B5) of the differentiation process until the entire course was over. Intracellular fat accumulation in differentiated adipocytes was determined by oil red O staining. The value of optical absorption was measured at 492 nm with enzyme-linked immunosorbent assay. The expression of PPAR-gamma mRNA was detected by reverse transcription polymerase chain reaction.@*RESULTS@#The light absorption value (A) and PPAR-gamma mRNA expression of differentiated cells in Group A,B1,B2,and B3 decreased successively,and there was significant difference in any of the 2 groups among Group A, B1 and B2, and B3 (P<0.05). The value A and PPAR-gamma mRNA expression of differentiated cells in Group A, B4, and B2 decreased successively, and the difference in any of the 2 groups among these 3 groups was significant. However, there were no significant difference between Group A and B5.@*CONCLUSION@#Mevastatin inhibits the differentiation of TAO derived orbital preadipocytes by blocking PPAR-gamma mRNA expression. The degree of inhibition is not only concentration-dependent but also associated with the stage of differentiation. The earlier the differentiation, the stronger the inhibition.

Influences of Panax notoginsenosid on spontaneous contraction of small intestine smooth muscle of rabbits in vitro / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the influences of Panax notoginsenosid(a compound of Chinese Traditional Medicine) on the spontaneous contraction of small intestine smooth muscle of rabbits in vitro and explore the mechanism.</p><p><b>METHODS</b>The influences of Panax notoginsenosid on the spontaneous contraction of small intestine in intacted rabbits(male or female) after the isothermal perfuse of small intestine in vitro were observed. Bay K8644 and nitro-L-arginine methylester (L-NAME) were added to the normal Tyrode's solution respectively before Panax notoginsenosid. In the Ca2+ free Tyrode's solution, rynodine was added before Panax notoginsenosid. The mechanism of Panax notoginsenosid was studied.</p><p><b>RESULTS</b>Panax notoginsenosid reduced the amplitude of contraction of small intestine smooth muscle in rabbits in a does-depended manner. Bay K8644 and L-NAME could completely block the inhibition of Panax notoginsenosid on the contraction of small intestine smooth muscle. Panax notoginsenosid inhibited significantly the intracellular calcium-depended contraction induced by rynodine in the Ca2+ free Tyrode's solution.</p><p><b>CONCLUSION</b>Panax notoginsenosid inhibits significantly the contraction of small intestine smooth muscle of rabbits in vitro. The mechanism may be related to increase NO concentration in small intestine smooth muscle so that inhibit extracellular Ca2+ inflowing via cell membrane and intracellular Ca2+ releasing via sarcoplasmic reticulum.</p>

Effect of baicalin on protease-activated receptor-1 expression and cell apoptosis in brain of rat with intracerebral hemorrhage / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the protective effect and mechanism of baicalin on nerve tissue in rat with intracerebral hemorrhage (ICH).</p><p><b>METHODS</b>Rats were randomly divided into five groups: the sham-operated group, the ICH model group, and the three baicalin treated groups treated respectively with small, medium and large doses of baicalin. ICH rat model was established by injecting collagenase VII into caudate nucleus. Baicalin was given by peritoneal injection to the baicalin treated groups, and saline was given to the other two groups once a day started from 2 h after modeling. Animals were sacrificed in batches on the 1st, 3rd, 5th and 10th day of treatment to take their brains for detecting protease-activated receptor-1 (PAR-1) expression and cell apoptosis in brain tissue surrounding hematoma by Western blot and TUNEL method, respectively. And the water content of brain was estimated by dry-wet weight method.</p><p><b>RESULTS</b>Compared with the model group, the PAR-1 expression and TUNEL-positive cells were significantly reduced in the baicalin treated groups; and brain edema was also significantly reduced (P<0.01).</p><p><b>CONCLUSIONS</b>The up-regulated PAR-1 expression after ICH in rats might play an important role in inducing cell apoptosis and brain edema. Baicalin shows significant protective effect on ICH rats, which may be related to its effects in inhibiting PAR-1 expression and decreasing apoptosis cells, so as to reduce brain edema.</p>

Endothelin-1 and nitric oxide mediated the lipopolysaccharide-induced cardiac negative inotropic role / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.</p><p><b>METHODS</b>Experimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.</p><p><b>RESULTS</b>(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.</p><p><b>CONCLUSION</b>ET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.</p>

Effects of Honeysuckle flower and Scutellaria Baicalensis Georgi on constraction and electric activity of rabbit small intestine smooth muscle / 中国应用生理学杂志

<p><b>AIM</b>To investigate the effect of Honeysuckle flower (HF) and Scutellaria Baicalensis Georgi (SBG) on contraction and electric activity of small intestine smooth muscle in rabbit and the underlying mechanisms.</p><p><b>METHODS</b>Using organ bath technique to observe the effect of HF and SBG on contractive and electric activity of small intestine smooth muscle in rabbit.</p><p><b>RESULTS</b>HF and SBG significantly decreased the amplitude, frequency and area under the curve of contractive, as well as electric activity in a dose-depended manner. IC50 of the contractive amplitude was 6.30 g/L and 1.56 g/L by Logit Loglinear analysis. The inhibitive effect of HF and SBG on contractive activity could be partly decreased by beta-receptor blocker Propranolol, NO synthase inhibitor L-NAME, and K+ channel blocker Glibenclamide. Also HF and SBG inhibited acetylcholine-induced both intracellular and extracellular calcium-depended contraction significantly.</p><p><b>CONCLUSION</b>HF and SBG obviously inhibit the contractive and electric activity of small intestine smooth muscle of rabbit. The mechanisms are related to several pathways.</p>

O abuso de êxtase no Brasil: uma droga de final de semana ou algo mais? / The abuse of ecstasy in Brasil: a weekend drug or something else?

O 3,4-metilenodioximetanfetamina (MDMA) popularmente conhecido por ’êxtase’ é uma droga sintéticaque chegou ao Brasil nos anos 90, portanto poucos estudos científicos estão disponíveis sobre a epidemiologia e os padrões de consumo desta droga. O perfil dos usuários de êxtase é na maioria das vezes composto por indivíduos jovens de até 25 anos, poliusuários de drogas, homens, heterossexuais, solteiros, de nível superior completo ou incompleto e pertencente às classes sócio-econômicasmais elevadas. Farmacologicamente o êxtase atua sobre o sistema serotonérgico, promovendo aumentoda liberação e inibição da recaptação de 5-HT pelos terminais nervosos, aumentando efetivamente a concentração de 5-HT na fenda sináptica. Além disso, o êxtase também promove ativação de vias noradrenérgicas e dopaminérgicas centrais. Todas estas alterações neuroquímicas podem desencadear uma série de manifestações clínicas, tais como euforia, bem-estar, desinibição,sudorese e alucinações. O uso do êxtase também pode provocar complicações como hipertemia fulminante, complicações cardiovasculares e psiquiátricas, que podem inclusive levar a morte o indivíduo. Adicionalmente,o abuso de êxtase pode causar dependência e tolerância em humanos. Em conclusão, torna útil enfatizar a importância de programas educacionais na prevenção ao consumo de drogas, dando particular ênfase ao êxtase.Outro fator que merece atenção é a capacitação dos profissionais da saúde para atuarem em intervenções deemergência em casos de intoxicações decorrentes do uso abusivo de êxtase.

3,4-methylenedioxymethamphetamine (MDMA) popularly named ecstasy is a synthetic drug that arrived in Brazil in the 90’s. Due to this fact, few studies are still available about the pattern of ecstasy’s users in Brazil. However, many epidemiological studies indicate that the profile of ecstasy’s users is generally young people (up to 25 years old), drug polyusers, men, heterosexual, single, graduate or undergraduate students, and belonging to a privileged economic class. Pharmacologically, ecstasy acts on the serotonergic system, by increasing the release and inhibiting the re-uptake of serotonin in thenervous system. Together, these actions produce a robust increase of serotonin concentrations in the synaptic cleft. Despite serotonergic effects, ecstasy also acts on noradrenergic and dopaminergic pathways, thus promotinga very complex myriad of clinic symptoms, such as euphoria, disinhibition, sweat, hallucinations. Use of ecstasy also can promote hyperthermia, cardiovascular andpsychiatric alterations, which could lead the user to death, besides dependence and tolerance when chronically used. In conclusion, educational programs back toward the prevention of ecstasy consumption and training of heath professional workers is absolutely required for reducing the abuse of this drug and for improving the treatment of users.

Differentiation of 2 endothelial progenitor cells in vitro and inhibitory effect of asymmetric dimethylarginine on its proliferation / 中南大学学报(医学版)

OBJECTIVE@#To investigate the Methods for culturing two types of endothelial progenitor cells (EPC) from human umbilical cord blood and study their differentiation traits and the depressant effect of asymmetric dimethylarginine (ADMA) on its proliferation.@*METHODS@#Mononuclear cells were isolated from fresh cord blood by 6% hydroxyethyl starch(HES) and density gradient centrifugation.Isolated cells were cultured in the medium supplemented with vascular endothelial growth factors (VEGF) and basic fibroblast growth factors (bFGF). The growth characteristics and biological features of the cells were observed at different time points and identified by morphology,immunofluorescence staining,reverse transcription polymerase chain reaction (RT-PCR), and flow cytometry.Attached cells were incubated with different concentrations of ADMA (1,5, and 10 micromol/L) for 24,48, and 72 hours. Methylthiazoletetrazolium (MTT) assay and quantified colony forming units (CFUs) were used to assess the proliferation of endothelial progenitor cells.@*RESULTS@#The attached cells were divided into 2 types:early EPC and late EPC. Early EPC changed from small sized round cells to spindle shaped cells and late EPC formed a typical cobblestone-like cells. Fluorescence microscopy showed that EPC were positive for both Dil-acLDL uptake and FITC-UEA-I binding.RT-PCR and FACS showed the difference of endothelial cell-specific,gene expression and changed AC133,CD34, and KDR among different times.Incubation of EPC with ADMA dose and time-dependently decreased the number and the proliferation of EPC.@*CONCLUSION@#There are 2 types of EPC from a source of human umbilical cord blood and ADMA may depress the EPC proliferation, providing a basis for further research.

Effect of xinkeshu tablet on heart rate variability in patients with coronary heart disease / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Xinkeshu Tablet (XKS) on heart rate variability (HRV) in patients with coronary heart disease (CHD).</p><p><b>METHODS</b>Sixty patients with their diagnosis of CHD confirmed by coronary angiography were randomized into two groups equally. Besides the conventional treatment for CHD, XKS and Metoprolol were given respectively to patients in the treated group and the control group for 8 weeks. Symptoms and 24 h dynamic ECG were observed before and after treatment.</p><p><b>RESULTS</b>Episode of angina pectoris decreased obviously in both groups after treatment, from 8.8 +/- 3.2 times per week (the same hereafter) to 4.4 +/- 2.1 in the treated group (P<0.05), and from 8.4 +/- 3.1 to 3.9 +/- 2.0 in the control group (P <0.05). HRV analysis showed that after treatment the average heart rate lowered from 85.44 +/- 2.89 beat/min to 77.32 +/- 2.17 beat/min in the treated group and from 83.80 +/- 4.30 beat/min to 76.70 +/- 2.93 beat/min in the control group (both P < 0.05), showing no significant difference in extent of lowering between groups (P > 0.05). The time-domain indexes elevated in both groups, showing no statistical difference between groups (P >0.05). As for the frequency-domain indexes, low frequency (LF), high frequency (HF) and total power raised, while LF/HF and very low frequency lowered in both groups, but the changes were more significant in the treated group (P <0.05).</p><p><b>CONCLUSION</b>XKS could improve HRV in patients of CHD and reduce the episode of angina pectoris in them.</p>

Antagonism of morphine-induced central respiratory depression by donepezil in the anesthetized rabbit

Morphine is often used in cancer pain and postoperative analgesic management but induces respiratory depression. Therefore, there is an ongoing search for drug candidates that can antagonize morphine-induced respiratory depression but have no effect on morphine-induced analgesia. Acetylcholine is an excitatory neurotransmitter in central respiratory control and physostigmine antagonizes morphine-induced respiratory depression. However, physostigmine has not been applied in clinical practice because it has a short action time, among other characteristics. We therefore asked whether donepezil (a long-acting acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease) can antagonize morphine-induced respiratory depression. Using the anesthetized rabbit as our model, we measured phrenic nerve discharge as an index of respiratory rate and amplitude. We compared control indices with discharges after the injection of morphine and after the injection of donepezil. Morphine-induced depression of respiratory rate and respiratory amplitude was partly antagonized by donepezil without any effect on blood pressure and end-tidal C0(2). In the other experiment, apneic threshold PaC0(2) was also compared. Morphine increased the phrenic nerve apnea threshold but this was antagonized by donepezil. These findings indicate that systemically administered donepezil partially restores morphine-induced respiratory depression and morphine-deteriorated phrenic nerve apnea threshold in the anesthetized rabbit.

Inhibitory effects of scorpion venom heat resistant protein on the excitability of acutely isolated rat hippocampal neurons / 生理学报

The effects of scorpion venom heat resistant protein (SVHRP) (National invention patent of China, 2004-10-20, No. ZL01 1 06166.92) on the excitability of acutely isolated rat hippocampal neurons were observed by whole-cell recording and the potential molecular mechanisms underlying its antiepileptic effect were investigated further. The results showed that SVHRP could decrease the excitability of hippocampal neurons. SVHRP (1x 10(-2) microg/mL) altered the action potential (AP) firing mode and decreased the AP firing frequency. Out of 52 neurons observed, 45 (86.54%) generated phasic firing, and 7 (13.46%) generated repetitive firing. Among the 45 neurons generating phasic firing, 8 (17.78%) neurons could still be induced phasic firing after treatment with 1x 10(-2) microg/mL SVHRP and 37 (82.22%) neurons had no responses to the stimulation. The AP firing of neurons was dramatically different after treatment with SVHRP (P<0.01, n=45). Among the 7 repetitive firing neurons, all of them could only generate 1 or 0 AP instead of repetitive firing when SVHRP was applied. The number of APs was 14.57 +/- 1.00 and 0.57 +/- 0.20 before and after SVHRP treatment (P<0.01, n=7). The AP rheobase was (75.10 +/- 8.99) pA and (119.85 +/- 12.73) pA before and after 1x 10(-4) microg/mL SVHRP application, respectively (P<0.01, n=8). The AP threshold was increased from (-41.17 +/- 2.15) mV to (-32.40 +/- 1.48) mV after 1x 10(-4) microg/mL SVHRP treatment (P<0.01, n=8). The peak amplitude of AP was (68.49 +/- 2.33) mV for the neurons before treatment with 1x 10(-4) microg/mL SVHRP and (54.71 +/- 0.81) mV after treatment (P<0.01, n=8). These results showed that SVHRP could decrease the AP firing frequency, increase the AP rheobase and threshold, but decrease the AP peak amplitude of hippocampal neurons. In other words, SVHRP can decrease the excitability of hippocampal neurons. SVHRP probably alters the excitability of hippocampal neurons by affecting sodium channels and this may be one of the underlying molecular mechanisms for its antiepileptic effect.

Inhibitory effect of xipayi mouth rinse on the secretion of IL-6 from human gingival fibroblast induced by lipopolysaccharide / 中南大学学报(医学版)

OBJECTIVE@#To observe the effects of xipayi mouth rinse of different concentrations on the activities of interleukin-6 (IL-6) from human gingival fibroblast (HGF) induced by lipopolysaccharide (LPS).@*METHODS@#HGF was stimulated with LPS at 25 g/mL, and the radioimmunoassay (RIA) was used to examine the effect of xipayi mouth rinse at 12.5 approximately 200 g/mL on the secretion of IL-6 in the supernatant of the cell culture.@*RESULTS@#IL-6 secreted by human gingival fibroblast was significantly inhibited by xipayi mouth rinse in a dose dependent manner.@*CONCLUSION@#Xipayi mouth rinse can inhibit the secretion of IL-6 from HGF induced by LPS, suggesting the anti-inflammatory effect of xipayi mouth rinse to treat and prevent periodontal diseases.

Inhibitory effect of resveratrol on the proliferation of synoviocytes in rheumatoid arthritis and its mechanism in vitro / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of resveratrol on the proliferation and apoptosis of synoviocytes in patients with rheumatoid arthritis (RA) in vitro and explore its mechanism.@*METHODS@#The levels of cell proliferation of synoviocytes in RA after 24 h treated with different concentrations of resveratrol were measured by monotetrazolium colourmetric assay method. The percentages of synoviocytes apoptosis in RA after 24 h treated with different concentrations of resveratrol were tested by TUNEL and flow cytometry. The relative activities of caspase-3 were determined by colorimetric assay after 4, 8, 12, 18, and 24 h treated with resveratrol (200 micromol/L) and 12 h treated with different concentrations of resveratrol. The cleavages of pro-caspase-3 were analyzed by Western blot after 24 h treated with different concentrations of resveratrol.@*RESULTS@#The levels of cell proliferation of synoviocytes with RA after 24 h treated with different concentrations of resveratrol were significantly decreased compared with the control group (P<0.01). The percentages of the apoptotic cells were increased of resveratrol-treated after 24 h, the apoptosis rates between the treated groups and the control group were significantly different (P<0.01). When the synoviocytes in RA were treated with 200 micromol/L resveratrol for different time respectively, the caspase-3 activity began to rise significantly at 4h, reaching the peak at 12 h, and was still much higher than that of the control group at 24 h (P<0.01). After the cells were treated with different concentrations of resveratrol for 12 h, caspase-3 activity increased in a concentration-dependent manner. After synoviocytes in RA were treated with different concentrations of resveratrol for 24 h, the expressions of pro-caspase-3 decreased as the concentration increased, the caspase-3 active fragment P11 (11 kD) appeared at 100 micromol/L and was increased at 400 micromol/L.@*CONCLUSION@#Resveratrol inhibits the proliferation of synoviocytes and induces cell apoptosis in rheumatoid arthritis in vitro, which may relate to the activation of caspase-3.

PPARalpha agonist--fenofibrate inhibits LPS-induced tissue factor expression in THP-1 cells / 中国实验血液学杂志

This study was aimed to investigate the influence of PPARalpha agonist on the expression of TF (tissue factor) in THP-1 cells. THP-1 cells were pretreated with different concentrations of PPARalpha agonist (fenofibrate) for definite time. Lipopolysaccharide (LPS)-induced TF mRNA and protein levels were detected by RT-PCR and Western blot respectively. The results showed that fenofibrate decreased tissue factor protein and mRNA expression in supernatants of LPS-stimulated human monocytes in a concentration-dependent manner (P < 0.05 - 0.01, n = 5). It is concluded that fenofibrate inhibit TF expression induced by LPS in THP-1 cells, which may be involved in the anti-atherosclerotic effects of PPARalpha agonist.