T-type Ca2+ channels and their relationship with pre-neoplastic and neoplastic lesions in the human breast

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Mechanistic study of endothelium independent vasodilation effects of wogonin

Scutellaria baicalensis Georgi, locally known as HuangQin, and commonly as Baikal or Chinese skullcap, is an important herb in Chinese traditional medicine. The flavonoids from this plant are main active substances responsible for its medicinal applications. Wogonin is one such active ingredient derived from this plant. Here, we investigated the mechanism of the vasodilation effect of wogonin on isolated rat thoracic aortas. For this study, endothelium intact and endothelium removed thoracic aortic rings were prepared from rats. Using a tension transducer, the tension of the rat thoracic aortic rings was recorded. Results showed that wogonin is able to relax the endothelium-intact aortic rings, but L-NAME, indomethacin (Indo), and methylene blue (MB) could not reduce the tension in these rings. Wogonin was also able to relax endotheliumremoved rings. However, treatment with tetraethylammonium (TEA), BaCl2, glibenclamide (Gly), 4-aminopyridine (4-AP), and verapamil (Ver) had no effect on vasodilation induced by wogonin. Using wogonin to pre-treat endothelium-removed aortic rings reduced the contraction induced by K+. Pre-treatment of endothelium-removed aortic rings with wogonin markedly reduced the contraction induced by 10-6 M PE in Ca2+-free solution. It could be concluded that L-type calcium channels and intracellular Ca2+ release is inhibited by wogonin.

IL-6 exacerbates potential arrhythmia of Chan Su intravenous injection / 中国药理学通报

Aim To explore the arrhythmic risk of Chan Su intravenous injection(CS)and its underlying mechanismin in the absent or presence of IL-6.Methods The recording techniques of guinea pig in vivo ECG, the action potential, L-type Ca2+ and Na+ currents from left ventricular myocytes were used to analyze heart rate(HR), P-R, QRS and QTc intervals and the underlying mechanism.Results① CS at one time CRD(clinically relevant dose)insignificantly changed the guinea pig in vivo ECG.However, the IL-6(18.4 μg·kg-1)only and the combinational use of IL-6(18.4 μg·kg-1)plus CS(one time CRD)remarkably prolonged the P-R and QTc intervals.② The CS at one time CRC(clinically relevant concentration)had no significant change in the action potential duration at 90% repolarization level(APD90).The IL-6(20 μg·L-1)only and the combination of CS at one time CRC plus IL-6(20 μg·L-1)significantly prolonged APD90.③ Moreover, the IL-6(20 μg·L-1)combined with CS at one time CRC significantly inhibited the L-type Ca2+ current. CS at one, five, ten time CRC, IL-6(20 μg·L-1)alone and IL-6(20 μg·L-1)combined with CS had no significant effects on Na+current.Conclusions CS intravenous injection has low risk of arrhythmia in the clinical settings.However, in presence of high titer of IL-6 characterized by inflammation, CS may induce the atrioventricular conduction block due to the blockade effect on Ca2+ current by both of CS and IL-6.

Ligustrazine suppresses platelet aggregation through inhibiting the activities of calcium sensors

Abstract Ligustrazine is widely used for the treatment of cardiovascular diseases in traditional Chinese medication. It has been reported that Ligustrazine decreases the concentration of intracellular calcium ions (Ca2+); however, the underlying mechanism remains unknown. In the present study, the effect of Ligustrazine on adenosine diphosphate (ADP)-induced platelet aggregation was evaluated using a turbidimetric approach. The changes in concentration of intracellular Ca2+ stimulated by ADP was measured using fluo-4, a fluorescent Ca2+ indicator dye. The mRNA expression of stromal interaction molecule l (STIM1) and Orai1, calcium sensor, was determined using real-time PCR. In addition, the protein expression of STIM1, Orai1, and serum/glucocorticoid-regulated protein kinase 1 (SGK1) was determined using Western blot analysis. The data demonstrated that Ligustrazine significantly suppressed platelet aggregation in a dose-dependent manner and reduced the concentration of intracellular Ca2+ triggered by ADP. Our data showed that Ligustrazine treatment inhibited the expression of STIM1 and Orai1 induced by ADP at both mRNA and protein levels, and suppressed the protein expression of SGK1. Taken together, our data indicated that Ligustrazine suppressed platelet aggregation by partly inhibiting the activities of calcium sensors, thereby suggesting that Ligustrazine may be a promising candidate for the treatment of platelet aggregation.

Effects of site specific antibody of Na+-Ca2+exchanger on calcium transient in single ventricular myocytes of rats / 中国免疫学杂志

Objective:To investigate the effects of site specific (124 HNFTAGDLGP STIVGSAAFNMF145 ) antibody of Sodium calcium exchanger ( NCX) on calcium transient in single ventricular myocytes of normal adult rats .Methods: Isolated adult rat hearts were perfused using Langendorff method and single ventricular myocytes were then obtained .The ventricular myocytes were incubated with Fuar-2/AM and 2% bovine serum albumin for about 40 min and then,the fluorescence images were recorded when excitation wavelengths were 340 nm and 380 nm using ion imaging system.Fluorescence value F340/F380,length of cell shortening ,time to 90%restore( TR90 ) and calcium sensitivity ( ratio of F340/F380 and cell shortening ) were calculated.Results:The site specific antibody of NCX increased F340/F380 and decreased TR90 in single ventricular myocytes ,but had no more significant effect on calcium sensitivi-ty.Pretreatment with KB-R7943 or Nicardipine could significantly inhibit the TR 90 decrease or F340/F380 increase induced by the anti-body.Pretreating ventricular myocytes with combination of KB-R7943 and Nicardipine ,the antibody had no more significant effects on calcium transient.Conclusion:Site specific ( 124 HNFTAGDLGPSTIVGSAAFNMF145 ) antibody of NCX could increase calcium transient and accelerate the decrease of intracellular calcium during diastole ,which mainly related to its effects of activating L-type Ca2+channel and NCX.

Chronic Ca²⁺ influx through voltage-dependent Ca²⁺ channels enhance delayed rectifier K⁺ currents via activating Src family tyrosine kinase in rat hippocampal neurons

Excessive influx and the subsequent rapid cytosolic elevation of Ca²⁺ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca²⁺ level in normal as well as pathological conditions. Delayed rectifier K⁺ channels (I(DR) channels) play a role to suppress membrane excitability by inducing K⁺ outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca²⁺-mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of IDR channels to hyperexcitable conditions induced by high Ca²⁺ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca²⁺-treatment significantly increased the amplitude of IDR without changes of gating kinetics. Nimodipine but not APV blocked Ca²⁺-induced IDR enhancement, confirming that the change of I(DR) might be targeted by Ca²⁺ influx through voltage-dependent Ca²⁺ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I(DR) enhancement was not affected by either Ca²⁺-induced Ca²⁺ release (CICR) or small conductance Ca²⁺-activated K⁺ channels (SK channels). Furthermore, PP2 but not H89 completely abolished I(DR) enhancement under high Ca²⁺ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca²⁺-mediated I(DR) enhancement. Thus, SFKs may be sensitive to excessive Ca²⁺ influx through VDCCs and enhance I(DR) to activate a neuroprotective mechanism against Ca²⁺-mediated hyperexcitability in neurons.

The modulatory effects of heat shock protein 70 on membrane calcium homeostasis of PC12 cells induced by ischemic/hypoxia / 中华危重病急救医学

Objective To investigate the effects of lentivirus-mediated heat shock protein 70 (HSP70) gene on voltage-gated calcium channels on the cell membrane of pheochromocytoma cell 12 (PC 12 cells) induced by ischemic/hypoxia and its mechanisms.Methods PC12 cells at logarithmic phase were collected,which were challenged with hypoxia for 6 hours and reoxygenation for 12 hours to stimulate the nerve cells suffered ischemia/reperfusion pathological process in vitro.PC12 cells were divided into non-infection group,infected by lentivirus containing green fluorescent protein (GFP) without HSP70 gene lentivirus control group (GFP lentivirus control group),and infected by lentivirus containing HSP70 and GFP gene recombined lentiviral infection group (HSP70 recombined lentiviral infection group).Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot were used to determine mRNA and protein expressions of L-type voltage-gated Ca2+ channel subunits cav1.2 and cav1.3,receptor gated channel subunits NR1 and NR2,and Na+/Ca2+ exchange (NCX) in PC12 cells.Results After being challenged with hypoxia/reoxygenation,the mRNA and protein expressions of cav1.2,NR1 and NR2 in the PC12 cells were significantly lower in HSP70 recombined lentiviral infection group than those of GFP lentivirus control group and non-infection group [cav1.2 mRNA (2-△△Ct):3.13 ± 0.46 vs.5.12 ± 0.52,5.13 ± 0.66;NR1 mRNA (2-△△△Ct):1.61 ± 0.44 vs.3.23 ±0.82,3.31 ±0.78;NR2 mRNA (2-△△Ct):2.09±0.41 vs.3.91 ±0.64,3.88±0.62;cav1.2 protein (gray value):2.82±0.39 vs.3.98±0.23,3.96±0.24;NR1 protein (gray value):1.84±0.35 vs.2.79±0.21,2.86±0.23;NR2 protein (gray value):0.87±0.24 vs.1.57±0.31,1.33±0.44;all P ＜ 0.01].But there were no statistical differences in the mRNA and protein expressions of cav1.2,NR1 and NR2 between GFP lentivirus control group and non-infection group (all P ＞ 0.01).There were no statistical differences in the mRNA and protein expressions of cav1.3 and NCX among non-infection group,GFP lentivirus control group and HSP70 recombined lentiviral infection group [cav1.3 mRNA (2-△△Ct):4.82 ± 0.32,4.72 ± 0.36,4.82 ± 0.29;NCX mRNA (2-△△Ct):3.49 ± 0.78,3.47 ± 0.71,3.56 ± 0.65;cav 1.3 protein (gray value):2.63±0.40,2.64±0.39,2.68±0.39;NCX protein (gray value):3.27±0.48,3.34±0.48,3.31 ±0.42;all P ＞ 0.01].Conclusion Exogenous HSP70 affects the expression of L-type voltage-gated Ca2+ channel subunit cav1.2 and receptor gated channel subunits NR1 and NR2,which may protect PC12 cells from the injury caused by ischemic/hypoxia.

Vasodilatory effect of Ferulic acid on in-vitro rat coronary artery / 中国药理学通报

Aim To investigate the vasodilatory effect of Ferulic acid on in vitro rat coronary artery and its possible mechanism. Methods By using the mi-crovessel tension recorder system, the vasodilatory effect of FA on resting and contractin-vitro rat coronary artery was determined;the influence of endothelial in-tegrity to FA-induced vasorelaxation was observed; the relationship of FA on [ Ca2+] ex-influx-induced and [ Ca2+] in-efflux-induced contractions was discussed;the mechanism of vasodilatory effect of FA was ex-plored by applying the inhibitors of KCa(TEA),KATP channel ( Gli ) , KIR channel ( BaCl2 ) , KV ( 4-AP ) , NOS( L-NAME) and COX( Indo) . Results FA had no effect on the resting tension of in vitro rat coronary artery. FA dilated the in-vitro rat coronary artery pre-treated with KCl ( 60 mmol · L-1 ) , U46619 ( 1 μmol · L-1 ) and PE ( 10μmol · L-1 ) in a concentration-dependent fashion ( P 0. 05 ) . Conclusion The diastolic func-tion could be related to the activation of KV channel on vascular smooth muscle cells, the free Ca2+ from Sar-coplasmic reticulum cells and blockade extracellular Calcium channel do not depend on KCa, KATP, KIR channel, nor the endothelial function.

Impact of anti-hypertension therapy on seasonal variability of blood pressure, urinary 8-OHdG levels in essential hypertension / 中国综合临床

Objective To investigate anti-hypertension threapy on seasonal variability of blood pressure,urinary 8-OHdG levels in essential hypertension in order to provide a basis for seasonal antihypertensive treatment.Methods Fifty hypertensive patients admitted the hospital of Erdos Clinical Medical College of Inner Mongolia Medical University at summer 2013 were selected as our subjects.The final subjects was 42 cases due to 8 lost cases.The patients were randomly divided into two groups,including 30 cases in renin angiotensin aldosterone system inhibitors(RASI) group and 12 cases in Ca2+ channel blocker(CCB) group.Epidata 3.1 software was applied to perform statistic analysis.Urinary 8-OHdG concentration was measured by enzyme-linked immunosorbent assay (ELISA).Blood pressure was measured in spring,summer,autumn and winter.Results Systolic blood pressure(SBP) in RASI group and CCB group at winter periods were (158±20) mmHg,(158 ± 20) mmHg,higher than that in summer periods ((145 ± 12) mmHg,(141 ± 9) mmHg;P＜ 0.05).Diastolic blood pressure(DPB) in RASI group and CCB group at winter periods were (101 ± 13)mmHg and (100±4)mmHg,significant high than that in summer periods ((93 ±7) mmHg,(90±7) mmHg;P＜0.05).8-OhdG levels in RASI group at summer and autumn periods were (243.20±30.94) ng/L and (240.40±47.99) ng/L,significantly higher than that in winter and spring periods((190.80± 15.56) ng/L and (189.06± 13.56) ng/L),and the differences were significant(P＜0.001).No significant differences were seen in CCB group among 4 seasons in terms of 8-OhdG levels (P ＞ 0.05).Conclusion Blood pressure change still occur among 4 seasons in hypertensive patients after a single CCB containing RASI-based drug antihypertensive therapy.And blood pressure in winter periods is higher than that in summer,which indicates that therapy medication based on RASI might reduce the level of oxidative stress at winter periods.

Static Magnetic Field Effect on Cardiovascular Regulation: A Review.

Mounting evidence suggests that environmental and occupational magnetic fields affect cardiovascular system. In this review, supported by original hemodynamic recordings - direct experimental evidence of the effect - static magnetic field (SMF) effects on arterial baroreflex cardiovascular control mechanism have been summarized. Local exposure of 120 - 350 mT SMF to sinocarotid baroreceptors in rabbits and healthy volunteers exerted a stimulatory effect on arterial baroreflex - normalized arterial blood pressure in hypertensive and hypotensive conditions, significantly increased microcirculation, heart rate variability, arterial baroreflex sensitivity and sodium nitroprusside (spontaneous nitric oxide donor) microcirculatory vasodilatory effect. The improvement of the vasodilator responsiveness to nitric oxide by baroreceptor stimulation suggested to be a new mechanism in baroreflex physiology with potential implementation in a spectrum of cardiovascular diseases where endothelial dysfunction and sympathovagal imbalance that results from a loss of baroreflex control over autonomic activity increases the risk of morbidity and mortality substantially. The modulation of the baroreflex-mediated autonomic cardiovascular control is a new concept for understanding environmental magnetic fields effect on cardiovascular system and an effective strategy to prevent their potential public health hazards.

Mibefradil reduces blood glucose concentration in db/db mice

OBJECTIVE: Numerous recent studies suggest that abnormal intracellular calcium concentration ([Ca2+]i) is a common defect in diabetic animal models and patients. Abnormal calcium handling is an important mechanism in the defective pancreatic β-cell function in type 2 diabetes. T-type Ca2+ channel antagonists lower blood glucose in type 2 diabetes, but the mechanism remains unknown. METHODS: We examined the effect of the Ca2+ channel antagonist mibefradil on blood glucose in male db/db mice and phenotypically normal heterozygous mice by intraperitoneal injection. RESULTS: Mibefradil (15 mg/kg, i.p., b.i.d.) caused a profound reduction of fasting blood glucose from 430.92±20.46 mg/dl to 285.20±5.74 mg/dl in three days. The hypoglycemic effect of mibefradil was reproduced by NNC 55-0396, a compound structurally similar to mibefradil but more selective for T-type Ca2+ channels, but not by the specific L-type Ca2+ channel blocker nicardipine. Mibefradil did not show such hypoglycemic effects in heterozygous animals. In addition, triglycerides, basal insulin and food intake were significantly decreased by mibefradil treatment in the db/db mice but not in the controls. Western blot analysis, immunohistochemistry and immunofluorescence staining showed a significantly increased expression of T-type Ca2+ channel α-subunits Cav3.1 and Cav3.2 in liver and brain tissues from db/db mice compared to those from heterozygous animals. CONCLUSIONS: Collectively, these results suggest that T-type Ca2+ channels are potential therapeutic targets for antidiabetic drugs. .

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, omega-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (I(Ca-N)) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by omega-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of I(Ca-N) which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension.

Bile Acid Inhibition of N-type Calcium Channel Currents from Sympathetic Ganglion Neurons

Under some pathological conditions as bile flow obstruction or liver diseases with the enterohepatic circulation being disrupted, regurgitation of bile acids into the systemic circulation occurs and the plasma level of bile acids increases. Bile acids in circulation may affect the nervous system. We examined this possibility by studying the effects of bile acids on gating of neuronal (N)-type Ca2+ channel that is essential for neurotransmitter release at synapses of the peripheral and central nervous system. N-type Ca2+ channel currents were recorded from bullfrog sympathetic neuron under a cell-attached mode using 100 mM Ba2+ as a charge carrier. Cholic acid (CA, 10(-6) M) that is relatively hydrophilic thus less cytotoxic was included in the pipette solution. CA suppressed the open probability of N-type Ca2+ channel, which appeared to be due to an increase in null (no activity) sweeps. For example, the proportion of null sweep in the presence of CA was ~40% at +40 mV as compared with ~8% in the control recorded without CA. Other single channel properties including slope conductance, single channel current amplitude, open and shut times were not significantly affected by CA being present. The results suggest that CA could modulate N-type Ca2+ channel gating at a concentration as low as 10(-6) M. Bile acids have been shown to activate nonselective cation conductance and depolarize the cell membrane. Under pathological conditions with increased circulating bile acids, CA suppression of N-type Ca2+ channel function may be beneficial against overexcitation of the synapses.

STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg

Highly efficient mechanisms regulate intracellular calcium (Ca2+) levels. The recent discovery of new components linking intracellular Ca2+ stores to plasma membrane Ca2+ entry channels has brought new insight into the understanding of Ca2+ homeostasis. Stromal interaction molecule 1 (STIM1) was identified as a Ca2+ sensor essential for Ca2+ store depletion-triggered Ca2+ influx. Orai1 was recognized as being an essential component for the Ca2+ release-activated Ca2+ (CRAC) channel. Together, these proteins participate in store-operated Ca2+ channel function. Defective regulation of intracellular Ca2+ is a hallmark of several diseases. In this review, we focus on Ca2+ regulation by the STIM1/Orai1 pathway and review evidence that implicates STIM1/Orai1 in several pathological conditions including cardiovascular and pulmonary diseases, among others.

The Influences of G Proteins, Ca2+, and K+ Channels on Electrical Field Stimulation in Cat Esophageal Smooth Muscle

NO released by myenteric neurons controls the off contraction induced by electrical field stimulation (EFS) in distal esophageal smooth muscle, but in the presence of nitric oxide synthase (NOS) inhibitor, L-NAME, contraction by EFS occurs at the same time. The authors investigated the intracellular signaling pathways related with G protein and ionic channel EFS-induced contraction using cat esophageal muscles. EFS-induced contractions were significantly suppressed by tetrodotoxin (1 micrometer) and atropine (1 micrometer). Furthermore, nimodipine inhibited both on and off contractions by EFS in a concentration dependent meaner. The characteristics of 'on' and 'off' contraction and the effects of G-proteins, phospholipase, and K+ channel on EFS-induced contraction in smooth muscle were also investigated. Pertussis toxin (PTX, a Gi inactivator) attenuated both EFS-induced contractions. Cholera toxin (CTX, Gs inactivator) also decreased the amplitudes of EFS-induced off and on contractions. However, phospholipase inhibitors did not affect these contractions. Pinacidil (a K+ channel opener) decreased these contractions, and tetraethylammonium (TEA, K+ Ca channel blocker) increased them. These results suggest that EFS-induced on and off contractions can be mediated by the activations Gi or Gs proteins, and that L-type Ca2+ channel may be activated by G-protein alpha subunits. Furthermore, K+ Ca-channel involve in the depolarization of esophageal smooth muscle. Further studies are required to characterize the physiological regulation of Ca2+ channel and to investigate the effects of other K+ channels on EFS-induced on and off contractions.

Drug inhibition of wear particles induced osteolysis in rabbits / 中国矫形外科杂志

[Objective]To study the possibility of drug inhibition of wear particle induced osteolysis and aseptic prosthesis loosening in vivo.[Methods]4?8 mm transverse holes were made in femur condyle and tibia plateau of 12 adult rabbits bilaterally.One milligram of CoCr alloy(mean 5.38 ?m),Ti-6Al-4V(mean 3.21 ?m) and UHMWPE(12～200 ?m) particles were implanted into the holes separately.The animals were divided into 4 groups and each group had the same particles combination.Oral drug therapy twice a day was adopted with non-selective COX inhibitor(indomethacin,0.5 mg/kg BW),membrane Ca2+ channel inhibitor(nitrendipine,0.1 mg/kg BW),osteoclast inhibitor(alendronate sodium,0.1mg/kg BW) and blank control(0.9% saline) to the 4 groups separately and randomly according to the double blind principle,which started on the 2nd day postoperatively until 12 weeks at the time of sacrifice.Routine histological observation and calculation of the ratio of bone area(BA) to total tissue area(TTA) were done under the computerized analysis system.[Results]CoCr and Ti alloy particles could seldom be seen in the slices of the groups which showed normal cancellous bone.There were obvious macrophage infiltration and fibroblast proliferation round the particulate UHMWPE in the group of blank controls.It was similar in the groups of indomethacin and nitrendipine though the histological reaction was a little bit weaker and osteotoid tissue could occasionally be seen.UHMWPE particles were totally enclosed in the cancellous bone with little fibrous tissue proliferation in the group of alendronate sodium and the BA/TTA ratio was significantly higher than those at the other groups(P0.05).[Conclusion]This indicates the possibility of inhibition or prevention of osteolysis induced by wear particles by drug therapy especially when alendronate sodium is adopted,and it has significant clinical implications for controlling the most common cause of implant failure.

VOCC and BKCa mRNA expression in kidney tissues of IgA nephropathy patients / 上海第二医科大学学报

0.05). ConclusionThe expression of VOCC mRNA and BKCa mRNA in kidney tissues of IgA nephropathy patients are abnormal.There is positive correlation between the abnormal expression of VOCC mRNA and BKCa mRNA and total glomerular pathological lesions integrals.The expression of VOCC mRNA and BKCa mRNA in kidney tissues of IgA nephropathy may serve as the indictor for the disease progression.

Protective Effects of Ginsenosides Rb_1 and Re on Injury of the Neonate Rat Cardiomyocyte Induced by Aconitine Alkaloids / 中国中医药信息杂志

Objective To investigate the protective effect of ginsenoside Rb1 and Re on injury of the neonate rat cardiomyocyte induced by aconitine alkaloids.Methods The influence of aconitine and ginsenoside Rb1,Re together in neonate rat cardiomyocyte was observed respectively.The influence of these components in neonate rat cardiomyocyte was examined by myocard zymogram.The expression of Ca2+ channel gene Cav1.2 mRNA of neonate rat cardiomyocyte after treatment was observed by RT-PCR.Results The ginsenoside Rb1 and Re were able to decrease the release of AST and LDH,reverse Cav1.2 mRNA abundance induced by aconitine.Conclusion The ginsenoside Rb1 and Re which together with aconitine can alleviate the side effects and boost up the therapeutic effects of aconitine.The action mechanism may be relation with that the ginsenoside Rb1 and Re can decrease injuries of the neonate rat cardiomyocytes and abundant expression of Cav1.2 mRNA induced by aconitine.

Toosendanin Modifies K~+-and Ca~(2+)-Channel Activity and Intracellular Ca~(2+) Concentration / 生物化学与生物物理进展

Usage of the fruit and bark of a Melia-family plant as a digestive tract-parasiticide and agricultural insecticide was recorded about two thousant years ago in ancient China. Toosendanin (TSN), a triterpenoid, is an effectual ingredient extracted from the plant. Studies have demonstrated that TSN selectively affects neurotransmitter release, effectively antagonizes botulism, induces cell differentiation and apoptosis and inhibits proliferation of various human cancer cells, inhibits feeding and dovelopment in insects and modifies K+- and Ca2+-channel activity. The research data to demonstrate that TSN inhibits K+-channel and facilitates L-type Ca2+-channel are summarized, and the mechanism of action of TSN is discussed.

Effects of pH on Vascular Tone in Rabbit Basilar Arteries

Effects of pH on vascular tone and L-type Ca2+ channels were investigated using Mulvany myograph and voltage-clamp technique in rabbit basilar arteries. In rabbitbasilar arteries, high K+ produced tonic contractions by 11+/-0.6 mN (mean+/-S.E., n=19). When extracellular pH (pHo) was changed from control 7.4 to 7.9 ([alkalosis]o), K+-induced contraction was increased to 128+/-2.1% of the control (n=13). However, K+-induced contraction was decreased to 73+/-1.3% of the control at pHo 6.8 ([acidosis]o, n=4). Histamine (10 micrometer) also produced tonic contraction by 11+/-0.6 mN (n=17), which was blocked by post-application of nicardipine (1 micrometer). [alkalosis]o and [acidosis]o increased or decreased histamine-induced contraction to 134+/-5.7% and 27+/-7.6% of the control (n=4, 6). Since high K+- and histamine-induced tonic contractions were affected by nicardipine and pHo, the effect of pHo on voltage-dependent L-type Ca2+ channel (VDCCL) was studied. VDCCL was modulated by pHo: the peak value of Ca2+ channel current (IBa) at a holding of 0 mV decreased in [acidosis]o by 41+/-8.8%, whereas that increased in [alkalosis]o by 35+/-2.1% (n=3). These results suggested that the external pH regulates vascular tone partly via the modulation of VDCC in rabbit basilar arteries.