Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration.

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

[Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics].

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics / 中国中药杂志

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Association between Iron Supplementation, Dietary Iron Intake and Risk of Moderate Preterm Birth: A Birth Cohort Study in China.

BACKGROUND: To evaluate the independent and collective effects of maternal iron supplementation and dietary iron intake upon the risk of moderate preterm birth and its subtypes. METHODS: In this birth cohort study, 1019 pregnant women with moderate preterm birth and 9160 women with term birth were recruited at Gansu Provincial Maternity and Child Care Hospital from 2010-2012 in China. Unconditional logistic regression models were utilized to evaluate the association between maternal iron supplementation, dietary iron intake, and the risk of moderate preterm birth and its subtypes. RESULTS: Compared with non-users, iron supplement users exerted a protective effect upon the overall (OR=0.54, 95%CI=0.40-0.72) and spontaneous moderate preterm birth (OR=0.39, 95%CI=0.33-0.83). Compared with the 25th quartiles of dietary iron intake, either before or during pregnancy, it exerted a significantly protective effect upon those who had the highest quartiles of dietary iron intake (OR=0.87, 95%CI=0.82-0.95 for the highest quartiles of dietary iron intake before pregnancy OR=0.85, 95%CI=0.79-0.91). Positive association was observed between the additive scale and multiplicative scale for preterm birth, spontaneous preterm rather than medically indicated preterm. CONCLUSION: Iron supplements (60 mg/day) and high-iron intake (>25.86 mg/day before pregnancy, >30.46 mg/day during pregnancy) reduced the risk of moderate preterm birth. Positive correlation is found between the additive scale and multiplicative scale for preterm birth, spontaneous preterm birth.

[Tapping at acupoints along meridian combined with thunder-fire moxibustion for upper-limb hemiplegia after stroke].

OBJECTIVE: To observe the effect of tapping at acupoints along meridian combined with thunder-fire moxibustion on upper-limb muscle strength and activities of daily living in patients with upper-limb hemiplegia after stroke. METHODS: A total of 140 patients with upper-limb hemiplegia after stroke were randomly divided into a combination group (35 cases, 2 cases dropped off), an acupoint-tapping group (35 cases), a moxibustion group (35 cases, 2 cases dropped off) and a routine group (35 cases). The patients in the routine group were only treated with routine treatment and nursing. On the basis of the treatment in the routine group, the patients in the acupoint-tapping group were treated with tapping along the large intestine meridian of hand yangming, with Hegu (LI 4), Shousanli (LI 10), Quchi (LI 11), Shouwuli (LI 13) and Jianyu (LI 15) as the key acupoints, once a day, 10 min each time; the patients in the moxibustion group were treated with thunder-fire moxibustion at the affected-side Shousanli (LI 10), Quchi (LI 11) and their surrounding area, once a day, 15 min each time. The patients in the combination group were treated with tapping at acupoints along meridian, followed by thunder-fire moxibustion. The treatment was 6 days a week for 4 weeks in the 4 groups. The body mass index of joint activity (shoulder abduction, elbow extension, wrist flexion) and Barthel index (BI) score were observed before and after treatment in the four groups. RESULTS: Compared before treatment, body mass indexs of shoulder abduction, elbow extension, wrist flexion as well as BI scores in the four groups were significantly increased after treatment (P<0.05). After treatment, the body mass indexs of joint activity in the combination group were higher than those in the other three groups (P<0.05). The BI scores in the acupoint-tapping group, the moxibustion group and the combination group were higher than those in the routine group (P<0.05). The BI score in the combination group was higher than the acupoint-tapping group and the moxibustion group (P<0.05). CONCLUSION: Tapping at acupoints along meridian combined with thunder-fire moxibustion could effectively improve the upper-limb muscle strength and activities of daily living in patients with upper-limb hemiplegia after stroke, and its effect is superior to simple tapping at acupoints along meridian or thunder-fire moxibustion.

An injectable, dual crosslinkable hybrid pectin methacrylate (PECMA)/gelatin methacryloyl (GelMA) hydrogel for skin hemostasis applications.

Biomaterials for effective hemorrhage control are urgently needed in clinics as uncontrolled bleeding is associated with high mortality. Herein, we developed an injectable and in situ photo-crosslinkable hybrid hemostatic hydrogel by combining pectin methacrylate (PECMA) and gelatin methacryloyl (GelMA). This modular material system combines ionic- and photo-crosslinking chemistries to design interpenetrating networks (IPN) exhibiting tunable rheology, highly porous structure, and controllable swelling and mechanical properties. By simply changing the calcium (0-15 mM) and polymer (1.5-7%) content used for the sequential crosslinking of hydrogels via calcium gelation and UV-photopolymerization, it was possible to precisely modulate the injectability, degradation, and swelling ratio. Moreover, it is demonstrated that PECMA/GelMA hydrogels present good cytocompatibility and uniquely synergize the hemostatic properties of calcium ions on PECMA, the amine residues on GelMA, and the highly porous network toward rapid blood absorption and fast coagulation effect. An in vitro porcine skin bleeding model confirmed that the hydrogel could be directly injected into the wound and rapidly photo-crosslinked, circumventing the bleeding and decreasing the coagulation time by 39%. Importantly, the crosslinked hydrogel could be easily removed to prevent secondary wound injury. Overall, this injectable hybrid PECMA/GelMA hydrogel stands as a promising hemostatic material.

ß­Ecdysterone promotes autophagy and inhibits apoptosis in osteoporotic rats.

Osteoporosis is an aging process of skeletal tissues with characteristics of reductions in bone mass and microarchitectural deterioration of bone tissue. The present study aimed to investigate the effects of glucocorticoid­induced osteoporosis on osteoblasts and to examine the roles of ß­ecdysterone (ß­Ecd) involved. In the present study, an in vivo model of osteoporosis was established through the subcutaneous implantation of prednisolone (PRED) into Sprague­Dawley rats, with or without a subcutaneous injection of ß­Ecd (5 or 10 mg/kg body weight). Expression of Beclin­1 and microtubule­associated protein 1A/1B­light chain 3I/II and apoptosis in lumbar vertebrae tissues was measured by immunofluorescence and TUNEL assays, respectively. Serum concentration of calcium and phosphorus, and the activity of tartrate­resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were measured by biochemical assay. Reverse transcription­quantitative polymerase chain reaction and western blotting was used for detect the expression of related genes and proteins. PRED treatment inhibited bone formation by decreasing bone mineral density, and suppressing the expression of Runt­related transcription factor 2 and bone morphogenetic protein 2, while enhancing the activity of alkaline phosphatase, upregulating the expression of receptor activator of nuclear factor-κB ligand, and increasing the serum content of calcium, phosphorus and tartrate­resistant acid phosphatase in rats. Additionally, PRED was revealed to inhibit autophagy through the downregulation of Beclin­1, autophagy protein 5 and microtubule­associated protein 1A/1B­light chain 3I/II expression, whereas it induced the apoptosis, through the activation of caspase­3 and the suppression of apoptosis regulator BCL2 expression. Notably, the PRED­induced alterations in bone formation, autophagy and apoptosis were revealed to be attenuated by ß­Ecd administration. In conclusion, the findings of the present study suggested that ß­Ecd may be a promising candidate for the development of therapeutic strategies for the treatment of osteoporosis, through the induction of autophagy and the inhibition of apoptosis in vivo.

1H NMR spectroscopy-guided isolation of new sucrose esters from Physalis alkekengi var. franchetii and their antibacterial activity.

Ten new sucrose esters, physakengoses A-J (1-10), were isolated from the aerial parts of Physalis alkekengi var. franchetii under the guidance of 1H NMR spectroscopy. Their structures were determined by spectroscopic analyses (HRESIMS, 1D and 2D NMR, and ESIMS) and chemical methods. These new compounds were tested for antibacterial activities against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli. Among them, compounds 2 and 5-8 showed potent inhibitory effects against test strains with MIC values ranging from 3.5 to 14.9µg/mL. These findings may indicate that the P. alkekengi var. franchetii has potential application as an ingredient in pharmaceuticals.

Folic acid supplementation, dietary folate intake and risk of preterm birth in China.

PURPOSE: Folic acid supplementation has been suggested to reduce the risk of preterm birth. However, results from previous epidemiologic studies have been inconclusive. We investigated the hypothesis that folic acid supplementation and dietary folate intake during pre- and post-conception reduces the risk of preterm birth. METHODS: We analyzed data from a birth cohort study conducted between 2010 and 2012 in Lanzhou, China, including 10,179 pregnant women with live singleton births. RESULTS: Compared to non-users, folic acid supplement users with >12-week duration had a reduced risk of preterm birth (OR 0.67, 95 % CI 0.55-0.83) with a significant dose-response relationship (P for trend = 0.01). A similar pattern was observed for spontaneous preterm birth. Stronger associations were seen for ever use of folic acid supplement and very preterm birth (OR 0.50, 95 % CI 0.36-0.69) and spontaneous very preterm birth (OR 0.42, 95 % CI 0.29-0.63). Dietary folate intake during preconception and pregnancy were also associated with reduced risk of preterm birth (OR 0.68, 95 % CI 0.56-0.83, OR 0.57, 95 % CI 0.47-0.70 for the highest quartiles, respectively), particularly for spontaneous very preterm (OR 0.41, 95 % CI 0.24-0.72, OR 0.26, 95 % CI 0.15-0.47 for the highest quartiles, respectively). There were also decreased risks of preterm birth observed per 10-µg increase in dietary folate intake, and similar associations were found after stratification by folic acid supplementation status. CONCLUSIONS: Our results suggest that folic acid supplementation and higher dietary folate intake during preconception and pregnancy reduces the risk of preterm birth, and the protective effect varies by preterm subtypes.

Single-pulsed electromagnetic field therapy increases osteogenic differentiation through Wnt signaling pathway and sclerostin downregulation.

Pulsed electromagnetic field (PEMF) therapy has been used for more than three decades to treat bone diseases. The main complaint about using PEMF is that it is time-consuming. Previously, we showed single-pulsed electromagnetic field (SPEMF) applied for 3 min daily increased osteogenic differentiation of mesenchymal stem cells and accelerated bone growth in a long bone defect model. In the current study, we investigated the mechanism of SPEMF to increase osteogenic differentiation in osteoblastic cells. We found that both short-term (SS) and long-term (SL) SPEMF treatment increased mineralization, while alkaline phosphatase (ALP) activity increased during the first 5 days of SPEMF treatment. SS treatment increased gene expression of Wnt1, Wnt3a, Wnt10b, Fzd9, ALP, and Bmp2. Also, SPEMF inhibited sclerostin after 5 days of treatment, and that inhibition was more significant with SL treatment. SL SPEMF increased expression of parathyroid hormone-related protein (PTHrP) but decreased expression of Sost gene, which encodes sclerostin. Together, the early osteogenic effect of SPEMF utilizes the canonical Wnt signaling pathway while the inhibitory effect of long-term SPEMF on sclerostin may be attributable to PTHrP upregulation. This study enhances our understanding of cellular mechanisms to support the previous finding and may provide new insight for clinical applications.

Antipyretic and anti-inflammatory activities of Thais luteostoma extracts and underlying mechanisms.

Thais luteostoma has been utilized as a crude drug whose shell and soft tissue have been widely used for the treatment of heat syndrome in China for thousands of years. The present study was designed to investigate the antipyretic and anti-inflammatory activities of T. luteostoma. T. luteostoma was divided into shell (TLSH) and soft tissue (TLST) samples in the present study. The rat model of yeast-induced fever was used to investigate their antipyretic effects; and the rat model of hind paw edema induced by carrageenan was utilized to study their anti-inflammatory activities, and at the same time, the concentration variations of the central neurotransmitter [prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP)], inflammatory mediators [tumor necrosis factor (TNFα), interleukin-1ß (IL-1), interleukin-2 (IL-2) and interleukin-6 (IL-6)] and ion (Na(+) and Ca(2+)) were also tested. The results showed that TLSH and TLST extracts significantly inhibited yeast-induced pyrexia in rats (P < 0.05), and exhibited more lasting effects as compared to aspirin, and TLSH had the better antipyretic activity than TLST, and that TLSH and TLST could significantly prevent against carrageenan induced paw edema in rats (P < 0.05); and markedly reduced levels of PGE2, cAMP, TNFα, IL-1ß, IL-2, IL-6, and Na(+)/Ca(2+). In fever model, TLST could significantly reduce the levels of PGE2 (P < 0.01) in rats' homogenate and TNFα (P < 0.05), IL-1ß (P < 0.01) in the plasma than TLSH, whereas TLSH could reduce the content of IL-2 (P < 0.01) and IL-6 (P < 0.01) in plasma and increase the content of Ca(2+) (P < 0.01) in plasma and homogenate more significantly than TLST. In conclusion, T. luteostoma extract has antipyretic and anti-inflammatory activities, which may be mediated through the suppression of production of PGE2, cAMP, Na(+)/Ca(2+), TNFα, IL-1ß, IL-2, and IL-6.

Anti-inflammatory effects of Gualou Guizhi decoction in transient focal cerebral ischemic brains. [Corrected].

The aim of the present study was to explore the neuroprotective effects of Gualou Guizhi decoction (GLGZD) in a rat model of middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were divided into three groups: Sham (no MCAO), MCAO (MCAO with no GLGZD treatment) and GLGZD (MCAO with GLGZD treatment). Rats in the MCAO and GLGZD groups were subjected to permanent occlusion of the left middle cerebral artery. Neurological function and infarct volume were measured. Microglial activation and inflammatory cell accumulation were measured using immunohistochemistry. mRNA and protein expression of inflammatory mediators were examined using reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The expression of proteins associated with the nuclear factor κ-B (NF-κB) inflammation signaling pathway was analyzed using western blotting. The results of the present study suggested that infarct size was significantly reduced and neurological behavior function was improved in rats with MCAO treated with GLGZD compared with rats in the MCAO group. Amoeboid microglial expansion and inflammatory cell migration were observed in the infarcted areas of rats in the GLGZD group and were not identified in those of the MCAO group. Target mRNA and protein levels, and inflammatory cell infiltration were significantly reduced in the GLGZD group compared with the MCAO model group. Notably, GLGZD treatment induced neuroprotective effects, reducing inflammation and inhibiting NF-κB signaling compared with the MCAO group. Therefore, GLGZD may exhibit anti-inflammatory effects against ischemia-reperfusion brain injury and may be a therapeutic target for ischemic stroke.

Effects of circuit residual volume salvage reinfusion on the postoperative clinical outcome for pediatric patients undergoing cardiac surgery.

This study aimed to evaluate the effects of washed cardiopulmonary (CPB) circuit residual blood reinfusion on the postoperative clinical outcome for pediatric patients undergoing cardiac surgery. A total of 309 consecutive Chinese cardiac patients receiving CPB between October 2010 and April 2011 were prospectively analyzed. For 217 patients, CPB circuit residual blood was reinfused after the cell-saving procedure [cell-salvage group (CS)]. The remaining 92 patients were directly transfused with allogenic red blood cells (RBCs) after their operation [control group (CON)]. Assessment included perioperative transfusion of RBCs, postoperative hematocrit (HCT), chest tube drainage during the first 24 h after the operation, intrahospital mortality, respiratory morbidity, and renal dysfunction. The two groups were well matched in terms of demographics, CPB data, and complexity of surgical procedure. The patients in the CS group had a significantly higher HCT level postoperatively (p = 0.018) and a less allogenic RBCs transfusion (p = 0.000). The two groups did not differ in terms of chest tube drainage during the first 24 h postoperatively, intrahospital mortality, or respiratory morbidity. The incidence of serum creatinine (≥ 2-folds) during the first 72 h after the operation was significantly lower in the CS group (2.3 %) than in the CON group (8.7 %) (p = 0.010). Reinfusion of washed CPB circuit residual blood significantly raised the postoperative HCT level, reduced the allogeneic blood transfusion, decreased the incidence of early postoperative renal dysfunction, and did not increase the chest tube drainage after the operation in pediatric cardiac surgery.

Subacute combined degeneration caused by nitrous oxide intoxication: case reports.

PURPOSE: Case reports with a comprehensive review of the current literature concerning subacute combined degeneration induced by nitrous oxide inhalation. A differential diagnosis should be considered when young patients present with progressive myelopathy because that the misuse of nitrous oxide has potentially serious outcomes. CASES REPORT: Three young patients aged from 18 to 24, one male and two females, were diagnosed with progressive ascending numbness in four limbs or both legs and ataxia. They all had been inhaling nitrous oxide from whipped-cream containers for several months. A cervicothoracic magnetic resonance imaging scan revealed long segmental hyperintensity changes at the posterior column of the spinal cord. Serological examination showed a low level of vitamin B12. Subacute combined degeneration of the spinal cord was diagnosed and the etiology was considered related to nitrous oxide misuse. Their neurological status, neuroimage, and neurophysiologic condition improved after vitamin B12 supplementation and cessation of nitrous oxide inhalation. CONCLUSION: Iatrogenic usage of nitrous oxide apparently resulted in subacute combined degeneration in our three patients. Recently, nitrous oxide misuse has increased among young people. Subacute combined degeneration of the spinal cord should be considered as a possible outcome of such abuse.

[Histochemical localization of ginsenosides in Gynostemma pentaphyllum and the content changes of total gypenosides].

The light microscopy technique, histochemistry and phytochemistry methods were applied in the study of the localization of gingsenosides in the vegetative organs in Gynostemma pentaphyllum, and the content of total gypenosides related to different growing periods, organs and genders. The results showed that ginsenosides distributed mainly in the assimilating tissue and phloem parenchyma cells, very little in collenchyma, epidermis and phelloderm, and no coloration in xylem and pith parenchyma. The accumulation of gingsenosides in the leaf occupied first place, the stem came second, and the root was the lowest. The content of total gypenosides showed a changing trend from low to high, then to low, during the whole growing period from vegetative growth to florescence and fructescence, and withering period. The content in leaf is higher than that in stem, and of male is higher than of female. It is suggested that harvest the above-ground parts only and remaining the rhizome and root in florescence and fructescence (Sept. to Oct.) is of benefit to both improving herbal quality and quantity, and accelerating the sustainable utilization for wild resources.

Pinacidil improves contractile function and intracellular calcium handling in isolated cardiac myocytes exposed to simulated cardioplegic arrest.

BACKGROUND: We examined the effects of pinacidil on contractile function and intracellular calcium in isolated rat cardiomyocytes exposed to cardioplegic solution. METHODS: Rat myocytes were incubated at 24 degrees C for 2 hours in cardioplegic solution with or without pinacidil (50 micromol/L), then they were perfused with Krebs-Henseleit solution with a gas phase of 95% O2/5% CO2 at the same temperature. Contraction and intracellular calcium transients were then measured by video tracking and spectrofluorometry. RESULTS: During 20 minutes of perfusion after 2 hours in cardioplegic solution with pinacidil, (1) the recovery of contractile function was significantly increased in terms of both amplitude of contraction (98.30% +/- 9.90% versus 81.00% +/- 11.25%; p < 0.05) and peak velocity of cell shortening (100.90% +/- 13.79% versus 76.89% +/- 18.14%; p < 0.01) when compared with myocytes in cardioplegic solution without pinacidil; (2) the amplitudes of the intracellular calcium transients evoked by electrical stimulation and caffeine (10 mmol/L) increased by 23.31% to approximately 40.72% and 61.73%, respectively, compared with those in cardioplegic solution without pinacidil; and (3) the decay time of the caffeine-induced intracellular calcium transient decreased by 36.64% +/- 15.10% relative to that measured in cardioplegic solution without pinacidil. The effects induced by supplementing the cardioplegic solution with pinacidil were diminished in the presence of glibenclamide (10 micromol/L). CONCLUSIONS: Addition of the adenosine triphosphate-sensitive potassium-channel opener, pinacidil, to a high potassium cardioplegic solution improves recovery of contractile properties and cytosolic calcium in isolated rat cardiac myocytes.

New lignans and cytotoxic constituents from Wikstroemia lanceolata.

Two new lignans, (-)-aptosimon ( 1) and (-)-diasesamin-di-gamma-lactone ( 2), together with twenty-two known compounds, have been isolated from the stems and roots of Wikstroemia lanceolata. The structures of the new compounds were determined through spectral analyses. The proton and carbon assignments of the known sesquiterpenoid, 1alpha,7alpha,10alpha H-guaia-4,11-dien-3-one ( 24) were revised by 2D NMR techniques. Among the isolates, three compounds, (+)-hinokinin ( 6), 2,6-dimethoxy- p-benzoquinone ( 17), and 1alpha,7alpha,10alpha H-guaia-4,11-dien-3-one ( 24) exhibited effective cytotoxicities (ED50 values < 4.0 microg mL-1) against P-388 and HT-29 tumor cell lines.