Maternal cardiac arrest: a retrospective analysis.

OBJECTIVES: To describe the characteristics and factors which may influence the maternal outcomes of maternal cardiac arrest (MCA). DESIGN: Retrospective analysis of cases. SETTING: China. POPULATION OR SAMPLE: A total of 61 MCA patients admitted or transferred to The Third Affiliated Hospital of Guangzhou Medical University from January 2000 to December 2019. METHODS: Clinical data for MCA were analysed retrospectively. The indicators included maternal age; BMI; gestational age; antenatal examination; income; MCA cause and place; cardiopulmonary resuscitation (CPR); mode of delivery; maternal prognosis; and neonatal outcome. MAIN OUTCOME MEASURES: The impact of case characteristics on maternal prognosis of MCA. RESULTS: The hospital received 61 patients with MCA, 36 of whom died (mortality 59.0%, 95% CI 46.3-71.7%). MCA was predominantly caused by treatable complications. Those who died were more likely to have collapsed in the ICU. CONCLUSIONS: Regular antenatal examination and early intervention can reduce the incidence of adverse pregnancy outcomes. The location of MCA occurred may be related to maternal prognosis. The leading causes of MCA were postpartum haemorrhage and amniotic fluid embolism. TWEETABLE ABSTRACT: A retrospective analysis describes the correlation between case characteristics of MCA and maternal outcomes.

[Efficacy of mitral valve repair versus replacement in severe ischemic mitral regurgitation].

Objective: To compare the mortality, survival rate and the therapeutic efficacy between mitral valve repair and replacement as treatment for severe ischemic mitral regurgitation (IMR), and explore the middle- and long-term outcomes. Methods: Between January 2000 and January 2016, 378 patients with severe IMR underwent coronary artery bypass grafting (CABG) combined with mitral valve repair (n=162) or mitral valve replacement (n=216) in the Department of Cardiovascular Surgery of Nanjing First Hospital. Clinical data, in-hospital morbidity and mortality of patients were retrospectively reviewed. The patients were followed up for the long term survival rate, heart function and re-admission. Results: No statistically significant differences of baseline data and operation details were found between the two groups except for left ventricular end-diastolic diameter[(61.3±10.2)mm in replacement group vs (56.2±9.0)mm in repair group, P<0.001]. Seven patients died during the perioperative period, with a total operation mortality of 1.9%.No significant difference of mortality was found between the two groups (5 cases in the replacement group and 2 cases in the repair group). The early outcome after the surgery showed that the rate of low cardiac output and ventricular arrhythmia of patients were significantly higher in the replacement group compared with the repair group (both P<0.05). The mortality of patients received mitral valve replacement was better than who received mitral valve repair when left ventricular end-diastolic diameter was over 65 mm (5.9% vs 10.0%, P=0.036). No significant differences were observed between the two groups in the middle- and -long term survival rate (87% for replacement group vs 85% for repair group, P=0.568). The follow-up time was 1-85 (52.8±21.5) months and the follow-up rate was 93%. The rate of valve-related complications was significantly higher in the repair group compared with the replacement group (8.82% vs 3.82%, P=0.003). Conclusions: We should choose the surgical methods carefully (replacement or repair) for severe IMR patients according to degree of left ventricular remodeling and pathological changes of mitral valve. Mitral valve replacement with preservation of the subvalvular apparatus is a safe and effective surgical alternative for mitral valve repair, especially for patients with complications or complex reflux.

Role of TLR4 for paclitaxel chemotherapy in human epithelial ovarian cancer cells.

BACKGROUND: Paclitaxel has been reported to be a ligand to Toll like receptor 4 (TLR4). Myeloid differentiation factor 88(MyD88) was described as a myeloid differentiation primary response gene. TLR4 signalling owns two pathways: MyD88-dependent and MyD88-independent pathways. XIAP is a key member of the inhibitor of apoptosis protein family. Akt is a major downstream target of growth factor receptor tyrosine kinases, which negatively regulates apoptotic pathways through phosphorylation (pAkt). The aim of the present study is to investigate the role of TLR4 in paclitaxel resistance of ovarian cancer cells. MATERIALS AND METHODS: We reconstructed the RNA interference expression vector, pGenesil-1-U6 specifically targeting TLR4 mRNA, which was stable transfected into the human ovarian cancer cell line SKOV3 (MyD88-positive expression) and A2780 (MyD88-negative expression). Cell proliferation, cell cycle distribution and cell apoptosis were assessed in the cells transfected with scramble control shRNA (SKOV3/shControl, A2780/shControl) and TLR4 shRNA (SKOV3/shTLR4, A2780/shTLR4) to explore the possible functions of TLR4 in ovarian cancer cells growth. The expression of TLR4, MyD88, XIAP, Akt and pAkt was analysed by Western blot analysis. RESULTS: A knockdown of TLR4 levels down-regulated the expression of XIAP and pAkt. And it restored the inhibitory effect of paclitaxel on cell proliferation and impeding cell cycle progression in SKOV3 cells. CONCLUSIONS: It suggests that TLR4 negatively regulates paclitaxel chemotherapy and MyD88 is an essential downstream factor to TLR4 signalling for this resistance. Knockdown of TLR4 induces paclitaxel chemosensitivity which might depress the Akt pathway. The TLR4-MyD88 signalling represents an important source to promote tumour growth.

A study of CCND1 with epithelial ovarian cancer cell proliferation and apoptosis.

OBJECTIVE: Ovarian cancer is a gynecological malignancy with high mortality rates all over the world. Markers for diagnosis, prognosis and therapy are urgently required to improve the mortality rates. As a key proto-oncogene, CCND1 is known to be amplified in many different carcinomas, including breast cancer, esophageal cancer, bladder cancer, endometrial cancer and ovarian cancer, etc. CCND1 plays an important role in cancer development and progression. However, its function and mechanism have not been completely elucidated in ovarian cancer. MATERIALS AND METHODS: In the present study, we use cisplatin in vitro to inhibit the cell proliferation and promote cell apoptosis in epithelial ovarian cancer cell line SKOV-3. CCND1 expression, cell proliferation and cell cycle analysis were carried out by real-time PCR, CCK-8 and flow cytometry respectively. RESULTS: Our results demonstrated that cisplatin could inhibit the expression of CCND1 in human epithelial ovarian cancer cell line, which is related to the decreased cell proliferation and increased cell apoptosis. CONCLUSIONS: This study demonstrated that CCND1 is a potential therapeutic target for epithelial ovarian cancer treatment.

Tumor recurrence and drug resistance properties of side population cells in high grade ovary cancer.

INTRODUCTION: The presence of subset of cancer stem cells (CSCs) called "Side population" (SP) cells has been identified in several solid tumors, responsible for treatment failure especially chemotherapy, and cancer relapse. The present study was aimed to isolate and characterize cancer stem like cells side population cells from high grade ovarian cancer. METHODS: The collected cancer samples were analyzed for presence of SP cells by FACS using Hoechst 33342 exclusion technique. Further the FACS sorted SP and non-SP cells were subjected to analysis of stem cell surface protein expression by western blot and immunocytochemistry, drug resistance and sphere formation assay. RESULTS: By FACS, we have identified 3.7% of cancer stem cell like side population cells in ovarian cancer whose prevalence was reduced to 0.5% upon treatment with verapamil an inhibitor of ABC transporter. Further, these sorted SP cells showed over expression of ABCG2 (ABC transporter), stem cell proteins such as CD144, CD44, EpCAM and antiapoptotic factor Bcl-2. Also the SP cells showed high resistance to chemotherapy drugs, have high survival rate and they are highly potential to form tumor spheres. CONCLUSION: Our data suggest that ovarian cancer contain small sub-population of side population cells which shares some characteristics of stem cells. The co-expression of ABC transporters and stem cells surface markers in SP cells may associate with resistance to chemotherapeutic agents, apoptosis and also supports a role for these cells in tumor recurrence, metastasis and invasion.

Underlying mechanism of 2-methoxyestradiol-induced apoptosis and growth arrest in SKOV3 human ovarian cancer cells.

OBJECTIVE: In this study, we sought to investigate the effects of 2-methoxyestradiol (2-ME) on cisplatin-induced apoptosis and growth inhibition in SKOV3 ovarian cancer cells. MATERIALS AND METHODS: Cells were treated with 2-ME, carboplatin, or both, the control group, and cell viability and growth inhibition assays were performed using the MTT method. Apoptosis was detected by flow cytometry analysis. Reverse transcription polymerase chain reaction and western blotting were used to monitor the mRNA and protein expression of the pro-apoptotic genes bax and caspase-3 and the anti-apoptotic gene bcl-2. The phosphorylation of Bcl-2 protein was monitored by western blotting. RESULTS: Cell viability was inhibited by all three treatments in a time-dependent manner. Importantly, the combination treatment resulted in significantly reduced cell growth compared with the other groups. The mRNA and protein expression of Bax and caspase-3 were increased in the combination treatment group, and the expression of Bcl-2 was decreased in the combination treatment group as compared with the other two groups. The ratio of bax to Bcl-2 mRNA in the combination treatment group was higher than that in the carboplatin-treated group. Finally, phosphorylation of Bcl-2 protein was increased stronger in the combination treatment group compared with the carboplatin-treated group. CONCLUSIONS: 2-ME promoted the growth inhibitory and apoptosis-inducing effects of platinum-based agents in SKOV3 ovarian cancer cells. The mechanism mediating this effect may be related to the phosphorylation of Bcl-2 protein, which reduces the formation of dimers and, thereby, increases apoptosis. Moreover, 2-ME promoted the mRNA and protein expression of Bax, thereby, increasing the Bax/Bcl-2 expression ratio and activating the mitochondrial apoptosis pathway.

6-0-butanoylcastanospermine (MDL 28,574) inhibits glycoprotein processing and the growth of HIVs.

The antiviral activity of 6-0-butanoylcastanospermine (MDL 28,574) [50% inhibitory concentration (IC50: 1.1 microM)] in JM cells infected with a recent isolate of HIV-1 (GB8), was compared with other inhibitors of glycoprotein-processing enzymes. N-butyldeoxynojirimycin (BuDNJ), deoxynojirimycin (DNJ), castanospermine (CAST) or the reverse transcriptase inhibitor 2'3'-dideoxycytidine (ddC) had activities of 56, 560, 29 and 0.1 microM, respectively. MDL 28,574 was at least 50 times more active than BuDNJ and less active but better tolerated in cell culture than ddC, two compounds currently undergoing clinical trials. The CAST derivative showed good protection in H9 cells infected with HIV-1 (RF; IIIB; U455), and HIV-2 (ROD), although the potency was less than that seen in the JM/GB8 system. HIV-1 glycoproteins, gp160 and gp120, synthesized in H9 cells chronically infected with HIV-1 (RF) and treated with MDL 28,574, were characterized by an increase in relative molecular weight of approximately 7-8000 kD. The ratio of gp120 to gp160 was markedly reduced in treated cells and provided further evidence that cleavage of the gp160 precursor molecule is a major consequence of the inhibition of glycoprotein processing. The intracellular target for MDL 28,574 was verified as alpha-glucosidase-I of the processing enzymes by the analysis of high-glucose glycopeptides recovered from treated mouse cells. This activity correlated with the antiviral effect observed against the growth of a mouse retrovirus, Moloney murine leukemia virus (MOLV), in mouse cells.

Na(+)-dependent Ca2+ influx in bovine adrenal chromaffin cells.

Bovine adrenal chromaffin cells were loaded with Na+ via either acetylcholine receptor-associated ion channels or voltage-sensitive Na+ channels. There were increases in [Ca2+]i, 45Ca2+ uptake and catecholamine secretion in both types of Na(+)-loaded cells relative to control cells in which Na+ loading had been prevented by hexamethonium and tetrodotoxin, respectively. These results show the presence of Na(+)-dependent Ca2+ influx activity in chromaffin cells which is probably mediated by the reverse mode of a Na+/Ca2+ exchanger.

Cyclic urea nucleosides. Cytidine deaminase activity as a function of aglycon ring size.

Five beta-D-ribofuranosyl cyclic urea nucleosides (14-18), ranging in ring size from five to eight membered, were synthesized and evaluated as cytidine deaminase (CDA) inhibitors. The precursor protected nucleosides (9-13) were prepared by a condensation procedure utilizing persilylated ureas with a halo sugar under the specific catalytic activity of a HgO/HgBr2 mixture which provided exclusively the beta-anomers. Catalytic hydrogenation of known 1-(2,3,5-tri-O-benzoyl-beta-ribofuranosyl)-1,2-dihydropyrimidin-2-one (19) afforded nucleoside 10 identical with that obtained by the mercury-catalyzed condensation procedure. CDA activity varies significantly with the ring size of the urea aglycon the reaches its maximum level for the seven-membered analogues 16 and 17. The unexpected high potency of nucleoside 17 (Ki = 2.5 X 10(-8) M, human liver enzyme) is reported. This compound represents the most potent inhibitor of human liver CDA yet discovered.

Antitumor properties of 2(1H)-pyrimidinone riboside (zebularine) and its fluorinated analogues.

2(1H)-Pyrimidinone riboside (zebularine, 1b) and its 5-fluoro (6b) and 2'-ara-fluoro (7b) analogues have been synthesized and evaluated in vivo as antitumor agents. Zebularine provides increase in life span (ILS) values of ca. 70% against intraperitoneal (ip) murine B16 melanoma and 50% against P388 leukemia. This compound is active when administered either ip or orally against ip or subcutaneously implanted L1210 leukemia, producing ILS values of about 100% at an optimum dose of 400 mg/kg. 1b is also active (60% ILS) against ara-C-resistant L1210. The analogous unsubstituted purine riboside nebularine (2) has modest activity against P388 leukemia (60% ILS). While 2'-ara-fluorozebularine (7b) is only marginally active (40% ILS) at high doses against L1210 leukemia, 5-fluoro analogue 6b is more active than zebularine and is ca. 100 times more potent. Although the activity of 6b is about the same as that of 1b against P388 leukemia, greater potency also is realized in this model. Zebularine is a strong inhibitor of cytidine deaminase, but in contrast to tetrahydrouridine, 1b is acid-stable. In an attempt to use this property to advantage in oral administration, 1b and ara-C have been orally coadministered to mice with ip L1210 leukemia. When zebularine is given in divided doses, up to a 2-fold increase in activity is realized, relative to treatment with the same dose of ara-C alone.

Castanospermine-glucosides as selective disaccharidase inhibitors.

Castanospermine (CS) is a potent but non-selective inhibitor of many glycohydrolases including the intestinal disaccharidases. Several CS-glucosides were synthesized to investigate the effect of an attached glucopyranosyl residue on the potency and selectivity of CS toward inhibition of intestinal disaccharidases. 8 alpha-glucosyl-CS and 7 alpha-glucosyl-CS were nearly as potent against sucrase activity as CS (IC50 values = 30, 40, and 20 nM respectively) but were 1/50 or less as potent as CS against lactase and trehalase activities. 8 beta-glucosyl-CS was 1/20 to 1/140 as potent as CS and 1 alpha-glucosyl-CS was 1/57 to 1/1500 as potent as CS against disaccharidase activities. 1 alpha-glc-CS was less selective than CS, whereas the other CS-glucosides were more selective. 7 alpha-glc-CS and 8 alpha-glc-CS were the most sucrase selective and were particularly ineffective against trehalase and lactase activities. 8 beta-glc-CS was similar to CS except for relatively weaker trehalase inhibition. In summary, selectivity toward certain disaccharidases was achieved by glucosylation of CS hydroxyls. However, a simple structural comparison of the CS-glucoside to a disaccharide substrate did not reliably predict which disaccharidase would be more inhibited by the CS-glucoside.

Dehydroepiandrosterone sulfate (DHEAS) suppresses P2X purinoceptor-coupled responses in PC12 cells.

Some steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels in addition to their well-known genomic effects via intracellular steroid receptors. Such effects were found in GABA receptor, nicotinic receptors, yet not investigated in P2X purinoceptors. In this study, the effects of dehydroepiandrosterone sulfate on the P2 purinoceptor was investigated. Results show that dehydroepiandrosterone sulfate acutely inhibits P2X purinoceptor functions in PC12 cells. Dehydroepiandrosterone sulfate suppressed ATP-induced cytosolic free calcium concentration ([Ca(2+)](i)) rise, cytosolic free sodium concentration ([Na(+)](i)) rise, and dopamine secretion in the presence of external calcium, but had no effect on ATP-induced [Ca(2+)](i) rise in the absence of external calcium or on UTP-induced [Ca(2+)](i) rise in the absence or presence of external calcium. Our data show that dehydroepiandrosterone sulfate exerted its effect on P2X, but not on the P2Y purinoceptors found in PC12 cells. Estradiol and estrone have similar effects on P2X purinoceptor, but dehydroepiandrosterone and progesterone do not.

Inhibition of glycoprotein processing and HIV replication by castanospermine analogues.

Inhibitors of glycoprotein processing enzymes have been shown to have activity against HIV. Several analogues of the known glucosidase I inhibitor, castanospermine (CAST), were synthesized and evaluated for their inhibitory effect on glucosidases and for antiviral activity against Moloney murine leukemia virus (MOLV) and HIV-1. The most effective analogue was 6-O-butanoyl CAST (B-CAST, MDL 28,574) with an IC50 of 0.05 micrograms/mL against MOLV. A correlation between inhibition of glucosidase I and MOLV replication was observed. This analogue was further evaluated against HIV-induced syncytial formation in HeLa T4+ cells and against productive infection in JM cells infected with HIV 1 (GB8 strain). B-CAST showed an IC50 of 0.3 micrograms/mL in the HeLa T4+ assay, compared to CAST at 11 micrograms/mL. The compound also was more potent (IC50:0.15 micrograms/mL) than CAST (4-6 micrograms/mL) in JM cells. The antiretroviral activity of B-CAST was further confirmed in Friend leukemia virus (FLV) infection in mice. B-CAST showed equivalent activity to AZT and was more potent than CAST in inhibiting FLV-induced splenomegaly in mice. The data presented herein suggest the potential of these novel glucosidase inhibitors as anti-HIV agents.

Effects of caffeine on Ca2+ fluxes and secretion in bovine chromaffin cells.

The effects of caffeine on Ca2+ fluxes and catecholamine secretion in bovine adrenal chromaffin cells were examined. Caffeine inhibited secretion. 45Ca2+ uptake and cytosolic Ca2+ concentration ([Ca2+]i) rise induced by the nicotinic receptor agonist 1.1-dimethyl- 4-phenylpiperazinium (DMPP) and the Na+ channel activator veratridine. The inhibitory effect of caffeine on high K(+)-induced secretion was smaller than that on DMPP- and veratridine-induced responses. Caffeine only slightly inhibited high K(+)-induced 45Ca2+ uptake and did not affect [Ca2+]i rise. Caffeine also inhibited muscarinic receptor-mediated inositol phosphate generation. Our results suggest that the inhibitory effects of caffeine on bovine chromaffin cells mainly occur at both muscarinic and nicotinic receptors as well as at the voltage-dependent Na+ channels and to a smaller extent at site(s) distal to Ca2+ entry. The effects of caffeine on nicotinic receptors but not on muscarinic receptors can be explained by its ability to raise intracellular cAMP.

Dehydroepiandrosterone sulfate inhibition of catecholamine secretion from bovine adrenal chromaffin cells.

Dehydroepiandrosterone sulfate (DHEAS) dose-dependently inhibited [3H]norepinephrine (NE) secretion and the corresponding [Ca2+]i rise induced by the nicotinic receptor agonist 1,1-dimethyl-4-phenylpoperazimium (DMPP) in bovine chromaffin cells. DHEAS at 10 microM, the physiological concentration in human serum, significantly inhibited both the release of [3H]NE and the rise of [Ca2+]i induced by DMPP in chromaffin cells. DHEAS also inhibited the [3H]NE release induced by the Na+ channel activator veratridine. However, DHEAS did not affect either the [3H]NE release, or the corresponding [Ca2+]i rise induced by high K+. Moreover, DHEAS suppressed the [Na+]i rise induced by either DMPP or high K+ as monitored by the fluorescence 340/380 ratio of SBFI loaded chromaffin cells. Our results suggest that the inhibitory effects of DHEAS on secretion mainly occur at nicotinic receptors as well as at the voltage-dependent Na+ channels.

The distribution patterns of trace elements in the brain and erythrocytes in a rat experimental model of iodine deficiency.

Cretinism is a disease characterized by neurological defects associated with severe iodine deficiency. In a rat model of severe iodine deficiency, we investigated the distribution pattern of trace elements (iodine [I], selenium [Se], and bromine [Br] in brain tissue samples; potassium [K], calcium [Ca], manganese [Mn], iron [Fe], copper [Cu], zinc [Zn], rubidium [Rb], and lead [Pb] in erythrocytes) after supplementing the rats with I and/or Se. Neutron activation analysis, proton induced x-ray emission and x-ray fluorescence were used. The serum levels of total and free thyroxine (T4, FT4), and of total, free, and reverse triiodothyronine (T3, FT3, rT3, respectively) were assessed by radioimmunoassay. The results were statistically evaluated by one-way analysis of variance and bivariate correlation. The study indicated that the levels of T4, FT4, and rT3 increased in the serum of iodine-deficient rats supplemented with I or I + Se. In the same animals, we documented alterations of the content of Br in the brain, and of Zn, Mn, Cu, and Rb in erythrocytes, whereas the brain content of I and Se was unchanged. Thus, I and I + Se supplementation improves thyroid hormone metabolism but affects the content of selected trace elements in erythrocytes and of Br in the brain. The data stimulate further clarification of the role of trace elements in the central nervous system.

Biphasic effects of chromium compounds on catecholamine secretion from bovine adrenal medullary cells.

CrO3 was found to affect norepinephrine release in a biphasic manner: at concentrations above 100 microM, it inhibited, while at concentrations below 10 microM, it enhanced DMPP- and high K+-induced [3H]norepinephrine (NE) release from bovine adrenal medullary cells. Similar effects were found for K2Cr2O7. CrO3 inhibited the 45Ca2+ uptake induced by DMPP and high K+, suggesting that the voltage-gated Ca2+ channels are possible sites of the inhibitory action of CrO3. CrCl3, possessing a trivalent state in contrast to the hexavalent states of CrO3, K2Cr2O7, inhibited DMPP-induced [3H] release and inhibited, to a lesser extent, high K+-induced [3H]-NE release, suggesting that nicotinic receptors are also possible sites of Cr3+ action. In medullary cells permeabilized with digitonin, both CrO3 and CrCl3 induced [3H]-NE release from cells preloaded with [3H]-NE. In intact cells, CrO3 but not CrCl3 enhanced secretagogue-induced [3H]-NE release and entered into the cells as demonstrated by fluorescence quenching experiments. These results suggest that chromium compounds can induce catecholamine secretion after entering the cytoplasm. The enhancement of norepinephrine release induced by chromium ions appears to be due to interference with the intracellular functions of Ca2+ in the cytoplasm.

Organophosphates inhibit catecholamine secretion and calcium influx in bovine adrenal chromaffin cells.

The lethality of organophosphorous compounds has been attributed to their inhibitory effect on acetylcholinesterase (AChE) in the nervous system. However, subacute exposure of humans to organophosphates induces cognitive and emotional defects which might not solely be attributable to AChE inhibition. Therefore we investigated the toxic effects of methyl parathion and malathion on bovine adrenal chromaffin cells. Catecholamine secretion and 45Ca2+ uptake evoked by either a nicotinic agonist (DMPP) or high [K+] were inhibited by methyl parathion and malathion. The [Ca2+]i rise induced by DMPP was inhibited by both compounds. We conclude that in addition to AChE, voltage-gated Ca2+ channels and nicotinic receptors are possible sites of action of organophosphates in mammalian systems.

Castanospermine blocks the hyperglycemic response to carbohydrates in vivo: a result of intestinal disaccharidase inhibition.

Castanospermine is a potent inhibitor of rat intestinal glycohydrolases in vitro and prevents the hyperglycemic response to an oral sucrose challenge in vivo. Among the glycohydrolases tested, castanospermine was most effective against sucrase with an IC50 of 1.1 x 10(-7) M. In vivo, a significant effect was seen at doses less than 1 mg/kg in both normal and streptozotocin-treated rats. Castanospermine has a prolonged duration of activity in vivo with significant activity when administered 4 hours before sucrose.

Statistical pattern classification with binary variables.

Binary random variables are regarded as random vectors in a binary-field (modulo-2) linear vector space. A characteristic function is defined and related results derived using this formulation. Minimax estimation of probability distributions using an entropy criterion is investigated, which leads to an A-distribution and bilinear discriminant functions. Nonparametric classification approaches using Hamming distances and their asymptotic properties are discussed. Experimental results are presented.