A new phenanthrene with a spirolactone ring from Dendrobium ochreatum.

Dendroochreatene (1), a new phenanthrene derivative with a spirolactone ring, was isolated from the whole Dendrobium ochreatum plant together with 11 known compounds (2-12). The structure of the new compound was elucidated spectroscopically and phenolic compounds were firstly reported from D. ochreatum. Moscatilin (4), major compound isolated from D. ochreatum, was found to be cytotoxic toward H460 lung-cancer cells, with an IC50 value of 147.3 ± 0.9 µM, while loddigesiinol C (7), C-α-methoxy derivative was inactive.

Spirolactone-type and enmein-type derivatives as potential anti-cancer agents derived from oridonin.

Natural products (NPs) are always the important sources in the field of drug discovery, among which spirolactone-type and enmein-type compounds exhibit a wide range of biological activities, especially anti-tumor activity. Based on previous studies, the spirolactone-type and enmein-type compounds could be derived from natural oridonin (1) by several chemical reactions. Herein, a series of novel spirolactone-type and enmein-type derivatives with different aryl allyl ester substitutions at their C-14 hydroxyl group were designed and synthesized. The anti-tumor activity results showed that most of the compounds exhibited better anti-proliferative activities than parent compound oridonin, and the most potent compound had an IC50 value of 0.40 µM in K562 cells. Further mechanistic studies revealed that the optimal compound could arrest K562 cells at G2/M phase by inhibiting cdc-2, cdc-25c and cyclin B1 expression. In addition, the optimal compound induced apoptosis in K562 cells through increasing ROS production and depolarizing mitochondrial membrane potential. Collectively, these valuable results suggested that the most potent compound could be an anti-tumor agent candidate and is worthy of further investigation.

Highly Efficient and Mild Gold (I) Catalyzed Synthesis of 3,8-Diarylidene-2,7-dioxaspiro[4.4]nonane-1,6-diones.

The gold-catalyzed cyclization of 2,2-bis(3-arylprop-2-yn1-yl)malonic acid has been proposed as an efficient approach to substituted 3,8-dibenzyl-2,7-dioxaspiro[4.4]nonane-1,6-diones. The reaction proceeds smoothly in mild reaction conditions to give the desired products in quantitative yields in the presence of variously substituted starting materials. In addition, the synthesis of γ-arylidene spirobislactone bearing different substituents on the two aromatic rings has been achieved. This kind of compound could be of great interest in pharmaceutical science given the widespread presence of this scaffold in bioactive natural and synthetic products.

Antioxidant spiropharanone, an undescribed variant of trans-decalin spiro-γ-lactone, from pharaoh cuttlefish Sepia pharaonis: Twin inhibitors of inflammatory 5-lipoxygenase and serine protease dipeptidyl peptidase-4.

Marine pharaoh cuttlefish Sepia pharaonis (family Sepiidae) is regarded as an economically important class of cephalopod in the coastal Mediterranean and Asian regions. Bioassay-guided chromatographic purification of solvent extract of S. pharaonis led to the identification of a trans-decalin based spirolactone, spiropharanone, which was characterized as 1-hydroxy-7-(4'-methoxy-3-methylbut-2-enyl)-3,9,15-trimethyl-8-oxo-octahydro-5H-spiro[furan-8,9-naphtho]-8-yl-acetate by spectroscopic techniques. Spiropharanone exhibited significantly greater anti-inflammatory activity by attenuating pro-inflammatory 5-lipoxygenase (IC50 1.02 mM) than the non-steroidal drug ibuprofen (IC50 4.61 mM, p ≤ .05). Superior antioxidant properties of spiropharanone against free radicals (EC50 ~1.20 mM) and other oxidants (hydroxyl [EC50 0.97 mM] and superoxide [EC50 1.47 mM] scavenging) also reinforced its promising anti-inflammatory activity. The studied spiropharanone also exhibited significant attenuation toward insulin secretion regulating enzyme dipeptidyl peptidase-4 (IC50 0.92 mM) recognizing its anti-hyperglycemic potential. Significantly higher electronic properties (topological polar surface area ~100) combined with balanced hydrophilic-lipophilic properties (partition coefficient of logarithmic octanol-water ~3) and lesser docking parameters of spiropharanone demonstrated that the compound could be utilized as an important bioactive lead against oxidative stress, inflammation, and hyperglycemic-related ailments. PRACTICAL APPLICATIONS: Nutritionally rich edible marine pharaoh cuttlefish Sepia pharaonis occupies a prominent place among seafood fisheries owing to the presence of bioactive nutrients and functional food ingredients. These marine cuttlefish are widely distributed along the Asian and Mediterranean coasts, and consumed as culinary delicacy for decades. An undescribed trans-decalin spirolactone, spiropharanone was isolated from the organic extract of S. pharaonis based on bioactivity-assisted sequential chromatographic fractionation. Spiropharanone displayed promising antioxidant potential along with attenuation properties against inducible pro-inflammatory 5-lipoxygenase and insulin secretion regulating enzyme dipeptidyl peptidase-4. This study established the ameliorating potential of a naturally derived marine food constituent against inflammatory and diabetic ailments, and thus anticipated as functional food lead in pharmaceutical formulations towards inflammation and maintaining glucose homeostasis.

Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime.

BACKGROUND: A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks. METHODS: Three European and American multicenter clinical trials have been conducted in more than 2500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9%) had a risk factor for VTE, while in the European studies, 261 patients (16.6%) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. RESULTS: No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed. CONCLUSIONS: The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors. TRIAL REGISTRATION: EudraCT registration numbers: 2010-021787-15 & 2011-002396-42 . Clincaltrials.gov: NCT02269241 .

Oestrogen-free oral contraception with a 4 mg drospirenone-only pill: new data and a review of the literature.

Purpose: The contraceptive pill is an effective and safe method of preventing pregnancy. The progestins used for contraception either are components of a combined hormonal contraceptive (tablets, patches or vaginal rings) or are used alone in progestin-only formulations. Progestin-only contraceptives are available as daily oral preparations, subcutaneous or intramuscular injectables (every 1-3 months), subdermal implants (every 3-5 years) and intrauterine systems (every 3-5 years). Long-acting progestins are highly effective in typical use and have a very low risk profile and few contraindications.Material and Methods: A new progestin-only, oestrogen-free contraceptive, drospirenone, in a dosage of 4 mg/day in a 24/4 regimen, has received regulatory approval in the USA and the EU. The molecule has antigonadotropic, antimineralocorticoid, antiestrogenic and antiandrogenic properties.Results: The regimen was chosen to improve the bleeding profile; maintain plasma oestradiol levels at those of the early follicular phase, to avoid hypoestrogenism; and preserve efficacy even with a missed pill, as drospirenone has a half-life of 30-34 h.Conclusions: Clinical studies have shown good efficacy, very low cardiovascular side effects and a favourable bleeding pattern, as well as maintenance of ovulation inhibition after scheduled 24 h delays in pill intake.

[Effectiveness of spirolactone on the treatment of laryngeal edema and complications after H-uvulopalatopharyngoplasty for patients with obstructive sleep apnea].

Objective:To determine whether taking spirolactone orally after H-UPPP may relieve laryngeal edema and complications for patients with obstructive sleep apnea（OSA）. Method:Fifty patients with OSA to undergo H-UPPP operation were randomly divided equally to the intervention group（taking spirolactone 20 mg orally twice a day for 7 days after H-UPPP） or the control group, all patients received conventional therapy after H-UPPP including anti-infection, hemostatic treatment, fluid replacement and expectorant by fogged absorption. The pharyngeal wound, diet, sleep and speaking pronunciation of all patients in each group were evaluated every other day in 7 days postoperation. The minimum oxygen saturation of blood（SaO2） during sleep at night each day and the period needed for staphyledema resolution of all patients were recorded and compared between each group. Result:Postoperatively, the intervention group had significantly slighter bleeding at wound site, better sleep and more legible speaking pronunciation than the control group after 3 days to 5 days（P<0.05）. The wound dehiscence of the intervention group was significantly slighter than the control group within 7 days after operation（P<0.05）. During 3 days to 7days after operation, the intervention group had a significantly better diet than the control group（P<0.05）. The average minimum SaO2during sleep at night in the intervention group was significantly higher than that in the control group from 3 days to 5 days post operation（P<0.05）. Period needed for staphyledema resolution in the intervention group（4.1±1.5） days was significantly shorter than that in the control group（5.9±1.8） days （P<0.05）. Conclusion:Taking spirolactone orally after H-UPPP may relieve laryngeal edema and complications for OSA patients, and it will also shorten the period needed for staphyledema resolution.

Inhibition of melanin production and promotion of collagen production by the extract of Kuji amber.

Kuji amber is fossilized tree resin of the Late Cretaceous in Japan. In this study, new biological activities of ethanol extract of Kuji amber (EtOH ext.) and supercritical carbon dioxide fluid extract of Kuji amber (scCO2 ext.) were examined. Both EtOH ext. and scCO2 ext. inhibited melanin production in B16 mouse melanoma cells and promoted collagen production in human skin fibroblast SF-TY cells. The scCO2 ext. had more potent activity than that of EtOH ext. and may depend on the efficiency of the extraction. The main new biologically active compound in Kuji amber, kujigamberol had no activities against melanin production, however, it promoted collagen production at low concentrations. A biologically active compound having a different structure, spirolactone norditerpenoid, showed both the inhibition activity against melanin production and the promotion activity of collagen production in a dose dependent manner. EtOH ext. and scCO2 ext., which include both kujigamberol and spirolactone norditerpenoid, have not only anti-allergy activity, but also inhibit melanin production and promote collagen production.

Cyclosporin population pharmacokinetics in pediatric refractory nephrotic syndrome based on real-world studies: Effects of body weight and spirolactone administration.

Different models of population pharmacokinetics (PPK) of cyclosporin have been established in various populations. However, the cyclosporin PPK model in patients with pediatric refractory nephrotic syndrome (PRNS) has yet to be constructed. The present study aimed to establish the cyclosporin PPK model in PRNS, and to identify factors that may account for any variability. Chinese patients with PRNS treated with cyclosporin between June 2014 and June 2018 at the Children's Hospital of Fudan University (Shanghai, China) were retrospectively analyzed. The impact of demographic features, laboratory parameters and concomitant medications was evaluated. A total of 18 PRNS patients from real-world studies were analyzed by non-linear mixed-effects modeling. A one-compartment model with first-order absorption and elimination was selected as the appropriate model in PRNS. Body weight (WT) and spirolactone intake were included as significant covariates for the apparent oral clearance (CL/F), and the WT was revealed to significantly influence the apparent volume of distribution (V/F). The final covariate models were as follows: CL/F=80.7 × (WT/70)0.75 × (1-0.265×θspirolactone), and V/F=2,030 × (WT/70), where θspirolactone is the coefficient of spirolactone. The inter-individual variability in CL/F and V/F was 44.6 and 53.1%, respectively. In conclusion, in the present study, a cyclosporin PPK model for patients with PRNS was successfully constructed, and the presence of a clinically significant interaction between spirolactone and cyclosporin in PRNS patients was determined based on real-world studies, indicating that concomitant medication with spirolactone was able to reduce cyclosporin clearance in the patients with PRNS.

Synthesis, bioactivity and mode of action of 5A 5B 6C tricyclic spirolactones as novel antiviral lead compounds.

BACKGROUND: Plant viral diseases cause tremendous decreases in yield and quality. Natural polycyclic compounds such as those containing carbocycles are often very important lead compounds for drug and pesticide development. Tricyclic spiranoid lactones with 5A 5B 6C -ring fusion topologies possess various bioactivities. In this study, 33 new 5A 5B 6C tricyclic spirolactones were rationally designed, synthesized, characterized and evaluated for antiviral activities. RESULT: These compounds showed no apparent toxicity against Italian honeybees up to 2.73 µg bee-1 . Spirolactones 14, 16, 19, 23 and 28 at a concentration of 100 µg mL-1 inactivated 90% of tobacco mosaic virus (TMV) infection, making these compounds much more potent than the positive controls. Significantly, compound 19 displayed the best inactivation activity causing inhibition of up to 98%. CONCLUSION: The results of the bioassays and QSAR studies indicated that the carbon-containing cyclic moiety was the antiviral pharmacophore, and derivative 19, which showed the best inactivation activity, could emerge as a potential antiviral agent against TMV. In vitro capsid protein (CP) assembly and TMV assembly inhibition determinations indicated that these compounds induced crosslinking in the TMV and prevented its uncoating, which was a putative new mode of action for TMV inactivation. © 2018 Society of Chemical Industry.

Bioactive Natural Spirolactone-Type 6,7-seco-ent-Kaurane Diterpenoids and Synthetic Derivatives.

Diterpenoids are widely distributed natural products and have caused considerable interest because of their unique skeletons and antibacterial and antitumor activities and so on. In light of recent discoveries, ent-kaurane diterpenoids, which exhibit a wide variety of biological activities, such as anticancer and anti-inflammatory activities, pose enormous potential to serve as a promising candidate for drug development. Among them, spirolactone-type 6,7-seco-ent-kaurane diterpenoids, with interesting molecular skeleton, complex oxidation patterns, and bond formation, exhibit attractive activities. Furthermore, spirolactone-type diterpenoids have many modifiable sites, which allows for linking to various substituents, suitable for further medicinal study. Hence, some structurally modified derivatives with improved cytotoxicity activities are also achieved. In this review, natural bioactive spirolactone-type diterpenoids and their synthetic derivatives were summarized.

Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in vitro synergistic anticancer activity as apoptosis inducer.

Herein, we reported the cytotoxicity, NO-releasing property, and apoptosis induced ability of two series of novel nitric oxide-releasing spirolactone-type diterpenoid derivatives (10a-f and 15a-f). All the title compounds were more potent than oridonin (7) and parent compound (9 or 14) against human tumor Bel-7402, K562, MGC-803 and CaEs-17 cells. SARs were concluded based on above data. Compound 15d exhibited the strongest antiproliferative activity with the IC50 of 0.86, 1.74, 1.16 and 3.75µM, respectively, and could produce high level (above 25µM) of NO at the time point of 60min. Further mechanism evaluation showed that 15d could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations in Bel-7402 cells via mitochondria-related pathways. It was expected that the remarkable biological profile of the synthetic NO-releasing spirolactone-type diterpenoid analogs make them possible as promising candidates for the development of anticancer agents.

A new approach towards the synthesis of drospirenone and steroidal spirolactones.

A general methodology for the synthesis of different steroidal 17-spirolactones is described. This method uses lithium acetylide of ethyl propiolate as the three carbon synthon and the method was successfully applied for the process development of drospirenone.

Comparison of the chemistry and diversity of endophytes isolated from wild-harvested and greenhouse-cultivated yerba mansa (Anemopsis californica).

With this study, we explored the identity and chemistry of fungal endophytes from the roots of yerba mansa [Anemopsis californica (Nutt.) Hook. & Arn. (Saururaceae)], a botanical traditionally used to treat infection. We compared the diversity of fungal endophytes isolated from a wild-harvested A. californica population, and those from plants cultivated for one year in a greenhouse environment. The wild-harvested population yielded thirteen fungal strains (eleven unique genotypes). Of the extracts prepared from these fungi, four inhibited growth of Staphylococcus aureus by >25% at 20 µg/mL, and three inhibited growth of Pseudomonas aeruginosa by ≥20% at 200 µg/mL. By comparison, A. californica roots after one year of cultivation in the greenhouse produced only two unique genotypes, neither of which displayed significant antimicrobial activity. The fungus Chaetomium cupreum isolated from wild-harvested A. californica yielded a new antimicrobial spirolactone, chaetocuprum (1). An additional fourteen known compounds were identified using LC-MS dereplication of the various fungal endophytes. This study provides new insights into the identity and chemistry of A. californica fungal endophytes, and demonstrates the importance of considering growing conditions when pursuing natural product drug discovery from endophytic fungi.

Molecular structure, vibrational and 13C NMR spectra of two ent-kaurenes spirolactone type diterpenoids rabdosinate and rabdosin B: a combined experimental and density functional methods.

The title compounds, rabdosinate and rabdosin B, were isolated from the leaves of Isodon japonica, and characterized by IR-NMR spectroscopy. The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO-13C) chemical shift values of the title compounds have been calculated by using DFT/B3LYP method with 6-311++G(d,p) basis set. In addition, obtained results were related to the linear regression of experimental 13C NMR chemical shifts values. The integral equation formalism polarized continuum model (IEFPCM) was used in treating chloroform solvation effects on optimized structural parameters and 13C chemical shifts. Besides, molecular electrostatic potential (MEP), HOMO-LUMO analysis were performed by the B3LYP method.

Effect of spirolactone on cardiac function and serum brain natriuretic peptide in patients with chronic heart failure / 中国综合临床

Objective To investigate the effect of spirolactone on cardiac function and serum brain natriuretic peptide in patients with chronic heart failure( CHF). Methods Eighty-four patients with CHF were randomly divided into control group( n=42 )and observation group( n=42 ). The patients in the control group were given conventional therapy,while in the observation group were given spirolactone( 20 mg/times,2 times/day)based on treatment of the control group for six months. The clinical effects and left ventricular end diastolic diameter( LVEDd ),left ventricular ejection fraction( LVEF ) and serum brain natriuretic peptide( BNP ) of pretherapy and post-treatment between the two groups were recorded and compared. Results The total effective rate of observation group was 95. 2%(40/42),obviously higher than that of control group(80. 9%(34/42),χ2=6. 468,P=0. 028). The levels of LVEDd and BNP in two groups after treatment were(57. 8 ± 6. 2)mm and (62. 4 ± 7. 8)mm,(364. 4 ± 32. 8)ng/L and(457. 4 ± 43. 2)ng/L,significantly lower than those at before treatment((64. 6 ± 7. 4)mm and(64. 8 ± 7. 6)mm,(867. 8 ± 78. 5)ng/L and(864. 4 ± 74. 8)ng/L),while LVEF in two groups after treatment were( 49. 8 ± 5. 4 )% and( 42. 6 ± 4. 6 )%,significantly higher than those before treatment((35. 2 ± 3. 9)% and(35. 4 ± 3. 5)%),and the differences were significant(t = -3. 264, 4. 626,-5. 373,-3. 932,5. 438,-6. 548;P﹤0. 05). Moreover the changes in observation group were obvious than those in control group in terms of LVEDd,BNP and LVEF( t = -3. 425,3. 644,-2. 846;P ﹤0. 05 ) . Conclusion Spironolactone can effectively decrease the serum brain natriuretic peptide levels,improve the cardiac function in patients with chronic heart failure,and it is worthy of popularization and application.

Protective effect of spirolactone on kidney damage in rats after amputation and its mechanism / 解放军医学杂志

Objective To explore the protective effect and its possible mechanism of spirolactone against kidney injury in rats after amputation. Methods Forty-two male Wistar rats were randomly divided into 6 groups: normal control, 6 hours, 24 hours, 48 hours, 72 hours after the operation and spirolactone intervention groups (n=7, each). Plasma angiotensin Ⅱ (Ang Ⅱ), aldosterone (ALD), myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6 (IL-6), nitric oxide (NO), urea nitrogen (Ur), creatinine (Cr) concentration and renal tissue ALD, MPO, MDA and calcineurin (CaN) mRNA levels were determined. Renal pathological changes were observed by light microscopy. Results At 6h after amputation, traumatic changes in rat kidney tissue were seen, and the levels of Cr, AngⅡ, MDA, MPO, IL-6 and CaN-mRNA were significantly elevated, while NO concentration was significantly lowered. Spirolactone intervention reduced the damage of kidney tissue, and the levels of MPO, IL-6, Ang Ⅱ in plasman, contents of MPO and ALD and expression level of CaN mRNA in kidney tissue were significantly lowered, but the levels of Cr, Ur, MDA and ALD in plasma and content of MDA in kidney tissue showed no significant change. Conclusion Spirolactone can provide protective effect against renal damage in rats after amputation, and it may be related to the mechanism that spirolactone inhibits secretion of ALD and lowers the expression and activation of CaN mRNA, thus reducing the release of pro-inflammatory factors.

Effect of aldosterone receptor antagonist on obesity-related glomerulonephropathy / 中华肾脏病杂志

Objective To examine whether aldosterone contribute to obesity related glomerular disease. Methods C57BL/6J mice were randomly divided into three groups: a control group (low?fat?diet, n=10), a model group (high?fat?diet, n=10) and a intervention group (high?fat?diet, n=12). After 8 weeks intervention group were treated with a mineralocorticoid receptor antagonist, spirolactone (SPL).The physicochemical indexes and the renal pathology of the three groups were all detected. The mRNA and protein expressions of podocyte marker protein were determined by real?time PCR and Western blotting, respectively. Results Compared with the control group, body weight, kidney weight, Lee ’s index, fat index, blood cholesterol, blood triglyceride, creatinine clearance rate, urinary protein excretion, glomerular average diameter, glomerular foot process average width were significantly up ? regulated (P<0.05); The mRNA and protein expression of nephrin, podocin, podoplanin and podocalyxin were significantly down?regulated in model group (P<0.05). Meanwhile, these changes were attenuated by SPL. Conclusion Aldosterone can participate in the process of obesity? related renal injury, and these can be attenuated by mineralocorticoid receptor antagonist, spirolactone. This gives us preliminary clues to treat ORG.

Hiperpotassemia na vigência de espironolactona em pacientes com insuficiência cardíaca descompensada / Hyperkalemia during spironolactone use in patients with decompensated heart failure

FUNDAMENTO: A incidência de hiperpotassemia relacionada à espironolactona é baixa na insuficiência cardíaca estável, entretanto não foi estudada durante a descompensação. OBJETIVO: Avaliar a influência da espironolactona na insuficiência cardíaca descompensada sobre o potássio sérico. MÉTODOS: Em um estudo de coorte, selecionamos pacientes hospitalizados por descompensação da insuficiência cardíaca, FEVE < 0,45 e potássio sérico entre 3,5 e 5,5 mEq/l. Os pacientes foram divididos segundo o uso da espironolactona (grupo E) ou não (grupo C). O desfecho foi aumento do potássio (> 6,0 mEq/l) e uso de poliestireno de cálcio. Realizou-se a análise multivariada pela regressão logística, e p < 0,05 foi considerado significante. RESULTADOS: Foram estudados 186 pacientes (grupo E: 56; grupo C: 130), FEVE 0,25, idade 55,5 anos e 65,2 por cento de homens. A incidência de hiperpotassemia foi de 10,7 por cento no grupo E e de 5,4 por cento no grupo C (p = 0,862). A análise multivariada mostrou que a uréia sérica > 60,5 mg/dl, durante a internação, apresenta risco relativo de 9,6 (IC 95 por cento 8,03 - 11,20; p = 0,005) para a ocorrência de hiperpotassemia. CONCLUSÃO: A incidência de hiperpotassemia foi duas vezes maior com espironolactona, mas não estatisticamente significante. Elevação da uréia foi associada à hiperpotassemia. Estudos randomizados são necessários para esclarecer o assunto.

BACKGROUND: The incidence of hyperkalemia related to spironolactone use is low in stable heart failure; however, it has not been studied during decompensation. OBJECTIVE: To evaluate the influence of spironolactone on serum potassium in decompensated heart failure (HF). METHODS: In a cohort study, patients that had been hospitalized due to decompensated HF, with left ventricular ejection fraction (LVEF) < 0.45 and serum potassium between 3.5 and 5.5 mEq/l were selected. The patients were divided according to spironolactone use (Group S) or no use (Group C). The outcome was potassium increase (> 6.0 mEq/l) and the use of calcium polystyrene. A multivariate analysis through logistic regression was carried out and values of p < 0.05 were considered significant. RESULTS: A total of 186 patients (group S: 56; group C: 130) were studied; LVEF of 0.25, aged 55.5 years and 65.2 percent of them males. The incidence of hyperkalemia was 10.7 percent in group S and 5.4 percent in group C (p = 0.862). The multivariate analysis showed that serum urea > 60.5 mg/dl during the hospitalization presents a relative risk of 9.6 (95 percentCI 8.03 - 11.20; p = 0.005) for the occurrence of hyperkalemia. CONCLUSION: The incidence of hyperkalemia was two-fold higher with spironolactone use, but it was not statistically significant. The increase in urea levels was associated to the hyperkalemia. Randomized studies are necessary to clarify this issue.

Flavonoids and spiro-lactones from Hypericum hookerianum / 中草药

Objective To study the chemical constituents in plants of Hypericum hookerianum and their activities by pharmacological experiment. Methods Cytotoxicity screening of the extracts from H. hookerianum were carried to isolate and purify the chemical constituents. The chemical structures were (identified) by physicochemical properties and spectral data analysis. Results Seven compounds were isola-(ted) and (established) as quercetin (Ⅰ), luteolin (Ⅱ), apigenin (Ⅲ), hyperin (Ⅳ), astragalin (Ⅴ), hyper-(olactone) A (Ⅵ), and hyperolactone C (Ⅶ). Conclusion All the compounds are isolated from H. hookerianum for the first time. Compounds Ⅲ and Ⅴ are isolated from the plants of Hypericum Linn. for the first time. In addition, the fractions by chlorform and ethylacete extracting, quercetin, and luteolin possess the cytotoxicity.