Studies on the acetogenins of Formosan annonaceous plants. II. Cytotoxic acetogenins from Annona reticulata

Using cytotoxicity as a guide to fractionation, one novel acetogenin, annoreticuin-9-one [3], and four known cytotoxic acetogenins, squamone [4], solamin [5], annomonicin [6] and rolliniastatin 2 [7], were isolated from active extracts of the leaves of the Formosan plant Annona reticulata. Their structures were elucidated on the basis of uv, ir, 1H- and 13C-nmr, and ms data of the natural compounds and their derivatives.     

Anti-platelet aggregation constituents from Formosan Toddalia asiatica

Examination on the wood of Formosan Toddalia asiatica led to the isolation of 30 compounds, including coumarins, alkaloids, a benzoquinone and an amine. Among the isolates, (+/-)-toddanin and (-)-isocoreximine are new compounds, while cyclohexylamine was isolated for the first time from nature. The structures of the compounds were elucidated from spectroscopic data and chemical evidence. Bioassay-guided fractionation led to the isolation of seven compounds showing strong anti-platelet aggregation activity in vitro.     

Cytotoxic isoflavans from Eysenhardtia polystachya

Two new cytotoxic isoflavans, (3S)-7-hydroxy-2',3',4',5', 8-pentamethoxyisoflavan (1) and (3S)-3',7-dihydroxy-2',4',5', 8-tetramethoxyisoflavan (2), were isolated from the bark and trunks of Eysenhardtia polystachya (Leguminosae), together with the known constituents stigmasterol, isoduartin, cuneatin, 7-hydroxy-2',4', 5'-trimethoxyisoflavone, and 3,4-dimethoxy-8, 9-(methylenedioxy)pterocarpan. The structures of 1 and 2 were elucidated on the basis of spectroscopic methods. The antimicrobial, cytotoxic, and insecticidal potential of some of these compounds were evaluated. The isoflavans 1, 2, and isoduartin (2', 7-dihydroxy-3',4',8-trimethoxyisoflavan) displayed moderate cytotoxic activity against KB cell lines.     

Insect-control chemicals from plants. III. Toxic lignans from Libocedrus bidwillii

Feeding tests showed that the powdered dried leaves and leaf extracts of L. bidwilli are toxic to the larvae of the housefly (Musca domestica), and the codling moth (Laspeyresia pomonella). The powdered material was not toxic to the light-brown apple moth (Epiphyas postvittana). The most active toxin is the lignan beta-peltatin-A methyl ether (II) and at a concentration of 100 ppm in a chemically defined diet it gave 98% mortality of housefly larvae.     

Cytotoxic sesquiterpene lactones from Inula britannica

Cytotoxicity-guided fractionation of the flowers of Inula britannica led to the isolation of four sesquiterpene lactones, 4 alpha, 6 alpha-dihydroxyeudesman-8 beta, 12-olide (1), ergolide (2), 8-epi-helenalin (3), and bigelovin (4). Compound 1 was isolated as a new natural product. These compounds showed cytotoxicity against human tumor cell lines.     

Novel cytotoxic diterpenes, excavatolides A-E, isolated from the Formosan gorgonian Briareum excavatum

The chemistry of Briareum excavatum, a Formosan gorgonian coral, was investigated. This study has led to the isolation of five novel marine natural products, excavatolides A-E (1-5), together with brianolide (6). The structures of the above compounds were established by spectral and chemical methods. The relative configuration of excavatolide B (2) was further confirmed by a single-crystal X-ray structure analysis. Cytotoxicity of these compounds toward various cancer cell lines also is described.     

Cytotoxic and antiparasitic activity from Annona senegalensis seeds

Several extracts of Annona senegalensis (Annonaceae) seeds were tested for antiparasitic activity against Leishmania major, Leishmania donovani, Trypanosoma brucei brucei, and for cytotoxic activity against KB and VERO cell lines. Fractionation of seeds extracts was mainly guided by means of a biocidal assay against Artemia salina nauplii. The biological activities resulted from extract-isolated acetogenins.     

Cytotoxic and antitumour principles from Ixora coccinea flowers

Susceptibility of four major rat tissues to oxidative damage in terms of lipid peroxidation induced by in vitro by ascorbate-Fe2+ in homogenates and mitochondria has been examined. Lipid peroxidation, as assessed by thiobarbituric acid reactive substances (TBARS) and conjugated dienes was maximum in brain followed by liver, kidney and heart. However, the time course of lipid peroxidation showed different patterns in tissues examined. The higher susceptibilities of brain and liver can be explained by substrate availability and to a lesser extent the level of antioxidants. The differences observed in the tissues studied may reflect their susceptibility to degenerative diseases and xenobiotic toxicity which are considered as a result of oxidative damage to membranes.     

Cytotoxic and leishmanicidal aminoglycosteroids and aminosteroids from Holarrhena curtisii

The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.     

Cytotoxic scalarane sesterterpenes from a sponge, Hyrtios erecta

PURPOSE: Claimed clinical advantages of the locking-head mandibular reconstruction plating system include the ability to achieve stability with fewer numbers of screws per bony segment as compared with conventional screws. The purpose of this study was to test the hypothesis that increased resistance to displacement will be obtained when using locking-head as compared with the same number of conventional screws per segment in both fracture and reconstruction models. MATERIALS AND METHODS: Eight groups were tested based on the screw number (two or four), screw type (locking-head or conventional), and fracture (bony apposition) or reconstruction model (1-cm defect). Two-dimensional beam mechanics using adult bovine ribs and the Instron machine were used to develop a load-displacement curve up to 150 N for each specimen. An osteotomy was then created and the segments were reduced, with preload (fracture model) or with a 1-cm defect (reconstruction model), and plated using the Synthes locking-head plate with either two or four bicortical locking-head (4.0-mm) or conventional (2.7-mm) screws per segment. The fixed ribs were loaded to 150 N, and the displacement was recorded. RESULTS: Locking-head screws provided superior resistance when using two screws per segment in the reconstruction model as compared with conventional screws. Minimal difference was seen between other screw types within a model. The fracture model offered significantly greater (3.1 to 3.7X) resistance to displacement than did the reconstruction model. CONCLUSIONS: Locking-head screws provided significantly increased resistance to displacement when only two screws per segment were used in the reconstruction model. When four screws per segment were used, there was no significant difference between locking-head and conventional screw types in either model. The effect of bony buttressing is significant and may explain why miniplates often fail in the atrophic mandible but are successful in the fully dentate patient.     

Cytotoxic 2,3-secoaromadendrane-type sesquiterpenoids from the liverwort Plagiochila ovalifolia

The ether extract of the Japanese liverwort, Plagiochila ovalifolia Mitt. (Plagiochilaceae) yielded three 2,3-secoaromadendrane-type sesquiterpenoids, plagiochiline-A-15-yl octanoate, 14-hydroxyplagiochiline-A-15-yl 2E,4E-dodecadienoate and 14-hydroxyplagiochiline-A-15-yl 2E,4E,8Z-tetradecatrienoate. The two latter compounds were first isolated from the Plagiochila species. The structures of the new compounds were elucidated by spectroscopy. Plagiochiline-A-15-yl octanoate and 14-hydroxyplagiochiline-A-15-yl 2E,4E-dodecadienoate showed significant cytotoxicity against P-388 murine leukemia tumor cells, both compounds exhibiting an ID50 of 0.05 microgram/ml. Plagiochiline A also showed cytotoxic activity. The ID50 was 3.0 micrograms/ml.     

Cytotoxic and ichthyotoxic compounds from marine Opisthobranchia and soft coral

Epidural analgesia in labour using local anaesthetics is very efficient, but the technique has been associated with undesired motor block and an increased use of instrumental deliveries. A new epidural analgesia technique, using a combination of low-dose local anaesthetics and opioids (fentanyl and sufentanil), has recently come into practice. The new epidural technique provides excellent analgesia, minimises motor block, allows the mother to ambulate, and minimises the need for instrumental delivery. Furthermore, it constitutes a good alternative to parenteral pethidine. We are of the opinion that all pregnant women should be given detailed information about both the benefits and the possible side-effects of epidural analgesia in good time before they go into labour. This will allow them to participate more actively in deciding whether or not to use analgesia during labour. Optimal use of epidural analgesia not only depends on the availability of a 24-hour anaesthesia service, but also on adequate knowledge and the cooperation and enthusiasm of all those involved, namely midwives, obstetricians and anaesthesiologists.     

Flavonoids and lignans from Virola surinamensis twigs and their in vitro activity against Trypanosoma cruzi

A 26-year-old woman developed marked increases in levels of aminotransferases about 24 hours after ingestion of 70 mL of 50% cresol. Responding to supportive measures, the patient recovered without any significant complications. Cresol and/or its metabolite may have caused transient hepato-cellular injury in this patient. In cresol poisoning, hepato-cellular injury can manifest even after a 24-hour asymptomatic period.     

Cytotoxic therapy in systemic lupus erythematosus. Experience from a single center

The present survey of cytotoxic therapy from a single large lupus clinic has shown that approximately 33% of the patients have received cytotoxic therapy at some point in their course. These agents were initiated for a variety of manifestations, with renal manifestations being the major indication, accounting for 28.2% of the cytotoxic agents used. Other common indications for initiation of cytotoxic therapy included steroid sparing (18.4%), global flare (12.5%), neurologic manifestations (11.4%), and musculoskeletal (8.6%). Azathioprine, methotrexate, and cyclophosphamide accounted for 98% of all cytotoxic agents used. Azathioprine was the most frequently used cytotoxic drug (70%), followed by methotrexate (21.5%) and cyclophosphamide (9.4%). Cytotoxic agents were used sequentially in 12.5% of patients and in combination in 4.2% of the patients. Overall, the use of cytotoxic therapy appears to be beneficial in reducing global disease activity, as the mean SLEDAI fell by 2.59 (33%) over 6 months of cytotoxic therapy, and the mean steroid dose was reduced by 37% over the same time period. There was also an improvement in most organ-specific indications with the use of cytotoxic agents. Overall the cytotoxic agents were well tolerated, with 17% of the courses being discontinued due to a side effect. Cytopenia was the most common side effect necessitating discontinuation of cytotoxic agents.     

Cytotoxic effect against HeLa cells of polysaccharides from the lichen Ramalina celastri

The most active polysaccharides which show anti-tumoral activity are (1-->3)-beta-D-glucans, branched or not at O-6. Since these structures are sometimes poorly soluble in aqueous media, alpha-D-glucans and their chemical derivatives, which are more soluble, were also studied. The present object is to observe morphological alterations in HeLa cells caused by two different polysaccharides obtained from the lichen Ramalina celastri, which are (1-->3),(1-->4)-linked alpha-D-glucan and its sulphated derivative. The cells were incubated in Eagle's medium in the absence or presence of each polysaccharide and routinely processed and analysed by light and electron microscopy. Even though the alpha-D-glucan altered the cellular volume, cytoplasmic densities, and mitosis, the resulting monolayer was similar to the control. TEM analysis showed cytoplasmic blebbing and the presence of an amorphous electron-dense material free in the cytoplasm and interior membranes. The enhanced injury caused by the sulphated derivative was apparent, altering cell adhesion and causing cell aggregation. Nuclear modifications such as fragmentation and condensation of chromatin under the nuclear envelope, which showed to be convoluted, suggested the occurrence of cell death by apoptosis.     

Cytotoxic activity of platelets and peripheral blood mononuclear cells from oncology patients and healthy donors

Testicular germ cell tumour is said to be a model for curable neoplasm. However, the prognosis of primary extragonadal germ cell tumour does not appear to be as promising. Though similar in histology, the biology of primary extragonadal germ cell tumour is different as exemplified by the patients in this review. Eight patients with primary mediastinal germ cell tumours were treated with intensive cisplatin-based chemotherapy. All, except one, had non-seminomatous components. The poor prognosis of mediastinal germ cell tumour is due to a combination of poor treatment results with the cisplatin-based regimen and the development of non-germ cell and haematological malignancies.     

The influence of flaxseed and lignans on colon carcinogenesis and beta-glucuronidase activity

Two grazing trials were conducted to determine the ruminally degradable protein requirement of gestating beef cows in the last half of pregnancy grazing winter native Sandhills range. In Trial 1, 80 crossbred cows (522 +/- 9 kg) were assigned randomly to one of the following ruminally degradable protein (RDP) treatments: 50%, 75%, 100%, or 125% of the estimated supplemental requirement. In Trial 2, 80 crossbred cows (529 +/- 8 kg) were assigned to 29%, 65%, 100%, or 139% of the estimated supplemental RDP requirement. In Trial 1, daily gain and condition score (CS) were not different (P > .15) among treatments. In Trial 2, gain responded quadratically, being higher (P = .14) for the 65% level than for the 29%, 100%, and 139% levels (.18, .05, .06, and .01 kg/d, respectively). Condition score was maintained at 65% and lost at 29%, 100%, and 139% (cubic effect, P = .06; 0, -.2, -.4, -.3, respectively). In both experiments, forage intake did not differ among treatments although OM digestibility increased linearly (P = .08) in Trial 1 with increasing level of RDP but not in Trial 2. Diet samples were collected in both experiments to estimate total nutrient intake. Forage RDP intake was 322 g/d in Trial 1 and 279 g/d in Trial 2. We conclude that gestating beef cows grazing native winter Sandhills range need between 62 and 140 g/d of supplemental RDP to meet their daily requirement of 340 to 430 g/d or 7.1% of the digestible OM.