Structures and cytotoxicity relationship of isoaaptamine and aaptamine derivatives.

A series of 9-O-acylisoaaptamine (3-14) and 4-N-acyl-dihydroaaptamine (16-19) derivatives have been prepared and evaluated for antitumor activity against murine P-388 and human tumor cells including KB16, A549, and HT-29 cell lines. All of compounds showed significant cytotoxicity against P-388 cells. Among them, compounds 9-11 showed potent activity as isoaaptamine (1). There was an apparent lack of linear relationship between cytotoxicity and carbon number of the side chain. The structure and activity relationship for these particular compounds are discussed.     

Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura

Two new dihydrochalcones, 2',4'-dihydroxy-3'-methoxydihydrochalcone, (-)-3'-methoxy-2',4',beta-trihydroxydihydrochalcone, a new flavanone, (2 S)-(-)-5'-hydroxy-7,3',4'-trimethoxyflavanone, and a new flavonol derivative, muntingone, along with sixteen known compounds, were isolated from the leaves of Muntingia calabura. The structures of these new compounds were determined using spectral analyses including extensive 2D NMR data. Among the isolates, (2 S)-5'-hydroxy-7,3',4'-trimethoxyflavanone, 4'-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, and 2',4'-dihydroxy-3'-methoxychalcone exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.     

A cytotoxic lobane diterpene from the formosan soft coral Sinularia inelegans

A new cytotoxic lobane diterpene, ineleganene (1), was isolated from the Formosan soft coral Sinularia inelegans. The structure of compound 1 was determined by 1D and 2D spectral analysis.     

MAGNOLOL REDUCES INFARCT SIZE AND SUPPRESSES VENTRICULAR ARRHYTHMIA IN RATS SUBJECTED TO CORONARY LIGATION

1. Magnolol is an active component of Magnolia officinalis. It is 1000-times more potent than α-tocopherol in inhibiting lipid peroxidation in rat heart mitochondira. In the present study, the in vivo antiarrhythmic and anti-ischaemic effects of magnolol in coronary ligated rats were investigated. 2. Male Sprague-Dawley rats were anaesthetized with urethane. Magnolol, at dosages of 10^?7, 10^?8 and 10^?9 g/kg, was adminstered intravenously 15 min before ligation of the coronary artery. 3. The incidence and duration of ventricular tachycardia and ventricular fibrillation during 30 min coronary ligation were significantly reduced by magnolol. Ventricular arrhythmias during 10 min reperfusion after the relief of coronary ligation were also reduced. 4. In rats subjected to 4h coronary ligation, 10^?7 and 10^?8 g/kg magnolol significantly reduced infarct size. 5. We conclude that magnolol may protect the myocardium against ischaemic injury and suppress ventricular arrhythmia during ischaemia and reperfusion.     

A cytotoxic butenolide,two new dolabellane diterpenoids,a chroman and a benzoquinol derivative formosan Casearia membranacea

Investigation of a cytotoxic chloroform-soluble fraction of the stem of Casearia membranacea (Flacourtiaceae) led to the isolation of five new compounds, including one butenolide, casealactone (1), one chroman, caseamemin (2), two dolabellane diterpenoids, casearimene A (3) and casearimene B (4), one benzoquinol ether, casearinone (5), together with fifteen known compounds, including two amides, N- trans-feruloyltyramine (6) and N- cis-feruloyltyramine (7), six steroids, beta-sitosterol (8), stigmast-5-ene-3beta,7alpha-diol (9), stigmast-5-ene-3beta,7beta-diol (10), stigmastane-3beta,5alpha,6beta-triol (11), beta-sitostenone (12), beta-sitosterol 3- O-beta-glucoside (13), two triterpenoids, squalene (14) and friedelin (15), one lignan, (+/-)-syringaresinol (16), two benzenoids, syringaldehyde (17) and vanillic acid (18), one ester, methyl hexadecanoate (19), and anthraquinone (20), respectively. Among these isolates, 1 showed cytotoxicity against P-388 and HT-29 cancer cell lines in vitro, and 6 and 7 showed cytotoxicity against the P-388 cancer cell line. The structures of these compounds were determined by means of spectroscopic techniques, and the structure of 3 was confirmed by X-ray crystallographic analysis.     

Hepatoprotection of Graptopetalum paraguayense E. Walther on CCl₄-induced liver damage and inflammation

Aim of this study

Graptopetalum paraguayense E. Walther, a vegetable consumed in Taiwan, has been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain. Therefore, we investigated the protective effects of Graptopetalum paraguayense E. Walther against carbon tetrachloride (CCl₄)-induced liver damage in rats.

Materials and methods

Water extracts of Graptopetalum paraguayense E. Walther (WGP) were administered for 8 consecutive weeks to male Sprague-Dawley rats. And a dose-dependent manner in preventing liver damage was confirmed. Moreover, the major ingredient of WGP, gallic acid, was also orally administrated in the CCl₄-induced rats. The hepatoprotective activity was assessed using various biochemical parameters such as antioxidant enzymes and histopathological studies.

Results

WGP ranging from 50 to 300 mg/kg bw administrations significantly lowered serum aspartate transaminase (AST) and alanine transaminase (ALT) levels, and inhibited malondialdehyde (MDA) generation in CCl₄-treated rats. WGP increased cellular GSH level and antioxidant enzymes, including superoxide dismutase, glutathione reductase, and catalase. Serum tumor necrosis factor-alpha (TNF-α) was decreased in the group treated with CCl₄ plus WGP (150 and 300 mg/kg bw). Histopathological examination of livers showed that WGP reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl₄-treated rats. In contrary, 10 mg/kg bw of gallic acid was administrated, this dose was related with WGP (300 mg/kg bw), and had significantly decreased the AST and ALT compared to the CCl₄-treated group. Aforesaid results suggested that gallic acid from WGP offered antioxidative activity against CCl₄-induced oxidative liver damage.

Conclusions

Taken together, this study is the first time to suggest that Graptopetalum paraguayense E. Walther exerts hepatoprotection via promoting antioxidative and anti-inflammatory properties against CCl₄-induced oxidative liver damage.     

Parathyroid localization. Clinical review

Recent advances in the techniques of preoperative parathyroid localization include ultrasonography, computed tomography, thallium-technetium subtraction scanning, magnetic resonance imaging, digital subtraction angiography with selective venous catheterization for PTH measurement, and ultrasound or CT-guided needle aspiration biopsy for cytological examination or PTH assay. These techniques are helpful for patients with hyperparathyroidism undergoing the initial operation, and essential for patients with persistent or recurrent hyperparathyroidism undergoing reoperation. Noninvasive procedures should be performed first, and the combination of any two positive studies localizes the tumor with near certainty. Invasive procedures have a higher risk of complications and are recommended only in selected patients before reoperation.     

Pleiotropic effects of thyroid stimulating hormone in a differentiated thyroid cancer cell line. Studies on proliferation, thyroglobulin secretion, adhesion, migration and invasion.

Thyroid stimulating hormone (TSH) causes differentiation and epidermal growth factor (EGF) causes dedifferentiation of thyroid cells in vitro. In undifferentiated thyroid cancer cell lines, TSH stimulates tumor cell migration and invasion, a dedifferentiated function, presumably due to an escape of tumor cells from the control of differentiating growth factors. In a highly differentiated thyroid carcinoma cell line of Hürthle cell origin (XTC), we tested the hypothesis that TSH would stimulate thyroglobulin secretion (a differentiated function) more than EGF, and EGF would stimulate invasion (a de-differentiated function) more than TSH. Proliferation, adhesion, cell migration and invasion were measured by the MTT assay, human thyroglobulin by RIA and protease activity by substrate-gel zymography. TSH induced differentiated morphologic changes in XTC cells and stimulated secretion of human thyroglobulin in a dose dependent manner, whereas EGF did not. The effects of TSH on growth, adhesion, migration and invasion were dose dependent and biphasic, with an increase at low and a decrease at high concentrations of TSH. These effects were always more pronounced than those observed with EGE Gelatinolytic activity, consistent with metalloproteinase activity was revealed by zymography, but the pattern of secretion was not altered by neither TSH nor EGF. These results suggest, that TSH has pleiotropic effects on differentiated thyroid cancer cells in vitro that involve differentiated morphology and function but also affect features commonly associated with the malignant in vitro phenotype.     

Subpopulations of intrathyroidal lymphocytes in Graves' disease

Subsets of T- and B-lymphocytes were immunophenotyped in frozen thyroid tissues from 20 patients with Graves' disease by using the avidin-biotin-complex peroxidase method. A panel of B- and T-cell monoclonal antibodies were employed to detect the subsets of T cells, activated T cells, natural killer cells and B cells. Serum thyroglobulin and microsomal antibodies were also measured simultaneously from both the thyroid vein and the peripheral vein in 9 patients. The quantitative results found that an almost equal ratio of lymphocytes stained positively for Leu 3a (CD4) and T8 (CD8) in almost all specimens. Activated lymphocytes expressing T9, T10, and Tac (CD25) were sporadically noted in the interstitial areas. The lymphoid aggregates and follicles were B cell clusters. Natural killer cells appear to play an insignificant role in Graves' disease. The thyroid epithelial cells expressed HLA-DR (Ia+) and HLA-ABC, suggesting a possible localized immune reaction between antigen-presenting thyroid epithelial cells and lymphocytes. The titers of serum thyroglobulin and microsomal antibodies from either the thyroid vein or the peripheral vein showed no definite correlation with the lymphoid distribution of the thyroid tissues, implying that the in situ or local immunologic reaction may not reflect the status of systemic antibody production. The immunologic mechanism and pathogenesis of Graves' disease is reviewed and discussed.