For postmenopausal women who fear hormone therapy, women 60 years of age with continuous, severe hot flushing or women with a history of breast cancer, we should consider selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) as therapeutic agents. Base on the results from a meta-analysis and clinical trials regarding hot flushing, paroxetine and the conetrolled-release formultation of paroxetine have been shown to effectively reduce hot flushing by 30~40% and 60~70%, respectively, and 13~41% more reductions as compared to placebo. Venlafaxine reduced hot flushes by 30~60% (133% reductions compared to placebo), and desvenlafaxine reduced hot flushes by 30~70%. Fluoxetine and citalopram were shown to be less effective than paroxetine and venlafaxine, by 20% (113% reductions compared to placebo) and 40~50%, respectively. Sertraline reduced hot flushes 3~18% compared to the placebo group, but was considered ineffective. Citalopram (20 mg), paroxetine (10 mg), venlafaxine (37.5~150 mg), and desvenlafaxine (100~200 mg) not only reduced vasomotor symptoms, but demonstrated additional beneficial outcomes with respect to sleep disturbances, mood, the vigor index, and improved quality of life. Citalopram (20 mg), fluoxetine (20 mg), paroxetine (10 mg), venlafaxine (75~150 mg), and desvenlafaxine (150 mg) are recommended at the corresponding doses after weighing the risks and benefits of these medications. SSRIs and SNRIs were shown to interrupt the conversion of tamoxifen into the active metabolite, endoxifen, and thus SSRIs and SNRIs must not be used in breast cancer patients who are taking tamoxifen. Paroxetine suppressed vasomotor symptoms most potently, followed by fluoxetine, sertraline, citalopram, and venlafaxine.
Breast Neoplasms ; Citalopram ; Cyclohexanols ; Female ; Fluoxetine ; Flushing ; Humans ; Menopause ; Norepinephrine ; Paroxetine ; Quality of Life ; Risk Assessment ; Serotonin ; Serotonin Uptake Inhibitors ; Sertraline ; Tamoxifen ; Desvenlafaxine Succinate ; Venlafaxine Hydrochloride

Venlafaxine is among the most widely prescribed antidepressants. It is extensively metabolized to O-desmethylvenlafaxine via cytochrome P450 (CYP) 2D6. We report a case of acute toxic hepatitis resulting from venlafaxine in a 54-year-old woman with pain disorder. During venlafaxine treatment, laboratory tests revealed elevated liver enzymes with a maximum of 169 IU/L for aspartate transaminase (AST) and 166 IU/L for alanine transaminase (ALT). AST and ALT levels returned to normal after 6 days of discontinuation of venlafaxine. The patient was finally diagnosed with acute toxic hepatitis through liver biopsy. This case indicates the importance that clinicians should be aware of the hepatotoxicity of venlafaxine in practice.
Alanine Transaminase ; Antidepressive Agents ; Aspartate Aminotransferases ; Biopsy ; Cyclohexanols ; Cytochrome P-450 Enzyme System ; Drug Toxicity ; Drug-Induced Liver Injury ; Female ; Humans ; Liver ; Middle Aged ; Somatoform Disorders ; Desvenlafaxine Succinate ; Venlafaxine Hydrochloride

AIMTo establish the differential scanning calorimetric (DSC) methodology for controlling the crystal-type B form of nateglinide.

METHODSAccurately weighed pure dried (P2O5 as desiccant for 4 h at 80 degrees C in vacuum) fine powder of crystal-type B and H of nateglinide were measured dQ/dT by DSC at heating rate of 10 degrees C. min-1 and temperature between 100 degrees C and 200 degrees C to calculate the enthalpy delta HB and delta HH. Accurately weight a series of uniform mixtures of crystal-type B and H of dried fine powder of nateglinide in different proportions. The enthalpy of the mixtures is measured by DSC as above to calculate the enthalpy (sigma delta H). Using B% as X, sigma delta H as Y, the regression equation was obtained. According to this equation, the unknown composition of mixed crystal was evaluated by the sigma delta H values. The method was used to control the limitation of crystal-type B of nateglinide by the sigma delta H value of mixture of known composition as reference.

RESULTSThe results measured from different laboratories showed that the repeatability was 0.61% and the recoveries were 86.2%-127% when the amounts of crystal-type B were between 0-15%.

CONCLUSIONThis method can be used to evaluate the crystal-type B composition of nateglinide.

OBJECTIVE: To investigate the effect of reactive oxygen species (ROS) on GDC-0152-induced apoptosis and autophagy of acute promyelocytic leukemia cell line NB4. METHODS: Different concentrations of GDC-0152 combined with Z-VAD-FMK was applied to NB4 cells. Cell proliferation was detected by CCK8 method. Apoptosis rate, autophagy and ROS level were detected by flow cytometry. The autophagy was observed by Cyto-ID staining fluorescence microscopy, and flow cytometry were used to detect the fluorescence expression. The expression of autophagy-related protein LC3B was detected by Western blot. RESULTS: GDC-0152 increased proliferation inhibition rate and apoptosis rate in NB4 cells (P＜0.05); GDC-0152 induced increase of ROS level of NB4 cells; GDC-0152 increased autophagy of NB4 cells that was found by Cyto-ID staining fluorescence microscopy and flow cytometry (P＜0.05). Western blot showed that GDC-0152 increased LC3B expression in NB4 cells and promoted the conversion of LC3BI to LC3BII; as compared with GDC-0152 (100 ng/ml), GDC-0152 (100 ng/ml) combined with ROS inhibitor YCG063 (10 μmol/L) decreased apoptosis and autophagy (P＜0.05). CONCLUSION GDC-0152 inhibits cell proliferation by inducing apoptosis and autophagy of NB4 cells. ROS can promote GDC-0152-induced apoptosis and autophagy of NB4 cells.
Apoptosis ; Autophagy ; Cell Line, Tumor ; Cyclohexanes ; Humans ; Leukemia, Promyelocytic, Acute ; Pyrroles ; Reactive Oxygen Species

Lignin peroxidase (LiP) hosted in Brij 30/cyclohexane/water nonionic reversed micelle could express its catalytic activity, but in Triton X-100/n-pentanol/cyclohexane/water nonionic reversed micelle LiP didn't show any catalytic activity. Some key factors that affected the catalytic activity of LiP in Brij 30 reversed micelle were studied at 20 degrees C. The optimum conditions were:omega0 = 8.5, pH = 2.2, [Brij30] = 600 mmol/L; under these conditions the half time of LiP was ca. 50 hours. As compared with the properties of LiP in aqueous solution, the activity of LiP hosted in Brij 30 reversed micelle dropped, but its stability improved greatly. To reveal the role of normal alcohol, which was a necessary component for forming Triton X-100 reversed micelles, the effect of n-pentanol on the catalytic activity of LiP in Brij 30 reversed micelle was investigated. Results indicated that high concentration of the alcohol deactivated LiP. So it was deduced that the phenomenon that LiP hosted in the Triton X-100 reversed micelles could not express its activity was mainly due to the alcohol co-surfactant.
Catalysis ; Cyclohexanes ; chemistry ; Enzyme Activation ; drug effects ; Micelles ; Octoxynol ; chemistry ; Pentanols ; chemistry ; Peroxidases ; metabolism ; Surface-Active Agents ; chemistry

BACKGROUND: All-trans-retinoic acid metabolism by cytochrome P450 is one of the major mechanisms that can regulate the level of retinoids in cells. Therefore, enhanced metabolism of all-trans retinoic acid by all-trans retinoic acid induced cytochrome P450 would probably decrease the therapeutic effects of active retinoids. We previously reported that the tail of all-trans retinoic acid (the carboxyl-terminus) may bind to a binding site of cytochrome P450 in part by electrostatic forces, and the head of RA (the beta-cyclogeranylidene ring) may bind to an active site of cytochrome P450 in part by hydrophobic forces. It is very interesting to study the interactions between the RA binding site of cytochrome P450 induced by all-trans retinoic acid and the structural analogs of all-trans retinoic acid and its effects of RA metabolism. OBJECTIVE: The purpose of this study is to examine the effects of sorbic acid, that has a similar structure with the tail of all-trans retinoic acid, on RA metabolism in head-neck squamous cell carcinoma cell line AMC-HN-6 which showed a much increased induction of cytochrome P450 by all-trans retinoic acid. METHODS: We examined the effects of sorbic acid on RA metabolism in all-trans retinoic acid specific cytochrome P450-inducible AMC-HN-6 cell line using cytochrome P450 enzyme assay with total cell lysates and microsomal proteins. Radioisotope-labeled polar metabolites of all-trans retinoic acid were separated by thin layer chromatography and the radioactivity was measured by beta-counter. Metabolic activity was expressed as the percentage of total radioactivity of polar metabolites. RESULTS: The results are summurized as follows: 1. RA metabolism of AMC-HN-6 cell line was inhibited by actinomycin D and cyclohexamide and was also inhibited by ketoconazole, the cytochrome P450 inhibitor, in a concentration-dependent manner. 2. Cytochrome P450-mediated oxidation was induced by all-trans retinoic acid, 13-cis-RA, 9-cis-RA, and retinal, but not by retinol in AMC-HN-6 cell line.3. Sorbic acid inhibited RA metabolism of AMC-HN-6 cell line in a concentration-dependent manner when the enzyme assay was performed on microsomal protein but could not inhibit RA metabolism in total cell lysate enzyme assay. CONCLUSION: The conversion of all-trans retinoic acid to polar metabolites is inhibited by sorbic acid in microsomal enzyme assay of AMC-HN-6 cell line, but not in total cell assay. These results suggest that sorbic acid can bind to the active binding site of cytochrome P450 but binding affinity of sorbic acid to RA binding molecules such as CRABP-I,-II, RARs, RXRs may be stronger than that of sorbic acid to cytochrome P450.
Binding Sites ; Carcinoma, Squamous Cell ; Catalytic Domain ; Cell Line* ; Chromatography, Thin Layer ; Cytochrome P-450 Enzyme System ; Cytochromes ; Dactinomycin ; Enzyme Assays ; Head ; Ketoconazole ; Metabolism* ; Radioactivity ; Retinaldehyde ; Retinoids* ; Sorbic Acid* ; Tretinoin* ; Vitamin A

Retinoids are compounds with pleiotropic functions, selectively targeting certain skin structures. They are vitamins which must be derived from diet because retinol(vitamin A) is not synthesized in the body, and also they are hormones with intracrine activity, because retinol is transformed into molecules that bind to nuclear receptors, exhibit their activity, and are subsequently inactivated. Enhanced healing of full-thickness skin wounds has been demonstrated in early wound healing studies. OBJECTIVE: Our purpose is to observe the chemical and histologic effects of topical retinoid derivatives(0.05%) applied directly to the dermal wound of guinea pig. METHODS: We prepared five kinds of retinoid derivative, applied each one on the wound on back of guinea pig. After 4 and 8 weeks, each wound was observed under microscope and analyzed for the amount of the collagen. RESULTS: Among the newly developed retinoid derivatives, PVP-RA(ester form) was the most effective in wound healing of the dermal damaged guinea pig. CONCLUSION: Retionid derivatives were effective in dermal wound healing if well prepared.
Animals ; Collagen ; Diet ; Guinea Pigs ; Polyethylene* ; Polyvinyls* ; Receptors, Cytoplasmic and Nuclear ; Retinoids ; Skin ; Tretinoin* ; Vitamin A ; Vitamins ; Wound Healing* ; Wounds and Injuries*

BACKGROUND AND OBJECTIVE: Retinoids, including vitamin A and its synthetic analogs, are known to suppress carcinogenesis in various epithelial tissues and also to inhibit the cell growth of head and neck squamous cell carcinomas (HNSCC). However, the exact mechanism of retinoids is not yet known. The aim of this study is to investigate the effect of all-trans-retinoic acid (RA) on the cell cycle in HNSCCs and to see if the inhibition of cell growth by RA is due to the arrest of cell cycle. MATERIALS AND METHODS: For in vitro study, AMC-HN-4 and AMC-HN-6 (HNSCC cell lines) were treated with 1 nM of RA and cultured for 6 days. CellTiter 96(TM) AQ(ueous) Non-Reactive Cell Proliferation Assay kit was used to analyze the inhibition of cell growth. Flow cytometric analysis was performed for cell cycle analysis. For in vivo study, AMC-HN-4 and AMC-HN-6 were injected subcutaneously into athymic nude mice and RA (20 mg/kg) was orally administered once a day for 30 days. Tumor volumes were measured with digimatic caliper and the cell cycle was analyzed using frozen specimens. RESULTS: The growth of AMC-HN-4 and AMC-HN-6 were inhibited by RA in vitro and in vivo. The inhibitory effect of RA was more significant in AMC-HN-4 than in AMC-HN-6. RA had no significant effect on the cell cycle in the medium containing 10% fetal bovine serum (FBS), but there was a mild increase in the G1 phase in the medium containing 0.5% FBS in vitro. In vivo, the increase in G1 phase was observed in both AMC-HN-4 and AMC-HN-6. Also, G1 arrest was more significant in AMC-HN-4 than in AMC-HN-6. CONCLUSION: This study suggests that RA may induce G1 arrest, which might be associated with the inhibition of cell growth in HNSCCs.
Animals ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Cycle* ; Cell Proliferation ; G1 Phase ; Head* ; Mice ; Mice, Nude ; Neck* ; Retinoids ; Tretinoin* ; Vitamin A

BACKGROUND: Glutaraldehyde (GA) is a widely used cross-linking agent for improving mechanical properties and resistance to enzymatic degradation of collagenous tissue, but it has several drawbacks such as calcification and cytotoxicity. The aim of this study was to find the alternative effective cross-linking methods to GA. MATERIALS AND METHODS: Bovine pericardium was processed with GA with ethanol+octanol and glycine detoxification, and polyethylene glycol (PG) space filler, dimethyl 3,3'-dithiobispropionimidate (DTBP), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) treatment, and the physical fixation of ultraviolet irradiation were done. The biologic material properties of variously treated pericardial tissues were assessed by biochemical, mechanical and histological tests. Treated pericardial tissues were also implanted subcutaneously or intramuscularly into the rabbit for 10 weeks to assess the xenoreactive antibody response of immunoglobulin G and M, their anti-calcification effect. RESULTS: The biochemical and mechanical properties of EDC fixed pericardial tissues were comparable to the GA fixed tissue. The cytotoxicity was lowest in space filler treated GA fixed group. In rabbit subcutaneous or intramuscular implantation models, decellularization, space filler, EDC treatment group showed significantly lower calcium content than GA only and DTBP treatment group (p<0.05, analysis of variance). The titer of anti Galalpha1-3Galbeta1-4GlcNAc-R antibodies did not change in the postimplantation serial enzyme-linked immunosorbent assay. Hematoxylin and eosin and von Kossa staining showed that decellularization, space filler, EDC, and ultraviolet treatment had less inflammatory cell infiltration and calcium deposits. CONCLUSION: The decellularization process, PG filler, and EDC treatments are good alternative cross-linking methods compared to GA only fixation and primary amine of DTBP treatment for cardiovascular xenograft preservation in terms of the collagen cross-linking stability and in vivo anti-calcification effects.
Antibodies ; Antibody Formation ; Bioprosthesis ; Calcium ; Collagen ; Cyclohexanes ; Enzyme-Linked Immunosorbent Assay ; Eosine Yellowish-(YS) ; Glutaral ; Glycine ; Hematoxylin ; Imidoesters ; Immunoglobulin G ; Pericardium ; Polyethylene Glycols ; Transplantation, Heterologous ; Trisaccharides

Animals ; Blood Glucose ; drug effects ; Crystallization ; Cyclohexanes ; chemistry ; pharmacology ; Female ; Hyperglycemia ; blood ; Hypoglycemic Agents ; pharmacology ; Male ; Mice ; Mice, Inbred ICR ; Phenylalanine ; analogs & derivatives ; chemistry ; pharmacology ; X-Ray Diffraction