Biomedical subjects

A S Hedayat

Publications and source records attributed to A S Hedayat.

4 recordsLinked to original sources

PubMed2006

Seasonal variation of red clover (Trifolium pratense L., Fabaceae) isoflavones and estrogenic activity.

Red clover (Trifolium pratense L., Fabaceae) dietary supplements are currently used to treat menopausal symptoms because of their high content of the mildly estrogenic isoflavones daidzein, genistein, formononetin, and biochanin A. These compounds are estrogenic in vitro and in vivo, but little information exists on the best time to harvest red clover fields to maximize content of the isoflavones and thus make an optimal product. Samples of cultivated red clover above-ground parts and flower heads were collected in parallel over one growing season in northeastern Illinois. Generally, autohydrolytic extracts of above-ground parts contained more isoflavones and had more estrogenic activity in Ishikawa endometrial cells as compared with extracts of flower heads. Daidzein and genistein contents peaked around June to July, while formononetin and biochanin A contents peaked in early September. Flower head and total above-ground parts extracts exhibited differential estrogenic activity in an Ishikawa (endometrial) cell-based alkaline phosphatase induction assay, whereas nondifferential activity was observed for most extracts tested in an MCF-7 (breast) cell proliferation assay when tested at the same final concentrations. Ishikawa assay results could be mapped onto the extracts' content of individual isoflavones, but MCF-7 results did not show such a pattern. These results suggest that significant metabolism of isoflavones may occur in MCF-7 cells but not in Ishikawa cells; therefore, caution is advised in the choice of bioassay used for the biological standardization of botanical dietary supplements.

Breast Neoplasms↗

PubMed2006

Optimal designs in stability studies.

New optimality criteria for stability studies are proposed, and the related optimal designs are investigated. For each optimality criterion, optimal designs are identified within a class of competing designs. The property of the optimal designs for detecting slope differences is discussed.

Drug Industry↗

PubMed2005

Comparison of the in vitro estrogenic activities of compounds from hops (Humulus lupulus) and red clover (Trifolium pratense).

Because the prevailing form of hormone replacement therapy is associated with the development of cancer in breast and endometrial tissues, alternatives are needed for the management of menopausal symptoms. Formulations of Trifolium pratense L. (red clover) are being used to alleviate menopause-associated hot flashes but have shown mixed results in clinical trials. The strobiles of Humulus lupulusL. (hops) have been reported to contain the prenylflavanone, 8-prenylnaringenin (8-PN), as the most estrogenic constituent, and this was confirmed using an estrogen receptor ligand screening assay utilizing ultrafiltration mass spectrometry. Extracts of hops and red clover and their individual constituents including 8-PN, 6-prenylnaringenin (6-PN), isoxanthohumol (IX), and xanthohumol (XN) from hops and daidzein, formononetin, biochanin A, and genistein from red clover were compared using a variety of in vitro estrogenic assays. The IC50 values for the estrogen receptor alpha and beta binding assays were 15 and 27 microg/mL, respectively, for hops and 18.0 and 2.0 microg/mL, respectively, for the red clover extract. Both of the extracts, genistein, and 8-PN activated the estrogen response element (ERE) in Ishikawa cells while the extracts, biochanin A, genistein, and 8-PN, significantly induced ERE-luciferase expression in MCF-7 cells. Hop and red clover extracts as well as 8-PN up-regulated progesterone receptor (PR) mRNA in the Ishikawa cell line. In the MCF-7 cell line, PR mRNA was significantly up-regulated by the extracts, biochanin A, genistein, 8-PN, and IX. The two extracts had EC50 values of 1.1 and 1.9 microg/mL, respectively, in the alkaline phosphatase induction assay. On the basis of these data, hops and red clover could be attractive for the development as herbal dietary supplements to alleviate menopause-associated symptoms.

Alkaline Phosphatase↗

PubMed2003

Optimal and efficient crossover designs under different assumptions about the carryover effects.

In certain studies it is desirable or necessary that a subject, such as a patient in a medical trial, receive a treatment in each period. This facilitates a within-subject comparison of the treatments. Designs for studies of this type are called crossover designs or repeated measurements designs. If there are s subjects in p periods, the design should specify which of the t treatments is assigned to subject j in period i, i = 1,... ,p,j = 1,..., s. Equivalently we may think of a design as assigning each subject to one of the t(p) possible treatment sequences. The choice of a design will clearly depend on the values of p, s, and t, to which we will refer as the design parameters. But for any set of design parameters, we will typically still have many design choices. To distinguish between different designs for the same design parameters, we will compare the designs under criteria that are related to the objective of the study. Often the objective is a comparison of the treatments, and we would choose a design that, in some sense, provides good estimates of the treatment differences. For these criteria, a design that is optimal under one statistical model may not be optimal under another. It is therefore also of interest to identify designs that are efficient (relative to an optimal design) for more than one model. The main difference in the models that we will consider is in how the possible first-order carryover effects are modeled. This is a controversial issue, and it is by no means our intent to resolve this here. But a design that is efficient under a variety of plausible models is preferable to one that performs well under one model but poorly under another. Our main focus will be on two models. One of these models has been considered extensively in the literature, while the other is relatively new. For selected design parameters, we will compare selected designs under these models.

Clinical Trials as Topic↗