Daily oral administration of Formo for 12 weeks has a substantial anabolic effect, thus raising the possibility of its use in postmenopausal osteoporosis.

A convenient synthesis of natural and synthetic pterocarpans was achieved in three steps. Optical resolution of the respective enantiomers was accomplished by analytical and semi-preparative HPLC on a chiral stationary phase. For medicarpin and its synthetic derivative 9-demethoxymedicarpin, the absolute configuration was confirmed by a combination of experimental LC-ECD coupling and quantum-chemical ECD calculations. (-)-Medicarpin and (-)-9-demethoxymedicarpin are both 6aR,11aR-configured, and consequently the corresponding enantiomers, (+)-medicarpin and (+)-9-demethoxymedicarpin, possess the 6aS,11aS-configuration. A comparative mechanism study for osteogenic (bone forming) activity of medicarpin (racemic versus enantiomerically pure material) revealed that (+)-(6aS,11aS)-medicarpin (6a) significantly increased the bone morphogenetic protein-2 (BMP2) expression and the level of the bone-specific transcription factor Runx-2 mRNA, while the effect was opposite for the other enantiomer, (-)-(6aR,11aR)-medicarpin (6a), and for the racemate, (±)-medicarpin, the combined effect of both the enantiomers on transcription levels was observed.

Summary:We report four patients who developed severe adverse reactions to protamine sulfate following cardiac surgery. Two types of reactions were seen. First, an immediate anaphylaxis which is a complementdependent IgG antibody-mediated reaction. In the literature, 80% of patients who had similar reactions have had previous exposure to protamine. All patients adequately tested had positive skin tests and there is 6 % mortality. The second reaction to pmtamine during cardiac surgery is characterized by delayed onset and profound vascular damage presenting as noncardiogenic pulmonary edema or total vascular collapse with prolonged hypotension and anasarca. These patients have negative skin tests and in our studies, no evidence of antibody mediated reaction, suggesting some other mechanisms may play a part. The mortality is high (30% of patients reported) and survivors have significant morbidity.

Protein kinase B (Akt) plays a very significant role in various cancers including oral cancer. However, it has three isoforms (Akt1, Akt2, and Akt3) and they perform distinct functions and even play contrasting roles in different cancers. Therefore, it becomes essential to evaluate the isoform-specific role of Akt in oral cancer. In the present study, an attempt has been made to elucidate the isoform-specific role of Akt in oral cancer. The immunohistochemical analysis of oral cancer tissues showed an overexpression of Akt1 and 2 isoforms but not Akt3. Moreover, the dataset of “The Cancer Genome Atlas” for head and neck cancer has suggested the genetic alterations of Akt1 and 2 tend to be associated with the utmost poor clinical outcome in oral cancer. Further, treatment of oral cancer cells with tobacco and its components such as benzo(a)pyrene and nicotine caused increased mRNA levels of Akt1 and 2 isoforms and also enhanced the aggressiveness of oral cancer cells in terms of proliferation, and clonogenic and migration potential. Finally, silencing of Akt1 and 2 isoforms caused decreased cell survival and induced cell cycle arrest at the G2/M phase. Akt1/2 silencing also reduced tobacco-induced aggressiveness by decreasing the clonogenic and migration potential of oral cancer cells. Moreover, silencing of Akt1 and 2 isoforms was found to decrease the expression of proteins regulating cancer cell survival and proliferation such as cyclooxygenase-2, B-cell lymphoma 2 (Bcl-2), cyclin D1, and survivin. Thus, the important role of Akt1 and 2 isoforms have been elucidated in oral cancer with in-depth mechanistic analysis.