A pharmacogenetics-based dosing algorithm has been developed for improvement in the time to reach the stable dosing of warfarin. This model may be useful in helping the clinicians to prescribe warfarin with greater safety and efficiency.

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Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) (V. M. Tesmer, A. Rajadhyaksha, J. Babin, and M. Bina, Proc. Natl. Acad. Sci. USA 90:7298-7302, 1993). We have determined the functional role of C/EBP proteins and C/EBP sites in regulating transcription from the HIV-1 LTR in monocytes/macrophages. Inhibition of endogenous C/EBP proteins, using either an excess of C/EBP binding sites or a trans-dominant negative inhibitor, demonstrated that C/EBP proteins are required for basal and activated levels of HIV-1 LTR transcription in the promonocytic cell line U937. Northern (RNA) blots and binding assays showed that NF-IL6 is the only known C/EBP family member which is increased when U937 cells are activated. Mutational analyses of the HIV-1 LTR showed that one C/EBP site is required for normal LTR transcription both before and after cellular activation and that the two 3 C/EBP sites are functionally equivalent. However, transcription from crippled HIV-1 LTRs lacking C/EBP sites can still be induced following activation of U937 cells. Several models are suggested for how elevated NF-IL6 may participate in an autostimulatory loop involving HIV infection, macrophage activation, cytokine expression, and HIV replication.

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Abstract:We investigated the effect of ginsenoside Rb1 on cardiac function and remodeling in heart failure (HF). Four weeks after HF induction, the rats were administrated with ginsenoside Rb1 (35 and 70 mg/kg) and losartan (4.5 mg/kg) for 8 weeks. Losartan was used as a positive control. Cardiac function was assessed by measuring hemodynamic parameters. Histological changes were analyzed by HE and Masson's trichrome staining. Cardiac hypertrophy, fibrosis, mitochondrial membrane potential and glucose transporter type 4 (GLUT4) levels were evaluated. In the present study, high dose of (H−) ginsenoside Rb1 decreased heart rate, improved cardiac function and alleviated histological changes induced by HF. H-ginsenoside Rb1 attenuated cardiac hypertrophy and myocardial fibrosis by decreasing left ventricular (LV) weight/heart weight ratio and cardiomyocyte cross-sectional area and reducing the levels of atrial natriuretic factor (ANF), β-myosin heavy chain (β-MHC), periostin, collagen I, Angiotensin II (Ang II), Angiotensin converting enzyme (ACE) and Ang II type 1 (AT1) receptor. Moreover, H-ginsenoside Rb1 decreased mitochondrial membrane potential and enhanced the translocation of GLUT4 to plasma membrane. The TGF-β1/Smad and ERK signaling pathways were inhibited and the Akt pathway was activated. These findings suggest that ginsenoside Rb1 might restore cardiac/mitochondrial function, increase glucose uptake and protect against cardiac remodeling via the TGF-β1/Smad, ERK and Akt signaling pathways.

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