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BACKGROUND: Genistein increases CPT1A, a rate-limiting enzyme in the beta-oxidation pathway, enzyme activity by increasing CPT1A transcription in HepG2 cells and, consequently, suppresses high fat induced obesity in C57BL/6J mice. Genistein and daidzein are the most abundant isoflavones in soy.AIM OF STUDY: To investigate the effect of co-treatment of genistein and L-carnitine on CPT1A enzyme activity and to determine whether daidzein also increases CPT1A activity and to establish a cell line that can be used to screen chemicals to regulate CPT1A transcription.METHODS: The enzyme activities of CPT1A were determined after HepG2 cells were incubated with 10muM genistein or 10muM daidzein or 1 mM L-carnitine or in combination with 10muM genistein and 1 mM L-carnitine or in combination with 10muM daidzein and 1 mM L-carnitine. The mRNA expression levels of CPT1A were determined by real time PCR method after HepG2 cells were incubated with 10muM genistein or 10muM daidzein. A suggested CPT1A promoter region was cloned from human genomic DNA and the CPT1A promoter-luciferase reporter gene construct was made, and the promoter-reporter gene construct was transfected into human hepatoma cell line Huh7.RESULTS: The enzyme activity of CPT1A was at least 2.3- fold higher in L-carnitine and genistein co-treated HepG2 cells than either single-agent treated cells. Daidzein also significantly increased the mRNA expression of CPT1A as well as the enzyme activity of CPT1A. A stable Huh7 cell line, which was selected after Huh7 cells were transfected with CPT1A promoter luciferase reporter gene construct, was characterized by confirming that luciferase activity of the cell line can be regulated by genistein and daidzein as well as clofibrate, a well-known CPT1A mRNA up-regulating drug.CONCLUSIONS: Genistein and daidzein can up-regulate CPT1A enzyme activity through up-regulation of CPT1A transcription. Co-treatment of L-carnitine and genistein additively increases CPT1A enzyme activity in HepG2 cells. A stable Huh7 cell line transfected with the CPT1A promoter luciferase reporter gene was established and characterized. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA carboxylase (MCC) deficiency in which peripheral venous blood samples were collected.

Pulmonary venous flow (PVF) is influenced by changes in left atrial (LA) pressure and function in various diseases. In mitral stenosis (MS), there is an alteration of LA hemodynamic due to the impaired ventricular filling caused by the stenotic valve and elevation of LA pressure. Although a variety of altered patterns of PVF have been described in MS, the potential influence of pulmonary hypertension, which is frequently associated with MS and has an adverse effect on the functional status and the prognosis of MS, on the PVF pattern is not clearly defined. The aim of this study is to determine the effects of pulmonary hypertension on PVF in patients with MS. Thirty-eight consecutive patients with pure MS and sinus rhythm (30 females, mean age 40 years old) underwent transthoracic and transesophageal echocardiography. Right heart and transseptal catheterization was also performed to measure pulmonary artery systolic pressure (PASP), pulmonary artery diastolic pressure (PADP), pulmonary capillary wedge pressure (PCWP), and left atrial pressure (LAP). The subjects were divided into two groups: group 1 (n = 25)included subjects with PASP < 50 mmHg, group 2(n = 13)included subjects with PASP 50 mmHg. LA size, mitral valve area (MVA), mean mitral gradient (MG), LAP, PASP, PADP, PCWP, and the peak velocity of PV systolic (PVFS), diastolic (PVFD) and atrial reversal flow (PVFAr) were also measured and compared between the two groups. There was no significant difference in age, heart rate, MVA, and LA size between the two groups. LAP, PASP, PADP, PCWP, and MG were significantly higher in group 2. However, PVFS and PVFAr were significantly lower in group2 (46.6 +/- 15.8 vs 29.9 +/- 12.8 cm/sec, P < 0.005; 22.1 +/- 6.8 vs 17.3 +/- 5.9 cm/sec, P < 0.05). There was no significant difference of PVFD between the two groups. PVFS had negative correlation to LAP, MG, PASP, PADP, and PCWP. PVFAr had negative correlation with PASP, PADP, and PCWP. There was no significant correlation between PVFAr and MVA. LA size and LAP. In conclusion, in patients with pure MS and sinus rhythm, PVF, especially PVFAr, is influenced by the presence of pulmonary hypertension. [ABSTRACT FROM AUTHOR]