Cardiac Remodeling Biomarkers as Potential Circulating Markers of Left Ventricular Hypertrophy in Heart Failure with Preserved Ejection Fraction.

Soluble suppressor of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor (GDF)-15 and syndecan-1 represent biomarkers of cardiac remodeling, involved in heart failure (HF) progression. We hypothesize that their plasma concentrations, together with brain natriuretic peptide (BNP), are different in HF stratified by ejection fraction (EF), demonstrating correlations with echocardiographic parameters that indicate left ventricular (LV) hypertrophy; LV mass index (LVMI) and posterior wall and septum diameters. HF patients (n = 77) were classified according to EF: reduced EF < 40% (HFrEF), mid-range EF = 40-49% (HFmrEF), preserved EF > 50% (HFpEF). We found that plasma concentrations of four cardiac remodeling biomarkers were highest in HFrEF and lowest in HFpEF, p < 0.001. In HFpEF, remodeling biomarkers independently correlated with LVMI: sST2 (p = 0. 002), galectin-3 (p < 0.001), GDF-15 (p = 0.011), and syndecan-1 (p = 0.006), whereas galectin-3 correlated after multivariable adjustments (p = 0.001). Independent correlates of septum and posterior wall diameters, in HFpEF, were sST2 (p = 0.019; p = 0.026), galectin-3 (p = 0.011; p = 0.009), GDF-15 (p = 0.007; p = 0.001), and syndecan-1 (p = 0.005; p = 0.002). In HFrEF, only sST2, adjusted, correlated with LVMI (p = 0.010), whereas BNP correlated with LVMI (p = 0.002) and EF (p = 0.001). GDF-15 correlated with diastolic dysfunction in HFpEF (p = 0.046) and HFrEF (p = 0.024). Cardiac remodeling biomarkers are potential circulating indicators of LV hypertrophy in HFpEF, which may ensure timely recognition of disease progression among high-risk patients.

HPLC method development for determination of doxycycline in human seminal fluid.

The present paper reports the development and validation of an analytical method for doxycycline quantification in human seminal fluid by HPLC with UV detection. The separation of doxycycline was achieved at 40°C on a reversed-phase C18 column using isocratic elution. The mobile phase consisted of acetonitrile (A) and water buffered at pH 2.5 with a concentrated orthophosphoric acid (B) in the volume ratio of 20:80 (v/v), respectively. The detection was performed at 350nm. As an internal standard (IS), tetracycline was used. The proposed method involves the extraction of doxycycline from seminal fluid based on acidic precipitation of the proteins using perchloric acid. The method showed good intra- and inter-day precisions (RSD<7.0%), good accuracy (recovery for doxycycline>80%), and high correlation coefficient (r=0.998) for standards subjected to the entire procedure. The detection and quantification limits were 0.087µg/ml and 0.264µg/ml. The developed method was used to analyze doxycycline in the seminal fluids obtained from male subjects who were treated with doxycycline-hyclate. The mean doxycycline concentrations of 0.89±0.07µg/ml and 0.45±0.26µg/ml were detected in seminal fluid after 6h and 12h, respectively. This is the first study reporting extraction and HPLC determination of doxycycline in this complex sample and can be very useful in support of clinical and pharmacokinetic studies on this antibiotic.

[Drug interactions with grapefruit].

INTRODUCTION: The concentration of many orally given medications may be affected by grapefruit or grapefruit juice consumption. It may result in numerous harmful effects. INTERACTION OF GRAPEFRUIT WITH DRUGS: Taking only one cup of juice may induce interactions with different drugs even during the period of a few days. The effect is induced by suppression of cytochrome P450 isoenzyme CYP3A4 in the intestinal wall. The Latin name of grapefruit, Citrus paradisi, is quite opposite to the effects which could be induced by taking grapefruit and some medications at the same time. It is necessary to avoid taking grapefruit with the drugs whose pharmacokinetics could be altered by the active principles found in that fruit. DISCUSSION: The coloured grapefruit contains less furanocoumarins, but there is no difference in induction and intensity of pharmacokinetic interaction with drugs related to its colour. Other citrus fruits (orange, lemon) do not have such effects, but some other fruits (pomegranate, stella fruit, banpeiyu, hassaku, takaoka-buntan and kinkan) exert inhibitory effects on the activity of cytochrome P450 isoenzyme.