The aim of the present study was to investigate the effects of various decellularization methods on the histological and biomechanical properties of rabbit tendons. In total, six chemical reagents, including 1% t-octyl-phenoxypolyethoxyethanol (Triton-X 100), 0.5% sodium dodecyl sulfate (SDS), 1% tri-n-butyl phosphate (TnBP), 1% Triton-X 100 + 0.5% SDS, 1% TnBP + 0.5% SDS and 1% TnBP + 1% Triton-X 100, were used on rabbit semitendinosus muscles and flexor digitorum tendons for 24 h to remove cells. Hematoxylin and eosin staining was applied for histological observation, while tension testing was used for biomechanical studies. The effects of the various decellularization methods on the histological structure and biomechanical properties of rabbit tendons were evaluated. A group of fresh tendons treated with phosphate-buffered saline served as controls. The various decellularization methods resulted in different effects on the tendons. All the treatment groups exhibited a decrease in tendon biomechanical properties, but no statistically significant differences were observed among the experimental groups. The extensibility of the 1% TnBP-treated group was found to be greater than that of the other groups; however, the difference was not statistically significant. Histologically, the 1% TnBP + 0.5% SDS treatment was shown to have the least impact on the rabbit tendon structure, with good decellularization and no clear cellular remnants observed. The 1% Triton-X 100 + 0.5% SDS treatment had a pronounced effect on the tendon collagen structure and a number of collagen ruptures were observed. Overall, 1% TnBP + 0.5% SDS was found to be the most effective compared with the other treatments, as this treatment preserved the tendon collagen structure while completely removing the cells. Tendons treated with 1% TnBP + 0.5% SDS were histologically similar to normal tendon tissue and biomechanically similar to the tendons in the control group.

To evaluate the behavior of cardiac arrhythmias in dipper and nondipper hypertensive patients, 48-h ambulatory blood pressure monitoring, 24-h Holter electrocardiogram recording and echocardiographic studies were performed in 56 untreated outpatients with essential hypertension. These patients were divided into 2 groups according to the presence (dipper, n=33) or absence (nondipper, n=23) of reduction of both systolic and diastolic blood pressure during nighttime by an average of more than 10% of daytime blood pressure. Mean 48-h systolic and diastolic blood pressures did not differ between the 2 groups. Nondipper patients had a significantly larger left atrial dimension (31.9+/-3.8 vs 35.6+/-3.7 mm; p<0.01), left ventricular mass index (114+/-26 vs 136+/-36 g/m2; p<0.05), as well as a larger number of total supraventricular (16+/-19 vs 89+/-197 beats; p<0.05) and ventricular ectopic beats (7+/-14 vs 47+/-96 beats; p<0.05) during daytime as compared with dippers. In conclusion, nondipper hypertensive patients are likely to experience supraventricular and ventricular arrhythmias more frequently than dippers. A blunted nocturnal blood pressure fall may be involved in the appearance of cardiac arrhythmias in patients with essential hypertension.

The aim of this study was to identify the relationship of QT dispersion on 12-lead electrocardiograms and left ventricular mass index on echocardiograms associated with the circadian rhythm of blood pressure (BP). Heart rate and BP were monitored every 30 min for 48 h in 62 patients with essential hypertension using an ambulatory BP monitoring device. The patients were divided into four groups according to gender and circadian BP pattern (nocturnal BP dipper or nondipper). The patients were classified as dippers if their daytime BP decreased by at least 10% during the night and all the other subjects were classified as nondippers. Age, body mass index, and 48-h mean BP were similar among the four groups. During the night-rest period, the systolic and diastolic BP were significantly decreased in dipper-type hypertensives. The maximum QTc interval and QTc dispersion were longer in nondippers than in dippers. Left ventricular mass index (LVMI) had a tendency to increase in nondippers. The nocturnal reduction of BP significantly correlated with QTc dispersion and LVMI. The QTc dispersion significantly correlated with LVMI and interventricular septum thickness.

Development of non-viral vectors for treatment of diseases such as genetic disorders, inflammation or cancer remains an important goal for gene therapy. However, gene therapy is experimental and has not been proven to be very successful in clinical trials. The primary hurdle to the clinical success of gene therapy has been the absence of carriers (vectors) that can deliver DNA and RNA into target cells safely and efficiently. Basically, there are two kinds of gene delivery vectors, viral and nonviral. Viral vectors are very efficient in delivering plasmids into mammalian cells, however, their usefulness is limited due to immunogenicity, low loading capacity and insertional mutagenesis. 1) Nonviral gene delivery systems based on cationic liposomes and polymers have recently received increasing attention, although the gene transfection efficiency is still lower than viral vector systems, there are some unique advantages for practical use such as easy manipulation, stability, low cost, safety and their induction of a less immune response. Polycations have emerged as efficient transfection vectors and are able to condense DNA into nanocomplexes suitable for endocytic uptake. Among the polycationic polymers, polyethylenimine (PEI), has shown high transfection efficiency both in vitro and in vivo, 1,2) probably due to its stable complex structure which is appropriate for being taken by cells; the following "proton sponge" effect from PEI facilitates the escape of the complex from an endosomal compartment. The gene delivery efficiency and cytotoxicity of PEI vary according to its molecular weight. The high density of primary, secondary and tertiary amino groups of high molecular weight PEI (HMW PEI), may partially account for the high transfection efficiency of PEI-based complexes. On the other hand, the huge amount of cationic charge frequently results in a rather high toxicity, 3,4) which can be regarded as one of the major factors limiting its use in vivo. Another problem of using polycation DNA complexes is their poor solubility. 5) They may immediately precipitate out of a solution when being prepared at a higher concentration. Many in vivo gene administrations are limited by the volume of a solution. To improve its biocompatibility, PEI has been modified by human serum albumin, 6) dextran, 7) or hydrophilic copolymers such as poly[N-(2-hydroxypropyl) methacrylamide] (pHPMA) 8,9) and poly(ethylene glycol) (PEG).10-12) Such hydrophilic and biocompatible polymers can improve the solubility of the complexes, minimize the aggregation of particulates and reduce their interaction with proteins in the physiological fluid. The less cytotoxic PEI derivatives, however, showed reduced gene transfection efficiency compared to those unmodified due to decreased cellular association and internalization. 13,14) Amphiphilic copolymers-Pluronic, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO x -b-PPO y -b-PEO x triblock copolymer) that self-assemble to form micelles in aqueous solution were used as additiv...

The purpose of the study was to identify differences in the patterns of efficacy and duration of effects of imidapril administered at different times of the day (morning versus evening) in dipper and nondipper hypertensive patients. Twenty patients with untreated hypertension were classified into two groups: dippers (n = 9) and nondippers (n = 11). Imidapril (10 mg) was given at 07:00 or 18:00 for 4 weeks in a crossover fashion. Blood pressure (BP) and heart rate (HR) were monitored before and after morning and evening treatment every 30 min for 48h by ambulatory BP monitoring (ABPM). In dipper hypertension, the mean 48h BP was reduced with both doses. The decrease in the diurnal BP was stronger when the drug was administered in the evening than morning, but without significant difference. In nondipper hypertension, the systolic BP decreased at night with both doses, but the extent of the nocturnal reduction in systolic BP was greater after morning therapy. There were no significant differences in the decrease in BP during the day or night between the morning and evening administrations. When imidapril was administered in the morning, its serum concentration reached a maximum at 16:00, and when the drug was administered in the evening, it reached a maximum at 6:00. In dipper hypertension, the time taken for the blood concentration of imidapril to reach a maximum changed depending on its time of administration, and the time when the maximum antihypertensive effect of the drug appeared was different. In nondipper hypertension, decreases in the BP were confirmed at night regardless of the time of administration; this might be caused by angiotensin converting enzyme (ACE) inhibitors effectively blocking the BP from increasing by activating the parasympathetic nervous system. Therefore, when assessing the effectiveness of antihypertensive agents, factors such as the various patterns of BP before therapy and administration time must be considered.