Endurance training-induced cardiac remodeling in a guinea pig athlete's heart model.

Besides the health benefits of regular exercise, high-level training-above an optimal level-may have adverse effects. In this study, we investigated the effects of long-term vigorous training and its potentially detrimental structural-functional changes in a small animal athlete's heart model. Thirty-eight 4-month-old male guinea pigs were randomized into sedentary and exercised groups. The latter underwent a 15-week-long endurance-training program. To investigate the effects of the intense long-term exercise, in vivo (echocardiography, electrocardiography), ex vivo, and in vitro (histopathology, patch-clamp) measurements were performed. Following the training protocol, the exercised animals exhibited structural left ventricular enlargement and a significantly higher degree of myocardial fibrosis. Furthermore, resting bradycardia accompanied by elevated heart rate variability occurred, representing increased parasympathetic activity in the exercised hearts. The observed prolonged QTc intervals and increased repolarization variability parameters may raise the risk of electrical instability in exercised animals. Complex arrhythmias did not occur in either group, and there were no differences between the groups in ex vivo or cellular electrophysiological experiments. Accordingly, the high parasympathetic activity may promote impaired repolarization in conscious exercised animals. The detected structural-functional changes share similarities with the human athlete's heart; therefore, this model might be useful for investigations on cardiac remodeling.

Application of ventricular tachyarrhythmia definitions of the updated Lambeth Conventions provides incompatibility with earlier results, masks antifibrillatory activity and reduces inter-observer agreement.

The Lambeth Conventions (LC I), a landmark guidance document for arrhythmia research was updated and arrhythmia definitions were changed in the new Lambeth Conventions II (LC II). This study examined whether the arrhythmia definitions of LC I and LC II yield the same qualitative results and whether LC II improves inter-observer agreement. Two independent investigators performed blinded arrhythmia analysis of the electrocardiograms of isolated, Langendorff rat hearts subjected to regional ischemia and perfused with Class I antiarrhythmics with 3 or 5 mM K+ in the perfusate. Data obtained with arrhythmia definitions of LC I and LC II were compared within and between observers. Applying ventricular fibrillation (VF) definition of LC II significantly increased VF incidence and reduced VF onset time irrespective of treatment by detecting 'de novo' VF episodes not found by LC I. LC II reduced the number of ventricular tachycardia (VT) episodes and simultaneously increased the number of VF episodes as compared with the respective values obtained according to LC I. Using VF definition of LC II masked the significant antifibrillatory effects of flecainide and the high K+ concentration identified with the VF definition of LC I. When VF incidence was tested, a very strong inter-observer agreement was found according to LC I, whereas using VF definition of LC II reduced inter-observer agreement. It is concluded that LC II shifts some tachyarrhythmias from VT to VF class, and thus results obtained by arrhythmia definitions of LC I and LC II are not compatible; VF definition of LC II may change the conclusion of pharmacological, physiological and pathophysiological arrhythmia investigations and may reduce inter-observer agreement. Thus, VT and VF definitions of LC II should be amended in order to increase compatibility and inter-observer agreement.

Silica@zirconia@poly(malic acid) nanoparticles: promising nanocarriers for theranostic applications.

Silica@zirconia@poly(malic acid) nanocarriers of 110 nm mean diameter were designed, synthesized and characterized for the targeted delivery of diagnostic and therapeutic 99mTc to folate-overexpressing tumors. An important achievement was that a multifunctional l-(-)-malic-acid-based copolymer was formed in situ at the surface of the inorganic cores in a single synthetic step incorporating l-(-)-malic acid, ß-cyclodextrin rings, folic acid moieties, and polyethylene glycol chains. Morphological and in-depth structural analysis of the particles proved their core@shell structure. Stability experiments in aqueous media evidenced that stable suspensions can be obtained from the lyophilized powder in 10 mM phosphate buffer at pH 7.4. During 14-day degradation experiments, the nanoparticles were found to be slowly dissolving (including inorganic core) in saline and also in total cell medium. An in vitro toxicity assay on hepatocytes showed a concentration-dependent decrease of cell viability down to 63 ± 1% at the highest applied concentration (0.5 mg ml-1). Proof of concept experiments of technetium-99m radiolabelling and in vivo labelling stability are presented.

Inherently fluorescent and porous zirconia colloids: preparation, characterization and drug adsorption studies.

Porous, fluorescent zirconia particles of nearly 380 nm diameter were prepared without template molecules or labeling dyes. The porous structure is the result of aggregation-induced particle formation. The inherent fluorescence is assigned to coordinatively unsaturated Zr4+ ions at the sol-gel derived ZrO2 surface. After physico-chemical characterization of the native zirconia particles carboxyl and/or amine bearing drug molecules (d,l-α-difluoromethylornithine - DFMO, ursolic acid - UA and doxorubicin - DOX) were adsorbed onto their surface, and the products were analyzed with Fourier-transform infrared spectroscopy (FTIR), thermogravimetry (TG), small-angle X-ray scattering (SAXS), fluorimetry and zeta potential vs. pH measurements. We have found that DOX complexes coordinatively unsaturated Zr4+ ions without dislocating them, while carboxyl-bearing drugs interact with basic surface Zr-OH sites eliminating some of the carbonate species. The adsorption of UA at the zirconia surface shifts considerably the isoelectric point of the surface and thus provides kinetic stability to the particles at physiological pH. An in vivo biodistribution study in two healthy dogs performed by SPECT/CT detection after 99mTc labeling of the nanocarriers has shown the possibility of drug delivery application.

Sentinel lymph node detection with large human serum albumin colloid particles in breast cancer.

Detection of metastatic involvement of lymph nodes is essential for management and prognostic evaluation in breast cancer patients. The success of lymphatic mapping depends on identifying the sentinel lymph node(s) draining the primary tumour. However, when mapping is performed with a radiocolloidal agent, the number of hot lymph nodes varies with the agent and its size, among other factors. In this study, we evaluated prospectively the detection rate of sentinel lymph nodes in breast cancer when injecting large particles (100-600 nm) of human serum albumin colloids (Senti-Scint). In 128 consecutive breast cancer patients without palpable lymph nodes, pre-operative static lymphoscintigraphic mapping of the breast was performed after subcutaneous injection of 15 MBq of the radiocolloid. Lymphoscintigrahic results were compared with intra-operative surgical gamma detection probe and blue dye mapping data. Pre-operative lymphoscintigraphy and surgical gamma detection probe both correctly detected 203 sentinel lymph nodes in 122/128 patients (95%), while blue dye mapping showed only 183 sentinel lymph nodes in 82% of the patients. Only one or two sentinel lymph nodes were identified in each patient, which allowed the surgeon easily to find the sentinel lymph node(s) intra-operatively. In conclusion, lymphoscintigraphy with large particles of human serum albumin colloids is a helpful and reliable procedure for the surgical management of breast cancer.

Evaluation of T-lymphocyte subsets present in semen and peripheral blood of healthy donors: a report from the heterosexual transmission study.

The purpose of this study was to accurately determine the T-lymphocyte subsets found in semen from healthy volunteers, to evaluate the impact of repeated ejaculation on the frequency or type of immune cells present in semen, and to compare subset analysis in semen to that in the peripheral blood. To accomplish this, a flow cytometric method was developed to identify and count immunophenotypically distinct cells present in semen. Fresh semen samples and peripheral blood were collected over three consecutive days from nine healthy donors. Donors had normal ejaculate volume, sperm count, sperm motility, morphology, and leukocyte count. No significant intra-donor differences were seen in these parameters over time. No significant differences were observed in the percentage of CD3+ cells, CD4+ cells, CD8+ cells, and the CD4:CD8 ratio in semen on consecutive days. However, within the CD4+ subset, when naive and memory CD4+ cells were measured, some day to day variability was suggested. No significant differences in CD3+, CD4+, CD8+, CD4/CD8 ratio, or naive and memory subsets were seen in the peripheral blood between sampling days. When semen was compared to peripheral blood some differences in immune subset values were observed, with an increase in the percentage of memory CD4+ cells in semen being the most striking. This finding may be relevant to HIV transmission, since others have shown that this cell may be preferentially infected with HIV and is the primary reservoir for virus in infected individuals.