MRI-based finite-element analysis of left ventricular aneurysm

Tagged MRI and finite-element (FE) analysis are valuable tools in analyzing cardiac mechanics. To determine systolic material parameters in three-dimensional stress-strain relationships, we used tagged MRI to validate FE models of left ventricular (LV) aneurysm. Five sheep underwent anteroapical myocardial infarction (25% of LV mass) and 22 wk later underwent tagged MRI. Asymmetric FE models of the LV were formed to in vivo geometry from MRI and included aneurysm material properties measured with biaxial stretching, LV pressure measurements, and myofiber helix angles measured with diffusion tensor MRI. Systolic material parameters were determined that enabled FE models to reproduce midwall, systolic myocardial strains from tagged MRI (630 +/- 187 strain comparisons/animal). When contractile stress equal to 40% of the myofiber stress was added transverse to the muscle fiber, myocardial strain agreement improved by 27% between FE model predictions and experimental measurements (RMS error decreased from 0.074 +/- 0.016 to 0.054 +/- 0.011, P < 0.05). In infarct border zone (BZ), end-systolic midwall stress was elevated in both fiber (24.2 +/- 2.7 to 29.9 +/- 2.4 kPa, P < 0.01) and cross-fiber (5.5 +/- 0.7 to 11.7 +/- 1.3 kPa, P = 0.02) directions relative to noninfarct regions. Contrary to previous hypotheses but consistent with biaxial stretching experiments, active cross-fiber stress development is an integral part of LV systole; FE analysis with only uniaxial contracting stress is insufficient. Stress calculations from these validated models show 24% increase in fiber stress and 115% increase in cross-fiber stress at the BZ relative to remote regions, which may contribute to LV remodeling.     

The structure and function of the outer coat protein VP9 of Banna virus

Banna virus (BAV: genus Seadornavirus, family Reoviridae) has a double-shelled morphology similar to rotavirus and bluetongue virus. The structure of BAV outer-capsid protein VP9 was determined by X-ray crystallography at 2.6 A resolution, revealing a trimeric molecule, held together by an N-terminal helical bundle, reminiscent of coiled-coil structures found in fusion-active proteins such as HIV gp41. The major domain of VP9 contains stacked beta sheets with marked structural similarities to the receptor binding protein VP8 of rotavirus. Anti-VP9 antibodies neutralize viral infectivity, and, remarkably, pretreatment of cells with trimeric VP9 increased viral infectivity, indicating that VP9 is involved in virus attachment to cell surface and subsequent internalization. Sequence similarities were also detected between BAV VP10 and VP5 portion of rotavirus VP4, suggesting that the receptor binding and internalization apparatus, which is a single gene product activated by proteoloysis in rotavirus, is the product of two separate genome segments in BAV.     

Role of K-ras and Pten in the development of mouse models of endometriosis and endometrioid ovarian cancer

Epithelial ovarian tumors present a complex clinical, diagnostic and therapeutic challenge because of the difficulty of early detection, lack of known precursor lesions and high mortality rates. Endometrioid ovarian carcinomas are frequently associated with endometriosis, but the mechanism for this association remains unknown. Here we present the first genetic models of peritoneal endometriosis and endometrioid ovarian adenocarcinoma in mice, both based on the activation of an oncogenic K-ras allele. In addition, we find that expression of oncogenic K-ras or conditional Pten deletion within the ovarian surface epithelium gives rise to preneoplastic ovarian lesions with an endometrioid glandular morphology. Furthermore, the combination of the two mutations in the ovary leads to the induction of invasive and widely metastatic endometrioid ovarian adenocarcinomas with complete penetrance and a disease latency of only 7 weeks. The ovarian cancer model described in this study recapitulates the specific tumor histomorphology and metastatic potential of the human disease.     

Structural dynamics of nucleosome core particle: comparison with nucleosomes containing histone variants

The present study provides insights on the dominant mechanisms of motions of the nucleosome core particle and the changes in its functional dynamics in response to histone variants. Comparative analysis of the global dynamics of nucleosomes with native and variant H2A histones, using normal mode analysis revealed that the dynamics of the nucleosome is highly symmetric, and its interaction with the nucleosomal DNA plays a vital role in its regulation. The collective dynamics of nucleosomes are predicted to be dominated by two types of large-scale motions: (1) a global stretching-compression of nucleosome along the dyad axis by which the nucleosome undergoes a breathing motion with a massive distortion of nucleosomal DNA, modulated by histone-DNA interactions; and (2) the flipping (or bending) of both the sides of the nucleosome in an out-of-plane fashion with respect to the dyad axis, originated by the highly dynamic N-termini of H3 and (H2A.Z-H2B) dimer in agreement with the experimentally observed perturbed dynamics of the particular N-terminus under physiological conditions. In general, the nucleosomes with variant histones exhibit higher mobilities and weaker correlations between internal motions compared to the nucleosome containing ordinary histones. The differences are more pronounced at the L1 and L2 loops of the respective monomers H2B and H2A, and at the N-termini of the monomers H3 and H4, all of which closely interact with the wrapping DNA.     

Influence of aluminum tristearate and sucrose stearate as the dispersing agents on physical properties and release characteristics of Eudragit RS microspheres

The purpose of this research was to investigate the effects of different concentrations of polymer and sucrose stearate, aluminum tristearate as dispersing agents on microsphere properties and performance. The yield values of microspheres were over the 78%, and the encapsulation efficiencies were found to be ∼735. Particle sizes of microspheres prepared with aluminum tristearate were between 76 and 448 μm, while that of the microspheres containing sucrose stearate were between 521 and 2000 μm. Morphological and physicochemical properties of microspheres were investigated by scanning electron micrography and differential scanning calorimetry (DSC). DSC analysis indicated that verapamil hydrochloride formed a solid solution with acrylic polymers. In vitro release studies were performed using the flow-through cell method. While ∼80% of drug was released from the microspheres containing aluminum tristearate in 480 minutes, the same amount of drug was released from microspheres containing sucrose stearate in only 60 minutes. Chemical structures and concentrations of the dispersing agents were clearly effective on the physical properties of microspheres and their drug-release characteristics. Published: February 24, 2006     

The effect of levamisole and levamisole + vitamin C on oxidative damage in rats naturally infected with Syphacia muris

This study was performed to determine the effects of levamisole and levamisole + vitamin C against Syphacia muris naturally infection in rats and to detect its effect on the oxidative parameters in blood and tissues of host. For this purpose, natural infection was diagnosed using the cellophane tape method on the perianal region of rats. Infected rats (total 18) were divided into three groups. On the other hand six without helminth rats were used in this study as negative control group. Group 2 was given an orally levamisole HCl treatment with gastric gavage at a dose level of 20 mg/kg body weight in distilled water, every alternate day. Group 3 was given levamisole HCl via gastric gavage at a dose level of 20 mg/kg and vitamin C was given 1 g/L added to the drinking water. All the treatments continued for a period of 7 days. As a result; levamisole administered to rats at dose of 20 mg/kg orally 98.34% was found to be effective against adult S. muris in the rats. In addition to levamisole + vitamin C is effective to alleviate the oxidative damage in rats infected with S. muris.     

In vitro activity of sodium benzoate against clinically relevant Enterococcus faecalis and Enterococcus faecium isolates

The antimicrobial effects of sodium benzoate against Enterococcus faecalis and Enterococcus faecium were investigated. The MIC(90) of sodium benzoate were 64 mg/L for E. faecalis and 32 mg/L for E. faecium, while the MBC(90) were 128 mg/L and 64 mg/L, respectively. Although further studies are required for clinical evidence, sodium benzoate seems to be effective against Enterococcus spp.     

Crotalic and emarginellic acids: two triterpenes from Crotalaria emarginella and anti-inflammatory and anti-hepatotoxic activity of crotalic acid

The aerial parts of Crotalaria emarginella Vatke (Leguminosae) has afforded two triterpenes, characterized as 3alpha-hydroxy-arbor-12-ene-28-carboxylic acid, designated as crotalic acid (1), and 2beta,3beta,21-trihydroxy-arbor-12-ene-29-carboxylic acid, designated as emarginellic acid (2). The structures of the isolated products were elucidated on the basis of spectral and chemical studies. On screening the biological activity, the crotalic acid (1) exhibited a significant anti-inflammatory activity (dose: 10mg/kg), which showed 53% inhibitory effect. Whereas, the standard oxyphenyl butazone (100mg/kg) exhibited 69% inhibition with respect to carrageenan (0.05ml, 1%) used to cause inflammation in rat paw method. In addition, it also showed anti-hepatotoxic activity by 13-30% with respect to standard silybon-70 (35-57%) against CCl(4) induced toxicity in Wistar rats.     

Bistability in apoptosis: roles of bax, bcl-2, and mitochondrial permeability transition pores

We propose a mathematical model for mitochondria-dependent apoptosis, in which kinetic cooperativity in formation of the apoptosome is a key element ensuring bistability. We examine the role of Bax and Bcl-2 synthesis and degradation rates, as well as the number of mitochondrial permeability transition pores (MPTPs), on the cell response to apoptotic stimuli. Our analysis suggests that cooperative apoptosome formation is a mechanism for inducing bistability, much more robust than that induced by other mechanisms, such as inhibition of caspase-3 by the inhibitor of apoptosis (IAP). Simulations predict a pathological state in which cells will exhibit a monostable cell survival if Bax degradation rate is above a threshold value, or if Bax expression rate is below a threshold value. Otherwise, cell death or survival occur depending on initial caspase-3 levels. We show that high expression rates of Bcl-2 can counteract the effects of Bax. Our simulations also demonstrate a monostable (pathological) apoptotic response if the number of MPTPs exceeds a threshold value. This study supports our contention, based on mathematical modeling, that cooperativity in apoptosome formation is critically important for determining the healthy responses to apoptotic stimuli, and helps define the roles of Bax, Bcl-2, and MPTP vis-à-vis apoptosome formation.