Agomelatine protects heart and aorta against lipopolysaccharide-induced cardiovascular toxicity via inhibition of NF-kß phosphorylation.

The aim of this study was to investigate the possible ameliorating effects of agomelatine (AGO) on lipopolysaccharide (LPS)-induced endothelial and cardiac damage. Twenty-four female Wistar Albino rats divided into 3 groups as follows: Control, LPS and LPS + AGO. Total oxidant status (TOS), total antioxidant status (TAS), nuclear factor kappa beta (NF-kß)/p65, p-NF-kß, full caspase-8 (Cas-8) and cleaved cas-8 levels were measured in cardiac tissues and creatine kinase MB (CKMB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels in blood biochemically. In addition; cas-8, sirtuin-1 (SIRT-1), interleukin-4 (IL-4), interleukin-10 (IL-10), haptoglobin measured histopathologically in cardiac and aortic tissues. The levels of CKMB, AST, LDH and TOS were increased and TAS were decreased in the LPS group. In Western blot analyses NF-kß/p65, p-NF-kß/p65, full and cleaved cas-8 protein levels increased in cardiac tissues of LPS group. In histopathological and immunohistochemical evaluation of the heart sections; hyperemia, micro-hemorrhages and inflammatory cell infiltrations, increase of cas-8, haptoglobin, IL-4 and IL-10 and decrease of SIRT-1 levels were observed in cardiac and endothelial tissues of LPS groups. AGO treatment reversed all these parameters. It was shown that LPS-induced inflammation, oxidative stress and apoptosis via increasing of NF-kß/p65 signaling, decreasing of SIRT-1 levels and increase of cas-8 levels in heart and endothelial tissues respectively. AGO corrected all these parameters by its antioxidant, antiinflammatory and antiapoptotic activities.

Mid-infrared optical characterization of thin SiNx membranes.

The investigation of the optical constants (e.g., the refractive index n and the extinction coefficient κ) has been performed in the mid-infrared spectrum for various silicon nitride (SiNx) configurations. By exploiting the transfer matrix method formulation, photometric measurements of transmission and reflection have been used for iteratively calculating the optical parameters of interest. To ensure the reliability of the n and κ, the same material from which such parameters were extracted was deposited for three different thicknesses, e.g., 600, 200, and 100 nm. While the former is optically characterized, the remaining two are used for validation purposes. For each experimental/calculated comparison, the average (made over the whole considered spectrum interval) of the relative error never exceeds 1.5%, which ensures the correctness of the given n and κ. For the sake of completeness, a detailed analysis of the intrinsic limitations arising from the very nature of the method will also be conducted.

The Impact of Prophylactic Lacosamide on LPS-Induced Neuroinflammation in Aged Rats.

Sepsis-induced central nervous system damage is called sepsis-associated encephalopathy (SAE). In addition to neuroinflammation, oxidative stress and apoptosis act in the development of SAE. In the current study, we evaluated the protective effects of lacosamide (LCM) on neuroinflammation induced by lipopolysaccharide (LPS). Twenty-four Wistar albino rats were divided into 3 groups as controls, LPS group (5 mg/kg i.p.), and LPS plus LCM group (5 mg/kg i.p and 40 mg/kg i.p, respectively). In the rat brain, LPS-induced tissue damage was revealed histopathologically as hyperemia and microhemorrhages. LCM pretreatment ameliorated these histopathological changes. LPS decreased brain TAS levels and significantly increased MDA, CRP, HSP, IL-1ß, and TNF-α expressions in the cortex, hippocampus, and cerebellum. Western analysis revealed increased brain tissue levels of TNF-α, NF-Kß, and caspase-3 following LPS. Prophylactic LCM treatment reversed these parameters including oxidative stress, inflammation, and apoptosis in the cortex, hippocampus, and cerebellum.

Preparation and evaluation of furosemide containing orally disintegrating tablets by direct compression.

The purpose of this research was to develop and prepare orally disintegrating tablets (ODTs) containing furosemide by direct compression method. Furosemide, microcrystalline cellulose (MCC), low-substituted hydroxypropylcellulose LH-11 (L-HPC), aspartame, sodium stearyl fumarate were used for ODT formulation. MCC and L-HPC were used in ratios of 1:9 (ODT1) and 1:4 (ODT2). The results of the quality control parameters obtained for bulk powders (angle of repose, compressibility index, Hausner ratio, bulk density and volume, apparent density and volume, swelling of superdisintegrants and powder moisture) were taken as an indication of good compressibility of tablets. Both ODT1 and ODT2 disintegrated within 15 s and fulfilled the required disintegration time given by the European Pharmacopoeia (3 min). The average weight variation was less than 5% for both tablets. The friability of the tablets was less than 1%. Wetting time of both tablets was in the range of 12-21.7 s. Water absorption ratio was 1.41±0.03 for ODT1 and 1.96±0.10 for ODT2. Dissolution studies revealed that more than 85% of furosemide was dissolved in 15 min from both ODTs. Based on cell culture studies, permeability of furosemide was low (Papp=1x10-5 cm/s) but increased when prepared in the ODT form (ODT1: Papp=2x10-5 cm/s; ODT2: Papp=3.6x10-5 cm/s). Collectively, all these results showed that ODT formulations of furosemide were developed successfully. To improve patient compliance, ODT approach can be suggested for development and manufacturing of furosemide ODTs.

On-pump coronary artery bypass surgery in high-risk patients aged over 65 years (EuroSCORE 6 or more): impact on early outcomes.

The results of on-pump coronary artery bypass graft (CABG) surgery in 166 high-risk elderly patients (EuroSCORE 6 or more; over age 65 years [mean 71.8 years]) were compared with 176 low-risk elderly patients (EuroSCORE below 6; over age 65 years [mean 68.8 years]). There was no significant difference in hospital mortality or number of grafts between the two groups. Rates of inotropic agent use, intra-aortic balloon pump insertion and atrial fibrillation, and the duration of intensive care unit and hospital stay were significantly higher in high-risk than low-risk patients. There were no significant differences in the incidence of major complications between the two groups. The results suggest that, in selected patients, on-pump CABG can be safely performed in high-risk patients over 65 years old with no effect on mortality.

Hepatic disposition of trimethoprim and sulfamethoxazole.

Hepatic disposition of trimethoprim (TMP) and sulfamethoxazole (SMX) and the liver distributional volumes were investigated in the in situ perfused rat liver preparation. Perfusion experiments were conducted using Krebs-bicarbonate buffer delivered via the portal vein (15 ml/min) in a single-pass mode. Erythrocytes (intravascular marker) and Evans blue (extracellular marker) were used for the estimation of liver distributional volumes, and desiccation and freeze-drying methods were used for the estimation of liver water content. TMP and SMX were administered together as a bolus in the presence (1%) and absence of protein. Although SMX profiles displayed a characteristic sharp peak followed by a slower eluting tail in all cases, TMP profiles were dependent on protein; in the absence of protein, the early sharp peak was replaced by a flatter profile with a later peak. Fractional effluent recovery (F; 0.77 vs. 0.82) and hepatic clearance (CL(H); 3.44 vs. 2.70 ml/min) for TMP were not influenced by albumin; with SMX, F increased (0.32 vs. 0.60) and CL(H) decreased (10.2 vs. 6.0 ml/min) with an increase in the perfusate protein concentration. Hepatic extraction of TMP was low (<0.30), whereas it was intermediate (<0.70) for SMX. In addition, distributional volumes and total water content of the liver were successfully determined.

Hemostatic effects of microporous polysaccharide hemosphere in a rat model with severe femoral artery bleeding.

An appropriate hemostatic dressing for prehospital use should lower mortality due to uncontrolled hemorrhage. In this study, the investigators explored the hemostatic effects of Microporous Polysaccharide Hemosphere (MPH) applied in a rat model with severe femoral artery bleeding. Twelve rats were randomly assigned to MPH and control groups: The femoral artery of each rat was pierced to initiate bleeding. Then, 0.25 g MPH was poured into the bleeding site. A 200-g scale weight was placed over the bleeding site for 30 sec. At 30-sec intervals, the scale weight was removed, and hemostasis was assessed visually. After 30 sec, if the bleeding had ceased, the test was scored and checked as "passed at 30 sec." If the bleeding had not stopped, the same procedures were repeated a maximum of 3 times. If hemostasis could not be achieved even after the third application, the test was scored as failed. The same sequence of procedures was repeated for the control group without use of MPH and with only standard compression. Application of MPH resulted in complete control of bleeding in 2 of 6, 4 of 6, and 6 of 6 rats at 30, 60, and 90 sec, respectively. In the control group, however, hemostasis could not be achieved in all 6 rats, even at 90 sec. The difference between the 2 groups was statistically significant (P=.007). Application of MPH and compression with a scale weight significantly decreased the time of hemostasis in the rat model with femoral arterial bleeding.

Potential use of freeze-drying technique for estimation of tissue water content.

Desiccation and freeze-drying methods were used for the estimation of water content of various rat tissues. In the desiccation method, the tissue samples were cut into small pieces and subsequently dried at 40 degrees C to constant weight. In the freeze-drying method, the prefrozen tissue samples were freeze-dried (-50 degrees C) for 24 h. Tissue water contents obtained by the desiccation and freeze-drying methods were very similar, with no significant difference between them. Regardless of the method, the highest tissue water content was found in testes (0.841 +/- 0.010 ml/g for freeze-drying and 0.865 +/- 0.002 ml/g for desiccation); the lowest values were obtained in bone (0.254 +/- 0.007 ml/g for freeze-drying and 0.267 +/- 0.003 ml/g for desiccation). Upon correction for the water content of residual tissue blood, regardless of the drying method, significant differences were found between corrected and uncorrected tissue water values of all tissues. However, for a given method, the difference between the tissue water contents was not significant after correcting for residual blood. The water content values for all tissues (except bone) agree well with those published previously and obtained by desiccation. All these clearly suggest that the freeze-drying method can be used as an alternative to desiccation for estimation of tissue water content.

Reliability and efficiency of interphase-fish with alpha-satellite probe for detection of aneuploidy.

Early diagnosis is very important in pre- and postnatal diagnosis of Down syndrome. This study examines the use of fluorescence in situ hybridization (FISH) to detect trisomy 21 in interphase nuclei and metaphase chromosome obtained from fifty-four Down syndrome patients with a regular type trisomy 21. Three of them showed six hybridization signals on both interphase nuclei and metaphase spreads instead of five signals corresponding to two chromosomes 13 and three chromosomes 21 although they were cytogenetically trisomy 21. Simultaneous application of probe combination revealed that one of the extra signals of chromosomes 13/21 a-satellite probe was located on chromosome 22 in two cases and one extra signal on chromosomes 15 in one case. In addition, another case showed four hybridization signals on both interphase nuclei and metaphase spreads instead of five signals, indicating deletion of the chromosome specific alpha-satellite DNA sequence of chromosome 13/21. These centromeric sequence changes may have pathological significance in the appearance of aneuploidy because they may be involved in the important centromere function.

Hyperdiploid karyotype in a childhood MDS patient.

We present a rare case of a paediatric myelodysplastic syndrome (MDS) with congenital anomalies (frontal bossing and premature closure of anterior fontanelle). The case showed the clinical and biological features of a refractory anaemia excess blasts (RAEB). Bone marrow (BM) cytogenetics demonstrated a hyperdiploid karyotype, with several numerical abnormalities and unidentified rearrangements. Fluorescence in situ hybridization (FISH) using chromosome specific alpha-satellite and whole chromosome-specific painting probes verified the hyperdiploid karyotype, and confirmed the origin of the unknown markers and rearrangements more reliably than would be possible using conventional cytogenetic techniques.

VLSI implementation of neural networks.

Currently, fuzzy controllers are the most popular choice for hardware implementation of complex control surfaces because they are easy to design. Neural controllers are more complex and hard to train, but provide an outstanding control surface with much less error than that of a fuzzy controller. There are also some problems that have to be solved before the networks can be implemented on VLSI chips. First, an approximation function needs to be developed because CMOS neural networks have an activation function different than any function used in neural network software. Next, this function has to be used to train the network. Finally, the last problem for VLSI designers is the quantization effect caused by discrete values of the channel length (L) and width (W) of MOS transistor geometries. Two neural networks were designed in 1.5 microm technology. Using adequate approximation functions solved the problem of activation function. With this approach, trained networks were characterized by very small errors. Unfortunately, when the weights were quantized, errors were increased by an order of magnitude. However, even though the errors were enlarged, the results obtained from neural network hardware implementations were superior to the results obtained with fuzzy system approach.