Synaptic noise facilitates the emergence of self-organized criticality in the Caenorhabditis elegans neuronal network.

Avalanches with power-law distributed size parameters have been observed in neuronal networks. This observation might be a manifestation of self-organized criticality (SOC). Yet, the physiological mechanisms of this behaviour are currently unknown. Describing synaptic noise as transmission failures mainly originating from the probabilistic nature of neurotransmitter release, this study investigates the potential of this noise as a mechanism for driving the functional architecture of the neuronal networks towards SOC. To this end, a simple finite state neuron model, with activity dependent and synapse specific failure probabilities, was built based on the known anatomical connectivity data of the nematode Ceanorhabditis elegans. Beginning from random values, it was observed that synaptic noise levels picked out a set of synapses and consequently an active subnetwork that generates power-law distributed neuronal avalanches. The findings of this study bring up the possibility that synaptic failures might be a component of physiological processes underlying SOC in neuronal networks.

Intact neurovascular coupling during executive function in migraine without aura: interictal near-infrared spectroscopy study.

An altered neurovascular coupling has been proposed in migraine. We aimed to investigate neurovascular coupling during a mental task interictally in patients with migraine without aura (MO) by near-infrared spectroscopy (NIRS). Twelve migraineurs and 12 healthy controls were included. Using NIRS, we recorded the magnitude and latency of cortical changes in oxyhaemoglobin (HbO(2)) and deoxyhaemoglobin (Hb) during the colour-word matching Stroop test via 16 channels covering the forehead. We found no differences in the magnitude of responses between migraineurs and healthy subjects in the incongruent Stroop task subtracted by the neutral Stroop task on either side of the frontal cortex for HbO(2) (left, P = 0.984; right, P = 0.406) or Hb (left, P = 0.689; right, P = 0.406) values. No differences in error rate (P = 0.611) or reaction time (P = 0.936) were found between healthy subjects and MO patients for incongruent tasks. The present study suggests that vascular reactivity and oxygen supply during a mental task in patients with MO are intact interictally.

Quantification of neurometabolites in subacute sclerosing panencephalitis by 1H-MRS.

The authors studied 20 patients with subacute sclerosing panencephalitis (SSPE) to investigate the correlations between MRI, magnetic resonance spectroscopy (MRS), and clinical status. MRI findings did not correlate with clinical status. By contrast, all patients had reductions in N-acetyl aspartate (NAA) and increase in myoinositol (mI) (p < 0.01), and NAA and mI concentrations correlated with clinical severity (p < 0.05). During follow-up, NAA continued to decline. (1)H-MRS may be a useful measure of disease severity and progression in SSPE.

Adaptive modeling of sound transmission in the respiratory system.

In this study, adaptive filtering techniques have been used in an attempt to model the respiratory system. The respiratory system has been considered as a dynamic system for which input-output relationship is to be defined. Simultaneous measurement of the respiratory sounds over the trachea and posterior chest were made, with the signal from the trachea forming the input to a finite impulse response filter and the signal from the posterior chest forming the desired response of the filter. The chest cavity was stimulated with speech sounds. Least-mean square algorithm was used to update filter coefficients. The learning curves of the filter are presented in the paper. It can be concluded that adaptive filtering is a promising way to characterize transmission characteristics of the respiratory system and further improvement may be obtained if anatomical information is integrated in the modeling process.

Using lung sounds in classification of pulmonary diseases according to respiratory subphases.

Auscultation-based diagnosis of pulmonary disorders relies heavily on the presence of adventitious sounds and on the altered transmission characteristics of the chest wall. The phase information of the respiratory cycle within which adventitious sounds occur is very helpful in diagnosing different diseases. In this study, respiratory sound data belonging to four pulmonary diseases, both restrictive and obstructive, along with healthy respiratory data are used in various classification experiments. The sound data are separated into six subphases, namely, early, mid, late inspiration and expiration and classification experiments using a neural classifier are carried out for each subphase. The AR parameters acquired from segmented sound signals, prediction error and the ratio of expiration to inspiration durations are used to construct the feature set to the neural classifier. Classification experiments are carried out between healthy and pathological sound segments, between restrictive and obstructive sound segments and between two different disease sound segments. The results indicate that the classifier performance demonstrates subphase dependence for different diseases. These results may shed light in eliminating redundant feature spaces in building an expert system using lung sounds for pulmonary diagnosis.

Characterization of poly((N-trimethylammonium) ethyl methacrylate)-based gene delivery systems.

We have synthesized a hydrophilic cationic homopolymer of N-trimethylammonium ethyl methacrylate chloride (pTMAEM) and its copolymers with 1-vinyl-2-pyrrolidone (VP) and methyl methacrylate (MMA) at various monomer ratios and examined the physicochemical and biological characteristics of polymer/DNA complexes. All the (co)polymers were able to condense DNA to small particles and protect it from nuclease degradation. The particle size of pTMAEM/DNA complexes was smaller (550-175 nm) than the other polymers (1200-300 nm) tested. The zeta potential of the complexes was increased with increasing (co)polymer/DNA weight ratios and reached the constant value. The plateau value slightly decreased from +28 mV to +21 mV (P > 0.05) when the monomer content was increased. The optimal transfection efficiency of pTMAEM/DNA (655 mU/mg protein) was found at 0.5 polymer/DNA weight ratio and was reduced with increasing weight ratios due to increased cytotoxicity. The maximum transfection efficiency of copolymer/DNA was observed at a weight ratio of one and transfection efficiency slightly decreased with increasing monomer content in the copolymers. Overall, pTMAEM-VP/DNA complexes showed reduced cytotoxicity and increased transfection efficiency as compared with the other (co)polymers tested.

Enhanced plasmid DNA transfection with lysosomotropic agents in cultured fibroblasts.

Transfer of plasmid DNA into mammalian cells has posed major challenges for gene therapy. Most non-viral vectors are known to internalize in the cells by endocytosis. Therefore, low transfection efficiency of non-viral vectors may be due to intracellular degradation of input DNA in the endosomes and/or lysosomes. DNA degradation can be inhibited either by inactivating the lysosomal enzymes or obliterating endosome fusion to lysosomes using lysosomotropic agents. We report here the effects of individual lysosomotropic agents such as chloroquine, polyvinylpyrolidone (PVP) and sucrose on beta-gal expression in cultured fibroblasts COS, 293 and CHO. Cell viability was influenced by type, exposure time and concentration of lysosomotropic agents. Exposure to chloroquine at high concentration (1000 microM) or more than 4 h at any concentration (10-1000 microM) caused extensive cell death, however, cytotoxicity due to sucrose (5-500 mM) and PVP (0.01-1 mg/ml) was minimal in the cell lines tested. All the agents utilized in this study enhanced the gene expression and the transfection efficiency followed the order of sucrose>chloroquine>PVP at the concentrations used in all cell lines. Results suggest that lysosomotropic agents can enhance transfection efficiency but the degree of transgene expression may be cell- and agent-specific. Of the agents studied, sucrose appears to be an attractive agent in improving gene expression without toxic effect in the cultured fibroblasts. Thus, it can be used as an excipient in the formulation of new gene delivery systems.

Applications of genetic engineering in veterinary medicine.

A mutation of just one gene will cause abnormal cell behavior leading to the synthesis of a dysfunctional protein. This mutation will inevitably result in the cell functioning only marginally or not at all. Other genetic mutations interfere with the cell's normal life cycle, especially the cell-division cycle. The goal behind recombinant DNA technology is to deliver the correct version of a mutated gene to the cell so that the expression will lead to the normal production of protein and the restoration of normal cell function. This can be considered qualitatively different from other conventional treatments due to genetic material being a putative therapeutic agent. By altering the genetic material of cells, gene therapy may correct, or one day cure, the specific disease pathophysiology. Genetic engineering has been used in veterinary medicine to diagnose, prevent and treat diseases, breed different species and produce transgenic animals for therapeutic proteins or xenografting. In this review the current status of recombinant DNA technology and its application in veterinary medicine together with the obstacles to, and applications of, genetic engineering in veterinary medicine are discussed.

Solid tumor chemotherapy and in vivo distribution of fluorouracil following administration in poly(L-lactic acid) microspheres.

The physicochemical properties and in vivo distribution of poly(L-lactide) (L-PLA) microspheres containing 5-fluorouracil (5-FU) prepared by a solvent evaporation method were evaluated for potential use in the treatment of liver cancers. Two different molecular weight polymers of L-PLA [L-PLA1 (152,500 Da) and L-PLA2 (52,000 Da)] were used to prepare 5-FU-loaded microspheres. The mean particle size of the microspheres was 3-6 microns, and there was a direct relationship between the mean particle size and the molecular weight of the polymers. The drug release behavior from microspheres exhibited a diffusion mechanism in different dissolution media, with the molecular weight of the polymer being a major factor in controlling the drug release and degradation rates. Following intravenous injection of 99mTc-labeled L-PLA microspheres, with or without 5-FU, or free 5-FU into mice, L-PLA2 microspheres localized mainly in the liver. The disappearance rate of radioactivity from the tissue was very slow in comparison to that of free 5-FU. The results were confirmed by histological examination of liver tissue following administration of fluorescein particles. In addition, growth of a human liver tumor as first transplant generation under the renal capsule of immunocompetent rats and antitumor activity of L-PLA2 microspheres were investigated. Histological examination by optical microscopy showed that there was no neoplastic tissue of the kidney or in other tissues examined after treatment.

Pre- and postprandial total serum bile acid concentration following acute liver damage in dogs.

The importance of preprandial and postprandial total bile acids were investigated in dogs with liver damage induced by carbon tetrachloride (CCl4) administration. Six healthy and mature dogs were used. After base-line clinical and biochemical examinations, hepatocellular damage was induced by oral CCl4 administration. Determinations of plasma total protein (TP), albumin (Alb), total and direct bilirubin (TBil, DBil), alanine aminotransferase (ALT) and alkaline phosphate (ALP) along with histologic examination of the livers 10 days following CCl4 administration were conducted to ensure that hepatic damage was in fact induced by the CCl4 administration. Twelve h fasting preprandial and 2 h postprandial serum total bile acids (PRSBA, POSBA) concentrations were also measured. The median plasma TP, Alb, TBil and DBil concentrations did not show any difference (P > 0.05) during the study. Plasma ALT activities increased significantly (P < 0.05, P < 0.01) between on the 3rd and 10th days of the experiment. The median serum values of PRSBA and POSBA were significantly different (P < 0.01) on the first day and continued to be different during the experiment. In conclusion, POSBA seemed to be more reliable than PRSBA in the diagnosis of hepatic necrosis.

Formulation and in vitro-in vivo evaluation of sustained-release lithium carbonate tablets.

The release of lithium carbonate incorporated into polymethylmethacrylate, polyvinyl chloride, hydrogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.