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Biomedical subjects

Sachin Patil

Publications and source records attributed to Sachin Patil.

5 recordsLinked to original sources
PubMed2006

Palmitic acid-treated astrocytes induce BACE1 upregulation and accumulation of C-terminal fragment of APP in primary cortical neurons.

High-fat diet is a significant risk factor for the development of Alzheimer's disease (AD). In addition, the AD brain is characterized by elevated levels of fatty acids as compared to that of healthy controls. Despite this, it is unclear how elevated levels of fatty acids are related to the pathogenesis of AD. The present study examines the role of saturated fatty acid, palmitic acid (PA), in causing BACE1 upregulation and consequent amyloidogenic processing of beta-amyloid precursor protein (APP), one of the main characteristic signatures of AD pathology. Here, primary rat cortical neurons and astrocytes were treated with pathological concentration of PA. There was no change in the BACE1 levels in the rat cortical neurons treated directly with PA as compared to controls. The conditioned medium from PA-treated astrocytes, however, caused BACE1 upregulation in the cortical neurons. Moreover, there was a consequent increase in the cleavage of APP leading to the accumulation of the C-terminal fragment of APP (C99) in the cortical neurons. Co-treatment of neurons with 1,3-dimethyl urea (DMU), an antioxidant, decreased PA-induced upregulation in the levels of BACE1 and C99. The present results establish an important role of saturated fatty acids in AD-associated amyloidogenesis through astroglia-mediated oxidative stress.

Alzheimer Disease↗
PubMed2006

Cellular to tissue informatics: approaches to optimizing cellular function of engineered tissue.

Tissue engineering is a rapidly expanding, multi-disciplinary field in biomedicine. It provides the ability to manipulate living cells and biomaterials for the purpose of restoring, maintaining, and enhancing tissue and organ function. Scientists have engineered various tissues in the body, from skin substitutes to artificial nerves to heart tissues, with varying degrees of success. Although the field of tissue engineering has come a long way since its first successful demonstration by Bisceglie in the 1930s, methods of coaxing them into functional tissues have been predominantly empirical to date. To successfully develop tissue-engineered organs, it is important to understand how to maintain the cells under conditions that maximize their ability to perform their physiological roles, regardless of their environment. In that context, a methodology that combines empirical data with mathematical and statistical techniques, such as metabolic engineering and cellular informatics, to systematically determine the optimal (1) type of cell to use, (2) scaffold properties and the corresponding processing conditions to achieve those properties, and (3) the required types and levels of environmental factors and the operating conditions needed in the bioreactor, will enable the design of viable and functional tissues tailored to the specific requirements of individual situations.

Animals↗
PubMed2006

Study of formulation variables on properties of drug-gellan beads by factorial design.

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3(3) factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85-1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48-98.28% w/w and 72.52-92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12-35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3-4 h in pH 7.4 phosphate buffer.

Calcium Chloride↗
PubMed2005

Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of tau in primary rat cortical neurons.

Epidemiological studies suggest that high fat diets significantly increase the risk of Alzheimer's disease (AD). In addition, the AD brain is characterized by high fatty acid content compared to that of healthy subjects. Nevertheless, the basic mechanism relating elevated fatty acids and the pathogenesis of AD remains unclear. The present study examines the role of fatty acids in causing hyperphosphorylation of the tau protein, one of the characteristic signatures of AD pathology. Hyperphosphorylation of tau disrupts the cell cytoskeleton and leads to neuronal degeneration. Here, primary rat cortical neurons and astrocytes were treated with saturated free fatty acids (FFAs), palmitic and stearic acids. There was no change in the levels of phosphorylated tau in rat cortical neurons treated directly with these FFAs. The conditioned media from FFA-treated astrocytes, however, caused hyperphosphorylation of tau in the cortical neurons at AD-specific phospho-epitopes. Co-treatment of neurons with N-acetyl cysteine, an antioxidant, reduced FFA-induced hyperphosphorylation of tau. The present results establish a central role of FFAs in causing hyperphosphorylation of tau through astroglia-mediated oxidative stress.

Alzheimer Disease↗