Effects of subtoxic concentrations of benzoyl peroxide on cell lipid metabolism

Benzoyl peroxide (BP), a tumor promoter, has been shown to cause free-radical-induced lipid peroxidation and membrane damage at toxic concentrations. However, its effects on lipid metabolism at concentrations that were not overtly toxic have not been investigated. The purpose of the current study was to examine the effects of BP and its final degradation product, benzoic acid (BA), on lipid metabolism. Two cell lines, hamster cheek pouch (HCP) and human monocytes (THP-1), were used to determine the effects of BP, BA, and BP combined with FeCl2 on cell lipid metabolism. Cells were exposed to BP and 14C acetate for 24 h, or cells with prelabeled lipids were harvested, and the lipids were extracted and separated with the use of thin-layer chromatography. Lipid metabolism of some neutral lipids such as triglycerides was altered for both cell types in response to BP. Also, cholesterol content was reduced in THP-1 cells and a phospholipid, phosphatidylethanolamine (PE), was reduced in HCP cells. The final degradation product of BP, BA, failed to elicit any response in lipid metabolism. Subtoxic concentrations of BP induced changes in neutral lipids such as triglycerides and cholesterol. The metabolism of major phospholipids except PE remained unchanged. The effects were related to BP and its degradation and varied with the cell type.     

Correction to: Optimization of Ultrasonic Extraction of Major Phenolic Components from Flowers of Ghav-Patta (Argyreia Speciosa Linn.) Via Response Surface Model

Pharmaceutical Chemistry Journal -     

LM-PCR permits highly representative whole genome amplification of DNA isolated from small number of cells and paraffin-embedded tumor tissue sections.

Analysis of genetic changes is often hampered by insufficient starting DNA from limited clinical tissue specimens. We employed ligation-mediated PCR (LM-PCR) for global amplification of the genome to overcome this limitation, generating up to 5 microg of representative amplicons of genomic DNA from as little as one cell. We demonstrate successful global genome amplification in high-quality starting DNA source like laser-captured cultured cells, as well as partially degraded starting DNA from old formalin-fixed paraffin-embedded tissue sections. This process generates adaptor-tailed templates that can be repeatedly amplified almost ad infinitum. We have further modified this technique such that, instead of a single endonuclease digest, we can achieve higher amplicon coverage by combining 3 endonuclease digests prior to LM-PCR. As tested by examining amplification of STS sequences scattered genome-wide, the coverage was improved from the published 70% to 96%. The faithful representation of global losses and gains in the amplified genomic DNA was confirmed by array-comparative genomic hybridization. Further, we exemplify the utility of this technique for finer p53 point mutation analysis by PCR-SSCP. This technique is thus a clinically useful tool for globally amplifying and archiving DNA from finite sources like paraffin tissue sections, providing a potentially unlimited resource for genetic analyses.     

A novel synthetic route for the preparation of hydrolytically degradable synthetic hydrogels

A variety of approaches have been described for the modification of synthetic, water soluble polymers with hydrolytically degradable bonds and terminal vinyl groups that can be crosslinked in situ by photo- or redox-initiated free radical polymerization. However, changes in macromer concentration, functionality, and molecular weight commonly used to achieve variable degradation rates simultaneously alter hydrogel mechanical properties. Herein, we describe a novel, two-step synthetic route for the preparation of hydrolytically degradable, crosslinkable PEG-based macromers based on chemical intermediaries that form ester linkages with variable alkyl chain length. Changes in the concentration of a single macromer were shown to provide effective variation of degradation, but with corresponding significant changes in tensile properties. Through variation in the alkyl chain length of the chemical intermediary, variable degradation times ranging from weeks to months are achieved, without significantly affecting initial gelation efficiency, swelling, or tensile properties. When modified with adhesive ligands, hydrogels supported viability of encapsulated and adherent cells. Controlled release of a model protein (Immunoglobulin G) was attained as a function of hydrogel degradation rate. Independent control of hydrogel degradation and mechanical properties will offer improved flexibility for studying the effect of these material characteristics on cellular function and may be useful in the design of matrices for tissue engineering and controlled release of bioactive molecules.     

Fibrosarcoma of the maxillary antrum

A case of fibrosarcoma, arising from the right maxillary antrum, in a 40 year old female, is reported. Local recurrence occured within five months despite a complete excision through a lateral rhinotomy approach. The local spread involved the palate, causing severe dysphagia and a rapid deterioration of the general condition. Chemotherapy, using intra-arterial “Endoxan”, produced an initial transient relief of pain lasting for a few days only.     

Pediatric pulmonary arterial hypertension: current and emerging therapeutic options

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare disease in neonates, infants and children that is associated with significant morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking and although mortality has decreased as therapeutic options have increased over the past several decades, outcomes remain unacceptable. AREAS COVERED: This review summarizes the currently available therapies for neonates, infants and children with PAH and describes emerging therapies in the context of what is known about the underlying pathophysiology of the disease. EXPERT OPINION: All of the currently approved PAH therapies impact one of three endothelial-based pathways: nitric oxide-guanosine-3'-5'cyclic monophosphate, prostacyclin or endothelin-1. The beneficial effects of these agents may relate to their impact on pulmonary vascular tone, and/or their antiproliferative and antithrombotic properties. Fundamental advances in PAH therapy are likely to relate to: i) a better understanding of PAH subpopulations, allowing for therapies to be better tailored to individual patients and pathophysiologic processes; and ii) therapies that promote the regression of advanced structural remodeling.     

Grid cells generate an analog error-correcting code for singularly precise neural computation

Entorhinal grid cells in mammals fire as a function of animal location, with spatially periodic response patterns. This nonlocal periodic representation of location, a local variable, is unlike other neural codes. There is no theoretical explanation for why such a code should exist. We examined how accurately the grid code with noisy neurons allows an ideal observer to estimate location and found this code to be a previously unknown type of population code with unprecedented robustness to noise. In particular, the representational accuracy attained by grid cells over the coding range was in a qualitatively different class from what is possible with observed sensory and motor population codes. We found that a simple neural network can effectively correct the grid code. To the best of our knowledge, these results are the first demonstration that the brain contains, and may exploit, powerful error-correcting codes for analog variables.     

Plasma fucosyltransferase as an indicator of imminent blastic crisis

Plasma fucosyltransferase activity was evaluated as an indicator of an impending blastic transformation in 25 patients with chronic granulocytic leukemia (CGL). Fifteen age-and sex-matched controls were also studied. The level of enzyme activity was significantly higher in the plasma of patients with blastic transformation (1,630 ± 570 units) compared with steady state chronic granulocytic leukemia (509 ± 110 units) and normal controls (354 ± 57 units). In three patients with CGL, a rise in fucosyltransferase activity preceded any other clinical or laboratory parameter of blastic transformation by 16–20 weeks.