Caffeic Acid, a versatile pharmacophore: an overview.

The caffeic acid scaffold, which is abundant in nature, is extremely versatile and is found in a number of biologically active molecules. The purpose of this review is to provide an overview of the pharmacological activity of synthetic caffeic acid analogs including recent reports of anti-inflammatory, anti-cancer, and antiviral activities of these compounds.

Evidence for in vitro binding of pectin side chains to cellulose.

Pectins of varying structures were tested for their ability to interact with cellulose in comparison to the well-known adsorption of xyloglucan. Our results reveal that sugar beet (Beta vulgaris) and potato (Solanum tuberosum) pectins, which are rich in neutral sugar side chains, can bind in vitro to cellulose. The extent of binding varies with respect to the nature and structure of the side chains. Additionally, branched arabinans (Br-Arabinans) or debranched arabinans (Deb-Arabinans; isolated from sugar beet) and galactans (isolated from potato) were shown bind to cellulose microfibrils. The adsorption of Br-Arabinan and galactan was lower than that of Deb-Arabinan. The maximum adsorption affinity of Deb-Arabinan to cellulose was comparable to that of xyloglucan. The study of sugar beet and potato alkali-treated cell walls supports the hypothesis of pectin-cellulose interaction. Natural composites enriched in arabinans or galactans and cellulose were recovered. The binding of pectins to cellulose microfibrils may be of considerable significance in the modeling of primary cell walls of plants as well as in the process of cell wall assembly.

Isolation from sugar beet cell walls of arabinan oligosaccharides esterified by two ferulic acid monomers.

Side chains of sugar beet (Beta vulgaris) pectins, which are mainly composed of arabinose (Ara) and galactose (Gal) residues, are esterified by ferulic acid units. Enzymatic hydrolysis of beet cell walls yielded several feruloylated oligosaccharides, which were separated by hydrophobic interaction chromatography. Two new oligomers were isolated in the fraction eluted by 25:75 (v/v) ethanol:water. An arabinotriose and an arabinotetraose esterified by two ferulic acid residues were obtained, and their structure was elucidated by mass spectrometry. It is shown that feruloyl groups are linked to O-5 of Ara residues, in addition to the known O-2 position. This work establishes for the first time, to our knowledge, that two neighboring Ara units may be esterified by two ferulic acid units. This close proximity may have important biochemical implications.

Texture analysis of the brain: from animal models to human applications.

Magnetic resonance imaging (MRI) is widely used to image brain in vivo both in studies in animal models and for human diagnosis. A large part of the value of MRI is due to the fact that soft tissue contrast is enhanced by the substantial variation in the T(1) and T(2) relaxation times between tissues. It may be possible to use an alternative approach, which does not rely on the absolute measurement of relaxation times. Generally speaking, textures are complex visual patterns composed of entities, or subpatterns, that have characteristic brightness, color, slope, size, etc. Thus, texture can be regarded as a similarity grouping in an image. The properties of the local subpattern give rise to the perceived lightness, uniformity, density, roughness, regularity, linearity, frequency, phase, directionality, coarseness, randomness, fineness, smoothness, and granulation. The purpose here is to illustrate how texture analysis can be used in animal models and in human clinical applications, as well as in the search for further pharmacological applications in humans. Thus, this article summarzes three different MRI studies in (i) rats, using the lipocarpine epileptic rat model as an animal model; (ii) patients with Alzheimer's disease; and (iii) patients with schizophrenia.

Spinal mechanisms contribute to analgesia produced by epidural sufentanil combined with bupivacaine for postoperative analgesia.

UNLABELLED: When used alone, lipid-soluble epidural opioids are thought to produce analgesia supraspinally via systemic absorption. However, spinal opioids and local anesthetics have been shown to act synergistically at the spinal level in animal studies. We, therefore, tested the hypothesis that sufentanil requirements will be less when given epidurally than IV in patients simultaneously given epidural bupivacaine after major abdominal surgery. Forty patients were anesthetized with isoflurane and epidural bupivacaine for major abdominal surgery. After surgery, each was given a continuous epidural infusion of bupivacaine at a rate of 5 mg/h and sufentanil patient-controlled analgesia (PCA). In a randomized, double-blinded fashion, the sufentanil was given either epidurally or IV. PCA settings were the same in each group. For 60 hrs after surgery, the following variables were measured: pain scores at rest, during mobilization, and during coughing; extension of sensory block; side effects; and sufentanil consumption. Pain scores, extension of sensory block, and the incidence of side effects did not differ between the two groups. Consumption of sufentanil in the epidural group was half that of the IV group (48 h after surgery: 107 +/- 57 microg versus 207 +/- 100 microg for the epidural and IV groups, respectively; P < 0.05). We conclude that spinal mechanisms contribute to the analgesia produced by epidural sufentanil in combination with a local anesthetic. IMPLICATIONS: When combined with epidural bupivacaine, the sufentanil requirement was 50% less when given epidurally than IV. Epidural sufentanil thus appears to have a spinal mechanism of action.

Immobilization of L-asparaginase into a biocompatible poly(ethylene glycol)-albumin hydrogel: evaluation of performance in vivo.

The L-asparaginase of Escherichia coli (ASNase) is currently used in combination with antineoplastic drugs to treat various lymphoblastic leukaemias. However, its use is limited by severe immunological reactions and the short serum half-life associated with the enzyme. Immobilization of ASNase into a biocompatible matrix can greatly decrease the immunogenicity of the enzyme, increase its half-life in vivo and its therapeutic index. Thus the E. coli ASNase was immobilized in a biocompatible hydrogel made of rat serum albumin and poly(ethylene glycol) (PEG; molecular mass 10 kDa). The effectiveness of this enzymic bioreactor to deplete serum L-asparagine was evaluated after its peritoneal implantation in rats. Seven units of immobilized ASNase/rat depleted serum asparagine to an undetectable level (< 1 microM) during 6 days, while 5 units of immobilized ASNase/rat decreased the level of serum asparagine by 85-90% during at least 2 days. Under both conditions asparagine levels returned to normal about 10 days after surgery, and hydrogels still retained 80% of their enzymic activity when assayed in vitro. After 10-14 days in vivo, hydrogels became opaque and surrounded by a fibrotic capsule with a few inflammatory sites. Nevertheless, the enzymic hydrogel showed great stability in vivo, and, after 4 months of implantation, 12% of the initial ASNase activity was still present. At 6 months, histological analysis showed stabilization of the fibrotic capsule thickness. Assays on the levels of ASNase and asparagine synthetase indicated an induction of the latter activity, mainly in the pancreas when compared with the level observed in spleen or liver. ELISA tests at 28 days and 120 days showed the presence of anti-ASNase (and, in lower amounts, anti-PEG) antibodies in sera of implanted rats. As observed with other enzyme-immobilization systems used in vivo, the formation of fibroblast-like cell layers around the implant, which block the translocation of the substrate into the enzymic matrix, is the major factor affecting the performance and longevity of the bioreactor.

Immobilization of L-asparaginase into a biocompatible poly(ethylene glycol)-albumin hydrogel: I: Preparation and in vitro characterization.

The feasibility of the immobilization of Escherichia coli L-asparaginase into a hydrogel matrix made of poly-(ethylene glycol) (PEG) and BSA was demonstrated. After immobilization a 200-fold increase in the Km value was observed. The use of an L-aspartic acid analogue, carbobenzoxy-L-aspartic acid and surface modification by methoxy-PEG of molecular mass 5 kDa cause a only a slight gain in affinity of the enzyme for its natural substrate. The immobilized L-asparaginase has an optimal activity over a larger range of pH than the native enzyme, owing to the effect of the matrix. At a physiological pH of 7.3, the immobilized enzyme retained 90% of its activity compared with only 43% for the native form. The immobilized enzyme retained a high proportion of its initial activity, more than 90% after 50 days of incubation at 37 degrees C, even in the presence of its substrate. This may be compared with a half-life of 2 days observed for native enzyme incubated under the same conditions. These results suggest that the BSA-PEG matrix can be very useful for enzyme immobilization and, taking into account the good biocompatibility of the matrix, one can expect that this matrix will provide a functional bioreactor for use in vivo.

Poly(ethylene glycol)-serum albumin hydrogel as matrix for enzyme immobilization: biomedical applications.

Poly(ethylene glycol)-albumin hydrogels were implanted in mice in subcutaneous position to study their biocompatibility. After one month of implantation, the fibrous capsule formed around the implant was thin and the inflammatory tissue was limited. Acid phosphatase (AP) was selected to evaluate the hydrogel as matrix for enzyme immobilization. AP-hydrogels were prepared using activated PEG (PEGa) of different molecular weights (M.W. 4,600 to 20,000) to evaluate the effect of the matrix composition on the activity of AP. The apparent Km of the immobilized AP was 16 to 20 times higher than the Km of the soluble enzyme. The apparent Km value decreases with the increase of the chain length of the PEGa used. This can be correlated to an increase in the hydrogel porosity. The operational stability of the AP was markedly improved after immobilization by 110 to 160 times according to the PEGa molecular weight involved. Also, asparaginase (ASNase) was immobilized in PEGa (M.W. 10,000)-albumin-hydrogel as a model for in vivo bioreactor. ASNase hydrogels were implanted in the peritoneal cavity of rats; 7 days later, 75% of the initial enzyme activity were retrieved.