In-depth synthetic, physicochemical and in vitro biological investigation of a new ternary V(IV) antioxidant material based on curcumin.

Curcumin is a natural product with a broad spectrum of beneficial properties relating to pharmaceutical applications, extending from traditional remedies to modern cosmetics. The biological activity of such pigments, however, is limited by their solubility and bioavailability, thereby necessitating new ways of achieving optimal tissue cellular response and efficacy as drugs. Metal ion complexation provides a significant route toward improvement of curcumin stability and biological activity, with vanadium being a representative such metal ion, amply encountered in biological systems and exhibiting exogenous bioactivity through potential pharmaceuticals. Driven by the need to optimally increase curcumin bioavailability and bioactivity through complexation, synthetic efforts were launched to seek out stable species, ultimately leading to the synthesis and isolation of a new ternary V(IV)-curcumin-(2,2'-bipyridine) complex. Physicochemical characterization (elemental analysis, FT-IR, Thermogravimetry (TGA), UV-Visible, NMR, ESI-MS, Fluorescence, X-rays) portrayed the solid-state and solution properties of the ternary complex. Pulsed-EPR spectroscopy, in frozen solutions, suggested the presence of two species, cis- and trans-conformers. Density Functional Theory (DFT) calculations revealed the salient features and energetics of the two conformers, thereby complementing EPR spectroscopy. The well-described profile of the vanadium species led to its in vitro biological investigation involving toxicity, cell metabolism inhibition in S. cerevisiae cultures, Reactive Oxygen Species (ROS)-suppressing capacity, lipid peroxidation, and plasmid DNA degradation. A multitude of bio-assays and methodologies, in comparison to free curcumin, showed that it exhibits its antioxidant potential in a concentration-dependent fashion, thereby formulating a bioreactivity profile supporting development of new efficient vanado-pharmaceuticals, targeting (extra)intra-cellular processes under (patho)physiological conditions.

Mystery root ingestion.

Patients frequently come to the emergency department or contact a poison center following exposure to plants. These cases are often challenging owing to difficulty in correct identification of the involved plant. A case of two patients who demonstrated anticholinergic syndromes after ingesting an unknown, wild plant is described. Chemical analysis of two suspect plants collected in the same location allowed a probable diagnosis of poisoning from ingestion of henbane (Hyoscyamus niger).

Isotonic water transport in secretory epithelia.

The model proposed by Diamond and Bossert [1] for isotonic water transport has received wide acceptance in recent years. It assumes that the local driving force for water transport is a standing osmotic gradient produced in the lateral intercellular spaces of the epithelial cell layer by active solute transport. While this model is based on work done in absorptive epithelia where the closed to open direction of the lateral space and the direction of net transport are the same, it has been proposed that the lateral spaces could also serve as the site of the local osmotic gradients for water transport in secretory epithelia, where the closed to open direction of the lateral space and net transport are opposed, by actively transporting solute out of the space rather than into it. Operation in the backward direction, however, requires a lower than ambient hydrostatic pressure within the lateral space which would seem more likely to cause the space to collapse with loss of function. On the other hand, most secretory epithelia are characterized by transport into a restricted ductal system which is similar to the lateral intercellular space in the absorptive epithelia in that its closed to open direction is the same as that of net transport. In vitro micropuncture studies on the exocrine pancreas of the rabbit indicate the presence of a small but statistically significant increase in juice osmolality, 6 mOsm/kg H(2)O, at the site of electrolyte and water secretion in the smallest extralobular ducts with secretin stimulation which suggests that the ductal system in the secretory epithelia rather than the lateral intercellular space is the site of the local osmotic gradients responsible for isotonic water transport.

Micropuncture analysis of the cellular mechanisms of electrolyte secretion by the in vitro rabbit pancreas.

Micropuncture techniques have been used to study electrolyte secretion by the spontaneously secreting in vitro rabbit pancreas over a wide range of environmental conditions. Pancreatic secretion does not have a strong requirement for HCO3 and secretion continues at nearly normal rates when exogenous HCO3 is replaced by acetate. Acetate concentration in the juice averages 70 meq/liter, nearly three times the environmental concentration. The similar characteristics exhibited by HCO3 and acetate secretion indicate that they are secreted by a common mechanism involving active H transport. In vitro acid-base alterations demonstrate that the secretion rate is controlled by the environmental HCO3 concentration and to a much lesser extent by the pCO2. Secretion also requires active Na transport across the mucosal membrane. The effects of ouabain and a low Na environment strongly suggest coupling between the transport of Na and H and a cellular mechanism for electrolyte secretion is proposed involving Na-H exchange mechanisms at both the mucosal and serosal membranes.

A micropuncture investigation of the whole tissue mechanism of electrolyte secretion by the in vitro rabbit pancreas.

Micropuncture techniques have been used to examine electrolyte secretion by the in vitro rabbit pancreas. The concentration profiles of the major secreted ions and digestive protein and the electrical potential profile within the pancreatic ductal system have been determined during spontaneous and secretin-stimulated secretion. The active transport of both Na and HCO(3) are the rate-controlling steps in primary secretion. Spontaneous secretion is produced primarily within the intralobular ducts. The anion composition of this primary secretion depends on the secretion rate with HCO(3) ranging from about 70 meq/liter at low rates to about 110 meq/liter at high rates. With secretin stimulation the smaller extralobular ducts also secrete and this extralobular secretion has a higher HCO(2) content than that of the intralobular secretion. In the main collecting duct the anion composition of the juice is modified further by Cl-HCO(3) exchange which appears to be a passive process depending on the average residence time of the juice in the main duct.