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Coordination of Fe(III) to carboxylates in polyuronic acid hydrogels was used to impart photochemical reactivity to polysaccharide-based hydrogels. This photochemical reaction was then used for light-initiated polymerization to create hydrogels with advanced mechanical and conductive properties by capturing the photogenerated radical with a monomer, either acrylamide, methyl methacrylate, or aniline. The photopolymerization of acrylamide using the Fe(III)-polyuronic acid was quantified in solution and the polymerization efficiency was determined under different conditions. Poly(methyl methacrylate) (PMMA)-modified hydrogels were analyzed by the contact angle, optical microscopy, and rheology. This confirmed formation of a stiff, hydrophobic, PMMA layer on polysaccharide hydrogels after light irradiation in methyl methacrylate. Polyaniline-modified hydrogels were characterized by current-voltage sweeps, which showed the formation of conductive polyaniline integrated into the hydrogel after light irradiation in the aniline monomer. This strategy provided a facile approach to create either layered hydrogels with different stiffness and hydrophobicity or hybrid conductive hydrogels using the simple photochemical reaction of blue light irradiation of Fe(III) coordinated to polyuronic acids.

The title compound, [Cu2(C19H23N7O)(C2H3O2)4] n , was obtained via reaction of copper(II) acetate with the coordinating ligand, 6-ethoxy-N 2,N 4-bis[2-(pyridin-2-yl)ethyl]-1,3,5-triazine-2,4-diamine. The crystallized product adopts the monoclinic P21/c space group. The metal core exhibits a paddle-wheel structure typical for dicopper tetraacetate units, with triazine and pyridyl nitrogen atoms from different ligands coordinating to the two axial positions of the paddle wheel in an asymmetric manner. This forms a coordination polymer with the segments of the polymer created by the c-glide of the P21/c setting of the space group. The resulting chains running along the c-axis direction are held together by intramolecular N—H...O hydrogen bonding. These chains are further packed by dispersion forces, producing an extended three-dimensional structure.

The photochemistry of Fe(III) coordinated to natural uronate-containing polysaccharides has been investigated quantitatively in aqueous solution. It is demonstrated that the photoreduction of the coordinated Fe(III) to Fe(II) and oxidative decarboxylation occurs in a variety of uronate-containing polysaccharides. The photochemistry of the Fe(III)-polyuronic acid system generated a radical species during the reaction which was studied using the spin trapping technique. The identity of the radical species from this reaction was confirmed as CO2•- indicating that both bond cleavage of the carboxylate and oxidative decarboxylation after ligand to metal charge transfer radical reactions may be taking place upon irradiation. Degradation of the polyuronic acid chain was investigated with dynamic light scattering, showing a decrease in the hydrodynamic radius of the polymer assemblies in solution after light irradiation that correlates with the Fe(II) generation. A decrease in viscosity of Fe(IIII)-alginate after light irradiation was also observed. Additionally, the photochemical reaction was investigated in plant root tissue (parsnip) demonstrating that Fe(III) coordination in these natural materials leads to photoreactivity that degrades the pectin component. These results highlight that this Fe(III)-polyuronic acid can occur in many natural systems and may play a role in biogeochemical cycling of iron and ferrous iron generation in plants with significant polyuronic acid content.

Inexpensive and sustainable methods are needed to reclaim nutrients from agricultural waste solutions for use as a fertilizer while decreasing nutrient runoff. Fe(III)–polysaccharide hydrogels are able to flocculate solids and absorb nutrients in liquid animal waste from Confined Animal Feeding Operations (CAFOs). Fe(III)–alginate beads absorbed 0.05 mg g–1 NH4+ and NO3- from 100 ppm solutions at pH = 7, with > 80% phosphate uptake and ∼30% uptake of ammonium and nitrate. Ammonium uptake from a raw manure solution (1420 ppm NH4+) showed a significant 0.7 mg g–1 uptake. Tomato plant trials carried out with Fe(III)–alginate hydrogel beads in greenhouse conditions showed controlled nutrient delivery for the plants compared to fertilizer solution with the same nutrient content. Plants showed an uptake of Fe from the gel beads, and Fe(III)–alginate hydrogel beads promoted root growth of the plants. The plants treated with nutrient-loaded Fe(III)–alginate hydrogels yielded comparable tomato harvest to plants treated with the conventional fertilizer solution.

Photoresponsive hydrogels from polysaccharides and Fe(III) were used as a new system to capture and release PO43– from waste solutions. Uptake of 0.6–1.5 mg of phosphate per gram of hydrogels was d...

Made available in DSpace on 2020-12-12T01:58:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The locus coeruleus (LC) is a pontine nucleus important for respiratory control and central chemoreception. It is affected in Alzheimer's disease (AD) and alteration of LC cell function may account for respiratory problems observed in AD patients. In the current study, we tested the electrophysiological properties and CO2/pH sensitivity of LC neurons in a model for AD. Sporadic AD was induced in rats by intracerebroventricular injection of 2 mg/kg streptozotocin (STZ), which induces behavioral and molecular impairments found in AD. LC neurons were recorded using the patch clamp technique and tested for responses to CO2 (10% CO2, pH = 7.0). The majority (~60%) of noradrenergic LC neurons in adult rats were inhibited by CO2 exposure as indicated by a significant decrease in action potential (AP) discharge to step depolarizations. The STZ-AD rat model had a greater sensitivity to CO2 than controls. The increased CO2-sensitivity was demonstrated by a significantly stronger inhibition of activity during hypercapnia that was in part due to hyperpolarization of the resting membrane potential. Reduction of AP discharge in both groups was generally accompanied by lower LC network activity, depolarized AP threshold, increased AP repolarization, and increased current through a subpopulation of voltage-gated K+ channels (KV). The latter was indicated by enhanced transient KV currents particularly in the STZ-AD group. Interestingly, steady-state KV currents were reduced under hypercapnia, a change that would favor enhanced AP discharge. However, the collective response of most LC neurons in adult rats, and particularly those in the STZ-AD group, was inhibited by CO2. Department of Physiology Kirksville College of Osteopathic Medicine A.T. Still University of Health Sciences Department of Animal Morphology and Physiology Sao Paulo State University–UNESP/FCAV at Jaboticabal Department of Biology Truman State University Department of Animal Morphology and Physiology Sao Paulo State University–UNESP/FCAV at Jaboticabal FAPESP: 2017/21750-9

To study light-triggered self-healing in supramolecular materials, we synthesized supramolecular thermoplastic elastomers with mechanical properties that were reversibly modulated with temperature. By changing the supramolecular architecture, we created polymers with different temperature responses. Detailed characterization of the hydrogen-bonding material revealed dramatically different temperature and mechanical stress response due to two different stable states with changes in the hydrogen bonding interactions. A semi-crystalline state showed no response to oscillatory shear deformations while the melt state behaved as a typical energy dissipative material with a clear crossover between storage and loss moduli. Comparison studies on heat generation after light excitation revealed no differences in photo-thermal conversion when an Fe(II)-phenanthroline chromophore was either physically blended into the H-bonding polymer or covalently attached to the supramolecular network. These materials showed healing of scratches with light-irradiation, as long as the overlap of material absorbance and laser excitation was sufficient. Differences in the efficiency and rate of photohealing were observed, depending on the type of supramolecular interaction, and these were attributed to the differences in the thermal response of the materials' moduli. Such results provide insight into how materials can be designed with chromophores and supramolecular bonding interactions to tune the light-healing efficiency of the materials. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018.

While polycarboxylates and hydroxyl-acid complexes have long been known to be photoactive, simple carboxylate complexes which lack a significant LMCT band are not typically strongly photoactive. Hence, it was somewhat surprising that a series of reports demonstrated that materials synthesized from iron(III) and polysaccharides such as alginate (poly[guluronan-co-mannuronan]) or pectate (poly[galacturonan]) formed photoresponsive materials that convert from hydrogels to sols under the influence of visible light. These materials have numerous potential applications in areas such as photopatternable materials, materials for controlled drug delivery, and tissue engineering. Despite the near-identity of the functional units in the polysaccharide ligands, the reactivity of iron(III) hydrogels can depend on the configuration of some chiral centers in the sugar units and in the case of alginate the guluronate to mannuronate block composition, as well as pH. Here, using temperature- and field-dependent transmission Mössbauer spectroscopy, we show that the dominant iron compound detected for both the alginate and pectate gels displays features typical of a polymeric (Fe

When designing photoresponsive materials, the impact of a polymer host matrix on the photophysical and photochemical properties of chromophores can be dramatic and advantageous for correlating macromolecular properties. Some compounds possess changes in their photophysical response with variation in the surrounding media (e.g., crystalline glass vs solution). This study demonstrates how changes in the excited state dynamics of [Cu(dmp)2]+, where dmp = 2,9-dimethyl-1,10-phenanthroline, are used to quantitatively probe the viscosity of the surrounding polymer matrix. A correlation of both excited state lifetime and photoluminescence emission wavelength on viscosity was observed in different supramolecular materials containing [Cu(dmp)2]+. These effects were attributed to restricted photoinduced structural distortion of the Cu(I) complex as the polymer matrix hardened. This photoluminescence sensor features a greater dynamic range for viscosity sensing (6 orders of magnitude) and displayed larger changes in ...

It is well known that bacteria and fungi have evolved sophisticated systems for acquiring the abundant but biologically inaccessible trace element iron. These systems are based on high affinity Fe(III)-specific binding compounds called siderophores which function to acquire, transport, and process this essential metal ion. Many hundreds of siderophores are now known and their numbers continue to grow. Extensive studies of their isolation, structure, transport, and molecular genetics have been undertaken in the last three decades and have been comprehensively reviewed many times. In this review we focus on a unique subset of siderophores that has only been recognized in the last 20 years, namely those whose iron complexes display photoactivity. This photoactivity, which typically results in the photooxidation of the siderophore ligand with concomitant reduction of Fe(III) to Fe(II), seemingly upsets the siderophore paradigm of forming and transporting only extremely stable Fe(III) complexes into microbial cells. Here we review their structure, synthesis, photochemistry, photoproduct coordination chemistry and explore the potential biological and ecological consequences of this photoactivity.

We have demonstrated the ability to control the mechanical properties of metallosupramolecular materials via choice of ligand binding group, as well as with external light irradiation. These photoresponsive Cr(III)-based materials were prepared from a series of modified hydrogenated poly(ethylene-co-butylene) polymers linked through metal-ligand interactions between a Cr(III) metal center and pyridyl ligand termini of the polymers. The introduction of these Cr(III)-pyridine bonds gave rise to new mechanical and optical properties of the polymer materials. Depending on the type of pyridyl ligand, density functional theory calculations revealed changes in coordination to the Cr(III), which ultimately led to materials with significantly different mechanical properties. Electronic excitation of the Cr(III) materials with 450 and 655 nm CW lasers (800 mW/cm(2)) resulted in generation of excited state photophysical processes which led to temporary softening of the materials up to 143 kPa (41.5%) in storage modulus (G') magnitude. The initial mechanical strength of the materials was recovered when the light stimulus was removed, and no change in mechanical properties was observed with light irradiation where there was no absorbance by the Cr(III) moiety. These materials demonstrate that introduction of metal-ligand bonding interactions into polymers enables the design and synthesis of photoresponsive materials with tunable optical-mechanical properties not seen in traditional polymeric materials.

For solar-driven macroscopic motions, we assert that there is a local heating that facilitates large-scale deformations in anisotropic morphologic materials caused by thermal gradients. This report specifically identifies the fate of heat generation in photonastic materials and demonstrates how heat can perform work following excitation of a nonisomerizing dye. Utilizing the electrospinning technique, we have created a series of anisotropic nanofibrous polymer mats that comprise nonisomerizing dyes. Polymers are chosen because of their relative glass transition temperatures, elastic moduli, and melting temperatures. Light irradiation of these polymer mats with an excitation wavelength matching the absorption characteristics of the dye leads to macroscopic deformation of the mat. Analysis of still images extracted from digital videos provides plots of angular displacement vs power. The data were analyzed in terms of a photothermal model. Analyses of scanning electron microscopy micrographs for all samples are consistent to local melting in low T

Visible-light responsive gels were prepared from two plant-origin polyuronic acids (PUAs), alginate and pectate, coordinated to Fe(III) ions. Comparative quantitative studies of the photochemistry of these systems revealed unexpected differences in the photoreactivity of the materials, depending on the polysaccharide and its composition. The roles that different functional groups play on the photochemistry of these biomolecules were also examined. Mannuronic-rich alginates were more photoreactive than guluronic acid-rich alginate and than pectate. The microstructure of alginates with different mannuronate-to-guluronate ratios changed with polysaccharide composition. This influenced the gel morphology and the photoreactivity. Coordination hydrogel beads were prepared from both Fe-alginate and Fe-pectate. The beads were stable carriers of molecules as diverse as the dye Congo Red, the vitamin folic acid, and the antibiotic chloramphenicol. The photoreactivity of the hydrogel beads mirrored the photoreactivity of the polysaccharides in solution, where beads prepared with alginate released their cargo faster than beads prepared with pectate. These results indicate important structure-function relationships in these systems and create guidelines for the design of biocompatible polysaccharide-based materials where photoreactivity and controlled release can be tuned on the basis of the type of polysaccharide used and the metal coordination environment.

Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H2O2) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown. Here we evaluate the effect(s) of H2O2on cytosolic Ca2+(via fura-2 imaging) and voltage-dependent calcium currents in dissociated rat nTS neurons. H2O2perfusion (200 µM; 1 min) induced a delayed, slow, and moderate increase (~27%) in intracellular Ca2+concentration ([Ca2+]i). The H2O2-mediated increase in [Ca2+]iprevailed during thapsigargin, excluding the endoplasmic reticulum as a Ca2+source. The effect, however, was abolished by removal of extracellular Ca2+or the addition of cadmium to the bath solution, suggesting voltage-gated Ca2+channels (VGCCs) as targets for H2O2modulation. Recording of the total voltage-dependent Ca2+current confirmed H2O2enhanced Ca2+entry. Blocking VGCC L, N, and P/Q subtypes decreased the number of cells and their calcium currents that respond to H2O2. The number of responder cells to H2O2also decreased in the presence of dithiothreitol, suggesting the actions of H2O2were dependent on sulfhydryl oxidation. In summary, here, we have shown that H2O2increases [Ca2+]iand its Ca2+currents, which is dependent on multiple VGCCs likely by oxidation of sulfhydryl groups. These processes presumably contribute to the previously observed delayed hyperexcitability of nTS neurons in in vitro brainstem slices.

Hydrogen peroxide (H₂O₂) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H₂O₂ is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. We determined the extent to which H₂O₂ modulates synaptic and membrane properties in nTS neurons in rat brainstem slices. Stimulation of the tractus solitarii (which contains the sensory afferent fibers) evoked synaptic currents that were not altered by 10-500 μM H₂O₂. However, 500 μM H₂O₂ modulated several intrinsic membrane properties of nTS neurons, including a decrease in input resistance (R(i)), hyperpolarization of resting membrane potential (RMP) and action potential (AP) threshold (THR), and an initial reduction in AP discharge to depolarizing current. H₂O₂ increased conductance of barium-sensitive potassium currents, and block of these currents ablated H₂O₂-induced changes in RMP, Ri and AP discharge. Following washout of H₂O₂ AP discharge was enhanced due to depolarization of RMP and a partially maintained hyperpolarization of THR. Hyperexcitability persisted with repeated H₂O₂ exposure. H₂O₂ effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H₂O₂ initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes.

Reported are quantitative studies of the energy transfer from water-soluble CdSe/ZnS and CdSeS/ZnS core/shell quantum dots (QDs) to the Cr(III) complexes trans-Cr(N(4))(X)(2)(+) (N(4) is a tetraazamacrocycle ligand, X(-) is CN(-), Cl(-), or ONO(-)) in aqueous solution. Variation of N(4), of X(-), and of the QD size and composition allows one to probe the relationship between the emission/absorption overlap integral parameter and the efficiency of the quenching of the QD photoluminescence (PL) by the chromium(III) complexes. Steady-state studies of the QD PL in the presence of different concentrations of trans-Cr(N(4))(X)(2)(+) indicate a clear correlation between quenching efficiency and the overlap integral largely consistent with the predicted behavior of a Förster resonance energy transfer (FRET)-type mechanism. PL lifetimes show analogous correlations, and these results demonstrate that spectral overlap is an important consideration when designing supramolecular systems that incorporate QDs as photosensitizers. In the latter context, we extend earlier studies demonstrating that the water-soluble CdSe/ZnS and CdSeS/ZnS QDs photosensitize nitric oxide release from the trans-Cr(cyclam)(ONO)(2)(+) cation (cyclam = 1,4,8,11-tetraazacyclotetradecane) and report the efficiency (quantum yield) for this process. An improved synthesis of ternary CdSeS core/shell QDs is also described.

The chromium(III) nitrito complex trans-Cr(cyclam)(ONO)(2)(+) (1) is a very promising photochemical precursor for nitric oxide delivery to physiological targets. Here, we demonstrate that visible wavelength excitation of 1 in solutions containing thiol reductants such as the biological antioxidant glutathione (GSH) leads to permanent reaction even under anaerobic conditions, resulting in high quantum yield NO release. The nitric oxide formed under such conditions is sufficient, even at muM concentrations of 1 and using a low-intensity light source, to activate the enzyme soluble guanylyl cyclase (sGC). We also demonstrate that photolysis of 1 in the nM concentration range with a portable blue LED leads to vasorelaxation of porcine coronary arterial rings, a process also attributed to the NO activation of sGC.

Various diameters of polyaniline (PANI) nanofibers were easily made by varying the sweep rate in the electrochemical polymerization of the aniline monomer. At a sweep rate of 5 mV/s, the PANI nanofibers have an average diameter of 450 nm with a median of 440 nm. The fibers are short, on the order of a few microns in length, and exhibit a branched geometry. Increasing the sweep rate to 50 mV/s produced longer nanofibers with a smaller average diameter of 200 nm. Nanofibers synthesized at 100 mV/s were noted to be smaller with an average and median diameter of 100 nm. These results illustrate the ease in which the morphology of nanostructured PANI can be altered and indicate that the method has the potential to create multi-diameter fibers or mixed-morphology materials.

Described is the photoluminescence (PL) of water-soluble CdSe/ZnS core/shell quantum dots (QDs) as perturbed by salts of the chromium(III) complexes trans-Cr(cyclam)Cl2+ (1), trans-Cr(cyclam)(ONO)2+ (2), and trans-Cr(cyclam)(CN)2+ (3) (cyclam = 1,4,8,11-tetraazacyclo-tetradecane). The purpose is to probe the characteristics of such QDs as antennae for photosensitized release of bioactive agents (in the present case, the bioregulatory molecule NO) from transition metal centers. Addition of 1 or 2 to a QD solution results in concentration-dependent quenching of the band edge emission, but 3 has a minimal effect. Added KCl strongly attenuates the quenching by 1, and this suggests that the Cr(III) cations and the QDs form electrostatic assemblies via ion pairing on the negatively charged QD surfaces. Quenching by 2, a known photochemical NO precursor, was accompanied by photosensitized NO release. All three, however, do quench the broad red emission ( approximately 650-850 nm) attributed to radiative decay of surface trapped carriers. The effect of various concentrations of 1 on time-resolved PL and absorbance were explored using ultrafast spectroscopic methods. These observations are interpreted in terms of the Förster resonance energy-transfer mechanism for quenching of the band edge PL by multiple units of 1 or 2 at the QD surface, whereas quenching of the low-energy trap emission occurs via a charge-transfer pathway.

Elemental selenium generated by the photobleaching of selenomerocyanine dyes forms conjugates with serum albumin and serum lipoproteins that are toxic to leukemia and selected solid tumor cells but well tolerated by normal CD34-positive hematopoietic stem and progenitor cells. Serum albumin and lipoproteins act as Trojan horses that deliver the cytotoxic entity (elemental selenium) to tumor cells as part of a physiological process. They exploit the fact that many tumors have an increased demand for albumin and/or low-density lipoprotein. Se(0)-protein conjugates are more toxic than selenium dioxide, sodium selenite, selenomethionine, or selenocystine. They are only minimally affected by drug resistance mechanism, and they potentiate the cytotoxic effect of ionizing radiation and several standard chemotherapeutic agents. The cytotoxic mechanism of Se(0)-protein conjugates is not yet fully understood. Currently available data are consistent with the notion that Se(0)-protein conjugates act as air oxidation catalysts that cause a rapid depletion of intracellular glutathione and induce apoptosis. Drugs modeled after our Se(0)-protein conjugates may prove useful for the local and/or systemic therapy of cancer.

Photochemical Nitric oxide releasing composite materials (Photo-NORMs) were prepared using biocompatible polymers and the photochemical nitric oxide donor complex (CrONO). We have demonstrated nitric oxide (NO) release from the solid composites for extended (30 hours) and controlled (20-100 pmoles s(-1)) durations after visible light irradiation. Quantitation of the efficiency of NO release from the composites shows that polymer gas permeability most dramatically affects the overall efficiency (QY) of photochemical NO release, where polymers with higher gas permeability have a higher QY of nitric oxide release. Composites were also prepared with β-phase lanthanide-doped NaYF4 upconverting nanoparticles (UCNPs). Controlled Nitric oxide release was achieved via near infrared (NIR) irradiation. A prototype LED device shows proof-of-concept that such photoresponsive NO-releasing composites could be applied to implantable systems, where the amount of NO released is modulated by changing irradiation time and light intensity. This research provides the guidelines necessary to move towards device fabrication and testing in actual tissue to evaluate the photo-NORMS as a reliable option for nitric oxide release in vivo.

Serotonin (5-HT), and its 5-HT1A receptor (5-HT1AR) subtype, is a powerful modulator of the cardiorespiratory system and its sensory reflexes. The nucleus tractus solitarii (nTS) serves as the first central station for visceral afferent integration and is critical for cardiorespiratory reflex responses. However, the physiological and synaptic role of 5-HT1ARs in the nTS is relatively unknown. In the present study, we examined the distribution and modulation of 5-HT1ARs on cardiorespiratory and synaptic parameters in the nTS. 5-HT1ARs were widely distributed to cell bodies within the nTS but not synaptic terminals. In anesthetized rats, activation of 5-HT1ARs by microinjection of the 5-HT1AR agonist 8-OH-DPAT into the caudal nTS decreased minute phrenic neural activity via a reduction in phrenic amplitude. In brain stem slices, 8-OH-DPAT decreased the amplitude of glutamatergic tractus solitarii-evoked excitatory postsynaptic currents, and reduced overall spontaneous excitatory nTS network activity. These effects persisted in the presence of GABAA receptor blockade and were antagonized by coapplication of 5-HT1AR blocker WAY-100135. 5-HT1AR blockade alone had no effect on tractus solitarii-evoked excitatory postsynaptic currents, but increased excitatory network activity. On the other hand, GABAergic nTS-evoked inhibitory postsynaptic currents did not change by activation of the 5-HT1ARs, but spontaneous inhibitory nTS network activity decreased. Blocking 5-HT1ARs tended to increase nTS-evoked inhibitory postsynaptic currents and inhibitory network activity. Taken together, 5-HT1ARs in the caudal nTS decrease breathing, likely via attenuation of afferent transmission, as well as overall nTS network activity.

Summary Aim: D-Tagatose (D-tag), a hexose bulk sweetener, does not affect plasma glucose levels when orally administered to rodents. Additionally, D-tag attenuates the rise in plasma glucose after mice are administered oral sucrose. The current study was undertaken to investigate the acute glycaemic effects of oral D-tag alone or in combination with oral glucose in human subjects with and without type 2 diabetes mellitus. Glycaemic responses to D-tag also were investigated in subjects after oral sucrose to examine whether the glucose-lowering effects of D-tag in rodents may result from a direct inhibition of intestinal disaccharidases. Methods: Eight normal and eight subjects with diabetes mellitus were administered 75 g of glucose, 75 g of D-tag, or 75 g of D-tag 30 min prior to a 75 g oral glucose tolerance test (OGTT). Five patients with diabetes mellitus were challenged with a 75 g oral sucrose tolerance test (OSTT) with and without oral pre-treatment with 75 g of D-tag. Patients with diabetes mellitus also received separate 0, 10, 15, 20 and 30 g of D-tag 30 min prior to a 75 g OGTT. Results: Oral loading with D-tag alone led to no changes in glucose or insulin levels in either normal patients or those with diabetes mellitus. Pre-OGTT treatment with 75 g D-tag, however, attenuated the rise in glucose levels in patients with diabetes mellitus (p

Described are photochemical studies of the nitric oxide precursors, trans-Cr(L)(ONO)(2)(+) (L = cyclam = 1,4,8,11-tetraazacyclotetradecane, CrONO, or L = mac = 5,7-dimethyl-6-anthracenylcyclam, mac-CrONO) encapsulated in phosphatidylcholine liposomes. The liposomes provide a means to maintain a localized high concentration of NO releasing complexes and are easily modified for in vivo targeting through self-assembly. Steady, controlled release of NO is seen after photolysis of the liposome-encapsulated CrONO as compared to the burst of NO release seen by the unencapsulated complex in oxygenated solutions. The quantum yields for photochemical NO release from liposome-encapsulated CrONO and mac-CrONO were determined in both oxygenated and anoxic solutions. The quantum yield for NO release in oxygenated solution for encapsulated CrONO was more than 5 times larger than that of unencapsulated CrONO, thus the net NO released after photolysis in oxygenated solutions is enhanced by encapsulation of CrONO in liposomes. Encapsulated mac-CrONO shows NO release after photolysis with low-intensity blue light. Furthermore, the fluorescence of mac-CrONO can be detected through the liposomes, thus allowing for development of theranostic NO delivery vessels where tracking and imaging can occur simultaneously with therapeutic NO release. This work provides insight into the development of multifunctional liposome constructs for disease theranostics.

Experimental and density functional theory (DFT) studies are described that are focused on outlining the reactivity of the known photochemical nitric oxide precursor trans-Cr(cyclam)(ONO)(2)(+) ("CrONO", cyclam = 1,4,8,11-tetrazacycltetradecane). Studies in both aerated and deaerated aqueous media are described as are the roles of both the oxidant O(2) and a reductant such as glutathione in trapping the apparent Cr(IV) photoreaction intermediate trans-Cr(cyclam)(O)(ONO)(+). Also reported and characterized structurally is the Cr(V) product of long-term photolysis in the absence of reducing agents, the trans-dioxo species [trans-Cr(cyclam)(O)(2)](ClO(4)). Photosensitization experiments indicate that at least a significant fraction of the reaction occurs from the lowest energy doublet excited state(s). Lastly, cell culture experiments demonstrate that CrONO has little or no acute toxicity either before or after photolysis.

The report on recent preparative, n.m.r. spectroscopic and structural results concerning steric effects in organoselenium and -tellurium chemistry covers: 1. extremely bulky ditellurides and diselenides, including rotational barriers and unusual conformations, 2. bulky metal arylselenelolates and tellurolates, including compounds with bonds from Se or Te to Li, Na, K, Si, Ge, Sn, Zn, Cd, Hg and Au, 3. steric effects on silyltelluride/acyl halide and silylphosphane/tellurium reactions, 4. reaction of various diselenides and ditellurides with iodine and bromine, including iodine catalysis of Se-Se bond cleavage/bond formation equilibria.

The bioregulatory molecule NO plays key roles in cancer biology and has been implicated in both tumor growth and suppression. Furthermore, it is a gamma-radiation sensitizer that may enhance selective killing of neoplastic tissues. For these reasons, there is considerable interest in developing methods for NO delivery to specific physiological targets. In this Perspective, we describe ongoing investigations focused on photochemical methodologies to deliver therapeutic doses of NO to such targets utilizing transition metal complexes that are nitric oxide precursors. The photochemical strategy has the advantages that it allows for precise control of the timing, location, and dosage for the targeted delivery of a bioactive agent.

OBJECTIVE To examine the persistence of the original treatment effects 10 years after the Diabetes Control and Complications Trial (DCCT) in the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. In the DCCT, intensive therapy aimed at near-normal glycemia reduced the risk of microvascular complications of type 1 diabetes mellitus compared with conventional therapy. METHODS Retinopathy was evaluated by fundus photography in 1211 subjects at EDIC year 10. Further 3-step progression on the Early Treatment Diabetic Retinopathy Study scale from DCCT closeout was the primary outcome. RESULTS After 10 years of EDIC follow-up, there was no significant difference in mean glycated hemoglobin levels (8.07% vs 7.98%) between the original treatment groups. Nevertheless, compared with the former conventional treatment group, the former intensive group had significantly lower incidences from DCCT close of further retinopathy progression and proliferative retinopathy or worse (hazard reductions, 53%-56%; P < .001). The risk (hazard) reductions at 10 years of EDIC were attenuated compared with the 70% to 71% over the first 4 years of EDIC (P < .001). The persistent beneficial effects of former intensive therapy were largely explained by the difference in glycated hemoglobin levels during DCCT. CONCLUSION The persistent difference in diabetic retinopathy between former intensive and conventional therapy ("metabolic memory") continues for at least 10 years but may be waning. TRIAL REGISTRATION (clinicaltrials.gov) Identifiers: NCT00360815 and NCT00360893.

Silicone materials pose a contamination control challenge because of their ubiquity in satellite hardware, the tendency of the material and its outgassed contaminants to migrate along surfaces, and the difficulty in cleaning away the residue. To devise effective mitigation strategies, accurate knowledge of the chemical identity and properties of the outgassed species is needed. This information is critical for modeling silicone outgassing deposition processes and for developing effective cleaning methods. To this end, a chemical analysis study of several common silicone materials was conducted to identify and characterize the outgassed contaminants. Gas Chromatography-Mass Spectrometry (GC-MS) and other laboratory techniques were used to identify and characterize the outgassed species. In this report, the results of this study will be discussed with a particular emphasis on comparing the outgassing properties of the species collected from these materials to DC704, which is typically used to model silicone outgassing.

The photoluminescence from CdSe/ZnS core/shell quantum dots, modified to make them water-soluble by exchanging the surface ligands with dihydrolipoic acid, is partially quenched by adding the chromium(III) complex trans-Cr(cylcam)(ONO)2+ (1, BF4- salt). This quenching, attributed to the formation of electrostatic assemblies due to ion pairing of 1 with the negatively charged QD surface, is accompanied by the release of NO owing to photosensitized reaction of the Cr(III) nitrito complex.

Many Type II photosensitizers are substrates of the singlet oxygen they generate. They are, therefore, converted to photoproducts when exposed to light in the presence of oxygen. While most photoproducts appear to be biologically inert, one of the photoproducts generated by selenomerocyanine photosensitizers is a form of elemental selenium that is surprisingly toxic to tumor cells if allowed to form conjugates with serum albumin or lipoproteins. Albumin and lipoproteins act as delivery vehicles for the cytotoxic entity, exploiting the fact that many tumor cells have an increased capacity to bind and internalize albumin and/or lipoproteins. The cytotoxic mechanism of Se(0)-protein conjugates is not yet fully understood but is obviously quite different from the singlet oxygen-mediated mechanism of merocyanine-mediated photodynamic therapy (PDT). Whereas merocyanine-PDT is directed against the plasma membrane, is more effective at 4 °C than at room temperature, and is inhibited by excess albumin and lipoproteins, selenomerocyanine-derived cytotoxic photoproducts act on intracellular targets, are ineffective at low temperatures, and require albumin or lipoproteins as carrier molecules. The discovery of cytotoxic Se(0)-protein conjugates provides a rare example of photoproducts contributing substantially to the cytotoxic effect of PDT and challenges the widely held notion that elemental selenium is biologically inert.

Electron microscopes are often badly sited in rooms with ambient magnetic fields high enough to blur high-resolution images, particularly at low magnification. The method of compensation presented here deals with magnetic fields at power supply frequencies, which are often difficult to eliminate. Sensors located near the microscope provide signals which are amplified and fed to room-sized compensating coils. These are connected to give feedback which nulls the field at the sensors themselves. Typically, the ambient field at the microscope is reduced by a factor of around 20. The system has been in operation with several EMs for many years.

Glycine max L. Merr. cv. Maple Arrow protoplasts were prepared from both tissue-cultured root cells and symbiotically-infected (fix+) nodule cells. Whilst both cell types showed glucan synthetase II (GS II; EC 2.4.1.29) activity, neither cell type, whole or gently disrupted, showed glucan synthetase I activity. After sucrose density gradient centrifugation one of the several GS II activity peaks co-sedimented with the single radioactive particulate peak from [125I]-labelled protoplasts at 1.14 g ml−1. This peak is presumed to be the plasma membrane peak because labelling of protoplasts with colloidal gold prior to disruption moved the 125I peak and the corresponding glucan synthetase II activity into denser regions of the gradient, leaving endoplasmic reticulum-contaminating IDPase (EC 3.1.3.31) and other glucan synthetase II peaks unmoved. Results are discussed in relation to various strategies of plasma membrane isolation.