Stretchable and Bioadhesive Gelatin Methacryloyl-Based Hydrogels Enabled by in Situ Dopamine Polymerization.

Hydrogel patches with high toughness, stretchability, and adhesive properties are critical to healthcare applications including wound dressings and wearable devices. Gelatin methacryloyl (GelMA) provides a highly biocompatible and accessible hydrogel platform. However, low tissue adhesion and poor mechanical properties of cross-linked GelMA patches (i.e., brittleness and low stretchability) have been major obstacles to their application for sealing and repair of wounds. Here, we show that adding dopamine (DA) moieties in larger quantities than those of conjugated counterparts to the GelMA prepolymer solution followed by alkaline DA oxidation could result in robust mechanical and adhesive properties in GelMA-based hydrogels. In this way, cross-linked patches with ∼140% stretchability and ∼19 000 J/m3 toughness, which correspond to ∼5.7 and ∼3.3× improvement, respectively, compared to that of GelMA controls, were obtained. The DA oxidization in the prepolymer solution was found to play an important role in activating adhesive properties of cross-linked GelMA patches (∼4.0 and ∼6.9× increase in adhesion force under tensile and shear modes, respectively) due to the presence of reactive oxidized quinone species. We further conducted a parametric study on the factors such as UV light parameters, the photoinitiator type (i.e., lithium phenyl-2,4,6-trimethylbenzoylphosphinate, LAP, versus 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, Irgacure 2959), and alkaline DA oxidation to tune the cross-linking density and thereby hydrogel compliance for better adhesive properties. The superior adhesion performance of the resulting hydrogel along with in vitro cytocompatibility demonstrated its potential for use in skin-attachable substrates.

Dual-Signal Luminescent Detection of Dopamine by a Single Type of Lanthanide-Doped Nanoparticles.

Detection of dopamine, an important neurotransmitter, is vital for understanding its roles in mammals and disease diagnosis. However, commonly available methods for dopamine detection typically rely on a single signal readout, which can be susceptible to interference by internal or external factors. Here, we report a dual-signal detection of dopamine based on label-free luminescent NaGdF4:Tb nanoparticles. In the presence of dopamine, the NaGdF4:Tb nanoparticles exhibit luminescence quenching under the excitation of 272 nm, while they give enhanced luminescence under 297 nm excitation, realizing both turn off and turn on detection of dopamine. The nanoparticle-based dual-signal sensors exhibit high sensitivity, with a detection limit of ∼30 nM, and good selectivity, which offers the possibility to identify potential interferents in the samples. We further demonstrate that the dual-signal response results from different energy-transfer processes within the nanoparticles under the excitation of different light. The new strategy demonstrated here should pave the way for the development of multiresponse nanosensors based on lanthanide-doped luminescent nanomaterials.

Bioinspired near-infrared-excited sensing platform for in vitro antioxidant capacity assay based on upconversion nanoparticles and a dopamine-melanin hybrid system.

A novel core-shell structure based on upconversion fluorescent nanoparticles (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant capacity of biological fluids. In this approach, dopamine-melanin nanoshells facilely formed on the surface of UCNPs act as ultraefficient quenchers for upconversion fluorescence, contributing to a photoinduced electron-transfer mechanism. This spontaneous oxidative polymerization of the dopamine-induced quenching effect could be effectively prevented by the presence of various antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great selectivity and sensitivity toward antioxidants relative to other compounds at 100-fold higher concentration. A satisfactory correlation was established between the ratio of the "anti-quenching" fluorescence intensity and the concentration of antioxidants. Besides the response of the upconversion fluorescence signal, a specific evaluation process for antioxidants could be visualized by the color change from colorless to dark gray accompanied by the spontaneous oxidation of dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay platform was further used to evaluate the antioxidant capacity of cell extracts and human plasma, and satisfactory sensitivity, repeatability, and recovery rate were obtained. This approach features easy preparation, fluorescence/visual dual mode detection, high specificity to antioxidants, and enhanced sensitivity with NIR excitation, showing great potential for screening and quantitative evaluation of antioxidants in biological systems.

Long-term effects of irradiation with iron-56 particles on the nigrostriatal dopamine system.

Exposure to heavy ions during a Mars mission might damage the brain, thus compromising mission success and the quality of life of returning astronauts. Several workers have suggested that the dopamine system is particularly sensitive to heavy ion radiation, but direct evidence for this notion is lacking. We examined measures of brain dopamine viability at times up to 15 months after acute exposure of rats to (56)Fe (1.2-2.4 Gy). No effects were seen in brain sections stained for tyrosine hydroxylase, the classical marker for dopamine cells and nerve terminals. Locomotion stimulated by cocaine, which directly activates the dopamine system, was reduced at 6 months but not at 12 months. Furthermore, in a visually cued lever-pressing test, reaction times, which are prolonged by dopamine system damage, were identical in irradiated and control animals. However, learning times were increased by irradiation. Our data suggest that the midbrain dopamine system is not especially sensitive to damage by (56)Fe particles at doses much higher than would be associated with travel to and from Mars.

Vitamin B-sensitized photo-oxidation of dopamine.

Kinetics and mechanism of the photo-oxidation of the natural catecholamine-type neurotransmitter dopamine (DA) has been studied in aqueous solution, under aerobic conditions, in the presence of riboflavin (Rf, vitamin B(2)) as a photosensitizer. Results indicate the formation of a weak dark complex Rf-DA, with a mean apparent association constant K(ass) = 30 m(-1), only detectable at DA concentrations much higher than those employed in photochemical experiments. An intricate mechanism of competitive reactions operates upon photoirradiation. DA quenches excited singlet and triplet states of Rf, with rate constants of 4.2 x 10(9) and 2.2 x 10(9) m(-1) s(-1), respectively. With the catecholamine in a concentration similar to that of dissolved molecular oxygen in air-saturated water, DA and oxygen competitively quench the triplet excited state of Rf, generating superoxide radical anion (O(2)) and singlet molecular oxygen (O(2)((1)Delta(g))) by processes initiated by electron and energy-transfer mechanisms, respectively. Rate constants values of 1.9 x 10(8) and 6.6 x 10(6) m(-1) s(-1) have been obtained for the overall and reactive (chemical) interaction of DA with O(2)((1)Delta(g)). The presence of superoxide dismutase increases both the observed rates of aerobic DA photo-oxidation and oxygen uptake, due to its known catalytic scavenging of O(2), a species that could revert the overall photo-oxidation effect, according to the proposed reaction mechanism. As in most of the catecholamine oxidative processes described in the literature, aminochrome is the DA oxidation product upon visible light irradiation in the presence of Rf. It is generated with a quantum yield of 0.05.

[Effect of high-frequency EMF on public health and its neuro-chemical investigations].

Influence of stressors, namely antennas of mobile phones, clearly has an effect on public health. Biochemical changes, which were manifested with changes in composition of amino-acids and biogenic amines in blood, have shown that dopamine system has vital role in prolactine secretion. Depression of dopamine is causing increase of prolactine secretion, which leads to hyperprolactinemy, while deaminization of amino-acids is causing disturbance of ammonia utilization. We can not stop fast grow of mobile telephony but public should have access to modern medico-biological investigations for the prevention of medical conditions associated with the influence of high-frequency EMF.

Manipulating the light/dark cycle: effects on dopamine levels in optic lobes of the honey bee (Apis mellifera) brain.

This study examines the relationship between cyclical variations in optic-lobe dopamine levels and the circadian behavioural rhythmicity exhibited by forager bees. Our results show that changing the light-dark regimen to which bees are exposed has a significant impact not only on forager behaviour, but also on the levels of dopamine that can be detected in the optic lobes of the brain. Consistent with earlier reports, we show that foraging behaviour exhibits properties characteristic of a circadian rhythm. Foraging activity is entrained by daily light cycles to periods close to 24 h, it changes predictably in response to phase shifts in light, and it is able to free-run under constant conditions. Dopamine levels in the optic lobes also undergo cyclical variations, and fluctuations in endogenous dopamine levels are influenced significantly by alterations to the light/dark cycle. However, the time course of these changes is markedly different from changes observed at a behavioural level. No direct correlation could be identified between levels of dopamine in the optic lobes and circadian rhythmic activity of the honey bee.

Effects of HZE particle on the nigrostriatal dopaminergic system in a future Mars mission.

Because of long duration travel outside the Earth's magnetic field, the effect of iron-rich high charge and energy (HZE) particles in Galactic Cosmic Rays on human body is the major concern in radiation protection. Recently attention has been directed to effects on the central nervous system in addition to mutagenic effects. In particular, a reduction in striatal dopamine content on nigrostriatal dopaminergic system has been reported by investigators using accelerated iron ions in ground-based mammalian studies. In addition, studies of the pathophysiology of Parkinson's disease demonstrated that excess iron cause a reduction in the dopamine content in the substantia nigra. This suggests an intriguing possibility to explain the selective detrimental effects of HZE particles on the dopaminergic system. Should these particles have biochemical effects, possible options for countermeasures are: (1) nutritional prevention, (2) medication, and (3) surgical placement of a stimulator electrode at a specific anatomic site in the basal ganglia.

Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an [11C]raclopride positron emission tomography study in anesthetized macaque monkeys.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been used as a treatment for neuropsychiatric disorders such as depression and Parkinson's disease (PD). Despite the growing interest in therapeutic application of rTMS, precise mechanisms of its action remain unknown. With respect to PD, activation of the mesostriatal dopaminergic pathway is likely to be a candidate mechanism underlying the therapeutic effects; however, modulating effects of rTMS over the primary motor cortex (M1) on the dopaminergic system have not been studied. METHODS: We used [11C]raclopride positron emission tomography to measure changes of extracellular dopamine concentration after 5Hz rTMS over the M1 in eight anesthetized monkeys. RESULTS: rTMS over the right M1 induced a reduction of [11C]raclopride binding potential (BP) in the bilateral ventral striatum, including the nucleus accumbens, and a significant increase of BP in the right putamen; no significant BP reduction was found in the dorsal striatum. These data indicate that rTMS over the motor cortex induces a release of endogenous dopamine in the ventral striatum. CONCLUSIONS: Our results suggest that therapeutic mechanisms of rTMS may be explained in part by an activation of the mesolimbic dopaminergic pathway, which plays critical roles in rewards, reinforcement, and incentive motivation.

The effects of proton exposure on neurochemistry and behavior.

Future space missions will involve long-term travel beyond the magnetic field of the Earth, where astronauts will be exposed to radiation hazards such as those that arise from galactic cosmic rays. Galactic cosmic rays are composed of protons, alpha particles, and particles of high energy and charge (HZE particles). Research by our group has shown that exposure to HZE particles, primarily 600 MeV/n and 1 GeV/n 56Fe, can produce significant alterations in brain neurochemistry and behavior. However, given that protons can make up a significant portion of the radiation spectrum, it is important to study their effects on neural functioning and on related performance. Therefore, these studies examined the effects of exposure to proton irradiation on neurochemical and behavioral endpoints, including dopaminergic functioning, amphetamine-induced conditioned taste aversion learning, and spatial learning and memory as measured by the Morris water maze. Male Sprague-Dawley rats received a dose of 0, 1.5, 3.0 or 4.0 Gy of 250 MeV protons at Loma Linda University and were tested in the different behavioral tests at various times following exposure. Results showed that there was no effect of proton irradiation at any dose on any of the endpoints measured. Therefore, there is a contrast between the insignificant effects of high dose proton exposure and the dramatic effectiveness of low dose (<0.1 Gy) exposures to 56Fe particles on both neurochemical and behavioral endpoints.

Absence of circadian clock regulation of horizontal cell gap junctional coupling reveals two dopamine systems in the goldfish retina.

In fish and other vertebrate retinas, although dopamine release is regulated by both light and an endogenous circadian (24-hour) clock, light increases dopamine release to a greater extent than the clock. The clock increases dopamine release during the subjective day so that D2-like receptors are activated. It is not known, however, whether the retinal clock also activates D1 receptors, which display a much lower sensitivity to dopamine in intact tissue. Because activation of the D1 receptors on fish cone horizontal (H1) cells uncouples the gap junctions between the cells, we studied whether the clock regulates the extent of biocytin tracer coupling in the goldfish retina. Tracer coupling between H1 cells was extensive under dark-adapted conditions (low scotopic range) and similar in the subjective day, subjective night, day, and night. An average of approximately 180 cells were coupled in each dark-adapted condition. However, bright light stimulation or application of the D1 agonist SKF38393 (10 microM) dramatically reduced H1 cell coupling. The D2 agonist quinpirole (1 microM) or application of the D1 antagonist SCH23390 (10 microM) and/or the D2 antagonist spiperone (10 microM) had no effect on H1 cell coupling in dark-adapted retinas. These observations demonstrate that H1 cell gap junctional coupling and thus D1 receptor activity are not affected by endogenous dopamine under dark-adapted conditions. The results suggest that two different dopamine systems are present in the goldfish retina. One system is controlled by an endogenous clock that activates low threshold D2-like receptors in the day, whereas the second system is controlled by light and involves activation of higher threshold D1 receptors.

Electron paramagnetic resonance study on free radical scavenging and/or generating activity of dopamine-4-O-sulfate.

The free radical scavenging and/or generating activity of dopamine-4-O-sulfate was examined and compared with that of dopamine. In humans, dopamine mostly exists in two isomeric forms of sulfate ester conjugates as metabolites; i.e., dopamine-3-O-sulfate and dopamine-4-O-sulfate in the circulation. Dopamine is generally believed to be oxidized by molecular oxygen or another reactive oxygen species under physiological conditions, to form oxidized dopamine derivatives that are cytotoxic. However, it is not known whether dopamine conjugates are generated on interaction with reactive oxygen species or not. In the present study, we measured the susceptibility to oxidization of dopamine-4-O-sulfate by using electron paramagnetic resonance (EPR) spectroscopy and optical absorption spectrometry. Dopamine was easily oxidized and dopamine-derived radicals appeared, whereas dopamine-4-O-sulfate was not oxidized under physiological conditions. Furthermore, dopamine-4-O-sulfate did not react with a strong oxidizing agent, sodium periodate. These results suggest that dopamine-4-O-sulfate has resistance against autoxidation, and seems to be a stable metabolite of dopamine.

Effects of ultraviolet irradiation on melanogenesis from tyrosine, Dopa and dopamine: a matrix-assisted laser desorption/ionization mass spectrometric study.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry experiments were applied to study the influence of ultraviolet (UV) irradiation in melanogenesis. Samples were prepared starting from three different precursors, tyrosine, Dopa and dopamine, in the presence or absence of tyrosinase, the enzyme responsible for the synthesis of melanin. Enzymatic reactions were carried out for 10, 30, 60 and 120 min under UV irradiation at 365 nm, and aliquots were then immediately ultrafiltered and lyophilized. Samples obtained by irradiation of tyrosine solution revealed the formation of 5,6-dihydroxyindole (DHI) oligomers up to pentamers at 120 min; the reaction kinetics were markedly enhanced in the presence of tyrosinase. In the case of Dopa, UV irradiation favored melanogenesis only in the presence of the enzyme; in this case, many reaction pathways were activated, originating various oligomeric species of Dopa, DHI and 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Conversely, when dopamine was used as tyrosinase substrate under UV light, mechanisms of melanogenesis different from those generated by simple enzymatic reaction without irradiation were not activated, as the same oligomeric species were present.

Radiation effects on dopamine and norepinephrine.

PURPOSE: Radiation sterilization is becoming increasingly popular for the sterilization of many pharmaceutical products. We have investigated the gamma radiation induced effects on dopamine and norepinephrine by ESR spectroscopy. RESULTS AND DISCUSSION: Equations to describe the evolution of the ESR curves versus doses and time of storage are presented. Linear regression is, for dopamine hydrochloride, applicable for doses ranging from 10 to 25 kGy. Since the radiation dose selected must always be based upon the bioburden of the products and the degree of sterility required, doses in the range 10-25 kGy could be investigated and linear regression would appear to be the least expensive route to follow and gives good results. The comportment of noradrenaline bitartrate is more complex and the use of linear regression would appear more hazardous especially for low doses. For doses higher than 25 kGy, a more general equation is required. Power function using only 2 parameters could give good results but must be validated. Decay kinetics for radicals versus storage were considered. Non-homogeneous kinetics with time dependent rate constant and bi-exponential function appeared valid to reproduce the decay of radicals for, respectively, dopamine and norepinephrine. CONCLUSIONS: It is worth noting that, at present, ESR is the only technique which proved to be suitable for identification and quantification purposes in irradiated pharmaceuticals. Moreover, other features such as sensitivity, precision, ease and non-destructive readout make ESR superior to other proposed analytical techniques.

Combining 'caged-dopamine' photolysis with fast-scan cyclic voltammetry to assess dopamine clearance and release autoinhibition in vitro.

We have developed a methodology for inducing a rapid rise in extracellular dopamine concentrations. The clearance of the applied dopamine, as well as its effect on the endogenous dopamine release (i.e., autoinhibition), was then examined using fast scan cyclic voltammetry. In a recording chamber mounted on a Nikon Optiphot epifluorescence microscope, coronal rat brain slices containing either the caudate nucleus or prefrontal cortex were perfused with ACSF containing 100-200 microM 'caged-DA.' UV illumination (100-200 ms) focused at the tip of the recording electrode produced a peak DA concentration of 1-2 microM within 100-200 ms of terminating the illumination. The caudate nucleus exhibited a faster clearance rate for photo-released DA compared to the prefrontal cortex. Cocaine reduced the clearance rates in both the caudate nucleus and prefrontal cortex. In the prefrontal cortex a combination of desipramine/clomipramine also reduced dopamine clearance, suggesting heterologous uptake of the applied DA by noradrenergic and/or serotonergic terminals. Photo-released dopamine inhibited release of endogenous caudate DA release evoked by single electrical stimulation. The advantages of this methodology are discussed.

[Early effects of neutron-gamma or gamma irradiation on the group toxicity induced by (+) amphetamine in mice]. / Effets précoces de l'irradiation neutron-gamma ou gamma sur la toxicité de groupe induite par la (+) amphétamine chez la souris.

To better understand the mechanism of action of gamma and neutron radiation on the dopaminergic system, the influence of the two irradiation modalities on the group toxicity of (+) amphetamine was studied in mice. Neutron-gamma irradiation (3.6-4.95 Gy) leads to an early toxicity reduction, while gamma-exposure (7-12 Gy) induces an increase in toxicity. This suggests that these two types of radiation induce different early effects on central dopaminergic system. Possible mechanisms are discussed.

[The effect of ionizing radiation at superhigh doses on the processes of dopamine release and reuptake by nerve endings in different sections of the brain]. / Vliianie ioniziruiushchego izlucheniia v sverkhvysokikh dozakh na protsessy vysvobozhdeniia i obratnogo zakhvata dofamina nervnymi terminaliami razlichnykh otdelov golovnogo mozga.

Rats exposed to fast 24 MeV electrons (100 Gy) at the state of early transient incapacity (ETI) exhibited active release and reuptake of dopamine in nerve terminals of the striatum. No changes in the indices under study were found in rats exposed to 25 Gy radiation that did not cause the ETI development. The in vitro irradiation of the isolated synaptosomes (100 Gy) inhibited dopamine reuptake and increased the number of sites of 3H-spiperone binding to D2-receptors in a membrane fraction isolated from the striatum.

The use of microwave irradiation with low formalin concentrations to enhance the conversion of dopamine into norsalsolinol in rat brain: a pilot study.

The fixation of the neurotransmitter dopamine in the central nervous system by perfusion with formalin solutions seems to take place mainly via the formalin-induced condensation product norsalsolinol. In the present investigation the influence of microwave irradiation of the formalin-induced condensation of dopamine was studied in vitro and in vivo by making use of different, relatively low, formalin concentrations. It appeared that in vitro and in vivo the dopamine conversion was complete with 4% formalin and no influence of microwaves was noted. However, by making use of much lower formalin concentrations (0.2% and 0.4%) the condensation of dopamine was strongly augmented, in vitro (200%) and in vivo (at least 500%) using microwave techniques. There was a considerable loss in non-microwaved tissue (30%) after perfusion in vivo. This was lower (10%) in microwaved tissue. In experiments with perfused brain tissue which allowed a more complete calculation, a loss was found. This might be caused by a strong binding of dopamine and/or norsalsolinol to tissue components or to side reactions that could not be traced by the present experimental techniques.

The effect of ionizing radiation on advanced life support medications.

Advanced life support medications stored in emergency department stretcher areas, diagnostic radiology rooms, and radiotherapy suites are exposed to ionizing radiation. We hypothesized that radiation may decrease the potency and thus the shelf life of medications stored in these areas. Atropine, dopamine, epinephrine, and isoproterenol were exposed to a wide range of ionizing radiation. The potency of the four drugs was unaffected by levels of radiation found in ED stretcher areas and high-volume diagnostic radiograph rooms (eg, chest radiograph, computed tomography, fluoroscopy). The potency of atropine may be reduced by gamma radiation in high-use radiotherapy suites. However, dopamine, epinephrine, and isoproterenol were unaffected by high doses of gamma radiation. Atropine, dopamine, epinephrine, and isoproterenol may be safely kept in ED stretcher areas and diagnostic radiology rooms without loss of potency over the shelf life of the drugs.

[The effect of irradiation on dopamine level and metabolism in the rat brain]. / Vliianie oblucheniia na soderzhanie i obmen dofamina v golovnom mozge krys.

In experiments on rats it was shown that after 20 Gy irradiation dopamine and homovanilic acid content increases in the caudate nucleus and limbic structures of the forebrain: dopamine disappears more readily when its biosynthesis is blocked. The rate of the mediator degradation in the brain increases by 1.5-2 times, and the rate of the synthesis, by 3-5 times at early times after irradiation.