917 resultados para Therapeutics, Physiological.
Resumo:
Limitation to an aqueous habitat is the most fundamental physiological constraint imposed upon fish, phrases such as 'like a fish of water', convey our acceptance of the general unsuitability of fish for terrestrial existence. The constraints that restrict fish to an aquatic habitat relate to respiration, acid-base regulation, nitrogenous excretion, water balance and ionic regulation. A fish not adapted for an amphibious lifestyle when removed from water, becomes hypoxic and hypercapnic and soon succumbs to respiratory acidosis because the problem of excretion of H super(+) and C0 sub(2) are more immediate than lack of oxygen. This happen because fish gills collapse in air, while the ventilator arrangements that moves an incompressible medium (water) oven them become ineffective
Resumo:
Nicotinic acetylcholine receptors (nAChRs) are pentameric, ligand-gated, cation channels found throughout the central and peripheral nervous system, whose endogenous ligand is acetylcholine, but which can also be acted upon by nicotine. The subunit compositions of nAChR determine their physiological and pharmacological properties, with different subunits expressed in different combinations or areas throughout the brain. The behavioral and physiological effects of nicotine are elicited by its agonistic and desensitizing actions selectively on neuronal nAChRs. The midbrain is of particular interest due to its population of nAChRs expressed on dopaminergic neurons, which are important for reward and reinforcement, and possibly contribute to nicotine dependence. The α6-subunit is found on dopaminergic neurons but very few other regions of the brain, making it an interesting drug target. We assayed a novel nicotinic agonist, called TI-299423 or TC299, for its possible selectivity for α6-containing nAChRs. Our goal was to isolate the role of α6-containing nAChRs in nicotine reward and reinforcement, and provide insight into the search for more effective smoking cessation compounds. This was done using a variety of in vitro and behavioral assays, aimed dually at understanding TI-299423’s exact mechanism of action and its downstream effects. Additionally, we looked at the effects of another compound, menthol, on nicotine reward. Understanding how reward is generated in the cholinergic system and how that is modulated by other compounds contributes to a better understand of our complex neural circuitry and provides insight for the future development of therapeutics.
Sensitivity of sturgeons to environmental hypoxia: a review of physiological and ecological evidence
Resumo:
In this essay, three lines of evidence are developed that sturgeons in the Chesapeake Bay and elsewhere are unusually sensitive to hypoxic conditions: 1. In comparison to other fishes,sturgeons have a limited behavioral and physiological capacity to respond to hypoxia. Basal metabolism, growth, feeding rate, and survival are sensitive to changes in oxygen level, which may indicate a relatively poor ability of sturgeons to oxyregulate. 2. During summertime, temperatures >20°C amplify the effect of hypoxia on sturgeons and other fishes due to a temperature oxygen "squeeze" (Coutant 1987). In bottom waters, this interaction results in substantial reduction of habitat; in dry years, sturgeon nursery habitats in the Chesapeake Bay may be particularly reduced or even eliminated. 3. While evidence for population level effects due to hypoxia is circumstantial, there are corresponding trends between the absence of Atlantic sturgeon reproduction in estuaries like the Chesapeake Bay where summertime hypoxia predominates on a system-wide scale. Also, the recent and dramatic recovery of shortnose sturgeon in the Hudson River (4-bid increase in abundance from 1980 to1995) may have been stimulated by improvement of a large portion of the nursery habitat that was restored from hypoxia to normoxia during the period 1973-1978.
Resumo:
The results are described of eco-physiological investigations of the broad-pincered (Astacus astacus L.J.) crayfish and the long-pincered (Astacus astacus Esch.) crayfish, conducted in 1963—64 in the Institute of Zoology and Parasitology of the Academy of Science of the Lithuanian SSR, for the purpose of studying the interspecific relationship of these two species. In the course of the investigation were determined: the influence of the temperature of the environment on the consumption of oxygen by full grown individuals of both species and on the respiratory movements of the scaphognathites, the threshold temperatures and the saturation of the water by oxygen, the diel activity in the winter period.
Resumo:
The osmotic pressure of the perivitelline fluid and the yolk of trout (Salmo trutta) eggs were measured separately by the Drucker-Schrein method. The permeability of the egg membrane and the variations in the osmotic pressure of the eggs when placed in salt solutions were also investigated.
Resumo:
The life cycle of the river lamprey, L. fluviatilis, is reviewed. The larval lamprey, or ammocoete, is a blind, filter-feeding animal, which normally lies concealed in the silt deposits of streams and rivers. After a period of 3-5 years in fresh water the ammocoete undergoes a metamorphosis in the summer months into a sexually immature, non-feeding stage known as the macrophthalia, which is active. This stage migrates downstream in late winter. It adopts a parasitic existence, in intertidal areas. After 18 months it returns to spawn in fresh water, after a final freshwater stage lasting up to 9 months. The river lamprey dies within a few days after the spawning period of 3-4 weeks, and none survive to spawn the following year.
Resumo:
Loxodes faces special problems in living close to the oxic-anoxic boundary. In tightly-stratified ponds like Priest Pot its optimum environment may be quite narrow and it can be displaced by the slightest turbulence. Loxodes cannot sense an O sub(2) gradient directly but its ability to perceive gravity allows it to make relatively long vertical migrations. It is also sensitive to light and oxygen and it uses these environmental cues to modulate the parameters of its random motility: in the dark, it aggregates at a low O sub(2) tension and in bright light it aggregates in anoxic water. The oxic-anoxic boundary is also a zone where O sub(2) may be a scarce and transient resource, but Loxodes) can switch to nitrate respiration and exploit the pool of nitrate that often exists close to the base of the oxycline.
Resumo:
Chronic diseases of the central nervous system are poorly treated due to the inability of most therapeutics to cross the blood-brain barrier. The blood-brain barrier is an anatomical and physiological barrier that severely restricts solute influx, including most drugs, from the blood to the brain. One promising method to overcome this obstacle is to use endogenous solute influx systems at the blood-brain barrier to transport drugs. Therapeutics designed to enter the brain through transcytosis by binding the transferrin receptor, however, are restricted within endothelial cells. The focus of this work was to develop a method to increase uptake of transferrin-containing nanoparticles into the brain by overcoming these restrictive processes.
To accomplish this goal, nanoparticles were prepared with surface transferrin molecules bound through various liable chemical bonds. These nanoparticles were designed to shed the targeting molecule during transcytosis to allow increased accumulation of nanoparticles within the brain.
Transferrin was added to the surface of nanoparticles through either redox or pH sensitive chemistry. First, nanoparticles with transferrin bound through disulfide bonds were prepared. These nanoparticles showed decreased avidity for the transferrin receptor after exposure to reducing agents and increased ability to enter the brain in vivo compared to those lacking the disulfide link.
Next, transferrin was attached through a chemical bond that cleaves at mildly acidic pH. Nanoparticles containing a cleavable link between transferrin and gold nanoparticle cores were found to both cross an in vitro model of the blood-brain barrier and accumulate within the brain in significantly higher numbers than similar nanoparticles lacking the cleavable bond. Also, this increased accumulation was not seen when using this same strategy with an antibody to transferrin receptor, indicating that behavior of nanoparticles at the blood-brain barrier varies depending on what type of targeting ligand is used.
Finally, polymeric nanoparticles loaded with dopamine and utilizing a superior acid-cleavable targeting chemistry were investigated as a potential treatment for Parkinson’s disease. These nanoparticles were capable of increasing dopamine quantities in the brains of healthy mice, highlighting the therapeutic potential of this design. Overall, this work describes a novel method to increase targeted nanoparticle accumulation in the brain.
Resumo:
In this study we employed a dynamic recurrent neural network (DRNN) in a novel fashion to reveal characteristics of control modules underlying the generation of muscle activations when drawing figures with the outstretched arm. We asked healthy human subjects to perform four different figure-eight movements in each of two workspaces (frontal plane and sagittal plane). We then trained a DRNN to predict the movement of the wrist from information in the EMG signals from seven different muscles. We trained different instances of the same network on a single movement direction, on all four movement directions in a single movement plane, or on all eight possible movement patterns and looked at the ability of the DRNN to generalize and predict movements for trials that were not included in the training set. Within a single movement plane, a DRNN trained on one movement direction was not able to predict movements of the hand for trials in the other three directions, but a DRNN trained simultaneously on all four movement directions could generalize across movement directions within the same plane. Similarly, the DRNN was able to reproduce the kinematics of the hand for both movement planes, but only if it was trained on examples performed in each one. As we will discuss, these results indicate that there are important dynamical constraints on the mapping of EMG to hand movement that depend on both the time sequence of the movement and on the anatomical constraints of the musculoskeletal system. In a second step, we injected EMG signals constructed from different synergies derived by the PCA in order to identify the mechanical significance of each of these components. From these results, one can surmise that discrete-rhythmic movements may be constructed from three different fundamental modules, one regulating the co-activation of all muscles over the time span of the movement and two others elliciting patterns of reciprocal activation operating in orthogonal directions.
Resumo:
Microglia are largely known as the major orchestrators of the brain inflammatory response. As such, they have been traditionally studied in various contexts of disease, where their activation has been assumed to induce a wide range of detrimental effects. In the last few years, a series of discoveries have challenged the current view of microglia, showing their active and positive contribution to normal brain function. This Research Topic will review the novel physiological roles of microglia in the developing, mature and aging brain, under non-pathological conditions. In particular, this Research Topic will discuss the cellular and molecular mechanisms by which microglia contribute to the formation, pruning and plasticity of synapses; the maintenance of the blood brain barrier; the regulation of adult neurogenesis and hippocampal learning; and neuronal survival, among other important roles. Because these novel findings defy our understanding of microglial function in health as much as in disease, this Research Topic will also summarize the current view of microglial nomenclature, phenotypes, origin and differentiation, sex differences, and contribution to various brain pathologies. Additionally, novel imaging approaches and molecular tools to study microglia in their non-activated state will be discussed. In conclusion, this Research Topic seeks to emphasize how the current research in neuroscience is challenged by never-resting microglia.
Resumo:
A central question in Neuroscience is that of how the nervous system generates the spatiotemporal commands needed to realize complex gestures, such as handwriting. A key postulate is that the central nervous system (CNS) builds up complex movements from a set of simpler motor primitives or control modules. In this study we examined the control modules underlying the generation of muscle activations when performing different types of movement: discrete, point-to-point movements in eight different directions and continuous figure-eight movements in both the normal, upright orientation and rotated 90 degrees. To test for the effects of biomechanical constraints, movements were performed in the frontal-parallel or sagittal planes, corresponding to two different nominal flexion/abduction postures of the shoulder. In all cases we measured limb kinematics and surface electromyographic activity (EMB) signals for seven different muscles acting around the shoulder. We first performed principal component analysis (PCA) of the EMG signals on a movement-by-movement basis. We found a surprisingly consistent pattern of muscle groupings across movement types and movement planes, although we could detect systematic differences between the PCs derived from movements performed in each sholder posture and between the principal components associated with the different orientations of the figure. Unexpectedly we found no systematic differences between the figute eights and the point-to-point movements. The first three principal components could be associated with a general co-contraction of all seven muscles plus two patterns of reciprocal activatoin. From these results, we surmise that both "discrete-rhythmic movements" such as the figure eight, and discrete point-to-point movement may be constructed from three different fundamental modules, one regulating the impedance of the limb over the time span of the movement and two others operating to generate movement, one aligned with the vertical and the other aligned with the horizontal.
Resumo:
In the early 20th century, a blue mussel species from the Mediterranean invaded the California coast and subsequently out-competed the native species south of Monterey Bay. Like other invasive species, Mytilus galloprovincialis has physiological traits that make it successful in habitats formerly occupied by the native M. trossulus, namely its adaptation to warm sea surface temperatures. This study looks at the current genotype distributions and enzymatic activities of field-acclimatized mussels within the hybrid zone where the species co-occur as well as mussels that have been acclimated for four weeks to different temperature and salinity conditions. In the field-acclimatized and laboratory-acclimated mussels, the native species exhibited significantly higher enzyme rates, which may reflect an evolutionary adaptation to compensate to low habitat temperatures. Indeed, the results of the laboratory acclimation indicate that these differences are genetically based. Whether an acclimation capacity exists may require even longer-term acclimation to different temperatures. Current findings suggest that the further spread of the invasive species is likely to be governed in large measure by the potentially counteracting effects of rising temperatures, which would favor the northerly spread of M. galloprovincialis, and increased winter precipitation, which would favor the persistence of M. trossulus. However, the success of M. galloprovincialis during acclimation to ‘dilute’ salinity (25 ppt) suggests that the invasive species can tolerate a greater salinity range than previously thought. Thus, further investigation is needed to build a comprehensive predictive model of the movement of M. galloprovincialis and the hybrid zone along the California coast.
Resumo:
Measurement of the physiological effects of the red algal epiphytes Smithora naiadum (Anders.) Hollenberg and Melobesia mediocris (Fosl.) Setch. and Mason on Phyllospadix torreyi Wats. were made near Hopkins Marine Station, Pacific Grove, California. Field studies revealed a significant influence of these epiphytes on both the breakage incidence and length, with that of Melobesia being the most pronounced. Analysis of the photosynthetic rate of the seagrass shows a decrease in the photosynthetic maxima in both epiphytized samples at a light saturating intensity. Under light limiting conditions, an increase in photosynthetic efficiency and a change in chlorophyll a composition in both epiphytized sample types suggest an adaptive mechanism similiar to those found in terrestrial and aquatic shade plants.