Biomedical subjects

David Alonso

Publications and source records attributed to David Alonso.

17 recordsLinked to original sources

PubMed2007

The nitric oxide donor LA 419 decreases ischemic brain damage.

Stroke represents a major clinical problem with limited available therapeutic treatments. Nitric oxide (NO) and the enzymes that produce it are involved in the pathogenesis of this disease. Here we investigated whether the novel NO donor LA 419 was able to ameliorate the consequences of stroke in an experimental model of global ischemia. We observed a sharp increase in the amounts of inducible NO synthase (iNOS) and nitrotyrosine in the cerebral cortex of experimental rats and a moderate increase of neuronal NO synthase (nNOS), as demonstrated by immunohistochemistry, Western blotting, and enzymatic activity assays. Treatment of these animals with LA 419 completely prevented ischemia-induced upregulation of nitrergic markers. Magnetic resonance imaging of the experimental brains showed a marked decrease in apparent diffusion coefficient (ADC) following ischemia-reperfusion, which was significantly corrected by pre-treatment with LA 419. These results clearly show that LA 419 is an efficient modulator of NO-related pathophysiological events and could eventually be used for the treatment of patients with cerebrovascular pathologies.

Animals↗

PubMed2006

Comment on "A keystone mutualism drives pattern in a power function".

Vandermeer and Perfecto (Reports, 17 February 2006, p. 1000) reported a general power law pattern in the distribution of a common agricultural pest. However, there is an exact analytical solution for the expected cluster distribution under the proposed null model of density-independent growth in a patchy landscape. Reanalysis of the data shows that the system is not in a critical state but confirms the importance of a mutualism.

Animals↗

PubMed2006

The merits of neutral theory.

Hubbell's neutral theory of biodiversity has challenged the classic niche-based view of ecological community structure. Although there have been many attempts to falsify Hubbell's theory, we argue that falsification should not lead to rejection, because there is more to the theory than neutrality alone. Much of the criticism has focused on the neutrality assumption without full appreciation of other relevant aspects of the theory. Here, we emphasize that neutral theory is also a stochastic theory, a sampling theory and a dispersal-limited theory. These important additional features should be retained in future theoretical developments of community ecology.

Animals↗

PubMed2006

Theoretical biology: comparing models of species abundance.

Ecologists are struggling to explain how so many tropical tree species can coexist in tropical forests, and several empirical studies have demonstrated that negative density dependence is an important mechanism of tree-species coexistence. Volkov et al. compare a model incorporating negative density dependence with a dispersal-limited neutral model and claim that each predicts six empirical species-abundance distributions of tropical-tree communities equally well. However, we show here that their main conclusion is premature: when the two models are compared in an improved analysis, we find that the dispersal-limited model outcompetes the density-dependent model in all six cases. Hence, although density dependence is certainly an important diversity-maintaining mechanism, our improved approach indicates that the dispersal-limited model provides a more parsimonious explanation of empirical species-abundance distributions.

Biodiversity↗

PubMed2006

[How much primaquine is needed to eradicate Plasmodium vivax hypnozoites?].

INTRODUCTION: Primaquine is now the only drug available to eradicate Plasmodium vivax malaria. The optimal dose of primaquine to prevent relapses of P. vivax remains under discussion. CLINICAL CASES: We describe three cases of P. vivax malaria from different geographical areas, in which a tolerance to standard doses of primaquine and, in some cases, to much higher doses has been observed. COMMENTS: P. vivax tolerance to primaquine is an emerging problem in daily practice. Reassessment of the primaquine dose required to eradicate P. vivax intrahepatic hypnozoites is needed.

Adult↗

PubMed2006

Failure of standard treatment with praziquantel in two returned travelers with Schistosoma haematobium infection.

A single 40 mg/kg dose of praziquantel (PZQ) continues to be the standard treatment for schistosomiasis caused by S. mansoni and S. haematobium in all clinical settings. Experimental development of drug resistance and the recent isolation of S. mansoni strains with a natural tolerance to high doses of PZQ have raised concerns over the adequacy of such a dose. We describe two Spanish travelers with genitourinary schistosomiasis caused by S. haematobium in whom repeated standard treatment failed to clear the infection.

Adult↗

PubMed2004

Analytic solution of Hubbell's model of local community dynamics.

Recent theoretical approaches to community structure and dynamics reveal that many large-scale features of community structure (such as species-rank distributions and species-area relations) can be explained by a so-called neutral model. Using this approach, species are taken to be equivalent and trophic relations are not taken into account explicitly. Here we provide a general analytic solution to the local community model of Hubbell's neutral theory of biodiversity by recasting it as an urn model, i.e. a Markovian description of states and their transitions. Both stationary and time-dependent distributions are analysed. The stationary distribution-also called the zero-sum multinomial-is given in closed form. An approximate form for the time-dependence is obtained by using an expansion of the master equation. The temporal evolution of the approximate distribution is shown to be a good representation for the true temporal evolution for a large range of parameter values.

Biodiversity↗

PubMed2004

Nitric oxide in the rat cerebellum after hypoxia/ischemia.

Nitric oxide is a regulatory biological substance and an important intracellular messenger that acts as a specific mediator of various neuropathological disorders. In mammals and invertebrates, nitric oxide is synthesized from L-arginine in the central and peripheral neural structures by the endothelial, neuronal and inducible enzymatic isoforms of nitric oxide synthase. Nitric oxide may affect the function of various neurotransmitter-specific systems, and is involved in neuromodulation, reproductive function, immune response, and regulation of the cerebral blood circulation. This makes nitric oxide the main candidate in brain responses to brain ischemia/hypoxia. The cerebellum has been reported to be the area of the brain that has the highest nitric oxide synthase activity and the highest concentration of glutamate and aspartate. By glutamate receptors and physiological action of nitric oxide, cyclic guanisine-5'-monophosphate may be rapidly increased. The cerebellum significantly differs with respect to ischemia and hypoxia, this response being directly related to the duration and intensity of the injury. The cerebellum could cover the eventual need for nitric oxide during the hypoxia, boosting the nitric oxide synthase activity, but overall ischemia would require de novo protein synthesis, activating the inducible nitric oxide synthase to cope with the new situation. The specific inhibitors of nitric oxide synthesis show neuroprotective effects.

Animals↗

PubMed2003

Generation and role of angiostatin in human platelets.

Platelets regulate new blood vessel growth, because they contain a number of angiogenesis promoters and inhibitors. Additionally, platelets contain matrix metalloproteinases (MMPs), which when released mediate platelet adhesion and aggregation, and plasminogen, a fibrinolytic system enzyme that serves to limit blood clot formation. Enzymatic cleavage of plasminogen by MMPs generates angiostatin, an angiogenesis inhibitor. Therefore, we examined whether platelets generate angiostatin during aggregation in vitro. Platelets were isolated from healthy human donors and then aggregated with collagen, thrombin, or HT-1080 fibrosarcoma cells. Angiostatin was detected by Western blot analysis in the platelet releasates of all blood donors irrespective of the aggregating agent used. Platelet pellet homogenates showed the presence of angiostatin in all donors, which was released upon aggregation. Furthermore, platelet-derived angiostatin was isolated and purified by lysine-Sepharose affinity chromatography from collagen-aggregated platelet releasates. Bioassay of platelet-derived angiostatin showed that it inhibited the formation of capillary structures by human umbilical vein endothelial cells (HUV-EC-Cs) in an in vitro angiogenesis model. Inhibition of angiostatin in platelet releasates promoted the formation of capillary structures by HUV-EC-Cs. We conclude that healthy human platelets contain angiostatin, which is released in active form during platelet aggregation, and platelet-derived angiostatin has the capacity to inhibit angiogenesis.

Angiogenesis Inhibitors↗

PubMed2003

Postnatal changes in the nitric oxide system of the rat cerebral cortex after hypoxia during delivery.

The impact of hypoxia in utero during delivery was correlated with the immunocytochemistry, expression and activity of the neuronal (nNOS) and inducible (iNOS) isoforms of the nitric oxide synthase enzyme as well as with the reactivity and expression of nitrotyrosine as a marker of protein nitration during early postnatal development of the cortex. The expression of nNOS in both normal and hypoxic animals increased during the first few postnatal days, reaching a peak at day P5, but a higher expression was consistently found in hypoxic brain. This expression decreased progressively from P7 to P20, but was more prominent in the hypoxic group. Immunoreactivity for iNOS was also higher in the cortex of the hypoxic rats and was more evident between days P0 and P5, decreasing dramatically between P10 and P20 in both groups of rats. Two nitrated proteins of 52 and 38 kDa, were also identified. Nitration of the 52-kDa protein was more intense in the hypoxic animals than in the controls, increasing from P0 to P7 and then decreasing progressively to P20. The 38-kDa nitrated protein was seen only from P10 to P20, and its expression was more intense in control than in the hypoxic group. These results suggest that the NO system may be involved in neuronal maturation and cortical plasticity over postnatal development. Overproduction of NO in the brain of hypoxic animals may constitute an effort to re-establish normal blood flow and may also trigger a cascade of free-radical reactions, leading to modifications in the cortical plasticity.

Animals↗

PubMed2003

Expression of nitrergic system and protein nitration in adult rat brains submitted to acute hypobaric hypoxia.

Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, and NO synthase (NOS) activity assays in adult rats submitted for 30 min to hypoxia, in a hypobaric chamber at a simulated altitude of 38,000 ft (11000 m) (154.9 mm Hg). The cerebral cortex was studied after different survival times, 0 and 24 h, 5, 8, 15, and 30 days of reoxygenation. This situation led to morphological alterations in the large type I interneurons, as well as immunoreactive changes in the appearance and number of the small neurons (type II), both containing neuronal NOS (nNOS). Some of these small neurons showed immunoreactive cytoplasm and short processes; others, the more numerous during all reoxygenation periods, contained the immunoreactive product mainly related to a perinuclear ring. Ultrastructurally, these small neurons exhibited changes in nuclear structures as in the shape of the nuclear membrane, in the distribution of heterochromatin, and in the nucleolar morphology. The reaction product for nitrotyrosine, as a marker of protein nitration, showed modifications in distribution of the immunoreactive product. No expression was found for inducible NOS (iNOS). All these modifications were accompanied by increased nNOS and nitrotyrosine production as demonstrated by Western blotting and calcium-dependent activity, returning to control conditions after 30 days of reoxygenation, suggesting a reversible NO mechanism of action.

Animals↗

PubMed2003

The nitric oxide-endothelin-1 connection.

Nitric oxide (NO) and endothelin-1 (ET-1) are endothelium-derived mediators that play important roles in vascular homeostasis. This review is focused on the role and reciprocal interactions between NO and ET-1 in health and diseases associated with endothelium dysfunction. We will also discuss the clinical significance of NO donors and drugs that antagonize ET receptors.

Endothelin Receptor Antagonists↗

PubMed2003

Nitric oxide, platelet function, myocardial infarction and reperfusion therapies.

Platelets play an important role in physiologic hemostasis and pathologic thrombosis that complicate the course of vascular disorders. A number of platelet functions including adhesion, aggregation and recruitment are controlled by nitric oxide (NO) generated by platelets and the endothelial cells. Derangements in this generation may contribute to the pathogenesis of thrombotic complications of vascular disorders. The pharmacologic supplementation of the diseased vasculature with drugs releasing NO may help to restore the hemostatic balance.

Blood Platelets↗

PubMed2002

Adrenomedullin over-expression in the caudate-putamen of the adult rat brain after ischaemia-reperfusion injury.

The expression of adrenomedullin (AM) was studied in the caudate-putamen of the adult rat brain using a global cerebral ischaemia model. The animals were subjected to 30 min of glucose and oxygen deprivation, and the brains were collected after 0, 2, 4, 6, 8 and 10 h of reperfusion. Coronal sections of the caudate-putamen were studied by immunocytochemistry using a specific polyclonal antibody against AM and examined by light microscopy. Under these experimental conditions AM immunoreactivity increased in the wall of the blood vessels and in three different types of neurons distributed throughout the caudate-putamen. Our findings suggest that the over-expression of AM and its changes in its intracellular location might be involved in the neuronal responses to brain ischaemia with a possible neuroprotector role.

Adrenomedullin↗

PubMed2002

Self-organized instability in complex ecosystems.

Why are some ecosystems so rich, yet contain so many rare species? High species diversity, together with rarity, is a general trend in neotropical forests and coral reefs. However, the origin of such diversity and the consequences of food web complexity in both species abundances and temporal fluctuations are not well understood. Several regularities are observed in complex, multispecies ecosystems that suggest that these ecologies might be organized close to points of instability. We explore, in greater depth, a recent stochastic model of population dynamics that is shown to reproduce: (i) the scaling law linking species number and connectivity; (ii) the observed distributions of species abundance reported from field studies (showing long tails and thus a predominance of rare species); (iii) the complex fluctuations displayed by natural communities (including chaotic dynamics); and (iv) the species-area relations displayed by rainforest plots. It is conjectured that the conflict between the natural tendency towards higher diversity due to immigration, and the ecosystem level constraints derived from an increasing number of links, leaves the system poised at a critical boundary separating stable from unstable communities, where large fluctuations are expected to occur. We suggest that the patterns displayed by species-rich communities, including rarity, would result from such a spontaneous tendency towards instability.

Animals↗

PubMed2002

Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex.

Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS-immunoreactive band and calcium-dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV-V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium-independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham-perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L-NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia-reperfusion contributes to cerebral injury.

Animals↗

PubMed2002

Extinction dynamics in mainland-island metapopulations: an N-patch stochastic model.

A generalization of the well-known Levins' model of metapopulations is studied. The generalization consists of (i) the introduction of immigration from a mainland, and (ii) assuming the dynamics is stochastic, rather than deterministic. A master equation, for the probability that n of the patches are occupied, is derived and the stationary probability Ps(n), together with the mean and higher moments in the stationary state, determined. The time-dependence of the probability distribution is also studied: through a Gaussian approximation for general n when the boundary at n = 0 has little effect, and by calculating P(0, t), the probability that no patches are occupied at time t, by using a linearization procedure. These analytic calculations are supplemented by carrying out numerical solutions of the master equation and simulations of the stochastic process. The various approaches are in very good agreement with each other. This allows us to use the forms for Ps(0) and P(0,t) in the linearization approximation as a basis for calculating the mean time for a metapopulation to become extinct. We give an analytical expression for the mean time to extinction derived within a mean field approach. We devise a simple method to apply our mean field approach even to complex patch networks in realistic model metapopulations. After studying two spatially extended versions of this nonspatial metapopulation model--a lattice metapopulation model and a spatially realistic model--we conclude that our analytical formula for the mean extinction time is generally applicable to those metapopulations which are really endangered, where extinction dynamics dominates over local colonization processes. The time evolution and, in particular, the scope of our analytical results, are studied by comparing these different models with the analytical approach for various values of the parameters: the rates of immigration from the mainland, the rates of colonization and extinction, and the number of patches making up the metapopulation.

Animals↗