PubMed Health⌕ Search

Biomedical subjects

O Marti

Publications and source records attributed to O Marti.

15 recordsLinked to original sources
PubMed2003

Novel ligands for the investigation of imidazoline receptors and their binding proteins.

New ligands for imidazoline receptors are described so that these receptors can be more fully explored and understood. BU224, (2-(4,5-dihydroimidaz-2-yl)-quinoline, shows high affinity and is selective for the imidazoline-2 (I(2)) class of receptors. BU224 was tested in the rat Porsolt forced swim paradigm where it was found to decrease time spent immobile and increase the time spent swimming, consistent with an antidepressant profile. BU224 was tritiated and, in radioligand binding studies, was found to label a single population of saturable sites with high affinity. In vitro brain autoradiography with [(3)H]BU224 also showed a pattern of distribution similar to the known labeling of I(2) receptors. A new series of four 2BFI (2-(benzofuranyl)-2-imidazoline) derivatives were investigated as potential ligands for imaging brain I(2) receptors using positron emission tomography (PET). At least two, BU20012 and BU20013, retained high affinity and moderate selectivity and penetrated the brain when administered peripherally in the mouse. 2BFI has undergone the Mannich reaction to immobilized diaminodipropyl amine to fabricate an affinity column, which was used to isolate a protein from rabbit brain; this protein was sequenced and identified as the enzyme creatine kinase.

Animals↗
PubMed2001

Simulating the amplification of orbital forcing by ocean feedbacks in the last glaciation.

According to Milankovitch theory, the lower summer insolation at high latitudes about 115,000 years ago allowed winter snow to persist throughout summer, leading to ice-sheet build-up and glaciation. But attempts to simulate the last glaciation using global atmospheric models have failed to produce this outcome when forced by insolation changes only. These results point towards the importance of feedback effects-for example, through changes in vegetation or the ocean circulation-for the amplification of solar forcing. Here we present a fully coupled ocean-atmosphere model of the last glaciation that produces a build-up of perennial snow cover at known locations of ice sheets during this period. We show that ocean feedbacks lead to a cooling of the high northern latitudes, along with an increase in atmospheric moisture transport from the Equator to the poles. These changes agree with available geological data and, together, they lead to an increased delivery of snow to high northern latitudes. The mechanism we present explains the onset of glaciation-which would be amplified by changes in vegetation-in response to weak orbital forcing.

Journal Article↗
PubMed2000

Near-field scanning optical microscopy of zinc-porphyrin crystals.

Using a near-field scanning optical microscope (NSOM), crystals of zinc-porphyrin network materials are characterized with respect to morphology and fluorescence. Needle-shaped crystals are observed. While the topography is flat, the fluorescence intensity profile in the width direction is approximately triangular. A numerical calculation shows that differences between the topographic and optical images cannot be due to an artifact. In some needle-shaped crystals, the fluorescence emission is strongly peaked at one or both ends, possibly indicating a polar crystal structure.

Crystallization↗
PubMed1998

Piezoelectrical shear-force distance control in near-field optical microscopy for biological applications.

We present a piezoelectrical shear-force distance control setup for scanning near-field optical microscopy. The setup is compact and tip exchange is easy. The topographical sensitivity is comparable to optical feedback systems. With an acceptable vibration amplitude of 5-10 nm we obtained a topographical resolution of 5 pm/square root of Hz. Because there is no laser necessary for tip position feedback, there is no extraneous light to interfere with spectroscopic and other low-light level experiments. Our technique permits measurements of soft biological samples in aqueous solution, which opens up many possible applications of near-field optical microscopy in biology and medicine.

Animals↗
PubMed1998

Emergent immunoregulatory properties of combined glucocorticoid and anti-glucocorticoid steroids in a model of tuberculosis.

In Balb/c mice with pulmonary tuberculosis, there is a switch from a protective Th1-dominated cytokine profile to a non-protective profile with a Th2 component. This switch occurs while the adrenals are undergoing marked hyperplasia. Treatment with the anti-glucocorticoid hormones dehydroepiandrosterone or 3 beta, 17 beta-androstenediol, during the period of adrenal hyperplasia, maintains Th1 dominance and is protective. We investigated the effects of these hormones as therapeutic agents by administering them from day 60, when the switch to the non-protective cytokine profile was already well established. Given at this time (day 60), doses that were protective when given early (from day 0) were rapidly fatal. A physiological dose of the glucocorticoid corticosterone was also rapidly fatal. However when the corticosterone and the anti-glucocorticoid (AED or DHEA) were co-administered, there was protection, with restoration of a Th1-dominated cytokine profile, enhanced DTH responses, and enhanced expression of IL-1 alpha and TNF alpha. Therefore this combination of steroids has an emergent property that is quite unlike that of either type of steroid given alone. It may be possible to exploit the ant-inflammatory properties of glucocorticoids while preserving a Th1 bias, by combining glucocorticoids with DHEA or suitable metabolites.

Adjuvants, Immunologic↗
PubMed1998

Alteration of central serotonin modifies onset and severity of adjuvant-induced arthritis in the rat.

OBJECTIVE: Previous studies have determined that depletion of serotonin reduces the severity of hind-paw inflammation in adjuvant-induced arthritis (AA) in the rat. We wished to (i) test the hypothesis that this effect may be mediated, at least in part, through a central mechanism and (ii) to investigate further the pro-inflammatory role of serotonin we determined whether increasing serotonin using a selective serotonin reuptake inhibitor (SSRI), to increase serotonin availability at the active site of release, would increase inflammation. METHODS: (i) Serotonin was depleted in the brain of rats with the selective neurotoxin 5'7'-dihydroxytryptamine. (ii) Rats were treated with an SSRI on days 10, 11 and 12 following adjuvant injection. Hind-paw inflammation was determined with plethysmometry as an index of severity of inflammation, and brain, pituitaries and blood were collected for assessment of changes in the hypothalamo -pituitary adrenal (HPA) axis. RESULTS: (i) Serotonin depletion significantly reduced hind-paw inflammation. (ii) SSRI-treated animals developed hind-paw inflammation sooner, and the severity was increased compared to vehicle-treated AA rats. The changes in the HPA axis associated with inflammation were partly reversed by this treatment. CONCLUSION: These data suggest a pro-inflammatory role for central serotonin in this disease model and indicate that treatment with SSRIs may exacerbate the development of inflammation.

5,7-Dihydroxytryptamine↗
PubMed1997

The hypothalamic-pituitary-adrenal axis in autoimmunity.

We have characterized the activation of the HPA axis in the chronic inflammatory stress model of adjuvant-induced arthritis. Alteration in the hypothalamic control mechanism, where CRF is no longer the major corticotrophin-releasing factor, has been noted in a number of other immune-mediated disease models, including experimental allergic encephalomyelitis, eosinophilia myalgia syndrome, systemic lupus erythematosus, and leishmaniasis. These changes occur in both the mouse and the rat, suggesting this may be a common mechanism to chronic immune activation. We have good evidence to suggest that AVP takes over as the major stimulator of the axis. The arthritic rat is unable to mount a response to acute stressors, such as restraint or ip hypertonic saline. However, these animals are able to mount a response to an acute immune challenge. These data provide further evidence for a differential activation of the HPA by acute stress or acute immune stimulation. This presumably reflects an adaptive response to the development of chronic inflammation. We have demonstrated that central neurotransmitter systems are able to influence the severity of peripheral inflammation. In particular we have shown that depletion of serotonin at the time of the development of the inflammatory episode reduces the severity of the inflammation. These findings suggest the possibility of novel therapeutic strategies targeting neurotransmitter systems to alleviate inflammation.

Animals↗
PubMed1996

Acute stress markers in humans: response of plasma glucose, cortisol and prolactin to two examinations differing in the anxiety they provoke.

Although the endocrine response to psychological stressors has been extensively studied both in animals and humans, the sensitivity of these variables to the intensity of stress experienced by exposure to psychologically stressful situations has not been studied in humans. In the present work this was assessed by measuring plasma levels of glucose, cortisol and prolactin in female medical students just before taking two examinations clearly differing in the anxiety they provoke. It was found that both examinations increased anxiety just before taking them, but the physiology examination (EPh) caused higher anxiety than the psychology (EPs). Prolactin increased in response to both examinations as compared to the non-stress condition, but its levels were greater in the EPh than in the EPs. Cortisol followed the same pattern as prolactin, but increased only marginally in the EPs. Finally, glycemia rose to the same extent in response to both examinations. A significant positive correlation was found between anxiety and glucose, and between cortisol and prolactin when data from all situations were included. On the basis of these results, it appears that the three variables might be useful as putative markers of stress in humans, although glucose might reflect different underlying psychological processes than cortisol and prolactin. In addition, it was found for the first time that prolactin is able to discriminate between stressful situations of different intensity. The response of these physiological variables to other stressful situations differing both in quantitative and in qualitative terms merits to be studied in further work.

Adult↗
PubMed1992

Na,K-ATPase in crystalline form investigated by scanning force microscopy.

Na,K-ATPase has been isolated in purified membrane fragments from kidney tissue and crystallized by phospholipase treatment to obtain two-dimensional, membrane-bound protein crystals. Scanning force microscopy has been used to identify and analyze the topography of the membrane fragments. Specific patterns in accordance with electron microscopic images have been found. In biological material under physiological conditions the scanning force is a crucial parameter for the resulting image at high resolution.

Animals↗
PubMed1990

Blockade of opioid receptors with naltrexone inhibits thyrotropin increase after noise stress but does not prevent the decrease caused by immobilization.

The influence of naltrexone-induced opioid receptor blockade on the response of thyrotropin to two different acute stressors was studied in adult male rats. Naltrexone slightly but significantly reduced basal thyrotropin levels and abolished the increase in serum thyrotropin caused by acute noise stress. In contrast, the opioid antagonist did not prevent the decrease in serum thyrotropin caused by another much more severe stressor such as immobilization. The present data offer the first evidence that endogenous opioids could play a stimulatory role in the control of thyrotropin secretion in a presumably physiological condition such as the response to a mild stressor. In addition, factors other than opioids could be involved in the inhibition of thyrotropin secretion under severe stress.

Acoustic Stimulation↗
PubMed1989

The scanning ion-conductance microscope.

A scanning ion-conductance microscope (SICM) has been developed that can image the topography of nonconducting surfaces that are covered with electrolytes. The probe of the SICM is an electrolyte-filled micropipette. The flow of ions through the opening of the pipette is blocked at short distances between the probe and the surface, thus, limiting the ion conductance. A feedback mechanism can be used to maintain a given conductance and in turn determine the distance to the surface. The SICM can also sample and image the local ion currents above the surfaces. To illustrate its potential for imaging ion currents through channels in membranes, a topographic image of a membrane filter with 0.80-micrometer pores and an image of the ion currents flowing through such pores are presented.

Cell Membrane↗
PubMed1988

Scanning tunneling microscopy and atomic force microscopy: application to biology and technology.

The scanning tunneling microscope (STM) and the atomic force microscope (AFM) are scanning probe microscopes capable of resolving surface detail down to the atomic level. The potential of these microscopes for revealing subtle details of structure is illustrated by atomic resolution images including graphite, an organic conductor, an insulating layered compound, and individual adsorbed oxygen atoms on a semiconductor. Application of the STM for imaging biological materials directly has been hampered by the poor electron conductivity of most biological samples. The use of thin conductive metal coatings and replicas has made it possible to image some biological samples, as indicated by recently obtained images of a recA-DNA complex, a phospholipid bilayer, and an enzyme crystal. The potential of the AFM, which does not require a conductive sample, is shown with molecular resolution images of a nonconducting organic monolayer and an amino acid crystal that reveals individual methyl groups on the ends of the amino acids. Applications of these new microscopes to technology are demonstrated with images of an optical disk stamper, a diffraction grating, a thin-film magnetic recording head, and a diamond cutting tool. The STM has even been used to improve the quality of diffraction gratings and magnetic recording heads.

Animals↗
PubMed1988

Atomic force microscopy of an organic monolayer.

Atomic force microscope images of polymerized monolayers of n-(2-aminoethyl)-10,12-tricosadiynamide revealed parallel rows of molecules with a side-by-side spacing of approximately equal to 0.5 nanometer. Forces used for imaging (10(-8) newton) had no observable effect on the polymer strands. These results demonstrate that atomic force microscope images can be obtained for an organic system.

Amides↗
PubMed1988

Scanning probe microscopy of biological samples and other surfaces.

Scanning probe microscopes derived from the scanning tunnelling microscope (STM) offer new ways to examine surfaces of biological samples and technologically important materials. The surfaces of conductive and semiconductive samples can readily be imaged with the STM. Unfortunately, most surfaces are not conductive. Three alternative approaches were used in our laboratory to image such surfaces. 1. Crystals of an amino acid were imaged with the atomic force microscope (AFM) to molecular resolution with a force of order 10(-8) N. However, it appears that for most biological systems to be imaged, the atomic force microscope should be able to operate at forces at least one and perhaps several orders of magnitude smaller. The substitution of optical detection of the cantilever bending for the measurement by electron tunnelling improved the reliability of the instrument considerably. 2. Conductive replicas of non-conductive surfaces enabled the imaging of biological surfaces with an STM with a lateral resolution comparable to that of the transmission electron microscope. Unlike the transmission electron microscope, the STM also measures the heights of the features. 3. The scanning ion conductance microscope scans a micropipette with an opening diameter of 0.04-0.1 micron at constant ionic conductance over a surface covered with a conducting solution (e.g., the surface of plant leaves in saline solution).

Crystallization↗