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At least 1,225 records · Page 68Linked to original sources
PubMed2004

Thyroid hormone stimulates myoglobin gene expression in rat cardiac muscle.

T3 increases the heart activity, O2 consumption and the reactive O2 species production. Myoglobin (Mb) is highly expressed in the heart, where it facilitates O2 diffusion, mitochondrial respiration, and scavenges reactive O2 species. Here we investigate, by dose-response (0.3-100 microg/100 g BW, i.p., 5 days) and time-course studies (100 microg/100 g BW, i.v., from 0.5 to 24h), whether T3 affects the Mb mRNA and protein expression in atrium (A) and ventricle (V), by Northern and Western blot. We show that the Mb gene is controlled by T3 in A and V, as indicated by Mb mRNA and protein content decrease in thyroidectomized (Tx) rats, and restoration by T3 treatment. In the A, the different doses of T3 induced the Mb mRNA and protein recovery to the euthyroid levels; in the time-course study, this occurred only with the protein levels. In the V, T3 progressively increased the Mb mRNA above the euthyroid levels at a dose of 25 microg/100g BW; higher doses decreased it to the euthyroid levels. Mb protein increased only to the euthyroid levels at all T3 doses injected. The time-course study showed a progressive increase in the ventricular Mb mRNA and protein, which exceeded the euthyroid levels from 6 to 24h, and at 2 and 6 h of the T3 treatment, respectively. We conclude that heart Mb gene expression is influenced by thyroid status.

Animals↗
PubMed2006

Are intramural suction-squeezing effects generated by the variations in radial wall stress during each heart beat the motor of atherosclerosis? A new concept.

In the early sixties, the existence of predilection sites for atherosclerotic lesions inside the arterial circulation led to the concept that low wall shear stress (WSS) was responsible, together with systemic factors like high blood pressure, hypercholesterolemia, or diabetes, for the genesis and progression of atherosclerosis. It was found later that oscillating WSS and high WSS gradients could also be incriminated. Yet, this concept, which is broadly accepted today, fails to explains several facts, for instance that some arteries (e.g. epicardial coronary arteries) are more prone to become atherosclerotic than other ones exposed to the same systemic factors (e.g. hepatic and brain arteries). In this paper, we present a quite different concept. It is based on the fact that the increase in intravascular pressure and flow that occur in the arteries during systole generates, at the predilection sites of atherosclerotic lesions (bends, bifurcations, and branchings), an increase of radial wall stress in the outer layers of the arterial wall so that this stress becomes momentarily tensile. These cyclic stress increases have a suction effect that is likely to facilitate the diffusion of atherogenic cells and substances inside the wall. Furthermore, since arteries are not primarily structured to resist inversions of radial stress, they may also create damages (e.g. disruptions of cell membranes and elastic lamellae) followed by inflammations and micro-haemorrhages in the wall. This new concept may provide a complementary (or possibly alternative) explanation of atherosclerosis.

Animals↗
PubMed2004

The human brain hexacoordinated neuroglobin three-dimensional structure.

Neuroglobin, mainly expressed in vertebrate brain and retina, is a recently identified member of the globin superfamily. Augmenting O2 supply, neuroglobin promotes survival of neurons upon hypoxic injury, potentially limiting brain damage. In the absence of exogenous ligands, neuroglobin displays a six-coordinated heme. O2 and CO bind to the heme-iron, displacing the endogenous HisE7 heme distal ligand. Hexacoordinated human neuroglobin displays a classical globin fold, adapted to host the reversible bis-histidyl heme complex, and an elongated protein matrix cavity, held to facilitate O2 diffusion to the heme. The structure of neuroglobin suggests that the classical globin fold is endowed with striking adaptability, indicating that hemoglobin and myoglobin are just two examples within a wide and functionally diversified protein homology superfamily.

Globins↗
PubMed2004

Cognitive impairment in PDAPP mice depends on ApoE and ACT-catalyzed amyloid formation.

Biochemical and genetic studies indicate that the inflammatory proteins, apolipoprotein E (ApoE) and alpha(1)-antichymotrypsin (ACT) are important in the pathogenesis of Alzheimer's disease (AD). Using several lines of multiply transgenic/knockout mice we show here that murine ApoE and human ACT separately and synergistically facilitate both diffuse A beta immunoreactive and fibrillar amyloid deposition and thus also promote cognitive impairment in aged PDAPP(V717F) mice. The degree of cognitive impairment is highly correlated with the ApoE- and ACT-dependent hippocampal amyloid burden, with PDAPP mice lacking ApoE and ACT having little amyloid and little learning disability. A analysis of young mice before the onset of amyloid formation shows that steady-state levels of monomeric A beta peptide are unchanged by ApoE or ACT. These data suggest that the process or product of amyloid formation is more critical than monomeric A beta for the neurological decline in AD, and that the risk factors ApoE and ACT participate primarily in disease processes downstream of APP processing.

Aging↗
PubMed2004

Zn2+ modulates currents generated by the dopamine transporter: parallel effects on amphetamine-induced charge transfer and release.

The psychostimulant drug amphetamine increases extracellular monamines in the brain acting on neurotransmitter transporters, especially the dopamine transporter. Mediated by this plasmalemmal pump, amphetamine does not only induce release but also charge transfer which might be involved in the release mechanism. To study a potential link between the two phenomena, we used Zn(2+) as an acute regulatory agent which modulates dopamine uptake by a direct interaction with the transporter protein. Charge transfer was investigated in patch-clamp experiments on HEK 293 cells stably expressing the human dopamine transporter, release was studied in superfusion experiments on cells preloaded with the metabolically inert transporter substrate [(3)H]1-methyl-4-phenylpyridinium. Ten micromoles of Zn(2+) had only minor effects in the absence of amphetamine but stimulated release and inward currents induced by amphetamine depending on the concentration of the psychostimulant: the effect of 0.2 microM was not significantly modulated, whereas the effect of 1 and 10 microM amphetamine was stimulated, and the stimulation by Zn(2+) was significantly stronger at 10 microM than at 1 microM amphetamine. The stimulatory action of Zn(2+) on release and inward current was in contrast to its inhibitory action on dopamine uptake. This supports a release mechanism of amphetamine different from facilitated exchange diffusion but involving ion fluxes through the dopamine transporter.

Amphetamine↗
PubMed2004

Distribution and possible roles of aquaporin 9 in the brain.

Aquaporin 9 (AQP9) is a member of the aquaporin channel family involved in water flux through plasma membranes and exhibits the distinct feature of being also permeable to monocarboxylates, such as lactate, and various solutes, including glycerol, carbamides, purines, pyrimidines, and urea. AQP9 is constitutively expressed at high levels in the liver. In the brain under physiological conditions, AQP9 was first observed in tanycytes, and then in astrocytes. Only recently, its expression was also shown in neurons. Neurons expressing AQP9 are catecholaminergic and glucose sensitive. The expression of neuronal AQP9 can be negatively regulated by insulin and in diabetic animals an increase in AQP9 expression is observed in the catecholaminergic nuclei of the hindbrain, similar to the regulation of AQP9 by insulin in the liver. Furthermore, after transient brain ischemia, AQP9 expression is increased in astrocytes and its regulation may implicate the MAP-kinase pathways stimulated in such pathological conditions. Despite these new data, the exact role of AQP9 in the brain is still unclear. However, we may hypothesize that AQP9 is implicated in brain energy metabolism, as a neutral solute channel. AQP9 could facilitate the diffusion of lactate from the astrocyte to the neuron. In glucose sensitive neurons, diffusion of lactate and glycerol could stimulate these neurons in a similar manner to glucose and could regulate the energy balance. In pathological conditions, induction of AQP9 in astrocytes could participate in the clearance of excess lactate in the extracellular space. These hypotheses concerning the function of brain AQP9 are still speculative and open new areas of investigation.

Animals↗
PubMed2005

[Setting up a data collection and assessment system of the Permanent Healthcare Access Activities (PASS)].

INTRODUCTION: Five years after introducing the Permanent Access to Healthcare activity (PASS), it became necessary to analyse how it works. MATERIAL AND METHODS: A computerized data collection and assessment system intended to evaluate the PASS health activities has been set up in 11 University Hospitals and ten General Hospitals. From January 1st to June, 30th 2003 data was captured in a computer. RESULTS: The patients requiring medical advice are young (with an average age of 35 years) and present several signs of poverty in terms of accommodation, social relationships and financial means. Besides, almost all of them are uninsured. The PASS public corresponds completely to the created system. Poverty risk factors vary according to the geographic origin. Indeed, French people often suffer from isolation, whereas foreign patients present financial problems. The major part of patients are foreigners and more than a third of them do not speak French, which is an additional obstacle to care. Most of the time, the PASS patients present digestive disorders, nevertheless there are some differences between French and foreign patients. Indeed, foreigners very frequently have digestive and osteoarticluar problems, whereas French patients suffer from psychic disorders and present addictive behaviours. Some patients are sent to physicians downtown (9%) and to external medicosocial assistance centres (39.5%). DISCUSSION: This study (first one in France) provides us with homogenous data regarding the activities of PASS centres nationwide. The usefulness of computers and its acceptability facilitate data diffusion, with possibilities of adapting to each centre while preserving a common basis.

Adult↗
PubMed2006

Rh proteins vs Amt proteins: an organismal and phylogenetic perspective on CO2 and NH3 gas channels.

Rh (Rhesus) proteins are homologues of ammonium transport (Amt) proteins. Physiological and structural evidence shows that Amt proteins are gas channels for NH(3), but the substrate of Rh proteins, be it CO2 as shown in green alga, or NH3/NH4+ as shown in mammalian cells, remains disputed. We assembled a large dataset generated of Rh and Amt to explore how Rh originated from and evolved independently of Amt relatives. Analysis of this rich data implies that Rh was split from Amt first to emerge in archaeal species. The Rh ancestor underwent divergence and duplication along speciation, leading to neofunctionalization and subfunctionalization of the Rh family. The characteristic organismal distribution of Rh vs. Amt reflects their early separation and subsequent independent evolution: they coexist in microbes and invertebrates but do not in fungi, vascular plants or vertebrates. Rh gene-duplication was prominent in vertebrates: while epithelial RhBG/RhCG displayed strong purifying selection, erythroid Rh30 and RhAG experienced different episodes of positive selection in each of which adaptive evolution occurred at certain time points and in a few codon sites. Mammalian Rh30 and RhAG were subject to particularly strong positive selection in some codon sites in the lineage from rodents to human. The grounds of this adaptive evolution may be driven by the necessity to increase the surface/volume ratio of biconcave erythrocytes for facilitative gas diffusion. Altogether, these results are consistent with Rh proteins not being the orthologue of Amt proteins but having gained the function for CO2/HCO3- transport, with important roles in systemic pH regulation.

Amino Acid Sequence↗
PubMed1998

Modulation of amphetamine-stimulated (transporter mediated) dopamine release in vitro by sigma2 receptor agonists and antagonists.

Some sigma receptor ligands have been shown to bind with low affinity to the dopamine transporter and to inhibit [3H]dopamine uptake. It has not previously been shown whether any of these compounds influence release of dopamine via facilitated exchange diffusion. To further examine the nature of the interaction between sigma receptor ligands and the dopamine transporter, the effects of sigma receptor ligands on amphetamine-stimulated [3H]dopamine release were examined in slices prepared from rat caudate putamen. In the absence of exogenous Ca2+, both (+)-pentazocine and (-)-pentazocine potentiated amphetamine-stimulated [3H]dopamine release at concentrations consistent with their affinities for sigma2 receptors. In contrast, BD737 (1S.2R-(-)-cis-N-¿2-(3,4-dichlorophenyl)ethyl¿-N-methyl-2-(1-pyrrolidiny l)cyclohexylamine), a sigma1 receptor agonist, had no effect on amphetamine-stimulated release. Neither isomer of pentazocine alone had any effect on basal [3H]dopamine release under these conditions. Three antagonists at sigma receptors, one of which is non-selective for subtypes, and two of which are sigma2-selective, all blocked the enhancement of stimulated release produced by (+)-pentazocine. Enhancement of stimulated release by (-)-pentazocine was similarly blocked by sigma2 receptor antagonists. Our data support the contention that it is possible to regulate transporter-mediated events with drugs that act at a subpopulation of sigma receptors pharmacologically identified as the sigma2 subtype.

Amphetamine↗
PubMed2003

Myoglobin gene expression attenuates hepatic ischemia reperfusion injury.

BACKGROUND: Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression. MATERIAL AND METHODS: After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat. RESULTS: Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver. CONCLUSION: These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.

Adenosine Triphosphate↗
PubMed2003

Zn(II) metabolism in prokaryotes.

It is difficult to over-state the importance of Zn(II) in biology. It is a ubiquitous essential metal ion and plays a role in catalysis, protein structure and perhaps as a signal molecule, in organisms from all three kingdoms. Of necessity, organisms have evolved to optimise the intracellular availability of Zn(II) despite the extracellular milieu. To this end, prokaryotes contain a range of Zn(II) import, Zn(II) export and/or binding proteins, some of which utilise either ATP or the chemiosmotic potential to drive the movement of Zn(II) across the cytosolic membrane, together with proteins that facilitate the diffusion of this ion across either the outer or inner membranes of prokaryotes. This review seeks to give an overview of the systems currently classified as altering Zn(II) availability in prokaryotes.

Adenosine Triphosphatases↗
PubMed2001

Diplopia and ptosis following injection of local anesthesia without hyaluronidase.

In a university ophthalmology department, a cluster of postoperative diplopia and ptosis cases occurred in the initial 3 months after hyaluronidase (Wydase) became unavailable for use with injection anesthesia. These cases suggest that hyaluronidase, when used with injection anesthesia, may protect extraocular muscles and nerves from the toxic effects of local anesthetic agents. The spreading action of hyaluronidase facilitates uniform diffusion of anesthetic agents. This prevents elevated extracellular tissue pressure, a cause of ischemic damage to extraocular muscles or nerves. Hyaluronidase may also prevent focal accumulations and concentrations of local anesthetic agents, which at high enough levels may cause myotoxic or neurotoxic damage, fibrosis, and contracture of extraocular muscles or nerves.

Adult↗
PubMed1997

Further genetic analysis of the C-terminal external loop region in Escherichia coli maltoporin.

LamB specifically facilitates the diffusion of maltose and maltodextrins through the bacterial outer membrane, and acts as a general (i.e. non-specific) porin for small hydrophilic molecules (< 600 daltons). We reported previously that deletion of the last predicted external domain near the C-terminus of the Eschirichia coli LamB protein (residues 376 to 405), affected in vivo the binding and transport of maltodextrins (specific pore functions), and also increased bacterial sensitivity to large antibiotics. The residues covered by this deletion correspond almost exactly to the major cell surface loop of LamB on the structural model based on X-ray crystallography (loop L9, residues 375 to 405). The L9 loop comprises a large central portion, which varies in size and sequence between the LamB proteins from different species. This variable region is flanked by two highly charged and conserved portions, which overlap with the adjacent beta strands. To identify subregions in L9 that influence the pore properties of LamB, we constructed and analysed nine mutants in loop L9 and its flanking sequences. Deletion of the 23-amino-acids central variable portion of the loop (residues 379 to 401), and deletion of the downstream conserved region (residues 402 to 409), only moderately affected specific maltoporin function. In contrast, deletion of the conserved region (residues 372 to 378) upstream of the variable portion strongly decreased specific maltoporin function and also increased sensitivity to large antibiotics, accounting for most, if not all, of the effects of the complete deletion of L9.

Amino Acid Sequence↗
PubMed2002

Enhancement in the sensitivity of a gas biosensor by using an advanced immobilization of a recombinant bioluminescent bacterium.

A genetically engineered bioluminescent bacterium (lac::luxCDABE) was immobilized to develop a whole cell biosensor for the detection of toxic gaseous chemicals. The toxicity of chemicals can be evaluated through the bioluminescent reaction as it reduces in intensity when the cells experience toxic or lethal conditions. This whole cell biosensor was fabricated, using an immobilization technique utilizing solid agar medium, for the measurement of toxicity through direct contact of the cells with the gas. To enhance the sensitivity of the biosenor, glass beads were used and the thickness of the agar layer was reduced. The bioluminescent response was measured using a fiber optic probe connected between the biosensor kit and a luminometer. As sample gaseous toxic chemicals, BTEX (Benzene, Toluene, Ethylbenzene, and Xylene) gases were selected and their vapors were produced by a gas generation system. The concentrations of the gaseous chemicals injected into the chamber were controlled by the time of exposure and were measured using a portable gas chromatograph (Allstech., USA). Additions of glass beads facilitated gas diffusion through the solid medium, making the biosensor more sensitive. In addition, a thinner matrix layer was more advantageous for the detection of gas toxicity.

Bacteria↗
PubMed2000

Microbial MIP channels.

MIP channels occur in all classes of organism ranging from bacteria to man. There are two major categories of MIP channels, aquaporins and glycerol facilitators, which facilitate the diffusion across biological membranes of water or glycerol and other uncharged compounds, respectively. As a result of their involvement in osmoregulation and metabolism, MIP channels are believed to affect a wide range of biological processes.

Aquaporins↗
PubMed1992

[Fluorocarbon emulsions as injectable oxygen carriers. Recent progress and perspectives].

Fluorocarbon emulsions are presently being developed to serve as injectable oxygen carriers (so-called "blood substitutes"). In this approach oxygen is simply dissolved in the liquid carrier and the amount of gas dissolved is proportional to its partial pressure. Increasing the O2-delivering capacity is therefore achieved more easily by increasing the oxygen content of the air breathed by the patient than by increasing the dose of fluorocarbon administered. The absence of a chemical bond between the gas and its carriers allows over 90% of the transported oxygen to be delivered. The fluorocarbon droplets act as oxygen carriers , and also appear to facilitate its diffusion. Chemically and biologically highly inert, fluorocarbons are excreted by exhalation without being metabolized. The first generation of emulsions, exemplified by Fluosol has only limited efficacy due to its low fluorocarbon content, low intravascular persistence and insufficient stability. It has to be stored and distributed frozen, then reconstituted prior to use. Fluosol has nevertheless been licensed by the Food and Drug Administration for use during high risk PTCA. The second generation of injectable fluorocarbon emulsions, exemplified by Oxygent is 4-5 times more concentrated and consequently more efficacious than Fluosol. Considerably more stable, this emulsion can be stored for over one year at 5-8 degrees C and is ready for use. The fluorocarbon used has a significantly shorter organ-retention time. The applications of the present emulsions are still limited by their short intravascular persistence, and are those for which prolonged efficacy is not required, which includes perioperative hemodilution, ischemia, cardioplegia, reperfusion, sensitization of tumors to radio- and chemotherapy, organ preservation and diagnosis. The efficacy of the new emulsions has been established in various animal models. The mild side-effects observed in Phase I clinical trials appear to result from a transient activation of the monocyte/macrophage system and to be suppressed prophylactically by cyclooxygenase inhibitors or corticosteroids. Research is presently oriented towards controlling intravascular persistence better, increasing emulsion stability further, minimizing side-effects and optimizing emulsion characteristics for specific indications.

Animals↗
PubMed2001

The role of tissue plasminogen activator in the successful treatment of infected cardiac thrombus in children.

Infected cardiac thrombus is rare in children, with antibiotic or antifungal agents used as the first line of treatment. Persistence is an indication for surgical intervention. We describe two children who were treated successfully with a combination of antibiotic and antithrombotic agents. Use of antithrombotic agents promotes degeneration of fibrin, thus reducing the mass and facilitating the diffusion of the antibiotic and/or antifungal agents.

Anti-Bacterial Agents↗
PubMed2004

High-speed electrochemically modulated liquid chromatography.

The performance advantages of carrying out electrochemically modulated liquid chromatography (EMLC) at elevated temperatures and mobile-phase flow rates are investigated. EMLC has the unique ability to manipulate analyte retention and enhance separation efficiencies through changes in the potential applied to a conductive stationary phase. Operation of high-performance liquid chromatography systems at elevated column temperatures also provides pathways to improve chromatographic performance by enhancing analyte diffusivity and facilitating the use of higher mobile-phase flow rates than conventionally attainable. The results show that performing EMLC separations at elevated temperatures (e.g., 100 degrees C) reduces the analysis time of a mixture of aromatic sulfonates in a mixed mobile phase by more than a factor of 20. Moreover, use of higher operating temperatures enables the separation of this mixture with an entirely aqueous mobile phase in less than 2 min.

Chromatography, High Pressure Liquid↗