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Biomedical subjects

P Poulin

Publications and source records attributed to P Poulin.

At least 37 records · Page 2Linked to original sources

Vagal CCK and 5-HT(3) receptors are unlikely to mediate LPS or IL-1beta-induced fever.

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT(3) receptors in the febrile response after intraperitoneal human recombinant interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented with abdominal thermistors were given intraperitoneal CCK-8 sulfate (100 or 150 microgram/kg) or 2-methyl-5-hydroxytryptamine maleate (4 mg/kg). In other experiments, rats were treated with either antagonists to the 5-HT(3) receptor (ondansetron HCl; 100 microgram/kg) or the CCK-A receptor (L-364,718, 100 or 200 microgram/kg) in combination with LPS or IL-1beta. CCK administration caused a short-lived hypothermia, but interference with the action of endogenous CCK at CCK-A receptors was without effect on IL-1beta- or LPS-induced fever. Neither activation of 5-HT(3) receptors nor blockade of 5-HT(3) receptors affected body temperature or LPS fever. Taken together, our data support the idea that vagal afferents responsive to pyrogenic cytokines may be different from those responsive to CCK or 5-HT.

Animals↗

Particle-stabilized defect gel in cholesteric liquid crystals

Dispersions of colloidal particles in cholesteric liquid crystals form an unusual solid by stabilizing a network of linear defects under tension in the ideal layered structure of the cholesteric. The large length scales of the cholesteric liquid crystals allowed direct observation of the network structure, and its properties were correlated with rheological measurements of elasticity. This system serves as a model for a class of solids formed when particles are mixed with layered materials such as thermotropic and lyotropic smectic liquid crystals and block copolymers.

Journal Article↗

Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation.

Stem cells that can give rise to neurons, astroglia, and oligodendroglia have been found in the developing and adult central nervous system (CNS) of rodents. Yet, their existence within the human brain has not been documented, and the isolation and characterization of multipotent embryonic human neural stem cells have proven difficult to accomplish. We show that the developing human CNS embodies multipotent precursors that differ from their murine counterpart in that they require simultaneous, synergistic stimulation by both epidermal and fibroblast growth factor-2 to exhibit critical stem cell characteristics. Clonal analysis demonstrates that human C NS stem cells are multipotent and differentiate spontaneously into neurons, astrocytes, and oligodendrocytes when growth factors are removed. Subcloning and population analysis show their extensive self-renewal capacity and functional stability, their ability to maintain a steady growth profile, their multipotency, and a constant potential for neuronal differentiation for more than 2 years. The neurons generated by human stem cells over this period of time are electrophysiologically active. These cells are also cryopreservable. Finally, we demonstrate that the neuronal and glial progeny of long-term cultured human CNS stem cells can effectively survive transplantation into the lesioned striatum of adult rats. Tumor formation is not observed, even in immunodeficient hosts. Hence, as a consequence of their inherent biology, human CNS stem cells can establish stable, transplantable cell lines by epigenetic stimulation. These lines represent a renewable source of neurons and glia and may significantly facilitate research on human neurogenesis and the development of clinical neural transplantation.

Animals↗

Steroid hormone regulation of vasopressinergic neurotransmission in the central nervous system.

Vasopressinergic neurotransmission is intimately linked to steroid hormone signaling. Both arginine vasopressin (VP) and the extrahypothalamic VP V1a receptors are regulated by steroid hormones. Here, we present work that has been done in our laboratory, investigating mechanisms underlying steroid hormone effects on the expression of both VP and its primary receptor in the brain, the VP V1a receptor. Data on VP receptors, their coupling to second messenger pathways, their localization in brain, and their regulation by peptide exposure are discussed. We also cover the regulation of the V1a receptor by adrenal hormones, and the molecular basis of this effect. Evidence for the existence of other receptors for VP in the brain is presented. Lastly, the regulation of the VP peptide by gonadal hormones is discussed at the transcriptional level in the rodent brain. Finally, the potential significance of the 'cross-talk' between the vasopressinergic system and the steroid hormone system is addressed.

Animals↗

Noise exposure profile among heavy equipment operators, associated laborers, and crane operators.

This study, conducted in 1987 and 1988, has made it possible to quantify exposure to noise among heavy equipment operators, associated laborers, and crane operators. The average daily noise exposure was 84 to 99 dBA for heavy equipment, 90 dBA for the laborer, and 74 to 97 dBA for the crane operator. The main sources of noise to which heavy equipment operators are exposed are vehicle engines and the muffler exhaust system, usually located near the operator. The presence of insulated cabs such as those found on power shovels, backhoes, wheel loaders, and graders help reduce noise exposure. The type of tasks carried out by the laborers, the sources of noise from heavy equipment around which they work, and the manual equipment they use determine the noise levels to which such workers are exposed. In the case of crane operators, an insulated cab significantly reduces the operator's exposure to engine noise.

Environmental Monitoring↗

Novel Colloidal Interactions in Anisotropic Fluids

Small water droplets dispersed in a nematic liquid crystal exhibit a novel class of colloidal interactions, arising from the orientational elastic energy of the anisotropic host fluid. These interactions include a short-range repulsion and a long-range dipolar attraction, and they lead to the formation of anisotropic chainlike structures by the colloidal particles. The repulsive interaction can lead to novel mechanisms for colloid stabilization.

Journal Article↗

A tissue composition-based algorithm for predicting tissue:air partition coefficients of organic chemicals.

The objectives of the present study were (i) to develop an algorithm for predicting the tissue:air partition coefficients (PCs) of volatile organic chemicals (VOCs) and (ii) to apply this algorithm to predict the rat tissue:air PCs of 45 VOCs. The approach consisted of estimating the tissue:air PCs by dividing the tissue solubility of chemicals by their saturable vapor concentrations. The tissue solubility of chemicals was calculated as the sum total of their solubility in neutral lipid, phospholipid, and water fractions of tissues. The rat liver:air, muscle:air, and adipose tissue:air PCs predicted using this algorithm compared well with literature data available for several ketones, alcohols, acetate esters, alkanes, haloalkanes, aromatic hydrocarbons, and diethyl ether. The average ratios between the predicted and experimental values of the tissue:air PC values were 0.94 (liver), 0.93 (muscle), and 1.10 (adipose tissue). The mechanistic algorithm developed in the present study should be useful for predicting tissue:air PCs of VOCs and for verifying the current default assumption of considering tissue:air PCs to be species-invariant.

Adipose Tissue↗

A mechanistic algorithm for predicting blood:air partition coefficients of organic chemicals with the consideration of reversible binding in hemoglobin.

The objectives of the present study were (i) to develop a mechanistic algorithm for predicting blood:air partition coefficients (PCs) of volatile organic chemicals (VOCs), and (ii) to apply this algorithm to predict the rat blood:air PCs of several VOCs. The approach consisted initially of developing an algorithm to predict the blood:air PCs of VOCs solely based on the solubility phenomenon and then of extending the algorithm to include protein binding. The algorithm based on solubility phenomenon predicted blood:air PCs by dividing the estimated solubility of chemicals in blood by their saturable vapor concentrations at 37 degrees C. The rat blood:air PCs predicted using this algorithm were in close agreement with the experimental values for relatively hydrophilic VOCs such as ketones, alcohols, acetate esters, and diethyl ether (with an average ratio of 0.80 between predicted and experimental values), whereas there was a marked discrepancy in the case of relatively lipophilic VOCs such as alkanes, haloalkanes, and aromatic hydrocarbons (with an average ratio of 0.21 between predicted and experimental values). This discrepancy was hypothesized to be due to the occurrence of reversible binding of these substances in rat hemoglobin based on literature evidence of the existence of hydrophobic holes (or "xenon-binding" pockets). The association constants (Ka) for the presumed reversible hemoglobin binding of several alkanes, haloalkanes, and aromatic hydrocarbons were estimated from the difference between chemical concentration in rat erythrocytes predicted by the solubility-based algorithm and that deduced from the previously published experimental blood:air PCs for these chemicals (which presumably included contribution of hemoglobin binding in addition to "true" solubility). The Ka values estimated in this manner ranged from 504 to 4725 M-1 for the chemicals investigated in the present study. The a priori predictions of the percentage of several VOCs (diethyl ether, methyl isobutyl ketone, n-hexane, toluene, and chloroform) in rat erythrocytes obtained with the algorithm using these Ka estimates corresponded well with previously published experimental data. The mechanistic algorithm developed in the present study should be useful for predicting the "apparent" blood:air PCs of VOCs regardless of exposure concentrations, by accounting for the relative contributions of both the true chemical solubility and reversible hemoglobin binding.

Alcohols↗

Vasopressin-induced sensitization: involvement of neurohypophyseal peptide receptors.

Rats pretreated with an intracerebroventricular (i.c.v.) injection of 10 pmol of vasopressin or vasopressin analogs, including deamino-D-vasopressin, [pGlu4,Cyt6]vasopressin, [pGlu-Asn-Cys(Cys)]Pro-Leu-Gly-NH2, des-Gly-NH9(2)-vasopressin, Pro-Leu-Gly-NH2, Pro-Arg-Gly-NH2, became markedly hyper-responsive to the motor effects, 24 h later, to a subsequent challenge dose of vasopressin, but not vasopressin-related peptides. A vasopressin V1 receptor antagonist, [d(CH2)1(5),Tyr(Me)2]vasopressin, but not the vasopressin V2 receptor antagonist, [d(CH2)1(5),Tyr(Et)2,Val4]vasopressin, or a more selective vasopressin V2 receptor antagonist, [d(CH2)1(5),D-Ile2,Ile4]vasopressin, or the oxytocin receptor antagonist, [d(CH2)1(5),Tyr(Me)2,Thr4,Orn8,Tyr-NH9(2)]vasotocin ([d(CH2)1(5),Tyr(Me)2,Thr4,Tyr-NH9(2)]OVT), blocked vasopressin and vasopressin analog-induced sensitization. Furthermore, both vasopressin V2 receptor antagonists were found to sensitize the brain to a subsequent vasopressin injection. This vasopressin V2 receptor antagonist-induced sensitization was also blocked by the vasopressin V1 receptor antagonist. Next, we wanted to determine if this sensitization process could involve the release of endogenous vasopressin in the brain as reflected in an amplification of vasopressin mRNA expression. However pretreatment of rats with an i.c.v. vasopressin injection was not associated with an increase in vasopressin mRNA expression in the bed nucleus of the stria terminalis, medial amygdala or the paraventricular nucleus of the hypothalamus when measured 0, 1, 3, 7, 12, or 24 h after the first vasopressin injection. As many vasopressin analogs can induce sensitization, we suggest that a novel type of receptor may be involved in the sensitization process.

Amino Acid Sequence↗

An algorithm for predicting tissue: blood partition coefficients of organic chemicals from n-octanol: water partition coefficient data.

The objectives of the present study were (1) to develop an algorithm to predict tissue:blood partition coefficients (PCs) of organic chemicals from n-octanol: water (Ko/w) PC data, and (2) to apply this algorithm to predict the rat tissue:blood PCs of some relatively hydrophilic organics, particularly ketones, alcohols, and acetate esters. The algorithm, developed by modifying a previously published one, involved predicting tissue:blood PCs of chemicals by dividing their partitioning into tissues by the sum of their partitioning into erythrocytes and plasma. The partitioning of a chemical into tissues, erythrocytes, and plasma was expressed as an additive function of its partitioning into neutral lipids, phospholipids, and water contained in them. The muscle, liver, and adipose tissue:blood PCs predicted with the present method were compared with the experimental values obtained from the literature for five ketones, eight alcohols, and eight acetate esters. The predicted muscle:blood and liver:blood PCs for the set of 21 hydrophilic organics were within a factor of 1.01 and 0.99 (on an average), respectively, of the experimental values. However, the predicted adipose tissue:blood PCs of the hydrophilic organics were greater than the experimental values by a factor of 4.13, which improved when vegetable oil:saline (Ko/s) PCs were used instead of Ko/w PCs (factor of 1.51). Overall, the use of the present algorithm should enable the prediction of tissue:blood PCs for organic chemicals for which Ko/w or Ko/s data are available.

Acetates↗

A biologically-based algorithm for predicting human tissue: blood partition coefficients of organic chemicals.

A biologically-based algorithm for predicting the tissue: blood partition coefficients (PCs) of organic chemicals has been developed. The approach consisted of (i) describing tissues and blood in terms of their neutral lipid, phospholipid, and water contents, (ii) obtaining data on the solubility of chemicals in n-octanol and water, and (iii) calculating the tissue: blood PCs by assuming that the solubility of a chemical in n-octanol corresponds to its solubility in neutral lipids, the solubility in water corresponds to the solubility in tissue/blood water fraction, and the solubility in phospholipids is a function of solubility in water and n-octanol. The adequacy of this approach was verified by comparing the predicted values with previously published experimental data on human tissue (liver, lung, muscle, kidney, brain, adipose tissue): blood PCs for 23 organic chemicals. In the case of liver, lung, and muscle, the predicted PC values were in close agreement with the higher-end of the range of experimental PC values found in the literature. The predicted brain: and kidney: blood PCs were greater than the experimental PCs in most cases by approximately a factor of two. Whereas the adipose tissue: blood PCs of relatively less hydrophilic chemicals were adequately predicted, the predicted PCs for relatively more hydrophilic chemicals were much greater than the experimentally-determined values. There was a good agreement between the predicted and experimentally-determined blood solubility of the 23 chemicals chosen for this study, indicating that the over-estimation of tissue:blood PCs by the present method is not due to under-estimation of blood solubility of chemicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Enhanced pressor responses to ICV vasopressin after pretreatment with oxytocin.

The role of oxytocin (OT) in the modulation of arginine vasopressin (AVP)-induced cardiovascular effects within the central nervous system was investigated in urethan-anesthetized rats. Intracerebroventricular injection of AVP (1-10 pmol) produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR). These responses were enhanced in rats pretreated 24 h earlier with OT (10 pmol icv). The enhanced cardiovascular effects of AVP in OT-pretreated animals were dose dependent, blocked by the V1 antagonist d(CH2)5Tyr(Me)AVP, not evoked by OT alone, and occurred in the absence of changes in basal (nonstimulated) MAP and HR. In addition, central administration of AVP in OT-pretreated rats, but not in saline-pretreated controls, caused dose-dependent oscillations of the MAP and HR responses and, at higher doses, death of the animals. The enhanced cardiovascular actions of centrally injected AVP in OT-pretreated rats do not appear to be secondary to skeletal muscle contractions or the result of cerebral ischemia. Our data point to an interaction between the central oxytocinergic and vasopressinergic systems in cardiovascular control.

Animals↗

Arginine vasopressin-induced sensitization in brain: facilitated inositol phosphate production without changes in receptor number.

Arginine vasopressin (AVP) has been shown to have a unique sensitization effect whereby repeated injection of AVP into a lateral cerebral ventricle or a mediobasal region of the rat forebrain below the lateral septum and including the anterior hypothalamus referred to as the ventral septal area, causes enhanced motor responses to the ligand. To elucidate possible neuronal mechanisms responsible for AVP sensitization, 1) we determined the dose and the time required for the development and expression of AVP sensitization, and 2) we tested the hypotheses that AVP sensitization may result in a) alteration of septal AVP V1 receptor affinity or number, and/or b) alteration of septal AVP V1 receptor signal transduction (phosphatidylinositol hydrolysis) mechanisms. Our behavioral data show that the magnitude of AVP sensitization varies with dose and time, and the effect is dependent on the time interval between injections, in that an initial intracerebroventricular AVP injection enhances the sensitivity of the animals to the motor effects of similar AVP injections given 6 h to 6 days later but not to injections given hourly or weekly. No changes in septal AVP binding site density and affinity, as measured by [3H]AVP binding to septal synaptic plasma membrane, were found in sensitized animals; [3H]inositol monophosphate stimulation in response to AVP in septal slices, however, was found to be significantly enhanced. This enhanced [3H]inositol monophosphate stimulation appears specific to a V1-type receptor because it was significantly reduced in the presence of the V1 receptor antagonist, d(CH2)5Tyr(Me)AVP, and was not found using oxytocin or the V2 receptor agonist, DDAVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Oxytocin pretreatment enhances arginine vasopressin-induced motor disturbances and arginine vasopressin-induced phosphoinositol hydrolysis in rat septum: a cross-sensitization phenomenon.

The recent observation that the central oxytocin (OT) receptor has high affinity for both OT and arginine vasopressin (AVP) raises the possibility that it may be involved in some of the central actions of AVP. Repeated intracerebroventricular (icv) injections of AVP in rats evoke an unusual sensitization phenomenon in that a first exposure to the peptide enhances the sensitivity (sensitization) of the brain to a second exposure. This report investigates the possibility that the OT receptor may be involved in the mediation of the phenomenon of sensitization, using OT, a specific OT receptor agonist, [Thr4,Gly7]OT, and a specific OT receptor antagonist, d(CH2)5,[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT (compound 6; cpd 6), as well as a V1 AVP receptor antagonist, d(CH2)5Tyr(Me)AVP. Peptides were injected icv in conscious, adult male Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Possible involvement of brain oxytocin in modulating vasopressin antipyretic action.

Experiments were undertaken to test whether oxytocin (OT) may modulate the antipyretic action of arginine vasopressin (AVP) and to determine whether the action of endogenously released OT and/or AVP evoked by fever may modulate the motor actions of exogenous AVP. Intracerebroventricular (icv) injection of interleukin-1 alpha (IL-1 alpha, 40 ng) elicited a significantly attenuated rise in body temperature during the 2nd h of the febrile responses in OT-pretreated (0.1-10 pmol icv, 24 h earlier) rats. At the end of the 2nd h, administration of AVP (1 pmol icv), but not OT (10 pmol icv), significantly suppressed the febrile response in OT-pretreated but not in saline-pretreated rats. In nonfebrile OT-pretreated rats, 10 but not 1 pmol of AVP (icv) caused a significant decrease in body temperature. In rats pretreated with IL-1 alpha (40 ng icv) injection of AVP (100 pmol icv) induced enhanced motor responses. In summary, the ability of OT pretreatment to alter the febrile response to IL-1 alpha and the antipyretic action of AVP suggests a role for this peptide in fever. Furthermore, the observation that fever pretreatment can lower the threshold for convulsive-like behavior evoked by subsequent exposure to AVP raises the possibility that central OT and/or AVP released during fever could play a role in the genesis of febrile convulsions.

Animals↗