The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein sub... more The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory G␣ i , stimulatory G␣ s , G␣ q/11 , and G) in platelets of unipolar depressed patients to assess the status of these signal transduction proteins in depression and the effects of antidepressant drug treatment. Blood platelets were collected from 22 drug-free depressed patients and 22 age-and sex-matched healthy controls. The levels of the various G protein subunits were assessed by immunoblotting techniques. The immunoreactivity of G␣ i2 was increased (41%) and that of G␣ i3 decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (G␣ s , G␣ q/11 , G) did not change significantly with respect to those of control subjects. Chronic administration of cyclic antidepressant drugs (citalopram, clomipramine, imipramine) decreased the immunoreactivity of the up-regulated G␣ i2 protein (31%). Since platelet G␣ i2 proteins mediate the signaling of ␣ 2A -adrenoceptors, the higher expression of G␣ i2 is in line with the existence of supersensitivity of these receptors in major depression.
This study was designed to determine the affinity and binding profile of h-carbolines for imidazo... more This study was designed to determine the affinity and binding profile of h-carbolines for imidazoline I 2 receptors and catalytic sites of monoamine oxidase (MAO)-A/B in rat brain and liver. The aim was also directed to assess the in vivo effects of norharman (h-carboline) and LSL 60101 (I 2 ligand) on brain 3,4-dihydroxyphenylalanine (DOPA) synthesis in morphine-dependent rats. Competition experiments against [ 3 H]2-BFI revealed that h-carbolines recognize the high-and low-affinity components of the brain imidazoline I 2 receptor with the rank order of potency (K iH in nM): noreleagnine (12) > norharman (20) > harmalol (82) > harmaline (177) H harmine (630) > harman (700) H FG-7142 (> 100,000). In liver, this rank was different: harmine (51) > harmaline (103) = noreleagnine (103) H harmalol (1290) > harman (2000) H norharman (12,382) H FG-7142 (> 100,000). In brain and liver, competition curves for h-carbolines against [ 3 H]Ro41-1049 (MAO-A) and [ 3 H]Ro19-6327 (MAO-B) were monophasic and resulted in different drug potencies for the two MAO isozymes (higher affinities for MAO-A) and in similar pharmacological profiles in both tissues. In morphine-dependent rats, naloxone (2 mg/kg, 2 h)precipitated withdrawal increased the synthesis of DOPA in the cerebral cortex and hippocampus (50%). Pretreatment with norharman (20 mg/kg) or LSL 60101 (20 mg/kg) (30 min before naloxone) fully prevented the stimulatory effect of opiate withdrawal on DOPA synthesis. Norharman and LSL 60101 also attenuated the severity of the withdrawal syndrome. The results indicate that h-carbolines bind with high affinity to imidazoline I 2B receptors, and similarly to I 2 ligands (LSL 60101) can block the behavioural and biochemical effects of opiate withdrawal. D
A new apparent viscosity function for shear thickening fluids has been recently published , which... more A new apparent viscosity function for shear thickening fluids has been recently published , which is able to cover the three characteristic regions typically exhibited by these materials (thinning/thickening/thinning). The proposed function was shown to provide an excellent fitting to several independent data sets used. However, although its formulation has the Cross model as a starting point, the K i -parameter time constants were enforced to be negative, which is counter-intuitive. In the light of the original work of Cross [2], the present short communication introduces small changes to the viscosity function developed in [1] to make the fitting parameters more natural. The original microstructural ideas of Cross are also considered in order to provide additional intuition and interpretation. Finally, the fitting values of the model parameters for all of the curves considered in the original manuscript are included here so that results can be reproduced or used for numerical simulations.
A new apparent viscosity function for shear thickening fluids is proposed, contemplating the thre... more A new apparent viscosity function for shear thickening fluids is proposed, contemplating the three characteristic regions typically exhibited by these materials: slight shear thinning at low shear rates, followed by a sharp viscosity increase over a threshold shear rate value (critical shear rate), and a subsequent pronounced shear thinning region at high shear rates. The proposed function has a continuous derivative, making it appropriate in numerical simulations. Moreover, the function is shown to provide an excellent fit to several independent experimental data sets.
The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein sub... more The aim of this study was to quantitate the density of guanine nucleotide-binding (G) protein subunits (inhibitory G␣ i , stimulatory G␣ s , G␣ q/11 , and G) in platelets of unipolar depressed patients to assess the status of these signal transduction proteins in depression and the effects of antidepressant drug treatment. Blood platelets were collected from 22 drug-free depressed patients and 22 age-and sex-matched healthy controls. The levels of the various G protein subunits were assessed by immunoblotting techniques. The immunoreactivity of G␣ i2 was increased (41%) and that of G␣ i3 decreased (25%) in platelets of depressed patients. The levels of other G protein subunits (G␣ s , G␣ q/11 , G) did not change significantly with respect to those of control subjects. Chronic administration of cyclic antidepressant drugs (citalopram, clomipramine, imipramine) decreased the immunoreactivity of the up-regulated G␣ i2 protein (31%). Since platelet G␣ i2 proteins mediate the signaling of ␣ 2A -adrenoceptors, the higher expression of G␣ i2 is in line with the existence of supersensitivity of these receptors in major depression.
This study was designed to determine the affinity and binding profile of h-carbolines for imidazo... more This study was designed to determine the affinity and binding profile of h-carbolines for imidazoline I 2 receptors and catalytic sites of monoamine oxidase (MAO)-A/B in rat brain and liver. The aim was also directed to assess the in vivo effects of norharman (h-carboline) and LSL 60101 (I 2 ligand) on brain 3,4-dihydroxyphenylalanine (DOPA) synthesis in morphine-dependent rats. Competition experiments against [ 3 H]2-BFI revealed that h-carbolines recognize the high-and low-affinity components of the brain imidazoline I 2 receptor with the rank order of potency (K iH in nM): noreleagnine (12) > norharman (20) > harmalol (82) > harmaline (177) H harmine (630) > harman (700) H FG-7142 (> 100,000). In liver, this rank was different: harmine (51) > harmaline (103) = noreleagnine (103) H harmalol (1290) > harman (2000) H norharman (12,382) H FG-7142 (> 100,000). In brain and liver, competition curves for h-carbolines against [ 3 H]Ro41-1049 (MAO-A) and [ 3 H]Ro19-6327 (MAO-B) were monophasic and resulted in different drug potencies for the two MAO isozymes (higher affinities for MAO-A) and in similar pharmacological profiles in both tissues. In morphine-dependent rats, naloxone (2 mg/kg, 2 h)precipitated withdrawal increased the synthesis of DOPA in the cerebral cortex and hippocampus (50%). Pretreatment with norharman (20 mg/kg) or LSL 60101 (20 mg/kg) (30 min before naloxone) fully prevented the stimulatory effect of opiate withdrawal on DOPA synthesis. Norharman and LSL 60101 also attenuated the severity of the withdrawal syndrome. The results indicate that h-carbolines bind with high affinity to imidazoline I 2B receptors, and similarly to I 2 ligands (LSL 60101) can block the behavioural and biochemical effects of opiate withdrawal. D
A new apparent viscosity function for shear thickening fluids has been recently published , which... more A new apparent viscosity function for shear thickening fluids has been recently published , which is able to cover the three characteristic regions typically exhibited by these materials (thinning/thickening/thinning). The proposed function was shown to provide an excellent fitting to several independent data sets used. However, although its formulation has the Cross model as a starting point, the K i -parameter time constants were enforced to be negative, which is counter-intuitive. In the light of the original work of Cross [2], the present short communication introduces small changes to the viscosity function developed in [1] to make the fitting parameters more natural. The original microstructural ideas of Cross are also considered in order to provide additional intuition and interpretation. Finally, the fitting values of the model parameters for all of the curves considered in the original manuscript are included here so that results can be reproduced or used for numerical simulations.
A new apparent viscosity function for shear thickening fluids is proposed, contemplating the thre... more A new apparent viscosity function for shear thickening fluids is proposed, contemplating the three characteristic regions typically exhibited by these materials: slight shear thinning at low shear rates, followed by a sharp viscosity increase over a threshold shear rate value (critical shear rate), and a subsequent pronounced shear thinning region at high shear rates. The proposed function has a continuous derivative, making it appropriate in numerical simulations. Moreover, the function is shown to provide an excellent fit to several independent experimental data sets.
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Papers by Andre Sevilla