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A Rousseau

Publications and source records attributed to A Rousseau.

At least 73 records · Page 4Linked to original sources

Enhancement by endothelin-1 of microvascular permeability via the activation of ETA receptors.

1. The objective of the present experiments was to assess the involvement of endothelin-A (ETA) receptors in mediating the effects of endothelin-1 on microvascular permeability in conscious rats. 2. Bolus injection of endothelin-1 (0.1 and 1 nmol kg-1, i.v.) resulted in a dose-dependent prolonged pressor effect preceded by a transient depressor response. These changes were accompanied by a dose-dependent loss of plasma volume. Endothelin-1 (1 nmol kg-1) enhanced the vascular permeability of the upper and lower bronchi, kidney, stomach, duodenum and spleen (up to 270%) as measured by the extravasation of Evans blue dye. 3. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg kg-1, i.v.) significantly blunted the pressor response to endothelin-1 without affecting the depressor response. BQ-123 inhibited by 87% the endothelin-1 (1 nmol kg-1)-induced plasma volume loss. BQ-123 markedly attenuated protein extravasation elicited by endothelin-1 in the upper and lower bronchi and kidney, whereas it completely inhibited the permeability effect of endothelin-1 in the stomach and duodenum. BQ-123 by itself had no significant effect on the parameters studied. 4. The endothelin-1 analogue, [Trp(For)21]-endothelin-1, in which Trp21 is formylated, was as potent a pressor agent as endothelin-1, but had no depressor action. Bolus injection of [Trp(For)21]-endothelin-1 (0.1 and 1 nmol kg-1, i.v.) evoked similar plasma volume losses to those observed following administration of equimolar doses of endothelin-1. Furthermore, 1 nmol kg-1 [Trp(For)21]-endothelin-l evoked increases in protein extravasation similar to endothelin-l, 1 nmol kg-1.5. The present findings suggest that endothelin- 1 enhances microvascular permeability, in part, via the activation of ETA receptors.

Amino Acid Sequence↗

Vascular responses to endothelin-1 following inhibition of nitric oxide synthesis in the conscious rat.

1. The objectives of the present experiments were to assess the role of endogenous nitric oxide (NO) in mediating and/or modulating the effects of endothelin-1 (ET-1) on blood pressure and microvascular permeability in conscious rats. 2. Intravenous administration of the NO synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME) at a dose (25 mg kg-1 or 2 mg kg-1, respectively) which evoked maximum increase in mean arterial blood pressure (MABP) significantly attenuated (by about 40%) the vasodepressor response and potentiated (by 100-180%) the pressor response to ET-1 (1 nmol kg-1, i.v.) compared to the effects of ET-1 in animals where the peripheral vasoconstrictor effects of L-arginine analogues were mimicked by an infusion of noradrenaline (620-820 ng kg-1 min-1). Similar inhibition of the depressor and potentiation of the pressor actions of ET-1 were observed when the MABP which had been elevated by L-NMMA or L-NAME was titrated to normotensive levels with hydralazine or diazoxide before injection of ET-1. 3. L-NAME (2 mg kg-1) increased the vascular permeability of the large airways, stomach, duodenum, pancreas, liver, kidney and spleen (up to 280%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, skeletal muscle and skin was not affected significantly by L-NAME treatment. Elevation of MABP by noradrenaline infusion did not evoke protein extravasation in the vascular beds studied with the exception of the lung. In the large airways, tissue Evans blue content was similar following noradrenaline infusion and L-NAME.4. Both the pressor and permeability effects of L-NAME (2 mg kg-1) were effectively reversed by L-arginine (300 mg kg- 1) but not by D-arginine (300 mg kg-1 ). The D-enantiomer of L-NAME, D-NAME(2 mg kg-1) had no effect on the parameters studied.5. Protein extravasation was significantly enhanced by ET-1 (1 nmol kg-1) in the upper and lower bronchi, stomach, duodenum, kidney and spleen (up to 285%). This was potentiated by L-NAME(2 mg kg-1), resulting in marked increases in tissue Evans blue accumulation (up to 550%) in these tissues. The effects of L-NAME and ET-1 were additive in the trachea, duodenum, pancreas and liver.Combined administration of L-NAME plus ET-1 significantly increased protein extravasation in the pulmonary parenchyma, where neither L-NAME nor ET-1 alone caused significant increases.6. Noradrenaline infusion (620-820 ng kg-1 min-1) potentiated the permeability action of ET-1(1 nmol kg-1) in the pulmonary circulation, whereas it did not modify ET-1-induced protein extravasation in the other vascular beds.7. These results indicate that endogenous NO mediates, in part, the vasodepressor effect and attenuates the vasopressor action of ET-1 and modulates the effects of ET-1 on vascular permeability. These findings confirm the role of NO in the maintenance of blood pressure and suggest an important role for NO in the regulation of microvascular permeability.

Animals↗

Synthesis and antithyroid activity of pyridine, pyrimidine and pyrazine derivatives of thiazole-2-thiol and 2-thiazoline-2-thiol.

A series of compounds was synthesized by linking various derivatives of pyridine, pyrimidine or pyrazine to thiazole-2-thiol or to its partially hydrogenated derivative 2-thiazoline-2-thiol. The reactions of the compounds with molecular iodine and lactoperoxidase were examined in vitro. Their antithyroid activity was also examined in vivo in the rat. T4 and TSH levels were determined, and the thyroid gland was examined histologically. 2-(3-Hydroxy-2-pyridyl)-2-thiothiazoline had the highest antithyroid activity of the compounds tested (Kc = 14931.mol(-1),IC(50)0.65 x 10(-4) M, activity of thyroid gland).

Animals↗

Structure-activity relationship of analogues of endothelin-1: dissociation of hypotensive and pressor actions.

The structural requirements of endothelin-1 to evoke depressor and pressor responses were studied in conscious rats. Formylation of the C-terminal Trp eliminated the depressor but not the pressor activity of endothelin-1. Oxidation of Met7 in this analogue restored the hypotensive activity. Destruction of the Cys1-Cys15 disulphide bridge led to a weak agonist with both depressor and pressor activities. Formylation of Trp21 in this analogue resulted in a complete loss of biological activity. These results indicate that Met7 and the indole moiety of Trp21 are important for the expression of the depressor activity of endothelin-1 whereas the intramolecular loop structure is less important. The results also provide further evidence that the depressor and pressor effects of endothelin-1 are mediated through different receptors.

Animals↗

Endothelin-1 enhances vascular permeability in the rat heart through the ETA receptor.

Intravenous injection of endothelin-1 (ET-1, 0.1 and 1 nmol/kg) resulted in a dose-dependent increase in vascular permeability in the coronary circulation of conscious rats. The increase was almost completely abolished by the selective ETA receptor antagonist, BQ-123 (1 mg/kg). The ET-1 analogue, [Trp(For)21]ET-1, which is devoid of the depressor but not the pressor activity, evoked changes in protein extravasation similar to those with ET-1. These data indicate that the permeability effect of ET-1 is mediated through the ETA receptor.

Animals↗

Endothelin-1 enhances vascular permeability in conscious rats: role of thromboxane A2.

The purpose of the present experiments was to study the effects of endothelin-1 (ET-1) on vascular permeability and the involvement of the cyclooxygenase metabolites in the vascular responses to ET-1. Bolus intravenous injection of ET-1 (0.1-1.0 nmol/kg) into conscious rats induced immediate hypotension lasting for 30 s followed by sustained dose-dependent hypertension. A low dose of ET-1 (0.1 nmol/kg) did not modify the hematocrit value but the 1.0-nmol/kg dose increased the hematocrit value from 39.7 to 44.4%. Pretreatment of the animals with BM-13505 (1 mg/kg), a thromboxane A2 (TxA2) receptor antagonist, prolonged the duration of the hypotensive response to ET-1 (1.0 nmol/kg) but had no effect on the pressor response. Pretreatment with OKY-046 (10 mg/kg), a TxA2 synthesis inhibitor, or indomethacin (10 mg/kg), a cyclooxygenase inhibitor, had no significant effect on ET-1-induced changes in blood pressure. Evans blue dye extravasation, a marker of vascular permeability, increased up to 235% over control levels in specific vascular beds including the upper and lower bronchi, stomach, duodenum and kidney of ET-1 (1.0 nmol/kg)-treated animals. Pretreatment of the animals with BM-13505, OKY-046 or indomethacin reduced by 60-100% the Evans blue extravasation in these tissues. These results suggest that the effect of ET-1 on vascular permeability is partly mediated and/or modulated by the secondary release of TxA2, whereas its action on arterial blood pressure appears to be independent from prostanoid release in conscious rats.

Animals↗

[Metastatic tumors of the soft tissues of the hand. Apropos of a case. Review of the literature].

Soft tissue metastases of the hands are rare tumours, representing 0.1% of all metastases. The authors report a personal case and review the literature concerning another 21 cases. The primary tumour is generally a lung or breast cancer. These metastases appear to be more frequent in men than in women. Their rarity can be explained by the absence of routine investigation of such sites. The development of such metastases always indicates a poor prognosis.

Adenocarcinoma↗

Characterization of gangliosides in human uveal melanoma cells.

We have evaluated the ganglioside composition of 20 primary uveal melanomas, of 2 cell lines derived from 2 uveal melanomas, of a liver metastasis from an uveal melanoma, and of 8 normal choroids. The results show that normal choroid tissue has a ganglioside content similar to the primary tumors of uveal melanoma except for GD1a, GD1b, and GT1b, which are present only on normal choroid tissues. On the other hand, the uveal melanomas have similarities with cutaneous melanomas, since GM3 (74%) and GD3 (25%) are found in both tissues and are present in about the same amounts. However, GM1 was found in 50%, GM2 in 20% and GD2 in none of the uveal melanomas. According to data published by others, cutaneous melanoma biopsies have no GM1, whereas GM2 is present in 100% and GD2 in 71% of tumor tissues. Transplantation of the 2 cell lines subcutaneously into nude mice resulted in the growth of tumors which had a ganglioside profile larger than that of the primary tumors. GM3 was significantly diminished and GD3 significantly increased in the primary uveal melanoma from patients who had received radiotherapy before enucleation compared with those who did not have radiotherapy. These results show that uveal melanomas contain gangliosides that could be used as targets for monoclonal antibody therapy.

Aged↗

Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor.

1. The objectives of the present experiments were to assess the effects of endothelin-1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet-activating factor (PAF) in vascular responses to endothelin-1 and to examine the vascular effects of combined administration of endothelin-1 and PAF in conscious rats. 2. Intravenous bolus injection of endothelin-1 (0.1-2 nmol kg-1) resulted in a dose-dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose-dependent increase in haematocrit values. 3. Endothelin-1 (0.1 and 1 nmol kg-1) increased dose-dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin-1 treatment. 4. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1, i.v.) or BN 52021 (10 mg kg-1, i.v.) reduced the endothelin-1 (1 nmol kg-1)-induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin-1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin-1.5. When low doses of endothelin-1 (0.1 nmolkg-')and PAF (0.19nmolkg-')were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin-1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP.6. Combined administration of higher doses of endothelin-1 (1nmolkg-') and PAF (1.9nmolkg-') resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin-1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin-1 and PAF resulted in a slight, but significant increase in MABP.7. The present findings show that endothelin-1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin-1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.

Animals↗

Uptake and degradation of virus-associated fluorescent sulfatide by skin fibroblasts.

A fluorescent derivative of cerebroside sulfate, pyrene-dodecanoyl sphingosylgalactosylsulfate (P12-CS) was incorporated into the envelope of vesicular stomatitis virus (VSV). When the P12-CS-containing virus was incubated for 24 h with skin fibroblasts, up to 40% of the sulfatide was located in the cells--a value at least 10 fold greater than that observed using sulfatide suspensions without virus. In a similar experiment, in which the 24 h 'pulse' was followed by a 48 h 'chase', about 15-20% of the virus-associated fluorescence was recovered in the skin fibroblasts. Of the latter, about one-third was present as desulfated degradation products of P12-CS. The high uptake and degradation of the virus-associated sulfatide by intact skin fibroblasts suggested that enveloped viruses could be used for introducing other lipids into cells. This could be utilized for studying lipid catabolism and diagnosing lipid storage disorders in intact living cells.

Endocytosis↗

Canthaxanthin retinopathy. Anatomic and functional reversibility.

Canthaxanthin intake is associated with golden yellow crystalline deposits in the retina around the macula and low static luminance threshold. Our study assesses the anatomic and functional reversibility of canthaxanthin retinopathy. The number of retinal deposits was evaluated in nine patients, two to four times over a mean period of 55 months. There was no significant difference after a nine-month follow-up. A statistically significant decrease in the number of retinal deposits was found after an observation period of 26 months. The deposits disappeared slowly, while some remained even seven years after canthaxanthin therapy was discontinued. Threshold static perimetry performed on eight patients with retinopathy and seven controls did not differ significantly between the two groups at the end of the follow-up period. The results demonstrate that canthaxanthin retinopathy is reversible.

Adult↗

[Neurodepressive effects of the essential oil of Lavandula angustifolia Mill].

Mice Swiss are orally given essential oil of lavander diluted at 1/60 in olive oil. Sedative effects are observed with some tests (hole board test, four plates test, plus-maze test, potentiation of barbiturate sleeping time). A significant interaction exists with pentobarbital: the sleeping time is increased and the asleeping time shortened.

Animals↗

[ Neuro-depressive properties of essential oil of lavender].

Toxicity for albino rats is very low. In mice an anxiolytic effect is exhibited and the pentobarbital evokated sleeping time is increased in animals given essential oil, but this effect disappears if they are administrated during five days.

Animals↗

Static perimetry in canthaxanthin maculopathy.

We performed threshold static perimetry on 19 patients who had ingested canthaxanthin; 11 had maculopathy and eight did not. Patients with no history of canthaxanthin ingestion served as controls. All patients had visual acuity of 6/9 or better. Threshold static perimetry was reevaluated two to three years after cessation of canthaxanthin ingestion. For both testing sessions, patients with maculopathy presented lower retinal sensitivity than controls, while patients without maculopathy did not differ significantly from the control group. These results suggest that canthaxanthin retinopathy can adversely affect the neurosensory retina.

Adult↗

Utilization of membranous lipid substrates by membranous enzymes: activation of the latent sphingomyelinase of hen erythrocyte membrane.

Previous studies demonstrated that hen erythrocytes have an inoperative, latent sphingomyelinase which is activated when the cells are hemolyzed in a hypotonic medium. Within minutes after hemolysis about 60-80% of the sphingomyelin (SPM) of the RBC "ghost" membrane was hydrolyzed. In this paper, expression of sphingomyelinase activity was further investigated. The percentage of total SPM hydrolyzed depended on the volume of the hypotonic hemolyzing buffer. Thus, suspending the erythrocytes in 4 vol of the buffer resulted in clumping of the hemolyzed "ghosts" and no hydrolysis of SPM. In comparison, suspension in 19 vol of the hypotonic buffer showed no clumping and sphingomyelinase activity was fully expressed. But centrifugation of the latter or, alternatively, addition of concanavalin A induced clumping and elimination of sphingomyelinase activity. Hen RBC could also be hemolyzed in an isotonic medium in the presence of Triton X-100, mellitin, halothane, and phospholipase C. Activation of the latent sphingomyelinase occurred at concentrations of these reagents which caused cell lysis. Hen RBC were dispersed in an isotonic medium containing glutaraldehyde (0.1%) or formaldehyde (10%). This rendered the cells resistant to hemolysis, even when subsequently dispersed in a hypotonic medium or water. But incubation of the "fixed" cells in a hypotonic or isotonic medium activated the enzyme, resulting in hydrolysis of 60% of the cellular SPM. In contrast, when glutaraldehyde was included in the hypotonic buffer, hemolysis occurred but sphingomyelinase activity was eliminated.

Animals↗