Pressor response induced by clenbuterol treatment in immobilized normotensive rats

Short-term treatment with clenbuterol [0.6 mg/kg-1 subcutaneously (s.c.) daily] produces a pressor effect in stressed rats after a period of immobilization (40 min). The stress applied markedly increases the plasma concentrations of norepinephrine (NE) and epinephrine. After bilateral adrenal demedullation, the increased levels of catecholamines and the hypertensive response obtained after clenbuterol treatment in the stressed animals were reduced to the values of the control rats. Clenbuterol treatment produced desensitization of the beta 2-adrenoceptor-mediated effect and thus reduced the vasodilator response induced by isoproterenol and increased the vasoconstriction produced by epinephrine but not that caused by NE. This desensitization may be responsible for the hypertensive response after clenbuterol treatment in stressed animals which is attenuated after adrenal demedullation. In conclusion, our results provide evidence that clenbuterol treatment induces pressor effect in normotensive animals under stress.     

Time course of vascular prostanoid production in the fructose‐hypertensive rat

1 There is a relationship between hypertension, insulin resistance and an altered plasmatic lipid profile known as ‘metabolic syndrome’. Fructose (F) overload induces in the rat a mild hypertension associated with metabolic alterations such as hyperglycemia, hypertriglyceridemia and insulin resistance, resembling such syndrome. 2 Prostanoids (PR), metabolites of arachidonic acid, include vasoactive substances synthesized and released by the vessel wall. An altered pattern of PR release has been previously found in mesenteric vessels of experimental diabetic rats. 3 This study analyzed the effects of F‐overload during different periods (4, 9, 15 and 22 weeks) on PR release in aorta (A) and mesenteric vascular beds (MVB). Animals received tap water (control) or F solution (10% w/v) to drink. 4 Rats with F overload showed significantly higher systolic blood pressure, glycemia and triglyceridemia than controls; but no differences in this parameters were found among periods of treatment either in controls or experimental animals. 5 In A, prostacyclin was decreased at 9, 15 and 22 weeks of treatment when compared to 4 weeks and controls. In MVB, prostacyclin showed different patterns of release in the studied periods of F overload. Prostaglandin (PG) E₂ diminish in MVB at the same extent in all periods. No changes were observed in A. The vasoconstrictor thromboxane was elevated in the MVB at 9 weeks. PGF₂α, also a vasoconstrictor, remains unchanged. 6 In conclusion, F overload provokes in the rat a decrease in the vascular production of vasodilator PR and, in one of the studied periods, an increase in the release of the vasoconstrictor thromboxane, leading to a negative imbalance in the prostacylin/thromboxane ratio. This could be involved in the blood pressure alterations found in this experimental model of metabolic syndrome.     

Biochemical characteristics and antigenic structures of Chlamydia

New biotechnology in immunology and molecular biology has enabled the identification and definition of the structure of glycolipids and especially membrane proteins of Chlamydia. Chlamydia antigen lipopolysaccharide, major outer membrane protein, protein 74 kDa, eukaryotic cell binding protein and cysteine rich proteins are all carriers of antigenic determinants, genus, species or type specific. They are very usefull for diagnosis of Chlamydial infections and epidemiological studies. These membranous antigens have an important role in the pathogenesis of these bacteries. Finally these studies have contributed to the isolation of a new species: C. pneumoniae (TWAR strains).     

The effect of 2 bleaching agents on the enamel surface. An in-vitro study]

We present a study "in vitro" of the effect of bleaching agents on dental surfaces using the "Walking bleaching technique". We found that hydrogen peroxide bleached more quickly than carbamide although, after a period of six weeks, the results were the same as far as whitening was concerned. In the scanning electron microscope we observed significantly different changes in each case. Carbamide caused a regular and uniform opening of the enamel prisms of the surface while hydrogen peroxide produced more severe superficial destruction with the appearance of patterning similar to the acid etching, and the presence of some crystalline areas emerging from the body of the prisms.     

Synthesis and in vitro anti-HIV activity in human monocyte-derived macrophages of 2-oxothiazolidine-4(R)-carboxylic acid derivatives

Oxidative stress and glutathione (GSH) deficit may play an important role in HIV infection pathogenesis, and oral administration of GSH-replenishing drugs such as N-acetylcysteine (NAC) and 2-oxothiazolidine-4(R)-carboxylic acid (OTC) may be associated with an increased survival rate of HIV-infected patients. Nevertheless, beneficial effects of these molecules are restricted in vivo by the high concentrations that are necessary to obtain biological effects, rapid extracellular metabolization, and low availability and plasma concentrations. We synthesized OTC derivatives that are more lipophilic than OTC and theoretically able to overcome these limitations and to generate, in addition to cysteine, other substrates of the gamma-glutamyl cycle. Their antiviral effects were investigated in human HIV-1/Ba-L-infected monocyte-derived macrophages. In our experimental conditions, OTC exhibited anti-HIV-1 effects and little cytotoxicity at high doses. None of the nine tested derivatives showed higher cytotoxicity than OTC, nor anti-HIV-1/Ba-L activity.     

Lack of pharmacokinetic and pharmacodynamic interaction between rizatriptan and paroxetine

Rizatriptan is a potent, oral 5-HT(1B/1D) agonist with a rapid onset of action being investigated for the acute treatment of migraine. This study examined the clinical and pharmacolinetic interaction between rizatriptan and the selective serotonin reuptake inhibitor, paroxetine. In this two-period crossover study, 12 healthy young subjects (6 males and 6 females) received 1 mg rizatriptan following 14 days of treatment with placebo or paroxetine (20 mg once daily). Plasma was sampled for rizatriptan and N-monodesmethyl rizatriptan, a minor but active metabolite of rizatriptan. Safety evaluations included monitoring for adverse events, vital signs, and visual analog scale assessment of mood. Plasma levels of rizatriptan and N-monodesmethyl rizatriptan were not altered when rizatriptan was administered with paroxetine compared to the placebo. Clinically, coadministration of rizatriptan with paroxetine was well tolerated. Blood pressure, heart rate, and temperature changes during the observation period did not differ to a clinically significant degree when rizatriptan was administered with paroxetine compared to the placebo. No effects on mood occurred following treatment with the combination compared to rizatriptan alone. Adverse events following rizatriptan administration with paroxetine were similar to those reported when rizatriptan was given with the placebo.     

A high‐fat plus fructose diet produces a vascular prostanoid alterations in the rat

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Human pharyngeal and sellar pituitary glands: differences and similarities revealed by an immunocytochemical study

Fifteen pharyngeal and sellar pituitary glands, obtained at autopsy from unselected adult patients, were compared in an attempt to elucidate the functional significance of the pharyngeal pituitary. The study was carried out using light microscopy and an indirect peroxidase technique to detect the presence of prolactin, GH, ACTH, LH, FSH, TSH and lipotrophin (LPH) immunoreactive cells. A quantitative analysis of these cell types in each gland was performed. Neither the pharyngeal nor the sellar pituitaries were abnormal in six cases. In this group the average percentage of immunoreactive cells in the sellar vs the pharyngeal pituitary was 11.3 vs 7.4 for FSH cells, 13.3 vs 4.4 for LH cells, 6.4 vs 5.2 for TSH cells, 14 vs 1.5 for ACTH cells, 13.1 vs 6 for LPH cells, 29.4 vs 5.2 for GH cells and 21.2 vs 8.5 for prolactin cells. A comparative statistical evaluation of the seven hormone-producing cell types indicated that, in most cases, the percentage of immunoreactive cells was significantly higher in the sellar pituitary. Examination of serial sections revealed hyperplasia, with or without microadenomas, in nine sellar pituitaries. In these abnormal cases most of the pharyngeal pituitary glands showed hyperplasia of the same cell type as was found hyperplastic in the sellar adenohypophysis. However, hyperplasia restricted to the sellar pituitary was also seen. There were two cases in which the pharyngeal pituitary was almost lacking in immunoreactive cells; in one of them the sellar pituitary had GH and prolactin cell hyperplasia. The results obtained confirm that under normal conditions the pharyngeal pituitary is not an important source of adenohypophyseal hormones.(ABSTRACT TRUNCATED AT 250 WORDS)     

sPLA2-V inhibits EPCR anticoagulant and antiapoptotic properties by accommodating lysophosphatidylcholine or PAF in the hydrophobic groove

The endothelial protein C receptor (EPCR) plays an important role in cardiovascular disease by binding protein C/activated protein C (APC). EPCR structure contains a hydrophobic groove filled with an unknown phospholipid needed to perform its function. It has not been established whether lipid exchange takes place in EPCR as a regulatory mechanism of its activity. Our objective was to identify this phospholipid and to explore the possibility of lipid exchange as a regulatory mechanism of EPCR activity driven by the endothelially expressed secretory group V phospholipase A(2) (sPLA(2)-V). We identified phosphatidylcholine (PCh) as the major phospholipid bound to human soluble EPCR (sEPCR). PCh in EPCR could be exchanged for lysophosphatidylcholine (lysoPCh) and platelet activating factor (PAF). Remarkably, lysoPCh and PAF impaired the protein C binding ability of sEPCR. Inhibition of sPLA(2)-V, responsible for lysoPCh and PAF generation, improved APC binding to endothelial cells. EPCR-dependent protein C activation and APC antiapoptotic effect were thus significantly enhanced. In contrast, endothelial cell supplementation with sPLA(2)-V inhibited both APC generation and its antiapoptotic effects. We conclude that APC generation and function can be modulated by changes in phospholipid occupancy of its endothelial cell receptor.