Biomedical subjects

R Wiest

Publications and source records attributed to R Wiest.

25 records · Page 2Linked to original sources

PubMed1999

Bacterial translocation in cirrhotic rats stimulates eNOS-derived NO production and impairs mesenteric vascular contractility.

Nitric oxide (NO) has been implicated in the arterial vasodilation and associated vascular hyporesponsiveness to vasoconstrictors observed in liver cirrhosis. Bacteria, potent activators of NO and TNF-alpha synthesis, are found in the mesenteric lymph nodes (MLNs) of ascitic cirrhotic rats. Here, we investigated the impact of bacterial translocation (BT) to MLNs on TNF-alpha production, vascular NO release, and contractility in the mesenteric vasculature of ascitic cirrhotic rats. Vascular response to the alpha-adrenoagonist methoxamine, which is diminished in the superior mesenteric arterial beds of cirrhotic rats, is further blunted in the presence of BT. BT promoted vascular NO release in cirrhotic rats, an effect that depended on pressure-induced shear stress and was blocked by the NO inhibitor N(omega)-nitro-L-arginine. Removing the endothelium had the same effect. Endothelial NO synthase (eNOS), but not the inducible isoform (iNOS), was present in mesenteric vasculature of cirrhotic rats with and without BT, and its expression was enhanced compared with controls. TNF-alpha was induced in MLNs by BT and accumulated in parallel in the serum. This TNF-alpha production was associated with elevated levels of tetrahydrobiopterin (BH(4)), a TNF-alpha-stimulated cofactor and enhancer of eNOS-derived NO biosynthesis and NOS activity in mesenteric vasculature. These findings establish a link between BT to MLNs and increased TNF-alpha production and elevated BH(4) levels enhancing eNOS-derived NO overproduction, further impairing contractility in the cirrhotic mesenteric vasculature.

Animals↗

PubMed1998

Enhanced release of nitric oxide in response to changes in flow and shear stress in the superior mesenteric arteries of portal hypertensive rats.

Increased nitric oxide (NO) release has been implicated in the pathogenesis of the hyperdynamic circulation in portal hypertension. NOS 3 (eNOS) causes NO release from the endothelium in response to physical stimuli, such as increased blood flow and shear stress. We evaluated the functional activity of the endothelium in the superior mesenteric arterial bed of portal hypertensive rats through direct measurement of NO metabolites (NOx) during changes in flow and shear stress. The in vitro perfusion system (McGregor) was used in sham and portal vein-ligated (PVL) rats. Shear stress was applied gradually to superior mesenteric arterial beds by increasing the perfusion rate. Flow studies were performed serially before and after incubation with either Krebs solution alone or with the NO-inhibitor, NG-monomethyl-L-arginine (L-NMMA). NOx concentrations in the perfusate were measured using chemiluminescence. The slope of NOx release versus flow-induced shear stress was calculated. Before L-NMMA administration, NOx concentrations and release of NO in PVL rats were significantly elevated in comparison with sham rats at flow rates of 32, 40, and 48 mL/min. The slope of NOx production versus shear stress index was significantly higher in PVL than in sham rats. After L-NMMA incubation, the decrease in slope was significantly larger in PVL rats. This study provides direct evidences of an increased NO synthesis by the superior mesenteric arterial vascular endothelium of PVL animals in response to shear stress. The increased NO output in response to shear stress suggests an adaptative mechanism developed by the vascular endothelial cells in response to a chronic increase in flow-mediated shear stress.

Animals↗

PubMed1995

Potentiation of agonist-stimulated cyclic AMP accumulation by tyrosine kinase inhibitors in rat pinealocytes.

To study cross-talk mechanisms in rat pinealocytes, the role of tyrosine kinase or kinases in the regulation of adrenergic-stimulated cyclic AMP production was investigated. Both norepinephrine- and isoproterenol-stimulated cyclic AMP accumulation were increased by two distinct tyrosine kinase inhibitors, genistein or erbstatin, in a concentration-dependent manner. A similar increase was observed with two other inhibitors, tyrphostin B44 and herbimycin. In contrast, daidzein, an inactive analogue of genistein, was ineffective; whereas vanadate, a phosphotyrosine phosphatase inhibitor, reduced the adrenergic-stimulated cyclic AMP accumulation. The tyrosine kinase inhibitors were effective in potentiating the cholera toxin-or forskolin-stimulated cyclic AMP accumulation, indicating that their sites of action are at the postreceptor level. Neither an activator nor inhibitors of protein kinase C influenced the potentiation of the cyclic AMP responses by genistein, suggesting that the potentiation effect by tyrosine kinase inhibitors does not involve the phospholipase C/protein kinase C pathway. However, when the phosphodiesterase was inhibited by isobutylmethylxanthine, genistein failed to potentiate and vanadate did not inhibit the adrenergic-stimulated cyclic AMP accumulation, indicating that the phosphodiesterase is a probable site of action for these inhibitors. These results suggest that cyclic AMP metabolism in the pinealocytes is tonically inhibited by tyrosine kinase acting on the cyclic AMP phosphodiesterase.

Animals↗

PubMed1991

Electron distributions in peptides and related molecules. 1. An experimental and theoretical study of N-acetyl-L-tryptophan methylamide.

The thermal vibrations and electron density of N-Ac-L-Trp-NHMe have been analyzed using single-crystal X-ray diffraction data measured at 103 K with Mo K alpha radiation to a resolution corresponding to (sin theta max)/ lambda = 1.17 A-1. Measurements of 10,527 reflections gave 4913 unique data [R(int)(magnitude of F2) = 0.019] of which 2641 had I greater than 3 sigma (I). A multipolar atomic density model was fitted [R(magnitude of F) = 0.028] in order to calculate phases for the crystal structure factors and map the valence-electron distribution. The phase problem for determining deformation densities by Fourier synthesis for noncentrosymmetric crystals is discussed. The experimental density agrees well with the theoretical density from an ab initio SCF molecular wave function calculated at the crystallographic molecular geometry with a split-valence basis set. Both the experimental and theoretical analyses confirm that the electron distribution is the same in the two different peptide groups in the molecule. Crystal data: C14H17N3O2, Mr = 259.31, orthorhombic, P2(1)2(1)2(1), Z = 4, F(000) = 522 e from 295 to 103 K; at 295 K, a = 8.152(2), b = 11.170 (2), c = 15.068 (3) A, V = 1372 A3, Dx = 1.26 mg mm-3; at 103 K, a = 8.209 (3), b = 11.016 (2), c = 14.760 (4) A, V = 1135 A3, Dx = 1.29 mg mm-3, mu = 0.083 mm-1 for lambda = 0.7107 A.

Chemical Phenomena↗

PubMed1991

[High dose 7S-immunoglobulin therapy in collagenoses. Clinical observations and effects on the lymphocyte subsets and immunoglobulin production].

Therapy with 7S-immunoglobulins in 8 patients with various connective tissue diseases led to a decrease of clinical disease activity. In vitro experiments showed that treatment induces change of B-cell function. Significant quantitative alteration of relative lymphocyte subpopulations did not occur. CRP, C3c, C4 and circulating immune complexes tended to normalization.

Arthritis, Rheumatoid↗

PubMed1991

[Macrophage activity during high dose steroid pulse therapy and 7S-immunoglobulin administration in patients with collagenoses. Comparison with in vitro studies].

Patients with connective tissue diseases show increased neopterin levels indicating the activation of the monocyte system. Corticosteroids reduce the release of neopterin in vivo and in vitro. After i.v. 7S-Ig administration neopterin increases in vivo transiently and decreases beyond the pretherapeutic levels. Addition of 7S-Ig to cell cultures reduces the macrophage activation.

Arthritis, Rheumatoid↗

PubMedDate not supplied

Epigastric sensations as an unusual manifestation of adult absence epilepsy.

We report the case of a 39-year-old woman with onset of daily epigastric sensations associated with brief episodes of unresponsive blank stare, which have been interpreted as complex partial seizures with occasional secondary generalisation. Phenytoin as monotherapy and in combination with valproate had not been effective. During video-EEG we recorded typical absences with brief 3 second spike, and slow-wave discharges of up to 5 seconds, which were recognized by the patient herself. All absences were preceded by epigastric sensations. There was no indication of focal epilepsy. Monotherapy with valproate substantially decreased the frequency of the absences. In conclusion, this case is peculiar for several reasons: 1) late onset of absence epilepsy, 2) epigastric sensation at onset of absence seizures, 3) recognition of brief "phantom" absences and 4) presumable adverse effects of phenytoin.

Adult↗