Vascular hyporesponsiveness in aortic rings from cirrhotic rats: role of nitric oxide and endothelium

1. The role of nitric oxide as mediator of the vascular alterations present in different models of experimental liver cirrhosis is controversial. In the present study, we evaluated the role of nitric oxide and that of the endothelium in the response to phenylephrine and acetylcholine of isolated aortic rings from chronic bile duct-ligated (29 days) rats and their corresponding controls. Experiments were performed in rings with or without endothelium, in rings pretreated with N-omega-nitro-L-arginine methyl ester (10(-4) mol/l) to inhibit nitric oxide synthesis and in rings pretreated with aminoguanidine (10(-4) mol/l) to inhibit inducible nitric oxide synthesis. 2. Under basal conditions, the maximum absolute tension developed in response to cumulative addition of phenylephrine was significantly decreased in rings from bile duct-ligated animals (1.62 +/- 0.06 g) compared with the control rings (2.15 +/- 0.099). This hyporesponsiveness to phenylephrine of rings from bile duct-ligated animals was corrected after treatment with N-omega-nitro-L-arginine methyl ester and reduced, but not completely eliminated, in rings without endothelium. In contrast, aminoguanidine did not modify the lower response to phenylephrine rings from bile duct-ligated animals. ED50 values were not different between groups under any experimental conditions. 3. The endothelium-dependent vasodilatation to acetylcholine in phenylephrine-constricted rings was similar in both groups of animals, control and bile duct ligated, under all experimental conditions. N-omega-nitro-L-arginine methyl ester pretreatment and removal of the endothelium completely abolished the response to acetylcholine in cirrhotic and control rings. 4. These results demonstrate that in aortic rings from cirrhotic, bile duct-ligated rats, increased production of nitric oxide, mainly of endothelial origin, is responsible for the lower contractile response to phenylephrine. Our data, however, do not support the involvement of the inducible nitric oxide synthase isoform in this alteration. In contrast, endothelial vasodilatory response to acetylcholine is not altered in this model of cirrhosis, which indicates that not all mechanisms of nitric oxide release are abnormal.     

Screening sigmoidoscopy. Factors associated with utilization

Although screening sigmoidoscopy (SS) reduces colorectal cancer mortality, surveys indicate that fewer than half of primary care physicians routinely recommend SS and less than 10% of eligible patients receive this test. The purpose of this study was to explore barriers to compliance with SS through a cross-sectional survey of general medicine patients. Clinician advice, perceived benefit of the test, and having a family member who has had the test are associated with SS, while perceived pain is a barrier to compliance and can negate the positive effects of clinician advice. These factors can be targeted as part of efforts to improve compliance with SS.     

CHL1 encodes a component of the low-affinity nitrate uptake system in Arabidopsis and shows cell type-specific expression in roots

The Arabidopsis CHL1 (AtNRT1) gene confers sensitivity to the herbicide chlorate and encodes a nitrate-regulated nitrate transporter. However, how CHL1 participates in nitrate uptake in plants is not yet clear. In this study, we examined the in vivo function of CHL1 with in vivo uptake measurements and in situ hybridization experiments. Under most conditions tested, the amount of nitrate uptake by a chl1 deletion mutant was found to be significantly less than that of the wild type. This uptake deficiency was reversed when a CHL1 cDNA clone driven by the cauliflower mosaic virus 35S promoter was expressed in transgenic chl1 plants. Furthermore, tissue-specific expression patterns showed that near the root tip, CHL1 mRNA is found primarily in the epidermis, but further from the root tip, the mRNA is found in the cortex or endodermis. These results are consistent with the involvement of CHL1 in nitrate uptake at different stages of root cell development. A functional analysis in Xenopus oocytes indicated that CHL1 is a low-affinity nitrate transporter with a K(m) value of approximately 8.5 mM for nitrate. This finding is consistent with the chlorate resistance phenotype of chl1 mutants. However, these results do not fit the current model of a single, constitutive component for the low-affinity uptake system. To reconcile this discrepancy and the complex uptake behavior observed, we propose a "two-gene" model for the low-affinity nitrate uptake system of Arabidopsis.     

Characterization and distribution of basic fibroblast growth factor-containing cells in the rat hippocampus

Basic fibroblast growth factor (bFGF), a member of the heparin-binding growth factor family, is present in relatively high levels in the brain where it may play an important role in the maintenance, repair, and reorganization of the tissue. Although bFGF is associated mainly with astrocytes throughout most of the central nervous system (CNS), a narrow but prominent band of pyramidal neurons, which coincides with the CA2 subregion of Ammon's horn in the hippocampus, stains intensely for bFGF. In order to gain an understanding of which cells express bFGF and whether or not BFGF is a good marker for CA2 neurons, we have used a mouse monoclonal antibody directed against recombinant human bFGF to characterize the distribution and localization of bFGF expression in the hippocampus. We find that about one-quarter of the neurons in CA2 are bFGF positive, and they appear smaller and have more irregular-shaped nuclei than their unstained counterparts. In addition, all glial fibrilary acidic protein (GFAP)-positive astrocytes in the hippocampus stain for bFGF, and the distribution of these astrocytes is heterogeneous in the hippocampus. Finally, in both astrocytes and CA2 pyramidal neurons, bFGF immunoreactivity is localized primarily in the nucleus and to a lesser extent in the cytoplasm and processes of stained cells.     

A pilot study of the marginal adaptation and surface morphology of glass-cermet cements

This study investigated changes in the marginal adaptation and surface morphology of Ketac-Silver and Chelon-Silver glass-current cements over time. Dispersalloy amalgam was used as a control. Contralateral pairs of carious primary molars were restored with the test materials and amalgam. Clinical evaluations were scheduled at 12, 18, and 24 months after placement. Gold-plated replicas of the restorations were observed with scanning electron microscopy. Fractures and cracks in the surface of the Dispersalloy and Chelon-Silver increased the surface roughness; however, the damage was superficial and self-limiting in the Dispersalloy restorations, while in Chelon-Silver the fractures caused the material to break down in layers. A substantial quantity of pores, usually smaller than 50 microns in diameter, were observed throughout the surface of the Chelon-Silver restorations. The pores in the surface of Ketac-Silver were fewer and smaller. The incidence of cavomarginal breakdown increased with time. Chelon-Silver restorations had a higher rate of cavomarginal breakdown than did Ketac-Silver and Dispersalloy restorations up to 18 months. However, there was no statistically significant difference in the marginal adaptation of the three groups at 24 months.     

Patients' experiences of patient-controlled analgesia

We examined patients' experiences of patient-controlled analgesia by the use of semistructured interviews in 26 patients shortly after discontinuation of the device. The options expressed by the patients were examined qualitatively to identify recurring themes in their experience of patient-controlled analgesia. The areas of interest were analgesia, factors influencing whether the patient pressed the button or not, whether they felt in control and side effects. Negative as well as the expected positive evaluations were found. The negative evaluations reflected problems with nausea and vomiting and inadequate analgesia. No clear strategy for pressing, or not pressing, the button emerged and the principle of control by the patient over their pain relief was not considered important.     

Analysis and purification of phorbol esters using normal phase HPLC and photodiode-array detection

For the first time a normal-phase HPLC method using photodiode-array detection is described for the analysis and purification of phorbol esters. The use of the method is demonstrated with examples of 10 different tigliane and daphnane esters (TPA, DOPP, DOPPA, Sap A, Sap B, Sap C, Sap D, Thy A, Ro and Rx). Both analytical and semipreparative techniques were developed. The method has been used in the final purification of DOPP and Rx from plant extracts. The method can be employed in the areas of phytochemistry, biochemistry and pharmacology/toxicology, where small samples of the toxic materials are required for research.