Contribution of standard oesophageal manometry in sliding hiatal hernia: from the gastro-oesophageal pressure gradient to the diagnosis.

OBJECTIVE: We tested whether gastro-oesophageal pressure gradient is augmented in sliding hiatal hernia and the yield of oesophageal manometry in diagnosing sliding hiatal hernia. METHODS: Patients with equivalent body mass index were categorised according to manometry and endoscopy in groups: (1) no sliding hiatal hernia (n=147); (2) sliding hiatal hernia solely at endoscopy (n=46); and (3) sliding hiatal hernia at manometry (n=22). The yield of manometry was assessed taking endoscopy as referential. RESULTS: Gastro-oesophageal pressure gradient was similar between groups both at inspiration (13.3+/-5.7 mm Hg vs. 13.6+/-5.4 mm Hg vs. 12.6+/-4.4 mm Hg; P=0.874) or expiration (5.1+/-3.8 mm Hg vs. 5.2+/-3.6 mm Hg vs. 5.1+/-3.7 mm Hg; P=0.767). Group 3 patients were older than those of groups 1 and 2 (59+/-10 vs. 42+/-15 vs. 45+/-13 years; P<0.001). Sliding hiatal hernia was larger when characterised by manometry than at endoscopy [4 cm (2.25-4.75) vs. 2 cm (2-3); P<0.001]. Manometry showed sensitivity of 28% (95%CI 19-40%), specificity of 97% (95%CI 93-99%) and positive predictive value of 82% (95%CI 63-92%) in diagnosing sliding hiatal hernia. CONCLUSIONS: By using manometry in patients with equivalent body mass index, sliding hiatal hernia presence and size are related with age rather than gastro-oesophageal pressure gradient. This technique may be clinically useful when positive for sliding hiatal hernia.

Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target.

SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.

New thymidylate synthase inhibitors induce apoptosis in melanoma cell lines.

Malignant melanoma is particularly resistant to conventional chemotherapy and radiotherapy. For this reason in the past years a huge variety of new compounds has been developed with potential chemotherapeutic activity which needs to be tested in vitro and in vivo. We investigated the in vitro action of three new experimental antifolate substances (MR7, MR21 and MR36) with a critical target for thymidylate synthase (TS), an essential enzyme for DNA synthesis. The response of two melanoma cell lines (SK-MEL-2 derived from malignant melanoma metastasis and SK-MEL-28 derived from primary malignant melanoma) was examined after treatment with these substances. The antifolate agents induced apoptosis in SK-MEL-2 and SK-MEL-28 cells as confirmed by the TUNEL technique and Comet Assay. Western-blot analysis showed a down-regulation of Bcl-2 protein level and PARP cleavage, otherwise p53 and Bax expressions were not modulated. Moreover, these antifolate-induced apoptosis was accompanied by both pro-caspase-9 and -8 activations. These results were supported by the use of the pan-caspases inhibitor Z-VAD-FMK that almost completely decreased the amount of apoptosis in both the melanoma cell lines treated with antifolate. In conclusion our results show that TS inhibitors are able to induce apoptosis through a caspase-mediated pathway, but without the involvement of the p53/Bax signalling.

Analysis of mandelonitrile lyase and beta-glucosidase from sweet almonds by combined electrophoretic techniques.

Almonds are a rich source of mandelonitrile lyase (oxynitrilase) and beta-glucosidase. The isolation of these two enzymes from sweet almonds requires fractional ammonium sulfate precipitation followed by ion-exchange chromatography on diethylaminoethyl-(DEAE) and carboxymethylcellulose (CMC) columns. In the present investigation different electrophoretic techniques such as sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing in immobilized pH gradients (IEF-IPG), and capillary electrophoresis were used to characterize these two enzymes. For the first time, beta-glucosidase and oxynitrilase were separated in an immobilized pH gradient of one pH unit. Capillary zone electrophoresis (CZE) was an excellent tool for analysis of the purity of enzyme preparations, achieving complete separation of various protein constituents in only 15 min. CZE showed a resolving capacity for the separation of enzyme forms comparable to that of isoelectric focusing in an immobilized pH gradient.

Synthesis and characterization of capillary columns coated with glycoside-bearing polymer.

Fused silica capillary columns were coated with a polymer obtained by radical polymerization of a novel acrylamido derivative, [(N-acryloylamino)ethoxy]ethyl-ß-d-glucopyranose (AEG). This monomer, bearing a monosaccharide residue, was synthesized by direct coupling of [(N-acryloylamino)ethoxy]ethanol with glucose. The aim of this work was to demonstrate that weak, reversible interactions that take place between wall polymer coatings and protein analytes lead to poor reproducibility of transit times and capillary performance degradation. The pronounced hydrophilicity of the new poly(AEG) phase improves the reproducibility of transit times and the peak efficiency, as demonstrated by a complete series of tests carried out at various pH values.

von Recklinghausen's neurofibromatosis. Case report with extensive involvement of the sciatic nerve.

The authors report a case of neurofibromatosis with extensive involvement of the sciatic nerve and associated manifestations in the skin and spine. The main features of von Recklinghausen's disease are recalled. Particular emphasis is placed on the surgical treatment of the sciatic nerve neoplasm and on postoperative management.