Acetyl-11-keto-β-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis

The gum resin extract from Boswellia serrata (H15), an herbal product, was recently shown to have positive therapeutic effects in inflammatory bowel disease (IBD). However, the mechanisms and constituents responsible for these effects are poorly understood. This study examined the effect of the Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Rats also received oral treatment with the Boswellia extract (H15) or AKBA at two different doses (low and high) equivalent to recommendations in human disease over 2 days. Controls received only the carriers NaHCO3 (subcutaneously) and tylose (orally). Effects of treatment were assessed by intravital microscopy in ileal submucosal venules for changes in the number of rolling and adherent leukocytes and by macroscopic and histological scoring. Increased leukocyte-endothelial cell adhesive interactions and severe tissue injury accompanied indomethacin-induced ileitis. Treatment with the Boswellia extract or AKBA resulted in a dose-dependent decrease in rolling (up to 90%) and adherent (up to 98%) leukocytes. High-dose Boswellia extract as well as both low- and high-dose AKBA significantly attenuated tissue injury scores. Oral therapy with the Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features normally associated with indomethacin administration, indicating that the anti-inflammatory actions of the Boswellia extract in IBD may be due in part to boswellic acids such as AKBA.     

Cationic polymerization of 1,2-epoxy-3-nitropropane in the presence of ethylene glycol, 3 Determination of the mechanism

Cationic polymerization of 1,2-epoxy-3-nitropropane was performed in the presence of ethylene glycol and borontrifluoride etherate under conditions meant to favor the Activated Monomer Mechanism. In two previous papers, we showed that the Activated Monomer Mechanism prevails until the number-average molecular weight M?_n reaches a value of about 350. In this article, we show that beyond this value another mechanism competes effectively with the latter one: oxygen atoms of the oligomeric chains react with the protonated monomer leading to the formation of non-cyclic tertiary oxonium ions. These ions may react with various nucleophiles during polymerization or upon deactivation, which explains the M?_n limitation as well as the excess of hydroxyl groups observed.     

Mediators of antigen-induced gastrin release: role of antigen-antibody complexes and the complement system

That orally administered antigen was shown to induce gastrin release in immunized animals was a new aspect of gastrointestinal physiology. The mediators responsible for this immunological effect are still unclear. In an attempt to discover more about the mechanisms regarding antigen-induced gastrin release, we developed an in vitro system where fragments of rat antral mucosa were challenged. This makes it possible to determine the role of antigen-antibody complexes and the complement system in the mechanism of antigen-induced gastrin release. Wistar rats were immunized in vivo with NIP-OVA and mucosal fragments were challenged in vitro with NIP-HGG. Gastrin was determined after a preincubation and a challenged incubation period without supernatants. After antigenic challenge, supernatants were used for in vitro challenge in order to rule out the presence of a soluble mediator and activation of complement. In a second group of experiments Wistar rats were used to study in vitro the release of specific antibodies after antigenic challenge. With this experimental design we were able to show increased gastrin secretion after antigenic challenge in vitro in the presence of intact tissue. It is shown that the increased gastrin release is most probably mediated by activation of the complement system in the presence of antigen-antibody complexes. These are built up by specific anti-NIP antibodies and NIP-HGG used for the challenge. The complement system might be the final pathway of the observed in-creased gastrin release.     

SynthèSe de copolymères triséquencés polybutyramide-polystyrène et polybutyramide-polyisoprène

The synthesis of triblock copolymers with crystalline outer blocks of polybutyramide and a central block of polystyrene or polyisoprene was performed. First polystyrene (or polyisoprene) fitted at both ends with acyllactam functions were obtained. In a second step these endstanding functions promote the lactame polymerization to yield the polyamide blocks. A careful characterization of the resulting samples was carried out. The behaviour of these block copolymers is typically that of a thermoplastic elastomer, whereby the crystalline blocks constitute the physical crosslinks in the samples.     

Surgical management and long-term outcome of complicated liver hydatid cysts caused by Echinococcus granulosus

BACKGROUND: The aim of this retrospective study was to evaluate clinical presentation and long-term outcome of patients treated surgically for complicated liver hydatid cysts. PATIENTS AND METHODS: Eighty-four patients with liver hydatid cysts underwent an operation at the Geneva University Hospital between 1980 and 1999. Clinical presentation, postoperative morbidity, mortality, and long-term recurrence rate were evaluated. RESULTS: Among the 84 patients with liver hydatid disease, 35 patients (41%) presented complicated cysts (ie, cysts that had developed a fistula into adjacent structures or organs). In most patients, the fistula communicated with the biliary tree (n = 25), but we also observed communication with the right lung (n = 3), the right diaphragm (n = 2), liver parenchyma (n = 1), and peritoneal cavity (n = 1). Complete removal of the cystic disease was possible in 24 of 35 patients (70%). In 11 patients, fragments of cysts were not removed because of their location adjacent to main vessels. Postoperatively, 8 patients (23%) developed a severe complication (grade II and III). There were no postoperative deaths, and no recurrences of hydatid disease were observed with a median follow-up of 8.6 years (complete follow-up was obtained in 69% of patients). CONCLUSIONS: Complicated liver hydatid disease is frequent and was observed in almost half of patients operated for liver hydatid cysts at our center. Using a surgical strategy aimed at complete removal of cystic and pericystic tissue with simultaneous treatment of the fistulous tract, we observed 23% postoperative morbidity, no mortality, and no recurrence of disease with a median follow-up of >8 years.     

Therapeutic failure of cinacalcet in a renal transplant patient presenting hyperparathyroidism with severe hypercalcaemia

Sir, In our experience, 10% of renal allograft recipients developsustained hyperparathyroidism and hypercalcaemia during thefirst year following renal transplantation. Persistent hypercalcaemiausually requires parathyroidectomy, which represents the onlydefinitive treatment currently available. Cinacalcet, a calcimimeticdrug, represents from now on an alternative     

Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells.