[Portal vein embolization: Present and future]. / Embolisation portale préopératoire : présent et futur.

Portal vein embolization consists of occluding a part of the portal venous system in order to achieve the hypertrophy of the non-embolized liver segments. This technique is used during the preoperative period of major liver resection when the future remnant liver (FRL) volume is insufficient, exposing to postoperative liver failure, main cause of death after major hepatectomy. Portal vein embolization indication depends on the FRL, commonly assessed by its volume. Nowadays, FRL function evaluation seems more relevant and can be measured by 99mTc labelled mebrofenin scintigraphy. Portal vein embolization procedure is mostly performed with percutaneous trans-hepatic access by using ultrasonography guidance and consists of embolic agent injection, such as cyanoacrylate, in the targeted portal vein branches with fluoroscopic guidance. It is a safe and well-tolerated technique, with extremely low morbi-mortality. Portal vein embolization leads to sufficient FRL hypertrophy in about 80% of patients, allowing them to undergo surgery from which they were initially rejected. The two main reasons of non-resection are tumor progression (≈15% of cases) and FRL insufficient hypertrophy (≈5% of cases). When portal vein embolization is not enough to obtain adequate FRL regeneration, hepatic vein embolization may potentiate its effect (liver venous deprivation technique).

Preorganized Peptide Scaffolds as Mimics of Phosphorylated Proteins Binding Sites with a High Affinity for Uranyl.

Cyclic peptides with two phosphoserines and two glutamic acids were developed to mimic high-affinity binding sites for uranyl found in proteins such as osteopontin, which is believed to be a privileged target of this ion in vivo. These peptides adopt a ß-sheet structure that allows the coordination of the latter amino acid side chains in the equatorial plane of the dioxo uranyl cation. Complementary spectroscopic and analytical methods revealed that these cyclic peptides are efficient uranyl chelating peptides with a large contribution from the phosphorylated residues. The conditional affinity constants were measured by following fluorescence tryptophan quenching and are larger than 10(10) at physiological pH. These compounds are therefore promising models for understanding uranyl chelation by proteins, which is relevant to this actinide ion toxicity.

In situ generation of iminodiacetic acid groups on nanoporous alumina for the reversible immobilization of enzymes and other biomolecules.

Nanoporous alumina membranes were silanized with aminopropylsilane and iminodiacetic acid (IDA) groups were generated in situ by reaction with iodoacetate. The membranes were mounted in standard filter holders, connected to a HPLC system and saturated with selected metal ions. Cu(II) allowed the capture of chicken muscle lactate dehydrogenase with such stability, repeatability and reproducibility that Michaelis-Menten kinetics could be studied. The IDA surface was stable for months and could be depleted and regenerated with metal ions multiple times without appreciable loss of capacity. The binding of lactate dehydrogenase influenced the backpressure to the extent that could be expected for a monolayer according to Poiseuilles law.

In vitro characterization of magnetic electrospun IDA-grafted chitosan nanofiber composite for hyperthermic tumor cell treatment.

Magnetic nanoparticles were the thermoseeds under an alternating magnetic field and can be used to produce highly localized hyperthermia effect on deep-seated tumor. Nevertheless, effective and precisive delivery of nanoparticles to the treatment-intended site remains a challenge. In this study, Fe3O4 nanoparticles were incorporated onto the crosslinked electrospun chitosan nanofibers using chemical co-precipitation from the Fe ions adsorbed. Such magnetic nanoparticle-nanofiber composites could be delivered to the treatment site precisely by surgical or endoscopic method. Iminodiacetic acid (IDA) functionality was grafted onto the chitosan with an aim to increase the amount of magnetic nanoparticles formed in the electrospun magnetic nanofiber composite. The morphology, crystalline phase as well as the magnetism characteristic of the magnetic electrospun nanofiber matrixes, was analyzed. Results have indicated that, with the incorporation of IDA functionality, more magnetic nanoparticles were formed in the electrospun chitosan nanofiber matrix. In addition, the magnetic IDA-grafted chitosan nanofiber composite can effectively reduced the tumor cell proliferation under the application of magnetic field. This finding suggested the magnetic electrospun chitosan nanofiber composite can be of potential for hyperthermia treatment.

Adsorption behavior of uranium(VI) and other ionic species on cross-linked chitosan resins modified with chelating moieties.

Cross-linked chitosan resins with catechol (catechol-type chitosan, type 1 and type 2), iminodiacetic acid (IDA-type chitosan), iminodimetylphosphonic acid (IDP-type chitosan), phenylarsonic acid (phenylarsonic acid-type chitosan), or serine (serine-type chitosan) were prepared for the collection and concentration of uranium(VI). The adsorption behavior of U(VI) and other ionic species, such as metal ions and oxo-acid ions, on the cross-linked chitosan (base material) and chitosan resins modified with chelating moieties was examined using a column procedure. Especially, the catechol-type chitosan (type 2) adsorbed U(VI) at pH 2-7, and selectively collected U(VI) at acidic pH regions by forming a stable chelate with hydroxyl groups of catechol moiety introduced to the chitosan. Also, the adsorption properties of cationic and anionic species present in aquatic media were elucidated. The adsorption ability for U(VI) was in the order: catechol-type chitosan (type 2)>serine-type chitosan>phenylarsonic acid-type chitosan>the others. The catechol-type chitosan (type 2) was useful for the collection and concentration of uranium(VI).

Laparoscopic Right Hemicolectomy and Cholecystectomy for a Cholecystocolic Fistula

A cholecystocolic fistula (CF) is an uncommon complication of the gallbladder and colonic disease. We report a case of a CF that was successfully managed by using a laparoscopic right hemicolectomy and cholecystectomy. A 49-yr-old woman was admitted to the Department of Internal Medicine because of intermittent and progressive right upper quadrant pain. She was obese (body mass index: 34 kg/m2) and had a previous history of three abdominal surgeries. She was diagnosed with a CF by using abdominal computed tomography. The fistula between the gallbladder and the hepatic flexure of the colon was also characterized by using technetium-99m diisopropyl iminodiacetic acid ((99m)Tc-DISIDA) cholescintigraphy, a double-contrast Barium enema, and colonoscopy. Multiple polyps with severe inflammation were observed around the orifice of the fistula. Because of the risk of malignancy and appendicolith on CT, a laparoscopic en block excision of the gallbladder and the right colon following adhesiolysis was performed. The postoperative course was uneventful, and the patient was discharged on postoperative day 9. This case shows that the laparoscopic combined resection is safe and effective in the experienced hands of the laparoscopic surgeon even though a CF has traditionally been considered as a contraindication to laparoscopic surgery. While the incidence of successful management of biliary-enteric fistulas through laparoscopic repair is increasing, this is the first report of a laparoscopic combined resection of a CF in an obese patient with severe intraabdominal adhesion.

Preparation and in-vivo evaluation of 99mTc-IOTIDA for cholescintigraphy.

The synthesis, radiolabeling and in vivo evaluation of 99mTc-IOIDA(3-iodo 2,4,6-trimethylpheyl carbamoylmethyl iminodiacetic acid) for the assessment of hepatocytic function and the functional status of the cystic duct and the gallbladder are described. For a scintigraphic imaging comparison, three different 99mTc-IDA derivatives, 99mTc-DISIDA, 99mTc-mebrofenin and 99mTc-IOTIDA, were prepared and evaluated for their in vivo pharmacokinetic behavior through animal studies. Serial static image scans of rabbits injected with 99mTc-IOTIDA revealed that none of the tissues except the hepatobiliary system showed radioactivity concentrations. A scintigraphic study in a healthy volunteer showed that most of the administrated radioactivity accumulated in the liver and was rapidly excreted through the hepatobiliary system, visualizing the gallbladder within 15 min. In conclusion, 99mTc-IOTIDA is a potential hepatobiliary imaging agent for the evaluation of the functional status of hepatocytes and the patency of the biliary duct.

Cycloalliin, a cyclic sulfur imino acid, reduces serum triacylglycerol in rats.

Allium species such as onions and garlic are used as foodstuff, condiment, flavoring, and folk medicine. Onions may decrease hyperlipidemia and improve atherosclerosis. However, the ingredients in onion that are responsible for this phenomenon are not known. In the present study, we investigated the effects of cycloalliin, a sulfur-containing imino acid in onions, on lipid metabolism in Sprague-Dawley rats. When supplemented at the 0.1% and 0.3% levels to the atherogenic diet, cycloalliin reduced serum triacylglycerol (TAG) concentration by approximately 40% compared to the control. Serum cholesterol ester level also showed a tendency to decrease in cycloalliin groups. Hepatic lipid levels were comparable among the groups, although TAG and phospholipid contents were slightly higher in both cycloalliin groups. Dietary cycloalliin had no significant effect on hepatic enzyme activities responsible for TAG synthesis (phosphatidate phosphohydrolase, malic enzyme, and glucose-6-phosphate dehydrogenase (G6PDH)). In conclusion, dietary cycloalliin has serum TG-lowering effect without affecting hepatic TAG synthesis and content in rats, suggesting an alteration of lipoprotein assembly and secretion processes in the liver.

Hepatobiliary clearance of labelled mebrofenin in normal and D-galactosamine HCl-induced hepatitis rats and the protective effect of turmeric extract.

This study was carried out to see the hepatobiliary clearance of 99m Tc-Mebrofenin radiopharmaceutical in D-galactosamine induced hepatic rats. Furthermore, protective effect of turmeric extract has been studied in these hepatitis rats. Hepatitis was induced with intraperitoneal injection of D-galactosamine (400 mg/kg b. wt) in these rats. 1% turmeric extract was given along with their normal diet for 15 days. Turmeric extract treatment significantly increased the hepatic uptake of radioactivity and accelerated the excretion of 99m Tc-Mebrofenin as compared to control rats. (P < 0.001). In D-galactosamine administered rats, a significant delay was observed in 99m Tc-Mebrofenin excretion as compared to controls. However, D-galactosamine administered rats, pretreated with turmeric extract or concurrently treated with turmeric extract showed a near normal pattern of 99m Tc-Mebrofenin excretion. Hence, it can be suggested that turmeric extract may improve the liver function by detoxification.

Carbonic anhydrase inhibitors. A general approach for the preparation of water-soluble sulfonamides incorporating polyamino-polycarboxylate tails and of their metal complexes possessing long-lasting, topical intraocular pressure-lowering properties.

Reaction of polyamino-polycarboxylic acids or their dianhydrides with aromatic/heterocyclic sulfonamides possessing a free amino/imino/hydrazino/hydroxy group afforded mono- and bis-sulfonamides containing polyamino-polycarboxylic acid moieties in their molecule. The acids/anhydrides used in synthesis included IDA, NTA, EDDA, EDTA and EDTA dianhydride, DTPA and DTPA dianhydride, EGTA and EGTA dianhydride, and EDDHA, among others. All the newly prepared derivatives showed strong affinity toward isozymes I, II, and IV of carbonic anhydrase (CA). Metal complexes of the new compounds have also been prepared. Metal ions used in such preparations included di- and trivalent main-group and transition cations, such as Zn(II), Cu(II), Al(III), etc. Some of the new sulfonamides/disulfonamides obtained in this way, as well as their metal complexes, behaved as nanomolar CA inhibitors against isozymes II and IV, being slightly less effective in inhibiting isozyme I. Some of these sulfonamides as well as their metal complexes strongly lowered intraocular pressure (IOP) when applied topically, directly into the normotensive/glaucomatous rabbit eye, as 1-2% water solutions/suspensions. The good water solubility of these sulfonamide CA inhibitors, correlated with the neutral pH of their water solutions used in the ophthalmologic applications and the long duration of action of the IOP-lowering effect, makes them interesting candidates for developing novel types of antiglaucoma drugs devoid of serious topical side effects.

Zinc supplementation prevents liver injury in chlorpyrifos-treated rats.

The present study was performed to investigate the protective effects of zinc (227 mg/L in drinking water) treatment in chlorpyrifos (13.5 mg/kg body weight, orally) induced hepatotoxicity in male rats. Animals received chlorpyrifos and/or zinc treatments for 8 wk. A 99mTc-mebrofenin clearance test was done to determine the biological half-life (Tbiol) of the radiopharmaceutical in liver for the determination of the hepatobiliary function of the animals. At the end of treatment periods, samples were collected for the measurement of zinc levels in serum and liver. Electron microscopic studies were performed to study hepatic ultrastructure following various treatments. When compared to normal controls, chlorpyrifos treatment resulted in reduced hepatic and serum zinc levels (p < 0.01). The biological half-life (Tbiol) of 99mTc-mebrofenin in liver was increased (p < 0.01) significantly in chlorpyrifos-treated animals, reflecting a poor excretion of the radiopharmaceutical from the liver. Simultaneous zinc supplementation retained the increased hepatic Tbiol values of 99mTc-mebrofenin within normal limits. Zinc treatment also protected hepatocytes from the marked disruptions in the membranous organelles and narrowing/blocking of biliary channels, which was otherwise a common observation following chlorpyrifos treatment. These data clearly show the protective effects of zinc in animals subjected to organophosphate poisoning.

Isolation and characterization of an Achromobacter xylosoxidans strain B3 and other bacteria capable to degrade the synthetic chelating agent iminodisuccinate.

Three bacterial strains were isolated, which used the synthetic chelating agent iminodisuccinate (IDS) as sole carbon source for growth in mineral salts media (MSM). Taxonomic analysis and 16S rDNA sequence analysis identified one of these isolates (B3), which was isolated from sewage sludge, as a strain of Achromobacter xylosoxidans subsp. xylosoxidans. It exhibited a doubling time of approximately 3 h in liquid MSM supplemented with IDS and grew even in the presence of 1.0% (w/v) IDS. Since photometric and high performance liquid chromatography analysis showed that IDS, which came onto the market only recently as an alternative for ethylenediaminetetraacetate, was completely degraded by axenic cultures of bacteria; it will probably be readily degraded in the environment.

Effects of iron chelates on the transferrin-free culture of rat dermal fibroblasts through active oxygen generation.

Effects of nonchelating and chelating agents at 10 mM on the serum-free culture of rat dermal fibroblasts were investigated. A strong iron-chelating agent, iminodiacetic acid (IDA), and a weak one, dihydroxyethylglycine (DHEG), decreased iron permeation into preconfluent fibroblasts. A weak iron-chelating agent, glycylglycine (GG), a nonchelating agent, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), and human apotransferrin (10 micrograms/ml) increased the permeation with time. Iron may be essential for survival of fibroblasts because subconfluent fibroblasts exposed to 100 microM FeSO4 in combination with transferrin, HEPES, or GG significantly decreased to release lactate dehydrogenase into the medium. Superoxide dismutase and dimethyl sulfoxide blocked the enzyme release, suggesting that superoxide and hydroxyl radical induce cellular damage but hydrogen peroxide (H2O2) generated by superoxide dismutation does not. GG significantly reduced H2O2 cytotoxicity. DHEG acted as a potent promoter of the iron-stimulated cellular damage if ascorbate or H2O2 was added to the medium. FeSO4 and FeCl3 (50 to 100 microM) individually combined with IDA maximally promoted fibroblast proliferation. Ascorbate increased formation of thiobarbituric acid-reactive substances from deoxyribose in the medium supplemented with FeSO4 and either IDA or DHEG. Conversely, ascorbate decreased the formation in the medium with FeSO4 and with or without other agents. Fibroblast proliferation may thus be stimulated through the active oxygen generation mediated by a redox-cycling between Fe3+ and Fe2+, which are dissolved in the medium at a high concentration, rather than through delivery of iron into the cells.

Production of recombinant human monoclonal antibody using ras-amplified BHK-21 cells in a protein-free medium.

A ras oncogene-amplified recombinant BHK-21 cell line (ras-rBHK-IgG) has been established, and was shown to hyperproduce the recombinant IgG chimeric human monoclonal antibody (hMAb) AE6F4, which recognizes lung cancer cells. We found that the ras-rBHK-IgG cell could be easily cultured in a protein-free ERDF medium supplemented with iron(III) nitrate, hydroxyethyliminodiacetic acid, and non-protein synthetic attachment factor as well as in a serum-free ERDF medium supplemented with insulin, transferrin, ethanolamine, and sodium selenite. The productivity of recombinant hMAb from the cells cultured in dishes at high cell densities was higher in protein-free medium than in serum-containing medium. True high density culture of the ras-rBHK-IgG cells was done in protein-free medium using the Tecnomouse, which is a novel hollow fiber bioreactor system. After culture for 30 days in protein-free culture, a total amount of about 14 mg of the recombinant hMAb AE6F4 was obtained, and was shown to be reactive against lung cancer cells in tissues.

Quantitative evaluation of tourniquet leak during i.v. regional anaesthesia of the upper and lower limbs in human volunteers.

Although it is accepted that during i.v. regional anaesthesia (IVRA) local anaesthetic can leak under the tourniquet into the systemic circulation, no published study has evaluated this leak quantitatively. In volunteers, during two random sessions, we have simulated IVRA using standard techniques with a radiolabelled compound which is chemically similar to lignocaine and has comparable tissue distribution (0.1 mg of HIDA labelled with 100 muCi of 99mTc in 40 ml of saline). The decrease in radioactivity was measured with a gamma camera for the 20 min of tourniquet inflation and for the 20 min of washout after cuff deflation. While the tourniquet was inflated, the leak for the lower limb (mean 29 (SD 8) %) was significantly greater (P < 0.004) than the leak for the upper limb (15 (5) %). Moreover, in each of 10 volunteers, the leak was always greater for the lower than the upper limb. During the first 3 min after tourniquet deflation the loss of radioactivity was 58 (8) % of the maximal amount for the upper limb and 39 (8) % for the lower limb (P < 0.001). As the leak under the tourniquet was significantly greater for the lower than the upper limb, we conclude that IVRA for the lower limb can be associated more frequently with a shorter duration of successful anaesthesia and/or failure.

[Diagnosis, prevention and treatment of postoperative reflux gastritis]. / Diagnostika, profilaktika i lechenie posleoperatsionnogo refliuks-gastrita.

Postoperative reflux gastritis in persons who were operated on for peptic ulcer occurs much more frequently after resection of the stomach (68.6%) than after organ-preserving operations on the stomach (39.4%). The incidence of reflux gastritis after gastric resection depends on the type of gastroenteroanastomosis. It is encountered much less frequently after Roux' operation (9.2%). The pronounced character and frequency of reflux gastritis after organ-preserving operations on the stomach are determined by the type of stomach-draining operations, the localization of the ulcer before the operation, whether in the stomach or the duodenum, the existence of duodenogastric reflux (DGR) before the operation. Measures for the prevention of postoperative reflux gastritis in the management of peptic ulcer are as follows: (a) wide introduction of organ-preserving operations, preferably SPV by itself or in combination with duodenoplasty; (b) formation of Roux' gastroenteroanastomosis when resection of the stomach is indicated. Reflux gastritis must be treated by nonoperative methods, including medicinal, dietetic, and spa therapy. Surgery is indicated in reflux gastritis combined with other diseases of a stomach which had been operated on, for which an operation is necessary, and in occasional cases of erosive reflux gastritis.

131I-rose bengal therapy in hepatoblastoma patients.

If conventional treatment modalities have failed in hepatoblastoma patients and no distant metastases can be demonstrated therapy with radionuclide agents can be considered. In 6 patients diagnostic technetium-99m (99mTc)-disofenin and two iodine-131 (131I)-rose bengal scans were made. 2 patients demonstrated specific uptake of disofenin. One of these had a positive scintigram with radiolabelled rose bengal. This patient was subsequently treated with 1.1 GBq 131I-rose bengal. No toxicity was observed. A clear decrease in the level of alpha-fetoprotein indicated a response and demonstrated that this radiopharmaceutical can be used for tumour targeted radiation therapy in selected patients with therapy resistant tumours.

Food-stimulated cholescintigraphy as a supplement to ERC in patients with suspected bile flow obstruction. A preliminary study.

Cholescintigraphy after food stimulation was carried out in 40 patients (13 patients with biliary enteric bypass, 14 patients with bile duct stenosis, demonstrated by ERC, 5 patients with endoprothesis and 8 patients with clinically suspected post-cholecystectomy syndrome. Biliary-bowel transit time of one hour or less was considered to be normal. In patients with biliary enteric bypass 11 had a normal transit time; however, one with a concomitant anastomotic leakage, and 2 patients had prolonged transit time and a significant obstruction by the anastomosis. All 14 patients with demonstrated biliary stricture had normal transit time. In 5 patients with endoprothesis, 2 had prolonged transit time in spite of patent endoprothesis. Finally, in the 8 patients with suspected post-cholecystectomy syndrome, 4 had normal sphincter of Oddi manometry and normal transit time, and 4 had abnormal sphincter of Oddi manometry, but only one with prolonged transit time. It is concluded that in patients with biliary enteric bypass (hepatico-jejunostomia) or biliary strictures a biliary-bowel transit time of one hour will be discriminatory between normal and abnormal conditions. This is in contrast to patients with endoprothesis and suspected sphincter of Oddi dysmotility, where a transit time of one hour only will have limited predictive value.

Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans.

The present study was undertaken to investigate the gastric and intestinal phase of stimulation of postprandial gallbladder contraction and endogenous cholecystokinin secretion in patients with truncal vagotomy and pyloroplasty. Gallbladder emptying, measured by cholescintigraphy, and endogenous cholecystokinin secretion, measured by radioimmunoassay, were studied after both intragastric and intraduodenal administration of corn oil. In addition, the gallbladder responsiveness to cholecystokinin was investigated by infusion of stepwise increasing doses of exogenous cholecystokinin. In the 6 patients with truncal vagotomy, plasma CCK and gallbladder responses to intraduodenal fat were significantly delayed compared to normal subjects. In contrast, the onset of the plasma cholecystokinin increase and gallbladder emptying after intragastric fat was significantly earlier in the vagotomized patients compared with the normal subjects. In the normal subjects, plasma cholecystokinin and gallbladder responses to intragastric fat were significantly lower during the first 25 min after stimulation compared with the results after intraduodenal fat, whereas in the patients with truncal vagotomy and pyloroplasty, no differences in plasma cholecystokinin and gallbladder responses were found according to the site of fat stimulation. The gallbladder-emptying response to exogenous cholecystokinin increased significantly in patients who had undergone truncal vagotomy. It is concluded (a) that truncal vagotomy with pyloroplasty influences the timing but not the magnitude of fat-stimulated gallbladder contraction and endogenous cholecystokinin secretion; and (b) that the sensitivity of the gallbladder to endogenous and exogenous cholecystokinin is significantly increased in patients with truncal vagotomy.

Fungitoxic effects of nonprotein imino acids on growth of saprophytic fungi isolated from the leaf surface of Calliandra haematocephala.

Four saprophytic and pathogenic fungi were isolated from the leaf surface of Calliandra haematocephala, a tropical legume known to contain large amounts of rare nonprotein imino acids in its leaves and seeds. The fungi Aspergillus niger, Aspergillus sp., Curvularia sp., and Penicillium sp. were cultured in the laboratory and tested for susceptibility to leaf extracts of the host plant and to proline, pipecolic acid, cis-5-hydroxypipecolic acid, and 2,4-trans-4,5-cis-4,5-dihydroxypipecolic acid. Fungal spore germination and germ tube growth were measured. Aspergillus sp. was inhibited by plant extracts and by pipecolic acid and cis-5-hydroxypipecolic acid. Curvularia sp. growth was stimulated by plant extracts and by pipecolic acid. The other two fungi were unaffected by any of the treatments. The data indicate that imino acids may play a role in the specific resistance of Calliandra spp. to Aspergillus sp.