Digital multi-filter auditory prosthesis: study of its efficiency in function of number of filters and their programming

A new method to determine a rate constant and total reaction product using data of reaction product kinetics is proposed. The method is based on the solution of the system of irrational equations (for special case), which describes such processes. This method was used to determine the reaction rate constant of interaction of some monoclonal antibodies with the antigens immobilized on immunological plates.     

Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.     

Synaptosomal binding of 125I-labelled daboiatoxin, a new PLA2 neurotoxin from the venom of Daboia russelli siamensis

Daboiatoxin (DbTx), the PLA2 neurotoxin from Daboia russelli siamensis venom, was shown to bind specifically and saturably to rat cerebrocortical synaptosomes and synaptic membrane fragments. Two families of binding sites were detected by equilibrium binding analysis in the presence and absence of Ca2+. Scatchard analysis of biphasic plateaus revealed Kdl 5 nM and Bmax1, 6 pmoles/mg protein, and Kd2 80 nM and Bmax2 20 pmoles/mg protein, respectively, for the high- and low-affinity binding sites. The binding of 125I-DbTx to synaptosomes did not show marked dependence on Ca2+, Mg2+, Co2+ and Sr2+. Native DbTx was the only strong competitor to 125I-DbTx synaptosomal binding (IC50 12.5 nM, KI 5.5 nM). Two other crotalid PLA2 neurotoxins, crotoxin CB and mojave toxin basic subunit, and nontoxic C. Atrox PLA2 enzyme, were relatively weaker inhibitors, while two viperid PLA2 neurotoxins, ammodytoxin A and VRV PL V, were very weak inhibitors. Crotoxin CA was a poor inhibitor even at microM concentrations, whereas no inhibitory effect at all was observed with crotoxin CACB, ammodytoxin C, VRV PL VIIIa, taipoxin, beta-bungarotoxin, or with PLA2 enzymes from N. naja venom, E. schistosa venom, bee venom and porcine pancreas. All other pharmacologically active ligands examined (epinephrine, norepinephrine, histamine, choline, dopamine, serotonin, GABA, naloxone, WB-4101, atropine, hexamethonium and alpha-bun-garotoxin) also failed to interfere with 125I-DbTx binding. As those competitors that showed partial inhibition were effective only at microM concentration range compared to the Kd (5 nM) of 125I-DbTx synaptosomal binding, DbTx could well recognize a different neuronal binding site. Rabbit anti-DbTx polyclonal antisera completely blocked the specific binding. When a range of Ca2+ and K+ channels modulators were examined, Ca2+ channel blockers (omega-conotoxins GVIA and MVIIC, taicatoxin, calciseptine and nitrendiprene) did not affect the binding even at high concentrations, while charybdotoxin was the only K+ channel effector that could partially displace 125I-DbTx synaptosomal binding amongst the K+ channel blockers tested (apamin, dendrotoxin-I, iberiotoxin, MCD-peptide, 4-aminopyridine and tetraethylammonium), suggesting that neither K+ nor Ca2+ channels are associated with DbTx binding sites.     

Raltitrexed (Tomudex): an alternative drug for patients with colorectal cancer and 5-fluorouracil associated cardiotoxicity

Two patients with proven 5-fluorouracil (5-FU)-associated cardiotoxicity were treated with the specific thymidylate synthase inhibitor raltitrexed safely, without evidence of cardiotoxicity. Raltitrexed might be an alternative for patients with advanced colorectal cancer and 5-FU-associated cardiotoxicity. 5-FU cardiotoxicity is not due to the antineoplastic mechanisms via thymidilate synthase.     

Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1

The sphingolipid metabolite sphingosine-1-phosphate (SPP) has been implicated as a second messenger in cell proliferation and survival. However, many of its biological effects are due to binding to unidentified receptors on the cell surface. SPP activated the heterotrimeric guanine nucleotide binding protein (G protein)-coupled orphan receptor EDG-1, originally cloned as Endothelial Differentiation Gene-1. EDG-1 bound SPP with high affinity (dissociation constant = 8.1 nM) and high specificity. Overexpression of EDG-1 induced exaggerated cell-cell aggregation, enhanced expression of cadherins, and formation of well-developed adherens junctions in a manner dependent on SPP and the small guanine nucleotide binding protein Rho.     

The sequential metabolic and histological changes occurring in dog leg muscles as a consequence of ischemia (author's transl)

The present study was undertaken to investigate the sequential metabolic and histological changes occurring in dog leg muscles as a consequence of ischemia. The left hind limbs of 45 dogs were amputated at the middle of their thighs and after preserving them in ice water and room temperature for 6 and 12 hours, re-circulation was established. Observation was undertaken on 1) activity of muscle enzymes-CPK, GOT-m, and LDH in the venous blood from the re-circulated limbs, and 2) histological changes of muscles through light microscopy and electron microscopy. Leakage of muscle enzymes into the serum was little in the group preserved in ice water for 6 hours, but resulted in a marked increase in the group preserved in room temperature for 6 hours and 12 hours ischemic groups. This remarkable leakage of muscle enzymes seems to reflect the amount of muscle degeneration. Histologically prominent changes of muscles were characterized by cell swelling and separation of sarcoplasma from endomysium through light microscopic study, and by widening of myofibril space, virtual absence of glycogen granules in sarcoplasma, swelling of mitochondria and appearance of intramitochondrial dense body through electron microscopic study. These histological changes of muscles are well correlated with the leakage of muscle enzymes and demonstrated some extent of irreversible changes had developed already, even in the group preserved in ice water for 6 hours.     

Automated urinary steroid profiles by capillary column gas-liquid chromatography and a computing integrator

13 Urinary steroid metabolites have been determined by automated gas-liquid chromatography with a 20-m glass capillary column and a computing integrator. Concentrations up to 2 mg/24 h computed by the integrator compare well with those obtained by peak height measurements. At higher concentrations discrepancies occurred, paticularly for the C21 steroids where falsely low values were calculated using peak heights. Mean excretion by healthy males and females of seven steroid metabolities is presented.