Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomized trial.

Objectives: To compare the efficacy and safety of indinavir 800 mg three times a day, ritonavir 600 mg twice a day, and a combination of ritonavir 400 mg twice a day and saquinavir 400 mg twice a day, when administered with two nucleoside analogues.

Design: A randomized, open-labelled, controlled trial. Two hundred and eighty-four patients started randomized treatment.

Metal-Free Haloperoxidases: Fact or Artifact?

Lipases can catalyze halogenations (see scheme for an example) under the same experimental conditions as "metal-free haloperoxidases". This activity should, therefore, not be attributed to a new unique class of enzymes, or even to metal-free haloperoxidases, but should rather be regarded as a side activity of well-known hydrolases.

Changes in use of antiretroviral therapy in regions of Europe over time. EuroSIDA Study Group.

Objectives: To analyse use of antiretroviral therapy within Europe between 1994 and 1997.

Design: From September 1994, the EuroSIDA study (cohorts I-III) has prospectively followed unselected HIV-infected patients from 50 clinical centres in 17 European countries (total, 7230).

Methods: Patients under follow-up at half-year intervals from September 1994 (n=2871) to September 1997 (n=3682) were classified according to number of drugs currently used (none, one, two, three, four or more).

Effect of mutations in Candida antarctica B lipase.

Three variants of the Candida antarctica B lipase have been constructed and characterized. The variant containing the T103G mutation, which introduces the consensus sequence G-X-S-X-G found in most other known lipases, shows an increased thermostability but retains only half the specific activity of the native enzyme. Also in ester synthesis the activity is lowered but the specificity and enantioselectivity remains unchanged.

Stimulation by hexose esters of lactate production by rat erythrocytes: insensitivity to 3-O-methyl-D-glucose and inhibition by 2-deoxy-D-glucose and its tetraacetic ester.

Selected esters of D-glucose were recently proposed as tools to provide the sugar to cells, whilst bypassing the carrier system for hexose transport across the plasma membrane. In the present study, alpha-D-glucose pentaacetate, beta-D-glucose pentaacetate, alpha-D-mannose pentaacetate and, to a lesser extent, 6-O-acetyl-D-glucose, all tested at a 1.7 mM concentration, were found to increase lactate production above basal value in rat erythrocytes.

Insulinotropic action of 6-O-acyl-D-glucose esters.

Several 6-O-acyl-D-glucose esters were examined for their possible insulinotropic action in rats islets incubated for 90 minutes in the absence or presence of either D-glucose or L-leucine. As a rule, 6-O-acetyl-D-glucose and either medium- and long-chain acyl-D-glucose esters only exerted modest effects upon insulin release, much less pronounced than those previously recorded with hexose pentaacetate esters. Nevertheless, under suitable experimental conditions, 6-O-octanoyl-D-glucose and 6-O-decanoyl-D-glucose significantly augmented insulin output, suggesting that such esters could be used, instead of D-glucose itself, as cell nutrients.

Insulinotropic action of alpha-D-glucose pentaacetate: functional aspects.

The functional determinants of the insulinotropic action of alpha-D-glucose pentaacetate were investigated in rat pancreatic islets. The ester mimicked the effect of nutrient secretagogues by recruiting individual B cells into an active secretory state, stimulating proinsulin biosynthesis, inhibiting 86Rb outflow, and augmenting 45Ca efflux from prelabeled islets. The secretory response to the ester was suppressed in the absence of Ca2+ and potentiated by theophylline or cytochalasin B.

Cationic and secretory effects of 6-O-acetyl-D-glucose in rat pancreatic islets.

Selected esters of D-glucose were recently proposed as tools to supply the sugar to cells affected by a defect in the carrier-mediated process of hexose transport across the plasma membrane. The present study extends this knowledge to 6-O-acetyl-D-glucose. At a 2.

Stimulation of insulin release by alpha-D-glucose pentaacetate.

Insulin release from rat pancreatic islets was stimulated by alpha-D-glucose pentaacetate (1.7 mM), but not by an equimolar concentration of beta-D-galactose pentaacetate. The secretory response to alpha-D-glucose pentaacetate was not reproduced by D-glucose and/or acetate, tested at concentrations equimolar to that of the hexose ester, and failed to be adversely affected by 3-O-methyl-D-glucose, even when used at a concentration sufficient to inhibit glucose-stimulated insulin release.

Glucagon-like peptide-1(7-37) has a larger volume of distribution than glucagon-like peptide-1(7-36)amide in dogs and is degraded more quickly in vitro by dog plasma.

The pharmacokinetic properties of glucagon-like peptide-1(7-36)amide (GLP-1(7-37) were compared. Four beagle dogs received on 4 separate occasions s.c.

Comparison of sandwich enzyme-linked immunoadsorbent assay and radioimmunoassay for determination of exogenous glucagon-like peptide-1(7-36)amide in plasma.

A sensitive sandwich enzyme-linked immunoadsorbent assay (ELISA) for determination of exogenous glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) in plasma samples from pharmacokinetic studies is described. The assay employs an N-terminally directed antibody and a C-terminally directed antibody. The ELISA has a working range from 10 to 500 pmol l-1, and can be applied to plasma samples from humans, dogs, pigs, minipigs, cats, rabbits, and rats.

Glucagon and glucagon-like peptide 1: selective receptor recognition via distinct peptide epitopes.

Glucagon and glucagon-like peptide 1 (GLP-1) are homologous peptide hormones that are recognized by likewise homologous, but highly selective receptors. Analogs of glucagon and GLP-1, in which the divergent residues were systematically exchanged, were employed to identify the structural requirements for their selective receptor recognition. Substitutions in the NH2-terminal part of the glucagon molecule with the corresponding GLP-1 residues, as for example in [Ala2,Glu3]-glucagon and [Val10,Ser12]glucagon, reduced the binding affinity for the glucagon receptor several hundred-fold without increasing the affinity for the GLP-1 receptor.

Structure-activity studies of glucagon-like peptide-1.

A series of analogs of glucagon-like peptide-1 (GLP-1) was made replacing each amino acid with L-alanine to identify side-chain functional groups required for interaction with the GLP-1 receptor. In the case of L-alanine being the parent amino acid, substitution was made with the amino acid found in the corresponding position in glucagon. Binding assays were performed using the cloned rat GLP-1 receptor, and receptor activation was monitored using RIN 2A18 plasma membranes.

Using capillary electrophoresis in the optimization of a carboxypeptidase Y catalyzed transpeptidation reaction.

A peptide amide, R-Arg-NH2, was produced by carboxypeptidase Y (CPDY)-catalyzed transpeptidation of a peptide, R-Ala-OH in presence of a large excess of Arg-NH2. Baseline separation of R-Ala-OH and R-Arg-NH2 was achieved by free solution capillary electrophoresis (CE) analysis. With CE the reactions could be closely followed with an analysis frequency of 3-6 h-1.

Sonographic features of xanthogranulomatous pyelonephritis.

The ultrasonic findings of three patients with surgically confirmed xanthogranulomatous pyelonephritis are presented. All of the involved kidneys were markedly enlarged, had a large central echogenic area, and demonstrated an increased parenchymal anechoic pattern. The appearance correlated well with the other radiographic and gross pathologic findings.

Posterior fossa intra-axial tumors: a comparison of computed tomography with other imaging methods.

Fifty patients with posterior fossa intra-axial tumors were evaluated by computed tomography and the results compared with routine skull films, radionuclide brain scanning vertebral angiography, and cerebral air studies. The routine skull series was found to be of little benefit. Computed tomography was more sensitive than the radionuclide brain scan in detecting all of the lesions except astrocytoma, for which sensitivity was comparable.

Imaging the bowel with technetium--an aid in gallium studies.

Three cases are present to demonstrate the usefulness of oral or rectal technetium-99m preparations in locating the stomach and bowel in relation to abnormal accumulation of gallium-67 within the abdomen. In this way, the concentration of gallium in an abscess or a tumor may be distinguished from its physiologic excretion into the bowel.

A simplified approach to radionuclide venography: concise communication.

A simplified method has been developed for performing radionuclide venography. The method makes use of the scintillation camera and a synchronized whole-body scanning bed. This technique permits a more integrated presentation of the data and is performed in conjunction with a standard ventilation-perfusion lung study.