PubMed Health⌕ Search

Biomedical subjects

S Conde

Publications and source records attributed to S Conde.

18 recordsLinked to original sources

Towards single screening tests for brucellosis.

This paper describes an indirect enzyme-linked immunosorbent assay (I-ELISA) and a fluorescence polarisation assay (FPA), each capable of detecting antibody in several species of hosts to smooth and rough members of the genus Brucella. The I-ELISA uses a mixture of smooth lipopolysaccharide (SLPS) and rough lipopolysaccharide (RLPS) as the antigen, and a recombinant protein A/G conjugated with horseradish peroxidase as the detection reagent. When using individually determined cutoff values, the SLPS/RLPS combined-antigen I-ELISA detected antibody in slightly more animals exposed to SLPS or to RLPS than did I-ELISA procedures using each individual antigen separately. Similarly, the assay using combined antigens detected antibody in slightly fewer animals not exposed to Brucella sp. When a universal cutoff of 10% positivity was used (relative to strongly positive control sera of each species), the overall performance index (percentage sensitivity plus percentage specificity) value decreased by 1.0 (from 199.4 to 198.4). In the FPA, it was not possible to use a universal cutoff without significant loss of performance. The overall sensitivity value for the FPA using the combined FPA antigen was 1.0% lower than using the O-polysaccharide (OPS) from SLPS and 9.1% higher than using the core antigen (CORE) from RLPS. When the combined antigen was used, the FPA specificity was slightly higher (1.2%) than from only the OPS, and considerably higher (12.6%) than the CORE. Overall, both the I-ELISA and the FPA with combined antigens were suitable as screening tests for all species of Brucella in the animal species tested.

Animal Diseases↗

Enzyme immunoassay for the diagnosis of brucellosis: chimeric Protein A-Protein G as a common enzyme labeled detection reagent for sera for different animal species.

A recombinant protein combining the immunoglobulin binding sites of Proteins A and G, conjugated with horseradish peroxidase was used as a universal detection reagent for the assessment of antibodies against Brucella spp. The reagent was applied in an indirect enzyme immunoassay for detection of antibodies to smooth lipopolysaccharide antigen in sera from Brucella spp. exposed and non-exposed cattle, sheep, goats and pigs and to antibodies to rough lipopolysaccharide in sheep, dogs and cattle. The results were similar to those obtained when murine monoclonal antibody-enzyme conjugates were used. An added advantage was that a universal cut-off for all tests using the proteins A and G detection reagent could be established, simplifying diagnostic interpretation of the data.

Animals↗

Rough lipopolysaccharide of Brucella abortus RB51 as a common antigen for serological detection of B. ovis, B. canis, and B. abortus RB51 exposure using indirect enzyme immunoassay and fluorescence polarization assay.

Rough lipopolysaccharide (RLPS) antigens were prepared from cultures of Brucella abortus RB51, B. ovis, and B. canis. The preparations were standardized by weight and tested with sera from cattle immunized with B. abortus RB51, sheep infected with B. ovis, and dogs infected with B. canis. Populations of unexposed animals of each species were also tested. The tests used were the indirect enzyme immunoassay (IELISA) using RLPS and the fluorescence polarization assay (FPA) using RLPS core fractions, labeled with fluorescein isothiocyanate. The IELISA using B. abortus RB51 RLPS antigen resulted in sensitivity and specificity values of 94.8% and 97.3%, respectively, when testing bovine sera, 98.5% and 97.8% when testing ovine sera, and 95.8% and 100% when testing dog sera. The IELISA using B. ovis RLPS antigen gave sensitivity and specificity values of 80.5% and 91.7%, respectively with bovine sera, 98.9% and 93.8% with sheep sera, and 70.8% and 79.8% with dog sera. The IELISA using B. canis RLPS antigen resulted in sensitivity and specificity values of 97.0% and 97.4%, respectively, with bovine sera, 96.2% and 96.3% with sheep sera, and 95.8% and 98.8% with dog sera. Labeling RLPS core from B. ovis and B. canis with fluorescein was not successful. B. abortus RB51 core labeled with fluorescein resulted in sensitivity and specificity values of 93.5% and 99.8%, respectively, with bovine sera and 78.1% and 99.0% with sheep sera. It was not possible to test the dog sera in the FPA.

Animals↗

A prospective study of gemcitabine and carboplatin as first-line therapy in advanced non-small cell lung cancer: toxicity of a three- versus a four-week schedule.

We evaluated the toxicity and activity of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and carboplatin on a 3-week (trial A) versus a 4-week (trial B) schedule in patients with advanced/metastatic non-small cell lung cancer. Chemotherapy-naive patients in trial A received gemcitabine 1,000 mg/m(2) on days 1 and 8 plus carboplatin area under the curve of 5 on day 1, every 3 weeks. In trial B, patients received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and carboplatin area under the curve of 6 on day 1, every 4 weeks. Thirty patients were enrolled in trial A and 28 in trial B. Patients received a total of 142 cycles in trial A and 134 in trial B. Despite more frequent treatment delays (82 cycles in trial B and 20 cycles in trial A), and dose reductions/omissions (mainly on day 15), gemcitabine mean dose intensities of both schedules were similar. The principal dose-limiting toxicity was grade 3/4 thrombocytopenia. Objective response rates were 40% in trial A and 68% in trial B (no complete response). Gemcitabine and carboplatin administered on days 1 and 8 every 3 weeks is associated with lower myelotoxicity than that of a 4-week schedule, although both schedules were active against non-small cell lung cancer. Semin Oncol 28 (suppl 10):10-14.

Adult↗

N-Benzylpiperidine derivatives of 1,2,4-thiadiazolidinone as new acetylcholinesterase inhibitors.

A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzylpiperidine fragment has been synthesised. The acetylcholinesterase (AChE) inhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 13 was as active as tacrine in reversing the blockade induced by tubocurarine at rat neuromuscular junction. Additionally, receptor binding studies provided new lead compounds for further development of alpha2-adrenergic and sigma-receptor antagonists. Molecular dynamic simulation using X-ray crystal structure of AChE from Torpedo californica was used to explain the possible binding mode of these new compounds.

Acetylcholinesterase↗

Lipase-catalysed synthesis of new acetylcholinesterase inhibitors: N-benzylpiperidine aminoacid derivatives.

New acetylcholinesterase inhibitors were synthetized via a lipase-mediated regioselective amidation using Candida antarctica lipase B as a biocatalyst in the key step. The new compounds have two different structural fragments: a N-benzylpiperidine moiety to anchor the enzyme active site and a dicarboxylic aminoacid to act as a biological carrier. Some analogues of N-benzylpiperazine were also synthesised and studied but they did not display AChE inhibitor activity. A preliminary structure activity relationship study was performed employing some computational techniques as similarity indices and electrostatic potential maps.

Acetylcholinesterase↗

Thienothiadiazine 2,2-dioxide acyclonucleosides: synthesis and antiviral activity.

The synthesis of acyclonucleosides derived from thieno[3,2-c] and thieno[2,3-c][1,2,6]thiadiazine 2,2-dioxides was achieved following the silylation method. Lipase-mediated methodology was employed for deprotection of the acyclic moieties. The antiviral effects were determined against a broad spectrum of viruses, including cytomegalovirus (CMV) and varicella zoster virus (VZV). Only minor antiviral activity against VZV was observed for those acyclonucleosides carrying a benzyl group.

Antiviral Agents↗

Novel potential agents for human cytomegalovirus infection: synthesis and antiviral activity evaluation of benzothiadiazine dioxide acyclonucleosides.

The first acyclonucleosides based on the benzothiadiazine dioxide system were synthesized following the silylation procedure. Several acyclic moieties, including acetoxyethoxymethyl, benzyloxymethyl, and propargyloxymethyl groups, were introduced. Two synthetic strategies were designed to selectively obtain the N-1 or N-3 derivatives. Lipase-mediated deacylation was used for the deprotection of the acyclonucleosides. Some of the benzothiadiazine dioxide acyclonucleosides, in particular 16, proved active against human cytomegalovirus (CMV) at concentrations slightly higher than that found for ganciclovir [50% inhibitory concentration (IC50) = 3. 5-3.7 micrograms/mL, cytotoxicity (CC50) >/= 40 micrograms/mL, MCC = 20 micrograms/mL]. Additionally, compound 16 inhibited the replication of human immunodeficiency virus type 1 (HIV-1) and HIV-2 in CEM cells at concentrations that were 5-fold lower than its cytotoxic concentration.

Anti-HIV Agents↗

Detection of Lassa virus antinucleoprotein immunoglobulin G (IgG) and IgM antibodies by a simple recombinant immunoblot assay for field use.

The nucleoprotein of Lassa virus, strain Josiah, was expressed in Escherichia coli as an N-terminally truncated, histidine-tagged recombinant protein. Following affinity purification the protein was completely denatured and spotted onto nitrocellulose membrane. A total of 1 microgram of protein was applied for detection of Lassa virus antibodies (LVA) in a simple immunoblot assay. Specific anti-Lassa immunoglobulin M (IgM) antibodies could be detected by increasing the amount of protein to 5 microgram. A panel of 913 serum specimens from regions in which Lassa virus was endemic and from regions in which Lassa virus was not endemic was used for evaluating the sensitivity and specificity of the LVA immunoblot in comparison to those of an indirect immunofluorescence (IIF) assay. The sera originated from field studies conducted in the Republic of Guinea (570 serum samples) and Liberia (99 serum samples), from inpatients of the clinical department of the Bernhard-Nocht-Institute, Hamburg, Germany (94 serum samples), and from healthy German blood donors (150 serum samples). In comparison to the IIF assay the LVA immunoblot assay had a specificity of 90.0 to 99.3%, depending on the origin of the specimens. The sensitivity was found to be highest for the Guinean samples (90.7%) and was lower for the Liberian samples (75%). Acute Lassa fever was diagnosed by PCR in 12 of 59 (20.3%) patients with fever of unknown origin (FUO) from the Republic of Guinea. On admission to the hospital, nine Lassa fever patients (75%) were reactive by the IgM immunoblot assay. One of the patients was infected with a new Lassa variant, which showed 10.4% variation on the amino acid level in comparison to the prototype strain of Lassa virus, Josiah. Seven PCR-negative patients were reactive by immunoblotting. The positive and negative predictive values of a single IgM immunoblot result for acute, PCR-confirmed Lassa fever were therefore 53.6 and 93.0%, respectively. Because of its high negative predictive value, a single IgM immunoblot result will be valuable for excluding acute Lassa fever for cases of FUO in areas where Lassa fever is endemic.

Amino Acid Sequence↗

Selective carriers of norepinephrine and ammonium ions: ionophoric properties and molecular modelling studies of diester crown compounds containing a 1,3-bis(1H-pyrazol-1-yl)propane unit.

Ionophoric properties of dipyrazolic crowns and podands containing a 1,3-bis(1H-pyrazol-1-yl)propane unit in their structure are described. They show selectivity of ammonium vs alkali cations and interesting norepinephrine transport rates. A molecular modelling study has been used to elucidate the superstructures of the crown and ammonium cation complexes.

Esters↗

[Comparison of the effect of amisulpride and viloxazine in the treatment of dysthymia].

An evaluation of the therapeutic efficacy of Amisulpride as compared with Viloxazine in a group of patients diagnosed as dysthymic, according to the DSM-III-R criteria is presented. Study was a double-blind, randomized controlled trial: Subjects were assessed during an initial examination with informed consent, then entering a 4-week treatment trial. The Hamilton Depression Scale, the Widlocher Psychomotor Retardation Scale, and the Andreasen Negative Symptoms Scale were used for evaluating cases. Both the efficacy and safety of drugs were assessed. An analysis of results suggests a better therapeutic response among the Amisulpride group subjects.

Adolescent↗

Effects of thiophene analogues of chloroamphetamines on central serotonergic mechanisms.

Ring-chlorinated thienylisopropylamines, thiophene analogues of chloroamphetamines, have been synthesized and their effects on serotonergic mechanisms in the rat brain have been evaluated. With 4,5-dichlorothienylisopropylamine (3e), a pharmacological profile similar to that of p-chloroamphetamine, consisting in a marked and long-lasting serotonin depletion and a rather strong and prolonged inhibition of synaptosomal uptake of serotonin, was found. Chloro substitution in position C3 of the thiophene ring did not determine brain serotonin depletion nor serotonin uptake inhibition but enhanced brain MAO inhibitory activity present in all these compounds. 3,5-Dichlorothienylisopropylamine (3g) was the only compound of the series in which the inhibition of serotonin uptake was more marked than the serotonin depleting property.

Amphetamines↗

beta-Adrenoceptor blocking activity of halogenated thienylethanolamine derivatives.

The synthesis of a number of ring-halogenated N-isopropyl- and N-tert-butyl-2-amino-1-(2-thienyl)ethanols has been carried out in order to ascertain the influence of chloro or bromo substitution at the thiophene moiety on their blocking beta-adrenoceptor activity. It was found that chloro- and bromo-substituted compounds exhibited a similar activity. Monohalo substitution at positions C4 or C5 of the thiophene ring resulted in comparable blocking potency, whereas C3 halo-substituted compounds were practically devoid of activity. The highest activity in these series was observed with compounds dihalogenated at C4 and C5, their effect on myocardial beta-receptors being comparable to that of propranolol.

Adrenergic beta-Antagonists↗

[Lung cancer and women].

The epidemiology of lung cancer has changed in the last years in several countries all over the world. In the 19th century, the lung cancer was rare but it incidence increase drastically during the 20th century, and the tendency is to continue in the 20th century. Actually the lung cancer's incidence and mortality are higher in the developed countries, especially in Europe and Unites States of America, with a increasing in the women incidence. These geographic differences and gender differences are related with smoking habits. Women begin to smoke earlier and have more difficulty to stop, because of problems related with obesity; they have more sensibility to the carcinogens and the risk of lung cancer is 1.5 times higher than the men with the same habits. Adenocarcinoma is the more frequent histological type in young people, in the total of the women and in non-smokers. Many factors since tobacco, home and professional pollution, nutritional, associated diseases even genetic and hormonal factors have been investigated to define its influence in development in women lung cancer. It specificity in women with lung cancer is the common problem for the medical people to treat this disease (pathology).The literature about this problem is not clear, and is necessary to advance with many studies in this area with the objective to clarify this important question.

Air Pollution, Indoor↗