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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 253 records · Page 14Linked to original sources
PubMed1994

Serodiagnosis of Helicobacter pylori: evaluation of a rapid, miniaturized immunochromatographic test.

Diagnosis and successful eradication of Helicobacter pylori infection has been shown to be significantly related to symptom improvement in patients affected by chronic gastritis, duodenal and gastric ulcer. There is, therefore, an increasing need for the development of new, easy to use, reliable and non-invasive techniques to detect this organism. One such test is Flex-Sure (SmithKline Diagnostics Inc., United States), a new, rapid immunochromatographic test which requires a drop of the patient's serum to be placed on the absorbent pad of a strip. If specific antibodies to H. pylori are present a red colour line appears. The present study compared Flex-Sure with a homologous quantitative immunoenzymatic test (HM-CAP, EPI, US) using the same antigen (high molecular weight protein), the second generation GAP test (Bio-Rad, USA), a rapid urease test, culture and histology in a cohort of dyspeptic patients. We produced a semiquantitative visual scale with which to perform this comparison. Our results show that Flex-Sure possesses a sensitivity of 96.1%, a specificity of 73.9%, an overall accuracy of 78.8%, a positive predictive value of 72% and a negative predictive value of 91.6%. It showed a highly significant correlation with histological and cultural results (P < 0.001), and with the other serological tests (P < 0.0001). Based on our data we conclude that Flex-Sure may yield quick (within 4 min), simply readable, qualitative, and according to our colourimetric scale, even semiquantitative results. Furthermore, it does not require any sample dilution, any particular equipment, or any specialized training for the operator.

Adolescent↗
PubMed1994

Interleukin-1 beta and interleukin-6 stimulate neurohypophysial hormone release in vitro.

Interleukin-1 (IL-1) and interleukin-6 (IL-6) have been reported to stimulate the release of corticotrophin-releasing hormone (CRH) in vitro, the response being antagonized by the cyclo-oxygenase inhibitor, indomethacin. The effects of cytokines on the other major ACTH-releasing hormone, vasopressin (AVP), and the other neurohypophysial hormone, oxytocin, have been little studied, and the published data are conflicting. We have therefore used a previously validated rat hypothalamic explant model to evaluate whether IL-1 beta and IL-6 can directly activate the AVP and oxytocin neurosecretory system. In addition, we have also investigated the effects of inhibition of cyclo-oxygenase (CO) and lipoxygenase (LO) activities on the stimulated release of AVP and oxytocin by means of a series of antagonists, including a specific LO pathway inhibitor. The static rat hypothalamic incubation system used involves fresh hypothalamic explants with consecutive 20-min incubations, and estimation of AVP and oxytocin concentrations in the medium by specific and sensitive radioimmunoassays. It was found that IL-1 beta produced a dose-dependent increase in the release of AVP and oxytocin at doses of 10 and 100 U/ml (P < 0.005). Only at the higher dose of 100 U/ml was IL-6 able to increase significantly AVP and oxytocin release (P < 0.05). These stimulatory effects of IL-1 beta and IL-6 were blocked by cyclo-oxygenase inhibitors, indomethacin (28 microM) and ibuprofen (100 nM), but not by the lipoxygenase inhibitor, BW A4C (10 micrograms/ml), suggesting that prostaglandins are involved in this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Endothelin-1 stimulates the in vitro release of neurohypophyseal hormones, but not corticotropin-releasing hormone, via ETA receptors.

The endothelins consist of a family of vasoconstrictor peptides originally isolated from endothelial tissue which are now known to be involved in neuroendocrine regulation. However, while there are data indicating the involvement of endothelins in the modulation of the hypothalamo-pituitary-adrenal (HPA) axis, the precise mechanisms involved have been unclear. We have therefore used a previously validated rat hypothalamic explant system in order to investigate the possible modulation of the neurohypophyseal hormones vasopressin and oxytocin, and corticotropin-releasing hormone (CRH), by endothelin-1 (ET-1) and endothelin-3 (ET-3). Following a period of stabilisation, the release of vasopressin, oxytocin and CRH remained approximately constant in successive 20-min incubations. Addition of ET-1 stimulated the release of vasopressin at a dose of 0.1 nmol/l (p < 0.05), and both vasopressin and oxytocin at 10 nmol/l (p < 0.01 and 0.05, respectively). The release of vasopressin and oxytocin induced by 10 nmol/l ET-1 were both totally blocked by co-incubation with either 1 or 10 mumol/l of the specific ETA receptor subtype antagonist cyclo (D-Trp-D-Asp-Pro-D-Val-Leu) (BQ-123). ET-1 had no effect on CRH release in the dose range of 0.1-1,000 nmol/l. In case any possible stimulation of CRH might be masked by simultaneous generation of nitric oxide (NO), an inhibitor of CRH secretion, addition of ET-1 was also carried out in the presence of the NO synthase inhibitor, L-NO-Arg: ET-1 was again without effect in this dose range.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Cerebrospinal fluid and therapy of isolated angiitis of the central nervous system.

BACKGROUND: Serial cerebral angiograms, computed tomography, and magnetic resonance imaging are among the proposed methods for monitoring disease activity and response to therapy in isolated angiitis of the central nervous system. Cerebrospinal fluid has not proved to be useful in monitoring clinical course. CASE DESCRIPTION: We describe a 45-year-old man with histological diagnosis of isolated angiitis of the central nervous system that was treated with prednisone plus azathioprine and monitored for 2 years. Samples of the cerebrospinal fluid were obtained for cytological and routine chemical examination, as well as albumin and immunoglobulin content. Before treatment, cerebrospinal fluid showed marked plasmatic transudation of albumin and intrathecal synthesis of immunoglobulins. During the first year of immunosuppression no events were noticed, and the previously abnormal aspects of the cerebrospinal fluid showed improvement. During the weaning of azathioprine, a new stroke occurred in conjunction with a marked deterioration of cerebrospinal fluid parameters. Immunosuppression was resumed at previous levels, and during the following year no further events occurred. Once again, abnormal cerebrospinal fluid values improved significantly. CONCLUSIONS: We report a case of isolated angiitis of the central nervous system in which the serial cerebrospinal fluid examinations (albumin and immunoglobulin content) showed a close correlation with clinical course. This method may be useful in monitoring response to therapy.

Albumins↗
PubMed1994

Lipopolysaccharide modulation of eicosanoid and corticotrophin-releasing hormone release from rat hypothalamic explants and astrocyte cultures in vitro: evidence for the involvement of prostaglandin E2 but not prostaglandin F2 alpha and lack of effect of nerve growth factor.

Bacterial lipopolysaccharide (LPS) and prostaglandins (PG) E2 and F2 alpha are putative activators of the hypothalamo-pituitary-adrenal axis. Certain of the biological effects of LPS may be mediated by cytokines such as interleukin-1 beta (IL-1 beta), while IL-1 beta itself may operate via induction of the prostaglandins and/or nerve growth factor (NGF). As IL-1 beta stimulates the release of corticotrophin-releasing hormone (CRH) from acute rat hypothalamic explants directly, the effects of these substances on the release of CRH in vitro were investigated in short- and medium-term (20 and 60 min) incubations. The effect of LPS on the release of PGE2 and PGF2 alpha from these explants, as well as from cortical astrocyte cultures, was also studied. LPS did not modify the release of CRH, PGE2 or PGF2 alpha in 20-min incubations. In 60-min incubations, LPS stimulated the release of PGE2, whereas the release of CRH was weakly, but significantly, reduced; PGF2 alpha was not altered. PGE2 significantly stimulated CRH release in the 60-min but not in the 20-min experiments. This effect appeared to be selective for PGE2, since PGF2 alpha did not modify CRH release, alone or in combination. LPS also selectively released PGE2 but not PGF2 alpha from cortical astrocyte cultures after 24-h incubation. NGF had no effect on the release of explant CRH, regardless of the length of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Biodistribution and pharmacokinetic screening in humans of monoclonal antibody AR-3 as a possible immunoscintigraphy agent in patients with pancreatic cancer.

This pharmacokinetic study was performed in order to assess the potential usefulness of the murine monoclonal antibody (MoAb) AR-3-IgG1 as an immunoscintigraphy agent for pancreatic cancer. This MoAb, which defines a mucin-like antigen (CAR-3) expressed by a large fraction of pancreatic cancers, shows in fact favourable in vivo localizing properties in the experimental animal model of human tumor xenograft. 131I-AR-3-IgG1 was injected i.v. into 5 patients with suspected pancreatic cancer. Whole-body maps and spot views of the abdominal area were recorded with a computerized gamma-camera, and specific regions of interest drawn over the liver and spleen helped to define the kinetics of activity in these organs. Blood samples taken from 0.1-144 hours post-injection and daily urine collections over the same interval served to define the kinetics of plama distribution and removal of activity from the body. Different multicompartmental models were tested to fit the experimental data, assuming as the starting hypothesis that there was to be significant nonspecific tracer accumulation in the liver, spleen and bone marrow, as already observed for the majority of radioiodinated murine MoAbs injected into humans. Surgery confirmed pancreatic cancer in 3 out of the 5 patients (chronic pancreatitis and periampullary cancer in one each); in all these 3 patients immunostaining with the MoAb AR-3 demonstrated the presence of the CAR-3 antigen (with a cytoplasmic and endoluminal/secretory pattern of distribution). Nonspecific radioactivity accumulation in the liver, spleen and bone marrow was extremely low, linked essentially to the blood pool effect of circulating activity in these organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Gastric tuberculosis].

A 37 year old woman with duodenal ulcer not responsive to medical treatment was operated. Antrectomy, truncal vagotomy and Bilroth II gastrojejunostomy were performed. The histopathology revealed epithelioid cell granulomas with multinucleated cells and central ceseation, in the gastric side of the pylorus and in three isolated lymph nodes. With Ziehl-Neelsen staining there were multiple acid-fast bacilli. There was no evidence or previous history, personal or familial, or tuberculosis in an other localization. Epidemiology, pathology, diagnosis, and treatment of gastric tuberculosis are discussed according to the literature.

Adult↗
PubMed1994

Investigation of chloroquine intake in Biombo region, Guinea Bissau.

The use of chloroquine (CQ), during the dry season was determined for 236 patients from 5 villages in Biombo, Republic of Guinea Bissau, West Africa. The antimalarial drug was measured in whole blood (dried samples) using High Performance Liquid Chromatography (HPLC) and in urine samples by Enzyme Linked Immunosorbent Assay (ELISA). The results showed that CQ consumption is low.

Animals↗
PubMed1994

Factors affecting plasma retinol decline during long-term administration of the synthetic retinoid fenretinide in breast cancer patients.

Administration of the synthetic retinoid Fenretinide lowers circulating retinol and may thus affect night vision. We have recently shown that plasma retinol levels below 100 ng/ml are associated with moderate alterations of the dark adaptometry test. To identify which patients are more likely to experience a decrease of plasma retinol under this threshold, we measured plasma levels of retinol, Fenretinide, and its metabolite 4-MPR in a cohort of 28 women receiving Fenretinide at the daily dose of 200 mg and studied their relationship with clinical characteristics such as age, menstrual status, body mass index, and time on treatment. Our results show that patients aged over 55 years with a higher percentage of adipose tissue had higher plasma concentrations of 4-MPR, which turned out to be the major determinant of the retinol decrease. This subgroup may thus deserve careful ophthalmological surveillance.

Adipose Tissue↗
PubMed1994

[The Ellis-Van Creveld syndrome. Apropos 2 clinical cases].

The chondroectodermal dysplasia--Ellis-Van Creveld Syndrome--is an unusual form of congenital disease, genetically transmitted with a recessive autosomal pattern, which involves the skeletal system, nails and teeth. In about 50 to 60 percent of cases, the affected individuals show cardiac abnormalities, and the most common are single atrium, large atrial septal defect, ostium primum type. Other abnormalities may accompany these lesions, such as aortic atresia, hypoplasia of the ascending aorta or of the left ventricle. About half of the patients die in the childhood due to cardiorespiratory complications. Two cases are described with this syndrome, a male and a female, with 54 and 45 years old respectively; they were followed in our Departments and showed congestive heart failure and single atrium. These cases led us to review the subject; we believe that the unusual longevity of these patients can be related to their relatively benign cardiac disease.

Ellis-Van Creveld Syndrome↗
PubMed1993

N-(4-hydroxyphenyl)retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid.

N-(4-Hydroxyphenyl)retinamide (HPR) is a synthetic retinoid of particular clinical interest in cancer chemoprevention. We have examined the in vitro effects of HPR on lymphoid and myeloid malignant cell lines and found that at concentrations between 10(-5) and 3 x 10(-7) M it induces a dose-dependent growth inhibition (the peak plasma concentration in patients treated with HPR is 1 to 2 x 10(-6) M). The antiproliferative effect of HPR was, in all cell lines except K422, more potent than that induced by an equimolar dose of all-trans retinoic acid (RA). Also, this effect was irreversible on HL60 and DoHH2 cells that had been exposed to HPR (3 x 10(-6) M) for 24 h, but reversible on Raji and DHL4 exposed to the retinoid for 48 and 72 h, respectively. Time-course growth analysis showed that HPR at 3 x 10(-6) M or below induces a rapid fall of thymidine uptake and viability (> 90%), whereas between 10(-6) and 3 x 10(-7) M exhibits cytostatic effects. Interestingly, the RA-resistant HL-60R and NB306 cells, characterized by a point mutation in the retinoic acid receptor (RAR) and by the loss of the pml/RAR protein, respectively, were, like the parental RA-inducible HL-60 and NB4 cell lines, fully responsive to HPR, thereby suggesting that HPR and RA could act through different receptors or pathways. DNA flow-cytofluorimetric analysis revealed that HPR does not block cells in a specific phase of the cell cycle but triggers programmed cell death or apoptosis. This phenomenon was evidenced both by the visualization, on gel electrophoresis, of fragmented DNA, and by the "in cell" enzymatic labeling of DNA breaks with fluorescent dUTP. With the latter method, apoptotic cells become detectable by 6 h following exposure to 3 x 10(-6) M HPR. Ultrastructural examination of HPR-treated samples showed cells with chromatin compaction and cytoplasm condensation, characteristic of apoptotic cells. In conclusion, our study demonstrates that HPR suppresses malignant cell growth and induces apoptosis at pharmacologically relevant doses. The differential responsiveness by a number of cell lines, especially HL-60R and NB306, to HPR and RA indicates that these compounds may act through different receptors. The clinical use of HPR, particularly in retinoic acid-unresponsive acute promyelocytic leukemia patients, is suggested.

Apoptosis↗
PubMed1993

Flunarizine as a modulator of doxorubicin resistance in human colon-adenocarcinoma cells.

The potential of the calcium-entry blocker flunarizine in modulating the cytotoxicity of doxorubicin was investigated in human colon-adenocarcinoma cell lines sensitive to (LoVo) or with experimentally induced resistance (LoVo/DX) to doxorubicin. Exposure to 1 to 2 micrograms/ml flunarizine for intervals of up to 24 hr did not affect cell survival in either line. Simultaneous exposure to flunarizine and doxorubicin for 1 hr selectively enhanced doxorubicin activity in the resistant cell line and not in the sensitive cell line. In particular, the doxorubicin concentration able to reduce cell survival by 50% dropped to one third. Moreover, simultaneous exposure to flunarizine significantly increased intracellular doxorubicin accumulation, as evaluated by fluorescence spectrophotometry. Again, flow-cytometric analysis showed hyperpolarization of the membrane in resistant cells, starting from 15 min of exposure to 2 micrograms/ml flunarizine. Finally, in LoVo/DX cells, which normally express gp170, a 24-hr treatment with flunarizine markedly reduced the immunoreactivity of cells with 2 monoclonal antibodies (MAb57 and MRK16) directed against different external epitopes of the glycoprotein. The results from our study indicate the ability of flunarizine to positively modulate doxorubicin-resistance in human colon-adenocarcinoma cells expressing the multidrug-resistance phenotype.

Adenocarcinoma↗
PubMed1993

The synthetic retinoid fenretinide lowers plasma insulin-like growth factor I levels in breast cancer patients.

We studied the effect of fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)], a synthetic analogue of retinoic acid, on plasma insulin-like growth factor I (IGF-I) levels in a consecutive cohort of stage I breast cancer patients belonging to a randomized phase III trial of breast cancer chemoprevention. Thirty-two women receiving 4-HPR 200 mg/daily and 28 untreated controls entered the study. IGF-I levels were determined after acid-ethanol extraction, on plasma obtained at randomization and after a mean time of 10.8 +/- 0.3 months. At baseline, there was no difference in IGF-I levels between the two groups [152.9 +/- 9.4 versus 159.2 +/- 7.0 ng/ml in treated and control group (P = 0.59), respectively]. After follow-up time, while plasma IGF-I levels were unchanged in control patients (163.3 +/- 7.4 ng/ml; P = 0.5), they were significantly reduced to 134.6 +/- 8.1 ng/ml in the patients treated with 4-HPR (P = 0.003 and P = 0.011 versus baseline and control values, respectively). Multiple regression analysis showed that treatment was the only determinant of IGF-I decline. Moreover, the interaction between treatment and age was significant, in that the decrease of IGF-I levels induced by 4-HPR administration was much more pronounced in younger patients, while an age-related decline was observed in controls. We conclude that the synthetic retinoid 4-HPR lowers circulating IGF-I levels in early breast cancer patients. Although the importance of this observation for the clinical prevention of breast cancer remains to be established, it further substantiates the rationale of the combination of 4-HPR with tamoxifen, which is known to decrease IGF-I as well and to act synergistically with the retinoid in preclinical models.

Anticarcinogenic Agents↗