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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 163 records · Page 9Linked to original sources
PubMed1998

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines.

The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+) breast cancer cell lines. We studied and compared the effects of N-(4-hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231) breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced a dose- and time-dependent inhibition of proliferation in both breast cancer cell lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231 cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by 1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%, respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately 20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I binding and Scatchard analysis revealed a decrease of more than 50% in maximum binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately 30% in both tumour cell lines. We conclude that 4-HPR induces a significant down-regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast cancer cell lines. These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR.

Antineoplastic Agents↗
PubMed1998

Tamoxifen reduces plasma homocysteine levels in healthy women.

Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day(-1) or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no contraindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean +/- s.d. plasma levels of tHcy were 7.59 +/- 1.71 micromol l(-1), 7.25 +/- 1.61 and 7.09 +/- 1.33 in the tamoxifen group and 8.07 +/- 2.06, 7.93 +/- 1.77 and 8.12 +/- 2.04 in the placebo group at 0, 2 and 6 months (P = 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day(-1) for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction.

Adult↗
PubMed1998

Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial. Italian Chemoprevention Group.

The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 12-month measurements of total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n = 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL- and HDL-cholesterol of approximately -9%, -19% and +0.2% in continuous HRT users compared with -9%, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

Breast Neoplasms↗
PubMed1998

p53 expression in human carcinomas: could flow cytometry be an alternative to immunohistochemistry?

Several studies have shown that p53 expression has important clinical implications as an indicator of prognosis and response to chemotherapy or radiotherapy in different human tumor types. Determination of p53 expression by immunohistochemistry (IHC) has been incorporated into routine practice and its reliability has been consolidated. However, flow cytometric (FCM) analysis might represent an important objective and rapid approach. In the present study we determined p53 expression by IHC and FCM on a series of 118 human solid tumors. IHC determination was performed on histological sections and FCM analysis on cell suspensions. Low correlation coefficients (rs from 0.22 to 0.57) were observed between IHC and FCM data from individual tumors. By considering the IHC approach as the gold standard, high sensitivity and low specificity were found for FCM in detecting p53 expression. The FCM analysis of p53 expression and DNA content showed p53-positive cells in all cell cycle phases. Moreover, in most breast, lung, and colon aneuploid tumors (77%), p53-positive cells were detected only in the subpopulations with abnormal DNA content. In conclusion, FCM-p53 expression cannot be used alternatively to IHC determination, and its clinical relevance remains to be validated. Nevertheless, FCM may provide important information about p53 protein expression in the different subpopulations and cell cycle phases. (J Histochem Cytochem 46:41-47, 1998)

Aneuploidy↗
PubMed1998

Headache coding and diagnostic-related groups: a survey of one year's admissions to a neurological department.

In 1995, the introduction of Diagnostic Related Groups (DRGs) within the Italian National Health Service (NHS) significantly changed the mode of payment for hospital admissions. The ICD-IX system is the fundamental instrument by which to identify various clinical entities; however, its codes still refer to an old international classification of diseases. Headache disorders are now diagnosed according to the new classification of the International Headache Society, and their recognition using ICD-IX codes appears to be increasingly inadequate. We evaluated 1-year admissions for "headache" in our Department of Neurology according to the new DRG system, and paid particular attention to the problems related to compilation of the patient discharge schedule. The most common mistakes affecting the definition of DRGs and the admission costs for the NHS were also examined.

Data Collection↗
PubMed1998

Effects of phoneme repertoire on phoneme decision.

In three experiments, listeners detected vowel or consonant targets in lists of CV syllables constructed from five vowels and five consonants. Responses were faster in a predictable context (e.g., listening for a vowel target in a list of syllables all beginning with the same consonant) than in an unpredictable context (e.g., listening for a vowel target in a list of syllables beginning with different consonants). In Experiment 1, the listeners' native language was Dutch, in which vowel and consonant repertoires are similar in size. The difference between predictable and unpredictable contexts was comparable for vowel and consonant targets. In Experiments 2 and 3, the listeners' native language was Spanish, which has four times as many consonants as vowels; here effects of an unpredictable consonant context on vowel detection were significantly greater than effects of an unpredictable vowel context on consonant detection. This finding suggests that listeners' processing of phonemes takes into account the constitution of their language's phonemic repertoire and the implications that this has for contextual variability.

Humans↗
PubMed1998

Nucleotide fractional incorporation: a simple metabolic feature potentially related to clinical outcome in colorectal cancer patients.

Among the different investigated biomarkers, cell proliferation has provided valuable information on the clinical outcome of patients with malignant tumors. In the present study, we analyzed the potential relevance of fractional incorporation (FI) of a nucleotide precursor (3H-thymidine, 3H-dT) into DNA of tumor cells, determined on the primary tumor, on long-term clinical outcome of a series of patients with colorectal cancer. Determination of 3H-dT FI was carried out on fresh tumor material obtained at surgery as part of the clinical management of the primary tumor in 28 patients with colorectal cancer. Analysis of the relation between the FI and clinico-pathological characteristics of the tumor showed a trend of an inverse relation between the biomarker and Dukes' stage and no relation with tumor site. At 6 year follow-up, alive patients had a statistically significant higher median FI value (2.4%; range: 1.1-6.5%) than dead patients (1%; range: 0.3-4.5%) (p=0.02). Owing to the simplicity of this inexpensive methodology, the preliminary results of our study would indicate the potential of FI, a metabolic-kinetic parameter, to give prognostic information in colorectal cancer patients.

Colorectal Neoplasms↗
PubMed1998

[Hereditary fructose intolerance].

Hereditary fructose intolerance (HFI) is a rare autosomal recessive, metabolic disorder, that results from a deficiency of aldolase B (fructose-biphosphate aldolase) in the liver, kidney and intestine. Recent molecular studies have identified the mutation A149P in most European patients. We describe the first case of HFI with molecular analysis in a Portuguese child, presenting the same mutation of the aldolase B gene. The role of molecular studies in the diagnosis of HFI risk patients and their families is emphasized.

Alleles↗
PubMed1998

Pure red cell aplasia due to persistent B19 parvovirus infection in patient infected with human immunodeficiency virus type 1. Recovery with alpha-interferon therapy.

B19 parvovirus (PV) infection is ordinarily resolved with the production of specific antibodies that neutralize virus infectivity for erythroid host cells. Nevertheless persistent infection with B19 PV and pure red blood cell aplasia have been documented. A 27 year-old male. i.v. drug abuser, HIV+ and HCV was diagnosed of pure red cell aplasia. Six months later we had serologic evidence of persistent parvovirus infection. Interferon therapy, started for HCV infection, showed a marked improvement of anaemia and anti parvovirus IgM became negative. It is discussed the possible role of interferon therapy in persistent parvovirus infection.

Adult↗
PubMed1998

[Spironolactone protection from hydralazine-induced stress in the rat myocardium].

OBJECTIVES: We wished to verify the possible protective action of spironolactone (SPIRO), through its blocking action of slow calcium channels, in what concerns behavioural, morphologic, histochemical and ultrastructural alterations caused by experimental exposure to hydralazine (HZ), due to the excess release of catecholamines and the cellular influx of calcium. MATERIAL AND METHODS: Forty-eight adult male Wistar rats [correction of mice] were divided into 4 groups. The control group (CON) was administered olive oil for 4 days and distilled water i.v. on the last day, the hydralazine group (HZ) was administered olive oil for 4 days and 40 mg/kg i.v. of hydralazine on the last day; the spironolactone group (SPIRO) was administered 20 mg/kg of spironolactone diluted in olive oil for 4 days and distilled water on the last day; and the hydralazine with spironolactone group (HZ + SPIRO) was administered 20 mg/kg of spironolactone diluted in olive oil for 4 days and 40 mg/kg i.v. of hydralazine on the last day. The rats [correction of mice] were dissected and fragments of the myocardium removed for electron microscopy, and suprarenal fragments removed for light microscopy. Mitochondrial alterations characterised by ridge edema, lysis and vacuolisation (Cristolysis rate = damaged mitochondria/total mitochondria) were considered in the ultrastructural study. RESULTS: Light microscopy of the HZ group showed intense depletion of lipids in the cortical region of the suprarenals. The HZ + SPIRO group did not present significant alterations and was similar in appearance to the CON group. The ultrastructural study of the myocardium revealed the following rates of Cristolysis: CON group = 5.8%, HZ group = 91.9%, SPIRO group = 10.9%, HZ + SPIRO group = 10.2%*. (* = p < 0.001 chi-square test). CONCLUSION: The use of spironolactone in a model of stress induced by hydralazine caused: 1. Myocardial protection shown by reduced lesion of cardiomyocytes; 2. Protection of the suprarenals.

Adrenal Glands↗
PubMed1998

Miniscrews as orthodontic anchorage: a preliminary report.

The problems related to anchorage for orthodontic tooth movements in patients with deficient dentition are discussed, and various solutions suggested in the literature, including "onplants," implants, and zygoma wires, are evaluated. A miniscrew is presented as alternative anchorage, and possible locations for placement are discussed, based on studies of bone quality in dry skulls. Application of the miniscrew as anchorage for various types of tooth movement is demonstrated. Miniscrews are easily placed and removed and can be loaded immediately following insertion. However, stability is limited after loading with torsion.

Bone Screws↗
PubMed1998

[Importance of J. Brazy's neurobiological index. Prediction of the number and severity of complications in very low birth weight infants].

The objective of this study was to evaluate the neurodevelopment outcome of Very-Low-Birth-Weight Infants (VLBW), between 1987 and 1993, and correlate these findings with J.Brazy's Neurobiologic Risk Score (NBRS). The minimum corrected age at follow-up was 12 months. The neurodevelopmental assessment was performed using Mary Sheridan and Ruth Griffiths scales, Auditory and Visual Brainstem Evoked Responses and Stycar test. The NBRS was applied to 77 children. According to the score, three groups of risk were defined: Low < or = 4; Intermediate 5-7; High > or = 8. We obtained the following results: children with NBRS < 4, 20% had handicaps (5% of which major); children with NBRS 5-7, 41% had handicaps (23% of which major); in children with NBRS > 8, 95% had handicaps (80% of which major). The incidence of handicaps, (all grades included) was 71.4% for those weighing less than 1000 gr at birth, and 39.2% for those weighing 1000-1499 gr at birth. Major handicaps, mainly motor deficits, occurred in 26.8% of VLBW infants and minor to moderate handicaps were observed in 18.3% of patients in this group. These results were compared to J.Brazy's originals. We concluded that the NBRS, which is simple and objective to perform, is a good predictor of subsquent abnormal development in VLBW infants, allowing the infant's integration as soon as possible in high-risk follow-up programs, to place as soon as possible.

Developmental Disabilities↗
PubMed1998

[Myocardial protection against cold stress with pravastatin].

The CARE study showed that the myocardial infarction recurrence rate in patients with moderate cholesterol blood level decreases early during pravastatin treatment. Our goal is to evaluate the possible role of pravastatin in preventing the myocardial lesions induced by cold stress. Twenty Wistar-EPM rats were divided into four groups: Control (CON); PR (Pravastatin) treated with 10 mg/kg/d for 15 days; S (Stress group) in which the rats were submitted to cold stress (-8 degrees C for four hours); and PR + S group treated with pravastatin like PR group and also submitted to the cold stress. The animals were sacrificed and heart fragments were removed for optic and electronic microscopic analysis. The variable considered was mitochondria abnormality (edema, lyses and vacuolization) that was interpreted as crystolyses indices (CI) (n degree of abnormal mitochondria/n degree total of mitochondria). The following crystolyses indices, were found for each group respectively: CON, 2.0%; S, 95.5%; PR, 19.9% and PR + S group, 27.7%*(*p < 0.01). In conclusion, pravastatin prevented myocardial lesions induced by cold stress significantly.

Animals↗
PubMed1998

[Diltiazem compared with placebo in the prevention of myocardial ischemia during non-cardiac surgery].

OBJECTIVE: The aim of this study was to assess the efficacy and safety of intravenous diltiazem to prevent myocardial ischemia during surgery on patients with ischemic heart disease undergoing non cardiac surgery under general anesthesia. PATIENTS AND METHOD: Sixty patients scheduled for elective non cardiac surgery under general anesthesia were randomly assigned to two groups to receive diltiazem or placebo under double blind conditions. After an intravenous dose of 0.15 mg/kg of diltiazem or an equivalent amount of placebo, an infusion of 3 micrograms/kg/min of diltiazem or placebo was begun and continued until three hours after surgery. Thirty minutes after starting the infusion, anesthesia was induced by 0.1 mg/kg diazepam, 3 micrograms/kg of fentanyl and 0.3 mg/kg of etomidate. Intubation followed administration of 0.6 mg/kg of atracurium. Anesthesia was maintained with N2O/O2 and halothane and was the same for both groups. DII and V5 leads were monitored on a Cardiowiss CM-8 ECG machine that allowed us to set the alarm when ST segment variations reached 1 mm above or below baseline. We analyzed the number, intensity and duration of ischemic episodes recorded, as well as hemodynamic variables and side effects. RESULTS: Data for 46 patients were valid. At least one ischemic episode was experienced by 15% of patients in the placebo group and 1 in the diltiazem group (p < 0.05). The episodes were related to increased systolic arterial pressure (p = 0.04). ST segment decreases were 1.1 to 3.6 mm (1.75 +/- 0.7) (mean +/- SD) and lasted between 1 and 45 minutes (11.62 +/- 13.26) (mean +/- SD). No significant side effects were observed. CONCLUSIONS: Intravenous diltiazem administered to patients with ischemic heart disease under general anesthesia for non cardiac surgery was effective in our study for preventing intraoperative ischemic episodes.

Aged↗
PubMed1997

Alternatively spliced focal adhesion kinase in rat brain with increased autophosphorylation activity.

pp125 focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase transducing signals initiated by integrin engagement and G protein-coupled receptors, is highly expressed in brain. FAK from brain had a higher molecular weight and an increased autophosphorylation activity, than from other tissues. In addition to a 9-base insertion in the 3'-coding region, which defines FAK+, rat striatal FAK mRNAs contained several additional short exons, coding for peptides of 28, 6, and 7 residues, respectively (termed boxes 28, 6, and 7), surrounding the autophosphorylated Tyr-397. In transfected COS 7 cells, the presence of boxes 6 and 7 conferred an increased overall tyrosine phosphorylation, a higher phosphorylation of Tyr-397 assessed with a phosphorylation state-specific antibody, and a more active autophosphorylation in immune precipitates. The presence of box 28 did not alter further these parameters. Two-dimensional phosphopeptide maps of hippocampal FAK were identical to those of FAK+6,7. The presence of the various exons did not alter the interaction of FAK with c-Src, n-Src, or Fyn. Thus, several splice isoforms of FAK are preferentially expressed in rat brain, some of which have an increased autophosphorylation activity, suggesting that FAK may have specific properties in neurons.

Alternative Splicing↗
PubMed1997

Opposite effects of L-arginine and nitroglycerin on cerebral blood velocity: nitric oxide precursors and cerebral blood velocity.

Nitric oxide (NO), a gaseous molecule synthesized in the arteriolar endothelium from the amino acid L-arginine (L-arg), has been identified as the previously described Endothelium-Derived Relaxing Factor (EDRF): nitroderivatives such as nitroglycerin are known to induce vasodilation via NO release. The aim of this study was to evaluate by Transcranial Doppler (TCD) monitoring any changes in cerebral hemodynamics induced by both the infusion of L-arg and the sublingual administration of nitroglycerin in 20 healthy subjects. L-arg infusion induced a significant increase in blood velocity compared to the baseline value (mean +/- S.D. percent change = 18 +/- 8.71; p<0.0001 ) and a slight but significant decrease in Pulsatility Index. By contrast, nitroglycerin was able to cause a significant decrease in blood velocity (mean +/- S.D. percent change = 24.8 +/- 7.68; p<0.0001), while leaving Pulsatility Index unchanged. These data suggest that L-arg and nitroglycerin, both hypothesized to use NO as the final product at the vascular level, result in opposite blood velocity patterns within the cerebral circulation. This may be due to the particular type of artery and/or to the local endothelial environment whereby the released NO may act.

Adult↗