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Biomedical subjects

C Costa

Publications and source records attributed to C Costa.

At least 37 records · Page 2Linked to original sources

Computed tomography features of liparitosis: a pneumoconiosis due to amorphous silica.

The purpose of this study was to describe the radiological features of pleural, parenchymal and mediastinal damage due to occupational inhalation of pumice. In total, 31 workers were evaluated for annual follow-up. Spiral computed tomography (CT) was obtained in the three patients with evident parenchymal abnormalities at chest radiograph. High-resolution computed tomography (HRCT) was performed in the remaining 28 subjects with no radiographical evidence of pleuropulmonary damage or evidence of pleural plaques, in order to exclude parenchymal involvement. Pumice samples were analysed by radiograph diffraction and scanning electron microscopy. Spiral CT showed parahilar conglomerate masses containing fine reticular calcifications in three of 31 (9.7%) patients. HRCT showed several bilateral pleural plaques, without any parenchymal lesion in eight of 28 (28.6%) cases. Statistical analysis indicated correlation between CT findings and pulmonary function, as well as exposure to pumice. The analysis of pumice excluded the presence of asbestos. The findings from this study suggest that pleural plaque may be the only sign of disease in patients with a history of pumice inhalation. However, conglomerate parahilar masses are probably due to exposure to massive amounts of heated pumice, and seem to have different pathogenesis and histopathological characteristics to silicosis.

Aged↗

Lamotrigine and remacemide protect striatal neurons against in vitro ischemia: an electrophysiological study.

In the present study, we investigated the cellular and synaptic mechanisms underlying the neuroprotective action of lamotrigine and remacemide. Both drugs, in fact, have been reported to exert a neuroprotective action in in vivo animal models of ischemia. To address this issue, electrophysiological recordings and cell swelling measurements were performed from striatal neurons in control condition and during combined oxygen and glucose deprivation (in vitro ischemia) in a brain slice preparation. Lamotrigine, remacemide, and the active desglycinyl metabolite of remacemide, D-REMA, induced a concentration-dependent reduction of both repetitive firing discharge and excitatory postsynaptic potentials. However, while remacemide and D-REMA exerted their inhibitory action on glutamatergic transmission by blocking NMDA receptors, lamotrigine exerted a preferential presynaptic action, as indicated by its ability to increase paired-pulse facilitation. Both remacemide and lamotrigine were found to be neuroprotective against the irreversible field potential loss and cell swelling induced by in vitro ischemia, and coadministration of low concentrations of these drugs exerted an additive neuroprotective action. A combined use of lamotrigine and remacemide could be employed in clinical trials to enhance neuroprotection in neurological disorders involving an abnormal striatal glutamatergic transmission.

Acetamides↗

Corticostriatal LTP requires combined mGluR1 and mGluR5 activation.

Metabotropic glutamate receptors (mGluRs) have been demonstrated to play a role in synaptic plasticity. It has been recently shown that mGluR1 is involved in corticostriatal long-term depression, by means of pharmacological approach and by using mGluR1-knockout mice. Here, we report that both mGluR1 and mGluR5 are involved in corticostriatal long-term potentiation (LTP). In particular, the mGluR1 antagonist LY 367385, as well as the mGluR5 antagonist MPEP, reduce LTP amplitude. Moreover, blockade of both mGluR1 and mGluR5 by LY 367385 and MPEP co-administration fully suppresses LTP. Accordingly, group II and group III mGluRs antagonists fail to affect LTP induction. Interestingly, LTP amplitude is also significantly reduced in both mGluR1- and mGluR5-knockout mice. The differential function of mGluR1 and mGluR5 in corticostriatal synaptic plasticity may play a role in the modulation of the motor activity mediated by the basal ganglia, thus providing a substrate for the pharmacological treatment of motor disorders involving the striatum.

Animals↗

Mutational spectrum and DNA-based prenatal diagnosis in carnitine-acylcarnitine translocase deficiency.

Carnitine-acylcarnitine translocase (CAC) deficiency is a rare autosomal recessive disorder of long-chain fatty acid oxidation with a severe outcome. We report mutation analysis in a cohort of 12 patients. Twelve mutations were identified of which 9 have not been reported so far (G28C, D32N, R178Q, P230R, D231H, 179delG, 802delG, 69-70insTGTGC, and 609-1g>a). Altogether, including our results, 22 mutations of the CAC gene have been published to date in 23 patients demonstrating the allelic heterogeneity of CAC deficiency. DNA-based prenatal diagnosis was performed for the first time in pregnancies at risk for CAC deficiency. Two fetuses were affected and one pregnancy was terminated by family decision. Two other fetuses had normal genotype and five others were heterozygotes. All the offspring of these seven pregnancies are alive and apparently healthy.

Amniotic Fluid↗

Atrazine catabolism by a combined bacterial association (KRA30) under carbon- and nitrogen-limitations in a retentostat.

AIMS: Nutrient-limited atrazine catabolism study in continuous cultures with biomass retention to mimic in situ environmental conditions and thus gain insight of the efficacy of biosupplementation/biostimulation to eliminate reduced herbicide bioavailability. METHODS AND RESULTS: Carbon- and nitrogen-limited retentostat (1 and 5 l) cultivation of a combined atrazine (100 mg l-1)-catabolizing association KRA30 was made. As a nitrogen source, through citrate supplementation, increased herbicide catabolism resulted and was complete in the absence of NH4-N. Co-metabolism of the molecule in the presence of succinate was identified. Population characterization by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) indicated component species numerical dominance shifts in response to changes in nutrient limitation, mineral salts composition and biofilm formation, although the total species complement and catabolic potential were retained. CONCLUSIONS: Biomass and catabolic capacity maintenance, through cost-effective biosupplementation/biostimulation, should promote atrazine bioavailability and so ensure successful amelioration. SIGNIFICANCE AND IMPACT OF THE STUDY: All planning, implementation and monitoring of bioremediation programmes should be underpinned by a combination of molecular and (continuous) culture-based methods.

Atrazine↗

Neovascularisation is a prognostic factor of early recurrence in T1/G2 urothelial bladder tumours.

BACKGROUND: Of patients with superficial bladder cancer, a group are still at risk of disease recurrence, progression and death from their cancer after curative treatment. Angiogenesis is a crucial pathogenic mechanism for this type of urothelial cell carcinoma (UCC), and is a potential therapeutic target. However, the selection of the appropriate patients remains a dilemma. PATIENTS AND METHODS: Vascular endothelial growth factor (VEGF) expression and the presence of angiogenesis and occurrence of CD31, CD34, endoglin and factor VIII immunoexpression, were evaluated in 66 superficial papillary UCCs of the bladder and were correlated with classical histopathological factors and disease outcome. RESULTS: VEGF immunoreactivity was observed in 100% of cases, and more intensely in the luminal surface. The presence of microvessel clusters independently of a fibrovascular core was observed in 22.7% of cases. Of these, the T1/G2 subgroup had an independent and significantly lower recurrence-free survival (P = 0.0002). CONCLUSIONS: These results indicate that the presence of angiogenesis in tumour urothelium is a potential prognostic factor in superficial UCC, particularly in T1/G2 tumours, and may be used to select patients for anti-angiogenic treatments.

Antigens, CD↗

Effects of caffeine, vitamin D, and other nutrients on quantitative phalangeal bone ultrasound in postmenopausal women.

OBJECTIVE: We investigated the controversial effects of coffee and other nutrients on bone mass. METHODS: In a study of 93 healthy postmenopausal women (mean +/- standard deviation: 57.3 +/- 7.1 y old and 8.9 +/- 7.5 y since menopause) selected on the basis of not having changed their eating habits since premenopause, not smoking, not exercising, not receiving hormone-replacement therapy, and having a weight in the range of 70% to 130% of their ideal weights, amplitude-dependent speed of sound (Ad-SOS) was determined by quantitative bone ultrasound, and a prospective 7-d diet survey evaluated the intake of caffeine and nutrients involved in calcium metabolism. Women were stratified according to their caffeine, calcium, and vitamin D intakes and ratios of calcium to phosphorus and to protein. Ad-SOS differed only with vitamin D intake and was greater in the group taking at leasst 400 IU/d (P < 0.0001). RESULTS: In simple and multiple regression analyses, the only significant variable that affected Ad-SOS and nutrient intake was vitamin D (P < 0.0001). Phalangeal bone Ad-SOS was influenced only by the intake of vitamin D, not of caffeine or other nutrients. CONCLUSIONS: This lack of effect of caffeine and protein may be related to good nutritional intake or the low levels of caffeine consumed.

Body Mass Index↗

Systemic administration of a calpain inhibitor reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhage in the rat.

Increases in intracellular calcium and subsequent activation of calcium-activated proteases (e.g., calpains) may play a critical role in central nervous system injury. Several studies have implicated calpain activation following subarachnoid hemorrhage (SAH). This study evaluated the effect of a calpain inhibitor administration following SAH in the rat on behavioral deficits (postinjury days 1-5, employing a battery of well-characterized assessment tasks), and blood-brain barrier permeability changes (48 h post-SAH, quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique). Rats were injected with 400 microl of autologous blood into the cisterna magna to induce SAH. Within 5 min after the surgical procedure, Calpain Inhibitor II or vehicle was continuously administered intravenously for 2 days. Results indicated that Calpain Inhibitor II treatment after SAH significantly improved (a) beam balance time (day 1, p < 0.05), but not beam balance score, (b) latency to traverse the beam on days 1-4 (day 1-3, p < 0.001; day 4, p < 0.01), and (c) loss in body weight on days 4-5 (p < 0.05). Evans Blue dye extravasation was significantly less in SAH Calpain Inhibitor II-treated rats compared to SAH vehicle-treated rats in seven out of the eight brain regions studied (p < 0.001, 0.01, and 0.05). These results suggest that pharmacological inhibition of a relatively selective, membrane-permeant calpain inhibitor can significantly reduce some pathophysiological SAH consequences, and indicate that the inhibition of calpain may be a beneficial therapeutic approach to reduce post-SAH global brain dysfunction.

Animals↗

Cyclo-oxygenase 2 expression is associated with angiogenesis and lymph node metastasis in human breast cancer.

AIMS: Cyclo-oxygenases 1 and 2 (COX-1 and COX-2) are key enzymes in prostaglandin biosynthesis. COX-2 is induced by a wide variety of stimuli, and present during inflammation. COX-2 overexpression has been observed in colon, head and neck, lung, prostate, stomach, and breast cancer. In colon and gastric cancer, COX-2 expression was associated with angiogenesis. The aim of this study was to determine the relation between COX-2 expression and angiogenesis in breast cancer, and to correlate the expression of this enzyme with classic clinicopathological parameters. METHODS: COX-2 expression was investigated by immunohistochemistry and western blotting analysis. The expression of COX-2 was then related to age, histological grade, nodal status, oestrogen receptor status, p53 expression,c-erb-B2 overexpression, mitotic counts, MIB-1 labelling index, apoptotic index, sialyl-Tn expression, transforming growth factor alpha expression, microvessel density, and disease free survival in 46 patients with invasive ductal breast carcinoma. RESULTS: By means of immunohistochemistry, COX-2 expression was detected in eight of the 46 carcinomas studied. Western blotting showed COX-2 protein expression in the same breast tumours, but not in normal adjacent tissues. The density of microvessels immunostained with anti-F-VIII related antigen was significantly higher in patients with COX-2 expression than in those without expression (p = 0.03). In addition, COX-2 was significantly associated with the presence of sialyl-Tn expression (p = 0.02), lymph node metastasis (p = 0.03), a high apoptotic index (p = 0.03), and a short disease free survival (p = 0.03) in univariate analyses. CONCLUSIONS: These data suggest that COX-2 expression is associated with angiogenesis, lymph node metastasis, and apoptosis in human breast cancer. Moreover, these results warrant further studies with larger series of patients to confirm the association with short disease free survival in patients with breast cancer.

Adult↗

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Adult↗

BMRI in early detection of breast cancer in patients with increased genetic risk: our preliminary results.

Because of the higher risk of developing breast cancer and the early onset of the disease in women proved or suspected to be carriers of a breast cancer susceptibility gene, a dedicated screening should be offered as a less invasive approach with respect to the otherwise suggested prophylactic mastectomy. This should be optimized in order to overcome the limitations of conventional breast imaging with the application of new technologies such as Breast Magnetic Resonance Imaging (BMRI). A diagnostic protocol for routine control in patients with high risk for developing breast cancer has been prepared. Within a 7 months period, 23 patients suspected or proved to carry a breast cancer susceptibility gene underwent BMRI. Four breast cancers were identified with BMRI. In these cases mammography was negative because of the density of the parenchyma or for its fibroglandular pattern. US was negative in two cases, not specific for malignancy in one case and considered as only possibly malignant but with biopsy recommendation on the basis of MR findings in the last one. Clinic analysis was positive for mass in two cases. The accuracy of BMRI is known to be higher than that of conventional imaging in the study of breast parenchyma. High spatial resolution and no breast density influence can give more detailed information about smaller lesions and the right extent of the disease.

Adult↗

Shape changes and growth trajectories in the early stages of three species of the genus Diplodus (Perciformes, Sparidae).

The larvae of three species of the genus Diplodus (Diplodus vulgaris, D. sargus, and D. puntazzo) colonize shallow waters along the Mediterranean coasts and, after a short period spent in the water column, they settle. For all three species this habitat transition is characterized by important shape changes mostly related to swimming capacity and feeding behavior. In this study, geometric morphometrics are used to characterize shape changes during the early juvenile life of specimens collected in a single locality in order to compare growth curves and allometric relationships. Size-related shape changes proved to be similar for all three species and are consistent with the ecological transition. A nonparametric smoothing technique (Loess) was used to fit the scatter of shape on size. The graphical representation (of most size-related shape variability) of this fitting technique shows how major shape changes are rapid for small sizes and slow down successively. The approach allows for the visualization of allometry and the fitting technique might help in defining the allometric growth pattern, thus contributing to the study of the autoecology of the species and in establishing terms for comparison with other ecologically or phylogenetically related species.

Animals↗

Cloned pigs generated from cultured skin fibroblasts derived from a H-transferase transgenic boar.

Cloned pigs were produced from cultured skin fibroblasts derived from a H-transferase transgenic boar. One 90 day fetus and two healthy piglets resulted from nuclear transfer by fusion of cultured fibroblasts with enucleated oocytes. The cells used in these studies were subjected to an extensive culture time, freezing and thawing, and clonal expansion from single cells prior to nuclear transfer. PCR and FACS analysis determined that the cloned offspring contained and expressed the H-transferase transgene. Microsatellite analysis confirmed that the clones were genetically identical to the boar. The cell culture and nuclear transfer procedures described here will be useful for applications requiring multiple genetic manipulations in the same animal.

Animals↗

Development of two real-time quantitative TaqMan PCR assays to detect circulating Aspergillus fumigatus DNA in serum.

Several PCR assays have been developed for detecting Aspergillus fumigatus DNA in blood of patients with invasive aspergillosis. However, the best blood fraction to be assayed has not been defined and the multicopy genes used as the DNA targets for amplification not characterized. Firstly, we developed a real-time PCR assays based on the TaqMan technology targeted to a single copy gene. To compare serum, white cell pellet, and plasma for effectiveness as blood assay fractions, we spiked whole blood with A. fumigatus DNA and processed these fractions similarly. The difference between white cell pellet and serum was not significant. In contrast, the yield from plasma was 10 times lower than from serum. Then, we compared serum processed immediately or after 24 h at room temperature and observed a lower yield after 24 h. Secondly, a real-time PCR assay targeted to a mitochondrial gene was also developed. The copy number was estimated between 9 and 10 mitochondrial genes per single copy gene. Therefore, we recommend serum, stored and frozen as soon as possible, to be used for detecting circulating A. fumigatus DNA for diagnosis. Moreover, the mitochondrial multicopy gene was characterized in order to compare results from different patients.

Aspergillosis↗

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia).

OBJECTIVE: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995-1999). METHODS: The study involves three groups: a control, a "moderate", and a "high" intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. RESULTS: Children in the intervention groups--especially the high group--were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. CONCLUSION: Intensive school-based interventions can reduce tanning and reported sun exposure in children.

Child↗