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D C Costa

Publications and source records attributed to D C Costa.

At least 19 recordsLinked to original sources
PubMed2006

Modulation of the production of reactive oxygen species (ROS) by cAMP-elevating agents in granulocytes from diabetic patients: an Akt/PKB-dependent phenomenon.

BACKGROUND: Granulocytes from healthy subjects and from patients suffering from diabetes mellitus present differences in reactivity to stimulation with cyclic nucleotide-elevating agents. The production of reactive oxygen species (ROS) is inhibited in cells from non-diabetic subjects following such stimulation, but activated through a PKA-independent signaling pathway in granulocytes from type 1 and type 2 diabetic patients. The aim of the present study was to understand better the changes in signaling mechanisms induced by the disease. METHODS: ROS production in granulocytes from healthy subjects and from type 1 and type 2 diabetic patients was measured using a luminol-dependent chemiluminescence assay. Granulocytes were stimulated by the addition of the cAMP-elevating agent dibutyryl cAMP. In some experiments, granulocytes were pre-treated with an inhibitor of PKA or Akt/PKB prior to cAMP stimulation. RESULTS: Intracellular elevation of cAMP induced a PKA-dependent and Akt/PKB-independent inhibition of ROS production in granulocytes from healthy subjects, but a significant activation in cells from both type 1 and type 2 diabetic patients. Most significantly, activation of ROS generation in cells from diabetic patients was shown to be Akt/PKB-dependent and PKA-independent. CONCLUSIONS: These results suggest that chronic hyperglycaemia could induce metabolic adaptation in cAMP-related signaling mechanisms. Epac (exchange protein directly activated by cAMP) is a novel cAMP receptor besides PKA involved in different signaling pathways. The cAMP-stimulated inverse ROS response in granulocytes from type 1 and type 2 diabetic patients may be due to a change in signaling pathways from cAMP/PKA to cAMP/Epac/Akt/PKB. These preliminary results require further studies in order to evaluate their consequences on innate immunity and pathogenesis of diabetes mellitus.

Adult↗
PubMed2005

Clinical evaluation of 2D versus 3D whole-body PET image quality using a dedicated BGO PET scanner.

PURPOSE: Three-dimensional positron emission tomography (3D PET) results in higher system sensitivity, with an associated increase in the detection of scatter and random coincidences. The objective of this work was to compare, from a clinical perspective, 3D and two-dimensional (2D) acquisitions in terms of whole-body (WB) PET image quality with a dedicated BGO PET system. METHODS: 2D and 3D WB emission acquisitions were carried out in 70 patients. Variable acquisition parameters in terms of time of emission acquisition per axial field of view (aFOV) and slice overlap between sequential aFOVs were used during the 3D acquisitions. 3D and 2D images were reconstructed using FORE+WLS and OSEM respectively. Scatter correction was performed by convolution subtraction and a model-based scatter correction in 2D and 3D respectively. All WB images were attenuation corrected using segmented transmission scans. Images were blindly assessed by three observers for the presence of artefacts, confidence in lesion detection and overall image quality using a scoring system. RESULTS: Statistically significant differences between 2D and 3D image quality were only obtained for 3D emission acquisitions of 3 min. No statistically significant differences were observed for image artefacts or lesion detectability scores. Image quality correlated significantly with patient weight for both modes of operation. Finally, no differences were seen in image artefact scores for the different axial slice overlaps considered, suggesting the use of five slice overlaps in 3D WB acquisitions. CONCLUSION: 3D WB imaging using a dedicated BGO-based PET scanner offers similar image quality to that obtained in 2D considering similar overall times of acquisitions.

Aged↗
PubMed2004

Striatal dopamine transporter in dementia with Lewy bodies and Parkinson disease: a comparison.

OBJECTIVE: To study the nigrostriatal pathways in 21 patients with dementia with Lewy bodies (DLB), 19 drug naive Parkinson disease (PD) patients, and 16 controls using a dopaminergic presynaptic ligand [123I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT) and SPECT in order to assess similarities or differences between DLB and PD. METHODS: A SPECT scan was carried out 3 to 4 hours after administration of 185 MBq (IV) of FP-CIT. Using occipital cortex as a radioactivity uptake reference, ratios for the caudate nuclei and the anterior and posterior putamina of both hemispheres were calculated. From the FP-CIT binding measurements, asymmetry indices and caudate:putamen ratios were derived. RESULTS: The DLB and PD groups had lower FP-CIT binding in all striatal areas than controls (analysis of variance: p < 0.001 in all measures). DLB patients also had significantly lower binding in the caudate nucleus than the PD patients. There was greater asymmetry of uptake in the posterior putamina of PD patients than DLB patients (p < 0.04) and controls (p < 0.01). The mean caudate:putamen ratio for the DLB group was not significantly different from that of the controls, while the mean caudate:putamen ratio of the PD group was higher than that of the control group (p < 0.001) and the DLB group (p < 0.001). CONCLUSION: This study showed differences between PD and DLB in the pattern of striatal dopaminergic dysfunction. DLB patients do not have the characteristic selective degeneration of ventrolateral nigral neurons seen in PD. This could explain some of the clinical differences between DLB and PD.

Caudate Nucleus↗
PubMed2004

Comparison of methodologies for the in vivo assessment of 18FLT utilisation in colorectal cancer.

Fluorine-18 3'-deoxy-3'-fluorothymidine (18FLT) is a tissue proliferation marker which has been suggested as a new tumour-specific imaging tracer in positron emission tomography (PET). The objectives of this study were to investigate the pharmacokinetics of 18FLT in patients with colorectal cancer, defining methodologies for the quantitative analysis of the in vivo 18FLT uptake and subsequently assessing the accuracy of semi-quantitative measures. Dynamic acquisitions over a single field of view of interest identified by computed tomography were carried out for up to 60 min following injection of 18FLT (360 +/- 25 MBq). Dynamic arterial blood sampling was carried out in order to provide a blood input function. Simultaneous venous samples were also taken in order to investigate their potential utilisation in deriving a hybrid input function. Arterial and venous blood samples at 5, 15, 30, 60 and 90 min p.i. were used for metabolite analysis. Eleven patients with primary and/or metastatic colorectal cancer were studied on a lesion by lesion basis (n = 21). All acquired images were reconstructed using ordered subsets expectation maximisation and segmented attenuation correction. Time-activity curves were derived by image region of interest (ROI) analysis and image-based input functions were obtained using abdominal or thoracic aorta ROIs. Standardised uptake values (SUVs) were calculated to provide semi-quantitative indices of uptake, while non-linear regression (NLR) methodology in association with a three-compartment model and Patlak analysis were carried out to derive the net influx constant Ki. The metabolite analysis revealed two radioactive metabolites, with the parent compound representing approximately 80% of the total radioactivity in the 30-min plasma sample. In the case of NLR, better fits were obtained with a 3k model (i.e. k4 = 0) for both lesion and bone marrow time-activity curves. For the same lesions, a high correlation was observed between the Ki derived from either Patlak analysis or NLR(3k) and the corresponding SUVs. Our results also suggest that the quantitative behaviour of 18FLT in vivo (up to 60 min p.i.) may be characterised using a 3k model or Patlak analysis in combination with image-derived input functions. The good correlation found between the SUVs (at 60 min) and Ki values supports the use of semi-quantitative indices to assess the proliferation rate of colorectal cancer lesions in vivo with 18FLT.

Aged↗
PubMed2004

Dopamine transporter binding in Gilles de la Tourette syndrome: a [123I]FP-CIT/SPECT study.

OBJECTIVE: To investigate dopamine transporter binding in Gilles de la Tourette syndrome (GTS) with SPECT and [123I]FP-CIT. METHOD: Ten neuroleptic naïve/free patients with GTS, and 10 age- and gender-matched normal volunteers were studied. Subjects were clinically evaluated. GTS severity and affective symptoms were measured and the presence of GTS-related behaviours were recorded. RESULTS: The GTS group showed significantly higher binding in both caudate and putamen nuclei than the controls. No associations were found between striatal binding ratios and measures of affect or GTS-related behaviours. CONCLUSION: Patients with GTS show higher striatal binding of FP-CIT to the striatum in comparison with age- and gender-matched control subjects, indicating that dopamine transporter abnormalities are involved in the pathophysiology of GTS. These abnormalities appear to be distributed across both caudate and putamen.

Adolescent↗
PubMed2003

Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer.

Fluorine-18 labelled fluoro-2-deoxy- d-glucose ((18)FDG) positron emission tomography (PET) imaging demonstrates the increased glucose consumption of malignant cells, but problems with specificity have led to the development of new PET tracers. [(18)F]3'-deoxy-3'-fluorothymidine ((18)FLT) is a new tracer which images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study we compared the cellular uptake of (18)FLT and (18)FDG in patients with colorectal cancer (CRC). Seventeen patients with 50 primary or metastatic CRC lesions were prospectively recruited. Lesions were initially identified using computed tomography. Patients underwent both (18)FDG and (18)FLT scanning. Semi-quantitative analysis of tracer uptake was carried out using standardised uptake values. All the primary tumours ( n=6) were visualised by both tracers, with (18)FDG showing on average twice the uptake of (18)FLT. Similar uptake of both tracers was seen in lung and peritoneal lesions, with (18)FLT imaging five of the six lung lesions and all of the peritoneal lesions. Of the 32 colorectal liver metastases, 11 (34%) were seen as avid for (18)FLT, compared with 31 (97%) for (18)FDG. No correlation was seen between the uptake of the two tracers ( R(2)=0.03). (18)FLT shows a high sensitivity in the detection of extrahepatic disease but poor sensitivity for the imaging of colorectal liver metastases, making it unlikely to have a role as a diagnostic tracer in CRC. We have demonstrated that (18)FDG and (18)FLT image two distinct processes. The prognostic implications of the uptake of (18)FLT need to be assessed in terms of response to chemoradiotherapy and survival.

Aged↗
PubMed2003

Modulation of the reactive oxygen species (ROS) generation mediated by cyclic AMP-elevating agents or Interleukin 10 in granulocytes from type 2 diabetic patients (NIDDM): a PKA-independent phenomenon.

UNLABELLED: SUMMARY-BACKGROUND: The present study investigates the hypothesis that cells from ill patients and from healthy subjects may have different reactivity under metabolic stimulation as a consequence of an disease-induced metabolic adaptation. METHODS: Granulocytes either from healthy subjects or from type II-Non Insulin Dependent Diabetes Mellitus (NIDDM) patients were compared in their capacities to generate Reactive Oxygen Species (ROS). The ROS generation was comparatively determined in a chemiluminescence assay, luminol-dependent, after cell incubation in the presence of either cyclic AMP - elevating agents or Interleukin 10. In some experiments the cells were pretreated with H89 compound (a PKA inhibitor) or with diphenylene iodonium (DPI), a NADPH-oxidase inhibitor. RESULTS: Our results showed an increased ROS generation in granulocytes from diabetic patients in absence of cyclic AMP-elevating agents or IL-10. In the presence of cyclic AMP-elevating agents was observed an inverse metabolic response in granulocytes from diabetic patients in comparison to cells from healthy subjects. The granulocytes were pre-incubated in the presence of cyclic AMP-elevating agents--amminophylline (AMF) or dibutyryl cyclic AMP (dbcAMP)--or interleukin 10 (IL-10). The AMF, dbcAMP and IL-10 inhibited ROS production by granulocytes from healthy subjects. By contrast, AMF and dbcAMP activated cells from diabetic patients while IL-10 had no effect. The inhibition of ROS induced by AMF, dbcAMP or IL-10 was promptly abolished by the pretreatment of the cells with either PKA H89 inhibitor or NADPH-oxidase inhibitor (DPI) in granulocytes from healthy subjects. In relation to the granulocytes from type 2 diabetics patients, the activation of ROS generation mediated by AMF and dbcAMP was fully abolished by NADPH-oxidase DPI-inhibitor, but not by PKA H89 inhibitor. CONCLUSIONS: Our present results reinforce the hypothesis that cells from ill patients (type II diabetic) when compared to cells from healthy subjects have different reactivity under metabolic stimulation. ROS production by human granulocytes was modulated by cyclic AMP elevating agents and IL-10. The inhibition of the ROS production in cells from healthy subjects was PKA-dependent while the activation in granulocytes from patients was PKA-independent. This inverse metabolic response, in cells from patients, suggests the use of an alternative metabolic pathway PKA-independent, possible cAMP/Epac/PKB-dependent. The correlation between activation of ROS production in granulocytes from diabetic patients and pathogenesis of diabetes can be suggested, however, further and extensive studies are needed for demonstrating this suggestion.

Aged↗
PubMed2003

Positron emission and computed X-ray tomography: a coming together.

We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the investigation of patients with cancer. The first such unit in the UK and its mode of operation is discussed and initial applications shown. Five hundred and thirty-five patients have been scanned with 2-[18F]fluoro-2-deoxy-D-glucose from mid-January 2002 to the end of August 2002. From this initial experience a clear view of the impact of this technology is emerging. It can now be stated that (1) PET/CT does speed up the throughput of patient studies by at least 25% and hence adds to the comfort of patients scanned; and (2) PET/CT leads to greater accuracy in the interpretation of data. In view of the routine availability of high quality PET and CT fused maps a significant development in radiotherapy planning is on the horizon. We discuss our experience at present and point to further developments in the near future.

Equipment Design↗
PubMed2003

In vivo imaging of cellular proliferation in colorectal cancer using positron emission tomography.

BACKGROUND: and aims: Positron emission tomography (PET) using (18)F labelled 2-fluoro-2-deoxy-D-glucose ((18)FDG) is an established imaging tool, although the recent development of a biologically stable thymidine analogue [18F] 3'-deoxy-3-fluorothymidine ((18)FLT) has allowed PET to image cellular proliferation by utilising the salvage pathway of DNA synthesis. In this study, we have compared uptake of (18)FLT and (18)FDG with MIB-1 immunohistochemistry to evaluate the role of PET in quantifying in vivo cellular proliferation in colorectal cancer (CRC). PATIENTS AND METHODS: Patients with resectable, primary, or recurrent CRC were prospectively studied. Thirteen lesions from 10 patients (five males, five females), median age 68 years (range 54-87), were evaluated. Patients underwent (18)FDG and (18)FLT PET scanning. Tracer uptake within lesions was quantified using standardised uptake values (SUVs). Histopathological examination and MIB-1 immunohistochemistry were performed on all lesions, and proliferation quantified by calculating a labelling index (% of MIB-1 positively stained nuclei within 1500 tumour cells). RESULTS: Histology confirmed adenocarcinoma in 12 of 13 lesions; the remaining lesion was reactive. All eight extrahepatic lesions were visualised using both (18)FLT and (18)FDG. Three of the five resected liver metastases were also avid for (18)FLT and showed high proliferation, while the remaining two lesions which demonstrated no uptake of (18)FLT had correspondingly very low proliferation. There was a statistically significant positive correlation (r =0.8, p<0.01) between SUVs of the tumours visualised with (18)FLT and the corresponding MIB-1 labelling indices. No such correlation was demonstrated with (18)FDG avid lesions (r =0.4). CONCLUSIONS: (18)FLT PET correlates with cellular proliferation markers in both primary and metastatic CRC. This technique could provide a mechanism for in vivo grading of malignancy and early prediction of response to adjuvant chemotherapy.

Adenocarcinoma↗
PubMed2002

CT-based attenuation correction in the calculation of semi-quantitative indices of [18F]FDG uptake in PET.

The introduction of combined PET/CT systems has a number of advantages, including the utilisation of CT images for PET attenuation correction (AC). The potential advantage compared with existing methodology is less noisy transmission maps within shorter times of acquisition. The objective of our investigation was to assess the accuracy of CT attenuation correction (CTAC) and to study resulting bias and signal to noise ratio (SNR) in image-derived semi-quantitative uptake indices. A combined PET/CT system (GE Discovery LS) was used. Different size phantoms containing variable density components were used to assess the inherent accuracy of a bilinear transformation in the conversion of CT images to 511 keV attenuation maps. This was followed by a phantom study simulating tumour imaging conditions, with a tumour to background ratio of 5:1. An additional variable was the inclusion of contrast agent at different concentration levels. A CT scan was carried out followed by 5 min emission with 1-h and 3-min transmission frames. Clinical data were acquired in 50 patients, who had a CT scan under normal breathing conditions (CTAC(nb)) or under breath-hold with inspiration (CTAC(insp)) or expiration (CTAC(exp)), followed by a PET scan of 5 and 3 min per bed position for the emission and transmission scans respectively. Phantom and patient studies were reconstructed using segmented AC (SAC) and CTAC. In addition, measured AC (MAC) was performed for the phantom study using the 1-h transmission frame. Comparing the attenuation coefficients obtained using the CT- and the rod source-based attenuation maps, differences of 3% and <6% were recorded before and after segmentation of the measured transmission maps. Differences of up to 6% and 8% were found in the average count density (SUV(avg)) between the phantom images reconstructed with MAC and those reconstructed with CTAC and SAC respectively. In the case of CTAC, the difference increased up to 27% with the presence of contrast agent. The presence of metallic implants led to underestimation in the surrounding SUV(avg) and increasing non-uniformity in the proximity of the implant. The patient study revealed no statistically significant differences in the SUV(avg) between either CTAC(nb) or CTAC(exp) and SAC-reconstructed images. The larger differences were recorded in the lung. Both the phantom and the patient studies revealed an average increase of approximately 25% in the SNR for the CTAC-reconstructed emission images compared with the SAC-reconstructed images. In conclusion, CTAC(nb) or CTAC(exp) is a viable alternative to SAC for whole-body studies. With CTAC, careful consideration should be given to interpretation of images and use of SUVs in the presence of oral contrast and in the proximity of metallic implants.

Algorithms↗
PubMed2002

Evaluation of terbinafine treatment in Leishmania chagasi-infected hamsters (Mesocricetus auratus).

The objective of the present study was to assess the effect of terbinafine treatment in hamsters infected with Leishmania chagasi. Four of five groups of hamsters were infected with 3 x 10(7) L. chagasi promastigotes by the intracardiac route and submitted to different treatments of 30 days duration starting on the 30th day after inoculation. Group 1 was treated with 100mg/kg terbinafine PO, group 2 was treated with 80 mg/kg Glucantime IM, and group 3 was treated with a combination of the same dose of each drug by the same routes. Group 4 (control) received vehicle (Tween 80 [0.1%]+CMC[0.5%]+H(2)O [0.5 ml], PO). Spleen parasite burden and spleen relative weight were determined 3 days after the end of the treatment. The results were analyzed by the Kruskal-Wallis test (P < 0.05). There was no difference between the infected untreated and terbinafine-treated groups in spleen parasite burden (15.81+/-15.81 vs. 13.00+/-12.94, respectively). Terbinafine plus Glucantime (6.11+/-5.90) and Glucantime alone (4.83+/-4.82) significantly reduced spleen parasite burden compared to the infected untreated group (15.81+/-15.81, P<0.01). There was a difference in the relative weight of the spleen between the naïve and the infected untreated groups (2.5+/-0.2 vs. 9.8+/-1.0, respectively) as well as between the naïve and terbinafine groups (2.5+/-0.2 vs. 10.0+/-1.4, respectively). Glucantime alone and Glucantime plus terbinafine (2.5+/-0.2 and 4.2+/-0.6) significantly reduced the weight of the spleen in comparison with the infected untreated group. Even so, the spleen parasite burden was directly related to spleen weight. Terbinafine alone at the dose and schedule used had no effect on spleen parasite burden or relative spleen weight of L. chagasi-infected hamsters.

Animals↗
PubMed2002

Oviposition and predation by Speciomerus revoili (Coleoptera, Bruchidae) on seeds of Acrocomia aculeata (Arecaceae) in Brasília, DF, Brazil.

Oviposition and predation levels by Speciomerus revoili bruchid beetles were quantified on fruits and seeds of the macaúba palm, Acrocomia aculeata, collected from below mother-trees within the Sarah Kubitschek Park of Brasília, DF, Brazil. A maximum of 12 eggs per fruit were found, with high variations observed between samples. No clear pattern was found for the distribution of the number of eggs per fruit, perhaps due to the artificial conditions of the study area, the absence of dispersers and/or the plasticity in the oviposition behavior of the insect. The number of eggs per fruit was not related to fruit size, but was associated with their availability under the tree-mother. This suggests that the density of eggs per fruit is a balance between the availability of this resource and the number of females in the beetle population. The observed mortality rate, from the egg phase to the final larval stages, was over 75%. About 40% of the seeds of Acrocomia aculeata were predated by Speciomerus revoili.

Animals↗
PubMed2002

Nuclear medicine in primary breast cancer imaging.

The application of nuclear medicine techniques to study patients with breast cancer has recently raised its profile, particularly in the investigation 'indeterminate mammographic lesions'. This review briefly points out some of the difficulties encountered with other more conventional imaging modalities and describes the radionuclide techniques most frequently employed in the investigation of those patients with breast cancer. Both planar and single photon emission tomography methods are discussed including the use of monoclonal antibodies, perfusion ligands, receptor binding hormones and other specific radiotracers, non-specific tumour markers, as well as deoxyglucose and other amino acids labelled with positron emitting radionuclides.

Antibodies, Monoclonal↗
PubMed2002

Fluorodeoxyglucose positron emission tomography in clinical oncology: the referrer's perspective.

From January 2000 to April 2002 a prospective audit based on a questionnaire was carried out concerning the attitudes and viewpoints of clinicians referring patients to fluorodeoxyglucose positron emission tomography (FDG PET) scanning. A standard and structured audit form was posted to each referring doctor with the formal clinical report issued by the nuclear medicine consultant. Three hundred and thirty evaluable forms were analysed, a return rate of approximately 22%, from a total of 1500 PET patients studied during this period. FDG PET scanning was deemed by the referring physician to have altered the staging of cancer patients in 39% of all cases. Twenty-five per cent of patients were upstaged with FDG PET and 14% of patients downstaged. Patient management was changed in 39% of cases whilst a change in treatment occurred in 10% of cases. The reported FDG PET study was judged as being helpful in over 75% of all cases. These data further support evidence of the increasing role of FDG studies in the investigation of patients with cancer.

Adolescent↗