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Biomedical subjects

C Costa

Publications and source records attributed to C Costa.

At least 19 recordsLinked to original sources

The inclusion complexes of hesperetin and its 7-rhamnoglucoside with (2-hydroxypropyl)-beta-cyclodextrin.

The effect of (2-hydroxypropyl)-beta-cyclodextrin (HP-beta-CyD) on the solubility properties and spectroscopic features of hesperetin and its 7-rhamnoglucoside, hesperidin, was qualitatively and quantitatively investigated in water, by means of UV-vis absorption and fluorescence spectroscopy. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility measurements; in both cases type-A(L) diagrams have been obtained (soluble 1:1 complexes). The higher degree of interaction showed by hesperetin may be attributed to the higher hydrophobicity and smaller size of the aglycone molecule, which therefore exhibits a greater affinity for the CyD and fits better into the cavity. The effect of molecular encapsulation on the two flavanones antioxidant activity was afterwards evaluated by means of different biological assays, concerned to the different mechanisms of in vivo action. The protection efficacy was in all cases higher for the complexed drugs, with respect to the free ones; these results are of great interest for their potential usefulness in pharmaceutics.

2-Hydroxypropyl-beta-cyclodextrin↗

The rutin/beta-cyclodextrin interactions in fully aqueous solution: spectroscopic studies and biological assays.

In the present work the feasibility of beta-cyclodextrin complexation was explored, as a tool for improving the aqueous solubility and antioxidant efficacy of rutin. By means of 1H NMR, UV-vis and circular dichroism spectroscopy the single aromatic ring of rutin was found to be inserted into the beta-cyclodextrin cavity to form a 1:1 inclusion complex. The effect of beta-cyclodextrin on the spectral features of rutin was quantitatively investigated, in fully aqueous medium, by holding the concentration of the guest constant and varying the host concentration. The associated binding constants were estimated to be 142+/-20 and 153+/-20 M(-1), respectively, on the basis of the observed UV-vis absorption and circular dichroism intensities. The antioxidant activity of rutin was also investigated, as affected by molecular encapsulation within beta-cyclodextrin (batophenanthroline test; comet assay; lipid peroxidation); the inclusion complex revealed improved antioxidant efficacy that may be in part explained by an increased solubility in the biological moiety.

Animals↗

Effects of epidural anaesthesia-analgesia on intravenous anaesthesia with propofol.

The main purpose of this study was to demonstrate that the use of epidural anaesthesia-analgesia reduces the amount of propofol necessary to maintain surgical anaesthesia in dogs during ovariohysterectomy. The study was carried out on 28 bitches undergoing ovariohysterectomy with general anaesthesia using an intravenous infusion of propofol. Dogs were allocated to one of two groups. Group 1 received systemic buprenorphine together with epidural analgesia using lidocaine and buprenophine, and in Group 2 systemic buprenorphine only was given. The mean propofol infusion rate was significantly lower in dogs with epidural analgesia (P < 0.0001). In addition, the mean endotracheal extubation time was significantly longer in dogs with epidural analgesia (P < 0.0001). No significant differences were detected in any of the physiological parameters measured.

Analgesia, Epidural↗

Low rate of occult hepatitis B virus infection among anti-HBc positive blood donors living in a low prevalence region in Brazil.

OBJECTIVE: The aim of this study was to determine the rate of occult hepatitis B virus (HBV) infection among blood donors living in a geographic region of low (5.6%) anti-HBc prevalence. SUBJECTS AND METHODS: Sera from 150 candidate blood donors whose blood was rejected due to total anti-HBc reactivity (despite absence of HBsAg) were tested for anti-HBs and IgM anti-HBc antibodies, as well as for HBeAg/anti-HBe. Serum HBV DNA was sought by using a PCR assay able to amplify part of the surface gene. Viral load was measured in the PCR positive samples. RESULTS: The pattern 'anti-HBc alone' (without HBsAg and anti-HBs antibodies) was found in 64 (42.7%) subjects. IgM anti-HBc and anti-HBe antibodies were detected in 2 (1.3%) and 80 (53.3%) samples, respectively. No sample was HBeAg-reactive. HBV DNA was repeatedly found in five (3.3%) samples, three of which were anti-HBs positive and two anti-HBs negative. All five HBV DNA positive samples showed a low viral load (<1000copies/ml). CONCLUSIONS: The data indicated a low rate of occult infection among anti-HBc positive, HBsAg negative blood donors living in a region of low prevalence of infection. Viral load was very low in all HBV infected subjects.

Adult↗

Effects of alpha- and beta-cyclodextrin complexation on the physico-chemical properties and antioxidant activity of some 3-hydroxyflavones.

Inclusion complexes of some flavonols (3-hydroxyflavone, morin and quercetin) have been obtained with alpha- and beta-cyclodextrins, by the co-evaporation method. Different analytical techniques (DSC, XRPD, FT-IR, 1H-NMR, UV-Vis) have been employed for a throughout investigation of the structural characteristics of such supramolecular aggregates, which exhibited distinct spectroscopic features and properties from both "guest" and "host" molecules. The stoichiometric ratios and stability constants describing the extent of formation of the complexes have been determined by phase-solubility studies; in all cases type-AL diagrams have been obtained (soluble 1:1 complexes). The effect of molecular encapsulation on the flavonols antioxidant activity has been afterwards evaluated, by means of different biological assays (Bathophenanthroline test; Comet assay; Lipid peroxidation). Complexation with cyclodextrins further improved the antioxidant activity, increasing drugs solubility in the biological moiety.

Antioxidants↗

Pet-therapy: a trial for institutionalized frail elderly patients.

Twenty-eight subjects with chronic age-related disabilities living in the nursing home"Istituto di Riposo per la Vecchiaia" in Torino were assigned to a pet-therapy intervention group, consisting of 3/week sessions of almost one-hour visit for 6 weeks with a little cat, of to a control group undergoing usual activity programs. The purpose of this study was to evaluate the effects of pet-therapy on nursing home inpatients. There were no differences in demographic or clinical characteristics and in mean duration of institutionalization between the two groups. Results showed that patients with animal interaction had improved depressive symptoms and a significant decrease in blood pressure values. The pet-therapy programs are desirable components of the multidisciplinary treatment for frail elderly patients in long-term care.

Aged↗

Cyclosporine increases endothelin-1 plasma levels in renal transplant recipients.

Endothelin-1 (ET-1) has been associated with the development of hypertension in cyclosporine-treated renal transplant recipients. To clarify this association, this observational study compared ET-1 levels in 33 patients taking cyclosporine therapy versus 10 controls. Three hours after cyclosporine administration, ET-1 levels were higher than in the controls, namely 1.81 + 0.99 versus 1.17 + 0.46 pg/mL (P <.04). These results suggest a role of ET-1 in the pathogenesis of post-renal transplantation hypertension in cyclosporine-treated recipients.

Adult↗

Cytotoxicity evaluation after coexposure to perchloroethylene and selected peroxidant drugs in rat hepatocytes.

There is evidence of hepatotoxic effects caused by Perchloroethylene (PCE), presumably due to reactive metabolic intermediates; lipid peroxidation is under study as a potential mechanism of toxicity. We aimed to verify if PCE levels comparable to those reached in the blood of exposed subjects can cause cell damage and lipid peroxidation. The association of PCE with lipid peroxidation inducing drugs (cyclosporine A, valproic acid and amiodarone) was also tested on rat isolated hepatocytes. AST and LDH release, MTT test and lipid peroxidation assay showed that PCE determines dose-dependent effects on rat isolated hepatocytes. The toxic potential resulting from our data would be valproic acid < cyclosporine A < amiodarone. While valproic acid and cyclosporine caused a mild toxicity, the effects of amiodarone were more severe; in particular, the association of PCE with amiodarone showed a clear additive effect. The role of lipid peroxidation in the liver toxicity exerted by the tested compounds was confirmed by our data, and resulted relevant after treatment of cells with amiodarone and PCE. Extrapolating these results to human, we can suggest that a subject professionally exposed to PCE, who chronically assumes a lipid peroxidation inducing drug like amiodarone, may be potentially exposed to a higher risk of liver toxicity.

Amino Acid Oxidoreductases↗

Creating SunSmart schools.

Kidskin was a sun-protection intervention study involving 1776 children attending 33 primary schools in Perth, Western Australia. There were three study groups: a control group, a moderate intervention group and a high intervention group. In addition to receiving a specially designed curricular intervention (1995-1998), the moderate and high intervention groups received an environmental intervention aimed at creating SunSmart schools (1996-1998). The environmental intervention focused on encouraging implementation of 'No hat, no play' policies and reducing sun exposure at lunchtime. In 1995 and 1998, observational methods were used to measure children's lunchtime sun exposure (i.e. polysulfone film badges) and hat wearing (i.e. video-taping of children). The proportion of children wearing broad-brimmed hats or legionnaire caps increased in seven of the eight high intervention schools between 1995 and 1998. In three schools, however, the impact was very positive with almost all children wearing these hats in 1998. There was no improvement in wearing these types of hats in either the moderate intervention group or the control group. In terms of sun exposure, there were only small non-significant differences among the three groups in terms of lunchtime sun exposure. The Kidskin program had a positive effect on hat wearing in the playground, but did not change children's use of shade at lunchtime. In this study, disseminating policy guidelines to schools using a mail-only strategy was ineffective, even when combined with an awards program. More information on 'champions' who bring about change in schools is required.

Child↗

Use of porcine tumor necrosis factor receptor 1-Ig fusion protein to prolong xenograft survival.

BACKGROUND: Delayed rejection of xenografts is a major hurdle that needs to be addressed to achieve long-term engraftment in the pig-to-primate transplant setting. Both vascular and avascular xenografts are susceptible to a delayed rejection process that comprises humoral and cellular responses. Tumor necrosis factor (TNF) is believed to play a role in this process by promoting cell activation, apoptosis and the recruitment of inflammatory cells. To address this problem, we engineered the donor cell in such a way that it could block both human and porcine TNF. METHODS: We produced a recombinant fusion protein containing the extracellular domain of the porcine TNF-Receptor 1 and an IgG Fc moiety (pTNFR1Ig). We first evaluated by flow cytometry the pTNFR1Ig capacity to prevent TNF alpha-induced expression of SLAI, SLAII, VCAM-1, ICAM-1 and E-selectin on the cell surface of porcine aortic endothelial cells (PAEC). The effect on TNF alpha-mediated cell death was also assessed by propidium iodide staining after incubating PAEC with TNF alpha plus cycloheximide for 24 h. PAEC and porcine fibroblasts were subsequently engineered by retroviral infection to express and secrete pTNFR1Ig and their resistance to the TNF alpha effects was tested in vitro. Finally, we transplanted mock-control and pTNFR1Ig-expressing PAEC under the kidney capsule of BALB/c mice in the absence of immunosuppression and examined the degree of rejection at 2 and 3 weeks post-transplantation. RESULTS: Treatment with pTNFR1Ig resulted in a very potent blockade of human, porcine and murine TNF alpha activity on porcine cells. It inhibited the upregulation of all cell surface markers of activation tested as well as the TNF alpha-mediated cell death. Moreover, pTNFR1Ig-expressing PAEC showed prolonged engraftment in a pig-to-mouse xenotransplant model. CONCLUSIONS: Incorporation of strategies that block TNF may prove useful in the development of xenografts resistant to delayed rejection.

Animals↗

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↗