Biomedical subjects

Tiago Rodrigues

Publications and source records attributed to Tiago Rodrigues.

7 recordsLinked to original sources

PubMed2026

Optimizing prostate biopsy decision making - (MUSIC-screen): A 1:1 randomized controlled trial comparing micro-ultrasound versus multiparametric magnetic resonance imaging for prostate cancer diagnosis.

BACKGROUND: Micro-ultrasound (microUS) represents a potential alternative to multiparametric magnetic resonance (mpMRI) in guiding prostate biopsy, with level 1 evidence demonstrating non-inferiority to detect Grade Group ≥2 (GG ≥ 2) prostate cancer in biopsy-naïve men. However, a critical gap remains in the screening pathway, in which imaging is needed to identify men at risk and determine whether biopsy is warranted. METHODS: MUSIC-Screen is a phase 3, open-label, noninferiority 1:1 randomized controlled trial evaluating microUS as an alternative imaging compared to mpMRI for determining the need for prostate biopsy in biopsy- and imaging- naïve men at risk for GG ≥ 2. A total of 1284 men will be randomized to undergo either microUS or mpMRI. Men with PRI-MUS 3-5 or PI-RADS 3-5 lesion will undergo targeted and systematic biopsy. Men with negative imaging and PSA density ≥ 0.15 will undergo systematic biopsy, while those with PSA density < 0.15 will defer biopsy. RESULTS: The primary outcome is GG ≥ 2 detection in each study arm. The primary hypothesis is that microUS is non-inferior to mpMRI for screening and detection of GG ≥ 2. Secondary objectives include comparison of GG ≥ 2 detection rates in targeted cores among patients with PRI-MUS or PI-RADS scores of 3-5, proportion of men who defer biopsy but are diagnosed with GG ≥ 2 within 8 years, assessment of the negative predictive value of each imaging modality, and health economic analyses. CONCLUSION: MUSIC-Screen will determine whether microUS can be used as an imaging modality to inform biopsy decision making that is non-inferior to mpMRI for GG ≥ 2 prostate cancer detection. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06626022.

Humans↗

PubMed2006

Photochemically generated stable cation radical of phenothiazine aggregates in mildly acid buffered solutions.

This work characterizes, for the first time, the photochemical behavior of the antipsychotic drugs thioridazine (TR), trifluoperazine (TFP), and fluphenazine (FP) influenced by the aggregation state of the molecules. Samples of monomeric and aggregated forms of phenothiazines were submitted to 20 min of irradiation at 254 nm for intervals of 1, 5, 10, 15, 20, or 25 days. In high phenothiazine concentrations, the irradiation led to the appearance of absorbance bands in the visible region peaking at 633 nm for TR and 509 nm for FP and TFP. In the dark, at room temperature and at 4 degrees C, these bands disappeared, after approximately 15 and approximately 60 min, respectively, but reappeared after a new irradiation session. These visible bands were assigned to stable cation radicals that were characterized by direct EPR measurements and by flash photolysis. Photogenerated stable cation radicals in the phenothiazine aggregates at room temperature are formed probably due to the stacking of the thiazine phenyl moieties. For the monomeric forms of phenothiazines, the spectral changes observed during the irradiation suggested the formation of sulfoxide and hydroxylated derivates. Oxidized derivates were detected by mass spectrometry of the aggregated forms of phenothiazines (>100 microM) only in the samples irradiated for more than 20 days. In contrast, monomeric phenothiazines were totally converted to the oxidized forms after 20 min of irradiation. Surface tension measurements of phenothiazines revealed that, in concentrations above 100 microM, the drugs formed aggregates. In the case of TR, small-angle X-ray scattering measurements indicated that this compound forms large lamellar-like aggregates in aqueous solutions.

Acids↗

PubMed2006

Effects of isocoumarins isolated from Paepalanthus bromelioides on mitochondria: uncoupling, and induction/inhibition of mitochondrial permeability transition.

Isolated mitochondria may undergo uncoupling, and in presence of Ca(2+) at different conditions, a mitochondrial permeability transition (MPT) linked to protein thiol oxidation, and demonstrated by CsA-sensitive mitochondrial swelling; these processes may cause cell death either by necrosis or by apoptosis. Isocoumarins isolated from the Brazilian plant Paepalanthus bromelioides (Eriocaulaceae) paepalantine (9,10-dihydroxy-5,7-dimethoxy-1H-naptho(2,3c)pyran-1-one), 8,8'-paepalantine dimer, and vioxanthin were assayed at 1-50 microM on isolated rat liver mitochondria, for respiration, MPT, protein thiol oxidation, and interaction with the mitochondrial membrane using 1,6-diphenyl-1,3,5-hexatriene (DPH). The isocoumarins did not significantly affect state 3 respiration of succinate-energized mitochondria; they did however, stimulate 4 respiration, indicating mitochondrial uncoupling. Induction of MPT and protein thiol oxidation were assessed in succinate-energized mitochondria exposed to 10 microM Ca(2+); inhibition of these processes was assessed in non-energized organelles in the presence of 300 microM t-butyl hydroperoxide plus 500 microM Ca(2+). Only paepalantine was an effective MPT/protein thiol oxidation inducer, also releasing cytochrome c from mitochondria; the protein thiol oxidation, unlike mitochondrial swelling, was neither inhibited by CsA nor dependent on the presence of Ca(2+). Vioxanthin was an effective inhibitor of MPT/protein thiol oxidation. All isocoumarins inserted deeply into the mitochondrial membrane, but only paepalantine dimer and vioxantin decreased the membrane's fluidity. A direct reaction with mitochondrial membrane protein thiols, involving an oxidation of these groups, is proposed to account for MPT induction by paepalantine, while a restriction of oxidation of these same thiol groups imposed by the decrease of membrane fluidity, is proposed to account for MPT inhibition by vioxanthin.

Animals↗

PubMed2005

The interaction of flavonoids with mitochondria: effects on energetic processes.

The study addressed aspects of energetics of isolated rat liver mitochondria exposed to the flavonoids quercetin, taxifolin, catechin and galangin, taking into account influences of the 2,3 double bond/3-OH group and 4-oxo function on the C-ring, and o-di-OH on the B-ring of their structures, as well as mitochondrial mechanisms potentially involved in cell necrosis and apoptosis. The major findings/hypothesis, were: The 2,3 double bond/3-OH group in conjugation with the 4-oxo function on the C-ring in the flavonoid structure seems favour the interaction of these compounds with the mitochondrial membrane, decreasing its fluidity either inhibiting the respiratory chain of mitochondria or causing uncoupling; while the o-di-OH on the B-ring seems favour the respiratory chain inhibition, the absence of this structure seems favour the uncoupling activity. The flavonoids not affecting the respiration of mitochondria, induced MPT. The ability of flavonoids to induce the release of mitochondria-accumulated Ca(2+) correlated well with their ability to affect mitochondrial respiration on the one hand, and their inability to induce MPT, on the other. The flavonoids causing substantial respiratory chain inhibition or mitochondrial uncoupling, quercetin and galangin, respectively, also decreased the mitochondrial ATP levels, thus suggesting an apparent higher potential for necrosis induction in relation to the flavonoids inducing MPT, taxifolin and cathechin, which did not decrease significantly the ATP levels, rather suggesting an apparent higher potential for apoptosis induction.

Adenosine Triphosphate↗

PubMed2003

A proposed sequence of events for cadmium-induced mitochondrial impairment.

Cadmium is a very important environmental toxicant, the cytotoxicity mechanism of which is likely to involve mitochondria as a target. In the present study we addressed the cause/effect relationship between the multiple cadmium-induced responses involving the mitochondrial energetic and oxidative status. Assays were performed with succinate-energized rat liver mitochondria incubated with 5 microM CdCl(2) for 0-25 min, in the absence or presence, respectively, of N-ethylmaleimide (NEM), butylhydroxytoluene (BHT), ruthenium red (RR), and cyclosporine A+ADP. A sequence of events accounting for cadmium-induced mitochondrial impairment is proposed, beginning with an apparent interaction of Cd(2+) with specific protein thiols in the mitochondrial membrane, which stimulates the cation's uptake via the Ca(2+) uniporter, and is followed by the onset of mitochondrial permeability transition (MPT); both effects dissipate the transmembrane electrical potential (Deltapsi), causing uncoupling, followed by an early depression of mitochondrial ATP levels. The respiratory chain subsequently undergoes inhibition, generating reactive oxygen species which together with iron mobilized by the cation, cause late, gradual mitochondrial membrane lipid peroxidation.

Adenosine Triphosphate↗

PubMed2002

Thioridazine interacts with the membrane of mitochondria acquiring antioxidant activity toward apoptosis--potentially implicated mechanisms.

We evaluated the effects of the phenothiazine derivative thioridazine on mechanisms of mitochondria potentially implicated in apoptosis, such as those involving reactive oxygen species (ROS) and cytochrome c release, as well as the involvement of drug interaction with mitochondrial membrane in these effects. Within the 0 - 100 microM range thioridazine did not reduce the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH) nor did it chelate iron. However, at 10 microM thioridazine showed important antioxidant activity on mitochondria, characterized by inhibition of accumulation of mitochondria-generated O2*-, assayed as lucigenin-derived chemiluminescence, inhibition of Fe2+/citrate-mediated lipid peroxidation of the mitochondrial membrane (LPO), assayed as malondialdehyde generation, and inhibition of Ca2+/t-butyl hydroperoxide (t-BOOH)-induced mitochondrial permeability transition (MPT)/protein-thiol oxidation, assayed as mitochondrial swelling. Thioridazine respectively increased and decreased the fluorescence responses of mitochondria labelled with 1-aniline-8-naphthalene sulfonate (ANS) and 1-(4-trimethylammonium phenyl)-6 phenyl 1,3,5-hexatriene (TMA-DPH). The inhibition of LPO and MPT onset correlated well with the inhibition of cytochrome c release from mitochondria. We conclude that thioridazine interacts with the inner membrane of mitochondria, more likely close to its surface, acquiring antioxidant activity toward processes with potential implications in apoptosis such as O2*- accumulation, as well as LPO, MPT and associated release of cytochrome c.

Anilino Naphthalenesulfonates↗

PubMed2002

The critical role of mitochondrial energetic impairment in the toxicity of nimesulide to hepatocytes.

We described the effects of nimesulide (N-[4-nitro-2-phenoxyphenyl]-methanesulfonamide) and its reduced metabolite in isolated rat hepatocytes. Nimesulide stimulated the succinate-supported state 4 respiration of mitochondria, indicating an uncoupling effect of the drug. Incubation of hepatocytes with nimesulide (0.1-1 mM) elicited a concentration- and time-dependent decrease in cell viability as assessed by lactate dehydrogenase leakage, a decrease of mitochondrial membrane potential as assessed by rhodamine 123 retention, and cell ATP depression. Nimesulide also decreased the levels of NAD(P)H and glutathione in hepatocytes, but the extent of the effects was less pronounced in relation to the energetic parameters; in addition, these effects did not imply the peroxidation of membrane lipids. The decrease in the viability of hepatocytes was prevented by fructose and, to a larger extent, by fructose plus oligomycin; it was stimulated by proadifen, a cytochrome P450 inhibitor. In contrast, the reduced metabolite of nimesulide did not present any of the effects observed for the parent drug. These results indicate that: 1) nimesulide causes injury to the isolated rat liver cells, 2) this effect is mainly mediated by impairment of ATP production by mitochondria due to uncoupling, and 3) on account of the activity of its nitro group, the parent drug by itself is the main factor responsible for its toxicity to the hepatocytes.

Adenosine Triphosphate↗