Maria Vieira-coelho - Academia.edu (original) (raw)

Papers by Maria Vieira-coelho

Pharmacological Research, Jul 1, 2022

BMC Psychiatry

Background Impulsivity and substance use disorders (SUD) have been both associated with changes i... more Background Impulsivity and substance use disorders (SUD) have been both associated with changes in dopaminergic processes. In this study, we intended to evaluate the dopaminergic function in imprisoned SUD offenders through the determination of s-COMT activity. Methods The study included 46 male individuals from a Portuguese penal institution. The participants were assessed through a battery of standardised instruments: Psychopathy Checklist-Revised (PCL-R), Barratt Impulsivity Scale Version 11 (BIS-11), and the European version of the Addiction Severity Index (EuropASI). In addition, s-COMT erythrocyte activity was evaluated. Results Overall, 73.9% (n = 34) of the individuals had Antisocial personality disorder (ASPD) and 58.7% (n = 27) presented SUD. We evidenced, for the first time, that, in individuals with SUD, s-COMT activity was correlated with the severity of drug dependence (EuropASI) (p = 0.009), and with BIS-11 factors self-control (p < 0.0001) and non-planning (p = 0....

Scientific Reports, 2020

The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed... more The use of cannabinoids to treat fibrotic skin diseases is an emergent issue. Therefore, we aimed to evaluate systemic and skin endocannabinoid responses in the wound-healing process in humans. A prospective study was performed in 50 patients who underwent body-contouring surgery. Anandamide (N-arachidonoylethanolamine, AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified using LC–MS/MS. Ten (20%) patients developed hypertrophic (HT) scars. No significant changes were observed between the normal (N) scar and HT scar groups in terms of plasma and skin endocannabinoids. Nevertheless, a positive correlation between plasma and skin AEA concentrations was found in the N group (r = 0.38, p = 0.015), which was absent in the HT group. Moreover, the AEA concentration was significantly lower in HT scar tissue than in normal scar tissue (0.77 ± 0.12 ng/g vs 1.15 ± 0.15 ng/g, p < 0.001). Interestingly, in all patients, the surgical int...

Fundamental & Clinical Pharmacology, 2021

Previous studies showed that cannabinoid 2 (CB2) receptor is involved in skin inflammation, fibro... more Previous studies showed that cannabinoid 2 (CB2) receptor is involved in skin inflammation, fibrogenesis and re‐epithelialization in mice, indicating that this receptor may be implicated in wound healing. Thus, topical use of cannabinoids may have a role in local fibrotic and wound healing diseases such as scars or keloids. We investigate the effect of the CB2 selective receptor agonist (6aR,10aR)‐3‐(1,1‐Dimethylbutyl)‐6a,7,10,10a‐tetrahydro‐6,6,9‐trimethyl‐6H‐dibenzo[b,d]pyran (JWH133) and the CB2 selective receptor antagonist (6‐Iodo‐2‐methyl‐1‐[2‐(4‐morpholinyl)ethyl]‐1H‐indol‐3‐yl)(4‐methoxyphenyl)‐methanone (AM630), on primary cultures of human fibroblasts. Primary cultures of adult human fibroblasts were obtained from abdominal human skin samples. Fibroblasts pretreated with JWH133 and/or AM630 were stimulated with TGF‐β (10 ng/ml). Fibroblast activation into myofibroblasts was quantified by the expression of alpha‐smooth muscle actin (α‐SMA) using Immunocytochemistry and West...

European Journal of Pharmacology, 2021

Previous studies showed that cannabinoid 1 receptor (CB1) is linked with skin fibrosis and scar t... more Previous studies showed that cannabinoid 1 receptor (CB1) is linked with skin fibrosis and scar tissue formation in mice. Therefore, the topical use of cannabinoids may have a role in the prevention or treatment of local fibrotic and wound healing diseases as hypertrophic scars or keloids. In this study, we asked whether CB1 activation or inactivation would change fibroblast differentiation into myofibroblast and collagen deposition in skin human fibroblast. Primary cultures of adult human fibroblasts were obtained from abdominal human skin. Cells were stimulated with transforming growth factor-beta (TGF-β, 10ng/ml) and treated with a CB1 selective agonist (arachidonyl-2-chloroethylamide, ACEA 1μM) and an antagonist (AM251 1, 5 and 10μM). Alpha-smooth muscle actin (α-SMA) was quantified using Immunocytochemistry and Western Blot. Collagen was quantified with Sirius Red staining assay. Significance was assessed by One-way ANOVA. P<0.05 was considered signiﬁcant. TGF-β significantly increases α-SMA expression. ACEA 1μM significantly increases collagen deposition but does not change α-SMA expression. AM251 10μM added in the absence and the presence of ACEA reduces α-SMA expression and collagen content in TGF-β treated cells. AM251 shows a concentration-dependent effect over collagen deposition with a pIC50 of 5.5 (4.6-6.4). TGF-β significantly increases CB1 receptor expression. CB1 inactivation with AM251 prevents fibroblasts differentiation and collagen deposition, induced by TGF-β in human fibroblasts. The outcome supports that CB1 is a molecular target for wound healing disorders and in vivo and pre-clinical studies should be implemented to clarify this premise.

Plastic and Reconstructive Surgery - Global Open, 2018

were narrowed in fundus examination, fundus images and fluorescein angiography, while in the othe... more were narrowed in fundus examination, fundus images and fluorescein angiography, while in the other two transplants retinal vasculature seemed similar to the control eyes. There appeared to be decreased retinal perfusion in the animals with narrowed retinal arteries as compared to controls. CONCLUSION: FA results have confirmed that retinochoroidal circulation can be established after WET in a rat model. Although 2 out of 4 rats exhibited some vascular attenuation in comparison to naïve rats, all rats exhibited a normal vascular filling pattern and the absence of vessel leakage which indicates that the structural integrity of blood-retinal barriers can be maintained after WET. The etiology of vascular attenuation and presumed decrease in retinal perfusion will be investigated in future studies.

Obesity Surgery, 2017

Background Hypertrophic scars are a consequence of wound healing. Objective The objective of the ... more Background Hypertrophic scars are a consequence of wound healing. Objective The objective of the present study is to evaluate vitamin D and inflammatory biomarker plasma levels during wound healing. Methods A prospective study was performed in patients (n = 63) submitted to body contouring surgery. Blood samples were collected before (t 0) and 5 days after surgery (t 5). Blood cell count, protein inflammatory biomarkers, and circulating plasma levels of 25(OH)D, vitamin A and vitamin E were quantified. Six months after surgery, scars were evaluated and classified as normal or hypertrophic. Results At the end of the study, 73% of the patients developed a normal scar (control group, n = 46) and 27% of the patients presented hypertrophic scars (HT group, n = 17). The patients in the HT group presented higher eosinophil (0.145 × 10 9 /L vs. 0.104 × 10 9 /L, p = 0.028) and basophil count (0.031 × 10 9 /L vs. 0.22 × 10 9 /L, p = 0.049) and C-reactive protein levels (6.12 mg/L vs. 2.30 mg/L, p = 0.015) in t 0 than the patients in the control group. At t 5 , the patients in the HT group showed a decrease in neutrophil (3.144 × 10 9/L vs. 4.03 × 10 9 /L, p = 0.031) and an increase in basophil (0.024 × 10 9 /L vs. 0.015 × 10 9 /L, p = 0.005) and lymphocyte count (1.836 × 10 9 /L vs. 1.557 × 10 9 /L; p = 0.028). Before surgery, vitamin D plasma levels were found to be decreased by almost 50% (23.52 ng/mL vs. 15.46 ng/mL, p = 0.031) in the patients who developed hypertrophic scars. Thirty-one percent of the patients submitted to bariatric surgery had more hypertrophic scars, versus 24% of the patients with no previous bariatric surgery. Conclusion There is a different systemic inflammatory profile response in the patients during the formation of hypertrophic scars. Vitamin D plasma levels are marked reduced in these patients. Considering the powerful anti-inflammatory effect of vitamin D, these findings could be related.

F1000Research, 2022

Aggression can be conceptualised as a physical act towards another person, verbal offenses, destr... more Aggression can be conceptualised as a physical act towards another person, verbal offenses, destructive acts towards objects, and self-inflicted harmful acts. It is highly frequent in the context of Antisocial Personality Disorder (ASPD) and has been correlated to disturbances in the dopaminergic system. In the prefrontal cortex, the dopamine metabolism depends on catechol-O-methyltransferase (COMT). DRD2 receptors also play a role in the expression of aggression by modulating dopamine metabolism, in the striatum. In this study, we evaluated the association between COMT activity and type of aggression, in a sample of violent male offenders. Participants were subjected to sociodemographic, clinical, and psychometric evaluation through standardised instruments. Erythrocyte S-COMT activity was measured, and COMT and the DRD2 genotypes were analysed. Individuals displaying impulsive aggression showed lower S-COMT erythrocyte activity (p=0.026) and lower frequency of Val/Val (rs4680) gen...

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2001

The present study was aimed at evaluating the role of D1- and D2-like receptors and investigating... more The present study was aimed at evaluating the role of D1- and D2-like receptors and investigating whether inhibition of Na+transepithelial flux by dopamine is primarily dependent on inhibition of the apical Na+/H+exchanger, inhibition of the basolateral Na+-K+-ATPase, or both. The data presented here show that opossum kidney cells are endowed with D1- and D2-like receptors, the activation of the former, but not the latter, accompanied by stimulation of adenylyl cyclase (EC50= 220 ± 2 nM), marked intracellular acidification (IC50= 58 ± 2 nM), and attenuation of amphotericin B-induced decreases in short-circuit current (28.6 ± 4.5% reduction) without affecting intracellular pH recovery after CO2removal. These results agree with the view that dopamine, through the activation of D1- but not D2-like receptors, inhibits both the Na+/H+exchanger (0.001933 ± 0.000121 vs. 0.000887 ± 0.000073 pH unit/s) and Na+-K+-ATPase without interfering with the Na+-independent HCO[Formula: see text] tran...

American Journal of Physiology-Cell Physiology, 1998

The aim of the present study was to examine the kinetic characteristics of thel-3,4-dihydroxyphen... more The aim of the present study was to examine the kinetic characteristics of thel-3,4-dihydroxyphenylalanine (l-DOPA) transporter and the fate of newly formed dopamine in Caco-2 cells. In the presence of 50 μM benserazide (an inhibitor of aromaticl-amino acid decarboxylase), l-DOPA was rapidly accumulated in Caco-2 cells. At equilibrium (30 min of incubation) the intracellular l-DOPA concentration was 10.2 ± 0.1 μM at a medium concentration of 0.5 μM. In saturation experiments the accumulation of l-DOPA was saturable with a Michaelis-Menten constant ( Km) of 60 ± 10 μM and a maximal reaction velocity ( Vmax) of 6.6 ± 0.3 nmol ⋅ mg protein−1⋅ 6 min−1; at 4°C the amount of l-DOPA accumulated in the cells was nonsaturable. When cells were incubated with increasing concentrations of l-DOPA (10–100 μM) in the absence of benserazide, a substantial amount of thel-DOPA that was taken up was decarboxylated to dopamine, with an apparent Kmof 27.2 μM. In experiments performed in cells cultured i...

Circulation, Oct 31, 2007

Neurobiol Aging, 2010

This study investigates α2-adrenergic receptor (α2AR) mediated feedback inhibition of catecholami... more This study investigates α2-adrenergic receptor (α2AR) mediated feedback inhibition of catecholamine release from the adrenal medulla of adult (52 weeks) and old (98 weeks) spontaneously hypertensive rats (SHR) and normotensive controls Wistar Kyoto (WKY) rats. Adrenal epinephrine content as well as the spontaneous and the nicotinic-evoked release of epinephrine were similar between adult SHR and WKY rats. Aging produced a significant reduction in epinephrine synthesis in WKY rats. In contrast, in SHR aging produced a significant increase in epinephrine release without significant changes in epinephrine synthesis. The α2AR agonist medetomidine abolished (80–90% inhibition) the nicotinic-evoked release of epinephrine in adult SHR and WKY rats. With aging, this effect was unaltered in WKY rats but was significantly decreased in SHR (30% inhibition). Adrenal α2AAR mRNA levels were significantly reduced in old SHR compared with age matched WKY rats. In conclusion, in aging the α2AR mediated feedback inhibition of epinephrine release from the adrenal medulla is preserved in WKY rats but compromised in SHR, resulting in increased epinephrine release.

Journal of Medicinal Chemistry

A novel series of potent, peripherally selective, and long-acting inhibitors of catechol-O-methyl... more A novel series of potent, peripherally selective, and long-acting inhibitors of catechol-O-methyltransferase (COMT) has been synthesized. The introduction and nature of heteroatom-containing substituents to the side-chain of the nitrocatechol pharmacophore was found to have a profound effect on both peripheral selectivity and duration of COMT inhibition in the mouse. This approach led to the discovery of 1-(3,4-dihydroxy-5-nitrophenyl)-3-[4-[3-(trifluoromethyl)phenyl]-1-piperazinyl]-1-propanone hydrochloride 35 (BIA 3-335), which was found to possess a superior inhibitory profile in vivo over both the nonselective inhibitor tolcapone 1 and the peripherally selective but short-acting entacapone 2. In this model, 35 retained 75% inhibition of peripheral COMT at 6 h after oral administration, yet significantly, only a minor reduction of central (cerebral) COMT activity was observed. Molecular modeling techniques were applied to review the analysis of the ternary enzyme-inhibitor comple...

The Journal of nutrition, 2000

The aim of the present study was to evaluate whether the sensitivity of jejunal Na(+),K(+)-ATPase... more The aim of the present study was to evaluate whether the sensitivity of jejunal Na(+),K(+)-ATPase to inhibition by dopamine (DA) in young rats is related to the type of food (breast milk vs. solid) or reflects a developmental adaptation. When 18-d-old rats were separated from their dams and fed solid food (the same used to feed adult rats) for 2 d, intestinal Na(+),K(+)-ATPase activity was significantly greater than that of breast-fed pups of the same age (20 d) (127 +/- 8 vs. 52 +/- 4 nmol Pi. mg protein(-1). min(-1); P < 0.05). Activity in rats fed solid food was insensitive to inhibition by 1 micromol/L DA. Na(+),K(+)-ATPase activity in 60-d-old rats (117. 4 +/- 4.2 nmol Pi. mg protein(-1). min(-1)) was also higher (P < 0. 05) than in breast-fed rats, and DA (1 micromol/L) did not inhibit enzyme activity. The B(max) value for binding of [(3)H]-Sch 23390 in 20-d-old breast-fed rats did not differ from that in age-matched rats fed a solid food for 2 d and or that in 60-d-old ...

Journal of Pharmacological Sciences, 2012

Up-regulation of kidney α 2-adrenoceptor expression has been implicated in the development of hyp... more Up-regulation of kidney α 2-adrenoceptor expression has been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). This study was carried out to evaluate renal sodium excretion in response to clonidine administration in SHR and control normotensive Wistar-Kyoto (WKY) rats. SHR and WKY rats (12-week-old) were placed in metabolic cages for 4 days: the first 2 days in control conditions and the following 2 days under oral clonidine treatment (100 μg/kg body weight). Clonidine produced a similar reduction in systolic blood pressure values in SHR and WKY rats, although SHR remained hypertensive. At the end of the study SHR and WKY rats presented similar noradrenaline plasma levels. However, noradrenaline kidney tissue levels were significantly higher in SHR compared to WKY rats. Under control conditions, SHR presented lower urine flow compared to WKY rats. Clonidine produced a significant decrease in urine flow in WKY rats but not in SHR. Furthermore, clonidine also produced a significant reduction in urinary sodium, potassium, and creatinine excretion in WKY rats, but had no effect in SHR. In conclusion, in SHR the reduction in systolic blood pressure and sympathetic activity produced by clonidine was not accompanied by a decrease in urine volume and sodium excretion.

British Journal of Dermatology, 2012

as adjuvant therapy to create a corticoid-sparing regimen, but was discontinued soon because of g... more as adjuvant therapy to create a corticoid-sparing regimen, but was discontinued soon because of gastrointestinal side-effects. Two months later, the patient achieved complete remission. We, for the first time, identify laminin-332 antibodies as the cause of orf-induced pemphigoid. The mechanism involved in the relation between orf and pemphigoid is still unclear. There might be a homology between laminin-332 and virus proteins, leading to a cross-reactivity also known as molecular mimicry. We performed a protein-protein blast of all protein sequences of the four orf strains whose complete genomes are deposited at NCBI GenBank (NZ2, OV-SA00, OV-18A2 and D1701) against all seven transcript variants of laminin-332. Unlike the situation described for the torque teno virus and the 180-kDa bullous pemphigoid antigen we found no overlap that was the size of an epitope (6–7 amino acids). The largest overlap was restricted to only four consecutive amino acids. If molecular mimicry of orf underlies pemphigoid here then it probably is a conformational epitope, which would also account for it binding to native skin substrate but not on immunoblot. On the other hand, it has been suggested that orf could alter basement membrane proteins, making them more antigenic. Using knockout skin for future cases could demonstrate if laminin-332 is the consistently targeted antigen in orf-induced pemphigoid.

The Journal of Physiology, 2003

The a 2-adrenergic receptors (a 2 ARs) belong to the seven transmembrane domain superfamily of G ... more The a 2-adrenergic receptors (a 2 ARs) belong to the seven transmembrane domain superfamily of G proteincoupled receptors (GPCRs) and mediate many of the physiological effects of the native catecholamines, adrenaline and noradrenaline (Guimaraes & Moura, 2001). The primary signal transduction pathway of a 2 ARs is through pertussis toxin (PTX)-sensitive G i/o proteins, which leads to inhibition of adenylyl cyclase and a reduction in intracellular cAMP (Cotecchia et al. 1990). However, under certain circumstances a 2 ARs can also couple to G s proteins leading to activation of adenylyl cyclase (Eason et al. 1992). Other physiological signalling pathways mediated by a 2 ARs include stimulation of phospholipases (A 2 , C and D), and inhibition of voltagegated Ca 2+ channels (Graham et al. 1996). Three distinct a 2 AR subtypes have been described (a 2A , a 2B and a 2C AR) based on molecular and pharmacological criteria (Guimaraes & Moura, 2001). These subtypes exhibit different cellular and tissue distributions, suggesting distinct physiological functions. The presence of a 2 ARs in the intestinal mucosa has been demonstrated in earlier studies (Valet et al. 1993). These receptors were shown to be of the a 2A subtype, and their distribution suggested preferential localization in the basolateral membranes of the proximal colon. The source of native a 2 AR agonists may be the noradrenergic fibres that extensively innervate the intestinal mucosa, endocrine cells within the epithelial layer, or circulating catecholamines. While the presence of a 2 ARs on enterocyte membranes implies a direct interaction between catecholamines and the epithelium, the mechanisms of a 2 AR-mediated effects and the nature of their molecular interaction with ion channels remain poorly defined. Classically, regulation of epithelial transport processes occurs in response to agents that alter cyclic nucleotide or

… Nutrition & Food …, 2011

We assessed the impact of oligofructose (OFS) and dextrin (DEX) as diet supplements on hepatic re... more We assessed the impact of oligofructose (OFS) and dextrin (DEX) as diet supplements on hepatic redox state. Rats were fed either a 10% OFS or a 10% DEX supplemented diet for 9 wk. In the DEX diet group, the levels of hepatic protein carbonylation were decreased by ...

LIBRO COMUNICACIONES

Objetivos: El trastorno psicótico inducido por cannabis (CIP) es cada vez más frecuente sin embar... more Objetivos: El trastorno psicótico inducido por cannabis (CIP) es cada vez más frecuente sin embargo no tiene una intervención terapéutica dirigida ni específica. La CIP puede tener una evolución aguda benigna o evolucionar a un trastorno psicótico funcional crónico como la Esquizofrenia (SZE). A pesar de que los estudios en animales proporcionan evidencia de que el cannabis desencadena mecanismos epigenéticos que interfieren con el desarrollo de procesos neurológicos y el uso de cannabis se considera un factor de riesgo para el desarrollo de SZE, la información sobre la epigenética de la psicosis inducida por cannabis es escasa. Este estudio tiene como objetivo evaluar la presencia de mecanismos epigenéticos en genes relacionados con la SZE en pacientes con un trastorno psicótico inducido por cannabis y determinar la estabilidad de los marcadores epigenéticos con el tratamiento habitual frente a la intervención con psicoterapia grupal. Material y métodos: Proponemos un ensayo de dis...

Psychiatry Research, 2016