Biomedical subjects

Eugénia Pinto

Publications and source records attributed to Eugénia Pinto.

11 recordsLinked to original sources

PubMed2006

Antifungal activity of the essential oil of Thymus pulegioides on Candida, Aspergillus and dermatophyte species.

The composition of the essential oil of Thymus pulegioides and its antifungal activity on Candida, Aspergillus and dermatophyte fungal strains were studied. Essential oil from the aerial parts of the plant was obtained by hydrodistillation and analysed by GC and GC-MS. The oil showed high contents of carvacrol and thymol. The MIC and minimal lethal concentration were used to evaluate the antifungal activity against Candida (seven clinical isolates and four ATCC type strains), Aspergillus [five clinical isolates, and two Colección Española de Cultivos Tipo (CECT) and two ATCC type strains] and five clinical dermatophyte strains. Antifungal activity was evaluated for the essential oil and for its main components. To clarify its mechanism of action on yeasts and filamentous fungi, flow-cytometric studies of cytoplasmic membrane integrity were performed, and the effect on the amount of ergosterol was investigated. Results showed that T. pulegioides essential oil exhibited a significant activity against clinically relevant fungi, mainly due to lesion formation in the cytoplasmic membrane and a considerable reduction of the ergosterol content. The present study indicates that T. pulegioides essential oil has considerable antifungal activity, deserving further investigation for clinical applications.

Antifungal Agents↗

PubMed2004

Characterization of phorbol esters activity on individual mammalian protein kinase C isoforms, using the yeast phenotypic assay.

An alternative in vivo assay, based on growth inhibition of yeast expressing an individual mammalian protein kinase C (PKC) isoform (proportional to the degree of PKC activation), was used to characterize the activities of phorbol-12-myristate-13-acetate (PMA) and its analogues on classical (alpha and betaI), novel (delta and eta) and atypical (zeta) PKC isoforms. Effects of PMA, 4alpha-PMA, phorbol-12-myristate-13-acetate-4-O-methyl-ether (MPMA), phorbol-12-monomyristate (PMM), phorbol-12,13-diacetate (PDA), phorbol-13-monoacetate (PA), phorbol-12,13-dibutyrate (PDB), phorbol-12,13-didecanoate (PDD) and 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA), on growth of yeast expressing individual PKC isoforms was determined. PMA-induced growth inhibition on all isoforms tested (except on PKC-zeta). PDD and PDB presented an efficacy similar to PMA; the other PMA-analogues presented lower efficacies. MPMA and 4alpha-PMA stimulated growth of yeast expressing classical PKCs and reduced the PMA-induced growth inhibition, effects similar to those exhibited by the PKC inhibitors chelerythrine and R-2,6-diamino-N-[[1-(1-oxotridecyl)-2-piperidinyl]methyl]-hexanamide dihydrochloride (NPC 15437). This study reveals that phorbol esters differ on their potency to activate a given PKC isoform, and presents their isoform-selectivity. Furthermore, MPMA and 4alpha-PMA caused effects similar to those expected from PKC inhibition.

Animals↗

PubMed2004

Prevalence of lysosomal storage diseases in Portugal.

Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders individually considered as rare, and few data on its prevalence has been reported in the literature. The overall birth prevalence of the 29 different LSDs studied in the Portuguese population was calculated to be 25/100000 live births, twice the prevalence previously described in Australia and in The Netherlands. The comparison of the prevalence profile of the LSDs presenting a prevalence higher than 0.5/100000 in the Portuguese, Dutch and Australian populations showed, in the Portuguese, the existence of a higher prevalence of GM2 gangliosidoses (B variant), mucolipidoses (II and III), Niemman-Pick type C and metachromatic leukodystrophy (MLD), and a lower prevalence of Pompe and Fabry. The highest prevalence value for a single LSD is the one of GM2 gangliosidoses (B variant), corresponding to 3/100000, a value which is significantly higher than the prevalence of the most frequent LSD in Dutch, Pompe disease (2/100000) and Australians, Gaucher's disease (GD) (1.8/100000). It is worth noting that the highest prevalence of GM2 gangliosidoses found in the Portuguese is mainly due to the existence of a unique subtype, the rare juvenile B1 variant.

Humans↗

PubMed2003

Inhibition of protein kinase C by synthetic xanthone derivatives.

The modulatory activity of two xanthones (3,4-dihydroxyxanthone and 1-formyl-4-hydroxy-3-methoxyxanthone) on isoforms alpha, betaI, delta, eta and zeta of protein kinase C (PKC) was evaluated using an in vivo yeast phenotypic assay. Both xanthones caused an effect compatible with PKC inhibition, similar to that elicited by known PKC inhibitors (chelerythrine and NPC 15437). PKC inhibition caused by xanthones was confirmed using an in vitro kinase assay. The yeast phenotypic assay revealed that xanthones present differences on their potency towards the distinct PKC isoforms tested. It is concluded that 3,4-dihydroxyxanthone and 1-formyl-4-hydroxy-3-methoxyxanthone may become useful PKC inhibitors and xanthone derivatives can be explored to develop new isoform-selective PKC inhibitors.

Alkaloids↗

PubMed2003

Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population.

A series of 53 Portuguese patients (derived from 43 families) born in the period 1963-1999 have been diagnosed with neuronal ceroid lipofuscinosis (NCL) based on clinicopathological findings. Plotting the cumulative number of new cases per year against the year of birth resulted in a slightly S-shaped curve, with a nearly straight central segment over a period of 14 years (1977-1990) indicating a continuous registration of new cases born during the corresponding time period. In this period the prevalence of overall NCL in the Portuguese population was calculated to be 1.55 per 100.000 live births.Twenty-six patients from 20 unrelated families were further evaluated by combining clinicopathological with biochemical and genetic data. No intra-familial heterogeneity was observed. Four sub-types of childhood NCL were identified: infantile NCL (INCL) with granular osmiophilic inclusions (GROD) and PPT1 deficiency (1/26), classical LINCL with curvilinear (CV) inclusions and tripeptidyl peptidase (TPP1) deficiency (3/26), variant late infantile NCL (LINCL) with fingerprint/curvilinear (FP/CV) inclusions and normal TPP1 enzyme activity (11/26) and juvenile NCL (JNCL) with a mix of FP/CV (11/26). Eight of 11 JNCL patients were homozygous for the 1.02-kb deletion in the CLN3 gene, and 3 were heterozygous with an unidentified mutation in the second allele. The 1.02-kb deletion in the CLN3 gene accounted for 86.3 % (19/22) of CLN3-causing alleles and 36.5 % (19/52) of childhood NCL defects. The causal mutations for CLN1 and CLN2 were V181M (2/2) and R208X (4/6), respectively. CLN1, CLN2 and CLN3 affected 3.8 %, 11.5 % and 42.3 % of NCL Portuguese patients, respectively. In 42.3 % of patients affected by the vLINCL form, CLN3, CLN5 and CLN8 gene defects were excluded by direct sequencing of cDNA. Genetic variants such as CLN6 might therefore cause a significant portion of childhood NCL in the Portuguese population. The relative frequency of classical childhood forms of NCL in the Portuguese population is reported and contributes to the knowledge of genetic epidemiology of these world-widely distributed disorders.

Adolescent↗

PubMed2003

ARSA-PD associated alleles in the Portuguese population: frequency determination and haplotype analysis.

Arylsulfatase A pseudodeficiency (ARSA-PD) may be related to increased susceptibility to neuro-psychiatric disorders. An association of allele 2417G/3352A with schizophrenia was found in a group of Portuguese patients. In the Portuguese population, at least one PD associated alteration exists in 18.3% of the ARSA alleles. Allele 2417G/3352G was invariably associated with a conserved haplotype, while 2417G/3352A and the rare 2417A/3352G alleles appeared on different haplotypes.

Adolescent↗

PubMed2003

Inhibition of alpha, betaI, delta, eta, and zeta protein kinase C isoforms by xanthonolignoids.

The effect of the xanthonolignoids trans-(+/-)-kielcorin C, cis-(+/-)-kielcorin C, trans-(+/-)-kielcorin D, trans-(+/-)-isokielcorin D and trans-(+/-)-kielcorin E on isoforms alpha, betaI, delta, eta and zeta of protein kinase C (PKC) was studied using the yeast phenotypic assay. All the compounds tested revealed an effect compatible with PKC inhibition, similar to that exhibited by the well established PKC inhibitor chelerythrine, and with differences in their potency towards the distinct isoforms tested, being, in general, potent inhibitors of the atypical PKC isoform (PKC-zeta). PKC inhibition caused by these kielcorins was confirmed using an in vitro kinase assay. The present study constitutes the first attempt to unravel the molecular mechanism of kielcorins activity, and shows that xanthonolignoids are a promising group of compounds to investigate for isoform selective PKC inhibitors.

Alkaloids↗

PubMed2003

Isoform-selectivity of PKC inhibitors acting at the regulatory and catalytic domain of mammalian PKC-alpha, -betaI, -delta, -eta and -zeta.

The aim of the present study was to compare the potency of a series of widely used PKC inhibitors acting either at the regulatory (NPC 15437, tamoxifen and D-sphingosine) or at the catalytic domain (Ro 32-0432, chelerythrine and rottlerin) on individual mammalian PKC isoforms of the classical (alpha and betaI), novel (delta and eta) and atypical (zeta) PKC families, using the yeast phenotypic assay, in order to determine their isoform-selectivity. The PKC inhibitors studied presented differences in their ability to reduce the effect of the appropriate PKC activator (estimated as EC50 ratios) which was interpreted as an index of PKC inhibitory potency. In general, the more marked inhibition was observed on novel PKC isoforms, particularly on PKC-eta. This study indicates promising isoform-selectivity of some PKC inhibitors, namely NPC 15437 for PKC-eta or rottlerin for both novel PKC isoforms. It also suggests that the PKC domain involved in the inhibition does not seem to be relevant for the potency and isoform-selectivity of PKC inhibitors.

Acetophenones↗

PubMed2002

Synthesis and in vivo modulatory activity of protein kinase C of xanthone derivatives.

The modulatory activity of a series of 20 simple xanthones on isoforms alpha, betaI, delta, eta and zeta of protein kinase C (PKC) was evaluated using an in vivo yeast phenotypic assay. Hydroxy and/or methoxyxanthones were synthesised. The majority of these compounds caused an effect compatible with activation of PKC and some showed to be more effective than the standard PKC activator (PMA or arachidonic acid). The xanthones tested differ in their efficacy and potency towards individual PKC isoforms and some showed higher selectivities for PKC-delta, -eta or -zeta, suggesting that xanthone derivatives can become valuable research tools to elucidate the physiological roles of these isoforms.

Animals↗

PubMed2002

Differential activation of protein kinase C isoforms by euxanthone, revealed by an in vivo yeast phenotypic assay.

The protein kinase C (PKC) modulatory effects of euxanthone, isolated from the wood of Cratoxylum maingayi, on isoforms alpha, betaI, delta, eta and zeta were characterised using an alternative in vivo yeast phenotypic assay. The present study shows that euxanthone can activate isoforms alpha, betaI, delta, eta and zeta, being more effective on PKC-betaI, -delta, -eta and -zeta than the established PKC activators used (the phorbol ester PMA and arachidonic acid for PKC-zeta). Furthermore, euxanthone presents differences on its potency towards individual PKC isoforms, showing a remarkable selectivity for PKC-zeta. These results can help to clarify the molecular basis of the euxanthone-mediated effects.

Clusiaceae↗

PubMedDate not supplied

[Broncho-pulmonary adenomas].

Adenomas of solitary gland type together with papillomas are the true benign tumours in or around the bronchial tree. Alveolar adenoma and papillary adenoma are more frequently observed in peripheral parenchime although this group of tumours is very rare and often incidentally diagnosed. Presenting usually as solitary nodules in adults after 45 years, are easily recognized because of distinct morphology but alveolar adenomas may be difficult to evaluate in frozen sections. Two cases of pleomorphic adenoma and alveolar adenoma are presented and a review of literature is made.

Adenoma↗