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Biomedical subjects

E Lopes

Publications and source records attributed to E Lopes.

15 recordsLinked to original sources
PubMed2006

Graded maternal short gastrulation protein contributes to embryonic dorsal-ventral patterning by delayed induction.

Establishment of the dorsal-ventral (DV) axis of the Drosophila embryo depends on ventral activation of the maternal Toll pathway, which creates a gradient of the NFkB/c-rel-related transcription factor dorsal. Signaling through the maternal BMP pathway also alters the dorsal gradient, probably by regulating degradation of the IkB homologue Cactus. The BMP4 homologue decapentaplegic (dpp) and the BMP antagonist short gastrulation (sog) are expressed by follicle cells during mid-oogenesis, but it is unknown how they affect embryonic patterning following fertilization. Here, we provide evidence that maternal Sog and Dpp proteins are secreted into the perivitelline space where they remain until early embryogenesis to modulate Cactus degradation, enabling their dual function in patterning the eggshell and embryo. We find that metalloproteases encoded by tolloid (tld) and tolkin (tok), which cleave Sog, are expressed by follicle cells and are required to generate DV asymmetry in the Dpp signal. Expression of tld and tok is ventrally restricted by the TGF-alpha ligand encoded by gurken, suggesting that signaling via the EGF receptor pathway may regulate embryonic patterning through two independent mechanisms: by restricting the expression of pipe and thereby activation of Toll signaling and by spatially regulating BMP activity.

Animals↗
PubMed2001

BI- and tricyclic diterpenoids from Halimium viscosum.

The study of the acid and neutral parts of the n-hexane extract of Halimium viscosum (S. João da Pesqueira, Portugal) has led to the isolation of various known diterpenoids with the ent-halimane skeleton. Five new compounds have now been isolated, one with the ent-halimane skeleton, and four with the valparane skeleton, two of them with the valparane skeleton degraded. The structures of these compounds, determined by spectroscopic methods using 2D experiments (1H-13C, HMQC and HMBC), were dimethyl 1(10)-halimen-15,18-dioate, dimethyl 3,19-dinor-15-valparen-2,4-dioate, methyl 16-nor-2,3-secovalpara-3,15-dioxo-2-oate, 1,3,5,1 5-valparatetraene and 3R-4alpha-methoxy-15-valparen-2-one.

Cistaceae↗
PubMed2000

Polymeric colloidal systems containing ethionamide: preparation and physico-chemical characterization.

The association of ethionamide with different colloidal systems was evaluated. Nanocapsules (NC), nanospheres (NS), and nanoemulsions (NE) were prepared by interfacial deposition and spontaneous emulsification techniques. Ethionamide was incorporated before (B) and after (A) preparation of nanoparticles. Ethionamide was assayed by HPLC, the particle size was determined using a Nanosizer, and the zeta potential using a Zetasizer 4. Free ethionamide was determined using a combined ultrafiltration-centrifugation technique. The drug release was determined by direct dilution of the nanoparticle dispersion in phosphate-buffer pH 7. All preparations retained acceptable particle size distribution (+/- 300 nm), except the NE. The zeta potential of all formulations was between -36.6 mV and -46.1 mV. Percentages of ethionamide associated were: NC (B: 62.4%, A: 56.2%), NS (B: 53.0%, A: 43.2%), and NE (B: 38.5%). After 45 days, the percentage of drug association with NC increased (B: 66.8%, A: 60.6%). The release profiles demonstrated that associated ethionamide was more readily released from the NC and NS prepared by procedure A rather than B. The ethionamide amount not released (B) was greater in NS than NC. The drug is mainly adsorbed onto the surface of nanoparticles. However, approximately 10% of ethionamide is encapsulated into NC and 20% entrapped into NS, respectively.

Antitubercular Agents↗
PubMed1996

Heterogenous point mutations in the BRCA1 breast cancer susceptibility gene occur in high frequency at the site of homonucleotide tracts, short repeats and methylatable CpG/CpNpG motifs.

Heterogeneous mutations in the BRCA1 tumour suppressor gene are responsible for a large percentage of inherited breast cancers as well as breast/ovarian cancers in families with a high incidence of both cancer types. Over a hundred BRCA1 mutations have been reported, but little is known of the mechanism(s) responsible for BRCA1 mutagenesis. To determine the significance of specific nucleotide sequences at mutational sites within the BRCA1 gene, we assessed how frequently independent BRCA1 mutations occur at the site of short direct repeats, single nucleotide repeats (homonucleotides) and at CpG and CpNpG motifs. We found that homonucleotide and short direct repeats are commonly associated with small deletions and insertions. Substitution mutations are frequently associated with homonucleotide repeats and with methylatable CpG dinucleotides and CpNpG trinucleotides. Our methylation and sequencing experiments show that CpG and certain CpNpG motifs are methylated, supporting the hypothesis that DNA methylation specificity at these sites may be an important contributor to BRCA1 mutagenesis. We suggest that BRCA1 mutations are acquired by replication errors and are retained by cells through an intricate balancing of replication and repair mechanisms. Such mutations may provide a proliferative advantage for a cell, leading to the tumour phenotype.

BRCA1 Protein↗
PubMed1994

Ivermectin treatment of bancroftian filariasis in Recife, Brazil.

To determine the effectiveness of single oral dosages of ivermectin ranging between 20 and 200 micrograms/kg and to make detailed observations of both the kinetics of parasite killing and the adverse reactions induced by treatment, the present double-blind study on ivermectin treatment of lymphatic filariasis caused by Wuchereria bancrofti was undertaken with 43 microfilaremic patients in Recife, Brazil. Follow-up at one year indicated equivalent efficacy for the 20-, 100-, and 200-micrograms/kg drug dosages in reducing microfilaremia to geometric means of 13-25% of pretreatment levels. Adverse clinical reactions (predominantly fever, headache, weakness, and myalgia) occurred to some degree in almost all patients but generally lasted only 24-48 hr and were easily managed symptomatically. Adverse reactions were significantly milder in those receiving the lowest (20 micrograms/kg) ivermectin dose, and they were significantly correlated with individuals' pretreatment microfilaremia levels in all groups. Posttreatment eosinophilia was a regular feature of the response to treatment, with the magnitude and kinetics also proportional to pretreatment microfilarial levels. Transient pulmonary function abnormalities (16 of 42, 38%), liver enzyme elevations (10 of 43, 23%), and hematuria (9 of 42, 22%) developed posttreatment, but all cleared without significant complications. The results indicate that W. bancrofti from Brazil is similar to strains of the parasites studied elsewhere in susceptibility to ivermectin, that the drug's systemic adverse reactions are essentially those resulting from parasite clearance, and that the intensity of these reactions can be significantly reduced by using the low (20 micrograms/kg) dose of ivermectin. This detailed dose-finding study provides information necessary for developing optimal regimens to treat bancroftian filariasis with ivermectin either alone or in combination with other medications.

Adult↗
PubMed1992

Essential thrombocythemia--clinical features, therapy and follow-up of 12 cases.

The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyurea (HU) in conventional dosage. A clinical response was seen in seven patients treated with IFN-alpha 2b (4 CR and 2 PR), and in four patients treated with HU (3 CR and 1 PR). No significant side effects were observed. Our findings indicate that IFN-alpha 2b offers a non-leukaemogenic and very promising therapeutic alternative for E.T.

Aged↗
PubMedDate not supplied

Tolerance of diethylcarbamazine by microfilaraemic and amicrofilaraemic individuals in an endemic area of Bancroftian filariasis, Recife, Brazil.

To determine the tolerance to diethylcarbamazine (DEC) treatment of patients with Bancroftian filariasis, 193 individuals (138 asymptomatic microfilaraemic, 30 amicrofilaraemic diseased patients and 25 asymptomatic amicrofilaraemic endemic residents) were enrolled in a prospective trial with different dose schedules, in a hospital and outpatient clinic setting in Brazil. Systemic adverse reactions, localized adverse reactions, and side effects, related to microfilariae, adult worms and the drug itself, were evaluated. Systemic reactions occurred irrespective of the DEC dose and schedule in about 40% of the microfilariae carriers, but not in amicrofilaraemic diseased patients or residents; they usually consisted of microscopic haematuria, followed by fever and malaise. Localized reactions were manifested by the appearance of inflammatory reactions, mainly in the scrotal area. Nodules containing degenerating adult worms developed mainly in the scrotal lymphatics of microfilaraemic patients, diseased amicrofilaraemic patients, and residents. Drowsiness, which increased with higher doses of DEC, was the most common side effect in both microfilaraemic and amicrofilaraemic individuals, followed by nausea and gastric upset. The results indicate that the occurrence of systemic and local adverse reactions was unrelated to either the dose of DEC or the pretreatment microfilarial density. The severity of systemic reactions was proportional to the microfilarial density. Side effects were dependent on the drug dosage irrespective of infection status.

Adolescent↗