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Biomedical subjects

A S Santos

Publications and source records attributed to A S Santos.

16 recordsLinked to original sources
PubMed2006

Structure-activity relationship study of flavone compounds with anti-HIV-1 integrase activity: a density functional theory study.

Human immunodeficiency virus type-1 integrase (HIV-1 IN) is an essential enzyme for effective viral replication. Flavone compounds have been very much studied due to their activity during the inhibition process of HIV-1 IN. In this study, we employed density functional theory (DFT) using the B3LYP hybrid functional to calculate a set of molecular properties for 32 flavonoid compounds with anti-HIV-1 IN activity. The stepwise discriminant analysis (SDA), principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods were employed to reduce dimensionality and investigate possible relationship between the calculated properties and the anti-HIV-1 IN activity. These analyses showed that the molecular hydrophobicity (ClogP), charge on atom 11 and electrophilic index (omega) are responsible for the separation between anti-HIV-1 IN active and inactive compounds.

Cluster Analysis↗
PubMed2006

Human exposure to Anaplasma phagocytophilum in Portugal.

A retrospective study to detect Anaplasma phagocytophilum antibodies by indirect immunofluorescence (IFA) and Western blot (WB) assay was conducted in 367 potentially exposed patients from Portugal. The study included 26 patients with confirmed Lyme borreliosis (LB), 77 with suspected LB, 264 seronegative patients studied for possible tick-transmitted LB and boutonneuse fever (LB/BF) infection, and 96 healthy blood donors. Overall, patients with LB and suspected LB (n = 2 [7.7%] and n = 6 [7.8%], respectively) were more often seropositive (n = 8 [7.8%]; P < 0.001), whereas only 1 (0.4%; P = 0.046) patient in the LB/BF seronegative group had confirmed disease. This study is the first evidence of human exposure to A. phagocytophilum or an antigenically similar bacterium in Portugal, and suggests that LB patients are significantly more likely to contact A. phagocytophilum.

Anaplasma phagocytophilum↗
PubMed2006

Ticks and tick-borne Rickettsiae surveillance in Montesinho Natural Park, Portugal.

This study constitutes the first contribution to the knowledge of tick dynamics and its implication in the epidemiology of rickettsial diseases in Montesinho Natural Park (MNP), Bragança district of Portugal. Of 76 ticks collected, 12 (15.8%) were Dermacentor (D.) marginatus, 36 (47.4%) D. reticulatus, and 28 (36.8%) Rhipicephalus (R.) sanguineus. Isolation assays were performed by shell-vial technique on 41 ticks. Israeli spotted fever strain was an isolate from R. sanguineus, and three isolates of Rickettsia slovaca were obtained from D. reticulatus. All 76 ticks were screened by PCR for Rickettsia sp., Ehrlichia (E.) chaffeensis, and Anaplasma (A.) phagocytophilum. Rickettsia RpA4 strain DNA was detected in 10 D. marginatus and 2 D. reticulatus, and Israeli spotted fever strain in 1 R. sanguineus. No E. chaffeensis or A. phagocytophilum infection was detected. New host records are provided for D. reticulatus. Also described for the first time in Portugal is the isolation of R. slovaca from D. reticulatus and the isolation of Israeli spotted fever strain from R. sanguineus. This confirms the association of the last rickettsiae strain with the same vector tick as previously described in Israel and Sicily.

Animals↗
PubMed2006

Monoid sublingual immunotherapy.

Sublingual monoid immunotherapy with monomeric allergoids has been largely used in Europe in the last few years. An open trial of allergoid in tablets has been done in rhinitic patients allergic to house dust mites, grass pollens and Parietaria with clear improvement in clinics and drug consumption scores. In a second phase a double blind placebo controlled trial of grass pollens allergoids have been done in hay fever patients with significant decrease on the scores of rhinorrea, sneezing and conjunctivitis nasal steroid consumption and clinical score after serial nasal challenges. Monomeric allergoids are an efficace and safe immunotherapy in allergic rhinitis.

Administration, Sublingual↗
PubMed2005

Detection of a non-pathogenic variant of Anaplasma phagocytophilum in Ixodes ricinus from La Rioja, Spain.

Our aim was to identify variants of Anaplasma phagocytophilum 16S rRNA gene sequences among products amplified from Ixodes ricinus collected in La Rioja, Spain. A. phagocytophilum AP-variant 1, reported as non-pathogenic, was detected in 12 samples (two adults and ten nymphs). This finding could justify the low incidence of human anaplasmosis in our area, despite the high prevalence of A. phagocytophilum in ticks.

Anaplasma phagocytophilum↗
PubMed2002

Ultrastructural study of the infection process of Rickettsia conorii in the salivary glands of the vector tick Rhipicephalus sanguineus.

This work was designed to study the infection process of Rickettsia conorii in the salivary glands of experimentally infected Rhipicephalus sanguineus ticks. One hundred six uninfected engorged nymphs were intracelomically inoculated with approximately 2 x 10(3) plaque-forming units of a rickettsial suspension. After the molt, unfed and fed adults were dissected, and the salivary glands were extracted and processed for transmission electron microscopy observation. Three different uninfected control groups were used for (1) evaluating the impact of the inoculation procedure, (2) establishing the feeding period of infected ticks, and (3) ultrastructural characterization of the salivary glands. Overall, 75.5% (80 of 106) of the nymphs inoculated with rickettsiae died during the molt or soon after hatching into adult instars; 50% (12 of 24) of the remaining infected adults showed severe malformations compromising their viability. In apparently healthy specimens, time of engorgement was longer. The contrast with the negative control groups was statistically significant, suggesting that R. conorii exerts a strong negative effect on the vector ticks. The ultrastructural study showed that in the salivary glands of infected ticks, rickettsial growth occurs preferentially in central, peripheral, and interstitial acini cells.

Animals↗
PubMed2001

Assessment of the antitumour activity of targeted immunospecific albumin microspheres loaded with cisplatin and 5-fluorouracil: toxicity against a rodent ovarian carcinoma in vitro.

The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay is used successfully to estimate the number of viable cells in drug screening trials. We used the MTT assay to assess the viability of a rodent ovarian carcinoma cell line (DMBA-OC-1R) after exposure to combinations of cisplatin and 5-fluorouracil as free drug and in encapsulated (conjugated and unconjugated) forms. After 48 h of exposure to free drugs, a significant trend towards cell cytotoxicity could be observed and this was well established by 120 h. Cells treated with drug-containing immuno-microspheres showed a similar initial decrease in cell viability after 96 h, and this was maintained for 128 h. These results suggest that immuno-microspheres loaded with chemotherapeutic drugs have the potential to be successfully used in the treatment of ovarian cancer.

Animals↗
PubMed2001

Leukotriene receptor antagonists (Montelukast) in the treatment of asthma crisis: preliminary results of a double-blind placebo controlled randomized study.

OBJECTIVE: Evaluate the efficacy of oral Montelukast 10 mg as an add-on therapy to the usual emergency therapy of an asthma crisis in an emergency room (ER). POPULATION: Twenty adults that sought medical attention in the ER of our Hospital and in whom, on admission, it appeared unnecessary to give systemic steroids. METHODS: All patients received the usual therapy of the asthma crisis. Simultaneously it was randomly administered a capsule containing 10 mg Montelukast or placebo, in a double-blind protocol. In both groups we evaluated the evolution of Peak-Flow values, the duration of stay in the ER as well as the need for additional therapy with systemic aminophylline or steroids, representing an insufficient response to the initial treatment. Student's T test was used to evaluate the statistical differences between these two groups. RESULTS: Both the Montelukast (MK) and Placebo (PL) groups were comparable regarding age and sex distribution, Peak-Flow values and Arterial O2 values on admission. During therapy, MK group had a shorter duration of ER stay (MK = 2.5 h; PL = 2.9 h) and a better evolution of Peak-Flow values (medium increase of 55% from baseline versus 44% in PL group). However these differences did not reach statistical significance. In the MK group one patient needed systemic steroids and 4 received systemic aminophylline while in the PL group 4 patients received systemic steroids and 8 aminophylline. This difference was significant (p = 0.03). We did not observe any significant side effects during therapy. CONCLUSIONS: Despite a small trend favourable to Montelukast we did not observe significant differences between groups regarding duration of stay or Peak-Flow evolution during therapy in ER, most probably due to the small sample size. However patients in the MK group needed significantly less systemic therapy with aminophylline or steroids. These data, in view of the very good safety profile of Montelukast, allow us to conclude that this is a useful additional therapy, which should be considered in the ER treatment of the asthma crisis.

Acetates↗
PubMed2001

Effect of specific immunotherapy versus loratadine on serum adhesion molecules.

OBJECTIVE: To evaluate comparatively the effect on serum ICAM-1 and VCAM-1 values of specific immunotherapy versus loratadine in the treatment of allergic rhinitis. POPULATION: 65 patients with mild to moderate House Dust Mite allergic rhinitis. METHODS: Patients were divided into three groups, according to patients' preference: a control group with patients receiving only rescue therapy (antihistamines and/or nasal cromoglycate when needed); an antihistamine group with patients receiving daily loratadine 10 mg (and nasal cromoglycate as rescue therapy); an immunotherapy group with patients receiving subcutaneous house dust mite specific immunotherapy (and antihistamines or nasal cromoglycate when needed). In all groups we measured soluble ICAM-1 and VCAM-1 serum levels before the start of the study period and at the end of the study period. The duration of the study was one year for the control group and for the immunotherapy group. In patients taking daily antihistamines we measured serum adhesion molecules one month after the beginning of the therapy. We used Student's T test for statistical analysis. RESULTS: Patients in the control group didn't have significant variations in serum ICAM-1 (p = 0.239) or VCAM-1 (p = 0.38) levels. Patients receiving loratadine showed significant decreases in serum VCAM-1 levels (p = 0.0012) but not in serum ICAM-1 levels (p = 0.224). Patients receiving immunotherapy also showed a similar pattern, with significant decreases in serum VCAM-1 levels (p = 0.012) but not in serum ICAM-1 levels (p = 0.254). CONCLUSIONS: Specific house dust mite immunotherapy and regular daily loratadine therapy are able to lower significantly serum levels of soluble VCAM-1. However, this effect, which can be interpreted as an anti-inflammatory action, is not applied to soluble ICAM-1 levels, which raises the possibility of a differential action of these therapies on the mechanisms of allergic inflammation. Patients on rescue medication alone did not show any significant differences in these parameters.

Adolescent↗
PubMed1998

Short-term efficacy of nasal immunotherapy.

The purpose of this study was to evaluate the efficacy of nasal immunotherapy in the management of allergic rhinitis. Sixteen patients (10 Female; 6 Male) aged 15-60 years (mean age--31.9) were selected on the bases of clinical history, skin prick tests and RAST positivity. Allergen extract is a "macronized" powder form (Allerkin), it was supplied by Laboratorio Farmaceutico Lofarma (Milano Italy) and administered for 12 months to 8 patients with perennial rhinitis (Dermatophagoides extract) and for 6 months to 8 patients with seasonal rhinitis (grass or Parietaria pollens extract). This treatment was carried out by self administration in two phases: the first one (3 months) consisted of administration of increasing doses; the second phase (maintenance period) was carried out 3 months in seasonal rhinitis and 9 months in perennial rhinitis. All the patients were evaluated before and after immunotherapy and scores from 0 to 3 were attributed according to the symptoms presented and need of drugs for symptomatic relief. Scores before and after immunotherapy were compared using the Wilcoxon Matched-Pairs Signed-Ranks Test and a significant decrease was observed for every symptom in seasonal and perennial rhinitis (p < 0.05). In conclusion, this trial shows that nasal immunotherapy in powder form can be a valuable short-term option in patients with allergic rhinitis.

Administration, Intranasal↗
PubMed1998

Programme for the surveillance of influenza in Portugal: results of the period 1990-1996.

OBJECTIVES: To describe the situation of the influenza in Portugal through the estimates of the incidence rates and the identification of the viral strains implicated on it during the period 1990-1996. DESIGN: The integrated clinical and laboratory surveillance system for influenza in Portugal is based on the Portuguese sentinel network. Influenza cases are identified by general practitioners (GP) and notified to Division of Epidemiology (DEP) and to National Influenza Centre. Clinical and epidemiological data based on the clinical diagnosis are recorded and incidence rates are computed for the whole country. Throat swabs and blood samples are taken from the patients with influenza and sent to the National Influenza Centre to identify and classify the viral strains implicated. PARTICIPANTS: Lists of patients of the GPs collaborating on "Médicos-Sentinela" network. RESULTS: In 1990-1991, 1992-1993, and 1994-1995 there was a higher prevalence of influenza B virus and the highest influenza activity occurred in February and March in contrast with 1991-1992, 1993-1994, and 1995-1996 where the highest numbers of influenza cases occurred in November and December, and were associated with influenza A. CONCLUSIONS: During the past six years, 1990-1996, the influenza activity has been moderate in Portugal. From 1990-1996 influenza A and B viruses were prevalent every second year. The prevalence of influenza A was associated with the occurrence of the highest number of influenza cases during December and January and the prevalence of influenza B with the occurrence of the highest number of influenza cases during February and March.

Family Practice↗
PubMed1998

[Pediatric varicocele].

The treatment of pediatric varicocele has recently been given a special importance due to clinical and experimental evidence of testicular atrophy and histological changes in 50% of homolateral and sometimes in contralateral testis. Those changes are progressive and similar to those in infertile adults with varicocele. Between 1st January 1990 and 31st December 1994, 41 boys (five to 15 years old--mean age 11.9 years) were presented for evaluation of primary varicocele at the Pediatric Surgery Department of Dona Estefânia Hospital. The varicocele was left sided in 39 boys, bilateral in one and another on the right, with a predominance of grade II. Forty patients underwent varicocelectomy, 31 (77%) by the Ivanisevìc technique. Varicocele recurred in four cases (10%). The authors discuss the results and make some considerations concerning the management of varicocele in children.

Adolescent↗
PubMed1997

Frequency of the different mutations causing spinocerebellar ataxia (SCA1, SCA2, MJD/SCA3 and DRPLA) in a large group of Brazilian patients.

Spinocerebellar ataxia type 1 (SCA1), spinocerebellar ataxia type 2 (SCA2) and Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) are three distinctive forms of autosomal dominant spinocerebellar ataxia (SCA) caused by expansions of an unstable CAG repeat localized in the coding region of the causative genes. Another related disease, dentatorubropallidoluysian atrophy (DRPLA) is also caused by an unstable triplet repeat and can present as SCA in late onset patients. We investigated the frequency of the SCA1, SCA2, MJD/SCA3 and DRPLA mutations in 328 Brazilian patients with SCA, belonging to 90 unrelated families with various patterns of inheritance and originating in different geographic regions of Brazil. We found mutations in 35 families (39%), 32 of them with a clear autosomal dominant inheritance. The frequency of the SCA1 mutation was 3% of all patients; and 6% in the dominantly inherited SCAs. We identified the SCA2 mutation in 6% of all families and in 9% of the families with autosomal dominant inheritance. The MJD/SCA3 mutation was detected in 30% of all patients; and in the 44% of the dominantly inherited cases. We found no DRPLA mutation. In addition, we observed variability in the frequency of the different mutations according to geographic origin of the patients, which is probably related to the distinct colonization of different parts of Brazil. These results suggest that SCA may be occasionally caused by the SCA1 and SCA2 mutations in the Brazilian population, and that the MJD/SCA3 mutation is the most common cause of dominantly inherited SCA in Brazil.

Adolescent↗
PubMed1997

Nasal allergen challenge and mediators release.

Nasal allergen challenges, despite not reproducing exactly natural allergen exposure, are a very useful method to understand the complex cellular kinetics and cellular interactions that occur in allergic rhinitis. Cell-specific soluble mediator measurements can give useful diagnostic information. In this paper we present data concerning eosinophil cationic protein (ECP) and tryptase measurements after nasal allergen challenge.

Allergens↗
PubMedDate not supplied

Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen carbamylated allergoid in rhinitic patients. A double-blind, placebo-controlled study.

BACKGROUND: The aim of this study was to confirm the clinical efficacy and safety of a preseasonal sublingual immunotherapy (SLIT) in a group of allergic patients with seasonal rhinoconjunctivitis with or without mild intermittent or mild persistent asthma. The immunotherapy was administered through the oral mucosa with a monomeric carbamylated allergoid (allergoid SLIT) for grass pollens. A secondary endpoint was to evaluate the effect of the allergoid SLIT on nasal reactivity. METHODS AND RESULTS: A single-center, randomized, double-blind, placebo-controlled study was performed. Patients were selected and randomly allocated to two groups: one group received active treatment (allergoid SLIT) for 2 years and the other received placebo. Both groups received the necessary drug treatment throughout the trial. Thirty-three outpatients (20 men and 13 women, mean age: 30 years; range: 19-43) attending our center were enrolled in the study. Symptoms and medications were scored on diary cards during the pollen season. An allergen nasal challenge was performed at baseline and after 2 years of SLIT to evaluate nasal reactivity. Because the clinical scores were non-normally distributed, the Mann-Whitney and the Chi-square tests for intergroup comparisons and the Wilcoxon test for intragroup comparisons were used. The results were evaluated after 1 and 2 years of treatment. Between the first and second years of treatment, no changes in the scores for the placebo group were found, while for the active vaccine group significant decreases were found in rhinorrhea (p < 0.03), sneezing (p < 0.03), and conjunctivitis (p < 0.02). Symptom scores after nasal challenge decreased (p < 0.03) after 2 years' treatment. Nasal steroid use significantly decreased in the active treatment group during May and June in both the years of treatment (p < 0.02). Only two mild local adverse events were reported in the active group and none was reported in the placebo group. CONCLUSIONS: The results of this study show that the allergoid SLIT is safe and effective in decreasing symptom scores and drug use in rhinitic patients allergic to grass pollen.

Administration, Sublingual↗