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Biomedical subjects

A Magalhães

Publications and source records attributed to A Magalhães.

At least 19 recordsLinked to original sources
PubMed2006

Spatial and temporal distribution in density and biomass of two Pseudodiaptomus species (Copepoda: Calanoida) in the Caeté river estuary (Amazon region--North of Brazil).

Spatial and temporal density and biomass distribution of the planktonic copepods Pseudodiaptomus richardi and P. acutus along a salinity gradient were investigated in the Caeté River Estuary (North-Brazil) in June and December, 1998 (dry season) and in February and May, 1999 (rainy season). Copepod biomass was estimated using regression parameters based on the relation of dry weight and body length (prosome) of adult organisms. The Caeté River Estuary was characterized by high spatial and temporal variations in salinity (0.8-37.2). Exponential length-weight relationships were observed for both Pseudodiaptomus species. Density and biomass values oscillated between 0.28-46.18 ind. m-3 and 0.0022-0.3507 mg DW. m-3 for P. richardi; and between 0.01-17.02 ind. m-3 and 0.0005-0.7181 mg DW. m-3 for P. acutus. The results showed that the contribution of P. richardi for the secondary production in the Caeté River Estuary is more important in the limnetic zone than in other zones where euhaline-polyhaline regimes were predominant. However, it was not possible to observe a clear pattern of spatial and temporal distribution for P. acutus.

Animals↗
PubMed2000

Action of metalloproteinases mutalysin I and II on several components of the hemostatic and fibrinolytic systems.

The zinc endopeptidases mutalysin I (100 kDa) and mutalysin II (22.5 kDa) have been previously isolated from bushmaster (Lachesis muta muta) snake venom. Hemorrhagic activity was observed with as little as 0.5 microg (2000 units/mg) and 17.8 microg (56.2 units/mg) for mutalysin I and II, respectively. Additionally, the proteases hydrolyse the Aalpha>Bbeta chain of fibrinogen without clot formation. The specific fibrinogenolytic activity was estimated as 5. 25 and 16.3 micromol fibrinogen/min/micromol protein for mutalysin I and II, respectively. In vitro, the enzymes act directly on fibrin and are not inhibited by serine proteinase inhibitors (SERPINS). Analysis by SDS-PAGE of fibrin hydrolysis by both enzymes showed that mutalysin II (0.22 microM) completely digested the alpha- and gamma-gamma chains and partially the beta-chain (in 120 min incubation). In contrast, mutalysin I (three fold higher concentration than mutalysin II) hydrolyzed selectively the alpha-chain of fibrin leaving the beta and gamma-gamma chains unaffected. Unlike with the plasminogen activator-based thrombolytic agents (e.g., streptokinase), mutalysins do not activate plasminogen. Neither enzyme had an effect on protein C activation. Mutalysin II does not inhibit platelet aggregation in human PRP induced by collagen or ADP. However, mutalysin I showed a selective inhibitory effect on collagen-induced aggregation of human PRP; it did not affect platelet aggregation with ADP as the agonist. The present investigation demonstrates that both native and EDTA-inactivated mutalysin I dose dependently blocked aggregation of human PRP elicited by 10 microg/mL of collagen with an IC(50) of 180 and 580 nM, respectively. These studies suggest that, in addition to the metalloprotease region of mutalysin I, the disintegrin-like domain also participates in the inhibitory effect. The proteolytic activity of mutalysin II against dimethylcasein and fibrin was completely abolished by alpha2-macroglobulin (alpha2-M). The stoichiometry of inhibition was 1.0 mol of enzyme per mol of alpha2-M. In contrast, the proteolytic effect of mutalysin I against the same substrates was not significantly inhibited by alpha2-M. Therefore, the data explain why mutalysin I contributes significantly not only to local but also to systemic bleeding associated with the observed pathological effects of the venom.

Animals↗
PubMed2000

p53 gene status and expression of p53, mdm2, and p21Waf1/Cip1 proteins in colorectal cancer.

Abrogation of the normal p53 pathway is the most common molecular alteration in human cancer. p53 Gene status can be potentially assessed through the expression of proteins known to be activated by the wild-type p53 (wt p53) system, such as mdm2 and p21Waf1/Cip1. In this study, the frequency of mdm2, p21Waf1/Cip1, and p53 protein expression was investigated using immunohistochemistry (IHC) in 88 colorectal carcinomas (CRCs). The relationship between these expressions and p53 status was examined. p53 status and the immunophenotypes characterizing these tumors were correlated with standard prognostic variables. Mutation of p53 was detected using single-strand conformational polymorphism (SSCP) analysis and sequencing. Concordance between p53 gene status and p53 immunoreactivity was seen in 62 of 88 (70.45%) carcinomas. Mdm2 expression was found in 22 of 45 (48.88%) and 5 of 43 (11.62%) of the tumors with wt p53 and mutated p53 (P<0.0001), respectively. Predominantly, higher p21Waf1/Cip1 expression was associated with wt p53 (P<0.001). All wt p53 cases that expressed mdm2 also expressed p21Waf1/Cip1. These results suggest that there is a subgroup of CRCs in which p53 is functionally active, inducing transcription of mdm2 and Waf1/Cip1. Their combined evaluation may provide important clues for planning adjuvant systemic therapy and gene therapy based on the restitution of p53 function. However, no significant association was found between the immunophenotypes and the standard prognostic variables investigated.

Adult↗
PubMed2000

Arenosclerins A-C and haliclonacyclamine E, new tetracyclic alkaloids from a Brazilian endemic Haplosclerid sponge Arenosclera brasiliensis.

Arenosclerins A (2), B (3), and C (4), as well as haliclonacyclamine E (1), are new tetracyclic alkylpiperidine alkaloids isolated from a new species of marine sponge belonging to the order Haplosclerida, Arenosclera brasiliensis, a species endemic to the southeastern Brazilian coast. The alkaloids were isolated as their hydrochloride salts and identified by analysis of spectroscopic data. Data obtained from (1)H-(1)H COSY, HMBC, and HSQC-TOCSY NMR experiments allowed complete assignment of the (1)H and (13)C resonances, and analysis of the NOESY and ROESY spectra showed that the only differences between 2, 3, and 4 were the relative stereochemistries of the bispiperidine ring system. Arenosclerins A-C are the first haliclonacyclamine/halicyclamine-related alkaloids with a hydroxy group in the bridging alkyl chain.

Alkaloids↗
PubMed2000

Human immune responses to Schistosoma mansoni vaccine candidate antigens.

To determine the naturally occurring immunological responses to the Schistosoma mansoni antigens paramyosin, IrV-5, Sm-23 (MAP-3), and triose phosphate isomerase (MAP-4), a total of 119 subjects from an area of endemicity for schistosomiasis, including "resistant" subjects (n = 17) were evaluated. Specific immunoglobulin G1 (IgG1), IgG2, IgG3, IgG4, and IgA levels for each of the antigens and the cytokine profile in culture supernatants from antigen-stimulated peripheral blood mononuclear cells (PBMC) were determined. Although all the subjects had a high degree of contaminated water exposure, their infection levels were variable (0 to 1,128 eggs/g of stool). There were direct correlations between infection levels and levels of SWAP- and paramyosin-specific IgG1 and IgG4 (P < 0.05). However, an inverse correlation between infection levels and specific IgG2 to IrV-5 (P < 0.01) was observed. The evaluation of the cytokine profile (interleukin 5 [IL-5], IL-10, gamma interferon [IFN-gamma], and tumor necrosis factor alpha) in response to these antigens showed inverse correlations between the degree of infection and IFN-gamma levels in PBMC supernatants stimulated with paramyosin (P < 0.05) and IrV-5 (P < 0.01). Additionally, inverse correlations between the degree of infection and IL-5 levels in MAP-3- and MAP-4-stimulated PBMC supernatants (P < 0.01) were found. Logistic regression analysis was performed to adjust the results of cytokine profile by age. IL-5 production in MAP-3-stimulated PBMC supernatants was associated with lower infection levels (odds ratio = 11.2 [95% confidence interval, 2.7 to 45.8]).

Adult↗
PubMed1999

Studies on the specificity of CNF, a phospholipase A2 inhibitor isolated from the blood plasma of the South American rattlesnake (Crotalus durissus terrificus). I. Interaction with PLA2 from Lachesis muta muta snake venom.

A phospholipase A2 inhibitor has been previously purified and cloned from the blood plasma of the South American rattlesnake, Crotalus durissus terrificus. This inhibitor, named CNF for Crotalus neutralizing factor, interacts with crotoxin, the main neurotoxin from C. d. terrificus venom, abolishing its phospholipase A2 activity. Crotoxin is a heterodimer of an acidic subunit (CA) and a basic phospholipase A2 (CB). CNF acts by forming a stable non-toxic complex with CB, replacing CA in the toxic CA-CB of crotoxin. In the present investigation, we have shown that CNF has a broader specificity. It is able to inhibit the PLA2 activity of the whole venom from the bushmaster snake (Lachesis muta muta), a species evolutionary related to Crotalus. Inhibition experiments have been carried out with four PLA2 active components isolated from L. m. muta venom, one basic and three acidic ones. CNF inhibition is not restricted to the basic PLA2, but extended to the three acidic forms as well.

Animals↗
PubMed1998

Multicentre randomised study of computerised anticoagulant dosage. European Concerted Action on Anticoagulation.

BACKGROUND: The demand for anticoagulant treatment is increasing. We compared the benefits of computer-generated anticoagulant dosing with traditional dosing decided by experienced medical staff in achieving target international normalised ratios (INRs). METHODS: In five European centres we randomly assigned 285 patients in the stabilisation period and stabilised patients to the computer-generated-dose group (n=137) or traditional-dose group (n=148). Centres had a specialist interest in oral anticoagulation but no previous experience with computer-generated dosing. The computer program calculated doses and times to next visit. Our main endpoint was time spent in target INR range (Rosendaal method). FINDINGS: For all patients combined, computer-generated dosing was significantly beneficial overall in achieving target INR (p=0.004). The mean time within target INR range for all patients and all ranges was 63.3% (SD 28.0) of days in the computer-generated-dose group compared with 53.2% (27.7) in the traditional-dose group. For the stabilisation patients alone, computer-generated doses led to a non-significant benefit in all INR ranges (p=0.06), whereas in the stable patients the benefit was significant (p=0.02). INTERPRETATION: The computer program gave better INR control than the experienced medical staff and at least similar standards to the specialised centres should be generally available. Clinical outcome and cost effectiveness remain to be assessed.

Administration, Oral↗
PubMed1997

Thrombin-like enzyme from Lachesis muta muta venom: isolation and topographical analysis of its active site structure by means of the binding of amidines and guanidines as competitive inhibitors.

A serine protease enzyme was purified from Lachesis muta muta venom, with 40% yield, by gel filtration on Sephadex G-100 and affinity chromatography on Sepharose-agmatin. Homogeneity of the enzyme preparation was demonstrated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and the enzyme had a relative mol. wt of 45,000. The molar extinction coefficient at 280 nm was 62,127 (M x cm)-1. The enzyme hydrolysed Bz-Arg-Nan with Ks = 0.233 +/- 0.08 mM and kcat = 2.80 +/- 0.07 sec-1. All the amidines and guanidines tested for their inhibitory effect on thrombin-like enzyme behaved as competitive inhibitors of the enzyme with Ki values in the range 6.2 microM to 42.3 mM for amidines and 0.19 mM to 9.31 mM for guanidines. Dissociation constant values were analyzed in terms of the binding of the inhibitors with the subsite S1, the specificity pocket of the enzyme, Ki values were discussed in accordance with those for trypsin inhibition. beta-Naphthamidine was the strongest inhibitor, while guanidine was the weakest. The differences among the Ki values were interpreted in terms of the shape of the enzyme active site. For meta- and para-substituted benzamidinium ions a good correlation was found between log l/Ki and sigma Hammett values of the substituents. The substituent effects in the pi-electrons of the benzamidine ring were considered in the frame of Hückel molecular orbital theory. A model for the binding of p-benzamidine derivatives with the primary specificity S1 subsite of the enzyme active site was proposed.

Animals↗
PubMed1997

Purification and stability studies of immunoglobulins from Lachesis muta muta antivenom.

Immunoglobulins were isolated from hyperimmune horse plasma against Lachesis muta muta venom by ammonium sulfate precipitation and immunoaffinity technique (Sepharose-venom L. m. muta column). When necessary, limited proteolysis with pepsin was used to generate a bivalent antigen-binding fragment (F(ab')2). Solutions with immunoglobulins or F(ab')2 fragments were fractionated by molecular filtration chromatography (Superose 12) and the expected mol. wt species were observed. The L. m. muta venom shows caseinolytic and haemorrhagic activities. Incubation of the venom with these purified antibodies resulted in a decrease of both activities. High temperatures promote aggregation and the formation of protein precipitates. Sorbitol (1.0 M) was used as an osmolyte (a natural substance or an organic compound capable of stabilizing proteins) and decreased the formation of protein precipitates in solutions of antibodies, as judged by a spectrophotometric assay (280 nm), by nephelometry or when tested by enzyme-linked immunosorbent assay. Circular dichroism was used to study the spectra of antibodies in the presence of phosphate-buffered saline or sorbitol. Up to an osmolyte concentration of 1.0 M, there was no significant perturbation of the F(ab')2 fragments spectra in the amide region. However, whole immunoglobulins in the presence of 1.0 M sorbitol presented a small spectral perturbation, suggesting that the beta-structure was reinforced. The effect of osmolyte on the affinity of antibodies was observed by enzyme-linked immunosorbent assay. There was no significant difference in the results when the antibodies were previously incubated with venom in phosphate-buffered saline or in the presence of 1.0 M sorbitol. In conclusion, an osmolyte (sorbitol) was shown to be capable of stabilizing antibodies at high temperatures, with no significant perturbation in the secondary structure or affinity to L. m. muta venom. These results point to the possibility of using sorbitol, or other osmolytes, as stabilizers of immunoglobulin preparations.

Animals↗
PubMed1996

The importance of technology for achieving superior outcomes from intensive care. Brazil APACHE III Study Group.

OBJECTIVE: To test the hypothesis that technology availability, staffing, and diagnostic diversity in an intensive care unit (ICU) are associated with the ability to decrease hospital mortality. DESIGN: Prospective multicenter descriptive cohort study. SETTING: Ten Brazilian medical-surgical ICUs. PATIENTS: 1734 consecutive adult ICU admissions. MEASUREMENTS AND RESULTS: We recorded the amount of technology, number of diagnoses, and availability of nurses at each ICU. We also used demographic, clinical and physiologic information for an average of 173 admissions to each ICU to calculate standardized mortality ratios (SMRs) for each ICU. The mean SMR for the ten ICUs was 1.67 (range 1.01-2.30). A greater availability of ICU equipment and services was significantly (p < 0.001) associated with a lower SMR. CONCLUSION: The ability of Brazilian ICUs to reduce hospital mortality is associated with the amount of technology available in these units.

Adult↗
PubMed1996

Purification and characterization of a fibrinogen-clotting enzyme from the venom of jararacuçu (Bothrops jararacussu).

A clotting enzyme of the venom of Bothrops jararacussu, denoted FC-Bj, was purified by gel chromatography on Sephadex G-100 followed by HPLC on DEAE-5PW-PAK and gel filtration on Sephacryl S-200HR. The enzyme was identified as an acidic glycoprotein which probably consists of a single polypeptide chain with isoelectric point values in the range 3.3-4.4 and containing approx. 19% carbohydrates. On polyacrylamide gel electrophoresis (PAGE) at pH 8.3, the enzyme presented a diffuse protein band. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), the enzyme showed two protein bands corresponding to mol. wts of 50,600 and 60,000. After treatment of the enzyme with neuraminidase, a strongly stained band and a band weaker in staining intensity were observed on SDS-PAGE, thereby reducing the mol. wts to 44,500 and 56,300, respectively. The clotting factor possessed N-alpha-benzoyl-DL-arginine p-nitroanilide hydrolysing activity and coagulated fibrinogen to fibrin. These activities were 0.548 units/mg and 50.55 NIH thrombin units/mg, respectively. The proteinase was of the serine type, as indicated by sensitivity to phenylmethanesulfonyl fluoride and benzamidine. However, the amidolytic activity of this enzyme was resistant to inhibitors such as heparin, aprotinin, agmatine, EDTA, I-2581 and TLCK. The importance of disulfide bridges for the structural integrity of the purified enzyme was indicated by the loss of amidolytic activity in the presence of beta-mercaptoethanol and dithiothreitol. SDS-PAGE of fibrinogen degraded with this enzyme revealed the disappearance of the A alpha and B beta chains and the appearance of lower mol. wt fragments. The enzyme was able to hydrolyse synthetic chromogenic substrates with arginine as the C-terminal residue, and the kinetic parameters were determined. It hydrolysed the plasma kallikrein substrate H-D-Pro-Phe-Arg-pNA (S-2302) and produced kinin-releasing activity causing ileum contraction. In addition, hypotension and bradycardia were observed in urethane-anesthetized rats upon i.v. injection of the enzyme.

Agmatine↗
PubMed1995

Survival predictors in advanced non-small cell lung cancer.

The authors studied the influence on survival of 21 clinical, anatomical, haematological and biochemical factors evaluated, at diagnosis, of 411 patients (pts) with advanced Non Small Cell Lung Cancer (NSCLC) followed in our department between 1984 and 1990. Most of the patients were male (347--84.4%) and only 64 (15.6%) were females. Median age was 62 years, but was slightly higher in females. Only 34 patients were aged under 45 years. Squamous cell carcinoma (215 pts--52%) and adenocarcinoma (152 pts--37%) were the most frequent histologic types. Performance status was poor--only 103 (25%) continued active; 120 (29%) spent at least half of the time in bed; 188 (46%) were severely limited. After staging, 179 (44%) presented locally advanced disease (stage IIIB) and 232 (56%) metastatic dissemination (stage IV). Therapy was defined by the oncologic group according to individual characteristics and based on clinical grounds. Anti-neoplastic therapy was performed in 225 (55%), chemotherapy alone in 121 (30%), radiation therapy alone in 67 (16%), and sequential combined treatment (chemotherapy and thoracic radiation) in 37 (9%). Until 1987, the main chemotherapy regimen was MACC (Metrotrexate + Adriamycine + Cyclophosphamide + Lomustin), afterwards VP(M) (Cisplatin + Vimblastin + Mitomycine). Radiation therapy was performed using Co60, 2 Gy/day, 5 days a week, for 4 weeks (approximately 45 Gy total). The response rate was poor--four complete responses (2%), 42 (19%) partial responses. The overall median survival was 4.3 months and only 5% of patients were alive after 18 months of follow up. Prognostic importance of each characteristic studied was initially done by unifactorial analysis, followed by multifactorial analysis according to two methods: Cox proportional hazards model and recursive partitioning amalgamation--RECPAM. Regardless of the method used, the main determinants of survival were found to be performance status (Zubrod), weight loss and serum albumin. Other factors such as the staging (presence or absence of metastasis), lymphocytes, lactic dehydrogenase, and hoarseness were also significant. It is noteworthy that age and histological type were irrelevant; sex and hoarseness only proved important when integrated within a multifactorial model. The overall prognostic evaluation and therapeutic decision of advanced NSCLC patients could be improved by combining the prognostic value of TNM with that of performance status, weight loss and serum albumin. These prognostic guidelines must be taken into account when designing new clinical trials.

Adenocarcinoma↗
PubMed1995

[The epidemiology of proximal femur fracture at the Hospital da Horta (Azores)].

The aim of this study was to know the incidence of osteoporotic hip fracture in a defined area of the Azores. The catchment area included the islands of Faial, Pico, Flores and Corvo, with 11,617 subjects aged 50 or more: 5,373 males and 6,244 females. The time period of the survey was 1991 to 1993. Data was obtained from the records of the Orthopedic Department of Hospital Horta. Thirty seven fractures were diagnosed during the time survey: 12 in 1991, 13 in 1992 and 12 in 1993. The age-adjusted mean incidence rates of hip fracture for the population over 49 years old was 10.3/10,000: 5.6/10,000 in men and 14.4/10,000 in women. Most fractures occurred in women over the age of 65 years. The ratio of male to female cases was 1:3. The mean age of all patients was 77 +/- 8 years of age: 72 +/- 8 in males and 79 +/- 6 in females (p = 0.05). About 70 percent of these patients were treated surgically. The acute mortality rate was 8 percent and the mean age of the deceased patients, 82 +/- 6, was significantly higher than the mean age of the survivors, 73 +/- 6 (p = 0.01).

Age Distribution↗
PubMed1994

[Prevalence of asthma in the city of Porto].

It is possible that asthma epidemiology will contribute to the definition of asthma precipitant factors. This work is enrolled in an international study co-ordinated by COMAC-EPI. In Oporto, among 137.000 residents in the same town region, a standardised sample of 4.047 male and female individuals aged from 20 to 44 years was defined. A screening questionnaire was sent with a stamped envelope. Four months later the same questionnaire was sent to the individuals who did not answer it and finally those who do not answer the second letter were visited in their own residence. We got 2075 answers. Among the responders about half were women: 1075, 25.39% belonging (273) to the 20-29 years age group; 42.69% (459) 30-39 years; 31.90% (343) 40-44 years. In men the percentage of distribution by age groups was similar. Question nQ 5 was answered affirmatively by 60 individuals, corresponding to the prevalence of 2.89%. Seventy-one (3.42%) said they had been under asthma treatment during the last year. Among the symptoms that usually define the attack of asthma, those inquired in the group of question 1 show a prevalence close to that of the asthma diagnosis: 6.45%. The prevalence of being awakened by tightness in the chest, shortness of breath and coughing, with values of 16.17%, 10.69% and 25.68% is quite superior than in question nQ 5. The prevalence obtained with the Hay Fever question was 18.84%. Data obtained is similar to the data of other centers.

Adult↗
PubMed1991

Doppler demonstration of cystic vein dilatation secondary to portal vein thrombosis.

High-resolution duplex ultrasound was used to demonstrate vascular dilatation in the gallbladder wall in eight patients with portal vein thrombosis. Gallbladder thickening, combined with a higher incidence of gallstone disease in patients with chronic hepatic disease can be misinterpreted as acute cholecystitis. The Doppler is helpful in detecting the vascular cause of the gallbladder wall thickening thus helping to reduce the frequency of inappropriate cholecystectomy.

Dilatation, Pathologic↗
PubMed1991

Purification and partial characterization of an L-amino acid oxidase from bushmaster snake (Surucucu Pico de Jaca) Lachesis muta muta venom.

1. L-amino acid oxidase (L-AO) from the venom of Lachesis muta muta was purified 72 times (38%) by gel filtration on Sephadex G-100, followed by ion exchange chromatography on DEAE-cellulose and gel filtration on Sephacryl S-300. 2. The protein was shown to be homogeneous by polyacrylamide gel electrophoresis at pH 8.5, immunoelectrophoresis, immunodiffusion and isoelectric focusing. Its specific activity was 44.4 units/mg protein, using 7.5 mM L-leucine as substrate and O-dianisidine as electron donor, at pH 7.6 and 25 degrees C. The increase in absorbance at 436 nm was recorded. 3. The enzyme was characterized as a glycoprotein with an S20,w = 6.72, MW = 138,000 and pI = 5.2. It presented maxima at 389 and 460 nm and contained 2 mol of FAD per mole protein.

Amino Acid Oxidoreductases↗
PubMed1990

The effect of stepwise iodination on biological properties of Bothrops jararaca venom.

By titrating 5 mg of native venom with aliquots of a 2 x 10(-2) M iodine monochloride solution, neutralization of lethality by the incorporation of iodine was found with 200 +/- 5 microliters of solution, and above, up to 310 +/- 10 microliters, when saturation with iodine was attained. Doses up to 1500 micrograms (equivalent to 32 LD50 of native venom), where injected i.p. in mice without lethal effects. Proteolytic, phospholipase A2 and esterolytic activities were greatly reduced, but a low activity persisted even in fully iodinated samples. Direct hemolysis was markedly inhibited, and incapacity to coagulate fibrinogen and horse plasma was also observed in the iodinated samples. Hemorrhage and necrosis in rat skin, caused by 20 micrograms of iodinated venom were not elicited by doses up to 120 micrograms of iodinated anavenom. In mice, the myonecrosis that resulted from direct i.m. injection of native venom, and the massive hemorrhage caused by 5 LD50 doses injected i.p. were abolished by venom iodination. Blood congestion in liver, spleen, kidneys, and lungs, almost disappeared with iodination to the level of neutralization, and was barely seen with venom samples iodinated to saturation. The clinical signs of impaired physical activity, appearing in mice injected with 700 to 1500 micrograms of the iodinated anavenom were intensified by captopril and attenuated by epinephrine.

Animals↗