Biomedical subjects

E Fernandes

Publications and source records attributed to E Fernandes.

At least 19 recordsLinked to original sources

PubMed2005

Morbidity and mortality rates following gastric cancer surgery and contiguous organ removal, a population based study.

BACKGROUND: Complete surgical (R0) resection remains the only potentially curative intervention for patients with localised gastric cancer. To achieve a curative resection, patients may require complex operations with resection of contiguous organs. The aim of this study was to assess how the extent of surgical resection influenced morbidity, mortality and survival in an aged non-selected population with significant comorbid disease. PATIENTS AND METHODS: Data were extracted from the Scottish Audit of Gastric and Oesophageal Cancer (SAGOC), a prospective population-based audit of all oesophageal and gastric cancers in Scotland between 1997 and 1999 with a minimum of 1-year follow-up. RESULTS: A total of 646 patients underwent surgical exploration for gastric cancer. A significantly higher incidence of chest infections (18.5 vs 11%, p< 0.05) and anastomotic leaks (14.3 vs 2.2%, p< 0.05) were associated with total gastrectomy (n=168) when compared to distal gastrectomy (n=272) resections. A 9.2% mortality rate and a 60% 1-year survival were associated with gastric resection alone. Removal of the spleen (n=131), pancreas (n=30) or liver resection (n=5) was associated with a significantly higher mortality rates, 18.3, 23.3 and 40%, respectively (p< 0.05), and significantly lower 1-year survival rates, 50.9, 39.1 and 20%, respectively (p< 0.05). CONCLUSIONS: The risk of more extensive resection is not balanced by improved survival in this population based series. Extending gastric resection to involve contiguous organs should be confined to highly selected cases.

Adult↗

PubMed2004

The radiation field characteristics of a 137Cs source used for calibration of radiation protection instruments.

In this work, an experimental study of the radiation beam characteristics of the photon beams produced by commercial irradiator that uses a single collimated 137Cs source is performed. A set of lead attenuators are placed at the exit window of the irradiator to vary the air Kerma that is required to cover the instrument scales at a particular calibration distance. The results strongly enhance the findings of previous studies that a single source with appropriate attenuation and collimation is a practical solution for calibration laboratories with an acceptable overall accuracy.

Brazil↗

PubMed2004

Evaluation of toxic/protective effects of the essential oil of Salvia officinalis on freshly isolated rat hepatocytes.

For this study the essential oil (EO) of sage (Salvia officinalis L.) was isolated from air-dried vegetative aerial parts of the plants by hydrodistillation and analysed by GC and GC-MS. A total yield of 12.07 mg of EO per g of plant dry mass was obtained and more than 50 compounds identified. The major compounds were cis-thujone (17.4%), alpha-humulene (13.3%), 1,8-cineole (12.7%), E-caryophyllene (8.5%) and borneol (8.3%). The EO fraction of sage tea was also isolated by partition with pentane and the respective components identified. The toxic and antioxidant protective effects of S. officinalis EO were evaluated on freshly isolated rat hepatocytes. Cell viability (LDH leakage), lipid peroxidation and glutathione status were measured in experiments undertaken with cells (suspensions of 1 x 10(6) cells per millilitre) exposed to EO alone (toxicity of the EO;t-BHP as positive control); and with cells exposed to EO and an oxidative compound (t-BHP) together (in EO protection evaluation; quercetin as positive control) for 30 min. The results show that the EO is not toxic when present at concentrations below 200 nl/ml; it was only at 2000 nl EO/ml that a significant LDH leakage and GSH decrease were observed indicating cell damage. In the range of concentrations tested, the EO did not show protective effects against t-BHP-induced toxicity.

Animals↗

PubMed2004

D-amphetamine-induced hydrogen peroxide production in skeletal muscle is modulated by monoamine oxidase inhibition.

The aim of this paper was to study the influence of d-amphetamine administration as a sympathomimetic drug on the synthesis of hydrogen peroxide (H2O2) in mouse soleus muscle and to investigate the modulating effects of pargyline, an inhibitor of monoamine oxidase (MAO) in this context. Charles River mice were assigned to four groups: Control, d-amphetamine treated, pargyline treated, and amphetamine + pargyline treated. Their soleus muscles were removed 0, 15, 30, 60, and 120 min after treatment. The amount of hydrogen peroxide formation within the muscles was estimated using an indirect method. The control data showed a continuous production of hydrogen peroxidase. Pargyline administration lead to an initial increase of H2O2 production that later faded below control levels. Administration of amphetamine finally stimulated H2O2 production much above control levels. When combining amphetamine and pargyline treatment, H2O2 production was accelerated in the initial phase but dropped to control levels at 30 min. It is concluded that in skeletal muscle MAO is an important source of hydrogen peroxide production triggered by amphetamine administration and that this tissue plays a hitherto not described role in oxidizing circulating biogenic monoamines.

Animals↗

PubMed2003

Hydroxyl radical and hypochlorous acid scavenging activity of small centaury (Centaurium erythraea) infusion. A comparative study with green tea (Camellia sinensis).

Small centaury (Centaurium erythraea Rafin.) is a herbal species with a long use in traditional medicine due to its digestive, stomachic, tonic, depurative, sedative and antipyretic properties. This species is reported to contain considerable amounts of polyphenolic compounds, namely xanthones and phenolic acids as the main constituents. Although the antiradicalar activity of some pure polyphenolic compounds is already known, it remains unclear how a complex mixture obtained from plant extracts functions against reactive oxygen species. Thus, the ability of small centaury infusion to act as a scavenger of the reactive oxygen species hydroxyl radical and hypochlorous acid was studied and compared with that of green tea (Camellia sinensis L.). Hydroxyl radical was generated in the presence of Fe3+-EDTA, ascorbate and H2O2 (Fenton system) and monitored by evaluating hydroxyl radical-induced deoxyribose degradation. The reactivity towards hypochlorous acid was determined by measuring the inhibition of hypochlorous acid-induced 5-thio-2-nitrobenzoic acid oxidation to 5,5'-dithiobis(2-nitrobenzoic acid). The obtained results demonstrate that small centaury infusion exhibits interesting antioxidant properties, expressed both by its capacity to effectively scavenge hydroxyl radical and hypochlorous acid, although with a lower activity against the second than that observed for green tea. Green tea exhibited a dual effect at the hydroxyl radical scavenging assay, stimulating deoxyribose degradation at lower dosages.

Antioxidants↗

PubMed2002

Indications and results of resection for hepatocellular carcinoma.

AIM: In this retrospective series we evaluate our experience in surgical treatment of HCC and examine early and long-term results of 46 hepatic resections. METHODS: Eighty-eight patients with HCC have been observed at our Department. Fifty patients (57%) have been operated, but only 46 (92%) could be resected; 43 patients (93.5%) carried liver cirrhosis. We performed 28 non-anatomical resections (60.8%) and 18 anatomical resections (39.2%). Tumour clearance at resection margin of at least 1cm was considered for a curative resections. RESULTS: Overall mortality and morbidity were 8.7 and 30.4% respectively. These rates significantly decreased in the last years: from 1995 to 2000 no hospital mortality has been recorded. Hospital mortality among non-anatomical and anatomical resection subgroups was 3.5 and 16.6% respectively (P<0.02). After a median f.u. of 41 months, 19 patients (45.2%) had recurrences: it was intrahepatic in 16 (84.4%). We observed a 3-, 5- and 10-years actuarial survival rate 62, 51.1 and 22.5% respectively. Long term survival significantly differed between non-anatomical and anatomical resections, with 5-year and 10-year values of 61.1 and 34.3% vs 37.7 and 18.8% respectively (P=0.0224). CONCLUSIONS: Early results after hepatic resection for HCC can be improved by using a limited surgical approach. Long-term results are still unsatisfactory, because of the high recurrence rate that is not influenced by different surgical approaches.

Adolescent↗

PubMed2002

Progress towards the discovery of xanthine oxidase inhibitors.

Xanthine oxidase (XO) is a highly versatile flavoprotein enzyme, ubiquitous among species (from bacteria to human) and within the various tissues of mammals. The enzyme catalyses the oxidative hydroxylation of purine substrates at the molybdenum centre (the reductive half-reaction) and subsequent reduction of O(2) at the flavin centre with generation of reactive oxygen species (ROS), either superoxide anion radical or hydrogen peroxide (the oxidative half-reaction). Many diseases, or at least symptoms of diseases, arise from a deficiency or excess of a specific metabolite in the body. For an example of an excess of a particular metabolite that produces a disease state is the excess of uric acid which can led to gout. Inhibition of XO decreases the uric acid levels, and results in an antihyperuricemic effect. Allopurinol, first synthesised as a potential anticancer agent, is nowadays a clinically useful xanthine oxidase inhibitor used in the treatment of gout. There is overwhelming acceptance that xanthine oxidase serum levels are significantly increased in various pathological states like hepatitis, inflammation, ischemia-reperfusion, carcinogenesis and aging and that ROS generated in the enzymatic process are involved in oxidative damage. Thus, it may be possible that the inhibition of this enzymatic pathway would be beneficial. In this review the State of the Art will be presented, which includes a summary of the progress made over the past years in the knowledge of the structure and mechanism of the enzyme, associated pathological states, and in the efforts made towards the development of new xanthine oxidase inhibitors.

Drug Design↗

PubMed2001

Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis.

The fibroblast growth factor (FGF) family of signaling molecules has been implicated in normal developmental and physiological processes, as well as in human malignancy. Using a homology-based genomic DNA mining process, we identified a human gene encoding a novel member of the FGF family, that we designate FGF-20. The FGF-20 cDNA was isolated, and its sequence confirmed the gene prediction. FGF-20 is expressed in normal brain, particularly the cerebellum, and in some cancer cell lines. Recombinant FGF-20 protein induces DNA synthesis in a variety of cell types and is recognized by multiple FGF receptors. Ectopic expression of FGF-20 in NIH 3T3 cells renders the cells transformed in vitro and tumorigenic in nude mice. These results underscore the utility of mining genomic DNA databases and reveal FGF-20 to be a novel oncogene that may play a role in human cancer.

3T3 Cells↗

PubMed2001

Hydrogen peroxide production in mouse tissues after acute d-amphetamine administration. Influence of monoamine oxidase inhibition.

The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (H2O2) by metabolic or non-metabolic redox pathways, the main objective of this work was to evaluate d-amphetamine-induced H2O2 production in mice liver, kidney and heart. The contribution of monoamine oxidase (MAO) to H2O2 production after d-amphetamine administration was studied using the MAO inhibitor pargyline. H2O2 production was measured indirectly using the catalase-H2O2 complex I irreversible inhibitor 3-amino-1,2,4-triazole (AT). Using this method, the measurement of residual catalase activity following administration of AT permits the monitoring of H2O2 production in vivo. Charles River CD-1 mice (30-35 g body weight) were injected with AT just before the injection of d-amphetamine sulphate (20 mg/kg). d-Amphetamine stimulated the production of H2O2 in all tissues studied, although to different degrees. MAO inhibition by itself led to a remarkable decrease of basal H2O2 production in the kidney and a slight decrease in the liver, although no effect was observed in the heart. d-Amphetamine-induced H2O2 production in the heart and kidney was reduced in MAO-inhibited mice. However, in the liver, H2O2 production was transiently potentiated at 30 min under MAO inhibition. In conclusion, d-amphetamine administration leads to an increase in H2O2 production in mouse liver, kidney and heart, and monoamine oxidase plays an important role in this effect.

Animals↗

PubMed2001

Antioxidant activity of Centaurium erythraea infusion evidenced by its superoxide radical scavenging and xanthine oxidase inhibitory activity.

Centaurium erythraea Rafin. (Gentianaceae) has long been used in traditional medicine. This plant contains considerable amounts of polyphenolic compounds, namely, xanthones and phenolic acids as the main constituents. Because phenolic groups exhibit activity as radical scavengers and/or metal chelators, this study evaluated the superoxide radical scavenging properties of a lyophilized infusion obtained from C. erythraea flowering tops. Superoxide radical scavenging activity was assayed using enzymatic (xanthine/xanthine oxidase) and nonenzymatic (NADH/phenazine methosulfate) superoxide generating systems. This study provided evidence that C. erythraea exhibits interesting antioxidant properties, expressed either by the capacity to scavenge superoxide radical or to noncompetitively inhibit xanthine oxidase. The main phenolic compounds present in this extract were several esters of hydroxycinnamic acids, namely, p-coumaric, ferulic, and sinapic acids.

Antioxidants↗

PubMed2001

PDGF-D, a new protease-activated growth factor.

Platelet-derived growth factor (PDGF) has been directly implicated in developmental and physiological processes, as well as in human cancer, fibrotic diseases and arteriosclerosis. The PDGF family currently consists of at least three gene products, PDGF-A, PDGF-B and PDGF-C, which selectively signal through two PDGF receptors (PDGFRs) to regulate diverse cellular functions. After two decades of searching, PDGF-A and B were the only ligands identified for PDGFRs. Recently, however, database mining has resulted in the discovery of a third member of the PDGF family, PDGF-C, a functional analogue of PDGF-A that requires proteolytic activation. PDGF-A and PDGF-C selectively activate PDGFR-alpha, whereas PDGF-B activates both PDGFR-alpha and PDGFR-beta. Here we identify and characterize a new member of the PDGF family, PDGF D, which also requires proteolytic activation. Recombinant, purified PDGF-D induces DNA synthesis and growth in cells expressing PDGFRs. In cells expressing individual PDGFRs, PDGF-D binds to and activates PDGFR-beta but not PDGFR-alpha. However, in cells expressing both PDGFRs, PDGF-D activates both receptors. This indicates that PDGFR-alpha activation may result from PDGFR-alpha/beta heterodimerization.

3T3 Cells↗

PubMed2001

Paralytic poliomyelitis associated with the Sabin 3 revertant strain of poliovirus in Bahrain.

We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in Bahrain. The case occurred in an 8-week-old infant who had received a dose of oral polio vaccine (OPV) 7 days after birth. She was in contact with two vaccinees who had received OPV during the national immunisation campaign conducted 10 days before her birth. Specimens from the infant were sent to the WHO Collaborating Centre for Virus Reference and Research Laboratory for serological testing and virus detection, including genomic sequencing. Clinical and virological features are presented of a case of VAPP caused by the Sabin 3 strain of poliovirus that had reverted towards neurovirulence. The case represents one in 51,879 first doses of OPV distributed between 1995 and 1998. In order to reduce further the risk of VAPP, the dose of OPV at birth has been discontinued and a sequential schedule of inactivated polio vaccine (IPV) followed by OPV will be recommended.

Antibodies, Viral↗

PubMed2000

Malignancy in HIV/AIDs: a single hospital experience.

BACKGROUND AND OBJECTIVES: Our hospital serves an area with a significant number of patients seropositive for the human immunodeficiency virus (HIV). Intravenous drug abuse and heterosexual exposure are by far the predominant risk factors for HIV and acquired immunodeficiency syndrome (AIDS). Seven percent of these patients develop malignancies. Our aim was to study the types of tumor, their distribution, and to evaluate the patients' outcome. METHODS: Of 3,578 patients with HIV infection or AIDS treated between 1993 and 1998, 245 had 1 or more malignancies. Information was collected on age, sex, race, predisposing risk factors for AIDS, malignancies, symptoms at presentation, the time of the onset of AIDS, CD4 cell counts, pathology findings, and mortality. RESULTS: Although aspects of our patients resembled those of previously studied groups of patients with AIDS, there also were ways in which our patients differed from those other groups. Of our patients, 21. 6% had non-AIDS-defining (NAD) invasive malignancies. This was considerably higher than the rate in most studies. Twenty-seven patients with such malignancies died during the study. Forty-two other patients had pre-invasive cancers. Among patients having AIDS-defining (AD) malignancies, 55.9% died, a fact that was related to patients' low CD4 cell counts and late presentation. Our 97 patients with Kaposi sarcoma included 22 women, a relatively high number that may be related to the fact that most of our patients were intravenous drug abusers or had become infected by heterosexual transmission of HIV. CONCLUSIONS: AIDS is associated with a high risk of malignancy and an unusual spectrum of tumors. Patients with invasive tumors have advanced disease at the time of initial presentation. Those with AD tumors have a worse prognosis than patients with NAD tumors. The impact of highly active antiretroviral therapy on both AD and NAD tumors needs to be further evaluated.

AIDS-Related Complex↗

PubMed2000

Diagnosis and treatment of hypertension in children and adolescents.

OBJECTIVE: To review the current recommendations regarding the diagnosis and treatment of hypertension in children to provide education to practitioners. DATA SOURCES AND STUDY SELECTION: Review of recent recommendations of the Task Force on Blood Pressure Control in Children and the current literature, specifically regarding ambulatory blood pressure monitoring in children. In general, search criteria were restricted to studies with a primary focus of blood pressure for subjects 18 years of age or less, focusing on important studies of the past 20 years. DATA SYNTHESIS: Optimal determination of blood pressure in children requires use of appropriate technique, particularly the use of an appropriately sized cuff, and then comparison with normal values based on age, sex and height. Ambulatory blood pressure monitoring is a research tool that, in selected high risk patients, may facilitate detection of occult hypertension. Careful clinical assessment is the key tool for identifying secondary causes or a predisposition to primary hypertension, with laboratory testing reserved if a specific underlying cause is suspected. Management is directed at secondary causes, and general cardiovascular risk reduction is aimed at dietary modification, increased exercise and attainment or maintenance of ideal body weight. Institution of drug therapy depends on the degree of hypertension and the risk of future end-organ damage or cardiovascular disease. CONCLUSIONS: Hypertension is an under-recognized clinical entity in children. Studies are needed to define the mechanisms and magnitude of cardiovascular risk, the role of ambulatory blood pressure monitoring, and the efficacy and safety of drug therapy.

Adolescent↗

PubMed1999

Effect of d-amphetamine repeated administration on rat antioxidant defences.

The purpose of this study was to evaluate rat tissue antioxidant status after repeated administration of d-amphetamine. Three groups of four rats each were used: control, d-amphetamine sulphate dosed (s.c., 20 mg/kg per day), and pair-fed. After 14 days of d-amphetamine daily administration, superoxide dismutase (CuZnSOD and MnSOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GRed), glutathione-S-transferase (GST), glutathione (GSH), cysteine and thiobarbituric acid reactive substances (TBARS) were measured in liver, kidney, and heart. Various serum and urine parameters were also analysed. d-Amphetamine treatment induced an increase of liver GSH, as well as a decrease of cysteine and MnSOD levels in this organ. A small increase in serum transaminases was also observed in comparison to the pair-fed group. Hepatic levels of TBARS, GPx, GRed and CuZnSOD were found to be similar among the three groups of rats. d-Amphetamine treatment induced an increase of kidney GST, GRed and catalase levels, and an elevation of N-acetyl-beta-D-glucosaminidase efflux to the urine, accompanied by a decrease in urinary creatinine, compared to the pair-fed group. In d-amphetamine treated animals, heart cysteine levels were significantly depleted when compared to the pair-fed group, but all three groups of rats were found to have similar heart antioxidant enzyme levels. These results indicate that repeated administration of d-amphetamine caused a certain degree of stress in liver and kidney, which was followed by adaptations of antioxidant defences. The mechanisms involved in d-amphetamine-induced toxicity may explain the different adaptations observed for the studied organs.

Animals↗

PubMed1999

Ecto-phosphatase activities on the cell surface of the amastigote forms of Trypanosoma cruzi.

Live Trypanosoma cruzi amastigotes hydrolyzed p-nitrophenylphosphate (PNPP), phospho-amino-acids and 32P-casein under physiologically appropriate conditions. PNPP was hydrolysed at a rate of 80 nmol.mg-1.h-1 in the presence of 5 mM MgCl2, pH 7.2 at 30 degrees C. In the absence of Mg2+ the activity was reduced 40% and we call this basal activity. At saturating concentration of PNPP, half-maximal PNPP hydrolysis was obtained with 0.22 mM MgCl2. Ca2+ had no effect on the basal activity, could not substitute Mg2+ as an activator and in contrast inhibited the PNPP hydrolysis stimulated by Mg2+ (I50 = 0.43 mM). In the absence of Mg2+ (basal activity) the stimulating half concentration (S0.5) for PNPP was 1.57 mM, while at saturating MgCl2 concentrations the corresponding S0.5 for PNPP for Mg(2+)-stimulated phosphatase activity (difference between total minus basal phosphatase activity) was 0.99 mM. The Mg-dependent PNPP hydrolysis was strongly inhibited by sodium fluoride (NaF), vanadate and Zn2+ but not by tartrate and levamizole. The Mg-independent basal phosphatase activity was insensitive to tartrate, levamizole as well NaF and less inhibited by vanadate and Zn2+. Intact amastigotes were also able to hydrolyse phosphoserine, phosphothreonine and phosphotyrosine but only the phosphotyrosine hydrolysis was stimulated by MgCl2 and inhibited by CaCl2 and phosphotyrosine was a competitive inhibitor of the PNPP hydrolysis stimulated by Mg2+. The cells were also able to hydrolyse 32P-casein phosphorylated on serine and threonine residues but only in the presence of MgCl2. These results indicate that in the amastigote form of T. cruzi there are at least two ectophosphatase activities, one of which is Mg2+ dependent and can dephosphorylate phospho-amino acids and phosphoproteins under physiological conditions.

4-Nitrophenylphosphatase↗

PubMed1998

Epidemics of aseptic meningitis due to enteroviruses following national immunization days in Bahrain.

We report two successive epidemics of aseptic meningitis due to enteroviruses (EV) observed after national immunization days against polio. Meningitis due to echovirus 30 occurred from July 1995 to the end of January 1996, mostly among children aged 0-12 years (95.1% of cases), and meningitis due to echovirus 4 occurred from May 1996 to the end of September 1996 in the same age group. There were 286 and 169 cases, respectively. Specimens from several representative cases were sent to the WHO Collaborating Center for Virus Reference and Research Laboratory for serological testing and virus detection, including polymerase chain reaction (PCR) studies. Using those tests, evidence of echovirus 30 infection was found in 44% of the children who were sampled during the first epidemic and 45.5% during the second. During echovirus 30 and echovirus 4 epidemics, a similar decline in the age-specific attack rate from 19.1/10,000 and 10.1/10,000 population aged 12 years to 2.4/10,000 and 3.6/10,000 population aged 13 years was observed, respectively.

Adolescent↗

PubMed1995

Proton-pump inhibition and gastric giardiasis: a causal or casual association?

Two patients who developed gastric giardiasis after 2 weeks of treatment with omeprazole 20 mg b.i.d. followed by omeprazole 20 mg per day for 2-6 weeks are described. In one patient, gastric giardiasis occurred in the presence of only mild intestinal metaplasia. In the other patient, Giardia lamblia infection had resolved 4 weeks after the cessation of omeprazole treatment, which, to our knowledge, is the first case reported in the literature. It is tempting to speculate that gastric giardiasis can develop in the absence of mucosal abnormalities during hypochlorhydria induced by treatment with a high dose of a proton-pump inhibitor. Specific treatment may not be required if the drug can be stopped and no other gastric disease causing hypochlorhydria is present.

Aged↗