Microbubble ultrasound: how can it help detect melanoma metastasis?
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Biomedical subjects
Publications and source records attributed to F Teixeira.
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Animal-type melanoma is a rare variant of melanoma in humans.1 Its name is derived from its histological appearance, which is similar to that described in melanomas occurring in white or gray horses.2 All tumors are dermally located, and characterized by a proliferation of deeply pigmented elongated or rounded cells, showing moderate atypia and a low mitotic rate. In some tumors, secondary infiltration of the epidermis has been noted. More than half of the patients are younger than 30 years, and prognosis seems to be much better than that expected for a superficial spreading or nodular melanoma of the same size. We report the first case of animal-type melanoma in situ.
Congenital splenic cysts are uncommon entities, especially in children. Few cases diagnosed in the prenatal period have been reported in the literature. We describe two cases that were identified by prenatal sonography at 34 and 30 gestational weeks. Their follow-up until spontaneous full regression at 5 months and 2 years, respectively, is discussed. The etiology, clinical findings, and clinical course of this entity are reviewed.
The two-compound product calcipotriol/betamethasone dipropionate is arising as a first-line treatment for mild-to-moderate plaque psoriasis. Its beneficial action is attributed to the synergistic effect of its components on keratinocyte proliferation and differentiation, and on inflammation. The good tolerability of the two-compound product is thought to be due to the anti-inflammatory effect of betamethasone. Evidence from short-term (4-12 weeks) and long-term use (> 1 year) has shown a good safety profile. Areas such as the face or skin folds, which are sensitive to the components of the combination, should be avoided. Finally, it is unsuitable for use in unstable psoriasis, in which potent steroids may lead to an increased inflammatory response.
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1. The aim of the present study was to evaluate the effect of preventive and curative isosorbide-5-mononitrate (Is-5-Mn) treatment on the development of hypertension, cGMP content, thromboxane (TX) A(2)/prostaglandin (PG) I2 balance, the peripheral serotonergic system, platelet activation, lipid peroxidation and plasma lipids in cyclosporine A (CsA)-induced hypertensive rats. 2. Control, CsA (5 mg/kg per day) and Is-5-Mn (150 mg/kg per day, b.i.d.) rat groups were treated orally over a period of 7 weeks. The preventive Is-5-Mn group (Is-5-Mn + CsA) was first treated for 2 weeks with Is-5-Mn, followed by 7 weeks with both drugs; the curative Is-5-Mn group (CsA + Is-5-Mn) was treated for a period of 7 weeks with CsA and with both drugs for an additional 5 weeks. The control group received oral vehicle. 3. Whereas in the group undergoing preventive treatment the CsA-induced increase in blood pressure (BP), compared with the control group, was avoided, in the group undergoing curative treatment, the increase in BP was even higher. The decreased arterial cGMP content in the CsA group was prevented and reverted when Is-Mn was administered either preventatively or curatively with CsA. Platelet TXA2 production, although unaffected in the Is-5-Mn + CsA group, was significantly higher in the CsA + Is-5-Mn group compared with the group receiving CsA alone. Furthermore, plasma TXA2 was reduced following preventive Is-5-Mn treatment, but was worsened in the group undergoing curative therapy. Aortic PGI2 synthesis was identical in all groups. Consequently, the TXA2/PGI2 ratio was only altered in the CsA + Is-5-Mn group, demonstrating a markedly higher value. In both groups treated simultaneously with CsA and Is-5-Mn, a higher platelet 5-hydroxytryptamine (5-HT) content was obtained compared with CsA treatment alone, but only preventive treatment with Is-5-Mn resulted in a significant reduction in plasma 5-HT. Changes in ADP and collagen-induced platelet aggregation paralleled those of plasma 5-HT and TXA2: the hyperaggregation profile of the CsA group, although partially prevented, was not reverted by simultaneous treatment with Is-5-Mn and CsA. Lipid peroxidation and lipid profile values also worsened in the CsA + Is-5-Mn group compared with the group administered CsA alone. 4. In conclusion, the beneficial effects of concomitant Is-5-Mn and CsA treatment were demonstrated when Is-5-Mn was administered preventatively because not only was arterial hypertension prevented, but platelet aggregation and plasma TXA2 and 5-HT levels were also reduced. In contrast, following curative treatment, the BP, platelet/vascular vasoconstrictor balance, lipid peroxidation and plasma lipids were aggravated, recommending a judicious evaluation of the impact of nitrate therapy throughout the period of its administration.
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BACKGROUND: Psoriasis is a common chronic and recurrent inflammatory skin disorder. Oxygen metabolites and proteases released by activated inflammatory cells may induce oxidative and proteolytic damage to plasma constituents and red blood cells (RBCs). RBCs have a limited biosynthesis capacity and poor repair mechanisms. OBJECTIVES: To study RBCs as a potential cumulative marker of oxidative and proteolytic stress in psoriasis, and as a marker of worsening of the disease. METHODS: The study was performed in 70 patients with mild or severe psoriasis and in 40 control individuals. We evaluated total and differential leucocyte count and, as markers of leucocyte activation, plasma elastase and lactoferrin. Besides the basic RBC study (RBC count, haematocrit, haemoglobin concentration and haematimetric indices) we evaluated antioxidant defences (catalase, superoxide dismutase, glutathione peroxidase and selenium), osmotic fragility and reticulocyte count; in the RBC membrane we evaluated lipid peroxidation and susceptibility to lipid peroxidation, membrane fluidity, levels of cholesterol and phospholipids, membrane-bound haemoglobin, band 3 profile and levels of vitamin E; serum levels of bilirubin, total plasma antioxidant capacity, lipid profile and lipid peroxidation were also evaluated. RESULTS: Psoriasis patients showed a rise in leucocytes, mainly neutrophils, which was associated with a rise in elastase and lactoferrin. Patients had a reduced RBC count, antioxidant defences and membrane fluidity, elevated membrane lipid peroxidation, membrane-bound haemoglobin, osmotic fragility and reticulocyte count, and a different band 3 profile. Most of these modifications were enhanced in severe psoriasis. CONCLUSIONS: In summary, our data show that the RBCs are at a lower number in psoriasis patients, and present several changes denoting an enhanced damage and/or ageing process, which seem to be strongly connected with neutrophil activation, oxidative stress and worsening of psoriasis.
BACKGROUND: Psoriasis is a chronic and recurrent inflammatory skin disease. The inflammatory response represents a fundamental ability of the organism to protect itself from infectious agents and from injury. OBJECTIVES: To evaluate the inflammatory response in mild and in severe psoriasis, to evaluate the endogenous systems counterbalancing the deleterious effects of the inflammation products, and to establish values of prognostic significance. METHODS: The study was performed in a control group (n = 40) and in 60 patients with psoriasis vulgaris, half presenting with mild psoriasis, and the other half with severe psoriasis. We evaluated total and differential leucocyte count; elastase, lactoferrin and lipid peroxidation as markers of neutrophil activation; total plasma antioxidant capacity (TAS), transferrin, ceruloplasmin, alpha(1)-antitrypsin and alpha(2)-macroglobulin as markers of the endogenous antioxidant and antiprotease systems; and fibrinogen, erythrocyte sedimentation rate, C-reactive protein (CRP), haptoglobin, C3 and C4 complement proteins as markers of inflammation. RESULTS: Our data suggested that psoriasis is an inflammatory condition in which neutrophils seem to play a crucial role by contributing to the development of oxidative and proteolytic stress. The worsening of the disease seemed to be linked to the enhancement of the inflammatory response and of the imbalance between neutrophil activation products and their inhibitors. CONCLUSIONS: We propose values for elastase, CRP, elastase/alpha(2)-macroglobulin, elastase/alpha(1)-antitrypsin, thiobarbituric acid/TAS and elastase/neutrophil ratios with prognostic significance for the worsening of psoriasis.
Arterial hypertension is one of the main side effects of cyclosporin treatment and seems to be due to activation of the sympathetic nervous system. Some authors hypothesized that cyclosporin may act on the sympathetic nervous endings increasing catecholamine release, in agreement with our previous works which demonstrated an increase in rat plasma catecholamine levels after 30 mg/kg per day cyclosporin treatment for 7 weeks. Therefore, the aim of this work was to study the cyclosporin mechanism responsible for that increase in plasma catecholamines. Male Wistar rats were used. Noradrenaline release was performed in vitro experiments after loading rat aorta abdominal segments with 3H-noradrenaline (3H-NA). The release of 3H-NA was measured after electrical stimulation in the presence of 10(-6)M cyclosporin. In another set of experiments electrical stimulation was replaced by a pulse addition of cyclosporin (10(-6)M). Another group of rats was treated with 30 mg/kg per day cyclosporin for 7 weeks and catecholamine contents in aorta abdominal segments and adrenals were measured by high performance liquid chromatography system with electrochemical detection (HPLC-ECD). An increase in the 3H-NA release was observed in both types of in vitro experiments. Since cocaine abolished these cyclosporin effects, the obtained results suggest that cyclosporin may act on the catecholamine transporter across the membrane. In addition, after the 7 weeks of cyclosporin treatment, a significant decrease in catecholamine aorta contents was verified but in adrenals there was no difference regarding to controls. However, the dopamine synthesis/degradation ratio measured by the DA/DOPAC ratio suggests an increase in dopamine synthesis. These facts are in agreement with the enhanced plasma catecholamine levels and with the hypothesis of tissue catecholamine depletion. However, they do not explain the increase in plasma adrenaline levels, since adrenaline is a reflex of adrenal activity. The synthesized dopamine in adrenals seems to be unable to reach vesicles and to be metabolized in adrenaline. The observed decrease in HVA adrenal levels may be a consequence of extraneuronal uptake inhibition or inhibition by cyclosporin of the direct o-methylation of DOPAC. In conclusion, our results suggest that cyclosporin increases catecholamine release from the sympathetic nervous endings by a tyramine-like effect, i.e. by acting directly on the catecholamine transporter of the membrane.
Oxidized cellulose and collagen are two absorbable hemostatic scaffolding materials that are used widely in surgery. A histomorphological study was undertaken to determine the tissue response and extent of healing brought about by intraosseously implanting these two materials in the femur and tibia of sheep. There was no major difference in the rate of repair of the bone defects brought about by these two materials, with the bone defects being completely repaired by lamellar bone at 6-8 weeks. Therefore, our results suggest that, in most instances where collagen is presently used in surgical applications, it could be substituted by oxidized cellulose.
OBJECTIVES: To evaluate agreement between causality assessments of reported adverse drug reactions (ADRs) obtained from decisional algorithms, with those obtained from an expert panel using the WHO global introspection method (GI), according to different levels of imputability and to evaluate the influence of confounding variables. METHOD: Two hundred reports were included in this study. An independent researcher used decisional algorithms, while an expert panel assessed the same ADR reports using the GI, both aimed at evaluating causality. Reports were divided according to the presence, absence or lack of information on confounding variables. RESULTS: The rates of concordance between assessments made using the algorithms and GI according to levels of imputability were: 45% for 'certain', 61% for 'probable', 46% for 'possible' and 17% for drug unrelated terms. When confounding variables were taken into account, the rates of concordance for the 'absence of information', 'lack of information' and 'presence of confounding variables' in the 'certain' group were 49, 69 and 7%, respectively. The corresponding values for the 'probable' group were 80, 68 and 24% and 30, 51 and 51%, respectively for the 'possible' group. CONCLUSION: Full agreement with global introspection was not found for any level of causality assessment. Confounding variables were found to be associated with low levels of agreement between decision algorithms and the GI method compromising the algorithms' sensitivity and specificity.
Coenzyme Q10 (CoQ10) or ubiquinone, a redox component of the mitochondrial electron transport chains, is a powerful antioxidant and membrane stabilizer that may prevent cellular damage during myocardial ischemia and reperfusion therapy. Coenzyme Q10 has been used primarily as an adjuvant therapy for some cardiomyopathies. However, one of the main problems in CoQ10 administration is the high variability of endogenous plasma and tissue levels, which seems to be dependent on several factors. This work explores temporal 24h and seasonal variation as well as gender and racial differences in endogenous plasma ubiquinone concentration. Coenzyme Q10 measurements (quantified by HPLC-UV) of 16 healthy volunteers were done during the daytime hours of activity beginning at 09:00h one day and ending at 09:00h the next day (13 different determinations) in two distinct months. April and October, of the year. A statistically significant circadian rhythm in plasma ubiquinone concentration that includes only the fundamental 24h component was demonstrated both in the April and October data. Furthermore, the time-point means of the ubiquinone concentration in the October study were invariably higher than those obtained in the April study. No statistically significant differences were found in CoQ10 concentration between male and female subjects, both in April and in October. In addition, racial differences were demonstrated; lower plasma ubiquinone levels were found in Caucasian compared to African subjects. However, the latter small group of subjects failed to demonstrate a circadian rhythm, neither in the April nor in the October analysis.
A possible explanation for cyclosporin-induced arterial hypertension may be its action on the adrenergic system. In spite of the controversial results reported in literature, it seems that cyclosporin changes the vascular response to noradrenaline. Therefore, after observation that two cyclosporin doses increase rat blood pressure and vascular reactivity in response to noradrenaline, the aim of this work was to study the cellular mechanisms beside the cyclosporin-induced changes in response to noradrenaline. Therefore, the cyclosporin influence on alpha(1)-adrenoceptors as well as on their transduction mechanism in smooth muscle cells was studied. Through Scatchard analysis of specific [(3)H]-prazosin binding, the alpha(1)-adrenoceptor number and related affinity were studied, before and after cyclosporin exposure. The cyclosporin influence on alpha1-adrenoceptor transduction mechanisms was also evaluated by the quantification of intracellular free calcium contents [Ca2+]i and inositol phosphate (InsP) turnover. All in vitro experiments were performed in rat aortic smooth muscle cells in culture. Results showed that both cyclosporin concentrations (10(-6) and 10(-7) M) changed alpha1-adrenoceptor number but only 10(-7) M cyclosporin increased its affinity for [(3)H]-prazosin. Compared with control cells, only 10(-7) M cyclosporin increased InsP levels. Stimulation by noradrenaline increased InsP in 10(-7) M cyclosporin-treated cells but decreased InsP in the presence of 10(-6) M cyclosporin. Both cyclosporin concentrations increased [Ca2+]i in basal conditions and after noradrenaline stimulation. The results suggest that after noradrenaline stimulation cyclosporin increases [Ca2+]i, probably through different mechanisms, depending on the cyclosporin concentration used. However, 10(-7) M cyclosporin increases alpha1-adrenoceptor affinity and their related transduction mechanisms. The higher cyclosporin concentration (10(-6) M) seems to induce downregulation of alpha1-adrenoceptors, probably by activation of protein kinase C.
Psoriasis is a common chronic and recurrent inflammatory skin disorder that has been associated with oxidative stress, abnormal plasma lipid metabolism and with high frequency of cardiovascular events. This prevalence seems to be related to the severity of psoriasis, as it occurs more frequently in patients presenting large areas of the body affected with psoriasis lesions. The aim of our work was to evaluate the development of oxidative stress and of dislipidemia in psoriasis, and to look for a correlation between their levels and worsening of psoriasis. We evaluated lipid profile, total antioxidant capacity, antioxidant vitamins A and E, and lipoperoxidation products. The study was performed in controls and in patients presenting mild and severe psoriasis. Patients presented risk changes in lipid profile (a rise in cholesterol (P<0.01), triglycerides (P<0.001), low density lipoprotein cholesterol (P<0.01), very low density lipoprotein cholesterol (P<0.01), apolipoprotein B (P<0.001) and lipoprotein(a) (P<0.001); and a reduction in high density lipoprotein cholesterol (P<0.001)), a rise in lipoperoxidation products (P<0.001) and a reduction in total antioxidant capacity (P<0.001) and in antioxidant vitamins A (P<0.001) and E (P<0.05). Moreover, we found that the worsening of psoriasis was associated with the enhancement of oxidative stress and of the lipid risk changes. Our data suggest that psoriasis patients must be considered as a group at risk for cardiovascular disease and that this risk seems to be higher in severe psoriasis. In addition, a possible benefit of an enriched diet or of a supplement of vitamins A and E in psoriasis patients should be further studied.
The increase in absolute number of deaths from ischemic heart disease (IHD) in the population aged > or = 65 years, in both sexes, in Madeira, when comparing the years 1987 and 1996, led to significant increases in the corresponding standardized death rates that go against the stabilization seen at national level. Significant increases in these rates for the same years were also seen in the district of Beja and in the Azores. The aim of this study was to ascertain the trends for the incidence, morbidity and mortality from acute myocardial infarction (AMI) in patients admitted in Madeira and its contribution to the increase in these rates, particularly in the population aged < 65 years of both sexes, which the number of deaths from ischemic heart disease did not increase. We studied 119 pts with AMI admitted in 1987 (year A), of whom 53 were aged < 65 years, and 186 pts with AMI admitted in 1996 (year B), of whom 72 were aged < 65 years, whose data were included in the Madeira Ischemic Heart Disease Register (RECIMA), an IHD hospital register that covers 1792 patients admitted with AMI in the Coronary Intensive Care Unit of the Department of Medical and Surgical Cardiology of Funchal Hospital over a period of 15 years (1984-1998). Mortality by the 28th day (fatal AMI admissions) in all ages fell slightly in both sexes in the two years studied (A = 19.3%; B = 16.1%). The number of fatal AMI admissions rose among females in the two age groups considered A = 11; B = 20; delta% = +45) and fell among males (A = 12; B = 10; delta% = -20). In males aged > or = 65 years, this number remained the same (A = 7; B = 7) and fell in males aged > or = 65 years (A = 5; B = 3; delta% = -40). The number of pts who survived to the 28th day (non-fatal AMI admissions) rose in all age groups for both sexes (A = 96; B = 156; delta% = +38.46), as did the ratios with deaths from IHD. These increases were roughly double in the group of patients aged 65 years compared to patients aged < 65 years. We found highly significant positive correlations in the population aged < 65 years between the number of non-fatal AMI admissions (morbidity data) and the number of deaths from IHD (mortality data) recorded in every year of the 10-year period 1987-96, these values being highly significant in both sexes (r = 0.89; p < 0.0001), in males (r = 0.87; p < 0.0001) and in females (r = 0.77; p < 0.0001). Since our study was carried out on an island on which all AMI cases are admitted to a single treatment center, we can conclude that these positive correlations represent a trend towards worsening of morbidity and mortality from IHD in Madeira in the population aged < 65 years, even though the number of deaths from IHD did not rise. The establishment of IHD registers similar to RECIMA in other regions of the country would help to identify trends in morbidity, mortality, and morbidity plus mortality in this population that would be useful in improving the orientation of resources allocated to the prevention and treatment of cardiovascular diseases.