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Biomedical subjects

P Marco

Publications and source records attributed to P Marco.

At least 19 recordsLinked to original sources

Genetics of Euglossini bees (Hymenoptera) in fragments of the Atlantic Forest in the region of Viçosa, MG.

With uncontrolled deforestation, forest fragments remain, which in most cases are in different stages of regeneration and present isolated populations. In the present study we analyzed the genetic patterns of Eulaema nigrita populations in seven Atlantic Forest fragments of different sizes and successional stages in the region of Viçosa, MG. This was done by RAPD molecular markers. We observed that the area of the fragments had no effect on the genetic variability of E. nigrita in the direction predicted by meta-population models. Medium-sized well-preserved woods presented the lowest variability, whereas large and small woods were statistically identical. The evidence supports the notion that rural areas present greater dispersal among fragments, implying greater similarity between the populations of fragments located in rural areas when compared to fragments in urban areas.

Animals↗

Mutations in the shutter region of antithrombin result in formation of disulfide-linked dimers and severe venous thrombosis.

BACKGROUND: Missense mutations causing conformational alterations in serpins can be responsible for protein deficiency associated with human diseases. However, there are few data about conformational consequences of mutations affecting antithrombin, the main hemostatic serpin. OBJECTIVES: To investigate the conformational and clinical effect of mutations affecting the shutter region of antithrombin. PATIENTS AND METHODS: We identified two families with significant reduction of circulating antithrombin displaying early and severe venous thrombosis, frequently associated with pregnancy or infection. Mutations were determined by standard molecular methods. Biochemical studies were performed on plasma samples. One variant (P80S) was purified by heparin-affinity chromatography and gel filtration, and evaluated by proteomic analysis. Finally, we modelled the structure of the mutant dimer. RESULTS: We identified two missense mutations affecting the shutter region of antithrombin: P80S and G424R. Carriers of both mutations presented traces of a similar abnormal antithrombin, supporting inefficiently expressed rather than non-expressed variants. The abnormal antithrombin purified from P80S carriers is an inactive disulfide-linked dimer of mutant antithrombin whose properties are consistent with head-to-head insertion of the reactive loop. CONCLUSIONS: Our data support the conclusion that missense mutations affecting the shutter region of serpins have specific conformational effects resulting in the formation of mutant oligomers. The consequent inefficiency of secretion explains the accompanying deficiency and loss of function, but the severity of thrombosis associated with these mutations suggests that the oligomers also have new and undefined pathological properties that could be exacerbated by pregnancy or infection.

Adult↗

Plasma von Willebrand factor, soluble thrombomodulin, and fibrin D-dimer concentrations in acute onset non-rheumatic atrial fibrillation.

OBJECTIVE: To investigate whether new onset acute atrial fibrillation (AF) of < 48 hours' duration creates a prothrombotic state in the absence of anticoagulation and to assess the evolution in research indices after spontaneous or pharmacological cardioversion. METHODS: 24 patients were recruited with first onset acute non-rheumatic AF, in whom sinus rhythm was restored within 48 hours of arrhythmia onset, without anticoagulant treatment. Atrial mechanical function was assessed by transmitral inflow. Soluble thrombomodulin and von Willebrand factor concentrations (both as indices of endothelial damage or dysfunction) and fibrin D-dimer concentrations (as an index of thrombogenesis) were measured. Blood samples were drawn and echocardiographic studies were performed at days 1, 3, 7, and 30 after cardioversion. Research indices were compared with those of 24 healthy participants, 24 patients with chronic AF, and 24 patients with ischaemic heart disease in sinus rhythm. RESULTS: Patients with AF had higher concentrations of soluble thrombomodulin (acute AF 12.1 (4.1) ng/ml; chronic AF 11.8 (4.6) ng/ml), von Willebrand factor (acute AF 137.2 (36.9) ng/ml; chronic AF 133.1 (25.0) ng/ml), and fibrin D-dimer concentrations (acute AF 2.35 (2.68) microg/ml; chronic AF 1.12 (0.65) microg/ml) than did healthy controls (5.9 (2.7) ng/ml, 86.7 (33.2) ng/ml, and 0.39 (0.28) microg/ml, respectively) and patients with ischaemic heart disease (7.4 (3.7) ng/ml, 110.0 (29.0) ng/ml, and 0.99 (0.73) microg/ml, respectively) (all p < 0.05). Day 30 concentrations of fibrin D-dimer were higher in patients with acute AF than in patients with chronic AF (p = 0.038) but sTM and von Willebrand factor concentrations were not different (both not significant). There were no significant changes in research indices or echocardiographic parameters after cardioversion (all p > 0.05). CONCLUSIONS: There was evidence among patients with acute onset AF of endothelial damage or dysfunction and increased thrombogenesis, which persisted up to 30 days after cardioversion.

Acute Disease↗

Tissue factor/tissue factor pathway inhibitor system and long-term prognosis after acute myocardial infarction.

UNLABELLED: The tissue factor and tissue factor pathway inhibitor (TFPI) system has been studied in the acute phase of coronary disease but its prognostic importance has been less well assessed. We evaluated its association with recurrent coronary events during long-term follow-up after a myocardial infarction. METHODS: We studied 55 consecutive patients with the following criteria for inclusion: (1) first myocardial infarct; (2) aged < 70 years; (3) non-complicated infarct; (4) low risk effort-test. Blood samples were taken 60-80 days after infarction. Tissue factor, total and free-TFPI were measured. A 4-year follow-up was carried out. Death, unstable angina and new myocardial infarction were considered as poor prognosis. RESULTS: There were no statistical differences in tissue factor/TFPI levels between patients and controls. Total-TFPI showed statistical correlation with total cholesterol (r = 0.59), triglycerides (r = 0.34), LDL-cholesterol (r = 40) and Lipoprotein(a) (r = 0.48). Patients with high levels of cholesterol, LDL-cholesterol and triglycerides showed elevated levels of total-TFPI with no differences in free-TFPI. During follow-up, 8 patients showed poor prognosis. There were no statistical associations between tissue factor/TFPI levels and prognosis. CONCLUSIONS: After acute myocardial infarction, we did not find any differences in the tissue factor/TFPI system between controls and patients. The tissue factor/TFPI system showed little value as a prognostic factor.

Aged↗

Prognostic value of fibrinolytic tests for hospital outcome in patients with acute upper gastrointestinal hemorrhage.

GOALS: We assessed the predictive value of fibrinolytic tests for hospital outcome in a prospective study of 84 nonconsecutive patients with acute upper gastrointestinal hemorrhage. STUDY: Six readily available parameters of activated fibrinolysis (fibrinogen, D-dimer, tissue plasminogen activator [TPA], plasminogen activator inhibitor type 1 [PAI-1], TPA--PAI-1 complexes, and plasmin-alpha 2-antiplasmin complexes) were tested for association with hospital outcome. Patients were divided into the following three groups: patients who survived and did not require transfusion or surgery, those who survived without surgery but required transfusion, and those who required surgery or died. RESULTS: Patients with adverse outcome (surgery and/or death) showed significantly higher plasma levels of D-dimer than patients with favorable outcome (p = 0.01). Plasma concentrations of D-dimer >300 ng/mL showed a 20.5% positive predictive value of adverse outcome, with a relative risk of 7.5 (95% CI: 1--57%). Patients who required transfusion showed significantly higher plasma levels of TPA (p = 0.01). A positive correlation between endoscopic bleeding stigmata and D-dimer in the subgroup of patients without liver cirrhosis was found (p = 0.02); however, in the multivariate logistic regression analysis the concentration of D-dimer did not appear as an independent predictor of adverse outcome. CONCLUSIONS: These findings are consistent with the role of increased local fibrinolysis in the digestive tract, particularly of D-dimer, in patients with upper gastrointestinal hemorrhage and adverse outcome. Accordingly, plasma fibrinolytic tests may constitute an appropriate prognostic marker in upper gastrointestinal bleeding.

Aged↗

An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients.

OBJECTIVE: To determine whether early enteral feeding in a septic intensive care unit (ICU) population, using a formula supplemented with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), improves clinical outcomes, when compared with a common use, high protein enteral feed without these nutrients. DESIGN: A prospective, randomized, multicentered trial. SETTING: ICUs of six hospitals in Spain. PATIENTS: One hundred eighty-one septic patients (122 males, 59 females) presenting for enteral nutrition in an ICU. INTERVENTIONS: Septic ICU patients with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of > or =10 received either an enteral feed enriched with arginine, mRNA, and omega-3 fatty acids from fish oil (Impact), or a common use, high protein control feed (Precitene Hiperproteico). MEASUREMENTS AND MAIN RESULTS: One hundred seventy-six (89 Impact patients, 87 control subjects) were eligible for intention-to-treat analysis. The mortality rate was reduced for the treatment group compared with the control group (17 of 89 vs. 28 of 87; p < .05). Bacteremias were reduced in the treatment group (7 of 89 vs. 19 of 87; p = .01) as well as the number of patients with more than one nosocomial infection (5 of 89 vs. 17 of 87; p = .01). The benefit in mortality rate for the treatment group was more pronounced for patients with APACHE II scores between 10 and 15 (1 of 26 vs. 8 of 29; p = .02). CONCLUSIONS: Immune-enhancing enteral nutrition resulted in a significant reduction in the mortality rate and infection rate in septic patients admitted to the ICU. These reductions were greater for patients with less severe illness.

APACHE↗

Lipid peroxidation in proliferative vitreoretinopathies.

PURPOSE: To study the lipid hydroperoxide activity in vasoproliferative and fibroproliferative retinal disorders. METHODS: Vitreous body samples from patients undergoing vitrectomy because of proliferative vitreoretinopathy (PVR; n = 12) or proliferative diabetic retinopathy (PDR; n = 15), and rhegmatogenous retinal detachment/macular hole/epiretinal membranes as the comparison group (CG; n = 14), were analysed for protein content and basal and induced lipid peroxidation (LPO), as determined by the thiobarbituric acid reactive substances (TBARS) test and LPO 586 commercial kit. The antioxidant activity for superoxide dismutase (SOD) and catalase (CAT) was also assayed. RESULTS: Malondialdehyde (MDA)-like metabolites and 4-hydroxynonenal (4-HNE) mean values were first measured to assess basal LPO, and found to be significantly higher in the PVR and PDR cases than in the CG (p < or = 0.0001). LPO induced by nicotine adenine dinucleotide phosphate iron (NADPH-Fe) was then assayed and the data showed that MDA mean values were 5-fold greater for the PVR and PDR eyes than in the case of basal LPO (p < or = 0.0001). SOD activity was significantly smaller in the PVR (p = 0.0010) and PDR (p < or = 0.0001) groups than in the CG. CAT levels displayed significantly lower values in the PVR and PDR cases than in the CG (p < or = 0.0001). No significant differences in free radical (FR) formation and antioxidant status between PVR and PDR patients were observed. CONCLUSIONS: Fibrovascular proliferative vitreoretinopathies correlate with increased FR formation and decreased antioxidant activity in the human vitreous body.

Adult↗

Macular edema computer-aided evaluation in ocular vein occlusions.

This paper is concerned with the use of digital fundus imaging to detect, quantify, and follow up macular angiographic leakage due to retinal vein occlusions. Images were matched automatically. We detected those pixels with a high increment in gray level within the closest area to the foveal center. Binary images displaying leakage were obtained. The procedure was checked against two observers' agreement. Twenty-one angiographic studies were collected. Two images of each sequence were selected for digitalization. Numerical descriptors of the leakage were proposed and quantification plots were designed for each pair of images. Interobserver concordance ranged between 82 and 98% when manually detected leakage was compared with computer segmented areas. The detection and quantification of leakage areas may serve as a guide for severity evaluation and treatment planning. Moreover, they permit a precise follow-up of macular edema.

Adult↗

Local changes in GTP-binding protein immunoreactivities in human epileptogenic neocortex.

The relative levels of guanine nucleotide-binding protein alpha-subunits Gi1alpha, Gi2alpha, Gi3alpha, Go(alpha), Gs(alpha), and Gx/z(alpha) were measured in neocortex removed at surgery from patients with intractable temporal lobe epilepsy. Immunoreactivity was quantified using specific polyclonal antisera against the Galpha-subunits according to the Laurell "rocket" immunoelectrophoresis technique. We compared the G protein contents of spiking (active) and nonspiking (nonactive) cortical regions, based on intraoperative electrocorticography, within the same and different patients. There were no clear trends for lower or higher levels of G-protein subtypes to be found in the samples of protein extracts from nonspiking regions as compared to spiking regions. However, comparison of paired samples of spiking and nonspiking cortex within the same patient demonstrated that levels of certain G-protein subtypes were either increased or decreased in all patients. This indicates that cortical regions with enhanced neuronal activity may produce microzonal alterations in the levels of G proteins. Moreover, our results suggest that high levels of Gi1alpha and low levels of the other G-protein subtypes appear to be associated with a greater susceptibility to maintaining spiking activity.

Adult↗

Hypofibrinolysis in atrial fibrillation.

BACKGROUND: There is a high incidence of systemic embolism in patients with chronic atrial fibrillation. A hypercoagulable state has been demonstrated, but the fibrinolytic system is rarely studied. METHODS: Plasma levels of modified antithrombin III (ATM), tissue plasminogen activator (TPA), its inhibitor (PAI-1), TPA-PAI-1 complexes and plasmin-antiplasmin complexes (PAP), d -dimer, and fibrinogen were measured in plasma from 36 patients with chronic atrial fibrillation. Fifteen patients had rheumatic mitral stenosis and 21 had nonrheumatic atrial fibrillation. Levels were compared with those found in the plasma of 20 healthy subjects. Transthoracic echocardiographic studies were done. RESULTS: Patients with atrial fibrillation had higher plasma levels of ATM, d -dimer, PAI-1, and TPA-PAI-1 complexes than controls (P <.001). The rheumatic atrial fibrillation group also showed elevated levels of fibrinogen (P <. 05). No significant differences were found in TPA and PAP. There were no differences between rheumatic and nonrheumatic atrial fibrillation. CONCLUSIONS: Atrial fibrillation shows a hypofibrinolytic state caused by elevated PAI-1 levels with no increase in PAP complex concentration. Elevated plasma d -dimer levels suggest increased intravascular thrombogenesis. This may contribute to increased risk of thrombosis.

Aged↗

[Langerhans cell histiocytosis. Report of four cases].

Langerhans cell histiocytosis implies the proliferation and accumulation of anomalous, cytologically benign tissue macrophages in a given site. In the Hospital General y Universitario of Alicante, Spain, from 1975 to 1996 four patients presented with granulomatosis and otorhinolaryngological signs and symptoms: a 7-year-old girl with a right mastoid eosinophil granuloma, a 2-month-old boy with Letterer-Siwe syndrome whose illness started as acute mastoiditis, a 23-month-old boy who developed eosinophil granulomas of both mastoids and one ischium, and an 8-month-old girl with a right zygomatico-temporal eosinophil granuloma. The treatment and clinical course of each case is described and compared with the results of other authors.

Child↗

Immunocytochemical and electron microscope observations on astroglial interlaminar processes in the primate neocortex.

At variance with the rat, previous observations disclosed the presence of long interlaminar astroglial processes in the cerebral cortex of adult nonhuman primates. To examine its presence in human cerebral cortex, samples of frontal and temporal cerebral cortices were obtained during programmed brain surgery from a young patient with an intraventricular astrocytoma, and from one young and two adult patients with frontal and temporal lobe focal epilepsy, respectively. Samples of the visual cortex were also obtained at an autopsy of an 84-year-old woman without any known neurological disease. Brain tissues were processed for GFAP-IR immunocytochemistry. Long, interlaminar, GFAP-IR astroglial processes of usually 300-500 microm, but occasionally reaching almost 1,000 microm, were observed. These processes resembled those previously described in the cerebral cortex of adult New World monkeys. Available data suggest that they may represent a predominant characteristic in postnatal primate cerebral cortex. EM analysis of club-like endings disclosed a multilamellar organization of GFAP-IR intermediate filaments, and the presence of mitochondria and amorphous, electron dense material. Their possible function is yet to be determined.

Adolescent↗

Altered synaptic circuitry in the human temporal neocortex removed from epileptic patients.

Quantitative electron microscopic methods were used to study possible alterations in presumptive excitatory and inhibitory synaptic circuits in human neocortex removed from patients with intractable temporal lobe epilepsy. Synaptic density was compared between normal and abnormal regions as identified by Nissl staining and immunocytochemistry for the Ca2+-binding protein parvalbumin (PV). The normal regions showed a normal cytoarchitecture and normal pattern of staining for PV, whereas the abnormal regions displayed focal neuronal cell loss and a decrease in immunostaining for PV. In the abnormal regions the overall synaptic density (per 100 microm2 and per mm3) was approximately 30% higher than in normal regions, which corresponded to an increase of approximately 300 million synapses per mm3. The number of excitatory and inhibitory synapses was significantly higher and lower, respectively, than in normal regions. We suggest that these changes are a result of a focal sprouting of excitatory axon terminals and loss of inhibitory terminals which leads to hyperexcitatory synaptic circuits. These circuits may represent a neural substrate for the initiation or propagation of seizure activity in human epileptogenic neocortex.

Adolescent↗

Loss of inhibitory synapses on the soma and axon initial segment of pyramidal cells in human epileptic peritumoural neocortex: implications for epilepsy.

The peritumoural neocortex removed from epileptic patients represents an important region for research because of its possible relationship to the generation, maintenance, and propagation of seizures. The peritumoural neocortex removed from an epileptic patient showing a regrowth of an anaplastic astrocytoma was examined in detail using immunocytochemistry for gamma-aminobutyric acid, glutamic acid decarboxylase, parvalbumin, nonphosphorylated neurofilament protein, glial fibrillary acidic protein, and histocompatibility antigen HLA-DR. The patterns of immunostaining were compared with the cytoarchitecture and myeloarchitecture in adjacent sections, and with the patterns of immunostaining observed in normal control neocortex. Furthermore, quantitative electron microscopy was used to compare the synaptic densities of presumptive excitatory and inhibitory synapses between regions showing different grades of cytoarchitectural and neurochemical alterations in the peritumoural neocortex, and to compare these regions with normal neocortex. A variety of changes in synaptic circuits in the peritumoural neocortex was found, but it appears that neurons within the less abnormal-looking regions were involved in altered synaptic circuits that might contribute to epileptic activity. In these regions, the most prominent change was the loss of inhibitory synapses on the soma and axon initial segment of pyramidal cells, but numerous excitatory synapses were present on their dendrites that would make these neurons hyperexcitable. However, the most abnormal regions histologically were likely a primary zone for progression of the tumour, with many surviving neurones, but which received and formed very few synapses; thus, they were probably unrelated to the initiation, maintenance, or propagation of seizures.

Adult↗