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Biomedical subjects

A Ortega

Publications and source records attributed to A Ortega.

At least 19 recordsLinked to original sources

[Posterior spinal artery infarction and nonbacterial thrombotic endocarditis].

Nonbacterial thrombotic endocarditis (NBTE) has been described as an important complication in patients affected by different kind of illnesses, above all underlying malignancies. Fifty % of the patients affected by NBTE will have embolic events in different organs. The poverty of specific symptomatology appears to difficult seriously its diagnosis. In fact, systemic embolic infarctions are usually asymptomatic, except when central nervous system is involved. We present a patient affected by NBTE with an asymptomatic cervical spinal cord infarction, which diagnosis was made by pathologic study. The difficulty to explore typical sings of spinal lesion and the absence of previous reported cases of NBTE with posterior spinal artery infarction, make this one fairly interesting. We think that fibrinoplatelet embolism from NBTE should be included in the etiology of the posterior spinal artery infarction.

English Abstract↗

Glutamate activates PP125(FAK) through AMPA/kainate receptors in Bergmann glia.

Glial glutamate receptors are likely to play a role in plasticity, learning, and memory and in a number of neuropathologies. An enhanced glutamate-dependent tyrosine phosphorylation has been detected in such processes. Using primary cultures of chick Bergmann glia cells and chick cerebellar slices, we addressed whether glial glutamate receptors can activate the nonreceptor tyrosine kinase pp125 focal adhesion kinase (pp125(FAK)). A dose- and time-dependent tyrosine phosphorylation of pp125(FAK) was found in both preparations upon glutamate treatment. This effect was mediated through alpha-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate (AMPA)/kainate (KA) receptors, as shown by its inhibition by the specific antagonists 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7- sulfonamide (NBQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX) and the lack of effect of metabotropic agonists. FAK tyrosine phosphorylation was dependent on phosphatidylinositol 3-kinase activity. As expected, an increase in pp125(FAK) catalytic activity was found upon glutamate treatment. Immunprecipitation experiments demonstrated that FAK associates with ionotropic glutamate receptors. Taken together, these results suggest a role for glial glutamate receptors in cytoskeletal rearrengments and focal adhesion contact formation and provide new insight into the signaling transactions elicited by this neurotransmitter in glial cells.

Animals↗

Involvement of pp125FAK and p60SRC in the signaling through Fc gamma RII-Fc gamma RIII in murine macrophages.

Cross-linking the FcgammaRs can activate a wide variety of biological responses in macrophages. Receptor stimulation induces activation of protein tyrosine kinase cascades that result in phagocytosis, a process known to involve cytoskeletal rearrangements. Therefore, an involvement of non-receptor tyrosine kinases such as pp125FAK, in FcgammaR signaling is likely. Using the murine macrophage cell line J774, we demonstrate that FcgammaRII-RIII cross-linking induces a time- and dose-dependent increase in tyrosine phosphorylation of the focal adhesion kinase pp125FAK that correlates with an increase in its catalytic activity. Interestingly enough, pp125FAK activation results in its association both to the FcgammaRII-III and to p60Src. The results presented here define a novel-signaling pathway likely to be important in low affinity FcgammaRII-III mediated phagocytosis.

Animals↗

A phase I clinical trial of a multi-epitope polypeptide TAB9 combined with Montanide ISA 720 adjuvant in non-HIV-1 infected human volunteers.

A phase I clinical trial was performed to examine the safety and immunogenicity of a multi-epitope polypeptide comprising the central 15 amino acids of the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsified in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males. Three immunisations were given at months 0, 1 and 6 in a randomised, double blind, placebo controlled clinical trial. The placebo was generally well tolerated. However, severe local reactions were observed in TAB9 vaccinated subjects after the second and third inoculations. Seven out of eight volunteers from the lower dose group showed moderate or severe local inflammation, while four out of eight subjects from the higher dose group developed granulomas and sterile abscesses. In general, the reactogenicity depended on the number of inoculations given and the dose of TAB9. Both doses were immunogenic, all immunised volunteers seroconverted and antibodies were broadly reactive against the V3 peptides included in the protein. All vaccine's sera reacted against gp120 in Western blot and 50% of them also neutralised at least one out of five laboratory isolates tested. No differences between doses were found. Anti TAB9 lymphoproliferative responses were observed, being more intense in the high dose group. Due to the strong local reactions that were found in this study, a change in the formulation will be required for further trials with this vaccine candidate in humans.

AIDS Vaccines↗

Amarisolide monohydrate, a 2-(beta-glucosyl)neoclerodane.

The absolute configuration of the neoclerodane glycoside amarisolide, presented here as the monohydrate, C26H36O9*H2O, has been determined by association with the known configuration of the glucose moiety. Its structure was established as 2beta-(O-beta-D-glucopyranosyl)neocleroda-3,13(16),14-trien-15,16-epoxy-18,19-olide. Extensive hydrogen bonding among the hydroxyl groups of the sugar moiety forms layers which are interconnected by water molecules.

Asteraceae↗

Tumoricidal activity of endothelial cells. Inhibition of endothelial nitric oxide production abrogates tumor cytotoxicity induced by hepatic sinusoidal endothelium in response to B16 melanoma adhesion in vitro.

The mechanism of NO- and H(2)O(2)-induced tumor cytotoxicity was examined during B16 melanoma (B16M) adhesion to the hepatic sinusoidal endothelium (HSE) in vitro. We used endothelial nitric-oxide synthetase gene disruption and N(G)-nitro-l-arginine methyl ester-induced inhibition of nitric-oxide synthetase activity to study the effect of HSE-derived NO on B16M cell viability. Extracellular H(2)O(2) was removed by exogenous catalase. H(2)O(2) was not cytotoxic in the absence of NO. However, NO-induced tumor cytotoxicity was increased by H(2)O(2) due to the formation of potent oxidants, likely ( small middle dot)OH and (-)OONO radicals, via a trace metal-dependent process. B16M cells cultured to low density (LD cells), with high GSH content, were more resistant to NO and H(2)O(2) than B16M cells cultured to high density (HD cells; with approximately 25% of the GSH content found in LD cells). Resistance of LD cells decreased using buthionine sulfoximine, a specific GSH synthesis inhibitor, whereas resistance increased in HD cells using GSH ester, which delivers free intracellular GSH. Because NO and H(2)O(2) were particularly cytotoxic in HD cells, we investigated the enzyme activities that degrade H(2)O(2). NO and H(2)O(2) caused an approximately 75% (LD cells) and a 60% (HD cells) decrease in catalase activity without affecting the GSH peroxidase/GSH reductase system. Therefore, B16M resistance to the HSE-induced cytotoxicity appears highly dependent on GSH and GSH peroxidase, which are both required to eliminate H(2)O(2). In agreement with this fact, ebselen, a GSH peroxidase mimic, abrogated the increase in NO toxicity induced by H(2)O(2).

Cell Communication↗

Calorimetric investigations of the structural stability and interactions of colicin B domains in aqueous solution and in the presence of phospholipid bilayers.

The effects of pH and temperature on the stability of interdomain interactions of colicin B have been studied by differential-scanning calorimetry, circular dichroism, and fluorescence spectroscopy. The calorimetric properties were compared with those of the isolated pore-forming fragment. The unfolding profile of the full-length toxin is consistent with two endothermic transitions. Whereas peak A (T(m) = 55 degrees C) most likely corresponds to the receptor/translocation domain, peak B (T(m) = 59 degrees C) is associated with the pore-forming domain. By lowering the pH from 7 to 3.5, the transition temperature of peaks A and B are reduced by 25 and 18 degrees C, respectively, due to proton exchange upon denaturation. The isolated pore-forming fragment unfolds at much higher temperatures (T(m) = 65 degrees C) and is stable throughout a wide pH range, indicating that intramolecular interactions between the different colicin B domains result in a less stable protein conformation. In aqueous solution circular dichroism spectra have been used to estimate the content of helical secondary structure of colicin B ( approximately 40%) or its pore-forming fragment ( approximately 80%). Upon heating, the ellipticities at 222 nm strongly decrease at the transition temperature. In the presence of lipid vesicles the differential-scanning calorimetry profiles of the pore-forming fragment exhibit a low heat of transition multicomponent structure. The heat of transition of membrane-associated colicin B (T(m) = 54 degrees C at pH 3.5) is reduced and its secondary structure is conserved even at intermediate temperatures indicating incomplete unfolding due to strong protein-lipid interactions.

Calorimetry↗

[Utility of SPECT with 99m Tc-tetrofosmin and stimulus with dipyridamole in patients with permanent ventricular pacemakers].

BACKGROUND AND OBJECTIVE: Patients with permanent ventricular pacemakers (PP) are a difficult subgroup to assess in the study of coronary artery disease. The objective of this study was to evaluate the diagnostic value of the myocardial perfusion scintigraphy with 99mTC-Tetrofosmin (Tc-Tf) and stimulus with dipyridamole in patients with PP and suspected coronary artery disease. PATIENTS AND METHODS: Fourteen patients with suspected coronary artery disease and without structural cardiopathy, who underwent Tc-Tf and cardiac catheterization, were studied retrospectively. Sensitivity, specificity, predictive values and Kappa index were calculated for the diagnosis of coronary artery disease, multivessel disease, and for each one of the coronary arteries (left anterior descending, right coronary, and circumflex). In addition, the correlation between the number of territories with perfusion defects and the number of diseased vessels was studied. RESULTS: In regards to the diagnosis of coronary artery disease, sensitivity, specificity, positive predictive value, negative predictive value and the Kappa index were 100%, 50%, 83%, 100% and 0.55, respectively. For multi-vessel disease, these values were 83%, 64%, 64%, 83% and 0.43 respectively. The correlation coefficient between the number of territories with perfusion defects and the number of diseased vessels was 0.61 (p = 0.02). In the diagnosis of anterior descending disease, sensitivity and specificity were 83% and 88% respectively. For the right coronary artery, these values were 100% and 44% and for the circumflex artery 38% and 83%, respectively. CONCLUSION: In patients with PP and suspected coronary artery disease, myocardial perfusion scintigraphy with Tc-Tf and stimulus with dipyridamole is of great value in the diagnosis of coronary artery disease and in the assessment of its extension.

Aged↗

[Regional diastolic function is more preserved in viable than non-viable myocardium. Demonstration by pulsed-wave Doppler tissue imaging in basal conditions].

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the differences in regional diastolic function between viable and non-viable myocardium when assessed by pulsed-wave Doppler tissue imaging performed in basal conditions. PATIENTS AND METHODS: The study population included 21 patients with three-vessel disease and regional systolic dysfunction. These patients underwent transthoracic echocardiographic study and pulsed-wave Doppler tissue imaging in basal conditions and, in addition, stress echocardiography with dobutamine performed by a different investigator. RESULTS: Three-hundred and twenty-two segments were studied, 140 of which (43%) had systolic dysfunction. Of the 140 segments with systolic dysfunction, 52 (37%) were considered hypokinetic by transthoracic echocardiography, 80 (57%) akinetic and 8 (6%) dyskinetic. As assessed by dobutamine echocardiography, 67 segments (48%) were considered viable and 73 (52%) non-viable. Viable segments had a higher peak velocity of the early diastolic wave e (5.5 +/- 1.9 vs. 4.7 +/- 2.0 cm/s; p = 0.03). An e/a ratio < 1 was more frequent in non-viable versus non-viable segments (52 vs. 70%; p < 0.05). There were no differences in relation to regional isovolumetric relaxation time and peak velocity of a wave. Although peak velocity of s wave was lower in non-viable segments, differences were not statistically significant. CONCLUSION: Compared with non-viable segments, viable myocardial segments have less impaired regional diastolic function as assessed by pulsed-wave Doppler tissue imaging.

Echocardiography, Doppler, Pulsed↗

Histamine H1 receptor activation stimulates mitogenesis in human astrocytoma U373 MG cells.

In human astrocytoma U373 MG cells that express histamine H1 receptors (180 +/- 6 fmol/mg protein) but not H2 or H3 receptors, histamine stimulated mitogenesis as assessed by [3H]-thymidine incorporation (173 +/- 2% of basal; EC50, 2.5 +/- 0.4 microM). The effect of 100 microM histamine was fully blocked by the selective H1 antagonist mepyramine (1 microM) and was markedly reduced (93 +/- 4% inhibition) by the phospholipase C inhibitor U73122 (10 microM). The activator of protein kinase C (PKC) phorbol 12-tetradecanoyl-13-acetate (TPA, 100nM) stimulated [3H]-thymidine incorporation (270 +/- 8% of basal), and this response was not additive with that to 100 microM histamine. The incorporation of [3H]-thymidine induced by 100 microM histamine was partially reduced by the PKC inhibitor Ro 31-8220 (57 +/- 7% inhibition at 300 nM) and by the compound PD 098,059 (30 microM, 62 +/- 14% inhibition), an inhibitor of the mitogen-activated kinase (MAPK) kinases MEK1/MEK2. These results show that histamine H1 receptor activation stimulates the proliferation of human astrocytoma U373 MG cells. The action of histamine appears to be partially mediated by PKC stimulation and MAPK activation.

Astrocytoma↗

Up-regulation of parathyroid hormone-related protein in folic acid-induced acute renal failure.

BACKGROUND: Parathyroid hormone (PTH)-related protein (PTHrP) is present in many normal tissues, including the kidney. Current evidence supports that PTHrP is involved in renal pathophysiology, although its role on the mechanisms of renal damage and/or repair is unclear. Our present study examined the changes in PTHrP and the PTH/PTHrP receptor (type 1) in folic acid-induced acute renal failure in rats. The possible role of PTHrP on the process of renal regeneration following folic acid administration, and potential interaction between angiotensin II (Ang II) and endothelin-1, and PTHrP, were examined in this animal model. METHODS: PTHrP, PTH/PTHrP receptor, ACE, and preproendothelin-1 (preproET-1) mRNA levels in the rat kidney were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and/or RNase protection assay. Immunohistochemistry also was performed for PTHrP, the PTH/PTHrP receptor, and Ang II in the renal tissue of folic acid-injected rats. The role of PTHrP on tubular cell proliferation following folic acid injury was investigated in vitro in rat renal epithelial cells (NRK 52E). PTHrP secretion in the medium conditioned by these cells was measured by an immunoradiometric assay specific for the 1-36 sequence. RESULTS: Using RT-PCR, PTHrP mRNA was rapidly (1 hour) and maximally increased (3-fold) in the rat kidney after folic acid, decreasing after six hours. At 72 hours, renal function was maximally decreased in these rats, associated with an increased PTHrP immunostaining in both renal tubules and glomeruli. In contrast, the PTH/PTHrP receptor mRNA (RNase protection assay) decreased shortly after folic acid administration. Moreover, PTH/PTHrP receptor immunostaining dramatically decreased in renal tubular cell membranes after folic acid. A single subcutaneous administration of PTHrP (1-36), 3 or 50 microg/kg body weight, shortly after folic acid injection increased the number of tubular cells staining for proliferating cell nuclear antigen by 30% (P < 0.05) or 50% (P < 0.01), respectively, in these rats at 24 hours, without significant changes in either renal function or calcemia. On the other hand, this peptide failed to modify the increase (2-fold over control) in ACE mRNA, associated with a prominent Ang II staining into tubular cell nuclei, in the kidney of folic acid-treated rats at this time period. The addition of 10 mmol/L folic acid to NRK 52E cells caused a twofold increase in PTHrP mRNA at six hours, without significant changes in the PTH/PTHrP receptor mRNA. The presence of two anti-PTHrP antibodies, with or without folic acid, in the cell-conditioned medium decreased (40%, P < 0.01) cell growth. CONCLUSIONS: Renal PTHrP was rapidly and transiently increased in rats with folic acid-induced acute renal failure, featuring as an early response gene. In addition, changes in ACE and Ang II expression were also found in these animals. PTHrP induces a mitogenic response in folic acid-damaged renal tubular cells both in vivo and in vitro. Our results support the notion that PTHrP up-regulation participates in the regenerative process in this model of acute renal failure and is a common event associated with the mechanisms of renal injury and repair.

Acute Kidney Injury↗

Accumulation of metals in autopsy tissues of subjects living in Tarragona County, Spain.

The concentrations of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V) and zinc (Zn) were determined in autopsy tissues collected from subjects who at the time of death had lived in Tarragona (Catalonia, Spain) over a period of, at least, the previous 10 years. Samples of liver, lung, kidney, brain and bone were obtained from a total of 78 non-occupationally exposed subjects, autopsied between 1997 and 1999. Arsenic, Cd, Co, Cr, Cu, Pb, Mn, Hg, Ni, Sn, V and Zn were determined by inductively coupled plasma spectrometry (ICP/MS). The results were analyzed with respect to age, sex, smoking and drinking habits, and the subject's place of residence. Most tissue concentrations of As, Co, Cr, Hg and V were near to the analytical detection limit or, in some cases, even below it. However, the levels of Cu were slightly higher than the average concentrations found in other studies. Also, tissue concentrations of Mn, Sn and Zn were similar to those found in previous surveys, while those of Ni were lower than previously reported. Although the current levels of tissue Cd and Pb were comparatively lower than in studies in other areas, the distribution of both metals was similar to previously-reported trends. From the tissue metal concentrations observed in the present study, it would appear that neither environmental exposure nor a dietary excess of these elements could be considered a health hazard to people living in the study area.

Age Factors↗

Effects of topical tumoricidal agents on port-site recurrence of colon cancer: an experimental study in rats.

BACKGROUND: Reports of metastatic spread of colon and rectal cancer to port sites after laparoscopic resection of potentially curable lesions has raised doubt regarding the efficacy and safety of laparoscopic technology in cancer surgery. Experimental study in animals has led us to believe that the mode of spread of these metastases is via the direct route. We hypothesized, therefore, that we could decrease the rate of trocar-site recurrences by treating the individual port sites with a topical tumoricidal agent. MATERIALS AND METHODS: Male BD-IX rats weighing 240 to 360 g were injected with syngeneic colon cancer to simulate free intraperitoneal cancer spread to trocar sites. All rats were subjected to a sham laparoscopic operation after 2 x 10(5) viable cancer cells had been injected into their peritoneal cavities. Five-millimeter trocars were inserted into each rat after abdominal insufflation to 10 mm Hg. Pneumoperitoneum was maintained for 10 minutes before the trocars were removed simultaneously. Trocar sites were then subjected to one of three treatments, with each animal receiving a maximum of two different treatments. Sites were treated with 70% ethanol (N = 42), povidine/ iodine (N = 40), or no topical treatment (N = 46). Three weeks later, the animals were euthanized and autopsied. Subcutaneous tumors at trocar sites or tumors with >50% volume within the wound were considered implants. RESULTS: Control sites revealed a metastasis rate of 41% (19/46). The tumor implant rate was 36% (15/42) at alcohol-treated sites and 20% (8/40) at sites treated with povidone-iodine (P < 0.05). CONCLUSION: Topical administration of povidone-iodine to trocar wounds after laparoscopic surgery can significantly reduce the incidence of port-site metastasis in a syngeneic animal model of colon cancer.

Administration, Topical↗

Incremental validity of the MMPI-2 Content Scales: a preliminary study with brain-injured patients.

OBJECTIVE: To examine the usefulness of the MMPI-2 Content Scales among traumatic brain injury (TBI) patients. DESIGN: Hierarchical stepwise regression analyses with the SCL-90-R scales as the criterion variables were conducted to determine the incremental validity of the Content Scales beyond the information provided by the Clinical Scales. PARTICIPANTS: 27 persons with moderate to severe TBI who had been discharged to the community from inpatient rehabilitation between 6 months and 4 years before the beginning of the study. RESULTS: The Content Scales accounted for an additional 4% to 36% of the variance of SCL-90-R scales beyond that predicted by the Clinical Scales. CONCLUSIONS: Interpretation of the Content Scales may be particularly valuable with TBI patients, because they provide an additional avenue for the identification of distressing symptoms.

Adult↗

Alpha-vascular responses after short-term and long-term inhibition of nitric oxide synthesis.

Apart from the direct actions of nitric oxide (NO) on vascular smooth muscle, this factor may regulate cardiovascular functions through specific actions on alpha-adrenergic constrictor mechanisms. In this study we aim to establish whether the inhibition of the synthesis of this mediator could alter the vasoconstrictor responses mediated by alpha-adrenoceptor stimulation. We have been able to demonstrate that the blockage of the NO synthase really does exist, when both short- and long-term treatments with Nomega-nitro-Larginine methyl ester (L-NAME) are carried out. We have evaluated the concentration-dependent contractions induced by the selective alpha1-adrenoceptor agonists methoxamine and phenylephrine in isolated rat aorta rings in the following groups of animals: control, short-term L-NAME-treated (100 mg/kg i.p. 20 min before subjecting the animals to the experiments) and long-term L-NAME-treated (100 mg/kg per day in the drinking water for 7, 21, or 45 days). We have also evaluated the pressor responses to methoxamine and to the selective alpha-adrenoceptor agonist B-HT 920 using the pithed rat preparation in the same groups of animals. The contractile responses to methoxamine and phenylephrine were similar in the rat aorta preparations from control and short-term L-NAME-treated animals. On the contrary, in the rat aorta preparations from long-term L-NAME-treated animals these responses were clearly reduced when compared with the corresponding responses in those from control animals, the reduction being more marked when the treatment lasted longer. The pressor responses to methoxamine were also similar in control and short-term L-NAME-treated pithed rats. Nevertheless, the responses to B-HT 920 were greater in the latter. On the other hand, the dose-response curves to both alpha-adrenoceptor agonists were shifted to the right in a non-parallel manner in rats treated long term with L-NAME, the shift being, in the case of B-HT 920, more accentuated when the treatment lasted 21 or 45 days than when it lasted only 7 days. These results indicate that the short-term decrease in NO synthesis does not modify the vascular smooth muscle responses mediated by alpha1-adrenoceptor stimulation, but it does induce a potentiation of sympathetic vasoconstriction mediated by alpha2-adrenoceptors. Nevertheless, the long-term inhibition of NO synthesis causes a compensating decrease in the alpha1- and alpha2-vascular smooth muscle contractile responses.

Adrenergic alpha-Agonists↗

A multinational study to measure the value that patients with cancer place on improved emesis control following cisplatin chemotherapy.

BACKGROUND: The neurokinin-1 (NK1) receptor antagonists are a new class of agents designed to reduce the risk of emesis following chemotherapy, particularly with cisplatin. Early data from double-blind randomised trials suggest that an orally administered NK1 antagonist can reduce the absolute risk of acute and delayed emesis following cisplatin by 20 and 30%, respectively. OBJECTIVE: To measure the value that patients with cancer place on improved emesis control and quality of life. DESIGN: Willingness-to-pay analysis. SETTING: Five study sites in Canada, Italy, Spain and Greece. PATIENTS AND PARTICIPANTS: 245 patients with cancer either receiving chemotherapy with cisplatin or who had received cisplatin-based chemotherapy within the previous 6 months. METHODS: After background information had been presented, patients were asked to define the maximum that they would pay per day for a drug that reduced their risk of acute and delayed (days 2 to 5) emesis by 20 and 30%, respectively. Costs were converted to US dollars ($US) using year 2000 exchange rates. RESULTS: For a 20% improvement in acute emesis, Canadian, Italian and Spanish patients with cancer were willing to pay $US46, $US34 and $US63 per day, respectively, compared with $US8 for patients from Greece (p < 0.001). For a 30% improvement in delayed emesis, Canadian, Italian and Spanish patients with cancer were also willing to pay more than their Greek counterparts (SUS41, $US31, $US50 and $US9 daily for 4 days, respectively; p < 0.001). These significant differences in patient value between countries remained, even after adjusting for socioeconomic variables and previous history of emesis. CONCLUSIONS: There are substantial cultural differences in how patients with cancer value benefit and improved quality of life. Since the majority of the world's population resides outside North America and Western Europe, there may be a need to re-evaluate perceived levels of patient benefit and measures of quality of life.

Antiemetics↗