Biomedical subjects

Francisco Rubio

Publications and source records attributed to Francisco Rubio.

15 recordsLinked to original sources

PubMed2006

D-dimer local expression is increased in symptomatic patients undergoing carotid endarterectomy.

BACKGROUND: Although atherosclerosis is a silent widespread disease, the focal character of the lesions triggering the clinical manifestations is unquestionable. We hypothesized that symptomatic patients with advanced, unstable carotid plaques have increased local intraplaque and circulating levels of fibrin-fibrinogen related products. METHODS: Plaque tissue and plasma samples were studied in 106 patients undergoing endarterectomy for symptomatic and asymptomatic carotid disease. Fibrin-fibrinogen related products were evaluated by ELISA, Western-blotting, and histology. All tested parameters were compared with patient carotid symptomatology, multiple vascular risk factors (VRF), bilateral carotid pathology, ultrasound examination, and previous therapies with statins and/or antiplatelet drugs. RESULTS: In symptomatic patients, plasma D-dimer was elevated in patients with unstable carotid plaques (UNS) compared with stable (STA) ones (857+/-121 vs. 692+/-156 ng/ml, p=0. 026). Furthermore, plasma D-dimer was significantly increased in patients with a coexistence of carotid and coronary artery disease, compared to others (976+/-325 vs. 714+/-197 ng/ml; p<0.001). Intra-plaque D-dimer content was increased in ulcerated-complicated (UC) plaques compared with fibrous non-complicated (F) plaques in symptomatic patients (5.9+/-1 vs. 1.8+/-1, p<0.001), and in patients with hypercholesterolaemia, compared with those with normal cholesterol levels (6.1+/-1 vs. 2.9+/-0.7; p=0.027). However, there was no correlation between D-dimer content in the carotid plaque and plasma D-dimer levels. CONCLUSIONS: Hypercholesterolemia and UC plaques appear to be associated with high fibrin intraplaque turnover as demonstrated by higher intraplaque D-dimer. Plasma markers of fibrin turnover were increased in UNS plaques, and in patients with coexisting carotid and coronary artery disease. Although, both plasma and plaque D-dimers were associated with unstable carotid disease, the usefulness of the measurement of plasma D-dimer in these patients should be confirmed by prospective studies.

Aged↗

PubMed2006

Changes in hyaluronan production and metabolism following ischaemic stroke in man.

The extent of recovery from stroke is dependent on the survival of neurons, particularly in peri-infarcted regions. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion and better recovery. Hyaluronan (HA) is an important component of the brain extracellular matrix and a regulator of cellular differentiation, migration, proliferation and angiogenesis. We have found that the production of total HA and low molecular mass 3-10 disaccharides of HA (o-HA) was increased in post-mortem tissue and in the serum of patients 1, 3, 7 and 14 days (peaking at 7 days) after ischaemic stroke. Hyaluronidase activity was also increased in serum samples (peaking after 3 days), which might explain the subsequent increase in o-HA. Affinity-histochemical staining was performed using a HA-specific biotinylated binding protein, and it showed enhanced deposition of HA in blood vessels and intracellularly as well as in the nuclei of peri-infarcted neurons. Western blotting and immunohistochemistry demonstrated upregulation of HA synthases (HAS1 and 2) and hyaluronidases (HYAL1 and 2) in inflammatory cells from both stroke and peri-infarcted regions of the brain. HYAL1 was upregulated in microvesssels and intracellularly in neurons, whilst HAS2 became translocated into the nuclei of neurons in peri-infarcted areas. Receptor for HA-mediated motility was observed intracellularly and in the nuclei of neurons, in the tunica media of larger blood vessels and in the endothelial cells of microvessels in stroke-affected tissue, whilst expression of other receptors for HA, CD44 and tumour necrosis factor-stimulated gene 6 (TSG-6) were mainly increased in infiltrating mononuclear cells from inflammatory regions. The data presented here demonstrate that HA breakdown is a feature of the acute stage of stroke injury. Increased o-HA production soon after stroke may be detrimental through enhancement of the inflammatory response, whilst activation of HA and/or o-HA-induced cellular signalling pathways in neurons and microvessels may impact on the remodelling process by stimulating angiogenesis and revascularization, as well as the survival of susceptible neurons.

Aged↗

PubMed2006

Endogenous expression of C-reactive protein is increased in active (ulcerated noncomplicated) human carotid artery plaques.

BACKGROUND AND PURPOSE: There is growing evidence suggesting that C-reactive protein (CRP) is an effecter molecule able to induce and promote atherothrombosis. The presence of CRP in atherosclerotic plaques may reflect local production or infiltration from circulating CRP increased in general inflammatory responses. Our aim was to analyze the presence of CRP in human advanced carotid artery plaques with differential anatomo-pathological characteristics and to assess local expression of CRP and other proinflammatory genes in these lesions. METHODS: Human carotid artery specimens from 38 patients undergoing scheduled endarterectomy were classified into 3 groups: ulcerated (noncomplicated) (UNC, n=19), fibrous (F, n=12) and ulcerated (complicated/hemorrhagic) plaques (UC, n=7). The presence of CRP was evaluated by immunohistochemistry, and plasma samples were screened for circulating high-sensitivity C-reactive protein. TaqMan Low-density Arrays were used for study of genes related to inflammation (CRP, interleukin-6, macrophage colony-stimulating factor-1, monocyte chemotactic protein-1, cyclooxygenase-2). RESULTS: CRP mRNA levels were predominantly detected in UNC-high risk plaques but not in UC (P=0.001). UNC also exhibit the highest expression levels of other genes involved in the inflammatory responses: cyclooxygenase-2 (P<0.005 versus F and versus UC), IL-6 (P<0.005 versus F and versus UC) and monocyte chemoattractant protein-1 (P<0.01 versus F and versus UC). Plaque CRP mRNA levels correlated with immunohistochemical findings but were independent of plasma high-sensitivity CRP. In UNC plaques endothelial cells and inflammatory cells were strongly positive for CRP around areas of newly formed microvessels. CONCLUSIONS: In human high-risk carotid artery plaques (UNC) CRP expression reflects an active proinflammatory stage. Local synthesis of CRP could be involved in plaque neovascularization and increased risk of hemorrhagic transformation.

Aged↗

PubMed2006

Citicoline in intracerebral haemorrhage: a double-blind, randomized, placebo-controlled, multi-centre pilot study.

BACKGROUND: In experimental models citicoline has shown beneficial effects in intracerebral haemorrhage. Citicoline is a neuroprotectant drug with some beneficial effects in human ischaemic stroke and with an excellent safety profile. We decided to carry out a pilot study to test its safety and efficacy in human intracerebral haemorrhaging. METHODS: In this double-blind, placebo-controlled pilot study, patients had to be previously independent, aged between 40 and 85 years, and had to be admitted within 6 h after onset of symptoms of an acute primary supratentorial hemispheric cerebral haemorrhage diagnosed by neuroimaging (CT or MRI). Baseline severity was defined as patients with a score larger than 8 points on the Glasgow Coma Scale and larger than 7 on the National Institutes of Health Stroke Scale. Patients received either a placebo or 1 g/12 h citicoline for 2 weeks (orally or intravenously). The primary aim was to evaluate safety with respect to the number of adverse events that occurred. The efficacy endpoint was the percentage of patients with a modified Rankin Score (mRS) at 3 months. RESULTS: 19 patients in each group were included in the study. The incidence of serious adverse events was not different among groups (4 patients in each group). One patient in the placebo group was categorised as independent (mRS<or=2) in comparison with 5 patients in the citicoline group (OR, 5.38; 95% CI, 0.55-52). CONCLUSIONS: Citicoline seems to be a safe drug in human intracerebral haemorrhage with a positive trend regarding efficacy. These data should be confirmed in a larger trial.

Activities of Daily Living↗

PubMed2006

High-affinity potassium and sodium transport systems in plants.

All living cells have an absolute requirement for K+, which must be taken up from the external medium. In contrast to marine organisms, which live in a medium with an inexhaustible supply of K+, terrestrial life evolved in oligotrophic environments where the low supply of K+ limited the growth of colonizing plants. In these limiting conditions Na+ could substitute for K+ in some cellular functions, but in others it is toxic. In the vacuole, Na+ is not toxic and can undertake osmotic functions, reducing the total K+ requirements and improving growth when the lack of K+ is a limiting factor. Because of these physiological requirements, the terrestrial life of plants depends on high-affinity K+ uptake systems and benefits from high-affinity Na+ uptake systems. In plants, both systems have received extensive attention during recent years and a clear insight of their functions is emerging. Some plant HAK transporters mediate high-affinity K+ uptake in yeast, mimicking K+ uptake in roots, while other members of the same family may be K+ transporters in the tonoplast. In parallel with the HAK transporters, some HKT transporters mediate high-affinity Na+ uptake without cotransporting K+. HKT transporters have two functions: (i) to take up Na+ from the soil solution to reduce K+ requirements when K+ is a limiting factor, and (ii) to reduce Na+ accumulation in leaves by both removing Na+ from the xylem sap and loading Na+ into the phloem sap.

Adenosine Triphosphatases↗

PubMed2005

Carotid endarterectomy: is it still a gold standard?

Extracranial internal carotid artery stenosis accounts for 15-20% of ischemic strokes. Carotid endarterectomy has high efficacy in stroke prevention in selected patients with symptomatic (age <80 years) and asymptomatic carotid stenosis (age <75 years). Randomized clinical trials demonstrated that carotid endarterectomy reduces the stroke risk, compared to medical therapy alone, for patients with 70-99% symptomatic stenosis with 16% absolute risk reduction at 5 years. The benefit for patients with 50-69% symptomatic stenosis is lower i.e. absolute risk reduction 4.6% at 5 years. Endarterectomy is not indicated for symptomatic patients with <50% stenosis. There is no need for time-delay for surgery in patients after transient ischemic attack or minor stroke. Patients with more extensive strokes or hemorrhage should undergo surgery after 4-6 weeks following initial symptoms. Carotid endarterectomy for asymptomatic stenosis reduces the risk of ipsilateral stroke, and any stroke, by approximately 30% over 3 years. However, the absolute risk reduction is small over the first few years and decision should be based on individual institutional experience. In all situations, the best medical therapy should accompany surgery. In the recent years, appearance of angioplasty, stenting, and distal protection procedures provides competitive alternatives to classical endarterectomy. However, long-term benefits of carotid angioplasty should be confirmed by bigger, randomized, comparative clinical trials.

Angioplasty↗

PubMed2005

Intraplaque MMP-8 levels are increased in asymptomatic patients with carotid plaque progression on ultrasound.

Carotid atherosclerotic plaque remodelling and increased risk of symptomatic plaque rupture seem to be partially mediated by matrix metalloproteinases (MMPs). In this study, we have investigated whether different MMPs are related to carotid atherosclerosis or to recent ischaemic brain disease. Eighty-four consecutive patients undergoing carotid endarterectomy for symptomatic and asymptomatic disease were studied. Plaques were analysed by ultrasound and later by morphology. Plasma MMP-2, MMP-8 and MMP-9 levels were quantified by ELISA. MMP expression and activity in carotid plaques was analysed by Western blotting and in situ zymography. Results were analysed with respect to plaque stability, morphology, symptomatic disease, presence of vascular risk factors and plasma markers of acute inflammation as high sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer and white blood cell counts. Patients with hypoechogenic plaques on ultrasound had more plasma MMP-8 (p = 0.04) and increased MMP activity as assessed by in situ zymography. Asymptomatic patients with plaque progression had more active intraplaque MMP-8 than asymptomatic patients without plaque progression. Presence of recent intraplaque haemorrhage or past history of CAD was related to increased activity of MMPs as assessed by in situ zymography (p < 0.01, CI 95% 0.8-1.0). Plasma MMP-8 and MMP-9, but not MMP-2 levels, decrease with time after ischaemic stroke. Patients with hypertension had more intraplaque active MMP-9 than normotensive (p = 0.03, CI 95% 0.7-1.0). Hypoechogenic carotid plaques had increased MMP activity and asymptomatic patients with plaque progression show increase intraplaque MMP-8 levels.

Aged↗

PubMed2005

High-affinity K+ uptake in pepper plants.

High-affinity K+ uptake is an essential process for plant nutrition under K+-limiting conditions. The results presented here demonstrate that pepper (Capsicum annuum) plants grown in the absence of NH4+ and starved of K+ show an NH4+-sensitive high-affinity K+ uptake that allows plant roots to deplete external K+ to values below 1 microM. When plants are grown in the presence of NH4+, high-affinity K+ uptake is not inhibited by NH4+. Although NH4+-grown plants deplete external K+ below 1 microM in the absence of NH4+, when 1 mM NH4+ is present they do not deplete external K+ below 10 microM. A K+ transporter of the HAK family, CaHAK1, is very likely mediating the NH4+-sensitive component of the high-affinity K+ uptake in pepper roots. CaHAK1 is strongly induced in the roots that show the NH4+-sensitive high-affinity K+ uptake and its induction is reduced in K+-starved plants grown in the presence of NH4+. The NH4+-insensitive K+ uptake may be mediated by an AKT1-like K+ channel.

Biological Transport, Active↗

PubMed2005

Laser evoked potentials and prepulse inhibition of the blink reflex in patients with Wallenberg's syndrome.

Spinothalamic tract lesions in patients with Wallenberg's syndrome can be demonstrated by abnormalities in the laser evoked potentials (LEPs) to stimulation of the affected side. However, before reaching the structures generating LEPs, laser stimuli can induce effects at a subcortical level. We examined LEPs and laser-induced prepulse inhibition of the blink reflex in seven patients with Wallenberg's syndrome within a month after the infarct. All patients had abnormally elevated thresholds for temperature and pain sensation, and for pinprick pain induced by laser stimuli, in the affected vs the non-affected side. LEPs to stimulation of the affected side were abnormal because of absent, reduced or delayed responses. However, the same laser stimuli that were unable to induce LEPs generated normal inhibition of the blink reflex response when applied 250ms before a trigeminal nerve electrical stimulus. The percentage inhibition induced in the R2 response of the blink reflex by laser stimulation of the affected side was not different from that induced by stimulation of the non-affected side, or in control subjects. These results are compatible with either a different pathway for prepulse inhibition and evoked potentials or a reduced energy requirement of the sensory input generating prepulse inhibition in comparison to that generating evoked potentials.

Adult↗

PubMed2005

Meningeal lymphomatosis as the first manifestation of splenic marginal zone lymphoma.

Meningeal lymphomatosis (ML) as the first manifestation of a splenic marginal zone lymphoma (SMZL) is rare. The descriptions of only 2 cases with this complication, one of which had ML as the first manifestation, have been published to date. We describe a 53-year-old man, an ex-smoker, who presented with transitory episodes of bilateral loss of visual acuity. On examination, only papilledema and splenomegalia were observed. The hemogram showed a predominance of lymphocytes with a villous morphology. Cytochemical staining and an immunophenotypic analysis revealed a positive reaction to tartrate-sensitive acid phosphatase and B-lineage markers (CD19+, CD20+, CD79b+, surface immunoglobulin 3 expression, immunoglobulin D+, CD5-, CD23-, CD10-, CD25-, CD103-, and CD11c-). Magnetic resonance imaging of the brain showed tumoral infiltration in both optic nerves and in the cervicodorsal meninges. The cerebrospinal fluid examination revealed significant pleocytosis, and all lymphocytes had a phenotype identical to that of the peripheral blood, confirming the presence of ML. The bone marrow section also showed lymphocytes with an immunophenotype identical to that of the peripheral blood.A splenectomy confirmed the SMZL diagnosis. Treatment with corticosteroids and intrathecal chemotherapy was administrated; however, the response was not good, and the patient died. In this report, we discuss the other 2 cases and ML in B-cell chronic lymphoproliferative disorders.

Adrenal Cortex Hormones↗

PubMed2004

Cloning and functional characterization of the high-affinity K+ transporter HAK1 of pepper.

High-affinity K+ uptake in plants plays a crucial role in K+ nutrition and different systems have been postulated to contribute to the high-affinity K+ uptake. The results presented here with pepper (Capsicum annum) demonstrate that a HAK1-type transporter greatly contributes to the high-affinity K+ uptake observed in roots. Pepper plants starved of K+ for 3 d showed high-affinity K+ uptake (Km of 6 microM K+) that was very sensitive to NH and their roots expressed a high-affinity K+ transporter, CaHAK1, which clusters in group I of the KT/HAK/KUP family of transporters. When expressed in yeast ( Saccharomyces cerevisiae ), CaHAK1 mediated high-affinity K+ and Rb+ uptake with Km values of 3.3 and 1.9 microM, respectively. Rb+ uptake was competitively inhibited by micromolar concentrations of NH and Cs+, and by millimolar concentrations of Na+.

Blotting, Northern↗

PubMed2004

Usefulness of anticoagulants in the prevention of ischemic stroke.

Oral anticoagulants are drugs commonly used in the prevention of vascular diseases, especially in embolic-type processes. Although several studies have assessed the possibility of using them in arterial processes, the experience has not been satisfactory so far. Heart diseases with major emboligenic flow are still the main indication, while the prevention of other low-risk heart diseases and treatment of large- or small-artery disease can be based on antiaggregant treatment. Other groups study the problem in large series.

Anticoagulants↗

PubMed2003

Three-dimensional structure and survival of newly formed blood vessels after focal cerebral ischemia.

Penumbra tissue becomes highly angiogenic after ischaemic stroke in man, and the re-establishment of a functional vasculature might be beneficial to patients. Unilateral ischaemia was induced in male Sprague-Dawley rats by permanent occlusion of the distal left middle cerebral artery (MCAO). Animals with stroke were kept alive for 1, 7, 14, 21 or 28 days after which time they were terminally anaesthetized. Vascular casts of infarcted areas, analyzed by scanning electron microscopy demonstrated that radially arranged neocortical arterioles and venules lost their regular patterns within one day of occlusion, and soon afterwards started to form a very dense network of anastomosing microvessels. At 1 week, vascular budding was visible at many sites. The smallest microvessels (4-10 microm) formed connections with the surrounding proliferating vessels similar to those in the normal brain. Survival of microvascular endothelial cells (ECs) was studied by double labeling of tissue sections using immunohistochemistry and antibodies to caspase-3, and TUNEL staining for apoptotic cells. ECs demonstrated intensive staining for caspase-3 and also staining by TUNEL, particularly near the infarct border, 14 days post-MCAO. These data support the hypothesis that growing blood vessels in ischaemic tissue form new connections, the pattern of which is similar to that in normal rat brain, but different to those formed in growing tumours. This normal growth pattern might be essential in future therapies involving induction of vascularization and neuroprotection to enhance long-term survival of the penumbra.

Animals↗

PubMed2003

Meningeal carcinomatosis as the first manifestation of a transitional cell carcinoma of the bladder.

Meningeal carcinomatosis (MC) as first manifestation of a transitional cell carcinoma (TCC) of the bladder is rare. We report a 66-year-old man, smoker, who presented with two episodes of secondarily generalized partial motor seizures. The routine blood test, brain computed tomography (CT) scan, brain magnetic resonance imaging and electroencephalogram were normal. Cerebral spinal fluid (CSF) revealed a significant pleocytosis and a morphology compatible with non-differentiated non-small cell carcinoma. Broncofiberscopy, gastrofiberscopy, thoracicoabdominopelvic CT-scan and bone scintigraphy were normal but the urine cytology revealed malignant cells similar to those found in the CSF. TCC was diagnosed by cystoscopy and later necropsy confirmed the MC of this tumor. In this report we review the literature and analyze patient survival.

Aged↗

PubMed2003

Public perception of stroke in Spain.

BACKGROUND AND PURPOSE: Stroke is one of the leading causes of death and disability in western countries. Improving attention to stroke demands better public information about the illness. The aim of the present study was to determine the current knowledge of stroke among the Spanish population. METHODS: We conducted a population-based telephone interview in Spain. A total of 3,000 respondents were selected at random following a systematic procedure aimed at filling the sex/age community quotas. RESULTS: A total of 16,016 telephone calls were made. Three thousand respondents were eligible and 2,884 completed the telephone interview. Only 4.5% of respondents knew the term stroke, 1,719 (59.6%) participants were able to mention at least one stroke risk factor, and only 940 (32.6%) could mention at least one stroke sign without prompting. Most respondents considered stroke to be a severe and dangerous illness that can be treated, but less than half of the respondents went immediately to a hospital when faced with a stroke event. Suitable stroke knowledge was only achieved by 302 (10.5%) respondents. Those who had home-based occupations and no previous stroke experience were less likely to have suitable stroke knowledge. CONCLUSIONS: This study confirms that our community is still unfamiliar with stroke. Wide population-based educational programs are needed to increase public knowledge of stroke. Our results indicate that people with home-based occupations should be the main target of our education campaigns.

Adult↗