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Biomedical subjects

A Rábano

Publications and source records attributed to A Rábano.

At least 19 recordsLinked to original sources
PubMed2006

Classification of surgical procedures for epidemiologic assessment of sporadic Creutzfeldt-Jakob disease transmission by surgery.

BACKGROUND: In this preparatory phase of a case-control study, we propose and evaluate a new tool for classifying surgical procedures (SPs) in categories useful for epidemiologic research on surgical transmission of sporadic Creutzfeldt-Jakob disease (sCJD). METHODS: All SPs reported to the Swedish National Hospital Discharge Registry in the period 1974-2002, and undergone by 212 Swedish patients with registered diagnosis of CJD at death, hospital discharge or notification, in the period 1987-2002, 1060 age-, sex- and residence-matched controls and 1340 randomly chosen population controls, were reclassified into one of six categories of hypothetical transmission risk level. For that purpose the following two attributes were used: non-disposable instruments involved; and highest assigned ad-hoc risk level for four tissues or anatomical structures contacting such instruments. RESULTS: A total of 1170 different SP codes were reclassified as follows: 3.1% in the high-risk, 59.1% in the lower-risk, 24.4% in the lowest-risk, and 2.1% in the no-risk groups, with 11.3% procedures negatively defined by rubric as "other than..." being assigned to two spurious diluted-high and diluted-lower risk categories. The high-risk group mainly comprised neurosurgical (53%) and ophthalmic (39%) procedures. Sensitivity of neurosurgery and of ophthalmic surgery excluding neurosurgery, for the high- and diluted-high risk vs. other categories was 46% and 84%, while specificity was 98% and 95%, respectively. Sensitivity analysis based on these indices revealed that non-significant odds ratio effects of 1.4 and 1.3 for neurosurgery and ophthalmic surgery corresponded to statistically significant values of 5.1 after reclassification. CONCLUSIONS: This classification might contribute to quantify effects masked by use of body-system SP-categories in case-control studies on sCJD transmission by surgery.

Case-Control Studies↗
PubMed2005

Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection.

Transgenic (Tg) mice carrying four extra octapeptide repeats (OR) in the bovine PrP gene (10OR instead of 6) have been generated. In these mice, neuropathological changes were observed depending upon the level of transgene expression. These changes primarily involved a slowly advancing neurological disorder, characterized clinically by ataxia, and neuropathologically, by vacuolization in different brain areas, gliosis, and loss of cerebellar granule cells. Accumulation of insoluble bovine 10OR-PrP (bo10OR-PrP) was observed depending on the level of expression but no infectivity was found associated with this insoluble form. We also compared the behavior of bo6OR-PrP and bo10OR-PrP Tg mouse lines in response to BSE infection. BSE-inoculated bo10ORTg mice showed an altered course of BSE infection, reflected by reduced incubation times when compared to bo6ORTg mice expressing similar levels of the wild type 6OR-PrP. In BSE-inoculated mice, it was possible to detect PrP(res) in 100% of the animals. While insoluble bo10OR-PrP from non-inoculated bo10ORTg mice was non-infectious, brain homogenates from BSE-inoculated bo10ORTg mice were highly infectious in all the Tg mouse lines tested. This Tg mouse model constitutes a new way of understanding the pathobiology of bovine transmissible spongiform encephalopathy. Its potential applications include the assessment of new therapies against prion diseases.

Animals↗
PubMed2004

Different behavior toward bovine spongiform encephalopathy infection of bovine prion protein transgenic mice with one extra repeat octapeptide insert mutation.

In humans, insert mutations within the repetitive octapeptide region of the prion protein gene (Prnp) are often associated with familial spongiform encephalopathies. In this study, transgenic mice expressing bovine PrP (boTg mice) bearing an additional octapeptide insertion to the wild type (seven octapeptide repeats instead of six) showed an altered course of bovine spongiform encephalopathy (BSE) infection, reflected as reduced incubation times when compared with boTg mice expressing similar levels of the wild-type six-octapeptide protein. In both boTg mouse lines (bo6ORTg and bo7ORTg), incubation times were affected drastically depending on transgene expression levels and the inoculum used. In accordance with the lack of an interspecies barrier to BSE infection, we detected the typical signs of CNS spongiform degeneration by histopathological analysis and the presence of the bovine prion PrP(res) by Western blot or immunohistochemical analyses. When 7OR-PrP(res) was propagated in bo7ORTg mice, a similar earlier onset of clinical signs was observed compared with bo6ORTg mice. Proteins PrP(C) and PrP(res) containing seven octapeptides (7OR-PrP(C) and 7OR-PrP(res)) showed similar protease sensitivity and insolubility in nondenaturing detergents to homologous 6OR-PrP(C) and 6OR-PrP(res). In addition, bo7ORTg mice showed a higher sensitivity than bo6ORTg mice for detecting prion infection in specimens previously diagnosed as negative by conventional biochemical techniques. In the absence of clinical signs of disease, 7OR-PrP(res) could be detected as early as 120 d after inoculation by immunohistochemical and Western blot analyses. These findings may help us improve the current mouse bioassays and understand the role of the octapeptide repeat region in susceptibility to disease.

Age of Onset↗
PubMed2002

Fatty acid amide hydrolase localization in the human central nervous system: an immunohistochemical study.

Recent discoveries have opened new fields for research on the biochemistry and pharmacology of cannabinoids. Among them, and most importantly, are the characterization and molecular cloning of central and peripheral cannabinoid receptors as well as the isolation of the first putative endogenous ligands that bind to them, anandamide and 2-arachidonylglycerol. The enzyme that degrades these so-called "endocannabinoids" is an integral membrane protein, fatty acid amide hydrolase. Its distribution and biochemistry in rat brain suggest that it plays a critical role in the regulation of the endocannabinoid system. However, few data exist regarding its distribution and mechanism of action in human tissues. To that end, we have studied its cellular distribution in the human central nervous system by immunohistochemistry. Using an affinity-purified antibody, we report that fatty acid amide hydrolase is localized to specific and well-delimited cell populations, including cortical pyramidal neurons, subcortical white matter astrocytes, striatal and striatoefferent projecting neurons, hypothalamic and midbrain nuclei, granular and molecular layers of the cerebellum, Purkinje neurons, dentate cerebellar nucleus, inferior olivary nuclei and others. This distribution resembles that of the central cannabinoid receptors as well as that of the enzyme distribution in the rat brain. In summary, the cellular localization of the degradative enzyme of the endogenous cannabinoid ligands in human central nervous system reveals its presence on both neuronal and glial elements and shows a significant overlapping with that of central cannabinoid receptors, mainly in areas related with motor control, confirming the notion that the endocannabinoid system plays a critical role in the control of movement.

Adult↗
PubMed2000

Paradoxical effects of temperature on vascular tone.

Temperature may have significant influence on vascular tone in such cases as organ preservation, coronary bypass surgery, and extracorporeal circulation. The aim of this research was to study the direct effect of temperature variation on vascular tone in an attempt to elucidate the mechanisms involved. In a first series of experiments, the isometric tension of two different vessels (rat thoracic aorta and pig renal branch artery) was studied at different temperatures. To study the role of calcium in this response, a second series of experiments was performed. In this the vessels were incubated with the intracellular chelator BAPTA/AM. Further experiments were performed to test the effect of cold storage. Our results show that changes in temperature lead to different results in pig renal artery and rat aorta. A decrease in temperature induced a highly reproducible relaxation in rat aorta, whereas pig renal artery presented cooling-induced contraction. Moreover, whereas calcium depletion failed to inhibit cooling-induced relaxation in rat aorta, it did not provoke cooling-induced contraction in pig renal artery. Similar responses were obtained with cold storage and calcium depletion. We intend to demonstrate that, just as the effect of temperature variation on pig renal artery is due to a metabolic mechanism, its effect on rat aorta may be due to structural factors. This hypothesis is supported by the result of histological studies which demonstrate a higher proportion of elastin fibres in rat aorta than in pig renal artery.

Animals↗
PubMed2000

Perfusate lactate dehydrogenase level and intrarenal resistance could not be adequate markers of perfusion quality during isolated kidney perfusion.

The main goal of this work was to study the influence of perfusion pressure and flow waveform during kidney perfusion, and the relationship between renal vascular resistance (RVR) and lactate dehydrogenase (LDH) concentration in the perfusate. Simultaneous constant pressure kidney perfusions were performed with either pulsatile or continuous flow at either 30 or 80 mm Hg of constant perfusion pressure. Mean flow, pressure, and RVR were displayed online during perfusion. Perfusate samples for LDH, creatine phosphatase kinase (CPK), and alkaline phosphatase (AP) determinations were taken. At the end of the perfusion, 2 ml of Evans blue was injected into the circuit to obtain images of perfusate distribution, and the kidneys were weighed. Also, hematoxylin/eosine studies were performed, showing more Bowman's space and tubular dilation in kidneys perfused with high pressure. We did not find differences in RVR between kidneys perfused at 30 and 80 mm Hg; nevertheless, perfusate distribution was better in the 80 mm Hg perfusions. We did not find any correlation between enzyme release and RVR in kidneys perfused with different mean pressures. These findings suggest that vascular resistance and LDH concentration cannot be independently considered as adequate markers of perfusate distribution.

Alkaline Phosphatase↗
PubMed1999

Clinical genetics of familial progressive supranuclear palsy.

Recent studies have shown that progressive supranuclear palsy (PSP) could be inherited, but the pattern of inheritance and the spectrum of the clinical findings in relatives are unknown. We here report 12 pedigrees, confirmed by pathology in four probands, with familial PSP. Pathological diagnosis was confirmed according to recently reported internationally agreed criteria. The spectrum of the clinical phenotypes in these families was variable including 34 typical cases of PSP (12 probands plus 22 secondary cases), three patients with postural tremor, three with dementia, one with parkinsonism, two with tremor, dystonia, gaze palsy and tics, and one with gait disturbance. The presence of affected members in at least two generations in eight of the families and the absence of consanguinity suggests autosomal dominant transmission with incomplete penetrance. We conclude that hereditary PSP is more frequent than previously thought and that the scarcity of familial cases may be related to a lack of recognition of the variable phenotypic expression of the disease.

Adult↗
PubMed1999

[Diagnosis of transmissible spongiform encephalopathies in Spain. Population perspective].

OBJECTIVES: To describe specific aspects of the diagnostic process of transmissible spongiform encephalopathies in Spain and to evaluate the 14-3-3 protein test in cerebrospinal fluid. METHODS: The annual pattern of diagnostic certainty as well as those of demand and results of biochemical and genetic studies were studied using two sets of patients, those diagnosed for the 1993-1998 period, notified to a National Creutzfeldt-Jakob Disease Register (NCDJR), and those referred to the Tissue Bank for Neurological Research Laboratory (TBNRL). The 14-3-3 protein test was validated taking as a reference two clinical populations. RESULTS: Two-hundred and four Creutzfeldt-Jakob disease cases were registered at the NCDJR: 39 out of them and 28 other patients had been studied at the TBNRL. The proportion of definite Creutzfeldt-Jakob Disease cases decreased since 1996. Among those registered in 1997-1998, 35.5%, 36% and 20% had undergone 14-3-3 protein in LCR, histopathologic and genetic studies. The 14-3-3 test grave, for definite, sporadic Creutzfeldt-Jakob disease as compared for patients with other dementing disorders, the following data: 12/13 sensitivity; 33/35 specificity; and 12/14 and 33/34 predictive values of positive and negative test. Two familial cases were diagnosed by identification of mutations in the TBNRL. CONCLUSIONS: The results suggest that: a) the diagnostic certainty of Creutzfeldt-Jakob disease in Spain decreased due to a drop in autopsy rates; b) the 14-3-3 cerebrospinal fluid test has a high diagnostic value, and its use diffused rapid but incompletely; c) genetic studies are useful in some cases, and d) Creutzfeldt-Jakob disease undereporting may be considerable. Creutzfeldt-Jakob disease diagnosis and surveillance, are closely related and being consolidated in Spain.

Creutzfeldt-Jakob Syndrome↗
PubMed1998

Effects of chronic combined treatment with captopril and pravastatin on the progression of insulin resistance and cardiovascular alterations in an experimental model of obesity in dogs.

Obesity is a metabolic disorder in which multiple clinical and biochemical alterations coexist. However, the progression of these alterations in relation to weight gain has not been investigated in detail. Therefore, we studied the evolution of insulin resistance and associated risk factors in a model of experimental obesity in dogs. We also studied whether chronic exposure to these pathogenic factors could induce cardiac and vascular alterations. Twenty male age- and body weight-matched beagle dogs were divided into four groups (n = 5), according to diet and pharmacologic therapy received, and followed for 2 years. Control animals were maintained with a regular diet, while the 15 remaining animals were fed a high-fat diet. The Obese group of dogs received no therapy, whereas the Capto group received 25 mg/12 h captopril, and the Prava+Capto was treated with 10 mg/24 h pravastatin plus the same dose of captopril throughout the study. Periodical determinations of clinical and biochemical parameters were made, and the degree of insulin resistance was also estimated. After the 2-year follow-up, the dogs were killed and vascular thickening in the aorta and the coronary arteries was evaluated. In addition, cardiac hypertrophy was estimated by heart weight and free-wall left ventricular width. Chronic pravastatin plus captopril treatment, together with decreasing weight gain rate, ameliorated the progression of insulin resistance and associated risk factors (hyperinsulinemia, hypercholesterolemia) related to this severe model. In addition, this combined therapy showed cardioprotective action, as cardiac and vascular hypertrophy observed in the Obese group was prevented. These positive results seems to emerge from the synergistic effects of both drugs, as captopril as monotherapy induced only a slight benefit on these parameters.

Animals↗
PubMed1998

Ferritin is associated with the aberrant tau filaments present in progressive supranuclear palsy.

Tau-containing filaments purified from the brain of progressive supranuclear palsy (PSP) patients were isolated and characterized. These filaments co-purify with regular particles that biophysical and biochemical methods identified as ferritin shells. In vivo, brain tau accumulation in PSP co-localized with ferritin. These results suggest that ferritin/iron could modulate the formation of tau aggregates in PSP.

Brain↗
PubMed1997

Effects of cicaprost and fosinopril on the progression of rat diabetic nephropathy.

We have studied the effects of chronic therapy with cicaprost (a PGI2 analog), fosinopril (a converting enzyme inhibitor), and the combination of both drugs on the progression of experimental diabetic nephropathy. Uninephrectomized streptozotocin-induced diabetic rats were maintained for 8 months with plasma glucose between 13.7 and 22.0 mmol/L to hasten renal damage. Systemic and renal parameters were measured periodically, and at sacrifice structural and morphometrical renal studies were performed to evaluate diabetic injury. Control rats exhibited characteristic features of this model, such as high blood pressure and plasma creatinine and urinary albumin excretion, together with prominent alterations in the kidney (renal and glomerular hypertrophies, mesangial matrix expansion, and tubular alterations). The three therapies attenuated equivalently the progression of diabetic renal injury, as estimated by lower urinary albumin excretion, renal and glomerular hypertrophies, and a better renal architectural preservation. No synergistic action was appreciated with the combined therapy. However, renal preservation achieved with cicaprost was not linked to reductions in systemic blood pressure, whereas in the groups treated with fosinopril the hypotensive effect of this drug could have contributed to the positive outcome of the therapy. Therefore, nephroprotection exerted by this PGI2 analog in this model seems more related to the derangement of renal local mechanisms than to systemic blood pressure control. Finally, the possibility that an impaired prostacyclin synthesis or bioavailability is involved in the pathogenesis of the diabetic nephropathy in this model underlies our results.

Albuminuria↗
PubMed1997

Effects of UP269-6, a new angiotensin II receptor antagonist, and captopril on the progression of rat diabetic nephropathy.

To estimate the effects of UP269-6, a nonpeptide angiotensin II receptor antagonist, and captopril, a converting enzyme inhibitor, on the progression of nephropathy, 77 uninephrectomized diabetic rats were maintained for 8 months with plasma glucose levels from 300 to 500 mg/dL. Systemic and renal parameters were periodically measured, and, at the time of death, a histological evaluation of renal damage was performed. Control rats (no additional treatment but insulin) showed increased blood pressure and urinary albumin levels, together with prominent alterations in the kidney (renal and glomerular hypertrophies, tubular atrophy, and 19% of sclerotic glomeruli). Captopril (50 mg/kg/day) and UP269-6 (10 mg/kg/day) reduced blood pressure and albumin excretion levels, and improved histological renal preservation (lower renal and glomerular hypertrophies, tubular atrophy, and percentage of sclerotic glomeruli: 5% and 7%, respectively). Finally, a low dose of UP269-6 (1 mg/kg/day), which induced an intermediate level of blood pressure between control and the other treated groups, produced an equivalent degree of nephroprotection. Our data demonstrate the efficacy of this new angiotensin II receptor antagonist on the progression of diabetic renal damage. These results also reinforce the role attributed to angiotensin II in the development of renal derangement in this model, as UP269-6 is devoid of agonistic effect on the kinin system.

Albuminuria↗
PubMedDate not supplied

Effects of hyperinsulinemia on vascular blood flows in experimental obesity.

Human obesity, which is very common in Polycystic Ovaries Syndrome and in "X Syndrome", constitutes an insulin-resistance state in which multiple clinical, biochemical and hemodynamic alterations coexist. Insulin resistance in the obese has been recently associated with an endothelial dysfunction. To investigate the possibility that clinical and metabolic derangements related to insulin resistance could induce changes in vascular blood flows, we have studied the levels of mesenteric (MBF), renal (RBF) and femoral (FBF) blood flows in Beagle dogs kept for 2 years on a normal (control group) or high fat diet (obese group). This experimental model exhibits many of the abnormalities with the human syndrome. In addition, we have tested the effects of chronic treatment with captopril (capto group) in monotherapy or in association with pravastatin (prava+capto group) on the hemodynamic changes associated with this diet. After the two year follow-up, Transonic flow probes were placed around the three arteries to measure basal blood flows and their response to a hyperinsulinemic-normoglycemic test in anesthetized animals. During this test the degree of insulin sensitivity was estimated. In association with higher body weight, blood pressure, insulin resistance, and fasting levels of insulin and total cholesterol, the obese group exhibited decreased basal levels of FBF and a greater femoral vasoconstriction during hyperinsulinism (P < 0.05 vs control). Combined therapy with captopril and pravastatin ameliorated the reduction in basal FBF and hyperinsulinism-induced vasoconstriction (P < 0.05), in addition to the beneficial effects on insulin sensitivity, and clinical and metabolic parameters. Synergistic beneficial effects of both drugs on lipid and carbohydrate profiles may account for this positive outcome, by attenuating the atherogenic process associated with this model.

Animals↗
PubMedDate not supplied

Emboli in bulls killed in Spanish traditional bullfighting.

The finding of brain tissue fragments in blood and lungs of cattle stunned in slaughterhouses has raised concerns about food safety in the context of the bovine spongiform encephalopathy epidemic. In the present study, the possible occurrence of brain tissue emboli in animals killed in traditional Spanish bullfighting was investigated. Thorough histological analysis of multiple possible target organs was carried out in 434 bulls. No evidence of brain tissue embolism was obtained, but emboli from diverse sources were detected in pulmonary and hepatic tissue of a significant number of animals. These emboli seem to have been caused by the use of a long sword, which extensively disrupts intra-thoracic and intra-abdominal organs and vascular structures.

Animals↗