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N Borges

Publications and source records attributed to N Borges.

15 recordsLinked to original sources
PubMed1998

Experimental traumatic cerebral contusion: morphological study of brain microvessels and characterization of the oedema.

Several experimental brain oedema models are currently available, but most of them are very different from what happens in clinical practice. As it is simple and seems to replicate the range of injuries seen in man we decided to evaluate Marmarou's model of head injury in order to test physiopathogenic and therapeutic hypotheses. Three groups of Wistar rats weighting 360-400 gr, anaesthetized with sodium pentobarbitone and breathing spontaneously, without tracheal intubation, were studied. In the first group six animals were killed two hours after injury and the brain's water content compared with that of nine controls. In another group Evans blue (100 mg/kg) was injected one hour before trauma and dye's extraction ratio determined at various times after injury: five animals at 15 minutes, six at 30 minutes, five at 60 minutes and nine at 120 minutes. A total of twenty-eight animals served as controls. In the last group morphological studies with light and electron microscopy were performed in the traumatized brain tissue from rats killed 5 and 120 minutes after injury and in brain tissue from control rats. Results showed that Marmarou's brain trauma model induced perivascular brain oedema, already visible at the ultrastructural level 5 minutes after the injury. Endothelial cells themselves were "oedematiated", rich in pinocytotic vesicles and membrane blebs, and presented intact tight junctions. Two hours after trauma the perivascular oedema was more marked. At this time the brain water content was significantly higher than that in controls. Evans blue extraction ratio increased linearly with time, being significantly higher than in controls 120 minutes after injury. We conclude that Marmarou's model is a suitable model for the study of brain oedema induced by trauma, and that this oedema, assessed by three different methodologies, was statistically significant two hours after injury.

Animals↗
PubMed1998

Effect of mechanogated membrane ion channel blockers on experimental traumatic brain oedema.

Traumatic head injury leads to marked swelling of endothelial cells, both in human patients and in Marmarou's rat model. We used this model to test the hypothesis of mechanogated ion channels being involved in the formation of traumatic brain oedema. All mechanogated channel blockers tested (gadolinium, amiloride, gentamicin) significantly reduced traumatic brain oedema evaluated by Evans blue extraction ratio, either when given 15 minutes before or 30 minutes after induction of trauma (evaluation 2 hours after trauma). These results clearly support our hypothesis, opening a new way for the investigation of the treatment of a clinical situation endowed with high morbidity and mortality.

Amiloride↗
PubMed1998

Cerebral edema associated with meningiomas: the role of peritumoral brain tissue.

We undertook a morphological study of small pieces of peritumoral brain tissue removed from seven patients with meningiomas submitted to surgery. All patients had cerebral edema, as shown by preoperative C.T. and N.M.R.. Control specimens were obtained from five patients undergoing ventriculo-peritoneal shunt. The tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In semi-thin sections observed under light microscopy peritumoral endothelial cells exhibited voluminous cytoplasm and nucleus. Morphometrical evaluation confirmed that these endothelial cell nuclei were significantly larger than controls. Under the electron microscope those cells showed nuclei rich in euchromatin and cytoplasm rich in pinocytotic vesicles. The morphological changes observed suggest a process of dedifferentiation of brain peritumoral capillary cells and are compatible with an increase in permeability. Both events, which may be due to diffusion of a tumoral vascular permeability factor, favour the hypothesis that peritumoral brain tissue contributes to edema fluid that accumulates around meningiomas.

Adult↗
PubMed1998

Rat liver catechol-O-methyltransferase kinetics and assay methodology.

In mammals, catechol-O-methyltransferase (COMT) is distributed throughout various organs, the highest activities being found in the liver and kidney. However, comparisons of the kinetic parameters are difficult to perform, since the experimental procedures in the enzyme assay vary quite considerably. The present work was aimed at studying the optimal liver COMT assay conditions for determining the kinetics of the enzyme. The COMT assay was performed with liver homogenates from 60 days old male Wistar rats with adrenaline (AD) as the substrate. Time course experiments using 100 microM S-adenosyl-L-methionine (SAMe) and 300 microM AD showed linearity of O-methylation reaction upto 10 min. Using 100 microM SAMe, Vmax (nmol mg protein-1 h-1) and Km (microM) values progressively decreased respectively from 22.1 and 104.8 at 5 min down to 5.8 and 24.62 at 60 min incubation periods. This decrease was not due to end-product inhibition. Using 2500 microM AD, Km values (microM) for the methyl donor SAMe increased progressively from 174 at 5 min upto 1192.5 at 60 min; upto 30 min of incubation Vmax values did not change. When a 5 min incubation period and 500 microM SAMe were used, Vmax and Km values for liver COMT were 63.4 nmol mg protein-1 h-1 and 261.1 microM, respectively. It is concluded that an incubation period of 5 min and a SAMe concentration of 500 microM provide optimal conditions for the liver homogenate COMT assay.

Animals↗
PubMed1997

Ultrastructural study of brain microvessels in patients with traumatic cerebral contusions.

Brain tissue from 11 patients with traumatic cerebral contusions submitted to surgery was studied. Control biopsy specimens were obtained from 5 patients undergoing ventriculo-peritoneal shunts for "communicating" hydrocephalus. After collection, the small fragments were fixed by immersion in glutaraldehyde-osmium and embedded in Epon. Semi-thin sections stained with toluidine blue were observed with the light microscope. Thin sections stained with lead citrate and uranyl acetate were observed using a Jeol electron microscope. In tissues from patients with head trauma a clear space most probably corresponding to fluid accumulation was systematically observed around microvessels. Ultrastructurally endothelial cells from these specimens exhibited signs of marked intracellular oedema, tight junctions being intact. Pinocytotic activity was increased, mainly at the abluminal surface. Swelling of astrocytic perivascular processes and the appearance of macrophagic cells with voluminous lysosomes were also observed. The authors conclude that the oedema of endothelial cells probably represent a central fact in the pathophysiology of traumatic brain oedema and speculate on the putative involvement of stretch-activated receptors in this condition.

Adult↗
PubMed1997

Studies on the tight-binding nature of tolcapone inhibition of soluble and membrane-bound rat brain catechol-O-methyltransferase.

Catechol-O-methyltransferase (COMT) is an enzyme that plays an important role in the inactivation of catecholamine neurotransmitters. Experimental and clinical data suggest that COMT inhibitors may be useful in Parkinsonian patients. Among COMT inhibitors, nitrocatechol derivatives are the most potent and selective. In this study, we evaluated the kinetics of rat brain COMT, as well as its mechanisms of inhibition by tolcapone. Rat whole-brain homogenates and the corresponding soluble and membrane-bound fractions were evaluated for their epinephrine 3-O-methylating activity. Tolcapone exhibited a very low IC50 in all the three enzyme preparations. In whole-brain homogenates, saturation curves made in the presence of 1 nM tolcapone displayed, when compared with controls, a reduction in Vmax without changes in Km, which suggested a noncompetitive type of inhibition. This was confirmed by experiments in which the IC50 value for tolcapone was not affected by substrate concentration. Nevertheless, this classic kinetic analysis is not suitable for a tight-binding inhibitor. A very low IC50, an inhibition potency that is dependent on the previous contact time of the inhibitor with the enzyme and an enzyme titrating capacity were the three criteria that tolcapone met as a tight-binding inhibitor in the rat brain. In conclusion, our results show that tolcapone is a highly potent tight-binding inhibitor of brain soluble and membrane-bound COMT, but because of difficulties in determining the type of inhibition for this type of compound, we cannot confirm previous claims about the competitive type of COMT inhibition produced by tolcapone.

Animals↗
PubMed1996

Reversion of phenotype of endothelial cells in brain tissue around glioblastomas.

With the aim of studying the putative involvement of peritumoral microvessels in the formation of brain edema, small pieces of peritumoral brain tissue were removed from six patients with glioblastoma multiforme submitted to surgery. All patients had cerebral edema, as shown by preoperative C.T. and N.M.R. Control specimens were obtained from four patients undergoing ventriculo-peritoneal shunt. The tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In semi-thin sections observed under light microscopy peritumoral endothelial cells exhibited voluminous cytoplasm and nucleus. Under the electron microscope, capillary cells from glioblastoma patients differed from controls mainly by showing nuclei rich in euchromatin, cytoplasm rich in pinocytotic vesicles and with occasional fenestrations. All these morphological characteristics are compatible with a process of reversion of phenotype of capillaries around glioblastomas to that of periphery as well as an increase in permeability. Both events may be due to diffusion of a tumoral vascular permeability/endothelial growth factor. This peripheral vessel phenotype of peritumoral microvessels supports their participation in the formation of brain edema and may provide a new clue for therapeutic intervention: for example it fits quite well to the known increase in permeability by leukotrienes and decrease in permeability by corticosteroids in tumoral edema.

Aged↗
PubMed1995

Birth dates.

Explore the source record for details and available documents.

Brain↗
PubMed1994

Changes in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs.

Brain microvessel endothelial cell monolayers have been shown to be a suitable blood-brain barrier in vitro system to study adrenergic regulation of permeability. We tested adrenergic drugs on bovine brain microvessel endothelial cell monolayer permeability to a biomembrane impermeant molecule, sodium fluorescein. Endogenous catecholamines noradrenaline and adrenaline were tested as well as the alpha-adrenoceptor agonist phenylephrine, the beta-adrenoceptor agonist clenbuterol and the alpha-adrenoceptor antagonist prazosin. Results showed an alpha-adrenoceptor mediated increase and a beta-adrenoceptor mediated decrease in monolayer permeability. Both alpha- and beta-adrenoceptor mediated changes in permeability were abolished by inhibiting fluid-phase pinocytosis, either by vincristine or by avoiding bovine brain microvessel endothelial cell's energy utilization. The reverse transport (i.e., from brain to blood side) was also influenced by adrenergic drugs; alpha- or beta-adrenoceptor stimulation induced a permeability-reducing effect. We conclude that alpha-adrenoceptor stimulation increases bovine brain microvessel endothelial cell monolayer permeability and that beta-adrenoceptor stimulation has the opposite effect. Reverse transport results obtained with beta-adrenoceptor stimulation seem controversial and deserve further study. These results also support in vivo findings that demonstrated adrenergic influences on blood brain barrier permeability.

Adrenergic Agents↗
PubMed1994

Influence of electrical stimulation of locus coeruleus on the rat blood-brain barrier permeability to sodium fluorescein.

The role of central adrenergic innervation of the brain capillaries is still a matter of discussion. The hypothesis that these nerves control the blood-brain barrier permeability was tested by electrically stimulating the locus coeruleus, the major central adrenergic nucleus, in the anaesthetized rat. Frequencies of 5, 15, and 30 Hz were used. A frequency dependent increase in blood-brain barrier permeability to sodium fluorescein was verified. Prior administration of the alpha-adrenoceptor antagonist phenoxybenzamine (10 mg/kg i.p., 24 h before electrical stimulation) totally blocked the effect of 15 Hz stimulation. The same dose of pindolol (a beta-adrenoceptor antagonist) given 1 h before electrical stimulation potentiated the effect of 5 Hz stimulation. Thus, blood-brain barrier permeability is increased, in a frequency dependent manner, by electrical stimulation of the locus coeruleus. The results obtained with phenoxybenzamine and pindolol suggest an opposite effect of alpha and beta-adrenoceptors on the control of sodium fluorescein transport through the blood-brain barrier.

Adrenergic Fibers↗
PubMed1993

Age-induced nerve cell loss in the myenteric plexus of the small intestine in man.

We examined the number of nerve cells of the myenteric plexus and the thickness of the smooth muscle in the small intestine in autopsy material of 6 young and 6 old persons. Neurons in the myenteric plexus have been visualised by a nonhistochemical method (Giemsa) in laminar preparations of the muscularis externa. Significant reductions of at least 34% in the number of neurons in the ganglia of the myenteric plexus of the old subjects were recorded in all regions of the small intestine, especially in the duodenum where the number of neurons decreased by over 38%. However, there was no significant correlation between nerve cell count and thickness of intestinal smooth muscle since no difference was found in thickness of intestinal smooth muscle between young and old subjects. The decrease in the neuron density with age could affect the potential of the enteric nervous system to influence control over several small intestinal functional parameters.

Adult↗
PubMed1993

[Use of spreadsheet for statistical and graphical processing of records from the ambulatory blood pressure monitor Spacelabs 90207].

The introduction of portable devices for non-invasive ambulatory blood-pressure measurement is recognized as an advance in the study of human arterial hypertension, allowing a significant improvement in the selection of hypertensive patients as well as in the analysis of the effects of antihypertensive drugs during clinical trials. The Spacelabs 90207 is a recent example of this kind of apparatus, possessing high levels of portability and being highly classified in validation studies. Nevertheless, the software of this apparatus (like other similar devices) has severe limitations in what concerns the calculation of the area under the curve of blood pressure during the time of measurement, as well as in the possibility of grouping several records in a database for easy statistic and graphic analysis of different groups of records. In order to overcome these difficulties, the authors describe the development of a group of programs, using Microsoft Excel v3.0 spreadsheets and macros, that allow a direct import of individual files from the Spacelabs software to a spreadsheet and its further processing in three phases. These three phases, which we designated by "conversion", "export to database" and "statistic and graphic analysis", will permit an easy and fast statistic and graphic analysis of selected groups of records.

Blood Pressure Determination↗
PubMed1992

Effects of nebivolol stereoisomers on the action of adrenaline on blood pressure, heart rate and blood levels of noradrenaline and DOPEG.

1. Nebivolol (a new beta 1-adrenoceptor blocking drug) has particular effects on the cardiovascular system, i.e. it induces hypotension without affecting cardiac function or increasing peripheral vascular resistances. In this study, we aimed to evaluate the effects of nebivolol and its stereoisomers on the actions of adrenaline (AD) at the cardiovascular level as well as at the prejunctional level (as ascertained by modification of noradrenaline (NA) and dihydroxyphenylglycol (DOPEG) plasma levels in the anaesthetized dog. 2. AD infusion (0.1 micrograms kg-1 min-1) did not induce statistically significant changes in mean blood pressure and heart rate; it caused a pronounced and sustained rise of AD levels, no significant alterations in NA levels and a marked, progressive and sustained increase in DOPEG levels. 3. Mean blood pressure was not affected by any of the nebivolol isomers. d- and dl-nebivolol in the two doses used (0.3 and 0.03 mg kg-1 in 15 min) caused a significant and dose-dependent decrease in heart rate. Plasma levels of AD and NA were not changed by any of the nebivolol isomers tested. However, all of them significantly reduced the increase in plasma levels of DOPEG induced by adrenaline infusion. 4. We conclude (1) that AD infusion in the dog facilitates NA release and that DOPEG is a good index of this effect; and (2) nebivolol appears to act at the prejunctional level, reducing the increase in NA release induced by adrenaline, as shown by the effect on DOPEG plasma levels.

Adrenergic beta-Antagonists↗
PubMed1991

Adrenergic influences on the control of blood-brain barrier permeability.

The central adrenergic innervation of the cerebral microvessels may play a role in the control of blood-brain barrier permeability. To pursue the study of this hypothesis we investigated the effect of noradrenaline on both the permeability of the blood-brain barrier to sodium fluorescein and on the pinocytotic activity of cerebral endothelial cells in the rat. Noradrenaline, stereotactically injected in the right lateral cerebral ventricle, significantly increased the cerebral extraction ratio of sodium fluorescein in a dose-dependent way. The same effect was induced by phenylephrine. Prostaglandin F2 alpha had no significant effect on the passage of sodium fluorescein through the blood-brain barrier. The effect of noradrenaline (150 micrograms) on the cerebral extraction ratio of sodium fluorescein was totally blocked by phenoxybenzamine (25 mg/kg i.p., 24 h before noradrenaline). Noradrenaline (150 micrograms) significantly increased the pinocytotic activity of cerebral endothelial cells. Phenoxybenzamine (as above) reduced the effect of noradrenaline on pinocytosis. It is concluded that noradrenaline increases the blood-brain barrier's permeability to sodium fluorescein, most probably through an effect on alpha adrenoceptors. The increase induced in the blood-brain barrier's permeability by noradrenaline seems to be due, at least in part, to an increase in the pinocytotic activity of endothelial cells.

Animals↗