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Biomedical subjects

J Cervos-Navarro

Publications and source records attributed to J Cervos-Navarro.

At least 19 recordsLinked to original sources
PubMed2000

Regional differences of cerebrovascular reactivity effected by calcium channel blocker - dotarizine.

Dotarizine, a novel antimigraine prophylactic drug, is chemically related to Diphenylbutylpiperazines, which are known to have Ca(2+)-antagonistic, alpha-adrenolytic and antihistaminic properties. Additionally, Dotarizine exhibits strong 5-HT2 receptor-specific antiserotoninergic properties. The vasostabilizing effect of Dotarizine on cerebrovascular reactivity during different ventilation conditions was demonstrated in various in vitro and in vivo studies. In the presented study, the effect of chronic oral administration of the drug on vascular reactions of different areas of cerebral vessels following hyperventilation was investigated. The experiments were carried out on two groups of experimental animals (rabbits). In the first group (6) 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally for 5 days twice daily. The control group of animals (6) was fed with agar of the same concentration according to the same time schedule. During the experiment, 15 min hyperventilation was performed and blood flow velocity (BFV) in the middle cerebral artery (MCA) and the basilar artery (BA) was recorded using Transcranial Doppler apparatus (TCD) before and after hyperventilation state. The obtained results revealed a strong antivasoconstrictive effect of Dotarizine on cerebral vessels reactivity during hyperventilation. In the control experimental group, the 15 min hyperventilation caused a decrease in the mean BFV in MCA and BA by 36 and 14%, respectively, and in the drug-treated group under the same ventilation conditions the decrease of the mean BFV in BA was only 6% and even a slight increase (8% as compared with control values) of BFV in MCA was observed. Comparison of the pulsatility index (PI) values demonstrated a significant decrease of vascular resistance in MCA in the Dotarizine-treated group of animals (P<0.1). From the obtained results it can be concluded that chronic oral administration of a novel compound (Dotarizine) diminishes the vasoconstrictive effect of hyperventilation on cerebral vessels in rabbits. The influence of this drug demonstrates regional differences in the cerebrovascular reactivity and it appears to change the vascular resistance in the small arteries of the cerebrovascular system. Thus, it can be recommended as a good prophylactic antimigraine compound due its vasostabilizing properties.

Animals↗
PubMed2000

Vasostabilizing effect of Dotarizine (Ca(2+)-channel blocker) on cerebrovascular reactivity in rabbits.

Disturbances of the cerebrovascular reactivity in cases of migraine with aura are well-known. It has been suggested that the vasostabilizing effects of novel prophylactic pharmaceuticals are determined by their antiserotoninergic and/or nitric oxide releasing properties. Dotarizine, a representative of Ca2+ channel blockers from diphenilbutilpiperazines group also reveals antiserotoninergic 5-HT2A and 5-HT2C receptor-specific properties. The vasodilatatory and antivasoconstrictive properties of this compound were reported previously. In this study the efficacy of Dotarizine chronic oral administration on cerebrovascular reactivity during hyperventilation was examined with respect to its duration of action. Experiments were carried out on 13 rabbits. There was an interval of two days between a five days compound administration and performed hyperventilation. Blood flow velocities (BFV) in the middle cerebral artery (MCA) and basilar artery (BA) were measured in control conditions, after 10 min hyperventilation and in the tenth minute of recovery of normoventilation. Our data reveal a decrease of antivasoconstrictive properties of Dotarizine between its administration and vasoconstrictive test. Subsequent normoventilation showed a distinct vasostabilising effect of this compound with evident regional differences in its influence on cerebral vessels. Thus Dotarizine might be useful as prophylactic medication in migraine therapy, due to its Ca2+ channel blocking and antiserotoninergic properties, but the time-frame of its efficacy has to be defined.

Animals↗
PubMed1999

Effect of oral administration of dotarizine on cerebrovasculature subjected to constriction followed by dilatation in rabbits.

In the study presented the effect of Dotarizine on blood flow velocity in cerebral arteries - in middle cerebral artery (MCA), and basilar artery (BA)- was investigated and compared utilising transcranial Doppler sonography during normoventilation, 15 min hyperventilation with subsequent 3 min anoxia in anaesthetized rabbits. In the Dotarizine treated group (12 rabbits) 25 mg/kg of Dotarizine dissolved in 0,25% agar was administered orally for five days twice daily. In the control group (9 rabbits) animals were fed with agar of the same concentration. The results revealed that decrease of flow velocity caused by hyperventilation and increase during anoxia were less pronounced in the Dotarizine treated group than in control group of animals. A difference between changes of flow velocity in MCA and BA during anoxia was found and the different reactivity of both vessels was established.

Administration, Oral↗
PubMed1998

The histopathological and clinical relevance of apoptotic cell death in medulloblastomas.

We studied apoptosis in 40 medulloblastomas by in situ end labeling (ISEL) of DNA strand breaks. In situ end labeling was performed on paraffin-embedded material from classical and desmoplastic medulloblastomas and medulloblastomas with glial and combined differentiation. The number of labeled apoptotic cells varied considerably from tumor to tumor as well as between different areas in the same tumor. However, there was no significant difference in the averaged numbers or in the pattern of apoptotic tumor cells between the different differentiations of medulloblastoma. Unlabeled tumor cells displaying features of apoptosis were found in small numbers, indicating that tumor cells may also be able to undergo cell death different from classical apoptosis. A significantly higher number of apoptotic tumor cells in male patients could be demonstrated corresponding to the reported difference in survival rates between male and female patients suffering from medulloblastoma. A clear cut trend of a negative relation between apoptosis and age by operation was found.

Adolescent↗
PubMed1998

The effect of Dotarizine--(Ca2+ channel blocker)--on vascular reactivity and ultrastructure of cerebral capillaries in animals subjected to anoxia.

Dotarizine--the novel piperazine derivative--belongs to wide spectrum Ca2+ channel antagonists. It was reported to have strong vasodilatatory and antiserotoninergic activities. Comparing with other Ca2+ channel blockers Dotarizine was found to have lower oral toxicity. In the present study the influence of the oral administration of the novel compound on the blood flow velocity changes in different cerebral arteries--in basilar artery (BA) and middle cerebral artery (MCA)--was investigated under hypoxic conditions. The ultrastructural morphological changes of intracerebral vessels endothelium in treated and untreated anoxic animal groups were also demonstrated. The experiments were carried out on rabbits. In the experimental group 25 mg/kg of Dotarizine dissolved in 0.25% agar was administered orally three times at the 10 hours' intervals. The sham group of animals was fed with agar of the same concentration. During anoxic conditions strong vasodilatory effects were observed in both investigated vessels of drug-treated animals. In the experimental group marked ultrastructural differences in parenchymal vessel endotheliumin comparison to sham group were revealed. Thus, the oral administration of Dotarizine might have effect on the various parts of the cerebrovascular system and can play significant role in improvement of various cerebrovascular disorders.

Animals↗
PubMed1997

CAG repeat analyses in frozen and formalin-fixed tissues following primer extension preamplification for evaluation of mitotic instability of expanded SCA1 alleles.

Neurodegenerative disorders, including spin-ocerebellar ataxias (SCA), Huntington disease (HD) and dentatorubral-pallidoluysian atrophy (DRPLA), are associated with unstable CAG repeats. To investigate the mitotic stability of the repetitive element in the genes for SCA1, SCA3, HD, and DRPLA we extracted DNA from up to 13 tissue samples from four deceased individuals with progressive neurological disorders and neuropathological signs. Due to the formalin fixation of some tissues the genomic DNA was highly degraded and unsuitable for amplification of fragments longer than 150 bp. After size selection and primer extension preamplification, specific analyses could be performed even for expanded alleles. In all four patients the SCA1 mutation could be demonstrated, in one case with remarkable somatic heterogeneity of the elongated allele, whereas alleles of the normal range were stable in all tissues examined.

Adult↗
PubMed1996

Effects of the calcium channel blockers Dotarizine and Flunarizine on cerebrovascular reactivity.

Dotarizine and Flunarizine are piperazine derivatives considered to be effective compounds for the treatment of various cerebrovascular disorders. In the present study the influence of these two drugs on changes in cerebral vessel diameter and blood flow velocity were measured and compared utilising transcranial Doppler sonography during hyperventilation in anaesthetized cats. Drugs were administered in 15 min intravenous infusions at a dose of 0.05 mg/kg/min. This investigation revealed that the 15 min intravenous administration of both compounds abolished the cerebral vasoconstrictor effects of hyperventilation and due to vasodilator effects they increased blood flow velocity to initial values. No statistically significant differences were found between the vasodilator effects of Dotarizine and Flunarizine. Results obtained suggest that Dotarizine, a novel piperazine derivative, has similar vasodilator and Ca2+ channel blocking effects on cerebrovascular reactivity compared to the widely clinically applied Flunarizine.

Animals↗
PubMed1996

p53 gene mutations in human astrocytic brain tumors including pilocytic astrocytomas.

Recent molecular biological studies have shown evidence for a distinct pathogenesis of pilocytic astrocytomas based on alterations other than mutations of the tumor suppressor gene p53. To prove these data, the authors screened a series of 42 astrocytic human brain tumors with a relatively high proportion (16.6%) of the pilocytic variant for the presence of p53 mutations, using the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis, followed by DNA sequencing. Mutations were found in one of seven (14.3%) pilocytic astrocytomas, in one of 18 (5.6%) low grade astrocytomas, and in one of four (25%) anaplastic astrocytomas, but in none of 13 glioblastomas. Sites of missense mutations were in exon 8 (codons 281 and 282), and exon 5 (codon 151). Silent mutation was found in exon 9 (codon 324), which was related to pilocytic astrocytoma. This is, to the authors' knowledge, the first report that shows a p53 mutation in pilocytic astrocytomas. However, the p53 mutation was only found in one of seven tumors of this entity and was a silent mutation, which does not lead to change of amino acids. Thus, the significance of this alteration for the development of this special tumor type seems to be low. Nevertheless, it may be a sign of genetic instability and is thus suggested to be of certain pathogenetic relevance. The p53 findings concerning the other tumors are in accordance with the view of p53 gene mutations to be early events in astrocytoma formation.

Adolescent↗
PubMed1996

Microthromboemboli in acute infarcts: analysis of 40 autopsy cases.

BACKGROUND AND PURPOSE: We investigated the distribution and frequency of microthromboemboli (MTE) in acute infarcts in humans and determined whether MTE in the contralateral circulation resulted in histological changes. METHODS: Forty patients dying within the first month after unilateral infarct were investigated. Infarct etiology was determined mainly on the pathological findings. Whole brain sections from the region of maximal necrosis were stained for fibrin. Fibrin-containing MTE were transferred to a schematic drawing and counted. Sections from 20 patients without infarcts served as controls. RESULTS: Infarct sections had significantly more MTE than controls. Infarcts of thrombotic (n=6) and thromboembolic (n=21) origin had more MTE than infarcts of embolic origin (n=13). Thromboembolic infarcts had the highest number of MTE within the region assumed to be the ischemic penumbra, other arterial territories, and the contralateral hemisphere. Patients with large infarcts and those with short clinical courses had a higher number of MTE. Sixteen patients had recent micronecroses in the contralateral hemisphere. CONCLUSIONS: There seems to be a pattern of MTE in acute infarcts that is dependent on cause, size, and clinical duration. Our findings of contralateral micronecroses emphasize that acute infarcts may result in more widespread cerebral injury than clinically expected. Given the many variables influencing stroke and death in humans, the results have to be interpreted with caution.

Acute Disease↗
PubMed1995

Effect of dotarizine on CO2-dependent cerebrovascular reactivity.

Dotarizine is chemically related to calcium antagonist cinnarizine and flunarizine. The study presented investigates the influence of the drug on the diameter of cortical arteries and cerebral blood velocity measured in the MCA in two groups of anaesthetized cats. Changes of vessel diameter were measured indirectly using photographs of the cerebral cortex during experiments, and flow velocity was measured using transcranial Doppler sonography. Dotarizine was administrated by 20 minute intravenous infusion in a dose of 0.05 mg/kg/min. In the first group of animals the infusion was started during normoventilation, in the next group the infusion started during 30th minute of hyperventilation. The most conspicuous data were obtained in experiments conducted in hyperventilated animals where dotarizine abolished the vasoconstrictive effect of hyperventilation. The results suggest that dotarizine has a pronounced effect on basal as well as cortical arteries of the brain.

Animals↗
PubMed1994

Role of serotonin and prostaglandins in brain edema induced by heat stress. An experimental study in the young rat.

The possibility that serotonin and prostaglandins participate in edema formation following heat stress (HS) was examined in young rats. Exposure of conscious young animals (8-9 weeks old) to heat at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%; wind velocity 20-25 cm/s) for 4 h resulted in marked increase in the whole brain water content (about 3%) as compared to animals kept at room temperature (21 degrees C). A marked extravasation of Evans blue and 131I-sodium occurred in the brain of heat exposed animals as compared to normal animals. Morphological examination using electron microscopy of selected brain regions of heat stressed animals showed profound cell changes. Thus perivascular edema, swollen neuronal and glial cells, membrane damage, vesiculation of myelin, axonal swelling and synaptic damage was frequent in this group of untreated animals. Pretreatment with ketanserin (a selective serotonin2 receptor antagonist) or indomethacin (an inhibitor of prostaglandin synthesis) markedly reduced edema formation after 4 h HS in young animals. These heat stressed animals had considerably less extravasation of protein tracers as compared to the untreated group. Cell changes and edema at the ultrastructural level were mainly absent. Our results suggest that serotonin and prostaglandins are involved in heat stress induced breakdown of the BBB permeability, edema formation, and cell damage.

Animals↗
PubMed1994

Composite cerebral metastasis and oligodendroglioma: an exceptional form of mixed neoplasia.

Our report describes the uncommon case of a 61 year old female patient who underwent a left parietooccipital craniotomy and extirpation of a malignant tumor. Histological examination revealed a metastatic carcinoma of mammary origin intimately intermingled with a calcified oligodendroglioma WHO II. The preexisting oligodendroglial part had been detected four years before, but since then had been misinterpreted as a glious scar resulting from a previous brain trauma. Three years before neurosurgical intervention, the patient had undergone a left side mastectomy. The histological finding at that time was a solid breast tumor WHO T1N0. The occurrence of cerebral mixed neoplasias and possible causal factors are discussed.

Brain Neoplasms↗
PubMed1994

Bombesin receptor gene expression in rat pancreatic acinar AR42J cells: transcriptional regulation by glucocorticoids.

BACKGROUND/AIMS: This study investigated the correlation between glucocorticoid-regulated gene expression of the bombesin receptor (BR) and cellular sensitivity to bombesin stimulation in the rat pancreatic acinar cell line AR42J. METHODS: BR gene expression was assessed using a cloned complementary DNA probe and radioligand binding assays. Intracellular Ca2+ mobilization was assessed by dual wavelength spectrophotometry using fura-2 in single cells. RESULTS: Dexamethasone resulted in a rapid dose- and time-dependent decrease of BR messenger RNA levels with maximal inhibition to 25% +/- 2% of controls (n = 4) after 6 hours of hormone treatment. BR messenger RNA half-life was approximately 120 minutes and was not affected by dexamethasone pretreatment; nuclear run-on analysis showed a decreased transcription rate of the BR to approximately 25% of control after hormonal treatment. Radioligand binding studies showed a time-dependent decrease of specific bombesin binding to 25% +/- 8% of control after 48 hours of hormone treatment. Down-regulation of BR gene expression by dexamethasone resulted in a time- and dose-dependent decrease of intracellular Ca2+ mobilization after bombesin stimulation compared with untreated controls. CONCLUSIONS: Glucocorticoids decrease BR gene transcription. The subsequent decrease in cellular BR number renders AR42J cells less sensitive for bombesin-stimulated intracellular Ca2+ mobilization.

Animals↗
PubMed1993

The use of immunomorphology to differentiate choroid plexus tumors from metastatic carcinomas.

BACKGROUND: The histologic and immunohistologic differential diagnosis of choroid plexus papillomas/plexus carcinomas (PP/PC) versus metastatic carcinoma in the brain is problematic. METHODS: Thirty-four choroid PP/PC from 28 patients, 5 normal choroid plexus, and 45 cerebral metastatic carcinomas were immunohistochemically examined with the monoclonal anti-epithelial noncytokeratin antibodies HEA 125 and Ber EP4 using the alkaline phosphatase anti-alkaline phosphatase (APAAP) method. RESULTS: Normal choroid plexus epithelium was consistently negative. Sections from PP/PC of 3 of 28 patients demonstrated immunoreactivity for these antibodies. In contrast, 43 of 45 cerebral metastatic carcinomas displayed positive immunostaining for HEA 125, and 44 of these 45 carcinomas were positive for Ber EP4. Thus, sensitivity was higher for these antibodies than for the monoclonal anticytokeratin antibody KL1 (41/45). All three HEA 125/Ber EP4-positive PP/PC contained periodic acid-Schiff (PAS)-positive, tall columnar tumor cells. The intensively HEA 125, Ber EP4, and PAS-positive PP/PC were interpreted as possible transitional forms of the mucus-secreting and acinar PP/PC: CONCLUSIONS: Despite this restriction, the authors proposed the application of HEA 125 and Ber EP4 as a reliable tool in the differential diagnosis of PP/PC versus metastatic carcinoma, especially in combination with glial fibrillary acid protein and transthyretin. Currently, all HEA 125/Ber EP4-positive PP/PC in patients older than 20 years proved to be metastatic carcinomas during their clinical course.

Adolescent↗
PubMed1993

Morphometrical evaluation of triflusal in brain infarction.

MCA occlusion in animals is a common model for experimental stroke. In previous studies we have shown that one of the factors, which influence evolution of an infarct is microthrombosis in the area of infarction and in the surrounding brain tissue. The present study was undertaken for assessment of the number of microthrombi and of the size of brain infarcting in rats treated with the antiaggregatory substance Triflusal. 7 groups of Sprague-Dawley rats, each group consisting of 6 animals, underwent transsphenoidal MCA occlusion. The animals received Triflusal in various amounts from day 2 till day 6. At day 7 animals were decapitated and the brains were fixed in formaldehyde. The brain was dissected at the level of the optic chiasm and embedded in paraffin. Fresh microthrombi were detected py PTAH (Phosphotungstic acid hematoxylin) staining. In each animal the hemisphere with the ischemic lesion as well as the contralateral hemisphere were examined. The area of both hemispheres was calculated by subtraction of the ventricle area from the total brain area of a section. Infarct was defined as the region of necrosis which was sharply demarcated from normal brain. The infarcted area was planimetrically measured to obtain a ratio of infarcted to normal brain. A correlation between the effect of Triflusal, number of microthrombi and size of the infarcted area could be demonstrated. The pathogenetic role of the microthrombi in the evolution of cerebral infarction as well as the effect of Triflusal in different dosages on the number of microthrombi could be clearly assessed by quantitative morphometry.

Animals↗
PubMed1993

Factor XIIIa immunoreactivity in primary and secondary tumours of the meninges.

Occasionally variants of meningeal hemangiopericytomas (HPC) may be confused with primary and secondary tumours of the meninges by virtue of their features and patterns of growth. Until now, a specific immunohistochemical marker for HPC could not be identified. HPC are reported to express factor XIIIa (F XIIIa) in the cytoplasm of the tumour cells. In an effort to assess the diagnostic value of F XIIIa for meningeal HPC, we investigated 38 primary meningeal tumours (6 HPC, 28 meningiomas of various subtypes, 4 meningeal sarcomas) and 23 secondary meningeal tumors (8 metastatic carcinomas, 6 gliosarcomas, 9 anaplastic gliomas) with anti-F XIIIa antibody. All HPC revealed 5%-20% of F-XIIIa-positive neoplastic cells. Malignant fibrous histiocytomas and gliosarcomas with MFH-like structures also exhibited multiple F-XIIIa-positive cells. Most of the F-XIIIa-positive cells in meningiomas were identified as macrophages. Furthermore, there was a population of small dark cells of uncertain histogenesis. Cells with positive immunoreactivity for F-XIIIa in metastatic carcinomas and gliomas apparently were of macrophage lineage. Though, in some cases, it would have been difficult to distinguish reactive from neoplastic cells without simultaneous immunohistochemical investigation with antibodies for macrophages, cytokeratin, EMA and GFAP. Because of these uncertainties, wo believe that the potential of F XIIIa-antibody in obtaining precise differential diagnostic information is limited.

Carcinoma↗
PubMed1993

How to run a "brain bank"? Clinical and institutional requirements for "brain banking".

"Brain Banking" or prospective sampling of tissues relevant to the study of neurological disease is a complex task which needs organization at various levels of operation such as the establishment of a donor system, recruitment of clinical assessment centres, establishment of standardized assessment protocols, the inauguration of logistic structures for brain removal and transport to the bank, proper storage of patient data and tissues, histological verification of the disease and availability of tissue and clinical data to researchers. This effort certainly promises to bear fruit since there is a striking lack of precise prospective studies into etiology and pathogenesis in most neurological diseases especially in the field of the neurodegenerative diseases.

Brain↗