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Biomedical subjects

M Zurita

Publications and source records attributed to M Zurita.

At least 19 recordsLinked to original sources

Early administration of methylprednisolone decreases apoptotic cell death after spinal cord injury.

The purpose of this study is to evaluate, in an experimental model of spinal cord injury (SCI), the presence of apoptotic cell death after trauma and if early administration of a single bolus of methylprednisolone (MP) influences apoptosis in the zone of trauma and in adjacent spinal cord segments. For this study, a total of 96 adult female Wistar rats were subjected to spinal contusion at the T6-T8 level, producing immediate paraplegia. Forty-eight animals (treated group) received a single intraperitoneal injection of MP, at a dose of 30 mg/kg body weight, 10 minutes later. Cells undergoing apoptosis were detected by means of immunohistochemical labeling with the monoclonal antibody Apostain (anti-ssDNA MAb F7-26), in the injured spinal cord tissue, both in the zone of the lesion and in the adjacent spinal segments (rostral and caudal zones), 1, 4, 8, 24 and 72 hours and 1 week after injury. Apoptosis was detected in neurons and glial cells in the zone of the lesion 1 hour after trauma, with a pattern that showed no changes 4 hours later. Between 4 and 8 hours postinjury, the number of apoptotic cells increased, after which it decreased over the following days. In the adjacent spinal segments, apoptotic cells were detected 4 hours after trauma, and increased progressively over the remainder of the study, the number of apoptotic cells being similar in the lesion zone and in rostral and caudal zones one week after injury. When the group of MP-treated animals was considered, significant decreases in the number of apoptotic cells were detected in the lesion zone 24 hours after injury, and in the rostral and caudal zones, at 72 hours and at 1 week after trauma. These findings show that early administration of a single bolus of MP decreases apoptotic cell death after SCI, supporting the utility of MP in reducing secondary damage in injured spinal cord tissue.

Animals↗

A new neovalve type in short bowel syndrome surgery.

The objective of this study was to compare the clinical and analytical repercussion of a new type of intestinal valve -which can be used in both massive resections and right hemicolectomies requiring the elimination of the ileocecal valve- on two historical series of patients: one group with ileocolic resections and end-to-end anastomoses (EE), and one group with Ricotta valves. We compared 23 patients with ileocolic resection and end-to-end anastomosis, 15 with Ricotta's valve, and 20 patients with a new valve made with a small intestinal invagination. There were no statistically significant differences in baseline characteristics among patients. Patients with the new valve showed less relevant weight loss and fewer stools at 3 months and one year when compared to patients with Ricotta's valve, and particularly those with ileocolic resection. Moreover, with the new valve technique there was neither colonization of the ileal mucosa nor bacterial overgrowth. In conclusion, in massive intestinal resections and right hemicolectomies, including the ileocecal valve, the new valve technique would be of choice.

Adult↗

Apoptosis is not correlated with the presence of CD57+ NK-cells in brain metastases.

BACKGROUND: Cell apoptosis in solid tumours has been related to immunological attack by NK-cells. The purpose of the present study is to verify in the tissue of brain metastases a possible relationship among the degree of NK-cell infiltration and the number of apoptotic tumour cells. METHODS: Twenty brain metastases whose tumour cells expressed CD95 (Fas/APO1) have been studied. NK-cells were identified by using the monoclonal antibody to CD57, and apoptotic tumour cells by means of the immunostain with the anti-ssDNA monoclonal antibody F7-26. The Spearman rank correlation test was used to study the relationship between the degree of CD57-NK-cell infiltration and the apoptosis labelling-index. FINDINGS: Positivity to F7-26 was present in all tumour samples, but the number of immunostained cells showed a wide variability, with a mean apoptosis labelling-index of 11.48%. All the studied tumours showed CD57 immunostained cells, with a number that ranged between 4 and 20 per microscopical field at 200x (mean+/-standard deviation: 8.4+/-3.7). Statistical studies showed that there was no correlation between the number of CD57 immunostained NK-cells and the apoptosis labelling-index (p>0.05). INTERPRETATION: These findings suggest that in brain metastases, apoptosis related to immune response is mainly mediated by activated tumour-infiltrating mononuclear cells other than CD57(+) NK-cells.

Adenocarcinoma↗

Imbalance between apostain expression and proliferative index can predict survival in primary glioblastoma.

BACKGROUND: Cell proliferation and cell death are opposing processes in tumour growth, with tumour progression reflecting the balance between proliferating and apoptotic cells. The purpose of the present study is to verify the hypothesis that an imbalance between apoptosis and proliferation can predict survival in patients with primary glioblastoma. METHODS: After the immunohistochemical study of Apostain and MIB-1 expression, the index of apoptosis (AI), the index of proliferation (PI), and the ratio AI/PI was recorded for each tumour specimen, in a series of 32 primary glioblastomas. Studies of correlation between AI and PI, between AI and survival, between PI and survival, and between the ratio AI/PI and survival, were performed using the Spearman rank correlation test. Furthermore, a comparative study of survival was performed for subgroups of patients with ratio AI/PI greater or lesser than 1, using the log rank test. FINDINGS: In the present series, values of AI and PI showed a wide distribution, with a mean +/- SD of 8.16 +/- 7.2, and of 12.69 +/- 21.1, respectively. The values for the ratio AI/PI ranged between 0.01 and 6.03 (mean +/- SD: 1.44 +/- 1.60). Statistical study failed to obtain correlation between AI and PI. Survival of patients not correlated with AI neither with PI. The ratio between AI and PI did not correlate with survival either. Nevertheless, when survival for the subgroups of patients showing a ratio AI/PI greater or lesser than 1 was compared, a significant difference was found (p: 0.02). Survival ranged between 50 and 81 weeks (mean of 58.5 +/- 11.05 weeks) for the 12 cases showing a ratio AI/PI greater than 1, and it ranged between 8 and 85 weeks (mean: 38.20 +/- 25.37 weeks) for the 20 cases showing a ratio AI/PI lesser than 1. INTERPRETATION: Our present results suggest that a clear imbalance between cell proliferation and apoptosis can predict outcome in patients operated on for a primary glioblastoma.

Aged↗

Vascular endothelial growth-permeability factor in granulation tissue of chronic subdural haematomas.

BACKGROUND: Vascular Endothelial Growth/Permeability Factor (VEG/PF) has been correlated with angiogenesis and vascular leakage in diverse pathological conditions of the brain. On the other hand, neoformation of capillaries and vascular hyperpermeability have been related to progressive enlargement of chronic subdural haematomas (CSDH). The purpose of the present study is to verify the presence of VEG/PF in tissue of CSDH, with the hypothesis that neovascularization and vascular hyperpermeabitity in CSDH can be related to the presence of this cytokine. METHODS: Immunohistochemical studies and Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis were performed in the neomembranes of 12 CSDH to verify presence of VEG/PF in this tissue. FINDINGS: Strong expression of VEG/PF was immunohistochemically disclosed in neomembranes of CSDH, as well as in inflammatory cells currently infiltrating this tissue. Furthermore, RT-PCR studies showed the presence of VEG/PF in all the studied samples. INTERPRETATION: These findings suggest a role for inflammatory cells, currently present in the granulation tissue of CSDH, in the release of VEG/PF and in the enlargement of these lesions, stating the possibility of a new therapeutic approach to CSDH, based on blocking the physiological effects of VEG/PF.

Aged↗

Antitumoral effect of irinotecan (CPT-11) on an experimental model of malignant neuroectodermal tumor.

Irinotecan (CPT-11) is a topoisomerase I inhibitor with antitumor activity on a wide variety of neoplasms in several preclinical studies, but it showed poor efficacy in patients with nervous system tumors. We have carried out an experimental study in order to evaluate the effect of CPT-11 on the growth of a subcutaneously implanted malignant neuroectodermal tumor, after administration by different routes. The results showed that CPT-11 administration by intraperitoneal injections (at dose 10 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period--one course--to a total of two courses) had no significant antitumor effect. Nevertheless, continuous infusion by intraperitoneal osmotic minipump over 28 days (at an infusion rate of 4.4 microg/h) showed a significant delay in tumor growth in 4 weeks of the implantation. The best antitumor effects were observed after CPT-11 intratumoral administration (at dose of 5 mg/kg, 5 days per week, for 2 weeks, followed by 7-days rest period, to a total of three courses) reaching tumor regression in the treated animals. These results suggest the utility of CPT-11, by means of intralesional administration, on malignant tumors of the nervous system.

Animals↗

Antitumor effect of TNP-470 is not associated to decrease of angiogenesis in an experimental malignant neuroectodermic tumor.

The hypothesis that tumor growth depends on neovascularization has been broadly used in oncology research. TNP-470 is a fumagillin synthetic analog that is isolated from Aspergillus fumigatus, and experimental studies suggested that it shows antitumor effect mediated by its strong antiangiogenic effect. Because limited experience exists about the antitumoral effect of TNP-470 in cerebral tumors, we have carried out a study in order to evaluate the effect of TNP-470 on tumor growth and the vascular area in an experimental malignant neuroectodermic tumor growing in the subcutaneous space of immunocompetent Wistar rats. Our results showed a significant tumor growth inhibition in animals treated with TNP-470 when compared to those in the control group (intratumoral injections were administered in 30 mg/kg dose, three times a week on alternate days during four consecutive weeks). Since the quantitative analysis of tumor vascular parameters--number of microvessels and total intratumor vascular area--in the experimental groups did not show significant statistical differences, we conclude that TNP-470 has a significant antitumor effect on our neuroectodermic tumor, but this effect is mediated by other antineoplastic mechanisms that are independent of its previously described angiostatic capacity.

Angiogenesis Inhibitors↗

Growth-inhibiting effects of intralesional docetaxel and paclitaxel on an experimental model of malignant neuroectodermal tumor.

Taxoids are effective agents against a wide variety of tumors, but their effectiveness on neuroectodermal tumors is not well-known. For this reason we have carried out an experimental study on the effect of intratumoral administration of docetaxel (DC) and paclitaxel (PC) on tumor growth, using a murine model of malignant neuroectodermal tumor. The results showed a delay in tumor growth in animals treated with PC compared with controls (dose of 5 mg/kg, three times per week every other day, forming a cycle; three cycles were completed with a break of a week between each cycle). The total dose administered to each animal was 45 mg/kg. When DC was administered, the results showed distinct tumor growth inhibition and tumor regression in 80% of animals (intratumoral administration at a dose of 5 mg/kg, three times per week every other day forming a cycle; three cycles were completed with a break of a week between each cycle). The total dose administered to each animal was 20 mg/kg. These results suggest the utility of taxoids, mainly DC, by intralesional administration, on malignant tumors of the nervous system.

Animals↗

Prognostic significance of tumor-enhancement and angiogenesis in oligodendroglioma.

OBJECTIVE: To study the prognostic significance of angiogenesis and enhancement on contrast-enhanced computerized tomography (CT) in oligodendrogliomas. MATERIAL AND METHODS: CD34 immunostaining was employed in samples of 26 low-grade oligodendrogliomas from patients treated by extensive resection and radiotherapy to determine the tumor angiogenesis index (TAI), calculated by measuring the immunostained endothelial surface area, in microm(2), per 1000 tumor cells. Preoperative CT scan was evaluated in each case, and the absence or presence of tumor enhancement after contrast administration was recorded. Survival was analyzed and statistically compared for subgroups of patients with lesions in which the TAI was less than or greater than 15, and for subgroups of patients having tumors showing presence or absence of enhancement on contrast-enhanced CT. RESULTS: Survival of patients with tumors showing a TAI of less than 15 was 100% and 71% at 5 and 10 years, respectively, vs a survival of 50% and 0% for patients showing a TAI of more than 15 (P < 0.05). The 14 patients whose tumors showed enhancement in preoperative contrast-enhanced CT had 5- and 10-year survival rates of 57% and 14%, respectively, vs 100% and 83% for the 12 patients whose tumors presented no enhancement (P < 0.05). Moreover, 79% of the tumors showing contrast enhancement had a TAI greater than 15, while 92% of those exhibiting no enhancement had a TAI of less than 15. CONCLUSION: These findings indicate a relationship between enhancement on preoperative CT scan and endothelial surface area in oligodendrogliomas, and suggest that this enhancement and the TAI may be considered angiogenesis-related factors with similar prognostic significance in terms of survival.

Antigens, CD34↗

Expression and significance of vascular permeability factor in tumour infiltrating lymphocytes of brain metastases.

BACKGROUND: Recently, vasogenic edema has been related to the expression of vascular permeability factor (VPF) by tumour cells in brain metastases. On the other hand, expression of VPF has been reported in inflammatory cells. Keeping in mind the current presence of tumour-infiltrating lymphocytes (TIL) in brain metastases, our objective is to study the expression and significance of VPF in TIL-cells from specimens of brain metastases. METHOD: Tumour samples from 16 brain metastases associated with peritumoural edema were immunohistochemically studied for demonstration of VPF. The degree of VPF-expression by tumour cells and TIL was determined, and correlated with the degree of peritumoural edema. FINDINGS: Our present results show that, independently of the VPF-positivity expressed by the tumour cells, VPF-expression is a constant finding in TIL-cells of brain metastases, and correlated with the amount of peritumoural edema. INTERPRETATION: Our present findings suggest a role for TIL-cells in the development of vasogenic edema associated with brain metastases.

Brain Edema↗

Genes and peptides from the scorpion Centruroides sculpturatus Ewing, that recognize Na(+)-channels.

Sixteen different genes were cloned from the venomous glands of Centruroides sculpturatus Ewing using RNA extracted from scorpions collected in Tucson, Arizona. Based on the amino acid sequence similarities of the proteins coded by these genes, all together there are 22 different structural components in this venom, thought to be specific for Na(+)-channels. The genes reported contain signal peptides with 19 amino acid residues followed by mature peptides of 63-66 amino acid residues in length. One of them correspond to toxin I (CsEI), a known scorpion toxin specific for Na(+)-channels. Four different genes are almost identical to variant 1 (Csv1), presenting only one amino acid change from the original protein. For variant 2 (Csv2) four related genes were found, with only one amino acid change in their primary sequences. Another gene resembles to variant 3 (Csv3, the best known Centruroides sculpturatus toxin), with only three amino acid changes in their primary sequences. Additionally, two genes show variations only on the nucleotide sequence at level of the signal peptides, and several genes clearly show sequences that suggest post-transcriptional modifications, during the maturation process. A phylogenetic tree was generated with the primary structures available and three main divergent branches were found.

Animals↗

Functional recovery in chronic paraplegic rats after co-grafts of fetal brain and adult peripheral nerve tissue.

BACKGROUND: In recent years, experimental studies have sought some type of functional improvement in traumatic paraplegia by transplanting neural tissue into the injured spinal cord. The aim of this work is to study the possibility of functional recovery in chronic paraplegic rats after co-transplantation of fetal cerebral tissue and adult peripheral nerve tissue. METHODS: Seventy adult female Wistar rats were subjected to spinal cord injury at the T6-T8 level, causing complete paraplegia. Three months later, in 50 rats (grafted group) the injured spinal cord tissue received a graft of fetal brain cortex associated with crushed adult peripheral nerve. All the animals (grafted and control groups) were subjected to daily rehabilitation procedures from the first week after the injury, and evaluated weekly for motor and sensory recovery. Statistical analysis of different behavioral data between control and grafted animals was performed using the Kruskal-Wallis ANOVA and the nonparametric Wilcoxon test. RESULTS: Between 8 and 12 months after transplantation, progressive signs of functional recovery were observed in the grafted animals, associated with an increase in muscle mass in the lower extremities, findings that were significantly different from those in nongrafted animals (p < 0.05). At this time, donor cerebral tissue is integrated into previously injured spinal cord and results in formation of bundles of nerve fibers that emerge from the area of the transplant and surround the spinal cord beneath the lesion. CONCLUSIONS: Delayed co-transplantation of fetal cerebral tissue and peripheral nerve tissue can be used to achieve anatomical remodeling and long-term functional recovery in rats rendered paraplegic as result of severe spinal cord injury. These findings support the possibility of functional recovery after chronic traumatic paraplegia.

Analysis of Variance↗

Prognostic significance of the endothelial surface in low-grade resected oligodendrogliomas.

The importance of angiogenesis as a prognostic factor in brain tumours has recently been reported. In this study, we analysed the long-term prognostic significance of a morphometric score expressing the endothelial area for every 1000 tumour cells, in tumour tissue from 26 patients with a low-grade oligodendroglioma that has been treated surgically and irradiated, and has a MIB-1 labelling index (MIB-1 LI) of less than 1%. In each tumour, a vascular endothelial surface index (VESI) was determined as the CD-34 immunostained endothelial area in micron 2 per 1000 tumour cells. Patients with a VESI of less than 15 (n = 12) showed a survival at 5 and 10 years of 100 and 71%, respectively, versus a survival of 50 and 0% for patients presenting a VESI greater than 15 (n = 14); p < 0.05). Our present findings suggest the usefulness of VESI as a long-term prognostic pathological factor in low-grade oligodendroglioma.

Adolescent↗

Increased UV light sensitivity in transgenic Drosophila expressing the antisense XPD homolog.

The XPD gene is required for excision repair of UV-damaged DNA and is an important component of nucleotide excision repair (NER). Mutations in the XPD gene generate the cancer-prone syndrome xeroderma pigmentosum, Cockayne's syndrome, and trichothiodystrophy. XPD is a component of the TFIIH transcription factor, which is essential for RNA polymerase II elongation. In this work, we report the construction of transgenic flies overexpressing the antisense RNA of the Drosophila melanogaster XPD homolog (DmXPD). These flies show an increased sensitivity to UV radiation compared with the wild-type. This is an expected phenotype if the XPD function is affected and indicates that the antisense approach may be an alternative in the study of TFIIH functions in Drosophila.

Animals↗

Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury.

OBJECT: A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI. METHODS: The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord. CONCLUSIONS: These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.

Animals↗

Fractal-like Aggregates: Relation between Morphology and Physical Properties.

A number of modern technological applications require a detailed calculation of the physical properties of aggregated aerosol particles. For example, in probing soot aerosols by the method called laser-induced incandescence (LII), the soot clusters are suddenly heated by a short, powerful laser pulse and then cool down to the temperature of the carrier gas. LII sizing is based on rigorous calculation of the soot aggregate heat-up and cooling and involves prediction of laser light absorption and energy and mass transfer between aggregated particles and the ambient gas. This paper describes results of numerical simulations of the mass or energy transfer between the gas and fractal-like aggregates of N spherical particles in either the free-molecular or continuum regime, as well as the light scattering properties of random fractal-like aggregates, based on Rayleigh-Debye-Gans (RDG) theory. The aggregate geometries are generated numerically using specially developed algorithms allowing "tuning" of the fractal dimension and prefactor values. Our results are presented in the form of easily applicable scaling laws, with special attention paid to relations between the aggregate gyration radius and the effective radius describing various transport processes between the aggregates and the carrier gas. Copyright 2000 Academic Press.

Journal Article↗