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Biomedical subjects

A Toledano

Publications and source records attributed to A Toledano.

At least 37 records · Page 2Linked to original sources

Spatial and temporal control of gene therapy using ionizing radiation.

Activation of transcription of the Egr-1 gene by X-rays is regulated by the promoter region of this gene. We linked the radiation-inducible promoter region of the Egr-1 gene to the gene encoding the radiosensitizing and tumoricidal cytokine, tumour necrosis factor-alpha (TNF-alpha) and used a replication-deficient adenovirus to deliver the Egr-TNF construct to human tumours growing in nude mice. Combined treatment with Ad5.Egr-TNF and 5,000 cGy (rad) resulted in increased intratumoral TNF-alpha production and increased tumour control compared with treatment with Ad5.Egr-TNF alone or with radiation alone. The increase in tumour control was achieved without an increase in normal tissue damage when compared to tissue injury from radiation alone. Control of gene transcription by ionizing radiation in vivo represents a novel method of spatial and temporal regulation of gene-based medical treatments.

Animals

Pyritinol facilitates the recovery of cortical cholinergic deficits caused by nucleus basalis lesions.

The effect of a nootropic, Pyritinol, on the recovery of cortical cholinergic deficits induced by injury of the nucleus basalis has been tested on two groups of unilateral quisqualic acid nbM-lesioned rats. The first group had a 30 nmol lesion producing a cortical cholinergic impairment at 21 days, with a spontaneous recovery at 45 days. The second group had a 50 nmol lesion that produced a deeper cholinergic deficit, which did not recover at 45 days. Pyritinol enhanced the recovery in the 30 nmol group of animals on the 21st day after surgery. The recovery was measured as an increase in the activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and the high affinity choline uptake system, and the histochemical densities of the cortical AChE network and the M2 receptor. Histochemical analysis of the nbM enabled cortical recovery to be related to the number of surviving neurons and also to their hypertrophy and AChE-ChAT hyperactivity. Pyritinol enhanced recovery in 30 nmol lesioned animals but in the other group, with a lower number of surviving neurons and a lower ability of the cells to become hypertrophic, the drug was unable to promote cortical recovery.

Animals

Pulmonary carcinoma metastatic to the larynx.

Metastases to the larynx from distant primaries are rare. We report a case of a pulmonary epidermoid carcinoma metastatic to the larynx that simulated a primary cancer. A review of the literature showed nine previously reported cases of pulmonary metastases to the larynx--only two of them were epidermoid carcinomas. Treatment of a secondary lesion in the larynx is justified only when other organs have not been affected. The diagnostic and therapeutic considerations of this condition are discussed.

Carcinoma, Squamous Cell

Volatile anesthetics decrease peristalsis in the guinea pig ureter.

BACKGROUND: The origin of renal dysfunction associated with anesthesia and surgery is complex and incompletely understood. The effects of the volatile anesthetic agents isoflurane, enflurane, and halothane on the renal pacemaker and ureteral peristalsis may play an important role. METHODS: Guinea pig ureter and pelvis were dissected and placed in a sample chamber that allowed immersion in a temperature-controlled bath with gas (O2 with or without volatile agent) bubbled through the chamber continuously. The baseline frequency and amplitude of peristaltic contractions were measured on a polygraph recorder. The preparations were then exposed to up to 4 vol% volatile agent incrementally to generate a cumulative dose-response curve, and the subsequent frequency of peristaltic contractions was determined. The concentration of the volatile agent in solution was measured by gas chromatography. RESULTS: There was a significant dose-related decrease in the frequency of ureteral contractions for all three agents. A statistical model relating percentage baseline frequency to millimolar concentrations of volatile anesthetics showed that halothane produced a more pronounced decrease in frequency than did isoflurane or enflurane. However, the decrease was directly related to the MAC multiples and did not differ for the three agents. CONCLUSIONS: Ureteral peristaltic contractions are decreased in a dose-dependent manner by enflurane, halothane and isoflurane.

Animals

Morphometric and neurosecretory changes in supraoptic neurons after D-amphetamine treatment.

Several morphological and immunochemical characteristics of the neurosecretory neurons of the supraoptic nucleus (SON) have been studied of rats treated for 1 month with D-amphetamine sulfate (AMP) (8 mg/kg weight, daily). An increase of SON volume (11%) has been observed as a consequence of the growth of the dorsoventral axis. Neurosecretory neurons increased their nucleolar area (11.4%), their nuclear area (8.3%), and their cytoplasmatic area (18.3%). Vasopressin immunoreaction did not show any differences between treated and control animals, but oxytocin immunostaining displayed an important increase (23.7%) in the neuronal cytoplasm of the treated rats. The SON hypertrophy of the AMP-treated rats corresponded to the hypertrophy/hyperfunction of its oxytocinergic neurons, and could be considered as a new mechanism of the action of the AMP. The results are discussed in relation to the plastic features of the SON and its central (neuronal) and peripheral (hormonal) function.

Animals

Autoradiographic localization of receptors for glucagon-like peptide-1 (7-36) amide in rat brain.

Glucagon-like peptide-1 (GLP-1) has a sparse but well defined distribution in the rat brain where it is co-localized with glucagon-like immunoreactivity due to other fragments of the glucagon precursor. We have investigated the localization of GLP-1 receptors in rat brain using mono-125I-iodinated GLP-1(7-36) amide, the biologically active form of the peptide that occurs in brain, as the tracer for binding and autoradiographic studies of tissue sections. Displaceable binding of the label was sharply localized to discrete areas, being high in mamillary nuclei, the arcuate nucleus, nucleus of the solitary tract and the pretectal area, intermediate in the lateral septal nuclei, olfactory bulb, dorsal tegmental nuclei and the interpenduncular nucleus, and low in other regions. These results indicate areas where GLP-1(7-36) amide may have a role as a neurotransmitter or neuromodulator.

Animals

Morphometric study on the development of magnocellular neurons of the supraoptic nucleus utilising immunohistochemical methods.

Vasopressin (VP)- and oxytocin (OXY)-producing neurons, components of the rat supraoptic nucleus, have been located with immunohistochemical methods, with the purpose of studying their morphofunctional characteristics during different phases of life (embryonic, juvenile, adult and senile). To carry out this study, an IBAS I (Kontron) computerised image analyser has been utilised. The hormone VP is first detected in the neuronal cytoplasm of 21 days old rat embryos and the hormone OXY appears in the neuronal cytoplasm later, in the newborn phase. The neuronal area with a positive reaction for the two neurohormones has been evaluated and it has been found that the quantity of reaction substance is proportional to the age. In the adult period, VP neurons possess a reaction area (198 microns 2) greater than that of OXY neurons (153 microns 2). In the SON, there are two neuronal shapes, fusiform and round; these shapes coexist in both hormonal types of neurons. Until Day 15 of postnatal development, the SON neurons are intermixed in the interior of the nucleus but in this period a neuronal redistribution is initiated. In the adult phase, OXY neurons are situated preferentially in the anterior, posterior and dorsal parts and VP neurons in the ventral and posterior parts, with both neurons being present in the intermediate part of the SON.

Aging

Dysphagia and lower esophageal sphincter abnormalities after proximal gastric vagotomy.

We studied 96 patients subjected to elective proximal gastric vagotomy for intractable duodenal ulceration. Dysphagia was a frequent finding and occurred in 32 percent. It appeared in the immediate postoperative period and usually lasted for 1 to 2 months without any abnormalities in lower esophageal sphincter function. In five patients, dysphagia was severe and, although transient, was associated with changes in lower esophageal function simulating those observed in achalasia. The mechanism of these motor abnormalities is probably due to a reversible neuromuscular dysfunction of the lower esophageal sphincter.

Adult