Biomedical subjects

M Bendayan

Publications and source records attributed to M Bendayan.

203 records · Page 12Linked to original sources

PubMedDate not supplied

Boronated epidermal growth factor as a potential targeting agent for boron neutron capture therapy of brain tumors.

In order for boron neutron capture therapy (BNCT) to be successful, a large number (approximately 10(9)) of 10B atoms must be delivered to each cancer cell in order to sustain a lethal 10B(n, alpha)7Li reaction. The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and increased numbers of EGFR are found on the cell surface. If a sufficiently large number of 10B atoms could be attached to EGF, the resulting bioconjugates might be useful for targeting brain tumors. In order to accomplish this, we have boronated a fourth-generation starburst dendrimer (SD) using an isocyanato polyhedral borane, Na(CH3)3NB10H8NCO. For conjugation, reactive thiol groups were introduced into the boronated SD using N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP), and EGF was derivatized with m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (sMBS). Subsequent reaction of thiol groups of derivatized BSD with maleimide groups of derivatized EGF produced stable BSD-EGF bioconjugates containing approximately 960 atoms of boron per molecule of EGF. As determined by electron spectroscopic imaging, the BSD-EGF initially was bound to the cell surface membrane and then was endocytosed, which resulted in accumulation of boron in lysosomes. The favorable in vitro properties of these bioconjugates suggest that they may be useful for the in vivo targeting of EGFR positive brain tumors.

Amino Acid Sequence↗

PubMedDate not supplied

Circulating glycated albumin and glomerular anionic charges.

Aiming to discern the mechanisms by which circulating glycated albumin alters the glomerular filtration properties that lead to glomerular dysfunction in diabetes, the authors studied the distribution and densities of anionic charges through the rat glomerular wall upon intravascular infusion of Amadori products, as well as in various conditions of increased glomerular permselectivity. Polylysine-gold was used as the probe to reveal the anionic charges. The study was carried on renal tissue sections of bovine serum albumin (BSA)- and glycated BSA-injected, normoglycemic animals. Results were generated through morphometrical evaluations of the gold labeling. Changes in glomerular anionic distribution were corroborated on renal tissue sections of short- and long-term diabetic rats and of normal newborn rats, situations known for abnormal glomerular filtration. Altered renal function in these conditions was clearly associated with changes in glomerular anionic charges. On the other hand, the infusion of glycated albumin in the circulation of normal rats, though altering glomerular filtration properties, did not modify the distribution and density of the polylysine-gold labeling through the glomerular basement membrane. Thus, anionic charges seem not to be the factor involved in the early changes of glomerular permeability induced by circulating glycated albumin.

Animals↗

PubMedDate not supplied

High-resolution ultrastructural study of the rat glomerular basement membrane in long-term experimental diabetes.

The ultrastructure of the glomerular basement membrane of the long-term diabetic and age-matched control rats was studied with the application of advanced high-resolution microscopy. By using the freeze substitution method for the preparation of the renal tissue, it was possible to observe that the glomerular basement membrane in control and diabetic animals is composed on only a single lamina densa without the presence of a lamina lucida interna or externa. High-resolution electron microscopy of the diabetic glomerular basement membrane showed significant alterations in its morphology and ultrastructure. First, the basement membrane in diabetic condition appeared to be split into two halves, endothelial and epithelial. In the epithelial half of the membrane, the network of distinct strands referred to as cords, which were clearly present in the glomerular basement membrane of age-matched control animals, became less distinct and showed a diffused appearance being evenly replaced by thin filaments. The openings of the network were filled with a granular material. In the endothelial half of the membrane, on the other hand, the cord network was variably lost in diabetic condition and, within the resulting vacant spaces, bundles of fibrils 12 nm in width, identified as basotubules, were deposited. Immunolabeling for type IV collagen was found to be enriched in the endothelial half of the basement membrane being associated with the bundles of basotubules. The ultrastructural changes reported by high-resolution microscopy could be related to the molecular alterations of the basement membrane components and to the loss in permselectivity occurring during diabetes.

Animals↗

PubMedDate not supplied

High-resolution ultrastructural study of the rat glomerular basement membrane in aminonucleoside nephrosis.

In the initial stages of aminonucleoside nephrosis, functional alterations in the glomerular basement membrane occur, as evidenced by the development of proteinuria. However, it has not been possible to observe important ultrastructural modifications at the level of the basement membrane, probably because the changes are taking place at the molecular level. In this study, by the use of high-resolution electron microscopy, an attempt was made to evaluate such changes in rat glomerular basement membrane during acute aminonucleoside nephrosis. As previously reported, in control animals the glomerular basement membrane is composed of a network of 4-nm-wide irregular anastomosing strands, referred to as "cords," which are known to contain a core filament of type IV collagen surrounded by a "sheath" of other components, such as laminin and heparan sulfate proteoglycan (HSPG). The most conspicuous ultrastructural alteration of the nephrotic glomerular basement membrane, recognizable only at high magnification, is that the cords were denuded leaving only the core filament through the loss of the sheath material. Thus, the cord network was transformed, with the progress of pathological conditions, into a network of fine filaments. On the other hand, abundance and distribution of HSPG molecules known to be present in the form of 4.5- to 5-nm-wide ribbon-like "double tracks," were found to be similar in control and nephrotic tissues. Since HSPG is one of the charge proteins of the basement membrane, the little changes observed for HSPG are difficult to interpret in view of reported decreases in basement membrane anionic sites in nephrosis. In conclusion, the glomerular basement membrane in aminonucleoside nephrosis loses its cord network components and replaces them with a more perforated network, which could be a cause for the increased permeability of this basement membrane.

Animals↗

PubMedDate not supplied

Lipoprotein lipase in experimental diabetic rats: beneficial effect of vanadate treatment.

Elevated values of circulating triglycerides were observed in streptozotocin-hyperglycemic rat while cholesterol concentrations did not differ from controls. Daily oral administration of sodium metavanadate to these diabetic animals normalized blood glucose values without raising the reduced levels of insulin. Concomitant with the normalization of the glycemia, the elevated triglyceride values found in diabetic rats were also corrected. Lipoprotein lipase activity in adipose and cardiac tissues was significantly decreased in the streptozotocin-diabetic animals. Similarly, the hepatic lipase activity was also depressed. After vanadate treatment, lipoprotein lipase as well as hepatic lipase activities were corrected towards normal values. Thus, vanadate treatment of streptozotocin-diabetic animals induces normalization of blood glucose and triglycerides levels, while maintaining low amounts of circulating insulin. It also restores the depressed activities of adipose and cardiac lipoprotein lipase and hepatic lipase.

Adipose Tissue↗