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Biomedical subjects

G Pasut

Publications and source records attributed to G Pasut.

8 recordsLinked to original sources

Polyethylene glycol and a novel developed polyethylene glycol-nitric oxide normalize arteriolar response and oxidative stress in ischemia-reperfusion.

Polyethylene glycol (PEG) has been shown to repair cell membranes and, thus, inhibit free radical production in in vitro and in vivo models. We hypothesized that PEG and newly developed organic nitrate forms of PEG (PEG-NO) could repair endothelial dysfunction in ischemia-reperfusion (I/R) injury in the hamster cheek pouch visualized by intravital fluorescent microscopy. After treatments, we evaluated diameter and RBC velocity and flow in arterioles, as well as lipid peroxides in the systemic blood, perfused capillary length, vascular permeability, leukocyte adhesion, and amount of von Willebrand factor (vWF) in the blood after I/R injury. A control group was treated with 5,000- or 10,000-Da PEG, and three groups were treated with PG1 (1 NO molecule covalently bound to PEG, 5,170 Da), PG8 (8 NO molecules covalently bound to PEG, 11,860 Da), and PG16 (16 NO molecules covalently bound to PEG, 14,060 Da). All animals received 0.5 mg/0.5 ml. Lipid peroxides increased at 5 and 15 min of reperfusion, whereas diameter, RBC velocity, and blood flow decreased in arterioles after I/R injury. Vascular permeability, leukocyte adhesion, and vWF increased significantly. PEG and PG1 attenuated lipid peroxides and vasoconstriction during reperfusion and decreased leukocyte adhesion and vascular permeability. PG8 maintained lipid peroxides at normal levels, increased arteriolar diameter, flow, and perfused capillary length, and decreased vWF level and leukocyte adhesion (P < 0.05). PG16 was less effective than PG1 and PG8. In conclusion, PEG-NO shows promise as a compound that protects microvascular perfusion by normalizing the balance between NO level and excessive production of free radicals in endothelial cells during I/R injury.

Animals↗

PEG-Ara-C conjugates for controlled release.

The antitumour agent 1-beta-D arabinofuranosilcytosyne (Ara-C) was covalently linked to poly(ethylene glycol) (PEG) in order to improve the in vivo stability and blood residence time. Eight PEG conjugates were synthesised, with linear or branched PEG of 5000, 10000 and 20000 Da molecular weight through an amino acid spacer. Starting from mPEG-OH or HO-PEG-OH, conjugation was carried out to the one or two available hydroxyl groups at the polymer's extreme. Furthermore, to increase the drug loading of the polymer, the hydroxyl functions of PEG were functionalised with a bicarboxylic amino acid yielding a tetrafunctional derivative and, by recursive conjugation with the same bicarboxylic amino acid, products with four or eight Ara-C molecules for each PEG chain were prepared. A computer graphic investigation demonstrated that aminoadipic acid was a suitable bicarboxylic amino acid to overcome the steric hindrance between the vicinal Ara-C molecules in the dendrimeric structure. In this paper we report the optimised conditions for synthesis and purification of PEG-Ara-C products with a low amount of remaining free drug, studies toward the hydrolysis of PEG-Ara-C and the Ara-C deamination by cytidine deaminase, pharmacokinetics in mice and cytotoxicity towards HeLa human cells were also investigated. Increased stability towards degradation of the conjugated Ara-C products, in particular for the highly loaded ones, improved blood residence time in mice and a reduced cytotoxicity with respect to the free Ara-C form was demonstrated.

Animals↗

Evaluation of the audioscope in an industrial setting.

In this study, the findings of a 25 dB hearing level Welch Allyn Audioscope test at 0.5, 1, 2, 4 kHz were compared with the standard of conventional pure-tone audiometry in 228 newly hired construction workers. The sensitivity for all frequency-specific comparisons combined was found to be lower than in previous studies done in a nonoccupational setting. After correction for sampling bias, the specificity for all frequencies combined was well within the range reported in other studies. Only 1.9% of ears (1/53) that were able to hear all four audioscope frequencies were found by conventional audiometry to have clinically important hearing loss defined as a 25 dB hearing level averaged over the speech frequencies. Hence, the audioscope can be used as a rapid initial test in workers who otherwise would not have access to hearing screening.

Adolescent↗

Public health in Canada: a comparative study of six provinces.

PURPOSE: To describe the public health systems and their projected futures in six provinces in the context of two developments: 1) the emerging discourse on population health and 2) the trend toward regionalization of the health care system. METHODS: Telephone interviews with key informants and key document review. RESULTS AND CONCLUSIONS: Communicable disease control and health protection are currently the "core businesses" of public health; the population health discourse has not resulted in mandated programming. The reality is a retrenchment of public health scope during a time that should be considered conducive to expansion. Only Ontario has not regionalized its health care system, although public health is already delivered regionally. Alberta, Saskatchewan and Manitoba have either evolved or are evolving toward an integrated health system. There were concerns about the potential impact on public health identity and funding of this "vertical integration". Regionalization of public health may result in units that are too small to support adequate local expertise and may jeopardize development and enforcement of province-wide programs.

Canada↗