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Biomedical subjects

P Thouvenot

Publications and source records attributed to P Thouvenot.

At least 19 recordsLinked to original sources

Individualized treatment of craniopharyngioma in children: ways and means.

BACKGROUND: Medium- and long-term prognosis of craniopharyngioma is overwhelmed by the risks of hypothalamic and visual impairment. This problem has been underestimated for a long time because the major concern for the neurosurgeon was the risk of recurrences, their best prevention being thought to be complete tumour resection. Today, we know that radical surgery not only is not an absolute guarantee against recurrences but also can cause hypothalamic and visual complications. METHODS: The authors suggest that instead of complete removal, the first choice treatment should be, when possible, a less aggressive, multistaged and personalized treatment. In this perspective they focus on other therapeutic methods: endocavity treatment of cysts with rhenium-186, triconformational radiotherapy, radiosurgery, and widespread use of the trans-sphenoidal approach. CONCLUSIONS: These simple methods should reduce the risks of visual aggravation and metabolic syndrome.

Child↗

Radiofrequency-induced carcinogenesis: cellular calcium homeostasis changes as a triggering factor.

The aim was to study the effects of radiofrequency (Rf) in a mice strain characterized by age-determined carcinogenesis of lymphatic tissues. Mice were treated with a 1?h/week Rf exposure for 4 months. A group submitted to sham exposure was used as control animals. The evolution of carcinogenesis was followed up to 18 months. The maximal life span of control mice was about 24 months. All dead animals were clinically and histologically examined to give an age-determined comparative quantification of the evolving carcinogenesis. A radiocalcium tracer method permitted the evaluation of Rf effects on transmembrane transport of extracellular calcium at 1 and 24 h after exposure. The determination of induced lipid peroxidation completed this second study. The findings show that Rf provoked an earlier general lymphocyte cell infiltration, formation of lymphoblastic ascites and extranodal tumours of different histological types, as well as an increased early mortality. The results suggest that in Rf-exposed mice, carcinogenesis may be induced earlier and with different pathological forms than in control animals. The modifications in cellular calcium homeostasis and the age-determined thymus involution appear to be important factors involved in this carcinogenesis process.

Animals↗

Natural polyphenols-iron interaction: its biological importance.

The iron-binding capacity of different fractions of natural polyphenols extracts was determined by chromatographic and electrophoretic methods. Their effects on iron-induced calcium homeostasis changes in liver tissue suspension showed that mate tea and green tea extracts provoke a very significant inhibition of the iron effects, whereas it is much less significant with red wine extract. The biological importance of this phenomenon is discussed.

Adenosine Triphosphate↗

Evaluation of peroral silicone dosage forms in humans by gamma-scintigraphy.

Gastric emptying of oral silicone dosage forms was studied in humans by gamma-scintigraphy. To achieve a constant and predictable residence time in the stomach, three different formulations based on known concepts such as controlled swelling were investigated. The importance of physical parameters such as size or shape were also examined to assess the feasibility of designing a dosage form for gastric retention. Three shapes: minimatrices, extruded rods and moulded slabs were screened. To label the silicone polymer, two isotopes, used routinely in nuclear medicine departments, were selected: iodine-123 and indium-111. To select the most suitable isotope, the yield and the stability of the labelling were determined in vitro on the pharmaceutical dosage forms. The residence time of these silicone formulations, labelled with iodine and administered in hard gelatine capsules, was monitored in 12 subjects with a gamma camera. The study was performed under fed conditions after ingestion of a standardised meal labelled with indium. The minimatrices provided at least 3 h retention, slabs exhibited 4 h 40 min retention. For the rods the mean residence time in the stomach was around 4 h 20 min. In addition, a correlation was established between the gastric emptying of rods and the half-gastric residence time of meal. On the contrary, such a correlation was not observed for the slabs.

Administration, Oral↗

Comparison of the biodistribution in mice of 111indium oxine encapsulated into poly(lactic-co-glycolic)-D,L-85/15 and poly(epsilon caprolactone) nanocapsules.

Poly(lactic-co-glycolic)-D,L-85/15 (PLAGA) nanocapsules and poly(epsilon caprolactone) (PCL) nanocapsules were labeled with a relatively long half-life compound that is usually used in humans; that is, 111In-labelled oxine (111In oxine). This labeling technique led to a high 111In oxine entrapment efficiency and good stability during dialysis against phosphate buffer and phosphate buffered albumin solution. Because of these characteristics, the nanocapsules biodistribution was followed up after intravenous administration for up to 96 h by determining the gamma activity in the tissues after sampling. The administration of the PCL-encapsulated 111In oxine led to a decrease in the blood radioactivity and an increase in the liver radioactivity compared with the solution. This effect was even more pronounced with the PLAGA nanocapsules. Finally, the activity level in other tissues, such as the kidneys, the lungs, and the spleen, appeared to be rather low and only slightly affected by the encapsulation into one or the other polymer.

Animals↗

Influence of different physicochemical conditions on the release of indium oxine from nanocapsules.

The main purpose of this study was to determine the influence of factors (pH, enzymes, etc.) chosen partially to mimic in vivo conditions on the release of a model drug, indium oxine, from polyepsiloncaprolactone (PCL) nanocapsules in vitro. A nanocapsule suspension, an emulsion (O/W), and a solution in olive oil were prepared in order to compare the release of a radioactive tracer, indium oxine, as a function of time by an in vitro dialysis method. Nanocapsules were prepared by interfacial deposition of PCL and characterized by particle size distribution (laser light scattering) and determination of the polymer molecular weight by gel permeation chromatography (GPC). The results of this study suggest that the partition coefficient between the acceptor medium and the olive oil is the major parameter governing the release of the isotope, at least in the absence of significant enzyme activity. The PCL wall of nanocapsules is a barrier that does not seem to retard the release of indium. The addition of porcine liver esterases accelerated the degradation of PCL. This study confirms that the release of a drug from nanocapsules may be very different depending on the in vivo location, that is, the administration site.

Dosage Forms↗

Effects of low-molecular-weight aluminum complexes on brain tissue calcium homeostasis.

The in vitro effects of low-molecular-weight aluminum complexes (citrate, lactate, and ATP complex) on the Ca2+ uptake and aluminum-induced lipid peroxidation of brain tissue show that the modification of the calcium homeostasis is determined by the nature of the ligand and that there is no correlation between the aluminum-induced lipid peroxidation and the Ca2+ uptake. The same characteristics have been shown by a similar study performed with Ehrlich carcinoma cells. The electrophoretic analyses of the aluminum lactate-albumin and aluminum lactate-ATP interactions indicate an aluminum transfer from the lactate to the albumin and ATP ligands. The increased Ca2+ uptake when ATP is present in the incubation medium with aluminum citrate and aluminum lactate corroborates the suggested mediator role of ATP in cellular calcium homeostasis modification induced by iron.

Aluminum Compounds↗

ATP in iron overload-induced intracellular calcium changes.

The cellular iron uptake from low molecular weight iron complexes (ferric citrate, ferric lactate and ferric ATP complex) is concentration-dependent, and only a small part of the iron penetrates the cell as shown by deferoxamine treatment. A threshold of iron concentration in the cell must be reached for the iron complex-induced increase of cellular Ca2+-uptake. ATP seems to play a key role in an iron translocation that enhances the effects of the iron complexes. A non-specific and competitive iron-binding by proteins seems to act as a buffer system that reduces the iron overload effects. Calcium channel blockers have no effects on the iron complex-cell interaction or iron-induced Ca2+-uptake modification. An iron complex concentration-dependent inhibition of the CaATPase activity, and its consequent Ca2+-extrusion impairment appear as the likely cause of calcium overload. The relevance of these findings in iron overload-induced pathologies is discussed.

Adenosine Triphosphate↗

Role of lipid peroxidation in iron-induced cellular calcium overload.

Calcium overload is the common pathway leading to cell injury. The role of iron-induced lipid peroxidation in the modification of Ehrlich carcinoma cells calcium homeostasis has been studied. There is a lack of correlation between that modification and the value of lipid peroxidation. The stability characteristics of low-mol-weight iron complexes affect lipid peroxidation and, to a lesser extent, cellular calcium uptake. Lipid peroxidation appears not as a triggering factor of cellular calcium homeostasis modification, but as a concomitant phenomenon.

Adenosine Triphosphate↗

Effect of egg consumption in healthy volunteers: influence of yolk, white or whole-egg on gastric emptying and on glycemic and hormonal responses.

The effects of the ingestion of 2 whole eggs (E), 2 egg whites, 2 egg yolks (Y), or no eggs with a standard breakfast on gastric emptying, glycemic and hormonal responses have been studied in 12 healthy young males. E and Y induce a significant delay of gastric emptying, together with reduced blood glucose and insulin peaks (Y). Egg ingestion, whatever the part, increases gastric inhibitory peptide level in blood. Cholecystokinin is enhanced after E or Y ingestion. The results indicate that egg ingestion, especially yolk ingestion, may be of interest in regulating metabolic variables of glucose metabolism.

Adolescent↗

Cardiotoxicity of parenterally administered iron complexes.

The role of cell calcium overload in the cardiotoxicity of low molecular weight iron complexes has been studied using 45Ca(2+)-uptake determinations in mice intraperitoneally injected with ferric lactate and ferric-ATP complex. Heart tissue shows a very high increase of 45Ca(2+)-uptake which appears to corroborate the hypothesis of cardiotoxicity by calcium overload. ATP seems to play a role in the degree of iron complex efficiency as cell calcium homeostasis modifier.

Adenosine Triphosphate↗

Liver calcium homeostasis modification by iron: a probable factor in its carcinogenesis.

Low molecular weight iron complexes, ferric lactate and ferric-ATP complex, induce an important increase of Ca(2+)-uptake by liver. The activity of ferric lactate increased by the presence of sodium ATP, and the steady high effect of ferric-ATP complex appear to indicate that ATP might play an important role in the in vivo formation of low molecular weight iron complexes that can induce the modification of the hepatocytes calcium homeostasis, the event that might be one of the factors triggering the malignant transformation.

Adenosine Triphosphate↗

Lymphatic targeting of polymeric nanoparticles after intraperitoneal administration in rats.

Following intraperitoneal administration, the lymphatic targeting of polyacrylic nanoparticles has been evaluated in thoracic duct cannulated rats. The dosage forms administered consisted of carbon-14 polyhexylcyanoacrylate nanoparticles (PHCA) and polymethylmethacrylate (PMMA) nanoparticles. The carbon-14 concentrations were much higher in the excreted thoracic lymph than in the blood for both types of particles. The most dramatic results were found in the mediastinal nodes since the carbon-14 concentrations of rats receiving PHCA and PMMA nanoparticles by the ip route were 70- to more than 2000-fold higher than in the corresponding nodes of animals treated by the intravenous route. This potential lymphatic targeting could prove valuable in cancerology to treat tumors that metastasize in the peritoneal cavity or via lymphatic pathways such as colon carcinomas.

Animals↗

Bifidobacterium from fermented milks: survival during gastric transit.

Two Bifidobacterium strains contained in two different fermented milks behave very differently when exposed to an in vitro simulated gastric environment. One strain survives very well during at least 90 min (greater than 10(7)/g), but the second strain studied is much less resistant. These in vitro results, with slight differences, were confirmed by an in vivo study in humans. The assessment of the gastric emptying rate of these products allows an estimation of the amount of Bifidobacterium that may pass into the small intestine.

Adult↗

Effects of iron-binding proteins on in vitro uptake of 67Ga-citrate by tumor cells.

A comparative study of carrier-free 67Ga-citrate uptake by Ehrlich ascites tumor cells in the presence of lactoferrin, transferrin and ferritin has demonstrated that lactoferrin considerably increases the uptake of 67Ga, and that this increase seems to be determined by its iron-load. The other iron-binding proteins assayed have a null or negative effect. Their behavior in the presence of sodium citrate supports the concept of lactoferrin-binding by the cells as responsible for the uptake. The different behavior of 67Ga-citrate iron-binding protein complexes appears to support this hypothesis.

Animals↗

Iron-binding proteins and 67Ga accumulation by tumor cells.

Tumor cells incubated with 67Ga-citrate plus lactoferrin showed a lactoferrin concentration-dependent increase of 67Ga uptake while for transferrin the effect was an inhibition. A correlation was observed between the binding of 131I-labelled lactoferrin or 131I-labelled transferrin and the uptake of 67Ga by the cells. Saturation with iron did not change significantly the effects of the iron-binding proteins. Preincubation with lactoferrin, transferrin or ferric citrate increased 67Ga uptake. The formation of a ternary complex in which 67Ga mimics iron is discussed.

Animals↗