Quantitative analysis of collagen and elastic fibers in the transversalis fascia in direct and indirect inguinal hernia

PURPOSE: Our previous studies demonstrated structural and quantitative age-related changes of the elastic fibers in transversalis fascia, which may play a role in inguinal hernia formation. To verify whether there were differences in the extracellular matrix between direct and indirect inguinal hernia, we studied the amount of collagen and elastic fibers in the transversalis fascia of 36 male patients with indirect inguinal hernia and 21 with direct inguinal hernia. MATERIAL AND METHODS: Transversalis fascia fragments were obtained during surgical intervention and underwent histological quantitative analysis of collagen by colorimetry and analysis of elastic fibers by histomorphometry. RESULTS: We demonstrated significantly lower amounts of collagen and higher amounts of elastic fibers in transversalis fascia from patients with direct inguinal hernia compared to indirect inguinal hernia patients. The transversalis fascia from direct inguinal hernia patients showed structural changes of the mature and elaunin elastic fibers, which are responsible for elasticity, and lower density of oxytalan elastic fibers, which are responsible for resistance. These changes promoted loss of resiliency of the transversalis fascia. CONCLUSION: These results improve our understanding of the participation of the extracellular matrix in the genesis of direct inguinal hernia, suggesting a relationship with genetic defects of the elastic fiber and collagen synthesis.

Risk assessment in a research laboratory during sol–gel synthesis of nano-TiO2

The occupational risks in the nanotechnology research laboratories are an important topic since a great number of researchers are involved in this area. The risk assessment performed by both qualitative and quantitative methods is a necessary step for the management of the occupational risks. Risk assessment could be performed by qualitative methods that gather consensus in the scientific community. It is also possible to use quantitative methods, based in different technics and metrics, as indicative exposure limits are been settled by several institutions. While performing the risk assessment, the information on the materials used is very important and, if it is not updated, it could create a bias in the assessment results. The exposure to TiO2 nanoparticles risk was assessed in a research laboratory using a quantitative exposure method and qualitative risk assessment methods. It was found the results from direct-reading Condensation Particle Counter (CPC) equipment and the CB Nanotool seem to be related and aligned, while the results obtained from the use of the Stoffenmanager Nano seem to indicate a higher risk level.

Direct angiotensin type 2 receptor (AT2R) stimulation attenuates T-cell and microglia activation and prevents demyelination in experimental autoimmune encephalomyelitis in mice.

In the present study, we evaluated stimulation of the angiotensin type 2 receptor (AT2R) by the selective non-peptide agonist Compound 21 (C21) as a novel therapeutic concept for the treatment of multiple sclerosis using the model of experimental autoimmune encephalomyelitis (EAE) in mice. C57BL-6 mice were immunized with myelin-oligodendrocyte peptide and treated for 4 weeks with C21 (0.3 mg/kg/day i.p.). Potential effects on myelination, microglia and T-cell composition were estimated by immunostaining and FACS analyses of lumbar spinal cords. The in vivo study was complemented by experiments in aggregating brain cell cultures and microglia in vitro. In the EAE model, treatment with C21 ameliorated microglia activation and decreased the number of total T-cells and CD4+ T-cells in the spinal cord. Fluorescent myelin staining of spinal cords further revealed a significant reduction in EAE-induced demyelinated areas in lumbar spinal cord tissue after AT2R stimulation. C21-treated mice had a significantly better neurological score than vehicle-treated controls. In aggregating brain cell cultures challenged with lipopolysaccharide (LPS) plus interferon-γ (IFNγ), AT2R stimulation prevented demyelination, accelerated re-myelination and reduced the number of microglia. Cytokine synthesis and nitric oxide production by microglia in vitro were significantly reduced after C21 treatment. These results suggest that AT2R stimulation protects the myelin sheaths in autoimmune central nervous system inflammation by inhibiting the T-cell response and microglia activation. Our findings identify the AT2R as a potential new pharmacological target for demyelinating diseases such as multiple sclerosis.

Direct analysis of peptide binding to cell-associated MHC class I molecules.

Exogenously added synthetic peptides can mimic endogenously produced antigenic peptides recognized on target cells by MHC class I-restricted cytolytic T lymphocytes. While it is assumed that exogenous peptides associate with class I molecules on the target cell surface, direct binding of peptides to cell-associated class I molecules has been difficult to demonstrate. Using a newly developed binding assay based on photoaffinity labeling, we have investigated the interaction of two antigenic peptides, known to be recognized in the context of H-2Kd or H-2Db, respectively, with 20 distinct class I alleles on living cells. None of the class I alleles tested, with the exception of H-2Kd or H-2Db, bound either of the peptides, thus demonstrating the exquisite specificity of peptide binding to class I molecules. Moreover, peptide binding to cell-associated H-2Kd was drastically reduced when metabolic energy, de novo protein synthesis or protein egress from the endoplasmic reticulum was inhibited. It is thus likely that exogenously added peptides do not associate with the bulk of class I molecules expressed at the cell surface, but rather bind to short-lived molecules devoid of endogenous peptides.

Differential allocation and deployment of direct and indirect defences by Vicia sepium along elevation gradients

Dissecting drivers of plant defence investment remains central for understanding the assemblage of communities across different habitats. There is increasing evidence that direct defence strategies against herbivores, including secondary metabolites production, differ along ecological gradients in response to variation in biotic and abiotic conditions. In contrast, intraspecific variation in indirect defences remains unexplored. Here, we investigated variation in herbivory rate, resistance to herbivores, and indirect defences in ant-attracting Vicia species along the elevation gradient of the Alps. Specifically, we compared volatile organic compounds (VOCs) and ant attraction in high and low elevation ecotypes. Consistent with adaptation to the lower herbivory conditions that we detected at higher elevations in the field, high elevation plants were visited by fewer ants and were more susceptible to herbivore attack. In parallel, constitutive volatile organic compound production and subsequent ant attraction were lower in the high elevation ecotypes. We observed an elevation-driven trade-off between constitutive and inducible production of VOCs and ant attraction along the environmental cline. At higher elevations, inducible defences increased, while constitutive defence decreased, suggesting that the high elevation ecotypes compensate for lower indirect constitutive defences only after herbivore attack. Synthesis. Overall, direct and indirect defences of plants vary along elevation gradients. Our findings show that plant allocation to defences are subject to trade-offs depending on local conditions, and point to a feedback mechanism linking local herbivore pressure, predator abundance and the defence investment of plants.

Effect of Antimalarial Drugs on Plasmodia Cell-Free Protein Synthesis

A cell-free system from Plasmodium falciparum able to translate endogenous mRNA was used to determine the effect of artemisinin, chloroquine and primaquine on the protein synthesis mechanism of the parasite. The antimalarial drugs did not inhibit the incorporation of [³H] methionine into parasite proteins even at concentrations higher than the ones found to strongly inhibit the parasite growth. Results clearly indicate that these compounds do not have a direct effect on protein synthesis activity of P. falciparum coded by endogenous mRNA.

The Network Company in Catalonia : ICT, Productivity, Competitiveness, Salaries and Performance in Catalonia's Companies. Research report (synthesis document)

Resum en anglès del projecte de recerca L'empresa xarxa a Catalunya. TIC, productivitat, competitivitat, salaris i beneficis a l'empresa catalana té com a objectiu principal constatar que la consolidació d'un nou model estratègic, organitzatiu i d'activitat empresarial, vinculat amb la inversió i l'ús de les TIC (o empresa xarxa), modifica substancialment els patrons de comportament dels resultats empresarials, en especial la productivitat, la competitivitat, les retribucions dels treballadors i el benefici. La contrastació empírica de les hipòtesis de treball l'hem feta per mitjà de les dades d'una enquesta a una mostra representativa de 2.038 empreses catalanes. Amb la perspectiva de l'impacte de la inversió i l'ús de les TIC no s'aprecia una relació directa entre els processos d'innovació digital i els resultats de l'activitat de l'empresa catalana. En aquest sentit, hem hagut de segmentar el teixit productiu català per a buscar les organitzacions en què el procés de coinnovació tecnològica digital i organitzativa és més present i en què la intensitat de l'ús del coneixement és un recurs molt freqüent per a poder copsar impactes rellevants en els principals resultats empresarials. Això és així perquè l'economia catalana, avui, presenta una estructura productiva dual.

Direct and indirect root defences of milkweed (Asclepias syriaca): trophic cascades, trade-offs and novel methods for studying subterranean herbivory

P>1. Entomopathogenic nematodes can function as indirect defence for plants that are attacked by root herbivores. By releasing volatile organic compounds (VOCs), plants signal the presence of host insects and thereby attract nematodes.2. Nonetheless, how roots deploy indirect defences, how indirect defences relate to direct defences, and the ecological consequences of root defence allocation for herbivores and plant biomass are essentially unknown.3. We investigate a natural below-ground tritrophic system, involving common milkweed, a specialist root-boring beetle and entomopathogenic nematodes, and asked whether there is a negative genetic correlation between direct defences (root cardenolides) and indirect defences (emission of volatiles in the roots and nematode attraction), and between constitutive and inducible defences.4. Volatiles of roots were analysed using two distinct sampling methods. First, we collected emissions from living Asclepias syriaca roots by dynamic headspace sampling. This method showed that attacked A. syriaca plants emit five times higher levels of volatiles than control plants. Secondly, we used a solid phase micro-extraction (SPME) method to sample the full pool of volatiles in roots for genetic correlations of volatile biosynthesis.5. Field experiments showed that entomopathogenic nematodes prevent the loss of biomass to root herbivory. Additionally, suppression of root herbivores was mediated directly by cardenolides and indirectly by the attraction of nematodes. Genetic families of plants with high cardenolides benefited less from nematodes compared to low-cardenolide families, suggesting that direct and indirect defences may be redundant. Although constitutive and induced root defences traded off within each strategy (for both direct and indirect defence, cardenolides and VOCs, respectively), we found no trade-off between the two strategies.6. Synthesis. Constitutive expression and inducibility of defences may trade off because of resource limitation or because they are redundant. Direct and indirect defences do not trade off, likely because they may not share a limiting resource and because independently they may promote defence across the patchiness of herbivore attack and nematode presence in the field. Indeed, some redundancy in strategies may be necessary to increase effective defence, but for each strategy, an economy of deployment reduces overall costs.

Glutamine synthesis rate in the hyperammonaemic rat brain using simultaneous localized in vivo H-1 and N-15 MRS

Objectives: Glutamine synthetase is a critical step in the glutamate-glutamine cycle, the major mechanism of glutamate neurotransmission and is implicated in the mechanism of ammonia toxicity. 15N MRS is an alternative approach to 13C MRS in studying glutamate- glutamine metabolism. 15N MRS studies allow to measure an apparent glutamine synthesis rate (Vsyn) which reflects a combination of the glutamate- glutamine cycle activity (Vnt) and net glutamine accumulation. The net glutamine synthesis (Vsyn-Vnt) can be directly measured from 1H NMR. Therefore, the aim of this study was to perform in vivo localized 1H MRS interleaved with 15N MRS to directly measure the net glutamine synthesis rate and the apparent glutamine synthesis rate under 15N labeled ammonia infusion in the rat brain, respectively. Methods: 1H and 15N MRS data were acquired interleaved on a 9.4T system (Varian/Magnex Scientific) using 5 rats. 15NH4Cl solution was infused continuously into the femoral vein for up to 10 h (4.5 mmol/h/kg).1 The plasma ammonia concentration was increased to 0.95±0.08 mmol/L (Analox GM7 analyzer). 1H spectra were acquired and quantified as described previously.2 15N unlocalized and localized spectra were acquired using the sequence;3 and quantified using AMARES and an external reference method.4 The metabolic model used to analyze the total Gln and 5-15N labeled Gln time courses is shown on Figure 1A. Results: Glutamine concentration increased from 2.5±0.3 to 15±3.3 mmol/kg whereas the total glutamate concentrations remained unchanged (Figure 1B). The linear fit of the time-evolution of the total Gln from the 1H spectra gave the net synthesis flux (Vsyn-Vnt), which was 0.021± 0.006 mmol/min per g (Figure 1D). The 5-15N Gln peak (_271 ppm) was visible in the first and all subsequent scans, whereas the 2-15N Gln/Glu peak (_342 ppm) appeared after B1.5 h (Figure 1C). From the in vivo 5-15N Gln time course, Vsyn = 0.29±0.1 mmol/min per g and a plasma NH3 fractional enrichment of 71%±6% were calculated. Vnt was 0.26±0.1 mmol/min/g, obtained assuming a negligible Gln efflux.5 Vsyn and Vnt were within the range of 13C NMR measurements.6 Conclusion: The combination of 1H and 15N NMR allowed for the first time a direct and localized measurement of Vnt and apparent glutamine synthesis rate. Vnt is approximately one order of magnitude faster than the net glutamine accumulation.

The Network Company in Catalonia : ICT, Productivity, Competitiveness, Salaries and Performance in Catalonia's Companies. Research report (synthesis document)

Resum en anglès del projecte de recerca L'empresa xarxa a Catalunya. TIC, productivitat, competitivitat, salaris i beneficis a l'empresa catalana té com a objectiu principal constatar que la consolidació d'un nou model estratègic, organitzatiu i d'activitat empresarial, vinculat amb la inversió i l'ús de les TIC (o empresa xarxa), modifica substancialment els patrons de comportament dels resultats empresarials, en especial la productivitat, la competitivitat, les retribucions dels treballadors i el benefici. La contrastació empírica de les hipòtesis de treball l'hem feta per mitjà de les dades d'una enquesta a una mostra representativa de 2.038 empreses catalanes. Amb la perspectiva de l'impacte de la inversió i l'ús de les TIC no s'aprecia una relació directa entre els processos d'innovació digital i els resultats de l'activitat de l'empresa catalana. En aquest sentit, hem hagut de segmentar el teixit productiu català per a buscar les organitzacions en què el procés de coinnovació tecnològica digital i organitzativa és més present i en què la intensitat de l'ús del coneixement és un recurs molt freqüent per a poder copsar impactes rellevants en els principals resultats empresarials. Això és així perquè l'economia catalana, avui, presenta una estructura productiva dual.

The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

The Protein quality control system manages plant defence compound synthesis

Jasmonates are ubiquitous oxylipin-derived phytohormones that are essential in the regulation of many development, growth and defence processes. Across the plant kingdom, jasmonates act as elicitors of the production of bioactive secondarymetabolites that serve in defence against attackers. Knowledge of the conserved jasmonate perception and early signalling machineries is increasing, but the downstream mechanisms that regulate defence metabolism remain largely unknown. Herewe showthat, in the legumeMedicago truncatula, jasmonate recruits the endoplasmic-reticulum-associated degradation (ERAD)quality control system tomanagethe production of triterpene saponins, widespread bioactive compounds that share a biogenic origin with sterols. An ERAD-type RING membraneanchor E3 ubiquitin ligase is co-expressed with saponin synthesis enzymes to control the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the rate-limiting enzyme in the supply of the ubiquitous terpene precursor isopentenyl diphosphate. Thus, unrestrained bioactive saponin accumulationis prevented and plant development and integrity secured. This control apparatus is equivalent to the ERAD system that regulates sterol synthesis in yeasts and mammals but that uses distinct E3 ubiquitin ligases, of the HMGR degradation 1 (HRD1) type, to direct destruction of HMGR. Hence, the general principles for the management of sterol and triterpene saponin biosynthesis are conserved across eukaryotes but can be controlled by divergent regulatory cues.

Study of the incorporation and the anti-tumour efficacy of radio-iododeoxyuridine according to the cellular cycle and in presence of synthesis inhibitor of thymidine

Résumé La iododeoxyuridine (IdUrd), une fois marqué au 123I ou au 125I, est un agent potentiel pour des thérapies par rayonnements Auger. Cependant, des limitations restreignent son incorporation dans l'ADN. Afin d'augmenter celle-ci, différents groupes ont étudié la fluorodeoxyuridine (FdUrd), qui favorise l'incorporation d'analogue de la thymidine, sans toutefois parvenir à une toxicité associé plus importante. Dans notre approche, 3 lignées cellulaires de glioblastomes humains et une lignée de cancer ovarien ont été utilisées. Nous avons observé, 16 à 24 h après un court pré-traitement à la FdUrd, un fort pourcentage de cellules s'accumulant en phase S. Plus qu'une accumulation, c'était une synchronisation des cellules, celles-ci restant capables d'incorporer la radio-IdIrd et repartant dans le cycle cellulaire. De plus, ces cellules accumulées après un pré-traitement à la FdUrd étaient plus radio-sensibles. Après le même intervalle de 16 à 24 h suivant la FdUrd, les 4 lignées cellulaires ont incorporé des taux plus élevés de radio-IdUrd que sans ce prétraitement. Une corrélation temporelle entre l'accumulation des cellules en phase S et la forte incorporation de radio-IdUrd a ainsi été révélée 16 à 24 h après pré-traitement à la FdUrd. Les expériences de traitement par rayonnements Auger sur les cellules accumulées en phase S ont montré une augmentation significative de l'efficacité thérapeutique de 125I-IdUrd comparé aux cellules non prétraitées à la FdUrd. Une première estimation a permis de déterminer que 100 désintégrations de 125I par cellules étant nécessaires afin d'atteindre l'efficacité thérapeutique. De plus, p53 semble jouer un rôle dans l'induction directe de mort cellulaire après des traitements par rayonnements Auger, comme indiqué par les mesures par FACS d'apoptose et de nécrose 24 et 48 h après le traitement. Concernant les expériences in vivo, nous avons observé une incorporation marquée de la radio-IdUrd dans l'ADN après un pré-traitement à la FdUrd dans un model de carcinomatose ovarienne péritonéale. Une augmentation encore plus importante a été observée après injection intra-tumorale dans des transplants sous-cutanés de glioblastomes sur des souris nues. Ces modèles pourraient être utilisés pour de plus amples études de diffusion de radio-IdUrd et de thérapie par rayonnement Auger. En conclusion, ce travail montre une première application réussie de la FdUrd afin d'accroître l'efficacité de la radio-IdUrd par traitements aux rayonnements Auger. La synchronisation des cellules en phase S combinée avec la forte incorporation de radio-IdUrd dans l'ADN différées après un pré-traitement à la FdUrd ont montré le gain thérapeutique attendu in vitro. De plus, des études in vivo sont tout indiquées après les observations encourageantes d'incorporation de radio-IdUrd dans les models de transplants sous-cutanés de glioblastomes et de tumeurs péritonéales ovariennes. Summary Iododeoxyuridine (IdUrd), labelled with 123I or 125I, could be a potential Auger radiation therapy agent. However, limitations restrict its DNA incorporation in proliferating cells. Therefore, fluorodeoxyuridine (FdUrd), which favours incorporation of thymidine analogues, has been studied by different groups in order to increase radio-IdUrd DNA incorporation, however therapeutic efficacy increase could not be reached. In our approach, 3 human glioblastoma cell lines with different p53 expression and one ovarian cancer line were pre-treated with various FdUrd conditions. We observed a high percentage of cells accumulating in early S phase 16 to 24 h after a short and non-toxic FdUrd pre-treatment. More than an accumulation, this was a synchronization, cells remaining able to incorporate radio-IdUrd and re-entering the cell cycle. Furthermore, the S phase accumulated cells post FdUrd pre-treatment were more radiosensitive. After the same delay of 16 to 24 h post FdUrd pre-treatment, the 4 cell lines were incorporating higher rates of radio-IdUrd compared with untreated cells. A time correlation between S phase accumulation and high radio-IdUrd incorporation was therefore revealed 16 to 24 h post FdUrd pre-treatment. Auger radiation treatment experiments performed on S phase enriched cells showed a significant increase of killing efficacy of 125I-IdUrd compared with cells not pre-treated with FdUrd. A first estimation indicates further that about 100 125I decays were required to reach killing in the targeted cells. Moreover, p53 might play a role on the direct induction of cell death pathways after Auger radiation treatments, as indicated by differential apoptosis and necrosis induction measured by FACS 24 and 48 h after treatment initiation. Concerning in vivo results, we observed a marked DNA incorporation increase of radio-IdUrd after FdUrd pre-treatment in peritoneal carcinomatosis in SCID mice. Even higher incorporation increase was observed after intra-tumoural injection of radio-IdUrd in subcutaneous glioblastoma transplants in nude mice. These tumour models might be further useful for diffusion of radio-IdUrd and Auger radiation therapy studies. In conclusion, these data show a first successful application of thymidine synthesis inhibition able to increase the efficacy of radio-IdUrd Auger radiation treatment. The S phase synchronization combined with a high percentage DNA incorporation of radio-IdUrd delayed post FdUrd pre-treatment provided the expected therapeutic gain in vitro. Further in vivo studies are indicated after the observations of encouraging radio-IdUrd uptake experiments in glioblastoma subcutaneous xenografts and in an ovarian peritoneal carcinomatosis model.