[Use of nanoparticles as radiosensitizing agents in radiotherapy: State of play]. / Utilisation de nanoparticules comme agent radiosensibilisant en radiothérapie : où en est-on ?

Nanomedicine has undergone significant development since the 2000s and it is only very recently that two metallic nanoparticles have emerged in clinical trials. The mechanism of these radiosensitizing agents is based on the presence of atoms with a high atomic number (Z) allowing a higher dose deposition into the tumor during irradiation. The first nanoparticle used in humans is NBTXR3, composed of hafnium (Z=79), with intratumor injection for the treatment of sarcoma. Another gadolinium-based nanoparticle (Z=64), AGuIX, has been used for intravenous injection in the treatment of brain metastases. The preliminary results are promising in terms of feasibility, safety and efficacy, as evidenced by the significant number of ongoing clinical trials. The upcoming challenges for the development of nanoparticles will be the targeting of cancer cells, their biodistribution into the body, their eventual toxicity and their industrial production. In the coming years, modalities of administration and optimal combinations with radiotherapy should be defined in connection with fundamental research.

Spatial and temporal variation of dung beetle assemblages in a fragmented landscape at eastern humid Chaco.

The aims of this study were to characterize the fauna of dung beetles and analyze their spatial and temporal diversity in a cattle ranch in the province of Chaco. Seven surveys were conducted in three environmental units: a forest fragment, a cattle pasture, and an open grassland. The efficiency of the sampling was assessed with non-parametric richness estimators, and attributes of the assemblage were evaluated. The species composition and the abundance distribution in each of the environmental units studied were compared using rank-abundance curves. The indicator value of each species was measured with the IndVal method. The relationship between richness, abundance, and environmental variables (temperature, precipitation, and relative humidity) was calculated by multivariate multiple regression analysis. A total of 3,356 adult individuals belonging to 29 species of the subfamily Scarabaeinae and to five species of Aphodiinae were captured. Dichotomius nisus (Olivier), Trichillum externepunctatum (Preudhomme), Canthon podagricus (Harold), Onthophagus hirculus (Mannerheim), Pseudocanthon aff. perplexus, Ontherus sulcator (Fabricius), and Ataenius platensis (Blanchard) were the most abundant. Diversity, species richness, and abundance were highest in the forest fragment and in spring and summer captures. Between 94% and 97% of the species present in the entire landscape were recorded. According to the analysis of similarity, the composition of the assemblage was different among habitats. Eurysternus caribaeus (Herbst), Eurysternus aeneus (Génier), and O. sulcator were indicators of the forest. In the three units, the coprophagous species represented more than 60% of the total species number. The rainfall regime, the temperature, and the heterogeneous use of the environmental units influenced the structure of dung beetle assemblages.

The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy.

A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.

Enhancement of radiation effect by heavy elements.

The enhancement of radiobiological effects by heavy elements is reviewed. As an underlying mechanism, Auger effects have been stressed which can be induced via inner-shell photoabsorption or via excitation and/or ionization by secondary electrons. Latter channel of Auger induction expands the applicability of Auger enhancing phenomena to electron and hadron therapy. After discussion on the required characteristics for radiosensitizers, possibility of nanoparticles of Au or Pt is mentioned since they could be synthesized or modified as ideal radiosensitizers.

[Composition of the Araneae (Arachnida) fauna of the provincial Iberá Reserve, Corrientes, Argentina]. / Composición de la fauna de Araneae (arachnida) de la Reserva provincial Iberá, Corrientes, Argentina.

A survey of the spider community composition and diversity was carried out in grasslands and woods in three localities: Colonia Pellegrini, Paraje Galarza and Estancia Rinc6n (Iberá province Reserve). Pit fall traps, leaf litter sifting, foliage beating, hand collecting and sweep nets were used. Shannon's diversity index, evenness, Berger-Parker's dominance index, beta and gamma diversity were calculated, and a checklist of spider fauna was compiled. Species richness was estimated by Chao 1, Chao 2, first and second order Jack-knife. A total of 4,138 spiders grouped into 150 species from 33 families of Araneomorphae and two species from two families of Mygalomorphae were collected. Five species are new records for Argentina and eleven for Corrientes province. Araneidae was the most abundant family (39.8%), followed by Salticidae (10.9%), Anyphaenidae (7.9%), Tetragnathidae (7.4%), and Lycosidae (5.5%). The other families represented less than 5% of the total catch. The web-builder guild had the highest number of specimens and the highest richness index. The abundance, observed richness, Shannon diversity and evenness indexes were highest in Colonia Pellegrini woodland and Paraje Galarza grassland. Alpha diversity represented 89% of the gamma; the remaining 11% corresponded to beta diversity. According to the indexes, between 67% and 97% of the existing spider fauna was represented in the collected specimens from Iberá.

Composición de la fauna de Araneae (Arachnida) de la Reserva provincial Iberá, Corrientes, Argentina

Composition of the Araneae (Arachnida) fauna of the provincial Iberá Reserve, Corrientes, Argentina. A survey of the spider community composition and diversity was carried out in grasslands and woods in three localities: Colonia Pellegrini, Paraje Galarza and Estancia Rincón (iberá province Reserve). Pit fall traps, leaf litter sifting, foliage beating, hand collecting and sweep nets were used. Shannon’s diversity index, evenness, Berger-Parker’s dominance index, ß and diversity were calculated, and a checklist of spider fauna was compiled. Species richness was estimated by Chao 1, Chao 2, first and second order Jack-knife. A total of 4 138 spiders grouped into 150 species from 33 families of Araneomorphae and two species from two families of Mygalomorphae were collected. Five species are new records for Argentina and eleven for Corrientes province. Araneidae was the most abundant family (39.8%), followed by Salticidae (10.9%), Anyphaenidae (7.9%), Tetragnathidae (7.4%), and Lycosidae (5.5%). The other families represented less than 5% of the total catch. The web-builder guild had the highest number of specimens and the highest richness index. The abundance, observed richness, Shannon diversity and evenness indexes were highest in Colonia Pellegrini woodland and Paraje Galarza grassland. Alpha diversity represented 89% of the gamma; the remaining 11% corresponded to ß diversity. According to the indexes, between 67% and 97% of the existing spider fauna was represented in the collected specimens from iberá. Rev. Biol. Trop. 57 (1-2): 339-351. Epub 2009 June 30.

Se estudió la composición y diversidad de la comunidad de arañas de la Reserva provincial iberá, Corrientes, Argentina. Se realizaron capturas en bosque y pastizal en Colonia Pellegrini, Paraje Galarza y Estancia Rincón por medio de las técnicas de muestreo: trampas "pit-fall", tamizado, golpeteo de follaje, observación directa y red de arrastre. Las arañas se agruparon en gremios y se compiló un inventario. La similitud entre localidades y unidades ambientales se midió con el índice de Jaccard, y se calcularon los índices de diversidad de Shannon, equitabilidad, dominancia de Berger-Parker, y la diversidad beta y gamma. Para estimar la riqueza de especies se utilizó Chao 1, Chao 2, Jackknife 1 y 2. En total se recolectaron 4 138 arañas, se identificaron 33 familias y 150 especies de Araneomorphae, y dos familias y dos especies de Mygalomorphae. Cinco especies son nuevos registros para Argentina y 11 para la provincia de Corrientes. Araneidae fue la familia más abundante (39.8%), seguida por Salticidae (10.9%), Anyphaenidae (7.9%), Tetragnathidae (7.4%), Lycosidae (5.5%), y las restantes familias representaron menos del 5% de la captura total. El gremio de arañas tejedoras de telas orbiculares fue el de mayor abundancia y riqueza de especies. Entre las unidades ambientales, la mayor abundancia, riqueza y diversidad se verificó en el bosque de Colonia Pellegrini y en el pastizal de Paraje Galarza. La diversidad a fue alta, representó el 89% de la diversidad gamma, y la diversidad ß constituyó el 11% restante. Según los diferentes índices se capturó entre el 67% y el 97% de las especies que están presentes en la Reserva.

Role of surfactant on the proteolysis of aqueous bovine serum albumin.

Nonionic and ionic surfactants diminish the initial rate of proteolysis of aqueous bovine serum albumin (BSA) by subtilisin Carlsberg. Surfactants studied include: nonionic tetraethylene glycol monododecyl ether (C12E4); anionic sodium dodecyl sulfate (SDS), anionic sodium dodecylbenzenesulfonate (SDBS), and cationic dodecyltrimethylamonium bromide (DTAB). Kinetic data are obtained using fluorescence emission. Special attention is given to enzyme kinetic specificity determined by fitting initial-rate data to the Michaelis-Menten model. All surfactants reduce the rate of proteolysis, most strongly at concentrations near and above the critical micelle concentration (CMC). Circular dichroism (CD), tryptophan/tyrosine fluorescence spectra, and tryptophan fluorescence thermograms indicate that BSA partially unfolds at ionic surfactant concentrations near and above the CMC. Changes in BSA conformation are less apparent at ionic surfactant concentrations below the CMC and for the nonionic surfactant C12E4. Subtilisin Carlsberg activity against the polypeptide, succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, decreased due to enzyme-surfactant interaction. At the concentrations and time frames studied, there was no enzyme autolysis. Importantly, aqueous proteolysis rates are significantly reduced at high surfactant concentrations where protein-micellar-surfactant aggregates occur. To explain the negative effect of surfactant on subtilisin Carlsberg proteolytic activity against BSA, we propose that micelle/protein complexes hinder enzyme access.

Effects of the sporulation conditions on the lovastatin production by Aspergillus terreus.

The production of biomass and lovastatin by spore-initiated submerged fermentations of Aspergillus terreus ATCC 20542 was shown to depend on the age of the spores used for inoculation. Cultures started from older spores produced significantly higher titers of lovastatin. For example, the lovastatin titer increased by 52% when the spore age at inoculation rose from 9 to 16 days. The lovastatin titer for a spore age of 16 days was 186.5+/-20.1 mg L(-1). The time to sporulation on surface cultures was sensitive to the light exposure history of the fungus and the spore inoculation concentration levels. A light exposure level of 140 muE m(-2 )s(-1) and a spore concentration of 1,320 spore cm(-2) produced the greatest extent of sporulation within about 50 h of inoculation. Sporulation was slowed in the dark and with diluted inoculants. A rigorous analysis of the data of statistically designed experiments showed the above observations to be highly reproducible.

Pellet morphology, culture rheology and lovastatin production in cultures of Aspergillus terreus.

Pellet growth of Aspergillus terreus ATCC 20542 in submerged batch fermentations in stirred bioreactors was used to examine the effects of agitation (impeller tip speed u(t) of 1.01-2.71 ms(-1)) and aeration regimens (air or an oxygen-enriched mixture containing 80% oxygen and 20% nitrogen by volume) on the fungal pellet morphology, broth rheology and lovastatin production. The agitation speed and aeration methods used did not affect the biomass production profiles, but significantly influenced pellet morphology, broth rheology and the lovastatin titers. Pellets of approximately 1200 microm initial diameter were reduced to a final stable size of approximately 900 microm when the agitation intensity was >/=600 rpm (u(t)>/=2.03 ms(-1)). A stable pellet diameter of approximately 2500 microm could be attained in less intensely agitated cultures. These large fluffy pellets produced high lovastatin titers when aerated with oxygen-enriched gas but not with air. Much smaller pellets obtained under highly agitated conditions did not attain high lovastatin productivity even in an oxygen-enriched atmosphere. This suggests that both an upper limit on agitation intensity and a high level of dissolved oxygen are essential for attaining high titers of lovastatin. Pellet size in the bioreactor correlated equally well with the specific energy dissipation rate and the energy dissipation circulation function. The latter took into account the frequency of passage of the pellets through the high shear regions of the impellers. Pellets that gave high lovastatin titers produced highly shear thinning cultivation broths.

Lovastatin inhibits its own synthesis in Aspergillus terreus.

Lovastatin suppresses its own synthesis in the microfungus Aspergillus terreus. The inhibitory effect was documented by spiking identical batch cultures with pure lovastatin (0, 50, 100 and 250 mg/l) 24 h after initiation from spores.

Infestacion domestica por Triatoma infestans y prevalencia de seropositivos al Trypanosoma cruzi en un area rural del nordeste argentino / Domestic infestation by Triatoma infestans and prevalence of seropositives to Trypanosoma cruzi in a rural population of the Northeast of Argentina

An epidemiological study was carried out from April 1991 to December 1993 to obtain a general view of T. cruzi domestic transmission in rural areas of San Miguei Department, Corrientes. From 100 analyzed households, 50.0 per cent was infested by T infestans (Klug, 1834) and 1.0 per cent by T. sordida (Stal, 1859). Domiciliary colonization by T. sordida is reported for first time in Corrientes province. T. cruzi infection of T. infestans was 23.1 per cent. Indirect hemagglutination and indirect immunofluorescence antibody tests were used for detection of anti T. cruzi antibodies in 388 human sera, 23.4 per cent showed serological reactivity. An important high rate (12.9 per cent) was observed in the age group of higher transmission risk. Seropositives percentages increased with age and reached 50.0 per cent in 31-40 years old group. Domestic infestation by T. infestans, seropositive human prevalence to T. cruzi and householders precarious life conditions prove that this endemic disease is still a problem in the studied area.

[Domestic infestation by Triatoma infestans and prevalence of Trypanosoma cruzi seropositives in a rural area of the Argentinian northeast]. / Infestacion domestica por Triatoma infestans y prevalencia de seropositivos al Trypanosoma cruzi en un area rural del nordeste argentino.

An epidemiological study was carried out from April 1991 to December 1993 to obtain a general view of T. cruzi domestic transmission in rural areas of San Miguei Department, Corrientes. From 100 analyzed households, 50.0% was infested by T infestans (Klug, 1834) and 1.0% by T. sordida (Stal, 1859). Domiciliary colonization by T. sordida is reported for first time in Corrientes province. T. cruzi infection of T. infestans was 23.1%. Indirect hemagglutination and indirect immunofluorescence antibody tests were used for detection of anti T. cruzi antibodies in 388 human sera, 23.4% showed serological reactivity. An important high rate (12.9%) was observed in the age group of higher transmission risk. Seropositives percentages increased with age and reached 50.0% in 31-40 years old group. Domestic infestation by T. infestans, seropositive human prevalence to T. cruzi and householders precarious life conditions prove that this endemic disease is still a problem in the studied area.

[Population statistics of Triatoma sordida Stäl 1859 (Hemiptera:Reduviidae) in experimental conditions]. / Estadísticos poblacionales de Triatoma sordida Stäl 1859 (Hemiptera:Reduviidae) en condiciones experimentales.

Four cohorts of 100 Triatoma sordida eggs were reared under standard laboratory conditions (28 degrees C, 63% R.H.) and fed weekly on hens during 40 minutes. The numbers of dead insects, moults and eggs laid were recorded weekly. A constant survival value was observed without any important peaks in the four cohorts. Life expectancy was 37.4 weeks for males and 36.8 weeks for females. The average generation time was 61.7 weeks. The average net reproduction rate suggests that this population would increase 143.2 times during each generation. The average intrinsic rate of natural increase was 0.082 per individual per week. The highest reproductive value was observed 3 weeks after entering the adult stage. The age structure, assuming stable age distribution, would be 32% eggs, 26% of first instar nymphs, 19% of second instar nymphs, 13% of third instar nymphs, 6% of fourth instar nymphs, 3% of fifth instar nymphs and 1% of adults. Our results suggest that this species behaves as a k-strategist under experimental conditions.

[Population interactions between Triatoma infestans and Triatoma sordida]. / Interacción entre poblaciones de Triatoma infestans y Triatoma sordida.

Populations of T. infestans and T. sordida were studied between September 1988 and April 1989 with a view to discovering if any kind of interaction took place between them while they lives together in the same experimental unit and exploited the same food resource (chicken). The initial age structure for each species was: 27 N1, 7 N2, 11 N3, 3 N4, 8 N5, 4 males and 10 females. The population dynamics nutritional status, predation and gregarious behavior were estimated by means of a monthly census. The colonizing success of T. infestans was greater than that of T. sordida in view of the values obtained: fecundity (146 eggs/female), longevity (157.8 days) and mortality (39.4) compared with the values recorded for T. sordida: 118 eggs/female, 81.1 days and 54.0% respectively. The population growth of T. insfestans followed an exponential model, with a high nymphal recruitment rate, while the T. sordida population was early extinguished. In general, the average weight of T. infestans remained close to the initial values while that of T. sordida declined. Gregarious groups were formed principally in the inferior sector of wall 1 (near the host) with a higher aggregation in T. infestans. These results make it possible to propose the hypothesis of the competitive superiority of T. infestans.

[Triatoma infestation in the San Luis del Palmar Department of Corrientes Province, Argentina]. / Triatomismo del Departamento San Luis del Palmar de la provincia de Corrientes, Argentina.

The purpose of this study was to determine domestic and peridomestic infestation of Triatominae, Trypanosoma cruzi infection rates, and the prevalence of human seroreactivity in rural areas of the Department of San Luis del Palmar, Corrientes, Argentina (Fig. 1). The study took place from April 1986 to May 1989. The Department of San Luis del Palmar covers an area of 2551 km2 and is part of the Neotropical biogeographic region, Chacoan Dominion and Province. The climate is of the subhumid type. The mean annual temperature is 21.6 degrees C. Some localities were chosen because of the presence of triatominae. Households were carefully examined and classified according to their building materials. A 0.2% solution of tetrametrine was sprayed in all possible hiding places to dislodge bugs, which were collected by capture/hour/man methods. A survey to determine the socioeconomical, sanitary, and cultural conditions of house-dwellers was carried out. The same method was used to examine peridomiciles and total demolition was carried out in the positive ones. Fecal examination was carried out to verify the presence of T. cruzi in collected insects and observed at 400X. Human blood was obtained through venipuncture. The serum was kept in a freezer until examined. Serologic studies included indirect hemagglutination test (IHAT) and indirect immunofluorescence antibody test (IFAT). Positive titer for IHAT and IFAT was 1/64. Seroreactives were those that had two positive assays. The whole data obtained was analyzed by chi 2 tests. From one hundred households studied, 80% belonged to huts and 20% to houses. Mud walls were predominant in huts while brick walls were predominant in houses.(ABSTRACT TRUNCATED AT 250 WORDS)

Triatomismo del Departamento San Luis del Palmar de la provincia de Corrientes, Argentina. / [Triatoma infestation in the San Luis del Palmar Department of Corrientes Province, Argentina]

The purpose of this study was to determine domestic and peridomestic infestation of Triatominae, Trypanosoma cruzi infection rates, and the prevalence of human seroreactivity in rural areas of the Department of San Luis del Palmar, Corrientes, Argentina (Fig. 1). The study took place from April 1986 to May 1989. The Department of San Luis del Palmar covers an area of 2551 km2 and is part of the Neotropical biogeographic region, Chacoan Dominion and Province. The climate is of the subhumid type. The mean annual temperature is 21.6 degrees C. Some localities were chosen because of the presence of triatominae. Households were carefully examined and classified according to their building materials. A 0.2

solution of tetrametrine was sprayed in all possible hiding places to dislodge bugs, which were collected by capture/hour/man methods. A survey to determine the socioeconomical, sanitary, and cultural conditions of house-dwellers was carried out. The same method was used to examine peridomiciles and total demolition was carried out in the positive ones. Fecal examination was carried out to verify the presence of T. cruzi in collected insects and observed at 400X. Human blood was obtained through venipuncture. The serum was kept in a freezer until examined. Serologic studies included indirect hemagglutination test (IHAT) and indirect immunofluorescence antibody test (IFAT). Positive titer for IHAT and IFAT was 1/64. Seroreactives were those that had two positive assays. The whole data obtained was analyzed by chi 2 tests. From one hundred households studied, 80

belonged to huts and 20

to houses. Mud walls were predominant in huts while brick walls were predominant in houses.(ABSTRACT TRUNCATED AT 250 WORDS)

Triatomismo del Departamento San Luis del Palmar de la provincia de Corrientes, Argentina. / [Triatoma infestation in the San Luis del Palmar Department of Corrientes Province, Argentina]

The purpose of this study was to determine domestic and peridomestic infestation of Triatominae, Trypanosoma cruzi infection rates, and the prevalence of human seroreactivity in rural areas of the Department of San Luis del Palmar, Corrientes, Argentina (Fig. 1). The study took place from April 1986 to May 1989. The Department of San Luis del Palmar covers an area of 2551 km2 and is part of the Neotropical biogeographic region, Chacoan Dominion and Province. The climate is of the subhumid type. The mean annual temperature is 21.6 degrees C. Some localities were chosen because of the presence of triatominae. Households were carefully examined and classified according to their building materials. A 0.2

solution of tetrametrine was sprayed in all possible hiding places to dislodge bugs, which were collected by capture/hour/man methods. A survey to determine the socioeconomical, sanitary, and cultural conditions of house-dwellers was carried out. The same method was used to examine peridomiciles and total demolition was carried out in the positive ones. Fecal examination was carried out to verify the presence of T. cruzi in collected insects and observed at 400X. Human blood was obtained through venipuncture. The serum was kept in a freezer until examined. Serologic studies included indirect hemagglutination test (IHAT) and indirect immunofluorescence antibody test (IFAT). Positive titer for IHAT and IFAT was 1/64. Seroreactives were those that had two positive assays. The whole data obtained was analyzed by chi 2 tests. From one hundred households studied, 80

belonged to huts and 20

to houses. Mud walls were predominant in huts while brick walls were predominant in houses.(ABSTRACT TRUNCATED AT 250 WORDS)