Global survey of dioxin- and thyroid hormone-like activities in consumer products and toys.

BACKGROUND: Children and consumers are exposed to increasingly complex mixtures of known and as-yet-unknown toxic chemicals from toys and products. However traditional chemical analysis methods only evaluate a small number of chemicals at a time thereby restricting consumer awareness of the full range of potentially harmful chemicals in products. METHODS: We used high-throughput effect-based non-animal methods to investigate exposures to complex chemical mixtures of several kinds of brominated flame retardants (BFRs) for their dioxin- and thyroid hormone-like activities in various kinds of consumer products and toys from 26 different countries, on four continents (Africa, America, Asia and Europe) in combination with chemical analysis of various polybrominated flame retardants (BFRs) and their impurities (such as polyhalogenated PCDD/Fs and PBDD/Fs). RESULTS: We found high levels of polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) in toys and now, for the first time, also in consumer products that are manufactured from black plastics containing certain brominated flame retardants (BFRs). The presence of PBDD/PBDFs as well as other BFRs in various black plastic materials from additional countries as well as additional kinds of consumer products as confirmed by effect-based in vitro reporter gene DR CALUX and TTR-TRß CALUX assays as well as congener-specific chemical analysis. We compared total Toxicity Equivalent (TEQ) levels of PBDD/F-TEQs analysed by chemical analysis to by CALUX bioassay measured Biological equivalence (BEQ) concentrations (for further info see at ISO 23196, ISO, 2022). In the case of TBBPA, both chemical and TTR-TRß CALUX analysis measure direct the amount of TBBPA. Finally, the daily ingestion of 2,3,7,8-TCDD equivalents from PBDD/Fs-contaminated plastic toys by child mouthing habits have been related to our earlier study (Budin et al., 2020). CONCLUSIONS: Interaction of children with such contaminated plastics may significantly contribute to the daily uptake of dioxin- and thyroid hormone transport disrupting-like compounds. Effect-based bioassays for dioxin- and thyroid hormone-like activities are relevant to pick-out such complex mixtures of known and yet unknown (and therefore not regulated) substances for safer and more sustainable plastics. Low POPs Content Levels and other mechanisms set under the Basel and Stockholm Conventions are set far too high to prevent a significant flow of BFRs and PBDD/Fs into consumer products.

A comprehensive dataset of microRNA misexpression phenotypes in the Drosophila eye.

microRNAs (miRNAs) are a broad class of ~22 nucleotide regulatory RNA, which collectively have broad effects on the transcriptome and are involved in diverse biology, from development and adult physiology, and from homeostasis to disease and pathology. We investigated the effects of systematically expressing microRNAs (miRNAs) during the development of the Drosophila compound eye using the GMR-Gal4 driver. The objective was to determine what fraction of miRNAs were capable of inducing aberrant morphology that was easily and reproducibly scored by visual inspection under a dissecting microscope. We assayed multiple independent insertions of 166 miRNA transgenes (536 lines), comprising solo miRNAs, miRNA operons and individual constituent miRNAs from operons. We find a substantial number reproducibly altered normal eye development and a smaller number induced lethality in most or all progeny. We provide the comprehensive results of this screen, documenting numerous miRNA transgenes that interfered with normal eye development when activated using GMR-Gal4. These data can be mined by the Drosophila community to query the in vivo effects of any individual miRNA of interest in the eye, as well as utilized as a foundation for more complex genetic perturbations that involve miRNA misexpression in the eye.

A comprehensive in vivo screen for anti-apoptotic miRNAs indicates broad capacities for oncogenic synergy.

microRNAs (miRNAs) are ~21-22 nucleotide (nt) RNAs that mediate broad post-transcriptional regulatory networks. However, genetic analyses have shown that the phenotypic consequences of deleting individual miRNAs are generally far less overt compared to their misexpression. This suggests that miRNA deregulation may have broader phenotypic impacts during disease situations. We explored this concept in the Drosophila eye, by screening for miRNAs whose misexpression could modify the activity of pro-apoptotic factors. Via unbiased and comprehensive in vivo phenotypic assays, we identify an unexpectedly large set of miRNA hits that can suppress the action of pro-apoptotic genes hid and grim. We utilize secondary assays to validate that a subset of these miRNAs can inhibit irradiation-induced cell death. Since cancer cells might seek to evade apoptosis pathways, we modeled this situation by asking whether activation of anti-apoptotic miRNAs could serve as "second hits". Indeed, while clones of the lethal giant larvae (lgl) tumor suppressor are normally eliminated during larval development, we find that diverse anti-apoptotic miRNAs mediate the survival of lgl mutant clones in third instar larvae. Notably, while certain anti-apoptotic miRNAs can target apoptotic factors, most of our screen hits lack obvious targets in the core apoptosis machinery. These data highlight how a genetic approach can reveal distinct and powerful activities of miRNAs in vivo, including unexpected functional synergies during disease or cancer-relevant settings.

Characterization of a TUTase/RNase complex required for Drosophila gametogenesis.

Post-transcriptional regulatory strategies that involve coupling between terminal uridyltransferase (TUTase) and exoribonuclease enzymes have recently been characterized in diverse species. Of note, the 3' exoribonuclease Dis3L2 has received substantial attention as a factor that metabolizes uridylated substrates in contexts such as general mRNA degradation, turnover of specific miRNAs, and quality control of noncoding RNAs. To date, most studies of Dis3L2 have focused on fungi and mammalian cells. Here, we introduce Drosophila as a system that permits analysis of molecular mechanisms as well as the ability to interrogate organismal phenotypes. We started with a structure-function analysis of the Drosophila TUTase Tailor, which we recently identified to inhibit biogenesis of splicing-derived miRNA hairpins. Next, we show that Tailor/Dis3L2 form a complex via N-terminal domains in the respective proteins that are distinct from their catalytic domains. In vitro, Dis3L2 has nuclease activity, but substrate oligouridylation by Tailor stimulates their degradation by Dis3L2, especially for structured substrates. We analyzed mutants of Tailor and Dis3L2, which are viable and lack overt morphological defects. Instead, these mutants exhibit defects in female and male fertility, implying specific requirements in the germline. Dis3L2 defects are more severe than Tailor, and their requirements appear stronger in males than in females. In particular, loss of Dis3L2 completely blocks productive spermatogenesis, causing male sterility. RNA-seq analysis from single- and double-mutant testes reveals aberrant gene expression programs and suggests that noncoding RNAs may be preferentially affected by Dis3L2. Overall, our studies of a new tailing/trimming complex reveal unexpectedly specific requirements during gametogenesis.

An ultrasonic orthopaedic surgical device based on a cymbal transducer.

An ultrasonic orthopaedic surgical device is presented, where the ultrasonic actuation relies on a modification of the classical cymbal transducer. All current devices consist of a Langevin ultrasonic transducer with a tuned cutting blade attached, where resonance is required to provide sufficient vibrational amplitude to cut bone. However, this requirement restricts the geometry and offers little opportunity to propose miniaturised devices or complex blades. The class V flextensional cymbal transducer is proposed here as the basis for a new design, where the cymbal delivers the required vibrational amplitude, and the design of the attached cutting insert can be tailored for the required cut. Consequently, the device can be optimised to deliver an accurate and precise cutting capability. A prototype device is presented, based on the cymbal configuration and designed to operate at 25.5kHz with a displacement amplitude of 30µm at 300V. Measurements of vibrational and impedance responses elucidate the mechanical and electrical characteristics of the device. Subsequent cutting tests on rat femur demonstrate device performance consistent with a commercial Langevin-based ultrasonic device and show that cutting is achieved using less electrical power and a lower piezoceramic volume. Histological analysis exhibits a higher proportion of live cells in the region around the cut site for the cymbal device than for a powered sagittal or a manual saw, demonstrating the potential for the ultrasonic device to result in faster healing.

A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs.

Although the impact of microRNAs (miRNAs) in development and disease is well established, understanding the function of individual miRNAs remains challenging. Development of competitive inhibitor molecules such as miRNA sponges has allowed the community to address individual miRNA function in vivo. However, the application of these loss-of-function strategies has been limited. Here we offer a comprehensive library of 141 conditional miRNA sponges targeting well-conserved miRNAs in Drosophila. Ubiquitous miRNA sponge delivery and consequent systemic miRNA inhibition uncovers a relatively small number of miRNA families underlying viability and gross morphogenesis, with false discovery rates in the 4-8% range. In contrast, tissue-specific silencing of muscle-enriched miRNAs reveals a surprisingly large number of novel miRNA contributions to the maintenance of adult indirect flight muscle structure and function. A strong correlation between miRNA abundance and physiological relevance is not observed, underscoring the importance of unbiased screens when assessing the contributions of miRNAs to complex biological processes.

Adaptive regulation of testis gene expression and control of male fertility by the Drosophila hairpin RNA pathway. [Corrected].

Although endogenous siRNAs (endo-siRNAs) have been described in many species, still little is known about their endogenous utility. Here, we show that Drosophila hairpin RNAs (hpRNAs) generate an endo-siRNA class with predominant expression in testes. Although hpRNAs are universally recently evolved, we identify highly complementary protein-coding targets for all hpRNAs. Importantly, we find broad evidence for evolutionary divergences that preferentially maintain compensatory pairing between hpRNAs and targets, serving as first evidence for adaptive selection for siRNA-mediated target regulation in metazoans. We demonstrate organismal impact of hpRNA activity, since knockout of hpRNA1 derepresses its target ATP synthase-ß in testes and compromises spermatogenesis and male fertility. Moreover, we reveal surprising male-specific impact of RNAi factors on germ cell development and fertility, consistent with testis-directed function of the hpRNA pathway. Finally, the collected hpRNA loci chronicle an evolutionary timeline that reflects their origins from prospective target genes, mirroring a strategy described for plant miRNAs.

Homeotic function of Drosophila Bithorax-complex miRNAs mediates fertility by restricting multiple Hox genes and TALE cofactors in the CNS.

The Drosophila Bithorax complex (BX-C) Hox cluster contains a bidirectionally transcribed miRNA locus, and a deletion mutant (Δmir) lays no eggs and is completely sterile. We show these miRNAs are expressed and active in distinct spatial registers along the anterior-posterior axis in the CNS. Δmir larvae derepress a network of direct homeobox gene targets in the posterior ventral nerve cord (VNC), including BX-C genes and their TALE cofactors. These are phenotypically critical targets, because sterility of Δmir mutants was substantially rescued by heterozygosity of these genes. The posterior VNC contains Ilp7+ oviduct motoneurons, whose innervation and morphology are defective in Δmir females, and substantially rescued by heterozygosity of Δmir targets, especially within the BX-C. Collectively, we reveal (1) critical roles for Hox miRNAs that determine segment-specific expression of homeotic genes, which are not masked by transcriptional regulation; and (2) that BX-C miRNAs are essential for neural patterning and reproductive behavior.

Nanotecnología: gestión y reglamentación de riesgos para la salud y medio ambiente en América Latina y el Caribe / Nanotechnology: risk management and regulation for health and environment in Latin America and in the Caribbean

Este artículo analiza la discusión sobre los riesgos de las nanopartículas manufacturadas llevada a cabo en las reuniones regionales de América Latina y el Caribe del SAICM (Strategic Approach to International Chemicals Management/Enfoque Estratégico para la Gestión de Productos Químicos a Nivel Internacional). Contextualiza esta discusión con un panorama del desarrollo de las nanotecnologías en la región y de las evidencias científicas disponibles sobre riesgos de las nanotecnologías. Propone un abordaje para identificar a los actores que deben participar en la discusión y gestión del riesgo basado en el ciclo de vida de las nanopartículas. El artículo propone, además, algunas condiciones necesarias para incentivar un desarrollo responsable de las nanotecnologías desde ámbitos como el SAICM, y trae a la discusión los ocho puntos relevados por más de cien organizaciones ambientalistas y de trabajadores acerca de la supervisión de las nanotecnologías y los nanomateriales.

This article addresses the discussion concerning the risks posed by manufactured nanoparticles held during regional meetings in Latin America and the Caribbean by the SAICM (Strategic Approach to International Chemicals Management/Enfoque Estratégico para la Gestión de Productos Químicos a Nivel Internacional). It contextualizes this discussion by overviewing the development of nanotechnology in the region and the scientific evidence available on the risks brought about by nanotechnology. It proposes an approach to identify the players that should be involved in the discussion and in risk management based on the nanoparticles' life cycle. The article also proposes a few of the conditions needed to encourage the responsible development of nanotechnology from sectors such as the SAICM, and brings into the discussion the eight relevant items from over a hundred environmental organizations and workers under the supervision of nanotechnologies and nanomaterials.

A genome-wide transgenic resource for conditional expression of Drosophila microRNAs.

microRNAs (miRNAs) are endogenous short RNAs that mediate vast networks of post-transcriptional gene regulation. Although computational searches and experimental profiling provide evidence for hundreds of functional targets for individual miRNAs, such data rarely provide clear insight into the phenotypic consequences of manipulating miRNAs in vivo. We describe a genome-wide collection of 165 Drosophila miRNA transgenes and find that a majority induced specific developmental defects, including phenocopies of mutants in myriad cell-signaling and patterning genes. Such connections allowed us to validate several likely targets for miRNA-induced phenotypes. Importantly, few of these phenotypes could be predicted from computationally predicted target lists, thus highlighting the value of whole-animal readouts of miRNA activities. Finally, we provide an example of the relevance of these data to miRNA loss-of-function conditions. Whereas misexpression of several K box miRNAs inhibited Notch pathway activity, reciprocal genetic interaction tests with miRNA sponges demonstrated endogenous roles of the K box miRNA family in restricting Notch signaling. In summary, we provide extensive evidence that misexpression of individual miRNAs often induces specific mutant phenotypes that can guide their functional study. By extension, these data suggest that the deregulation of individual miRNAs in other animals may frequently yield relatively specific phenotypes during disease conditions.

A Drosophila genetic screen yields allelic series of core microRNA biogenesis factors and reveals post-developmental roles for microRNAs.

Canonical animal microRNAs (miRNAs) are ∼22-nt regulatory RNAs generated by stepwise cleavage of primary hairpin transcripts by the Drosha and Dicer RNase III enzymes. We performed a genetic screen using an miRNA-repressed reporter in the Drosophila eye and recovered the first reported alleles of fly drosha, an allelic series of its dsRBD partner pasha, and novel alleles of dicer-1. Analysis of drosha mutants provided direct confirmation that mirtrons are independent of this nuclease, as inferred earlier from pasha knockouts. We further used these mutants to demonstrate in vivo cross-regulation of Drosha and Pasha in the intact animal, confirming remarkable conservation of a homeostatic mechanism that aligns their respective levels. Although the loss of core miRNA pathway components is universally lethal in animals, we unexpectedly recovered hypomorphic alleles that gave adult escapers with overtly normal development. However, the mutant photoreceptor neurons exhibited reduced synaptic transmission, without accompanying defects in neuronal development or maintenance. These findings indicate that synaptic function is especially sensitive to optimal miRNA pathway function. These allelic series of miRNA pathway mutants should find broad usage in studies of miRNA biogenesis and biology in the Drosophila system.

Insensitive is a corepressor for Suppressor of Hairless and regulates Notch signalling during neural development.

The Notch intracellular domain functions as a co-activator for the DNA-binding protein Suppressor of Hairless (Su(H)) to mediate myriad cell fate decisions. Notch pathway activity is balanced by transcriptional repression, mediated by Su(H) in concert with its Drosophila corepressor Hairless. We demonstrate that the Drosophila neural BEN-solo protein Insensitive (Insv) is a nuclear factor that inhibits Notch signalling during multiple peripheral nervous system cell fate decisions. Endogenous Insv was particularly critical when repressor activity of Su(H) was compromised. Reciprocally, ectopic Insv generated several Notch loss-of-function phenotypes, repressed most Notch targets in the E(spl)-C, and opposed Notch-mediated activation of an E(spl)m3-luc reporter. A direct role for Insv in transcriptional repression was indicated by binding of Insv to Su(H), and by strong chromatin immunoprecipitation of endogenous Insv to most E(spl)-C loci. Strikingly, ectopic Insv fully rescued sensory organ precursors in Hairless null clones, indicating that Insv can antagonize Notch independently of Hairless. These data shed first light on the in vivo function for a BEN-solo protein as an Su(H) corepressor in the Notch pathway regulating neural development.

miR-9a prevents apoptosis during wing development by repressing Drosophila LIM-only.

Loss of Drosophila mir-9a induces a subtle increase in sensory bristles, but a substantial loss of wing tissue. Here, we establish that the latter phenotype is largely due to ectopic apoptosis in the dorsal wing primordium, and we could rescue wing development in the absence of this microRNA by dorsal-specific inhibition of apoptosis. Such apoptosis was a consequence of de-repressing Drosophila LIM-only (dLMO), which encodes a transcriptional regulator of wing and neural development. We observed cell-autonomous elevation of endogenous dLMO and a GFP-dLMO 3'UTR sensor in mir-9a mutant wing clones, and heterozygosity for dLMO rescued the apoptosis and wing defects of mir-9a mutants. We also provide evidence that dLMO, in addition to senseless, contributes to the bristle defects of the mir-9a mutant. Unexpectedly, the upregulation of dLMO, loss of Cut, and adult wing margin defects seen with mir-9a mutant clones were not recapitulated by clonal loss of the miRNA biogenesis factors Dicer-1 or Pasha, even though these mutant conditions similarly de-repressed miR-9a and dLMO sensor transgenes. Therefore, the failure to observe a phenotype upon conditional knockout of a miRNA processing factor does not reliably indicate the lack of critical roles of miRNAs in a given setting.

Frequent unanticipated alleles of lethal giant larvae in Drosophila second chromosome stocks.

Forty years ago, a high frequency of lethal giant larvae (lgl) alleles in wild populations of Drosophila melanogaster was reported. This locus has been intensively studied for its roles in epithelial polarity, asymmetric neural divisions, and restriction of tissue proliferation. Here, we identify a high frequency of lgl alleles in the Bloomington second chromosome deficiency kit and the University of California at Los Angeles Bruinfly FRT40A-lethal P collection. These unrecognized aberrations confound the use of these workhorse collections for phenotypic screening or genetic mapping. In addition, we determined that independent alleles of insensitive, reported to affect asymmetric cell divisions during sensory organ development, carry lgl deletions that are responsible for the observed phenotypes. Taken together, these results encourage the routine testing of second chromosome stocks for second-site alleles of lgl.

Genetic and epigenetic mechanisms regulating hedgehog expression in the Drosophila wing.

Stable subdivision of Drosophila limbs into Anterior (A) and Posterior (P) compartments is a consequence of asymmetric signaling by Hedgehog (Hh) from P to A cells. The activity of the homeodomain protein Engrailed (En) in P cells has been reported to help to generate this asymmetry by inducing the expression of hedgehog and simultaneously repressing the expression of the essential downstream component of the Hh signaling pathway Cubitus interruptus (Ci). In A cells, Ci has a major role in the repression of hh. Here we have revised the genetic and epigenetic mechanisms involved in the regulation of hh in the P compartment. First, we present evidence that hh expression in P cells is a consequence of the repression of ci by the activity of En. Thus, in the absence of Ci and En activities, cells do express hh. We also present data supporting the maintenance of hh expression in P cells through epigenetic mechanisms, and a permissive role of Notch signaling in this process. Notch and Trithorax (TrxG) group of proteins exert their action through a previously defined hh Polycomb Responsive Element (PRE).

A gain-of-function suppressor screen for genes involved in dorsal-ventral boundary formation in the Drosophila wing.

The Drosophila wing primordium is subdivided into a dorsal (D) and a ventral (V) compartment by the activity of the LIM-homeodomain protein Apterous in D cells. Cell interactions between D and V cells induce the activation of Notch at the DV boundary. Notch is required for the maintenance of the compartment boundary and the growth of the wing primordium. Beadex, a gain-of-function allele of dLMO, results in increased levels of dLMO protein, which interferes with the activity of Apterous and results in defects in DV axis formation. We performed a gain-of-function enhancer-promoter (EP) screen to search for suppressors of Beadex when overexpressed in D cells. We identified 53 lines corresponding to 35 genes. Loci encoding for micro-RNAs and proteins involved in chromatin organization, transcriptional control, and vesicle trafficking were characterized in the context of dLMO activity and DV boundary formation. Our results indicate that a gain-of-function genetic screen in a sensitized background, as opposed to classical loss-of-function-based screenings, is a very efficient way to identify redundant genes involved in a developmental process.

Hedgehog restricts its expression domain in the Drosophila wing.

The stable subdivision of Drosophila limbs into anterior and posterior compartments is a consequence of asymmetrical signalling by Hedgehog (Hh), from the posterior to anterior cells. The activity of the homeodomain protein Engrailed in posterior cells helps to generate this asymmetry by inducing the expression of Hh in the posterior compartment and, at the same time, repressing the expression of the essential downstream component Cubitus interruptus (Ci). Therefore, only anterior cells that receive the Hh signal across the compartment boundary will respond by stabilizing Ci. Here, we describe a new molecular mechanism that helps to maintain the Hh-expressing and Hh-responding cells in different non-overlapping cell populations. Master of thickveins (mtv) - a target of Hh activity encoding a nuclear zinc-finger protein - is required to repress hh expression in anterior cells. Mtv exerts this action in a protein complex with Groucho (Gro) - the founding member of a superfamily of transcriptional corepressors that are conserved throughout eukaryotes. Therefore, Hh restricts its own expression domain in the Drosophila wing through the activity of Mtv and Gro.

The Drosophila RYBP gene functions as a Polycomb-dependent transcriptional repressor.

The Polycomb and trithorax groups of genes control the maintenance of homeotic gene expression in a variety of organisms. A putative participant in the regulation of this process is the murine RYBP (Ring and YY1 Binding Protein) gene. Sequence comparison between different species has identified the homologous gene in Drosophila, the dRYBP gene. We have investigated whether dRYBP participates in the mechanisms of silencing of homeotic genes expression. We first studied its expression by RNA in situ hybridisation and detected dRYBP expression ubiquitously and throughout development. Moreover, we generated a polyclonal anti-dRYBP antibody that recognises the dRYBP protein. dRYBP protein is nuclear and expressed maternally and ubiquitously throughout development. To study the transcriptional activity of dRYBP, we generated a fusion protein containing the entire dRYBP protein and the GAL4 DNA binding domain. This fusion protein functions, in vivo, as a transcriptional repressor throughout development. Importantly, this repression is dependent on the function of the Polycomb group genes. Furthermore, using the GAL4/UAS system, we have over expressed dRYBP in the haltere and the wing imaginal discs. In the haltere discs, high levels of dRYBP repress the expression of the homeotic Ultrabithorax gene. This repression is Polycomb dependent. In the wing discs, dRYBP over expression produces a variety of phenotypes suggesting the overall miss regulation of the many putative genes affected by high levels of dRYBP. Taking together, our results indicate that dRYBP is able to interact with PcG proteins to repress transcription suggesting that the dRYBP gene might belong to the Polycomb group of genes in Drosophila.

Function of the Trithorax-like gene during Drosophila development.

Maintenance of homeotic gene expression during Drosophila development relies on the Polycomb and the trithorax groups of genes. Classically, the Polycomb proteins act as repressors of homeotic gene function, whereas trithorax proteins function as activators. However, recent investigation has indicated that some of these maintenance genes may act both as repressors and activators. One of those is the Drosophila Trithorax-like gene that codes for the GAGA factor. To investigate its dual activator/repressor role, we have studied the function of the Trithorax-like throughout Drosophila development. Embryos lacking both the maternal and the zygotic Trithorax-like function do not develop suggesting that Trithorax-like might be required in oogenesis. Homozygous Trithorax-like null mutant embryos show reduced expression levels of some of the homeotic proteins. Trithorax-like mutant larval clones, however, do not show phenotypes indicative of either activation or repression of homeotic gene function. These results suggest that Trithorax-like is required during embryogenesis but not throughout larval development for the regulation of homeotic gene expression. Moreover, this temporal requirement seems also to regulate MCP-mediated silencing. Finally, lack of Trithorax-like function modulates the gain of function phenotypes caused by over-expression of homeotic genes. To explain Trithorax-like gene function, we propose a model where very early in development, GAGA factor probably establishes a chromatin ground state for transcription. The differential "on/off" transcriptional state of the homeotic genes is then established and propagated by the action of the specific regulatory proteins independently of the GAGA factor. We also suggest that GAGA factor may not have a dual activator/repressor function. Rather, Trithorax-like mutations may produce dual loss of activation and loss of repression effects.

El análisis de la mortalidad materna en el marco de la evolución socio economica y demográfica y su influencia en el proceso salud enfermedad en el Ecuador período: 1970-1995

Los avances significativos en el progreso de la ciencia con la finalidad de disminuir las altas tasas de mortalidad materna, pueden ser analizadas en el marco de la situación socio-económica y demográfica del proceso salud enfermedad en nuestro país. De esta forma, cada una de las tasas de mortalidad pueden ser interpretadas en conjunto con la situación social, económica y demográfica del país. sin olvidar naturalmente los presupuestos asignados para el sector salud. Con este objetivo recurrimos a diferentes instituciones del estado ecuatoriano on la finalidad de obtener los datos correspondientes a indicadores demográficos, de salud e indicadores económicos, dutrante el período comprendido entre 1970 y 1995. Estos datos fueron ingresados en una hoja electrónica, para posteriormente efectuar los análisis correspondientes. El análisis de los datos permite ver una tendencia a la baja de la fecundidad y de la natalidad en el país, especialmente marcada en los últimos años. Igualmemte se observa una lenta y escasa disminución de la tasa de mortalidad general, neonatal, postneonatal e infantil. Se observa que el número de profesionales en salud (médicos, odontólogos, enfermeras y auxiliares) se ha incrementado notablemente en el período que presentamos, en particular en la década del 80. Igualmente encontramos que la esperanza de vida al nacimiento se encuentra en aumento, así como el porcentaje de la población urbana. La infraestructura hospitalaria existente en la década del 70, no ha aumentado significativamente, existiendo una disminución del número de camas, pero al mismo tiempo una mayor ocupación de las mismas, hecho que se manifiesta por el aumento en el número de egresos hospitalarios. En general los indicadores económicos demuestran un crecimiento, los mismos que en su mayoría se correlacionan negativamente con la mortalidad materna, existiendo la tendencia a pensar que en el país se privilegia los indicadores económicos, en detrimento de los indicadores de salud y sin participar en la toma final de las decisiones oficiales. Como dato interesante vale recalcar que la inflación, durante este período de estudio se correlaciona significativamente en forma inversa con la mortalidad materna (p<0.05), particular que nos lleva a pensar la importancia de estos dos indicadores del desarrollo del país.