An early female lethal system of the New World screwworm, Cochliomyia hominivorax, for biotechnology-enhanced SIT.

BACKGROUND: The New World Screwworm fly (NWS), Cochliomyia hominivorax, is an ectoparasite of warm-blooded animals and a major pest of livestock in parts of South America and the Caribbean where it remains endemic. In North and Central America it was eradicated using the Sterile Insect Technique (SIT). A control program is managed cooperatively between the governments of the United States and Panama to prevent the northward spread of NWS from infested countries in South America. This is accomplished by maintaining a permanent barrier through the release of millions of sterile male and female flies in the border between Panama and Colombia. Our research team demonstrated the utility of biotechnology-enhanced approaches for SIT by developing a male-only strain of the NWS. The strain carried a single component tetracycline repressible female lethal system where females died at late larval/pupal stages. The control program can be further improved by removing females during embryonic development as larval diet costs are significant. RESULTS: The strains developed carry a two-component system consisting of the Lucilia sericata bottleneck gene promoter driving expression of the tTA gene and a tTA-regulated Lshid proapoptotic effector gene. Insertion of the sex-specifically spliced intron from the C. hominivorax transformer gene within the Lshid gene ensures that only females die when insects are reared in the absence of tetracycline. In several double homozygous two-component strains and in one "All-in-one" strain that had both components in a single construct, female lethality occurred at the embryonic and/or first instar larval stages when raised on diet without tetracycline. Laboratory evaluation for phenotypes that are relevant for mass rearing in a production facility revealed that most strains had fitness characteristics similar to the wild type J06 strain that is currently reared for release in the permanent barrier. Testing of an "All in one" strain under mass rearing conditions showed that the strain maintained the fitness characteristics observed in small-scale rearing. CONCLUSIONS: The early female lethal strains described here could be selected by the NWS Control Program for testing at large scale in the production facility to enhance the efficiency of the NWS eradication program.

Macroevolutionary shifts of WntA function potentiate butterfly wing-pattern diversity.

Butterfly wing patterns provide a rich comparative framework to study how morphological complexity develops and evolves. Here we used CRISPR/Cas9 somatic mutagenesis to test a patterning role for WntA, a signaling ligand gene previously identified as a hotspot of shape-tuning alleles involved in wing mimicry. We show that WntA loss-of-function causes multiple modifications of pattern elements in seven nymphalid butterfly species. In three butterflies with a conserved wing-pattern arrangement, WntA is necessary for the induction of stripe-like patterns known as symmetry systems and acquired a novel eyespot activator role specific to Vanessa forewings. In two Heliconius species, WntA specifies the boundaries between melanic fields and the light-color patterns that they contour. In the passionvine butterfly Agraulis, WntA removal shows opposite effects on adjacent pattern elements, revealing a dual role across the wing field. Finally, WntA acquired a divergent role in the patterning of interveinous patterns in the monarch, a basal nymphalid butterfly that lacks stripe-like symmetry systems. These results identify WntA as an instructive signal for the prepatterning of a biological system of exuberant diversity and illustrate how shifts in the deployment and effects of a single developmental gene underlie morphological change.

A transgenic male-only strain of the New World screwworm for an improved control program using the sterile insect technique.

BACKGROUND: The New World screwworm, Cochliomyia hominivorax, is a devastating pest of livestock endemic to subtropical and tropical regions of the Western hemisphere. The larvae of this species feed on the tissue of living animals, including man, and can cause death if untreated. Over 60 years ago, the sterile insect technique (SIT) was developed with the aim of eradicating this pest, initially from Florida but subsequently from all of North and Central America. From the outset it was appreciated that SIT would be more efficient if only sterile males were released in the field, but this was not possible until now. RESULTS: Here, we report on the development and evaluation of the first sexing strains of C. hominivorax that produce only males when raised on diet without tetracycline. Transgenic lines have been developed that possess a tetracycline repressible female-lethal genetic system. Ten of these lines show high female lethality at the late larval/pupal stages and three of them present dominant female lethality. Most of the lines were comparable to the wild type parental strain in several fitness parameters that are relevant to mass rearing in a production facility. Further, three lines performed well in male mating success and male competition assays, suggesting they would be sexually competitive in the field. Consequently, one transgenic line has been selected by the New World Screwworm Program for evaluation under mass rearing conditions. CONCLUSIONS: We conclude that the promising characteristics of the selected sexing strains may contribute to reduce production costs for the existing eradication program and provide more efficient population suppression, which should make a genetic control program more economical in regions were C. hominivorax remains endemic.

Priority pesticides in Chile: Predicting their environmental distribution, bioaccumulation, and transport potential.

Agriculture is one of the main economic activities in Chile and is associated with extensive use of pesticides, which can represent a risk to the environment and to human health. Currently, there are over 400 pesticides approved for commerce in Chile, including chemicals banned in other countries (e.g., flocoumafen and chlorfenapyr). An empirical analysis of their potential environmental effects is difficult due to this large number, thus opening the doors for the use of computational tools for prioritization efforts based on their persistence, bioaccumulation, and transport potential in the environment. The main objectives of this study were to estimate the properties and environmental distribution of pesticides approved for commerce in Chile and to generate a priority list for further evaluation in local environments. We used the Estimation Program Interface Suite interface to estimate the distribution coefficients, half-lives, and bioaccumulation potential of all pesticides registered in the Chilean Agriculture and Livestock Services. Additionally, the Pov & LRTP Screening Tool was used to estimate their overall persistence and long-range transport potential in the environment. The results were used to develop a P-B-lon range transport (LRT) score, which considered persistence, bioaccumulation, and long-range transport potential. All pesticides were compared to a group of polychlorinated biphenyls (PCBs), used as reference compounds, to generate a list of priority pesticides with persistent organic pollutants characteristics. The results showed that most pesticides were distributed between the organic phase and water, where they also showed the longest half-lives and bioaccumulation potential. A group of 21 pesticides showed relatively high P-B-LRT scores, compared to PCBs, and were classified as priority compounds. The list was further refined based on the volume of sales for each pesticide.  Integr Environ Assess Manag 2023;19:676-683. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Augmentative lag screws as a treatment for aseptic hypertrophic nonunion after internal fracture fixation.

BACKGROUND: Hypertrophic nonunion after intramedullary (IM) nailing and plating is Uncommon and the treatment remained controversial. The aim of this study was to show the result of a simple augmentative lag screws technique for vital non-unions after internal fixation PATIENTS AND METHODS: We retrospectively reviewed the patients with nonunion after internal fixation between January 2016 to August 2022. Patients with unacceptable shortening or deformity were excluded as well as nonunion septic cases. All the patients were followed up for at least 6 months. RESULTS: Seven patients achieved bony union in a median time of 12 weeks (IRQ 12-16). There was a failure case with persistent non-union and brokerage of the screws. DISCUSSION: Various techniques have been described to treat non-union after intramedullary nailing or plating. The existing nail is frequently removed, and the non-union site is either re-reamed and re-nailed or fixed with a plate or external fixation devices or rechanged by a nail in the case of plates. In our study of non-union, augmentative lag screws were successfully applied to treat eight patients with aseptic nonunion, resulting in the healing of non-union in all cases except one. CONCLUSION: Augmentative lag screws represent a simple technique for the management of aseptic hypertrophic nonunion after internal fixation with a significantly shorter operating time.

High level of novelty under the hood of convergent evolution.

Little is known about the extent to which species use homologous regulatory architectures to achieve phenotypic convergence. By characterizing chromatin accessibility and gene expression in developing wing tissues, we compared the regulatory architecture of convergence between a pair of mimetic butterfly species. Although a handful of color pattern genes are known to be involved in their convergence, our data suggest that different mutational paths underlie the integration of these genes into wing pattern development. This is supported by a large fraction of accessible chromatin being exclusive to each species, including the de novo lineage-specific evolution of a modular optix enhancer. These findings may be explained by a high level of developmental drift and evolutionary contingency that occurs during the independent evolution of mimicry.

Organisation and expression of a cluster of yolk protein genes in the Australian sheep blowfly, Lucilia cuprina.

The Australian sheep blowfly Lucilia cuprina is a major pest for the Australian and New Zealand sheep industries. With the long-term aim of making a strain of L. cuprina suitable for a genetic control program, we previously developed a tetracycline-repressible female lethal genetic system in Drosophila. A key part of this system is a female-specific promoter from a yolk protein (yp) gene controlling expression of the tetracycline-dependent transactivator (tTA). Here we report the sequence of a 14.2 kb genomic clone from L. cuprina that contains a cluster of three complete yp genes and one partial yp gene. The Lcyp genes are specifically expressed in females that have received a protein meal. A bioinformatic analysis of the promoter of one of the yp genes (LcypA) identified several putative binding sites for DSX, a known regulator of yp gene expression in other Diptera. A transgenic strain of L. cuprina was made that contained the LcypA promoter driving the expression of the Escherichia coli lacZ reporter gene. Transgenic females express high levels of ß-galactosidase after a protein meal. Thus the LcypA promoter could be used to obtain female-specific expression of tTA in transgenic L. cuprina.

Disruption of the odorant coreceptor Orco impairs foraging and host finding behaviors in the New World screwworm fly.

The evolution of obligate ectoparasitism in blowflies (Diptera: Calliphoridae) has intrigued scientists for over a century, and surprisingly, the genetics underlying this lifestyle remain largely unknown. Blowflies use odors to locate food and oviposition sites; therefore, olfaction might have played a central role in niche specialization within the group. In insects, the coreceptor Orco is a required partner for all odorant receptors (ORs), a major gene family involved in olfactory-evoked behaviors. Hence, we characterized the Orco gene in the New World screwworm, Cochliomyia hominivorax, a blowfly that is an obligate ectoparasite of warm-blooded animals. In contrast, most of the closely related blowflies are scavengers that lay their eggs on dead animals. We show that the screwworm Orco orthologue (ChomOrco) is highly conserved within Diptera, showing signals of strong purifying selection. Expression of ChomOrco is broadly detectable in chemosensory appendages, and is related to morphological, developmental, and behavioral aspects of the screwworm biology. We used CRISPR/Cas9 to disrupt ChomOrco and evaluate the consequences of losing the OR function on screwworm behavior. In two-choice assays, Orco mutants displayed an impaired response to floral-like and animal host-associated odors, suggesting that OR-mediated olfaction is involved in foraging and host-seeking behaviors in C. hominivorax. These results broaden our understanding of the chemoreception basis of niche occupancy by blowflies.

Cortex cis-regulatory switches establish scale colour identity and pattern diversity in Heliconius.

In Heliconius butterflies, wing colour pattern diversity and scale types are controlled by a few genes of large effect that regulate colour pattern switches between morphs and species across a large mimetic radiation. One of these genes, cortex, has been repeatedly associated with colour pattern evolution in butterflies. Here we carried out CRISPR knockouts in multiple Heliconius species and show that cortex is a major determinant of scale cell identity. Chromatin accessibility profiling and introgression scans identified cis-regulatory regions associated with discrete phenotypic switches. CRISPR perturbation of these regions in black hindwing genotypes recreated a yellow bar, revealing their spatially limited activity. In the H. melpomene/timareta lineage, the candidate CRE from yellow-barred phenotype morphs is interrupted by a transposable element, suggesting that cis-regulatory structural variation underlies these mimetic adaptations. Our work shows that cortex functionally controls scale colour fate and that its cis-regulatory regions control a phenotypic switch in a modular and pattern-specific fashion.

Heliconius butterflies have bright patterns on their wings that tell potential predators that they are toxic. As a result, predators learn to avoid eating them. Over time, unrelated species of butterflies have evolved similar patterns to avoid predation through a process known as Müllerian mimicry. Worldwide, there are over 180,000 species of butterflies and moths, most of which have different wing patterns. How do genes create this pattern diversity? And do butterflies use similar genes to create similar wing patterns? One of the genes involved in creating wing patterns is called cortex. This gene has a large region of DNA around it that does not code for proteins, but instead, controls whether cortex is on or off in different parts of the wing. Changes in this non-coding region can act like switches, turning regions of the wing into different colours and creating complex patterns, but it is unclear how these switches have evolved. Butterfly wings get their colour from tiny structures called scales, which each have their own unique set of pigments. In Heliconius butterflies, there are three types of scales: yellow/white scales, black scales, and red/orange/brown scales. Livraghi et al. used a DNA editing technique called CRISPR to find out whether the cortex gene affects scale type. First, Livraghi et al. confirmed that deleting cortex turned black and red scales yellow. Next, they used the same technique to manipulate the non-coding DNA around the cortex gene to see the effect on the wing pattern. This manipulation turned a black-winged butterfly into a butterfly with a yellow wing band, a pattern that occurs naturally in Heliconius butterflies. The next step was to find the mutation responsible for the appearance of yellow wing bands in nature. It turns out that a bit of extra genetic code, derived from so-called 'jumping genes', had inserted itself into the non-coding DNA around the cortex gene, 'flipping' the switch and leading to the appearance of the yellow scales. Genetic information contains the instructions to generate shape and form in most organisms. These instructions evolve over millions of years, creating everything from bacteria to blue whales. Butterfly wings are visual evidence of evolution, but the way their genes create new patterns isn't specific to butterflies. Understanding wing patterns can help researchers to learn how genetic switches control diversity across other species too.

Sexual development in Lucilia cuprina (Diptera, Calliphoridae) is controlled by the transformer gene.

Insects use an amazing variety of genetic systems to control sexual development. A Y-linked male determining gene (M) controls sex in the Australian sheep blowfly Lucilia cuprina, an important pest insect. In this study, we isolated the L. cuprina transformer (Lctra) and transformer2 (Lctra2) genes, which are potential targets of M. The LCTRA and LCTRA2 proteins are significantly more similar to homologs from tephritid insects than Drosophila. The Lctra transcript is alternatively spliced such that only females make a full-length protein and the presence of six TRA/TRA2 binding sites in the female first intron suggest that Lctra splicing is autoregulated as in tephritids. LCTRA is essential for female development as RNAi knockdown of Lctra mRNA leads to the development of male genitalia in XX adults. Analysis of Lctra expression during development shows that early and midstage male and female embryos express the female form of Lctra and males express only the male form by the first instar larval stage. Our results suggest that an autoregulatory loop sustains female development and that expression of M inhibits Lctra autoregulation, switching its splicing to the male form. The conservation of tra function and regulation in a Calliphorid insect shows that this sex determination system is not confined to Tephritidae. Isolation of these genes is an important step toward the development of a strain of L. cuprina suitable for a genetic control program.

Specific Gene Disruption in the Major Livestock Pests Cochliomyia hominivorax and Lucilia cuprina Using CRISPR/Cas9.

Cochliomyia hominivorax and Lucilia cuprina are major pests of livestock. Their larvae infest warm-blooded vertebrates and feed on host's tissues, resulting in severe industry losses. As they are serious pests, considerable effort has been made to develop genomic resources and functional tools aiming to improve their management and control. Here, we report a significant addition to the pool of genome manipulation tools through the establishment of efficient CRISPR/Cas9 protocols for the generation of directed and inheritable modifications in the genome of these flies. Site-directed mutations were introduced in the Chominivorax and Lcuprina yellow genes (ChY and LcY) producing lightly pigmented adults. High rates of somatic mosaicism were induced when embryos were injected with Cas9 ribonucleoprotein complexes (RNPs) pre-assembled with guide RNAs (sgRNAs) at high concentrations. Adult flies carrying disrupted yellow alleles lacked normal pigmentation (brown body phenotype) and efficiently transmitted the mutated alleles to the subsequent generation, allowing the rapid creation of homozygous strains for reverse genetics of candidate loci. We next used our established CRISPR protocol to disrupt the Chominivorax transformer gene (Chtra). Surviving females carrying mutations in the Chtra locus developed mosaic phenotypes of transformed ovipositors with characteristics of male genitalia while exhibiting abnormal reproductive tissues. The CRISPR protocol described here is a significant improvement on the existing toolkit of molecular methods in calliphorids. Our results also suggest that Cas9-based systems targeting Chtra and Lctra could be an effective means for controlling natural populations of these important pests.

Interplay between Developmental Flexibility and Determinism in the Evolution of Mimetic Heliconius Wing Patterns.

To what extent can we predict how evolution occurs? Do genetic architectures and developmental processes canalize the evolution of similar outcomes in a predictable manner? Or do historical contingencies impose alternative pathways to answer the same challenge? Examples of Müllerian mimicry between distantly related butterfly species provide natural replicates of evolution, allowing us to test whether identical wing patterns followed parallel or novel trajectories. Here, we explore the role that the signaling ligand WntA plays in generating mimetic wing patterns in Heliconius butterflies, a group with extraordinary mimicry-related wing pattern diversity. The radiation is relatively young, and numerous cases of wing pattern mimicry have evolved within the last 2.5-4.5 Ma. WntA is an important target of natural selection and is one of four major effect loci that underlie much of the pattern variation in the group. We used CRISPR/Cas9 targeted mutagenesis to generate WntA-deficient wings in 12 species and a further 10 intraspecific variants, including three co-mimetic pairs. In all tested butterflies, WntA knockouts affect pattern broadly and cause a shift among every possible scale cell type. Interestingly, the co-mimics lacking WntA were very different, suggesting that the gene networks that pattern a wing have diverged considerably among different lineages. Thus, although natural selection channeled phenotypic convergence, divergent developmental contexts between the two major Heliconius lineages opened different developmental routes to evolve resemblance. Consequently, even under very deterministic evolutionary scenarios, our results underscore a surprising unpredictability in the developmental paths underlying convergence in a recent radiation.

Caracterización del acto suicida en el servicio médico legal de Concepción, Chile entre 2011-2015 / Characterization of the suicide act according to the autopsy reports released by the legal medical service of Concepción, Chile 2011-2015

INTRODUCCIÓN: El suicidio se define como el acto donde la propia persona se quita la vida intencionalmente. Actualmente es una problemática mundial y en aumento. El objetivo es caracterizar el acto suicida según los reportes de autopsias realizados por el Servicio Médico Legal (SML) Concepción, durante el periodo 2011-2015. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y trasversal de los informes de autopsia con causa suicidio realizadas por el SML Concepción, periodo 2011-2015 utilizándose las variables: genero, edad, procedencia, lugar de ocurrencia, estado civil, ocupación, patologías asociadas, causa de muerte, alcoholemia, examen toxicológico, llegada al centro asistencial, intentos previos y carta de aviso. Los datos se analizaron y tabularon mediante Microsoft Excel. El trabajo fue aprobado por comité de ética. RESULTADOS: Del total de autopsias 511 fueron suicidios, 83,3% eran hombres, edad promedio 44,8 años, 49,9% casados, 83,6% correspondían a la provincia de Concepción, 75% ocurrió en su domicilio, 88,8% causado por asfixia por ahorcamiento, 57,3% poseían alcoholemia negativa y 67,7% examen toxicológico negativo y solo un 5,1% llego a un centro asistencial. DISCUSIÓN: Las variables más prevalentes de nuestro estudio fueron edad de 20-29 años, género masculino, estado civil soltero y ocupación en empleo técnico. El método y lugar más frecuentes fueron el ahorcamiento y el domicilio respectivamente. Se observa una prevalencia mayor de intoxicación alcohólica que en cifras internacionales. La sustancia más prevalente en los análisis toxicológicos fue la cocaína. Se necesita ampliar la investigación en nuestro medio analizando factores de riesgo y diseñando nuevas estrategias de prevención

INTRODUCTION: Suicide can be defined as the act where the person finish their life intentionally. It is currently an increasing worldwide problematic. The objective is to characterize the suicide act according to the autopsies reports performed by the Legal Medical Service (SML) Concepción, during the period 2011-2015 MATERIAL AND METHOD: We released a retrospective, descriptive and transversal study with the autopsies reports performed by the SML Concepción described as suicide, between 2011­2015. We used variables such as: gender, age, procedence, place of ocurrence, marital state, occupation, comorbidities, death cause, blood alcohol concentration, toxicological results, arrival at a care center, previus attempts and warning letter. Data was analized and tabulated using Microsoft Excel. The study was previusly approved by an ethic committee. RESULTS: From the total autopsies released, 12.6% were suicides (511), from which 83.3% were men, 49.9% were married, 83.6% were from Concepcion, 75% of the suicides occurred at home, 88.8% were asphyxiation by hanging, 57.3% had a negative result of alcohol in blood and 67.7% had a negative toxicological test, 5.1% arrived at a care center. DISCUSSION: The most prevalent variables of our study were age 20-29, male gender, single marital status and occupation in technical employment. The most frequent method and place were hanging and domicile respectively. We observed a higher prevalence of alcohol intoxication than international studies. The most prevalent substance in the toxicological analyzes was cocaine. It is necessary to expand the research in our environment by analyzing risk factors and designing new prevention strategies.

Efficient germ-line transformation of the economically important pest species Lucilia cuprina and Lucilia sericata (Diptera, Calliphoridae).

The green blowfly species Lucilia cuprina and Lucilia sericata are economically important pests for the sheep industries of Australia and New Zealand. L. cuprina has long been considered a good target for a genetic pest management program. In addition, L. sericata maggots are used in the cleaning of wounds and necrotic tissue of patients suffering from ulcers that are difficult to treat by other methods. Development of efficient transgenesis methods would greatly facilitate the development of strains ideal for genetic control programs or could potentially improve "maggot therapy". We have previously reported the germ-line transformation of L. cuprina and the design of a "female killing system" that could potentially be applied to this species. However, the efficiency of transformation obtained was low and transformed lines were difficult to detect due to the low expression of the EGFP marker used. Here we describe an efficient and reliable method for germ-line transformation of L. cuprina using new piggyBac vector and helper plasmids containing the strong promoter from the L. cuprina hsp83 gene to drive expression of the transposase and fluorescent protein marker gene. We also report, for the first time, the germ-line transformation of L. sericata using the new piggyBac vector/helper combination.

Conservation and sex-specific splicing of the doublesex gene in the economically important pest species Lucilia cuprina.

Genetic control of sex determination in insects has been best characterized in Drosophila melanogaster, where the master gene Sxl codes for RNA that is sex specifically spliced to produce a functional protein only in females. SXL regulates the sex-specific splicing of transformer (tra) RNA which, in turn, regulates the splicing of dsx RNA to produce functional male and female proteins. In the Australian sheep blowfly (Lucilia cuprina), the tra gene (Lctra) is required for female development and Lctra transcripts are sex-specifically spliced such that only female Lctra mRNA codes for functional protein. In males, a factor encoded by the Y-linked male determining gene is thought to prevent the female-mode of splicing of Lctra RNA. To further our understanding of the sex determination regulatory hierarchy in L. cuprina, we have isolated the dsx gene (Lcdsx) from this species. We found that the Lcdsx transcripts are sex-specifically spliced in a similar manner as their counterparts in D. melanogaster, housefly and tephritids. The LcDSX proteins are well conserved and the male form of DSX contains a motif encoded by a male-specific exon that is within the female-specific intron. This intron/exon arrangement had previously been found only in the housefly dsx gene, suggesting this may be a unique feature of dsx genes of Calyptratae species.

Microinjection of an antibody against the cysteine-protease involved in male chromatin remodeling blocks the development of sea urchin embryos at the initial cell cycle.

We reported recently that the inhibition of cysteine-proteases with E-64-d disturbs DNA replication and prevents mitosis of the early sea urchin embryo. Since E-64-d is a rather general inhibitor of thiol-proteases, to specifically target the cysteine-protease previously identified in our laboratory as the enzyme involved in male chromatin remodeling after fertilization, we injected antibodies against the N-terminal sequence of this protease that were able to inhibit the activity of this enzyme in vitro. We found that injection of these antibodies disrupts the initial zygotic cell cycle. As shown in this report in injected zygotes a severe inhibition of DNA replication was observed, the mitotic spindle was not correctly bipolarized the embryonic development was aborted at the initial cleavage division. Consequently, the injection of these antibodies mimics perfectly the effects previously described for E-64-d, indicating that the effects of this inhibitor rely mainly on the inhibition of the cysteine-protease involved in male chromatin remodeling after fertilization. These results further support the crucial role of this protease in early embryonic development.

Guías colombianas para el manejo del acné: una revisión basada en la evidencia por el Grupo Colombiano de Estudio en Acné

El acné es una enfermedad inflamatoria crónica que afecta, principalmente, adolescentes y adultos jóvenes. Se calcula que antes de los 21 años entre el 80 y el 90% de esta población ha estado expuesta a la enfermedad. Sin embargo, el acné puede persistir después de los 21 años y se sabe que 12% de las mujeres mayores de 25 años aún sufren de acné facial. El arsenal terapéutico para el acné consta de medicamentos tópicos y sistémicos que han demostrado su eficacia en la reducción de las lesiones. El mecanismo de acción de estos medicamentos está orientado, al menos, a uno de los cuatro factores fisiopatológicos reconocidos como responsables de la formación de las lesiones del acné, a saber: trastornos de la queratinización, hipersecreción sebácea, proliferación de Propionibacterium acnes o actividad inflamatoria in situ. La elección del tratamiento apropiado depende de varios factores, como la forma clínica de la enfermedad (de retención o inflamatoria), la gravedad de la misma y la respuesta del paciente a tratamientos previos. Asimismo, y entendiendo al acné como una enfermedad de carácter crónico, el tratamiento debe incluir una fase inicial con el objetivo de lograr una mayor reducción de la extensión y gravedad de las lesiones, y una fase de mantenimiento orientada a la prevención de las recaídas o exacerbaciones. Además, el resultado del tratamiento depende del cumplimiento del mismo y para lograrlo, es fundamental una adecuada relación médico-paciente. Este documento presenta el resultado de una revisión actualizada de la literatura, que incluye guías nacionales e internacionales para el manejo del acné y formula recomendaciones terapéuticas basadas en el mejor nivel de “evidencia” que se encontró. Su implementación permitirá la unificación de criterios con el objetivo de ofrecer un mejor manejo a los pacientes con la enfermedad, evitando así sus secuelas físicas y emocionales. Por otro lado, las guías presentan un marco científico y conceptual con la suficiente validez para su inclusión en los protocolos del plan obligatorio de salud.

Dermatilomanía y síndrome de Prader-Willi / Skin picking and Prader-Willi syndrome

Reportamos el caso de una mujer de 18 años con síndrome de Prader-Willi, con retardo mental, problemas de comportamiento –tales como hiperfagia y pellizcos en piel–, obesidad, hipogonadismo, estatura corta, manos pequeñas y ojos en “forma de almendra”; presentaba antecedentes de hipotonía en la edad neonatal. El síndrome de Prader-Willi es un trastorno congénito, raro, no hereditario, que afecta a 1 de cada 10.000 a 25.000 recién nacidos. Es causado por alteraciones en los genes paternos localizados en la región codificadora del cromosoma 15(q11.2-q13). Se caracteriza por hipotonía, retardo en el desarrollo, alteraciones en el comportamiento, obesidad, hiperfagia, facies característica, hipogonadismo, corta estatura y manifestaciones cutáneas.

Uso de anticuerpos monoclonales anti-CD20 (rituximab) en paciente con pénfigo vulgar grave / Use of monoclonal anti-CD20 (rituximab) in a patient with severe pemphigus vulgaris

El pénfigo vulgar es una enfermedad vesículo-ampollosa de carácter autoinmunitario que compromete la piel y las membranas mucosas, y presenta un curso crónico. La inmunopatogénesis se basa en la presencia de autoanticuerpos (IgG) producidos por linfocitos B y dirigidos contra la superficie de los queratinocitos, que generan pérdida de la adherencia intercelular y la formación de ampollas subepidérmicas. La morbimortalidad es variable, y es muy importante el manejo que se instaure. Se han utilizado múltiples tratamientos inmunosupresores, principalmente corticosteroides sistémicos y múltiples inmunorreguladores, sin embargo, en algunos casos resistentes o ante la presencia de efectos secundarios, la terapia inmunosupresora convencional es insuficiente para controlar la enfermedad y disminuir la morbimortalidad. Se presenta una revisión sobre el uso de anticuerpos monoclonales anti-CD20 de los linfocitos B (rituximab), para el manejo del pénfigo vulgar resistente y con mala respuesta a múltiples tratamientos convencionales a altas dosis y por periodos prolongados.