Chemically defended plant tissues present formidable barriers to herbivores. Although mechanisms to resist plant defenses have been identified in ancient herbivorous lineages, adaptations to overcome plant defenses during transitions to herbivory remain relatively unexplored. The fly genus Scaptomyza is nested within the genus Drosophila and includes species that feed on the living tissue of mustard plants (Brassicaceae), yet this lineage is derived from microbe-feeding ancestors. We found that mustard-feeding Scaptomyza species and microbe-feeding Drosophila melanogaster detoxify mustard oils, the primary chemical defenses in the Brassicaceae, using the widely conserved mercapturic acid pathway. This detoxification strategy differs from other specialist herbivores of mustard plants, which possess derived mechanisms to obviate mustard oil formation. To investigate whether mustard feeding is coupled with evolution in the mercapturic acid pathway, we profiled functional and molecular evolutionary changes in the enzyme glutathione S-transferase D1 (GSTD1), which catalyzes the first step of the mercapturic acid pathway and is induced by mustard defense products in Scaptomyza. GSTD1 acquired elevated activity against mustard oils in one mustard-feeding Scaptomyza species in which GstD1 was duplicated. Structural analysis and mutagenesis revealed that substitutions at conserved residues within and near the substrate-binding cleft account for most of this increase in activity against mustard oils. Functional evolution of GSTD1 was coupled with signatures of episodic positive selection in GstD1 after the evolution of herbivory. Overall, we found that preexisting functions of generalized detoxification systems, and their refinement by natural selection, could play a central role in the evolution of herbivory.
We describe the case of a 49-year-old, otherwise healthy, Hispanic male who underwent an uncomplicated vasectomy and was treated prophylactically with a one-week course of ciprofloxacin. Two days after completing the antibiotic course, he developed a pruritic, blistering rash that covered 90% of his body surface area. Punch biopsy of the skin lesions confirmed the diagnosis of Stevens-Johnson syndrome (SJS). Upon further questioning, it was revealed that the patient had consumed approximately 32 ounces of grapefruit juice each of the seven days following his vasectomy. We hypothesized that the cytochrome P450 inhibitory effect of grapefruit juice had dramatically elevated systemic levels of ciprofloxacin, increasing the risk of developing SJS. Literature review revealed that ciprofloxacin is metabolized primarily by CYP1A2 with partial CYP3A4 metabolism, while grapefruit juice is strictly an enterocyte CYP3A4 inhibitor. To the authors’ knowledge, consumption of grapefruit juice has never been demonstrated to increase systemic levels of ciprofloxacin or of other fluoroquinolones. We conclude that either this is the first reported case of a grapefruit juice-ciprofloxacin interaction causing SJS, or that this is simply ciprofloxacin-induced SJS. Importantly, ciprofloxacin is not recommended by the American Urological Association for a routine vasectomy without risk factors for infection. We remind clinicians that inappropriately prescribed antibiotic prophylaxis for routine procedures can cause serious morbidity, including SJS, and should only be prescribed when indicated.
Necrotizing fasciitis is a devastating infectious disease process that is characterized by extensive soft tissue necrosis along deep fascial planes, systemic toxicity, and high mortality. Ultrasound imaging is a rapid and non-invasive tool that can be used to help make the diagnosis of necrotizing fasciitis by identifying several distinctive sonographic findings. The purpose of this study is to describe the construction of a realistic diagnostic training model for necrotizing fasciitis using fresh frozen cadavers and common, affordable materials.Presently, fresh non-embalmed cadavers have been used at medical institutions for various educational sessions including cadaver-based ultrasound training sessions. Details for the preparation and construction of a necrotizing fasciitis cadaver model are presented here. This paper shows that the images obtained from the cadaver model closely imitate the ultrasound appearance of fluid and gas seen in actual clinical cases of necrotizing fasciitis.Therefore, it can be concluded that this cadaver-based model produces high-quality sonographic images that simulate those found in true cases of necrotizing fasciitis and is ideal for demonstrating the sonographic findings of necrotizing fasciitis.
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