Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes

1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.

2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CL_int) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.

3. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.

4. Apparent CL_int values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CL_int values for total metabolism (CYP and CES enzymes) per gram of adult human liver.

5. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

     

Exploring Coverage of the 2008 Irish Dioxin Crisis in the Irish and UK Newsprint Media

The 2008 dioxin crisis occurred as a result of contamination of Irish pork. The event had significant implications for Ireland’s economy and the reputation of its agricultural industry, as well as raising concerns for human health. This study describes the results of a content analysis of Irish and UK newspaper coverage of the 2008 Irish dioxin crisis, as this is likely to provide insight into how public perceptions of this issue were shaped. Articles from 16 print publications were systematically sampled for the period December 2008 to February 2009. The resulting data set of 141 articles was examined using a coding protocol developed based on previous research and refined during piloting. Results indicated that the dioxin crisis was primarily portrayed by the media as an industry/economic crisis, dominant in 26.9% of articles in the sample. Within this dominant portrayal, the agricultural industry was frequently cited as being in crisis (42.6%); however, the implications of the crisis on the wider economic environment also received attention (17.7%). Differences between Irish and UK-based media were also examined, revealing that while the Irish media most frequently described the crisis in terms of its impact on the industry and economy, the UK media were more likely to portray the crisis as a risk to health. These dominant media messages and message framings have implications for the public understanding of the issue in each country and potential consequences regarding perception of the adequacy of existing food policy and regulatory oversight.     

Immunomodulatory Metabolites Released by the Frog-Killing Fungus Batrachochytrium dendrobatidis

Batrachochytrium dendrobatidis is a fungal pathogen in the phylum Chytridiomycota that causes the skin disease chytridiomycosis. Chytridiomycosis is considered an emerging infectious disease linked to worldwide amphibian declines and extinctions. Although amphibians have well-developed immune defenses, clearance of this pathogen from the skin is often impaired. Previously, we showed that the adaptive immune system is involved in the control of the pathogen, but B. dendrobatidis releases factors that inhibit in vitro and in vivo lymphocyte responses and induce lymphocyte apoptosis. Little is known about the nature of the inhibitory factors released by this fungus. Here, we describe the isolation and characterization of three fungal metabolites produced by B. dendrobatidis but not by the closely related nonpathogenic chytrid Homolaphlyctis polyrhiza. These metabolites are methylthioadenosine (MTA), tryptophan, and an oxidized product of tryptophan, kynurenine (Kyn). Independently, both MTA and Kyn inhibit the survival and proliferation of amphibian lymphocytes and the Jurkat human T cell leukemia cell line. However, working together, they become effective at much lower concentrations. We hypothesize that B. dendrobatidis can adapt its metabolism to release products that alter the local environment in the skin to inhibit immunity and enhance the survival of the pathogen.     

Follow-Up Study of Over Three Years of Patients with Uveitis after Cataract Phacoemulsification: Outcomes and Complications

Purpose: To evaluate the rate and onset of intraoperative and postoperative complications post-phacoemulsification. Methods: One hundred sixty-two eyes of 145 patients with uveitis who underwent phacoemulsification between 2006 and 2009 were identified through surgical record review. Fifty-nine eyes of 46 patients met the inclusion criteria. Hazard ratio (HR) and Kaplan-Meier survival probability were calculated for each class of uveitis. Results: Macular edema (ME) resulted to be associated to chronic postoperative inflammation (r?=?0.6; p?=?0.00) and mostly related to patients who presented more than one postoperative relapse/year (r?=?0.2; p?=?0.02). Fuchs uveitis resulted to be a risk factor for posterior capsule opacification (PCO) (HR 3.36 IC95%1.0-10.5; p?=?0.03). Hypotony and elevated intraocular pressure (IOP) were detected in the anterior uveitis group (0.02 EY). Conclusion: The HR to develop ME was significantly related to chronic anterior uveitis. PCO and elevated IOP are most frequent in Fuchs uveitis. The postoperative visual acuity result was good among all the uveitis groups.     

Post-Lyme disease syndrome

About 10% of patients with Lyme disease continue to experience musculoskeletal pain and cognitive dysfunction after recommended antibiotic treatment. This condition is called post-Lyme disease syndrome (PLDS) or post-treatment Lyme disease syndrome. These two terms are used interchangeably. The pathogenesis of PLDS has been controversial. The hypothesis that patients with PLDS may harbor hidden reservoirs of Borrelia burgdorferi after their initial antibiotic treatment is difficult to accept. The prospective, double-blind studies contradict this point of view. Also, recently published research applying xenodiagnosis to PLDS supports the opinion that PLDS most likely has an autoimmune background. Lengthy courses of antibiotics are not justified in patients with PLDS because of the lack of benefit, and they are fraught with hazards. Most patients with PLDS recover from persistent symptoms with time. However, it can take months before they feel completely well.     

Anatomical structures at risk using different approaches for sacrospinous ligament fixation

For 50 years now, sacrospinous ligament fixation (SSLF) has been used to treat pelvic organ prolapse consequent on altered integrity of the pelvic myofascial structures. It is usually performed vaginally, but it has recently been performed laparoscopically through either an anterior or a posterior approach, with the broad ligament as a landmark to differentiate the two. In the present study, these two laparoscopic approaches were assessed using Thiel-embalmed cadavers. The anterior and posterior approaches were compared in terms of the closest distance to anatomical structures at risk, including pelvic viscera, the obturator nerve, and vascular structures. The posterior approach was more often closer to the investigated vessels and the rectum. The obturator nerve and the ureter were close to both the anterior and posterior approaches. The urinary bladder was closer using the anterior approach. From an anatomical standpoint, therefore, the anterior laparoscopic approach for SSLF is more likely to cause injury to the urinary bladder, whereas the posterior approach is more prone to causing rectal and vessel injuries. This study illustrates, from a basic science perspective, the importance of combining fascia research, novel endoscopic or minimally invasive surgical exposures informed by anatomy, and contemporary trends in gynecology in order to improve patient outcomes. Clin. Anat. 33:522–529, 2020. © 2019 Wiley Periodicals, Inc.     

Quality of Pulmonary Function Tests in Participants with Down Syndrome

IntroductionPeople with Down syndrome (DS) have high respiratory morbidity, evaluating their respiratory health with standardized, objective tests is desirable. Thus, the objective of this study was to evaluate the technical quality of Pulmonary Function Tests (PFTs) to determine which ones are most suitable for this population.MethodsParticipants included children, teenagers and adults with DS, 5 years of age or older (n = 302). The technical quality of the impulse oscillometry system (IOS), forced spirometry, lung-diffusing capacity for carbon monoxide (DL_CO), and 6-min walk test (6MWT) were analyzed by age group. Capnography and pulse oximetry were included in the study. Technical quality was determined on the basis of current international PFTs standards.ResultsFifty-one percent of participants were males. A total of 184 participants (71%) who completed the IOS fulfilled the quality criteria, while 210 (70%) completed the 6MWT. Performance on forced spirometry and DL_CO was poor. All pulse oximetries and 96% percent heart rates obtained had good quality, but exhaled carbon dioxide (PetCO₂) and respiratory rate (RR) showed deficient repeatability.ConclusionsIOS appears to be the most reliable instrument for evaluating lung mechanics in individuals with DS.     

Treatment of oral manifestations of toxic epidermal necrolysis with low‐level laser therapy in a pediatric patient

Drug‐induced reactions are complications associated with high mortality and significant morbidity. Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9‐year‐old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug‐induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low‐level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow‐up to improve symptoms, nutrition, systemic condition, and quality of life.