Exposure to an Environmental Mixture of Polycyclic Aromatic Hydrocarbons Induces Hepatic Cytochrome P450 Enzymes in Mice.

Cytochrome P450 enzymes (CYPs) play an important role in bioactivating or detoxifying polycyclic aromatic hydrocarbons (PAHs), common environmental contaminants. While it is widely accepted that exposure to PAHs induces CYPs, effectively increasing rates of xenobiotic metabolism, dose- and time-response patterns of CYP induction are not well-known. In order to better understand dose- and time-response relationships of individual CYPs following induction, we exposed B6129SF1/J mice to single or repeated doses (2-180 µmol/kg/d) of benzo[a]pyrene (BaP) or Supermix-10, a mixture of the top 10 most abundant PAHs found at the Portland Harbor Superfund Site. In hepatic microsomes from exposed mice, we measured amounts of active CYPs using activity-based protein profiling and total CYP expression using global proteomics. We observed rapid Cyp1a1 induction after 6 h at the lowest PAH exposures and broad induction of many CYPs after 3 daily PAH doses at 72 h following the first dose. Using samples displaying Cyp1a1 induction, we observed significantly higher metabolic affinity for BaP metabolism (Km reduced 3-fold), 3-fold higher intrinsic clearance, but no changes to the Vmax. Mice dosed with the highest PAH exposures exhibited 1.7-5-fold higher intrinsic clearance rates for BaP compared to controls and higher Vmax values indicating greater amounts of enzymes capable of metabolizing BaP. This study demonstrates exposure to PAHs found at superfund sites induces enzymes in dose- and time-dependent patterns in mice. Accounting for specific changes in enzyme profiles, relative rates of PAH bioactivation and detoxification, and resulting risk will help translate internal dosimetry of animal models to humans and improve risk assessments of PAHs at superfund sites.

Erosive rodent ulcer of the ear secondary to neglect.

Basal cell carcinomas (BCCs) are slow-growing, locally invasive lesions that rarely metastasise, however, if left untreated can progress to extensive destruction of local structures giving rise to the alternative name 'the rodent ulcer'. Here we present a case of BCC of the ear progressing to destruction of the pinna and mastoid, involving the facial nerve and breaching dura. This case presentation shows not only the seldom-seen natural progression of the rodent ulcer with impressive imaging and clinical photographs but also highlights a broader topic of capacity and consent in patients displaying maladaptive denial or abnormal illness behaviour, how this can affect patient outcomes and what we as clinicians can do to ensure the best care for our patients.

Changing the Landscape of Medical Oncology Training at the National University Hospital in the Philippines during the Coronavirus Disease 2019 (COVID-19) Pandemic.

Serving as one of the few training institutions of medical oncology in the Philippines, the University of the Philippines-Philippine General Hospital was faced with challenges brought by the coronavirus 2019 disease (COVID-19) pandemic. With the dismantling of routines and practices in the hospital, training activities such as daily rounds, conferences, and examinations were temporarily put on hold. Recognizing that the strength of any clinical training program is its wealth of patients, the immediate resumption of patient services, albeit limited at first, had been instrumental in ensuring the continuation of training in our institution. Opportunistic teaching-learning strategies between the faculty and fellows were devised. Innovative approaches to learning such as the use of online meeting platforms for division conferences, webinars, examinations, and other learning activities were initiated. Emphasis was given on the important considerations in the management of cancer patients during the COVID-19 pandemic. The emotional and psychological well-being of the faculty and fellows during this crisis were considered and a mental health assessment was conducted prior to the resumption of training activities.

Benzo[ a]pyrene Induction of Glutathione S-Transferases: An Activity-Based Protein Profiling Investigation.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated from combustion of carbon-based matter. Upon ingestion, these molecules can be bioactivated by cytochrome P450 monooxygenases to oxidized toxic metabolites. Some of these metabolites are potent carcinogens that can form irreversible adducts with DNA and other biological macromolecules. Conjugative enzymes, such as glutathione S-transferases or UDP-glucuronosyltransferases, are responsible for the detoxification and/or facilitate the elimination of these carcinogens. While responses to PAH exposures have been extensively studied for the bioactivating cytochrome P450 enzymes, much less is known regarding the response of glutathione S-transferases in mammalian systems. In this study, we investigated the expression and activity responses of murine hepatic glutathione S-transferases to benzo[ a]pyrene exposure using global proteomics and activity-based protein profiling for chemoproteomics, respectively. Using this approach, we identified several enzymes exhibiting increased activity including GSTA2, M1, M2, M4, M6, and P1. The activity of one GST enzyme, GSTA4, was found to be downregulated with increasing B[ a]P dose. Activity responses of several of these enzymes were identified as being expression-independent when comparing global and activity-based data sets, possibly alluding to as of yet unknown regulatory post-translational mechanisms.

Primary Non-Hodgkin's Lymphoma of the Scalp and Cranial Vault.

Primary Non-Hodgkin's Lymphoma of the cranial scalp and skull vault is a rare disease. We are describing a case of the same in a 50-year-old man. He was presented with a diffuse swelling in the left side scalp since 4 months of duration and progressively enlarging in size. On local Examination of the scalp, there was a diffuse swelling in the left parietal and occipital region of scalp. Imaging showed diffuse infiltration of the skull vault with extracranial soft tissue masses. Further investigations with CT scan chest, abdomen, and pelvis did not reveal any other evidence of systemic lymphoma. Biopsy of one of the scalp masses showed a small to intermediate cell B-cell lymphoma. Other nine previously reported cases of primary skull vault lymphoma were reviewed.

An uneventful pregnancy and delivery, in a case with chronic myeloid leukemia on imatinib.

The concomitant occurrence of pregnancy and chronic myelogenous leukemia is uncommon. We describe the successful management of a 24-year-old woman in the first trimester of her pregnancy with chronic myelogenous leukemia (CML) in the chronic phase, who was on treatment with imatinib, which was stopped by 10(th) week of pregnancy. Until, she completed full term of pregnancy she was on hydroxyurea. The use of imatinib did not have adverse effects on the fetus. The patient had a normal vaginal delivery and gave birth to a healthy 2500 g girl at 37 weeks of gestation. We conclude that imatinib in the first trimester of pregnant lady with CML, though has particular concern regarding the potential teratogenic and other adverse effects, has shown evidences of safe conception, pregnancy and delivery in ladies with CML.