Exocrine Pancreas in Type 1 and Type 2 Diabetes: Different Patterns of Fibrosis, Metaplasia, Angiopathy, and Adiposity.

The endocrine and exocrine compartments of the pancreas are spatially related but functionally distinct. Multiple diseases affect both compartments, including type 1 diabetes (T1D), pancreatitis, cystic fibrosis, and pancreatic cancer. To better understand how the exocrine pancreas changes with age, obesity, and diabetes, we performed a systematic analysis of well-preserved tissue sections from the pancreatic head, body, and tail of organ donors with T1D (n = 20) or type 2 diabetes (T2D) (n = 25) and donors with no diabetes (ND; n = 74).

Human pancreatic capillaries and nerve fibers persist in type 1 diabetes despite beta cell loss.

The autonomic nervous system regulates pancreatic function. Islet capillaries are essential for the extension of axonal projections into islets, and both of these structures are important for appropriate islet hormone secretion. Because beta cells provide important paracrine cues for islet glucagon secretion and neurovascular development, we postulated that beta cell loss in type 1 diabetes (T1D) would lead to a decline in intraislet capillaries and reduction of islet innervation, possibly contributing to abnormal glucagon secretion.

Synthesis and evaluation of etoposide and podophyllotoxin analogs against topoisomerase IIα and HCT-116 cells.

Etoposide is a widely-used anticancer agent that targets human type II topoisomerases. Evidence suggests that metabolism of etoposide in myeloid progenitor cells is associated with translocations involved in leukemia development. Previous studies suggest halogenation at the C-2' position of etoposide reduces metabolism.

MTG16 is a tumor suppressor in colitis-associated carcinoma.

MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16-/- mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models.

Selenoprotein P influences colitis-induced tumorigenesis by mediating stemness and oxidative damage.

Patients with inflammatory bowel disease are at increased risk for colon cancer due to augmented oxidative stress. These patients also have compromised antioxidant defenses as the result of nutritional deficiencies. The micronutrient selenium is essential for selenoprotein production and is transported from the liver to target tissues via selenoprotein P (SEPP1).

Structure of pyrazole derivatives impact their affinity, stoichiometry, and cooperative interactions for CYP2E1 complexes.

CYP2E1 plays a critical role in detoxification and carcinogenic activation of drugs, pollutants, and dietary compounds; however, these metabolic processes can involve poorly characterized cooperative interactions that compromise the ability to understand and predict CYP2E1 metabolism. Herein, we employed an array of ten azoles with an emphasis on pyrazoles to establish the selectivity of catalytic and cooperative CYP2E1 sites through binding and catalytic studies. Spectral binding studies for monocyclic azoles suggested two binding events, while bicyclic azoles suggested one.

Brentuximab vedotin: an anti-CD30 antibody-drug conjugate.

Purpose: The pharmacology, pharmacokinetics, clinical efficacy, and safety and tolerability of brentuximab vedotin are reviewed.

Summary: Brentuximab vedotin is a potent antibody-drug conjugate composed of the monoclonal antibody cAC10, which targets the CD30 antigen on Hodgkin lymphoma and systemic anaplastic large-cell lymphoma (sALCL) cells; a highly stable valine-citrulline linker; and a potent chemotherapeutic agent monomethyl auristatin E, which inhibits microtubule polymerization. Brentuximab is indicated for patients with relapsed Hodgkin lymphoma after autologous stem-cell transplantation (ASCT), for patients who are not candidates for ASCT who have not responded to at least two multiagent chemotherapy regimens, and for patients with ALCL who have not responded to at least one multiagent chemotherapy regimen.

Converting to transdermal fentanyl: avoidance of underdosing.

Background: Converting between the various opioid agents continues to be challenge for many practitioners. Specifically, variable recommendations for converting to the transdermal fentanyl patch may lead to confusion among clinicians and errors in dosing.

Objective: Our aim was to describe the inconsistencies among available opioid conversions with regard to transdermal fentanyl and to provide recommendations for safe and effective utilization of this product in patients with chronic pain.

Neutropenia-associated outcomes in adults with acute myeloid leukemia receiving cytarabine consolidation chemotherapy with or without granulocyte colony-stimulating factor.

Study Objective: To determine whether granulocyte colony-stimulating factor (G-CSF) prophylaxis after consolidation with high- or intermediate-dose cytarabine (H/IDAC) for treatment of acute myeloid leukemia (AML) reduces the frequency of neutropenia-associated complications.

Design: Retrospective medical record review.

Setting: Academic medical center.

Survey of learning opportunities in academia for pharmacy residents.

Purpose: The types of teaching experiences offered in academia in pharmacy residency programs affiliated with or offered through colleges of pharmacy throughout the United States were evaluated.

Methods: Two 15-item questionnaires were developed, one for programs that offer a concentrated rotation in academia and one for programs that offer longitudinal opportunities in academia. These questionnaires were developed to assess the activities incorporated into the different learning experiences, the number of residents completing concentrated rotations, the residency director's perception of the benefit to the residents, and barriers that exist for institutions that do not offer concentrated rotations.

MTG16 contributes to colonic epithelial integrity in experimental colitis.

Objective: The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8(-/-) and Mtgr1(-/-) mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity.

Methods: Baseline and stress induced colonic phenotypes were examined in Mtg16(-/-) mice.