Life After Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Introduction: Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness that is preventable via vaccination. Even with treatment, up to 10-15% of cases are fatal, and many survivors may experience severe long-term sequelae. Building upon the acute-phase findings presented in the Part 1 manuscript for this study, we describe the long-term physical, social, psychological, and economic burden of IMD on US survivors and their caregivers in this Part 2 manuscript.

Initial Experiences with Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Introduction: Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10-15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes.

Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice.

Increases in traditional serum lipid profiles are associated with obesity, cancer, and cardiovascular disease. Recent lipidomic analysis has indicated changes in serum lipidome profiles, especially in regard to specific phosphatidylcholines, associated with obesity. However, little work has evaluated murine hepatic liver lipidomic profiles nor compared these profiles across age, high-fat diet, or specific genotypes, in this case the lack of hepatic Cyp2b enzymes.

Gender differences in diet-induced steatotic disease in Cyp2b-null mice.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease; however, progression to nonalcoholic steatohepatitis (NASH) is associated with most adverse outcomes. CYP2B metabolizes multiple xeno- and endobiotics, and male Cyp2b-null mice are diet-induced obese (DIO) with increased NAFLD. However, the DIO study was not performed long enough to assess progression to NASH.

Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis.

Obesity is an endemic problem in the United States and elsewhere, and data indicate that in addition to overconsumption, exposure to specific chemicals enhances obesity. CYP2B metabolizes multiple endo- and xenobiotics, and recent data suggests that repression of Cyp2b activity increases dyslipidemia and age-onset obesity, especially in males. To investigate the role played by Cyp2b in lipid homeostasis and obesity, we treated wildtype and Cyp2b-null mice with a normal (ND) or 60% high-fat diet (HFD) for 10 weeks and determined metabolic and molecular changes.

Chemical Activation of the Constitutive Androstane Receptor Leads to Activation of Oxidant-Induced Nrf2.

Exposure to environmentally relevant chemicals that activate the xenobiotic receptors aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and peroxisome proliferator-activated receptor alpha (PPARα) in rodent test systems often leads to increases in oxidative stress (OS) that contributes to liver cancer induction. We hypothesized that activation of the oxidant-induced transcription factor Nrf2 could be used as a surrogate endpoint for increases in OS. We examined the relationships between activation of xenobiotic receptors and Nrf2 using previously characterized gene expression biomarkers that accurately predict modulation.

High fat diet induced obesity is mitigated in Cyp3a-null female mice.

Recent studies indicate a role for the constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity. Therefore, we examined whether Cyp3a-null mice show increased obesity and fatty liver disease following 8-weeks of exposure to a 60% high-fat diet (HFD). Surprisingly, HFD-fed Cyp3a-null females fed a HFD gained 50% less weight than wild-type (WT; B6) females fed a HFD.

Compensatory changes in CYP expression in three different toxicology mouse models: CAR-null, Cyp3a-null, and Cyp2b9/10/13-null mice.

Targeted mutant models are common in mechanistic toxicology experiments investigating the absorption, metabolism, distribution, or elimination (ADME) of chemicals from individuals. Key models include those for xenosensing transcription factors and cytochrome P450s (CYP). Here we investigated changes in transcript levels, protein expression, and steroid hydroxylation of several xenobiotic detoxifying CYPs in constitutive androstane receptor (CAR)-null and two CYP-null mouse models that have subfamily members regulated by CAR; the Cyp3a-null and a newly described Cyp2b9/10/13-null mouse model.