The circadian clock, shift work, and tissue-specific insulin resistance

Obesity and type 2 diabetes (T2D) have become a global health concern. The prevalence of obesity and T2D is significantly higher in shift workers compared to people working regular hours. An accepted hypothesis is that the increased risk for metabolic health problems arises from aberrantly timed eating behavior, that is, eating out of synchrony...

Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia

High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...

Chronic PYY3-36 treatment promotes fat oxidation and ameliorates insulin resistance in C57BL6 mice

PYY3-36 is a gut-derived hormone acting on hypothalamic nuclei to inhibit food intake. We recently showed that PYY3-36 acutely reinforces insulin action on glucose disposal in mice. We aimed to evaluate effects of PYY3-36 on energy metabolism and the impact of chronic PYY3-36 treatment on insulin sensitivity. Mice received a single injection of...

Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: Manufacture on PER.C6 cells, tropism and immunogenicity

Recombinant adenoviral vectors based on type 5 (rAd5) show great promise as a vaccine carrier. However, neutralizing activity against Ad5 is prevalent and high-titred among human populations, and significantly dampens Ad5-based vaccine modalities. The generation of alternative adenoviral vectors with low seroprevalence thus receives much...

The accuracy of extended histopathology to detect immunotoxic chemicals

The accuracy of extended histopathology to detect immunotoxic chemicals in female B6C3F1 mice was evaluated under the auspices of the National Toxicology Program (NTP). A workgroup was formed consisting of four pathologists who conducted extended histopathological evaluation of lymphoid tissues obtained from a subset of NTP toxicology studies,...

Bioavailability and metabolism

Mistaken self, a novel model that links microbial infections with myelin-directed autoimmunity in multiple sclerosis

Several findings indicate that infectious events play a role in the pathogenesis of multiple sclerosis (MS). At the same time, T-cell autoimmunity to myelin antigens is widely believed to be crucial to the development of MS lesions. Several mechanisms have been put forward to explain the presumed link between microbial infections and myelin...

Tolerance controls encephalitogenicity of αB-crystallin in the Lewis rat

The myelin-associated protein, αB-crystallin, is considered a candidate autoantigen in multiple sclerosis (MS). In the present study, we examined the potential of αB-crystallin to induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Attempts to induce EAE with either bovine, rat or murine αB-crystallin or αB-crystallin peptides...

Toxicology of chemical mixtures: Challenges for today and the future

A major challenge for the toxicologist involved in safety evaluation of chemical mixtures is to test the hypothesis that as a rule exposure to mixtures of chemicals at (low) non-toxic doses of the individual chemicals is of no health concern. A series of repeated dose studies in rats with defined mixtures of chemicals with the same or different...

Long-term changes in glial fibrillary acidic protein and calcium levels in rat hippocampus after a single systemic dose of kainic acid

Chemicals/CAS: calcium, 7440-70-2; kainic acid, 487-79-6; Biological Markers; Calcium, 7440-70-2; Glial Fibrillary Acidic Protein; Kainic Acid, 487-79-6; Neurotoxins

Characterization and fibrinolytic properties of human omental tissue mesothelial cells. Comparison with endothelial cells

It has been reported that omental fat tissue is a good source of human microvascular endothelial cells. By characterization we demonstrate that the epithelioid cells isolated from omental tissue are not endothelial cells, but mesothelial cells. They contain abundant cytokeratins 8 and 18, which are absent in endothelial cells, and vimentin. No...

Distribution of tissue-type plasminogen activator (activity and antigen) in rat tissues.

Tissue-type plasminogen activator (PA) activity and antigen was measured in nine different tissues from healthy rats (brain, lung, heart, liver, spleen, kidney, adrenal, aorta and skeletal muscle). After extraction in a KSCN buffer (for kidney) or in an acid acetate buffer (for all other tissues), total PA activity was determined by an improved...

Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo

The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the...