Effect of Simvastatin, an Established Lipid-Lowering Drug, on Pulmonary Chlamydia pneumoniae Infection in Mice

The effects of simvastatin treatment on Chlamydia pneumoniae lung infection, inflammation, and serum lipids in mouse model were studied. Simvastatin decreased viable chlamydial counts and increased inflammatory cell infiltrates in the lung tissue, suggesting that simvastatin treatment had both antichlamydial and immunomodulatory effects during an acute C. pneumoniae infection

Behaviour, stress and welfare of Sprague Dawley rats (Rattus norvegicus) on diet board feeding for 24 months

Abstract Diet board (DB) feeding aims to reduce the health hazards associated with ad libitum (AL) feeding. Rats have to gnaw wood to detach food from the DB, reducing their food consumption. We studied the welfare effects of DB by measuring faecal corticosterone metabolites (FCM), elevated plus-maze (EPM) behaviour and cage behaviour. In this two-year experiment, 147 group housed (n = 3) Hsd:Sprague Dawley® male and female rats were subjected to DB or AL feeding. DB feeding in females elevated FCMs and increased eating observations by 85%. The DB males were observed eating 30% more often and resting 4.2% less than their AL counterparts. The DB rats of both sexes had 19% increased cage exploration during daytime and 20% reduced grooming during night-time compared to the AL rats. The increased FCMs may indicate slight stress in DB females. The EPM results indicate there was no anxiety due to DB feeding at six months. The cage behaviour could point to mild chronic stress in DB rats, but the lack of effect on escape-related behaviour and agonism suggests that there were no substantial welfare problems. DB feeding did not seem to disturb the circadian rhythm. The smaller food requirements of DB females meant they had to sacrifice less time than males gnawing at the DB to satisfy their appetite

Caloric restriction ameliorates angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy

Angiotensin II-induced cardiac damage is associated with oxidative stress-dependent mitochondrial dysfunction. Caloric restriction (CR), a dietary regimen that increases mitochondrial activity and cellular stress resistance, could provide protection. We tested that hypothesis in double transgenic rats harboring human renin and angiotensinogen genes (dTGRs). CR (60% of energy intake for 4 weeks) decreased mortality in dTGRs. CR ameliorated angiotensin II-induced cardiomyocyte hypertrophy, vascular inflammation, cardiac damage and fibrosis, cardiomyocyte apoptosis, and cardiac atrial natriuretic peptide mRNA overexpression. The effects were blood pressure independent and were linked to increased endoplasmic reticulum stress, autophagy, serum adiponectin level, and 5' AMP-activated protein kinase phosphorylation. CR decreased cardiac p38 phosphorylation, nitrotyrosine expression, and serum insulin-like growth factor 1 levels. Mitochondria from dTGR hearts showed clustered mitochondrial patterns, decreased numbers, and volume fractions but increased trans-sectional areas. All of these effects were reduced in CR dTGRs. Mitochondrial proteomic profiling identified 43 dTGR proteins and 42 Sprague-Dawley proteins, of which 29 proteins were in common in response to CR. We identified 7 proteins in CR dTGRs that were not found in control dTGRs. In contrast, 6 mitochondrial proteins were identified from dTGRs that were not detected in any other group. Gene ontology annotations with the Panther protein classification system revealed downregulation of cytoskeletal proteins and enzyme modulators and upregulation of oxidoreductase activity in dTGRs. CR provides powerful, blood pressure-independent, protection against angiotensin II-induced mitochondrial remodeling and cardiac hypertrophy. The findings support the notion of modulating cardiac bioenergetics to ameliorate angiotensin II-induced cardiovascular complications