Serum levels of the pro-inflammatory apolipoprotein CIII (apoCIII) are increased in type-1 diabetic (T1D) patients and when β-cells are exposed to apoCIII they undergo apoptosis, which can be prevented by an antibody against apoCIII. We have previously investigated the BB rat, an animal model that develops a human-like T1D at the age of around 60 days, and found that apoCIII was also increased in sera from pre-diabetic rats and this promoted β-cell death. Lowering apoCIII with an oligonucleotide antisense during a phase of the pre-diabetic period prolonged the time to onset of T1D. In order to find other ways to lower apoCIII we in this study tested non-alcoholic red wine with medium and high concentrations of polyphenols and the lipid-lowering drug, fenofibrate, both reported to decrease the expression of apoCIII by activating peroxisome proliferator-activated receptors. Pre-diabetic BB-rats were treated orally for one month prior to the expected onset of diabetes with the two different wines or fenofibrate. None of the treatments prevented or prolonged the time to onset of diabetes and the expression of apoCIII was unaffected in this animal model for T1D. However, it must be emphasized that this does not exclude that other species can show a response to these substances.
Animals ; Apolipoprotein C-III ; Apoptosis ; Diabetes Mellitus* ; Fenofibrate* ; Humans ; Models, Animal ; Peroxisome Proliferator-Activated Receptors ; Polyphenols ; Rats ; Rats, Inbred BB* ; Wine*

BACKGROUND/AIMS: Type 1 diabetes is often accompanied by gastrointestinal motility disturbances. Vagal neuropathy, hyperglycemia, and alterations in the myenteric plexus have been proposed as underlying mechanism. We therefore studied the relationship between vagal function, gastrointestinal motiliy and characteristics of the enteric nervous system in the biobreeding (BB) rat known as model for spontaneous type 1 diabetes. METHODS: Gastric emptying breath test, small intestinal electromyography, relative risk-interval variability, histology and immunohistochemistry on antral and jejunal segments were performed at 1, 8 and 16 weeks after diabetes onset and on age-matched controls. RESULTS: We observed no consistent changes in relative risk-interval variability and gastric emptying rate. There was however, a loss of phases 3 with longer duration of diabetes on small intestinal electromyography. We found a progressive decrease of nitrergic neurons in the myenteric plexus of antrum and jejunum, while numbers of cholinergic nerve were not altered. In addition, a transient inflammatory infiltrate in jejunal wall was found in spontaneous diabetic BB rats at 8 weeks of diabetes. CONCLUSIONS: In diabetic BB rats, altered small intestinal motor control associated with a loss of myenteric nitric oxide synthase expression occurs, which does not depend on hyperglycemia or vagal dysfunction, and which is preceded by transient intestinal inflammation.
Animals ; Breath Tests ; Carbamates ; Diabetes Mellitus ; Electromyography ; Enteric Nervous System ; Gastric Emptying ; Gastrointestinal Motility ; Hyperglycemia ; Immunohistochemistry ; Inflammation ; Jejunum ; Myenteric Plexus ; Nitrergic Neurons ; Nitric Oxide Synthase ; Organometallic Compounds ; Rats ; Rats, Inbred BB

OBJECTIVETo study the changes of serum neuron specific enolase in rats with septic shock.

METHODSThe model of septic shock was set up by injection of lipopolysaccharide (LPS, from Escherichia coil O55: B5) at a dose of 25 mg/kg through femoral vein. Twenty male Wistar rats were randomly divided into 2 groups: normal control group (LPS was substituted by same volume of normal saline solution) and septic shock group. Six hours after the septic shock model formed, whole blood was taken for measuring the serum neuron specific enolase (NSE). The brains of the rats were taken for histopathological examination.

RESULTSThe serum NSE of septic shock group was significantly higher than that of control group [(10.0781 +/- 0.526) microg/L vs. (3.7188 +/- 0.602) microg/L, P < 0.05]. Neurons were severely damaged 6 hours after injection of LPS. Neuronal necrosis and the damage of blood-brain barrier were seen by light and electron microscope in septic shock group but not in the control group.

CONCLUSIONNSE in serum increased when septic encephalopathy occurred, which indicated that NSE might become a marker of neural damage in septic shock.

Animals ; Biomarkers ; blood ; Blood Pressure ; Blood-Brain Barrier ; ultrastructure ; Brain ; cytology ; pathology ; Cell Death ; Disease Models, Animal ; Male ; Microscopy, Electron ; Neurons ; pathology ; ultrastructure ; O Antigens ; toxicity ; Phosphopyruvate Hydratase ; blood ; Rats ; Rats, Inbred BB ; Shock, Septic ; blood ; enzymology ; pathology