Selective PPARdelta agonist treatment increases skeletal muscle lipid metabolism without altering mitochondrial energy coupling: an in vivo magnetic resonance spectroscopy study.

Peroxisome proliferator-activated receptor-delta (PPARdelta) activation results in upregulation of genes associated with skeletal muscle fatty acid oxidation and mitochondrial uncoupling. However, direct, noninvasive assessment of lipid metabolism and mitochondrial energy coupling in skeletal muscle following PPARdelta stimulation has not been examined. Therefore, in this study we examined the response of a selective PPARdelta agonist (GW610742X at 5 or 100 mg.

Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.

Two-dimensional electrophoresis of liver proteins: characterization of a drug-induced hepatomegaly in rats.

Two-dimensional electrophoresis (2-DE) of liver proteins was applied to further characterize an unusual drug-induced increase in hepatocellular rough endoplasmic reticulum (RER) in Sprague-Dawley rats given a substituted pyrimidine derivative. Absolute liver weights of drug-treated rats (9.9 +/- 0.

Intralesional cytokines in chronic oxazolone-induced contact sensitivity suggest roles for tumor necrosis factor alpha and interleukin-4.

An analysis was conducted of the cytokine profile and inflammatory response in oxazolone sensitized mouse skin. Following exposure to oxazolone, the intralesional production of inflammatory cytokines was demonstrable at the levels of both mRNA and protein. An initial challenge led to a transient increase in tumor necrosis factor-alpha production followed predominately by the T helper (Th)1 cytokine, interferon-gamma.

Immunohistochemical evaluation of chemically induced rhabdomyosarcomas in rats: diagnostic utility of MyoD1.

Monoclonal antibodies (mAbs) to selected muscle proteins were assessed as potential immunohistochemical markers to assist in the definitive diagnosis of poorly differentiated soft tissue sarcomas in rats. A series of 7 rat rhabdomyosarcomas (RMS) induced with nickel subsulfide were studied by light microscopy and were evaluated for immunoreactivity to desmin, vimentin, fast (type II isoform) skeletal myosin, alpha-actin (smooth muscle isoform), or MyoD1 (myogenic regulatory protein) mAbs using an avidin-biotin-chromogen technique. Consecutive RMS slices were fixed in 10% neutral buffered formalin (the fixative routinely used in carcinogenicity bioassays) for periods of 3 days or 2 mo prior to paraffin embedding to determine the effect of fixation time on immunoreactivity.

Persistent airway eosinophilia after leukotriene (LT) D4 administration in the guinea pig: modulation by the LTD4 receptor antagonist, pranlukast, or an interleukin-5 monoclonal antibody.

Aerosolized cysteinyl leukotrienes (CysLTs) elicit migration of eosinophils into guinea pig lungs and the airways of patients with asthma. The present studies were designed to analyze the concentration-response relationship, time course, and pharmacologic and histologic characteristics of leukotriene D4 (LTD4)-induced eosinophil influx into the airways of conscious guinea pigs. Animals were exposed to aerosols of 0.

Morphology and incidence of hepatic foci of cellular alteration in Sprague-Dawley rats.

Morphology and incidence of altered hepatocellular foci (AHF) were evaluated in standard H&E-stained liver sections from 3 groups of control Sprague-Dawley (SD) rats (initially 70/sex/group) used in 2 2-yr carcinogenicity studies. All AHF observed could be classified as basophilic, eosinophilic, clear, vacuolated, or mixed types using criteria applied previously to the Fischer-344 (F-344) rat. Some eosinophilic foci were large and posed a diagnostic challenge in differentiation from hepatocellular adenoma.

Conjunctival leukocyte infiltration evoked by leukotrienes: differing responses among rodent species.

Application of leukotrienes (LT) B4 or D4 to the guinea-pig eye evokes conjunctival eosinophil infiltration, providing an in vivo model of tissue eosinophilia. To determine if other rodent species would respond similarly, LTB4 or LTD4 were applied to the right eye of male mice and rats (three per group) at doses of 250, 1000 or 5000 ng/eye (mice) and 1000 or 5000 ng/eye (rats). Left eyes received the same volume (mice, 5 microliters; rats, 20 microliters) of vehicle (isotonic saline).

Inhibition of antigen-induced bronchoconstriction and eosinophil infiltration in the guinea pig by the cyclic AMP-specific phosphodiesterase inhibitor, rolipram.

Selective inhibition of the low Km cyclic AMP-specific phosphodiesterase has been shown to inhibit inflammatory cell function and relax airway smooth muscle. These studies were conducted to characterize the bronchodilator and anti-inflammatory activity of rolipram, an archetypical cyclic AMP-specific phosphodiesterase inhibitor, in in vitro and in vivo guinea pig airway models. In isolated tracheal rings from ovalbumin (OA)-sensitive guinea pigs, both R- and S-enantiomers of rolipram (1 microM) significantly antagonized OA-induced contractions.

cAMP-specific phosphodiesterase inhibitor, rolipram, reduces eosinophil infiltration evoked by leukotrienes or by histamine in guinea pig conjunctiva.

The effect of rolipram, an isozyme IV-selective inhibitor of cAMP-specific phosphodiesterase, was evaluated in a guinea pig eye model of tissue eosinophilia. (R)-rolipram was administered by gavage to guinea pigs 1 h prior to topical ocular challenge with a mixture of leukotrienes (LTs) (10 ng LTB4 + 1000 ng LTD4/eye) or with histamine dihydrochloride (1 mg/eye). Conjunctivae were evaluated histologically 6 h after challenge.

Agonist-related differences in the relationship between cAMP content and protein kinase activity in canine trachealis.

We investigated the relationships between relaxation, cyclic AMP (cAMP) accumulation and cAMP-dependent protein kinase (cAMP-PK) activity in canine tracheal smooth muscle. In time course and concentration-response studies, forskolin and isoproterenol elicited relaxation of isolated trachealis strips that was accompanied by an increase in cAMP content and an activation of cAMP-PK. Although these results were consistent with the proposal that cAMP is a second messenger mediating relaxation of airway smooth muscle, close inspection of the data revealed a discrepancy in the relationship between cAMP accumulation and relaxation.

Distribution of fibre types and fibre sizes in the tibialis cranialis muscle of beagle dogs.

The percentages of Type I muscle fibres were measured systematically in ATPase-stained, transverse cryostat sections of whole tibialis cranialis muscles from 8 young, adult beagles. The distance of the section from the origin of the muscle does not significantly affect the mean percentage. There are no identifiable differences in mean percentages between right and left muscles.

Technique for physiological examination of canine skeletal muscle in vivo.

A technique is described for studying the physiological function of canine skeletal muscle in vivo. The contractile properties of the tarsal flexor muscles were examined in three beagle dogs under general anaesthesia. The force responses to electrical stimulation of the common peroneal nerve were measured at various frequencies to determine the frequency:force relationship for this muscle group.

Acute Lantana camara toxicity in cattle.

An outbreak of acute Lantana camara poisoning in cattle is described in which 10 out of 91 animals died. The affected cattle became icteric and voided soft, black faeces. Necropsies were performed on three steers, and the macro- and microscopical changes in their livers and kidneys were compatible with those of L.

Myopathy with core-like structures in a dog.

Core-like structures were seen histologically in many of the fibres of the triceps and biceps femoris muscles of an 18-months-old male Great Dane with muscle weakness and moderate proximal muscular atrophy. The structures were lightly staining and lacked cross-striations. Some contained vacuoles and nuclei.

A suspected lipofuscin storage disease of sheep associated with ingestion of the plant, Trachyandra divaricata (Jacq.) Kunth.

Paresis afflicted 85 out of a flock of 770 young Merino ewes kept on old wheat lands in the western Cape during a period of drought. Many of the paretic ewes died. The vegetation was sparse and was dominated by Trachyandra divaricata.

A haemorrhagic syndrome in recently weaned pigs ascribed to hypovitaminosis K.

An outbreak of a haemorrhagic syndrome involved recently weaned, mixed-breed pigs in a large piggery. The pigs were fed a pelleted complete ration containing antibacterial drugs. Affected pigs failed to grow, became pale and developed large, subcutaneous haematomas.

An outbreak of cerebrocortical necrosis (polioencephalomalacia) in goats.

In a herd of 30 Boer goats, 3 young goats developed nervous signs including apparent blindness. In 2 of the goats a diagnosis of cerebrocortical necrosis was confirmed by the demonstration of lesions typical of the disease on histopathological examination. Lead concentrations in the renal cortex were well below the level regarded as indicative of lead poisoning in ruminants.

Resistance of sheep to poisoning by The plant, Marticaria nigellifolia DC.

The plant, Matricaria nigellifolia, was dosed to 2 sheep to reinvestigate whether or not sheep are susceptible to pushing disease ("stootsiekte"). Each sheep received a total dose of 370 g/kg of the milled, dried plant from a batch that had caused pushing disease in cattle when given at doses as low as 10 g/kg. Neither of the sheep developed clinical disease over the trial period of 60 days, and necropsies revealed no macro- or microscopical lesions.

A tremorgenic mycotoxicosis of cattle caused by maize sprouts infested with Aspergillus clavatus.

An outbreak of disease affecting a herd of 16 dairy cattle which were fed mouldy, sprouted maize is described. Eight of the cattle were affected, 5 of which died. The clinical signs included muscular tremors, hypersensitivity, ataxia, anorexia and salivation.

Pathology of a nervous disorder (pushing disease or "stootsiekte") in cattle caused by the plant Matricaria nigellifolia DC. (Asteraceae).

Brains from 10 bovine field cases of pushing disease, a nervous disorder caused by the plant, Matricaria nigellifolia, were examined by light microscopy. Moderate to marked encephalitis, characterized by predominantly perivascular microgliosis, perivascular lymphocytic infiltrates and reactive changes in astrocytes, was present in all the brains. The lesion was concentrated in the white matter throughout the forebrain and midbrain.

Measurements of mass, length and valve diameters from normal formalin-fixed ovine hearts.

Hearts from 60 Merino sheep of known age, sex and live mass and with no known history of disease were collected and fixed in buffered 10% formalin. Systematic light microscopical examination did not indicate any abnormality in hearts of any of the sheep. The mass of various parts of the hearts, the length of the hearts and the diameters of the heart valves were measured to establish a basis for quantitative assessment of possible pathological changes associated with the ingestion of cardiotoxic plants.

Myocardial pathology of domestic ruminants in southern Africa.

Myocardial pathology of ruminants in southern Africa, including lesions associated with toxic plants, other toxic agents, infectious agents and nutritional deficiency, is discussed with regard to recognition and to aetiological diagnosis. Findings are included which have not been published elsewhere. The importance and difficulties in recognition of myocardial lesions at an early stage are emphasized.