The codependence of angiogenesis and chronic inflammation.

Angiogenesis is the growth of new blood vessels from existing ones. It is an important aspect of new tissue development, growth, and tissue repair. It is also a component of many diseases including cancer, blindness, and chronic inflammation such as rheumatoid arthritis (RA) and psoriasis. There is considerable evidence to suggest that angiogenesis and chronic inflammation are codependent; recent studies have begun to reveal the nature of this link, which involves both augmentation of cellular infiltration and proliferation and overlapping roles of regulatory growth factors and cytokines. Through these studies, we have begun to understand the codependence of chronic inflammation and angiogenesis, the potential benefits of targeting angiogenesis in the treatment of chronic inflammation, and of targeting chronic inflammation to affect angiogenesis.

Hydronephrosis in rats associated with postnatal exposure to a fatty acid oxidation inhibitor.

Methyl palmoxirate, an inhibitor of long-chain fatty acid oxidation, was administered by gavage (0, 1, 5, or 20 mg/kg/day) to female rats over the last third of gestation and throughout lactation. Weight gain (mid- and high-dosage group) and survivability (high-dosage group) were significantly (p less than or equal to 0.05) reduced in offspring of methyl palmoxirate-treated dams as compared to control offspring. Mid- and high-dosage male offspring found dead after Day 4 of lactation exhibited grossly distended bladders and renal pelves. A dosage-related increased incidence of dilated renal pelves was observed in both sexes at necropsy of 21-day-old mid- and high-dosage group pups. Microscopic examination of the urinary tracts of a number of affected pups revealed renal parenchymal atrophy and urethral obstruction. Drug disposition studies indicated lactating pups were exposed to significant amounts of methyl palmoxirate via mammary secretions. Cross-fostering experimentation suggested that some of the adverse effects observed in offspring were due to lactational, rather than in utero, exposure.

Metabolic control of prevention of nephropathy by 2-tetradecylglycidate in the diabetic mouse (db/db).

The genetically diabetic mouse (db/db) exhibits hyperphagia, progressive weight gain, hyperglycemia, and hyperinsulinemia during the first few months of life during which time characteristic pathologic changes occur in several organ systems including the kidney. The extent to which long chain fatty acid oxidation (LCFAO) contributes to excessive gluconeogenesis and hyperglycemia in these animals in unknown. Therefore, the synthetic fatty acid analogue 2-tetradeclyglycidate (TDHA), a potent inhibitor of LCFAO, was given orally to db/db mice to evaluate its capacity to control the blood glucose and prevent their diabetic nephropathy. Five groups of diabetic mice (N = 6) were assigned to receive TDGA in a dose of 5, 10, and 25 mg/kg/day, vehicle (tragacanth), or nothing (control). TDGA had no observable effects on food intake or growth patterns. Drug-treated animals had significant lowering of fasting glucose at 0 and 4 h after dosing during the midportion of the study (2-6 wk). In the latter part of the study (wk 8-11), blood glucose 4 h after dosing was lowered in mice given 10 and 25 free fatty acids. Animals receiving TDGA 25 mg/kg/day exhibited significant inhibition of immunopathologic changes in the kidney. Heart weight was significantly increased in mice receiving TDGA 25 mg/kg/day, and the total amount of myocardial carnitine content was increased in all three drug-treated groups. Increased tissue deposition of lipid was not apparent on histologic examination of liver in drug-treated animals. Inhibition of long chain fat oxidation in the db/db mouse results in significant lowering of blood glucose, and decreased the renal immunopathologic features of diabetic nephropathy in this animal model.

Tumours of the pancreas.

Tumours of the pancreas occur most commonly in dogs and cats and only rarely in other domestic species. The incidence of neoplasms, both exocrine and endocrine, increases with age. Exocrine adenocarcinomas are the most common malignant tumours and have three fairly distinct morphological patterns: small tubular, large tubular, and acinar cell (rare). They readily metastasize, usually before clinical signs are apparent. A "starry sky" pattern with clear histiocytes scattered among tumour cells is a regular feature of poorly differentiated areas of small tubular adenocarcinomas and undifferentiated carcinomas. Islet cell tumours occur in a significant number only in dogs. Metastases are found in about half of the tumours, but malignancy cannot always be predicted by the morphological appearance. Slightly more than half of the islet cell tumours reported in the dog have been associated with clinical signs of hypoglycaemia. Nodular hyperplasia and exocrine adenomas are sometimes difficult to differentiate. Adenomas are considered rare while nodular hyperplasia is common in old animals.

Malignant teratoid medulloepithelioma in a dog.

A malignant teratoid medulloepithelioma that arose from the ciliary body was found in an adult Beagle. The anterior part contained relatively well-differentiated tumor cells, cartilage, and ganglion cells. These structures were interpreted as teratoid formations derived from the embryonic anlage of the medullary epithelium. The more posterior part was highly anaplastic and invasive. A transitional area contained neural rosettes of the Flexner-Wintersteiner type. This tumor is rare in both man and animals.

The pathology of subacute methylmerculialism in swine.

Clinical signs of toxicosis, neurologic lesions, and elevated tissue residues of methylmercury (MM) were produced in 12 pigs by oral administration of 1.29, 0.86, 0.64, and 0.43 mg mercury/kg of body weight daily as methylmercuric hydroxide (MMH). Clinical signs which began on day 17 were ataxia, dysmetria, blindness, convulsions, paresis, and death. Time of onset of signs was inversely related to size of daily dose. Microscopic lesions were found in the cerebrum brain stem, and spinal cord, and correlated well with clinical signs. The cerebrum in which severity of lesions was directly related to length of exposure was the most severely affected region of the central nervous system (CNS). Lesions were neuronal necrosis, neuronophagia, cortical vacuolation, axon swelling, gliosis, leptomeningitis, and vascular fibrinoid necrosis. Neuronal necrosis was most extensive within mid and deep cerebrocortical laminae. Brain residues of MM were directly proportional to the size of daily dose, and statistically significant. Distribution of MM among different tissues was rather uniform with highest concentrations found in liver, followed by kidney, muscle, spleen, and brain.

Tumours of the eye and adnexa.

Most types of epithelial tumour of the eyelids, conjunctiva, and cornea occur in all species; the most common type occurring in any species is bovine squamous cell carcinoma. Iridociliary epithelial tumours and malignant melanomas are the most important intraocular tumours. The histological features of the tumours are described under the following main headings: epithelial tumours of the eyelids, conjunctiva, and cornea; mesenchymal tumours (extraocular, optic nerve and nerve sheath, and uveal tract); neuroectodermal tumours; and melanogenic tumours of the eyelids and conjunctiva and of the uveal tract.