Pierre Duprat

Effect of chronic growth hormone administration on skeletal muscle in dogs.

Administration of growth hormone (GH) results in increased body weight gain in dogs. Increased body weight gain is believed to be a result of the trophic effect of GH on the musculoskeletal system. However, edema is one of the side effects described in man following exogenous GH administration. Thus, the objective of this study was to determine if the expected increased weight gain in GH-treated dogs is a result of increased muscle mass. Porcine growth hormone (pGH), administered subcutaneously to beagle dogs at doses of 0.025, 0.1, and 1 IU/kg/day for 14 wk, resulted in elevated serum GH and insulin-like growth factor-1 (IGF-1) levels (see accompanying paper, Prahalada et al). This was associated with a significant increase in body weight gain and weights of the cranial tibialis muscle in both male and female dogs. The increased muscle mass likely contributed to the significant increase in body weight gain seen in both sexes. Quantitative analysis of skeletal muscle sections stained for ATPase activity showed increases in type I (slow twitch) and type II (fast twitch) myofiber sizes in mid- and high-dose males and in high-dose females. The ratio of type I and type II muscle fibers remained unchanged. Hypertrophic myofibers were enlarged but had a normal histologic and ultrastructural organization when observed by light and transmission electron microscopy. The results of this study have demonstrated that increased muscle mass in pGH-treated dogs is related to hypertrophy of muscle fibers and not due to edema. Exogenous GH administration has an anabolic effect on skeletal muscle in dogs.

Rat Urinary Bladder Hyperplasia Induced by Oral Administration of Carbonic Anhydrase Inhibitors

The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium.

Spontaneous renal disease in laboratory animals.

Publisher Summary This chapter discusses spontaneously occurring renal diseases in laboratory animals. Spontaneously occurring renal diseases are common in laboratory animals. However, the diseases vary with each species examined. The chapter also discusses the importance of knowing the background disease patterns in laboratory animals. Knowing the background diseases in a species or strain of animal will aid an investigator in selecting or avoiding a given species for experiments. Such knowledge is also important to understand the similarities or differences between animal and human renal diseases. In some cases, the renal diseases in animals are identical to a human disease whereas in other cases, the diseases in animals have no human counterpart. An example of a disease occurring in animals but not in humans is the chronic renal disease of rats. All rat strains develop chronic renal disease. The cause is unknown, but it is rat-specific with no counterpart in humans. The renal anatomy, histology, and physiology of laboratory animals and humans are similar but not identical. Laboratory animals have a single renal papilla in contrast to humans where there are several conical regions called pyramids. Like humans, animals have a uniform tan to brown color and a smooth glistening capsular surface of the kidney. The functional unit of the kidney is the nephron and the distal tubule is connected to a system of collecting ducts. The nephrons and collecting ducts arise from different embryological primordial. The glomerulus consists of a tuft of capillaries enclosed within Bowmans capsule. The capillaries are lined by thin endothelium and a thin visceral layer of epithelium.

Morphological Changes in the Pituitary Gland of Dogs Chronically Exposed to Exogenous Growth Hormone

Growth hormone (GH) synthesis and release from the pituitary is regulated by hypothalamic releasing hormone, insulin-like growth factor-1 (IGF-1), and somatostatin. However, the potential effects of pharmacological doses of exogenous GH on the pituitary are not well studied. To determine the potential chronic effects of exogenous GH on pituitary morphology in dogs, porcine GH (pGH) was administered subcutaneously to 3 groups of dogs (4 animals/sex/group) at doses of 0.025, 0.1, and 1.0 IU/kg/day for 14 wk. A group (4/sex) of dogs served as the vehicle control. The pituitaries from all dogs were weighed and fixed in appropriate fixatives for light and electron microscopic examination; in addition, cells of the pars distalis were quantitated by a point counting method following immunostaining to identify cells containing GH, prolactin (PRL), and adrenocorticotrophic (ACTH) hormones. Administration of pGH resulted in a statistically significant (p ≤ 0.05) increased pituitary weight through the high dose. By light microscopy (LM), hypertrophy of pars distalis cells was evident in mid- and high-dose female dogs. The pituitaries of dogs given the lowest dose (0.025 IU/kg/day) of pGH were not remarkable based on weight and LM findings. In addition, transmission electron microscopic (TEM) examination of the pituitary gland of high-dose dogs demonstrated, in both sexes, pituitary cells with variably dilated rough endoplasmic reticulum and decreased numbers of secretory granules; some of these cells reacted positively to GH immunostaining. Quantitative analysis of the pituitary gland of high-dose males and females showed an increase in the absolute volume of all cell populations studied: GH-, PRL-, and ACTH-positive cells. Based on the LM and TEM findings, the increased volume of the cell populations studied is likely related to cellular hypertrophy. The expected elevation in serum GH levels following repeated administration of pGH and an associated elevation in serum IGF-1 levels resulted in morphologic changes in the pituitary gland of dogs given high doses (≥0.1 IU/kg/day) of pGH; these observations differed from the reported findings in pituitaries of transgenic mice secreting large quantities of bovine GH.

Lipidosis Induced in the Dog Gallbladder by a Direct 5-Lipoxygenase Inhibitor

The direct 5-lipoxygenase inhibitor L-739,010 was administered at a dose of 60 mg/kg/day per os to beagle dogs for 15 days. Histopathological examination of gallbladders from treated dogs showed epithelial vacuolation and submucosal infiltration by foamy macrophages that were positive for lipids in Sudan Black-and/or Oil Red O-stained sections. Scanning electron microscopic examination of gallbladder mucosa showed thickening of epithelial folds and multifocal epithelial membrane disruptions. Transmission electron microscopy confirmed these findings and showed mucosal epithelial cell lipid droplet accumulation and submucosal infiltration of macrophages filled with lipid droplets, myelin figures, heterophagosomes, and cholesterol clefts. These changes resembled those reportedly seen in the human gallbladder with cholesterolosis and/or chronic cholecystitis.

Morphological Changes in the Kidney of Dogs Chronically Exposed to Exogenous Growth Hormone

Porcine growth hormone was administered subcutaneously to beagle dogs at doses of 0.025,0.1, and 1 IU/kg/d for 14 weeks, markedly elevating serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. This was accompanied by a significant increase in body weight gain and kidney weights in both male and female dogs. The increase in kidney weight (6 to 54%) was slightly greater than the increase in body weight (6 to 40%). By light microscopy, glomerular deposits, mesangial thickening, and very slight cellular infiltration in glomeruli were seen in mid- and high-dose groups. Based on morphometric evaluation, there was an increase in the renal glomerular area, which was statistically significant (p ≤ 0.05) in the mid- and high-dose males and in the high-dose females. This was associated with a statistically significant (p ≤ 0.05) increase in the number of total glomerular cells in the mid- and high-dose males. By transmission electron microscopy, thickening of the glomerular basal lamina and diffuse increase of the mesangial matrix were observed in both male and female dogs in the mid- and high-dose groups. Immunohistochemical reactions were negative for IgG, IgM, and C3. The morphological changes in the kidney of dogs resemble the diffuse glomerulosclerosis described in human diabetic nephropathy.

Anatomy of the Ocular Surfaces, Cornea, and Conjunctiva, Rat and Mouse

The eyes are protected by eyelids and suspended in the orbit by ocular muscles, which are also responsible for eye movements. The eyeball is a multilayered structure: an external fibrous layer for protection, an intermediate vascular layer for nutrition, and an internal layer connected to the central nervous system (CNS) for photoreception. The other ocular structures - aqueous humor, lens, and vitreous body - are accessory visual structures.

Leiomyoma of the Iris, Sprague-Dawley Rat

A leiomyoma of the iris was composed of bundles of spindle-shaped cells with abundant myoglial fibres and represents the first observation of this rare tumour in a rat.

Suppurative Nephritis, Pyelonephritis, Rat

In the early stage, no changes are seen grossly. Advanced stages can be characterized by an increased size and discoloration of the kidneys. In suppurative nephritis, changes are mostly confined to the cortex. The inflammation produces numerous small yellow nodules, well delineated and surrounded by a red rim and usually more frequent in the cortex than in the medulla.

Suppurative Nephritis and Pyelonephritis, Rat

In the early stage, no changes are seen grossly. Advanced stages can be characterized by an increased size and discoloration of the kidneys. In suppurative nephritis, changes are mostly confined to the cortex. The inflammation produces numerous small, yellow nodules, well delineated and surrounded by a red rim and usually more frequent in the cortex than in the medulla.