Spontaneous nephroblastoma with oncocytic differentiation in a Japanese White rabbit.

Spontaneous nephroblastoma is an uncommon tumor in laboratory rabbits. We recently encountered this tumor, and we describe its histological characteristics in this report. A male 3-year-old Japanese White rabbit (JW/kbs), maintained as a stock animal, suddenly showed poor condition and was found dead a few days later. At necropsy, a large mass was found that extended from one side of the renal pelvis. The cut surface of the mass was dark red in color and velvety to the touch. The kidney on the contralateral side was normal. Microscopically, the tumor mass consisted of biphasic components, which consisted of epithelial (tubular and glomerular) and blastemal (nodular) elements. No sarcomatous proliferation was observed. In addition, some of the tubules were lined by cells with a large amount of eosinophilic cytoplasm. The cells were confirmed as oncocytes by immunohistochemical and electron microscopic examinations. The present case was therefore diagnosed as a nephroblastoma with oncocytic differentiation.

Trans-eyelid distribution of epinastine to the conjunctiva following eyelid application in rabbits.

PURPOSE: To reveal the penetration of epinastine, an anti-allergic ophthalmic agent, into the eyelid and its distribution to the conjunctiva after administration of a cream formulation on rabbit eyelid skin. STUDY DESIGN: Experimental study. METHODS: Rabbits were treated with 0.5% epinastine cream on hair-shaved eyelids, followed by preparation of eyelid tissue slices to determine spatial tissue distribution of epinastine by liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantification using laser-microdissected tissues and desorption electrospray ionization mass spectrometry imaging (DESI-MSI). In addition, following either eyelid application of 0.5% epinastine cream or ocular instillation of 0.1% epinastine eye drops, concentration-time profiles of epinastine in the palpebral conjunctiva and bulbar conjunctiva were determined using LC-MS/MS. RESULTS: Laser microdissection coupled with LC-MS/MS analysis detected high concentrations of epinastine around the outermost layer of the eyelid at 0.5 h post-administration that gradually diffused deeper into the eyelid and was distributed in the conjunctival layer at 8 and 24 h post-administration. Similar time-dependent drug distribution was observed in high-spatial-resolution images obtained using DESI-MSI. Epinastine concentrations in the conjunctival tissues peaked at 4-8 h after administration of 0.5% epinastine cream and then decreased slowly over 72 h post-administration. In contrast, epinastine concentrations peaked quickly and decreased sharply after epinastine eye drop administration. CONCLUSION: After the application of epinastine cream to the eyelid skin, epinastine gradually permeated the eyelid. The compound was retained in the conjunctiva for 8-24 h post-administration, indicating that epinastine cream is a promising long-acting formulation for treating allergic conjunctivitis.

MALDI imaging mass spectrometry revealed atropine distribution in the ocular tissues and its transit from anterior to posterior regions in the whole-eye of rabbit after topical administration.

It is essential to elucidate drug distribution in the ocular tissues and drug transit in the eye for ophthalmic pharmaceutical manufacturers. Atropine is a reversible muscarinic receptor used to treat various diseases. However, its distribution in ocular tissues is still incompletely understood. Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS) evaluates drug distribution in biological samples. However, there have been few investigations of drug distribution in ocular tissues, including whole-eye segments. In the present study, we explored the spatial distribution of atropine in the whole-eye segment by MALDI-IMS, and then evaluated the changes in atropine level along the anterior-posterior and superior-inferior axes. A 1% atropine solution was administered to a rabbit and after 30 min, its eye was enucleated, sectioned, and analyzed by MALDI-IMS. Atropine accumulated primarily in the tear menisci but was found at substantially lower concentrations in the tissue surrounding the conjunctival sacs. Relative differences in atropine levels between the anterior and posterior regions provided insights into the post-instillation behavior of atropine. Atropine signal intensities differed among corneal layers and between the superior and inferior eyeball regions. Differences in signal intensity among tissues indicated that the drug migrated to the posterior regions via a periocular-scleral route. Line scan analysis elucidated atropine transit from the anterior to the posterior region. This information is useful for atropine delivery in the ocular tissues and indicates that MALDI-IMS is effective for revealing drug distribution in whole-eye sections.

Bilateral hamartomatous medullary lipoma within the nasal turbinate bones in a cynomolgus monkey (Macaca fascicularis).

A 15-year-old male cynomolgus monkey (Macaca fascicularis) showed large bilateral masses in the maxillary sinus. In histopathological examination, both masses revealed benign medullary lipomas within the turbinate bones. The tumors were composed of well-developed lipocytes, trabecular bones and a few blood vessels. Although we initially diagnosed the tumor as bilateral lipomas in the nasal turbinates, it was not differentiated from lipomatous hamartoma. Findings, such as unique symmetrical proliferation, lack of border from the normal marrow and the intact surrounding tissue, indicated a lipomatous hamartoma/hamartomatous lipoma, thought to be a suitable diagnosis of the lesion. Of most interest was that such a proliferating lesion occurred in the nasal turbinate.