Extensive neurosarcoidosis and optic nerve complications

We present the case of a 35-year-old patient suffering from nasal obstruction and headache for 3 years. The patient was hospitalized for a recent and progressive decline of vision of the right eye associated with afferent pupillary deficit and inferior altitudinal hemianopsia. He was diagnosed with systemic sarcoidosis involving the central nervous system as illustrated by magnetic resonance imaging (MRI) scans showing different type diffuse lesions of meningo-encephalitis. Our case is characterized by severe cerebral pachyleptomeningeal lesions complicated by optic nerve compression and cervical spinal cord damage. MRI value of diagnosis for systemic neurosarcoidosis was supported by histological examination of a biopsy of the sphenoid sinus lesions that showed epithelioid granulomas presence without caseous necrosis. Thus, MRI of the brain and spinal cord is a powerful tool method in monitoring and diagnosing aymptomatic and symptomatic neurosarcoïodosis. MRI is also a powerful tool in monitoring the neurosarcoidosis during therapeutic treatments

Apoptosis Contributes to Amphotericin B- Induced Nephrotoxicity

The aim of this study was to investigate whether apoptosis contributes to nephrotoxicity caused by amphotericin B (AmB). By detecting apoptosis-specific DNA fragmentation, it is demonstrated that proximal tubular cells (LLC-PK(1)) and medullary interstitial cells (RMIC) respond with programmed cell death when treated with therapeutic doses of AmB. Concomitant application of AmB and recombinant human insulin-like growth factor-1 (rhIGF-1), a known antiapoptotic agent, abrogated apoptosis in vitro. To validate that the observed apoptotic effects on renal tissue culture cells are applicable to an in vivo setting, an animal model was used for verification. Therefore, Sprague-Dawley rats were treated with AmB. The drug caused hypokalemia, decreased weight gain, loss of renal concentrating ability, and dehydration in a dose-dependent fashion. Microscopic examination of renal tissue sections revealed apoptotic alterations predominantly in proximal and distal tubular epithelial cells. To verify that the observed clinical side effects were linked to apoptosis, rhIGF-1 was applied concomitantly with AmB. In all animals, rhIGF-1 prevented the above-mentioned clinical side effects. Moreover, significantly reduced apoptosis was observed in renal tissue sections of these animals, indicating the relevance of apoptosis in nephrotoxicity. This is the first report to demonstrate that AmB induces apoptosis in the rat kidney in a dose-dependent fashion. The incidence of apoptosis correlates with renal toxicity and can be abrogated by concomitant treatment with rhIGF-1

Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation

Apoptosis plays a central role not only in the physiological processes of kidney growth and remodeling, but also in various human renal diseases and drug-induced nephrotoxicity. We present in a synthetic fashion the main molecular and cellular pathways leading to drug-induced apoptosis in kidney and the mechanisms regulating it. We illustrate them using three main nephrotoxic drugs (cisplatin, gentamicin, and cyclosporine A). We discuss the main regulators and effectors that have emerged as key targets for the design of therapeutic strategies. Novel approaches using gene therapy, antisense strategies, recombinant proteins, or compounds obtained from both classical organic and combinatorial chemistry are examined. Finally, key issues that need to be addressed for the success of apoptosis-based therapies are underlined