Ex vivo porcine model for eye, eyelid, and orbit movement analysis of 4-mm ferromagnetic foreign bodies in MRI.

PURPOSE: Ferromagnetic foreign bodies (FFB) present during magnetic resonance imaging (MRI) explorations can lead to tissue injury due to movement, especially in and around the eyes. Ferromagnetic foreign bodies located in the intraocular area, eyelids, and orbit are thus prohibited from undergoing MRI. The aim of the study was to analyze movement of 4-mm ferromagnetic foreign bodies in MRI in the eye, eyelid, and orbit using computed tomography (CT) scan. METHOD: We developed a porcine model using 12 quarters of fresh porcine heads. Each porcine head included one whole orbit with the ocular globe, orbital fat, muscles, and eyelids. Four-millimeter FFB were implanted in the eye within 2 days post-slaughter, and images were acquired within 5 days post-slaughter. Four-millimeter FFB movement was analyzed after 1.5-Tesla (T) MRI. Four locations were tested: intravitreous, suprachoroidal, intraorbital fat, and intrapalpebral. Movement analysis was assessed using computed tomography (CT) scan. RESULTS: The intravitreous ferromagnetic ball moved 14.0 ± 8.8 mm (p < 0.01), the suprachoroidal ball moved 16.8 ± 5.4 mm (p < 0.01), the intraorbital fat ball moved 5.8 ± 0.9 mm (p > 0.05), and the intrapalpebral ball moved 2.0 ± 0.4 mm (p > 0.05). CONCLUSION: The ex vivo porcine model was able to study FFB movement. The 4-mm ferromagnetic balls moved in intravitreous and in suprachoroidal locations after MRI.

Presence of a retinoid responsive element in the promoter region of the human cytochrome P4501A1 gene.

Cytochrome P4501A1 (CYP1A1) plays a key role in the metabolic activation of procarcinogenic compounds, leading to skin carcinogenesis. It is therefore important to determine whether its enzymatic activity is altered by topically administered drugs. We investigated, in cultured normal human keratinocytes (NHK), the effects of retinoic acid (RA) and synthetic analogs on the regulation of the CYP1A1 gene. Using transient transfections and gel shift assays, we demonstrated that the human CYP1A1 gene promoter was differentially regulated by retinoid receptors. We report, for the first time, that a RA responsive element 5'-CTTAGGTCACCACGGGGCA-3' (RARE1A1) is present within the promoter region of the CYP1A1 gene.

Modulation of cellular cholesterol and its effect on cornified envelope formation in cultured human epidermal keratinocytes.

When cultured human epidermal keratinocytes (NHK) reach confluence they start to differentiate and an increase in the total cellular cholesterol content is observed. This increase parallels the appearance of a characteristic feature of terminal keratinocyte differentiation, the spontaneous formation of cornified envelopes (CE). Synthesis of CE is catalyzed by the plasma membrane-associated transglutaminase (TGm). Supplementation of the medium with inhibitors of cholesterologenesis suppressed increase in cholesterol levels and CE formation but did not interfere with TGm expression or TGm activity. Modulation of the plasma membrane cholesterol-phospholipid ratio of confluent NHK cultures using either pure phospholipid liposomes or liposomes enriched in cholesterol strongly affected spontaneous CE formation. Pure phospholipid liposomes completely inhibited CE formation, whereas cholesterol-enriched liposomes ensured envelope formation, even in the presence of inhibitors of cholesterol synthesis. From these results we conclude that in differentiating NHK an increase in the cellular cholesterol level is part of the differentiation program and is essential for the spontaneous CE formation.

Sodium butyrate selectively antagonizes the inhibitory effect of retinoids on cornified envelope formation in cultured human keratinocytes.

Sodium butyrate affects cell differentiation in confluent epidermal keratinocyte cultures by considerably increasing the spontaneous formation of cross-linked envelopes in normal human keratinocytes (NHK). It also favors the development of envelope competence in the Simian virus-40 (SV-40)-transformed human foreskin keratinocyte line SV-K14. It completely abolishes the inhibitory effect of serum and retinoic acid on the expression of plasma membrane-associated transglutaminase. However, other markers of epidermal differentiation that are also under the control of retinoids such as keratins or the enzyme cholesterol sulfotransferase are not affected by butyrate. The level of the cellular retinoic acid binding protein (CRABP) is considerably increased in its presence. Butyrate does not interfere with the binding of retinoids to their cellular binding proteins. Our observations suggest that sodium butyrate stimulates cornified envelope formation via the induction of the plasma membrane-associated transglutaminase required for cornified envelope synthesis and, additionally, by abolishing the inhibitory effect of retinoids on the expression of this enzyme.

Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings.

The authors report 2 familial cases of neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in the liver. In both cases, disorders started immediately after birth and were characterized by major neurological symptoms, acute metabolic acidosis with hyperketonemia and hyperammonemia. Course was rapidly fatal despite intensive care, bicarbonate therapy and several therapeutic attempts with biotin and thiamine. Hyperlactacidemia was associated with dramatic increase in lactate/pyruvate ratio, without anoxia, in contrast with decreased beta hydroxybutyrate/acetoacetate ratio. This unusual metabolic pattern may be assumed to result from decreased oxaloacetate synthesis as a result of pyruvate carboxylase deficiency, and impairment of oxaloacetate dependent mitochondrial redox shuttles. Post mortem enzymatic study of the liver and kidney showed biotin unresponsive total deficiency of pyruvate carboxylase. Other gluconeogenic enzyme activities were normal.