We present a case of juvenile hemangioma of the testis associated with hemangiomas of the liver and skin. The testicular hemangioma appeared to progress after therapy with interferon alpha-2a (IFN alpha-2a), whereas the liver and skin hemangiomas regressed. Analysis of growth factors responsible for proliferation of hemangioma revealed that the tumor expressed vascular endothelial growth factor but not basic fibroblast growth factor (bFGF), which is reported to be inhibited by IFN alpha-2a. This finding suggests that a possible explanation for the inadequate efficacy of IFN alpha-2a for testicular hemangioma is a lack of bFGF expression.

Angiogenesis Inducing Agents↗

PubMed1997

Prolyl 4-hydroxylase inhibitor (HOE 077) inhibits pig serum-induced rat liver fibrosis by preventing stellate cell activation.

BACKGROUND/AIMS: The aim of this study was to investigate the effect and mechanism of fibrosuppression by a newly synthesized prolyl 4-hydroxylase inhibitor [HOE 077, 2, 4-pyridine dicarboxylic acid bis [(2-methoxyethyl) amide]] on pig serum-induced liver fibrosis in the rat. METHODS: Male Wistar rats received 0.5 ml of pig serum twice a week for 10 weeks with 0, 100 or 200 ppm of HOE 077. At the end of the experiment, the hydroxyproline content of the liver, and alanine aminotransferase were measured. Histological stains used were HE, azan and a stain for alpha-smooth muscle actin (alpha-SMA). Electron microscopy was also performed. Messenger RNA expressions of type I and III procollagen were examined by Northern blot analysis. alpha-SMA positive cells and fibers with azan staining were assessed as percent area of the tissue specimen, using an image analysis system. RESULTS: Rats that received pig serum for 10 weeks showed an increased liver hydroxyproline content of 318+/-39 microg/g wet weight (n=15). HOE 077 at doses up to 200 ppm significantly (p<0.01) reduced this increase of liver hydroxyproline content (181+/-39 microg/g wet weight, n=15) in accordance with improved histological findings. 200 ppm of HOE 077 significantly reduced mRNA expressions of alpha2(I) (486+/-102 vs 151+/-36, p<0.01) and alpha1(III) (276+/-127 vs 160+/-67, p<0.05) procollagen and percent area of alpha-SMA positive cells (2.94+/-2.14 vs 1.17+/-0.88%). Electron microscopy revealed that 200 ppm of HOE 077 prevented the loss of fat droplets. CONCLUSIONS: A prolyl 4-hydroxylase inhibitor (HOE 077) prevented pig serum-induced rat liver fibrosis by inhibiting stellate cell activation.

Animals↗

PubMed1997

4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes.

Removal of extracellular glutamate at synapses, by specific high-affinity glutamate transporters, is critical to prevent excitotoxic injury to neurons. Oxidative stress has been implicated in the pathogenesis of an array of prominent neurodegenerative conditions that involve degeneration of synapses and neurons in glutamatergic pathways including stroke, and Alzheimer's, Parkinson's and Huntington's diseases. Although cell culture data indicate that oxidative insults can impair key membrane regulatory systems including ion-motive ATPases and amino acid transport systems, the effects of oxidative stress on synapses, and the mechanisms that mediate such effects, are largely unknown. This study provides evidence that 4-hydroxynonenal, an aldehydic product of lipid peroxidation, mediates oxidation-induced impairment of glutamate transport and mitochondrial function in synapses. Exposure of rat cortical synaptosomes to 4-hydroxynonenal resulted in concentration- and time-dependent decreases in [3H]glutamate uptake, and mitochondrial function [assessed with the dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)]. Other related aldehydes including malondialdehyde and hexanal had little or no effect on glutamate uptake or mitochondrial function. Exposure of synaptosomes to insults known to induce lipid peroxidation (FeSO4 and amyloid beta-peptide) also impaired glutamate uptake and mitochondrial function. The antioxidants propyl gallate and glutathione prevented impairment of glutamate uptake and MTT reduction induced by FeSO4 and amyloid beta-peptide, but not that induced by 4-hydroxynonenal. Western blot analyses using an antibody to 4-hydroxynonenal-conjugated proteins showed that 4-hydroxynonenal bound to multiple cell proteins including GLT-1, a glial glutamate transporter present at high levels in synaptosomes. 4-Hydroxynonenal itself induced lipid peroxidation suggesting that, in addition to binding directly to membrane regulatory proteins, 4-hydroxynonenal potentiates oxidative cascades. Collectively, these findings suggest that 4-hydroxynonenal plays important roles in oxidative impairment of synaptic functions that would be expected to promote excitotoxic cascades.

ATP-Binding Cassette Transporters↗

PubMed1997

Induction of a wide range of C(2-12) aldehydes and C(7-12) acyloins in the kidney of Wistar rats after treatment with a renal carcinogen, ferric nitrilotriacetate.

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces renal proximal tubular necrosis associated with lipid peroxidation and oxidative DNA damage that finally leads to a high incidence of renal cell carcinoma in rodents. In the present study, we investigated what kinds of C(2-12) saturated and unsaturated aldehydes and C(7-12) acyloins, metabolites of saturated aldehydes, are produced in the kidney and liver within 24 h after single i.p. administration of 15 mg Fe/kg of Fe-NTA, or after repeated (1 or 3 wk) i.p. administration of 5-10 mg Fe/kg of Fe-NTA. Amounts of twenty one aldehydes and five acyloins were determined by capillary column gas chromatography-negative-ion chemical ionization mass spectrometry with ammonia as reagent gas. Most of the aldehydes and all the acyloins measured revealed a significant dose-dependent increase 1 to 3 h after single administration in the kidney, among which 4-hydroxy-2-nonenal (HNE) showed the highest increase (27.3-fold) and malondialdehyde (MDA) was the most abundant aldehyde (2.40 nmol/100 mg wet tissue). In the liver, however, the increase in aldehydes and acyloins was less prominent. After repeated administration of Fe-NTA, only 9 aldehydes (ethanal; furfural; trans,trans-2,4-heptadienal; nonanal; trans-2,cis-6-nonadienal; HNE; decanal; trans-4,cis-4-decenal; MDA) and 4 acyloins (3-hydroxyheptan-2-one; 3-hydroxyoctan-2-one; 3-hydroxynonan-2-one; 3-hydroxydodecan-2-one) showed a significant increase. Immunohistochemistry further demonstrated an increased amount of HNE-modified and MDA-modified proteins in the renal proximal tubules after repeated Fe-NTA administration. Some of the aldehydes measured such as HNE and MDA are reportedly cytotoxic, genotoxic and mutagenic. Accumulation of these aldehydes may play a role in this renal carcinogenesis model.

Aldehydes↗

PubMed1997

Enhancement of potassium-, and angiotensin II-stimulated aldosterone production by the calcium chelator EGTA in bovine adrenal glomerulosa cells in vitro.

The present study was designed to assess the effect of the calcium chelator EGTA (ethylenglycolbis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; 1.0 mM) on potassium (8 mM)- and angiotensin II (AII; 10 nM)-stimulated aldosterone production in bovine adrenal glomerulosa cells in vitro. The combined administration of EGTA and potassium, or of EGTA and AII, yielded a significant increase in the levels of aldosterone production. The net increment in aldosterone production after the combined administration of EGTA and potassium, or that after the combined administration of EGTA and AII was also significantly higher than the sum of that evoked by EGTA and potassium alone, or the sum of that evoked by EGTA and AII alone, respectively. At similar concentrations of extracellular ionized calcium ([Ca2+]out) or magnesium, the levels of agonist-stimulated aldosterone production were markedly elevated by the administration of EGTA. These results indicate that lowering [Ca2+]out concentrations with EGTA enhances potassium- and AII-stimulated aldosterone production in bovine adrenal glomerulosa cells in vitro. This enhancement may be predominantly due to another effect of EGTA, in addition to the stimulation of calcium entry into the cells.

Aldosterone↗

PubMed1997

Ganglion cyst of the posterior longitudinal ligament causing lumbar radiculopathy: case report.

We describe a man aged 26 years who presented with a neurological syndrome, which was found on lumbar radioculopathy to be due to a ganglion cyst originating from the posterior longitudinal ligament. Based on MRI findings, cystic lesion was suspected, a round lesion at L4 level with no connection to the adjacent facet or to the dura matter. During surgery, a liquid-containing cystic lesion was found to originate from the posterior longitudinal ligament at L4 level. The resected cyst was diagnosed histologically as a ganglion cyst. A complete cure was established after surgery and no recurrence was noted at a follow-up 1.7 years postoperatively. A ganglion cyst of the posterior longitudinal ligament should be considered in the differential diagnosis of a cyst in the lumbar region causing neurological complications.

Adult↗

PubMed1997

Three-dimensional computed tomography for evaluation of cervical spinal canal enlargement after en bloc open-door laminoplasty.

We evaluated the use of three-dimensional (spiral) computed tomography (CT) to assess widening of the bony cervical spinal canal following en bloc open-door C3-C7 laminoplasty in 31 patients. Measurements were performed using a computerised image processing system. The increment in the anteroposterior spinal canal axis and volume of the bony spinal canal was investigated in relation to changes in cervical spine lordosis as well as postoperative neurological improvement. Neurological follow-up averaged 2.6 years (range, 1 to 7 years). A mean increase of 42% was observed in the anteroposterior axis of the canal between C3 to C7 after surgery, while the volume increased by 45%. Postoperatively, cervical spine lordosis correlated with increments in the volume of the enlarged bony canal rather than the anteroposterior axis. Postoperative neurological improvement correlated significantly with the increase in the canal volume. Our results indicate that spiral CT is useful for the assessment of the magnitude of cervical canal enlargement and evaluating the space available for the spinal cord following the relief of compression.

Adult↗

PubMed1997

Extraforaminal lumbar disc herniation at two contiguous intervertebral levels.

We describe two unusual surgical cases who presented with extraforaminal lumbar disc herniation that occurred at two adjacent vertebral levels simultaneously and unilaterally. Magnetic resonance imaging and selective nerve root infiltration followed by radiculography helped to outline the herniated disc material. Lateral fenestration and microsurgical foraminal widening of the affected vertebral levels allowed a complete and safe relief of the compressed nerves.

Female↗

PubMed1997

A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide.

Peroxidation of membrane lipids results in release of the aldehyde 4-hydroxynonenal (HNE), which is known to conjugate to specific amino acids of proteins and may alter their function. Because accumulating data indicate that free radicals mediate injury and death of neurons in Alzheimer's disease (AD) and because amyloid beta-peptide (A beta) can promote free radical production, we tested the hypothesis that HNE mediates A beta 25-35-induced disruption of neuronal ion homeostasis and cell death. A beta induced large increases in levels of free and protein-bound HNE in cultured hippocampal cells. HNE was neurotoxic in a time- and concentration-dependent manner, and this toxicity was specific in that other aldehydic lipid peroxidation products were not neurotoxic. HNE impaired Na+, K(+)-ATPase activity and induced an increase of neuronal intracellular free Ca2+ concentration. HNE increased neuronal vulnerability to glutamate toxicity, and HNE toxicity was partially attenuated by NMDA receptor antagonists, suggesting an excitotoxic component to HNE neurotoxicity. Glutathione, which was previously shown to play a key role in HNE metabolism in nonneuronal cells, attenuated the neurotoxicities of both A beta and HNE. The antioxidant propyl gallate protected neurons against A beta toxicity but was less effective in protecting against HNE toxicity. Collectively, the data suggest that HNE mediates A beta-induced oxidative damage to neuronal membrane proteins, which, in turn, leads to disruption of ion homeostasis and cell degeneration.

Aldehydes↗

PubMed1997

Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamptic placentas.

Lipid peroxides and their related free radicals have been implicated in the pathogenesis of placental dysfunction in preeclampsia. Recent studies suggest that the placenta is a source of the increased lipid peroxides in the maternal circulation of women with preeclampsia. We examined intracellular localization of 4-hydroxy-2-nonenal (HNE: a major aldehydic product of lipid peroxidation)-modified proteins in human placentas by immunohistochemistry, and immunoblotting. The trophoblast layer of the chorionic villi showed intense immunoreactivity for HNE-modified proteins in 4 of 12 preeclamptic placentas, whereas no staining was observed in 12 normal placentas. Immunoblotting revealed that three immunoreactive proteins with apparent molecular mass of 110 kDa, 75 kDa, and 70 kDa were localized in the mitochondrial fraction. The present results indicate that the damage to mitochondrial proteins by lipid peroxidation by products and subsequent dysfunction of trophoblasts contribute to the pathophysiology of preeclampsia.

Aldehydes↗