Virilizing Adrenocortical Oncocytoma in a Child: A Case Report

Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.

Efficacy of Embryonic Stem Cell-derived Dopaminergic Neurons and E12 Mesencephalic Neuronal-precursor Derived Dopaminergic Neurons as a Source for Transplantation in Parkinsonian Rats

BACKGROUND: This study was performed to compare efficiency of embryonic stem (ES) cell-derived dopaminergic (DA) neurons from E12 mesencephalic neuronal-precursor derived DA neuron, and to assess the value of these neurons as a donor cells to transplant in Parkinson's disease. METHODS: ES cell-derived DA neurons from E12 mesencephalic neuronal-precursor derived DA neuron were transplanted in Parkinsonian rats and analyzed TH immunoreactivity and apomorphin-induced rotation test. RESULTS: Transplanting of ES cell derived DA neurons into the rat striatum caused gradual increase of expression of tyrosine hydroxylase (TH) immunoreactivity 6 weeks after transplant in host striatum. Rotation behavior was gradually on the decrease, 6 weeks after transplant of ES cell derived DA neurons. In case of E12 mesencephalic precursor derived DA neurons, the TH immunoreactivity expressed 6 weeks after transplant in striatum, and the behavioral restoration of DA-mediated motor asymmetry sustained gradually. However, transplanted ES cell derived DA neurons appeared in wide regions among the needle tract with a relatively high density of TH immunoreactivity in comparison to the E12 mesencephalic precursor DA neurons, and graft volume of ES cell derived DA neurons were larger than E12 mesencephalic precursor derived DA neuron. In addition, both cells did not appear cancerous change after transplantation. CONCLUSIONS: These results suggest that ES cell is more efficient than E12 mesencephalic precursor derived dopaminergic neuron and will supply efficient donor cells for transplantation in Parkinson's disease.

Manganese-induced Oxidative Stress in the Corpus Striatum of the Rat Brain / 대한산업의학회지

OBJECTIVES: This study was undertaken to identify the effect of oxidative stress on the pathology of manganese intoxication through an analysis of manganese concentrations, superoxide dismutase (SOD) activities, malondialdehyde (MDA) concentrations, and the compositional changes of fatty acids from the corpus striatum of the rat brain. METHODS: Ten Sprague-Dawley rats were equally divided into two groups. Five rats in the experimental group were administered MnCl2 intraperitoneally for 4 weeks (4 mg/kg once daily, 5 days per week) and another five rats from the control group were given normal saline. Twenty-four hours after the last injection, the rats were decapitated and, the corpus striatum was isolated from the brain. RESULTS: In the corpus striatums of the experimental group, manganese concentrations increased significantly by 139 % (p<0.01). The SOD activities decreased significantly by 81 % (p<0.01) and the MDA concentrations increased significantly by 138 % (p<0.01) as compared to the control group. Among fatty acids, total n-6 polyunsaturated fatty acids (PUFAs) increased significantly by 325 % (p<0.01) as compared with the control group. Arachidonic acids (AA) increased by 341 % (p<0.01), and these increases were composed mostly of n-6 polyunsaturated fatty acids (PUFA). Among n-3 PUFAs, with the exception of linolenic acids, eicosapentanoic acid (EPA) decreased significantly by 72 % (p<0.05) and docosahexanoic acids (DHA) decreased by 67 % (p<0.05) as compared with the control group. CONCLUSIONS: Our results suggest that the oxygen free radicals produced by manganese may cause compositional changes of fatty acids in the corpus striatum of the rat brain. The characteristics of the fatty acids'compositional changes by manganese were a decrease of EPAs and DHAs (n-3 PUFAs), and an increase of AAs (n-6 PUFAs). These changes coupled with the decrease of SOD activity and the increase of MDA, suggest that manganese neurotoxicity is caused by lipid peroxidation mediated with oxygen free radicals, particularly superoxide radicals.

Changes of Superoxide Dismutase Activity in Cadmium-induced Acute Nephrotoxicity of Rats / 대한산업의학회지

OBJECTIVES: To investigate the role of superoxide dismutase(SOD) in the pathogenesis of cadmium-induced acute nephrotoxicity. METHODS: Rats treated with a single intraperitoneal injection of cadmium(as CdCl2, 1 mg/kg) were included in the cadmium-treated group; the control group comprised untreated rats. 24-hour urine samples were obtained prior to sacrifice on days 1, 2, 4, 8 and 16(N = 10 per group), respectively. The activity of SOD and concentration of cadmium were measured in the homogenates of the renal cortex. Nephrotoxicity indices such as N-acetyl-beta-D-glucosaminidase(NAG) activity, total protein, and 24-hour urine volume, and the cadmium concentrations in the urine were measured. RESULTS: The cadmium injection caused a significant increase of cadmium concentration in the renal cortex on days 1 and 2, and in the urine on days 1, 2 and 4. The NAG activities and total protein concentrations in urine were significantly increased on days 1, 2 and 4, and on days 1, 4 and 8, respectively. The peak values of NAG activity and total protein in urine were observed on days 1 and 4, respectively. A significant decrease of 24- hour urinary volume was induced on day 1. Renal SOD activity was significantly inhibited on day 1. Finally, on day 8, SOD activity was significantly increased and all nephrotoxicity indices except urinary total protein returned to the control level. CONCLUSIONS: These results suggest that cadmium induces initial depression of SOD enzyme activities in the renal cortex followed by a later activation, and that the initial depression of this enzyme plays an important role in mediating the proteinuric injury of cadmium-induced acute nephrotoxicity.

Urinary N-acetyl--D-glucosaminidase and Malondialdehyde as a Markers of Renal Damage in Burned Patients

This study was aimed to evaluate renal dysfunction during three weeks after the burn injuries in 12 patients admitted to the Hallym University Hankang Medical Center with flame burn injuries (total body surface area, 20-40%). Parameters assessed included 24-hr urine volume, blood urea nitrogen, serum creatinine, creatinine clearance, total urinary protein, urinary microalbumin, 24-hr urinary N-acetyl--D-glucosaminidase (NAG) activity, and urinary malondialdehyde (MDA). Statistical analysis was performed using repeated measures ANOVA test. The 24-hr urine volume, creatinine clearance, and urinary protein significantly increased on day 3 post-burn and fell thereafter. The urine microalbumin excretion showed two peak levels on day 0 post-burn and day 3. The 24-hr urinary NAG activity significantly increased to its maximal level on day 7 post-burn and gradually fell thereafter. The urinary MDA progressively increased during 3 weeks after the burn injury. Despite recovery of general renal function through an intensive care of burn injury, renal tubular damage and lipid peroxidation of the renal tissue suggested to persist during three weeks after the burn. Therefore, a close monitoring and intensive management of renal dysfunction is necessary to prevent burn-induced acute renal failure as well as to lower mortality in patients with major burns.

Relationship between Malondialdehyde in Renal Cortex and Urinary NAG Activity of Rats exposed to Cadmium

BACKGROUND: To investigate the relationship between malondialdehyde in renal cortex and Urinary NAG activity of rats exposed to cadmium. METHODS: Rats were treated with a single intraperitoneal injection of cadmium (as CdCl2, 1 mg/kg) for cadmium-treated group and 24-hour urine were obtained prior to sacrifice on days 1, 2, 4, 8 and 16 (N=10 per each group), respectively. The concentration of malondialdehyde by thiobarbituric acid reaction and cadmium were measured in the homogenates of renal cortex. Nephrotoxocity indices such as N-acetyl--D-glucosaminidase (NAG) activity, total protein, and 24 hours urine volume, and cadmium concentration were measured in the urine. RESULT: The cadmium injection caused significant increase of cadmium concentration in the renal cortex on days 1 and 2, and in urine on days 1, 2 and 4. NAG activity and total protein concentration in urine were significantly increased on days 1, 2 and 4, and on days 1, 4 and 8, respectively. The peak values of NAG activity and total protein in urine were observed on days 1 and 4, respectively. Significant decrease of 24 hours urinary volume was induced on day 1. These results indicated that cadmium induced acute nephrotoxicity in the rats. Urinary NAG activity was changed earlier and at a higher rate than urinary total protein, which suggest that NAG activity is a more sensitive biological index in terms of early diagnosis of cadmium-induced nephrotoxicity. Renal MDA concentration was significantly increased on day 2 and on day 4, and on day 8, MDA concentration and nephrotoxicity indices except urinary total protein were returned to control level. CONCLUSION: Based on the results obtained as above, it was concluded that the malondialdehyde in renal cortex, product of lipid peroxidation was related with the changes of urinary NAG activity indicating nephrotoxic injury.

Effects of Manganese on Lipid Peroxidation and Compositional Changes of Fatty Acids in Hippocampus of Rat Brain

BACKGROUND: To investigate the effect of manganese on lipid peroxidation and compositional changes of fatty acids in hippocampus of rat brain. METHODS: Seven rats in experimental group were given with MnCl2 intraperitoneally for 4 weeks (4 mg/kg once daily, 5 days per week). Twenty four hours after the last injection, rats were decapitated and, hippocampus were separated from the rat brain. RESULT: In Mn-treated group, manganese concentrations increased significantly in the hippocampus by 222% compared with control group (P<0.01). MDA concentrations increased significantly by 149% compared with control group (P<0.05). Among fatty acids, total n-6 polyunsaturated fatty acids (PUFAs) increased significantly by 237% compared with control group (P<0.05). Linoleic acid (LA) and arachidonic acids (AA) increased by 213%, 238% (P<0.05, P<0.01, respectively). Among n-3 PUFAs except linolenic acids, eicosapentanoic acid(EPA) and docosahexanoic acids (DHA) decreased significantly by 70%, 50% respectively compared with control group (both P<0.01). CONCLUSION: Our results suggest that manganese may cause compositional changes of fatty acids in hippocampus of rat brain. Characteristics of fatty acids compositional changes by manganese were the decrease of EPAs and DHAs (n-3 PUFAs), and increase of AA and LA (n-6 PUFAs). These changes with the increase of MDA, suggest that manganese neurotoxicity is caused by lipid peroxidation.

Primary role of posterior hypothalamic cholinergic receptors in central regulation of blood pressure and heart rate in rats

The purpose of the present study is to determine the role of muscarinic cholinergic receptors of posterior hypothalamus in the central blood pressure regulation when respiration is controlled. In anesthetized and artificially ventilated rats, vasodepressor response was evoked by injection of L-glutamate (10 nmol) neuroexcitatory amino acid into the posterior hypothalamic area. The injection of carbachol (0.5 ~ 8 nmol) into the same area induced dose-dependent vasodepressor and bradycardic responses. Pretreatment with atropine (4 nmol) completely blocked the vasodepressor response to carbachol (2 nmol). In contrast, in spontaneously breathing rats, the injection of carbachol (8 nmol) into the posterior hypothalamic area induced the vasopressor and tachycardic responses. These results suyggest that the muscarinic cholinergic receptors in the posterior hypothalamic area primarily play an inhibitory role in the central regulation of blood pressure and heart rate.

Effects of cyclic nucleotides and glipizide on the cardiovascular response of baclofen in the rats

The purpose of present study is to investigate the influence of a spinal gamma-aminobutyric acid B(GABA|B) receptor on a central regulation of blood pressure (BP) and heart rate (HR), and to define its mechanism in the spinal cord. In urethane-anesthetized, d-tubocurarine-paralyzed and artificially ventilated male Sprague-Dawley rats, intrathecal administration of drugs were carried out using injection cannula (33-gauge stainless steel) through the guide cannula (PE 10) which was inserted intrathecally at lower thoracic level through the puncture of a atlantooccipital membrane. Intrathecal injection of an GABA|B receptor agonist, baclofen (30, 60, 100 nmol) decreased both BP and HR dose-dependently. Pretreatment with 8-bromo-cAMP (50 nmol), a cAMP analog, or glipizide (50 nmol), a ATP-sensitive K+ channel blocker, attenuated the depressor and bradycardic effects of baclofen (100 nmol), but not with 8-bromo-cGMP (50 nmol), a cGMP analog. These results suggest that the GABA|B receptor in the spinal cord plays an inhibitory role in central cardiovascular regulation and that this depressor and bradycardic actions are mediated by the decrease of cAMP via the inhibition of adenylate cyclase and the opening of K+ channel.

Analysis of the Three Dimensional Structure of Envelope Protein of the Japnes Encephalitis virus Isolated in Korea

Three dimensional structures of envelope protein from Korean isolates and Nakayama-NIH strain of Japanese encephalitis virus (JEV) were deduced by a computer program (HyperChem 4.0 Chemplus 1.0) based on the data of the three dimentional structure of Tick-borne encephalitis virus. In the three dimensional structure of envelope protein, neutralizing epitope and T-helper cell recognition site of C-terminal region of Korean isolates were structually similar to those of Nakayama-NIH but the N-terminal region was not. Korean JE isolates were compared with Nakayama-NIH strain by using cross-neutralization antibody test. Neutralizing activities of Korean isolates derived from guinea pigs were higher than those of Nakayama-NIH strain against Korean isolates, although the polyclonal antibody titers of Nakayama-NIH showed 1:160 to 1:640 against Korean isolates. According to the results from three dimentional structures and cross-neutralization analyses, the antigenic difference between Korean JE isolates and Nakayama-NIH strain may be dependent on structural difference of envelope protein.