Dimethylthiourea ameliorates carbon tetrachloride-induced acute liver injury in ovariectomized mice.

AIMS: In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl4-induced ALI. MAIN METHODS: Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl4 administration. Sham and ovx mice were given DMTU, Melo or saline intraperitoneally 30 min before CCl4 or corn oil administration. KEY FINDINGS: ALT levels in ovx mice were significantly increased compared to those in sham mice. DMTU reduced ALT levels in ovx mice to the same levels as those in sham mice after CCl4 injection. CCl4 upregulated TNF-α, IL-6, cox-2 and iNOS expression in ovx mice compared to the levels in sham mice. DMTU significantly reduced cox-2 and iNOS expression levels upregulated by CCl4 in ovx mice. However, pretreatment with Melo had no effects on ALT levels and the gene expression levels of TNF-α, IL-6 and HO-1 in either sham or ovx mice, indicating that cox-2 may not participate in increase of CCl4-induced ALI caused by estrogen deficiency. SIGNIFICANCE: Ovariectomy accelerated the development of CCl4-induced acute liver injury, and DMTU reduced liver injury. These results suggest that estrogen may act as an antioxidant in the development CCl4-induced acute liver injury.

Rapid increase of 'brain-type' transferrin in cerebrospinal fluid after shunt surgery for idiopathic normal pressure hydrocephalus: a prognosis marker for cognitive recovery.

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity. The prognosis for cognitive improvement after shunt surgery has been difficult to predict. We therefore investigated various CSF proteins, hoping to find a biomarker predictive of cognitive performance one to two years after shunt surgery. CSF proteins of 34 iNPH and 15 non-iNPH patients were analysed by Western blotting, revealing two glycan isoforms of transferrin (Tf); 'brain-type' Tf with N-acetylglucosaminylated glycans and 'serum-type' Tf with α2, 6-sialylated glycans. Brain-type Tf levels decreased in iNPH but rapidly returned to normal levels within 1-3 months after shunt surgery. This change was positively correlated with recovery from dementia, per Mini-Mental State Examination and Frontal Assessment Battery scores at 11.8 ± 7.7 months post-operation, suggesting that brain-type Tf is a prognostic marker for recovery from dementia after shunt surgery for iNPH. Histochemical staining with anti-Tf antibody and an N-acetylglucosamine-binding lectin suggests that brain-type Tf is secreted from choroid plexus, CSF-producing tissue.

Sudden infant deaths from undiagnosed ventricular septal defect - Report of two autopsy cases.

Ventricular septal defect (VSD) has a relatively non-aggressive clinical course; either spontaneous closure or causing congestive heart failure treatable with surgical intervention. We present two autopsy cases of sudden infant deaths from clinically undiagnosed VSDs. Case 1 was an 18-day-old boy. As the deceased coughed and became limp after feeding, he was carried to a hospital. Heart murmur was not auscultated there, so he was brought back to home. He presented severe dyspnea and then he was pronounced dead the next day. Case 2 was a 3-week-old boy. Any abnormality was pointed out at physical examination, although his mother felt his wheeze. He developed respiratory arrest at home in the morning and then he was confirmed dead at the hospital. Heart weights of these babies were heavier than mean weights of each normal development. There were perimembranous VSDs in both cases. Histology revealed that the pulmonary arterial walls were thickened. We diagnosed the cause of death in these cases was cardiac collapse with pulmonary hypertension due to VSD. Congenital heart diseases can be diagnosed as early as before birth, because echocardiograph and fetal echography are prevalent in these days. Most VSDs can be noticed by systolic murmur even today. We consider that the failure of initial clinical diagnosis of VSD in primary physical assessment could lead unexpected sudden death. These two cases reminded us to the importance of auscultation which is conventional but as one of the indispensable measure to find a clue for the congenital abnormality.

Immunohistochemical study of microscopic globular bodies of normal human brain.

Microscopic globular bodies (MGBs) are brilliantly and homogenously eosinophilic spherical inclusions, 1-10 µm in diameter. They are mainly distributed in the cerebral neocortex and hippocampus in normal individuals ranged in age from first to tenth decade. Ultrastructurally, MGBs are composed of electron-dense granular material and are located in dendrites. However, immunohistochemical profile of MGBs is uncertain. Therefore, we immunohistochemically examined the hippocampus from five control subjects ranged from 25 to 76 years. The marginal portion of MGBs was positive for lysosomal proteases (cathepsins B, D and L), and markers of dendrite (MAP2) and dendritic spine (drebrin). In some cases, MGBs were entirely immunostained with anti-cathepsin D. Among the cathepsins, MGBs were most frequently immunolabeled with anticathepsin D. They were negative for ubiquitin, ubiquitin-proteasome system (p62, NUB1 and EDD1), autophagosome (LC3), cytoskeletal proteins (neurofilament, actin, tubulin and cytokeratin), tau, α-synuclein and TDP-43. These findings suggest that MGBs are sequestered by lysosome- protease system, but not by ubiquitin-proteasome system or autophagosome.

Spectrophotometric evaluation of the age of bruises in children: measuring changes in bruise color as an indicator of child physical abuse.

Physical abuse of children is a severe social problem and is usually identified by the presence of bruises of various ages. The visual appearance of bruises is widely used to identify victims of abuse. Therefore, to objectively evaluate the age of bruises, we used a spectrophotometer to examine 86 bruises that occurred accidentally in healthy child volunteers, with consent from appropriate guardians. The bruise color was measured using a spectrophotometer and plotted using the CIE-L*a*b* color system, a method that expresses color numerically. The differences [Delta] in L* (lightness), a* (red and green content) and b* (yellow and blue content) color values relative to neighboring healthy/unbruised skin were measured for 7-10 days until the bruise disappeared. A characteristic pattern was observed in 21 bruises; DeltaL* increased from the negative peak and returned to baseline, Deltaa* decreased from the positive peak to baseline, and Deltab* increased above baseline and then slowly returned to baseline. The pattern of these color changes could be classified into three phases according to the time between bruising and the peak values for DeltaL* (negative peak, 38.9 +/- 19.5 hours), Deltaa* (positive peak, 37.6 +/- 21.7 hours), and Deltab* (negative and positive peak, 43.5 +/- 18.7 and 132.6 +/- 40.4 hours). Thus, spectrophotometric measurement of the color of bruises is helpful to estimate the approximate age of bruises and to distinguish between old and new bruises. This objective method could be introduced to clinical practice and social care to evaluate possible cases of child abuse.

Significance of fatal head injuries associated with subependymal hemorrhage at the anterior horns of lateral ventricles.

We hypothesize the following items based on 41 autopsy cases with or without head injuries especially on subependymal injuries at the anterior horns of the lateral cerebral ventricles. The subependymal injuries at the regions (1) are not seen in fatal cases that did not have intracranial injuries, (2) have nothing to do with technical procedures for removal of the whole brain at autopsy, (3) are frequently associated with axonal injuries, (4) are presumed to be formed by rotating head injuries in a sagittal direction.

Traumatic dissection of extracranial vertebral artery with massive subtentorial cerebral infarction: report of an autopsy case.

We present an extremely rare autopsy case with traumatic dissection of the extracranial vertebral artery due to blunt injury caused by a traffic accident. The patient complained of nausea and numbness of the hands at the scene of the accident. His consciousness deteriorated and he fell into a coma within 12h, then died 4 days after the collision. Brain CT/MRI disclosed massive infratentorial cerebral infarction while MRA imaged neither of the vertebral arteries. Autopsy revealed a seatbelt mark on the right side of the lower neck, with fracture of the right transverse process of the sixth cervical vertebra. The right extracranial vertebral artery (V2) showed massive medial dissection from the portion adjacent to the fracture throughout the upper end of the extracranial part of the artery and was occluded by a thrombus. An intimal tear was confirmed near the starting point of the dissection. The brain disclosed massive infarction of posterior circulation territories with changes to the so-called respirator brain. The victim's left vertebral artery was considerably hypoplastic. We concluded that a massive infratentorial infarction was caused by dissection of the right extracranial vertebral artery and consecutive thrombus formation brought about by impact with the seatbelt at the time of the collision.

An autopsy case of early ("minimal change") olivopontocerebellar atrophy (multiple system atrophy-cerebellar).

We report a 57-year-old woman with multiple system atrophy (MSA) of 15-month duration. The patient developed dysarthria, followed by impaired balance of gait, mild limb ataxia, and saccadic eye movement. A postmortem examination performed after she was found dead in a bathtub revealed neuronal loss restricted to the olivopontocerebellar system, being more severe in the pontine nucleus. Mild neuronal loss was also found in the anterior vermis and inferior olivary nucleus. Alpha-synuclein immunohistochemistry demonstrated widespread occurrence of glial cytoplasmic inclusions in the central nervous system, which were more numerous in the pontine base and cerebellar white matter. In contrast, neuronal alpha-synuclein accumulation was confined to the pontine and inferior olivary nuclei. The number of neuronal intranuclear inclusions was much higher than that of neuronal cytoplasmic inclusions. Moreover, alpha-synuclein accumulation was more severe in the neurites than in the cytoplasm or nucleus. This case demonstrates the early pattern of brain pathology in MSA-cerebellar (olivopontocerebellar atrophy).

Multinucleated astrocytes in old demyelinated plaques in a patient with multiple sclerosis.

A 51-year-old woman with MS of 26 years duration is reported. The patient's MS history began at the age of 25 years with an initial relapsing-remitting course, followed by slow progression without distinct relapses. She became bed-ridden at the age of 40 years. A post-mortem examination revealed numerous demyelinated plaques that exhibited fibrillary gliosis with Rosenthal fibers, but without lymphocytic cuffing or foamy macrophages. Activated microglia were found mainly in the marginal portion of the plaques. These plaques were consistent with so-called 'slowly expanding plaques'. Interestingly, multinucleated astrocytes were observed within the plaques, being more numerous in the area where microglial infiltration had occurred. These findings suggest that mild persistent inflammatory processes are present even in old plaques and that certain inflammatory stimuli cause multinucleation of astrocytes. This might explain the gradual deterioration without definite relapses observed in the late stage of MS.

Hydranencephaly with extensive periventricular necrosis and numerous ectopic glioneuronal nests.

The case reported here relates to a male infant with hydranencephaly who was born at 37 weeks of gestation and died immediately after birth. Post-mortem examination revealed that the cerebral hemispheres had been replaced by fluid-filled cavities within a normal-sized cranium. The membranous hemispheric wall was composed of gliosed tissue with multiple foci of necrosis and hemosiderin-laden macrophages. The ependyma was absent. Many necrotic foci containing hemosiderin were also found around the aqueduct and fourth ventricle. These findings suggest that hemorrhagic necrosis had occurred throughout the periventricular region, and more severely in the cerebral hemispheres. Moreover, numerous glioneuronal nests were found throughout the subarachnoid space and ventricles. Glioneuronal nests, if present, are usually minimal in hydranencephaly, whereas it is one of the pathological features of multicystic encephalopathy. The transition of multicystic encephalopathy to hydranencephaly has been demonstrated repeatedly. The former is a condition resulting from a severe circulatory disturbance, most often at the end of gestation or in the perinatal period. These lesions date later than hydranencephaly. Considering that numerous glioneuronal nests were found in the present case, it is likely that the encephaloclastic process developed toward the end of gestation.

Acute coronary syndrome as a cause of sudden death in patients with old myocardial infarction: a pathological analysis.

Old myocardial infarction (OMI) is one of the most important pathological manifestations in sudden cardiac death. Fatal arrhythmia arising from a fibrotic scar has been determined as the cause of death in most cases with old myocardial infarction. However, the significance of acute plaque disruption/thrombosis of the coronary arteries in those patients has not been investigated. We examined a series of 33 hearts from individuals with OMI who died suddenly during the period from 1998 to 2001. Detailed coronary pathological findings on these hearts indicated fresh or recent rupture of the coronary plaque with thrombosis in 18 cases (55%). As a result of comprehensive analysis, the sudden deaths were explained by acute coronary syndrome in 18 cases (55%), fatal arrhythmia in eight (24%), cardiac pump failure in five (14%), and other causes in two (6%) cases. Our findings revealed that a new coronary plaque rupture independent of the old infarct was a major cause of sudden cardiac death with OMI.