Effects of Inducers and Epoxide Hydrase on the Metabolism of Benzo[a]pyrene by Liver Microsomes and a Reconstituted System: Analysis by High Pressure Liquid Chromatography

The mobilities of 24 potential metabolites of benzo[a]pyrene were examined with high pressure liquid chromatography. Twelve phenols, five quinones, four dihydrodiols, and three oxides were studied. The chromatographic procedure employed allowed the separation and quantitation of benzopyrene metabolites into three major groups consisting of phenols, quinones, and dihydrodiols. Two of the benzopyrene oxides were unstable during chromatography, whereas the third oxide was more stable and chromatographed in the quinone fraction.Treatment of rats with phenobarbital or 3-methylcholanthrene enhanced the metabolism of benzopyrene by liver microsomes and altered the relative amounts of the various metabolites formed. In the absence of epoxide hydrase (EC 4.2.1.63), benzopyrene was metabolized primarily to phenols and quinones but was not appreciably metabolized to dihydrodiols by a solubilized, reconstituted cytochrome P-448 monooxygenase system. Addition of partially purified epoxide hydrase resulted in the formation of benzopyrene dihydrodiols with a concomitant decrease in the formation of phenolic metabolites, indicating that benzopyrene undergoes metabolism via arene oxides that are precursors for dihydrodiols and phenols.     

Morel's laminar sclerosis showing apraxia of speech: Distribution of cortical lesions in an autopsy case

A 57‐year old man with chronic alcoholism presented with apraxia of speech and disturbance of consciousness. He had a history of gastrectomy and had been drinking alcohol. The symptoms improved with administration of thiamine, but he later developed diarrhea and delirium, and died approximately 40 days after the onset. Autopsy findings were consistent with Wernicke's encephalopathy and pellagra encephalopathy. Furthermore, laminar cortical necrosis with vacuoles and astrocytosis was found in the second and third layers of the bilateral frontal cortices, suggesting Morel's laminar sclerosis. The lesions were mainly located in the bilateral primary motor cortices. Involvement of the lower part of the left primary motor cortex may be associated with apraxia of speech in our case.     

Possible association of limbic tau pathology with psychosis or behavioral disturbances: Studies of two autopsied psychiatric patients

Tauopathies, including Alzheimer's disease and primary age-related tauopathy (PART), present heterogeneous clinico-pathological phenotypes that include dementia, aphasia, motor neuron diseases, and psychiatric symptoms. PART is neuropathologically characterized by the presence of neurofibrillary tangles in limbic regions without significant Aβ deposition, but its clinical features have not yet been fully established. Here, we present two patients with distinct psychosis and behavioral symptoms. At autopsy, these patients showed tau pathologies that could not be classified as typical PART, although PART-like neurofibrillary tangles were present in limbic regions. Clinically, both patients were admitted to mental hospitals due to severe delusions or other neuropsychiatric/behavioral symptoms. The first case presented with hallucination, delusion, and apathy at age 70, and died of pancreatic cancer at age 75. He had neuronal cytoplasmic inclusions with selective accumulation of 3Rtau in the striatum and thorn-shaped astrocytes in the amygdala. The second case, who presented with abnormal behaviors such as wandering, agitation and disinhibition, exhibited limbic neurodegeneration with massive 4R tau-positive oligodendroglial inclusions in the medial temporal white matter. His age at onset was 73, and the duration of disease was 15 years. These findings support the notion that distinct limbic tau pathology with concomitant degeneration of the related neural circuits might induce specific psychosis and behavioral symptoms. This underlines the importance of neuropathological evaluation for both clinical education and practice in the fields of neuropathology and neuropsychiatry.     

Formation of congenital cataract in the offspring of galactosemic rats]

It has been established that lenses of offspring of galactosemic rats form sugar cataracts. In the present study, in order to clarify the critical period in pregnancy for the cataract formation, lenses of offspring of pregnant rats which were fed galactose diets at each of three terms of pregnancy, were examined histologically and biochemically. Severe cataract and a large amount of galactitol in the lenses were found in the offspring of rats fed a galactose diet in the last term of pregnancy. Moreover, focal cataract was found in the offspring of rats fed a galactose diet in the middle term. These results indicate that the critical period in pregnancy for cataract formation of the offspring is the last term of pregnancy and that cataract formation begins in the middle term in offspring of galactosemic rats.     

Effects of Zopiclone on Slow Wave Sleep and Spontaneous K-complexes for Normal Healthy Young Adults

Abstract: Benzodiazepine (BZD) hypnotics have been known to decrease, to some degree, human slow wave sleep (SWS) although they elevate the arousal threshold during sleep. Zopiclone (ZPC), a cyclopyrrolone hypnotic, has attracted the interest of sleep researchers because an increase in human SWS has been reported. Since the increase has not been fully confirmed by all of the studies, the authors investigated the effects of ZPC 10 mg on SWS and the K-complexes for 7 healthy young adults because there is evidence indicating that delta waves consisting of SWS and the spontaneous K-complexes are identical. SWS and st. 4 sleep did not decrease on any of the ZPC nights but st. 3 sleep showed a tendency to reduce on the 1st ZPC night. The frequency of the K-complexes decreased significantly on the 2nd ZPC night and tended to reduce on the 1st ZPC night. Moreover, a significant positive correlation was noted between the decrease rates of SWS and the K-complexes on both the ZPC nights. The authors, therefore, could not obtain any findings suggesting an increase in SWS with ZPC.     

Case of creeping disease treated with ivermectin

We report a case of creeping disease treated successfully with ivermectin. A 46-year-old man presented with a 1-month history of pruriginous linear erythema on his right thigh after a visit to Indonesia. Although he had no history of eating raw fish or meat, he walked along the river and in the jungle without wearing shoes. Creeping disease caused by animal hookworm was strongly suspected. The presence of parasite larvae was not confirmed in biopsied skin specimens. In enzyme-linked immunosorbent assay, serum samples were negative for binding to hookworm antigens, including Ancylostoma canium , Necator americanus and Gnathostoma doloresi . He was treated with a single 12 mg oral dose (200 µg/kg) of ivermectin. The eruption and pruritus resolved within a few days after the administration and did not relapse.     

Usefulness of culture test and direct examination for the diagnosis of oral atrophic candidiasis

Background  Culture test and direct microscopy, which are currently used in the diagnosis of oral candidiasis, can yield false-negative results.
Methods  Forty patients with atrophic candidiasis of the tongue were evaluated. The diagnosis was confirmed by a favorable outcome consisting of tongue pain improvement and regeneration of filiform papilla after antifungal treatment in all patients. Specimens were examined by fungal culture and direct microscopy following rapid staining; the usefulness of these procedures for diagnosis was reevaluated retrospectively after treatment.
Results  In the culture test, 30 patients (75.0%) were positive for candidal species, most of which were confirmed to be Candida albicans . Twenty-three (57.5%) were positive for pseudohyphae of fungi on direct examination. Twenty-two (55.0%) were positive and nine (22.5%) were negative for both. With regard to the diagnosis of oral atrophic candidiasis, these examinations revealed false-negative results of 25% in the culture examination and 42.5% in the direct examination.
Conclusion  Careful clinical observation of the patient for signs, such as prolonged disease duration, pain on eating, and no benefit from topical steroid treatment, and cytologic examination are important in the diagnosis of this disease.     

Development of oligomeric prion‐protein aggregates in a mouse model of prion disease

In prion diseases the normal cellular isoform of prion protein (PrP), denoted PrP^C, is converted into an abnormal, pathogenic isoform of PrP (PrP^Sc). Diagnostic tools for prion diseases are conventionally based on the detection of protease‐resistant PrP (PrP^res) after proteinase K digestion. However, recent studies have revealed that protease‐sensitive abnormal PrP (sPrP^Sc) also exists in significant amounts in brains suffering from prion diseases. Here, we designed a simplified size‐exclusion gel chromatography assay, using disposable spin columns to examine PrP aggregates in the course of the disease, without proteinase K digestion. Brain homogenates of NZW mice, inoculated intracranially with Fukuoka‐1 strain, and which died at around 120 days post‐inoculation, were assayed by this gel‐fractionation method and eluted PrP molecules in each fraction were detected by western blot analysis. Oligomeric PrP molecules were well separated from monomers, as predicted. A conventional protease‐digestion assay was also performed to detect PrP^res and revealed that the ratio of PrP^res to total PrP increased drastically from 105 days. However, the increase of PrP oligomers became significant from 90 days. These PrP oligomers in the early disease stage would, therefore, be sPrP^Sc molecules that might affect the disease pathology, such as spongiform change and abnormal PrP deposition. We also observed that the resistance of PrP oligomers to proteinase K and insolubility in phosphotungstic acid precipitation increased with disease progression, which suggests that PrP oligomers are not clearly distinguished from cellular PrP or PrP^res but may overlap in a continuous spectrum. Our study casts light on the ambiguity of the definition of PrP^Sc and indicates that the abnormality of PrP molecules should be determined from various perspectives, more than protease resistance. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Neuropsychological profile of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) accounts for 10–25% of all dementia cases in clinical populations and is considered to be the second most common degenerative dementia in elderly people after Alzheimer's disease (AD). Dementia with Lewy bodies is characterized by the presence of cognitive, psychiatric, and motor symptoms. Although the neuropsychological profiles of patients with DLB often differ from those of patients with AD, the diagnostic sensitivity, specificity, and predictive values of these profiles remain largely unknown. The present paper reviews the neuropsychological profiling of DLB and attempts the neuropsychological differentiation of DLB from AD.