Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sensory and motor testing was performed on a group of termiticide workers primarily using chlorpyrifos-containing products to evaluate both the acute effects from current exposure and sensitivity of the measures to detect effects. The study group comprised 106 applicators and 52 nonexposed participants. Current exposure was measured by urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCP) collected the morning of testing. The mean TCP value for the 106 applicators was 200 microg/g creatinine. Participants received 4--5 h of testing and were evaluated using a sensory--motor test battery recommended by a National Institute for Occupational Safety and Health (NIOSH)-sponsored advisory panel to be appropriate for testing effects from pesticide exposures. Measurements testing olfactory dysfunction, visual acuity, contrast sensitivity, color vision, vibrotactile sensitivity, tremor, manual dexterity, eye--hand coordination, and postural stability were analyzed. Study results indicated limited acute effects from exposure to chlorpyrifos using urinary TCP as a measure of current exposure. The effects occurred primarily on measures of postural sway in the eyes closed and soft-surface conditions, which suggests a possible subclinical effect involving the proprioceptive and vestibular systems. Several other tests of motor and sensory functions did not show any evidence of acute exposure effects, although statistically significant effects of urinary TCP on the Lanthony color vision test scores and one contrast sensitivity test score were found. The visual measures, however, were not significant when a step-down Bonferroni correction was applied. Information also is presented on the sensitivity of the measures to detect effects in an occupationally exposed population using standard error of the parameter estimates.
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PMID:Evaluation of acute sensory--motor effects and test sensitivity using termiticide workers exposed to chlorpyrifos. 1148 41

One-day old domestic chicks (Gallus gallus domesticus) show concentration-dependent behavioural responses to olfactory cues. In the present study we investigated the lateralized olfactory responses of 1-day-old chicks to the odours of eugenol and iso-amyl acetate. In experiment 1 different concentrations of each odour were presented in repeated trials to chicks housed individually. The odours were presented together with a small coloured bead at which the chick pecked. When tested with the highest concentration of eugenol (100% v/v), the chicks demonstrated more head shaking when their left nostril was occluded (RN; right nostril in use) than when their right nostril was occluded (LN; left nostril in use). No such lateralization occurred in response to iso-amyl acetate. This result was confirmed in a second experiment in which the chicks were tested with unscented stimuli, 100% eugenol and 100% isoamyl acetate. In experiment 3 we found that occluding both the chicks' nostrils abolished the head shaking response to eugenol and to iso-amyl acetate. Thus, the chicks' head shaking responses to the odorants eugenol and iso-amyl acetate are mediated primarily by inputs from within the nasal cavity, and not by oral or occular inputs. The present results are consistent with the hypothesis that there is lateralization to olfactory cues and that it is dependent on the involvement of receptors inside the nasal cavity. We suggest that differences in lateralized olfactory responses to different odours are affected by the relative involvement of intranasal olfactory and trigeminal chemoreceptors.
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PMID:Chemosensory input and lateralization of brain function in the domestic chick. 1211 Apr 62

The study aimed to compare olfactory function in idiopathic Parkinson's disease (IPD) and nonidiopathic Parkinson's syndrome (PS). At their first visit 50 PS patients (age 38-80 years) received testing for odor threshold, olfactory discrimination and identification. All patients underwent extensive neurological diagnostics including PET scans. Patients were followed up for 6-12 months. Most of IPD patients were functionally anosmic (n=19), the remaining IPD patients had severe/moderate hyposmia (n=18). PS patients diagnosed with multiple system atrophy had less severe olfactory deficits (7 hyposmia, 1 normosmia). With the exception of 1 hyposmic patient, other PS patients had no olfactory deficits (progressive supranuclear palsy, corticobasal degeneration, psychogenic PS, essential tremor). This study added to previous findings: (1) there was no major difference betwesen olfactory function in IPD subtypes; (2) all olfactory tests differentiated IPD from nonIPD. These data suggest that olfactory probes improve the diagnostic armamentarium in IPD.
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PMID:Olfactory function in Parkinsonian syndromes. 1238 7

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese (Mn) compound added to unleaded gasoline. It has been suggested that the combustion products of MMT containing Mn, such as manganese phosphate, could cause neurological symptoms similar to Parkinson's disease in humans. The aim of this work was to investigate the exposure-response relationship of bioaccumulation, neuropathology, and neurobehavior following a subchronic inhalation exposure to manganese phosphate in Sprague-Dawley male rats. Rats were exposed 6 h/day, 5 days/week for 13 consecutive weeks at 30, 300, or 3000 microg/m(3) Mn phosphate and compared to controls. Some rats were implanted with chronic EMG electrodes in the gastrocnemius muscle of the hind limb to assess tremor at the end of Mn exposure. Spontaneous motor activity was measured for 36 h using a computerized autotrack system. Rats were then sacrificed by exsanguination and Mn level in different brain tissues and other organs was determined by instrumental neutron activation analysis. Neuronal cell counts were obtained by assessing the sum of five grid areas for the caudate/putamen and the sum of two adjacent areas for the globus pallidus. Increased manganese concentrations were observed in all tissues of the brain and was dose-dependent in olfactory bulb and caudate/putamen. In fact, beginning with the highest level of exposure (3000 microg/m(3)) and ending with the control group, Mn concentrations in the olfactory bulb were 2.47 vs 1.28 vs 0.77 vs 0.64 ppm (P < 0.05) while for the caudate/putamen, Mn concentrations were 1.06 vs 0.73 vs 0.62 vs 0.47 ppm (P < 0.05). The Mn concentrations in lung were also dose-dependent (10.30 vs 1.40 vs 0.42 vs 0.17 ppm; P < 0.05). No statistical difference was observed for loss of neurons in caudate/putamen and globus pallidus. Locomotor activity assessment and tremor assessment did not reveal in neurobehavioral changes between the groups. Our results reinforce the hypothesis that the olfactory bulb and caudate/putamen are the main brain tissues for Mn accumulation after subchronic inhalation exposure.
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PMID:Assessment of bioaccumulation, neuropathology, and neurobehavior following subchronic (90 days) inhalation in Sprague-Dawley rats exposed to manganese phosphate. 1238 53

Because olfactory dysfunction is a feature of neurodegenerative diseases, the authors hypothesized that it would be present in essential tremor. Thirty-seven cases and control subjects underwent the University of Pennsylvania Smell Identification Test. Mean score was lower in cases than in control subjects (29.0 +/- 6.1 vs 31.9 +/- 4.6, p = 0.02) and was not correlated with tremor severity or duration.
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PMID:Olfactory dysfunction in essential tremor: a deficit unrelated to disease duration or severity. 1450 51

Promethazine hydrochloride is a drug used for the management of allergic conditions, motion sickness and nausea, and as a sedative to (treat psychiatric disorders. This drug was nominated for testing by the Food and Drug Administration because of its widespread use in human medicine and because of lack of data on its potential carcinogenicity. Oral administration is the most common route of human exposure. Toxicology and carcinogenicity studies were conducted by administering promethazine hydrochloride (>99% pure) in distilled water by gavage to groups of male and female F344/N rats and B6C3F1 mice for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, in cultured Chinese hamster ovary cells, and in Drosophila melanogaster. 16-DAY STUDY IN RATS: Groups of five male and five female rats received 0, 18.5, 55.5, 166.5, 500, or 1,500 mg promethazine hydrochloride/kg body weight once daily, 5 days per week for a total of 12 doses in a 16-day period. All rats receiving 1,500 mg/kg, four males and four females receiving 500 mg/kg, and one male and one female receiving 166.5 mg/kg died during the study. No deaths occurred in the remaining dose groups. Final mean body weights of rats receiving 166.5 mg/kg were significantly lower (12% to 25%) than those of the controls. Clinical findings included decreased activity, ocular discharge, and labored breathing in males and females receiving 166.5, 500, and 1,500 mg/kg as well as tremors in females receiving 166.5 and 500 mg/kg. There were dose-related increases in the absolute and relative liver weights of rats. Focal suppurative inflammation occurred in the nose of some male and female rats receiving 55 or 166.5 mg/kg and in the trachea of some male and female rats receiving 166.5 mg/kg. 16-DAY STUDY IN MICE: Groups of five male and five female mice received 0, 18.8, 37.5, 75, 150, or 300 mg promethazine hydrochloride/kg body weight once daily, 5 days per week for a total of 12 doses in a 16-day period. Two females receiving 75 mg/kg, one male and one female receiving 150 mg/kg, and four females receiving 300 mg/kg died during the study. No deaths occurred in the remaining dose groups. Final mean body weights of mice receiving promethazine hydrochloride were similar to those of the controls. However, in male and female controls, the final mean body weights were 11% to 12% lower than the initial mean body weights. Clinical findings occurred as early as the first day of the study and included decreased activity in male and female mice receiving 150 and 300 mg/kg. Tremors occurred in one male and five females in the 300 mg/kg group on day 1 and in one male in the 150 mg/kg group and five males and one female in the 300 mg/kg group on day 2. Absolute and relative liver weights of male mice receiving 75, 150, or 300 mg/kg were significantly greater than those of the controls. No chemical related lesions were present in male or female mice. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats received 0, 3.7, 11.1, 33.3, 100, or 300 mg promethazine hydrochloride/kg body weight once daily, 5 days per week for 13 weeks. One female receiving 100 mg/kg and six males and nine females receiving 300 mg/kg died during the study. No deaths occurred in the remaining dose groups. Final mean body weights of male rats receiving 100 or 300 mg/kg were significantly lower (19% to 22%) than those of the controls. Mean body weight gain of females receiving 100 mg/kg was significantly lower (14%) than that of the controls. Clinical findings in rats included hunched posture and labored breathing. Absolute and relative liver weights of males receiving 11.1, 33.3, 100, or 300 mg/kg and females receiving 33.3 or 100 mg/kg were significantly greater than those of the controls. Focal suppurative inflammation of the nose and trachea occurred with an increased incidence in rats receiving 100 and 300 mg/kg. A dose-related increased incidence of vacuolar degeneration of the nasal olfactory epithelium occurred in male and female rats that received 11.1, 33.3, or urred in male and female rats that received 11.1, 33.3, or 100 mg/kg. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice received 0, 5, 15, 45, 135, or 405 mg promethazine hydrochloride/kg body weight once daily, 5 days per week for 13 weeks. One control female, one female receiving 5 mg/kg, two females receiving 45 mg/kg, four females receiving 135 mg/kg, and all mice receiving 405 mg/kg died during the study. No deaths occurred in the remaining dose group. Final mean body weights of mice receiving 135 mg/kg were significantly lower (8&percnt; to 9&percnt;) than those of the controls. Clinical findings of toxicity included labored breathing and decreased activity in one 135 mg/kg female. Absolute and relative liver weights increased in a dose-related trend in both sexes. No chemical-related lesions were observed in mice. 2-YEAR STUDY IN RATS: Based on mortality and body weight differences observed at higher levels, doses of promethazine hydrochloride selected for the 2-year study in rats were 0, 8.3, 16.6, and 33.3 mg/kg. Groups of 60 male or 60 female rats were administered promethazine hydrochloride in deionized water by gavage once daily, 5 days per week for up to 103 weeks. Up to ten male and ten female rats per dose group were evaluated at 15 months. Survival, Body Weights, and Clinical Findings: There was a significant dose-related decrease in survival of rats. The survival rates in the 16.6 and 33.3 mg/kg male groups and in the 33.3 mg/kg female group were significantly lower than those of the controls. The final mean body weight of male rats receiving 33.3 mg/kg promethazine hydrochloride was 10&percnt; lower than that of the controls. Final mean body weights of female rats in the 16.6 and 33.3 mg/kg groups were 9&percnt; and 11&percnt; lower than that of the controls, respectively. No chemical-related clinical findings were noted in any dose group. Significant increases in the absolute and relative liver weights of mid- and high-dose female rats and the relative liver weights of mid- and high-dose male rats were observed at the 15-month interim evaluation. There were no biologically significant differences in the hematology or clinical chemistry parameters measured at 15 months. Pathology Findings: No neoplasms that could be attributed to promethazine hydrochloride administration were found in male or female rats. Several neoplasms occurred with a significantly decreased incidence in rats receiving promethazine hydrochloride. These included adrenal medullary pheochromocytoma (benign or malignant) and pituitary gland adenoma in the 33.3 mg/kg males and uterine stromal polyp in the 33.3 mg/kg females. The decreased incidences of adrenal medullary pheochromocytoma were chemical related. The decreased incidences of pituitary gland adenoma and uterine stromal polyp may have been related to chemical administration. Diffuse fatty change of the liver of male rats increased with dose and was attributed to chemical administration. 2-YEAR STUDY IN MICE: Based on mortality and body weight differences observed at higher levels, the doses of promethazine hydrochloride selected for the 2-year study were 0, 11.25, 22.5, and 45 mg/kg for male mice and 0, 3.75, 7.5, and 15 mg/kg for female mice. Groups of 60 male or 60 female mice were administered promethazine hydrochloride in deionized water by gavage once daily, 5 days per week for up to 103 weeks. Up to 10 male and 10 female mice per dose group were evaluated at 15 months. Survival, Body Weights, and Clinical Findings: Survival of mice receiving promethazine hydrochloride was similar to that of the controls. Mean body weights of mice were within 7&percnt; of those of the controls throughout the study. There were no chemical-related clinical findings in male or female mice. There were no differences in hematology or clinical chemistry parameters measured at 15 months that were attributed to the administration of promethazine hydrochloride. Pathology Findings: There were no neoplasms or nonneoplastic lesions that were attributed to the administration of promethazine hydrochloride. GENETIC TOXICOLOGY: Promethazine hydrochloride did not induce gene mutations in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537, or a significant increase in chromosomal aberrations in cultured Chinese hamster ovary cells; both of these tests were conducted with and without exogenous metabolic activation (S9). A small dose-related increase in sister chromatid exchanges was observed in cultured Chinese hamster ovary cells in the presence of S9; this response was considered to be equivocal. No increase in sister chromatid exchanges was observed in the absence of S9. Promethazine hydrochloride did not induce sex-linked recessive lethal mutations in germ cells of male Drosophila melanogaster administered the chemical by feeding or injection. CONCLUSIONS: Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenic activity of promethazine hydrochloride in male or female F344/N rats receiving 8.3, 16.6, or 33.3 mg/kg. There was no evidence of carcinogenic activity of promethazine hydrochloride in male B6C3F1 mice receiving 11.25, 22.5, or 45 mg/kg. There was no evidence of carcinogenic activity of promethazine hydrochloride in female B6C3F1 mice receiving 3.75, 7.5, or 15 mg/kg. The decrease in the incidences of adrenal medullary pheochromocytoma in male rats was considered to be related to promethazine hydrochloride administration. The decrease in the incidences of pituitary gland adenoma in male rats and uterine stromal polyp in female rats may have been related to promethazine administration. Synonyms: Phenothiazine,10-(2-(dimethylamino)propyl)-,monochlorohydrate; 10H-phenothiazine-10-ethanamine;10-(2-dimethylamino-2-methylethyl)phenothiazine hydrochloride; N-(2 -dimethylamino-2 -methyl)ethylphenothiazine hydrochloride Trade names: Diprazi; Kinetosin; Phenergan; Phenergan hydrochloride; Promine; Pipolfen; Plletia; Prorex; Promantine; Pyrethia; Romergan hydrochlonde
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PMID:NTP Toxicology and Carcinogenesis Studies of Promethazine Hydrochloride (CAS No. 58-33-3) in F344/N Rats and B6C3F1 Mice (Gavage Studies). 1261 86

Benzyl acetate is used as a flavoring agent in foods, as a fragrance in soaps and perfumes, as a solvent for cellulose acetate and nitrate, and as a component of printing inks and varnish removers. The NTP previously studied the toxicology and carcinogenicity of this chemical in F344/N rats and B6C3F1 mice using the gavage route of administration and corn oil as a vehicle. Benzyl acetate increased the incidences of pancreatic acinar cell adenomas in male rats and the incidences of hepatocellular adenomas and forestomach neoplasms in male and female mice. Because of the confounding effect of corn oil on the incidences of pancreatic neoplasms and because of controversy over the use of the gavage route of administration, the NTP decided to restudy benzyl acetate using the dosed feed route of administration. In these repeat studies, male and female F344/N rats and B6C3F1 mice received benzyl acetate (at least 98% pure) in feed for 13 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium nunnery, cultured Chinese hamster ovary cells, LS178Y mouse lymphoma cells, Drosophila melanogaster, and mouse bone marrow and peripheral blood cells. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were fed diets containing 0, 3,130, 6,250,12,500, 25,000, or 50,000 ppm (0, 230, 460, 900,1,750, or 3,900 mg/kg body weight for males and 0, 240, 480, 930,1,870, or 4,500 mg/kg for females) benzyl acetate for 13 weeks. Nine male and nine female rats receiving 50,000 ppm benzyl acetate died or were killed moribund between weeks 2 and 8 of the study. The mean body weight gain and the final mean body weight of 25,000 ppm males were significantly lower (P</=0.01) than those of the control group. Feed consumption by exposed rats, except the 25,000 and S0,000 ppm males and 50,000 ppm females, was similar to that by the controls. The reduced feed consumption by 25,000 and 50,000 ppm males and 50,000 ppm females may have been due to toxicity or decreased palatability. Tremors and ataxia occurred only in the 50,000 ppm rats. These findings were first observed on day 15 in nine males and six females and continued until the end of the study. Cholesterol levels in 12,500 and 25,000 ppm females and triglyceride levels in 25,000 ppm females were lower than those in the controls. Chemical-related lesions occurred in the brain, kidney, tongue, and skeletal muscles of the thigh. Necrosis of the brain involving the cerebellum and/or hippocampus, degeneration and regeneration of the renal tubule epithelium, and degeneration and sarcolemma nuclear hyperplasia of the tongue and skeletal muscles occurred in most male and female 50,000 ppm rats. This effect was observed in the 1,000 mg/kg group in the previous gavage study (NTP, 1986). 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were fed diets containing 0, 3, 130, 6,250, 12,500, 25,000, or 50,000 ppm (0, 425, 1,000, 2,000, 3,700, or 7,900 mg/kg body weight for males and 0, 650, 1,280, 2,980, 4,300, or 9,400 mg/kg for females) benzyl acetate. One 50,000 ppm male mouse died and one 50,000 ppm female mouse was killed moribund before the end of the study. Mean body weight gains and final mean body weights of all exposed male and female mice were significantly lower than those of the controls and the mean body weight gains decreased with increased exposure level. Feed consumption by 3,130 ppm males and all exposed females was lower than that by the controls. Tremors occurred only in females and were first observed on day 16 in three females receiving 50,000 ppm, day 94 in one female receiving 25,000 ppm, and day 93 in one female receiving 12,500 ppm. The tremors continued until the end of the study. Necrosis of the brain involving the hippocampus occurred in four 50,000 ppm mice, one male and three females. Hepatocellular necrosis also occurred in the male with brain lesions. On reexamination of the previous 13-week gavage study (NTP, 1986), a similar lesion was seen in the brain of one 1,000 mg/kg female mouse; none were seen in 1,000 mg/kg male mi male mice. The lesion was less severe than that described in the present dosed feed study. The highest dose used in the gavage study was 1,000 mg/kg compared to an estimated high dose of 7,200 mg/kg for the feed study. 2-YEAR STUDY IN RATS: The doses selected for the 2-year feed study of benzyl acetate in F344/N rats were based on lower survival, mean body weights, and feed consumption, and on increased incidences of histopathologic brain lesions in 50,000 ppm male and female rats in the 13-week study. Groups of 60 male and 60 female F344/N rats were fed diets containing 0, 3,000, 6,000, or 12,000 ppm benzyl acetate for 2 years. Survival, Body Weights, Feed and Compound Consumption, and Clinical Pathology: Survival of exposed rats was similar to that of the controls. The mean body weights of the 12,000 ppm males and exposed females were approximately 5&percnt; lower than those of the controls throughout most of the study. The feed consumption by 12,000 ppm males was slightly lower than that by the controls. Dietary levels of 3,000, 6,000, and 12,000 ppm benzyl acetate were estimated to result in average daily consumption levels of 130, 260, and 510 mg/kg body weight (males) and 145, 290, and 575 mg/kg (females). No biologically significant changes in hematology or clinical chemistry parameters were found that could be attributed to benzyl acetate administration. Pathology Findings: No compound-related increased incidences of neoplasms or nonneoplastic lesions occurred in male or female F344/N rats receiving benzyl acetate for as long as 2 years. 2-YEAR STUDY IN MICE: The doses selected for the 2-year feed study of benzyl acetate in B6C3F1 mice were based primarily on lower body weight gains and lower final mean body weights of exposed mice in the 13-week study. Groups of 60 male and 60 female B6C3F1 mice were fed diets containing 0, 330, 1,000, or 3,000 ppm benzyl acetate for 2 years. Survival, Body Weights, Feed and Compound Consumption, and Clinical Pathology: Survival of all exposed mice, except the 3,000 ppm females, was similar to that of the control groups. Survival of 3,000 ppm females was significantly higher than that of the control group. Throughout the 2-year study, the mean body weights of 1,000 and 3,000 ppm males and females were 2&percnt; to 14&percnt; lower than those of the control groups. Dietary levels of 330, 1,000, and 3,000 ppm benzyl acetate were estimated to result in average daily consumption levels of 35, 110, and 345 mg/kg (males) and 40, 130, and 375 mg/kg (females). No biologically significant changes in hematology or clinical chemistry parameters were observed in mice receiving 330,1,000, or 3,000 ppm benzyl acetate. Pathology Findings: No increase in neoplasm incidence in mice could be attributed to benzyl acetate administration in feed. This contrasts with the previous finding that administration of benzyl acetate in corn oil by gavage once daily 5 days a week for as long as 2 years was carcinogenic to mice, causing increased incidences of hepatocellular neoplasms and forestomach neoplasms. The contrast in results between the two studies may be due to differences in the dose levels used (highest dose: gavage, 1,000 mg/kg a day; feed, 360 mg/kg a day). Dose-related increased incidences or severities of nonneoplastic nasal lesions occurred in the most posterior portions of the nasal cavity in all exposed groups. The lesions occurred in the majority of the exposed mice and consisted of atrophy and degeneration, primarily of the olfactory epithelium, cystic hyperplasia of the nasal submucosal glands, pigmentation of the mucosal epithelium, and exudate accumulation. GENETIC TOXICOLOGY: Benzyl acetate was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537, with or without exogenous metabolic activation (S9). However, a positive response was observed for benzyl acetate, with and without S9, in the mouse lymphoma assay for induction of trifluorothymidine resistance in L5178Y cells. No significant increases in the frequencies of sister chromatid exchanges or chromosomal aberrations occurred in cultured Chinese hamster ovary cells treated with benzyl acetate in vitro, with or without S9, and no increases in either sister chromatid exchanges or chromosomal aberrations occurred in bone marrow cells of male mice treated in vivo by intraperitoneal injection. No increase in sex-linked recessive lethal germ cell mutations occurred in male Drosophila melanogaster administered benzyl acetate in feed or by injection. Tests of benzyl acetate for induction of micronucleated erythrocytes in bone marrow and peripheral blood of mice were also negative. CONCLUSIONS: Under the conditions of these 2-year feed studies, there was no evidence of carcinogenic activity of benzyl acetate in male or female F344/N rats receiving 3,000, 6,000, or 12,000 ppm; however, rats may have tolerated higher doses. There was no evidence of carcinogenic activity of benzyl acetate in male or female B6C3F1 mice receiving 330, 1,000, or 3,000 ppm. Nasal lesions associated with benzyl acetate exposure in male and female mice included nasal mucosa atrophy and degeneration (primarily of the olfactory epithelium), cystic hyperplasia of the nasal submucosal gland, and luminal exudate and pigmentation of the nasal mucosal epithelium. In previous 2-year gavage studies (TR-250), benzyl acetate increased the incidence of acinar cell adenomas of the exocrine pancreas in male F344/N rats; the gavage vehicle may have been a contributing factor. There was no evidence of carcinogenic activity in female F344/N rats receiving 250 or 500 mg/kg a day. There was some evidence of carcinogenic activity in male and female B6C3F1 mice, indicated by the increased incidences of hepatocellular adenomas and squamous cell neoplasms of the forestomach. Synonyms: acetic acid benzyl ester, acetic acid phenyl methyl ester, (acetoxymethyl)benzene, acetoxytoluene, benzyl ethanoate, phenylmethyl acetate
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PMID:NTP Toxicology and Carcinogenesis Studies of Benzyl Acetate (CAS No. 140-11-4) in F344/N Rats and B6C3F1 Mice Feed Studies). 1261

There has been an increase of interest in olfactory dysfunction since it was realised that anosmia was a common feature of idiopathic Parkinson's disease (PD) and Alzheimer-type dementia (AD). It is an intriguing possibility that the first sign of a disorder hitherto regarded as one of movement or cognition may be that of disturbed smell sense. In this review of PD, parkinsonian syndromes, essential tremor, AD, motor neurone disease (MND) and Huntington's chorea (HC) the following observations are made: 1). olfactory dysfunction is frequent and often severe in PD and AD; 2). normal smell identification in PD is rare and should prompt review of diagnosis unless the patient is female with tremor-dominant disease; 3). anosmia in suspected progressive supranuclear palsy and corticobasal degeneration is atypical and should likewise provoke diagnostic review; 4). hyposmia is an early feature of PD and AD and may precede motor and cognitive signs respectively; 5). subjects with anosmia and one ApoE-4 allele have an approximate 5-fold increased risk of later AD; 6). impaired smell sense is seen in some patients at 50% risk of parkinsonism; 7). smell testing in HC and MND where abnormality may be found, is not likely to be of clinical value; and 8). biopsy of olfactory nasal neurons shows non-specific changes in PD and AD and at present will not aid diagnosis.
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PMID:Olfaction in neurodegenerative disorder. 1267 41

To study the incidence and topographic distribution of alpha-synuclein-positive inclusions in Parkinson's disease (PD), dementia with LB (DLB), and Alzheimer's disease (AD), 206 brains of elderly patients, including 53 patients with clinical PD, 110 autopsy-proven AD cases, 22 with dementia with LB (DLB), 1 case with essential tremor, and 20 age-matched controls were investigated using alpha-synuclein immunohistochemistry. For technical reasons, the olfactory system was not studied. In all PD brains, alpha-synuclein-positive inclusions and neuronal losses were present in medullary and pontine nuclei, locus coeruleus, and substantia nigra, with additional lesions in amygdala (24%), allocortex (58%), cingulate area (34%), and isocortex (26.5%). All PD cases corresponded to pathology stage 4-6 suggested by Braak et al. (2003, Neurobiol Aging 24:197). In most cases of DLB, the distribution of alpha-synuclein pathology and neurodegeneration corresponded to stages 5 and 6 of PD pathology. The case with essential tremor and 48.2% of the AD cases showed no LB pathology; in the other AD brains alpha-synuclein-positive inclusions were seen in various brain areas. None of the controls showed LB pathology. Among 12 cases of incidental Lewy body disease (without clinical parkinsonian signs), 7 corresponded morphologically to PD stage 3 or 4. In further 6 AD cases, 2 with parkinsonian symptoms, considerable damage to locus coeruleus, substantia nigra, nucleus basalis and allocortex with preservation of the medullary nuclei was seen. The preliminary data largely confirm the Braak staging of brain pathology, although some of the clinical PD cases corresponded to stage 3 often considered as "preclinical". In addition, some cases without demonstrable involvement of medullary nuclei showed extensive PD-like pathology in other brain areas, suggesting deviation from the proposed stereotypic expansion pattern and that incidental LB pathology may affect solely the locus coeruleus and substantia nigra. Striking similarity of LB pathology between DLB and PD suggests close morphological relationship between both disorders. Widespread LB lesions occurred in many sporadic AD cases without parkinsonian symptoms, the pathogenesis and clinical impact of which are unclear. The relationship between AD and PD with particular reference to alpha-synuclein-positive lesions needs further elucidation [corrected].
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PMID:Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution--a pilot study. 1284 52

In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.
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PMID:[Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura]. 1463 19


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