Assessment of dementia in patients with multiple system atrophy.

BACKGROUND AND PURPOSE: We investigated dementia in patients with multiple system atrophy (MSA) in order to characterize the prevalence and nature of impairments in these patients. METHODS: Fifty-eight MSA patients were recruited in our institution between April 1996 and December 2006 and investigated. RESULTS: Of 58 patients, 10 were diagnosed with dementia. There were no significant differences in age at onset, gender, duration of disease, or severity of cerebellar dysfunction between patients with and without dementia. The early and delayed heart to mediastinum (H/M) ratios obtained with (123)I-metaidobenylguanidine (MIBG) cardiac scintigraphy were significantly decreased in patients with dementia compared with those without dementia. Of the 10 patients with dementia, three were found to have cognitive decline that preceded onset of motor symptoms. White matter lesions were evident in these patients, whilst frontal atrophy was prominent in patients whose cognitive decline was preceded by onset of motor symptoms. CONCLUSIONS: Dementia in patients with MSA may be more common than previously thought, furthermore, we speculate that clinical features of dementia in these patients might be heterogeneous.

Executive dysfunction in non-demented Parkinson's disease patients with hallucinations.

OBJECTIVE: We investigated executive function in Parkinson's disease (PD) patients, and focused on executive dysfunction in PD with hallucinations, but without dementia. METHODS: PD patients were classified by cognitive or neuropsychotic status as PD group, PD with vivid dreaming group, PD with hallucinations group and Parkinson's disease dementia (PDD) group. Psychomotor speed tests, the Stroop test, a verbal fluency test and the Self-rating Depression Scale were performed. RESULTS: The PDD group showed poorer scores in every test compared with the PD group. The PD with hallucinations group showed results similar to those of the PDD group, while the PD with vivid dreaming group was similar to the PD group. CONCLUSIONS: The study suggests that PD patients with hallucinations, not extensive enough to qualify as dementia, already have executive dysfunction similar to that seen in PDD patients. Executive dysfunction may be an important substrate for hallucinations even when dementia is not yet apparent.

Assessment of hallucinations in Parkinson's disease using a novel scale.

OBJECTIVE: To assess hallucinations in Parkinson's disease (PD), we developed a novel practical rating scale that evaluates five items including variety, frequency, and severity of hallucinations, caregiver burden levels, and psychiatric status at nighttime. METHODS: Forty-one PD patients and their caregivers were examined regarding the status of the hallucinations associated with PD. RESULTS: As a measure of internal consistency, the Tottori University Hallucination Rating Scale (TUHARS) has a Cronbach's alpha of 0.88. Mini-Mental State Examination (MMSE) and Hoehn-Yahr stage were associated with the TUHARS scores in a multivariate regression analysis. Visual hallucinations are the most common. However, half of the patients who reported visual hallucinations also had other hallucinations. The scale scores in the PD patients with dementia (PDD) group were significantly greater than in the PD patients without dementia (PDnD) group. CONCLUSIONS: TUHARS appears to be a suitable and easily administered instrument for assessment of hallucinations in PD. PD patients experienced various kinds of hallucinations. Hallucinations may have a close relationship with cognitive decline in PD patients.

In vitro pharmacological characterisation of a novel cyclic nociceptin/orphanin FQ analogue c[Cys(7,10)]N/OFQ(1-13)NH (2).

Nociceptin/orphanin FQ (N/OFQ) is the endogenous 17 amino acid peptide ligand for the G(i)-protein-coupled N/OFQ receptor (NOP). In an attempt to improve the metabolic stability of N/OFQ, we have produced a truncated cyclic analogue with cysteine residues at positions 7 and 10, c[Cys(7,10)]N/OFQ(1-13)NH(2) (c[Cys(7,10)]). c[Cys(7,10)], the template N/OFQ(1-13)NH(2) and N/OFQ displaced the binding of [(3)H]N/OFQ to Chinese hamster ovary cells expressing recombinant human NOP (CHO(hNOP)) with pK ( i ) values of 9.98, 9.83 and 9.18, respectively. In addition, c[Cys(7,10)], N/OFQ(1-13)NH(2) and N/OFQ stimulated the binding of guanosine triphosphate gamma [(35)S] to CHO(hNOP) cells with pEC(50)/E (max) (stimulation factor) of 9.16/5.5, 9.11/4.9 and 8.35/5.5, respectively. c[Cys(7,10)], N/OFQ(1-13)NH(2) and N/OFQ inhibited forskolin-stimulated cyclic adenosine monophosphate (cAMP) formation with pEC(50) values of 10.08, 10.11 and 9.78, respectively. All ligands produced complete inhibition of cAMP formation. In both functional assays, c[Cys(7,10)] was a full agonist. In a series of metabolism experiments, incubation of 1 nM c[Cys(7,10)], N/OFQ(1-13)NH(2) and N/OFQ with a rat brain homogenate produced a time-dependent loss of peptide that was greatest for the native peptide N/OFQ. Amidation in N/OFQ(1-13)NH(2) produced some metabolic protection, but this was not significantly improved by further inclusion of c[Cys(7,10)]. In summary, c[Cys(7,10)] is a high-affinity, high-potency full agonist of the NOP receptor. However, we were unable to demonstrate clear metabolic protection.

Effects of kainate-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain.

Stress proteins play important roles in the protective mechanisms under critical conditions for cell survival. We report here the expression of A170 and MSP23, oxidative stress-inducible proteins, under kainate-mediated excitotoxicity in the rat brain. A170 mRNA was significantly induced in the brain 5-8 h after i.p. kainate administration. MSP23 mRNA was observed at quite a low level in the rat brain, and the induction of MSP23 mRNA was not observed during the period 24 h after kainate administration. Immunoblot analysis demonstrated that the maximal expression level of A170 protein occurred 8 h after treatment in each part of the brain. MSP23 protein was constitutively expressed in the brain and the level of this protein was significantly decreased during the period 24 h after kainate administration. In situ hybridization and immunohistochemical studies showed that A170 was expressed predominantly in neurons, especially in pyramidal neurons of the cerebrum and cerebellar Purkinje cells, while MSP23 was expressed in oligodendrocytes. The induction of A170 was observed in the regions which are affected by excitotoxicity and this induction was observed in the earlier phase than cell death. Also, the region which shows high vulnerability to excitotoxicity such as pyramidal cell layer in the hippocampus, showed lower A170 expression than that which shows resistance to excitotoxicity, such as the dentate gyrus in the hippocampus. These results suggest that A170 may play a protective role in the brain under kainate-mediated excitotoxicity.

Barbiturates inhibit K(+)-evoked noradrenaline and dopamine release from rat striatal slices--involvement of voltage sensitive Ca(2+) channels.

The cellular target site(s) for anaesthetic action remain unclear. In rat striatal slices we have previously demonstrated that K(+)-evoked noradrenaline (NA) and dopamine (DA) release is mediated predominantly via P/Q-type voltage sensitive Ca(2+) channels (VSCC). Using this model of Ca(2+) dependent transmitter release we have evaluated the effects of anaesthetic and non-anaesthetic barbiturates. Rat brain striatal slices were incubated in the absence and presence of barbiturate for 10 min at 37 degrees C. The slices were then incubated for 6 min with 40 mM KCl. All anaesthetic barbiturates produced a concentration-dependent inhibition of K(+)-evoked NA and DA release. Non-anaesthetic barbiturate, barbituric acid was ineffective. The pIC(50) for NA and DA release (thiopental: 4.90+/-0.13 and 5.00+/-0.10, pentobarbital: 4.39+/-0.07 and 4.43+/-0.14, phenobarbital: 3.85+/-0.08 and 3.59+/-0.10, respectively) correlated with lipid solubility (NA: r(2)=0.999, DA: r(2)=0.987). We therefore suggest that barbiturates inhibit catecholamine release via an interaction with P/Q VSCC further implicating this channel in anaesthetic action.

Co-induction of heme oxygenase-1 and peroxiredoxin I in astrocytes and microglia around hemorrhagic region in the rat brain.

Heme[none1] oxygenase-1 (HO-1) and peroxiredoxin I (PrxI) are known to be oxidative stress- and heme-related proteins. The antioxidant activity of PrxI is inhibited by heme, therefore co-expression of HO-1 and PrxI is considered to be a reasonable mechanism to maintain its antioxidative function. Immunoblotting demonstrated that HO-1 and PrxI were induced around the hemorrhagic region. Immunohistochemical studies revealed that, in acute phase, HO-1 and PrxI were induced primarily in microglia. In the subacute and chronic phase, the immunoreactivity of HO-1 and PrxI in astrocytes was the most intense. These data are the first to demonstrate co-induction of HO-1 and PrxI in the brain. Our results suggest that HO-1 and PrxI are localized in a similar manner to assure the antioxidant activity of PrxI under stress conditions associated with intracerebral hemorrhage.

Oxidative stress-related proteins A170 and heme oxygenase-1 are differently induced in the rat cerebellum under kainate-mediated excitotoxicity.

A170 and heme oxygenase-1 (HO-1) are characterized as oxidative stress-inducible proteins whose induction depends upon common transcription factor via antioxidant responsive element. We investigated the expression of A170 and HO-1 in the cerebellum after kainate administration. In situ hybridization showed constitutive expression of A170 and HO-1 mRNA in Purkinje cell layer; mild induction of A170 or HO-1 was detected, respectively, 8 or 24 h after kainate administration. Immunohistochemical studies also demonstrated that constitutive expression and the induction of A170 protein in Purkinje cells; the induction of HO-1 protein was detected in Bergmann glia but not in Purkinje cells. Thus, the transcription factors involved in the induction of A170 might be different from those in the induction of HO-1 under kainate-mediated excitotoxicity. The existence of cell type-specific stress response was suggested.

Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues c[Cys10,14]N/OFQ(1-14)NH2 and c[Nphe1,Cys10,14]N/OFQ(1-14)NH2.

In this study we describe the activity of two cyclic nociceptin/orphanin FQ (N/OFQ) peptides; c[Cys(10,14)]N/OFQ(1-14)NH(2) (c[Cys(10,14)]) and its [Nphe(1)] derivative c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH(2) (c[Nphe(1),Cys(10,14)]) in native rat and mouse and recombinant human N/OFQ receptors (NOP). Cyclisation may protect the peptide from metabolic degradation. In competition binding studies of rat, mouse and human NOP the following rank order pK(i) was obtained: N/OFQ(1-13)NH(2)(reference agonist)>N/OFQ=c[Cys(10,14)]>>c[Nphe(1)Cys(10,14)]. In GTPgamma(35)S studies of Chinese hamster ovary cells expressing human NOP (CHO(hNOP)) c[Cys(10,14)] (pEC(50) 8.29) and N/OFQ(1-13)NH(2) (pEC(50) 8.57) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. Following 30 min pre-incubation c[Nphe(1)Cys(10,14)] competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pA(2) and slope factor of 6.92 and 1.01 respectively. In cAMP assays c[Cys(10,14)] (pEC(50) 9.29, E(max) 102% inhibition of the forskolin stimulated response), N/OFQ(1-13)NH(2) (pEC(50) 10.16, E(max) 103% inhibition) and c[Nphe(1)Cys(10,14)] (~80% inhibition at 10 microM) displayed agonist activity. In the mouse vas deferens c[Cys(10,14)] (pEC(50) 6.82, E(max) 89% inhibition of electrically evoked contractions) and N/OFQ(1-13)NH(2) (pEC(50) 7.47, E(max) 93% inhibition) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. c[Nphe(1)Cys(10,14)] (10 microM) competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pK(B) of 5.66. In a crude attempt to assess metabolic stability, c[Cys(10,14)] was incubated with rat brain membranes and then the supernatant assayed for remaining peptide. Following 60 min incubation 64% of the 1 nM added peptide was metabolised (compared with 54% for N/OFQ-NH(2)). In summary, we report that c[Cys(10,14)] is a full agonist with a small reduction in potency but no improvement in stability whilst c[Nphe(1)Cys(10,14)] displays tissue (antagonist in the vas deferens) and assay (antagonist in the GTPgamma(35)S assay and agonist in cAMP assay) dependent activity.

Physicochemical properties of calcium polycarbophil, a water-absorbing polymer.

The physicochemical properties of calcium polycarbophil were examined. Calcium polycarbophil was decalcified rapidly under acidic conditions, affording polycarbophil. Polycarbophil absorbed about 10 times its own weight of water under acidic conditions, but the swelling ratio markedly increased at above pH 4.0 and reached 70 times the initial weight under neutral conditions. The swelling of polycarbophil was not affected by non-ionic osmolarity, but was affected by ionic strength, showing a decrease with increase of ionic strength. Monovalent metal ions such as sodium and potassium ions in gastrointestinal fluid did not reduce the equilibrium swelling of polycarbophil, but divalent ions such as calcium and magnesium ions did. However, calcium ion only slightly reduced the equilibrium swelling under sodium-rich conditions. The viscosity (as an indicator of fluidity) of polycarbophil was larger than that of CMC-Na at every shear rate and polymer content examined.

[Manifestation of primary biliary cirrhosis and Basedow's disease caused by exposure to carbon monoxide in a patient with HTLV-1 associated myelopathy].

A 55-year-old woman with HTLV-1 associated myelopathy (HAM) was discovered in a rentan kotatsu (Japanese foot warmer with a frame and a coverlet by burning briquet) with conscious disorder and admitted to an emergency hospital. Her conscious disturbance waned the 3rd day after admission with gradual improvement of communication and food intake. However, on the 18th day after admission, her orientation was poor again and she was unable to take food for herself and keep sitting. She was diagnosed as suffering from an interval form of acute carbon monoxide (CMO) poisoning and transferred to our hospital for the purpose of hyperbaric oxygen therapy on the 20th day after exposure to CMO. In the course of treatment she recovered but showed jaundice, pruritus, liver dysfunction and elevation of antimitochondrial antibody. She received liver biopsy and was found to have primary biliary cirrhosis (PBC). On the 150th day, she manifested perspiration and hypertension. The clinical and immunological feature revealed her Basedow's disease. The relationship between HAM and PBC due to the autoimmune process has been predicted by investigators. The implication of autoimmune disease and HLA haplotype is a main focus of attention. Our case supports their hypothesis, and suggested that the complication occurred with immunological and genetic correlation. Anti-HTLV-1 antibody was positive at a titer of 1:8192 before exposure to CMO. On transferring to us, it was negative and revealed excessive positive at a titer of 1:20,480 on the 80th day. Immunoglobulin analysis was normal on admission and increased during hospitalization. It was reported that prenatal exposure to relatively mild concentrations of CMO in rats reduces splenic macrophage phagocytosis and killing ability as well as macrophage respiratory burst. These data suggested that PBC and Basedow's disease were manifested by exposure to carbon monoxide.

[Excessive nitrous oxide exhalation by postoperative patients in the recovery room].

Expired nitrous oxide from patients in the recovery room is considered to be the major source of air pollution. We measured expired concentrations of nitrous oxide in three patients and three volunteers. After only 5 minute inhalation of 50% nitrous oxide, it took over 2 hours for exhaled N2O concentration to decrease to 25 ppm in volunteers and after 30 minute inhalation, it took over 4 hours. The patients inhaled 50% nitrous oxide for 60, 165, 150 minutes, respectively and all patients expired nitrous oxide, the concentrations of which exceed 100 ppm over 3 hours. As to the patient who inhaled nitrous oxide for 150 minutes, expired nitrous oxide over 25 ppm was detected 10 hours after the end of anesthesia, and it was 4 ppm even after 20 hours. Any personnel including anesthesiologists and nurses working in the operating room can be exposed to high concentrations of nitrous oxide exceeding the permissible limit of 25 ppm, whenever they take care closely of their patients. We do not have any effective measures to protect us from this kind of air pollution except employing total intravenous anesthesia.

[Changes in rectal temperature during tympanoplasty under general anesthesia].

We measured rectal temperature of 35 patients who underwent tympanoplasty under various types of general anesthesia. They were allocated at random to three groups according to the types of general anesthesia; 10 patients of enflurane-N2O (enflurane group); 10 patients of neuroleptic anesthesia with droperidol, pentazocine-N2O (NLA group); 15 patients of total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK group). After the induction of anesthesia, their rectal temperature was continuously monitored with an electric thermometer of NEC San-ei throughout the surgical procedure. Increase in rectal temperature was observed in all three groups, and increase in DFK group was significant compared with other two groups. It is possible that the significant increase in rectal temperature in DFK group is supposedly due to normally maintained hypothalamic thermoregulatory function as well as direct surgical stimulation to central nervous system.

[Clinical study on total intravenous anesthesia with droperidol, fentanyl, and ketamine--18. Effect on peripheral circulation as judged by core-peripheral temperature gradient].

Effect of total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) on peripheral circulation was studied by examining core-peripheral temperature gradient in twenty five patients who underwent abdominal surgery. A core temperature probe was attached on the forehead and peripheral probe on the palm of the hand of the side on which the blood pressure cuff was not applied. The temperature gradient was less than three degrees centigrade in 60% of the patients and the gradient was significantly less as compared with that of isoflurane anesthesia even at 300 minutes after the start of surgical operation. This advantage would have been caused by such factors as circulatory stimulating effect of ketamine, sympathetic blocking effect by droperidol and adequate postoperative analgesia by fentanyl and norketamine, a metabolite of ketamine. The results suggest that DFK would exert a beneficial effect on peripheral circulation, particularly during prolonged surgical procedures.

[Clinical study on intraoperative hyperketonemia in non-diabetic surgical patients under general anesthesia].

We measured plasma 3-hydroxybutyrate (3-OHBA) concentrations in 925 non-diabetic surgical patients who underwent various surgical procedures under various types of general anesthesia. Lactated Ringer's solution only was used as an intraoperative fluid. Among them, 46 patients (4.9%) developed high 3-OHBA levels of over 500 microM.l-1 during surgery. The causes of observed hyperketonemia would be surgical stress and preoperative fasting irrespective of 8 types of general anesthesia. Blood glucose, lactic acid, base excess and pH were not influenced by hyperketonemia. Prolonged recovery from anesthesia was not observed in any patients with hyperketonemia. Without any specific treatments, plasma 3-OHBA levels were unchanged or rather decreased in 70% of the patients whose 3-OHBA levels were over 500 microM. The results suggest that hyperketonemia below 500 microM.l-1 is not always disadvantageous in nondiabetic patients under general anesthesia.

[Clinical study on total intravenous anesthesia with droperidol, pentazocine and ketamine].

Fifty patients underwent various surgical procedures including abdominal, orthopedic, plastic and gynecological operations under total intravenous anesthesia with ketamine, pentazocine and droperidol. Neither nitrous oxide, inhaled anesthetics nor narcotics such as fentanyl were administered to the patients. Intraoperative muscle relaxation was achieved with vecuronium and the patients were ventilated manually throughout the surgical procedures. Thirty percent of the patients developed hypertension and tachycardia, but they were easily overcome with administration of calcium ion channel blocker. Their peripheral circulation as well as urine output was well maintained. No adverse effects on the liver and kidney were observed post-operatively. Their post-operative sedation and analgesia were evaluated excellent. A few patients had strange dream as if they might have missed their way into the "pink" tunnel. The data above described suggest that this anesthetic method would deserve further detailed clinical study.

[Effect of pirenzepine on gastric secretion during anesthesia and surgery].

Effect of pirenzepine on gastric secretion during anesthesia and surgery was evaluated in 46 surgical patients ranged in age from 18 to 68 years. The patients underwent orthopedic, ophthalmic, ENT, plastic or non-abdominal general surgery under neuroleptanesthesia except two patients who had enflurane or isoflurane anesthesia. They received either pirenzepine 10 mg, 20 mg or the combination of pirenzepine 10 mg and famotidine 20 mg intravenously just before the induction of anesthesia. Volume and acidity of gastric juice were measured for 3 hours after the administration of these agents. Decrease in volume and acidity of gastric juice after pirenzepine 10 mg as well as after pirenzepine 20 mg continued for more than 3 hrs after the administration of the agents. Efficacy of the combination of pirenzepine and famotidine on gastric secretion was more prominent than that of pirenzepine alone in a double dose.

Evaluation of Parkinson disease and Alzheimer disease with the use of neuromelanin MR imaging and (123)I-metaiodobenzylguanidine scintigraphy.

BACKGROUND AND PURPOSE: Progressive changes in the substantia nigra pars compacta and locus ceruleus of patients with Parkinson disease and Alzheimer disease visualized by neuromelanin MRI and cardiac postganglionic sympathetic nerve function on (123)I-metaiodobenzylguanidine scintigraphy have not been fully evaluated. We compared the diagnostic value of these modalities among patients with early Parkinson disease, late Parkinson disease, and Alzheimer disease. MATERIALS AND METHODS: We compared contrast ratios of signal intensity in medial and lateral regions of the substantia nigra pars compacta and locus ceruleus with those of the tegmentum of the midbrain and the pons, respectively, by use of neuromelanin MRI in patients with early Parkinson disease (n = 13), late Parkinson disease (n = 31), Alzheimer disease (n = 6), and age-matched healthy control subjects (n = 20). We calculated heart-to-mediastinum ratios on (123)I-metaiodobenzylguanidine scintigrams after setting regions of interest on the left cardiac ventricle and upper mediastinum. RESULTS: The signal intensity of the lateral substantia nigra pars compacta on neuromelanin MRI was significantly reduced in early and late Parkinson disease, and that of the medial substantia nigra pars compacta was gradually and stage-dependently reduced in Parkinson disease. The signal intensity of the locus ceruleus was obviously reduced in late Parkinson disease. Signal reduction was not significant in the substantia nigra pars compacta and locus ceruleus of patients with Alzheimer disease. The heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams was stage-dependently reduced in Parkinson disease and normal in Alzheimer disease. The signal intensity ratios in substantia nigra pars compacta and locus ceruleus on neuromelanin MRI positively correlated with the heart-to-mediastinum ratio on (123)I-metaiodobenzylguanidine scintigrams. CONCLUSIONS: Both neuromelanin MRI and (123)I-metaiodobenzylguanidine scintigraphy can help to evaluate disease progression in Parkinson disease and are useful for differentiating Parkinson disease from Alzheimer disease.

Probing the metal-insulator phase transition in the (DMEDO-EBDT)2PF6 single crystal by optical measurements.

The temperature and polarization dependence of the optical reflectivity  spectra of a quasi-one-dimensional 1/4-filled band system, (DMEDO-EBDT)(2)PF(6), have been investigated. We observed clear anisotropy in the electronic structures corresponding to the anisotropic transport properties. The appearance of a charge gap (E(g) > 0.1 eV) and transfer of the spectral weight accompanied by the metal-insulator phase transition were clearly observed. In addition, a split of the intramolecular vibrational modes was observed, which strongly suggested the existence of charge disproportionation in the low temperature phase. We also observed a photoinduced reflectivity change, which implied the occurrence of a photoinduced phase transition from the low temperature insulating phase to the high temperature metallic phase.