Toxicological assessment and developmental abnormalities induced by butylparaben and ethylparaben exposure in zebrafish early-life stages.

Toxicological effects of butylparaben (BuP) and ethylparaben (EtP) on zebrafish (Danio rerio) early-life stages are not well established. The present study evaluated, using zebrafish embryos and larvae, the toxicity of BuP and EtP through benchmark dose (BMD) approach. BuP was more toxic than EtP to zebrafish larvae. In fact, Lethal Concentration 50 (LC50) values at 96 h post-fertilization (hpf) for BuP and EtP were 2.34 mg/L and 20.86 mg/L, respectively. Indeed, BMD confidence interval (lower bound (BMDL) - upper bound (BMDU) was 0.91-1.92 mg/L for BuP and 10.8-17.4 mg/L for EtP. Zebrafish embryos exposed to 1 mg/L, 2.5 mg/L of BuP and 5 mg/L, 10 mg/L, 20 mg/L, 30 mg/L of EtP showed several developmental abnormalities and teratological effects compared to negative control. Exposed zebrafish developed reduced heartbeat, reduction in blood circulation, blood stasis, pericardial edema, deformed notochord and misshaped yolk sac. Embryos exposed to the highest concentrations of the chemicals (2.5 mg/L of BuP, 10 mg/L, 20 mg/L and 30 mg/L of EtP) showed the developmental abnormalities at 48 hpf while those treated with 1 mg/L of BuP and 10 mg/L of EtP reported behavioral changes at 72 hpf, including trembling of head, pectoral fins and spinal cord. This research identified the lethal and sublethal effects of BuP and EtP in zebrafish early-life stages and could be helpful to elucidate the developmental pathways of toxicity of parabens.

[Biomechanical study of different kinds of internal fixation for the typeâ Hangman fracture, type â ¡ odontoid fracture and the C(2/3) disc injury: a finite-element analysis].

Objectives: To analyze the biomechanical stability of four kinds of internal fixation for the type Ⅰ Hangman fracture, type Ⅱ odontoid fracture and the C(2/3) disc injury by finite element (FE) analysis. Methods: Thin-section spiral computed tomography (0.5 mm) was performed on C(1) to C(3) region of cervical vertebra in healthy male volunteers.A three-dimensional hexahedral FE model of upper cervical spine was established by software (Mimics, GEOMAGICS, Pro/E and Ansys). Then the weakening of the strength of grid was performed to simulate the FE model of the type Ⅰ Hangman fracture, type Ⅱ odontoid fracture and the C(2/3) disc injury (FE/Fracture), the four internal fixation models: anterior cervical plate+ odontoid screw+ cage (FE/ACP+ OS+ cage), affixing rods from pedicle screws in C(2) to lateral mass screws in C(3)+ odontoid screw + cage (FE/C(2)PS+ C(3)LMS+ OS+ cage), affixing rods from pedicle screws in C(1) to pedicle screws in C(2) and lateral mass screws in C(3) (FE/C(1)PS+ C(2)PS+ C(3)LMS), anterior odontoid screw plate fixation system (FE/AOSP) were simulated on the FE/Fracture model.Flexion, extension, lateral bending and axial rotation were imposed on the FE/Intact, FE/Fracture and the four fixation models respectively. Results: The intact model of upper cervical spine (C(1)-C(3)) was established successfully, consisting of 259 641 nodes and 403 674 units.There was no significant difference among the FE/ACP+ OS+ cage, the FE/ C(2)PS+ C(3)LMS+ OS+ cage and the FE/AOSP of ROMC(1/2).During flexion, extension, left axial rotation and right axial rotation of ROMC(2)-C(3), the FE/AOSP decreased 70.7%, 74.4%, 38.9%, 41.1% respectively compared with the FE/C(1)PS+ C(2)PS+ C(3)LMS.The ROMC(2)-C(3) during flexion, extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation in the FE/AOSP decreased for 82.2%, 82.8%, 73.2%, 64.8%, 72.2%, 81.5% respectively when compared with those in FE/ACP+ OS+ cage.The ROMC(2)-C(3) during flexion, extension, left lateral bending, right lateral bending, left axial rotation and right axial rotation in the FE/AOSP decreased 88.2%, 81.2%, 47.6%, 41.2%, 38.9%, 39.0% respectively when compared with those in FE/C(2)PS+ C(3)LMS+ OS+ cage.The stress concentrated on the connection between plate and screw in the FE/ACP+ OS+ cage, the FE/C(2)PS+ C(3)LMS+ OS+ cage and the FE/C(1)PS+ C(2)PS+ C(3)LMS, while it distributed evenly in the FE/AOSP. Conclusion: Anterior odontoid screw plate fixation system can be used to treat the type Ⅰ Hangman fracture, type Ⅱ odontoid fracture, and the C(2/3) disc injury and can reserve the function of atlanto-axial joint.

Influence of cigarette smoking on pemphigus - a systematic review and pooled analysis of the literature.

Epidemiological evidence suggests that smoking cigarettes may be beneficial in pemphigus, but no systematic evaluation exists to corroborate this assumption. Therefore, a systematic literature review with pooled data analysis of the smoking status in patients with pemphigus was conducted. Electronic searches using PubMed from inception to November 2017 identified 13 reports meeting predetermined inclusion and exclusion criteria. Most were case-control studies partly reporting that pemphigus vulgaris and foliaceus occurred less frequently in current and former smokers. Studies also indicated that duration of smoking and number of cigarettes smoked were lower in patients with pemphigus than controls and that remission may be achieved sooner in those who smoke. However, although a generally low prevalence of smoking was demonstrated in patients with pemphigus, which was lower than in controls by pooled analysis, some investigations found no difference regarding the smoking status compared with non-pemphigus subjects. One study demonstrated more severe mucosal involvement in non-smoking patients with pemphigus, whereas another observed no difference in the rate of cutaneous or mucosal lesions between smokers and non-smokers with pemphigus. This review indicates that smoking may be a possible protective factor in pemphigus, although some compromised study methodologies yet hinder any firm conclusion. Further investigations with a refined quality design are required to resolve the so far partly conflicting results in this area.

Erythrocyte glutathione transferase: a general probe for chemical contaminations in mammals.

Glutathione transferases (GSTs) are enzymes devoted to the protection of cells against many different toxins. In erythrocytes, the isoenzyme (e-GST) mainly present is GSTP1-1, which is overexpressed in humans in case of increased blood toxicity, as it occurs in nephrophatic patients or in healthy subjects living in polluted areas. The present study explores the possibility that e-GST may be used as an innovative and highly sensitive biomarker of blood toxicity also for other mammals. All distinct e-GSTs from humans, Bos taurus (cow), Sus scrofa (pig), Capra hircus (goat), Equus caballus (horse), Equus asinus (donkey) and Ovis aries (sheep), show very similar amino acid sequences, identical kinetics and stability properties. Reference values for e-GST in all these mammals reared in controlled farms span from 3.5±0.2 U/gHb in the pig to 17.0±0.9 U/gHb in goat; such activity levels can easily be determined with high precision using only a few microliters of whole blood and a simple spectrophotometric assay. Possibly disturbing factors have been examined to avoid artifact determinations. This study provides the basis for future screening studies to verify if animals have been exposed to toxicologic insults. Preliminary data on cows reared in polluted areas show increased expression of e-GST, which parallels the results found for humans.

Management of severe head injury with brain exposure in three loggerhead sea turtles Caretta caretta.

The loggerhead Caretta caretta is the most common sea turtle in the Mediterranean. Currently, sea turtles are considered endangered, mainly due to the impact of human activities. Among traumatic lesions, those involving the skull, if complicated by brain exposure, are often life-threatening. In these cases, death could be the outcome of direct trauma of the cerebral tissue or of secondary meningoencephalitis. This uncontrolled study aims to evaluate the use of a plant-derived dressing (1 Primary Wound Dressing®) in 3 sea turtles with severe lesions of the skull exposing the brain. Following surgical curettage, the treatment protocol involved exclusive use of the plant-derived dressing applied on the wound surface as the primary dressing, daily for the first month and then every other day until the end of treatment. The wound and peri-wound skin were covered with a simple secondary dressing without any active compound (non-woven gauze with petroleum jelly). Data presented herein show an excellent healing process in all 3 cases and no side effects due to contact of the medication with the cerebral tissue.

Behavioural and physiological indicators of shelter dogs' welfare: reflections on the no-kill policy on free-ranging dogs in Italy revisited on the basis of 15 years of implementation.

The Italian National Law 281 of 1991 forbids the euthanatization of free-ranging dogs, unless they have an incurable illness or are proved to be dangerous. Without neglecting the undeniable benefits of the "no-kill" policy, nevertheless it has brought about a chronic overpopulation in shelters and, as a result, higher costs of management and welfare problems since some dogs remain in the shelter for life. In 2004-2008, the Istituto Zooprofilattico Sperimentale of the Lazio and Tuscany regions carried out a survey in the Lazio Region to verify the effects of the Italian National Law 281/91 on free-ranging dog management following 15 years from its implementation. One of the aims of the study was an assessment of the welfare of dogs in a shelter sample (8 shelters out of 47 censused in the Lazio Region). 97 mixed-breed dogs were selected, their behaviour was studied and a blood sample was taken for each dog in order to determine the individual blood concentration of cortisol and the amount of oxidative damage (level of dRoms), as well as the amount of antioxidants to cope with it. Moreover, the total leukocyte count (leukogram) was accomplished. We ran general backward stepwise regression models using "level of antioxidant", "level of dRoms" and "level of serum cortisol" as dependent variables respectively. The results showed that the most important variable that improved the level of welfare of dogs consisted in having the opportunity to regularly go out of the cage for a walk, whereas other variables like gender, size of the cage (small, medium, large), being alone in the cage, and being neutered/entire, had no significant effect on the physiological indicators of welfare. Dogs that enjoyed the regular walk had a higher total antioxidant capacity, and performed a lower frequency of displacing activities and stereotyped behaviour. Moreover, oxidative stress parameters seem to be indicators well matched with behavioural indicators of stress. Thus, for the first time, markers of oxidative status are utilised for the welfare evaluation in the domestic dog. Furthermore, the results of this paper give some suggestion about how small steps can help to improve shelters and, furthermore, this paper intends to solicit the debate on the no-kill policy.

Changes in physiological and immunological parameters during the peripartum period in Zerasca sheep.

The aim of this study was to provide the picture of the dynamics of some blood parameters in the native Zerasca sheep breed during the peripartum period. Blood samples were collected from peripheral blood of 14 ewes at different times: from 21 d before lambing to 42 d after. Physiological and immunological parameters were evaluated: aspartate-aminotransferase, creatine kinase, lactate dehydrogenase, non-esterified fatty acids, total protein, total antioxidant capacity, free radicals, serum bactericidal activity and serum lysozyme. One-way repeated measures ANOVA test was performed. Results showed a significant influence of the peripartum and the deviation from the normal range on many parameters.

Randomized controlled trial of a good practice approach to treatment of childhood obesity in Malaysia: Malaysian Childhood Obesity Treatment Trial (MASCOT).

CONTEXT: Few randomized controlled trials (RCTs) of interventions for the treatment of childhood obesity have taken place outside the Western world. AIM: To test whether a good practice intervention for the treatment of childhood obesity would have a greater impact on weight status and other outcomes than a control condition in Kuala Lumpur, Malaysia. METHODS: Assessor-blinded RCT of a treatment intervention in 107 obese 7- to 11-year olds. The intervention was relatively low intensity (8 hours contact over 26 weeks, group based), aiming to change child sedentary behavior, physical activity, and diet using behavior change counselling. Outcomes were measured at baseline and six months after the start of the intervention. Primary outcome was BMI z-score, other outcomes were weight change, health-related quality of life (Peds QL), objectively measured physical activity and sedentary behavior (Actigraph accelerometry over 5 days). RESULTS: The intervention had no significant effect on BMI z score relative to control. Weight gain was reduced significantly in the intervention group compared to the control group (+1.5 kg vs. +3.5 kg, respectively, t-test p < 0.01). Changes in health-related quality of life and objectively measured physical activity and sedentary behavior favored the intervention group. CONCLUSIONS: Treatment was associated with reduced rate of weight gain, and improvements in physical activity and quality of life. More substantial benefits may require longer term and more intensive interventions which aim for more substantive lifestyle changes.

Serum biochemistry and electrophoretic patterns in the Eurasian Buzzard (Buteo buteo): reference values.

In avian medicine, hematologic and biochemical laboratory investigations are still in their infancy, because of the difficulty involved in collecting data. This has led to a lack of reference values and a nonstandardized approach to specimens obtained in critical conditions. The Eurasian Buzzard (Buteo buteo) is one of the most common raptors in Italy, yet little is known about the physiologic blood parameters of this species. Serum biochemistry and electrophoretic investigations were performed in 40 healthy Eurasian Buzzards in different Italian wildlife rescue centers waiting to be released after recovering from trauma injuries. Mean values for biochemistry parameters were pancreatic amylase 626.9 IU/l, uric acid 7.5 mg/dl, aspartate aminotransferase 330.9 IU/l, glucose 375.1 mg/dl, lipase 26.3 IU/ l, total protein 38.4 g/l, total bilirubin 0.04 mg/ dl, lactate dehydrogenase 2,008.4 IU/l, creatinine kinase 1,604.1 IU/l, alanine aminotransferase 40.4 IU/l, alkaline phosphatase 89.8 IU/l, magnesium 2.3 mg/dl, calcium 10.2 mg/dl, phosphorus 2.02 mg/dl, cholesterol 192.2 mg/ dl, triglyceride 116.4 mg/dl, albumin 14.5 g/l, creatinine 0.1 mg/dl. Mean electrophoretic values were prealbumin 1.4 g/l, albumin 14.2 g/l, alpha 1 globulin 5.9 g/l, alpha 2 globulin 4.7 g/l, beta globulin 7.5 g/l, gamma globulin 3.6 g/l, albumin/globulins ratio 0.8 g/l.

Pharmacokinetics of marbofloxacin after a single oral dose to loggerhead sea turtles (Caretta caretta).

The single-dose disposition kinetics of marbofloxacin (MBX) were determined in clinically healthy loggerhead sea turtles (n=5) after oral (PO) administration of 2 mg kg(-1) bodyweight. Marbofloxacin plasma concentrations were determined by DAD-HPLC (LOD/LOQ 0.015/0.05 microg ml(-1)). Data were subjected to non-compartmental analysis. Following PO administration, marbofloxacin achieved maximum plasma concentrations of 11.66+/-2.53 mg L(-1) at 15.00+/-3.00 h. The absence of general adverse reactions in the turtles of the study, and the favourable pharmacokinetic properties (long half-life and high maximum plasma concentration) of MBX administered PO at the single-dose of 2 mg kg(-1) suggest the possibility of its safe and effective clinical use in loggerhead sea turtles.

Polychlorinated biphenyls and organochlorine pesticide levels in tissues of Caretta caretta from the Adriatic Sea.

We detected concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) in the liver, muscle, and fat of 11 loggerhead sea turtles Caretta caretta from the central and southern Adriatic Sea. All samples contained PCBs at various concentrations, with Congener 138 (28%), 153 (27%), and 180 (32%) dominating the congener composition of the tissues. The dioxin-like congener (118, 13%) was detected in all tissues analyzed. The lower-chlorinated PCBs were not detected. The average of the total PCB concentrations, expressed in nanograms per gram wet weight, was 459.6 ng g(-1) in fat, 82.9 ng g(-1) in liver, and 5.8 ng g(-1) in muscle. Among 13 organochlorine pesticides for which analyses were conducted, 4 were detected: p,p'-DDE (57%); p,p'-DDD (16%); and p,p'-DDT and o,p'-DDT (27%). Spatial differences were found among OC concentrations in loggerheads from the central and southern Adriatic Sea. The only samples containing detectable concentrations of p,p'-DDT and o,p'-DDT were from the southern area.

Pharmacokinetics and mammary elimination of imidocarb in sheep and goats.

The pharmacokinetics and mammary excretion of imidocarb dipropionate, a therapeutic/prophylactic agent against a variety of tick-borne hemoparasitic diseases in domestic animals, have been investigated in sheep and goats. A commercial formulation of imidocarb di-propionate was injected i.m. at a single dose of 3 mg/kg of body weight in 7 mature lactating ewes and 8 lactating does in good health. Blood samples were collected for 48 h after administration and milk samples were collected every 12 h for 10 d. A weak cation-exchange solid-phase procedure was used to remove imidocarb from plasma. A hexane/isoamyl alcohol liquid-liquid procedure was adopted to extract the drug from the milk of sheep. The same method was used for goat milk after exposing the matrices to enzymatic digestion. The extracted samples were analyzed by HPLC. The i.m. disposition kinetics of imidocarb in the 2 species showed significant differences in the rate of elimination (0.0075 +/- 0.002 and 0.025 +/- 0.004 L/h in sheep and goats, respectively), being faster in ewes than in does. Nevertheless, a smaller area under the concentration-time curve (12.21 +/- 0.76 and 9.49 +/- 0.54 microg/mL per h in sheep and goats, respectively), a larger volume of distribution (4.18 +/- 0.44 and 7.68 +/- 0.57 L/kg in sheep and goats, respectively), and a longer mean residence time (9.07 +/- 0.77 and 14.75 +/- 2.20 h in sheep and goats, respectively) were found in goats, suggesting a more rapid and effective drug storage in tissues during the first 48 h after the injection. The concentrations of imidocarb in milk of both species were higher than in plasma. However, a fast passage through the blood-milk barrier and a high storage of imidocarb were observed in the milk of ewes, whereas the drug concentrations were not as high nor was the extent of drug penetration from blood to milk as great in the milk of goats (AUC(milk 0-48)/AUC(plasma 0-48) = 2.5 +/- 0.45 and 1.26 +/- 0.27 in sheep and goat, respectively). Despite the differences in pharmacokinetic behavior, and considering the sensitivity of pathogens to imidocarb, the same dosage regimen can be used for clinical efficacy against Babesia spp. infection in both species. In contrast, the differences in depletion of imidocarb residue in milk and the large variability in mammary drug elimination found in goats suggests that great care should be taken in defining the withdrawal time in small ruminant dairy species.

Interferometric coupling of the Keck telescopes with single-mode fibers.

Here we report successful interferometric coupling of two large telescopes with single-mode fibers. Interference fringes were obtained in the 2- to 2.3-micrometer wavelength range on the star 107 Herculis by using the two Keck 10-meter telescopes, each feeding their common interferometric focus with 300 meters of single-mode fibers. This experiment demonstrates the potential of fibers for future kilometric arrays of telescopes and is the first step toward the 'OHANA (Optical Hawaiian Array for Nanoradian Astronomy) interferometer at the Mauna Kea observatory in Hawaii. It opens the way to sensitive optical imagers with resolutions below 1 milli-arc second. Our experimental setup can be directly extended to large telescopes separated by many hundreds of meters.

Anthraquinones production, hydrogen peroxide level and antioxidant vitamins in Morinda elliptica cell suspension cultures from intermediary and production medium strategies.

The effects of medium strategies [maintenance (M), intermediary (G), and production (P) medium] on cell growth, anthraquinone (AQ) production, hydrogen peroxide (H2O2) level, lipid peroxidation, and antioxidant vitamins in Morinda elliptica cell suspension cultures were investigated. These were compared with third-stage leaf and 1-month-old callus culture. With P medium strategy, cell growth at 49 g l(-1), intracellular AQ content at 42 mg g(-1) DW, and H2O2 level at 9 micromol g(-1) FW medium were the highest as compared to the others. However, the extent of lipid peroxidation at 40.4 nmol g(-1) FW and total carotenoids at 13.3 mg g(-1) FW for cultures in P medium were comparable to that in the leaf, which had registered sevenfold lower AQ and 2.2-fold lower H2O2 levels. Vitamin C content at 30-120 microg g(-1) FW in all culture systems was almost half the leaf content. On the other hand, vitamin E content was around 400-500 microg g(-1) FW in 7-day-old cultures from all medium strategies and reduced to 50-150 microg g(-1) FW on day 14 and 21; as compared to 60 microg g(-1) FW in callus and 200 microg g(-1) FW in the leaf. This study suggests that medium strategies and cell growth phase in cell culture could influence the competition between primary and secondary metabolism, oxidative stresses and antioxidative measures. When compared with the leaf metabolism, these activities are dynamic depending on the types and availability of antioxidants.

Analysis of 1,2(2,3)- and 1,3-positional isomers of diacylglycerols from vegetable oils by reversed-phase high-performance liquid chromatography.

Separation of 1,2(2,3)- and 1,3-positional isomers of diacylglycerols (DAG) from vegetable oils by reversed-phase high-performance liquid chromatography (RP-HPLC) is investigated. The method is based on isocratic elution using 100% acetonitrile and UV detection at 205 nm. The following elution order of DAG molecular species is identified: 1,3-dilinolein < 1,2-dilinolein < 1,3-dimyristin < 1-oleoyl-3-linoleoyl-glycerol < 1,2-dimyristoyl-rac-glycerol < 1(2)-oleoyl-2(3)-linoleoyl-glycerol < 1-linolenoyl-3-stearoyl-glycerol < 1(2)-linolenoyl-2(3)-stearoyl-glycerol < 1,3-diolein < 1-palmitoyl-3-oleoyl-glycerol < 1,2-dioleoyl-sn-glycerol < 1(2)-palmitoyl-2(3)-oleoyl-glycerol < 1-linoleoyl-3-stearoyl-glycerol < 1,3-dipalmitin < 1(2)-linoleoyl-2(3)-stearoyl-glycerol < 1-oleoyl-3-stearoyl-glycerol < 1,2-dipalmitoyl-rac-glycerol < 1-palmitoyl-3-stearoyl-sn-glycerol < 1,3-distearin < 1,2-distearoyl-rac-glycerol. Linearity is observed over three orders of magnitude. Limits of detection and quantitation range 0.2-0.7 microg/mL for 1,3-dilinolein to 0.6-1.9 microg/mL for 1,2-dioleoyl-sn-glycerol, respectively. Precision and accuracy of the method are also demonstrated. The method is developed to separate mixtures of DAG molecular species produced from edible oils.

[3H]GR113808 binding to serotonin 5-HT(4) receptors in the postmortem neocortex of Alzheimer disease: a clinicopathological study.

Abnormalities in neural transmission of serotonin (5-HT) may play a role in both cognitive and neuropsychiatric features of Alzheimer disease (AD). We measured 5-HT(4) receptors in the postmortem frontal and temporal cortex of 34 AD subjects and 15 controls by radioligand binding with [3H]GR113808. Receptor binding data was then correlated with prospectively assessed cognitive (Mini-Mental State Examination, MMSE) and behavioral (Present Behavioural Examination, PBE) data. [3H]GR113808 binding affinity (K(D)) and density (B(max)) in AD were unchanged compared to controls in both cortical regions, and did not correlate with MMSE or PBE data. The binding parameters were also not related to disease duration, senile plaque and neurofibrillary tangle counts, and neuroleptic medication. We conclude that unlike other 5-HT receptors, 5-HT(4) receptor binding affinity and density do not seem to be affected in the frontal and temporal cortex in AD and may not have a direct role in the clinical features of the disease.

Pharmacokinetics of imidocarb dipropionate in horses after intramuscular administration.

The objective of this study was to determine the pharmacokinetic behaviour of imidocarb in horses following a single i.m. injection at the dose commonly administered to treat Babesia caballi infections or to prevent babesiosis. Eight horses were injected i.m. with a single dose of 2.4 mg imidocarb dipropionate/kg bwt and blood, faecal, urine and milk samples were collected. For imidocarb determination, a high-performance liquid chromatographic method (HPLC) was used after weak cation-exchange solid phase, or liquid-liquid, extraction procedures. Twelve hours after treatment, no detectable plasma concentrations were recorded in any of the treated animals. The distribution and elimination patterns of the drug suggested that it is quickly sequestrated in some storage tissues and remains in the body for a long time. Its prolonged presence in the body may confer a reservoir effect to imidocarb in some tissues, therefore making it undetectable in the plasma of animals but sufficient to produce its described therapeutic and prophylactic activities.

Psychosis of Alzheimer's disease is associated with elevated muscarinic M2 binding in the cortex.

OBJECTIVES: Results from recent drug trials suggest a role for the cholinergic system in the manifestation of neuropsychiatric symptoms in AD. To date, the status of muscarinic acetylcholine receptor subtypes in AD in relation to accompanying behavioral disturbances is unknown. This study aimed to measure alterations of muscarinic M(1) and M(2) receptor binding in the frontal and temporal cortex of AD and to correlate the neurochemical findings with clinical features. METHODS: The cognitive and behavioral features of 26 patients with AD were assessed prospectively using standardized tests. Together with 14 matched controls, the status of muscarinic M(1) and M(2) receptors in the postmortem frontal and temporal cortex of these patients were measured by radioligand binding assays and were correlated with clinical data. RESULTS: Compared with controls, M(2) receptor density was reduced only in the frontal cortex of AD, whereas M(1) was unaffected. Within the AD group, the neurochemical variables were not affected by demographic factors, disease severity, or cognition. Instead, M(2) receptor density was increased in the frontal and temporal cortex of patients with AD with psychotic symptoms compared with those without these symptoms. CONCLUSIONS: This study suggests a role for M(2) receptors in the psychosis of AD and may provide the rationale for treatment of behaviorally perturbed patients with AD with cholinomimetics and M(2) antagonists.

Aged care service delivery in Japan: preparing for the long-term care insurance scheme.

The implementation of Japan's Long-Term Care Insurance Scheme in early 2000 presaged many changes in service delivery and much debate among service providers, different levels of government, academic analysts, and major media interests. The first part of this paper gives an account of the major changes in the organization of service delivery that have increased opportunities for private sector providers, including large corporations, and restructured contractual relationships between municipalities and providers in all sectors. New arrangements for client assessment, classification, care management, and extended service types are then outlined. An assessment is then made of the likelihood that the expected outcomes of the scheme will be realized, with the concerns of welfare professionals that the public welfare system is under threat juxtaposed with bureaucratic goals of liberalizing the provision of long-term.