Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat.

Systemic administration of the muscarinic-receptor antagonists atropine and scopolamine produces cognitive deficits in humans, nonhuman primates and rodents. In humans, these deficits resemble symptoms of dementia seen in Alzheimer's disease. The passive avoidance (PA) task has been one of the most frequently used animal models for studying cholinergic mechanisms in learning and memory. The present study examined the ability of two selective 5-HT(1A) receptor antagonists WAY 100635 and NAD-299 (robalzotan) and two acetylcholinesterase (AChE) inhibitors tacrine and donepezil to attenuate the impairment of PA retention caused by the nonselective muscarinic receptor antagonist scopolamine in the rat. Although demonstrating differences in their temporal kinetics, both WAY 100635 and NAD-299 attenuated the impairment of PA caused by scopolamine (0.3 mg/kg s.c.). Donepezil did not block the PA deficit caused by the 0.3 mg/kg dose of scopolamine, but it prevented the inhibitory effects of the 0.2 mg/kg dose of scopolamine. In contrast, tacrine was effective vs both the 0.2 and 0.3 mg/kg doses of scopolamine. These results indicate that (1). a functional 5-HT(1A) receptor antagonism can attenuate the anterograde amnesia produced by muscarinic-receptor blockade, and (2). the AChE inhibitors tacrine and donepezil differ in their ability to modify muscarinic-receptor-mediated function in vivo. These results suggest that 5-HT(1A) receptor antagonists may have a potential in the treatment of cognitive symptoms in psychopathologies characterized by reduced ACh transmission such as Alzheimer's disease.     

Percent-free prostate specific antigen is elevated in men on haemodialysis or peritoneal dialysis treatment.

BACKGROUND: Men with chronic renal failure evaluated for transplantation are often tested for prostate specific antigen (PSA) to detect prostate cancer. PSA occurs in several different molecular forms in serum: free PSA (fPSA) and complexed PSA (cPSA), the sum of which corresponds to total PSA (tPSA). In addition to tPSA, percent fPSA to tPSA (%fPSA) is widely used to enhance discrimination of benign disorders from prostate cancer. The low molecular mass of fPSA suggests elimination by renal glomerular filtration and that renal failure may significantly influence %fPSA. We evaluated whether established reference levels for %fPSA are applicable also to patients treated with haemodialysis or continuous ambulatory peritoneal dialysis (CAPD). METHODS: The study included 20 men on intermittent haemodialysis with low-flux membranes and 25 men on CAPD, without known history of prostate cancer. The control group included 3129 men without known prostate cancer. We analysed fPSA and tPSA in serum by dual-label immunofluorometric assays, from which we calculated %fPSA and cPSA. Serum levels of different PSA forms were adjusted for age and presented as geometric means. RESULTS :Percent fPSA was significantly higher in patients on either haemodialysis (39.5%) or CAPD (39.6%) compared with controls (28.1%). Haemodialysis patients, but not CAPD patients, had significantly higher mean levels of fPSA. Levels of tPSA and cPSA for haemodialysis or CAPD patients did not differ significantly compared with controls. CONCLUSIONS: Recommended reference ranges for %fPSA, based on men with normal renal function, do not apply to uraemic men on dialysis. In these men, a high %fPSA should not be considered as a sign of benign disease. This is clinically important in the evaluation of dialysis patients for transplantation, as %fPSA is often used as a tool for detection of prostate cancer.     

Priority setting in the REACH system.

Due to the large number of chemicals for which toxicological and ecotoxicological information is lacking, priority setting for data acquisition is a major concern in chemicals regulation. In the current European system, two administrative priority-setting criteria are used, namely novelty (i.e., time of market introduction) and production volume. In the proposed Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) system, the novelty criterion is no longer used, and production volume will be the main priority-setting criterion for testing requirements, supplemented in some cases with hazard indications obtained from QSAR modelling. This system for priority setting has severe weaknesses. In this paper we propose that a multicriteria system should be developed that includes at least three additional criteria: chemical properties, results from initial testing in a tiered system, and voluntary testing for which efficient incentives can be created. Toxicological and decision-theoretical research is needed to design testing systems with validated priority-setting mechanisms.     

Traumatic intrusion of permanent teeth. Part 2. A clinical study of the effect of preinjury and injury factors, such as sex, age, stage of root development, tooth location, and extent of injury including number of intruded teeth on 140 intruded permanent teeth

Abstract –  A prospective study of 140 intruded permanent teeth was done to evaluate the following healing complications: pulp necrosis (PN), root resorption (surface, inflammatory and replacement resorption) (RR) and defects in marginal periodontal healing (MA). These complications were related to various preinjury and injury factors. Age appeared to be related to all three healing complications in that patients younger than 12 years had the lowest complication rate. Stage of root formation at the time of the injury was very strongly related to PN and MA, with immature root formation (i.e. incomplete root formation or completed root formation with wide open apex) having better prognosis than more mature root development. Lateral incisors showed significantly more defects in MA, a finding possibly explained by the observation that lateral incisors were more often involved in multiple intrusions compared to other teeth and noting that multiple intrusions had a significantly higher frequency of MA. An associated crown fracture with exposed dentin resulted in more frequent PN, a finding possibly related to bacterial invasion through dentinal tubules into an ischemic pulp. The presence of a gingival laceration added to both PN and MA. The extent of intrusion (in mm) showed some relation to both RR with intrusion 1–3 mm having the lowest frequency of RR, whereas PN and MA showed no significant relation to the extent of intrusion. Finally, multiple adjacent intruded teeth were more frequently involved in a significantly greater loss of interproximal marginal bone (MA) than single intrusions. In conclusion, the relationship between healing complications and preinjury and injury factors could generally be explained by better healing possibilities in teeth with immature root formation. A possible explanation for that could be the softer bone surrounding the tooth, whereby trauma to the periodontium might be diminished.     

Physical properties and microstructural characterization of dental porcelains mixed with distilled water and modeling liquid.

OBJECTIVE: The aim of this study was to microstructurally characterize and to make comparisons of the physical properties of sintered dental porcelains prepared by mixing with distilled water and with their modeling liquid. METHODS: Six commercial porcelain powders: IPS Classic (Ivoclar Vivadent AG, Schaan, Liechtenstein), IPS d.SIGN (Ivoclar Vivadent AG), IPS InLine (Ivoclar Vivadent AG), Vita VMK95 (Vita Zahnfabrik, Bad Sackingen, Germany), Vita OMEGA 900 (Vita) and Ceramco III (Ceramco-Dentsply, Burlington, NJ, USA) were used as starting powders. Following particle size and BET analyses of starting powders, each porcelain powder was mixed with distilled water and with its own modeling liquid. Disc specimens were sintered in accordance with each manufacturer's instructions. Specimens were characterized using X-ray diffraction (XRD), optical microscopy and SEM analysis and their physical properties such as bulk density, microhardness and biaxial flexural strength were determined. RESULTS: The sintered dental porcelains premixed with modeling liquid had density, biaxial flexural strength and microhardness values slightly higher than those premixed with distilled water. Mixing with distilled water and modeling liquid caused statistically significant differences between the density values of Vita VMK 95 and microhardness values of IPS d.SIGN and IPS InLine. Characterization investigations (XRD and SEM) revealed the coexistence of the tetragonal leucite (1-3 microm) and hexagonal fluorapatite crystals (0.4-1.2 microm) in a feldspathic glassy matrix in the microstructure of IPS d.SIGN and only leucite crystals (3-6 microm) in the microstructures of other porcelains. SIGNIFICANCE: Mixing the porcelain powders with distilled water or modeling liquid prior to sintering has no effect on the resultant sintered crystalline microstructure. On the other hand, significant differences exist between the physical properties of some porcelains.     

LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human acute myelogenic leukemia patients and protects leukemia cells from apoptosis <Emphasis Type="Italic">in vitro</Emphasis>

Background  

Relapse due to chemoresistant residual disease is a major cause of death in acute myelogenous leukemia (AML). The present study was undertaken to elucidate the molecular mechanisms of chemoresistance by comparing differential gene expression in blasts from patients with resistant relapsing AML and chemosensitive AML.     

Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory.

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.     

Clinical findings in nondemented mutation carriers predisposed to Alzheimer's disease: a model of mild cognitive impairment

Individuals carrying a mutation associated with Alzheimer's disease (AD) may serve as a model of mild cognitive impairment (MCI). Nondemented individuals from these families can be subdivided into asymptomatic and symptomatic groups. Four families were studied. Two families are associated with APP mutations (_KN670/671_ML, _E693_G) and two with PS1 mutation (_M146_V, _H163_Y). Clinical symptoms, level of global cognitive functioning as evaluated by Mini-Mental State Examination, neuropsychological test results, neuroradiological examinations (magnetic resonance imaging (MRI) and single-photon emission tomography (SPECT)), as well as cerebrospinal fluid (CSF) measurements of tau and β-amyloid are reported. Nondemented mutation carriers did not report any symptoms indicating cognitive decline. In addition, no clinical signs of dementia or marked cognitive impairment in neuropsychological tests were found. A reduction of temporal blood flow with SPECT was indicated in 5/13 nondemented mutation carriers. Two of these 13 individuals had moderate hyperintensities in deep white matter as observed on MRI. CSF measurements of Aβ_42/43 were inconclusive because of large biological variation. A nonsignificant elevation of tau was detected in mutation carriers. In conclusion, clinical examinations of relatively young individuals carrying an AD mutation did not reveal any marked abnormalities before the clinical onset of dementia.