Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.

中老年危机热线来电者的应激源与自杀危险性

Objective: Psychosocial crisis and psychiatric disorders are two stressors for suicide action. This study will explore the differences on demographic characteristics, severity of depression, and suicidality of middle-aged and elder crisis line callers under the influences of psychosocial crisis or psychiatric disorders or two simultaneously-mixed stressors, in order to develop effective intervention strategies for crisis line. Methods: Analysis data of 1,092 cases selected from national crisis line callers aged 45 and over who were assessed with “Suicide risk assessment” during the period from December, 2002 to December, 2008. The sample were divided into three groups of psychosocial crisis, mental health problems, and mixed-stressors of three types of general callers (48.2%, 32.3%, 19.5%), callers with current suicide ideation (43.7%, 33.0%, 23.3%) and callers attempted suicide 2 weeks prior to the call (33.6%, 42.3%, 24.1%) respectively according to the operators’ judgments of the callers’ claimed difficult situations and classification system of crisis line database. X2 test and Tukey-type and Multinomial Logistic Regression multiple comparison methods are applied to analysis the differences of the three groups. Results: In agreement with previous studies, more females (71.3%, X2=13.45, P<0.001), especially females influenced by relationship stressors (76.8%, X2=25.12, P<0.001) made the call for crisis. Among general callers, the check-out rates of Major Depression Episode of mixed-stressor callers (78.5%, P<0.001) and problem callers (68.7%, P<0.05) were significantly higher than that of crisis callers (57.1%). The check-out rates of suicide ideation of mixed-stressor callers (71.4%) were significantly higher than that in crisis callers (53.8%, P<0.001) and problem callers (60.9%, P<0.05). The check-out rates of prior suicide attempts of mixed-stressor (16.6%, P<0.05) and problem callers (18.5%, P<0.01) were significantly higher than that of crisis callers (9.8%). More than half of the mixed-stressor callers (51.8%) reported over 50% degree of hopelessness, which was significantly higher than that of crisis callers (35.6%, P<0.01) and problem callers (38.2%, P<0.05). Fewer crisis callers sought medical help than problem and mixed-stressor callers among three types of callers (X2=241.35, 146.56, 50.87; P<0.001). Compare to non-compound crisis callers, the proportion of minor, severe depression and prior depression diagnosis (14.0% vs. 17.4%; 54.9% vs. 65.2%; 0 vs. 2.2%; X2=14.35，P<0.01), suicide ideation (51.1% vs. 64.0%, P<0.05) and prior suicide attempts (8.4% vs. 15.0%, P<0.05) in compound crisis callers were significantly higher. There were more compound crisis callers with over 50% hopelessness (51.9% vs. 31.0%，X2=11.96，P<0.01). Conclusion: As predicted, among middle-aged and elderly participants, mixed-stressor and compound crisis callers were higher in degree of severity of depression and suicidality. Intervention strategies should be developed addressing to specific stressor or stressors. The promotions of crisis callers’ medical help seeking behavior need to be emphasized.

The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats

1 It has not been uniform to date that the Ginkgo biloba extracts enhance cognitive function in aged animals, and the mechanisms of action remain difficult to elucidate. In this study, the Morris water maze task and electrophysiological methods were used

Low-temperature heat capacity and thermodynamic properties of crystalline carboxin (C12H13NO2S)

Carboxin was synthesized and its heat capacities were measured with an automated adiabatic calorimeter over the temperature range from 79 to 380K. The melting point, molar enthalpy (Delta(fus)H(m)) and entropy (Delta(fus)S(m)) of fusion of this compound were determined to be 365.29 +/- 0.06K, 28.193 +/- 0.09 kJ mol(-1) and 77.180 +/- 0.02 J mol(-1) K-1, respectively. The purity of the compound was determined to be 99.55 mol% by using the fractional melting technique. The thermodynamic functions relative to the reference temperature (298.15 K) were calculated based on the heat capacity measurements in the temperature range between 80 and 360 K. The thermal stability of the compound was further investigated by differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis. The DSC curve indicates that the sample starts to decompose at ca. 290degreesC with the peak temperature at 292.7degreesC. The TG-DTG results demonstrate the maximum mass loss rate occurs at 293degreesC corresponding to the maximum decomposition rate. (C) 2003 Elsevier B.V All rights reserved.

Determination of heat capacities and thermodynamic properties of 2-(chloromethylthio)benzothiazole by an adiabatic calorimeter

The molar heat capacities of 2-(chloromethylthio)benzothiazole (molecular formula C8H6ClNS2, CA registry no. 28908-00-1) were measured with an adiabatic calorimeter in the temperature range between (80 and 350) K. The construction and procedures of the calorimeter were described in detail. The performance of the calorimetric apparatus was evaluated by heat capacity measurements on alpha-Al2O3. The deviation of experiment heat capacities from the corresponding smoothed values lies within 0.3%, whereas the uncertainty is within +/-0.5%, compared with that of the recommended reference data over the whole experimental temperature range. A fusion transition was found from the C-p-T curve of 2-(chloromethylthio)benzothiazole. The melting temperature and the molar enthalpy and entropy of fusion of the compound were determined to be T-m = (315.11 +/- 0.04) K, Delta(fus)H(m) = (17.02 +/- 0.03) kJ(.)mol(-1), and Delta(fus)S(m) = (54.04 +/- 0.05) J(.)mol(-1.)K(-1), respectively. The thermodynamic functions (H-T - H-298.15) and (S-T - S-298.15) were also derived from the heat capacity data. The molar fraction purity of the 2-(chloromethylthio)benzothiazole sample used in the present calorimetric study was determined to be 99.21 by fraction melting.

Heat capacity and enthalpy of fusion of fenoxycarb

Fenoxycarb was synthesized and its heat capacities were precisely measured with an automated adiabatic calorimeter over the temperature range from 79 to 360 K. The sample was observed to melt at (326.31 +/- 0.14) K. The molar enthalpy and entropy of fusion as well as the chemical purity of the compound were determined to be (26.98 +/- 0.04) kJ-mol(-1), (82.69 +/- 0.09) J-K-1-mol(-1) and 99.53% +/- 0.01%, respectively. The thermodynamic functions relative to the reference temperature (298.15 K) were calculated based on the heat capacity measurements in the temperature range between 80 and 360 K. The extrapolated melting temperature for the absolutely pure compound obtained from fractional melting experiments was (326.62 +/- 0.06) K. Further research on the melting process of this compound was carried out by means of differential scanning calorimetry technique. The result was in agreement with that obtained from the measurements of heat capacities.