Substance Use Restraint: An Extension of the Construct to a Clinical Population

Restraint is a construct of potential use forunderstanding addictive behaviors. In terms of alcoholand other drug use, restrained individuals arecognitively and behaviorally preoccupied withcontrolling their substance use. Previous work in thecontext of alcohol consumption suggests that whenregulation fails, alcohol and other drug users are morelikely to engage in excessive substance use. Thisproposition was evaluated in a clinical population ofalcohol and other substance users admitted to aninpatient treatment program. A confirmatory factoranalysis of alcoholics' responses to the Temptation andRestraint Inventory, a measure of drinking restraint,replicated the two second-order factors previouslyreported for social drinkers: Cognitive and EmotionalPreoccupation (CEP) and Cognitive and Behavioral Control (CBC). CEP scores were a negative predictor ofpretreatment percentage of days abstinent and a positivepredictor of percentage of drinking days engaged inheavy drinking, drinks per drinking day, and drinking consequences. CBC scores were a negativepredictor onlyof drinks per drinking day. An analysis ofdrug users' responses to a drug version of theTemptation and Restraint Inventory also replicated thepreviously found CEP and CBC factors. Scores on the CEPfactor were a positive predictor and scores on the CBCfactor a negative predictor of drug use frequency. CEPscores also were a positive predictor of drug use consequences. The data taken together representa potentially useful extension of the restraintconstruct to alcoholics and other drug users and supporta multifactorial characterization of substance use restraint as reflecting a reciprocalrelationship between restricted and excessive substanceuse.     

The effects of preweaning manganese exposure on spatial learning ability and p-CaMKIIα level in the hippocampus

BackgroundThe effects and mechanisms of preweaning Manganese (Mn) exposure on cognitive dysfunction remain unclear.ObjectiveThis study evaluated the effects of preweaning Mn exposure on spatial learning and memory as well as the protein expression of CaMKIIα and p-CaMKIIα.MethodsWe treated neonate rats with Mn²⁺ doses of 0 (control group), 10, 20 and 30 mg of Mn²⁺ per kg body weight (Mn-exposed groups) over postnatal day (PND) 1–21 by intraperitoneal injection. The ability of spatial learning and memory was tested on PND 22 using the Morris water maze (MWM), while the protein expressions of CaMKIIα and p-CaMKIIα in the hippocampus were evaluated by Western blotting. The levels of Mn in the blood and hippocampus were measured by inductively coupled plasma-mass spectrometry (ICP-MS).ResultsThe rats in Mn-exposed groups showed a significant delay in spatial learning ability on the third day of the MWM without dose-dependent differences, but there was no effect on the spatial memory ability. p-CaMKIIα, but not CaMKIIα protein expression significantly reduced in the Mn-exposed group.ConclusionThese findings suggested that the inhibition of p-CaMKIIα could be one of the mechanisms involved in the occurrence of Mn-induced cognitive impairments.     

慢性肺源性心脏病心肺相关规律研究

[目的]以五脏相关学说为理论基础,探讨心肺相关规律,进一步阐述及完善“五脏相关学说”及中医对慢性肺源性心脏病(简称肺心病)证候规律的认识.[方法]根据中医脏腑证候辨析制定临床信息采集表,详细采集并记录346例肺心病住院患者的症状、中医证候表现,在所列症状中,若涉及该系脏腑其中两项以上者即认定为病例涉及该系脏腑,再将临床...     

Sleep rebound attenuates context-dependent behavioural sensitization induced by amphetamine

We have recently demonstrated that paradoxical sleep deprivation (PSD) potentiates the induction of amphetamine (AMPH)-induced behavioural sensitization by increasing its conditioned component. In the present study, the effects of sleep rebound (induced by 24 h recovery period from PSD) were studied on AMPH-induced behavioural sensitization. Sleep rebound attenuated the acute locomotor-stimulating effect of AMPH. AMPH-induced behavioural sensitization was context-specific and was also attenuated by sleep rebound. These results strengthen the notion that sleep conditions can influence AMPH-induced behavioural sensitization.     

Increased IL‐6 Expression in Osteoclasts Is Necessary But Not Sufficient for the Development of Paget's Disease of Bone

Measles virus nucleocapsid protein (MVNP) expression in osteoclasts (OCLs) and mutation of the SQSTM1 (p62) gene contribute to the increased OCL activity in Paget's disease (PD). OCLs expressing MVNP display many of the features of PD OCLs. Interleukin‐6 (IL‐6) production is essential for the pagetic phenotype, because transgenic mice with MVNP targeted to OCLs develop pagetic OCLs and lesions, but this phenotype is absent when MVNP mice are bred to IL‐6^–/– mice. In contrast, mutant p62 expression in OCL precursors promotes receptor activator of NF‐κB ligand (RANKL) hyperresponsivity and increased OCL production, but OCLs that form have normal morphology, are not hyperresponsive to 1,25‐dihydroxyvitamin D₃ (1,25‐(OH)₂D₃), nor produce elevated levels of IL‐6. We previously generated p62^P394L knock‐in mice (p62KI) and found that although OCL numbers were increased, the mice did not develop pagetic lesions. However, mice expressing both MVNP and p62KI developed more exuberant pagetic lesions than mice expressing MVNP alone. To examine the role of elevated IL‐6 in PD and determine if MVNP mediates its effects primarily through elevation of IL‐6, we generated transgenic mice that overexpress IL‐6 driven by the tartrate‐resistant acid phosphatase (TRAP) promoter (TIL‐6 mice) and produce IL‐6 at levels comparable to MVNP mice. These were crossed with p62KI mice to determine whether IL‐6 overexpression cooperates with mutant p62 to produce pagetic lesions. OCL precursors from p62KI/TIL‐6 mice formed greater numbers of OCLs than either p62KI or TIL‐6 OCL precursors in response to 1,25‐(OH)₂D₃. Histomorphometric analysis of bones from p62KI/TIL‐6 mice revealed increased OCL numbers per bone surface area compared to wild‐type (WT) mice. However, micro‐quantitative CT (µQCT) analysis did not reveal significant differences between p62KI/TIL‐6 and WT mice, and no pagetic OCLs or lesions were detected in vivo. Thus, increased IL‐6 expression in OCLs from p62KI mice contributes to increased responsivity to 1,25‐(OH)₂D₃ and increased OCL numbers, but is not sufficient to induce Paget's‐like OCLs or bone lesions in vivo. © 2014 American Society for Bone and Mineral Research.