Precedence of bone loss over changes in body composition and body fat distribution within a few years after menopause

OBJECTIVE: The present study investigated the sequence of certain phenomena with a few years after menopause: bone mineral loss, decrease in lean body mass, increase in body fat mass, or the shift toward upper body fat distribution. METHODS: Subjects were 64 postmenopausal women aged 50-53 years with right side dominance (mean age+/-S.D., 51.4+/-1.1 years), and 59 age-matched regularly menstruating premenopausal women (51.7+/-1.2 years) serving as controls. Height, weight, body mass index (BMI, wt./ht.(2)), age at menopause (in postmenopausal women), and years since menopause (YSM) were recorded. Anthropometries, bone mineral density (BMD), and body fat distribution were assessed by dual-energy X-ray absorptiometry. RESULTS: Age at menopause and YSM in postmenopausal women were 51.7+/-1.2 and 2.3+/-1.7 years, respectively. Age, height, weight, BMI did not differ between the two groups. BMD of the bilateral arm, lumbar spine (L2-4), pelvis, and total body were significantly lower in postmenopausal women. However, leg BMD, trunk-leg fat ratio, body fat mass, and the lean body mass did not differ between the two groups. CONCLUSION: Within a few years after menopause, bone mineral loss precedes lean mass loss, increase in body fat mass, and a shift toward upper body fat distribution. We can say that bone tissue is more sensitive to hypogonadism than lean and fat tissues are.     

Being right is its own reward: load and performance related ventral striatum activation to correct responses during a working memory task in youth

The ventral striatum (VS) is a critical brain region for reinforcement learning and motivation. Intrinsically motivated subjects performing challenging cognitive tasks engage reinforcement circuitry including VS even in the absence of external feedback or incentives. However, little is known about how such VS responses develop with age, relate to task performance, and are influenced by task difficulty. Here we used fMRI to examine VS activation to correct and incorrect responses during a standard n-back working memory task in a large sample (n=304) of healthy children, adolescents and young adults aged 8-22. We found that bilateral VS activates more strongly to correct than incorrect responses, and that the VS response scales with the difficulty of the working memory task. Furthermore, VS response was correlated with discrimination performance during the task, and the magnitude of VS response peaked in mid-adolescence. These findings provide evidence for scalable intrinsic reinforcement signals during standard cognitive tasks, and suggest a novel link between motivation and cognition during adolescent development.     

Interactive effects of estrogen and serotonin on brain activation during working memory and affective processing in menopausal women

While cognitive changes and mood instability are frequent symptoms reported by menopausal women, the degree to which the decline in estrogen production is responsible is not yet clear. Several lines of evidence suggest that estrogen may produce its effects on cognition and mood through modulation of serotonergic function. To test this hypothesis, we used the tryptophan depletion (TD) paradigm to lower central serotonin levels and pharmacologically manipulated estrogen levels in healthy menopausal women. We examined the individual and combined effects of estradiol and serotonin on working memory, emotion processing and task-related brain activation. Eight healthy predominantly early postmenopausal women underwent TD or sham depletion followed by functional magnetic resonance imaging (fMRI) both before and after short-term transdermal estradiol 75-150 μg/d administration. There was an estradiol treatment by TD interaction for brain activation during performance on both the N-back Task (working memory) and Emotion Identification Task (affective processing). During the 2-back condition, TD attenuated activation prior to, but not after, estradiol treatment in the right and left dorsal lateral prefrontal and middle frontal/cingulate gyrus. During emotion identification, TD heightened activation in the orbital frontal cortex and bilateral amygdala, and this effect was attenuated by estradiol treatment. These results provide preliminary evidence that serotonergic effects directly mediate the impact of estrogen on brain activation during working memory and affective processing.     

Desensitization of transient receptor potential ankyrin 1 (TRPA1) by the TRP vanilloid 1-selective cannabinoid arachidonoyl-2 chloroethanolamine

Recent studies on cannabinoid-induced analgesia implicate certain transient receptor potential (TRP) channels as a therapeutic target along with metabotropic cannabinoid receptors. Although TRP ankyrin 1 (TRPA1)-selective cannabinoids, such as (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl) pyrrolo-[1,2,3-d,e]-1,4-benzoxazin-6-yl]-1-naphthalenyl-methanone (WIN55,212), are effective at desensitizing TRPA1 and TRP vanilloid 1 (TRPV1), there is a gap in knowledge in understanding the opposite situation, namely whether TRPV1-selective cannabinoids desensitize TRPA1. We selected the TRPV1-specific synthetic cannabinoid, arachidonoyl-2 chloroethanolamine (ACEA), to study peripheral antihyperalgesic properties because ACEA is known to activate TRPV1. Hence, we used in vitro as well as in vivo assays to evaluate the following: 1) the effects of ACEA on the TRPA1-selective agonist, mustard oil (MO), for calcitonin gene-related peptide (CGRP) release from rat hindpaw skin in vitro; 2) the effects of a peripherally selective dose of ACEA on MO-induced nocifensive behavior in vivo; and 3) the effects of five ACEA-insensitive TRPV1 mutations on ACEA-inhibition of MO-evoked calcium accumulation using a Chinese hamster ovary cell expression system. Our results demonstrate that 1) ACEA significantly attenuated (～40%) MO-evoked CGRP release from rat hindpaw skin, and this effect was not antagonized by the TRPV1 antagonist, capsazepine; 2) ACEA significantly inhibited (～40%) MO-induced nocifensive behavior in wild-type mice but not in TRPV1 knockout mice; and 3) all TRPV1 mutations insensitive to ACEA lacked the ability to inhibit MO-evoked calcium accumulation in Chinese hamster ovary cells transfected with TRPV1 and TRPA1. Taken together, the results indicate that a TRPV1-selective cannabinoid, ACEA, inhibits MO-evoked responses via a TRPV1-dependent mechanism. This study strengthens the hypothesis that cannabinoids mediate their peripheral analgesic properties, at least in part, via the TRP channels.     

A study on surgical cases of pulmonary aneurysm

We performed 830 cases of open heart surgery in the past 12 years and two of those cases were complicated by pulmonary aneurysm. The first case was a 21-year-old female with annuloaortic ectasia and treated by partial resection and plication of the pulmonary aneurysm associating of partial resection and plication of the pulmonary aneurysm associating of Bentall's procedure. Pathological examination revealed the findings of Aortitis syndrome, i.e., inflammatory granuloma with round cells infiltration and fragmentation of elastic fibers in the medial as well as adventitial layers. The second case, a reoperation case, was a 44-year-old female with valvular disease, MSR, TSR, Pr and treated by partial resection of the pulmonary aneurysm associating with MVR, TVR, and PA valve plasty. Pathological examination revealed hyalin and necrobiotic degeneration of the media. Both cases involved had pulmonary hypertension suggesting a role for pulmonary hypertension along with organic changes of the vessel in the pathogenesis of the aneurysm.     

μ-Opioid receptor availability in the amygdala is associated with smoking for negative affect relief

Rationale

Relapse is a persistent problem in the management of addiction. Drug-related cues are powerful instigators of relapse. Impulsive decision making may contribute to relapse through a poorly considered assessment of the consequences of drug use. Drug cues robustly increase subjective craving, which is frequently associated with relapse.

Objective

The present study explored the effects of drug-related cues on decision making and craving in heroin addicts at different abstinence times: 1, 3, 12, and 24?months.

Methods

The 75 male participants were given 5?min exposure to neutral and drug-associated cues while decision making performance, craving, blood pressure, heart rate, and emotional state pre- and post-exposure were assessed. The Iowa Gambling Task was used to evaluate decision making ability in heroin addicts.

Results

Drug-related cues exacerbated impulsive decision making and increased craving, heart rate, and systolic pressure in heroin addicts at all abstinence times.

Conclusions

Drug-related cues aggravated decision making and increased craving in former heroin addicts who had been drug-free for 1–24?months, which might have significant clinical implications for the prevention of relapse.     

In Vitro Sarcoma Cells Release a Lipophilic Substance That Activates the Pain Transduction System via TRPV1

Background

Despite success in treating many forms of cancer, pain associated with malignancy remains a serious clinical issue with a poorly understood etiology. This study determined if certain sarcoma cell lines produced a soluble factor that activates the TRPV1 ion channel expressed on nociceptive sensory neurons, thereby activating a major pain transduction system.

Materials and Methods

Trigeminal ganglia were harvested from rats and cultured. A rhabdomyosarcoma (CRL1598) and osteosarcoma (CRL 1543) cell line were grown to 75% confluency. Conditioned media (CM) was collected after 24 h of exposure and subjected to reverse phase chromatography. Neuronal activation in the presence of CM was measured using iCGRP RIA and calcium imaging after treatment with vehicle or I-RTX, a potent TRPV1 antagonist. Data were analyzed by ANOVA/Bonferroni or t test.

Results

The rhabdomyosarcoma CM produced a 4-fold increase in iCGRP release compared with control media (P < 0.001). The osteosarcoma cell line CM produced a 7-fold increase in iCGRP release compared with control media (P < 0.001). This evoked iCGRP release was via TRPV1 activation since the effect was blocked by the antagonist I-RTX. The application of rhabdomyosarcoma CM produced about a 4-fold increase in [Ca²⁺]I levels (P < 0.001), and this effect was blocked by pretreatment with the TRPV1 antagonist, I-RTX.

Conclusions

We have shown that certain sarcoma cell lines produce a soluble, lipophilic factor that activates the peripheral nociceptor transduction system via TRPV1 activation, thereby contributing to cancer pain. Further investigations are needed to develop tumor-specific analgesics that do not produce unwanted or harmful side-effects.     

Pitfalls in brain age analyses

Over the past decade, there has been an abundance of research on the difference between age and age predicted using brain features, which is commonly referred to as the “brain age gap.” Researchers have identified that the brain age gap, as a linear transformation of an out‐of‐sample residual, is dependent on age. As such, any group differences on the brain age gap could simply be due to group differences on age. To mitigate the brain age gap''s dependence on age, it has been proposed that age be regressed out of the brain age gap. If this modified brain age gap is treated as a corrected deviation from age, model accuracy statistics such as R ² will be artificially inflated to the extent that it is highly improbable that an R ² value below .85 will be obtained no matter the true model accuracy. Given the limitations of proposed brain age analyses, further theoretical work is warranted to determine the best way to quantify deviation from normality.