The rising rate of overweight/obesity among the ever-growing ageing population is imposing massive and rapidly changing burdens of ill health. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults, mainly through its reduced impact on coronary heart disease, has often been misinterpreted that obesity is not as harmful in the elderly, who suffer a large range of disabling consequences of obesity. All medical consequences of obesity are multi-factorial and most alleviated by modest, achievable weight loss (5–10 kg) with an evidence-based maintenance strategy. But severe obesity, e.g. BMI >40 may demand greater weight loss e.g. >15 kg to reverse type 2 diabetes. Since relatively reduced physical activity and reduced muscle mass (sarcopenic obesity) are common in the elderly, combining exercise and modest calorie restriction optimally reduces fat mass and preserves muscle mass – age presents no obstacle and reducing polypharmacy is a valuable outcome. The currently licensed drug orlistat has no age-related hazards and is effective in a low fat diet, but the risks from bariatric surgery begin to outweigh benefits above age 60. For the growing numbers of obese elderly with diabetes, the glucagon-like peptide-1 (GLP-1) receptor analogue liraglutide appears a safe way to promote and maintain substantial weight loss. Obesity and sarcopenia should be prevented from younger age and during life-transitions including retiral to improve future health outcomes and quality of life, with a focus on those in “obese families”.

The aim of this study was to identify a high-risk or low-risk population for chemotherapy-induced nausea and vomiting among patients with breast cancer treated with a current standard 3-drug antiemetic regimen and receiving anthracycline.We analyzed data from chemotherapy-naive Japanese patients with breast cancer, who had received the first cycle of anthracycline-based regimen and were treated with a 3-drug combination of aprepitant, palonosetron, and dexamethasone. This study was carried out at Ehime University Hospital (Toon, Japan) using electronic medical records from May 2011 to June 2017. The primary end point was complete response (CR), which was defined as no emesis and no use of rescue medication.A total of 103 patients were included in this study. The percentages of patients who had a CR in the overall, acute, and delayed phases were 35.0%, 40.8%, and 50.5%, respectively. Multivariate logistic regression analysis revealed that age <55 years and body mass index <27.5 kg/m2 were significantly associated with an increased risk for CR failure in the overall and acute phases. In contrast, a history of alcohol habit was significantly associated with a decreased risk for CR failure in overall phase.The present findings suggest that, among patients with breast cancer receiving anthracycline and treated with aprepitant, palonosetron, and dexamethasone, patients younger than 55 years and having a body mass index <27.5 kg/m2 are high-risk populations for chemotherapy-induced nausea and vomiting, whereas those with a history of habitual alcohol consumption is a low-risk one.

Caveolin is a major component of caveolae which is a plasma membrane microdomain. The emerging role of caveolin in tumorigenesis was based mainly on in vitro experiments with cancer cell lines. We performed semi-quantitative RT-PCR for caveolin, Akt and EGFR to understand the role of caveolins in colorectal tumor biology. Cancer tissue samples and the neighboring normal colon mucosa were obtained from 95 colorectal cancer patients who underwent operations at Ewha Womans University Mokdong Hospital. With these fresh tissues, semi-quantitative RT-PCR was performed by coamplification of the gene for caveolin-1, EGFR and Akt-1 with β-actin. The average age was 60.21 ± 13.33 years old, and sex ratio was 1.44:1. Caveolin-1 is more expressed in tumors than normal mucosa (P = 0.025). The expression of caveolin-1 and Akt-1 had a definitive positive relationship (P = 0.002). But, the expression of caveolin-1 and EGFR was not significantly related. We could not find correlations between caveolin-1 expression and clinical factors. In conclusion, caveolin-1 is more expressed in cancer tissues than normal colon and related with Akt-1, not with EGFR expression in colorectal cancer tissues, which suggests that signaling for caveolin-1 affects Akt-1 activation, but this reaction is not initiated by EGFR stimulation in colon cancer.

SB 269970, a 5-HT7 receptor antagonist may produce a faster antidepressant-like effect in animal models, than do antidepressant drugs, e.g., imipramine. The present work was aimed at examining the effect of single and repeated (14 days) administration of SB 269970 on the 5-HT7 receptor in the hippocampus.The reactivity of 5-HT7 receptors was determined using 5-carboxamidotryptamine (5-CT), which increased the bursting frequency of spontaneous epileptiform activity in hippocampal slices. Additionally, the effects of SB 269970 administration on the affinity and density of 5-HT7 receptors were investigated using [3H]-SB 269970 and the influence of SB 269970 and imipramine on mRNA expression levels of Gαs and Gα12 mRNA were studied using RT-qPCR.Acute and repeated treatment with SB 269970 led to attenuation of the excitatory effects of activation of 5-HT7 receptors. Neither single nor repeated administration of SB 269970 changed the mean affinity of 5-HT7 receptors for [3H]-SB 269970. Repeated, but not single, administration of SB 269970 decreased the maximum density of [3H]-SB 269970 binding sites. While administration of imipramine did not change the expression of mRNAs for Gαs and Gα12 proteins after both single and repeated administration of SB 269970, a reduction in Gαs and Gα12 mRNA expression levels was evident.These findings indicate that even single administration of SB269970 induces functional desensitization of the 5-HT7 receptor system, which precedes changes in the receptor density. This mechanism may be responsible for the rapid antidepressant-like effect of the 5-HT7 antagonist in animal models.

Polymorphisms within the DRD1, DRD2, DRD3, DAT1, 5-HTTLPR and HTR2A genes are being studied for association with lithium prophylaxis in a sample of 155 Sardinian unrelated probands affected by bipolar disorder (BP). No significant association was shown between the polymorphisms of the genes studied and response to lithium treatment.

Cocaine exhibits preferential (~ 15-fold) affinity for σ1 over σ2 sigma receptors, and previous research has shown an interaction of σ1 receptor-selective ligands and cocaine's behavioral effects. The present study investigated the effect of the putative sigma receptor agonist SA 4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride) on cocaine's locomotor stimulatory and discriminative stimulus properties. At doses without intrinsic activity, SA 4503 dose-dependently attenuated cocaine-induced hyperactivity in mice. This inhibition was overcome by increasing the cocaine dose. In rats trained to use cocaine as a discriminative stimulus in a drug discrimination task, doses of SA 4503 that did not substitute for the cocaine stimulus did not alter the cocaine substitution curve. However, SA 4503 potentiated the effect of methamphetamine to substitute for the cocaine stimulus. These data support a role for sigma receptors in the locomotor-activating properties of cocaine and, importantly, indicate a role for these receptors in the discriminative stimulus effects of methamphetamine. The data also suggest sigma receptors mediate the activity of different dopamine pathways responsible for the behavioral effects of psychostimulants.

The validity of delayed-matching-to-sample (DMTS) and related tasks executed in skinner boxes as an animal model for human working memory (WM) is confounded by the occurrence of mediating behaviour during delays. True matching, a supplementary task during delays and response similarity are ways to deal with this problem. However, until now rats have not been able to learn a true matching task in Skinner boxes and introduction of a supplementary task during delays does not sufficiently prevent mediating behaviour. Response similarity, on the other hand, effectively prevents the use of mediating behaviour by reducing the discriminative value of the behaviour during delays. Furthermore, it is argued that the interpretation of drug effects is confounded by baseline performance and mediating behaviour. It is shown that high baseline levels and high amounts of mediating behaviour can induce delay dependent drug effects, suggesting a specific effect on WM. We therefore assert that examination of delay-dependency of a drug effect alone is not sufficient to claim specific effects of a drug on WM. The delayed-conditional-discrimination (DCD) task uses response similarity to effectively reduce mediating behavior and does not generate high levels of baseline performance. The DCD task is therefore preferred over other tasks for the measurement of WM in rats using Skinner boxes.