Self-compassion,chronic age-related stressors,and diurnal cortisol secretion in older adulthood

Many older adults experience chronic age-related stressors (e.g., life regrets or health problems) that are difficult to control and can disturb cortisol regulation. Self-compassion may buffer adverse effects of these stressful experiences on diurnal cortisol secretion in older adulthood. To examine whether self-compassion could benefit older adults’ cortisol secretion in the context of chronic and largely uncontrollable age-related stressors, 233 community-dwelling older adults reported their levels of self-compassion, age-related stressors (regret intensity, physical health problems, and functional disability), and relevant covariates. Diurnal cortisol was measured over 3 days and the average area-under-the-curve and slope were calculated. Higher levels of self-compassion were associated with lower daily cortisol levels among older adults who reported higher levels of regret intensity, physical health problems, or functional disability (βs?<???.53, ps?<?.01), but not among their counterparts who reported lower levels of these age-related stressors (βs?<?.24, ps?>?.28). These results suggest that self-compassion may represent an important personal resource that could protect older adults from stress-related biological disturbances resulting from chronic and uncontrollable stressors.     

Role of endogenous adenosine as a predictive marker of vasoplegia during cardiopulmonary bypass and postoperative severe systemic inflammatory response

OBJECTIVE: Systemic inflammatory response (SIRS) and severe SIRS (SIRS with organ dysfunction) occurring after cardiopulmonary bypass (CPB) are common causes of morbidity and mortality among cardiac surgical patients. These syndromes are often preceded by a profound vasodilation, characterized by vasoplegia occurring during surgery. Many substances have been implicated in their pathophysiology. Adenosine is a strong endogenous vasodilating agent released by endothelial cells and myocytes under metabolic stress and may be involved in blood pressure failure during CPB induced by severe SIRS. DESIGN: A prospective comparative observational study. SETTING: The operating room and intensive care unit of a tertiary care university hospital. PATIENTS: Adenosine plasma levels (mean+/-sd; APLs) were measured before (baseline), during, and immediately after surgery in 35 patients who underwent aortic valve replacement involving CPB. APLs were correlated to operative and postoperative clinical courses. MEASUREMENTS AND MAIN RESULTS: APLs were significantly higher in seven patients with vasoplegia and postoperative severe SIRS (1.6 micromol.L [0.2-2.6] vs. 0.4 micromol.L [0.1-1.0]) at baseline and during surgery. The duration of mechanical ventilation and stay in the intensive care unit were significantly longer for patients with higher APLs. Mean arterial pressure was inversely correlated with mean arterial APLs (Pearson's correlation coefficient: R=-0.66; p<.001). CONCLUSIONS: High APLs were found in patients with operative vasoplegia and postoperative severe SIRS occurring after cardiopulmonary bypass. This suggests that adenosine release is involved in vasoplegia that occurs during the systemic inflammatory response to cardiac surgery. Further studies are needed to clarify the association between cytokine production and adenosine release in severe SIRS following cardiac surgery.     

Plasma vasopressin and interpersonal functioning

The neuropeptide vasopressin has traditionally been associated with vasoconstriction and water reabsorption by the kidneys. However, data from experimental animal studies also implicate vasopressin in social bonding processes. Preliminary work suggests that vasopressin also plays a role in social behaviors in humans. The goal of this cross-sectional study was to evaluate associations among plasma vasopressin and self-reported interpersonal functioning in a sample of married couples. During a 24-h admission to a hospital-based research unit, 37 couples completed measures of interpersonal functioning and provided blood samples for neuropeptide analyses. Results showed that vasopressin was associated with markers of interpersonal functioning, but not with general psychological distress. Specifically, greater plasma vasopressin levels were related to a larger social network, fewer negative marital interactions, less attachment avoidance, more attachment security, and marginally greater spousal social support. These results indicate that vasopressin is likely implicated in different relationship maintenance processes in humans.     

A new tool to test active ingredient using lactic acid in vitro,a help to understand cellular mechanism involved in stinging test: An example using a bacterial polysaccharide (Fucogel®)

The stinging test is an in vivo protocol that evaluates sensitive skin using lactic acid (LA). A soothing sensation of cosmetics or ingredients can be also appreciated through a decrease in stinging score. To predict the soothing sensation of a product before in vivo testing, we developed a model based on an LA test and substance P (SP) release using a co‐culture of human keratinocytes and NGF‐differentiated PC12 cells. A bacterial fucose‐rich polysaccharide present in Fucogel^® was evaluated as the soothing molecule in the in vivo stinging test and our in vitro model. Excluding toxic concentrations, the release of SP was significant from 0.2% of lactic acid for the PC12 cells and from 0.1% of lactic acid for the keratinocytes. When the pH was adjusted to approximately 7.4, LA did not provoke SP release. At these concentrations of LA, 0.1% of polysaccharide showed a significant decrease in SP release from the two cellular types and in co‐cultures without modifying the pH of the medium. In vivo, a stinging test using the polysaccharide showed a 30% decrease in prickling intensity vs the placebo in 19 women between the ages of 21 and 69. Our in vitro model is ethically interesting and is adapted for cosmetic ingredients screening because it does not use animal experimentation and limits human volunteers. Moreover, Fucogel^® reduced prickling sensation as revealed by the in vivo stinging test and inhibits the neurogenic inflammation as showed by our new in vitro stinging test based on SP release.     

Monitoring glycosidase activity for clustered sugar substrates,a study on β-glucuronidase

Determination of glycosidase hydrolysis kinetics for a monovalent sugar substrate is relatively straightforward and classically achieved by monitoring the fluorescence signal released from the sugar-conjugated probe after enzymatic hydrolysis. Naturally occuring sugar epitopes are, however, often clustered on biopolymers or at biological surfaces, and previous reports have shown that glycosidase hydrolytic rates can differ greatly with multivalent presentation of the sugar epitopes. New probes are needed to make it easier to interpret the importance of substrate clustering towards a specific enzyme activity. In this work, we developed multivalent glucuronide substrates attached to fluorescent amino-coumarines through self-immolative linkers to enable real time-monitoring of the hydrolysing activity of E.coli β-glucuronidases (GUS) towards clustered substrates. GUS are exoglycosidases of considerable therapeutic interest cleaving β-d-glucuronides and are found in the lysosomes, in the tumoral microenvironment, and are expressed by gut microbiota. GUS showed a much lower catalytic efficiency in hydrolysing clustered glucuronides due to a significantly lower enzymatic velocity and affinity for the substrates. GUS was 52-fold less efficient in hydrolysing GlcA substrates presented on an octameric silsequioxane (COSS) compared with a monovalent GlcA of similar chemical structure. Thus, kinetic and thermodynamic data of GUS hydrolysis towards multivalent glucuronides were easily obtained with these new types of enzymatically-triggered probes. More generally, adapting the substrate nature and valency of these new probes, should improve understanding of the impact of multivalency for a specific enzyme.

Enzymatically-triggered probes to determine glucuronidase hydrolysis kinetics for clustered substrates.     

Cytochrome P450 2C9 polymorphisms (CYP2C9) and warfarin maintenance dose in elderly patients

PURPOSE: Allelic variants of the gene coding for cytochrome P450 isoform 2C9 (CYP2C9), 2C9*2 and 2C9*3, were shown to increase sensitivity to warfarin in adults. In the elderly, the maintenance dose is influenced by acquired factors including comorbidities and polymedication. The aim of our purpose was to investigate whether a genetic factor, such as cyp2c9 genotype, does influence the warfarin maintenance dose in very elderly patients. METHODS: In-patients treated with warfarin were recruited with the following inclusion criteria: i/ 75 years-old or over; ii/ a stable INR within the therapeutic range (INR 2.0-3.0). Genotypes were coded as numbers of alleles for each of the three polymorphisms, namely 2C9*1 (wild-type), 2C9*2, and 2C9*3. RESULTS: CYP2C9 genotype was performed in 126 patients, mean age 87 +/-6 years (75-103), 29 males-97 females. The mean daily dose of warfarin was 3.0 +/-1.4 mg, with 3.1 mg in patients with the wild-type *1/*1 genotype (n =80), 2.7 mg in *1/*2 heterozygotes (n =20), 2.9 mg in *1/*3 heterozygotes (n =18), 1.2 mg in *2/*2 homozygotes (n =2), 2.3 mg in compound heterozygotes *2/*3 (n =6). The relationships between dose and potential factors were assessed using the correlation coefficient test for age and Fischer exact tests for the categorical variables. The only factors significantly linked to the dose were the numbers of 2C9*1 and 2C9*2 alleles. CONCLUSION: In elderly patients, a genetic influence on response to warfarin does exist as in younger patients.     

Low molecular weight heparin treatment in elderly subjects with or without renal insufficiency: new insights between June 2002 and March 2004

PURPOSE OF REVIEW: Low molecular weight heparin has become the treatment of choice for venous thromboembolism events and acute coronary syndromes. In contrast to unfractionated heparin, low molecular weight heparins are mainly excreted by the kidney. Thus, repeated administration of therapeutic doses of low molecular weight heparins may lead to overdosage and/or an accumulation effect in patients with renal impairment, such as the elderly. Moreover, older patients are often excluded from clinical trials. Little evidence is available to assess the risk/benefit ratio of low molecular weight heparins used at therapeutic dosages in elderly patients with or without renal insufficiency in normal clinical practice. RECENT FINDINGS: Pharmacovigilance data, case reports, and observational studies reporting major bleeding complications in the elderly highlight the potential risk of using low molecular weight heparins at therapeutic dosages in these patients. An evaluation of renal function is thus essential before therapy with low molecular weight heparins is begun. Moreover, multiple-dose pharmacokinetic studies in the elderly have shown that the pharmacokinetic response to impaired renal function, especially the risk of accumulation effect, may differ among preparations of low molecular weight heparins. SUMMARY: Three approaches to improve the safety of low molecular weight heparins in the elderly are discussed: (1) to replace low molecular weight heparin therapy with monitored unfractionated heparin therapy in cases of severe renal insufficiency, but comparative studies are necessary to clarify whether unfractionated heparin offers better safety in this setting; (2) to use initial reduced dosages in elderly patients with or without renal failure, but these regimens have to be validated for each low molecular weight heparin in terms of efficacy in controlled trials; and (3) to monitor anti-Xa activity to detect any overdosage and/or any accumulation effect of low molecular weight heparins.     

A generic simulation model to assess the performance of sterilization services in health establishments

The work presented here is with a view to improving performance of sterilization services in hospitals. We carried out a survey in a large number of health establishments in the Rhône-Alpes region in France. Based on the results of this survey and a detailed study of a specific service, we have built a generic model. The generic nature of the model relies on a common structure with a high level of detail. This model can be used to improve the performance of a specific sterilization service and/or to dimension its resources. It can also serve for quantitative comparison of performance indicators of various sterilization services.