Health and frailty among older spousal caregivers:an observational cohort study in Belgium

Abstract Background Among older couples, spouses are first in line to provide care, and they are key elements in the home support of dependent older persons. In this context, ensuring the health of these older spousal caregivers should be an important issue for all of the providers who care for older adults. The aim of this study was to longitudinally assess the health of older spousal caregivers considering frailty, nutrition, cognition, physical performance and mood disorders. Methods In this longitudinal, observational cohort study, participants were assessed at home in Wallonia, Belgium. At baseline, 82 community-dwelling spouses of older patients with cognitive deficits or functional impairment were assessed; 78 caregivers were assessed at follow-up (16 months). The clinical instruments used included Frailty Phenotype (Fried), the Mini Nutritional Assessment-short form (MNA-SF), Short Physical Performance Battery (SPPB), Geriatric Depression Scale (GDS-15), clock drawing test, medications, Zarit Burden Index (ZBI), and Caregiver Reaction Assessment (CRA). Biological assessments included plasma interleukin-6 (IL-6), ultrasensitive C-reactive protein (CRP), cortisol, albumin and insulin growth factor-1 (IGF-1). Results Among caregivers, 54% were women, and the mean age was 80 years. Among care-receivers, 83% had cognitive impairment. Caregivers were more likely to be in a pre-frail stage. In one-third of the caregivers, the frailty status worsened. Transitions were observed between each of the states, except from frail to robust. In contrast to frailty, items including nutrition, cognitive status, SPPB and mood assessments were stable over time, with approximately 70% of the caregivers not experiencing significant change at follow-up. Caregiver experiences assessed with the Zarit Burden Interview and CRA were relatively stable over 16 months. Conclusion Many caregivers of geriatric patients are spouses who are old themselves. A failure in the health of the caregiver may anticipate an undesired care breakdown. Caregiver health and its determinants should be explored in future longitudinal studies that cover a longer time period

What's new at the maternal-foetal interface: role of the hCG/LH-hCG receptor couple during embryo implantation

peer reviewedImplantation of the embryo into the maternal endometrium represents a unique biological process, combining an immunological (tolerance of an allograft) and biological (adhesion of two epitheliums) paradox. The success of implantation depends on a receptive endometrium, a functionally normal blastocyst and a synchronized cross-talk between embryonic and maternal tissues. Though sexual steroids control the process, a cascade of growth factors or cytokines are the prime paracrine mediators of the dialogue at the maternal-embryonic interface. HCG is one of the molecules most precociously produced by the embryo and is the most specific marker of its presence. HCG is a luteotropic factor which relays the inadequate support provided by the reduced rates of LH, but also influences the pregnancy on a paracrine mode by a local action on implantation process, probably by interacting with its receptor, the LH/hCG-R that we have evidenced on endometrial epithelium. We demonstrate that embryo actively participate into its implantation, tolerance and placentation

Human endometrial leukemia inhibitory factor and interleukin-6: control of secretion by transforming growth factor-beta-related members.

peer reviewed[en] OBJECTIVE(S): The implantation process is closely linked to the fundamental question of the tolerance of the maternal immune system. The main objective of this study was to investigate whether different members of the transforming growth factor-beta (TGF-beta) superfamily could intervene in the first steps of embryo implantation by modulating the secretion of proimplantatory leukemia inhibitory factor (LIF) and in the tolerance of the fetal graft by regulating proinflammatory interleukin (IL)-6 secretion by human endometrial epithelium (EEC) in vitro. METHODS: EEC were isolated from biopsies collected from 16 informed and consenting fertile women and were cultured for 72 h. Cytokine measurements (LIF and IL-6) were realized by ELISA. RESULTS: TGF-beta(1) (from 10(-12) to 10(-8)M), -beta(2), -beta(3) and activin A (10(-10) and 10(-8)M) increased LIF secretion by EEC cultures. Inhibin B (10(-10) and 10(-8)M) did not stimulate LIF production by human EEC. Contrastingly, TGF-beta(1) (from 10(-12) to 10(-8)M), -beta(2), -beta(3) and activin A (10(-10) and 10(-8)M) reduced IL-6 release by the same cells. Activin A at 10(-8) M also significantly reduced the stimulating effect of IL-1beta (10(-9)M) which is known to stimulate LIF production by EEC. Only the highest concentration of inhibin B (10(-8)M) reduced IL-6 secretion by EEC, but did not modulate IL-1beta-induced stimulation of IL-6 secretion. CONCLUSION(S): Besides their role in the control of the process of implantation and in the induction of embryonic mesoderm, different members of the TGF-beta superfamily may also contribute in the reproductive process by enhancing endometrial proimplantatory LIF secretion and reducing proinflammatory IL-6 release by EEC

Human chorionic gonadotropin and growth factors at the embryonic-endometrial interface control leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) secretion by human endometrial epithelium

peer reviewedBACKGROUND: The elucidation of the molecular mechanisms by which the embryo contributes to its implantation is an area of extensive research. The main objective of this study was to investigate the pattern of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) secretion by human endometrial epithelium, and their regulation by human chorionic gonadotropin (hCG) and other growth factors present at the embryonic-endometrial interface. METHODS: Endometrial epithelial cells (EEC) were isolated from biopsies collected at both proliferative and secretory phases of fertile women. RESULTS: HCG (1-50 IU/ml) increased LIF secretion by EEC cultures derived from follicular phase (up to 285+/-75%) or from secretory phase (up to 212+/-16%). In contrast, hCG reduced IL-6 secretion by EEC in both phases. The hCG/LH receptor gene was transcribed by EEC as evidenced by RT-PCR. Insulin-like growth factors 1 and 2 increased LIF secretion by EEC. Transforming growth factor beta1 stimulated LIF and reduced IL-6 secretion. CONCLUSIONS: Through hCG, the blastocyst may be involved in the control of its implantation (via an increase of proimplantatory LIF) and tolerance (via an inhibition of proinflammatory IL-6). Other growth factors present at the embryonic-endometrial interface are also involved in the control of LIF and IL-6 endometrial secretion

Neurohypophysial peptides stimulate the phosphorylation of pre-T cell focal adhesion kinases

Thymic oxytocin (OT) behaves as a cryptocrine signal targeted at the outer surface of thymic epithelial cell plasma membrane from where OT is able to interact with neurohypophysial peptide receptors expressed by pre-T cells. Immature T cells bear a receptor of the V1 subtype, while OT receptors are predominantly expressed by cytotoxic CD8+ lymphocytes. In both T cell types, neurohypophysial peptide receptors transduce OT via the phosphoinositide pathway. Protein tyrosine phosphorylation is an early event of T cell activation. Western blots of murine pre-T cells (RL12-NP line) proteins probed with anti-phosphotyrosine (PY-20) revealed a great number of proteins the phosphorylation of which increased either with OT or vasopressin treatment. Two were immunoprecipitated with anti-focal adhesion kinase (FAK) mAb 2A7 and were identified one as p125FAK and the other as a coprecipitating 130-kDa protein. The p125FAK is connected to the Ras/MAPK pathway and is also implicated in TCR/CD3 signalling in T cell. Another protein phosphorylated by OT in RL12-NP was identified as paxillin, a 68-kDa protein localised at focal adhesion sites and associated with p 125FAK. These results indicate that phosphorylation of focal adhesion kinase may be induced in pre-T cell by thymic OT

Impact of the somatotrope Growth Hormone (GH)/Insulin-like Growth Factor 1 (IGF-1) axis upon thymus function: Pharmacological implications in regeneration of immune functions

The thymus is the central lymphoid structure where T-cell differentiation takes place, and a crucial organ for the maintenance of homeostasis in the immune system. Thymopoiesis includes intrathymic proliferation of T-cell precursors, selection and output of both self-tolerant and competent effector T cells, as well as of natural regulatory T cells (nTreg). In the crosstalk between the neuroendocrine and immune systems, peptide hormones have been more and more implicated in immunomodulation for the last thirty years. The somatotrope growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in particular has been repeatedly shown to play a major regulatory role upon thymus function and T-cell development. This review will focus on the important thymotropic properties of the somatotrope GH/IGF-1 axis, and will try to discriminate these properties in function of the endocrine or paracrine/autocrine pathways involved in their mediation. Most importantly, in light of an increasing number of recent studies, GH and IGF-1 now appear as a novel therapeutic agents that could be used for enhancing thymopoiesis in different cases of immune deficiencies, including aging-related immune dysfunction