Personal resources and a sense of burden in carers of people with unipolar affective disorder.

Celem niniejszej pracy jest zbadanie związku pomiędzy zasobami osobistymi a poczuciem obciążenia u opiekunów osób z zaburzeniem afektywnym jednobiegunowym. W referowanym badaniu udział wzięło 30 osób będących opiekunami osób chorych. Zostali oni poproszeni o wypełnienie 5 kwestionariuszy, badających: poczucie obciążenia (Skala Obciążenia Opiekuna), postrzegane wsparcie społeczne (Kwestionariusz Spostrzeganego Wsparcia ISEL), odporność psychiczną (Skala Pomiaru Prężności SPP-25), własną skuteczność (Skala Uogólnionej Własnej Skuteczności GSES), koherencję (Kwestionariusz Orientacji Życiowej SOC-29). Analiza statystyczna wyników ujawniła, że: 1) mężczyźni wykazują większe poczucie zrozumiałości niż kobiety będące opiekunami osób cierpiących na depresję; 2) opiekunowie osób znajdujących się w epizodzie depresji wykazują większe poczucie obciążenia niż opiekunowie osób będących w okresie remisji.The aim of this study is to examine the relationship between personal resources and the sense of burden in caregivers of people with unipolar affective disorder. 30 people took part in the study. They were asked to fill in 5 questionnaires examining: the feeling of burden (Zarit Caregiver Burden Scale), perceived social support (Interpersonal Support Evaluation ISEL), mental resilience (Scale of Resilience SPP-25), own effectiveness (General Self-Efficacy Scale GSES), coherence (Sense of Coherence Scale SOC-29). Statistical analysis of the results revealed that: 1) men have a greater sense of understanding than women being carers of people suffering from depression; 2) caregivers of people in the episode of depression show a greater sense of burden than caregivers of people who are in the remission period

Effect of diosgenin, a steroidal sapogenin, on the rat skeletal system

Diosgenin is a steroidal sapogenin present in fenugreek and Dioscorea spp. as glycosides (saponins). Diosgenin has already been reported to inhibit osteoclastogenesis and to stimulate osteogenic activity of osteoblastic cells in vitro, and to exert some antiosteoporotic effects in rats in vivo. The aim of the present study was to investigate the effects of diosgenin administration on the skeletal system of rats with normal estrogen level and with estrogen deficiency induced by bilateral ovariectomy. The experiments were carried out on 3-month-old non-ovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving diosgenin (50 mg/kg p.o. daily) for 4 weeks. Serum bone turnover markers, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diosgenin improved some investigated parameters in both non-ovariectomized and ovariectomized rats, in which estrogen deficiency induced osteoporotic changes. Diosgenin increased compact bone formation and probably inhibited cancellous bone resorption, which led to improvement of mechanical properties of compact and cancellous bone. In conclusion, this in vivo study demonstrated that diosgenin may be one of sparse compounds increasing bone formation

Pancreatic islet cell stress induced by insulin-degrading enzyme deficiency promotes islet regeneration and protection from autoimmune diabetes

International audienceABSTRACT Appropriate tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with highly variable demand for insulin synthesis. An efficient UPR ensures a sufficient beta cell mass and secretory output but can also affect beta cell resilience to autoimmune aggression. The factors regulating protein homeostasis in the face of metabolic and immune challenges are insufficiently understood. We examined beta cell adaptation to stress in mice deficient for insulin-degrading enzyme (IDE), a ubiquitous protease with high affinity for insulin and genetic association with type 2 diabetes. IDE deficiency induced a low-level UPR in both C57BL/6 and autoimmune non-obese diabetic (NOD) mice, associated with rapamycin-sensitive beta cell proliferation strongly enhanced by proteotoxic stress. Moreover, in NOD mice, IDE deficiency protected from spontaneous diabetes and triggered an additional independent pathway, conditional on the presence of islet inflammation but inhibited by proteotoxic stress, highlighted by strong upregulation of regenerating islet-derived protein 2, a protein attenuating autoimmune inflammation. Our findings establish a key role of IDE in islet cell protein homeostasis, identify a link between low-level UPR and proliferation, and reveal an UPR-independent anti-inflammatory islet cell response uncovered in the absence of IDE of potential interest in autoimmune diabetes

Islet cell stress induced by insulin-degrading enzyme deficiency promotes regeneration and protection from autoimmune diabetes

Summary: Tuning of protein homeostasis through mobilization of the unfolded protein response (UPR) is key to the capacity of pancreatic beta cells to cope with variable demand for insulin. Here, we asked how insulin-degrading enzyme (IDE) affects beta cell adaptation to metabolic and immune stress. C57BL/6 and autoimmune non-obese diabetic (NOD) mice lacking IDE were exposed to proteotoxic, metabolic, and immune stress. IDE deficiency induced a low-level UPR with islet hypertrophy at the steady state, rapamycin-sensitive beta cell proliferation enhanced by proteotoxic stress, and beta cell decompensation upon high-fat feeding. IDE deficiency also enhanced the UPR triggered by proteotoxic stress in human EndoC-βH1 cells. In Ide−/− NOD mice, islet inflammation specifically induced regenerating islet-derived protein 2, a protein attenuating autoimmune inflammation. These findings establish a role of IDE in islet cell protein homeostasis, demonstrate how its absence induces metabolic decompensation despite beta cell proliferation, and UPR-independent islet regeneration in the presence of inflammation

The functioning of mammalian ClC-2 chloride channel in Saccharomyces cerevisiae cells requires an increased level of Kha1p

The mammalian chloride channel ClC-2 is a member of the CLC voltage-gated chloride channels family. This broadly expressed protein shows diverse cellular locations and despite numerous studies, its precise function is poorly understood. Disruption of ClC-2-encoding gene in mouse leads to retinal and testicular degeneration and mutations in CLC2 (gene encoding the ClC-2 channel) are associated with idiopathic generalized epilepsies. ClC-2 may also be responsible for Cl(−) transport in mouse salivary glands. The only CLC homologue of the yeast Saccharomyces cerevisiae, Gef1p, exhibits CLC activity. We expressed the mammalian ClC-2 protein in S. cerevisiae devoid of Gef1p in an attempt to identify yeast proteins influencing the functioning of ClC-2. The presence of such proteins in yeast could indicate the existence of their homologues in mammalian cells and would greatly aid their identification. Expression of ClC-2 in yeast required optimization of the sequence context of the AUG translation initiation codon. After obtaining an efficient translation, we found that rat ClC-2 cannot directly substitute for yeast Gef1p. Functional substitution for Gef1p was, however, achieved in the presence of an increased level of intact or C-terminally truncated yeast Kha1 protein. Based on the deduced amino acid sequence, the Kha1 protein can be classified as a Na(+)/H(+) transporter since it has a large N-terminal domain similar to the family of NHEs (Na(+)/H(+) exchangers). This suggests that the Kha1p may take part in the regulation of intracellular cation homoeostasis and pH control. We have established that Kha1p is localized in the same cellular compartment as Gef1p and yeast-expressed ClC-2: the Golgi apparatus. We propose that Kha1p may aid ClC-2-dependent suppression of the Δgef1-assocciated growth defects by keeping the Golgi apparatus pH in a range suitable for ClC-2 activity. The approach employed in the present study may be of general applicability to the characterization of poorly understood proteins by their functional expression in yeast