Calpastatin Subdomains A And C Are Activators of Calpain

The inhibitory domains of calpastatin contain three highly conserved regions, A, B, and C, of which A and C bind calpain in a strictly Ca2+-dependent manner but have no inhibitory activity whereas region B inhibits calpain on its own. We synthesized the 19-mer oligopeptides corresponding to regions A and C of human calpastatin domain I and tested their effect on human erythrocyte mu-calpain and rat m-calpain. The two peptides significantly activate both calpains: the Ca2+ concentration required for half-maximal activity is lowered from 4.3 to 2.4 mum for mu-calpain and from 250 to 140 mum for m-calpain. The EC50 concentration of the peptides is 7.5 mum for mu-calpain and 25 mum for m-calpain. It is noteworthy that at low Ca2+ concentrations (1-2 mum for mu-calpain and 70-110 mum for m-calpain) both enzymes are activated about 10-fold by the peptides. Based on these findings, it is suggested that calpastatin fragments may have a role in calpain activation in vivo. Furthermore, these activators open new avenues to cell biological studies of calpain function and eventually may alleviate pathological states caused by calpain malfunction

Sociodemographic factors and patient perceptions are associated with attitudes to kidney transplantation among haemodialysis patients

Background. Treatment decisions made by patients with chronic kidney disease are crucial in the renal transplantation process. These decisions are influenced, amongst other factors, by attitudes towards different treatment options, which are modulated by knowledge and perceptions about the disease and its treatment and many other subjective factors. Here we study the attitude of dialysis patients to renal transplantation and the association of sociodemographic characteristics, patient perceptions and experiences with this attitude. Methods. In a cross-sectional study, all patients from eight dialysis units in Budapest, Hungary, who were on haemodialysis for at least 3 months were approached to complete a self-administered questionnaire. Data collected from 459 patients younger than 70 years were analysed in this manuscript. Results. Mean age of the study population was 53 +/- 12 years, 54% were male and the prevalence of diabetes was 22%. Patients with positive attitude to renal transplantation were younger (51 +/- 11 versus 58 +/- 11 years), better educated, more likely to be employed (11% versus 4%) and had prior transplantation (15% versus 7%)(P < 0.05 for all). In a multivariate model, negative patient perceptions about transplantation, negative expectations about health outcomes after transplantation and the presence of fears about the transplant surgery were associated, in addition to incre- asing age, with unwillingness to consider transplantation. Conclusions. Negative attitudes to renal transplantation are associated with potentially modifiable factors. Based on this we suggest that it would be necessary to develop standardized, comprehensible patient information systems and personalized decision support to facilitate modality selection and to enable patients to make fully informed treatment decisions

Association between serum resistin level and outcomes in kidney transplant recipients.

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P &lt; 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft

Association of symptoms of insomnia and sleep parameters among kidney transplant recipients

Objective: Insomnia complaints are frequent among kidney transplant (kTx) recipients and are associated with fatigue, depression, lower quality of life and increased morbidity. However, it is not known if subjective insomnia symptoms are associated with objective parameters of sleep architecture. Thus, we analyze the association between sleep macrostructure and EEG activity versus insomnia symptoms among kTx recipients. Methods: Participants (n1 = 100) were selected from prevalent adult transplant recipients (n0 = 1214) followed at a single institution. Insomnia symptoms were assessed by the Athens Insomnia Scale (AIS) and standard overnight polysomnography was performed. In a subgroup of patients (n2 = 56) sleep microstructure was also analyzed with power spectral analysis. Results: In univariable analysis AIS score was not associated with sleep macrostructure parameters (sleep latency, total sleep time, slow wave sleep, wake after sleep onset), nor with NREM and REM beta or delta activity in sleep microstructure. In multivariable analysis after controlling for covariables AIS score was independently associated with the proportion of slow wave sleep (β = 0.263; CI: 0.026–0.500) and REM beta activity (β = 0.323; CI = 0.041–0.606) (p < 0.05 for both associations). Conclusions: Among kTx recipients the severity of insomnia symptoms is independently associated with higher proportion of slow wave sleep and increased beta activity during REM sleep but not with other parameters sleep architecture. The results suggest a potential compensatory sleep protective mechanism and a sign of REM sleep instability associated with insomnia symptoms among this population

Depressive symptoms are associated with objectively measured sleep parameters in kidney transplant recipients

STUDY OBJECTIVES: Both depression and sleep complaints are very prevalent among kidney transplant (kTx) recipients. However, details of the complex relationship between sleep and depression in this population are not well documented. Thus, we investigated the association between depressive symptoms and sleep macrostructure parameters among prevalent kTx recipients.  METHODS: Ninety-five kTx recipients participated in the study (54 males, mean age 51 ± 13 y, body mass index 26 ± 4 kg/m2, estimated glomerular filtration rate 53 ± 19 ml/min/1.73 m2). Symptoms of depression were assessed by the Center for Epidemiologic Studies - Depression Scale (CES-D). After 1-night polysomnography each recording was visually scored and sleep macrostructure was analyzed.  RESULTS: The CES-D score was significantly associated with the amount of stage 2 sleep (r = 0.20, p 0.05). In multivariable linear regression models the CES-D score was independently associated with the amount of stage 2 sleep (β: 0.205; confidence interval: 0.001-0.409; p = 0.05) and REM latency (β: 0.234; confidence interval: 0.001-0.468; p = 0.05) after adjustment for potential confounders.  CONCLUSIONS: Depressive symptoms among kTx recipients are associated with increased amount of stage 2 sleep and prolonged REM latency. Further studies are needed to confirm our findings and understand potential clinical implications

Sleep disorders, depressive symptoms and health-related quality of life-a cross-sectional comparison between kidney transplant recipients and waitlisted patients on maintenance dialysis

BACKGROUND: Kidney transplantation is believed to improve health-related quality of life (HRQoL) of patients requiring renal replacement therapy (RRT). Recent studies suggested that the observed difference in HRQoL between kidney transplant recipients (Tx) vs patients treated with dialysis may reflect differences in patient characteristics. We tested if Tx patients have better HRQoL compared to waitlisted (WL) patients treated with dialysis after extensive adjustment for covariables. METHODS: Eight hundred and eighty-eight prevalent Tx patients followed at a single outpatient transplant clinic and 187 WL patients treated with maintenance dialysis in nine dialysis centres were enrolled in this observational cross-sectional study. Data about socio-demographic and clinical parameters, self-reported depressive symptoms and the most frequent sleep disorders assessed by self-reported questionnaires were collected at enrollment. HRQoL was assessed by the Kidney Disease Quality of Life Questionnaire. RESULTS: Patient characteristics were similar in the Tx vs WL groups: the proportion of males (58 vs 60%), mean +/- SD age (49 +/- 13 vs 49 +/- 12) and proportion of diabetics (17 vs 18%), respectively, were all similar. Tx patients had significantly better HRQoL scores compared to the WL group both in generic (Physical function, General health perceptions, Energy/fatigue, Emotional well-being) and in kidney disease-specific domains (Symptoms/problems, Effect- and Burden of kidney disease and Sleep). In multivariate regression models adjusting for clinical and socio-demographic characteristics, sleep disorders and depressive symptoms, the modality of RRT (WL vs Tx) remained independently associated with three (General health perceptions, Effect- and Burden of kidney disease) out of the eight HRQoL dimensions analysed. CONCLUSIONS: Kidney Tx recipients have significantly better HRQoL compared to WL dialysis patients in some, but not all, dimensions of quality of life after accounting for differences in patient characteristics. Utilizing multidimensional disease-specific questionnaires will allow better understanding of treatment, disease and patient-related factors potentially affecting quality of life in patients with chronic medical conditions

Spatial risk assessment of hydrological extremities : Inland excess water hazard, Szabolcs-Szatmár-Bereg Country, Hungary

Inland excess water hazard was regionalized and digitally mapped using auxiliary spatial environmental information for a county in Eastern Hungary. Quantified parameters representing the effect of soil, geology, groundwater, land use and hydrometeorology on the formulation of inland excess water were defined and spatially explicitly derived. The complex role of relief was characterized using multiple derivatives computed from a DEM. Legacy maps displaying inland excess water events were used as a reference dataset. Regression kriging was applied for spatial inference with the correlation between environmental factors and inundation determined using multiple linear regressions. A stochastic factor derived through kriging the residual was added to the regression results,thus producing the final inundation hazard map. This may be of use for numerous landrelated activities