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1.

Objective

To describe patterns of weight loss and regain and their effect on the pro-inflammatory cytokines IL-6 and TNF-α, and anti-inflammatory cytokines adiponectin and IL-10 during a 24-month weight loss trial.

Materials/Methods

Participants were obese adults (N = 66) who lost and regained ≥ 10 lb during a 24-month clinical trial of behavioral weight loss treatment. Measurements of cytokines and weight were conducted at baseline, 6, 12, 18, and 24 months. Linear mixed modeling was used to determine percent change in weight and cytokines from baseline.

Results

The sample was predominantly female (80.3%) and White (86.4%), with a mean age of 48.4 ± 7.3 years and mean BMI of 34.5 ± 4.4 kg/m2. At baseline, men had higher waist circumference, body weight, and energy intake, and lower percent body fat and adiponectin. The largest decrease in weight was observed at 6 months with a mean 11% decrease (p < .0001).A significant gender-by-weight change interaction on percent change in adiponectin was observed [b(se) = 0.9 (0.2), p = .0003], with men having a larger increase in adiponectin with weight loss compared to women. There was a significant effect of weight gain over time with increases in IL-6 [b(se) = 0.9 (0.3), p = .001].

Conclusions

Overall, weight loss was significantly associated with improvements in adiponectin and IL-6. Those improvements remained at 24 months, following weight regain. The association between weight change and adiponectin was different between genders. Implementing strategies that support sustained weight loss can help prevent a state of chronic systemic inflammation and its associated adverse effects.  相似文献   

2.
Long-term memory (LTM) consolidation requires the synthesis of plasticity-related proteins (PRPs). In addition, we have shown recently that LTM formation also requires the setting of a “learning tag” able to capture those PRPs. Weak training, which results only in short-term memory, can set a tag to use PRPs derived from a temporal-spatial closely related event to promote LTM formation. Here, we studied the involvement of glutamatergic, dopaminergic, and noradrenergic inputs on the setting of an inhibitory avoidance (IA) learning tag and the synthesis of PRPs. Rats explored an open field (PRP donor) followed by weak (tag inducer) or strong (tag inducer plus PRP donor) IA training. Throughout pharmacological interventions around open-field and/or IA sessions, we found that hippocampal dopamine D1/D5- and β-adrenergic receptors are specifically required to induce PRP synthesis. Moreover, activation of the glutamatergic NMDA receptors is required for setting the learning tags, and this machinery further required α-Ca2+/calmodulin-dependent protein kinase II and PKA but not ERK1/2 activity. Together, the present findings emphasize an essential role of the induction of PRPs and learning tags for LTM formation. The existence of only the PRP or the tag was insufficient for stabilization of the mnemonic trace.  相似文献   

3.

Objective

Irisin is a recently identified myokine, suggested to mediate the beneficial effects of exercise by inducing browning of white adipocytes and thus increasing energy expenditure. In humans, the regulation of irisin by exercise is not completely understood. We investigated the effect of acute and chronic whole-body vibration exercise, a moderate-intensity exercise that resembles shivering, on circulating irisin levels in young healthy subjects.

Materials/Methods

Healthy untrained females participated in a 6-week program of whole-body vibration exercise training. Blood was drawn before and immediately after an acute bout of exercise at baseline (week 0) and after 6 weeks of training.

Results

The resting irisin levels were not different at baseline (week 0) and after 6 weeks of training. At both 0 and 6 weeks of training, an acute bout of vibration exercise significantly elevated circulating irisin levels by 9.5% and 18.1%, respectively (p = 0.05 for the percent change of irisin levels).

Conclusions

Acute bouts of whole-body vibration exercise are effective in increasing circulating irisin levels but chronic training does not change levels of baseline irisin levels in humans.  相似文献   

4.

Background

This study reports the outcomes of patients who underwent electrical cardioversion for atrial fibrillation recurrence following mitral valve surgery and associated radiofrequency ablation compared to those who did not undergo concomitant atrial fibrillation ablation.

Methods

The population consisted of 116 patients with persistent/long-standing persistent AF who underwent mitral valve surgery with (Group A, n = 54) or without (Group B, n = 62) associated radiofrequency ablation between January 2007 and January 2011 at three institutions and who subsequently underwent cardioversion for persistent atrial fibrillation within 12 months of their initial procedure.

Results

The mean follow-up duration was 30.7 ± 9.4 months. Of the 104 patients with acute restoration of SR 42 (40.3%) had AF recurrence. The average time to recurrence after cardioversion was 7.3 ± 4.2 days. Recurrence was significantly lower in patients undergoing ablation surgery (21.4%) than in those undergoing no ablation surgery (78.6%, p < 0.001). Non-performed ablation procedure (p < 0.001), time from surgery ≥ 88 days and left atrial dimensions ≥ 45.5 mm before cardioversion (both, p = 0.005) were multivariable predictors of atrial fibrillation recurrence. In Group B the use of amiodarone was inversely correlated with recurrence of AF (p < 0.001). This correlation was not significant (r = − 0.02, p = 0.85) in Group A.

Conclusions

Electrical cardioversion for recurrent AF showed better results and stable recovery of sinus rhythm in patients undergoing concomitant surgical ablation during mitral valve surgery. This might be attributable to substrate modification caused by surgical lesions. Amiodarone improved the ECV-success rate only in patients with no associate ablation. Further larger randomized studies are necessary to confirm our findings.  相似文献   

5.

Objective

Serum uric acid (sUA) is believed to contribute to the pathogenesis of metabolic comorbidities like hypertension, insulin-resistance (IR) and endothelial dysfunction (EDF) in obese children. The present pilot study investigated the association between sUA concentrations and loss of body weight following laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y-gastric bypass (RYGB) in severely obese adolescents.

Materials/Methods

10 severely obese adolescents underwent either LSG (n = 5) or RYGB (n = 5). 17 normal weight, healthy, age- and gender-matched adolescents served as a normal weight peer group (NWPG). Pre- and 12 months postoperatively, sUA and relevant metabolic parameters (glucose homeostasis, transaminases, lipids) were compared.

Results

Preoperatively, sUA was significantly elevated in patients with severe obesity compared to NWPG. Twelve months after LSG and RYGB, a significant decrease in sUA, BMI, CVD risk factors, hepatic transaminases, and HOMA-IR was observed. Reduction in SDS-BMI significantly correlated with changes in sUA.

Conclusions

sUA levels and metabolic comorbidities improved following bariatric surgery in severely obese adolescents. The impact of changes in sUA on long-term clinical complications of childhood obesity deserves further study.  相似文献   

6.
A key feature of sepsis is hypovolemia due to increased microvascular permeability. It has been suggested that the negative charge of albumin and of the endothelial glycocalyx is important for maintenance of the normally low permeability for albumin. Here we tested the hypothesis that charge effects contribute to the increased permeability in sepsis. Transcapillary escape rate (TER) and initial distribution volume for 125I-labeled bovine serum albumin (BSA, isoelectric point pH 4.6) and for 131I-labeled charge modified BSA (cBSA, average isoelectric point, pH 7.1) was measured 3 h after sepsis was induced by cecal ligation and incision (CLI) (n = 11) and in control animals (n = 12). The importance of charge for permeability in sepsis was estimated by comparing the ratio between TER for cBSA and TER for BSA during control conditions to that after CLI. Plasma concentration of the glycocalyx component glycosaminoglycans (GAGs) was measured in separate control and CLI animals. The initial distribution volume for BSA and cBSA in control animals was 38 ± 3 ml/kg and 47 ± 4 mL/kg and decreased by 17% and 19%, respectively, following CLI. TER for BSA increased from 16.7 ± 4.1% in the controls to 20.1 ± 1.9% following CLI. Corresponding values for cBSA were 26.7 ± 5.6% and 29.8 ± 3.5%, respectively. The ratio between TER for cBSA and TER for BSA was 1.62 ± 0.1 in the control group and 1.49 ± 0.1 following CLI (p < 0.05). Plasma GAG concentrations were higher in CLI animals than in the control group. We conclude that CLI induce hypovolemia secondary to increased microvascular permeability. Negative charge contributes to the normally low permeability of albumin and the importance of charge is decreased in early experimental sepsis. The observed charge effects are associated with CLI-induced breakdown of the glycocalyx.  相似文献   

7.

Aims

To investigate first-phase insulin release and peripheral insulin sensitivity of non-obese, normal-glucose tolerant, first-degree relatives of Chinese type 2 diabetic patients.

Methods

12 euglycemic first-degree relatives of type 2 diabetic patients (ERDM), 12 newly diagnosed type 2 diabetic patients (DM-2) and 12 healthy individuals (control) participated in the study. All subjects were non-obese (BMI < 25 kg/m2). Intravenous glucose tolerance test and euglycemic hyperinsulinemic clamp test were performed to evaluate first-phase insulin release and quantify insulin sensitivity, respectively.

Results

The first-phase insulin release did not differ between the ERDM and control subjects (p = 0.532), while the acute insulin response was absent in the DM-2 patients (p = 0.001). Peripheral glucose deposit rate (GDR) was significantly lower in the ERDM (10.6 ± 2.1 mg/kg·min, p = 0.000) and DM-2 (9.6 ± 1.1 mg/kg·min, p = 0.000) groups than that in the control group (13.2 ± 1.2 mg/kg·min). There was no statistical difference in GDR between the ERDM and DM-2 groups (p = 0.110). Fasting FFA levels of the ERDM (p = 0.007) and DM-2 (p = 0.000) subjects were significantly higher than those of the controls.

Conclusions

Non-obese, first-degree relatives of type 2 diabetic patients with normal glucose tolerance (NGT) exhibit remarkable impairment of insulin sensitivity and increased FFA levels. Insulin resistance is independent of obesity and blood glucose level. Progression from NGT to type 2 diabetes may mainly be attributed to deterioration of early insulin secretion.  相似文献   

8.

Objective

Higher insulin levels during an oral glucose test (OGTT) have been shown in South Asians. We aimed to investigate if this increased insulin response causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide-1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in this ethnic group.

Methods

A prolonged, 6-h, 75-g OGTT was performed in healthy, young Caucasian (n = 10) and South Asian (n = 8) men. The glucose, insulin and GLP-1 response was measured and indices of insulin sensitivity and beta-cell activity were calculated.

Results

Age (Caucasians (CAU) 21.5 ± 0.7 years vs South Asians (SA) 21.4 ± 0.7 years (mean ± SEM)) and body mass index (CAU 22.7 ± 0.7 kg/m2 vs SA 22.1 ± 0.8 kg/m2) were comparable between the two groups. South Asian men were more insulin resistant, as indicated by a comparable glucose but significantly higher insulin response, and a significantly lower Matsuda index (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1 response, as reflected by a higher area under the curve for GLP-1 (CAU 851 ± 99.8 mmol/l vs SA 1235 ± 155.0 mmol/L). During the whole 6-h period, no reactive hypoglycemia was observed.

Conclusion

Healthy, young South Asian men have higher insulin levels during an OGTT as compared to Caucasians. This does not, however, lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased levels of GLP-1. Whether this is an adaptive response to facilitate hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant state has yet to be elucidated.  相似文献   

9.
Hip trauma and surgery are associated with systemic inflammatory reaction. However, little evidence exists about the role of IL-6. In order to assess the inflammatory response, we evaluated white blood cell (WBC) count, C-reactive protein (CRP) and IL-6 dynamics in sequential pre- and postsurgical samples collected from 125 elderly patients (mean age 78 ± 9 years) undergoing osteosynthesis (OS) for extracapsular hip fractures (n = 69), hemiarthroplasty (HA) or urgent total hip arthroplasty for intracapsular fractures (UA) (n = 35), and elective total hip arthroplasty for osteoarthrosis (OA) (n = 21). Both preoperative CRP and IL-6 levels were higher in patients with intracapsular fractures. IL-6 levels reached peak values immediately after the surgery, while CRP peak levels were reached 48 h after the surgery. The overall inflammatory reaction was more intense in HA patients compared to the other subgroups. Independent of each other, older age and the hip fracture type affected the IL-6 response, while the CRP response depended only on the type of surgery. The abrupt increase in IL-6 immediately after the procedure suggests its involvement in the early stages of the postoperative inflammatory reaction after hip surgery. This reaction is particularly pronounced in elderly patients receiving HA.  相似文献   

10.

Background/objectives

To determine pacemaker (PM) dependency at follow-up visit in patients who underwent new permanent pacemaker implantation (PPI) following transcatheter aortic valve implantation (TAVI).

Methods

Single center prospective observational study including 167 patients without previous PM implantation who underwent TAVI with the self-expanding Medtronic CoreValve System (MCS) between November 2005 and February 2011. PM dependency was defined by the presence of a high degree atrioventricular block (HDAVB; second [AV2] and third degree [AV3B]), or a slow (< 30 bpm) or absent ventricular escape rhythm during follow-up PM interrogation.

Results

A total of 36 patients (21.6%) received a new PM following TAVI. The indication for PM was AV2B (n = 2, 5.6%), AV3B (n = 28, 77.8%), postoperative symptomatic bradycardia (n = 3, 8.3%), brady–tachy syndrome (n = 1, 2.8%), atrial fibrilation with slow response (n = 1, 2.8%) and left bundle branch block (n = 1, 2.8%). Long term follow-up was complete for all patients and ranged from 1 to 40 months (median (IQR): 11.5 (5.0–18.0 months). Of those patients with a HDAVB, 16 out of the 30 patients (53.3%) were PM independent at follow-up visit (complete or partial resolution of the AV conduction abnormality). Overall, 20 out of the 36 patients (55.6%) who received a new PM following TAVI were PM independent at follow-up.

Conclusion

Partial and even complete resolution of peri-operative AV conduction abnormalities after MCS valve implantation occurred in more than half of the patients.  相似文献   

11.

Purpose

Late-onset atrial arrhythmia after successful closure of atrial septal defect (ASD) is not uncommon. Right atrial (RA) enlargement and increased electrocardiographic P-wave dispersion (Pd) independently predict the development of atrial arrhythmia. Data on the degree of right atrial (RA) geometrical and electrical remodeling following device closure of ASD are limited.

Methods

Echocardiography and electrocardiography (ECG) were performed in 58 consecutive patients (47 ± 17 years) before and at 3 months after ASD closure. Persistent RA enlargement was defined as RA volume index (RAVI) ≥ 21 ml/m2 at 3 months. Pd was calculated as the difference between maximal and minimal P-wave durations in 12-lead ECG.

Results

RA size reduced (RAVI: 50 ± 28 vs. 26 ± 16 ml/m2, p < 0.001) and Pd on ECG decreased (53 ± 17 vs. 49 ± 20 ms, p < 0.05) significantly at 3 months when compared to baseline. However, persistent RA enlargement remained evident in 31 patients (53%). As a group, they were older with higher pulmonary arterial systolic pressure, larger Qp/Qs, longer maximal P-wave duration and Pd than those with normalized RA. Pd reduction only occurred in patients with normalized RA size. The 3-month Pd (hazard ratio: 1.033, p < 0.001) predicted the presence of incomplete RA geometrical remodeling. ROC curve revealed that Pd ≥ 45 ms at 3 months was 77% sensitive and 86% specific in revealing residual RA enlargement.

Conclusion

Both atrial geometrical and electrical reverse remodeling were evident at 3 months following ASD closure. However, only half of the included patients had normalization of RA size which could be revealed by a simple ECG surrogate of intra-atrial conduction disturbance.  相似文献   

12.
We tested here the impact of a long-term inhibition of dipeptidyl peptidase-4 (DPP-4) with sitagliptin on the deposition of amyloid-β within the brain and deficits in memory-related behavioral paradigms in a model of Alzheimer’s disease (AD): double transgenic mice B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/J. Mice began to receive sitagliptin at 7 months of age. Three different dose of sitagliptin (5, 10 and 20 mg/kg), were administered daily for 12 weeks by gastric gavage.  相似文献   

13.
The present study had as a goal to analyze the impact of a physical activity program (recreation and walking) over the aerobic resistance, the functional autonomy and the quality of life of elderly women. To this experimental study the elderly women (65 ± 6.40 years old) were randomly separated in experimental group (EG, n = 31) and a control group (CG, n = 28). A 6-min-walking test (aerobic resistance); a protocol of autonomy evaluation of the Latin-American Group for Maturity Development (functional autonomy), and the WHO QoL-old tests were utilized. The intervention happened with classes of recreation and walking practice, three times a week, for 1 h, during 4 months. The results found revealed significant improvement for the EG at the aerobic resistance (Δ% = 29.06%, p = 0.0001), functional autonomy (Δ% = −27.15%, p = 0.0001) and QoL (Δ% = 15.47%, p = 0.0001). It was concluded that the systematic physical exercise interferes in a positive way at the autonomy, aerobic resistance and QoL of the elderly women.  相似文献   

14.

Background

The 6-minute walk test (6WT) is an established tool in the assessment of endurance and prognosis in patients with chronic heart failure (CHF). For these patients there is very limited data on biological variation of 6WT distances. We determined the minimal important difference (MID) for the 6WT in patients with stable systolic CHF.

Methods

Two cohorts of patients with stable systolic CHF were included from the outpatients' clinic of the University of Heidelberg. In these cohorts, two 6WT measurements were performed – in cohort 1 (n = 461) 180 days and in cohort 2 (n = 512) 365 days apart. Stability was defined as the absence of clinical events (3 months before the first test, between both tests, and 6 months after the second test) and stability of symptoms (NYHA) between tests. Using a standard error of measurement (SEM)-based approach, we determined the MID for both cohorts.

Results

The intraclass correlation coefficient was 0.89 at 180 days and 0.88 at 365 days. The results were consistent for groups stratified for age, gender, etiology of CHF, and individual NYHA class. The MID for the 6WT in stable CHF patients was 35 m and 37 m between presentation and 180 and 365 days, respectively.

Conclusion

Submaximal exercise capacity as represented by the 6WT varies little in stable CHF patients for up to 1-year intervals. The MID for changes in 6WT values in patients with stable CHF over a period of 6 to 12 months is ~ 36 m.  相似文献   

15.
To explore the relationship between age-related hearing loss (presbycusis) and synaptic degeneration in the hippocampal CA3 region of C57BL/6J mice, we investigated both cognitive performance and synaptic changes within the hippocampus of C57BL/6J mice from three age groups of 6-8, 24-26, and 42-44 weeks; CBA/CaJ mice served as controls. The auditory brainstem response was used as a measure of hearing threshold, and cognitive behavior was evaluated using the Morris water maze. The ultrastructure of synapses was observed with transmission electron microscopy, and the quantity and distribution of the synaptic markers synaptophysin and PSD-95 were observed with immunohistochemistry. The hearing threshold of C57BL/6J mice was significantly higher at 24-26 weeks than at 6-8 weeks, and hearing loss was profound at 42-44 weeks. This was accompanied by progressive degeneration of synapses within the auditory cortex. In contrast, the hearing threshold of CBA/CaJ mice was relatively unchanged at 24-26 weeks of age, and these mice developed only mild hearing loss at 42-44 weeks of age. Interestingly, C57BL/6J, but not CBA/CaJ mice clearly exhibited both decreased performance in the Morris water maze and degeneration of synapses within the hippocampus. We therefore conclude that age-related hearing loss is accompanied by the degeneration of synapses in the hippocampal CA3 region of C57BL/6J mice.  相似文献   

16.

Background

The six-minute walk test (6MWT) is an established measure of functional exercise capacity associated with clinical prognosis in Chronic Heart Failure (CHF). The aim of this study is to evaluate the employment of tele-accelerometry for the remote assessment of 6MWT in CHF.

Methods

155 patients were subjected to tele-accelerometry in form of monthly 6MWTs in their home surroundings. Accelerometer output included steps/6 min and walking speed. Data was directly transferred via mobile network to the Telemedicine Centre subsequent to test completion. 6MWT distance was measured by hand wheel and steps were counted with a digital hand-counter at baseline (Test 1) and at 12 months follow-up (Test 2).

Results

Accelerometer accuracy was within the 99th percentile. There was a significant correlation between step count, walking speed and measured 6MWT distance (Test 1: steps: r = 0.80, P < 0.001; Test 2: steps: r = 0.90, P < 0.001 and Walking Speed Test 1: r = 0.80, P < 0.001; Walking Speed Test 2: r = 0.86, P < 0.001). The reproducibility of tele-accelerometry was within 95% margin for all performance parameters, which showed stronger associations to quality of life questionnaire (Short Form - 36) Physical Component Score (PCS) than New York Heart Association (NYHA) functional class.

Conclusion

Tele-accelerometry is feasible in patients with CHF and output parameters are indicative of exercise capacity. The benefit of this approach lies in its simplicity under every day circumstances by enabling routine performance testing to assess patients' functional status.  相似文献   

17.

Objective

We tested the hypothesis that women with adipocyte hypertrophy in either omental (OM) or subcutaneous (SC) adipose tissue are characterized by alterations in adipocyte lipolysis and adipose tissue expression of genes coding for proteins involved in adipocyte metabolism or inflammation, independent of overall adiposity and fat distribution.

Methods

OM and SC fat samples were obtained surgically in 44 women (age: 47.1 ± 5.0 years, BMI: 27.7 ± 5.3 kg/m2). In a given depot, women with larger adipocytes than predicted by the regression of adipocyte size vs. total and regional adiposity measurements were considered as having adipocyte hypertrophy, whereas women with smaller adipocytes than predicted were considered as having adipocyte hyperplasia.

Results

Women with OM adipocyte hypertrophy had significantly lower SC GLUT4 mRNA abundance (p ≤ 0.05), higher SC CEBPB mRNA expression (p ≤ 0.05) as well as higher mRNA expression of OM PLIN (p ≤ 0.05), CD68 (p ≤ 0.10), CD14 (p ≤ 0.10), CD31 (p ≤ 0.05) and vWF (p ≤ 0.05) compared to women with OM adipocyte hyperplasia. OM adipocyte isoproterenol- (10− 10 to 10− 5 mol/L), forskolin- (10− 5 mol/L) and dibutyryl cAMP- (10− 3 mol/L) stimulated lipolysis was higher in women with hypertrophic OM adipocytes (p ≤ 0.05, for all). Women with SC adipocyte hypertrophy had lower SC mRNA expression of GLUT4 (p ≤ 0.10), higher SC mRNA expression of CEBPB (p ≤ 0.05), lower plasma adiponectin concentrations (p ≤ 0.05) and higher SC adipocyte isoproterenol- (10− 9 to 10− 5 mol/L) stimulated lipolysis (p ≤ 0.05) compared to women with SC adipocyte hyperplasia.

Conclusion

Hypertrophic adipocytes in both fat compartments are characterized by alterations in adipocyte lipolysis and adipose tissue expression of genes coding for proteins involved in adipocyte metabolism or inflammation.  相似文献   

18.

Objective

C-reactive protein (CRP), inflammatory cytokines, and adipokines contribute to atherosclerosis, insulin resistance, and development of late-onset complication in patients with type 2 diabetes. We performed a systematic review to assess effects of exercise interventions on inflammatory markers/cytokines and adipokines.

Materials/Methods

We searched electronic databases (MEDLINE, EMBASE, and Cochrane Controlled Trials Registry) and reference lists in relevant papers for articles published in 1966–2013. We selected studies that evaluated the effects of exercise intervention on inflammatory markers/cytokines and adipokines in adult patients with type 2 diabetes. Weighted mean differences of exercise on outcomes were derived using fixed or random effect models; factors influencing heterogeneity were identified using meta-regression analysis.

Results

Fourteen randomized controlled trials (824 patients) were included in our meta-analysis. Exercise was associated with a significant in CRP = − 0.66 mg/l (95% CI, − 1.09 to − 0.23 mg/l; − 14% from baseline) and interleukin-6 (IL-6) = − 0.88 pg/ml (95% CI, − 1.44 to − 0.32 pg/ml; − 18% from baseline) but did not alter adiponectin or resistin levels; aerobic exercise program was associated with a significant change in leptin = − 3.72 ng/ml (95% CI, − 6.26 to − 1.18 ng/ml; − 24% from baseline). For IL-6, exercise was more effective in those with a longer duration in the program and larger number of sessions during study (p = 0.001).

Conclusions

Exercise decreases inflammatory cytokine (CRP and IL-6) in patients with type 2 diabetes. Exercise could be a therapeutic option for improving abnormalities in inflammation levels in patients with diabetes.  相似文献   

19.
Helium induces preconditioning (He-PC) by mitochondrial calcium-sensitive potassium (mKCa) channel-activation, but this effect is lost in the aged myocardium. Both, the upstream signalling pathway of He-PC and the underlying mechanisms for an age-related loss of preconditioning are unknown. A possible candidate as upstream regulator of mKCa channels is protein kinase A (PKA).We investigated whether 1) regulation of PKA is involved in He-PC and 2) regulation of PKA is age-dependent.Young (2-3 months) and aged (22-24 months) Wistar rats were randomised to eight groups (each n = 8). All animals underwent 25 min regional myocardial ischemia and 120 min reperfusion. Control (Con, Age Con) animals were not further treated. Young rats inhaled 70% helium for 3 × 5min (He-PC). The PKA-blocker H-89 (10 μg/kg) was administered with and without helium (He-PC + H-89, H-89). Furthermore, we tested the effect of direct activation of mKCa channels with NS1619. The adenylyl cyclase activator forskolin (For) was administered in young (300 μg/kg) and aged animals (300 and 1000 μg/kg).He-PC reduced infarct size from 60 ± 4% (Con) to 37 ± 10% (p < 0.05). Infarct size reduction was completely abolished by H-89 (58 ± 5%; p < 0.05), but H-89 alone had no effect (57 ± 2%). NS1619 reduced infarct size in the same concentration in both, young and aged rats (35 ± 6%; p < 0.05 vs. Con and 34 ± 8%; p < 0.05 vs. Age Con). Forskolin in a concentration of 300 μg/kg reduced infarct size in young (37 ± 6%; p < 0.05) but not in aged rats (48 ± 13%; n.s.). In contrast, 1000 μg/kg Forskolin reduced infarct size also in aged rats (28 ± 3%; p < 0.05).He-PC is mediated by activation of PKA. Alterations in PKA regulation might be an underlying mechanism for the age-dependent loss of preconditioning.  相似文献   

20.
Whether rehabilitation outcome can be maintained after discharged from GDH has not been thoroughly investigated. This study was conducted to examine the rehabilitation outcome and its predictors 6 months after discharged from GDH. We studied 418 patients attended a GDH in Hong Kong. All of them had post-6-month assessment. Cognitive status was assessed with Cantonese version of mini-mental state examination (C-MMSE). Functional independence measure (FIM) upon GDH admission (FIM-adm), discharge (FIM-dis) and 6 months after discharge (FIM-p6m) were measured. FIM gain was FIM-dis − FIM-adm while FIM efficiency was FIM gain divided by number of GDH visits. Of the study pool, 164 (39.2%) showed a drop of FIM-p6m. There was a significant drop of FIM-p6m as compared with FIM-dis (p < 0.001). However, the FIM-p6m remained significantly higher than FIM-adm (p < 0.001). Multivariate analysis revealed that FIM-dis was a negative predictor (p < 0.001) while Parkinsonism was a positive predictor for drop of FIM-p6m (p = 0.008). A proportion of functional gain can still be maintained 6 months after discharged from GDH. More studies are needed to look for strategies in maintaining functional gain in GDH discharged patients, especially those with Parkinsonism.  相似文献   

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