Effect of a Home-Based Exercise Program on Indices of Physical Function and Quality of Life in Elderly Maintenance Hemodialysis Patients.

Background: Patients on maintenance hemodialysis (MHD) exhibit muscle wasting and impaired physical function which can be reversed with regular exercise, but accessibility to exercise programs for this unique population is lacking. We assessed the efficacy of a home-based exercise program on a broad range of indices of physical function, quality of life (QoL), and cognitive decline in patients with MHD.

Design And Methods: Twenty-eight MHD patients, mean age 66 ± 7 years, were randomized to a 12-week home-based, case-managed aerobic and resistance exercise program or to usual care (13 exercise and 15 usual care).

SOCS2 Silencing Improves Somatic Growth without Worsening Kidney Function in CKD.

Background: Growth hormone (GH) resistance in CKD is partly due to increased expression of SOCS2, a GH signaling negative regulator. In SOCS2 absence, body growth is exaggerated. However, GH overexpression in mice causes glomerulosclerosis.

A randomized controlled trial of exercise to prevent muscle mass and functional loss in elderly hemodialysis patients: Rationale, study design, and baseline sample.

Background: Elderly maintenance hemodialysis (MHD) patients exhibit muscle wasting and impaired physical function. This trial determines whether MHD patients benefit from a 12-week home-based exercise program, protein supplementation, or both.

Design: and Methods: This is a randomized, blinded controlled trial involving 60 elderly MHD patients with impaired exercise capacity and function.

Prehabilitation for kidney transplant candidates: Is it time?

Many patients become frail with diminished cardiorespiratory fitness while awaiting kidney transplantation. Frailty and poor fitness powerfully predict mortality, transplant graft survival, and healthcare utilization after kidney transplantation. Efforts to intervene with post-transplant physical therapy have been met with limited success, in large part due to high study dropout.

Endurance exercise and growth hormone improve bone formation in young and growth-retarded chronic kidney disease rats.

Background: Childhood chronic kidney disease (CKD) is associated with both short stature and abnormal bone mineralization. Normal longitudinal growth depends on proper maturation of epiphyseal growth plate (EGP) chondrocytes, leading to the formation of trabecular bone in the primary ossification centre. We have recently shown that linear growth impairment in CKD is associated with impaired EGP growth hormone (GH) receptor signalling and that exercise improved insulin-like growth factor I (IGF-I) signalling in CKD-related muscle atrophy.

Acute acidosis attenuates leucine stimulated signal transduction and protein synthesis in rat skeletal muscle.

Background: Critical illnesses are often complicated by acute metabolic acidosis, which if persistent, adversely affects outcome. Among the harmful effects that it might cause are impaired utilization of nutrients, increased proteolysis and depressed protein synthesis, leading to muscle wasting. As the amino acid leucine stimulates protein synthesis by activating mTOR signaling, we explored whether in acidosis, impaired leucine-stimulated signaling might be a contributor to the depressed protein synthesis.

Impaired renal growth hormone JAK/STAT5 signaling in chronic kidney disease.

Background: Treatment with recombinant human growth hormone (GH) is the standard therapy for short stature in children with chronic kidney disease (CKD). However, concerns have been raised on the potential renal fibrogenic effects of GH. There is no information regarding the renal GH receptor (GHR)-JAK-STAT signaling pathway in CKD.

Effect of armodafinil on cognition in patients with HIV/AIDS and fatigue.

Fatigue and cognitive impairment are common in HIV+ adults and may occur independently or be causally linked. This study examined whether alleviation of fatigue with armodafinil in a placebo-controlled double-blind 4-week trial had an effect on cognitive function among those with and without mild neuropsychological impairment at baseline. Sixty-one patients completed a standard battery of neuropsychological tests at study entry and Week 4: A total of 33 were randomized to armodafinil and 28 to placebo.

Acute uremia suppresses leucine-induced signal transduction in skeletal muscle.

Adequate nutrient intake in acute uremia is a key part of patient management especially as food utilization is usually impaired. Leucine is important as it comprises about one-fifth of essential amino acid needs and, apart from serving as a substrate, it directly activates the mTOR signaling pathway stimulating protein synthesis and inhibiting autophagy. Here we tested whether leucine activation of the mTOR signaling pathway in muscle is severely disrupted in acute uremia.

Epiphyseal growth plate growth hormone receptor signaling is decreased in chronic kidney disease-related growth retardation.

Linear growth retardation in children with chronic kidney disease (CKD) has been ascribed to insensitivity to growth hormone. This resistance state has been attributed to impaired growth hormone signaling through the JAK2/STAT5 pathway in liver and skeletal muscle leading to reduced insulin-like growth factor-I (IGF-I). Here we determine whether systemic and growth plate alterations in growth hormone signaling contribute to CKD-induced linear growth retardation using partially nephrectomized and pair-fed control 20-day-old rats.

The effects of type 1 IGF receptor inhibition in a mouse model of diabetic kidney disease.

Objective: We have recently shown increased sensitivity to IGF-I induced signal transduction in kidneys of diabetic mice. Accordingly we investigated the effects of PQ401, a novel diarylurea compound that inhibits IGF1R autophosphorylation in type I diabetes.

Methods: Control (C) and Diabetic (D) mice were administered PQ401 (CP, DP) or vehicle (C, D) for 3weeks.

A marked deficiency in circulating and renal IGF-I peptide does not inhibit compensatory renal enlargement in uninephrectomized mice.

Objective: Increase in kidney IGF-I levels due to its increased trapping from the circulation was hypothesized to be a key mediator of compensatory renal enlargement. We tested this hypothesis using genetically engineered mice with extremely low circulating IGF-I levels.

Design: Both IGF-I deficient (ID) and normal (N) mice underwent a uninephrectomy (UNx) and sacrificed 2 or 9days later.

Leucine-stimulated mTOR signaling is partly attenuated in skeletal muscle of chronically uremic rats.

The branched-chain amino acid leucine stimulates muscle protein synthesis in part by directly activating the mTOR signaling pathway. Furthermore, leucine, if given in conjunction with resistance exercise, enhances the exercise-induced mTOR signaling and protein synthesis. Here we tested whether leucine can activate the mTOR anabolic signaling pathway in uremia and whether it can enhance work overload (WO)-induced signaling through this pathway.

Treatment of HIV-related fatigue with armodafinil: a placebo-controlled randomized trial.

Objective: To evaluate the efficacy and safety of armodafinil in the treatment of fatigue in HIV+ patients, and to assess its effect on depressive symptoms and behavior once fatigue remitted.

Method: HIV+ patients with clinically significant fatigue were treated in a placebo-controlled randomized double-blind trial for 4 weeks. Armodafinil responders and placebo non-responders or relapsers were treated openly for a total of 16 weeks with armodafinil.

Modafinil and armodafinil treatment for fatigue for HIV-positive patients with and without chronic hepatitis C.

Fatigue is prevalent among patients with hepatitis C virus (HCV) and with HIV/AIDS but there are no established fatigue treatments for either condition or their combination. We analysed data from three trials of modafinil or armodafinil for HIV-positive patients with fatigue, including 36 co-infected with HCV, to compare treatment response and safety parameters related to HCV status. One hundred and twenty patients received active drug and 70 were randomized to placebo.

Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study.

Objective: To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and to assess effect on depressive symptoms.

Method: Patients who were HIV+ and had clinically significant fatigue (according to the Fatigue Severity Scale [FSS]) were included in a 4-week randomized, placebo-controlled, double-blind trial. This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders.

Uremia attenuates growth hormone-stimulated insulin-like growth factor-1 expression, a process worsened by inflammation.

Growth hormone (GH) resistance is common in uremia and together with resistance to insulin-like growth factor-1 (IGF-1) contributes to uremic growth retardation and muscle wasting. Previously, we found decreased GH-stimulated janus-kinase 2-signal transducers and activators of transcription 5 (STAT5) phosphorylation and nuclear translocation in uremia; however, it is unclear whether there are more distal defects. Therefore, we tested whether the binding of phosphorylated STAT5b to DNA is intact in uremia.

Modafinil effects on cognitive function in HIV+ patients treated for fatigue: a placebo controlled study.

Both mild cognitive impairment and fatigue are common among people with HIV/AIDS. This study examined the efficacy of modafinil for HIV+ patients who sought treatment for fatigue in a placebo-controlled double-blind 4-week trial. A battery of standard neuropsychological tests was administered at study entry and Week 4, and change in performance was compared for 59 patients receiving modafinil versus 44 patients receiving placebo.

Endotoxin-induced growth hormone resistance in skeletal muscle.

Inflammation-induced skeletal muscle wasting is a serious clinical problem and arises in part because of resistance to GH-stimulated IGF-I expression. Although it is established that in the liver, resistance develops because of impaired signaling through the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) transduction pathway, together with a more distal defect in STAT5 DNA-binding activity, the situation in skeletal muscle is unclear. Accordingly, we set out to characterize the mechanisms behind the skeletal muscle resistance to GH in rats with acute inflammation induced by endotoxin.

Increased renal Akt/mTOR and MAPK signaling in type I diabetes in the absence of IGF type 1 receptor activation.

Growth hormone (GH) and IGF-I have been implicated in the pathogenesis of type I diabetic (DM) nephropathy. We investigated renal GH receptor (GHR) and IGF-type 1 receptor (IGF1R) signaling in an animal model of type I DM. Kidney tissue was examined for GHR and IGF1R key signaling molecules.

Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study.

Our objective was to determine whether modafinil alleviates fatigue in patients with amyotrophic lateral sclerosis (ALS). A placebo controlled trial with a 3:1 modafinil:placebo randomization in doses up to 300 mg/day for 4 weeks was followed by 8 weeks of open maintenance treatment. The primary endpoint was the Clinical Global Impressions-Improvement Scale.

Provigil (modafinil) plus cognitive behavioral therapy for methamphetamine use in HIV+ gay men: a pilot study.

Objectives: To evaluate the efficacy of modafinil combined with cognitive behavioral therapy (CBT) for treatment of methamphetamine (MA) dependence among HIV+ gay men.

Methods: In a single blind trial, modafinil was administered for 12 weeks, followed by a 4-week placebo phase. CBT was conducted for 18 sessions over the 16-week study.

Low-dose growth hormone is cardioprotective in uremia.

Growth hormone (GH) is required to maintain normal cardiac structure and function and has a positive effect on cardiac remodeling in experimental and possibly human disease. Cardiac resistance to GH develops in the uremic state, perhaps predisposing to the characteristic cardiomyopathy associated with uremia. It was hypothesized that administration of low-dosage GH may have a salutary effect on the cardiac remodeling process in uremia, but because high levels of GH have adverse cardiac effects, administration of high-dosage GH may worsen uremic cardiomyopathy.

Increased workload fully activates the blunted IRS-1/PI3-kinase/Akt signaling pathway in atrophied uremic muscle.

Muscle wasting in chronic renal failure is associated with increased morbidity and mortality; however, resistance exercise is effective at increasing muscle mass while improving muscle strength and function. To study the mechanism by which this occurs, we compared uremic and control rats where work overload was surgically induced unilaterally in the plantaris muscle. We found that work overload increases muscle insulin-like growth factor-1 and mechano-growth factor expression.