Manuela Verri

Is nutritional intake adequate in chronic heart failure patients

OBJECTIVES The goal of this study was to investigate the nutrition adequacy and energy availability for physical activity in free-living, clinically stable patients with chronic heart failure (CHF). BACKGROUND Little information exists regarding the nutrition adequacy and alimentary habits of patients with clinically stable CHF. We hypothesized that CHF patients have an inadequate intake of calories and protein, leading to a negative calorie and nitrogen balance, an expression of increased tissue breakdown. METHODS In 57 non-obese patients with CHF (52 males and 5 females; 52 +/- 3 years; body mass index <25 kg/m(2)) and in 49 healthy subjects (39 males and 10 females) matched for age, body mass index, and sedentary life style we evaluated total energy expenditure (TEE), calorie intake (kcal(I)), and nitrogen intake (N(I)) from a seven-day food diary, total nitrogen excretion (TNE), and energy availability (EA = kcal(I) - resting energy expenditure). A zero calorie balance (CB) occurred when kcal(I) = TEE; a nitrogen balance (NB) in equilibrium was set at NB (= N(I) - TNE) 0 +/- 1 g/day. RESULTS In patients and controls kcal(I) and N(I) were similar. However, in CHF patients the kcal(I) was <TEE with a consequent negative CB (-186 +/- 305 kcal/day vs. + 104.2 +/- 273 kcal/day of controls; p < 0.01). Nitrogen balance resulted negative in CHF (-1.7 +/- 3.2 g/24 h vs. + 2.2 +/- 3.6 g/24 h in controls; p < 0.01). Energy availability in CHF patients was 41% lower than in controls (p < 0.05). CONCLUSIONS Non-obese, free-living patients with clinically stable CHF have an inadequate intake of calories and protein and reduced energy availability for physical activity.

Mitochondrial Alterations, Oxidative Stress and Neuroinflammation in Alzheimer's Disease

Alzheimers disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The primary cause and sequence of its progression are only partially understood but abnormalities in folding and accumulation of insoluble proteins such as β-amyloid and Tau-protein are both associated with the pathogenesis of AD. Mitochondria play a crucial role in cell survival and death, and changes in mitochondrial structure and/or function are related to many human diseases. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. The mitochondrial toxicity induced by β-amyloid is still not clear but may include numerous mechanisms, such as the increased permeability of mitochondrial membranes, the disruption of calcium homeostasis, the alteration of oxidative phosphorylation with a consequent overproduction of reactive oxygen species. Other mechanisms have been associated with the pathophysiology of AD. Inflammatory changes are observed in AD brain overall, particularly at the amyloid deposits, which are rich in activated microglia. Once stimulated, the microglia release a wide variety of pro-inflammatory mediators including cytokines, complement components and free radicals, all of which potentially contribute to further neuronal dysfunction and eventually death. Clinically, novel approaches to visualize early neuroinflammation in the human brain are needed to improve the monitoring and control of therapeutic strategies that target inflammatory and other pathological mechanisms. Similarly, there is growing interest in developing agents that modulate mitochondrial function.

Adequate energy-protein intake is not enough to improve nutritional and metabolic status in muscle-depleted patients with chronic heart failure

An adequate energy‐protein intake (EPI) when combined with amino acid supplementation may have a positive impact nutritional and metabolic status in patients with chronic heart failure (CHF).

Pathogenic Gut Flora in Patients With Chronic Heart Failure

OBJECTIVES The goal of this study was to measure the presence of pathogenic gut flora and intestinal permeability (IP) and their correlations with disease severity, venous blood congestion, and inflammation in patients with chronic heart failure (CHF). BACKGROUND Evidence suggests that translocation of gut flora and/or their toxins from the intestine to the bloodstream is a possible trigger of systemic CHF inflammation. However, the relation between pathogenic gut flora and CHF severity, as well as IP, venous blood congestion as right atrial pressure (RAP), and/or systemic inflammation (C-reactive protein [CRP]), is still unknown. METHODS This study analyzed 60 well-nourished patients in stable condition with mild CHF (New York Heart Association [NYHA] functional class I to II; n = 30) and moderate to severe CHF (NYHA functional class III to IV; n = 30) and matched healthy control subjects (n = 20). In all subjects, the presence and development in the feces of bacteria and fungi (Candida species) were measured; IP according to cellobiose sugar test results was documented. The study data were then correlated with RAP (echocardiography) and systemic inflammation. RESULTS Compared with normal control subjects, the entire CHF population had massive quantities of pathogenic bacteria and Candida such as Campylobacter (85.3 ± 3.7 CFU/ml vs. 1.0 ± 0.3 CFU/ml; p < 0.001), Shigella (38.9 ± 12.3 CFU/ml vs. 1.6 ± 0.2 CFU/ml; p < 0.001), Salmonella (31.3 ± 9.1 CFU/ml vs 0 CFU/ml; p < 0.001), Yersinia enterocolitica (22.9 ± 6.3 CFU/ml vs. 0 CFU/ml; p < 0.0001), and Candida species (21.3 ± 1.6 CFU/ml vs. 0.8 ± 0.4 CFU/ml; p < 0.001); altered IP (10.2 ± 1.2 mg vs. 1.5 ± 0.8 mg; p < 0.001); and increased RAP (12.6 ± 0.6 mm Hg) and inflammation (12.5 ± 0.6 mg/dl). These variables were more pronounced in patients with moderate to severe NYHA functional classes than in patients with the mild NYHA functional class. Notably, IP, RAP, and CRP were mutually interrelated (IP vs. RAP, r = 0.55; p < 0.0001; IP vs. CRP, r = 0.78; p < 0.0001; and RAP vs. CRP, r = 0.78; p < 0.0001). CONCLUSIONS This study showed that patients with CHF may have intestinal overgrowth of pathogenic bacteria and Candida species and increased IP associated with clinical disease severity, venous blood congestion, and inflammation.

Branched-Chain Amino Acids May Improve Recovery From a Vegetative or Minimally Conscious State in Patients With Traumatic Brain Injury: A Pilot Study

OBJECTIVE To investigate whether supplementation with branched-chain amino acids (BCAAs) may improve recovery of patients with a posttraumatic vegetative or minimally conscious state. DESIGN Patients were randomly assigned to 15 days of intravenous BCAA supplementation (n=22; 19.6g/d) or an isonitrogenous placebo (n=19). SETTING Tertiary care rehabilitation setting. PARTICIPANTS Patients (N=41; 29 men, 12 women; mean age, 49.5+/-21 y) with a posttraumatic vegetative or minimally conscious state, 47+/-24 days after the index traumatic event. INTERVENTION Supplementation with BCAAs. MAIN OUTCOME MEASURE Disability Rating Scale (DRS) as log(10)DRS. RESULTS Fifteen days after admission to the rehabilitation department, the log(10)DRS score improved significantly only in patients who had received BCAAs (log(10)DRS score, 1.365+/-0.08 to 1.294+/-0.05; P<.001), while the log(10)DRS score in the placebo recipients remained virtually unchanged (log(10)DRS score, 1.373+/-0.03 to 1.37+/-0.03; P not significant). The difference in improvement of log(10)DRS score between the 2 groups was highly significant (P<.000). Moreover, 68.2% (n=15) of treated patients achieved a log(10)DRS point score of .477 or higher (3 as geometric mean) that allowed them to exit the vegetative or minimally conscious state. CONCLUSIONS Supplemented BCAAs may improve the recovery from a vegetative or minimally conscious state in patients with posttraumatic vegetative or minimally conscious state.

Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin

Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 µmol/kg; indomethacin 100 µmol/kg; and esomeprazole 10, 30, or 60 µmol/kg plus indomethacin 100 µmol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10–60 µmol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.

Preserved muscle protein metabolism in obese patients with chronic heart failure

BACKGROUND We hypothesized that obese chronic heart failure (CHF) patients, who are known to have less cardiac dysfunction, could show preserved muscle protein balance. The aim of this study was to relate muscle protein balance and cardiac function to body mass index (BMI) in order to provide further insight to the obesity paradox in CHF patients. METHODS Thirty stable CHF patients were categorized by BMI (n=6, normal; n=14, overweight; n=10, obese) and underwent post-absorptive: (i) right heart catheterization to determine cardiac hemodynamics and (ii) arterial and venous blood sampling to measure arterial and venous levels of essential amino acids (EAAs) and to calculate arterovenous differences (positive = uptake; negative = release). Muscle protein over-degradation was assessed by muscle release of the EAA phenylalanine. Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) was also determined. Twenty healthy subjects, matched for age, served as controls and underwent radial artery and vein sampling only. RESULTS Obese CHF patients had normal muscle protein balance, muscle EAA release, and arterial EAA concentration. Among the non-obese patients, normally weighted ones had more pronounced muscle protein over-degradation and greater reduction of arterial EAAs (p<0.01 for both) and EAA release (p<0.06) than overweight ones. Arterial leucine levels correlated negatively with NT-pro-BNP (r=-0.75; p<0.0001) and positively with LVEF (r=+0.68; p<0.0001). Within EAAs, branched chain amino acids were positively associated with stroke volume index (r=+0.51; p=0.004). CONCLUSIONS Only obese patients with CHF have balanced muscle protein metabolism. This may contribute to explain the obesity paradox.

Protein supplementation may enhance the spontaneous recovery of neurological alterations in patients with ischaemic stroke

Objective: To determine whether protein supplementation could enhance neurological recovery in subacute patients with ischaemic stroke. Design: Alimentation-independent patients with ischaemic stroke were randomly allocated to either 21 days of protein supplementation (protein-supplemented group; n=20) or to a spontaneous diet only (control group; n=21) in order to investigate the recovery of neurological changes (measured using the National Institute of Health (NIH) Stroke Scale). Setting: Tertiary care rehabilitation in Italy. Participants: Forty-two patients (27 male and 15 female; 66.4 ± 11 years) 16 ±2 days after the acute event. Intervention: Supplementation with a hyperproteic nutritional formula (10% protein). Main outcome measures: NIH Stroke Scale and protein intake. Results: At admission to rehabilitation, both groups of patients were homogeneous for demographic, clinical and functional characteristics. After 21 days from the start of the protocol, the NIH Stroke Scale was found to be enhanced in the group with supplemental proteins (-4.4 ± 1.5 score versus -3 ± 1.4 of control group; P<0.01). When expressed as difference (▵) between baseline and 21 days, the NIH Stroke Scale correlated negatively with change in protein intake (g/day) (r=-0.50, P= 0.001) and positively with change in carbohydrate/protein ratio (r=+0.40, P=0.01) Conclusions: Protein supplementation may enhance neurological recovery in subacute patients with ischaemic stroke.

Effects of oral amino acid supplementation on long-term-care-acquired infections in elderly patients

The very high general infection rate (IRI) observed in our Geriatric Intensive Rehabilitation Center (GIRC) led us to investigate whether patient supplementation with essential amino acids (EAAs), modulators of immuno-competence, could reduce IRI. Eighty elderly patients admitted to our GIRC (n=40; age 79.5 ± 7.71; male/female 14/26) or placebo (n=40; age 82.13 ± 6.15; male/female 13/27) were allocated to an 8 g/day oral EAAs group and were surveyed for infections (>48 h from admission) over the first month of their hospital stay. The IRI was 67% for the entire population of patients, 82.5% (33/40 patients) in the placebo group and 52% (21/40 patients) in the EAA group (p<0.02). When patients were divided into infection group (IG) and without-infection group (WIG), independently of post randomization allocation, the WIG had higher levels of serum albumin (p<0.001), blood hemoglobin (Hb) concentration (p=0.01), dietary protein (p=0.008) calorie intakes (p=0.05) but lower serum C-reactive protein (CRP) (p<0.001). The factor of CRP>0.8 mg/dl and Hb ≤ 12 in females, ≤13 in males was associated 4 times and 3.6 times risk of infection, respectively, by sex. EAAs supplementation may lower the risk of infection by 30% in the rehabilitative elderly population. CRP and blood hemoglobin levels can be considered risk markers of future infection.

Effect of calorie-protein supplementation on the cognitive recovery of patients with subacute stroke.

Abstract Introduction: The objective of this study was to investigate whether protein-calorie supplementation may enhance the cognitive retrieval of patients with stroke. Patients and methods: A randomized, double-blind, controlled pilot clinical trial was performed comparing diet and diet plus protein-calorie supplementation regimens. The subjects were 48 patients with subacute stroke (≥ 14 days from index event). Anthropometric and nutritional (3-day diary) variables, cognitive function (Mini-Mental State Examination; MMSE) were determined before and 21 days after randomization in control and daily supplemented group (formula providing 250 kcal + 20 g protein). Results: At day 21 after starting the protocol, only the supplemented group significantly improved their performance to MMSE (log10MMSE +0.6 ± 0.4 score; P = 0.01 from baseline). Conclusions: Protein-calorie supplementation may enhance the recovery of cognitive function in subacute stroke patients.