Annalisa Barbieri

Nutrition for Brain Recovery After Ischemic Stroke: An Added Value to Rehabilitation

In patients who undergo rehabilitation after ischemic stroke, nutrition strategies are adopted to provide tube-fed individuals with adequate nutrition and/or to avoid the body wasting responsible for poor functional outcome and prolonged stay in the hospital. Investigations have documented that nutrition interventions can enhance the recovery of neurocognitive function in individuals with ischemic stroke. Experimental studies have shown that protein synthesis is suppressed in the ischemic penumbra. In clinical studies on rehabilitation patients designed to study the effects of counteracting or limiting this reduction of protein synthesis by providing protein supplementation, patients receiving such supplementation had enhanced recovery of neurocognitive function. Cellular damage in cerebral ischemia is also partly caused by oxidative damage secondary to free radical formation and lipid peroxidation. Increased oxidative stress negatively affects a patients life and functional prognosis. Some studies have documented that nutrition supplementation with B-group vitamins may mitigate oxidative damage after acute ischemic stroke. Experimental investigations have also shown that cerebral ischemia changes synaptic zinc release and that acute ischemia increases zinc release, aggravating neuronal injury. In clinical practice, patients with ischemic stroke were found to have a lower than recommended dietary intake of zinc. Patients in whom daily zinc intake was normalized had better recovery of neurological deficits than subjects given a placebo. The aim of this review is to highlight those brain metabolic alterations susceptible to nutrition correction in clinical practice. The mechanisms underlying the relationship between cerebral ischemia and nutrition metabolic conditions are discussed.

Insulin-like growth factor-I ameliorates delayed kidney graft function and the acute nephrotoxic effects of cyclosporine.

BACKGROUND Delayed graft function (DGF) is a relatively common complication after cadaveric renal transplantation. The adverse effect of DGF on long-term graft survival has lead to intensive efforts to reduce ischemic graft injury. In this study we examined the effects of a new protective treatment based on insulin growth factor (IGF)-I. We evaluated the impact of the treatment on renal recovery and on the nephrotoxicity that is a common side effect of mainstream immunosuppressants. Because therapy with IGF-I or the analog des(1-3)IGF-I is effective in treating experimental ischemic renal failure, these peptides may be useful as perspective clinical treatments. METHODS We have addressed three areas relating to the potential use of IGF-I and its analog des(1-3)IGF-I. First, because of the immunogenic properties of IGF-I, we assessed the effect of des(1-3)IGF-I on the rejection of skin allografts in Lewis rats. Next we determined whether treatment with des(1-3)IGF-I influences the early function of transplanted kidneys in a model of DGF induced by a combination of warm and cold ischemia. Finally we tested whether IGF-I protects against acute cyclosporine nephrotoxicity. RESULTS Des(1-3)IGF-I did not accelerate the rejection of the skin grafts (P=0.57). The administration of this peptide in a model of syngenic renal transplant improved the early function of the graft. Postoperative values of creatinine and blood urea nitrogen were significantly better (P<0.05) in treated animals. IGF-I also ameliorated the nephrotoxicity of cyclosporine, with better values of creatinine and blood urea nitrogen (P<0.05). CONCLUSIONS In evaluating this study it should be recognized that the animal models studied, although widely used, differ from the human condition. However, IGF-I and des(1-3)IGF-I exhibit properties that strongly suggest their value in preventing clinical DGF, and they deserve further studies.

Isolated porcine bronchi provide a reliable model for development of bronchodilator anti-muscarinic agents for human use

Background and purpose: In human airways, muscarinic acetylcholine receptors (mAChRs) exert a predominant role in the control of airways resistance and anti‐muscarinic agents are currently included in the pharmacological treatment of chronic obstructive pulmonary disease (COPD). However, the development of more effective mAChR antagonists is hampered by considerable species variability in the ultrastrucural and functional control of airway smooth muscle, making extrapolation of any particular animal model questionable. This study was designed to characterize the mAChRs in a bronchial preparation from pigs, animals considered to provide close models of human biology.

Essential amino acids and exercise tolerance in elderly muscle-depleted subjects with chronic diseases: a rehabilitation without rehabilitation?

Exercise intolerance remains problematic in subjects with chronic heart failure (CHF) and/or chronic obstructive pulmonary disease (COPD). Recent studies show that supplemented essential amino acids (EAAs) may exert beneficial effects on CHF/COPD physical capacity. The results from 3 investigations (2 conducted on CHF and 1 on COPD subjects) served as the basis for this paper. The 3 studies consistently showed that elderly CHF and COPD improved exercise intolerance after 1–3 months of EAA supplementation (8 g/d). In CHF exercise capacity increased 18.7% to 23% (watts; bicycle test), and 12% to 22% (meters) in 6 min walking test. Moreover, patients reduced their resting plasma lactate levels (by 25%) and improved tissue insulin sensitivity by 16% (HOMA index). COPD subjects enjoyed similar benefits as CHF ones. They increased physical autonomy by 78.6% steps/day and decreased resting plasma lactate concentrations by 23%. EAA mechanisms explaining improved exercise intolerance could be increases in muscle aerobic metabolism, mass and function, and improvement of tissue insulin sensitivity (the latter only for the CHF population). These mechanisms could be accounted for by EAAs intrinsic physiological activity which increases myofibrils and mitochondria genesis in skeletal muscle and myocardium and glucose control. Supplemented EAAs can improve the physical autonomy of subjects with CHF/COPD.

Inhibition by glibenclamide of the effects of cromakalim on responses of rat vas deferens to naphazoline.

Cromakalim has been shown to inhibit naphazoline-induced contractions and spontaneous activity induced by exposure to naphazoline in the rat isolated vas deferens. Glibenclamide 10(-6) M blocked both these effects of cromakalim. Our data add to the list of data derived mainly from experiments on vascular smooth muscle; they suggest that the same glibenclamide-sensitive K+ channel is present in vascular and non-vascular smooth muscle and that it may be involved in the relaxant actions of cromakalim.

Liver Ischemia Modifies the Concentration of Plasmatic Catecholamines after Reperfusion in the Rat

Pulmonary hypertension is one of the most frequent and severe consequences of liver ischemia. The aim of this study is to evaluate the presence of humoral vasoactive mediators, generated during liver ischemia, which could be able to determine the onset of pulmonary hypertension. Thus, we evaluated the plasmatic concentration of catecholamines (adrenaline, noradrenaline, dopamine) during the immediate reperfusion period. Wistar rats were used. Animals (n = 89) were divided into four groups. Group 1 served as control (sham-operated). In group 2 animals underwent 60 min of left hepatic exclusion. In group 3 animals underwent to bilateral adrenectomy. In group 4 animals had both bilateral adrenectomy and liver ischemia. Ischemia in group 2 and 4 was induced by interrupting the vascular supply to the left and median lobes, so avoiding the use of a portal shunt. Blood samples were collected from the suprahepatic inferior caval vein immediately after reperfusion. Strips of the main pulmonary artery were put into an isolated organ bath and tested for the response to noradrenaline, adrenaline and plasma samples. Plasma samples collected after ischemia caused a significantly greater (p < 0.01) contraction of the pulmonary artery compared to controls. Plasma samples collected after adrenectomy caused a weak contraction which was not different from that obtained in the adrenectomy + ischemia group. Plasma concentrations of catecholamines after liver ischemia were significantly increased in the control group (p < 0.01). In adrenectomized rats only the adrenaline level was greatly reduced. However ischemia did not increase plasma catecholamines as it occurred in sham-operated rats.