Rehabilitation outcomes in Huntington disease patients with low body mass index.

OBJECTIVES: A catabolic state and a progressive body weight loss are a well-documented hallmark of Huntington Disease (HD). No study is still available on the effectiveness of intensive in-hospital rehabilitation in HD patients with low body mass index (BMI). METHODS: Twenty HD patients with low BMI value were enrolled in this study. Disease severity was assessed before and after rehabilitation by the Barthel Index, the Total Functional Capacity Scale, and the Physical Performance Test. RESULTS: BMI-scores correlated with clinical measures before and after rehabilitation. All patients showed an improvement in outcome measures (p<0.001), and an increase in BMI values (p<0.001) after rehabilitation. Effectiveness of rehabilitation correlated with the values of BMI assessed before reheducational programs (p=0.024) and with BMI values observed in each patient in the three months before admission to hospital (p=0.002). CONCLUSIONS: Findings of the current study show that the effectiveness of the rehabilitation is positively correlated with the BMI values and confirm the efficacy of in-hospital intensive rehabilitation as a valid strategy finalized to improve neuromotor performances and global functional recovery even in HD patients with low BMI and at risk of malnutrition.

Peripheral biomarkers of oxidative stress and their limited potential in evaluation of clinical features of Huntington's patients.

CONTEXT: Peripheral oxidative biomarkers could be useful for monitoring clinical features of Huntington's disease (HD). MATERIALS AND METHODS: Cu/Zn-superoxide dismutase (Cu/Zn-SOD), neuron-specific enolase (NSE) and 8-hydroxy-2'-deoxyguanosine (8-oxoGua) serum levels were analysed in 18 HD patients and 10 controls. Clinical measures were recorded from each HD patients. RESULTS: Cu/Zn-SOD, NSE and 8-oxoGua values were higher in HD patients than in controls. Cu/Zn-SOD and NSE correlated positively. No correlation was observed between the biomarkers analysed and the clinical measures assessed. DISCUSSION AND CONCLUSION: Serum oxidative biomarkers could express the neuronal oxidative processes going on in HD patients but are inadequate to evaluate clinical features of the disease.

Identification of Determinants of Biofeedback Treatment's Efficacy in Treating Migraine and Oxidative Stress by ARIANNA (ARtificial Intelligent Assistant for Neural Network Analysis).

Migraines are a public health problem that impose severe socioeconomic burdens and causes related disabilities. Among the non-pharmacological therapeutic approaches, behavioral treatments such as biofeedback have proven effective for both adults and children. Oxidative stress is undoubtedly involved in the pathophysiology of migraines. Evidence shows a complex relationship between nitric oxide (NO) and superoxide anions, and their modification could lead to an effective treatment. Conventional analyses may fail in highlighting the complex, nonlinear relationship among factors and outcomes. The aim of the present study was to verify if an artificial neural network (ANN) named ARIANNA could verify if the serum levels of the decomposition products of NO-nitrite and nitrate (NOx)-the superoxide dismutase (SOD) serum levels, and the Migraine Disability Assessment Scores (MIDAS) could constitute prognostic variables predicting biofeedback's efficacy in migraine treatment. Twenty women affected by chronic migraine were enrolled and underwent an EMG-biofeedback treatment. The results show an accuracy for the ANN of 75% in predicting the post-treatment MIDAS score, highlighting a statistically significant correlation (R = -0.675, p = 0.011) between NOx (nitrite and nitrate) and MIDAS only when the peroxide levels in the serum were within a specific range. In conclusion, the ANN was proven to be an innovative methodology for interpreting the complex biological phenomena and biofeedback treatment in migraines.

Influence of Oxidative Stress and Inflammation on Nutritional Status and Neural Plasticity: New Perspectives on Post-Stroke Neurorehabilitative Outcome.

Beyond brain deficits caused by strokes, the effectiveness of neurorehabilitation is strongly influenced by the baseline clinical features of stroke patients, including a patient's current nutritional status. Malnutrition, either as a pre-stroke existing condition or occurring because of ischemic injury, predisposes patients to poor rehabilitation outcomes. On the other hand, a proper nutritional status compliant with the specific needs required by the process of brain recovery plays a key role in post-stroke rehabilitative outcome favoring neuroplasticity mechanisms. Oxidative stress and inflammation play a role in stroke-associated malnutrition, as well as in the cascade of ischemic events in the brain area, where ischemic damage leads to neuronal death and brain infarction, and, via cell-to-cell signaling, the alteration of neuroplasticity processes underlying functional recovery induced by multidisciplinary rehabilitative treatment. Nutrition strategies based on food components with oxidative and anti-inflammatory properties may help to reverse or stop malnutrition and may be a prerequisite for supporting the ability of neuronal plasticity to result in satisfactory rehabilitative outcome in stroke patients. To expand nutritional recommendations for functional rehabilitation recovery, studies considering the evolution of nutritional status changes in post-stroke patients over time are required. The assessment of nutritional status must be included as a routine tool in rehabilitation settings for the integrated care of stroke-patients.

Oxidative stress in benign prostatic hyperplasia and prostate cancer.

OBJECTIVE: The aim was to verify whether oxidative stress could represent a common key factor of benign prostatic hyperplasia (BPH) and prostate cancer (PCa). SUBJECTS AND METHODS: 15 patients affected by BPH, 15 with PCa and 15 controls were enrolled. Blood samples were withdrawn systemically and locally during radical retropubic prostatectomy in patients with PCa and during transvesical retropubic adenomectomy in patients diagnosed with BPH. Plasma oxidized low-density lipoprotein, peroxides, and total equivalent antioxidant capacity (TEAC) including plasma superoxide dismutase (SOD) determination were analyzed as oxidative markers. RESULTS: With respect to the control group, high plasma peroxides and decreased TEAC levels were measured in patients affected by both PCa and BPH. Plasma peroxides were significantly higher in patients with PCa with respect to BPH. A positive correlation was found between peroxides and TEAC values in samples withdrawn locally in patients affected by PCa. An inverse correlation between peroxides and TEAC was observed in patients with BPH. No statistically significant modifications were observed as concerns SOD activity and LDL oxidability. CONCLUSIONS: Our findings confirm a significant unbalance of redox status in patients affected by BPH and PCa, and suggest a potential involvement of oxidative stress as a determinant in the pathogenesis of these diseases.

Influence of neurorehabilitation on stroke-induced modifications of the quadriceps muscle in elderly subacute stroke patients with paresis.

The influence of intensive multifunctional neurorehabilitation on post-stroke changes at the level of the paretic leg quadriceps muscle was examined in elderly subacute stroke patients. We assessed paretic leg muscle mass thickness and muscle fatty infiltration thickness, as well as clinical outcome measures (National Institutes of Health Stroke Scale, modified Ranking Scale, and Barthel Index) both before and after neurorehabilitation. Improved outcome measures (p ≤ 0.01) and increased muscle mass thickness (p = 0.005) with decreased muscle fatty infiltration thickness (p = 0.005) were observed after neurorehabilitation. No correlations were found between clinical outcome measures and muscle parameters either before or after neurorehabilitation. The findings of this study suggest that neurorehabilitation has a positive influence on global functional recovery and on remodelling of the quadriceps muscle, even in elderly stroke patients, but they do not support the hypothesis that post-stroke muscle changes might have prognostic significance in terms of the severity of neurological deficit and disability, nor do they suggest that these changes can be regarded as a determinant of stroke severity.

Detrimental effects of anabolic steroids on human endothelial cells.

The aim of this study is to investigate the effects in vitro induced by androgenic anabolic steroids (AAS) (testosterone, nandrolone, androstenedione, norandrostenedione, and norandrostenediol) used illicitly in sport competitions, on the proliferation ability, apoptosis and the intracellular calcium concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs), selected as a prototype of a biological target system whose structure and function can be affected by steroids. For this purpose, we evaluated the proliferation inhibition by cytotoxic assay expressed as the concentration of drug inducing a 50% decrease in growth (IC50). The IC50 was reached for testosterone at 100 microM, androstenedione at 375 microM, nandrolone at 9 microM, norandrostenedione at 500 microM. The IC50 value for norandrostenediol was not reached until a concentration of 6000 microM. The apoptotic effect was evaluated by flow cytometry at IC50 for each drug. We observed that testosterone induced 31% of apoptotic cells, norandrostenedione 25%, androstenedione 15% and nandrolone 18%. We have analyzed the effects of these drugs on [Ca2+]i both in the immediate and long-term continuous presence of each compound. Our data show a statistically significant increase of [Ca2+]i in the acute condition and in long-term treated cultures, suggesting that androgen steroids modulate intracellular levels of calcium independent of incubation time or compound identity. As a whole, this study demonstrates that AAS might alter endothelial homeostasis, predisposing to the early endothelial cell activation that is responsible for vascular complications observed frequently in AAS users.

Polymorphonuclear leukocyte membrane fluidity and cytosolic Ca2+ concentration in subjects with vascular atherosclerotic disease subdivided according to its extent.

An abnormal activation state of polymorphonuclear leukocytes (PMN) plays a key role in organ injury induced by vascular atherosclerotic disease (VAD) and diabetes mellitus (DM). PMN membrane fluidity and cytosolic Ca2+ content can be considered markers of PMN activation. In this research we evaluated the PMN membrane fluidity and cytosolic Ca2+ content in VAD subjects with and without type 2 DM and examined the association between these parameters and the mono- or polyvascular localization. We enrolled 155 VAD subjects, including 92 non-diabetic (group A: mean age 63.6 +/- 9.2 years) and 63 diabetic patients (group B: mean age 65.4 +/- 7.8 years). Among group A 63 patients had monovascular and 29 polyvascular disease; among group B 30 patients had monovascular and 22 polyvascular disease. In each patient we evaluated the PMN membrane fluidity labelling the cells with the fluorescent probe 1,4-(trimethylamino)-phenyl-4-phenylhexatriene (TMA-DPH) and the PMN cytosolic Ca2+ content marking the cells with the fluorescent probe Fura 2-AM. PMN membrane fluidity did not discriminate normal subjects from diabetic and non-diabetic VAD subjects, while cytosolic Ca2+ content was increased in both groups. PMN membrane fluidity did not distinguish normal subjects from mono- or polyvascular VAD patients with and without type 2 DM. PMN cytosolic Ca2+ content was increased especially in monovascular VAD patients; both mono- and polyvascular VAD subjects with DM had a PMN cytosolic Ca2+ content higher than normals. Our results show the presence of an increased PMN cytosolic Ca2+ content in diabetic and non-diabetic VAD subjects but no association was observed between this increase and the mono- or polyvascular localization.

Persistence of the altered polymorphonuclear leukocyte rheological and metabolic variables after 12 months in juvenile myocardial infarction.

Acute myocardial infarction (AMI) is associated with an elevated polymorphonuclear leukocyte (PMN) count and a PMN rheological impairment. In this study we evaluated two major rheological aspects (membrane fluidity and cytosolic Ca2+ concentration) in a group of young adults with AMI. We enrolled 41 AMI patients (39 men and 2 women; mean age 41.0 +/- 4.0 years), who were examined 5-10 days after AMI (T1) and 12 months later (T2). The membrane fluidity was obtained labelling granulocytes with the fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene (TMA-DPH) and considering the degree of fluorescence polarization, inversely correlated to the membrane lipid fluidity. The cytosolic Ca2+ content was obtained marking PMN cells with the fluorescent probe Fura-2AM and considering the ratio between the Fura 2-Ca2+ complex and the unchelated Fura 2 fluorescence intensity. Both parameters were evaluated at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate (PMA) at the concentration of 4.5 muM, prolonged for 5 and 15 minutes. At T1 the PMN membrane fluidity and cytosolic Ca2+ content in AMI patients were respectively decreased and increased in comparison with control group. At T2 the membrane fluidity was not any more different from control subjects, but there was also a further increase in cytosolic Ca2+ content. In vitro, PMN activation caused no significant variation of these parameters in the control group, while in AMI patients membrane fluidity significantly decreased and cytosolic Ca2+ content increased not only during the initial stage, but also after 12 months. The long-term functional alteration of PMN cells observed in young adults with AMI confirms the role of these cells in the inflammatory response following AMI. In the light of these data, the use of molecules able to modulate granulocyte activity, such as calcium channel blockers or pentoxifylline, should be reconsidered in myocardial infarction, together with the usual pharmacological treatment.

Uric acid and Cu/Zn superoxide dismutase: potential strategies and biomarkers in functional recovery of post-acute ischemic stroke patients after intensive neurorehabilitation.

No evidence is currently provided on the involvement of uric acid (UA) and Cu/Zn Superoxide Dismutase (Cu/Zn SOD) in functional recovery of stroke patients after neurorehabilitation. For this purpose, the relationship between UA and Cu/Zn SOD plasma levels and clinical and functional outcome measures were analysed in twenty-five post-acute stroke patients undergoing intensive neurorehabilitation. UA and Cu/Zn SOD plasma levels were evaluated in fifteen healthy subjects as control values. Neurorehabilitation was associated with improved scores (P<0.05) of the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the mPULSES profile. UA plasma levels were higher before neurorehabilitation, decreased after, but were still higher than control values. Conversely, Cu/Zn SOD plasma levels were lower than control values before neurorehabilitation and increased after, even though the absolute values were still lower than controls. An inverse correlation was found between variations of UA plasma levels observed before and after neurorehabilitation (Δ UA) and those of Cu/Zn SOD (Δ Cu/Zn SOD) (r= -0.386; P<0.001). No significant correlations were observed between ΔUA and the variations of the scores observed in all clinical outcome measures before and after neurorehabilitation (Δ scores of clinical outcome measures). Δ Cu/Zn SOD correlated positively with Δ NIHSS, Δ mRS and Δ mPULSES scores. Our data provide evidence of neurorehabilitation effectiveness on modulating UA and Cu/Zn SOD plasma levels and suggest that Cu/Zn SOD could assume the significance of biomarker of functional recovery, rather than UA that could be a marker of the magnitude of oxidative injury.

Influence of intensive multifunctional neurorehabilitation on neuronal oxidative damage in patients with Huntington's disease.

The influence of intensive multifunctional neurorehabilitation on serum levels of Cu/Zn-superoxide dismutase (Cu/Zn-SOD), neuron-specific enolase (NSE), and 8-hydroxy-2-deoxyguanosine (8-OHdG), as markers of oxidative damage, was evaluated in symptomatic patients with Huntington's disease (HD). Improved clinical outcome measures were observed after neurorehabilitation. Baseline levels of Cu/Zn-SOD, NSE and 8-OHdG were higher than those observed in controls. Cu/Zn-SOD and NSE values decreased after neurorehabilitation, but were still higher than those measured in controls. Cu/Zn-SOD and NSE correlated positively before (r=0.659; p=0.003) and after rehabilitation (r=0.553, p=0.017). 8-OHdG values decreased after neurorehabilitation without reaching significance when compared with baseline values (p=0.145). No correlation was observed between the measured oxidative markers and the assessed clinical outcome measures, either before or after neurorehabilitation. The findings reported in the present paper provide evidence of the effectiveness of neurorehabilitation in reducing oxidative damage in HD patients and underline the limit of serum oxidative markers for the evaluation of clinical features of HD.

Evidence of redox unbalance in post-acute ischemic stroke patients.

Measurements of the redox balance after the ischemic stroke occurrence might be useful to monitor the outcome of patients who suffered an ischemic stroke in terms of stroke recurrence and other vascular events. For this purpose, fifteen patients (mean age 71.40±2.50 years) with a first-ever ischemic stroke were included in the study within 30 days of stroke onset. Stroke severity was evaluated according to the National Institutes of Health Stroke Scale (NIHSS). Redox balance was assessed by measuring plasma amount of total peroxidative by-products, nitrite/nitrate metabolites (NOx), as expression of nitric oxide (NO) plasma bioavailability, total plasma antioxidant capacity (TEAC), Cu/Zn Superoxide Dismutase (Cu/Zn SOD) activity, serum urate concentration and autoantibodies against ox-LDL (OLAB) serum level. Total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C) were also measured. Fifteen apparently healthy controls (mean age 70.28±2.03 years) were investigated to compare redox markers. Stroke patients had higher plasma values of total peroxidative by-products, NOx stable metabolites and of total cholesterol, triglycerides, and LDL-C than controls (P < 0.05). No differences in OLAB levels, Cu/Zn-SOD activity, serum urate concentration, and plasma HDL-C amount were found in stroke patients when compared to controls. Total plasma antioxidant capacity was lower in stroke patients than in controls. NOx values correlated positively with the NIHSS score in stroke patients (r=0.668; P=0.0065). The observed presence of redox unbalance in stroke patients could represent an early indicator of diffuse endothelial activation during which patients may be at increased risk of stroke recurrence and other vascular events.

Moderate consumption of red wine and human platelet responsiveness.

Available studies showed an inverse association between red wine consumption and prevalence of vascular risk factors in coronary hearth disease and stroke. Effects were mainly associated to wine antioxidant and antiaggregant properties. Actually, in vitro studies indicate a favourable effect of wine and/or of its non-alcoholic components in decreasing platelet sensitivity and aggregability. In a 4-week supplementation in 15 healthy male volunteers, we evaluated whether moderate red wine consumption might improve antioxidant defence mechanisms and promote positive modulation of inflammatory cytokines and cell adhesion molecules in relation to platelet responsiveness. We did not find any change of ADP- and collagen-induced platelet aggregation ex vivo, any change of biomarkers of oxidative stress, and any change of plasma lipid profile and haemostatic parameters, with the only exception of decreased fibrinogen levels (P<0.05). We also found an increase of mean platelet volume (P<0.05) without any significant modification of CD40 Ligand and P-selectin levels. Increased expressions of intercellular adhesion molecule-1, soluble E-selectin and interleukin-6 (P<0.05) were also observed. According to our findings increased circulating levels of inflammatory and endothelial cell activation markers may indicate a low-grade systemic inflammation and vascular activation that could be responsible for the lack of inhibition or of decreased platelet responsiveness, possibly because the plasmatic increase of wine antioxidant compounds is insufficient to improve endothelial function and to counteract the influence of ethanol on endothelial activation.