Marco Invernizzi

1α,25-dihydroxycholecalciferol induces nitric oxide production in cultured endothelial cells

Background: Recently, 1α,25-dihydroxycholecalciferol (vitD) has received increasing interest for its effects on many tissues and organs other than bone. A number of experimental studies have shown that vitD may have an important role in modifying risk for cardiovascular disease. Aims: This study was planned to test the effects of vitD on endothelial nitric oxide (NO) production and to study the intracellular pathways leading to NO release. Methods: In human umbilical vein endothelial cells (HUVEC) cultures the effects of vitD on NO production and p38, Akt, ERK and eNOS phosphorylations were examined in absence or in presence of the NO synthase inhibitor L-NAME and protein kinases specific inhibitors SB203580, wortmannin and UO126. Results: VitD caused a concentration-dependent increase in NO production. The maximum effect was observed at a concentration of 1 nM and the optimal time of stimulation was 1 min. Effects induced by vitD were abolished by L-NAME and by pre-treatment with protein kinases inhibitors. To verify the effective involvement of vitD receptor (VDR) in the action mechanism of vitD, experiments were repeated in presence of the specific VDR ligands ZK159222 and ZK191784. Conclusions: The results of this study demonstrate that vitD can induce a significant increase in endothelial NO production. VitD interaction with VDR caused the phosphorylation of p38, AKT and ERK leading to eNOS activation.

Osteoporosis in Parkinson's disease

Patients affected by Parkinsons disease are at a high risk for fractures, mainly of the hip. These fractures are caused by falls due to postural imbalance, neurological impairment and reduced bone mass. The purpose of this study was (1) to investigate the correlations and the pathophysiological mechanisms underlying bone loss in Parkinsons disease and appraise bone loss or fracture risk reduction interventions; (2) to develop a research agenda that informs the design and development of risk reduction strategies. Osteoporosis and osteopenia are very common findings in patients with Parkinsons disease, affecting up to 91% of women and 61% of men. Reduced bone mass in Parkinsonian patients seems to be caused mainly by reduced mobility through a mechanism similar to that observed in other neurological diseases. Endocrine (such as vitamin D deficiency), nutritional and iatrogenic factors also play an important role in bone mass depletion. Female gender, disease duration and severity (Hoehn and Yahr stages III and IV), old age and low body mass index are related to more severe osteoporosis. Vitamin D supplementation and bisphosphonates seem to be effective in reducing the risk of nonvertebral fractures in patients affected by Parkinsons disease. Prevention and evaluation of osteoporosis through bone mass density assessment should be considered in all patients with Parkinsons disease.

Osteoporosis after Stroke: A Review of the Causes and Potential Treatments

Osteoporosis is a known consequence of stroke, associated with an increased incidence of fractures, mainly of the hip, leading to further disability. The pattern of bone loss seen in stroke patients is different from that usually encountered with postmenopausal osteoporosis, since it is limited to the paretic side and more evident in the upper extremities. Several factors appear to have an influence on bone mass in stroke patients, such as the degree of paresis, gait disability and the duration of immobilization. The pathogenesis of osteoporosis after stroke remains unclear. Paresis, reduced mobility and reduced bone load seem to play a major role. Other factors such as nutritional and iatrogenic ones may also play an important part. In this paper, the clinical evidence, pathophysiology and possible treatments of poststroke osteoporosis will be reviewed.

Casting, taping or stretching after botulinum toxin type A for spastic equinus foot: a single-blind randomized trial on adult stroke patients

Objective: To investigate the effect of different adjunctive treatments after botulinum toxin type A. Design: Single-blind, randomized trial, with three-month follow-up. Setting: Secondary rehabilitative care. Subjects: Convenience sample of 69 chronic hemiplegic adult patients with spastic equinus foot. Interventions: Following botulinum toxin type A injection at the plantar flexors, patients were randomly assigned to three groups and treated with either taping, casting or stretching for one week, and with stretching and gait training for the next week. Outcome measures: Modified Ashworth Scale at plantar flexors, passive range of motion at the ankle, six-minute walking test, 10-metre walking test, Functional Ambulation Categories, ankle dorsiflexor strength were evaluated before treatment (t0) at 20 days (t1) and 90 days (t2) after treatment. Results: At t1 only the taping and casting groups showed significant improvements in Modified Ashworth Scale, six-minute walking test, 10-metre walking test and passive range of motion (P < 0.02). At t2, while the results were maintained in the casting group, only six-minute walking test and Modified Ashworth Scale were still significantly improved in the taping group. Ankle dorsiflexor strength and Functional Ambulation Categories did not change in any of the groups at any time. At t2 the casting group performed better than the taping and stretching groups at Modified Ashworth Scale and passive range of motion, and better than the stretching group at six-minute walking test (P < 0.02). Conclusions: Combining botulinum toxin type A to the ankle plantar flexors with casting or taping gives better and longer lasting results than with stretching alone.

Development and validation of the Italian version of the Spinal Cord Independence Measure III

Purpose. To provide a translation and cultural adaptation of the Spinal Cord Independence Measure version III scale for Italy (i-SCIM3) and to validate this version of the scale. Method. i-SCIM3 was developed involving a forward–backward translation and administered to patients with spinal cord lesions (SCL) admitted to two centers. Two raters for each center evaluated patients at admission and discharge. Psychometric testing included reliability by internal consistency (Cronbachs α) and test–retest reliability. The validity of i-SCIM3 was assessed by comparing it with the Italian version of Functional Independence Measure™ (FIM™). Results. One hundred three adult patients with SCL (84 males) with a mean age of 50.33 ± 15.35 years were recruited. Seventy-four patients were paraplegic and 29 patients were tetraplegic. The median time elapsed between the two evaluations was 77.5 days (interquartile range, 53–144 days). Internal consistency, inter-rater reliability, and test–retest reliability were satisfactory overall, showing values higher than 0.90. The validity of i-SCIM3 was confirmed by the close correlation with FIM results both at admission and discharge (r = 0.91, p < 0.01). The sensitivity to change of i-SCIM3 was similar to that of FIM. Conclusion. i-SCIM3 was found to be a consistent, reliable, and valid scale for use in the clinical setting. It is the first validated scale in Italian for patients with SCL.

Robotic gait training is not superior to conventional treadmill training in parkinson disease: a single-blind randomized controlled trial.

Background. The use of robots for gait training in Parkinson disease (PD) is growing, but no evidence points to an advantage over the standard treadmill. Methods. In this randomized, single-blind controlled trial, participants aged <75 years with early-stage PD (Hoehn-Yahr <3) were randomly allocated to 2 groups: either 30 minutes of gait training on a treadmill or in the Lokomat for 3 d/wk for 4 weeks. Patients were evaluated by a physical therapist blinded to allocation before and at the end of treatment and then at the 3- and 6-month follow-up. The primary outcome measure was the 6-minute walk test. Results. Of 334 screened patients, the authors randomly allocated 30 to receive gait training with treadmill or the Lokomat. At baseline, the 2 groups did not differ. At the 6-month follow-up, both groups had improved significantly in the primary outcome measure (treadmill: mean = 490.95 m, 95% confidence interval [CI] = 448.56-533.34, P = .0006; Lokomat: 458.6 m, 95% CI = 417.23-499.96, P = .01), but no significant differences were found between the 2 groups (P = .53). Discussion. Robotic gait training with the Lokomat is not superior to treadmill training in improving gait performance in patients with PD. Both approaches are safe, with results maintained for up to 6 months.

Multimodal Analgesia in Total Knee Arthroplasty: A Randomized, Double-Blind, Controlled Trial on Additional Efficacy of Periarticular Anesthesia

Pain management is a main determinant of functional recovery after total knee arthroplasty (TKA). We performed a randomized, controlled, double blind study to evaluate additive efficacy of periarticular anesthesia in patients undergoing TKA in reducing post-operative pain, operated limb edema and improving post-operative mobility. Patients were randomly assigned to study or control group; all subjects received the same analgesic protocol; before wound closure, the study group received also a periarticular anesthesia (ropivacaine 1% 20 mL). The results show no statistical differences in any of the variable evaluated. Our data suggest that additive periarticular anesthetic protocol with ropivacaine 1% 20 mL is not superior to oral and intravenous analgesia alone in patients undergoing TKA, regarding post-operative pain control, operated limb edema reduction and post-operative mobility improvement.

NO-dependent proliferation and migration induced by Vitamin D in HUVEC.

Recently, Vitamin D (Vit. D) has gained importance in cellular functions of a wide range of extraskeletal organs and target tissues, other than bone. In particular, Vit. D has displayed important beneficial effects in the cardiovascular system. Although little is known about the mechanism by which this response is exerted, a Vit. D-induced eNOS-dependent nitric oxide (NO) production in endothelial cells (EC) has been reported. The aim of this study was to evaluate whether Vit. D administration could affect human EC proliferation and/or migration through NO production. For this purpose, HUVEC (human umbilical vein endothelial cells) were used to evaluate Vit. D effects on cell proliferation and migration in a 3D matrix. Experiments were also performed in the presence of the specific VDR ligand ZK159222 and eNOS inhibitor L-NAME. This study demonstrated that Vit. D can promote both HUVEC proliferation and migration in a 3D matrix. These effects were NO dependent, since HUVEC proliferation and migration were abrogated along with Vit. D induced MMP-2 expression by inhibiting eNOS activity by L-NAME. These findings support the role of Vit. D in the angiogenic process, suggesting new applications for Vit. D in tissue repair and wound healing.

Efficacy of a Hip Flexion Assist Orthosis in Adults With Hemiparesis After Stroke

Background During gait, the hip flexors generate 40% of the total power. Nevertheless, no device has been tested extensively for clinical purposes to cope with weakness in the hip flexors in patients with stroke. Objective The purpose of this study was to assess the efficacy and safety of a newly developed hip flexion assist orthosis in adult patients with hemiparesis after stroke. Design The study used a prospective, randomized, before-after trial design. The inclusion criteria were hemiparesis resulting from stroke (onset ≥8 weeks); ability to walk, even if with assistance; and hip flexion weakness (Medical Research Council Scale score ≤4). Methods The main outcome measures were the 10-Meter Walk Test and the Six-Minute Walk Test. Patients also were evaluated with the Trunk Control Test, the Functional Ambulation Categories, the Motricity Index, and hip flexor strength on the Medical Research Council Scale. Sixty-two survivors of stroke were tested in random order with and without the orthosis. Any adverse event associated with its use was recorded. Results Both the Six-Minute Walk Test and the 10-Meter Walk Test scores improved with the use of the orthosis. A significant negative correlation was found for improvement between scores on the 2 main outcome measures with the orthosis and the Functional Ambulation Categories scores. The improvement in Six-Minute Walk Test scores with the orthosis was related inversely to hip flexor strength. Conclusions The data showed that the use of a hip flexion assist orthosis can improve gait in patients with poststroke hemiparesis, particularly those with more severe walking impairment.

Possible synergism of physical exercise and ghrelin-agonists in patients with cachexia associated with chronic heart failure

The occurrence of cachexia of multifactorial etiology in chronic heart failure (CHF) is a common and underestimated condition that usually leads to poor outcome and low survival rates, with high direct and indirect costs for the Health Care System. Recently, a consensus definition on cachexia has been reached, leading to a growing interest by the scientific community in this condition, which characterizes the last phase of many chronic diseases (i.e., cancer, acquired immunodeficiency syndrome). The etiology of cachexia is multifactorial and the underlying pathophysiological mechanisms are essentially the following: anorexia and malnourishment; immune overactivity and systemic inflammation; and endocrine disorders (anabolic/catabolic imbalance and resistance to growth hormone). In this paper, we review the main pathophysiological mechanisms underlying CHF cachexia, focusing also on the broad spectrum of actions of ghrelin and ghrelin agonists, and their possible use in combination with physical exercise to contrast CHF cachexia.