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Biomedical subjects

A Ferri

Publications and source records attributed to A Ferri.

At least 19 recordsLinked to original sources

Antibodies to filamentous actin (F-actin) in type 1 autoimmune hepatitis.

AIMS: To evaluate the diagnostic significance of anti-filamentous actin antibodies (A-FAA) assessed with a commercial ELISA in comparison with immunofluorescence reactivity and patterns of anti-smooth muscle antibodies (SMA); and to correlate A-FAA positivity with clinical, immunogenetic, laboratory, and histological features in patients with autoimmune hepatitis type 1 (AIH-1). METHODS: We studied 78 consecutive untreated AIH-1 patients and 160 controls: 22 with autoimmune hepatitis type 2 (AIH-2), 51 with hepatitis C, 17 with coeliac disease (CD), 20 with primary biliary cirrhosis (PBC) and 50 blood donors. SMA was evaluated by indirect immunofluorescence (IIF) on frozen sections of rat tissues, and A-FAA with a modified commercial ELISA. RESULTS: SMA was detected by IIF in 61 (78%) of 78 AIH-1 patients, of whom 47 (60%) had the SMA-T/G and 14 (18%) the SMA-V pattern. Of the pathological controls, 32 (20%) had the SMA-V pattern (25 with hepatitis C, 2 with AIH-2, 2 with PBC, 3 with CD). A-FAA were present in 55 AIH-1 patients (70.5%; 46 with SMA-T/G, 7 with SMA-V, and 2 SMA-negative), and in 10 controls (6%), of whom five had hepatitis C, two AIH-2, two PBC and one CD. The association between A-FAA and the SMA-T/G pattern was statistically significant (p<0.0001). A-FAA levels were higher in SMA-T/G positive than SMA-V positive AIH-1 patients and controls (p<0.0001). A-FAA positivity was significantly associated with higher gamma-globulin and IgG levels, but did not correlate with other considered parameters. CONCLUSION: The modified A-FAA ELISA strictly correlates with the SMA-T/G pattern and is a reliable and operator independent assay for AIH-1. Detection of A-FAA, even if devoid of prognostic relevance, may be useful when interpretative doubts of standard IIF arise.

Actins↗

Detection of 2,4-dichlorophenoxyacetic acid in rat milk of dams exposed during lactation and milk analysis of their major components.

2,4-Dichlorophenoxyacetic acid (2,4-D) and its derivatives are herbicides widely used to control the growth of broadleaf and woody plant. Human and animal exposure to 2,4-D through agriculture use, food products, or use in lawn and garden care has been well documented, but little information is available on the transfer from serum to milk in exposed dams. In this study, we measured the content of 2,4-D in rat milk from mother exposed to 15, 25, 50 or 7 0mg 2,4-D/kg bw through the diet (4 treated groups, 8 dam each; 1 control group with 8 dams) over a period of 16 days starting on the post-natal day 1 (PND 1). The effect of 2,4-D on milk components was also evaluated. All doses tested caused a decrease in the body weight gain of the pups (4 groups, 64 pups each). It also produce a 30% in the content of total lipids and a changed the content of minor proteins in milk of the treated groups. 2,4-D produces an important decrease in some fatty acids content, being the polyunsaturated fatty acids the most affected. Further analysis showed that 2,4-D concentrations chromatographically detected both serum of dams and pups and milk were dose-dependent.

2,4-Dichlorophenoxyacetic Acid↗

Characterization of a 2D ion chamber array for the verification of radiotherapy treatments.

In this study we investigated the characteristics of a commercial ion chamber array and its performance in the verification of radiotherapy plans. The device was the 2D Array Seven29 model (PTW, Freiburg, Germany). This is a two-dimensional detector array with 729 ionization chambers uniformly arranged in a 27 x 27 matrix with an active area of 27 x 27 cm(2). The detector short-, medium- and long-term reproducibility have been tested through an extensive set of repeated measurements. Short-term reproducibility was well within 0.2%. Medium- and long-term reproducibility were within 1%, including set-up reproducibility errors and linac output fluctuations. Dose linearity was also assessed. The system response to dose was verified to be linear within the range 2-500 MU. Output factors matched very well pinpoint chamber measurements performed in the same experimental conditions with a maximum local percentage difference of 0.4%. Furthermore, the 2D Array sensitivity to millimetric collimator positional changes and to perturbation effect of irradiated area was tested. The comparison with ion chamber data carried out in water was very satisfying. Finally, measurements of wedge-modulated fields and IMRT beam sequence matched very well ion chamber dose profiles acquired in a water tank. The extensive tests performed in this investigation show that the 2D Array Seven29 is a reliable and accurate dosimeter and that it could be a useful tool for the quality assurance and the verification of radiotherapy plans.

Humans↗

Muscle function and functional ability improves more in community-dwelling older women with a mixed-strength training programme.

BACKGROUND: Supervised training can reach a limited number of elderly people. OBJECTIVE: To determine the impact of a 1-year mixed-strength training programme on muscle function (MF), functional ability (FA) and physical activity (PA). SETTING: Twice-a-week hospital-based exercise classes and a once-a-week home session. PARTICIPANTS: twenty-eight healthy community-dwelling men and women on the training programme and 20 controls aged over 75 years. METHODS: Training with two multi-gym machines for the lower limbs at 60% of the repetition maximum (1RM). At-home subjects used elastic bands. MEASUREMENTS: Maximum isometric strength of knee extensors (KE), ankle plantar flexors (PF), leg extensor power (LEP), functional reach (FR), chair rise 1 (CR1) and 10 times (CR10), bed rise (BR), six-minute walking test (6MWT), stair climbing (SC), get-up-and-go (GU&G), one-leg standing (1LS). PA was assessed with the Paqap questionnaire. RESULTS: Women were significantly weaker than men at baseline: -47% for KE and -59% for PF. Training induced significant gains in MF and FA in the training females; males improved significantly only in FA. PA levels increased non-significantly (2%) in all of the training group. CONCLUSIONS: Long-term mixed-strength programmes can improve MF and FA in elderly females, and FA in elderly males.

Activities of Daily Living↗

Progressive and selective degeneration of motoneurons in a mouse model of SMA.

Spinal muscular atrophy (SMA), an autosomal recessive disorder characterized by the degeneration of motoneurons of the spinal cord and brainstem, results from loss-of-function mutations in the survival motor neuron gene (smn). The goal of these experiments was to analyse axons and cell bodies of motoneurons in different regions of the CNS during disease progression in a mouse model of SMA carrying a deletion of the exon 7 directed to neurons. These experiments demonstrate a progressive loss of motor axons and of motoneurons in the CNS. This is the first study that describes a selective neurodegeneration in this line of mice and underlines the importance of exon 7 in some populations of motoneurons for survival in vivo.

Animals↗

Study of tyrosine hydroxylase immunoreactive neurons in neonate rats lactationally exposed to 2,4-dichlorophenoxyacetic Acid.

Dopaminergic neurons from the midbrain nuclei substantia nigra (SN; A9) and ventral tegmental area (VTA; A10) were investigated by tyrosine hydroxylase (TH) immunostaining in neonate rat brains exposed to 2,4-dichlorophenoxyacetic acid (2,4-D) through lactation. Dorsal raphe serotonin (5-HT) projections to SN and VTA were also studied by 5-HT transporter (5-HTT) immunostaining and results were quantified by image analysis. Twenty-five-day-old pups exposed to 2,4-D through mothers milk were used. Dams were intraperitoneally administered 70 or 100mg/kg/day of 2,4-D from the 9th to the 25th postpartum day. After 100mg/kg of 2,4-D exposure, a 25% diminution in the SN and a 33% diminution in the VTA neurons' TH immunostaining along with a significantly 5-HT fiber density diminution were observed. The present work supports previous reports which suggest that exposure to 2,4-D during development has multiple effects on CNS.

2,4-Dichlorophenoxyacetic Acid↗

Apoptosome inactivation rescues proneural and neural cells from neurodegeneration.

Deficiency of the apoptosome component Apaf1 leads to accumulation of supernumerary brain cells in mouse embryos. We observed that neural precursor cells (NPCs) in Apaf1(-/-) embryos escape programmed cell death, proliferate and retain their potential to differentiate. To evaluate the circumstances of Apaf1(-/-) NPC survival and investigate their fate under neurodegenerative conditions, we established cell lines of embryonic origin (ETNA). We found that Apaf1(-/-) NPCs resist common apoptotic stimuli and neurodegenerative inducers such as amyloid-beta peptide (typical of Alzheimer's disease) and mutant G93A superoxide dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results were obtained in Apaf1(-/-) primary cells. When death is prevented by Apaf1 deficiency, cytochrome c is released from mitochondria and rapidly degraded by the proteasome, but mitochondria remain intact. Under these conditions, neither activation by cleavage of initiator caspases nor release of alternative apoptotic inducers from mitochondria takes place. In addition, NPCs can still differentiate, as revealed by neurite outgrowth and expression of differentiation markers. Our findings imply that the mitochondrion/apoptosome pathway is the main route of proneural and neural cells to death and that its inhibition prevents them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell model is ideally suited for exploring the potential of novel cell therapies for the treatment of human neurodegenerations.

Amyloid beta-Peptides↗

Strength and power changes of the human plantar flexors and knee extensors in response to resistance training in old age.

AIM: The aim of the present study was to assess and compare the improvements of muscle strength and power induced by a 16-week resistive programme in a population of 16 older men aged 65-81 years. METHODS: Training was performed three times per week at an intensity of 80% of one repetition maximum (1RM) and consisted of both calf raise and leg press exercises. Before-, during- and after-training, maximum isometric and isokinetic torques, maximum power, 1RM, muscle cross-sectional area (CSA) and electromyographic activity (EMG) of the plantar flexors (PF) and knee extensors (KE) were examined. RESULTS: For the KE and PF, respectively, training resulted in a 29.9 +/- 4.4% (mean +/- SE) and 21.6 +/- 5.4% increase in 1RM (P < 0.001-0.01), a 19.4 +/- 4.3 and 12.4 +/- 4.7% (P < 0.001-0.05) increase in maximum isometric torque, and a 24.1 +/- 6.3 and 33.1 +/- 10.9% (P < 0.05) increase in maximum muscle power, calculated from torque-angular velocity curves. The large increase in torque and power was partly accounted by a significant increase in the CSA of the PF (5.0 +/- 0.7%) and KE (7.4 +/- 0.7%), while no significant changes in integrated EMG activity of vastus lateralis and soleus muscles, and in extrapolated maximum shortening velocity were found. After training, a significant increase in torque/CSA (10.3 +/- 4%, P < 0.05) was found for the KE but not for the PF. CONCLUSION: Hence, hypertrophy cannot alone justify the increase in torque, and other factors, such as an increase in individual fibre-specific tension (in the case of KE), a decrease in antagonist muscles' coactivation, an improved co-ordination and an increased neural drive of the other heads of quadriceps may have contributed to the increments in strength. The significant increase in muscle power seems particularly noteworthy with respect to daily activities involving the displacement of the body over time, namely, the generation of muscle power.

Activities of Daily Living↗

Effectiveness of a home-based strengthening program for elderly males in Italy. A preliminary study.

BACKGROUND AND AIMS: The practice of regular physical exercise has been shown to be effective in slowing the age-related progressive functional deterioration. Most exercise trials have been conducted with supervised training programs. The purpose of this study was to investigate the effectiveness of a 4-month home-based strength training on strength, function and personal satisfaction. METHODS: Ten elderly men (mean age 68.5 years) were enrolled for home-based training one month after completing a 4-month supervised program; 12 age-matched men served as the control group. Subjects were asked to perform 3 sessions a week consisting of six resistance exercises with elastic bands involving the major muscle groups of the upper and lower limbs. We had calculated the correlation between the elongation and resistance of the elastic bands. The subjects were instructed to keep a diary reporting the execution of the session. We measured dynamic concentric strength of the muscle groups involved in the resistance exercises and maximal isometric strength of the knee extensors and elbow flexors before and after the 4-month home training. The Satisfaction Profile (SAT-P) questionnaire was administered before and one month after the completion of the training program for assessing personal satisfaction. RESULTS: The final to baseline comparison showed a non-significant decrease in mean isometric maximal strength values for knee extensors and elbow flexors in the control group, while the exercise group significantly (p=0.001) improved the average baseline values. Maximal dynamic concentric strength values decreased significantly in the control group, while significant improvements were observed in the exercising subjects. The SAT-P questionnaire did not show any difference in either group from baseline. The adherence-to-protocol rate based on self-report was 78%. CONCLUSIONS: Home training with elastic bands appears to be an effective low-cost modality of maintaining strength and function in an elderly population.

Activities of Daily Living↗

5-HT1-receptor agonist sumatriptan modifies gastric size after 500 ml of water in dyspeptic patients and normal subjects.

Sumatriptan, a 5-HT1-receptor agonist has been shown to delay gastric emptying of liquids and solids in humans. However, no data are available of the effect of sumatriptan on gastric adaptation after distension with liquids and on symptoms induced by gastric distension. In 23 normal subjects and 30 dyspeptic patients with normal upper gastrointestinal endoscopy and real-time ultrasonography, the transverse gastric proximal and distal area and sagittal axis of the proximal stomach were determined by real-time ultrasonography and computed tomography after 500 ml of water. The area was determined by real-time ultrasonography and computed tomography twice at times 48 hr apart. Thirty minutes before real-time ultrasonography, placebo or sumatriptam were give subcutaneously in a double-blind fashion. Epigastric pain, bloating, heartburn, and nausea were also monitored through an intensity score from zero to 10 performed during the test. In six dyspeptic patients, the gastric distension was performed also with real-time ultrasonography and computed tomography after placebo and hyoscine butyl-bromide, a quaternary anticholinergic agent. Real-time ultrasonography and computed tomography demonstrated that after sumatriptan there is a reduction in proximal and distal transverse area and an increase in the sagittal axis of the proximal stomach. Hyoscine butyl-bromide increased all gastric measurements. Among the symptoms evaluated, only nausea was significantly reduced by sumatriptan (P < 0.01). Sumatriptan modifies gastric size, with a reduction in the transverse section and an increase of the sagittal axis of the proximal stomach and improves the nausea induced by gastric distension in dyspeptic patients.

Adult↗

IAPs are essential for GDNF-mediated neuroprotective effects in injured motor neurons in vivo.

During embryonic development, and in certain neurodegenerative diseases, neurons die by apoptosis. A new family of anti-apoptotic proteins, termed inhibitors of apoptosis (IAP), suppresses apoptosis through the direct inhibition of caspases. The anti-apoptotic activity of IAPs is inhibited by second mitochondria-derived activator of caspase (Smac)/DIABLO and XAF1 (ref. 8). IAPs, as well as neurotrophic factors, can protect degenerating neurons both in vivo and in vitro. However, the downstream targets of neurotrophic factors have not yet been identified. Here, we demonstrate that XIAP and NAIP, but not HIAP2, are directly involved in the intracellular response to glial cell-derived neurotrophic factor (GDNF). In newborn rats, GDNF regulates endogenous levels of XIAP and NAIP in motor neurons after sciatic nerve axotomy. The inhibition of XIAP or NAIP activity prevents GDNF-mediated neuroprotective effects. These results suggest that XIAP and NAIP are essential for intracellular signalling of GDNF in motor neuron survival.

Animals↗

Plantar flexor activation capacity and H reflex in older adults: adaptations to strength training.

The purpose of this study was to investigate whether the voluntary neural drive and the excitability of the reflex arc could be modulated by training, even in old age. To this aim, the effects of a 16-wk strengthening program on plantar flexor voluntary activation (VA) and on the maximum Hoffman reflex (H(max))-to-maximum M wave (M(max)) ratio were investigated in 14 elderly men (65-80 yr). After training, isometric maximum voluntary contraction (MVC) increased by 18% (P < 0.05) and weight-lifting ability by 24% (P < 0.001). Twitch contraction time decreased by 8% (P < 0.01), but no changes in half relaxation time and in peak twitch torque were observed. The VA, assessed by twitch interpolation, increased from 95 to 98% (P < 0.05). Pretraining VA, also evaluated from the expected MVC for total twitch occlusion, was 7% higher (P < 0.01) than MVC. This discrepancy persisted after training. The interpolated twitch torque-voluntary torque relationship was fitted by a nonlinear model and was found to deviate from linearity for torque levels >65% MVC. Compared with younger men (24-35 yr), the H(max)- to M(max) ratio and nerve conduction velocity (H index) of the older group were significantly lower (42%, P < 0.05; and 29%, P < 0.001, respectively) and were not modulated by training. In conclusion, older men seem to preserve a high VA of plantar flexors. However, the impaired functionality of the reflex pathway with aging and the lack of modulation with exercise suggest that the decrease in the H(max)- to M(max) ratio and H index may be related to degenerative phenomena.

Adaptation, Physiological↗

Beta amyloid precursor protein and patterns of HIV p24 immunohistochemistry in different brain areas of AIDS patients.

OBJECTIVES: To evaluate the correlation between immunohistochemical positive patterns (globular and filamentous structures) of beta-amyloid precursor protein (beta-APP), used as a marker of axonal damage, and the different distribution of HIV p24 antigens, in three different brain areas of AIDS patients. METHODS: Eighteen AIDS patients with HIV-related brain lesions were included in the study. Forty-nine sections from basal ganglia, frontal cortex and hippocampus were selected. After microwave oven pre-treatment, the sections were incubated with anti-HIV p24 and anti-beta-APP monoclonal antibodies; the reactions were developed with peroxidase/3,3'diaminobenzidine. The positivity was graded by semi-quantitative scores. Double immunohistochemical staining was used to evaluate the co-localization of the antigens. RESULTS: HIV p24 immunohistochemistry was positive in 44 of 49 sections (89%), with a prevalence of interstitial positive cells and positive microglial nodules in 27 and 13 sections respectively. beta-APP-positive structures were demonstrated in 23 of 44 sections (52%) with HIV-related lesions, and were absent from the five sections without viral expression. Globular and filamentous lesions were observed in 21 of 23 sections and 10 of 23 lesions respectively. Moreover, a high grade of globular type lesion was related to an elevated presence of diffuse interstitial HIV p24-positive cells in basal ganglia; double immunohistochemical reactions demonstrated the co-localization of beta-APP globules and HIV p24 antigens. CONCLUSIONS: The data obtained confirm the coexpression of beta-APP and viral antigens in particular areas of the brain with HIV-related lesions; there is a strict correlation between beta-APP globules (indicating chronic cerebral damage) and the interstitial pattern of HIV p24 immunohistochemistry.

Acquired Immunodeficiency Syndrome↗

Oxidative inactivation of calcineurin by Cu,Zn superoxide dismutase G93A, a mutant typical of familial amyotrophic lateral sclerosis.

Calcineurin is a serine/threonine phosphatase involved in a wide range of cellular responses to calcium mobilizing signals. Previous evidence supports the notion of the existence of a redox regulation of this enzyme, which might be relevant for neurodegenerative processes, where an imbalance between generation and removal of reactive oxygen species could occur. In a recent work, we have observed that calcineurin activity is depressed in two models for familial amyotrophic lateral sclerosis (FALS) associated with mutations of the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1), namely in neuroblastoma cells expressing either SOD1 mutant G93A or mutant H46R and in brain areas from G93A transgenic mice. In this work we report that while wild-type SOD1 has a protective effect, calcineurin is oxidatively inactivated by mutant SOD1s in vitro; this inactivation is mediated by reactive oxygen species and can be reverted by addition of reducing agents. Furthermore, we show that calcineurin is sensitive to oxidation only when it is in an 'open', calcium-activated conformation, and that G93A-SOD1 must have its redox-active copper site available to substrates in order to exert its pro-oxidant properties on calcineurin. These findings demonstrate that both wild-type and mutant SOD1s can interfere directly with calcineurin activity and further support the possibility of a relevant role for calcineurin-regulated biochemical pathways in the pathogenesis of FALS.

Aerobiosis↗

Effect of hyoscine N-butylbromide on gastroesophageal reflux in normal subjects and patients with gastroesophageal reflux disease.

OBJECTIVES: Recent studies have shown that atropine reduces gastroesophageal reflux in normal subjects and patients with gastroesophageal reflux. The aim of the study has been to assess the effects of an atropine derivative, hyoscine N-butylbromide in normal subjects and patients with gastroesophageal reflux disease by recording esophageal and gastric pH-metry for a 24-h period. METHODS: Ten normal subjects and 10 patients with gastroesophageal reflux disease were evaluated. PH-metry was performed using two glass pH flexible probes with distal incorporated electrodes. The two catheters were introduced nasally under fluoroscopy. One probe was positioned in the gastric body; the other was placed 5 cm above the lower esophageal sphincter which had been evaluated manometrically before the study. Recording lasted without interruption for 48 h. Patients and normal subjects were assigned to receive hyoscine N-butylbromide (10 mg p.o. t.i.d.) for 24 h followed by a placebo for another 24 h or vice versa in a random manner. The pH was analyzed for a total number of acid refluxes and percentage of the period with pH <4 in the esophagus and the mean gastric pH in 24 h, before and after treatment with hyoscine N-butylbromide. RESULTS: The number of reflux episodes was significantly greater with hyoscine N-butylbromide in comparison with a placebo in patients with gastroesophageal reflux disease and normal subjects (p < 0.02). The percentage of time with pH <4, was also significantly greater in patients with gastroesophageal reflux disease and in controls (p < 0.05). The mean 24-h gastric pH after hyoscine N-butylbromide was not different from placebo in gastroesophageal reflux disease and controls. CONCLUSIONS: Hyoscine N-butylbromide, an anticholinergic agent, increases the total number of esophageal acid refluxes in patients with gastroesophageal reflux disease and in controls, therefore it is not recommended in the treatment of gastroesophageal reflux disease.

Adult↗

New-onset delusions and hallucinations in patients infected with HIV.

OBJECTIVE: To assess the relationship between HIV-associated psychotic symptoms (i.e., delusions, hallucinations) and demographic, psychopathological and medical variables by comparing patients with and without cerebral opportunistic infections or metabolic encephalopathy. DESIGN: Cross-sectional study. PATIENTS: 26 patients admitted to hospital with HIV and new-onset psychotic symptoms, defined according to DSM-III-R criteria. OUTCOME MEASURES: A semistructured psychiatric interview using the Psychopathology Assessment Scale (AMDP-4) of the Association for Methodology and Documentation in Psychiatry system. Comprehensive medical assessments, including laboratory tests and computed tomographic scans, were also performed. RESULTS: Patients with cerebral opportunistic infections or metabolic encephalopathy (i.e., "secondary" psychosis, n = 13) were more likely to show disorders of consciousness, disorders of orientation and disturbances of attention and memory than those with no evidence of HIV-related cerebral disease (i.e., "primary" psychosis, n = 13); 10 patients (77%) with cerebral opportunistic infections or metabolic encephalopathy and only 1 (8%) patient without (p < 0.001) were diagnosed with delirium. These associations were stronger for the "secondary" patients with no focal brain lesions than for those with lesions. CONCLUSIONS: These findings suggest that "organic" symptoms of psychosis in those infected with HIV are related to the systemic and cerebral complications of HIV infection rather than to the psychotic process itself.

AIDS Dementia Complex↗

The role of peroxisome proliferator-activated receptor gamma in bladder cancer in relation to angiogenesis and progression.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) immunohistochemical expression was analyzed in 75 human bladder tumor specimens, where the expression of some angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PDECGF), and tumor progression markers, such as epidermal growth factor receptor (EGFr), p16, mutated p53, and normal pRB, were also analyzed. The results were then compared to the clinical and pathological characteristics of the disease. PPAR gamma was expressed more significantly in papillary tumors than in solid cancers, and its presence was associated with statistical significance to low incidence of tumor recurrence or progression. This significant association was observed also when PPAR gamma was expressed in the presence of PDECGF, which resulted, when considered alone, to an angiogenic factor typical of solid cancers and appeared related to poor prognosis. In the presence of bFGF, on the contrary, PPAR gamma expression no longer resulted to a significant association with low incidence of tumor recurrence or progression, suggesting a possible worsening role of this angiogenic factor, typical of papillary cancers, in its interaction with PPAR gamma.

Adult↗