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L Ballerini

Publications and source records attributed to L Ballerini.

At least 19 recordsLinked to original sources
PubMed2006

Early signs of motoneuron vulnerability in a disease model system: Characterization of transverse slice cultures of spinal cord isolated from embryonic ALS mice.

Mutations in the SOD1 gene are associated with familial amyotrophic lateral sclerosis. The mechanisms by which these mutations lead to cell loss within the spinal cord ventral horns are unknown. In the present report we used the G93A transgenic mouse model of amyotrophic lateral sclerosis to develop and characterize an in vitro tool for the investigation of subtle alterations of spinal tissue prior to frank neuronal degeneration. To this aim, we developed organotypic slice cultures from wild type and G93A embryonic spinal cords. We combined immunocytochemistry and electron microscopy techniques to compare wild type and G93A spinal cord tissues after 14 days of growth under standard in vitro conditions. By SMI32 and choline acetyl transferase immunostaining, the distribution and morphology of motoneurons were compared in the two culture groups. Wild type and mutant cultures displayed no differences in the analyzed parameters as well as in the number of motoneurons. Similar results were observed when glial fibrillary acidic protein and myelin basic protein-positive cells were examined. Cell types within the G93A slice underwent maturation and slices could be maintained in culture for at least 3 weeks when prepared from embryos. Electron microscopy investigation confirmed the absence of early signs of mitochondria vacuolization or protein aggregate formation in G93A ventral horns. However, a significantly different ratio between inhibitory and excitatory synapses was present in G93A cultures, when compared with wild type ones, suggesting the expression of subtle synaptic dysfunction in G93A cultured tissue. When compared with controls, G93A motoneurons exhibited increased vulnerability to AMPA glutamate receptor-mediated excitotoxic stress prior to clear disease appearance. This in vitro disease model may thus represent a valuable tool to test early mechanisms contributing to motoneuron degeneration and potential therapeutic molecular interventions.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Nosogogy: when the learner is a patient with chronic renal failure.

Patient education approaches are currently derived from a biomedical 'acute' model characterized by the sequence of health, disease, and recovery resulting from our professional intervention. Unfortunately, this model proves to be totally inadequate when applied to a chronic disease such as kidney failure. Our patients never fully regain their health and may continue to worsen under our care, even after many state-of-the-art treatments. The solution is represented in acquiring a new professional identity, shifting from the 'biomedical' acute model to a 'bio-psycho-social-educational model'. Within this model, a Therapeutic Education approach in predialysis has been proven to provide both short- and long-term positive results for renal patients. There is a tremendous difference between the learning processes in children and adults and two different sciences have already been described. 'Pedagogy' deals with child learning and 'Andragogy' with adult learning. Nevertheless, when the learner is a patient with a chronic disease, we believe that new considerations must be taken into account. We propose to create a novel science and to call it 'Nosogogy', derived from the ancient Greek word (see text), meaning 'disease'. Nosogogy could be defined as the science of teaching adults affected by chronic disease. The new educator is someone deeply involved in renal care who knows and understands the characteristic conflicts and dynamics that arise in the renal patient, and possesses adequate communication skills to deal with him. In our experience, we prefer to have educational sessions run by nephrologists and nurses who have great experience in the field.

Humans↗
PubMed2006

Patient re-training in peritoneal dialysis: why and when it is needed.

The aim of this multicenter, quantitative, observational study was to analyze compliance and re-training needs of patients on peritoneal dialysis (PD) through the assessment of patient knowledge (with a Patient Questionnaire; phase 1) and patient behavior (home visit with a Score Card; phase 2). A total of 353 patients from 11 Italian centers participated in the first phase and 191 patients from nine centers in the second phase. Overall, 66% of questions on the Patient Questionnaire were answered correctly. Correct answers were more frequent in females than males, in patients under 55 years of age, and in those with higher education. The lowest rate of correct answers involved questions related to diet and physical activity (67% and 51%, respectively). Data collected during the home visit showed that 25% of patients were partially compliant with their drug therapy. Twenty-three percent of patients were non-compliant with the exchange protocol procedures, with a significant association between compliance and the incidence of peritonitis, and 11% were non-compliant with the exit-site protocol procedures without a statistically significant correlation to peritonitis. By combining the two evaluations, we found that approximately one-third (29%) of patients needed reinforcement of knowledge and ability to correctly perform PD as related to infection control and 27% for the correct use of drugs. Looking at the combined evaluation of infection control and drug use, results showed that 47% of patients needed re-training. This need for re-training was greater for younger patients (less than 55 years old), patients with lower education degree and patients in the early or late phase of PD therapy (less than 18 months or more than 36 months). Gender and degree of autonomy had no effect on the need for re-training.

Aged↗
PubMed2006

Microcirculation as a novel marker of membrane biocompatibility.

BACKGROUND: It is possible to consider microcirculation as a kind of OwitnessO of the complex biological reactions triggered by the dialytic treatment. The reactivity of microcirculation to the dialytic stress may represent a measure of the overall biocompatibility of the membrane. In this study we tested the hypothesis that different synthetic membranes may have different biological effects, particularly related to microcirculation. SUBJECTS AND METHODS: In this crossover study, we observed 16 chronically hemodialyzed patients. All patients were treated with the EVAL membrane; we recorded the TcPO2 during the second treatment of the week. All patients were then switched to the hf-PS membrane. During the study observation we did not change the dialytic prescription or the pharmacologic treatment. RESULTS: From the beginning of the session until 90O, the behavior of TcPO2 is similar for both the membranes. From 120O to the end of the treatment in sessions with the EVAL membrane, the TcPO2 values come back to the starting level, whereas in the treatments with hf-PS the TcPO2, the values remain at a lower level; there was a significant difference between EVAL and hf-PS in the values recorded. Arterial blood gas values of paO2 and paCO2 are quite similar in the treatments with both the membranes, without any significant difference. CONCLUSIONS: The analysis of microcirculation by means of TcPO2 measurement is a useful tool to obtain a OclinicalO measure of biocompatibility of the dialytic treatment and different membranes may have different impacts on TcPO2.

Aged↗
PubMed2005

Interneurons transiently express the ERG K+ channels during development of mouse spinal networks in vitro.

During spinal cord maturation neuronal excitability gradually differentiates to meet different functional demands. Spontaneous activity, appearing early during spinal development, is regulated by the expression pattern of ion channels in individual neurons. While emerging excitability of embryonic motoneurons has been widely investigated, little is known about that of spinal interneurons. Voltage-dependent K+ channels are a heterogeneous class of ion channels that accomplish several functions. Recently voltage-dependent K+ channels encoded by erg subfamily genes (ERG channels) were shown to modulate excitability in immature neurons of mouse and quail. We investigated the expression of ERG channels in immature spinal interneurons, using organotypic embryonic cultures of mouse spinal cord after 1 and 2 weeks of development in vitro. We report here that all the genes of the erg family known so far (erg1a, erg1b, erg2, erg3) are expressed in embryonic spinal cultures. We demonstrate for the first time that three ERG proteins (ERG1A, ERG2 and ERG3) are co-expressed in the same neuronal population, and display a spatio-temporal distribution in the spinal slices. ERG immuno-positive cells, representing mainly GABAergic interneurons, were present in large numbers at early stages of development, while declining later, with a ventral to dorsal gradient. Patch clamp recordings confirmed these data, showing that ventral interneurons expressed functional ERG currents only transiently. Similar expression of the erg genes was observed at comparable ages in vivo. The role of ERG currents in regulating neuronal excitability during the earliest phases of spinal circuitry development will be examined in future studies.

Animals↗
PubMed2005

Phenotypic heterogeneity in two unrelated Danon patients associated with the same LAMP-2 gene mutation.

Danon disease, an X-linked cardioskeletal myopathy caused by primary deficiency of lysosome-associated membrane protein-2 (LAMP-2), is clinically characterized by cardiomyopathy, myopathy, and variable mental retardation. The pathological hallmark of the disease is the absence of LAMP-2 immunohistochemical staining in muscle. The LAMP-2 gene mutations reported thus far are generally private mutations. We describe two cases of Danon disease with different clinical presentation, in whom we identified the same exon skipping mutation c.928G>A in the LAMP-2 gene. The first patient was affected by an early onset myopathy and hypertrophic cardiomyopathy (HCM) that partially improved with drug treatment. A first muscle biopsy at age 4 months showed markedly increased glycogen, and acid maltase deficiency was ruled out biochemically. A second muscle biopsy, performed at age 3(1/2) years, showed very mild abnormalities. The second child at age 15 years had mild, diffuse muscle weakness and wasting, moderate mental deficiency, and HCM. Two serial biopsies performed at age 8 and 15 years showed similar findings of multiple esterase-positive vacuoles in type I myofibers. In both patients the immunohistochemical study demonstrated the absence of LAMP-2 in skeletal muscle.

Adolescent↗
PubMed2003

Spinal circuits formation: a study of developmentally regulated markers in organotypic cultures of embryonic mouse spinal cord.

In this study, we have addressed the issue of neural circuit formation using the mouse spinal cord as a model system. Our primary objective was to assess the suitability of organotypic cultures from embryonic mouse spinal cord to investigate, during critical periods of spinal network formation, the role of the local spinal cellular environment in promoting circuit development and refinement. These cultures offer the great advantage over other in vitro systems, of preserving the basic cytoarchitecture and the dorsal-ventral orientation of the spinal segment from which they are derived [Eur J Neurosci 14 (2001) 903; Eur J Neurosci 16 (2002) 2123]. Long-term embryonic spinal cultures were developed and analyzed at sequential times in vitro, namely after 1, 2, and 3 weeks. Spatial and temporal regulation of neuronal and non-neuronal markers was investigated by immunocytochemical and Western blotting analysis using antibodies against: a) the non-phosphorylated epitope of neurofilament H (SMI32 antibody); b) the enzyme choline acetyltransferase, to localize motoneurons and cholinergic interneurons; c) the enzyme glutamic acid decarboxylase 67, to identify GABAergic interneurons; d) human eag-related gene (HERG) K(+) channels, which appear to be involved in early stages of neuronal and muscle development; e) glial fibrillary acidic protein, to identify mature astrocytes; f) myelin basic protein, to identify the onset of myelination by oligodendrocytes. To examine the development of muscle acetylcholine receptors clusters in vitro, we incubated live cultures with tetramethylrhodamine isothiocyanate-labeled alpha-bungarotoxin, and we subsequently immunostained them with SMI32 or with anti-myosin antibodies. Our results indicate that the developmental pattern of expression of these markers in organotypic cultures shows close similarities to the one observed in vivo. Therefore, spinal organotypic cultures provide a useful in vitro model system to study several aspects of neurogenesis, gliogenesis, muscle innervation, and synaptogenesis.

Action Potentials↗
PubMed2001

Closure of the fenestration in the extracardiac Fontan with the Amplatzer duct occluder device.

We report the successful use of the Amplatzer duct occluder for the delayed closure of the fenestration in three patients who underwent an extracardiac modified Fontan procedure. At the moment of closure, the patients were 5.5, 2.7, and 3 years old (29 months, 3 months, and 14 months after the Fontan procedure, respectively). Immediate full occlusion was achieved in all cases. In addition, arterial saturation increased significantly (> 5%) with no hemodynamic deterioration. There were no complications during or after the procedure, and the patients were discharged in good conditions the day after and with uneventful follow-up. In conclusion, the Amplatzer duct is safe and effective for the closure of the fenestration in the extracardiac Fontan. Cathet Cardiovasc Intervent 2001;54:88-92.

Balloon Occlusion↗
PubMed2001

Minimally invasive or interventional repair of atrial septal defects in children: experience in 171 cases and comparison with conventional strategies.

OBJECTIVES: The goal of this study was to evaluate percutaneous interventional and minimally invasive surgical closure of secundum atrial septal defect (ASD) in children. BACKGROUND: Concern has surrounded abandoning conventional midline sternotomy in favor of the less invasive approaches pursuing a better cosmetic result and a more rational resource utilization. METHODS: A retrospective analysis was performed on the patients treated from June 1996 to December 1998. RESULTS: One hundred seventy-one children (median age 5.8 years, median weight 22.1 kg) underwent 52 device implants, 72 minimally invasive surgical operations and 50 conventional sternotomy operations. There were no deaths and no residual left to right shunt in any of the groups. The overall complication rate causing delayed discharge was 12.6% for minimally invasive surgery, 12.0% for midline sternotomy and 3.8% for transcatheter device closure (p < 0.01). The mean hospital stay was 2.8 +/- 1.0 days, 6.5 +/- 2.1 days and 2.1 +/- 0.5 days (p < 0.01); the skin-to-skin time was 196 +/- 43 min, 163 +/- 46 min and 118 +/- 58 min, respectively (p < 0.001). Extracorporeal circulation time was 49.9 +/- 10.1 min in the minithoracotomy group versus 37.2 +/- 13.8 min in the sternotomy group (p < 0.01) but without differences in aortic cross-clamping time. Sternotomy was the most expensive procedure (15,000 EUR +/- 1,050 EUR vs. 12,250 EUR +/- 472 EUR for minithoracotomy and 13,000 EUR +/- 300 EUR for percutaneous devices). CONCLUSIONS: While equally effective compared with sternotomy, the cosmetic and financial appeal of the percutaneous and minimally invasive approaches must be weighed against their greater exposure to technical pitfalls. Adequate training is needed if a strategy of surgical or percutaneous minimally invasive closure of ASD in children is planned in place of conventional surgery.

Analysis of Variance↗
PubMed2001

Homeostatic plasticity induced by chronic block of AMPA/kainate receptors modulates the generation of rhythmic bursting in rat spinal cord organotypic cultures.

Generation of spontaneous rhythmic activity is a distinct feature of developing spinal networks. We report that rat embryo organotypic spinal cultures contain the basic circuits responsible for pattern generation. In this preparation rhythmic activity can be recorded from ventral interneurons and is developmentally regulated. When chronically grown in the presence of an AMPA/kainate receptor blocker, this circuit expresses long-term plasticity consisting largely of increased frequency of fast synaptic activity and reduction in slow GABAergic events. We examined whether, once this form of homeostatic plasticity is established, the network could still exhibit rhythmicity with properties similar to controls. Control or chronically treated ventral interneurons spontaneously generated (with similar probability) irregular, network-driven bursts over a background of ongoing synaptic activity. In control cultures increasing network excitability by strychnine plus bicuculline, or by raising [K(+)](o), induced rapid-onset, regular rhythmic bursts. In treated cultures the same pharmacological block of Cl(-)-mediated transmission or high-K(+) application also induced regular patterned activity, although significantly faster and, in the case of high K(+), characterized by slow onset due to postsynaptic current summation. Enhancing GABAergic transmission by pentobarbital surprisingly accelerated the high-K(+) rhythm of control cells (though depressing background activity), whereas it slowed it down in chronically treated cells. This contrasting effect of pentobarbital suggests that, to preserve bursting ability, chronic slices developed a distinct GABAergic inhibitory control on over-expressed bursting circuits. Conversely, in control slices GABAergic transmission depressed spontaneous activity but it facilitated bursting frequency. Thus, even after homeostatic rearrangement, developing mammalian spinal networks still generate rhythmic activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2001

Coronary microvascular endothelial dysfunction in transplanted children.

AIMS: To assess the response of the coronary microcirculation to acetylcholine (endothelium-dependent vasodilator) and of adenosine (endothelium-independent vasodilator) in children after heart transplantation and to verify whether endothelial dysfunction is time-dependent. METHODS AND RESULTS: We studied the endothelial function of 26 asymptomatic children previously submitted to heart transplantation, with normal transplanted hearts and epicardial coronary arteries. Ten untransplanted children served as controls. The response of coronary blood flow velocity to intracoronary infusion of acetylcholine (1.8 microg x min(-1)) and adenosine (270 microg x min(-1)) was assessed using a Doppler wire positioned in an epicardial coronary branch. In the study group, coronary blood flow velocity increased slightly during acetylcholine infusion (peak/baseline ratio=1.17+/-0.22). The ratio was inversely correlated with the length of follow-up (r=-0.50;P=0.0078). The peak/baseline ratio in control children was 1.76+/-0.73 (P<0.0002 vs. study group). After adenosine infusion, the coronary blood flow velocity peak/baseline ratio was 3.75+/-1.54 in transplanted children and 3.72+/-1.34 in controls (P=ns). CONCLUSIONS: Endothelial dysfunction in paediatric transplanted patients becomes more evident in patients with longer follow-up. This finding could prove useful in the prevention of accelerated arteriosclerosis.

Acetylcholine↗
PubMed2001

Pulsatile flow and atherogenesis: results from in vivo studies.

Compliance mismatch between prosthetic vascular replacement (possibly stented) and native artery is considered to be an important factor in implant failure due, e.g., to vascular remodeling, tissutal growth or intimal hyperplasia (IH). From an in vivo study involving altered vascular mechanics (and, consequently, compliance mismatch), carried out using the Moncada model of atherosclerosis development and smooth muscle cell (SMC) proliferation, the hemodynamic assessment was followed by means of real-time multigated ultrasound profilometry, of collared carotid artery using two different models: non-constrictive and constrictive plastic collars, wrapped around the vessel. The experiments provided the real-time measurement of velocity profiles in vivo and the subsequent estimation of wall shear stresses, locally responsible for the altered hemodynamics. Endothelium modifications were correlated with local hemodynamic alterations by using statistical regression analysis of the development of intimal hyperplasia and the mechanical stimulus applied to the endothelium by means of the two different manipulation models. Different correlations were found between wall shear rate and IH in the two models, showing the importance of the vascular pulsatility in determining SMC proliferation. This result could be useful in minimizing the negative consequences of clinical interventions such as graft and/or stent implantation.

Animals↗
PubMed2000

Opposite changes in synaptic activity of organotypic rat spinal cord cultures after chronic block of AMPA/kainate or glycine and GABAA receptors.

1. The well-developed cytoarchitecture of rat organotypic spinal cord culture makes it a suitable model to explore how persistent suppression of certain synaptic inputs might be compensated by increased synaptic efficacy (homeostatic plasticity). 2. Spontaneous or electrically evoked synaptic transmission of patch-clamped ventral horn interneurons was studied in control solution after blocking, for the second week in culture, AMPA/kainate receptors with CNQX or glycine and GABAA receptors with strychnine and bicuculline, or indiscriminately removing inputs with tetrodotoxin (TTX). 3. In untreated cells, spontaneous postsynaptic currents (PSCs) had fast (tau < 5 ms) or slow (tau > 10 ms) decay. A similar separation was observed when recording miniature currents (mPSCs). Slow decay PSCs were suppressed by strychnine plus bicuculline while fast decay events were eliminated by CNQX. 4. After chronic CNQX treatment the frequency of spontaneous, fast PSCs (of larger amplitude) or mPSCs was almost doubled with respect to control. These events were blocked by acutely applied CNQX, which unmasked slow PSCs. 5. After chronic TTX treatment neither the frequency nor the amplitude of spontaneous events was changed. 6. After chronic strychnine and bicuculline treatment the frequency and amplitude of all PSCs was decreased in most cells. mPSCs were also decreased in frequency. Spontaneous or electrically evoked currents acquired a larger component mediated by NMDA receptor activity. 7. The developing spinal network thus operated distinct homeostatic processes which led to strong enhancement in glutamatergic transmission after CNQX block or to broad downregulation of synaptic activity following chronic exposure to strychnine and bicuculline.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Treatment of pulmonary artery stenosis after arterial switch operation: stent implantation vs. balloon angioplasty.

The development of pulmonary artery stenosis is a potential complication during the mid- to long-term follow-up after arterial switch operation (ASO) for transposition of the great arteries. Surgical results have been disappointing and conventional balloon dilation yields a fairly important incidence of failures and recurrences. We evaluated our results with implantation of balloon-expandable stents in 5 out of 13 patients with a previously attempted unsuccessful conventional balloon dilation of pulmonary artery branch stenosis after ASO. In two more cases, stents were used as a primary procedure. Balloon angioplasty achieved a 15% increase in mean diameter of the stenosis vs. 124% with the use of stents (P< 0.01), a 10% decrease of the pressure gradient across the stenosis vs. 71% of stents (P<0.01), and a 10% drop in RV/aorta pressure ratio vs. 43% of stents (P<0.01). Compared to conventional balloon angioplasty in our series, stents were more effective in the treatment of patients with peripheral pulmonary artery stenosis after ASO. Balloon dilation should be considered in selected cases unsuitable for treatment with endovascular stents.

Angioplasty, Balloon, Coronary↗
PubMed1999

Generation of rhythmic patterns of activity by ventral interneurones in rat organotypic spinal slice culture.

1. In the presence of certain excitatory substances the rat isolated spinal cord generates rhythmic oscillations believed to be an in-built locomotor programme (fictive locomotion). However, it is unknown whether a long-term culture of the same tissue can express rhythmic activity. Such a simplified model system would provide useful data on the minimal circuitry involved and the cellular mechanisms mediating this phenomenon. For this purpose we performed patch clamp recording (under whole-cell voltage or current clamp conditions) from visually identified ventral horn interneurones of an organotypic slice culture of the rat spinal cord. 2. Ventral horn interneurones expressed rhythmic bursting when the extracellular [K+] was raised from 4 to 6-7 mM. Under voltage clamp this activity consisted of composite synaptic currents grouped into bursts lasting 0.9 +/- 0.5 s (2.8 +/- 1.5 s period) and was generated at network level as it was blocked by tetrodotoxin or low-Ca2+-high-Mg2+ solution and its periodicity was unchanged at different potential levels. 3. In current clamp mode bursting was usually observed as episodes comprising early depolarizing potentials followed by hyperpolarizing events with tight temporal patterning. Bursting was fully suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and reduced in amplitude and duration by N-methyl-D-aspartate (NMDA) receptor antagonism without change in periodicity. Extracellular field recording showed bursting activity over a wide area of the ventral horn. 4. Regular, rhythmic activity similar to that induced by K+ also appeared spontaneously in Mg2+-free solution. The much slower rhythmic pattern induced by strychnine and bicuculline was also accelerated by high-K+ solution. 5. The fast and regular rhythmic activity of interneurones in the spinal organotypic culture is a novel observation which suggests that the oversimplified circuit present in this culture is a useful model for investigating spinal rhythmic activity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1999

Antagonism by (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid of synaptic transmission in the neonatal rat spinal cord in vitro: an electrophysiological study.

The effect of the novel GABAc receptor antagonist (1,2,5,6-tetrahydropyridine-4-yl)methyl-phosphinic acid (TPMPA) on synaptic transmission and GABA-mediated responses was investigated with electrophysiological recordings from the in vitro spinal cord preparation of the neonatal rat. Bath-applied TPMPA (10 microM) had no effect on spinal reflexes evoked by dorsal root stimulation, on ventral root polarization level or amplitude of ventral root depolarizations induced by exogenously applied GABA (0.5 mM). TPMPA significantly attenuated the depressant action of GABA on spinal reflexes without changing responses induced by the GABA(A) receptor agonist isoguvacine (50 microM) or the GABA(B) receptor agonist baclofen (0.5-2 microM). Following block of GABA(A) receptors by bicuculline (20 microM) and of glycine receptors by strychnine (1 microM), regular bursting activity recorded from ventral roots developed spontaneously and persisted unchanged for many hours. This bursting pattern, which is generated at the level of the interneuronal network, was significantly slowed down by TPMPA, which also increased the duration of individual bursts and the number of intraburst oscillations. These results suggest that in the neonatal rat spinal cord some functional GABAc receptors exist: their role was clearly unmasked following pharmacological block of GABA(A) (and glycine) receptors. Under these conditions GABAc receptors appeared to contribute to the excitation of spinal interneurons supporting rhythmic bursting activity.

Animals↗
PubMed1998

Patent ductus arteriosus occlusion using detachable coils.

Occlusion of patent ductus arteriosus was performed using detachable coils in 193 cases, with 181 successful implants and a low embolization rate. This technique is safe and effective for occlusion of ductuses of various sizes, and is low cost.

Adolescent↗