Localization of neuroglobin in the brain of R6/2 mouse model of Huntington's disease.

Neuroglobin (Ngb) is expressed in the central and peripheral nervous system, cerebrospinal fluid, retina, and endocrine tissues where it is involved in binding O2 and other gasotransmitters. Several studies have highlighted its endogenous neuroprotective function. Huntington's disease (HD), a dominant hereditary disease, is characterized by the gradual loss of neurons in discrete areas of the central nervous system. We analyzed the expression of Ngb in the brain tissue of a mouse model of HD, in order to define the role of Ngb with respect to individual cell type vulnerability in HD and to gender and age of mice. Our results showed different expressions of Ngb among neurons of a specific region and between different brain regions. We evidenced a decreased intensity of Ngb at 13 weeks of age, compared to 7 weeks of age. The double immunofluorescence and fluorescence resonance energy transfer (FRET) experiments showed that the co-localization between Ngb and huntingtin at the subcellular level was not close enough to account for a direct interaction. We also observed a different expression of Ngb in the striatum, depending on the sex and age of animals. These findings provide the first experimental evidence for an adaptive response of Ngb in HD, suggesting that Ngb may exert neuroprotective effects in HD beyond its role in reducing sensitivity to oxidative stress.

Miglustat Reverts the Impairment of Synaptic Plasticity in a Mouse Model of NPC Disease.

Niemann-Pick type C disease is an autosomal recessive storage disorder, characterized by abnormal sequestration of unesterified cholesterol within the late endolysosomal compartment of cells and accumulation of gangliosides and other sphingolipids. Progressive neurological deterioration and insurgence of symptoms like ataxia, seizure, and cognitive decline until severe dementia are pathognomonic features of the disease. Here, we studied synaptic plasticity phenomena and evaluated ERKs activation in the hippocampus of BALB/c NPC1-/- mice, a well described animal model of the disease. Our results demonstrated an impairment of both induction and maintenance of long term synaptic potentiation in NPC1-/- mouse slices, associated with the lack of ERKs phosphorylation. We then investigated the effects of Miglustat, a recent approved drug for the treatment of NPCD. We found that in vivo Miglustat administration in NPC1-/- mice was able to rescue synaptic plasticity deficits, to restore ERKs activation and to counteract hyperexcitability. Overall, these data indicate that Miglustat may be effective for treating the neurological deficits associated with NPCD, such as seizures and dementia.

Prognostic outcome of routine clinical noninvasive multidetector-row computed tomography coronary angiography in patients with suspected coronary artery disease: a 2-year follow-up study.

PURPOSE: The aim of the study was to assess the prognostic value of multidetector-row CT coronary angiography (MDCT-CA) in patients with suspected coronary artery disease (CAD) in a routine clinical context. MATERIALS AND METHODS: A total of 125 patients (82 men, age 57.4±10.3 years) with suspected CAD underwent MDCT-CA. All patients were assessed for cardiovascular risk factors, symptoms and coronary calcium score. A 2-year follow-up study for the occurrence of major adverse cardiac events was performed. RESULTS: According to the Morise pretest score, 76 patients (60.8%) were at intermediate risk. Patients with suspected CAD presented the following prognostic outcome (p<0.0001): in 41 patients with normal coronary arteries at MDCT-CA, the event rate was 0%; five of 49 patients with nonobstructive CAD had major cardiac events; two of 35 patients with obstructive CAD suffered cardiac death and 19 underwent revascularisation. At multivariate analysis, the presence of obstructive CAD is the only significant independent prognostic variable (hazard ratio, 10.1393; 95% confidence interval 3.2189-31.9379; p<0.0001). CONCLUSIONS: Routine clinical MDCT-CA provides an excellent prognostic value at 2-year follow-up in patients with normal coronary arteries. The cardiac event rate increases with CAD severity.

Prevalence of myocardial bridging and correlation with coronary atherosclerosis studied with 64-slice CT coronary angiography.

PURPOSE: This study aimed to assess the prevalence and characteristics of myocardial bridging in patients who underwent multislice computed tomography coronary angiography (MSCT-CA) and to evaluate the correlation between bridged coronary segments and atherosclerosis. MATERIALS AND METHODS: A total of 277 patients (mean age 60+/-11 years) we consecutively examined with 64-slice MSCT-CA for suspected or known coronary atherosclerosis were retrospectively reviewed for myocardial bridging. Segments proximal and distal to the bridging were evaluated for atherosclerotic plaque, as were the remaining coronary segments. RESULTS: Myocardial bridging was present in 82 patients (30%, mean age 59+/-12). Bridges were of variable length (<1 cm 58%; 1-2 cm 32%; >2 cm 10%) and depth (superficial 69%, intramyocardial 31%) and frequently localised in the mid-distal segment of the left anterior descending artery (95%). Myocardial bridging cannot be considered a significant risk factor for coronary atherosclerosis (odds ratio 0.49) compared with traditional cardiovascular risk factors. Coronary segments proximal to the bridge showed no atherosclerotic disease (33%), positive remodelling (27%), <50% stenosis (20%) or >50% stenosis (20%). We identified 12 noncalcified, 32 mixed and 17 calcified plaques. The distal segments were significantly less affected (p<0.0001). CONCLUSIONS: MSCT-CA is a reliable, noninvasive method that is able to depict myocardial bridging and associated atherosclerotic plaque in the proximal segments.

[The hospital: reality and proposable future]. / L'Ospedale: realtà e futuro proponibile.

In this work we run over hospital history from Middle ages to the present time. Hospitals were charitable institutions in fact they rise inside monasterys, churches or castles with an architecture in modum crucis as a symbolic expression of Christ crucifix. During Renaissance, new scientific Knowledges and the need of technical assistance in a suitable place, lead to a new kind of hospital included into the functional centres of the city were medical practice takes the places of spiritual assistance. In XVIII century hospital is like a "human diseases botanical garden" divided into departments with a circular structure in conformity with a functional model of control. To exceed the isolation of single room, rectangular rooms born with a radially arrangement. At the end of 700's born the pavilions structures typical of hospitals until half 900's when the "monobloc" take place. Today hospital becomes horizontal, include in the context of the city, with hall as a big hotel and with trading centres in accordance with Renzo Piano model and with a new vision of hospital as a welcome place were the patient is a guest to treat as a person of consequence.

[Evaluation of operating theatre for the risk prevention]. / Valutazione della qualità della Sala Operatoria in funzione della prevenzione del rischio.

In this study we analyse factors that predispose to risk and we value the importance of quality and reliability into operating theatre. Patient safety result from ability to plan and manage organizations able to reduce probability of mistakes (Prevention) and to recover and contain their consequences (Protection). The principal motives of mistakes are: - deficiency of sharing procedures between different professional figures for risk prevention; - deficiency of an effective integration between professional figures in operating theatre; - deficiency of charitable precise run to guarantee the continuity of interventions on patient. A risk management program have to take care on this sentinel events and to set up a survey-information system to characterize risks and correction strategies. To prevent patient change, wrong side identification, not working devices or deficiency of surgery materials, it would be useful for operating theatre figures and for anesthetists to work out all together a procedure for admission in operating theatre and a pre-operating check list. The best way to carry out a safety and quality attendance based on standardized procedures and protocols, is to set up risk management firm units. It is necessary to activate and to adjust survey system and effective management training.

Early-onset progressive ataxia associated with the first CACNA1A mutation identified within the I-II loop.

Familial hemiplegic migraine type 1, spinocerebellar ataxia type 6 (SCA6) and episodic ataxia type 2 (EA2) are allelic disorders associated with mutations in the CACNA1A gene, which encodes the alpha1 subunit of the P/Q-type calcium channel (Ca(V)2.1). SCA6 and EA2 share a number of clinical features, such as prominent cerebellar involvement and good response to acetazolamide therapy. However, while SCA6 develops as a late-onset, progressive ataxia, EA2 has an earlier, and episodic, onset. We report on two sisters with a heterogeneous clinical phenotype. The first developed progressive cerebellar ataxia after age 30, without noticeable episodes of vertigo or headache. A 1 year trial with acetazolamide did not produce significant results. The other reported episodes of vertigo, headache and gait imbalance since late childhood, with good response to acetazolamide, before developing moderate chronic cerebellar ataxia. Brain MRI showed cerebellar atrophy, especially in the vermis, in both patients. Direct sequencing of CACNA1A identified a heterozygous 1360G>A mutation in exon 11 resulting in the substitution of alanine for threonine at residue 454 (p.Ala454Thr). This is the first description of a change residing in the cytoplasmic I-II loop associated with a clinical phenotype.

miR-34a regulates cell proliferation, morphology and function of newborn neurons resulting in improved behavioural outcomes.

miR-34a is involved in the regulation of the fate of different cell types. However, the mechanism by which it controls the differentiation programme of neural cells remains largely unknown. Here, we investigated the role of miR-34a in neurogenesis and maturation of developing neurons and identified Doublecortin as a new miR-34a target. We found that the overexpression of miR-34a in vitro significantly increases precursor proliferation and influences morphology and function of developing neurons. Indeed, miR-34a overexpressing neurons showed a decreased expression of several synaptic proteins and receptor subunits, a decrement of NMDA-evoked current density and, interestingly, a more efficient response to synaptic stimulus. In vivo, miR-34a overexpression showed stage-specific effects. In neural progenitors, miR-34a overexpression promoted cell proliferation, in migratory neuroblasts reduced the migration and in differentiating newborn neurons modulated process outgrowth and complexity. Importantly, we found that rats overexpressing miR-34a in the brain have better learning abilities and reduced emotionality.

The mode of action of Y13-259 scFv fragment intracellularly expressed in mammalian cells.

The anti-p21ras Y13-259 single-chain Fv fragment (scFv) neutralizes the activity of p21-ras when intracellularly expressed in different systems. We have studied the mode of action of this inhibition in 3T3 K-ras fibroblasts and demonstrated that (i) this antibody fragment is highly aggregating when cytoplasmically expressed and (ii) the p21-ras antigen is sequestered in these aggregates in an antibody-dependent manner. This co-segregation leads to an efficient inhibition of DNA synthesis. These results suggest that an antigen can be diverted from its normal location inside the cells in an antibody mediated way, prospecting a new mode of action for intracellular antibodies in vivo.

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure.

BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN

Static magnetic fields generated by a 0.5 T MRI unit affects in vitro expression of activation markers and interleukin release in human peripheral blood mononuclear cells (PBMC).

PURPOSE: To investigate the effects of the static magnetic field (SMF) generated by a 0.5 T superconducting MRI unit on in vitro activation marker expression and interleukin release in human peripheral blood mononuclear cell (PBMC) samples from healthy volunteers. MATERIALS AND METHODS: PBMC samples were split into two groups: exposed and sham-exposed under isothermal conditions. PBMC were exposed for 2 h at 24 degrees C to the SMF of a 0.5 T superconducting MRI unit. Immediately after exposure, both samples were cultured for 24 h at 37 degrees C with or without mitogenic stimulation by phytohaemagglutinin (PHA). PBMC were examined for expression of CD25, CD69 and CD71 by immunofluorescence analysis and supernatants were assayed to quantify IFN-gamma, TNF-alpha and IL-4 by ELISA. RESULTS: The 0.5 T SMF produced, after 24 h of culture, a reduced expression of CD69 from PBMC in vitro, that was enhanced after PHA stimulation. An increased release of IFN-gamma and IL-4 was also found, which was reduced after PHA stimulation. The release of TNF-alpha, IL-6 and IL-10 was not modified. CONCLUSIONS: The SMF generated by a 0.5 T superconducting MRI unit modified in vitro activation marker expression and interleukin release from human PBMC.

Pregnancy at forty and over: a case-control study.

We compared obstetric prognosis in 327 women > or = 40 years old (148 nulliparas, 279 multiparas) with 20-30-year-old matched controls who delivered at our department between 1988 and 1990. Gestational diabetes and chronic hypertension were the only more frequent antepartum complications in cases than controls (2.4% vs. 0.3% and 3.4% vs. 0.3%, respectively). There were more premature deliveries in cases than controls (19% vs. 8%) but no difference in postdate deliveries. Cesarean section was more frequent in cases than controls in both nulliparas (64% vs. 30%) and multiparas (43% vs. 12%). Incidence of abdominal delivery for acute obstetrical indications was not increased in older gravidas. Significant differences were observed in low birthweight (17% vs. 5%) and 5-min Apgar score < 7 (8% vs. 2%). Most of the abnormal Apgar scores were recorded after cesarean section; values for vaginally-delivered infants were comparable in older and younger women. Perinatal mortality was similar in the two groups.

Succinate sumatriptan evaluation by Doppler echocardiography in patients with migraine.

Recent reports show that sumatriptan administration increases blood pressure and vascular resistance both in systemic and pulmonary circulation. This study was performed to evaluate by echo-Doppler technique the hemodynamic effects of subcutaneous sumatriptan administration. Forty-one migraine subjects (26 males, 15 females), mean age 36 +/- 2 years (range 36-39 years), and 20 healthy control subjects (14 males, six females), mean age 36 +/- 2 years (range 36-39 years) were randomized (double-blind) to receiving sumatriptan (group A) or placebo (group B). After a 2-week complete pharmacological washout, clinical examination, electrocardiogram, and Doppler echocardiography were performed at baseline, 15, 30, 45, and 60 min after sumatriptan or placebo administration. No significant differences were found between the two groups regarding Doppler echocardiographic parameters (aortic integral, pulmonary integral, end-systolic and end-diastolic diameters) and heart rate; only a slight but not significant increase in arterial blood pressure was observed in group A. Our data show that succinate sumatriptan can be used with safety in patients without hypertension and other cardiovascular disease.

Effect of subcutaneous sumatriptan on head temperature in migraines.

Sumatriptan, a selective 5-hydroxy-triptamine (5-HT1) receptor agonist, has been used recently in the treatment of acute migraine. Some in vitro experiments suggested that sumatriptan has vasoactive properties in vascular beds distinct from cerebral circulation. In view of this we investigated the vascular effects of the standard 6 mg subcutaneous (s.c.) dose of sumatriptan, on the surface areas of the head using thermography, a simple and reliable method for detecting temperature changes. The head temperature of 127 patients (double-blind), 102 migraines (52 during headache attack and 50 headache-free) and 25 healthy control subjects were evaluated using thermography in basal condition and 30, 60, 90, and 120 min after s.c. sumatriptan injection of placebo. During the entire observation period systemic blood pressure (SBP), heart rate (HR) and continuous electrocardiogram (ECG) were detected automatically. A significant head temperature decrease was observed after s.c. sumatriptan administration, in both healthy controls and migraine subjects; placebo administration did not show any change of temperature. In migraine patients during headache attack, head temperature reduction corresponded to the relief of headache symptoms. This vasoconstrictor effect detected with thermography is not isolated to cranial circulation but it is also systemic. In fact, we observed a significant increase (p < 0.05) in both systolic and diastolic systemic blood pressure. No significant changes in heart rate and ECG abnormalities were otherwise detected. These findings suggest that sumatriptan is effective in the treatment of migraine attack, but it must be used with caution in migraines with concomitant hypertension.

Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study.

This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.

Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure.

Thirty patients aged 65-85 years, with refractory New York Heart Association (NYHA) class IV congestive heart failure (CHF) were treated with an intravenous infusion of furosemide (250-2000 mg/d) and small-volume hypertonic saline solution (150 mL of 1.4-4.6% NaCl) twice a day for 6 to 12 days. A daily fluid oral intake of 1000 mL and previous cardiac therapy were maintained. Clinical signs and symptoms of CHF, such as dyspnea, edema and weakness, improved, as did severity of illness as defined by NYHA class. The infusion was well tolerated. After a 12-month follow-up, 24 patients (80%) were alive and in the NYHA class assigned on discharge from the hospital. This therapeutic combination is effective and well tolerated and should represent an innovative approach to the management of refractory CHF.

[Does CDDP have radiosensitizing properties in the treatment of solid tumors in advanced stage?]. / Ha il CDDP proprietà radiosensibilizzanti nel trattamento di tumori solidi in stadio avanzato?

Various experimental and clinical studies have signalled the radiosensitizing properties of CDDP (Cis-dichloro diammine platinum). Twenty eight patients with advanced solid tumours were included in a pilot study incorporating classic fraction (2.00 Gy X 5 weeks) radiotherapy and weekly doses of 30 g/sq.m CDDP. A complete response was obtained in 21 patients with 11 of them NED at a mean follow-up period of 4-16 months. The toxicity of the treatment was low and no kidney damage or ototoxicity was encountered. The results obtained by the combined treatment are encouraging but a correct assessment will require a randomised trial on a bigger patient sample.

[Echographic symptomatology of closed abdominal injuries]. / Semeiotica ecografica dei traumi addominali chiusi.

The importance of echography is emphasised in the diagnosis of closed abdominal injuries. The symptomatology of the possible types of alternative revealable by echography--fluid exudates and parenchymal injuries--are discussed in detail. Personal experience of parenchymal injuries to the liver, spleen and kidneys is then described.

[Biological effects of ultrasonics used in diagnosis. Experimental studies on the incorporation of tritiated thymidine into rat hepatocytes]. / Effetti biologici degli ultrasuoni impiegati a scopo diagnostico. Ricerche sperimentali sull'incorporazione di timidina tritiata in epatociti di ratto.

In order to evaluate the possible effects of diagnostically employed ultrasounds on DNA turnover, 35 Wistar strain rats were subjected to an ultrasonic frequency band of 2.25 MHz for exposure times varying from 10 to 500 seconds. Upon administration of thymidine tritiate, it was observed that capacity to absorb the substance remained largely normal in those rats exposed for up to 40 seconds, but was diminished where longer exposure times were employed.

Bioeffects of ultrasound: an experimental study on human embryos.

The foetuses of 10 women at 9-12 weeks gestation were irradiated with ultrasound under typical diagnostic exposure conditions immediately prior to abortion. Electron microscopy of liver fragments revealed neither morphological nor structural changes.