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Coumarin is one of the simplest plant secondary metabolites, widely distributed in the plant kingdom, affecting root form and function, including anatomy, morphology and nutrient uptake. Although, some plant responses to coumarin have been described, comprehensive knowledge of the physiological and molecular mechanisms is lacking. Maize seedlings exposed to different coumarin concentrations, alone or in combination with 200 μm nitrate (NO

The design in case of fire of steel structures for industrial buildings has been the subject of numerous research activities in Europe [1, 2], focused in particular on the application of the safety assessment criteria using performance-based approach. This issue was addressed with particular interest by the national Technical Committee for Fire Safety of Steel Constructions of Fondazione Promozione Acciaio [7-9], who wanted to provide useful contributions to the evolution of the national regulations, that on this issue has found a place in the Decree of Ministry of Interior of 3 August 2015 (Technical Code of Fire Prevention).

Liposomes and (smart-)nanoparticles represent two major classes of components widely employed for the development of ecient drug delivery systems. While liposomes are traditionally long recognized as excellent research models of biomembranes [1], nanoparticles such as proteins, natural and synthetic polymers and dendrimers reveal attractive properties for the delivery of substances to the interior of a living cell [2-3]. The study of the structure and interaction of nanoparticles during their entrapment and partitioning within model lipid membranes indicates that steric and electrostatic interaction are the crucial parameter that inuence the membrane stability in water solution, while nanoparticles incorporation into the bilayers produces a progressive instability which depends on their concentration and characteristics (such as geometry, surface charge, molecular rigidity) [3-5]. In this respect scattering experiments reveal a powerful tool in order to identify the main features of guest nanoparticles segregation into the lipid nanocarrier, while the modeling of the inter-particle interaction provides substantial insight into the fundamental mechanisms of nanoparticle-lipids interaction in solution [6-8]. The nding of the obtained results outline how the precise control of the interaction between model cell membranes and natural and synthetic nano-objects is of fundamental importance to preserve the releasing eciency at the target site thus increasing the therapeutic index of the incorporated drug and reducing its cytotoxicity.

1. 1. Glutathione (GSH), injected by slow intravenous (i.v.) infusion (7.9 μl/min, for 4 hr; total dose: 1.5 g/kg), starting 10 min after i.v. injection of kainic acid (KA; 12 mg/kg) in the rat reduced the decrease in local cerebral glucose utilization observed 48 hr following the administration of the neurotoxin. 2. 2. Furthermore, it blocked the neuronal loss in hippocampal CA1 and CA3 regions, and prevented, in the hippocampus, the development of edema and the marked depletion in the endogenous brain GSH pool. 3. 3. One can speculate that this protective effect of exogenous GSH is correlated to its capacity to scavenge free radicals, thus preventing the accumulation of oxidant chemical species and the consequent reduction of cellular antioxidant defense.

In the present study the water and ion (Na + , K + , Ca 2+ , Fe 3+ , Se 4+ , Mg 2+ , Mn 2 , Se 4+ , Cu 2+ ) content in the brain of genetically epilepsyprone rats (GEPRs) and of 21-, 45-, and 60-day-old DBA/2 mice were determined, and compared with those measured in normal controls (Sprague-Dawley rats and Swiss mice), to verify whether the predisposition to audiogenic seizures (AGS) may be partially related to changes in the cerebral osmotic and ionic state. Our findings clearly evidenziate two points: a) a more complex shift in brain ionic balance (rather than a peculiar modification in the concentration of a single ion) seems very likely involved in AGS susceptibility; b) brain Ca 2+ and Se 4+ amounts, together with the water content, appear to be really important factors to which a role in abnormal seizure predisposition may be attributed.

A battery of cardiovascular reflex tests is usually performed for the diagnosis of autonomic neuropathy. The tests discriminate well between normal and definitely abnormal autonomic function. However, in some patients the results are borderline and their autonomic status cannot be better defined. We performed multivariate statistical analysis of six cardiovascular autonomic tests with the aim of increasing their diagnostic efficiency. Eighty-five healthy subjects and 95 patients at risk for autonomic neuropathy were studied. Principal component analysis and two pattern recognition methods, the Bayesian technique and the SIMCA method, were applied. It was found that: (1) normal models obtained by Bayesian analysis showed very high specificity and sensitivity; (2) a battery of two tests for parasympathetic function (R-R interval variation test, deep breathing) and two tests for sympathetic function (blood pressure responses to standing and to sustained handgrip) provide an appropriate diagnostic approach, if multivariate analysis is used; (3) multivariate analysis allows a more precisely defined assessment of autonomic nervous system function in so-called borderline patients.

The aim of the present study was to investigate the existence of alterations of the blood-brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-α-aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg−1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg−1) was injected i.p. into methylatropine-pretreated rats, it induced a significant decrease of Kj values within the frontal cortex, parietal cortex, striatum and brain-stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB.

Mechanisms contributing to the rare but consistent neurotoxicity of contrast media currently in clinical use for the radiological examination of the subarachnoid space remain to be isolated. We assessed, by means of the (14C)-2-deoxy-D-glucose (2-DG) autoradiographic method, the effect of three non-ionic, low-osmolar contrast media, namely metrizamide, iopamidol and iohexol, on the local cerebral glucose utilization in the rat brain after intracisternal application. A significant (-30%) global reduction of the brain's metabolic activity occurred following intracisternal metrizamide injection. When compared with the mock-CSF control group the greater relative changes were observed in the supratentorial grey matter structures. In contrast, no significant changes were observed in metabolic brain activity in rats treated intracisternally with iopamidol and iohexol. These findings were consistent with the hypothesis that metrizamide is a competitive inhibitor of human brain hexokinase. The apparent lack of interference on neural tissue metabolism makes the second generation contrast media less neurotoxic and more suitable for neuroradiological subarachnoid investigations in clinical settings. The present experimental work establishes the 2-DG method as a viable laboratory approach to investigate aspects of neuronal dysfunction induced by contrast media.

Summary The dystrophin–glycoprotein complex and the vinculin–talin–integrin system constitute, together a protein machinery, called costameres. The dystrophin–glycoprotein complex contains, among other proteins, also dystrophin and the sarcoglycans subcomplex, proteins playing a key role in the pathogenesis of many muscular dystrophies and linking the cytoplasmic myofibrillar contractile elements to the signal transducing molecules of the extracellular matrix, also providing structural support to the sarcolemma. The vinculin–talin–integrin system connects some components of the extracellular matrix with intermediate filaments of desmin, forming transverse bridges between Z and M lines. In our previous reports we always studied these systems by confocal laser scanning microscopy (CLSM). In this paper we report on the first applications of optical near-field fluorescence microscopy to the spatial localization of α-sarcoglycan and β1D-integrin in human skeletal muscle fibres in order to better compare and test the images obtained with conventional CLSM and with scanning near-field optical microscopy (SNOM). In addition, the analysis of the surface morphology, and the comparison with the fluorescence map is put forward and analyzed for the first time on human muscle fibres. In aperture-SNOM the sample is excited through the nanometre-scale aperture produced at the apex of an optical fibre after tapering and subsequent metal coating. The acquisition of the topography map, simultaneously to the optical signal, by SNOM, permits to exactly overlap the fluorescence images obtained from the two consecutive scans needed for the double localization. Besides, the differences between the topography and the optical spatial patterns permit to assess the absence of artefacts in the fluorescence maps. Although the SNOM represented a good method of analysis, this technique remains a complementary method to the CLSM and it can be accepted in order to confirm the hypothesis advanced by CLSM.

The effect of the dopaminergic antagonist haloperidol on the permeability of the blood-brain barier (BBB) to [14C]α-aminoisobutyric acid was studied in 10–12- and 28–30-week old rats. Following the intraperitoneal injection of haloperidol (1 mg kg−1), an increase in the permeability of the BBB, with respect to younger animals, was observed within the occipital cortex, striatum, hippocampus and hypothalamus in the older rats. No correlation was found between haloperidol-induced changes and age-related differences in the permeability of the BBB. Such age-associated increase in the vulnerability of the BBB when challenged with haloperidol might be related to a deterioration of the dopaminergic control of cerebrovascular permeability.

The blood-brain barrier (BBB) arises from epithelial-like tight junctions that virtually cement adjoining capillary endothelium together in the brain microvasculature. Several experimental manipulations have been shown able to increase the permeability of brain capillaries, by altering endothelial cell membrane integrity or activating specific biochemical pathways involved in regulation of BBB functionality. Because of its amphiphilic nature, sodium dodecyl sulphate (an anionic surfactant widely used as solubilizer or stabilizer in several pharmaceutical preparations; SDS) may enter into interactions with the major membrane components, which are lipids and proteins. The aim of the present study was to determine the effect of an intracarotid infusion of SDS (25, 50 and 100 microg/kg; infusion rate: 3 ml/min for 30 s) on the functionality of the BBB in the rat. An extensive, dose-dependent Evans blue extravasation was observed, in the ipsilateral brain hemisphere, 15 min following SDS infusion. These results were confirmed by the significant increase in [14C]alpha-aminoisobutyric acid ([14C]AIB) transport (evaluated by calculating a unidirectional transfer constant, Ki, for the tracer from blood to brain) measured in several ipsilateral brain regions 2 min after SDS infusion; this SDS-elicited BBB opening to [14C]AIB proved to be reversible. Since the BBB is created by the plasma membrane and tight junctions of the endothelial cells, the change in BBB permeability caused by SDS might be explained as a nonspecific surfactant-membrane interaction. Furthermore, SDS might affect the functional characteristics of brain vascular endothelial cells by an interaction with specific BBB proteins and/or biochemical pathways. In conclusion, one can suggest that intracarotid infusion of SDS might provide a useful clinical approach for the intentional introduction of different substances into the brain. On the other hand, these findings should call attention to possible dangerous consequences of using SDS as solubilizer in drug excipients.

The efficacy of the dialysis in the heart failure non responsive to the traditional methods is well known. In our study we have evaluated the effects of three different dialytic methods (UFI: ultrafiltration isolate; HF: hemofiltration; CAVH: continuous arteriovenous hemofiltration). These methods are used to cause a good depletion in the patients with intractable heart failure following from ischaemic valvular or primitive cardiomiopathy. We have treated 18 patients (6 for each method) and the patients with organic or functional renal disease were treated with the methods (HF and CAVH) that have depletive and depurative effects. Each of these methods is capable, without important differences, of achieving the following aim: the hydro-sodium depletion, the correction of the haemodynamic alteration and the re-establishment of the response to the traditional medical treatment. Using the hemofiltration and continuous arteriovenous hemofiltration, both soft methods, we have obtained values of dehydratation, absolute and for each session, higher than isolated ultrafiltration. The follow-up has not pointed out differences, of both prognosis and survival among patients treated with the three methods studied, whose effects are always only temporary; only the heart transplantation or the valvular correction, by operating in a very important way on the basal cardiopathy, is the resolutive event.

The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional blood-to-brain transfer constant (Ki) for [14C] alpha-aminoisobutyric acid ([14C]AIB) and the cerebral residual blood volume were calculated 10 min following administration of cytokines (CKs; 1000 U/rat). The injection of IL-2 and IL-6 (but not of IL-1 beta) induced a significant enhancement of Ki values for [14C]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes appeared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administration. Our findings confirm the ability of some CKs to affect the permeability of the BBB and/or to act, probably indirectly, as vasomodulator agents of the cerebral microvessel endothelium.

After describing the main clinical features of primary empty sella syndrome and the main hormonal alterations in chronic renal failure, the authors report the results obtained in a group of 33 patients undergoing dialysis three times a week. Each patient had a complete ophthalmologic examination, with electroretinography and visual-evoked potentials, a complete radiologic examination, including skull stratigraphy (particularly of the sellar and parasellar bony structures), and a computed tomographic scan. In the whole group, visual acuity, ocular and lid motility, and visual fields were normal. In two patients, a slight bilateral papilledema, associated with a P100 latency increase and normal morphology and visual-evoked potentials, was reported. Two patients had initial unilateral papillary pallor associated with P100 amplitude alterations. In all four of these patients, radiologic examination showed a markedly pathologic sellar widening with thickening and double contour image of the floor. The report of a primary empty sella was confirmed by computed tomography in all four cases. The authors discuss the possible etiopathogenic mechanisms of the neuroophthalmologic symptoms associated with this syndrome.

The genetically epileptic-prone rat (GEPR) is a valuable model for the study of gene-linked abnormalities involved in epilepsy. In comparison with normal Sprague-Dawley controls, we found, in GEPRs, a marked depression in local cerebral glucose utilization, widespread throughout the brain. This depression was accompanied by a significant increase of blood-brain barrier permeability and a reduction in regional blood volume. Finally GEPRs showed lower plasma levels of total triiodothyronine than normal controls. One can speculate that alterations in cerebral metabolism and microvascular regulation and thyroid hormone imbalance may be gene-linked factors involved in seizure susceptibility.

Changes in blood-brain barrier (BBB) permeability and cerebral metabolic activity following intravenous injection of kainic acid (KA; 6, 12 mg/Kg) in rats were assessed by calculating respectively a blood-to-brain transfer constant (Ki) for [14C]alpha-aminoisobutyric acid and local cerebral glucose utilization (LCGU) values, at different times (1 h, or acute seizures phase, and 48 h, or chronic pathology phase) after the induction of seizures. A significant increase in the local permeability of the BBB was observed 1 h after the injection of KA 6 mg/Kg (eliciting no significant changes in cerebral metabolic activity, except within the frontal cortex and the hippocampus) and 12 mg/Kg (which induced a marked and widespread enhancement of LCGU). On the contrary, during the pathology phase, persistent regional increases in Ki values were evidenced in rats treated with the lowest dose of the convulsant, but not in rats injected with KA 12 mg/Kg (a dose able to cause extensive neuronal damage). Thus one can speculate that: 1) KA-induced regional changes in the permeability of the BBB are not correlated with changes in neuronal activity; 2) opening of the BBB is not reliably associated with neuronal injury.

A pattern recognition analysis of six cardiovascular reflex tests was performed with the aim to increase their diagnostic efficiency. A normal model was defined by SIMCA method using log-transformed values of 85 healthy subjects. The model was tested with data from 60 patients with chronic renal failure. Specificity resulted 94% and sensitivity 96%. 55% of the uremics were recognized affected by autonomic damage. The method allowed a better definition of autonomic function in those patients defined as "borderline" on conventional evaluation of the tests. Pattern recognition analysis of autonomic tests provides a global assessment of all the tests performed. Its use should be encouraged as a diagnostic tool.

We assessed, by means of the [14C]-2-deoxy-D-glucose autoradiography method, the effect of whole-brain x-radiation on local cerebral glucose utilization in the rat brain. Animals were exposed to conventional fractionation (200 +/- cGy/day given 5 days a week) to a total dose of 4000 cGy. Metabolic experiments were made 2 weeks after completion of the radiation exposure. In comparison with control and sham-irradiated animals, cerebral metabolic activity was diffusely decreased following irradiation. Statistically significant decreases in metabolic activity were observed in 13 of 27 brain regions studied. In general, brain areas with the highest basal metabolic rates showed the greatest percentage drop of glucose utilization. Post-irradiation metabolic alterations possibly provide an explanation for the syndrome of early delayed deterioration observed in humans after whole-brain radiotherapy.

We describe pattern recognition analysis of six cardiovascular reflex tests and its application in the diagnosis of autonomic neuropathy. A discriminating model was performed by SIMCA method using the results of 85 healthy subjects. The prediction ability of the model was then verified with data from 95 patients at risk for autonomic neuropathy. Specificity resulted 93% and sensitivity 97%. The method increases the diagnostic efficiency of the tests, being particularly useful in patients with borderline autonomic involvement.

The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. We observed that: a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging- and sex-related alterations in the permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels.

Pineal gland glucose utilization (GU) and capillary permeability (CP) were measured in unanesthetized rats, using complementary quantitative autoradiographic techniques. GU values within the pineal tissue were homogeneously distributed around 70 mumol of glucose/100 g each min, i.e., they were approximately 30% lower than in the cortical gray structures. The blood-to-brain transfer constant of [14C]-alpha-aminoisobutyric acid, as an index of CP, was up to ten orders of magnitude higher than that for the rest of the brain. These measurements were carried out at that point in the circadian rhythm that corresponds to the minimum level of neurosecretory activity of the pineal gland.