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In clinical practice, plastic surgeons are often faced with large skin defects that are difficult to close primarily. Management of large skin wounds e.g. burns or traumatic lacerations requires knowledge of skin biomechanic properties. Research into skin microstructural adaptation to mechanical deformation has only been performed using static regimes due to technical limitations. Here, we combine uniaxial stretch tests with fast second harmonic generation imaging and we apply this for the first time to investigate dynamic collagen rearrangement in reticular human dermis. Ex vivo human skin from the abdomen and upper thigh was simultaneously uniaxially stretched while either periodically visualizing 3D reorganization, or visualizing 2D changes in real time. We determined collagen alignment via orientation indices and found pronounced variability across samples. Comparing mean orientation indices at the different stages of the stress strain curves (toe, heel, linear) showed a significant increase in collagen alignment during the linear part of the mechanical response. We conclude that fast SHG imaging during uni-axial extension is a promising research tool for future studies on skin biomechanic properties.

Background Italy was heavily hit by the COVID-19 pandemic. According to official statistics, during 2020 there were more than 75,000 excess deaths compared to the average expected mortality in 2015-2019. General mortality (GM) is a good measure of both the direct and indirect effects of the pandemic because it's exempt from potential bias due to misclassification of events. Evidence shows a greater burden of disease and mortality attributable to COVID-19 among disadvantaged populations, with the risk of an exacerbation of existing health inequalities. We aim to analyse the trend of social inequalities in mortality during the first pandemic year in two Italian regions (Piedmont and Emilia-Romagna) using data from Administrative Population Registries (APR) and statistical databases. Methods Data on deaths occurred between Jan 2015 and Jan 2021 in subjects ≥65, stratified by educational level, were obtained from Regional APR and the Census. Using a time series approach, we computed Standardized Mortality Rates (SMR), Relative Index of Inequalities (RII) and Slope Index of Inequalities (SII), adjusted by age, gender, month and region. SMR, RII and SII from March 2020 were forecasted using Holt-Winters method and compared to the observed values in the same period. Results SMRs were higher than expected during the two 2020 epidemic waves (Mar-Apr, Oct-Dec) in both regions. RII didn't increase significantly. Absolute inequalities instead rose in Piedmont during both pandemic waves, mostly among women, and in Emilia-Romagna in March among men. Conclusions The impact of the pandemic on inequalities in GM has been at least of the same size of the impact of other mechanisms of unequal mortality. APR coupled with sociodemographic data are a quick and reliable source for assessing the unequal impact of the COVID-19 pandemic on health. Further research is needed to explore mechanisms underlying these effects e.g. inequalities in cause-specific mortality and access to health services. Key messages

A prototype of the laser in vessel viewing and ranging system (IVVS) was developed at ENEA laboratories in Frascati. It is based on amplitude modulated laser radar, especially designed to withstand the severe ITER conditions. IVVS (in vessel viewing system) probe was designed and built in order to perform sub-millimetric amplitude and range images inside ITER during maintenance procedure. The paper describes the first results of the characterization of the IVVS probe under room conditions at Frascati Labs. The characterization was performed on a full-scale mock-up of the first wall panel and divertor vertical target. The surfaces of these components are considered to be typical for several in-vessel components. Furthermore, the paper discusses and describes new developments expected to increase the overall IVVS performance and functionality.

A prototype of laser in vessel viewing and ranging system (IVVS) was developed at ENEA laboratories. It is based on an amplitude modulated (AM) laser radar specifically designed to withstand the severe ITER conditions. The system is able to perform viewing and ranging of in-vessel surfaces at the same time. The most critical part of the system, the fiber optic optical encoder, has been successfully tested by SCK-CEN laboratories in Mol under radiation at 15 KGy/h up to a dose of 2.47 MGy. The 15 KGy/h was estimated as a likely condition to be faced by the probe for unscheduled inspection (starting only a few hours after plasma). A series of viewing and ranging tests has been performed with the system to evaluate its main characteristics which comprise auto-illumination, large field of view, zoom capability, range measurement capability and high dynamic range. A test has been performed to determine the ranging capability of the system using a testing sample made of three groups of staircases of 10, 5 and 1 mm of step. A standard deviation of the range measurement of 320 μm with a 3 ms stay time of the laser beam was reached comparing the measurement with the CAD representation of the sample.

Background: The clinical and pathophysiological effects of a chronic reduction of cerebral blood flow in humans are not completely known. We investigated whether rats subjected to bilateral common carotid artery occlusion (bCCA-o) developed focal neurological deficits, gait dysfunction, and working memory alterations. Methods: Eighteen male Wistar rats were subjected to bCCA-o, 13 were sham-operated. We assessed sensorimotor functions, gait on a 60 cm-long elevated bridge, and working memory (object recognition and Y maze tests) before and 30, 60, and 90 days after surgery. Histological analysis was performed in a subgroup of 10 rats. Results: No rat showed sensorimotor alterations after surgery. Although gait performances of both bCCA-o and sham-operated rats declined over time, the differences reached statistical significance only for the bCCA-o group (mean±SE: 26.8±5.0; 22.4±4.9; 24.5±5.5 cm at 30, 60, and 90 days, respectively) in comparison with baseline (52.9±5.2 cm; P

An amplitude modulated laser radar has been developed by the Italian Agency for New Technologies, Energy and the Environment (ENEA) for periodic in-vessel inspection in large fusion machines. The viewing system is based on a transceiving optical radar using a radio frequency (RF) modulated single-mode 840-nm wavelength laser beam. The sounding beam is transmitted through a coherent optical fiber to a probe, on the tip of which a focusing optics and suitable scanning system, using a silica prism, steers the laser beam in order to obtain a complete 3-D mapping of the in-vessel surface. This paper describes the digital signal processing system used to modulate the laser beam, as well as to measure both the amplitude of the backscattered laser beam and the phase difference between it and the modulation signal. This information, together with the information on the scanning system position, are acquired and then used by the visualization system to produce both 2-D and 3-D images. The system is based on VME boards and directly acquires and processes in real-time three 79.5-MHz RF signals by using a digital receiver and four digital signal processors. The system principles, the mathematical algorithm, and the system architecture are described hereafter.

Tokamak machines need inspection systems to detect damages on the plasma facing components. The equipment currently in use for in-vessel inspection is mainly based on CCD (charged coupled device) cameras that cannot withstand heavy radiation in vessel operating conditions. To overcome this limit, JET decided to investigate the possibility to replace the actual IVVS TV camera with a radiation-resistant viewing system. For this purpose, ENEA has proposed an amplitude modulated (AM) laser system. Consequently, a new laser-based inspection device (laser in vessel viewing system (LIVVS)) has been designed, developed and tested in ENEA Frascati Laboratories. The system takes in-vessel surface images, scanning the target using a laser beam deflection system installed at the bottom end of a probe, matching the JET mechanical constraints. Experimental results are presented showing the main characteristics of the system.

A 32-year-old woman, gravida 1, para 0, was referred to our pregnancy ultrasound unit at 20 weeks’ gestation for obstetrics ultrasound because of her cardiac disease history. She was affected by a ...

The effects of metrifonate were investigated in 4-6- and 22-24-month-old rats. Extracellular acetylcholine levels were measured by transversal microdialysis in vivo. Baseline extracellular acetylcholine levels in the cerebral cortex and hippocampus were 42% and 60% lower, respectively, in old than in young rats. Old rats did not discriminate between familiar and novel objects. In old rats, metrifonate (80 mg/kg p.o.) brought about 85% inhibition of cholinesterase activity in the cortex and hippocampus, a 4-fold increase in extracellular acetylcholine levels in the cortex only, and restored object recognition. In young rats, metrifonate caused 75% cholinesterase inhibition in the cerebral cortex and hippocampus, a 2-fold increase in cortical and hippocampal extracellular acetylcholine levels, and no effect on object recognition. The slight cholinesterase inhibition following metrifonate (30 mg/kg) in aged rats had no effect on cortical acetylcholine levels and object recognition. In conclusion, metrifonate may improve the age-associated cholinergic hypofunction and cognitive impairment.

1. The effects of histamine and agents at histamine receptors on spontaneous and 100 mM K(+)-evoked release of acetylcholine, measured by microdialysis from the cortex of freely moving, rats, and on cognitive tests are described. 2. Local administration of histamine (0.1-100 microM) failed to affect spontaneous but inhibited 100 mM K(+)-stimulated release of acetylcholine up to about 50%. The H3 receptor agonists (R)-alpha-methylhistamine (RAMH) (0.1-10 microM), imetit (0.01-10 microM) and immepip (0.01-10 microM) mimicked the effect of histamine. 3. Neither 2-thiazolylethylamine (TEA), an agonist showing some selectivity for H1 receptors, nor the H2 receptor agonist, dimaprit, modified 100 mM K(+)-evoked release of acetylcholine. 4. The inhibitory effect of 100 microM histamine was completely prevented by the highly selective histamine H3 receptor antagonist, clobenpropit but was resistant to antagonism by triprolidine and cimetidine, antagonists at histamine H1 and H2 but not H3 receptors. 5. The H3 receptor-induced inhibition of K(+)-evoked release of acetylcholine was fully sensitive to tetrodotoxin (TTX). 6. The effects of intraperitoneal (i.p.) injection of imetit (5 mg kg-1) and RAMH (5 mg kg-1) were tested on acetylcholine release and short term memory paradigms. Both drugs reduced 100 mM K(+)-evoked release of cortical acetylcholine, and impaired object recognition and a passive avoidance response. 7. These observations provide the first evidence of a regulatory role of histamine H3 receptors on cortical acetylcholine release in vivo. Moreover, they suggest a role for histamine in learning and memory and may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

Object recognition was investigated in adult and aging male rats in a two-trials, unrewarded, test that assessed a form of working-episodic memory. Exploration time in the first trial, in which two copies of the same object were presented, was recorded. In the second trial, in which one of the familiar objects and a new object were presented, the time spent exploring the two objects was separately recorded and a discrimination index was calculated. Adult rats explored the new object longer than the familiar object when the intertrial time ranged from 1 to 60 min. Rats older than 20 months of age did not discriminate between familiar and new objects. Object discrimination was lost in adult rats after scopolamine (0.2 mg/kg SC) administration and with lesions of the nucleus basalis, resulting in a 40% decrease in cortical ChAT activity. Both aniracetam (25, 50, 100 mg/kg os) and oxiracetam (50 mg/kg os) restored object recognition in aging rats, in rats treated with scopolamine, and with lesions of the nucleus basalis. In the rat, object discrimination appears to depend on the integrity of the cholinergic system, and nootropic drugs can correct its disruption.

The nucleus basalis of male Charles River Wistar rats was injected with 10 micrograms of the beta-amyloid peptides beta-(1-40) and beta-(25-35) and changes in the morphology of the lesioned area, the release of acetylcholine from the cortex, and in behavior were investigated. Injections of saline and a scrambled (25-35) peptide were used as controls. One week after lesioning, a Congo Red-positive deposit of aggregated material was found at the beta-peptides injection site, which lasted for about 21 days in the case of the beta-(25-35) peptide and at least two months for beta-(1-40). No deposit was detected after scrambled peptide injection. At one week post injection, an extensive glial reaction surrounded the injection site of all peptides and saline as well. Such a reaction was still present but rather attenuated after two months. A decrease in the number of cholinergic neurons was detected in the nucleus basalis after one week with all treatments except saline. After two months, a reduction in the number of choline acetyltransferase-immunopositive neurons was still detectable in the rats injected with beta-(1-40) but not in the beta-(25-35)-or scrambled-injected. The reduction in choline acetyltransferase immunoreactivity was closely paralleled by a decrease in basal acetylcholine release from the parietal cortex ipsilateral to the lesion. Disruption of object recognition was observed in the first weeks after beta-(25-35) peptide injection, whereas the beta-(1-40) peptide impaired the performance only two months after lesion. Rats with lesions induced by beta-peptides may be a useful animal model of amyloid deposition for investigation of the pathogenetic mechanisms leading to Alzheimer's disease.

We describe the performance of an optical heterodyne sensor with a two‐wavelength coherent infrared beam, which is used to detect the motion of remote targets in a real environment with an unambiguous sensing of the instantaneous direction along the line‐of‐sight propagation path. The initial phase condition of maximum sensitivity of the transceiver is stabilized and held by an active feedback system which drives the phase of the optical field of the local oscillator. The experimental results show that this feedback is particularly useful in reducing the noise generated by low‐frequency environmental disturbances, leaving the signal unaffected when the respective frequency ranges are separated. Under certain circumstances, the signal can be recovered from the noise by the linearizing properties of the phase tracking on the interferometer response. The measurements reported show that the two‐wavelength infrared heterodyne transceiver generates signals which replicate the target vibration exactly up to ampl...

We present a new color (RGB) imaging 3D laser scanner prototype recently developed in ENEA (Italy). The sensor is based on AM range finding technique and uses three distinct beams (650nm, 532nm and 450nm respectively) in monostatic configuration. During a scan the laser beams are simultaneously swept over the target, yielding range and three separated channels (R, G and B) of reflectance information for each sampled point. This information, organized in range and reflectance images, is then elaborated to produce very high definition color pictures and faithful, natively colored 3D models. Notable characteristics of the system are the absence of shadows in the acquired reflectance images - due to the system's monostatic setup and intrinsic self-illumination capability - and high noise rejection, achieved by using a narrow field of view and interferential filters. The system is also very accurate in range determination (accuracy better than 10 -4 ) at distances up to several meters. These unprecedented features make the system particularly suited to applications in the domain of cultural heritage preservation, where it could be used by conservators for examining in detail the status of degradation of frescoed walls, monuments and paintings, even at several meters of distance and in hardly accessible locations. After providing some theoretical background, we describe the general architecture and operation modes of the color 3D laser scanner, by reporting and discussing first experimental results and comparing high-definition color images produced by the instrument with photographs of the same subjects taken with a Nikon D70 digital camera.

The propagation of polarized laser beams in turbid water is a subject of relevant interest in the field of underwater quantitative visualization with active sensors like amplitude modulated laser systems. In such devices, target range determination is based on the measurement of the phase difference ΔΦ between the fraction of the amplitude modulated laser beam reflected by the target and a reference signal. As water turbidity increases, the laser radiation backscattered from the water column shined by the sounding laser beam gives rise to an optical background with detrimental effects on the accuracy of range measurement. In this paper we analyze the possibility to increase the apparatus accuracy with a polarimetric technique based on the adoption of polarized laser radiation and polarization selective detection scheme for improving the underwater imaging of real scenes (e.g. archaeological sites). The method fully takes advantages of the different polarization properties of the laser radiation backscattered by turbid water and of the Lambertian component diffusively reflected by the target as described by the associated Mueller matrices. Measurements have been performed by adopting both a co-polarized and cross-polarized detection scheme with linearly and circularly polarized laser radiation. Various degrees of turbidity were realized by adding, as diffusive element, skim milk to water in order to obtain different scattering conditions. The effect of the transition from Rayleigh to Mie scattering regime on phase accuracy determination has been investigated together with the role played by high order scatterings as the medium approaches the optical thickness condition.

A prototype of the laser In Vessel Viewing and inspection System (IVVS) was developed at ENEA laboratories in Frascati. The IVVS probe has been conceived and designed to perform sub-millimetric 3D images inside ITER during the maintenance procedure. An amplitude modulated laser radar and an in-vessel scanning head designed to withstand the severe ITER conditions compose it. The paper describes the system and its general architecture, then the characterization phase is briefly described and the main characteristics of the system are reported relating them to the in vessel components and the foreseen operative conditions. Furthermore, the paper describes the new developments still in progress to increase the overall IWS performance and functionality.

A high resolution Amplitude Modulated Imaging Laser Radar (AM-LR) sensor has recently been developed, aimed to accurately reconstructing 3D digital models of real targets - either single objects or large amplitude complex scenes. The system sounding beam can be swept linearly across the object or circularly around it, by placing the object on a controlled rotating platform. Both intensity and phase shift of the back-scattered light are then collected and processed, providing respectively a shade-free photographic-like picture and accurate range data in the form of a range or depth image, with accuracy depending mainly on the laser modulation frequency. The development of software, suitable for simultaneous 3D rendering of the intensity and absolute distance data collected by the ITR, constitutes one of the main objectives of the research activity, whatever is the application pursued. In fact, high resolution AM-LR systems have a great interest for their potentials in accurate 3D imaging of valuable objects which must be preserved in digital archives. Examples range from artwork monitoring, cataloguing and restoration from sparse fragments, to medicine for non-hazardous diagnostics and fast design of bio-compatible prostheses, to microtechnology in the miniaturization of macro-components (plastic prototypes, quality control). Several meaningful results of measurements executed in various important European archaeological sites, in particular Santa Maria Antiqua church situated in Fori Imperiali area in Rome and Costanza (Romania), involving 3D color mapped representation are also presented.

A high performance Amplitude Modulated Laser Rangefinder (AM-LR) is presented, aimed at accurately reconstructing 3D digital models of real targets, either single objects or complex scenes. The scanning system enables to sweep the sounding beam either linearly across the object or circularly around it, by placing the object on a controlled rotating platform. Both phase shift and amplitude of the modulating wave of back-scattered light are collected and processed, resulting respectively in an accurate range image and a shade-free, high resolution, photographic-like intensity image. The best performances obtained in terms of range resolution are ~100 μm. Resolution itself can be made to depend mainly on the laser modulation frequency, provided that the power of the backscattered light reaching the detector is at least a few nW. 3D models are reconstructed from sampled points by using specifically developed software tools, optimized so as to take advantage of the system peculiarities. Special procedures have also been implemented to perform precise matching of data acquired independently with different sensors (LIF laser sensors, thermographic cameras, etc.) onto the 3D models generated using the AM-LR. The system has been used to scan different types of real surfaces (stone, wood, alloys, bones) and ca be applied in various fields, ranging from industrial machining to medical diagnostics, vision in hostile environments cultural heritage conservation and restoration. The relevance of this technology in cultural heritage applications is discussed in special detail, by providing results obtained in different campaigns with an emphasis on the system's multi-sensor data integration capabilities.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically transmitted cerebrovascular disease. Typically, the first clinical manifestation is migraine and the full clinical spectrum of the disease with recurrent strokes of the subcortical type, cognitive, and mood disorders is seen during the fourth and fifth decades of life. Vascular risk factors are usually absent in CADASIL patients and the diagnosis of the disease is particularly suspected in young adults with cerebrovascular events of unknown cause, diffuse leukoencephalopathy on computed tomography or magnetic resonance imaging, and a history of cerebrovascular diseases or dementia in many family members. We describe three Italian CADASIL patients who presented to medical attention for cerebrovascular events occurred after the age of 55 and had, in addition to hypertension and hyperlipidemia, thrombophilic risk factors such as hyperhomocysteinemia, elevated levels of lipoprotein(a), and antiphospholipid antibodies. Symptoms possibly related to cortical involvement, such as dysphasia and visual field deficits, were reported by two of these patients. We conclude that a diagnosis of CADASIL should not be disregarded in patients with vascular risk factors and presenting with symptoms not immediately referable to subcortical damage at ages more advanced than commonly reported.

The relation between chronic cerebral hypoperfusion and cognitive functions has not been completely clarified. The resolution of cerebral hypoperfusion states, such as those induced by arteriovenous malformations or carotid stenosis/occlusion, has been reported to improve mental decline in humans. Subcortical vascular dementia is another human condition supposed to be linked with chronic cerebral hypoxia/ischemia. The extent of this cause/effect relation is, however, difficult to be assessed in humans, where different factors, such as ageing or subtle degenerative processes, can coexist and interact influencing cognitive performances. Experimental studies can help to elucidate this relation because they can use models of pure chronic/moderate cerebral hypoperfusion. An experimental model of chronic ischemia is the bilateral common carotid artery occlusion in the rat. In this paper, we present a review of experimental studies that evaluated cognitive functions in the rat with bilateral common carotid artery occlusion. We then present an experimental model of bilateral common carotid artery occlusion in the rat modified with respect to previous papers regarding both the surgical procedure and the neurocognitive evaluation that is focused on cognitive domains depending on subcortical-frontal circuits. We propose this model to investigate subcortical vascular dementia.

FLAIR and diffusion-weighted MRI were obtained twice (mean interval 20 ± 4 months) in 10 patients with leukoaraiosis. At follow-up, visual extension of leukoaraiosis was unchanged, whereas the median of whole brain apparent diffusion coefficient (WB-ADC) histogram was increased ( p = 0.008) and brain volume index (BVI) was decreased ( p = 0.006). WB-ADC histogram and BVI are sensitive to leukoaraiosis and might be considered for monitoring progression of the disease.

In previous research we found that pre-training administration of histamine H 3 receptor agonists such as ( R )-α-methylhistamine and imetit impaired rat performance in object recognition and a passive avoidance response at the same doses at which they inhibited the release of cortical acetylcholine in vivo. Conversely, in the present study we report that the post-training administration of ( R )-α-methylhistamine and imetit failed to affect rat performance in object recognition and a passive avoidance response, suggesting that H 3 receptor influences the acquisition and not the recall processes. We also investigated the effects of two H 3 receptor antagonists, thioperamide and clobenpropit, in the same behavioral tasks. Pre-training administration of thioperamide and clobenpropit failed to exhibit any procognitive effects in normal animals but prevented scopolamine-induced amnesia. However, also post-training administration of thioperamide prevented scopolamine-induced amnesia. Hence, the ameliorating effects of scopolamine-induced amnesia by H 3 receptor antagonism are not only mediated by relieving the inhibitory action of cortical H 3 receptors, but other mechanisms are also involved. Nevertheless, H 3 receptor antagonists may have implications for the treatment of degenerative disorders associated with impaired cholinergic function.

An amplitude modulated laser radar has been developed by ENEA (Italian Agency for New Technologies, Energy and Environment) for periodic in-vessel inspection in large fusion machines. Its overall optical design has been developed taking into account the extremely high radiation levels and operating temperatures foreseen in large European fusion machines such as JET (Joint European Torus) and ITER (International Thermo- nuclear Experimental Reactor). The viewing system is based on a transceiving optical radar using a RF modulated single mode 840 nm wavelength laser beam. The sounding beam is transmitted through a coherent optical fiber and a focusing optic to the inner part of the nuclear reactor vessel by a stainless steel probe on the tip of which a suitable scanning silica prism steers the laser beam along a linear raster spanning a -90 degree(s) to +60 degree(s) in elevation and 360 degree(s) in azimuth for a complete mapping of the vessel itself. All the electronics, including the laser source, avalanche photodiode and all the active components are located outside the bioshield, while passive components (receiving optics, transmitting collimator, fiber optics), located in the torus hall, are made of fused silica so that the overall laser radar is radiation resistant. The signal is acquired, the raster lines being synchronized with the aid of optical encoders linked to the scanning prism, thus yielding a TV like image. Preliminary results have been obtained scanning large sceneries including several real targets having different backscattering properties, colors and surface reflectivity ranging over several decades to simulate the expected dynamic range of the video signals incoming from the vessel.

An optical amplitude modulated laser radar has been developed for periodic in-vessel inspection in large fusion machines and its overall optical aiming is developed taking into account the extremely high radiation levels and operating temperatures foreseen in the large European fusion machines (JET and ITER). In this paper an in vessel viewing system based on a transceiving optical radar using an RF modulated single mode 840 nm wavelength laser beam is illustrated. The sounding beam is transmitted through a coherent optical fiber and a focusing collimator to the inner part of the vessel by a stainless steel probe on the tip of which a suitable scanning silica prism steers the laser beam along a linear raster spanning a -90 degree to +90 degree in elevation and 360 degrees in azimuth for a complete mapping of the vessel itself. All the electronics, including laser source, avalanche photodiode and all the active components are located outside the bioshield, while passive components (receiving optics, transmitting collimator, fiber optics), located in the torus hall, are in fused silica so that the overall vision system is radiation resistant. The Active and passive components are contained in separated stainless steel boxes connected through two silica fiber optics. The laser radiation backscattered by the resolved surface element of the vessel is received by a collecting silica optics and remotely transmitted through a multimode fiber on the surface of an avalanche photodiode detector located in the active module at 120 m distance. The received signal is then acquired, the raster lines being synchronized with the aid of optical encoders linked to the scanning prism, to give a TV like image. The scanning accuracy expected in scanning process is less than 1 mm at 10 m of distance: this is a suitable resolution to yield a high quality image showing all the damages due to plasma disruptions. Preliminary results have been obtained scanning large sceneries including several real targets having different light backscattering properties, colors and surfaces reflectivity ranging over several decades to simulate the expected dynamic range of the video signals incoming from the vessel.

The effects of 21-day treatment with the acetylcholinesterase inhibitors metrifonate (80 mg kg−1 per os (p.o.)) and tacrine (3 mg kg−1 p.o.), twice daily, on cortical and hippocampal cholinergic systems were investigated in aged rats (24–26 months). Extracellular acetylcholine levels were measured by transversal microdialysis in vivo; choline acetyltransferase and acetylcholinesterase activities were measured ex vivo by means of radiometric methods. Basal cortical and hippocampal extracellular acetylcholine levels, measured 18 h after the last metrifonate treatment, were about 15 and two folds higher, respectively, than in control and tacrine-treated rats. A challenge with metrifonate further increased cortical and hippocampal acetylcholine levels by about three and four times, respectively. Basal extracellular acetylcholine levels, measured 18 h after the last treatment with tacrine were not statistically different from those of the control rats. A challenge with tacrine increased cortical and hippocampal extracellular acetylcholine levels by about four and two times. A 75% inhibition of cholinesterase activity was found 18 h after the last metrifonate administration, while only a 15% inhibition was detectable 18 h after the last tacrine administration. The challenge with metrifonate or tacrine resulted in 90 and 80% cholinesterase inhibition, respectively. These results demonstrate that in aging rats a subchronic treatment with metrifonate results in a long-lasting, cholinesterase inhibition, and a persistent increase in acetylcholine extracellular levels which compensate for the age-associated cholinergic hypofunction. Metrifonate is therefore a potentially useful agent for the cholinergic deficit accompanying Alzheimer's disease.

A coherent laser sensor, able to achieve measurement of absolute and relative distance of real targets, has been developed for advanced robotic applications. A brief theoretical description of the expected behavior of such system is reported for static and dynamic targets; the theoretical range error dependence from the signal to noise ratio is also described. Experimental results for measurements of static and vibrating real targets are discussed.

The activation of the cortical cholinergic system was investigated in 3- and 25-month-old male Wistar rats, by measuring by transversal microdialysis the changes in cortical extracellular acetylcholine (ACh) levels during the performance of simple spontaneous tasks involving exploratory activity and working memory. Two days after implantation of the microdialysis probe in the frontal cortex, object recognition was investigated by either moving the rats from the home cage to the arena containing the objects or keeping the rats in the arena and introducing the objects. Spontaneous alternation was investigated in a Y runway. Young rats discriminated between familiar and novel objects and alternated in the Y runway, while aged rats were unable to discriminate. Whenever rats were moved from the home cage to the arena, ACh release increased (+70–80%) during the exploratory activity. Handling per se had no effect on extracellular ACh levels. When young rats were left in the arena, introduction of the objects caused some exploratory activity and object recognition but no increase in ACh release. ACh release increased by about 300% during spontaneous alternation. In aging rats basal extracellular ACh levels and their increase after placement in the arena were less than half that in young rats. Our work demonstrates that a novel environment activates the cortical cholinergic system, which presumably is associated with arousal mechanisms and selective attentional functions. It also demonstrates that in aging rats the cortical cholinergic hypofunction is associated with a loss of non-spatial working memory.

The effect of oral tacrine administration on cortical and hippocampal extracellular acetylcholine (ACh) levels has been investigated by a microdialysis technique, coupled to a HPLC method, in 6- and 22-24-month-old rats. In order to assess whether the increase in extracellular ACh levels was associated with an improvement in the age-related cognitive impairment, the object recognition and step-trough passive avoidance tests were carried out in the treated rats. The extracellular ACh levels measured in the cortex and hippocampus of aged rats without cholinesterase inhibitor in the perfusion Ringer solution were 39 and 54% lower, respectively, than in the young rats. At the dose of 3 mg kg-1, tacrine brought about a three- to four-fold increase in extracellular ACh levels, both in young and aged rats, which peaked 60-80 min after administration and disappeared within the next 60 min. At the same dose, tacrine caused a twofold increase in extracellular ACh levels in the hippocampus of young rats and a sixfold increase in aged rats. The absolute ACh levels at the peak in aged rats were not significantly different from those of young rats. In the object recognition test, aging rats were unable to discriminate between the familiar and novel object. Discrimination was restored by the administration of tacrine at the dose of 1 and 3 mg kg-1, but not 0. 3 mg kg-1 given 30 min before the first trial. Tacrine (3 mg kg-1 p. o.) administered to aging rats before the training trial significantly improved the acquisition of the passive avoidance conditioned response. Our findings demonstrate that tacrine increased both cortical and hippocampal extracellular ACh levels and improved behavioural functions in aged rats.

Publisher Summary This chapter focuses on the actions of β-peptides in the nucleus basalis (NB) at longer times post-injection. The effects of β-peptides on acetyltransferase (ChAT) immunoreactivity (IR), cortical acetylcholine (ACh) release and behavior are examined. The chapter investigates the toxicity of β-peptides to the cholinergic neurons by direct injection in the forebrain of the rat. As it is reported that the neurotoxic activity of β-amyloid resides within the 25–35 portion of the peptide, the full-length peptide β and the β-peptide are studied. The chapter demonstrates that the administration of β-peptides into the medial septum is followed by a decrease in ACh release from the hippocampus. The chapter also studies the histological and functional changes due to the presence in the NB of β-peptide deposits. It concludes that local injections of amyloid peptides in the rat NB result in local damage and cholinergic hypofunction. However, only the β-(1-40) and β-(25-35) peptides, but not the scrambled form congophilic fibrillary deposits, and induce some behavioral impairment, with the most persistent decrease in the number of cholinergic neurons and ACh release brought about by β-(1- 40). Because the deposit formed by the β-(l-40) peptide lasts largely unaltered for a long time, the injection of this peptide may be a useful model for investigating the temporal progression and neurotoxic effects of an amyloid plaque.

Male Wistar rats (3- and 20-month-old) were perfused i.c.v. with 1.5 micrograms of either nerve growth factor (NGF) or cytochrome C daily for 14 days. At the end of the infusion, the object-recognition test was carried out and extracellular acetylcholine levels (ACh) were measured in the cortex and hippocampus by transversal microdialysis technique. In 20-month-old control rats, the cortical and hippocampal ACh levels were 35 and 45% lower, respectively, than in 3-month-old rats and the ability to discriminate between a familiar and new object was impared. In the old rats treated with NGF, the ACh release as well as the behavioral performance showed no difference from those of young rats. These findings indicate that both ACh levels and memory impairment are improved in aged rats by NGF treatment and suggest that there is a relationship between object recognition and the activity of the forebrain cholinergic system.

In this presentation the term “nootropic drugs” indicates a group of cognition enhancers with different chemical structures, but mostly pyrrolidinone derivatives (Merlini and Pinza, 1989), which enhance information acquisition, protect against learning and memory impairment induced by age, drugs and brain lesions, and have a low toxicity (Schindler et al., 1984). Interest in the potential usefulness of these drugs for treatment of cognitive disorders has resulted in recent years in a better understanding of their pharmacological properties. However, so far the clinical results have not matched the expectations borne out by the pharmacological experiments. This paper is a short overview of the state of the art of the pharmacology and clinical trials on the nootropics.

The extent and duration of cholinergic hypofunction induced by long-term ethanol consumption was investigated in the rat. Ethanol (20% v/v) was administered to male adult Wistar rats as the sole source of fluid for three or six months. Control rats received tap water. The body weight, food and fluid intake in ethanol-treated rats were lower than in control rats throughout the treatment. After three months of ethanol consumption, and one week withdrawal, acetylcholine release in freely moving rats, investigated by microdialysis technique coupled to high-performance liquid chromotagraphy quantification, was significantly decreased by 57 and 32% in the hippocampus and cortex, respectively, while choline acetyltransferase activity was significantly decreased (−30%) only in the hippocampus. A complete recovery of choline acetyltransferase activity and acetylcholine release was found after four ethanol-free weeks. Conversely, after four weeks of withdrawal following six months of ethanol treatment, the recovery in acetylcholine release was not accompanied by that in choline acetyltransferase activity, which remained significantly lower than in control rats in both cortex and hippocampus. The ability of rats to negotiate active and passive avoidance conditioned response tasks, tested after four ethanol-free weeks, was strongly impaired in both three- and six-month ethanol-treated rats. In conclusion, our experiments demonstrate that the development of a long-lasting cholingergic hypofunction requires at least six months of ethanol administration. The hypofunction affects choline acetyltransferase activity and acetylcholine release differently, and undergoes a remarkable recovery.

The effects of different doses of scopolamine, and of the nootropic drugs oxiracetam and aniracetam, were investigated on the performance of male Wistar rats in a T-maze requiring a spatial discrimination in the stem (reference memory) and an alternate discrimination in the arms (working memory). Criterion (90% correct responses) was reached within 3 days of daily training for stem and 9 days for arm discrimination. Scopolamine (0.1, 0.2, 0.6, and 1.0 mg/kg, SC, 60 min before session) significantly impaired working memory, as shown by a decrease in the number of correct alternations, without affecting reference memory. Both nootropic drugs (25–50 and 100 mg/kg PO) 30 min before scopolamine) attenuated the working memory impairment induced by scopolamine.

We report experimental evidence that in an amplitude-modulated laser optical radar system for underwater 3D imaging the observed contrast oscillations as a function of the modulation frequency originate from an interference-like effect between target signal VT and water backscattered radiation VW. The demonstration relies on the ability to perform a direct measurement of VW in a 25 m long test tank. The proposed data processing method enables one to remove the contribution of water backscattering from the detected signal and drastically reduce signal fluctuations due to the medium. Experiments also confirm the possibility to improve the signal to optical noise ratio and contrast by increasing the modulation frequency.

To the Editor: Strong and reliable outcome measures are required in laboratory studies that aim to appraise the extent of the damage in animals subjected to various forms of cerebral ischemia. In this regard, the assessment of histological changes, such as the volume of infarcted tissue or the number of necrotic cells, is considered the gold standard. However, the assessment of functional outcome can also be useful in animal studies that evaluate the effect of new therapeutic agents, since the clinical examination is effortless and not time demanding; moreover, physical testing of the animals can be repeated over time and thus provide data on the evolution of the neurological deficit. A simple neurological score to evaluate sensorimotor performance in rats has recently been developed by Garcia et al.1 It explores six different functions and attributes to each a 3- or 4-point score. The total score, which correlates closely with the severity of the histological injury (in particular with the number of necrotic neurons) in a model of middle cerebral artery (MCA) occlusion in the Wistar rat,1 has been used as one of the outcome measures in studies that estimate the effect of new drugs.2 3 Because of its simplicity and strong correlation with histological damage, this score might be used in other laboratories employing experimental procedures to cause cerebral ischemia. In this regard, evaluation of its reproducibility could be extremely useful, because it is known that the validity of scales evaluating neurological deficit can be affected by interobserver variability.4 5 We have conducted a study to evaluate the impact of personal judgment in the …

We report the results of underwater imaging with an amplitude-modulated single-mode laser beam and miniaturized piezoactuator-based scanning system. The basic elements of the device are a diode laser source at 405 nm with digital amplitude modulation and a microscanning system realized with a small-aperture aspheric lens mounted on a pair of piezoelectric translators driven by sawtooth waveforms. The system has been designed to be a low-weight and rugged imaging device suitable to operate at medium range (approximately 10 m) in clear seawater as also demonstrated by computer simulation of layout performance. In the controlled laboratory conditions a submillimeter range accuracy has been obtained at a laser amplitude modulation frequency of 36.7 MHz.

The effects of GM1 ganglioside (30 mg/kg i.p.) administration for 22 days on choline acetyltransferase (ChAT) activity and noradrenaline (NA) levels in the cerebral cortex and on the acquisition of active and passive avoidance-conditioned responses were investigated in both sham-operated rats and in rats with a unilateral electrolytic lesion of the magnocellular forebrain nuclei (MFN). A statistically significant ChAT decrease in cortical areas ipsilateral to the lesion was found in saline-treated lesioned rats. In the lesioned GM1-treated rats, ChAT activity was only reduced in the frontoparietal areas and was significantly increased in the ipsilateral parieto-occipital areas as well as in both contralateral regions. NA levels in the cortex were neither significantly affected by the lesion nor by GM1 treatment. The lesion impaired the acquisition of active and passive conditioned avoidance responses. GM1 treatment improved acquisition of the active avoidance response in the lesioned rats as indicated by a larger number of avoidances and a smaller number of escape failures during training in comparison with saline treatment. Ganglioside had no effect on the passive avoidance responses. These results demonstrate that GM1 administration facilitates the recovery of the cortical cholinergic system and of behavioral responses impaired by an electrolytic lesion of the cholinergic forebrain nuclei.

The neurochemical and behavioural recovery following unilateral and bilateral lesions of the nucleus basalis was investigated in adult male Wistar rats 20 days and 6 months after surgery. The lesions were made by stereotaxic injections of ibotenic acid. Twenty days after surgery there was a statistically significant choline acetyltransferase decrease in the frontal and parietal ipsilateral cortex of the unilaterally lesioned rats and in the cortex of both hemispheres after bilateral lesions. Cortical high affinity choline uptake rate was significantly decreased 4 days after lesions but showed a rapid recovery within 20 days post-lesion in unilaterally and bilaterally lesioned rats. However, at this time both groups of lesioned rats showed a marked impairment in the acquisition of passive and active (shuttle-box) avoidance conditioned responses. Six months after surgery the decrease in choline acetyltransferase activity was smaller and statistically significant in the ipsilateral frontal cortex only in the unilaterally lesioned rats and in the frontal and parietal cortex of both hemispheres in the bilaterally lesioned rats. High affinity choline uptake was increased in the contralateral hemispheres of the unilaterally lesioned rats and was significantly larger than in the bilaterally lesioned rats. There was no difference in the acquisition of both passive and active avoidance conditioned responses between the sham operated and unilaterally lesioned rats, while the bilaterally lesioned rats could only negotiate the active avoidance conditioned response. In conclusion, our experiments demonstrate a remarkable neurochemical and behavioural recovery within 6 months in rats with a unilateral lesion of the nucleus basalis and only a limited recovery in the bilateral lesioned rats.