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Biomedical subjects

E Marchetti

Publications and source records attributed to E Marchetti.

At least 19 recordsLinked to original sources

Involvement of tissue inhibition of metalloproteinases-1 in learning and memory in mice.

Tissue inhibitor of metalloproteinases (TIMP-1) is one of the four-member family (TIMPs-1-4) of multifunctional proteins that inhibit matrix metalloproteinases (MMPs). Its expression in the hippocampus is neuronal-activity-dependent and dramatically induced by stimuli leading to long-term potentiation (LTP), suggesting that TIMP-1 is a candidate plasticity protein potentially involved in learning and memory processes. We tested this hypothesis in a hippocampus-dependent task using the new olfactory tubing maze, with mice carrying a null mutation for TIMP-1 (TIMP-1 KO) and mice overexpressing TIMP-1 (TIMP-1 (tg)). The TIMP-1 KO mice were significantly impaired in making correct odor-reward associations when compared with their respective wild type (WT) littermates, while TIMP-1 overexpressing mice performed better than their WT controls. Both genetically modified mice learned the paradigm and the timing of the task, like their respective WTs, and no olfactory dysfunctioning was observed. These data suggest that TIMP-1 is involved in learning and memory processes related to the hippocampus, and support the hypothesis that the MMP/TIMP ratio, and hence MMP activity, modulates neuronal plasticity in normal learning and memory processes, while altered proteolytic activity could impair cognitive functions.

Animals↗

Strain differences in rewarded discrimination learning using the olfactory tubing maze.

We trained BALB/c Byllco (C), CD-1, SV 129/SvPasCr1 (129 SV), C57BL/6 (B6) and DBA/2J (D2) mice using the olfactory tubing maze with the hope of gaining insight into behavioral genetics related to learning and memory processes. All strains of mice acquired the odor-reward associations using this new task except the D2 strain. The C, CD-1, and 129 SV consistently remembered the associations from the sixth 20-trial training session, reaching 80% +/- 5 correct responses in session seven. The B6 mice required one more session to reach 76%, while the D2 mice never learned the correct odor-reward associations. All mice learned the paradigm and the timing of the task, although the 129 SV mice decreased slower the inter-trial intervals across sessions. With this new task, D2 mice, with a deficit totally devoted to an impairment on learning and memory, can be used as a model of hippocampal dysfunction, in some respects like that observed in human amnesic patients whose selective hippocampal-dependent memory is deeply impaired. The high-scoring strains (C, CD-1, and 129 SV) seem to be ideal in this task to study a gene-targeting mutation postulated to reduce behavioral performance, and inversely, for D2 mice. The moderate-scoring strain, B6, should be ideal for allowing gene-targeting to go either way. In addition, this new task, which enables automated training of odor associations, could be used for studying the phenomenon of transitivity in mice, as described in rats.

Animals↗

Radiographic appearance of apical closure in apexification: follow-up after 7-13 years.

AIM: This was the radiographic evaluation of 15 maxillary incisors apexification treatment carried out on 7-9 years old patients with periapical pathology due to pulpal necrosis after dental trauma. MATERIALS AND METHODS: The treatment consisted of two phases. The aim of first phase was the formation of a calcified apical barrier through calcium hydroxide medications repeated twice with a three months interval. The aim of the second phase was the obturation of the root canal system once achieved a radiographic evidence of the formation of an apical barrier. The treated teeth were radiographed at six months and then periodically once a year for a period of 7 and 13 years. RESULTS: The radiographic analysis allowed to underline three different kinds of apical formation: a physiological development of the apical portion with a final root length equal to the contralateral tooth; the formation of a cap tissue and an apical development with the final root length slightly shorter than the contralateral tooth; or the formation of different layers of mineralised tissue that aggregate together trough the years. CONCLUSION: Apexification is not a static phenomenon and the apexified area undergoes through the years to a conspicuous readjustment involving bone, apical root tissues and root filling material.

Calcium Hydroxide↗

Prevalence of atypical swallowing: a kinesiographic study.

AIM: The aim of this study was to investigate the prevalence of kinesiographic coincidence between the most cranial position during deglutition of mandible and habitual occlusal position and to evaluate the distribution of clinical diagnosis according to the kinesiographic pattern of deglutition. MATERIALS AND METHODS: 201 random patients in waiting list for dental treatment and classified as orthodontic patients, prosthetic patients, TMD patients and control patients, were evaluated. Kinesiographic records were acquired using K7I and positioning a magnetic sensor frame integral with the head and with the sensory field balanced on an artificial magnet adhering to the mucosa covering the roots of the lower mandibular incisors. The kinesiographic occlusal position was compared to the kinesiographic most cranial position of the mandible during swallowing. RESULTS: 99 patients displayed a discrepancy between the most cranial position during swallowing and the occlusal position. 102 patients did not show any discrepancy. In this group the kinesiographic most cranial position during swallowing coincided with the occlusal position. CONCLUSION: The finding suggests that computerised kinesiography could be useful to study deglutition, detecting in a reliable way the movement pattern. Atypical deglutition seems to be less atypical than previously though in dental patient population and, despite these data confirm its correlation with malocclusion, we noted an inverse correlation with necessity of prosthetic treatment and no higher prevalence in TMD patients.

Adolescent↗

Selective impairment of subcategories of long-term memory in mice with hippocampal lesions accessed by the olfactory tubing maze.

A new apparatus, the olfactory tubing maze for mice, was developed recently to study learning and memory processes in mice in regard to their ethological abilities. As in humans, BALB/c mice with selective bilateral lesions of the hippocampal formation showed selective impairment of subcategories of long-term memory when tested with the olfactory tubing maze. After three learning sessions, control mice reached a high percentage of correct responses. They consistently made the olfactory-reward associations, but antero-dorsal and postero-ventral hippocampal-lesioned mice did not. However, all lesioned mice learned the paradigm and the timing of the task as fast and as well as control mice. These data suggest that the olfactory tubing maze can be used to study subcategories of memory, such as declarative and non-declarative memory, which are similar in some respects to those observed in humans. Consequently, possible memory effects of classical approaches (i.e., pharmacological or lesion studies) or genetic modifications in transgenic or gene-targeting mice can be effectively analyzed using this new apparatus.

Animals↗

Modulation of memory processes and cellular excitability in the dentate gyrus of freely moving rats by a 5-HT4 receptors partial agonist, and an antagonist.

Firstly, olfactory association learning was used to determine the modulating effect of 5-HT4 receptor involvement in learning and long-term memory. Secondly, the effects of systemic injections of a 5-HT4 partial agonist and an antagonist on long-term potentiation (LTP) and depotentiation in the dentate gyrus (DG) were tested in freely moving rats. The modulating role of the 5-HT4 receptors was studied by using a potent, 5-HT4 partial agonist RS 67333 [1-(4-amino-5-chloro-2-methoxyphenyl)-3-(1-n-butyl-4-piperidinyl)-1-propanone] and a selective 5-HT4 receptor antagonist RS 67532 [1-(4-amino-5-chloro-2-(3,5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-propanone]. Agonist or antagonist systemic chronic injections prior to five training sessions yielded a facilitatory effect on procedural memory during the first session only with the antagonist. Systemic injection of the antagonist only before the first training session improved procedural memory during the first session and associative memory during the second session. Similar injection with the 5-HT4 partial agonist had an opposite effect. The systemic injection of the 5-HT4 partial agonist prior to the induction of LTP in the dentate gyrus by high-frequency stimulation was followed by a population spike increase, while the systemic injection of the antagonist accelerated the depotentiation 48 h later. The behavioural and physiological results pointed out the involvement of 5-HT4 receptors in processing related to the long-term hippocampal-dependent memory system, and suggest that specific 5-HT4 agonists could be used to treat amnesic patients with a dysfunction in this particular system.

Aniline Compounds↗

The olfactory tubing maze: a new apparatus for studying learning and memory processes in mice.

In order to have an ethologically relevant behavioral task, we developed the olfactory tubing maze to study learning and memory processes in mice. Mice have to make two olfactory-reward associations across three training sessions. The maze is made up of four identical testing chambers connected to each other by semicircular cylinders. After having chosen one of two odors presented on each side of a testing chamber, the mice have to run to the next testing chamber. From one testing chamber to the next, the side for presentating each odor is randomly assigned. The mouse must run through the entire circular maze to make a response at the four testing chambers. A complete session consists of 20 trials made by running five times clockwise through the maze with 4 trials per run. The training and data recording are fully automated by a custom-made software program. Three different experiments were performed. The results indicated that mice can easily make the olfactory discriminative associations in this new apparatus. Analysis of the data suggests that it would be possible using this olfactory tubing maze to study sub-categories of memory similar in some respects to those observed in humans. Consequently, possible effects on learning and memory of classical treatments (i.e. pharmacological or lesions) or genetic modifications in transgenic or gene-targeting mice could be tested.

Animals↗

Differential modulation of the 5-HT(4) receptor agonists and antagonist on rat learning and memory.

Recent data suggest that activation of 5-HT(4) receptors may modulate cognitive processes such as learning and memory. In the present study, the effects of two potent and selective 5-HT(4) agonists, RS 17017 [1-(4-amino-5-chloro-2-methoxyphenyl)-5- (piperidin-1-yl)-1-pentanone hydrochloride] and RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3- (1-n-butyl-4-piperidinyl)-1-propanone], were studied in an olfactory associative discrimination task. The implication of 5-HT(4) receptors in the associative discriminative task was suggested by the following observation. Injection of a selective 5-HT(4) receptor antagonist RS 67532 [1-(4-amino-5-chloro-2-(3, 5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-pentanone; 1 mg/kg: i.p.] before the third training session induced a consistent deficit in associative memory during the following training sessions. This deficit was absent when the antagonist was injected together with either a specific hydrophilic 5-HT(4) (RS 17017, 1 mg/kg) or a specific hydrophobic (RS 67333, 1 mg/kg) 5-HT(4) receptor agonist. RS 67333 was more potent than RS 17017. This difference in potency certainly reflects a difference in their capacity to enter into the brain. This is also likely to be the reason why, injected alone, the hydrophobic 5-HT(4) agonist (RS 67333) but not the hydrophilic 5-HT(4) agonist (RS 17017) improved learning and memory performance.

Aniline Compounds↗

Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing.

Neisseria meningitidis is a major cause of bacterial septicemia and meningitis. Sequence variation of surface-exposed proteins and cross-reactivity of the serogroup B capsular polysaccharide with human tissues have hampered efforts to develop a successful vaccine. To overcome these obstacles, the entire genome sequence of a virulent serogroup B strain (MC58) was used to identify vaccine candidates. A total of 350 candidate antigens were expressed in Escherichia coli, purified, and used to immunize mice. The sera allowed the identification of proteins that are surface exposed, that are conserved in sequence across a range of strains, and that induce a bactericidal antibody response, a property known to correlate with vaccine efficacy in humans.

Amino Acid Sequence↗

Adaptive-optics corrections available for the whole sky

Adaptive-optics systems can in principle allow a telescope to achieve performance at its theoretical maximum (limited only by diffraction), by correcting in real time for the distortion of starlight by atmospheric turbulence. For such a system installed on an 8-m-class telescope, the spatial resolution and sensitivity could be up to 100 times better than conventional imaging. Adaptive-optics corrections have hitherto been achieved only for regions of the sky within a few arcseconds of a bright reference source. But it has been proposed theoretically that by using multiple guide stars, the tomography of atmospheric turbulence could be probed and used to extend adaptive-optics corrections to the whole sky. Here we report the experimental verification of such tomographic corrections, using three off-axis reference stars approximately 15 arcsec from the central star. We used the observations of the off-axis stars to calculate the deformations of the wavefront of the central star, and then compare them with the real measured values. This tomographic approach is found to reduce variations in the wavefront by approximately 92%. Our result demonstrates that a serious barrier to achieving diffraction-limited seeing over the whole sky has been removed.

Journal Article↗

Correlations between electrophysiological observations of synaptic plasticity modifications and behavioral performance in mammals.

Within the past century it has been well established that most mature neurons lose their ability to divide. Since then, it has been assumed that behavioral performance leads to synaptic changes in the brain. The existence of these potential changes has been demonstrated in numerous experiments, and different mechanisms contributing to synaptic plasticity have been discovered. Many structures involved in different types of learning have now been identified. This article reviews the different methods used with mammals to detect electrophysiological modifications in synaptic plasticity following behavior. Evidence of long-term potentiation and long-term depression has been found in the hippocampus and cerebellum, respectively, and empirical data has been used to correlate these mechanisms with specific learning performance. Similar observations were made recently in the septum and amygdala. These phenomena seem to be involved in maintaining the performance in the cortical areas of the brain. Ongoing attempts to find the relationship between behavioral performance and modifications in synaptic efficacy allow to speculate upon the dynamics of cellular mechanisms that contribute to the ability of mammals to modify wide neuronal networks in the brain during their life.

Animals↗

Cephalometric study of posterior airway space in patients affected by Class II occlusion and treated with orthognathic surgery.

The posterior airway space (PAS) is delimited by hard and soft tissues with anomalies that may produce alterations in volume. In patients with severe hypoplasia of the middle and lower third of the face, a decrease in volume of the PAS is present, producing a polysyndromic condition that ranges from snoring to obstructive sleep apnea syndrome (OSAS). The aim of this report is to define PAS variations via a cephalometric study in patients affected by class II occlusion and treated with orthognathic surgery. The authors studied 44 patients affected by class II occlusion who underwent surgery to correct the maxillomandibular malformation. The patient cohort was classified according to the type of surgery performed: Le Fort I osteotomy with or without a sagittal split osteotomy. To evaluate PAS variation, cephalometric analyses were performed by pre- and postoperative lateral teleradiography. This study showed an increase in PAS volume, especially at the hypopharynx and the lower part of the oropharynx, when the sagittal split osteotomy was performed and/or the maxilla was moved anteriorly and/or superiorly. A decrease of PAS can be seen in downward and/or backward maxillary movements. In conclusion, cephalometric studies of hard and soft tissues (such as tongue, pharynx, soft palate, etc.) should be performed in all patients affected by maxillomandibular malformation. This approach may provide data for the diagnosis of respiratory pathologies that vary from snoring to OSAS.

Airway Obstruction↗

Obstructive sleep apnea in a growing patient.

Sleep apnea syndrome (SAS) is a complex respiratory disorder that is very difficult to diagnose and to treat surgically as well as medically. SAS can affect growing patients as well as adults. SAS shows a central, an obstructive, and a mixed form. Diagnosis is based on clinical examination of the patient and instrumental examinations such as teleradiography, nuclear magnetic resonance imaging (NMR), three-dimensional computed tomography, polysomnography, rhinomanometry, and spirometry. The patient presented has an obstructive form of SAS in addition to Crouzon's disease. He underwent a Le Fort III osteotomy to obtain an advancement of the orbitomaxillary complex, allowing an increase in volume of posterior airway space at the level of the hypopharynx.

Craniofacial Dysostosis↗

New approach to the surgical treatment of severe exophthalmos in Graves disease.

In the last few years, various surgical techniques to correct orbital decompression in patients with Graves ophthalmopathy have been proposed. In those patients in whom a high degree of exophthalmos is mainly the result of the hypertrophied endorbital muscles with respect to endorbital fat hypertrophy, lipectomy is insufficient to obtain an acceptable increase of endorbital volume. The authors propose a method that provides for the monobloc bilateral quadrantotomy by extracranial access. Despite traditional methods of decompression, the advantage of this technique is better advancement of the orbital margins. The bicoronal and endoral incisions guarantee no facial scars. Compared with the craniotomy, the extracranial access is also less stressful for the patient.

Adipose Tissue↗

Prenatal diagnosis: evolution in craniofacial surgery.

Prenatal diagnosis of craniomaxillofacial malformations permits early surgery, before 6 months of life and possibly, in the near future, in utero, thereby obtaining the best aesthetic and functional results. Increased knowledge of embryology has largely improved the diagnosis of craniomaxillofacial anomalies, their classification, and therapeutic protocols. We analyzed nine pregnancies (one twin) in which cleft lip and palate (CLP)--isolated or associated with, for example, holoprosencephaly, hypertelorism, and micrognathia--was diagnosed by ultrasonography. Only one fetus of these pregnancies was later operated on in our unit. This patient, with 7 years follow-up, represents our clinical case. For these cases, early diagnosis of CLP allowed informed parental choice regarding the continuation or termination of the affected pregnancy and planning of surgical procedures to correct the malformation. This is demonstrated by the presented clinical case involving an infant operated on within 6 months with success.

Child↗

Opposite effects depending on learning and memory demands in dorsomedial prefrontal cortex lesioned rats performing an olfactory task.

In this study, the functional properties of the dorsomedial prefrontal cortex (dmPFC) of the rat were examined in two olfactory tasks. In a successive cue olfactory discrimination task, dmPFC lesioned animals improved performance across sessions more rapidly than operated control animals. In an olfactory task using fixed interval training, animals with similar lesions were impaired. Both effects, although opposite, can be explained by a temporal processing deficit. The present results seem to indicate that the dmPFC is required for timing, classified as part of non-declarative memory. As reference memory improved in the lesioned animals, the finding is that the dmPFC supports non-declarative memory and thus interacts with declarative memory in the long-term formation of the associations between a particular stimulus (olfactory cue) and particular responses.

Animals↗

Stimulation of cardiac sarcoplasmic reticulum calcium pump by acylphosphatase. Relationship to phospholamban phosphorylation.

Ca2+ transport by cardiac sarcoplasmic reticulum is tightly coupled with the enzymatic activity of Ca2+-dependent ATPase, which forms and decomposes an intermediate phosphoenzyme. Heart sarcoplasmic reticulum Ca2+ pump is regulated by cAMP-dependent protein kinase (PKA) phospholamban phosphorylation, which results in a stimulation of the initial rates of Ca2+ transport and Ca2+ ATPase activity. In the present studies we found that acylphosphatase from heart muscle, used at concentrations within the physiological range, actively hydrolyzes the phosphoenzyme of cardiac sarcoplasmic reticulum Ca2+ pump, with an apparent Km on the order of 10(-7) M, suggesting an high affinity of the enzyme for this special substrate. In unphosphorylated vesicles acylphosphatase enhanced the rate of ATP hydrolysis and Ca2+ uptake with a concomitant significant decrease in apparent Km for Ca2+ and ATP. In vesicles whose phospholamban was PKA-phosphorylated, acylphosphatase also stimulated the rate of Ca2+ uptake and ATP hydrolysis but to a lesser extent, and the Km values for Ca2+ and ATP were not significantly different with respect to those found in the absence of acylphosphatase. These findings suggest that acylphosphatase, owing to its hydrolytic effect, accelerates the turnover of the phosphoenzyme intermediate with the consequence of an enhanced activity of Ca2+ pump. It is known that phosphorylation of phospholamban results in an increase of the rate at which the phosphoenzyme is decomposed. Thus, as discussed, a competition between phospholamban and acylphosphatase effect on the phosphoenzyme might be proposed to explain why the stimulation induced by this enzyme is less marked in PKA-phosphorylated than in unphosphorylated heart vesicles.

Acid Anhydride Hydrolases↗

Acylphosphatase stimulates Ca2+ transport and Ca(2+)-dependent ATPase activity in cardiac sarcoplasmic reticulum.

Acylphosphatase purified from heart muscle actively hydrolyzes the phosphoenzyme intermediate of cardiac sarcoplasmic reticulum Ca(2+)-ATPase. This effect was evident with acylphosphatase concentrations (up to 100 units/mg sarcoplasmic reticulum protein) that fall within the physiological range, and the low value of the apparent Km, on the order of 10(-7)M, suggests a high affinity towards this special substrate. Moreover, acylphosphatase addition to sarcoplasmic reticulum vesicles significantly enhanced the rate of Ca(2+)-dependent ATP hydrolysis. Maximal stimulation, observed with 100 units/mg vesicular protein, resulted in an ATPase activity which was about two folds over basal value. The same acylphosphatase concentration increased at a similar extent the rate of ATP driven Ca2+ influx into sarcoplasmic reticulum vesicles. Taken together these findings lead to suppose that acylphosphatase, owing to its hydrolytic activity, induces an accelerated turnover of the phosphoenzyme intermediate, whence an overall stimulation of heart sarcoplasmic reticulum Ca2+ pump, affecting both ATP hydrolysis and Ca2+ influx.

Acid Anhydride Hydrolases↗