Oxidative profile in patients with colon cancer: effects of Ruta chalepensis L.

AIM: To verify the involvement of free radicals in tumor progression and to investigate the effects of an ethanolic extract of Ruta Chalepensis L. and of rutin in blood of patients with colon cancer. MATERIALS AND METHODS: Leaves of Ruta Chalepensis L. were collected in the area around Catania (Italy). For the preparation of the ethanol extract of leaves, an exhaustive extraction of 100 g of the drug was carried out in Soxhlet with 800 ml of 95% ethanol. Fifty-six patients with colorectal cancer were randomly selected for this study; among these, 34 were affected by an early stage (T1 N0 M0 according to scale), while 22 were affected by an advanced stage (T4, N1-2, M0) of cancer. Data obtained from these patients were compared with those of a control group consisting of 20 healthy subjects. Plasma of each sample was used for determining non-proteic antioxidant capacity, thiol groups, lipid hydroperoxides and nitrite/nitrate levels, evaluated by spectrophotometric tests. In addition, percentage of haemolysis was evaluated incubating (for 2 hours at 37 degrees C) erythrocyte suspension with a free radical donor (50 mM 2,2'-azobis-amidino propane chloridrate), in the presence or absence of ethanolic extract of Ruta Chalepensis L. (250 microg/ml) or rutin (1 mM). RESULTS: Non-proteic antioxidant capacity was significantly lower in cancerous patients than in healthy subjects (p < 0.001). This decrease was stage-related. In fact, non-proteic antioxidant capacity resulted lower in advanced than in early colorectal cancer (p < 0.001). The same significant stage-related decrease was observed in plasma thiol groups (p < 0.001). Coherently with the decrease in non-proteic antioxidant capacity and thiol groups, higher levels of lipid hydroperoxides and nitrite/nitrate were observed in patients with colorectal cancer with respect to healthy subjects (p < 0.001) and the increase in these markers of oxidative stress was related to the cancer stadiation. Neoplastic patients also showed an increased percentage of oxidative hemolysis respect to controls and the haemolytic damage was correlated with the stage of colon cancer. Both the extract of Ruta Chalepensis L. and rutin were able to protect erythrocytes from oxidative stress induced by the free radical donor, but the extract of Ruta Chalepensis L. was more effective than rutin. This protective effect was significant only in erythrocytes from patients with early colorectal group, whereas no significant modification was induced by Ruta Chalepensis L. or rutin in red blood cells from advanced colorectal cancer patients exposed to the same experimental conditions. CONCLUSION: Oxidative stress correlates with colon cancer stadiation and both the extract of Ruta chalepensis and rutin are able to protect red blood cells from radical-induced damage. However, their effects are significant in early stages of cancer. So these natural antioxidants might be usefull to prevent carcinogenesis and/or tumor progression.

Noradrenaline modulates neuronal responses to GABA in vestibular nuclei.

The effects of noradrenaline (NA) on the inhibitory responses to GABA were studied in vivo in neurons of the vestibular nuclei of the rat using extracellular recordings of single unit electrical activity and a microiontophoretic technique of drug application in loco. NA application influenced GABA-evoked inhibitions in 82% of tested neurons, depressing them in 42% and enhancing them in 40% of cases. The more frequent action of NA on GABA responses was depressive in lateral and superior vestibular nuclei (50% of neurons) and enhancing in the remaining nuclei (56% of neurons). The most intense effect of NA application was the enhancement of GABA responses induced in a population of lateral vestibular nucleus neurons, characterized by a background firing rate significantly higher than that of other units. The alpha(2) noradrenergic receptor agonist clonidine mimicked the enhancing action of NA on GABA responses; this action was blocked by application of the specific alpha(2) antagonist yohimbine. The beta adrenergic agonist isoproterenol induced either depressive or enhancing effects on GABA responses; the former more than the latter were totally or partially blocked by application of the beta antagonist timolol. It is concluded that NA enhances GABA responses by acting on noradrenergic alpha(2) and to a lesser extent beta receptors, whereas depressive action involves beta receptors only. These results confirm the hypothesis that the noradrenergic system participates in the regulation of the vestibulospinal and the vestibulo-ocular reflexes and suggest that conspicuous changes of NA content in brain due to aging or stress could lead to a deterioration in the mechanisms of normal vestibular function.

Aminergic control of neuronal firing rate in thalamic motor nuclei of the rat.

The effects induced on neuronal firing by microiontophoretic application of the biological amines noradrenaline (NA) and 5-hydroxytryptamine (5-HT) were studied "in vivo" in ventral-anterior (VA) and ventrolateral (VL) thalamic motor nuclei of anaesthetized rats. In both nuclei the amines had a mostly depressive action on neuronal firing rate, the percentage of units responsive to NA application (88%) being higher than to 5-HT (72%). Short-lasting (less than 2 min) and long lasting (up to 20 min) inhibitory responses were recorded, the former mostly evoked by NA and the latter by 5-HT ejection. In some cases 5-HT application had no effect on the firing rate but modified the firing pattern. NA-evoked responses were significantly more intense in VL than in VA neurons. Short-lasting inhibitory responses similar to NA-induced effects were evoked by the alpha2 adrenergic receptor agonist clonidine and to a lesser extent by the beta adrenergic receptor agonist isoproterenol. Inhibitory responses to 5-HT were partially mimicked by application of the 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) and of the 5-HT2 receptor agonist alpha-methyl-5-hydroxytryptamine (ALPHA-MET-5-HT). The latter evoked excitatory responses in some cases. Both 5-HT agonists were more effective on VA than on VL neurons. The effects evoked by agonists were at least partially blocked by respective antagonists. These results suggest that although both 5-HT and NA depress neuronal firing rate, their effects differ in time course and in the amount of inhibition; besides aminergic modulation is differently exerted on VA and VL.

Effects of 5-hydroxytryptamine on the neuronal firing rate of bulbar reticular neurons.

The effects of 5-hydroxytryptamine (5-HT) on neuronal firing rate were studied in the reticular gigantocellular nucleus (GRN) and, for a comparison, in the interstitial (IRN), the parvicellular (PRN) and the lateral (LRN) nuclei, sharing some of GRN functional characteristics. Unitary extracellular recordings performed in anesthetized rats demonstrated that microiontophoretic application of 5-HT modulated the background firing rate in 92% of GRN, in 100% of IRN and LRN, and in 77% of PRN tested neurons. In GRN, 5-HT application induced excitatory responses in 49% of the neurons tested and inhibitions in 43% of them. Both types of effects were dose dependent and appeared scattered throughout the nucleus. Enhancements and decreases of firing rate in response to 5-HT application were also recorded in IRN (58% and 42% respectively), LRN (43% and 57%) and PRN (36% and 41%). The 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) mimicked 5-HT evoked inhibitions in all the nuclei tested and induced weak inhibitory responses also in neurons excited by 5-HT. The 5-HT2A receptor agonist alphamethyl-5-hydroxytryptamine (alpha-me-5-HT) mimicked excitatory as well as inhibitory responses to 5-HT, the former prevailing in GRN and the latter in the remaining reticular nuclei. Both excitatory and inhibitory responses to 5-HT were partially or totally blocked by the application of 5-HT2 receptor antagonist ketanserin. It is concluded that an extended, strong and differentiated control is exerted by 5-HT on the electrical activity of bulbar reticular neurons. Both 5-HT(1A) and 5-HT(2A) receptors mediate these effects, but the involvement of other receptors appears probable.

Noradrenergic modulation of glutamate-induced excitatory responses in single neurons of the red nucleus: an electrophysiological study.

The effect induced by noradrenaline (NA) on the spiking activity evoked by glutamate (Glu) on single neurons of the mesencephalic red nucleus (RN) of the rat was studied extracellularly. Long-lasting microiontophoretic applications of the amine induced a significant and reversible depression of the responsiveness of RN neurons to Glu. This effect was mediated by noradrenergic alpha2 receptors since it was mimicked by application of clonidine, an alpha2 adrenoceptor agonist, and blocked or at least reduced by application of yohimbine, an antagonist of NA for the same receptors. The effect appears homogeneously throughout the nucleus and is independent of the effect of NA on baseline firing rate. Application of isoproterenol, a beta adrenoceptor agonist, either enhanced or depressed neuronal responses to Glu in a high percentage (86%) of the tested neurons. Moreover, application of timolol, a beta adrenoceptor antagonist, was able to strengthen the depressive effects induced by NA application on neuronal responsiveness to Glu. Although these data suggest some involvement of beta adrenergic receptors in the modulation of neuronal responsiveness to Glu, the overall results indicate a short-term depressive action of NA, mediated by alpha2 receptors, on the responsiveness of RN neurons and suggest that stress initially leads to an attenuation of the relay function of the RN.

Effects of motor cortex and single muscle stimulation on neurons of the lateral vestibular nucleus in the rat.

The neuronal responses to stimulation of motor cortical sites and of forelimb single muscles were studied in the lateral vestibular nucleus of anaesthetized rats. Of the 228 neurons tested for response to stimulation of contralateral motor cortex, 63% responded to cortical sites controlling extensor muscles and 30% to those controlling flexors. The corresponding figures for responders to ipsilateral stimulation were 34 and 21%. Vestibulospinal units responded to cortical sites controlling extensor and flexor muscles whereas the remaining lateral vestibular nucleus neurons, very reactive to cortical sites controlling extensor muscles, responded little to contralateral and not at all to ipsilateral cortical sites controlling flexor muscles. The effects evoked by contralateral cortical sites controlling extensors varied, those induced by cortical sites controlling flexors were inhibitory in 77% of cases. The responses to ipsilateral motor cortex stimulation differed not so much by cortical sites controlling extensor or flexor muscles as by whether the neuron was in the dorsal or ventral zone of the lateral vestibular nucleus: mixed in the former, all inhibitory in the latter. Of the lateral vestibular nucleus units tested for response to stimulation of ipsilateral or contralateral forelimb distal muscles, only 11% responded. All the vestibulospinal units responsive to muscle stimulation lay in the dorsal zone of the nucleus. The remainder, dorsal or ventral, were not responsive to contralateral muscles. Single lateral vestibular nucleus cells influenced both by ipsilateral muscle and by contralateral motor cortex made up 24% of the pool, vestibulospinal and non-vestibulospinal. They fell into three groups: responsive to one or both structures but responding more strongly to combined stimulation; responsive to each of the two structures but showing a response to combined stimulation not significantly different from that evoked by the cortex alone; responsive only to combined stimulation. The lateral vestibular nucleus units included in these three groups accounted for 29% of those tested for response to extensor muscles and cortical sites controlling extensors and 15% of those tested for response to flexor muscles and cortical sites controlling flexors. Twenty-five per cent of the vestibulospinal neurons responded both to contralateral muscles and to ipsilateral motor cortex stimulation but none of the non-vestibulospinal neurons responded to both. All the responders to both were in the dorsal zone of the lateral vestibular nucleus and responded to extensor stimuli, always in the same way. These results indicate that motor cortex output exerts a major influence on lateral vestibular nucleus discharges, while the muscle afferents have a modulatory influence on the lateral vestibular nucleus responses to cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Pyramidal input to the intracerebellar nuclei of the cat.

In unanesthetized cats it has been found that pyramidal volleys elicited upon medullary pyramidal tract stimulation were capable of modifying the discharge of 41% of intracerebellar nuclear cells, via pontocerebellar systems impinging predominantly on the lateral cerebellar cortex. The incidence of responsive cells was 80% in the dentate nucleus compared with 10% in the fastigial nucleus, 11% in the anterior and 12% in the posterior division of the interpositus nucleus. The response was in 59% of the cases excitation followed by inhibition, in 30% of the cases a pure excitation and in 11% of the cases a pure inhibition. Excitation, pure or followed by inhibition, had a mean latency of 5.78 ms and a mean duration of 12.21 ms, while inhibition displayed a mean latency of 9.03 ms and a mean duration of 34.64 ms. The possible functional significance of the pyramidal input to the lateral cerebellum is briefly discussed in relation to a possible convergence of pyramidal and associative impulses in single cerebellar neurons.

Effects of noradrenaline on the firing rate of vestibular neurons.

The effects of microiontophoretic noradrenaline on the firing rate of neurons located in the vestibular complex have been studied in anaesthetized rats. Eighty-five per cent of the neurons tested in all the vestibular nuclei modified their background firing rate upon noradrenaline application, generally by reducing it (86% of them). In few cases inhibitions were followed by a rebound. Responses were dose-dependent. No significant difference was found between vestibular neurons projecting to the spinal cord and those delivering their fibres to the oculomotor complex. Phentolamine, an alpha-adrenergic antagonist, blocked the noradrenaline-evoked inhibitions, whereas beta-adrenergic antagonist timolol was ineffective or enhanced them. Furthermore, responses were blocked by yohimbine, an alpha 2-adrenergic antagonist, and mimicked by clonidine, an alpha 2-adrenergic agonist, in the majority of neurons. In few cases prazosin, an alpha 1-adrenergic antagonist, was able to antagonize weak inhibitions and phenylephrine, an alpha 1-adrenergic agonist, to evoke an inhibitory effect blocked by prazosin. Isoproterenol, a beta-adrenergic agonist was totally ineffective on the neuronal firing rate. It is concluded that noradrenaline can modify the level of neuronal activity in the vestibular complex by acting mostly, but not exclusively, through alpha 2-adrenergic receptors. An influence of noradrenergic systems on the vestibular function by a direct action of noradrenaline inside the vestibular nuclei is proposed.

Serotonin-evoked modifications of the neuronal firing rate in the superior vestibular nucleus: a microiontophoretic study in the rat.

Microiontophoretic ejection (10-100 nA) of serotonin (5-hydroxytryptamine) into the superior vestibular nucleus induced modifications of the mean firing rate in 87% of the neurons examined. The responses to 5-hydroxytryptamine application were excitatory in 48% of the cells, inhibitory in 29%, and biphasic (inhibitory/excitatory) in the remaining 10%. The excited neurons were scattered throughout the nucleus; the units inhibited or characterized by biphasic responses were distinctly more numerous in the ventrolateral sector of the nucleus. The magnitude of both excitatory and inhibitory effects was dose-dependent. The excitatory responses to 5-hydroxytryptamine were blocked or greatly reduced by two 5-hydroxytryptamine antagonists, methysergide and ketanserin, or even reversed in many cases. Inhibitory responses were enhanced by simultaneous application of 5-hydroxytryptamine antagonists in half of the units studied. In the remaining units, ketanserin left the response unmodified, whereas methysergide reduced but never quite blocked it. The application of 5-methoxy-N,N- dimethyltryptamine, a 5-hydroxytryptamine agonist more effective on 5-hydroxytryptamine1 than on 5-hydroxytryptamine2 receptors, and of 8-hydroxy-2(di-n-propyl-amino) tetralin, a 5-hydroxytryptamine1A-specific agonist, induced a decrease in the firing rate which was unaffected by methysergide. These results support the hypothesis that 5-hydroxytryptamine exerts various functions throughout the superior vestibular nucleus by various receptors and that the inhibitory action is limited to an area of it.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolactin induces chitotriosidase gene expression in human monocyte-derived macrophages.

Human chitotriosidase (Chit), a chitinolytic enzyme, is a member of the chitinase family. In human's plasma Chit activity have been proposed as a biochemical marker of macrophage activation in several lysosomal diseases. Recently we found that Chit activity is higher in patients affected by Plasmodium falciparum malaria infection suggesting that chitotriosidase may induce an immunological response. The pituitary hormone prolactin (PRL) is a multifunctional polypeptide also produced by immune cells and represents a key component of the neuroendocrine-immune loop. The presence of PRL receptors in macrophage suggests that PRL is involved in regulating functions in these cells. Our objective in this study was to investigate the effect of PRL in human monocyte-derived macrophages (HMMs) on Chit production. Administration of PRL in HMMs was found to increase both expression and activity of Chit in a time and dose dependent manner as quantified, respectively, by real time PCR and Chit activity assay. PRL-treated monocyte-derived macrophages showed also an enhanced release of superoxide anion (O2-) release. Our observations confirm that PRL regulates HMMs activation and suggest, for the first time, that it influences immune function also through the induction of Chit activity.

Electromyographic effects of serotonin application into the lateral vestibular nucleus.

Electromyographic responses (EMGs) of limb muscles were studied during microiontophoretic application of 5-hydroxytryptamine (5-HT) into the lateral vestibular nucleus (LVN) or the spinal vestibular nucleus (SpVe) of anaesthetized rats. The aim was to ascertain whether the level of 5-HT in these nuclei was able to modulate muscle responsiveness. Increased levels of 5-HT in LVN (and to a weaker extent in SpVe) enhanced the EMGs of proximal extensor muscles and depressed those of flexors. The 5-HT2A receptor antagonist ketanserin, applied into the LVN, prevented 5-HT effects on EMG-evoked responses. It is concluded that 5-HT can modulate the motor output via the vestibulospinal pathway, exerting a differential control over flexor and extensor muscles.

Noradrenaline modifies the spontaneous spiking activity of red nucleus neurons in the rat by activation of alpha 2- and beta-adrenoceptors.

We have investigated the effects of noradrenaline (NA) on the spontaneous firing activity of red nucleus (RN) neurons recorded extracellularly in anesthetized rats by using an in vivo electrophysiological technique. Microiontophoretic applications of NA (5-100 nA for 30 s) modified the background firing rate in 99 out of 124 neurons and three different patterns of response were observed in distinct cells. In 61% of the responding neurons NA decreased the mean firing rate, whereas 22% of the neurons responded to NA application with an increase of their spiking activity; in a smaller group of cells (17%) NA exerted a biphasic inhibitory/excitatory effect on the spontaneous firing rate. The effects of NA were reversible and dose-dependent. From histological examination, the neurons responding to NA with a purely inhibitory effect were scattered throughout the RN. On the other hand, the neurons responding to NA with an excitation were found to be more numerous in the dorso-medial part of the RN, whereas the neurons in which NA induced biphasic effects appeared to be segregated in the outer lateral portion of the RN. The alpha 2-adrenoceptor antagonist yohimbine completely blocked the inhibitory effect of NA but was unable to antagonize the excitatory response. In addition, the inhibitory effect of NA was mimicked by clonidine, a selective agonist of alpha 2-adrenoceptors; clonidine had no effect on those cells which responded to NA with an increase of the mean firing rate. The excitatory effect of NA was mimicked by the beta-receptor agonist isoprenaline and was antagonized by timolol, a selective antagonist of beta-adrenoceptors. Isoprenaline was ineffective in those cells in which NA exerted inhibitory responses. Taken together, our results indicate that the inhibitory effect of NA on the firing activity of rat RN neurons were mediated by alpha 2-adrenoceptors, whereas beta-adrenoceptors were responsible for the excitatory effects.

Excitatory and inhibitory effects of 5-hydroxytryptamine on the firing rate of medial vestibular nucleus neurons in the rat.

The effects of microiontophoretic application of 5-hydroxytryptamine (5-HT) on the neuronal firing rate of the medial vestibular nucleus (MVN) were studied in anaesthetized rats. Ninety-three % of the units modified their background activity following 5-HT iontophoresis, enhancements of the firing rate being recorded in 42%, decreases in 38% and biphasic effects in 13%. 5-HT antagonists methysergide and ketanserin blocked the excitatory but not the inhibitory responses to 5-HT. These latter were, however, mimicked by 5-HT agonists 5-methoxy-N,N-dimethyltryptamine (5MeODMT) and 8-hydroxy-2(di-n-propyl-amino)tetralin (8-OH-DPAT). It is concluded that 5-HT can variously influence the background activity of MVN neurons and that 5-HT2 and probably 5-HT1A receptors are involved in the responses.

Integration of cortical and peripheral information in the lateral vestibular nucleus in the cat.

Neuronal discharges in the lateral vestibular nucleus (LVN) of the cat were studied during stimulation of a forelimb muscle and of a site in the contralateral motor cortex (area 4) capable of activating the same muscle. About one third of the LVN units were reactive to both stimulations or at least responded to one (cortex or muscle) but modified the response pattern when the other was stimulated also. The patterns evoked by a muscle were mostly enhanced on simultaneous stimulation of the cortical zone controlling the same muscle and vice versa. Only in the dorsal division the excitatory responses to muscle stimulation were depressed by simultaneous cortical stimulation. Some functional implications are proposed.

Motor responses evoked by microstimulation of cerebellar interpositus nucleus in cats submitted to dorsal rhizotomy.

In cats with C4-T2 unilateral dorsal rhizotomy, stimulation of interpositus nucleus of the cerebellum, ipsilateral to the deafferented side, elicits in forelimbs single muscle contractions, which display threshold, latencies and spatial-temporal characteristics similar to those of the muscular responses produced in the other forelimb, upon stimulation of interpositus nucleus of the intact side. Motor effects induced by the interpositus nucleus-stimulation on the deafferented side disappear following red nucleus lesions. Single muscle contractions triggered from interpositus nucleus are, therefore, mediated by impulses impinging on alpha-motoneurons, via the rubrospinal pathway.

Neuronal responses in vestibular nuclei to dorsal raphe electrical activation.

The effects of dorsal raphe (DR) electrical stimulation on the neuronal activity of vestibular nuclei were studied in anaesthetized rats. The aim was to establish whether the central systems classically involved in nociceptive functions are able to influence vestibular secondary neurons. DR activation induced modifications of the firing in 70% of the tested neurons, the percentage being similar in the lateral (LVN), superior (SVN), and spinal (SpVN) vestibular nuclei. Three different types of responses were recorded: long-lasting modifications (generally enhancements) of the mean firing rate (43%), short-latency response patterns (14%), both (43%). Short-latency response patterns were more numerous in LVN than in SVN. Iontophoretic applications of 5-HT antagonists Methysergide and Ketanserin blocked long-lasting effects but were scarcely effective on the short-latency response patterns evoked by DR stimulation. It is concluded that DR exerts a double control on secondary vestibular neurons: a generalised excitatory influence by serotoninergic fibers and a specific action mostly targeted on LVN, by nonserotoninergic pathways.

Noradrenergic modulation of neuronal responses to n-methyl-d-aspartate in the vestibular nuclei: an electrophysiological and immunohistochemical study.

Excitatory responses evoked by N-methyl-d-aspartate (NMDA) in the vestibular nuclei (VN) of the rat were studied in vivo during microiontophoretic application of noradrenaline (NA) and/or its agonists and antagonists. Ejection of NA-modified excitatory responses mediated by NMDA receptors (NMDAR) in all neurons tested; the effect was enhancement in 59% of cases and depression in the remaining 41%. Enhancements prevailed in all VN with the exception of the lateral vestibular nucleus, where both effects were recorded in an equal number of cases. The enhancing action of NA on NMDAR-mediated responses was mimicked by the noradrenergic beta-receptor agonist isoproterenol, the beta1 specific agonist denopamine and the alpha2 agonist clonidine. These effects were blocked respectively by the generic beta-receptor antagonist timolol, the beta1 antagonist atenolol and the alpha2 antagonist yohimbine. In contrast, application of the alpha1 receptor agonist cirazoline and the specific alpha1 antagonist prazosin respectively mimicked and partially antagonized the depression of NMDAR-mediated excitations induced by NA. Double-labeling immunohistochemical techniques demonstrated broad colocalization of NMDAR (specifically NR1 and NR2 subunits) with noradrenergic receptors (alpha1, alpha2 and beta1) in many VN neurons; only minor differences were found between nuclei. These results indicate that NA can produce generalized modulation of NMDAR-mediated excitatory neurotransmission in VN, which may in turn modify synaptic plasticity within the nuclei.

[Craniofrontonasal syndrome: genetic aspects and description of a clinical case]. / La sindrome craniofrontonasale: aspetti genetici e descrizione di un caso clinico.

The authors describe the case of a child with craniofrontonasal syndrome (CFNS) (MIM 304110), the diagnostic process performed, the identification of the main clinical features in the proband (hypertelorism, facial asimmetry, bifid nasal tip, corpus callosum hypoplasia, broad thumb, curly and wiry hair), and the comparison with known data in literature. They also describe the detection, through gene sequencing of EFNB1, of responsible mutation and its correlation with the phenotypic variants. They explain the etiophatogenetic basis of the "unusual" inheritance pattern of CFNS: X-linked disease that occurs with greater severity in heterozygous females than hemizygous males. Finally, attention is placed on the need for careful genetic counseling for patients with CFNS, with special care in familial anamnesis taking. In the studied case, the presence of abnormalities of thumbs in the proband's mother and in two of her cousins, orientates principally toward a mutation of maternal origin or to a suspected somatic and germline mosaicism by creating a recurrence risk greater than general population. Because patients with CFNS reported in the literature are few, the AA consider that the observed case may help to improve understanding of the mechanisms of gene expression responsible for the syndrome, of its peculiar phenotypic manifestations and of its frequency in the population with known and easy to assign phenotypes, and possible mosaicisms that are difficult to detect.

[Coarctation of the aorta with aortic arch hypoplasia in newborn with partial trisomy 11q associated to 4q interstitial deletion]. / Coartazione aortica con ipoplasia dell'arco in una neonata con trisomia parziale 11q associata a delezione interstiziale 4q.

This article reports the case of newborn with multiple dimorphisms (microcephaly, hypertelorism, wide and flat nasal bridge, small nose, long philtrum, microretrognathia, malformed and low-set ears, short neck, redundant nuchal skin, genital anomalies), admitted in the hospital after two days from delivery for torpor, poor food and cyanosis. Babies were affected, at color-Doppler echocardiography, by coarctation of the aorta (CoA) with aortic arch hypoplasia. CoA is often associated to genetic and environmental factors that interact frequently. In this study the anamnestic absence of teratogen noxae and the presence of facial and genital anomalies suggest a genetic study to provide appropriate genetic information to parents. G-banding chromosomic analysis revealed a 46, XX der 4t(4;11) karyotype with partial 11q trisomy confirmed with FISH chromosome painting 4;11 and with FISH subtelomere specific 4(p/q)11(p/q). These techniques showed that derivative chromosome 4 was constituted by chromosome 4 with partial deletion in the q35 region and by 11q21 translocation. This rare anomaly is often inherited by an unbalanced segregation of a balanced translocation, present in one of the two parents. In the present study, the father carried a t(4q;11q) balanced translocation. A CGH-array analysis was executed to the child for the breakpoints definition. As 11q trisomy cases reported in literature are still few, this case can contribute to improve our knowledge on the genotype-phenotype correlation in this rare genetic anomaly.

[Afferents from a single muscle of the forelimbs and fastigial neurons of the cerebellum]. / Afferenze da singoli muscoli degli arti anteriori su neuroni fastigiali del cervelletto.

Responses of neurons in the medial nucleus of cerebellum (CBM) were studied on stimulation of ipsilateral and contralateral homonymous muscles, in decerebrated cats. The aim was to find out to what extent information from homonymous muscles of the forelimbs converge on the same CBM neurons and whether the probability of such a convergence depends on location (axial, proximal, distal) or function (flexor, extensor) of the tested muscles. The analysis was limited to the neurons belonging to the rostral part of the nucleus which is known to control the ipsilateral muscle periphery. Neuronal activity was recorded extracellularly using tungsten microelectrodes (5-12 M omega) and muscle stimulation was performed by bipolar coated steel electrodes, with the exception of the tip. At least 6 pairs of homonymous muscles were generally stimulated: two axial, two proximal and two distal in both forelimbs. Care was taken that, when a muscle was stimulated, the others were not activated either directly or in a reflex way. Out of the 65 neurons studied, 60 (92%) were responsive to muscle stimulation. It was specifically observed that a high percentage of cells reacted to stimulation of distal muscles (74% to ipsilateral and 71% to contralateral ones). More than half (55%) of the neurons were responsive to activation of a pair of homonymous distal muscles and about one third of them (31%) to both the pairs of distal muscles. On the contrary the percentage of responses to proximal muscles was reduced foremost in the ipsilateral ones (23%) and only an exiquous percentage of cells (15%) received information from the homonymous proximal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)