Neurobehavioral studies, in transgenic F3/CONTACTIN (C57BL/6J × CBA) mice, on cognitive and anxiety aspects during late-adolescential period.

OBJECTIVE: Besides than in the control of developmental events, axonal adhesive glycoproteins may be also involved in functions requiring fine organization and connectivity of the nervous tissue. We previously demonstrated morphological alterations and functional cerebellar deficits in transgenic mice (TAG/F3 mice) ectopically expressing the F3/Contactin axonal glycoprotein under the control of a selected regulatory region from the Transient Axonal Glycoprotein (TAG-1) gene. In the present study, the hippocampal function was explored by evaluating the ability of TAG/F3 mice to encode spatial and non-spatial relationships between discrete stimuli and to analyze an anxiety-related behavior. MATERIALS AND METHODS: To the first end, mice were placed in an "open-Field" containing five objects and, after three sessions of habituation (S2-S4), their reactivity to objects displacement (S5-S4) and object substitution (S7-S6) was examined.To the second end, mice were placed in the "elevated zero maze", a standard test to explore the anxiety-related behavior, in order to study, in transgenic mice, the effects of F3 misexpression on emotional reactivity by measuring the avoidance of the unsheltered open sectors. RESULTS: Statistical evaluations of reactivity to object novelty, TAG-F3 mice showed a lower DO exploration with respect to wild-type mice and, regarding DOs, TAG/F3 mice interacted less than wild-type mice, showing an impaired spatial change response. Furthermore, the number of HDIPS in transgenic TAG/F3 mice resulted significantly lower with respect to the controls (wild type). CONCLUSIONS: These results indicate that the coordinated expression of axonal adhesive glycoproteins may be relevant for the functional maturation of the hippocampus.

Arthroscopic debridement compared to intra-articular steroids in treating degenerative medial meniscal tears.

OBJECTIVES: Virtually all early cases of knee osteoarthritis have degenerative medial meniscus lesions accompanying the chondral defects on MRI. It is difficult to determine if the symptoms are caused by the unstable meniscus or by osteoarthritis, hence unclear guidance towards treatment. We, therefore, aimed to determine the clinical improvement following arthroscopic meniscectomy compared to intraarticular administration of corticosteroids for degenerative ruptures of the medial meniscus in the presence of early stage medial compartment knee osteoarthritis. PATIENTS AND METHODS: We included 120 consecutive cases of nontraumatic symptomatic knees which had degenerative lesions of the medial compartment (cartilage and meniscus) on MRI's. They were randomized to receive either intraarticular steroid injection or arthroscopic debridement. We also analyzed the correlation between BMI, age, gender, MRI, intraoperative aspect of the meniscus and cartilage and clinical improvement using the Oxford Knee Score up to one year. At one month there was significant improvement of the scores for all the examined cases. Also at one month, the arthroscopic group performed better in terms of symptom improvement. This was maintained for 79% of the knees in the arthroscopic group and 61% in the intraarticular steroid injection respectively, out of those available for follow up at one year. RESULTS: At one month, symptoms reappeared for 12 patients in the steroid group and 7 in the arthroscopy respectively. Gender and age did not correlate with treatment, whereas extrusion of the meniscus, bone marrow edema, duration of the clinical symptoms, obesity and a low preoperative score were negative prognostic factors. CONCLUSIONS: Degenerative medial meniscal tears, in the presence of osteoarthritis, can only marginally benefit from arthroscopic debridement over intraarticular steroid injections in short term follow up. When considering individual cases, factors become more predictive when analyzed in group.

Regenerative surgery performed with platelet-rich plasma used in sinus lift elevation before dental implant surgery: an useful aid in healing and regeneration of bone tissue.

OBJECTIVES: Aim of this work is to show the effectiveness of a protocol involving the use of platelet-rich plasma (PRP) as a grafting material in bone regeneration before dental implant rehabilitation. MATERIALS AND METHODS: 127 patients, requiring maxillary sinus lift, were enrolled in a follow-up study plan, which established clinical and radiological examinations on the day after surgery and six months later. PRP, in combination with autogenous bone, an organic bone material and organic bone substitutes, was used before implant-prosthetic rehabilitation. RESULTS AND CONCLUSIONS: After implant placement, 63 patients, previously treated with PRP, reached a statistically significant improvement in implant-prosthetic rehabilitation, established by primary stability and radiographic integration criteria, in comparison with the other 64 patients receiving implant-prosthetic rehabilitation without PRP treatment.

Effects of developmental fluoride exposure on rat ultrasonic vocalization, acoustic startle reflex and pre-pulse inhibition.

Rats receiving fluoride during the whole pregnancy up to the 9th day of lactation showed, when isolated at 10th day of life, a reduced rate of ultrasonic vocalizations (UV) in male pups (NaF 5.0 mg) and, in 90th days male rats, an increase of the Pre-Pulse Inhibition (PPI) with a reduction of the Peak response to the Startle stimulus given alone. Newborn rat reactivity could represent a useful and validated model in anxiety studies which could be moored with the Acoustic Startle Reflex (ASR) and PPI, appropriate models to study, in adulthood, particular neurological and psychiatric disorders showing deficits in attention and sensory-motor gating (Tourettes' syndrome, obsessive compulsive disorders, Huntington's disease and schizophrenia).

Secondary pathologic fractures in osteosarcoma: prognosis and evolution.

Secondary or pathologic fractures, associated with osteosarcoma, have been considered for a long time to be a negative prognosis regarding its evolution in the patients. The aim of this study was to evaluate the prognostic importance of such pathologic fractures in osteosarcoma patients receiving new therapies as well as the best conditions for surgery aiming at "limbs salvage". On a total of 22 patients affected by osteosarcoma, we performed a retrospective study with 12 patients showing pathologic fractures caused by osteosarcoma and 10 patients without any pathologic fracture. The patients enrolled into Timisoara University Hospital have been followed up along 5 years or until a reappearance of either the disease or metastases, distant or local.

Effects on rat sexual behaviour of acute MDMA (ecstasy) alone or in combination with loud music.

The effects on sexual behaviour of acute low doses of methylendioxymethamphetamine (MDMA) (0.3, 1, 3 mg/kg/i.p.), alone or in combination with exposure to loud music (1 h stimulation), were investigated in Wistar rats. Results indicate that acute MDMA, at dose of 3 mg/kg, notably impaired copulatory behavior of sexually experienced male rats. In particular, MDMA-exposed animals exhibited a significant increase in intromission and ejaculation latencies as well as a significant decrease in percentage of rats displaying copulatory activity (one intromission at least). Surprisingly, one hour exposure to loud music, which per se resulted ineffective, antagonized the suppressive effect of MDMA by increasing the percent of animals displaying sexual activity. However, combined treatment of MDMA and music stimulation did not fully restore normal sexual behavior as the animals reaching ejaculation still showed a marked reduction of copulatory efficiency. These findings demonstrate that the systemic administration of a single low dose of MDMA, alone or in combination with loud music, which is commonly present in certain environments such as rave parties, notably impairs copulatory activity of male rats.

Neurofunctional effects in rats prenatally exposed to fluoxetine.

In the treatment of depression fluoxetine [a selective serotonine reuptake inhibitor (SSRIs)] is a widely used drug in humans. The selectivity, efficacy, side effects and simplicity of dosage contributed to fluoxetine's clinical acceptance. Several psychiatric disorders (many of them responsive to SSRIs) are present during pregnancy; up to 10% of pregnant women fulfill diagnostic criteria for major or minor depression with an even higher percentage developing postpartum depression. Therefore, significant numbers of women may be taking SSRIs while pregnant. Since fluoxetine's safe use during pregnancy is not yet established and experimental studies inconclusive, we performed the present research in order to investigate the neurobehavioral effects produced in rats by prenatal exposure to fluoxetine (5 and 10 mg/kg/sc from day 13 to 20 of gestation) on cognitive functions, emotional reactivity and sexual performance.

Psoriasis disappearance after the first phase of an oncologic treatment: a serendipity case report.

Psoriasis is a multifaceted disorder with psychosocial and physical aspects that negatively impact the quality of life. Strategies of treatment must address both rapid control of the disease and maintenance of benefits. For short and long-term control of localized psoriasis, recent data support the combined use of topical corticosteroids and either calcipotriene or tazarotene which seem to be the most effective approach. For generalized disease, UVB treatment provides the safest means of achieving long-term control of the disease. Acitretin is a very helpful adjunct for improving the efficacy of phototherapy. For patients with severe, refractory disease, methotrexate may be most effective while cyclosporine may be most valuable for patients needing rapid, short-term improvement. Other molecules, with different pharmacological properties, are actually under consideration. Herein it is reported a case of a 55 year old male, who refers, 2 weeks after the fi rst cycle of oncologic therapy with gemcitabine and cisplatin for a lung neoplasm, about the complete remission of the psoriasis on both fingernails and scalp, suffered since almost ten years. Three months after the fortuitous detection of the psoriasis disappearance, there is no further evidence of psoriatic lesions.

Effects of prenatal exposure to the CB-1 receptor agonist WIN 55212-2 or CO on the GABAergic neuronal systems of rat cerebellar cortex.

The aim of this study was to assess the effects of prenatal exposures to cannabinoids or carbon monoxide (CO) in an animal experimental model reproducing the environmental conditions in which a fetus develops whose mother, during pregnancy, ingests by smoking low doses of cannabinoids or CO. Particular attention was devoted to analyses of the long-term effects of the exposures at the level of the cerebellar cortex, where already during prenatal development the GABAergic neuronal systems may be modulated by both cannabinoids and CO. Three groups of rats were subjected to the following experimental conditions: exposure to cannabinoids by maternal treatment during pregnancy with the cannabinoid CB-1 receptor agonist WIN 55212-2 (WIN) (0.5 mg/kg/day, s.c.); exposure to CO by maternal exposure during pregnancy to CO (75 parts per million, by inhalation); and exposure to WIN+CO at the above doses and means of administration; a fourth group was used as control. The body weight of dams, length of pregnancy, litter size at birth, body weight and postnatal mortality of pups were monitored in order to evaluate possible effects of the exposures on reproduction and on prenatal and postnatal development. In the different groups, the long-term effects of the exposures were studied in adult rats (120-150 days) by light microscopy analyses of the structure of the cerebellar cortex and of the distribution in the cortex of markers of GABAergic neurons, such as GAD and GABA itself. Results. Exposures to WIN or CO did not affect reproduction or prenatal/postnatal development. Moreover, the exposed rats showed no structural alterations of the cerebellar cortex and displayed qualitative distribution patterns of GAD and GABA immunoreactivities similar to those of the controls. However, quantitative analyses indicated significant changes of both of these immunoreactivities: in comparison with the controls, they were significantly increased in WIN-exposed rats and reduced in CO-exposed rats, but not significantly different in WIN+CO-exposed rats. The changes were detected in the molecular and Purkinje neuron layers, but not in the granular layer. Prenatal exposures of rats to WIN or CO, at doses that do not affect reproduction, general processes of development and histomorphogenesis of the cerebellar cortex, cause significant changes of GAD and GABA immunoreactivities in some GABAergic neuronal systems of the adult rat cerebellar cortex, indicating selective up-regulation of GABA-mediated neurotransmission as a long-term consequence of chronic prenatal exposures to cannabinoids or CO. Because the changes consist of overexpression or, vice versa, underexpression of these immunoreactivities, functional alterations of opposite types in the GABAergic systems of the cerebellum following exposure to WIN or CO can be postulated, in agreement with the results of behavioral and clinical studies. No changes in immunoreactivities were detected after prenatal exposure to WIN and CO in association.

Neurofunctional effects of developmental sodium fluoride exposure in rats.

Contrasting studies on the toxic effects of sodium fluoride (NaF) during developmental stages of Wistar rats, lead us to investigate the neurofunctional effects caused by its perinatal exposure, devoid of any overt sign of toxicity and/or gross malformation. NaF solution was administered to pregnant rats by intragastric gavage at a daily dose of 2.5 and 5.0 mg/kg from gestational day 0 to day 9 after parturition. Developmental NaF exposure caused sex and dose specific behavioural deficits which affected males more than females in the majority of the evaluated end-points. In particular, the perinatal exposure to NaF 5.0 mg/kg, significantly affected learning, memory, motor coordination and blood pressure only in male rats. Conversely, a lack of habituation upon the second presentation of the objects and failure in the ability to discriminate between the novel and the familiar object were observed only in NaF 5.0 mg/kg female rats. Finally, a significant impairment of sexual behaviour was observed in male rats at both NaF dose levels. The present data indicate that perinatal rat exposure to NaF results in long lasting functional sex-specific alterations which occur at fluoride levels approaching those experienced by offspring of mothers.

Non-traditional large neurons in the granular layer of the cerebellar cortex.

The granular layer of the cerebellar cortex is composed of two groups of neurons, the granule neurons and the so-called large neurons. These latter include the neuron of Golgi and a number of other, lesser known neuron types, generically indicated as non-traditional large neurons. In the last few years, owing to the development of improved histological and histochemical techniques for studying morphological and chemical features of these neurons, some non-traditional large neurons have been morphologically well characterized, namely the neuron of Lugaro, the synarmotic neuron, the unipolar brush neuron, the candelabrum neuron and the perivascular neuron. Some types of non-traditional large neurons may be involved in the modulation of cortical intrinsic circuits, establishing connections among neurons distributed throughout the cortex, and acting as inhibitory interneurons (i.e., Lugaro and candelabrum neurons) or as excitatory ones (i.e., unipolar brush neuron). On the other hand, the synarmotic neuron could be involved in extrinsic circuits, projecting to deep cerebellar nuclei or to another cortex regions in the same or in a different folium. Finally, the perivascular neuron may intervene in the intrinsic regulation of the cortex microcirculation.

Glutamic acid decarboxylase and GABA immunoreactivities in the cerebellar cortex of adult rat after prenatal exposure to a low concentration of carbon monoxide.

Glutamic acid decarboxylase and GABA immunoreactivities were qualitatively and quantitatively evaluated in the cerebellar cortex of adult rats prenatally exposed to a low concentration of carbon monoxide (75 parts per million). Carbon monoxide-exposed and control rats were perfused with modified Bouin's fluid and their cerebella were embedded in paraffin. Sections from the vermis of each cerebellum were stained with Toluidine Blue or assayed with anti-glutamic acid decarboxylase 65/67 or with anti-GABA antisera. In the Toluidine Blue-stained sections, no differences were observed in the microscopic structure of the cerebellar cortex between carbon monoxide-exposed rats and controls. The distribution patterns of glutamic acid decarboxylase and GABA immunoreactivities in the cerebellar cortex of the treated animals were qualitatively comparable to those of the controls, and in accordance with previous descriptions of glutamic acid decarboxylase and GABA immunoreactivities in the rat cerebellar cortex. However, quantitative analyses demonstrated a significant reduction of immunoreactivities to both substances in the exposed rats in comparison with the controls. The reduction regarded: in the molecular layer, the number of glutamic acid decarboxylase/GABA-immunoreactive neuronal bodies and of axon terminals and the area they covered; in the Purkinje neuron layer, the number and the area covered by glutamic acid decarboxylase/GABA immunoreactive axon terminals. The differences detected in the prenatally exposed adult rats could be due to carbon monoxide-induced impairment of the differentiation of cerebellar GABA synthesizing neurons. A consequently diminished synthesis of GABA might account for some behavioral disorders detected in adult rats submitted to the same experimental procedure.

Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex.

'Non-traditional' large neurons of the granular layer of the cerebellar cortex include all its large neuronal types, except the Golgi neuron, which is instead one of the five 'classic' types of corticocerebellar neurons. The morphological, chemical and functional characteristics of the 'non-traditional' large neurons have not been entirely ascertained. The aim of this study was to ascertain whether morphological evidence can be provided of GABA synthesis within the 'non-traditional' large neurons of the human cerebellar cortex by means of immunocytochemistry for glutamic acid decarboxylase (GAD). Fragments of postmortem cerebellar cortex of various lobules from the hemispheres and vermis were studied. Immunoreactions revealed large neurons distributed throughout the granular layer in all lobules examined. They were discriminated by analyzing the morphological features of their bodies and processes and were identified as Golgi neurons and as some 'non-traditional' types, such as the candelabrum, Lugaro and synarmotic neurons. In addition, immunoreactive large neurons, with their bodies and processes closely adjacent to microvessels, were observed throughout the layer: these perivascular neurons could represent a new type of 'non-traditional' neuron of the cerebellar cortex. This study supplies the first indication that in the human cerebellar cortex some types of 'non-traditional' large neurons are GAD-immunoreactive, in addition to those neurons already known to be GABAergic (i.e., stellate, basket, Purkinje and Golgi neurons). These morphological data further point out possible functional roles for GABA as a neurotransmitter/neuromodulator in intrinsic, associative and projective circuits of the cerebellar cortex.

Choline acetyltransferase-containing neurons in the human parietal neocortex.

A number of immunocytochemical studies have indicated the presence of cholinergic neurons in the cerebral cortex of various species of mammals. Whether such cholinergic neurons in the human cerebral cortex are exclusively of subcortical origin is still debated. In this immunocytochemical study, the existence of cortical cholinergic neurons was investigated on surgical samples of human parietal association neocortex using a highly specific monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine biosynthesising enzyme. ChAT immunoreactivity was detected in a subpopulation of neurons located in layers II and III. These were small or medium-sized pyramidal neurons which showed cytoplasmic immunoreactivity in the perikarya and processes, often in close association to blood microvessels. This study, providing demonstration of ChAT neurons in the human parietal neocortex, strongly supports the existence of intrinsic cholinergic innervation of the human neocortex. It is likely that these neurons contribute to the cholinergic innervation of the intracortical microvessels.

GABA immunoreactivity in the human cerebellar cortex: a light and electron microscopical study.

The distribution of gamma-aminobutyric acid (GABA) in surgical samples of human cerebellar cortex was studied by light and electron microscope immunocytochemistry using a polyclonal antibody generated in rabbit against GABA coupled to bovine serum albumin with glutaraldehyde. Observations by light microscopy revealed immunostained neuronal bodies and processes as well as axon terminals in all layers of the cerebellar cortex. Perikarya of stellate, basket and Golgi neurons showed evident GABA immunoreactivity. In contrast, perikarya of Purkinje neurons appeared to be negative or weakly positive. Immunoreactive tracts of longitudinally- or obliquely-sectioned neuronal processes and punctate elements, corresponding to axon terminals or cross-sectioned neuronal processes, showed a layer-specific pattern of distribution and were seen on the surface of neuronal bodies, in the neuropil and at microvessel walls. Electron microscope observations mainly focussed on the analysis of GABA-labelled axon terminals and of their relationships with neurons and microvessels. GABA-labelled terminals contained gold particles associated with pleomorphic vesicles and mitochondria and established symmetric synapses with neuronal bodies and dendrites in all cortex layers. GABA-labelled terminals associated with capillaries were seen to contact the perivascular glial processes, basal lamina and endothelial cells and to establish synapses with subendothelial unlabelled axons.

Glutamic acid decarboxylase-positive neuronal cell bodies and terminals in the human cerebellar cortex.

The distribution of gamma-aminobutyric acid (GABA) in the human cerebellar cortex was studied using immunohistochemistry for glutamic acid decarboxylase (GAD), the enzyme that catalyses GABA synthesis. Observations by light microscopy revealed, in all layers of the cerebellar cortex, strong, punctate positivity for GAD, related to putative GABAergic nerve terminals, as well as a diffuse cytoplasmic immunoreactivity within neuronal cell bodies. GAD-positive nerve terminals were found in close relationship with the walls of the cerebellar cortex microvessels. Observations by electron microscopy revealed positive nerve terminals in contact with the astrocyte perivascular sheath of capillaries. GAD immunoreactivity was also detected within astroglial perivascular endfeet and endothelial cells. The findings provide further insights into the GABAergic synapses of the circuitry of the human cerebellar cortex. The detection of 'vascular' GAD immunoreactivities suggests that GABAergic mechanisms may regulate cerebellar microvessel function.

Immunolocalization of glutamic acid decarboxylase in postmortem human cerebellar cortex. A light microscopy study.

The distribution of glutamic acid decarboxylase (GAD), the gamma-aminobutyric acid (GABA) synthesizing enzyme, was examined in the postmortem human cerebellar cortex by immunocytochemistry. The results, obtained on nervous tissues taken at autopsy and fixed within 24-36 h after death, enabled the authors to precisely reveal the topographical distribution of GAD-containing neurons and axon terminals in the human cerebellar cortex. Labeled neurons, corresponding to different neuronal cytotypes of the cerebellar cortex, showed a diffuse cytoplasmic immunoreactivity in both bodies and processes. Labeled axon terminals appeared as immunoreactive puncta. The use of immunocytochemistry in the detection of GAD in the postmortem human brain greatly increases the possibility of carrying out morphological studies on the GABAergic system, both in normal and in pathological conditions.