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1.
J Neurol ; 270(11): 5475-5482, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37491680

RESUMO

BACKGROUND: Given that the pathogenetic process of ALS begins many years prior to its clinical onset, examining patients' residential histories may offer insights on the disease risk factors. Here, we analyzed the spatial distribution of a large ALS cohort in the 50 years preceding the disease onset. METHODS: Data from the PARALS register were used. A spatial cluster analysis was performed at the time of disease onset and at 1-year intervals up to 50 years prior to that. RESULTS: A total of 1124 patients were included. The analysis revealed a higher-incidence cluster in a large area (435,000 inhabitants) west of Turin. From 9 to 2 years before their onset, 105 cases were expected and 150 were observed, resulting in a relative risk of 1.49 (P = 0.04). We also found a surprising high number of patients pairs (51) and trios (3) who lived in the same dwelling while not being related. Noticeably, these occurrences were not observed in large dwellings as we would have expected. The probability of this occurring in smaller buildings only by chance was very low (P = 0.01 and P = 0.04 for pairs and trios, respectively). CONCLUSIONS: We identified a higher-incidence ALS cluster in the years preceding the disease onset. The cluster area being densely populated, many exposures could have contributed to the high incidence ALS cluster, while we could not find a shared exposure among the dwellings where multiple patients had lived. However, these findings support that exogenous factors are likely involved in the ALS pathogenesis.


Assuntos
Esclerose Lateral Amiotrófica , Humanos , Esclerose Lateral Amiotrófica/epidemiologia , Esclerose Lateral Amiotrófica/etiologia , Risco , Incidência , Análise por Conglomerados
2.
Monaldi Arch Chest Dis ; 77(2): 76-82, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23193844

RESUMO

Strenuous exercise may cause progressive and proportional haemodynamic overload damage to the alveolar membrane, even in athletes. Despite the high incidence of arterial desaturation reported in endurance athletes has been attributed, into other factors, also to the damage of the alveolar-capillary membrane this evidence is equivocal. Some studies demonstrated flood of the interstitial space and consequent increase in pulmonary water content, but most of them were able to show this through indirect signs of interstitial oedema. The present review illustrates the literature's data in favour or against pulmonary interstitial edema due to intense exercise in athletes.


Assuntos
Atletas , Resistência Física/fisiologia , Edema Pulmonar/fisiopatologia , Capacidade Vital/fisiologia , Humanos
3.
Hand Surg Rehabil ; 36(2): 71-85, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28325431

RESUMO

Peripheral nerve injuries are a major public health problem. Nerve conduits have been developed in the recent years, although it is still not clear if they should replace nerve grafting and neurorrhaphy. This systematic review aims to gather evidence regarding the use of nerve conduits for peripheral nerve repair. The following electronic databases were searched: MEDLINE, Cochrane Library (CENTRAL) and Embase. Study selection and data extraction followed the PRISMA guidelines. The systematic review of the literature retrieved 6767 articles. Only 27 studies were retained accounting for 1022 patients: 10 randomized controlled trials, 15 case series and 2 cohort studies. Ten different types of tubes were described and a variety of evaluation methods were used to assess outcomes in terms of efficacy (motor and sensory recovery) and complications. The Semmes-Weinstein monofilament test and the static and moving 2-point discrimination test were the most commonly applied tests to evaluate nerve recovery. In general, outcomes showed no significant difference between groups. Synthetic conduits had more complications. Despite major methodological limitations in the studies, we can conclude that use of nerve conduits is preferable over suture repair and nerve grafting, as the functional recovery rates are above 80%. The choice of conduit is based on the surgeon's expertise, but use of synthetic conduits is discouraged due to their higher complication rates.


Assuntos
Microcirurgia , Regeneração Nervosa , Procedimentos Neurocirúrgicos , Traumatismos dos Nervos Periféricos/cirurgia , Próteses e Implantes , Aloenxertos , Colágeno , Humanos , Nervos Periféricos/transplante , Ácido Poliglicólico , Recuperação de Função Fisiológica , Silicones , Telas Cirúrgicas , Veias/transplante
4.
J Neurosci ; 20(22): 8596-606, 2000 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-11069968

RESUMO

Reduction in both presynaptic and postsynaptic structures in the aging neocortex may significantly affect functional synaptic properties in this area. To directly address this issue, we combined whole-cell patch-clamp recording of spontaneously occurring postsynaptic currents (PSCs) with morphological analysis of layer V pyramidal neurons in the parietal cortex of young adult (1- to 2-month-old) and aged (28- to 37-month-old) BN x F344 F(1) hybrid rats. Analysis of spontaneous PSCs was used to contrast functional properties of basal synaptic input with structural alterations in the dendritic tree of pyramidal neurons and density of terminals in contact with these cells. We observed significant changes in a number of morphological parameters of pyramidal neurons in aged rats. These include smaller cell body size and fewer basal dendritic branches (but not of oblique dendrites and dendritic tufts) and spines. Ultrastructural analysis also revealed a lower density of presynaptic terminals per unit length of postsynaptic membrane of labeled pyramidal neurons in the aged brain. This reduction in both presynaptic and postsynaptic elements was paralleled by a significant decrease in frequency of tetrodotoxin-insensitive miniature (action potential-independent) PSCs (mPSCs). The frequency of excitatory and inhibitory mPSCs was reduced to the same extent. In contrast, no significant change was observed in the frequency of spontaneous PSCs recorded in absence of tetrodotoxin (sPSCs), indicating an increase in action potential-dependent (frequency(sPSCs) - frequency(mPSCs)) input to pyramidal neurons in the aged group. This functional compensation may explain the lack of drastic loss of spontaneous neuronal activity in normal aging.


Assuntos
Potenciais de Ação/fisiologia , Envelhecimento/patologia , Envelhecimento/fisiologia , Neocórtex/ultraestrutura , Células Piramidais/ultraestrutura , Sinapses/ultraestrutura , Animais , Contagem de Células , Dendritos/ultraestrutura , Potenciais Pós-Sinápticos Excitadores/fisiologia , Técnicas In Vitro , Neocórtex/fisiologia , Lobo Parietal/fisiologia , Lobo Parietal/ultraestrutura , Técnicas de Patch-Clamp , Células Piramidais/fisiologia , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344 , Sinapses/fisiologia
5.
Cell Prolif ; 27(5): 257-67, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-10465010

RESUMO

The expression of the 170-kDa (alpha) and the 180-kDa (beta) isoforms of DNA topoisomerase II (topo II) was investigated with two specific monoclonal antibodies (MoAbs) in human peripheral blood lymphocytes (PBL), before and after phytohaemoagglutinin (PHA) stimulation. Binding of each MoAb was detected by indirect immunofluorescence labelling and quantified with flow cytometry. In resting PBL, the intensity of immunostaining was very low for both isozymes; however, topo IIbeta-associated immunofluorescence was about 2.5 times significantly higher (P<0.001) than that associated with the alpha isoform. Between 48 and 72 h of PHA stimulation, when the highest percentage of cells in S and G2+M phases was found, the levels of topo IIalpha and beta increased up to about 30 and 10 times the value measured in resting PBL, respectively. Thus, the two isoforms reached comparable immunofluorescence values. At longer stimulation periods (96-120 h), topo IIalpha immunofluorescence was not significantly changed, while that relative to topo IIbeta declined to about 50% of the peak value (P<0.02). At this time however, topo IIalpha-associated immunofluorescence was not significantly different from that related to the beta isozyme. These results suggest that in resting PBL topo IIalpha is required at levels lower than topo IIbeta, while in proliferating lymphocytes both isoforms are expressed to significantly higher levels.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Linfócitos/citologia , Linfócitos/metabolismo , Ciclo Celular/fisiologia , Divisão Celular/fisiologia , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/enzimologia , Fito-Hemaglutininas/farmacologia , Isoformas de Proteínas/metabolismo
6.
Eur Psychiatry ; 17 Suppl 4: 349s-354s, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23573604

RESUMO

Dopamine is implicated in the pathogenesis of both the positive and the negative symptoms of schizophrenia. Clinical efficacy of antipsychotic drugs, without the production of side-effects, may be achieved by a dose-response separation of pharmacological function, regional (i.e., anatomical) selectivity of action, or by the selective targeting of neuroreceptors. The atypical antipsychotics have many different ways of acting on receptors in the brain, but they have in common a decreased likelihood of producing extrapyramidal side-effects. Patients respond well to them by showing improvements of both positive and negative symptoms. The preclinical profile of amisulpride shows specificity for D2/D3 dopamine receptors and selective activity in the limbic system. There is evidence that amisulpride is effective in treating both the negative and positive symptoms of schizophrenia, and that it has a low propensity to induce motor side-effects. Therefore, both positive and negative symptoms can be treated, without inducing these side-effects, by selectively targeting dopamine receptors.


Assuntos
Córtex Cerebral/fisiopatologia , Dopamina/metabolismo , Sistema Límbico/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Animais , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Mapeamento Encefálico , Córtex Cerebral/efeitos dos fármacos , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/fisiopatologia , Humanos , Sistema Límbico/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiopatologia , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores Dopaminérgicos/fisiologia , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Resultado do Tratamento
7.
J Int Med Res ; 21(3): 138-46, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8299857

RESUMO

Mesoglycan is a preparation of natural glycosaminoglycans, containing mainly heparan sulphate and dermatan sulphate. A clinical trial was conducted to evaluate the efficacy and the tolerability of once-daily mesoglycan in 30 patients with clinical evidence of cerebrovascular insufficiency. Clinical effectiveness was assessed using psychometric and neurological scales: Sandoz Clinical Assessment for Geriatric Patients (SCAG); Parkside Behaviour Rating Scale Modified; Geriatric Depression Scale; and Anxiety Evaluation. Mesoglycan was given as a single oral once-daily dose of 100 mg for a period of 6 months. This treatment was shown to have positive effects on the cognitive and behavioural parameters evaluated. The effects on SCAG were already evident after 3 months' treatment and a significant improvement was observed after 6 months in those patients with a moderate to severe disease. During the treatment period only one patient suffered an adverse reaction attributed to the drug investigated.


Assuntos
Transtornos Cerebrovasculares/psicologia , Glicosaminoglicanos/uso terapêutico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Ansiedade , Comportamento , Transtornos Cerebrovasculares/tratamento farmacológico , Cognição , Depressão , Feminino , Glicosaminoglicanos/administração & dosagem , Humanos , Masculino , Escalas de Graduação Psiquiátrica
8.
J Am Mosq Control Assoc ; 10(1): 35-41, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8014626

RESUMO

The attraction of adult Chironomus salinarius to incandescent 3-W lamps of 7 different colors used in CDC traps was studied on a small island in the lagoon of Venice, Italy. An ANOVA indicated that the lamp type was a highly significant (P < 0.01) factor associated with differences in light trap catch (28% of total variation), as well as catch per lux (18% of total variation). The white lamp attracted higher numbers of adults than the other 6 color lamps. Yellow was the second most preferred, and red was the least attractive. There was a strong linear relationship (r = 0.93) between the catch and light intensity, which suggested that intensity was the primary factor influencing catch. However, catch per unit brightness (lux) tended to be inversely proportional to the peak wavelength associated with the lamp color (e.g., the violet lamp had the highest catch/lux, and the red lamp had the lowest). The corresponding regression model, Catch = 49 + [(48,013/lambda) - 63] . L, in which the slope associated with light intensity in lux (L) is inversely proportional to the peak wavelength in nm (lambda) explained 97% of the variation among lamp catch means. Manipulating light intensity and color could be useful to divert adult C. salinarius populations from midge-affected areas for control purposes.


Assuntos
Chironomidae/fisiologia , Entomologia/métodos , Luz , Análise de Variância , Animais , Cor , Ecologia , Itália , Controle de Mosquitos/métodos , Especificidade da Espécie
9.
J Am Mosq Control Assoc ; 8(4): 353-6, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1282149

RESUMO

Two formulations of the organophosphorus insecticide, temephos (Abathion Granulare, 1% AI granular and Tambro Compresse, 2% AI tablet) were evaluated against Chironomus salinarius midge larvae in 50 x 50 m experimental plots in the saltwater lagoon of Venice, Italy. Each formulation was applied at 0.2 and 0.4 kg AI/ha. Abathion Granulare produced 56 to 73% larval reduction at 0.2 kg AI/ha and 69 to 83% reduction at 0.4 kg AI/ha during 3 wk after treatment. Abathion Granulare lost effectiveness at 4 wk after application at both rates. Posttreatment larval reductions resulting from Tambro Compresse applications ranged from 77 to 86% for 3 wk, and 82 to 92% for 4 wk at rates of 0.2 and 0.4 kg AI/ha, respectively. The tablet formulation (Tambro Compresse) gave better control of C. salinarius (magnitude and duration) than the granular formulation (Abathion Granulare) in these evaluations.


Assuntos
Chironomidae , Controle de Insetos/métodos , Temefós/química , Animais , Ecologia , Itália , Larva
10.
Ann Ital Med Int ; 7(1): 30-3, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1524945

RESUMO

Serum insulin and C-peptide response to an oral glucose tolerance test (OGTT) and serum growth hormone (GH) response to an intravenous insulin tolerance test (IVITT) were investigated in six non-obese patients, with normal glucose tolerance, affected by diffuse idiopathic skeletal hyperostosis (DISH). Basal serum insulin, C-peptide and GH values were similar in DISH patients and in controls. After OGTT, insulin and C-peptide values were not significantly different in the two groups at any time interval. In contrast, after IVITT, a significant increase in GH concentrations was noted at 30 and 45 minutes in DISH patients when compared to controls. Growth hormone either acting alone or through somatomedin intermediaries results in new bone growth in acromegaly, and the same may be true for DISH. Recent reports suggest that GH promotes tissue growth by stimulating precursor cells in various tissues including cartilage and bone. The increased GH response to IVITT corroborates the hypothesis that GH may act as a bone growth-promoting factor in DISH.


Assuntos
Hormônio do Crescimento/metabolismo , Hiperostose Esquelética Difusa Idiopática/fisiopatologia , Glicemia/análise , Peptídeo C/sangue , Feminino , Teste de Tolerância a Glucose , Hormônio do Crescimento/sangue , Humanos , Hiperostose Esquelética Difusa Idiopática/sangue , Insulina/sangue , Masculino , Pessoa de Meia-Idade
11.
Minerva Chir ; 44(5): 923-6, 1989 Mar 15.
Artigo em Italiano | MEDLINE | ID: mdl-2725921

RESUMO

Aetiopathogenetic mechanisms and clinical aspects of carotid artery aneurysms are examined and personal experience of arterial reconstruction in one case reported.


Assuntos
Aneurisma , Doenças das Artérias Carótidas , Idoso , Aneurisma/etiologia , Aneurisma/cirurgia , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Interna , Humanos , Masculino
13.
Neuroscience ; 236: 320-31, 2013 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-23370321

RESUMO

Palatability is the hedonic food component that is considered to override the homeostatic mechanisms that control food intake, and we compared how much effort non food-deprived and food-deprived rats were willing to spend in order to earn a palatable caloric (sucrose) or non-caloric (saccharin) snack. We first studied the dopaminergic response, in terms of dopamine levels and dopamine and cAMP-regulated phosphoprotein Mr 32,000 (DARPP-32) phosphorylation pattern, to two consecutive palatable caloric or non-caloric snacks in the nucleus accumbens shell (NAcS) of non food-deprived and fasted rats. We report that non food-deprived rats developed rapid habituation in the NAcS dopaminergic response to the second consumption of both caloric and non-caloric palatable food, while food-deprived rats developed rapid habituation only to saccharin. Next, we show that in self-administration experiments, non food-deprived rats spent a similar effort when operating for sucrose or saccharin. However, the same rats showed an increased response specifically for sucrose after 18-h fasting. After pre-feeding devaluation, rats reduced their response to sucrose but not for saccharin. These results strengthen the hypothesis that food intake is mainly controlled by palatability in non food-deprived rats and by caloric content in food-deprived rats. Moreover, they show that rapid habituation development was associated with a similar, basal working activity aimed at ingesting both caloric and non-caloric food, as observed in non food-deprived rats consuming sucrose or saccharin and in fasted rats consuming saccharin. Conversely, lack of habituation, as present in fasted rats consuming a caloric food, was associated with extra energy expenditure.


Assuntos
Ingestão de Alimentos/fisiologia , Ingestão de Alimentos/psicologia , Comportamento Alimentar/fisiologia , Comportamento Alimentar/psicologia , Motivação/fisiologia , Animais , Regulação do Apetite/fisiologia , Dopamina/metabolismo , Privação de Alimentos/fisiologia , Immunoblotting , Masculino , Microdiálise , Núcleo Accumbens/metabolismo , Prazer , Ratos , Ratos Sprague-Dawley , Paladar
14.
Int J Pharm ; 393(1-2): 238-43, 2010 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-20399844

RESUMO

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the major psychoactive constituent of Cannabis sativa L., has been widely studied for its potential pharmaceutical application in the treatment of various diseases and disturbs. This sparingly soluble terpeno-phenolic compound is not easy to handle and to be formulated in pharmaceutical preparations. The aim of this work was to develop a stable aqueous Delta(9)-THC formulation acceptable for different ways of administration, and to evaluate the therapeutic properties of the new Delta(9)-THC based preparation for pain treatment. Due to the thermodynamic stability and advantages of microemulsion based systems, the study was focused on the identification of aqueous microemulsion based systems containing Delta(9)-THC. Oil in water Delta(9)-THC microemulsions were individuated through phase diagrams construction, using the non-ionic surfactant Solutol HS15, being this surfactant acceptable for parenteral administration in human. A selected microemulsion samples containing 0.2 wt% of Delta(9)-THC, stable up to 52 degrees C, was successfully assayed on animal models of pain. Significant antinociceptive activity has been detected by both intraperitoneal and intragastric administration of the new Delta(9)-THC pharmaceutical preparation. The effect has been highlighted in shorter time if compared to a preparation of the same active principle based on previously reported conventional preparation.


Assuntos
Analgésicos/farmacologia , Dronabinol/farmacologia , Limiar da Dor/efeitos dos fármacos , Dor/prevenção & controle , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/química , Animais , Química Farmacêutica , Modelos Animais de Doenças , Dronabinol/administração & dosagem , Dronabinol/química , Composição de Medicamentos , Estabilidade de Medicamentos , Emulsões , Injeções Intraperitoneais , Masculino , Camundongos , Dor/fisiopatologia , Medição da Dor , Polietilenoglicóis/química , Tempo de Reação , Solubilidade , Ácidos Esteáricos/química , Tensoativos/química , Tecnologia Farmacêutica/métodos , Temperatura , Fatores de Tempo
15.
Eur Psychiatry ; 25(2): 92-100, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19640686

RESUMO

It is proposed that to achieve a therapeutic effect in schizophrenia patients, dopamine D(2)-receptor occupancy by antipsychotics within the striatum must exceed 60-65%. However, at high levels of D(2)-receptor occupancy, the risk of extrapyramidal symptoms (EPS) is increased. Following oral dosing of antipsychotics, peaks and troughs in plasma drug concentrations may be mirrored by fluctuations in D(2)-receptor occupancy. Paliperidone, a novel antipsychotic available as extended-release tablets (paliperidone ER), is the major active metabolite of risperidone and exhibits a plasma pharmacokinetic profile with reduced peak-trough fluctuations and consistent D(2)-receptor occupancy compared with conventional oral antipsychotic formulations. Using formulations that resemble those in clinical practice, this study provides a preclinical evaluation of the pharmacological properties of paliperidone ER and risperidone immediate-release formulation in terms of consistent antipsychotic efficacy over time and extrapyramidal symptom liability. Significant fluctuations in inhibition of d-amphetamine-induced hyperlocomotion were observed for repeated subcutaneous (SC) risperidone injections, whereas stable inhibitory efficacy was demonstrated during continuous SC paliperidone infusion. Similarly, significant fluctuations in latency on-bar were observed with repeated SC risperidone injections, whereas significantly lower latency on-bar was demonstrated following continuous SC paliperidone infusion. These results in an animal model suggest that although risperidone and paliperidone demonstrate similar pharmacologic effects, continuous administration of paliperidone achieves more stable antipsychotic efficacy with reduced motor impairment, akin to the effects observed with paliperidone ER in clinical studies.


Assuntos
Antipsicóticos/administração & dosagem , Antipsicóticos/farmacologia , Infusões Subcutâneas/métodos , Injeções Subcutâneas/métodos , Isoxazóis/administração & dosagem , Isoxazóis/farmacologia , Locomoção/efeitos dos fármacos , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Animais , Dextroanfetamina/administração & dosagem , Dextroanfetamina/farmacologia , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/administração & dosagem , Inibidores da Captação de Dopamina/farmacologia , Esquema de Medicação , Masculino , Palmitato de Paliperidona , Ratos , Ratos Sprague-Dawley , Risperidona/administração & dosagem , Risperidona/farmacocinética
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