RESUMEN
Several studies report that endocrine disrupting chemicals (EDC) able to interfere with endocrine homeostasis may affect women's reproductive health. We analyzed EDC serum levels and nuclear receptors (NRs) expression in order to have an indication of the internal dose of biologically active compounds and a measurement of indicators of their effects, as a result of the repeated uptake from environmental source. The percentage of patients with detectable bisphenol A (BPA) concentrations was significantly higher in the infertile patients compared with fertile subjects. No significant difference was found between the groups with regard to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), mono-ethylhexyl phthalate (MEHP) and di-(2-ethylhexyl) phthalate (DEHP) concentrations. Among infertile women, the mean expression of estrogen receptor alpha (ERα) and beta (Erß), androgen receptor (AR) and pregnane X receptor (PXR) was significantly higher than fertile patients. The mean expression of aryl hydrocarbon receptor (AhR) and peroxisome proliferator-activated receptor gamma (PPARγ) did not show significant differences between two groups. Patients with endometriosis had higher levels of PPARγ than all women with other causes of infertility. This study led further support to EDC exposure as a risk factor for women's fertility.
Asunto(s)
Disruptores Endocrinos/efectos adversos , Infertilidad Femenina/inducido químicamente , Receptores Citoplasmáticos y Nucleares/metabolismo , Adulto , Estudios de Casos y Controles , Disruptores Endocrinos/sangre , Femenino , Humanos , Infertilidad Femenina/sangre , Leucocitos Mononucleares/metabolismo , EmbarazoRESUMEN
Placebo administration is known to affect the brain both in pain and in Parkinson disease. Here we show that placebo treatment caused reduced activity in single neurons in the subthalamic nucleus of placebo-responsive Parkinsonian patients. These changes in activity were tightly correlated with clinical improvement; no decrease in activity occurred when the clinical placebo response was absent.
Asunto(s)
Potenciales de Acción/fisiología , Neuronas/fisiología , Enfermedad de Parkinson/fisiopatología , Núcleo Subtalámico/fisiología , Potenciales de Acción/efectos de los fármacos , Apomorfina/farmacología , Apomorfina/uso terapéutico , Intervalos de Confianza , Electrodos Implantados , Humanos , Neuronas/efectos de los fármacos , Oportunidad Relativa , Enfermedad de Parkinson/tratamiento farmacológico , Efecto Placebo , Núcleo Subtalámico/efectos de los fármacosRESUMEN
We report a case of a Parkinson's disease patient treated by bilateral deep brain stimulation of the subthalamic nucleus, who developed freezing and hypokinesia of gait induced by stimulation through a left-side misplaced electrode which was more antero-medial than the planned trajectory. Subsequently, correct repositioning of the left electrode afforded complete relief of gait disturbances. Freezing and hypokinesia of gait may be side effects of deep brain stimulation of the subthalamic region due to current spreading antero-medially to the subthalamic nucleus. These side effects are not subject to habituation and restrict any increase in stimulation parameters. We hypothesize that pallidal projections to the pedunculopontine nucleus could be responsible for these gait disturbances in our patient.
Asunto(s)
Estimulación Encefálica Profunda/efectos adversos , Reacción Cataléptica de Congelación/efectos de la radiación , Hipocinesia/etiología , Enfermedad de Parkinson/patología , Núcleo Subtalámico/cirugía , Anciano , Lateralidad Funcional , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Enfermedad de Parkinson/cirugíaRESUMEN
This study reports the effects of intraoperative stimulation of the subthalamic nucleus on brain electrical activity in advanced Parkinson's patients. To our knowledge, this is the first study about electroencephalographic responses in the very early phase of deep brain stimulation, during the implantation of the electrodes. We found an increase of gamma band bilaterally over the sensorimotor cortex in the range 45-55 Hz, which was associated with clinical improvement as assessed by means of muscle rigidity decrease. These results indicate that the electroencephalographic gamma responses to deep brain stimulation are present at the very beginning of the treatment process, and may help better understand the short and long-tem effects of deep brain stimulation.
Asunto(s)
Corteza Cerebral/fisiopatología , Estimulación Eléctrica/métodos , Electroencefalografía , Núcleo Subtalámico/efectos de la radiación , Anciano , Mapeo Encefálico , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/cirugía , Análisis Espectral , Núcleo Subtalámico/cirugíaRESUMEN
Alterations of the phrenic nerve (PN) and pulmonary function tests (PFTs) have been described in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). This study was aimed at assessing the relationship between PN and respiratory function in CIDP patients without clinical signs of respiratory failure. Bilateral PN and right median nerve conduction studies were carried out along with blood gas analysis and PFTs: maximal inspiratory pressure; maximal expiratory pressure; forced vital capacity. The amplitude of the compound muscle action potential of the PN was seen to be altered in 19/24 (79%) patients and latency in 22 (92%). Eighteen patients (75%) showed at least one abnormal PFTs or CO2 partial pressure value. Electrophysiological alterations of the PN were observed in a high percentage of the CIDP patients studied. No statistically significant correlation was observed between PN and PFTs alterations.
Asunto(s)
Conducción Nerviosa/fisiología , Nervio Frénico/fisiopatología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Estimulación Eléctrica/métodos , Electromiografía/métodos , Potenciales Evocados Motores/fisiología , Potenciales Evocados Motores/efectos de la radiación , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Tiempo de Reacción/fisiología , Tiempo de Reacción/efectos de la radiación , Pruebas de Función Respiratoria/métodosRESUMEN
Internal levels of selected endocrine disruptors (EDs) (i.e., perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), di-2-ethylhexyl-phthalate (DEHP), mono-(2-ethylhexyl)-phthalate (MEHP), and bisphenol A (BPA)) were analyzed in blood/serum of infertile and fertile men from metropolitan, urban and rural Italian areas. PFOS and PFOA levels were also evaluated in seminal plasma. In peripheral blood mononuclear cells (PBMCs) of same subjects, gene expression levels of a panel of nuclear receptors (NRs), namely estrogen receptor α (ERα) estrogen receptor ß (ERß), androgen receptor (AR), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptor γ (PPARγ) and pregnane X receptor (PXR) were also assessed. Infertile men from the metropolitan area had significantly higher levels of BPA and gene expression of all NRs, except PPARγ, compared to subjects from other areas. Subjects from urban areas had significantly higher levels of MEHP, whereas subjects from rural area had higher levels of PFOA in both blood and seminal plasma. Interestingly, ERα, ERß, AR, PXR and AhR expression is directly correlated with BPA and inversely correlated with PFOA serum levels. Our study indicates the relevance of the living environment when investigating the exposure to specific EDs. Moreover, the NRs panel in PBMCs demonstrated to be a potential biomarker of effect to assess the EDs impact on reproductive health.
Asunto(s)
Disruptores Endocrinos/sangre , Infertilidad Masculina/sangre , Infertilidad Masculina/genética , Leucocitos Mononucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genética , Adulto , Ácidos Alcanesulfónicos/sangre , Compuestos de Bencidrilo/sangre , Biomarcadores/análisis , Caprilatos/sangre , Dietilhexil Ftalato/análogos & derivados , Dietilhexil Ftalato/sangre , Ambiente , Fertilidad , Fluorocarburos/sangre , Expresión Génica , Humanos , Masculino , Fenoles/sangre , Semen/químicaRESUMEN
The pigmentation of substantia nigra pars compacta dopaminergic neurons is due to the presence of neuromelanin, an irregular macromolecular pigment belonging to the family of melanins. Depletion of neuromelanin in Parkinson's disease is typically indicated by loss of brown color in this area. Unlike that from controls, the pigment extracted from substantia nigra of parkinsonian patients seems to be mainly composed by highly cross-linked, protease-resistant proteic material and the neuromelanin macromolecule appears to be a minor presence. In the present paper we describe the isolation by SDS-PAGE of this proteic component after cleavage of the melanin backbone under solubilizing conditions. A single band is observed, which has been identified as alpha-synuclein by western blotting. As expected, the same process performed on a control specimen did not show occurrence of any major proteic component. Nevertheless, extraction from a 91 years old control with Lewy bodies displayed minor alpha-synuclein immunoreactive aggregates, whereas inclusion of free alpha-synuclein was not observed at all. Results reported here support the view that alpha-synuclein accumulates within substantia nigra neurons and is entrapped in pigment granules during neuromelanin biosynthesis, i.e. before the melanin depletion characteristic of Parkinson's disease starts.
Asunto(s)
Melaninas/química , Proteínas del Tejido Nervioso/aislamiento & purificación , Enfermedad de Parkinson/metabolismo , Sustancia Negra/metabolismo , Anciano , Anciano de 80 o más Años , Western Blotting , Electroforesis en Gel de Poliacrilamida , Humanos , Sinucleínas , alfa-SinucleínaRESUMEN
Expectations about future events are known to trigger neural mechanisms that affect both perception and action. Here we report that different and opposite expectations of bad and good motor performance modulate the therapeutic effects of subthalamic nucleus stimulation in Parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation. By analyzing the effects of subthalamic stimulation on the velocity of movement of the right hand, we found hand movement to be faster when the patients expected a good motor performance. The expectation of good performance was induced through a placebo-like procedure, thus indicating that placebo-induced expectations have influence on the treatment outcome. All these effects occurred within minutes, suggesting that expectations induce neural changes very quickly.
Asunto(s)
Terapia por Estimulación Eléctrica/métodos , Enfermedad de Parkinson/psicología , Enfermedad de Parkinson/terapia , Desempeño Psicomotor , Anciano , Terapia por Estimulación Eléctrica/psicología , Electrodos Implantados , Femenino , Mano/fisiología , Humanos , Masculino , Persona de Mediana Edad , Movimiento/fisiología , Pacientes/psicología , Pacientes/estadística & datos numéricos , Efecto Placebo , Desempeño Psicomotor/fisiología , Núcleo Subtalámico , Resultado del TratamientoRESUMEN
Patients affected by Parkinson's disease (PD) often complain of disturbed sleep resulting from nighttime motor disabilities such as nocturnal akinesia, tremor and rigidity, motor behaviour during REM sleep or periodic leg movements (PLM) during sleep. Sleep may also be affected by dopaminergic and anticholinergic drugs or coexisting depressive syndrome. Deep brain stimulation (DBS) of subthalamic nucleus (STN) effectively reduces PD motor disability. The aim of this study is to evaluate the sleep architecture modifications after STN DBS. We assessed five patients (two men and three women, mean age 63.8+/-3.3 years, with a mean history of PD of 13.8+/-4.9 years) who underwent STN DBS. The mean levodopa equivalent dosage (LED) was 1010+/-318 mg before surgery and 116+/-93 mg 3 months after surgery. Polysomnography (PSG) with audiovisual recordings was performed on two separate nights, the first assessment in the week before surgery and the second 3 months after surgery. Three months after surgery, PSG showed an increase in total sleep time, in the longest period of uninterrupted sleep, and in the percentage of stage 3-4 NREM sleep, while there was a reduction of wakefulness after sleep onset. PLM, apnea-hyopnea index and REM sleep behaviour disorder were unaffected by STN DBS. STN DBS seems to be an effective therapeutic option for the treatment of advanced Parkinson's disease because it improves the cardinal symptoms and also seems to improve sleep architecture.
Asunto(s)
Terapia por Estimulación Eléctrica/instrumentación , Trastornos Parkinsonianos/terapia , Fases del Sueño/fisiología , Núcleo Subtalámico/cirugía , Antidepresivos/uso terapéutico , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/epidemiología , Femenino , Humanos , Lorazepam/uso terapéutico , Masculino , Persona de Mediana Edad , Síndrome de Mioclonía Nocturna/diagnóstico , Síndrome de Mioclonía Nocturna/tratamiento farmacológico , Síndrome de Mioclonía Nocturna/epidemiología , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/cirugía , Paroxetina/uso terapéutico , Polisomnografía , Cuidados Preoperatorios , Estudios Prospectivos , Sertralina/uso terapéutico , Encuestas y Cuestionarios , Grabación de Cinta de VideoRESUMEN
The authors investigated the impact of IVIg as first line treatment of diabetic patients suffering from chronic inflammatory demyelinating polyneuropathy (CIDP) concomitant with distal symmetric axonal polyneuropathy. Nine patients with these clinical and electrophysiological features were treated with IVIg (0.4 g/Kg/day for 5 days). Clinical and electrophysiological evaluations were performed before and after treatment. Following IVIg treatment there was no significant improvement in clinical deficit. However, there was a significant and persistent decrease in the Rankin scale score and an improvement in the demyelinating feature on nerve conduction studies. Our findings suggest that IVIg had small but detectable beneficial effects on diabetic patients with CIDP and a high degree of axonal damage.
Asunto(s)
Neuropatías Diabéticas/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Inmunoterapia/métodos , Fibras Nerviosas Mielínicas/efectos de los fármacos , Nervios Periféricos/efectos de los fármacos , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Adulto , Anciano , Enfermedad Crónica , Neuropatías Diabéticas/inmunología , Neuropatías Diabéticas/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/inmunología , Fibras Nerviosas Mielínicas/patología , Conducción Nerviosa/efectos de los fármacos , Conducción Nerviosa/inmunología , Nervios Periféricos/inmunología , Nervios Periféricos/fisiopatología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/inmunología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/inmunología , Resultado del TratamientoRESUMEN
OBJECTIVE: Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) represents a proper choice for the treatment of advanced Parkinson's disease (PD). A correct selection of the patients as candidates for the surgery is essential for a good outcome. In this study, we analyzed the exclusion causes of a series of PD patients hospitalized for the selection protocol. METHODS: Ninety-eight PD patients as potential candidates for the STN DBS were studied. All patients were hospitalized and underwent a clinical evaluation of the PD stage, a levodopa challenge, a MR of the brain and a neuropsychological assessment. RESULTS: The percentage of subjects considered not suitable for the surgery was 29.6%. A single cause of exclusion was present in 65.5% of not suitable patients, while multiple causes were present in 34.5%. The most frequent cause of exclusion was the finding of neuropsychological or psychic disorders (48.3%); in 37.9% of the patients, the motor disability was not severe enough to justify the surgery, while in 31%, we found relevant abnormalities at the brain MR. Three patients (10.3%) were poorly motivated for the surgery, while in three others (10.3%), we found a significant illness other than PD. CONCLUSIONS: The finding that about 30% of the PD patients potentially suitable for STN DBS presents some exclusion causes underlines the importance of a careful selection of the candidates for this surgery.
Asunto(s)
Ensayos Clínicos como Asunto/normas , Terapia por Estimulación Eléctrica/normas , Procedimientos Neuroquirúrgicos/normas , Enfermedad de Parkinson/terapia , Selección de Paciente , Núcleo Subtalámico/cirugía , Factores de Edad , Anciano , Encéfalo/patología , Encéfalo/fisiopatología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Terapia por Estimulación Eléctrica/estadística & datos numéricos , Epilepsia/epidemiología , Femenino , Enfermedades Hematológicas/epidemiología , Humanos , Levodopa/uso terapéutico , Masculino , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Motivación , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/fisiopatología , Núcleo Subtalámico/fisiopatologíaRESUMEN
Long-term trials have demonstrated the continued efficacy of interferon (IFN) beta treatment in patients with relapsing-remitting (RR) multiple sclerosis (MS) during prolonged administration. The objective of the work was to evaluate the effects of reducing IFN beta administration frequency and total weekly dose in patients with RR MS who have achieved clinical and MRI disease activity stabilization during long-term IFN beta-1b treatment. Prospective 1-year follow-up of 27 RR MS patients on long-term 250 microg every other day (standard dose) IFN beta-1b treatment were randomized either to gradually reduce dose to 30 microg once-a-week IFN beta-1a (13 patients), or to continue on IFN beta-1b standard dose (14 patients). We found significant differences in the two group of patients. In the group of patients continuously treated with IFN beta-1b standard dose, 79% remained relapse free compared to 23% in the group receiving once-weekly IFN beta-1a (p=0.006). The number of patients without new PD/T2 lesions was higher in the group of patients continuously treated with IFN beta-1b standard dose (77%) compared to the once-weekly IFN beta-1a group (23%) (p=0.04). IFN beta is a long-term treatment for MS. The reduction of IFN beta-1b administration frequency and dose is not advisable even in patients free from clinical and MRI disease activity for many years.
Asunto(s)
Sistema Nervioso Central/efectos de los fármacos , Interferón beta/administración & dosificación , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adulto , Sistema Nervioso Central/inmunología , Sistema Nervioso Central/fisiopatología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Estudios Prospectivos , Prevención Secundaria , Tiempo , Resultado del TratamientoRESUMEN
We performed a microstimulation study of the subthalamic region of Parkinsonian patients who underwent bilateral electrode implantation in the subthalamic nuclei and whose heart rate and heart rate variability were recorded. The stimulation of the dorsalmost region, which includes the zona incerta and the dorsal pole of the subthalamic nucleus, produced autonomic responses that were constant over time. In fact, hidden stimulations (the patient is not aware of being stimulated) and open stimulations (the patient is aware of being stimulated) always induced the same responses. By contrast, the stimulation of the ventralmost region, which includes the ventral pole of the subthalamic nucleus and the substantia nigra pars reticulata, produced autonomic and emotional responses that were inconstant over time and varied according to the condition. In fact, different responses were elicited with hidden and open stimulations. These data suggest that the dorsal subthalamic nucleus and/or the zona incerta are involved in autonomic control, whereas the ventral subthalamic nucleus and/or the substantia nigra reticulata are involved in associative/limbic-related autonomic activity. The difference between the open and hidden stimulations in the ventral subthalamic region can explain previous studies in which open and hidden stimulations produced different therapeutic outcomes.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Terapia por Estimulación Eléctrica/psicología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Subtálamo/fisiopatología , Anciano , Electrodos Implantados , Emociones/fisiología , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Microelectrodos , Persona de Mediana Edad , Enfermedad de Parkinson/terapiaRESUMEN
Within the PREVIENI project, infertile and fertile women were enrolled from metropolitan, urban and rural Italian areas. Blood/serum levels of several endocrine disrupters (EDs) (perfluorooctane sulfonate, PFOS; perfluorooctanoic acid, PFOA; di-2-ethylhexyl-phthalate, DEHP; mono-(2-ethylhexyl)-phthalate, MEHP; bisphenol A, BPA) were evaluated concurrently with nuclear receptors (NRs) gene expression levels (ERa, ERb, AR, AhR, PPARg, PXR) in peripheral blood mononuclear cells (PBMCs). Infertile women from the metropolitan area displayed significantly higher levels of: BPA compared to fertile women (14.9 vs. 0.5 ng/mL serum); BPA and MEHP compared to infertile women from urban and rural areas; enhanced expression levels of NRs, except PPARg. Infertile women from urban and rural areas had PFOA levels significantly higher than those from metropolitan areas. Our study indicates the relevance of the living environment when investigating the exposure to EDs and the modulation of the NR panel in PBMC as a suitable biomarker of the effect, to assess the EDs impact on reproductive health.
Asunto(s)
Disruptores Endocrinos/sangre , Exposición a Riesgos Ambientales/estadística & datos numéricos , Contaminantes Ambientales/sangre , Fluorocarburos/sangre , Infertilidad Femenina/inducido químicamente , Adolescente , Adulto , Compuestos de Bencidrilo/sangre , Compuestos de Bencidrilo/toxicidad , Biomarcadores/sangre , Ciudades , Dietilhexil Ftalato/sangre , Dietilhexil Ftalato/toxicidad , Disruptores Endocrinos/toxicidad , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/toxicidad , Femenino , Humanos , Infertilidad Femenina/epidemiología , Italia/epidemiología , Fenoles/sangre , Fenoles/toxicidad , Ácidos Ftálicos/sangre , Ácidos Ftálicos/toxicidad , Receptores Citoplasmáticos y Nucleares/sangre , Receptores Citoplasmáticos y Nucleares/genética , Población RuralRESUMEN
Significant evidence supports that many endocrine disrupting chemicals could affect female reproductive health. Aim of this study was to compare the internal exposure to bisphenol A (BPA), perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), monoethylhexyl phthalate (MEHP), and di(2-ethylhexyl) phthalate (DEHP) in serum samples of 111 infertile women and 44 fertile women. Levels of gene expression of nuclear receptors (ER α , ER ß , AR, AhR, PXR, and PPAR γ ) were also analyzed as biomarkers of effective dose. The percentage of women with BPA concentrations above the limit of detection was significantly higher in infertile women than in controls. No statistically significant difference was found with regard to PFOS, PFOA, MEHP and DEHP. Infertile patients showed gene expression levels of ER α , ER ß , AR, and PXR significantly higher than controls. In infertile women, a positive association was found between BPA and MEHP levels and ER α , ER ß , AR, AhR, and PXR expression. PFOS concentration positively correlated with AR and PXR expression. PFOA levels negatively correlated with AhR expression. No correlation was found between DEHP levels and all evaluated nuclear receptors. This study underlines the need to provide special attention to substances that are still widely present in the environment and to integrate exposure measurements with relevant indicators of biological effects.
RESUMEN
Perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been used as surfactants in various industry and consumer products. PFOS/PFOA are very persistent in the environment and bioaccumulate in humans. They are potential reproductive and developmental toxicants and are considered to be emerging endocrine disrupters (EDs). The Italian project PREVIENI, funded by the Italian Environment Ministry, aims to link environment and human health through the investigation of selected endocrine disrupters (EDs) exposure and associated biomarkers related to human infertility conditions. In the early PREVIENI phase, PFOS and PFOA were determined in 53 couples affected by an infertility status, enrolled in a metropolitan area, according to established inclusion criteria and informed consensus. Nuclear receptors related to chemical compounds interactions were selected as biomarkers of effect and their gene expression modulations were analyzed in human peripheral blood mononuclear cell (PBMC). Among couples, subjects not presenting infertility factors (IF--) were separated from affected subjects (IF++). Most IF-- serum samples showed PFOS and PFOA concentrations overlapping the limit of detection (LOD) of 0.5 ng/g wet weight (ww). A substantial percentage of IF++ serum samples showed PFOS concentrations >20-fold the LOD, i.e. from 3 to 50 ng/g ww. In male (50%, n=26) and from 3 to 144 ng/g ww in female (37%, n=30) samples. PFOA values were below the LOD levels in 90% of the total samples. Peroxisome proliferator-activated receptor-gamma (PPARγ) and aryl hydrocarbon receptor (AhR) showed a low level of expression in PBMC of both IF++ and IF-- groups. Whereas alpha and beta estrogen receptors (ERα and ERß), androgen receptor (AR), and pregnane X receptor (PXR) were all upregulated in IF++ of both sexes with respect to IF-- group. Our preliminary results related to the metropolitan area indicate that subjects affected by infertility factors tend to have both higher PFOS levels and higher gene expression of specific nuclear receptors.
Asunto(s)
Ácidos Alcanesulfónicos/sangre , Biomarcadores/sangre , Caprilatos/sangre , Fluorocarburos/sangre , Infertilidad Femenina/inducido químicamente , Infertilidad Masculina/inducido químicamente , Receptores Citoplasmáticos y Nucleares/sangre , Adolescente , Adulto , Estudios de Casos y Controles , Disruptores Endocrinos/sangre , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente/métodos , Monitoreo Epidemiológico , Femenino , Expresión Génica , Humanos , Infertilidad Femenina/epidemiología , Italia/epidemiología , Masculino , Reacción en Cadena de la Polimerasa , Receptor X de Pregnano , Receptores Citoplasmáticos y Nucleares/genética , Receptores de Esteroides/sangre , Distribución por Sexo , Adulto JovenAsunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Neuralgia/etiología , Neoplasias de la Médula Espinal/complicaciones , Femenino , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Humanos , Persona de Mediana Edad , Radiografía , Cuero Cabelludo/patología , Neoplasias de la Médula Espinal/diagnóstico por imagenRESUMEN
Parkinson's disease (PD) is a complex, multifactorial neurodegenerative disease affecting about 2% of the population over 65â years. Etiopathogenetic mechanisms of PD are not fully understood, although a number of factors contributing to the selective degeneration of substantia nigra neurons have been identified, including mitochondrial dysfunction, proteasomal impairment, oxidative stress, excitotoxicity, and inflammation. Although a global view of the disease at the molecular level can be obtained only from the biochemical analysis of the affected human tissue, difficulties in obtaining human specimens of the affected area have limited substantially the number of reports published to date. Therefore, cellular and animal models of the disease have been developed to investigate single factors contributing to disease pathogenesis, e.g., protein aggregation or altered dopamine homeostasis. In this review, we report how proteomic methodologies have been used so far to investigate cellular and animal models of PD, as well as to compare postmortem specimens of substantia nigra of affected patients to that of control subjects. Proteomic studies concur to highlight the role of a compromised antioxidant defense in PD pathogenesis. The proteomic approach in the investigation of etiopathogenetic mechanisms of PD is still at its beginning, however, the findings reviewed here should serve as a useful foundation to further work.
RESUMEN
Parkinson's disease is a common neurodegenerative disorder with a mainly sporadic aetiology, although a number of monogenic familiar forms are known. Most of the motor symptoms are due to selective depletion of dopaminergic, neuromelanin-containing neurones of the substantia nigra pars compacta. Neuromelanin is the dark insoluble macromolecule that confers the black (substantia nigra) or grey (locus coeruleus) colour to monoaminergic basal ganglia. In particular, nigral neurones are pigmented because of the accumulation of by-products of oxidative metabolism of the neurotransmitter dopamine. The occurrence of dopamine (and all the enzymatic machinery required for dopamine synthesis, re-uptake and disposal) and neuromelanin, and a large amount of iron ions that interact with them, makes dopaminergic nigral neurones peculiarly susceptible to oxidative stress conditions that, in turn, may become amplified by the iron-neuromelanin system itself. In this mini-review we describe biophysical evidence for iron-neuromelanin modifications that support this hypothesis. Furthermore, we discuss the formation of the covalent linkage between alpha-synuclein and neuromelanin from the early stages of the disease.