ObjectiveIn patients with spinocerebellar ataxia type 1 or 2 (SCA1 or SCA2) and in their asymptomatic gene-positive relatives (AsyRs) we investigated the event-related desynchronization and synchronisation (ERD/ERS) on magnetoencephalographic signals to assess the changes occurring before manifest ataxia, by comparing the results obtained in AsyRs and in their gene-negative healthy relatives (HRs).MethodsTwenty-four patients (12 SCA1, 12 SCA2), 24 AsyRs (13 SCA1, 11 SCA2) and 17 HRs performed a visually cued Go/No-go task. We evaluated the ERD/ERS in regions of interest corresponding to the frontal, central and parietal cortices.ResultsIn the SCA patients the main findings were a loss of side predominance for alpha and beta ERD and significantly weakened beta ERS. In AsyRs the main finding was a significantly enhanced alpha ERD, namely in those who were approaching the estimated time of symptom onset.ConclusionsIn ataxic patients, the loss of ERD lateralisation and the significantly reduction of beta ERS suggest defective bilateral processes that are involved in ending the movement. In AsyRs, enhanced alpha ERD proposes the presence of preclinical marker closely preceding symptom onset.SignificanceMovement-related ERD/ERS can detect the defective sensorimotor integration in ataxic patients, and reveals possible compensatory mechanisms in their AsyRs. 相似文献
1.?Organophosphorus pesticides (OPs) are known to interact with human ATP-binding cassette drug efflux pumps. The present study was designed to determine whether they can also target activities of human solute carrier (SLC) drug transporters.
2.?The interactions of 13 OPs with SLC transporters involved in drug disposition, such as organic cation transporters (OCTs), multidrug and toxin extrusion proteins (MATEs), organic anion transporters (OATs) and organic anion transporting polypeptides (OATPs), were mainly investigated using transporter-overexpressing cell clones and fluorescent or radiolabeled reference substrates.
3.?With a cut-off value of at least 50% modulation of transporter activity by 100?µM OPs, OAT1 and MATE2-K were not impacted, whereas OATP1B1 and MATE1 were inhibited by two and three OPs, respectively. OAT3 activity was similarly blocked by three OPs, and was additionally stimulated by one OP. Five OPs cis-stimulated OATP2B1 activity. Both OCT1 and OCT2 were inhibited by the same eight OPs, including fenamiphos and phosmet, with IC50 values however in the 3–30?µM range, likely not relevant to environmental exposure.
4.?These data demonstrated that various OPs inhibit SLC drug transporter activities, especially those of OCT1 and OCT2, but only when used at high concentrations not expected to occur in environmentally-exposed humans. 相似文献
IntroductionAsymptomatic intracranial atherosclerotic stenosis (AICAS) is a common cause of stroke. Elderly women were more likely than men to develop AICAS, although it indicated that a lifelong exposure to estrogen could lower the risks of cardiovascular disease (CVDs).ObjectiveThe present study aims to ascertain whether postmenopausal time is a risk factor of AICAS. Fostering a correct perception of menopause is of great significance for the overall well-being of the elderly women.MethodsAll participants received a questionnaire, physical examination, laboratory testing and transcranial Doppler. The menopausal population (n = 701) was divided into three groups by tertiles of postmenopausal time. Two-tailed testing and trend test were used to reveal the relationship between postmenopausal time and newly discovered AICAS. Other potential risk factors were also analyzed to ascertain whether there was a relation between postmenopausal time and the newly discovered ICAS.ResultsBoth mean age and mean postmenopausal time were gradually increased from G0 to G2. The same trend occurred in hypertension, diabetes mellitus, total cholesterol, triglyceride, C-reactive protein and serum homocysteine. Adjusting for various confounding factors, postmenopausal time was not a risk factor for newly discovered AICAS. Multifactor analysis and stratifying analysis showed no correlation between newly discovered AICAS and postmenopausal time.ConclusionsPostmenopausal time is not an independent risk factor of AICAS. No relationship was detected between postmenopausal time and newly discovered AICAS, while vigorous control of body weight, blood pressure/glucose/lipids and smoke cessation are vital for preventing the occurrence of AICAS. 相似文献
Duchenne muscular dystrophy (DMD) has been found to be associated with cognitive impairment. However, few studies have addressed cognitive impairment among mothers of children with DMD. In the present study, the neuropsychological profiles of both carrier mothers (C-Ms) and noncarrier mothers (NC-Ms) were examined, and the findings were compared with healthy control mothers (HC-Ms). There were 90 participants, consisting of 31 C-Ms, 24 NC-Ms, and 35 HC-Ms, each of whom completed a neuropsychological test battery. C-Ms had poorer cognition performance in attention, working memory, immediate verbal memory, visuospatial skills, and executive functions than NC-Ms, and HC-Ms. This study provides evidence that there may be cognitive impairment in mothers of patients with DMD. The cognitive impairment of C-Ms has similarities to that seen in children with DMD. 相似文献
IntroductionAlthough changes in liver function tests can be non-specific in numerous clinical conditions, they can be the first sign of a potentially serious disease in an asymptomatic patient.Material and methodsRetrospective cohort study, performed by reviewing the records of children of a reference hospital central laboratory with alanine aminorransferase enzyme (ALT) elevation during a 6 month aleatory period.Results572 blood tests with serum ALT elevation corresponding to 403 patients had been assessed during the period studied. 98 patients were excluded for presenting abnormal liver test before the study period of comorbidity that could produce ALT elevation. The remaining 305 patients, 22.6% were diagnosed with a medical condition during the first blood test that explained the ALT elevation, although only 33.3% of them were followed up until verifying their normalization. Final study sample consists of 236 patients with abnormal liver test without apparent liver disease. Adequate follow-up was found only in 29% of them. From this group, 9 patients (13%) were diagnosed with liver disease. The rest of the sample were not properly monitored. In patients with higher serum ALT levels, follow-up was early and more appropiate.ConclusionsIn our area, most children without apparent liver disease are no properly monitored. Therefore, an opportunity to diagnosis and treat a potential liver disease was lost in a great number of children. All children with unexplainedhypertransaminasaemia must be studied. 相似文献