Tremor is a manifestation of a variety of human neurodegenerative diseases, notably Parkinson’s disease (PD) and Essential Tremor (ET), both affecting millions worldwide. PD is primarily caused by a progressive loss ...Tremor is a manifestation of a variety of human neurodegenerative diseases, notably Parkinson’s disease (PD) and Essential Tremor (ET), both affecting millions worldwide. PD is primarily caused by a progressive loss of dopamine neurons in the nigrostriatal system that leads to widespread motor symptoms such as bradykinesia, rigidity, tremor and postural instability. ET typically involves a tremor of the arms, hands or fingers. No definitive test or biomarker is yet available for PD or ET, so the rate of misdiagnosis is relatively high. As tremor is a very common feature at the onset of both diseases, it is crucial to be able to characterize it. This is made possible using acce?lerometers to quantify the tremor amplitude and frequency. In this work we aim to find tasks involving upper limb movements that are suitable to modulate both types of tremor. Four tasks were tested, differing on whether the arms moved together or alternatingly and whether loads were added. Significant differences in tremor measures were found when patients were asked to perform simultaneous rapid arms movements with loads placed on their wrists. These results may allow the design of an efficient fMRI protocol for identifying the cortical circuits responsible for the modulation of tremor.展开更多
Light is an electromagnetic stimulus that in mammals is sensed by specialized neurons in the retina.The physiological response to light encompasses two fundamental and different functional outputs：image-forming and n...Light is an electromagnetic stimulus that in mammals is sensed by specialized neurons in the retina.The physiological response to light encompasses two fundamental and different functional outputs：image-forming and non-image forming.展开更多
The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ing...The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.展开更多
Introduction: Multidrug resistance (MDR) is one of the major problems of chemotherapy. Overexpression of efflux pumps, such as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP-1) and lung resistance pr...Introduction: Multidrug resistance (MDR) is one of the major problems of chemotherapy. Overexpression of efflux pumps, such as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP-1) and lung resistance protein (LRP) can lead to MDR. Verapamil and L-buthionine-sulfoximine (BSO) are two modulators of these proteins. This study aims to compare 99mTc-Sestamibi transport kinetics in human colorectal adenocarcinoma cell lines, in the presence and absence of the MDR modulators verapamil and BSO. Material and Methods: MDR proteins expression was evaluated in sensitive (WiDr) and resistant (LS1034) human colorectal adenocarcinoma cell lines. Intracellular and plasma membrane Pgp and MRP1, and LRP expression was analyzed by flow-cytometry and western blot. Cellular transport kinetics was assessed using 99mTc-Sestamibi. MDR modulation was evaluated though retention studies in resistant cells after incubation with the modulators. Results: Pgp expression was significantly higher (p≤0.001) in resistant cells. These results were confirmed by western blot analysis. 99mTc-Sestamibi uptake and retention percentage were significantly higher (p99mTc-Sestamibi, there were differences among the MDR modulators used (p99mTc-Sestamibi could indicate MDR phenotype in colorectal adenocarcinoma cells. As the modulators used showed a reversion of the retention profile only for the first minutes, their administration should occur immediately before the administration of cytotoxic drugs.展开更多
文摘Tremor is a manifestation of a variety of human neurodegenerative diseases, notably Parkinson’s disease (PD) and Essential Tremor (ET), both affecting millions worldwide. PD is primarily caused by a progressive loss of dopamine neurons in the nigrostriatal system that leads to widespread motor symptoms such as bradykinesia, rigidity, tremor and postural instability. ET typically involves a tremor of the arms, hands or fingers. No definitive test or biomarker is yet available for PD or ET, so the rate of misdiagnosis is relatively high. As tremor is a very common feature at the onset of both diseases, it is crucial to be able to characterize it. This is made possible using acce?lerometers to quantify the tremor amplitude and frequency. In this work we aim to find tasks involving upper limb movements that are suitable to modulate both types of tremor. Four tasks were tested, differing on whether the arms moved together or alternatingly and whether loads were added. Significant differences in tremor measures were found when patients were asked to perform simultaneous rapid arms movements with loads placed on their wrists. These results may allow the design of an efficient fMRI protocol for identifying the cortical circuits responsible for the modulation of tremor.
基金supported by the Spanish Ministry of Education and Science SAF2015-67643-PSpanish Ministry of Economy and Competitiveness ISCIII-FEDER “Una manera de hacer Europa” PI13/00643
文摘Light is an electromagnetic stimulus that in mammals is sensed by specialized neurons in the retina.The physiological response to light encompasses two fundamental and different functional outputs：image-forming and non-image forming.
文摘The development of biotechnology-based active pharmaceutical ingredients, such as GLP-1 analogs, brought changes in type 2 diabetes treatment options. For better therapeutic efficiency, these active pharmaceutical ingredients require appropriate administration, without the development of adverse effects or toxicity. Therefore, it is required to develop several quantification methods for GLP-1 analogs products, in order to achieve the therapeutic goals, among which ELISA and HPLC arise. These methods are developed, optimized and validated in order to determine GLP-1 analogs, not only in final formulation of the active pharmaceutical ingredient, but also during preclinical and clinical trials assessment. This review highlights the role of ELISA and HPLC methods that have been used during the assessment for GLP-1 analogs, especially for exenatide.
文摘Introduction: Multidrug resistance (MDR) is one of the major problems of chemotherapy. Overexpression of efflux pumps, such as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP-1) and lung resistance protein (LRP) can lead to MDR. Verapamil and L-buthionine-sulfoximine (BSO) are two modulators of these proteins. This study aims to compare 99mTc-Sestamibi transport kinetics in human colorectal adenocarcinoma cell lines, in the presence and absence of the MDR modulators verapamil and BSO. Material and Methods: MDR proteins expression was evaluated in sensitive (WiDr) and resistant (LS1034) human colorectal adenocarcinoma cell lines. Intracellular and plasma membrane Pgp and MRP1, and LRP expression was analyzed by flow-cytometry and western blot. Cellular transport kinetics was assessed using 99mTc-Sestamibi. MDR modulation was evaluated though retention studies in resistant cells after incubation with the modulators. Results: Pgp expression was significantly higher (p≤0.001) in resistant cells. These results were confirmed by western blot analysis. 99mTc-Sestamibi uptake and retention percentage were significantly higher (p99mTc-Sestamibi, there were differences among the MDR modulators used (p99mTc-Sestamibi could indicate MDR phenotype in colorectal adenocarcinoma cells. As the modulators used showed a reversion of the retention profile only for the first minutes, their administration should occur immediately before the administration of cytotoxic drugs.
