Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was co...Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.展开更多
Magnesium, Mg2+, is the second most abundant intracellular cation after potassium and the fourth most abundant in the body. It was first isolated in 1808 by the English chemist, Sir Humphrey Davy. Magnesium is essenti...Magnesium, Mg2+, is the second most abundant intracellular cation after potassium and the fourth most abundant in the body. It was first isolated in 1808 by the English chemist, Sir Humphrey Davy. Magnesium is essential to numerous biochemical reactions. It modulates key physiological processes such as metabolic biochemistry, nucleic acid synthesis, receptor-binding and ion flux. The western diet falls short of the recommended daily allowance of 4.5 mg/Kg/day and important dietary sources are seeds, grains, nuts and green vegetables. It is used as a therapeutic agent in a broad range of pathologies: neurological, cardiovascular, respiratory, gastrointestinal and obstetric. The pharmacokinetics and pharmacodynamics of magnesium, as a drug, are not well understood. Despite its fundamental importance to human physiology, it remains an electrolyte that is not routinely measured as part of the “urea & electrolytes” test and is the most overlooked electrolyte deficiency in hospital inpatients. This review will summarise the importance of magnesium homeostasis, its pharmacological effects and clinical applications.展开更多
Pheochromocytoma is a tumor that originates from eitherchromaffincells in adrenal medulla or in other paraganglia tissues of the sympathetic nervous system. The perioperative management is quite challenging especially...Pheochromocytoma is a tumor that originates from eitherchromaffincells in adrenal medulla or in other paraganglia tissues of the sympathetic nervous system. The perioperative management is quite challenging especially in view of hemodynamic fluctuations. Pheochromocytoma is challenging in view of the impact of excessive and depleted catecholamines in the perioperative period. It requires a through preoperative evaluation and optimization with meticulous intraoperative management. The postoperative period requires vigilance to prevent any untoward complication. In this review we review these concepts based on recent evidence for an optimal outcome.展开更多
基金funded by Egyptian Cultural and Educational Bureau in London,Egyptian mission sector and ministry of higher education in Egypt(grant No.GAM2649)。
文摘Dental pulp stem cells(DPSCs) secrete neurotrophic factors which may play an important therapeutic role in neural development, maintenance and repair. To test this hypothesis, DPSCs-conditioned medium(DPSCs-CM) was collected from 72 hours serum-free DPSCs cultures. The impact of DPSCs-derived factors on PC12 survival, growth, migration and differentiation was investigated. PC12 cells were treated with nerve growth factor(NGF), DPSCs-CM or co-cultured with DPSCs using Transwell inserts for 8 days. The number of surviving cells with neurite outgrowths and the length of neurites were measured by image analysis. Immunocytochemical staining was used to evaluate the expression of neuronal markers NeuN, microtubule associated protein 2(MAP-2) and cytoskeletal marker βIII-tubulin. Gene expression levels of axonal growth-associated protein 43 and synaptic protein Synapsin-I, NeuN, MAP-2 and βIII-tubulin were analysed by quantitative polymerase chain reaction(qRT-PCR). DPSCs-CM was analysed for the neurotrophic factors(NGF, brain-derived neurotrophic factor [BDNF], neurotrophin-3, and glial cell-derived neurotrophic factor [GDNF]) by specific ELISAs. Specific neutralizing antibodies against the detected neurotrophic factors were used to study their exact role on PC12 neuronal survival and neurite outgrowth extension. DPSCs-CM significantly promoted cell survival and induced the neurite outgrowth confirmed by NeuN, MAP-2 and βIII-tubulin immunostaining. Furthermore, DPSCsCM was significantly more effective in stimulating PC12 neurite outgrowths than live DPSCs/PC12 co-cultures over the time studied. The morphology of induced PC12 cells in DPSCs-CM was similar to NGF positive controls;however, DPSCs-CM stimulation of cell survival was significantly higher than what was seen in NGF-treated cultures. The number of surviving PC12 cells treated with DPSCs-CM was markedly reduced by the addition of anti-GDNF, whilst PC12 neurite outgrowth was significantly attenuated by anti-NGF, anti-GDNF and anti-BDNF antibodies. These findings demonstrated that DPSCs were able to promote PC12 survival and differentiation. DPSCs-derived NGF, BDNF and GDNF were involved in the stimulatory action on neurite outgrowth, whereas GDNF also had a significant role in promoting PC12 survival. DPSCs-derived factors may be harnessed as a cell-free therapy for peripheral nerve repair. All experiments were conducted on dead animals that were not sacrificed for the purpose of the study. All the methods were carried out in accordance with Birmingham University guidelines and regulations and the ethical approval is not needed.
文摘Magnesium, Mg2+, is the second most abundant intracellular cation after potassium and the fourth most abundant in the body. It was first isolated in 1808 by the English chemist, Sir Humphrey Davy. Magnesium is essential to numerous biochemical reactions. It modulates key physiological processes such as metabolic biochemistry, nucleic acid synthesis, receptor-binding and ion flux. The western diet falls short of the recommended daily allowance of 4.5 mg/Kg/day and important dietary sources are seeds, grains, nuts and green vegetables. It is used as a therapeutic agent in a broad range of pathologies: neurological, cardiovascular, respiratory, gastrointestinal and obstetric. The pharmacokinetics and pharmacodynamics of magnesium, as a drug, are not well understood. Despite its fundamental importance to human physiology, it remains an electrolyte that is not routinely measured as part of the “urea & electrolytes” test and is the most overlooked electrolyte deficiency in hospital inpatients. This review will summarise the importance of magnesium homeostasis, its pharmacological effects and clinical applications.
文摘Pheochromocytoma is a tumor that originates from eitherchromaffincells in adrenal medulla or in other paraganglia tissues of the sympathetic nervous system. The perioperative management is quite challenging especially in view of hemodynamic fluctuations. Pheochromocytoma is challenging in view of the impact of excessive and depleted catecholamines in the perioperative period. It requires a through preoperative evaluation and optimization with meticulous intraoperative management. The postoperative period requires vigilance to prevent any untoward complication. In this review we review these concepts based on recent evidence for an optimal outcome.
