[Show abstract][Hide abstract] ABSTRACT: Background
We investigated the effects of dietary calcium (Ca) and magnesium (Mg) intakes on cardiovascular disease risks in older patients with diabetes.Methods
In this cross-sectional study, 197 patients with type 2 diabetes aged 65 years and above were recruited. The 24-h dietary recalls and 1-week self-reported typical dietary intake patterns were collected. The Ca and Mg intakes of <67% of the recommended dietary allowance (RDA), 67%¿100% of RDA, and >100% of RDA were defined as low, moderate, and high Ca and Mg intakes, respectively. Anthropometric measurements were determined and biochemical analysis of blood and urine was performed.ResultsOur data indicated that 60.9% and 87.3% of our patients were Ca and Mg intakes below RDA, respectively. Patients whose Ca intake was high or low (81.2%) had significantly higher C-reactive protein (CRP) than those whose Ca intake was moderate (p¿=¿0.043). Furthermore, patients whose Mg intake was low (87.3%) had significantly higher CRP than that of those who took adequate Mg (p¿=¿0.025). The dietary Ca:Mg intake ratios were highly correlated with CRP, platelet counts, and red blood cell distribution (p¿<¿0.05). A dietary Ca:Mg intake ratio of 2.0¿2.5 was significantly correlated to lower CRP levels (p¿=¿0.013).Conclusions
High or low calcium intake increases cardiovascular disease risks. We suggest that ¿moderate¿ intake of 402¿600 mg Ca/day (approximately 67%¿100% of Taiwan RDA for Ca) and adequate Mg intake (or meeting RDA for Mg) with Ca:Mg intake ratio of 2.0¿2.5 are important for reducing cardiovascular disease risks in older patients with diabetes.
[Show abstract][Hide abstract] ABSTRACT: Serum magnesium (Mg) levels are closely controlled through a variety of Mg transporters and ionic channels during physiological conditions. These levels have been shown to increase during exercise. However, the effect of Mg transporter expression during exercise remains to be determined. The purpose of this study was to examine the gene expression of SLC41A1, a Na(+)/Mg(2+) exchanger, during exercise. In the present study, male C57BL/6JNarl mice (n=16, 8 weeks old) were subjected to 3 h forced exercise on a treadmill. The mice in the control and Mg groups were injected with saline and Mg (MgSO4, 90 mg/kg, intraperitoneal), respectively. Blood samples were obtained at three time points: prior to, following and 24 h after exercise. The gene expression levels of SLC41A1 were significantly downregulated to 23.6±4.6 and 12.6±10.2% following exercise in the control and Mg groups, respectively. The expression levels returned to the basal levels 24 h after exercise in the two groups and there was no significant difference found between the two groups. The downregulated role of SLC41A1 expression and its interaction with the Mg status in exercise requires further investigation.
[Show abstract][Hide abstract] ABSTRACT: A new version of the CatWalk XT system was evaluated as a tool for detecting very subtle alteration in gait based on higher speed sample rate; the system could also demonstrate minor changes in neurological function. In this study, we evaluated the neurological outcome of sciatic nerve injury intervened by local injection of hyaluronic acid. Using the CatWalk XT system, we looked for differences between treated and untreated groups and differences within the same group as a function of time so as to assess the power of the Catwalk XT system for detecting subtle neurological change.
Peripheral nerve injury was induced in 36 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into one of two groups: Group I: crush injury as the control; Group II: crush injury and local application with hyaluronic acid. These animals were subjected to neurobehavior assessment, histomorphology evaluation, and electrophysiology study periodically. These data were retrieved for statistical analysis.
The density of neurofilament and S-100 over the distal end of crushed nerve showed significant differences either in inter-group comparison at various time points or intra-group comparison from 7 to 28 days. Neuronal structure architecture, axon counts, intensity of myelination, electrophysiology, and collagen deposition demonstrate significant differences between the two groups. There was significant difference of SFI and angle of ankle in inter- group analysis from 7 to 28 days, but there were no significant differences in SFI and angle of ankle at time points of 7 and 14 days. In the Cat Walk XT analysis, the intensity, print area, stance duration, and swing duration all showed detectable differences at 7, 14, 21, and 28 days, whereas there were no significant difference at 7 and 14 days with CatWalk 7 testing. In addition, there were no significant differences of step sequence or regularity index between the two versions.
Hyaluronic acid augmented nerve regeneration as early as 7 days after crush injury. This subtle neurological alteration could be detected through the CatWalk XT gait analysis but not the SFI, angle of ankle, or CatWalk 7 methods.
Journal of NeuroEngineering and Rehabilitation 04/2014; 11(1):62. · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Glucose mobilization and utilization in the periphery and central nervous system are important during exercise and are responsible for exercise efficacy. Magnesium (Mg) is involved in energy production and plays a role in exercise performance. This study aimed to explore the effects of Mg on the dynamic changes in glucose and lactate levels in the muscle, blood and brain of exercising rats using a combination of auto-blood sampling and microdialysis. Sprague-Dawley rats were pretreated with saline or magnesium sulfate (MgSO4, 90 mg/kg, i.p.) 30 min before treadmill exercise (20 m/min for 60 min). Our results indicated that the muscle, blood, and brain glucose levels immediately increased during exercise, and then gradually decreased to near basal levels in the recovery periods of both groups. These glucose levels were significantly enhanced to approximately two-fold (P<0.05) in the Mg group. Lactate levels in the muscle, blood, and brain rapidly and significantly increased in both groups during exercise, and brain lactate levels in the Mg group further elevated (P<0.05) than those in the control group during exercise. Lactate levels significantly decreased after exercise in both groups. In conclusion, Mg enhanced glucose availability in the peripheral and central systems, and increased lactate clearance in the muscle during exercise.
PLoS ONE 01/2014; 9(1):e85486. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Object Neuropathic pain is debilitating, and when chronic, it significantly affects the patient physically, psychologically, and socially. The neurobehavior of animals used as a model for chronic constriction injury seems analogous to the neurobehavior of humans with neuropathic pain. However, no data depicting the severity of histomorphological alterations of the nervous system associated with graded changes in neurobehavior are available. To determine the severity of histomorphological alteration related to neurobehavior, the authors created a model of chronic constrictive injury of varying intensity in rats and used the CatWalk XT system to evaluate neurobehavior. Methods A total of 60 Sprague-Dawley rats, weighing 250-300 g each, were randomly assigned to 1 of 5 groups that would receive sham surgery or 1, 2, 3, or 4 ligatures of 3-0 chromic gut loosely ligated around the left sciatic nerve. Neurobehavior was assessed by CatWalk XT, thermal hyperalgesia, and mechanic allodynia before injury and periodically after injury. The nerve tissue from skin to dorsal spinal cord was obtained for histomorphological analysis 1 week after injury, and brain evoked potentials were analyzed 4 weeks after injury. Results. Significant differences in expression of nerve growth factor existed in skin, and the differences were associated with the intensity of nerve injury. After injury, expression of cluster of differentiation 68 and tumor necrosis factor-α was increased, and expression of S100 protein in the middle of the injured nerve was decreased. Increased expression of synaptophysin in the dorsal root ganglion and dorsal spinal cord correlated with the intensity of injury. The amplitude of sensory evoked potential increased with greater severity of nerve damage. Mechanical allodynia and thermal hyperalgesia did not differ significantly among treatment groups at various time points. CatWalk XT gait analysis indicated significant differences for print areas, maximum contact maximum intensity, stand phase, swing phase, single stance, and regular index, with sham and/or intragroup comparisons. Conclusions. Histomorphological and electrophysiological alterations were associated with severity of nerve damage. Subtle neurobehavioral differences were detected by the CatWalk XT system but not by mechanical allodynia or thermal hyperalgesia. Thus, the CatWalk XT system should be a useful tool for monitoring changes in neuropathic pain, especially subtle alterations.
Journal of Neurosurgery 11/2013; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Proper trace element level and antioxidant enzyme activity are crucial for the brain in maintaining normal neurological functions. To our knowledge, alteration of lipid peroxidation status, trace element level, and antioxidant activity in the homogenates of brain cortex after cerebral ischemia in gerbil, however, has not been investigated so far. Male Mongolian gerbils were divided into control and ischemic subjects. Cerebral ischemia was induced by occlusion of the right middle cerebral artery and right common carotid artery for 1 h. Experimental results showed that a significant increase (P < 0.01) of the malondialdehyde level was found in the ischemic brain as compared with the control group. Trace element analysis indicated that a remarkable elevation (P < 0.01) of the level of iron (Fe), chromium (Cr), and a statistical decrease of selenium (Se) and zinc (Zn) (P < 0.05) concentration were observed in the ischemic brain as compared with the control subject. No significant change (P > 0.05) of the copper (Cu) level was found in both experimental groups. Additionally, antioxidant activity of superoxide dismutase (P < 0.01) and catalase (P < 0.05) was significantly decreased in the ischemic brain as compared with the control subject. Taking all results together, it is conceivable to manifest the experimental findings that cerebral ischemia not only may result in an enhanced oxidative stress but also may lead to further oxidative injury. Moreover, disturbance of trace element level combined with declined antioxidant activity seems to play a significant role in responsible for the etiology of cerebral ischemia.
Biological trace element research 01/2013; · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Object Mobilization of hematopoietic progenitor cells (HPCs) from bone marrow involved in the process of peripheral nerve regeneration occurs mostly through deposits of CD34(+) cells. Treadmill exercise, with either differing intensity or duration, has been shown to increase axon regeneration and sprouting, but the effect of mobilization of HPCs on peripheral nerve regeneration due to treadmill exercise has not yet been elucidated. Methods Peripheral nerve injury was induced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were categorized into 2 groups: those with and without treadmill exercise (20 m/min for 60 minutes per day for 7 days). Cytospin and flow cytometry were used to determine bone marrow progenitor cell density and distribution. Neurobehavioral analysis, electrophysiological study, and regeneration marker expression were investigated at 1 and 3 weeks after exercise. The accumulation of HPCs, immune cells, and angiogenesis factors in injured nerves was determined. A separate chimeric mice study was conducted to assess CD34(+) cell distribution according to treadmill exercise group. Results Treadmill exercise significantly promoted nerve regeneration. Increased Schwann cell proliferation, increased neurofilament expression, and decreased Schwann cell apoptosis were observed 7 days after treadmill exercise. Elevated expression of S100 and Luxol fast blue, as well as decreased numbers of vacuoles, were identified in the crushed nerve 3 weeks after treadmill exercise. Significantly increased numbers of mononuclear cells, particularly CD34(+) cells, were induced in bone marrow after treadmill exercise. The deposition of CD34(+) cells was abolished by bone marrow irradiation. In addition, deposits of CD34(+) cells in crushed nerves paralleled the elevated expressions of von Willebrand factor, isolectin B4, and vascular endothelial growth factor. Conclusions Bone marrow HPCs, especially CD34(+) cells, were able to be mobilized by low-intensity treadmill exercise, and this effect paralleled the significant expression of angiogenesis factors. Treadmill exercise stimulation of HPC mobilization during peripheral nerve regeneration could be used as a therapy in human beings.
Journal of Neurosurgery 11/2012; · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Type 2 diabetes mellitus is a major global public health problem in the worldwide and is increasing in aging populations. Magnesium intake may be one of the most important factors for diabetes prevention and management. Low magnesium intake may exacerbate metabolic abnormalities. In this study, the relationships of magnesium intake with metabolic parameters, depression and physical activity in elderly patients with type 2 diabetes were investigated.
This cross-sectional study involved 210 type 2 diabetes patients aged 65 years and above. Participants were interviewed to obtain information on lifestyle and 24-hour dietary recall. Assessment of depression was based on DSM-IV criteria. Clinical variables measured included anthropometric measurements, blood pressure, and biochemical determinations of blood and urine samples. Linear regression was applied to determine the relationships of magnesium intake with nutritional variables and metabolic parameters.
Among all patients, 88.6% had magnesium intake which was less than the dietary reference intake, and 37.1% had hypomagnesaemia. Metabolic syndromes and depression were associated with lower magnesium intake (p < 0.05). A positive relationship was found between magnesium intake and HDL-cholesterol (p = 0.005). Magnesium intake was inversely correlated with triglyceride, waist circumference, body fat percent and body mass index (p < 0.005). After controlling confounding factor, HDL-cholesterol was significantly higher with increasing quartile of magnesium intake (p for trend = 0005). Waist circumference, body fat percentage, and body mass index were significantly lower with increase quartile of magnesium intake (p for trend < 0.001). The odds of depression, central obesity, high body fat percentage, and high body mass index were significantly lower with increasing quartile of magnesium intake (p for trend < 0.05). In addition, magnesium intake was related to high physical activity level and demonstrated lower serum magnesium levels. Serum magnesium was not significantly associated with metabolic parameters.
The majority of elderly type 2 diabetes who have low magnesium intake may compound this deficiency with metabolic abnormalities and depression. Future studies should determine the effects of increased magnesium intake or magnesium supplementation on metabolic control and depression in elderly people with type 2 diabetes.
[Show abstract][Hide abstract] ABSTRACT: Human amniotic fluid-derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell-derived factor-1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model.
Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 × 10(6) cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 × 10(6) cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed.
Stromal cell-derived factor-1α increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10-14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group.
Amniotic fluid-derived mesenchymal stem cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFMSCs paralleled the expression profiles of SDF-1α and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder.
Journal of Neurosurgery 04/2012; 116(6):1357-67. · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study compared the capabilities of dual-energy X-ray absorptiometry (DXA) and dental cone-beam computed tomography (CBCT) for predicting the cortical bone strength of rat femurs and tibias.
Specimens of femurs and tibias obtained from 14 rats were first scanned with DXA to obtain the areal bone mineral density (BMD) of the midshaft cortical portion of the bones. The bones were then scanned using dental CBCT to measure the volumetric cortical bone mineral density (vCtBMD) and the cross-sectional moment of inertia (CSMI) for calculating the bone strength index (BSI). A three-point bending test was conducted to measure the fracture load of each femur and tibia. Bivariate linear Pearson analysis was used to calculate the correlation coefficients (r values) among the CBCT measurements, DXA measurements, and three-point bending parameters.
The correlation coefficients for the associations of the fracture load with areal BMD (measured using DXA), vCtBMD (measured using CBCT), CSMI (measured using CBCT), and BSI were 0.585 (p = 0.028) and 0.532 (p = 0.050) (for the femur and tibia, respectively), 0.638 (p = 0.014) and 0.762 (p = 0.002), 0.778 (p = 0.001) and 0.792 (p<0.001), and 0.822 (p<0.001) and 0.842 (p<0.001), respectively.
CBCT was found to be superior to DXA for predicting cortical bone fracture loads in rat femurs and tibias. The BSI, which is a combined index of densitometric and geometric parameters, was especially useful. Further clinical studies are needed to validate the predictive value of BSI obtained from CBCT and should include testing on human cadaver specimens.
PLoS ONE 01/2012; 7(11):e50008. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased integration of CD34(+) cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34(+) cells. SDF-1α and its receptor mediate the recruitment of CD34(+) cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34(+) cell recruitment triggered by SDF-1α and the involvement of CD34(+) cells in peripheral nerve regeneration.
Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1α recombinant proteins; and Group 3, crush injury and local application of SDF-1α antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of SDF-1α, accumulation of CD34(+) cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after injury.
Application of SDF-1α increased the migration of CD34(+) cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1α, with a peak of 10-14 days postinjury, and this increased expression of SDF-1α paralleled the deposition of CD34(+) cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1α recombinant protein and abolished by administration of SDF-1α antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve.
Expression of SDF-1α facilitates recruitment of CD34(+) cells in peripheral nerve injury. The increased deposition of CD34(+) cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1α for enhancing the recruitment of CD34(+) cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders.
Journal of Neurosurgery 08/2011; 116(2):432-44. · 3.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Magnesium (Mg) supplements have been shown to significantly improve functional recovery in various neurological disorders. The essential benefits of Mg supplementation in peripheral nerve disorders have not been elucidated yet. The effect and mechanism of Mg supplementation on a sciatic nerve crush injury model was investigated. Sciatic nerve injury was induced in mice by crushing the left sciatic nerve. Mice were randomly divided into three groups with low-, basal- or high-Mg diets (corresponding to 10, 100 or 200% Mg of the basal diet). Neurobehavioral, electrophysiological and regeneration marker studies were conducted to explore nerve regeneration. First, a high Mg diet significantly increased plasma and nerve tissue Mg concentrations. In addition, Mg supplementation improved neurobehavioral, electrophysiological functions, enhanced regeneration marker, and reduced deposits of inflammatory cells as well as expression of inflammatory cytokines. Furthermore, reduced Schwann cell apoptosis was in line with the significant expression of bcl-2, bcl-X(L) and down-regulated expression of active caspase-3 and cytochrome C. In summary, improved neurological function recovery and enhanced nerve regeneration were found in mice with a sciatic nerve injury that were fed a high- Mg diet, and Schwann cells may have been rescued from apoptosis by the suppression of inflammatory responses.
Magnesium research: official organ of the International Society for the Development of Research on Magnesium 05/2011; 24(2):54-70. · 1.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Traumatic brain injury (TBI) results in neurological dysfunction and death through primary or secondary mechanisms. Here, we evaluated the effect of osmotic pump delivery of granulocyte colony-stimulating factor (G-CSF) on the histopathology and motor function recovery of rats after experimental TBI.
Sprague-Dawley rats were used as experimental model by fluid percussion device to cause brain injury on the motor cortex area. The rats were simultaneously subjected to TBI and were implanted of min-osmotic pump containing recombinant human G-CSF (300 μg/700 μl) via intraperitoneal injection. Motor function was assessed by rotarod test. 5-bromo-2'-deoxyuridine (BrdU) was used to label the proliferating cells and their differentiation was evaluated by histology and immunohistochemistry.
The G-CSF group showed significantly better motor function recovery than the control group, and the effect lasted up to 14 days after TBI. Moreover, the G-CSF group exhibited a greater increase in the number of BrdU-positive cells compared with the control group. The G-CSF group also had a significantly higher number of DCX-positive cells in the ipsilateral subventricular zone (SVZ) than the control group.
These data suggest that the beneficial effect of delivering G-CSF via an osmotic pump may improve the motor function and enhance neurogenesis in the SVZ of the injured brain.
Neurological Research 12/2010; 32(10):1041-9. · 1.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The developing neural cell must form a highly organized architecture to properly receive and transmit nerve signals. Neural formation from embryonic stem (ES) cells provides a novel system for studying axonogenesis, which are orchestrated by polarity-regulating molecules. Here the ES-derived motoneurons, identified by HB9 promoter-driven green fluorescent protein (GFP) expression, showed characteristics of motoneuron-specific gene expression. In the majority of motoneurons, one of the bilateral neurites developed into an axon that featured with axonal markers, including Tau1, vesicle acetylcholine transporter, and synaptophysin. Interestingly, one third of the motoneurons developed bi-axonal processes but no multiple axonal GFP cell was found. The neuronal polarity-regulating proteins, including the phosphorylated AKT and ERK, were compartmentalized into both of the bilateral axonal tips. Importantly, this aberrant axon morphology was still present after the engraftment of GFP(+) neurons into the spinal cord, suggesting that even a mature neural environment fails to provide a proper niche to guide normal axon formation. These findings underscore the necessity for evaluating the morphogenesis and functionality of neurons before the clinical trials using ES or somatic stem cells.
[Show abstract][Hide abstract] ABSTRACT: Magnesium sulfate (MgSO4) ameliorates focal ischemia-induced neuronal death in the rat and gerbil models. However, the molecular mechanisms for this neuroprotection are not known. Focal cerebral ischemia was produced by unilateral occlusion of the right common carotid artery and the right middle cerebral artery (CCAO + MCAO) for 30 min or 60 min. Treatment with MgSO4 significantly increased the level of mitogen-activated protein kinase/extra-cellular signal-regulated kinase kinase 1/2 (MEK1/2), extra-cellular signal-regulated kinase 1/2 (ERK1/2), cyclic-AMP response element binding protein (CREB) phosphorylation and the anti-apoptotic protein Bcl-2 both in the non-ischemic (contralateral) and ischemic (ipsilateral) cortex. However, these effects were reversed by administration of U0126, a MEK kinase inhibitor. In the ipsilateral cortex, a significant increase in the level of the proapoptotic proteins Bax, Bad, BNIP3 and activated caspase 3 were detected at the end of focal ischemia compared to the non-ischemic cortex. Treatment of MgSO4 prevented these ischemia-induced activations of the death cascade. Collectively, these data indicate that the ERK-CREB-Bcl-2 signaling pathway might be involved in MgSO4-induced neuroprotection following focal ischemia. Moreover, MgSO4 treatment also resulted in a reduction in pro-apoptotic proteins. These results enhance our understanding on the role of MgSO4 in treating cerebral ischemia.
The Chinese journal of physiology 10/2010; 53(5):299-309. · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rosiglitazone is a potent synthetic peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist which improves glucose control in the plasma and reduces ischemic brain injury. However, the pharmacokinetics of rosiglitazone in the brain is still unclear. In this study, a method using liquid chromatography-mass spectrometry coupled with microdialysis and an auto-blood sampling system was developed to determine rosiglitazone and glucose concentration in the brain and blood of gerbils subjected to treatment with rosiglitazone (3.0 mg kg(-1), i.p.). The results showed the limit of detection was 0.04 μg L(-1) and the correlation coefficient was 0.9997 for the determination of rosiglitazone in the brain. The mean parameters, maximum drug concentration (C(max)) and the area under the concentration-time curve from time zero to time infinity (AUC(inf)), following rosiglitazone administration were 1.06±0.28 μg L(-1) and 296.82±44.67 μg min L(-1), respectively. The time to peak concentration (C(max) or T(max)) of rosiglitazone occurred at 105±17.10 min, and the mean elimination half-life (t(1/2)) from brain was 190.81±85.18 min after administration of rosiglitazone. The brain glucose levels decreased to 71% of the basal levels in the rosiglitazone-treated group when compared with those in the control (p<0.01). Treatment with rosiglitazone decreased blood glucose levels to 80% at 1h after pretreatment of rosiglitazone (p<0.05). In addition, pretreatment with rosiglitazone significantly reduced the cerebral infarct volume compared with that of the control group. These findings suggest that this method may be useful for simultaneous and continuous determination of rosiglitazone and glucose concentrations in brain and plasma. Rosiglitazone was effective at penetrating the blood-brain barrier as evidenced by the rapid appearance of rosiglitazone in the brain, and rosiglitazone may contribute to a reduction in the extent of injuries related to cerebral ischemic stroke via its hypoglycemic effect.
Journal of pharmaceutical and biomedical analysis 10/2010; 54(4):759-64. · 2.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Statins have therapeutic benefits for the management of several disorders. A short-term course of a high-dose statin pretreatment has demonstrated neuroprotective effects against neurological diseases. However, the molecular basis underlying the neuroprotective action of statins remains unclear.
We investigated whether a short-term course of high-dose atorvastatin pretreatment has beneficial effects in protecting sciatic nerve from crush injury.
Atorvastatin (5 mg/kg) or saline was given orally to Sprague-Dawley rats for 7 days before injury. The rats were subjected to crush injury in the left sciatic nerve with a vessel clamp. Biochemical, functional, electrophysiological, and morphological alterations occurring during injury-induced degeneration/regeneration were examined.
Atorvastatin improved injury-induced neurobehavioral/electrophysiological changes and axonal loss. Damage-associated alterations, including structural disruption, oxidative stress, inflammation, and apoptosis, were attenuated by atorvastatin. After injury, regeneration-associated genes, including growth-associated protein-43, myelin basic protein, ciliary neurotrophic factor, and collagen, were upregulated by atorvastatin. The suppression of extracellular signal-regulated kinase, AKT, signal transducer and activators of transcription-1, and necrosis factor-kappaB and the elevated activation of c-Jun N-terminal kinase, Smad2/3, and activating protein-1 were associated with the neuroprotective action of atorvastatin.
These findings suggest that a short-term course of high-dose atorvastatin pretreatment can protect against sciatic nerve crush injury through modifying intracellular or extracellular environments, making it favorable for regeneration.
[Show abstract][Hide abstract] ABSTRACT: The amniotic membrane has been clinically applied as a therapeutic material in wound covering and corneal surface reconstruction. Recently, mesenchymal stem cells (MSCs) have been isolated from the placenta, specifically from the amniotic membrane. However, the localization of MSCs in the amniotic membrane has not been determined. In this study, term placenta was collected, and we performed immunohistochemical staining techniques to identify and localize MSCs in the mesoderm of the amniotic membrane in situ with MSC antibodies, including CD90 and CD105. We further directly cultured and characterized MSCs from the amniotic membrane mesoderm (AMSCs). The AMSCs were easily isolated and represented a homogenous fibroblastic morphology at early passages. In addition to MSC surface markers, AMSCs expressed Sox2, Oct-4 and Nanog. AMSCs could be induced into osteocytes, adipocytes and chondrocytes in vitro and show immunosuppressive effects on T-cell proliferation. Under appropriate conditions, AMSCs could differentiate into neuronal-like cells, which were identified by neuronal-specific markers and their ability to secrete dopamine. This study reveals that AMSCs provide a promising source for stem cell studies and also extend the clinical potential of the amniotic membrane in the field of regenerative medicine.
[Show abstract][Hide abstract] ABSTRACT: Human mesenchymal stromal cells (hMSC) play a crucial role in tissue engineering and regenerative medicine, and have important clinical potential for cell therapy. However, many hMSC studies have been restricted by limited cell numbers and difficult detection in vivo. To expand the lifespan, hMSC are usually immortalized by virus-mediated gene transfer. However, these genetically modified cells easily lose critical phenotypes and stable genotypes because of insertional mutagenesis.
We used a non-viral transfection method to establish human telomerase reverse transcriptase-immortalized cord blood hMSC (hTERT-cbMSC). We also established red fluorescent protein (RFP)-expressing hTERT-cbMSC (hTERT/RFP-cbMSC) by the same non-viral transfection method, and these cells were injected into a rat model with traumatic brain injury for in vivo detection analysis.
The hTERT-cbMSC could grow more than 200 population doublings with a stable doubling time and maintained differentiation capacities. hTERT/RFP-cbMSC could proliferate efficiently within 2 weeks at the injury location and could be detected easily under a fluorescent microscope. Importantly, both hTERT-cbMSC and hTERT/RFP-cbMSC showed no chromosomal abnormalities by karyotype analysis and no tumor formation in severe combined immunodeficient (SCID) mice by transplantation assay.
We have developed immortalized cbMSC with hTERT expression and RFP expression, which will be useful tools for stem cell research and translational study.