Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained defic...Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.展开更多
Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to...Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to evaluate the influ- ence of aging on DNA damage in whole blood cells from apolipoprotein E-deficient (apoE?/?) mice and compared the results to those found in cells from wild-type C57BL/6 (C57) mice. Using the alkaline comet assay and fluorescent ethidium bromide staining, DNA damage was analyzed in the peripheral whole blood (5 μL) cells that were isolated from either young (8-week-old) and elderly (72-week-old) apoE?/? mice or from age-matched C57 mice. The levels of total plasma cholesterol were approximately 6-fold higher in apoE?/? mice of both ages compared to C57 mice. Elderly apoE?/? mice showed significantly higher levels of DNA damage (19%) compared to elderly C57 mice (8%, p < 0.01) and young apoE?/? mice (10%, p < 0.01). The comet assay in whole blood cells is a suitable technique for the detection of DNA damage in the apoE?/? mouse;it is an easy, rapid, inexpensive and sensitive method. The novelty of this study is that DNA damage occurring in whole blood cells of this murine model requires the concurrence of aging and oxida- tive stress-related hypercholesterolemia.展开更多
The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the physiological production of NO in endo-thelial cells and platelets. There is evidence that the G894T polymorphism of the eNOS gene is asso...The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the physiological production of NO in endo-thelial cells and platelets. There is evidence that the G894T polymorphism of the eNOS gene is associated with this enzyme's basal activity and NO production, which could contribute to the pathogenesis of periodontal diseases (PD). Therefore, this study was designed to investigate the role of G894T polymorphism in the eNOS gene as a predisposing factor to periodontal disease. In this study we investigated the association of this polymorphism with PD in an admix-ture population (N = 119) separated into three groups: Healthy control, Moderate and Severe PD, without statistical differences among them for risk factors for PD, such as age, gender and smoking status. We observed that the GG ge-notype was associated with the progression of PD as indicated by an increase in frequency of approximately 18% in the Moderate and 26% in the Severe groups compared to the Healthy control group (p = 0.0302). This finding indicates that patients carrying the GG genotype have a greater chance of developing PD compared with those carrying the T allele, and it reinforces the notion that genetic factors contribute to the development and aggravation of PD.展开更多
Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about...Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.展开更多
文摘Background & Objective: Chronic excessive alcohol consumption causes white matter degeneration with myelin loss and impaired neuronal conductivity. Subsequent rarefaction of myelin accounts for the sustained deficits in cognition, learning, and memory. Correspondingly, chronic heavy or repeated binge alcohol exposures in humans and experimental models alter myelin lipid composition leading to build-up of ceramides which can be neurotoxic and broadly inhibitory to brain functions. Methods: This study examined the effects of chronic + binge alcohol exposures (8 weeks) and intervention with myriocin, a ceramide inhibitor, on neurobehavioral functions (Open Field, Novel Object Recognition, and Morris Water Maze tests) and frontal lobe white matter myelin lipid biochemical pathology in an adult Long-Evans rat model. Results: The ethanol-exposed group had significant deficits in executive functions with increased indices of anxiety and impairments in spatial learning acquisition. Myriocin partially remediated these effects of ethanol while not impacting behavior in the control group. Ethanol-fed rats had significantly smaller brains with broadly reduced expression of sulfatides and reduced expression of two of the three sphingomyelins detected in frontal white matter. Myriocin partially resolved these effects corresponding with improvements in neurobehavioral function. Conclusion: Therapeutic strategies that support cerebral white matter myelin expression of sulfatide and sphingomyelin may help remediate cognitive-behavioral dysfunction following chronic heavy alcohol consumption in humans.
文摘Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to evaluate the influ- ence of aging on DNA damage in whole blood cells from apolipoprotein E-deficient (apoE?/?) mice and compared the results to those found in cells from wild-type C57BL/6 (C57) mice. Using the alkaline comet assay and fluorescent ethidium bromide staining, DNA damage was analyzed in the peripheral whole blood (5 μL) cells that were isolated from either young (8-week-old) and elderly (72-week-old) apoE?/? mice or from age-matched C57 mice. The levels of total plasma cholesterol were approximately 6-fold higher in apoE?/? mice of both ages compared to C57 mice. Elderly apoE?/? mice showed significantly higher levels of DNA damage (19%) compared to elderly C57 mice (8%, p < 0.01) and young apoE?/? mice (10%, p < 0.01). The comet assay in whole blood cells is a suitable technique for the detection of DNA damage in the apoE?/? mouse;it is an easy, rapid, inexpensive and sensitive method. The novelty of this study is that DNA damage occurring in whole blood cells of this murine model requires the concurrence of aging and oxida- tive stress-related hypercholesterolemia.
文摘The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the physiological production of NO in endo-thelial cells and platelets. There is evidence that the G894T polymorphism of the eNOS gene is associated with this enzyme's basal activity and NO production, which could contribute to the pathogenesis of periodontal diseases (PD). Therefore, this study was designed to investigate the role of G894T polymorphism in the eNOS gene as a predisposing factor to periodontal disease. In this study we investigated the association of this polymorphism with PD in an admix-ture population (N = 119) separated into three groups: Healthy control, Moderate and Severe PD, without statistical differences among them for risk factors for PD, such as age, gender and smoking status. We observed that the GG ge-notype was associated with the progression of PD as indicated by an increase in frequency of approximately 18% in the Moderate and 26% in the Severe groups compared to the Healthy control group (p = 0.0302). This finding indicates that patients carrying the GG genotype have a greater chance of developing PD compared with those carrying the T allele, and it reinforces the notion that genetic factors contribute to the development and aggravation of PD.
文摘Cystic Fibrosis (CF) is the most common lethal autosomal inherited disorder that affects all races and ethnicities in the United States. However, it is mostly predominant in the Caucasian populace accounting for about 80% of all CF cases. CF most severe complication can be referred to as pulmonary bronchiectasis and infections of the airways, nonetheless, the devastating effects of the disease have far-reaching consequences beyond lung damage. CF is a heterogeneous disease that is caused by mutations in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. The impairment or absence of this gene can affect multiple organs and systems and is characterized not only by chronic lung blockage, infections, and inflammation but also by exocrine gland dysfunction, intestinal obstruction, liver pathology, elevated sweat chloride concentration, and in males, infertility due to the congenital bilateral absence of the vas deferens. To this end, we briefly explore the pathological effects of CF and how CF mediates the destruction of several critical organs in the body and some of the gene therapeutical approaches such as gene editing and viral-based strategies available for the treatment of this multi-organ disease.
