Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal g...Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal ganglia.The predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal degeneration.Among the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis pathway.Currently there is no effective treatment to prevent the inexorable course of these disorders.The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN.Recently,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative stress.In addition,PKAN fibroblasts showed a morphological senescence-like phenotype.Interestingly,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression.However,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein.The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts.Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations.Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment.The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate.The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available,and monitoring its effect on the pathophysiological changes,can help for a better therapeutic strategy.In addition,these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.展开更多
Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for ...Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for every nutrient in actual dietary practice. Design: We evaluated (1) whether the DRIs for all nutrients can be fulfilled in a formula with energy and protein exceeding their DRIs, (2) whether the DRIs for all nutrients can be fulfilled in a formula prepared in accordance with Japanese government-recommended weaning guidelines, and (3) what kinds of formulas can be prepared if the DRIs for all nutrients are fulfilled without referring to the weaning guidelines. Setting: Simulation of diet menu on the basis of published data in our university and survey of diet menu in a university hospital attached to a national medical school. Subjects: The three types of formulas were planned for ten days. Results: It was impossible to simultaneously fulfil the DRIs for 6 - 8-month-old infants concerning pantothenic acid, vitamin D, and iron and those for 9 - 11-month-old infants concerning these nutrients plus protein. Conclusion: According to the DRIs-2010, the DRI for all nutrients could not be fulfilled in an ingestible formula.展开更多
Objective: It has been suggested that pantothenic acid may have antibacterial and skin softening activity. The aim of this study was to explore the feasibility, tolerability, safety and preliminary efficacy of oral ad...Objective: It has been suggested that pantothenic acid may have antibacterial and skin softening activity. The aim of this study was to explore the feasibility, tolerability, safety and preliminary efficacy of oral administration of a dietary supplement containing pantothenic acid in healthy human males and females with mild to moderate facial acne vulgaris. Methods: An open-label, single arm study of healthy adults who had been previously diagnosed with mild to moderate acne vulgaris was performed. Subjects were asked to take the study agent, a dietary supplement containing pantothenic acid, for eight weeks. The primary endpoint of the study was to assess the feasibility of oral administration of the study agent in subjects over an eight week period. Safety and tolerability were measured utilizing the assessment of adverse events by the National Cancer Institute’s Common Criteria for Adverse Event Reporting. Secondary endpoints measuring the efficacy of an oral panthothetic acid dietary supplement for the treatment of mild to moderate facial acne utilized changes in the extent of global facial skin blemishes, assessment of quality of life utilizing the Dermatology Life Quality Index (DLQI) and analysis of questions about the subject's beliefs and attitudes towards skin care and lifestyle. Results: Eleven subjects were enrolled and ten completed the study (90.9%). There were no reported adverse events. Of the 10 evaluable subjects, the average age (mean ± SD) was 31.8 ± 8. Analysis of the global number of skin blemishes demonstrated a significant mean reduction in lesion count following the use of the study agent at week 8 (endpoint) (11.18 ± 6.38, p = 0.02) compared to the average number of baseline blemishes (20.45 ± 10.44). DLQI scores were significantly lower at week 8 vs. baseline (p = 0.0194). Conclusions: The results from this study indicated that the administration of a pantothenic based dietary supplement in healthy human adults with mild to moderate acne vulgaris is feasible, safe and well tolerated. Secondary analysis shows that administration of the study agent significantly reduced global facial blemishes. Further randomized, placebo-controlled trials are warranted.展开更多
基金supported by FIS PI16/00786 grant,Instituto de Salud Carlos Ⅲ,Spain and Fondo Europeo de Desarrollo Regional(FEDER-Unión Europea),Proyectos de Investigación de Excelencia de la Junta de Andalucía CTS-5725AEPMI(Asociación de Enfermos de Patología Mitocondrial) and ENACH(Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro)(to JASA)
文摘Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal ganglia.The predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal degeneration.Among the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis pathway.Currently there is no effective treatment to prevent the inexorable course of these disorders.The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN.Recently,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative stress.In addition,PKAN fibroblasts showed a morphological senescence-like phenotype.Interestingly,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression.However,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein.The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts.Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations.Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment.The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate.The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available,and monitoring its effect on the pathophysiological changes,can help for a better therapeutic strategy.In addition,these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.
文摘Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for every nutrient in actual dietary practice. Design: We evaluated (1) whether the DRIs for all nutrients can be fulfilled in a formula with energy and protein exceeding their DRIs, (2) whether the DRIs for all nutrients can be fulfilled in a formula prepared in accordance with Japanese government-recommended weaning guidelines, and (3) what kinds of formulas can be prepared if the DRIs for all nutrients are fulfilled without referring to the weaning guidelines. Setting: Simulation of diet menu on the basis of published data in our university and survey of diet menu in a university hospital attached to a national medical school. Subjects: The three types of formulas were planned for ten days. Results: It was impossible to simultaneously fulfil the DRIs for 6 - 8-month-old infants concerning pantothenic acid, vitamin D, and iron and those for 9 - 11-month-old infants concerning these nutrients plus protein. Conclusion: According to the DRIs-2010, the DRI for all nutrients could not be fulfilled in an ingestible formula.
文摘Objective: It has been suggested that pantothenic acid may have antibacterial and skin softening activity. The aim of this study was to explore the feasibility, tolerability, safety and preliminary efficacy of oral administration of a dietary supplement containing pantothenic acid in healthy human males and females with mild to moderate facial acne vulgaris. Methods: An open-label, single arm study of healthy adults who had been previously diagnosed with mild to moderate acne vulgaris was performed. Subjects were asked to take the study agent, a dietary supplement containing pantothenic acid, for eight weeks. The primary endpoint of the study was to assess the feasibility of oral administration of the study agent in subjects over an eight week period. Safety and tolerability were measured utilizing the assessment of adverse events by the National Cancer Institute’s Common Criteria for Adverse Event Reporting. Secondary endpoints measuring the efficacy of an oral panthothetic acid dietary supplement for the treatment of mild to moderate facial acne utilized changes in the extent of global facial skin blemishes, assessment of quality of life utilizing the Dermatology Life Quality Index (DLQI) and analysis of questions about the subject's beliefs and attitudes towards skin care and lifestyle. Results: Eleven subjects were enrolled and ten completed the study (90.9%). There were no reported adverse events. Of the 10 evaluable subjects, the average age (mean ± SD) was 31.8 ± 8. Analysis of the global number of skin blemishes demonstrated a significant mean reduction in lesion count following the use of the study agent at week 8 (endpoint) (11.18 ± 6.38, p = 0.02) compared to the average number of baseline blemishes (20.45 ± 10.44). DLQI scores were significantly lower at week 8 vs. baseline (p = 0.0194). Conclusions: The results from this study indicated that the administration of a pantothenic based dietary supplement in healthy human adults with mild to moderate acne vulgaris is feasible, safe and well tolerated. Secondary analysis shows that administration of the study agent significantly reduced global facial blemishes. Further randomized, placebo-controlled trials are warranted.
