Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau pro...Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.展开更多
Background: Alzheimer’s disease is the major neurodegenerative disease, affecting more than two third cases of dementia in the world. NSAIDs are widely used anti-inflammatory analgesic agents representing 7.7% of wor...Background: Alzheimer’s disease is the major neurodegenerative disease, affecting more than two third cases of dementia in the world. NSAIDs are widely used anti-inflammatory analgesic agents representing 7.7% of worldwide prescriptions of which 90% are in patients over 65 years old. Based on mixed findings observed by different RCTs, a systematic review and meta-analysis were conducted to develop a better understanding of the protective role of Non-steroidal anti-inflammatory drugs (NSAIDs) in AD. Methods: Database search was Pubmed, WebScience, and Embase. RCTs investigating the effect of NSAIDs on AD or test scores assessing cognitive function in people without AD at baseline were included. Three indicators were MMSE Score, ADAS-cog score, and CDR-sob. 10 studies were included in the present Meta-analysis. Results: For the ADAS-cog score, the pooled effect size was -0.31 with 95% CI -0.06 to 0.02, which was statistically significant (p = 0.03). MMSE score difference, the pooled effect size was -0.06 with 95% CI -0.22 to 0.10, which was statistically insignificant (p-value = 0.47). For the MMSE average score, the pooled effect size was -0.002 with 95% CI -0.03 to 0.07, which was statistically insignificant (p-value = 0.87). For the CDR-sob score difference, the pooled effect size calculated using the random effect model was -0.06 with 95% CI -0.39 to 0.05 which was statistically insignificant (p = 0.14). For CDR-sob average score, the pooled effect size calculated using the random effect model was 0.21 with 95% CI -0.09 to 0.51, which was statistically insignificant (p-value = 0.17). Conclusion: Present Meta-analysis shows that NSAIDs in general are not effective in the treatment of AD. They also have no protective effect against the development of AD on their sustained use.展开更多
Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous socia...Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous social and economic burden to the affected in- dividuals and their families, but is also a great scientific challenge. Currently 25-35 million people worldwide suffer from AD, the single largest cause of dementia in middle- to old-aged individuals. These numbers are projected to triple by 2050 if no treatment to prevent or reverse AD is developed.展开更多
AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutiv...AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days.For comparison,a gastric fistula model was used.Effects of ghrelin and esomeprazole,with or without pentagastrin,on gastric pH were studied.In addition,effects of esomeprazole on plasma ghrelin,gastrin and somatostatin were analyzed.RESULTS: All rats recovered after surgery.The average 24-h pH during free feeding was 2.3 ± 0.1 (n = 20) with a variation of 18% ± 6% over 5 d.Ghrelin,2400 pmol/kg,t.i.d.increased pH from 1.7 ± 0.1 to 3.1 ± 0.3 (P < 0.01) as recorded with the Bravo system.After esomeprazole (1 mg/kg,3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 ± 0.1,with day-to-day variation over the entire period of 8% ± 3%.The fistula and pH studies generated similar results.Acid inhibition with esomeprazole increased plasma ghrelin from 10 ± 2 pmol/L to 65 ± 26 pmol/L (P < 0.001),and somatostatin from 10 ± 2 pmol/L to 67 ± 18 pmol/L (P < 0.001).CONCLUSION: pH measurements with the Bravo capsule are reliable,and comparable to those of the gastric fistula model.The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short-and long-term evaluation of effects of drugs and hormones.展开更多
AIM: To determine existing correlates among diffusion tensor imaging(DTI)-derived metrics in healthy brains and brains with glioblastoma multiforme(GBM). METHODS: Case-control study using DTI data from brain magnetic ...AIM: To determine existing correlates among diffusion tensor imaging(DTI)-derived metrics in healthy brains and brains with glioblastoma multiforme(GBM). METHODS: Case-control study using DTI data from brain magnetic resonance imaging of 34 controls(mean, 41.47; SD, ± 21.94 years; range, 21-80 years) and 27 patients with GBM(mean, SD; 48.41 ± 15.18 years; range, 18-78 years). Image postprocessing using FSL software calculated eleven tensor metrics: fractional(FA) and relative anisotropy; pure isotropic(p) and anisotropic diffusions(q), total magnitude of diffusion(L); linear(Cl), planar(Cp) and spherical tensors(Cs); mean(MD), axial(AD) and radial diffusivities(RD). Partial correlation analyses(controlling the effect of ageand gender) and multivariate Mancova were performed.RESULTS: There was a normal distribution for all metrics. Comparing healthy brains vs brains with GBM, there were significant very strong bivariate correlations only depicted in GBM: [FA?Cl(+)], [FA?q(+)], [p?AD(+)], [AD?MD(+)], and [MD?RD(+)]. Among 56 pairs of bivariate correlations, only seven were significantly different. The diagnosis variable depicted a main effect [F-value(11, 23) = 11.842, P ≤ 0.001], with partial eta squared = 0.850, meaning a large effect size; age showed a similar result. The age also had a significant influence as a covariate [F(11, 23) = 10.523, P < 0.001], with a large effect size(partial eta squared = 0.834).CONCLUSION: DTI-derived metrics depict significant differences between healthy brains and brains with GBM, with specific magnitudes and correlations. This study provides reference data and makes a contribution to decrease the underlying empiricism in the use of DTI parameters in brain imaging.展开更多
X-linked adrenoleukodystrophy(X-ALD),an inborn error of peroxisomalβ-oxidation,is caused by defects in the ATP Binding Cassette Subfamily D Member 1(ABCD1)gene.X-ALD patients may be asymptomatic or present with sever...X-linked adrenoleukodystrophy(X-ALD),an inborn error of peroxisomalβ-oxidation,is caused by defects in the ATP Binding Cassette Subfamily D Member 1(ABCD1)gene.X-ALD patients may be asymptomatic or present with several clinical phenotypes varying from severe to mild,severe cerebral adrenoleukodystrophy to mild adrenomyeloneuropathy(AMN).Although most female heterozygotes present with AMN-like symptoms after 60 years of age,occasional cases of females with the cerebral form have been reported.Phenotypic variability has been described within the same kindreds and even among monozygotic twins.There is no association between the nature of ABCD1 mutation and the clinical phenotypes,and the molecular basis of phenotypic variability in X-ALD is yet to be resolved.Various genetic,epigenetic,and environmental influences are speculated to modify the disease onset and severity.In this review,we summarize the observations made in various studies investigating the potential modifying factors regulating the clinical manifestation of X-ALD,which could help understand the pathogenesis of the disease and develop suitable therapeutic strategies.展开更多
Approximately 35.0% of annual hospitals budget is spent on buying materials and supplies, including medicines. We can bring about substantial improvement in the hospital inventory and expenditures by the inventory con...Approximately 35.0% of annual hospitals budget is spent on buying materials and supplies, including medicines. We can bring about substantial improvement in the hospital inventory and expenditures by the inventory control techniques. Objective: To identify the categories of drugs which need stringent management control. Material and Method: The ABC and VED analysis of the medical store of a Neuropsychiatry hospital at Delhi, India was conducted for the year 2008-2009 to identify the categories of items needing stringent management control. Results: The total number of the drugs at the medical store was 145 drugs. The total annual drug expenditure (ADE) on these drug items was Rs. 19219594.79. ABC analysis revealed 3.45%, 6.9% and 89.65% items as A, B and C category items, respectively, accounting for 70.5%, 19.68% and 9.83% of ADE of the medical store. VED analysis showed 32.41%, 61.38% and 6.2% items as V, E, and D category items, respectively, accounting for 70.9%, 28.72% and 0.38% of ADE of the medical store. On ABC-VED matrix analysis, 33.8%, 60% and 6.2% items were found to be category I, II and III items, respectively, accounting for 92.33%, 7.29% and 0.38% of ADE of the medical store. Conclusion: It is suggested by the study that the management of Category I drugs should be done by the top management resulting in stringent control on the annual expenses. The Category II should be managed by the middle management level and Category III at lower managerial level.展开更多
Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor corte...Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.展开更多
Introduction: NSAIDs inhibit COX-2, which is responsible for regulating neurons leading to neurodegeneration in Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative disease affecting the geriatric populat...Introduction: NSAIDs inhibit COX-2, which is responsible for regulating neurons leading to neurodegeneration in Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative disease affecting the geriatric population, as it affects more than two third cases of dementia in the sphere. Results obtained from experimental and observational studies were unclear regarding the protective role of NSAIDs in AD, therefore this justifies the need for meta-analysis. Methods: Database search was PubMed, Web of Science, and Embase. Experimental studies and Observational studies investigating the effect of NSAIDs on AD. For experimental studies indicators used were MMSE score, ADAS-cog score, CDR-sob score, NPI score, and Hazard ratio. Similarly for Observational studies, Odds Ratio and Relative Risk are used. Results: As this is the study protocol, therefore it is not possible to write the results of the study in the study protocol. There is a total of 06 (MMSE, ADAS-cog, CDR-sob, HR, RR, and OR) indicators used in the study, so 06 results will be obtained showing the pooled effect size which will indicate the use of NSAIDs as a protective factor for Alzheimer’s disease. Discussion: The present systematic review will improve the understanding of the relative efficacies of NSAIDs in AD and possibly guide clinical practices by providing the current best evidence on the efficacy of various regimens of NSAIDs in the management of AD subjects. Conclusion: Conclusion can be drawn only after the final meta-analysis using three study design (RCT, Cohort and Case-control study designs) and six indicators.展开更多
The aggregation of Amyloid-β(Aβ)peptides is associated with neurodegeneration in Alzheimer's disease(AD).We previously identified novel naphtalene derivatives,including the lead compound Amylovis-201,able to for...The aggregation of Amyloid-β(Aβ)peptides is associated with neurodegeneration in Alzheimer's disease(AD).We previously identified novel naphtalene derivatives,including the lead compound Amylovis-201,able to form thermodynamically stable complexes with Aβspecies,peptides and fibrils.As the drug showed a chemical scaffold coherent for an effective interaction with theσ_(1) receptor chaperone and asσ_(1) agonists are currently developed as potent neuroprotectants in AD,we investigated the pharmacological action of Amylovis-201 on theσ_(1) receptor.We report that Amylovis-201 is a potentσ_(1) agonist by several in silico,in vitro and in vivo assays and that its anti-amnesic and neuroprotective effects involve a pharmacological action atσ_(1) receptors.Furthermore,we show for the first time that classicalσ_(1) receptor agonist(PRE-084),and antagonist(NE-100)are able to interact and disaggregate Aβ_(25-35) fibrils.Interestingly,Amylovis-201 was the only compound inhibiting Aβ_(25-35) aggregates formation.Our results therefore highlight a dual action of Amylovis-201 as anti-aggregating agent andσ_(1) receptor agonist that could be highly effective in long-term treatment against neurodegeneration in AD.展开更多
A cheap method allowing fabrication of biocompatible,ultra-small(2-10 nm)and fluorescent(λ_(em)=425-500 nm)nanohybrids(NHs)from coffee wastes is reported.The gadolinium-doped nanohybrids(GDNHs)or gadolinium-free carb...A cheap method allowing fabrication of biocompatible,ultra-small(2-10 nm)and fluorescent(λ_(em)=425-500 nm)nanohybrids(NHs)from coffee wastes is reported.The gadolinium-doped nanohybrids(GDNHs)or gadolinium-free carbon dots(GFCDs)can be synthesized in a domestic microwave oven according to green synthesis principles.Hydrodynamic sizes,chemical composition,impact on proton magnetic resonance relaxation time and optical properties of the GDNHs and GFCDs were studied in details and compared.In particular,doping of the NHs with Gd^(3+)ions,up to 1.87%w/w of gadolinium per particles’weight,will allow their application for magnetic resonance imaging(MRI).Furthermore,cell culture tests on human adenocarcinomic alveolar basal epithelial cells line(A549)have shown high biocompatibility of the GDNHs and in a wide concentration range 100-1000μg/ml.展开更多
Alzheimer’s disease(AD)is an age-related neurodegenerative disease with two major hallmarks:extracellular amyloid plaques made of amyloid-β(Aβ)and intracellular neurofibrillary tangles(NFTs)of abnormally hyperphosp...Alzheimer’s disease(AD)is an age-related neurodegenerative disease with two major hallmarks:extracellular amyloid plaques made of amyloid-β(Aβ)and intracellular neurofibrillary tangles(NFTs)of abnormally hyperphosphorylated tau.The number of NFTs correlates positively with the severity of dementia in AD patients.However,there is still no efficient therapy available for AD treatment and prevention so far.A deeper understanding of AD pathogenesis has identified novel strategies for the generation of specific therapies over the past few decades.Several studies have suggested that the prion-like seeding and spreading of tau pathology in the brain may be a key driver of AD.Tau protein is considered as a promising candidate target for the development of therapeutic interventions due to its considerable pathological role in a variety of neurodegenerative disorders.Abnormal tau hyperphosphorylation plays a detrimental pathological role,eventually leading to neurodegeneration.In the present review,we describe the recent research progresses in the pathological mechanisms of tau protein in AD and briefly discuss tau-based therapeutic strategies.展开更多
基金supported by the Neural Regeneration Co-innovation Center of Jiangsu Province,Nantong University(to DC)the National Natural Science Foundation of China,Nos.81872853(to DC),81870941(to JHG)the Science and Technology Project of Nantong City,Nos.JC22022022(to FW)and JC2021059(to JM)。
文摘Alzheimer's disease is characterized by two major neuropathological hallmarks—the extracellularβ-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein.Recent studies suggest that dysregulation of the microtubuleassociated protein Tau,especially specific proteolysis,could be a driving force for Alzheimer's disease neurodegeneration.Tau physiologically promotes the assembly and stabilization of microtubules,whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers,resulting in them gaining prion-like characteristics.In addition,Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner.This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments,investigates the role of specific truncations in physiological and pathological states of Alzheimer's disease,and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer's disease.
文摘Background: Alzheimer’s disease is the major neurodegenerative disease, affecting more than two third cases of dementia in the world. NSAIDs are widely used anti-inflammatory analgesic agents representing 7.7% of worldwide prescriptions of which 90% are in patients over 65 years old. Based on mixed findings observed by different RCTs, a systematic review and meta-analysis were conducted to develop a better understanding of the protective role of Non-steroidal anti-inflammatory drugs (NSAIDs) in AD. Methods: Database search was Pubmed, WebScience, and Embase. RCTs investigating the effect of NSAIDs on AD or test scores assessing cognitive function in people without AD at baseline were included. Three indicators were MMSE Score, ADAS-cog score, and CDR-sob. 10 studies were included in the present Meta-analysis. Results: For the ADAS-cog score, the pooled effect size was -0.31 with 95% CI -0.06 to 0.02, which was statistically significant (p = 0.03). MMSE score difference, the pooled effect size was -0.06 with 95% CI -0.22 to 0.10, which was statistically insignificant (p-value = 0.47). For the MMSE average score, the pooled effect size was -0.002 with 95% CI -0.03 to 0.07, which was statistically insignificant (p-value = 0.87). For the CDR-sob score difference, the pooled effect size calculated using the random effect model was -0.06 with 95% CI -0.39 to 0.05 which was statistically insignificant (p = 0.14). For CDR-sob average score, the pooled effect size calculated using the random effect model was 0.21 with 95% CI -0.09 to 0.51, which was statistically insignificant (p-value = 0.17). Conclusion: Present Meta-analysis shows that NSAIDs in general are not effective in the treatment of AD. They also have no protective effect against the development of AD on their sustained use.
基金supported in part by the New York State Office of People with Developmental Disabilities(OPWDD)Zenith Award ZEN-12-241233 from Alzheimer’s Associationa research grant#20121203 from Alzheimer’s Drug Discovery Foundation,New York
文摘Neurodegeneration is one of the biggest public health problems in modern society. Age-associated neurodegeneration, which is accelerated several-fold in Alzheimer＇s disease （AD） alone, is not only an enormous social and economic burden to the affected in- dividuals and their families, but is also a great scientific challenge. Currently 25-35 million people worldwide suffer from AD, the single largest cause of dementia in middle- to old-aged individuals. These numbers are projected to triple by 2050 if no treatment to prevent or reverse AD is developed.
文摘AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days.For comparison,a gastric fistula model was used.Effects of ghrelin and esomeprazole,with or without pentagastrin,on gastric pH were studied.In addition,effects of esomeprazole on plasma ghrelin,gastrin and somatostatin were analyzed.RESULTS: All rats recovered after surgery.The average 24-h pH during free feeding was 2.3 ± 0.1 (n = 20) with a variation of 18% ± 6% over 5 d.Ghrelin,2400 pmol/kg,t.i.d.increased pH from 1.7 ± 0.1 to 3.1 ± 0.3 (P < 0.01) as recorded with the Bravo system.After esomeprazole (1 mg/kg,3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 ± 0.1,with day-to-day variation over the entire period of 8% ± 3%.The fistula and pH studies generated similar results.Acid inhibition with esomeprazole increased plasma ghrelin from 10 ± 2 pmol/L to 65 ± 26 pmol/L (P < 0.001),and somatostatin from 10 ± 2 pmol/L to 67 ± 18 pmol/L (P < 0.001).CONCLUSION: pH measurements with the Bravo capsule are reliable,and comparable to those of the gastric fistula model.The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short-and long-term evaluation of effects of drugs and hormones.
基金Supported by The Medica Sur Clinic and Foundation(in part)David Cortez-Conradis was research fellow at the MRI Unit of Medica Sur Clinic and Foundation from 2012 to 2014Ernesto Roldan-Valadez was Coordinator of Research at the MRI Unit of Medica Sur Clinic and Foundation from 2010 to April 2015
文摘AIM: To determine existing correlates among diffusion tensor imaging(DTI)-derived metrics in healthy brains and brains with glioblastoma multiforme(GBM). METHODS: Case-control study using DTI data from brain magnetic resonance imaging of 34 controls(mean, 41.47; SD, ± 21.94 years; range, 21-80 years) and 27 patients with GBM(mean, SD; 48.41 ± 15.18 years; range, 18-78 years). Image postprocessing using FSL software calculated eleven tensor metrics: fractional(FA) and relative anisotropy; pure isotropic(p) and anisotropic diffusions(q), total magnitude of diffusion(L); linear(Cl), planar(Cp) and spherical tensors(Cs); mean(MD), axial(AD) and radial diffusivities(RD). Partial correlation analyses(controlling the effect of ageand gender) and multivariate Mancova were performed.RESULTS: There was a normal distribution for all metrics. Comparing healthy brains vs brains with GBM, there were significant very strong bivariate correlations only depicted in GBM: [FA?Cl(+)], [FA?q(+)], [p?AD(+)], [AD?MD(+)], and [MD?RD(+)]. Among 56 pairs of bivariate correlations, only seven were significantly different. The diagnosis variable depicted a main effect [F-value(11, 23) = 11.842, P ≤ 0.001], with partial eta squared = 0.850, meaning a large effect size; age showed a similar result. The age also had a significant influence as a covariate [F(11, 23) = 10.523, P < 0.001], with a large effect size(partial eta squared = 0.834).CONCLUSION: DTI-derived metrics depict significant differences between healthy brains and brains with GBM, with specific magnitudes and correlations. This study provides reference data and makes a contribution to decrease the underlying empiricism in the use of DTI parameters in brain imaging.
基金Supported by Department of Biotechnology,New Delhi,India.No.BT/PR26150/MED/12/768/2017.
文摘X-linked adrenoleukodystrophy(X-ALD),an inborn error of peroxisomalβ-oxidation,is caused by defects in the ATP Binding Cassette Subfamily D Member 1(ABCD1)gene.X-ALD patients may be asymptomatic or present with several clinical phenotypes varying from severe to mild,severe cerebral adrenoleukodystrophy to mild adrenomyeloneuropathy(AMN).Although most female heterozygotes present with AMN-like symptoms after 60 years of age,occasional cases of females with the cerebral form have been reported.Phenotypic variability has been described within the same kindreds and even among monozygotic twins.There is no association between the nature of ABCD1 mutation and the clinical phenotypes,and the molecular basis of phenotypic variability in X-ALD is yet to be resolved.Various genetic,epigenetic,and environmental influences are speculated to modify the disease onset and severity.In this review,we summarize the observations made in various studies investigating the potential modifying factors regulating the clinical manifestation of X-ALD,which could help understand the pathogenesis of the disease and develop suitable therapeutic strategies.
文摘Approximately 35.0% of annual hospitals budget is spent on buying materials and supplies, including medicines. We can bring about substantial improvement in the hospital inventory and expenditures by the inventory control techniques. Objective: To identify the categories of drugs which need stringent management control. Material and Method: The ABC and VED analysis of the medical store of a Neuropsychiatry hospital at Delhi, India was conducted for the year 2008-2009 to identify the categories of items needing stringent management control. Results: The total number of the drugs at the medical store was 145 drugs. The total annual drug expenditure (ADE) on these drug items was Rs. 19219594.79. ABC analysis revealed 3.45%, 6.9% and 89.65% items as A, B and C category items, respectively, accounting for 70.5%, 19.68% and 9.83% of ADE of the medical store. VED analysis showed 32.41%, 61.38% and 6.2% items as V, E, and D category items, respectively, accounting for 70.9%, 28.72% and 0.38% of ADE of the medical store. On ABC-VED matrix analysis, 33.8%, 60% and 6.2% items were found to be category I, II and III items, respectively, accounting for 92.33%, 7.29% and 0.38% of ADE of the medical store. Conclusion: It is suggested by the study that the management of Category I drugs should be done by the top management resulting in stringent control on the annual expenses. The Category II should be managed by the middle management level and Category III at lower managerial level.
基金supported by Consejo Nacional de Ciencia y Tecnología(CONACy T)project CB 2016-287614(to RGP and ABN)by Scholarship Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica de la Universidad Nacional Autónoma de México(PAPIIT-UNAM)IA203319 and PAPIIT-UNAM IN216221 to(LERL)。
文摘Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.
文摘Introduction: NSAIDs inhibit COX-2, which is responsible for regulating neurons leading to neurodegeneration in Alzheimer’s disease. Alzheimer’s disease is a neurodegenerative disease affecting the geriatric population, as it affects more than two third cases of dementia in the sphere. Results obtained from experimental and observational studies were unclear regarding the protective role of NSAIDs in AD, therefore this justifies the need for meta-analysis. Methods: Database search was PubMed, Web of Science, and Embase. Experimental studies and Observational studies investigating the effect of NSAIDs on AD. For experimental studies indicators used were MMSE score, ADAS-cog score, CDR-sob score, NPI score, and Hazard ratio. Similarly for Observational studies, Odds Ratio and Relative Risk are used. Results: As this is the study protocol, therefore it is not possible to write the results of the study in the study protocol. There is a total of 06 (MMSE, ADAS-cog, CDR-sob, HR, RR, and OR) indicators used in the study, so 06 results will be obtained showing the pooled effect size which will indicate the use of NSAIDs as a protective factor for Alzheimer’s disease. Discussion: The present systematic review will improve the understanding of the relative efficacies of NSAIDs in AD and possibly guide clinical practices by providing the current best evidence on the efficacy of various regimens of NSAIDs in the management of AD subjects. Conclusion: Conclusion can be drawn only after the final meta-analysis using three study design (RCT, Cohort and Case-control study designs) and six indicators.
基金supported by a PHC Carlos J.Finlay program from Campus France(project 47069SA)to TM and CRT.The authors thank Drs Tsung-Ping Su and Yukio Kimura(NIDA,NIH,Baltimore,MD,USA)for the gift of GFP-tagged l proteinoverexpressing CHO cells,and the CECEMA animal facility of the University of Montpellier and the ZebraSens behavioral phenotyping platform for zebrafish models at MMDN.
文摘The aggregation of Amyloid-β(Aβ)peptides is associated with neurodegeneration in Alzheimer's disease(AD).We previously identified novel naphtalene derivatives,including the lead compound Amylovis-201,able to form thermodynamically stable complexes with Aβspecies,peptides and fibrils.As the drug showed a chemical scaffold coherent for an effective interaction with theσ_(1) receptor chaperone and asσ_(1) agonists are currently developed as potent neuroprotectants in AD,we investigated the pharmacological action of Amylovis-201 on theσ_(1) receptor.We report that Amylovis-201 is a potentσ_(1) agonist by several in silico,in vitro and in vivo assays and that its anti-amnesic and neuroprotective effects involve a pharmacological action atσ_(1) receptors.Furthermore,we show for the first time that classicalσ_(1) receptor agonist(PRE-084),and antagonist(NE-100)are able to interact and disaggregate Aβ_(25-35) fibrils.Interestingly,Amylovis-201 was the only compound inhibiting Aβ_(25-35) aggregates formation.Our results therefore highlight a dual action of Amylovis-201 as anti-aggregating agent andσ_(1) receptor agonist that could be highly effective in long-term treatment against neurodegeneration in AD.
基金the support of EU Horizon 2020 Research and Innovation Staff Exchange Programme(RISE)under Marie Skłodowska-Curie Action(project 101008159“UNAT”).
文摘A cheap method allowing fabrication of biocompatible,ultra-small(2-10 nm)and fluorescent(λ_(em)=425-500 nm)nanohybrids(NHs)from coffee wastes is reported.The gadolinium-doped nanohybrids(GDNHs)or gadolinium-free carbon dots(GFCDs)can be synthesized in a domestic microwave oven according to green synthesis principles.Hydrodynamic sizes,chemical composition,impact on proton magnetic resonance relaxation time and optical properties of the GDNHs and GFCDs were studied in details and compared.In particular,doping of the NHs with Gd^(3+)ions,up to 1.87%w/w of gadolinium per particles’weight,will allow their application for magnetic resonance imaging(MRI).Furthermore,cell culture tests on human adenocarcinomic alveolar basal epithelial cells line(A549)have shown high biocompatibility of the GDNHs and in a wide concentration range 100-1000μg/ml.
基金This project was supported by National Natural Science Foundation of China(No.31870772).
文摘Alzheimer’s disease(AD)is an age-related neurodegenerative disease with two major hallmarks:extracellular amyloid plaques made of amyloid-β(Aβ)and intracellular neurofibrillary tangles(NFTs)of abnormally hyperphosphorylated tau.The number of NFTs correlates positively with the severity of dementia in AD patients.However,there is still no efficient therapy available for AD treatment and prevention so far.A deeper understanding of AD pathogenesis has identified novel strategies for the generation of specific therapies over the past few decades.Several studies have suggested that the prion-like seeding and spreading of tau pathology in the brain may be a key driver of AD.Tau protein is considered as a promising candidate target for the development of therapeutic interventions due to its considerable pathological role in a variety of neurodegenerative disorders.Abnormal tau hyperphosphorylation plays a detrimental pathological role,eventually leading to neurodegeneration.In the present review,we describe the recent research progresses in the pathological mechanisms of tau protein in AD and briefly discuss tau-based therapeutic strategies.
