Pub Date : 2019-10-04Print Date: 2019-12-01DOI: 10.3171/2019.7.PEDS1976
Ken Maynard, Melissa LoPresti, Ionela Iacobas, Peter Kan, Sandi Lam
Intracerebral arteriovenous malformations (AVMs) are high-flow collections of abnormal vessels and a common cause of pediatric intracranial hemorrhage. There are few treatment options available for AVMs not amenable to surgical resection, endovascular embolization, radiosurgery, or multimodality treatment. The authors sought to review the molecular and genetic pathways that have been implicated in the formation of AVMs, focusing on the possibility of medically targeting these pathways in the treatment of AVMs. In the novel case presented here, a pediatric patient who was diagnosed with an intracranial AVM unamenable to conventional treatments underwent alternative treatment with molecular pathway inhibitors.
{"title":"Antiangiogenic agent as a novel treatment for pediatric intracranial arteriovenous malformations: case report.","authors":"Ken Maynard, Melissa LoPresti, Ionela Iacobas, Peter Kan, Sandi Lam","doi":"10.3171/2019.7.PEDS1976","DOIUrl":"10.3171/2019.7.PEDS1976","url":null,"abstract":"<p><p>Intracerebral arteriovenous malformations (AVMs) are high-flow collections of abnormal vessels and a common cause of pediatric intracranial hemorrhage. There are few treatment options available for AVMs not amenable to surgical resection, endovascular embolization, radiosurgery, or multimodality treatment. The authors sought to review the molecular and genetic pathways that have been implicated in the formation of AVMs, focusing on the possibility of medically targeting these pathways in the treatment of AVMs. In the novel case presented here, a pediatric patient who was diagnosed with an intracranial AVM unamenable to conventional treatments underwent alternative treatment with molecular pathway inhibitors.</p>","PeriodicalId":9213,"journal":{"name":"Botanical Gazette","volume":"83 1","pages":"673-679"},"PeriodicalIF":2.1,"publicationDate":"2019-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82214202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-07-01Epub Date: 2016-01-01DOI: 10.1177/0271678X16668536
Joel Aanerud, Per Borghammer, Anders Rodell, Kristjana Y Jónsdottir, Albert Gjedde
Brain energy metabolism is held to reflect energy demanding processes in neuropil related to the density and activity of synapses. There is recent evidence that men have higher density of synapses in temporal cortex than women. One consequence of these differences would be different rates of cortical energy turnover and blood flow in men and women. To test the hypotheses that rates of oxygen consumption (CMRO2) and cerebral blood flow are higher in men than in women in regions of cerebral cortex, and that the differences persist with aging, we used positron emission tomography to determine cerebral blood flow and cerebral metabolic rate of oxygen as functions of age in healthy volunteers of both sexes. Cerebral metabolic rate of oxygen did not change with age for either sex and there were no differences of mean values of cerebral metabolic rate of oxygen between men and women in cerebral cortex. Women had significant decreases of cerebral blood flow as function of age in frontal and parietal lobes. Young women had significantly higher cerebral blood flow than men in frontal and temporal lobes, but these differences had disappeared at age 65. The absent sex difference of cerebral energy turnover suggests that the known differences of synaptic density between the sexes are counteracted by opposite differences of individual synaptic activity.
{"title":"Sex differences of human cortical blood flow and energy metabolism.","authors":"Joel Aanerud, Per Borghammer, Anders Rodell, Kristjana Y Jónsdottir, Albert Gjedde","doi":"10.1177/0271678X16668536","DOIUrl":"10.1177/0271678X16668536","url":null,"abstract":"<p><p>Brain energy metabolism is held to reflect energy demanding processes in neuropil related to the density and activity of synapses. There is recent evidence that men have higher density of synapses in temporal cortex than women. One consequence of these differences would be different rates of cortical energy turnover and blood flow in men and women. To test the hypotheses that rates of oxygen consumption (CMRO<sub>2</sub>) and cerebral blood flow are higher in men than in women in regions of cerebral cortex, and that the differences persist with aging, we used positron emission tomography to determine cerebral blood flow and cerebral metabolic rate of oxygen as functions of age in healthy volunteers of both sexes. Cerebral metabolic rate of oxygen did not change with age for either sex and there were no differences of mean values of cerebral metabolic rate of oxygen between men and women in cerebral cortex. Women had significant decreases of cerebral blood flow as function of age in frontal and parietal lobes. Young women had significantly higher cerebral blood flow than men in frontal and temporal lobes, but these differences had disappeared at age 65. The absent sex difference of cerebral energy turnover suggests that the known differences of synaptic density between the sexes are counteracted by opposite differences of individual synaptic activity.</p>","PeriodicalId":9213,"journal":{"name":"Botanical Gazette","volume":"133 1","pages":"2433-2440"},"PeriodicalIF":0.0,"publicationDate":"2017-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0271678X16668536","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82256396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2017-02-14Epub Date: 2017-02-01DOI: 10.1073/pnas.1616783114
Kinlin L Chao, Liudmila Kulakova, Osnat Herzberg
The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at 88DNVD91 within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport.
人gasdermin-B(GSDMB)调节上皮细胞的分化和生长,其确切功能尚待阐明。在人类表皮生长因子受体 2(HER2)阳性乳腺癌中,GSDMB 基因扩增和蛋白过表达表明对 HER2 靶向治疗的反应不佳。全基因组关联研究显示,GSDMB SNPs 与克罗恩病、溃疡性结肠炎和哮喘的易感性增加有关。所有 gasdermins 的 N 端和 C 端结构域分别具有脂质结合活性和调节活性。炎症性 caspases 可裂解 gasdermin-D 的结构域间连接器,但不能裂解 GSDMB。被裂解的 N 端结构域可结合磷脂和心磷脂,形成膜破坏孔,并执行热昏迷。我们的研究表明,全长 GSDMB 和 N 端结构域都能与固定了磷脂或硫酸盐的硝酸纤维素膜结合,但不能与心磷脂结合。此外,GSDMB N 端结构域还能与含有硫化物的脂质体结合。GSDMB C 端结构域的晶体结构揭示了与哮喘和炎症性肠病(IBD)有关的 SNP 编码的氨基酸对结构的影响。携带与健康个体相对应的多态性氨基酸(Gly299:Pro306)的环路表现出高度的构象灵活性,而携带在疾病风险增加的个体中发现的氨基酸(Arg299:Ser306)的环路则表现出明确的构象和较高的正表面电荷。凋亡刽子手 caspase-3、-6 和 -7(而非炎症性 caspases)会在 N 端结构域的 88DNVD91 处裂解 GSDMB。选择性硫化物结合可能表明 GSDMB 在细胞硫化物转运中可能具有功能。
{"title":"Gene polymorphism linked to increased asthma and IBD risk alters gasdermin-B structure, a sulfatide and phosphoinositide binding protein.","authors":"Kinlin L Chao, Liudmila Kulakova, Osnat Herzberg","doi":"10.1073/pnas.1616783114","DOIUrl":"10.1073/pnas.1616783114","url":null,"abstract":"<p><p>The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, <i>GSDMB</i> gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between <i>GSDMB</i> SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively. Inflammatory caspases cleave gasdermin-D in the interdomain linker but not GSDMB. The cleaved N-terminal domain binds phosphoinositides and cardiolipin, forms membrane-disrupting pores, and executes pyroptosis. We show that both full-length GSDMB and the N-terminal domain bind to nitrocellulose membranes immobilized with phosphoinositides or sulfatide, but not with cardiolipin. In addition, the GSDMB N-terminal domain binds liposomes containing sulfatide. The crystal structure of the GSDMB C-terminal domain reveals the structural impact of the amino acids encoded by SNPs that are linked to asthma and inflammatory bowel disease (IBD). A loop that carries the polymorphism amino acids corresponding to healthy individuals (Gly299:Pro306) exhibits high conformational flexibility, whereas the loop carrying amino acids found in individuals with increased disease risk (Arg299:Ser306) exhibits a well-defined conformation and higher positive surface charge. Apoptotic executioner caspase-3, -6, and -7, but not the inflammatory caspases, cleave GSDMB at <sub>88</sub>DNVD<sub>91</sub> within the N-terminal domain. Selective sulfatide binding may indicate possible function for GSDMB in the cellular sulfatide transport.</p>","PeriodicalId":9213,"journal":{"name":"Botanical Gazette","volume":"74 1","pages":"E1128-E1137"},"PeriodicalIF":0.0,"publicationDate":"2017-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82202271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-10-04DOI: 10.1186/s40199-016-0161-x
Seyedeh-Somayeh Zamani, Mohsen Hossieni, Mahmoud Etebari, Pirooz Salehian, Soltan Ahmad Ebrahimi
Background: Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents.
Method: A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined.
Results: The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Pharmacokinetics of xanthomicrol in rats.
{"title":"Pharmacokinetics of calycopterin and xanthmicrol, two polymethoxylated hydroxyflavones with anti-angiogenic activities from Dracocephalum kotschyi Bioss.","authors":"Seyedeh-Somayeh Zamani, Mohsen Hossieni, Mahmoud Etebari, Pirooz Salehian, Soltan Ahmad Ebrahimi","doi":"10.1186/s40199-016-0161-x","DOIUrl":"10.1186/s40199-016-0161-x","url":null,"abstract":"<p><strong>Background: </strong>Recently flavonoids have attracted the attention of researchers in the fight against cancer. Calycopterin and xanthomicrol, are two polymethoxylated flavonoids found in the aerial parts of Dracocephalum kotschyi Bioss.. We have recently shown that these compounds possess antiangiogenic activity and may be of value as potential anticancer agents. In order to demonstrate putative in vivo antitumor effect of these compounds we needed preliminary information on both pharmacokinetics and toxicological properties of these two agents.</p><p><strong>Method: </strong>A new online SPE HPLC method for measurement of calycopterin and xanthomicrol in rat plasma was developed. Pharmacokinetic parameters of calycopterin and xanthomicrol, after i.v. administration in rats, were determined.</p><p><strong>Results: </strong>The plasma half-life for both agents was around 4 h, however, the volume of distribution of calycopterin appeared to be about 8 times greater than xanthomicrol. This was probably due the greater hydrophobicity of the former which had other consequences such as much smaller maximum plasma concentration of calycopterin compared to its less methoxylated congener. Preliminary toxicological study of xanthomicrol failed to show any behavioral, histological and biochemical adverse effects after repeated administrations of high doses. Pharmacokinetics of xanthomicrol in rats.</p>","PeriodicalId":9213,"journal":{"name":"Botanical Gazette","volume":"141 1","pages":"22"},"PeriodicalIF":3.6,"publicationDate":"2016-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5051066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82265805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-04-01Epub Date: 2015-11-25DOI: 10.1177/0141076815616089
Claire Hilton
{"title":"Parity of esteem for mental and physical healthcare in England: a hundred years war?","authors":"Claire Hilton","doi":"10.1177/0141076815616089","DOIUrl":"10.1177/0141076815616089","url":null,"abstract":"","PeriodicalId":9213,"journal":{"name":"Botanical Gazette","volume":"11 1","pages":"133-6"},"PeriodicalIF":17.3,"publicationDate":"2016-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82087457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Present trends in hospital management are facilitating the utilization of more accurate costing methods, which potentially results in superior cost-related information and improved managerial decision-making. However, the Activity-Based Costing method (ABC), which was designed for cost allocation purposes in the 1980s, is not widely used by healthcare organizations. This study analyzes costs related to selected categories of patients, those suffering from psoriasis, varicose ulcers, eczema and other conditions, within a dermatology department at a Czech regional hospital.
Methods: The study was conducted in a hospital department where both inpatient and outpatient care are offered. Firstly, the diseases treated at the department were identified. Further costs were determined for each activity using ABC. The study utilized data from managerial and financial accounting, as well as data obtained through interviews with departmental staff. Using a defined cost-allocation procedure makes it possible to determine the cost of an individual patient with a given disease more accurately than via traditional costing procedures.
Results: The cost analysis focused on the differences between the costs related to individual patients within the selected diagnoses, variations between inpatient and outpatient treatments and the costs of activities performed by the dermatology department. Furthermore, comparing the costs identified through this approach and the revenue stemming from the health insurance system is an option.
Conclusions: Activity-Based Costing is more accurate and relevant than the traditional costing method. The outputs of ABC provide an abundance of additional information for managers. The benefits of this research lie in its practically-tested outputs, resulting from calculating the costs of hospitalization, which could prove invaluable to persons involved in hospital management and decision-making. The study also defines the managerial implications of the performed cost analysis for the hospital management. Based on the analysis results, it is possible to standardize activities and performance appraisal (Benchmarking), and provide all necessary information for hospital budgeting practices, especially Activity-Based Budgeting (ABB).
{"title":"Cost Analysis of Selected Patient Categories Within A Dermatology Department Using an ABC Approach.","authors":"Šárka Papadaki, Boris Popesko","doi":"10.5539/gjhs.v8n6p234","DOIUrl":"10.5539/gjhs.v8n6p234","url":null,"abstract":"<p><strong>Background: </strong>Present trends in hospital management are facilitating the utilization of more accurate costing methods, which potentially results in superior cost-related information and improved managerial decision-making. However, the Activity-Based Costing method (ABC), which was designed for cost allocation purposes in the 1980s, is not widely used by healthcare organizations. This study analyzes costs related to selected categories of patients, those suffering from psoriasis, varicose ulcers, eczema and other conditions, within a dermatology department at a Czech regional hospital.</p><p><strong>Methods: </strong>The study was conducted in a hospital department where both inpatient and outpatient care are offered. Firstly, the diseases treated at the department were identified. Further costs were determined for each activity using ABC. The study utilized data from managerial and financial accounting, as well as data obtained through interviews with departmental staff. Using a defined cost-allocation procedure makes it possible to determine the cost of an individual patient with a given disease more accurately than via traditional costing procedures.</p><p><strong>Results: </strong>The cost analysis focused on the differences between the costs related to individual patients within the selected diagnoses, variations between inpatient and outpatient treatments and the costs of activities performed by the dermatology department. Furthermore, comparing the costs identified through this approach and the revenue stemming from the health insurance system is an option.</p><p><strong>Conclusions: </strong>Activity-Based Costing is more accurate and relevant than the traditional costing method. The outputs of ABC provide an abundance of additional information for managers. The benefits of this research lie in its practically-tested outputs, resulting from calculating the costs of hospitalization, which could prove invaluable to persons involved in hospital management and decision-making. The study also defines the managerial implications of the performed cost analysis for the hospital management. Based on the analysis results, it is possible to standardize activities and performance appraisal (Benchmarking), and provide all necessary information for hospital budgeting practices, especially Activity-Based Budgeting (ABB).</p>","PeriodicalId":9213,"journal":{"name":"Botanical Gazette","volume":"112 1","pages":"234-49"},"PeriodicalIF":0.0,"publicationDate":"2015-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4954901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82242611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}