Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

Jose de Leon(Jose de Leon ) 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.3

This review article argues against trusting standard clozapine references, including the US package insert, because they do not include advances in the sciences of pharmacokinetics and pharmacovigilance and ignore the effects of ethnic ancestry on therapeutic dosing. The minimum therapeutic dose leading to the minimum therapeutic concentration of 350 ng/mL in serum/plasma can be used to compare individuals/groups with treatment-resistant schizophrenia. The US clozapine package insert recommends targeting doses of 300-450 mg/day and, subsequently, increments of up to 100 mg with a maximum dose of 900 mg/day. Ethnic ancestry is defined by DNA ancestry group. Asians (people with ancestry ranging from Pakistan to Japan) and Indigenous Americans are similar in clozapine dosing; their average clozapine minimum therapeutic dose ranged from 166 mg/day (female non-smokers) to 270 mg/day (male smokers). For those with European ancestry, average clozapine minimum therapeutic doses ranged from 236 mg/day (female non-smokers) to 368 mg/day (male smokers). Based on limited studies, Black (African sub-Saharan ancestry) patients may be treated with typical US doses (300-600 mg/day), assuming no poor metabolism (PM) status. Ancestry’s impact on clozapine lethality in four countries is discussed (two countries with highly homogenous populations, Denmark and Japan, and two countries with increasingly heterogenous populations due to immigration, Australia and the UK). An international guideline with 104 authors from 50 countries/regions was recently published, providing 6 personalized clozapine titration schedules for adult inpatients (3 ancestry groups and PM/non-PM schedules) and recommending c-reactive protein monitoring at baseline and weekly for 4 weeks.

Is Psychiatry Scientific? A Letter to a 21st Century Psychiatry Resident

Jose de Leon 대한신경정신의학회 2013 PSYCHIATRY INVESTIGATION Vol.10 No.3

During the development of the DSM-5, even the lay press questioned psychiatr's scientific validity. This review provides 21st century psychiatry residents with ways of answering these attacks by defining the concepts and history of psychiatry (a branch of medicine), medicine and science. Psychiatric language has two levels: first, describing symptoms and signs (19th century descriptive psychopathology developed in France and Germany), and second, describing disorders (psychiatric nosology was developed in the early 20th century by Kraepelin and resuscitated by the US neo-Kraepelinian revolution leading to the DSM-III). Science is a complex trial-and-error historical process that can be threatened by those who believe too much in it and disregard its limitations. The most important psychiatric advances, electroconvulsive therapy and major psychopharmacological agents, were discovered by "chance", not by scientific planning. Jaspers's General Psychopathology is a complex 100-year-old book that describes: 1) psychiatric disorders as heterogeneous and 2) psychiatry as a hybrid scientific discipline requiring a combination of understanding (a social science method) and explanation (a natural science method). In the 21st century Berrios reminds us of psychiatry's unfortunate methodological issues due to hybrid symptoms and disorders, some of which are better understood as problems in communication between interacting human beings; in those situations neuroscience methods such as brain imaging make no sense. A new language is needed in psychiatry. East Asian psychiatry residents, who are not particularly attached to the antiquated language currently used, may be particularly equipped for the task of recreating psychiatric language using 21st century knowledge.

Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing

de Leon Jose 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.4

This review article argues against trusting standard clozapine references, including the US package insert, because they do not include advances in the sciences of pharmacokinetics and pharmacovigilance and ignore the effects of ethnic ancestry on therapeutic dosing. The minimum therapeutic dose leading to the minimum therapeutic concentration of 350 ng/mL in serum/plasma can be used to compare individuals/groups with treatment-resistant schizophrenia. The US clozapine package insert recommends targeting doses of 300– 450 mg/day and, subsequently, increments of up to 100 mg with a maximum dose of 900 mg/day. Ethnic ancestry is defined by DNA ancestry group. Asians (people with ancestry ranging from Pakistan to Japan) and Indigenous Americans are similar in clozapine dosing; their average clozapine minimum therapeutic dose ranged from 166 mg/day (female non-smokers) to 270 mg/day (male smokers). For those with European ancestry, average clozapine minimum therapeutic doses ranged from 236 mg/day (female non-smokers) to 368 mg/day (male smokers). Based on limited studies, Black (African sub-Saharan ancestry) patients may be treated with typical US doses (300–600 mg/day), assuming no poor metabolism (PM) status. Ancestry’s impact on clozapine lethality in four countries is discussed (two countries with highly homogenous populations, Denmark and Japan, and two countries with increasingly heterogenous populations due to immigration, Australia and the UK). An international guideline with 104 authors from 50 countries/regions was recently published, providing 6 personalized clozapine titration schedules for adult inpatients (3 ancestry groups and PM/non-PM schedules) and recommending c-reactive protein monitoring at baseline and weekly for 4 weeks.

Effect of Pectin on the Expression of Proteins Associated with Mitochondrial Biogenesis and Cell Senescence in HT29-Human Colorectal Adenocarcinoma Cells

Jose Javier Zamorano-Leon,Sandra Ballesteros,Natalia de las Heras,Luis Alvarez-Sala,Mariano de la Serna-Soto,Khaoula Zekri-Nechar,Gala Freixer,Bibiana Calvo-Rico,Zhengguang Yang,Jose Manuel Garcia-Gar 한국식품영양과학회 2019 Preventive Nutrition and Food Science Vol.24 No.2

Mitochondria dynamic is regulated by different proteins, maintaining a balance between fission and fusion. An imbalance towards mitochondrial fission has been associated with tumor cell proliferation. The aim of this study was to analyze whether pectin modifies the viability of human colon cancer cells and the expression of proteins involved in mitochondrial fusion and fission. The human colon carcinoma cell line HT29 cells was growth in 10% fetal bovine serum in the absence and presence of pectin. Pectin reduced HT29 cell viability in a concentration-dependent manner, reaching a plateau at 150∼300 μ㏖/L pectin. The presence of 200 μ㏖/L pectin reduced the expression of dynamin-related protein-1 and increased expression of the mitochondrial fusion-associated proteins mitofusin-1 and 2. Expression of cyclin B1, a protein involved in G2/M transition, was found decreased in pectin-incubated HT29 cells. Moreover, expression of p53 protein, the amount of p53 in the nucleous and β-galactosidase activity, which are all biomarkers for cellular senescence, were significantly higher in pectin-incubated HT29 cells than in HT29 cells incubated without pectin. Expression of the protein B-cell lymphoma 2 (Bcl-2) homologous antagonist/killer was increased in response to incubation with pectin. However, incubation with pectin did not affect expression of Bcl-2-associated X protein or Bcl-2, or the caspase-3 activity. Overall, we concluded that pectin reduces the viability of human HT29 colon cancer cells, which is accompanied with a shift in the expression of proteins associated with mitochondrial dynamics towards mitochondrial fusion. Moreover, incubation with pectin favors cellular senescence over apoptosis in HT29 cells.

Influence of Culture Conditions on Production of NGPs by Aspergillus tubingensis

( Lopez De Leon Lilia ),( Caceres Isaura ),( Bornot Julie ),( Choque Elodie ),( Raynal Jose ),( Taillandier Patricia ),( Mathieu Florence ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.9

The filamentous fungus Aspergillus tubingensis that belongs to the black Aspergillus section has the capacity to produce high-value metabolites, for instance, naphtho-gamma-pyrones (NGPs). For these fungal secondary metabolites, numerous biological properties of industrial interest have been demonstrated, such as antimicrobial, antioxidant and anti-cancer capacities. It has been observed that production of these secondary metabolites is linked with fungal sporulation. The aim of this research was to apply osmotic and oxidative environmental stresses to trigger the production of NGPs in liquid cultures with CYB (Czapek Dox Broth). In addition, numerous parameters were tested during the experiments, such as pH value, incubation time, container geometry, and static and agitation conditions. Results demonstrate that the produced amount of NGPs can be enhanced by decreasing the water activity (a_w) or by adding an oxidative stress factor. In conclusion, this study can contribute to our knowledge regarding A. tubingensis to present an effective method to increase NGP production, which may support the development of current industrial processes.

Hepatolithiasis long term complication of choledochal cyst resection: Rase report

Ana Isabel ARGUETA,Francisco DE LEON,Jose CONTRERAS,Jimmy IXCAYAU,Haroldo PAIZ,Estuardo PORRAS,Erick SOTO 한국간담췌외과학회 2021 Annals of hepato-biliary-pancreatic surgery Vol.25 No.-

Argemone species: Potential source of biofuel and high-value biological active compounds

Alejandra Anahi Martinez-Delga,Jose de Anda,Janet Maria Leon-Morales,Juan Carlos Mateos-Diaz,Antonia Gutierrez-Mora,Jose Juvencio Castaneda-Nava 대한환경공학회 2022 Environmental Engineering Research Vol.27 No.2

The Argemone genus includes weed species of great importance in traditional medicine due to biological activities attributed to secondary metabolites, mainly alkaloids, distributed in all tissues of this species. In addition, their seeds contain a large amount of oil (30 to 40%). For this reason, several authors have discussed the potential of this species as a non-edible source to produce multi-purpose raw materials and a low cost-crop for example in the production of biofuels such as biodiesel. Argemone species grows in poor soils with low water and nutrient requirements. This makes the Argemone species an attractive economical and environmentally friendly candidate for biofuels production. Furthermore, the Argemone species can also provide high-value by-products for the agrochemical and pharmaceutical industry. In this work, we compiled the ethnomedical information, biochemical features, and biofuel production efforts that have been published by testing different Argemone species, in order to compare the research efforts and analyze its biotechnological potential. After analyzing the literature, we conclude that the genus has great potential for high-value pharmaceutical products and energy production purposes, and also to control plant pests. We also consider that other species of the genus may have also potential applications in this field.

The Role of Resveratrol in Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review

Daiene Santos Buglio,Ledyane Taynara Marton,Lucas Fornari Laurindo,Elen Landgraf Guiguer,Adriano Cressoni Arau´jo,Roge´rio Leone Buchaim,Ricardo de Alvares Goulart,Cla´udio Jose´ Rubira,Sandra M. Barb 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.8

Advancing age is one of the risk factors for developing many diseases, including cancer, cardiovascular disorders, and neurodegenerative alterations, such as mild cognitive impairment (MCI), and Alzheimer's Disease (AD). Studies have indicated that supplementation with resveratrol (RSV) might improve cerebrovascular function and reduce the risk of developing dementia. Thus, the aim of this systematic review was to assess the effects of RSV on MCI and AD. MEDLINE-PubMed, Cochrane, and EMBASE were used to perform the search, and PRISMA guidelines were followed. Five studies met the eligible criteria; three with AD and two with MCI. In AD patients, the use of RSV reduces Aβ levels, improves brain volume, reduces the Mini-mental status score, and improves AD scores. In patients with MCI, this polyphenol prevents decline in Standard Volumes of Interest and increases the Resting-state Functional Connectivity score. RSV can activate the human silent information regulator 2/sirtuin 1 (Sirt-1) and can inhibit the cyclooxygenase-2 (COX-2), 5-lipoxygenase, and nuclear factor-κB, resulting in the reduction of the proinflammation pathways. It is also associated with the increase in the levels of interleukin (IL)-10 and reduction of interferon-γ and IL-17. Both anti-inflammatory and antioxidant effects can be related to preventing neurodegenerative diseases, doing maintenance, and enabling the recovery of these conditions directly related to inflammation and oxidative stress. We suggest that the use of RSV can bring beneficial effects to patients with MCI or AD.