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.

Solubilization of Proteins from Human Lymph Node Tissue and Two-Dimensional Gel Storage

De Marqui, Alessandra Bernadete Trovo,Vidotto, Alessandra,Polachini, Giovana Mussi,De Mattos Bellato, Claudia,Cabral, Hamilton,Leopoldino, Andreia Machado,De Gois Filho, Jose Francisco,Fukuyama, Erica Korean Society for Biochemistry and Molecular Biol 2006 Journal of biochemistry and molecular biology Vol.39 No.2

In the present study, we compared six different solubilization buffers and optimized two-dimensional electrophoresis (2-DE) conditions for human lymph node proteins. In addition, we developed a simple protocol for 2-D gel storage. Efficient solubilization was obtained with lysis buffers containing (a) 8M urea, 4% CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), 40 mM Tris base, 65 mM DTT(dithiothreitol) and 0.2% carrier ampholytes; (b) 5M urea, 2M thiourea, 2% CHAPS, 2% SB 3-10 (N-decyl-N, N-dimethyl-3-ammonio-1-propanesulfonate), 40mM Tris base, 65 mM DTT and 0.2% carrier ampholytes or (c) 7M urea, 2M thiourea, 4% CHAPS, 65 mM DTT and 0.2% carrier ampholytes. The optimal protocol for isoelectric focusing (IEF) was accumulated voltage of 16,500 Vh and 0.6% DTT in the rehydration solution. In the experiments conducted for the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), best results were obtained with a doubled concentration (50 mM Tris, 384 mM glycine, 0.2% SDS) of the SDS electrophoresis buffer in the cathodic reservoir as compared to the concentration in the anodic reservoir (25 mM Tris, 192 mM glycine, 0.1% SDS). Among the five protocols tested for gel storing, success was attained when the gels were stored in plastic bags with 50% glycerol. This is the first report describing the successful solubilization and 2D-electrophoresis of proteins from human lymph node tissue and a 2-D gel storage protocol for easy gel handling before mass spectrometry (MS) analysis.

Effects of solvent volatilization time on the bond strength of etch-and-rinse adhesive to dentin using conventional or deproteinization bonding techniques

de Sousa, Jose Aginaldo Junior,Carregosa Santana, Marcia Luciana,de Figueiredo, Fabricio Eneas Diniz,Faria-e-Silva, Andre Luis The Korean Academy of Conservative Dentistry 2015 Restorative Dentistry & Endodontics Vol.40 No.3

Objectives: This study determined the effect of the air-stream application time and the bonding technique on the dentin bond strength of adhesives with different solvents. Furthermore, the content and volatilization rate of the solvents contained in the adhesives were also evaluated. Materials and Methods:Three adhesive systems with different solvents (Stae, SDI, acetone; XP Bond, Dentsply De Trey, butanol; Ambar, FGM, ethanol) were evaluated. The concentrations and evaporation rates of each adhesive were measured using an analytical balance. After acid-etching and rinsing, medium occlusal dentin surfaces of human molars were kept moist (conventional) or were treated with 10% sodium hypochlorite for deproteinization. After applying adhesives over the dentin, slight air-stream was applied for 10, 30 or 60 sec. Composite cylinders were built up and submitted to shear testing. The data were submitted to ANOVA and Tukey's test (${\alpha}=0.05$). Results: Stae showed the highest solvent content and Ambar the lowest. Acetone presented the highest evaporation rate, followed by butanol. Shear bond strengths were significantly affected only by the factors of 'adhesive' and 'bonding technique' (p < 0.05), while the factor 'duration of air-stream' was not significant. Deproteinization of dentin increased the bond strength (p < 0.05). Stae showed the lowest bond strength values (p < 0.05), while no significant difference was observed between XP Bond and Ambar. Conclusions: Despite the differences in content and evaporation rate of the solvents, the duration of air-stream application did not affect the bond strength to dentin irrespective of the bonding technique.

A FORMACAO DO BRASIL

de Andrade, Jose Antonio 이베로아메리카연구소 부산외국어대학교 1999 이베로아메리카 Vol.1 No.-

Numerical study of a new constructive sequence for movable scaffolding system (MSS) application

Teran, Jose Ramon Diaz de,Haach, Vladimir Guilherme,Turmo, Jose,Jorquera, Juan Jose Techno-Press 2016 Advances in concrete construction Vol.4 No.3

This paper consists in a study of a new contructive sequence of road viaducts with Movable Scaffolding System (MSS) using numerical tools based on finite element method (FEM). Traditional and new sequences are being used in Spain to build viaducts with MSS. The new sequence permits an easier construction of one span per week but implies some other issues related to the need of two prestressing stages per span. In order to improve the efficiency of the new sequence by reducing the number of prestressing stages per span, two solutions are suggested in this study. Results show that the best solution is to introduce the 100% of the prestressing force at the self-supporting core in order to improve the road viaduct construction with movable scaffolding system by reducing execution time without increasing economic costs.

Antidiabetic Effect of the Chrysobalanus icaco L. Aqueous Extract in Rats

Ana Paula de Oliveira Barbosa,Gabriela de Oliveira Silveira,Igor Alexandre Cortes de Menezes,Jose´ Melquiades Rezende Neto,Jose´ Leal C. Bitencurt,Charles dos Santos Estavam,Amanda do Carmo Bion de Li 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.6

Chrysobalanus icaco L. is a medicinal plant popularly known in Brazil as ‘‘Grageru’’ or ‘‘Abageru.’’ It is used in African and American continents as medicinal food in the treatment of several diseases, including diabetes. This study used phytochemical screening to determine the antioxidant and α-amylase inhibitor activities of the aqueous extract (AECI) of C. icaco, and evaluated its antidiabetic potential in rodents. Phytochemical screening was performed using colorimetric tests with specific reagents. The in vitro antioxidant activity was evaluated by the scavenging activity of 2,2-diphenyl-1-picril-hydrazyl. The lethality test and behavioral screening was performed using an oral administration of 5 g/kg of AECI. The antidiabetic potential of AECI was evaluated through the oral glucose tolerance test (OGTT) and chronic hypoglycemic test at the doses of 100, 200, and 400 mg/kg (orally). Metformin was used as a reference drug in all tests. Diabetes was induced by injection of alloxan (40 mg/kg; intravenously). Phytochemical screening showed the presence of various compounds, including tannins, flavones, triterpenoids, steroids, saponins, and alkaloids. The in vitro antioxidant test demonstrated that AECI presented potent antioxidant activity. The lethality test and behavioral screening did not show lethality signs. In the OGTT test, AECI administration was not able to inhibit the elevation of glycemia. However, chronically administrated, it was able to cause a significant (P < .05) reduction of glycemia from 335 ± 27 up to 197 ± 15 mg/dL. These results demonstrate that the AECI presents a potential beneficial effect for diabetes.

Sugarcane bagasse as exclusive roughage for dairy cows in smallholder livestock system

Gleidiana Amelia Pontes de Almeida,Marcelo de Andrade Ferreira,Janaina de Lima Silva,Juana Catarina Cariri Chagas,Antonia Sherlanea Chaves Veras,Leonardo Jose Assis de Barros,Gledson Luiz Pontes de Al 아세아·태평양축산학회 2018 Animal Bioscience Vol.31 No.3

Objective: The study aimed to evaluate sugarcane bagasse as roughage in lactating cow on feed intake, digestibility, ingestive behavior, milk production and composition, and microbial protein synthesis. Methods: Ten Girolando cows at initial body weight of 450±25.6 kg and at 143.7±30.7 days in milk were assigned in two 5×5 Latin square designs. Five 21-day experimental periods were adopted (1° to 14-day: diets adaptation period; 15° to 21-day: data collection and sampling period). The diets consisted of four different levels of sugarcane bagasse (45%, 50%, 55%, and 60%) and a control diet, commonly adopted in the region, based on spineless cactus (25% sugarcane bagasse), formulated to meet 12 kg/d milk yield. Results: The dry matter (DM), organic matter (OM), and total digestible nutrients intakes and DM and OM digestibilities observed for 45% and 50% bagasse inclusion were similar to control diet, while that 55% and 60% bagasse inclusion were lower. Cows fed control diet, and bagasse diets of 45%, and 50% levels had the nutritional requirements attended, that guaranteed 12 kg/d of milk yield. The crude protein intake and digestibility of cows fed 45%, 50%, and 55% of bagasse inclusion were similar to control diet. The neutral detergent fiber (NDF) intake and digestibility differ for all bagasse diets related to control diet, while the non-fiber carbohydrates intake and digestibility for cows fed 45% of bagasse were similar for control diet. The intakes and digestibilities of nutrients decreased linearly in function of bagasse inclusion; NDF and indigestible NDF intakes did not vary. The ruminating time, feeding and rumination efficiency, microbial protein synthesis and milk yield decreased linearly with sugarcane bagasse inclusion. Conclusion: Sugarcane bagasse decreases milk production; however, its inclusion level in between 45% to 50% associated to concentrate could replace diets based on spineless cactus for crossbred dairy cow's producing 12 kg/d of milk.

Rediscovery of the Golden Snapper Lutjanus Inermis (Peters, 1869) (Perciformes: Lutjanidae) in the Gulf of California

Jose Julian Tavera,Jose De la Cruz-Aguero 한국해양과학기술원 2006 Ocean science journal Vol.41 No.3

Two specimens of Lutjanus inermis, the most unusual species of the genus in the tropical eastern Pacific region, were collected at La Ventana, Baja California Sur, Mexico in November 2005, 400 km northward from the type locality. The golden snapper can be recognized by its long anal fin, and its yellowish peduncle and caudal fin that sometimes present a reddish phase. Present record is the first documented and verified report supported by voucher specimens of L. inermis inside the Gulf of California since its original description in the last quarter of the nineteenth century, setting the northern geographic limit to the Cortes Province.

금융개방의 정책적 교훈 : 금융개발과 자본통제 : 스페인의 경험

(Jose De Gregorio) 한국금융연구원 1994 정책조사보고서 Vol.94 No.1

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.