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1.
Rev. bras. ter. intensiva ; 32(3): 391-397, jul.-set. 2020. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1138519

ABSTRACT

RESUMO Objetivo: Investigar a efetividade da vancomicina contra Gram-positivos com concentração inibitória mínima de 1mg/L em pacientes pediátricos com base na razão entre área sob a curva e concentração inibitória mínima > 400. Métodos: População de 22 pacientes pediátricos (13 meninos) internados no centro de terapia intensiva pediátrica, com função renal preservada, que foram distribuídos em dois grupos (G1 < 7 anos e G2 ≥ 7 anos). Após a quarta dose de vancomicina (10 - 15mg/kg a cada 6 horas), duas amostras de sangue foram colhidas (terceira e quinta horas), seguidas da dosagem sérica por imunoensaios para investigação da farmacocinética e da cobertura do antimicrobiano. Resultados: Não se registrou diferença entre os grupos com relação à dose, ao nível de vale ou ainda na área sob a curva. A cobertura contra Gram-positivos com concentração inibitória mínima de 1mg/L ocorreu em apenas 46% dos pacientes em ambos os grupos. A farmacocinética se mostrou alterada nos dois grupos diante dos valores de referência, mas a diferença entre grupos foi registrada pelo aumento da depuração total corporal e pelo encurtamento da meia-vida biológica, mais pronunciados nos pacientes mais novos. Conclusão: A dose empírica mínima de 60mg/kg ao dia deve ser prescrita ao paciente pediátrico de unidade de terapia intensiva com função renal preservada. A utilização da razão entre área sob a curva e concentração inibitória mínima na avaliação da cobertura da vancomicina é recomendada para se atingir o desfecho desejado, uma vez que a farmacocinética está alterada nesses pacientes, podendo impactar na efetividade do antimicrobiano.


Abstract Objective: To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400. Methods: A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage. Results: There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients. Conclusion: A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.


Subject(s)
Humans , Male , Infant , Child, Preschool , Child , Adolescent , Vancomycin/administration & dosage , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacteria/drug effects , Anti-Bacterial Agents/administration & dosage , Vancomycin/pharmacology , Vancomycin/pharmacokinetics , Intensive Care Units, Pediatric , Microbial Sensitivity Tests , Pilot Projects , Age Factors , Area Under Curve , Dose-Response Relationship, Drug , Half-Life
2.
Rev. bras. ter. intensiva ; 32(2): 277-283, Apr.-June 2020. tab, graf
Article in English, Portuguese | LILACS | ID: biblio-1138494

ABSTRACT

RESUMO Objetivo: Determinar os níveis plasmáticos e o comportamento farmacocinético da micafungina em pacientes tratados com oxigenação por membrana extracorpórea. Métodos: As amostras foram colhidas por meio de pontos de acesso antes e depois da membrana, em dois hospitais espanhóis de nível terciário. Os momentos para o cálculo das curvas farmacocinéticas foram antes da administração do fármaco, e 1, 3, 5, 8, 18 e 24 horas após o início da infusão nos dias 1 e 4 de tratamento. Calcularam-se a área sob a curva, a depuração do fármaco, o volume de distribuição e a meia-vida plasmática por meio de análise farmacocinética não compartimental. Resultados: Os valores farmacocinéticos analisados no primeiro e quarto dias de tratamento não mostram qualquer diferença de concentração entre amostras colhidas antes da membrana e após a membrana, e o comportamento farmacocinético foi similar na vigência de diferentes falências de órgãos. A área sob a curva antes da membrana no dia 1 foi de 62,1 (IC95% 52,8 - 73,4) e a área sob a curva após a membrana nesse mesmo dia foi de 63,4 (IC95% 52,4 - 76,7), com p = 0,625. A área sob a curva antes da membrana no dia 4 foi de 102,4 (IC95% 84,7 - 142,8), enquanto a área sob a curva após a membrana nesse mesmo dia foi de 100,9 (IC95% 78,2 - 138,8), com p = 0,843. Conclusão: Os parâmetros farmacocinéticos da micafungina não foram alterados significantemente.


ABSTRACT Objective: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. Methods: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. Results: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. Conclusion: The pharmacokinetic parameters of micafungin were not significantly altered.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Extracorporeal Membrane Oxygenation , Micafungin/pharmacokinetics , Antifungal Agents/pharmacokinetics , Tissue Distribution , Prospective Studies , Area Under Curve , Tertiary Care Centers , Micafungin/administration & dosage , Half-Life , Antifungal Agents/administration & dosage
4.
Article in Korean | WPRIM | ID: wpr-785354

ABSTRACT

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). These mutations alter the synthesis, processing, function, or half-life of CFTR, the main chloride channel expressed in the apical membrane of epithelial cells in the airway, intestine, pancreas, and reproductive tract. Lung disease is the most critical manifestation of CF. It is characterized by airway obstruction, infection, and inflammation that lead to fatal tissue destruction, which causes most CF morbidity and mortality. This article reviews the pathophysiology of CF, recent animal models, and current treatment of CF.


Subject(s)
Airway Obstruction , Chloride Channels , Cystic Fibrosis Transmembrane Conductance Regulator , Cystic Fibrosis , Epithelial Cells , Epithelial Sodium Channels , Half-Life , Inflammation , Intestines , Lung Diseases , Lung , Membranes , Models, Animal , Mortality , Pancreas
5.
Article in English | WPRIM | ID: wpr-810952

ABSTRACT

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.METHODS: Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.RESULTS: The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.CONCLUSION: Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.


Subject(s)
Antiviral Agents , Carcinoma, Hepatocellular , Cohort Studies , DNA , Follow-Up Studies , Half-Life , Hepatitis B Surface Antigens , Hepatitis B virus , Hepatitis B , Hepatitis , Humans , Immunoglobulins , Korea , Liver Transplantation , Liver , Organ Transplantation , Polymerase Chain Reaction , Recurrence , Transplants
6.
Article in English | WPRIM | ID: wpr-763190

ABSTRACT

PURPOSE: Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied. MATERIALS AND METHODS: We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC. RESULTS: Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression. CONCLUSION: Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.


Subject(s)
Animals , Biliary Tract Neoplasms , Biliary Tract , Cell Line , Cisplatin , DNA Damage , G1 Phase Cell Cycle Checkpoints , Half-Life , Heterografts , Humans , In Vitro Techniques , Mice , Phosphorylation , Prognosis , PTEN Phosphohydrolase , RNA, Small Interfering , Transfection
7.
Article in English | WPRIM | ID: wpr-786472

ABSTRACT

PURPOSE: The effective half-life of radioiodine is an important parameter for dosimetry in differentiated thyroid cancer patients, particularly in children. We determined the pre-therapy and post-therapy effective half-life in different types of lesions, i.e., remnant, node, or lung metastases.METHODS: Of 84 patients recruited, 27 were < 18 years (group 1) and the remaining 57 were between 18 and 21 years (group 2). A total of 114 studies were conducted and 253 lesions were analyzed. Serial whole-body scans were acquired at 24, 48, and ≥ 72 h after administration of iodine-131. Region of interests was drawn over lesions to determine counts in the lesion. Time versus counts graphs were plotted and mono-exponentially fitted to determine effective half-life.RESULTS: The post-therapy effective half-life was found to be lesser than pre-therapy effective half-life in all types of lesions and in all groups. Median effective half-life was found maximum in intact lobe, minimum in the lung, and intermediate in remnant and nodes. In the assessment of all lesions together, pre- and post-therapy median and interquartile range (IQR) effective half-life were 59.8 (37–112) h and 48.6 (35.2–70.8) h (p < 0.0001) in group 1, 73.9 (46.2–112.7) h and 60 (57.4–85.9) h (p < 0.0001) in group 2, and 68.6 (41.53–112.36) h and 54.7 (36–80.6) h (p < 0.0001) in combined group, respectively. Importantly, the pre- and post-therapy median effective half-life serially dropped after each successive cycles of iodine-131.CONCLUSIONS: There was a significant difference in pre-therapy and post-therapy effective half-life in all types of lesions. These results may have implications in calculating the correct therapeutic dose in children and in young adults.


Subject(s)
Child , Half-Life , Humans , Lung , Neoplasm Metastasis , Thyroid Gland , Thyroid Neoplasms , Young Adult
8.
Article in Korean | WPRIM | ID: wpr-766601

ABSTRACT

Radon is a naturally occurring radioactive material classified as a carcinogen by the World Health Organization, and is known to be the factor with the second-greatest impact on lung cancer after smoking. An association between radon and lung cancer has consistently been reported in epidemiological studies on mine workers and residents of homes with indoor radon exposure. However, associations between radon and other diseases, such as leukemia and thyroid cancer, have yet to be confirmed due to a lack of consistent research findings and biological relevance. Such associations are unlikely because there is a very low likelihood that organs other than the lungs are exposed to radon upon inhalation due to the short half-life of radon and its progeny and the low permeability of alpha rays. In spring 2018, the radon bed mattress incident occurred, leading to a spike of concern and interest among the public regarding the health effects of radiation exposure. This paper presents a description of radon exposure and its health effects based on the current literature and provides practical information based on health consultations experienced following the 2018 radon mattress incident.


Subject(s)
Alpha Particles , Epidemiologic Studies , Half-Life , Inhalation , Leukemia , Lung , Lung Neoplasms , Miners , Permeability , Radiation Exposure , Radon , Referral and Consultation , Smoke , Smoking , Thyroid Neoplasms , World Health Organization
9.
Blood Research ; : 198-203, 2019.
Article in English | WPRIM | ID: wpr-763077

ABSTRACT

BACKGROUND: The efficacy and safety of extended half-life, full-length, pegylated recombinant factor VIII rurioctocog alfa pegol [BAX 855, ADYNOVATE (USA)/ADYNOVI (Europe); Baxalta US Inc., a Takeda company, Lexington, MA, USA] was investigated in previously treated Korean patients with severe hemophilia A (HA). METHODS: A post hoc data analysis from the international, multicenter, phase 2/3 PROLONG-ATE study of rurioctocog alfa pegol in patients with severe HA (NCT01736475) determined annualized bleeding rates (ABRs) and rates of adverse events (AEs) in Korean patients treated in this study. RESULTS: All 10 enrolled Korean patients receiving rurioctocog alfa pegol (9 prophylaxis, 1 on-demand) completed the study [median (range) age, 28.0 (12–50) yr; weight, 64.8 (45–90) kg; 8 patients had ≥1 target joint at screening]. Median (range) ABR was 1.9 (0.0–14.5) for patients on prophylaxis and 62.2 for the patient receiving on-demand treatment. The hemostatic efficacy of rurioctocog alfa pegol was rated “excellent” or “good” and only single infusions were required per bleeding episode. ABRs improved in most patients compared with prestudy values. No dose adjustments were required for prophylaxis, and the dosing frequency was reduced in 8 patients, compared with their previous prophylaxis regimen. No serious AEs were reported; all 9 nonserious AEs (in 3 patients) were mild in severity and unrelated to the study treatment. CONCLUSION: This post hoc analysis of a small group of Korean patients with severe HA indicated that rurioctocog alfa pegol was effective, and no serious AEs were observed. For most patients, the dosing frequency was also reduced compared with their previous regimen.


Subject(s)
Factor VIII , Half-Life , Hemophilia A , Hemorrhage , Humans , Joints , Statistics as Topic
10.
Article in English | WPRIM | ID: wpr-762443

ABSTRACT

BACKGROUND: Physiological changes during pregnancy, such as dilutional anemia and a reduced half-life of red blood cells, have prevented the use of glycated Hb (HbA1c) as a biomarker for gestational diabetes mellitus (GDM). Nevertheless, increasing evidence supports the use of HbA1c in GDM diagnostic strategies.We studied HbA1c as a biomarker of GDM and its possible use as a screening test to avoid the use of the glucose challenge test (GCT). METHODS: This case-control study involved 607 pregnant women between the 24th and 28th week of gestation. HbA1c level was determined, and GDM was diagnosed according to the National Diabetes Data Group criteria. The area under the ROC curve (AUC) was determined; two low and two high cut-off points were established to rule out GDM and classify high-risk pregnant women, respectively. For each cut-off, sensitivity (S), specificity (SP), and total number and percentage of GCTs avoided were determined. RESULTS: The AUC for HbA1c diagnostic performance was 0.68 (95% confidence interval 0.57–0.79). Using 4.6% HbA1c (27 mmol/mol) as the lower cut-off (S=100%), 14% of participants could avoid the GCT. Using 5.5% HbA1c (36 mmol/mol) as the upper cut-off (SP =94.5%), 6% of participants would be considered at high risk. CONCLUSIONS: HbA1c can be used as a screening test prior to the GCT, thereby reducing the need for the GCT among pregnant women at a low risk of GDM.


Subject(s)
Anemia , Area Under Curve , Case-Control Studies , Diabetes, Gestational , Erythrocytes , Female , Glucose , Half-Life , Glycated Hemoglobin A , Humans , Mass Screening , Pregnancy , Pregnant Women , ROC Curve , Sensitivity and Specificity
11.
Article in English | WPRIM | ID: wpr-758921

ABSTRACT

The effects of CYP1A enzyme on the pharmacokinetics of p-acetaminophen were studied in Bactrian camel. Twelve Bactrian camels were divided into 2 groups, then given a single dose of p-acetaminophen only or with the enzyme inhibitor lomefloxacin. Blood samples were collected after different intervals, and p-acetaminophen concentration was determined by high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by Phoenix WinNonLin v.7.0. The results show that lomefloxacin can significantly inhibit Bactrian camel CYP1A enzyme, as evidenced by the prolonged elimination half-life, increased maximum plasma concentration and area under the curve values and the shortened time to peak concentration for p-acetaminophenol in the substrate with inhibitor group. The results lay a foundation for revealing the particular characteristics of the CYP1A enzyme in Bactrian camels.


Subject(s)
Camelus , Chromatography, Liquid , Half-Life , Pharmacokinetics , Plasma
12.
Article in English | WPRIM | ID: wpr-719304

ABSTRACT

BACKGROUND AND PURPOSE: There is conflicting evidence in the literature on the association between benzodiazepines (BDZs) and the risk of dementia. This meta-analysis aimed to determine the relationship between the long-term usage of BDZs and the risk of dementia. METHODS: The PubMed and Embase databases were systematically searched for relevant publications up to September 2017. The literature search focused on observational studies that analyzed the relationship between the long-term use of BDZs and the risk of dementia. Pooled rate ratios (RRs) with 95% confidence interval (CI) were assessed using a random-effects model. The robustness of the results was checked by performing subgroup and sensitivity analyses. RESULTS: Ten studies were included: six case–control and four cohort studies. The pooled RR for developing dementia was 1.51 (95% CI=1.17–1.95, p=0.002) in patients taking BDZ. The risk of dementia was higher in patients taking BDZs with a longer half-life (RR=1.16, 95% CI=0.95–1.41, p=0.150) and for a longer time (RR=1.21, 95% CI=1.04–1.40, p=0.016). CONCLUSIONS: This meta-analysis that pooled ten studies has shown that BDZ significantly increases the risk of dementia in the elderly population. The risk is higher in patients taking BDZ with a longer half-life (>20 hours) and for a longer duration (>3 years).


Subject(s)
Aged , Benzodiazepines , Cohort Studies , Dementia , Half-Life , Humans
13.
Article in English | WPRIM | ID: wpr-739653

ABSTRACT

Suppressor of Variegation 3–9 Homolog 2 (SUV39H2) methylates the lysine 9 residue of histone H3 and induces heterochromatin formation, resulting in transcriptional repression or silencing of target genes. SUV39H1 and SUV39H2 have a role in embryonic development, and SUV39H1 was shown to suppress cell cycle progression associated with Rb. However, the function of human SUV39H2 has not been extensively studied. We observed that forced expression of SUV39H2 decreased cell proliferation by inducing G1 cell cycle arrest. In addition, SUV39H2 was degraded through the ubiquitin-proteasomal pathway. Using yeast two-hybrid screening to address the degradation mechanism and function of SUV39H2, we identified translationally controlled tumor protein (TCTP) as an SUV39H2-interacting molecule. Mapping of the interacting regions indicated that the N-terminal 60 amino acids (aa) of full-length SUV39H2 and the C-terminus of TCTP (120–172 aa) were critical for binding. The interaction of SUV39H2 and TCTP was further confirmed by co-immunoprecipitation and immunofluorescence staining for colocalization. Moreover, depletion of TCTP by RNAi led to up-regulation of SUV39H2 protein, while TCTP overexpression reduced SUV39H2 protein level. The half-life of SUV39H2 protein was significantly extended upon TCTP depletion. These results clearly indicate that TCTP negatively regulates the expression of SUV39H2 post-translationally. Furthermore, SUV39H2 induced apoptotic cell death in TCTP-knockdown cells. Taken together, we identified SUV39H2, as a novel target protein of TCTP and demonstrated that SUV39H2 regulates cell proliferation of lung cancer cells.


Subject(s)
Amino Acids , Apoptosis , Carrier Proteins , Cell Cycle , Cell Death , Cell Proliferation , Embryonic Development , Female , Fluorescent Antibody Technique , G1 Phase Cell Cycle Checkpoints , Half-Life , Heterochromatin , Histones , Humans , Immunoprecipitation , Lung Neoplasms , Lysine , Mass Screening , Pregnancy , Repression, Psychology , RNA Interference , Up-Regulation , Yeasts
14.
Article in English | WPRIM | ID: wpr-765083

ABSTRACT

BACKGROUND: Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. This study established an individualized HBV prophylaxis protocol, through optimization of hepatitis B immunoglobulin (HBIG) administration, with application of simulative half-life (SHL). METHODS: This study involved five parts: Part 1 developed the SHL estimation method with 20 patients; Parts 2 and 3 assessed the SHL variability and developed a simulation model to apply SHL in 100 patients; Part 4 validated the simulation model in 114 patients, and Part 5 was a cross-sectional study on the current status of HBIG infusion intervals in 660 patients. RESULTS: In Part 1, infusion of 10,000 IU HBIG induced add-on rise hepatitis B surface antibody (anti-HBs) titer of 5,252.5 ± 873.7 IU/L, which was 4.4% lower than actual measurement. Mean SHL of 20.0 ± 3.7 days was 2.2% longer than actual measurement. In Part 2, the medians of the intra- and inter-individual coefficient of variation in SHL were 13.5% and 18.5%, respectively. Pretransplant HBV DNA load and posttransplant antiviral therapy did not affect SHL. In Part 3, a simulation model was developed to determine the interval of HBIG infusion, by using SHL. In Part 4, all 114 patients were successfully managed with regular HBIG infusion intervals of ≥ 8 weeks, and the interval was prolonged to ≥ 12 weeks in 89.4%, with a target trough anti-HBs titer ≥ 200 IU/L. In Part 5, 47.4% of our patients received HBIG excessively, at a target trough titer of 500 IU/L. CONCLUSION: SHL estimation using only clinically available parameters seems to be reliably accurate when compared with actual measurements. We believe that SHL estimation is helpful to establish a personalized HBV prophylaxis protocol for optimizing HBIG administration.


Subject(s)
Cross-Sectional Studies , DNA , Half-Life , Hepatitis B virus , Hepatitis B , Hepatitis , Humans , Immunoglobulins , Liver Transplantation , Methods , Recurrence
15.
Article in English | WPRIM | ID: wpr-787002

ABSTRACT

Myocardial perfusion imaging using positron emission tomography (PET) has several advantages over single photon emission computed tomography (SPECT). The recent advances in SPECT technology have shown promise, but there is still a large need for PET in the clinical management of coronary artery disease (CAD). Especially, absolute quantification of myocardial blood flow (MBF) using PET is extremely important. In spite of considerable advances in the diagnosis of CAD, novel PET radiopharmaceuticals remain necessary for the diagnosis of CAD because clinical use of current cardiac radiotracers is limited by their physical characteristics, such as decay mode, emission energy, and half-life. Thus, the use of a radioisotope that has proper characteristics and a proper half-life to develop myocardial perfusion agents could overcome these limitations. In this review, the current state of cardiac PET and a general overview of novel ¹⁸F or ⁶⁸Ga-labeled radiotracers, including their radiosynthesis, in vivo characterization, and evaluation, are provided. The future perspectives are discussed in terms of their potential usefulness based on new image analysis methods and hybrid imaging.


Subject(s)
Coronary Artery Disease , Diagnosis , Half-Life , Myocardial Perfusion Imaging , Perfusion , Positron-Emission Tomography , Radiopharmaceuticals , Tomography, Emission-Computed, Single-Photon
16.
Article in English | WPRIM | ID: wpr-715043

ABSTRACT

The elimination half-lives of in Interleukin-6 (IL-6) and cytokine-induced neutrophil chemoattractant-1 (CINC-1) in rats after inflammatory stimulation were investigated. Five male Sprague-Dawley rats were used (age, 9 weeks; body weight, 235–375 g). Turpentine oil was intramuscularly injected at a dose of 2 mL/kg body weight to induce acute inflammation. Blood was collected pre-injection and 6, 12, 24, 36, 48, 60, 72, 84, and 96 h after the turpentine oil injection. Serum concentrations of IL-6, CINC-1, and α₂-macroglobulin (α2M) were measured by enzyme-linked immunosorbent assay. Half-lives were calculated as 0.693/elimination rate constant. The serum concentration of α2M peaked at 48 h after turpentine oil injection. Serum concentrations of IL-6 and CINC-1 increased and peaked at 12 and 24 h, respectively. The terminal elimination half-lives of IL-6 and CINC-1 were 15.5 and 29.9 h, respectively. The half-life of CINC-1 was significantly longer than that of IL-6 (P=0.006). These results suggested that these cytokines synthesized in response to inflammatory stimulation were rapidly eliminated in rats. The serum concentrations of these cytokines should be measured at an early stage if these cytokines will be used as surrogate inflammatory markers instead of acute-phase proteins.


Subject(s)
Acute-Phase Proteins , Animals , Body Weight , Cytokines , Enzyme-Linked Immunosorbent Assay , Half-Life , Humans , Inflammation , Interleukin-6 , Male , Neutrophils , Rats , Rats, Sprague-Dawley , Turpentine
17.
Article in English | WPRIM | ID: wpr-714203

ABSTRACT

Over the past several decades, hemophilia treatment in Korea has progressed dramatically. It has become possible to prevent hemophilia complications by maintenance treatment as well as on-demand treatment with the help of the National Health Insurance program. Treatment and prevention of hemorrhage, prevention of joint complications, treatment and prevention of infectious complications have greatly improved the quality of life and life expectancy of hemophilia patients. However, the development of inhibitor is the most serious and challenging complication of clotting factor replacement therapy, although immune tolerance regimens and bypassing agents have shown some efficacy in countering this complication. The development of novel methods of therapy, including the use of extended half-life factors and gene therapy, will further improve the outcome of hemophilia patients. Administering the right drug to the right patients with the right dose at the right time will be necessary for treating the patient. Achievement of optimal therapeutic goals will require continued cooperation between patients and medical staff.


Subject(s)
Factor VIII , Genetic Therapy , Half-Life , Hemophilia A , Hemorrhage , Humans , Immune Tolerance , Joints , Korea , Life Expectancy , Medical Staff , National Health Programs , Quality of Life
18.
Article in English | WPRIM | ID: wpr-713893

ABSTRACT

PURPOSE: This phase 1 dose-escalation portion of the study evaluated the safety, pharmacokinetics (PK), and antitumor activity of TAK-264 in Asian patients with advanced gastrointestinal (GI) carcinoma or metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma expressing guanylyl cyclase C (GCC). MATERIALS AND METHODS: Adult patients with advanced GI malignancies expressing GCC (H-score ≥ 10) received TAK-264 on day 1 of 3-week cycles as 30-minute intravenous infusions for up to 1 year or until disease progression or unacceptable toxicity. The primary objectives were to evaluate the safety profile including dose-limiting toxicities (DLTs) during cycle 1, determine the maximum tolerated dose (MTD), and characterize the PK profile of TAK-264. RESULTS: Twelve patients were enrolled and treated with 1.2 mg/kg (n=3), 1.5 mg/kg (n=3), or 1.8 mg/kg TAK-264 (n=6). Median number of treatment cycles received was two (range, 1 to 10). None of the patients experienced a DLT and the MTD was not determined. Ten patients (83%) experienced adverse events (AEs). The most common were neutropenia, anorexia, and nausea (each reported by four patients). Five patients (42%) experienced grade ≥ 3 AEs consisting of tumor hemorrhage and hypertension, ascites, adrenal insufficiency, neutropenia and asthenia. Serum exposure to TAK-264 increased proportionally with the dose and the median half-life was approximately 5.5-6.6 days. No patients experienced an objective response. CONCLUSION: TAK-264 demonstrated a manageable safety profile with limited antitumor activity consistent with studies conducted in Western patients with advanced GI malignancies. TAK-264 exposure increased proportionally with the dose.


Subject(s)
Adenocarcinoma , Adrenal Insufficiency , Adult , Anorexia , Ascites , Asian Continental Ancestry Group , Asthenia , Disease Progression , Esophagogastric Junction , Gastrointestinal Neoplasms , Guanylate Cyclase , Half-Life , Hemorrhage , Humans , Hypertension , Infusions, Intravenous , Maximum Tolerated Dose , Nausea , Neutropenia , Pharmacokinetics , Stomach
19.
Article in English | WPRIM | ID: wpr-716597

ABSTRACT

Adiponectin, a hormone predominantly originated from adipose tissue, has exhibited potent anti-inflammatory properties. Accumulating evidence suggests that autophagy induction plays a crucial role in anti-inflammatory responses by adiponectin. However, underlying molecular mechanisms are still largely unknown. Association of Bcl-2 with Beclin-1, an autophagy activating protein, prevents autophagy induction. We have previously shown that adiponectin-induced autophagy activation is mediated through inhibition of interaction between Bcl-2 and Beclin-1. In the present study, we examined the molecular mechanisms by which adiponectin modulates association of Bcl-2 and Beclin-1 in macrophages. Herein, we demonstrated that globular adiponectin (gAcrp) induced increase in the expression of AUF1 and ZFP36L1, which act as mRNA destabilizing proteins, both in RAW 264.7 macrophages and primary peritoneal macrophages. In addition, gene silencing of AUF1 and ZFP36L1 caused restoration of decrease in Bcl-2 expression and Bcl-2 mRNA half-life by gAcrp, indicating crucial roles of AUF1 and ZFP36L1 induction in Bcl-2 mRNA destabilization by gAcrp. Moreover, knock-down of AUF1 and ZFP36L1 enhanced interaction of Bcl-2 with Beclin-1, and subsequently prevented gAcrp-induced autophagy activation, suggesting that AUF1 and ZFP36L1 induction mediates gAcrp-induced autophagy activation via Bcl-2 mRNA destabilization. Furthermore, suppressive effects of gAcrp on LPS-stimulated inflammatory mediators expression were prevented by gene silencing of AUF1 and ZFP36L1 in macrophages. Taken together, these results suggest that AUF1 and ZFP36L1 induction critically contributes to autophagy induction by gAcrp and are promising targets for anti-inflammatory responses by gAcrp.


Subject(s)
Adiponectin , Adipose Tissue , Autophagy , Gene Silencing , Half-Life , Inflammation , Macrophages , Macrophages, Peritoneal , RNA, Messenger
20.
Electron. j. biotechnol ; 28: 52-57, July. 2017. ilus, graf, tab
Article in English | LILACS | ID: biblio-1015847

ABSTRACT

Background: Gardnerella vaginalis is a bacterial vaginosis (BV)-associated vaginal bacterium that produces the toxin vaginolysin (VLY). VLY is a pore-forming toxin that is suggested to be the main virulence factor of G. vaginalis. The high recurrence rate of BV and the emergence of antibiotic-resistant bacterial species demonstrate the need for the development of recombinant antibodies as novel therapeutic agents for disease treatment. Single-chain variable fragments (scFvs) generated against VLY exhibited reduced efficacy to neutralize VLY activity compared to the respective full-length antibodies. To improve the properties of scFvs, monospecific dimeric scFvs were generated by the genetic fusion of two anti-VLY scFv molecules connected by an alpha-helix-forming peptide linker. Results: N-terminal hexahistidine-tagged dimeric scFvs were constructed and produced in Escherichia coli and purified using metal chelate affinity chromatography. Inhibition of VLY-mediated human erythrocyte lysis by dimeric and monomeric scFvs was detected by in vitro hemolytic assay. The circulating half-life of purified scFvs in the blood plasma of mice was determined by ELISA. Dimeric anti-VLY scFvs showed higher neutralizing potency and extended circulating half-life than parental monomeric scFv. Conclusions: The protein obtained by the genetic fusion of two anti-VLY scFvs into a dimeric molecule exhibited improved properties in comparison with monomeric scFv. This new recombinant antibody might implement new possibilities for the prophylaxis and treatment of the diseases caused by the bacteria G. vaginalis.


Subject(s)
Animals , Mice , Bacterial Proteins/immunology , Bacterial Toxins/immunology , Antibodies, Neutralizing/metabolism , Single-Chain Antibodies/metabolism , Bacterial Proteins/toxicity , Bacterial Toxins/toxicity , Enzyme-Linked Immunosorbent Assay , Gardnerella vaginalis , Vaginosis, Bacterial , Dimerization , Virulence Factors , Gene Fusion , Antibodies, Neutralizing/immunology , Single-Chain Antibodies/immunology , Half-Life
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