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1.
Arch Orthop Trauma Surg ; 144(3): 1055-1063, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38114740

RESUMO

INTRODUCTION: Until now, a treatment protocol for Achilles tendon re-rupture (ATRR) occurring in the postoperative period 5-12 weeks following primary Achilles tendon repair has not been established. We refer to this time frame as the subacute postoperative phase, and the objective of this study was to assess the efficacy of conservative treatment for subacute ATRR in this phase. MATERIALS AND METHODS: We conducted a retrospective review of 390 cases (385 patients) who had undergone primary Achilles tendon repair using the 4-strand Krachow method between January 2010 and August 2021. All patients were subjected to more than 12 months of follow-up and were categorized into two groups based on the presence of subacute ATRR: Group 1 comprised 370 cases without ATRR, while Group 2 comprised 20 cases with ATRR. Following confirmation of ATRR, we immediately applied a below-knee cast in an ankle plantar flexed position (25°-30°), followed by bracing according to the same rehabilitation plan used for the primary repair. After administering conservative treatment to the patients with ATRR, we compared several outcome parameters between the two groups, including isokinetic plantar flexion power measured using a dynamometer, time required for a single heel raise (t-SHR), time needed for ten repetitive SHRs (t-SHR10), Achilles Tendon Total Rupture Score (ATRS), and Foot and Ankle Ability Measure (FAAM) scores. The baseline timepoints for Groups 1 and 2 were the dates of the primary repair and the re-injury event. RESULTS: After primary Achilles tendon repair, subacute ATRR occurred in 5.1% of patients. There were no significant differences between the groups in terms of t-SHR and t-SHR10 (P = 0.281, 0.486). Similarly, the isokinetic dynamometer measurements revealed no significant differences in peak torque for plantar flexion at angular velocities of 30°/s and 120°/s, both in absolute values and as a percentage of the contralateral side, between the groups (P > 0.05 for each). However, ATRSs were significantly lower in Group 2 compared to Group 1 before 6 months (P < 0.05), as were FAAM-Activities of Daily Living scores at 6 months (P < 0.05). After 12 months, there were no significant differences in these scores between the two groups (both P > 0.05). CONCLUSION: Conservative treatment for subacute ATRR following primary Achilles tendon repair yields clinical outcomes comparable to those without ATRR. Therefore, we recommend that surgeons consider relying on the patient's natural healing capabilities rather than opting for aggressive surgical interventions, as expediting such operations may be unnecessary for subacute injuries.


Assuntos
Tendão do Calcâneo , Traumatismos do Tornozelo , Traumatismos dos Tendões , Humanos , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Atividades Cotidianas , Tratamento Conservador , Resultado do Tratamento , Articulação do Tornozelo , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/reabilitação , Ruptura/cirurgia
2.
Int Orthop ; 45(11): 2933-2943, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34272980

RESUMO

PURPOSE: The effectiveness of minimally invasive surgery (MIS)-distal chevron metatarsal osteotomy (DCMO) for the correction of moderate-to-severe hallux valgus deformity is unclear. This study aimed to compare the radiographic and clinical outcomes of our novel MIS-proximal chevron metatarsal osteotomy (PCMO) with those of MIS-DCMO performed during the same timeframe. METHODS: We prospectively compared the outcomes of patients who underwent MIS-PCMO (n = 20 patients; 22 cases) with those of patients who underwent MIS-DCMO (n = 23 patients; 26 cases) for moderate-to-severe hallux valgus deformity (hallux valgus angle [HVA] ≥ 30° and first-to-second intermetatarsal angle [IMA] ≥ 13°) between June 2017 and January 2019. The minimum follow-up duration for study inclusion was two years. The HVA, IMA, distal metatarsal articular angle (DMAA), relative length of the second metatarsal, medial sesamoid position, and Meary's angle to evaluate the degree of deformity correction and its maintenance were measured pre-operatively and at the final follow-up. RESULTS: Compared with MIS-DCMO, MIS-PCMO resulted in significantly greater correction of the HVA (P < 0.001) and IMA (P = 0.01), along with Meary's angle improvement (P < 0.001); however, the DMAA worsened (P = 0 .01). Furthermore, a significantly greater change was found in the relative second metatarsal length in the MIS-DCMO group (P = 0.01). No significant between-group differences were noted in the correction of the medial sesamoid position (P = 0.445). CONCLUSION: Compared with MIS-DCMO, MIS-PCMO can be a better option for correcting moderate-to-severe hallux valgus deformities. However, this technique should be applied carefully when the pre-operative DMAA is already large because the DMAA can become worse post-operatively.


Assuntos
Hallux Valgus , Ossos do Metatarso , Articulação Metatarsofalângica , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Osteotomia , Estudos Prospectivos , Resultado do Tratamento
3.
Cancer Med ; 9(20): 7781-7791, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32857923

RESUMO

BACKGROUND: Regular clinic follow-up is a prerequisite for optimal antiviral therapy and surveillance of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). However, adherence to regular follow-up stays low in practice. This study investigated whether regular follow-up is associated with decreased liver cancer mortality in CHB patients. METHODS: A nationwide population-based historical cohort study was conducted using customized data from the National Health Insurance Service of Korea. The number of hospital visits every 3-month interval was counted for 2 years from the date of CHB diagnosis. Patients were classified into three follow-up groups: regular (four to eight visits), irregular (one to three visits), and no follow-up. The risk of liver cancer mortality was compared among the groups using Cox proportional hazard regression analysis. RESULTS: Of the 414 074 CHB patients, 22.9% had regular follow-up. In multivariable analysis, regular follow-up was independently associated with decreased risk of liver cancer mortality compared to no follow-up (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.50-0.63, P < .001). Regular follow-up was also associated with the lowest risk of all-cause mortality (HR, 0.60; 95% CI, 0.57-0.63, P < .001). Patients with regular follow-up received more curative treatment (23.1% vs 15.1%, P < .001). Patients were less motivated when they were female, >60 years, of low socioeconomic status, disabled, lived in a rural area, had a higher comorbidity rate, or did not have cirrhosis. CONCLUSIONS: Regular follow-up at least every 3-6 months is significantly associated with reduced liver cancer mortality in patients with CHB.


Assuntos
Carcinoma Hepatocelular/mortalidade , Hepatite B Crônica/epidemiologia , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/terapia , Causas de Morte , Estudos de Coortes , Feminino , Seguimentos , Hepatite B Crônica/complicações , Hepatite B Crônica/terapia , Humanos , Incidência , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Vigilância em Saúde Pública , República da Coreia/epidemiologia , Fatores Socioeconômicos , Adulto Jovem
4.
J Liver Cancer ; 20(2): 148-153, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37384326

RESUMO

Optimal treatments for patients with advanced hepatocellular carcinoma (HCC) are still limited and their prognosis remains dismal. Yet, there have been rare cases that have shed light on longer survival in these patients assisted by various treatments. This paper aims to present an extraordinary case of far advanced HCC that had been properly managed in spite of continuous recurrence. A patient visited the hospital with a ruptured large HCC with main portal vein tumor thrombosis but survived longer than 14 years owing to active and prompt interventions.

5.
Yonsei Med J ; 60(12): 1203-1208, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769252

RESUMO

Little is known about the benefits of statin use on liver cancer mortality among patients with chronic hepatitis B (CHB) considering hypercholesterolemia and obesity. A nationwide retrospective cohort study was conducted using data from a Health Examination Cohort of the National Health Insurance Service of Korea. Data on CHB patients with no other concurrent liver disease were acquired, and statin use was defined as a cumulative daily dose ≥28. A 3-year landmark analysis was performed to avoid immortal time bias. Patients who started statin therapy within the landmark date were considered statin users. A Cox regression analysis was applied to assess associations between statin use and liver cancer mortality considering hypercholesterolemia and obesity. Among 13063 patients, 193 (1.5%) died of liver cancer during the mean follow-up period of 10.6 years. After adjusting for demographic and metabolic factors, statin use [hazard ratio (HR), 0.17; 95% confidence interval (CI), 0.04-0.70] and hypercholesterolemia (HR, 0.46; 95% CI, 0.24-0.88 for total cholesterol ≥240 mg/dL) were associated with a decreased risk of liver cancer mortality, whereas body mass index (BMI) ≥30 kg/m² was associated with an increased risk of liver cancer mortality (HR, 2.46; 95% CI, 1.20-5.06). This study showed that statin use was associated with decreased liver cancer mortality when adjusting for cholesterol levels and BMI. This study found that hypercholesterolemia was independently associated with decreased liver cancer mortality regardless of statin use.


Assuntos
Hepatite B Crônica/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Obesidade/complicações , Idoso , Índice de Massa Corporal , Colesterol/metabolismo , Feminino , Humanos , Neoplasias Hepáticas/complicações , Masculino , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos
7.
Chin Med J (Engl) ; 131(14): 1645-1651, 2018 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-29998882

RESUMO

BACKGROUND: Until now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment. METHODS: Between June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis. RESULTS: HBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 log10U/ml vs. 7.5 log10U/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 log10U/ml vs. 4.0 log10U/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively. CONCLUSIONS: The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B/tratamento farmacológico , Interferon-alfa/uso terapêutico , DNA Viral , Antígenos E da Hepatite B , Hepatite B Crônica , Humanos , Polietilenoglicóis , Proteínas Recombinantes , República da Coreia , Resultado do Tratamento
8.
Liver Int ; 38(10): 1751-1759, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29377574

RESUMO

BACKGROUND: The serum alanine aminotransferase (ALT) level has been used to identify at-risk patients with chronic hepatitis B (CHB) who need antiviral therapy. However, the level associated with increased liver-related mortality requiring active treatment is still unclear. METHODS: We used a Health Examination Cohort of the National Health Insurance Service of Korea that included approximately 0.5 million individuals aged 40-79 years. In total, 12 486 patients with CHB and no other concurrent liver disease were enrolled, and patients' liver-related mortality, including that owing to liver cancer, was investigated over 9 years. RESULTS: The serum ALT level was correlated positively with liver-related mortality. The rates in men were 0.14, 0.17, 0.24, 0.57, 0.63 and 0.85 per 100 person-years (%) for serum ALT levels of <20, 20-29, 30-39, 40-49, 50-79 and ≥80 U/L, respectively, and the corresponding liver-related mortality rates in women were 0.03%, 0.09%, 0.12%, 0.63%, 0.65% and 0.32%. In patients with ALT levels of 40-79 U/L, the liver-related mortality rates were 0.60% in men and 0.64% in women, which were similar to the overall mortality rate of age- and sex-matched subjects without CHB (0.69%). The best cut-off values for liver-related mortality prediction were >34 U/L in men and >30 U/L in women. CONCLUSIONS: The liver-related mortality rate increased significantly, even in CHB patients with relatively low serum ALT levels. Careful monitoring or earlier antiviral therapy should be considered for patients aged >40 years with serum ALT levels above the upper limit of normal.


Assuntos
Alanina Transaminase/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/mortalidade , Adulto , Distribuição por Idade , Idoso , Estudos de Coortes , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Distribuição por Sexo
9.
Nanotechnology ; 29(3): 035606, 2018 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-29176070

RESUMO

We have developed a facile single-step synthesis of silver nanocomposite using a conventional spray dryer. We investigated the synthetic conditions by controlling the concentrations of the chemical reactants. Further, we confirmed the effect of the molecular weight of polyvinylpyrrolidones, and revealed that the molecular weight significantly affected the properties of the resultant silver nanocomposites. The long-term stability of the silver nanocomposites was tested, and little change was observed, even after storage for three months. Most of all, the simple commercial implementation, in combination with large-scale synthesis, possesses a variety of advantages, compared to conventional complicated and costly dry-process synthesis methods. Thus, our method presents opportunities for further investigation, for both lab-scale studies and large-scale industrial applications.

10.
Clin Mol Hepatol ; 23(4): 331-339, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28946736

RESUMO

BACKGROUND/AIMS: Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. METHODS: Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary objectives included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation. RESULTS: In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P<0.0001), and week 240 (95.0% vs. 47.6%, P<0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P<0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P<0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. CONCLUSIONS: Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Adolescente , Adulto , Alanina Transaminase/sangue , DNA Viral/sangue , Método Duplo-Cego , Esquema de Medicação , Feminino , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Resposta Viral Sustentada , Resultado do Tratamento , Adulto Jovem
12.
Small ; 13(43)2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28902976

RESUMO

A novel room-temperature aqueous synthesis for gold nanoparticle-embedded silver cubic mesh nanostructures using AgCl templates via a template-assisted coreduction method is developed. The cubic AgCl templates are coreduced in the presence of AuCl4- and Ag+ , resulting in the reduction of AuCl4- into gold nanoparticles on the outer region of AgCl templates, followed by the reduction of AgCl and Ag+ into silver cubic mesh nanostructures. Removal of the template clearly demonstrates the delicately designed silver mesh nanostructures embedded with gold nanoparticles. The synthetic mechanism, structural properties, and surface functionalization are spectroscopically investigated. The plasmonic photocatalysis of the cubic mesh nanostructures for the degradation of organic pollutants and removal of highly toxic metal ions is investigated; the photocatalytic activity of the cubic mesh nanostructures is superior to those of conventional TiO2 catalysts and they are catalytically functional even in natural water, owing to their high surface area and excellent chemical stability. The synthetic development presented in this study can be exploited for the highly elaborate, yet, facile design of nanomaterials with outstanding properties.

13.
BMC Cancer ; 17(1): 388, 2017 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-28558668

RESUMO

BACKGROUND: Mannose-binding lectin (MBL) acts in the innate immune response to Helicobacter pylori. Interleukin 8 (IL-8) is a potent cytokine produced by gastric epithelial cells in response to H. pylori. We aimed to investigate whether polymorphisms in MBL2 and IL-8 influence susceptibility to H. pylori infection, and the associations of these polymorphisms with the risk of gastroduodenal diseases in a Korean population. METHODS: We consecutively enrolled 176 H. pylori-negative control subjects, 221 subjects with H. pylori-positive non-atrophic gastritis, 52 mild atrophic gastritis (AG), 61 severe AG, 175 duodenal ulcer, and 283 gastric cancer (GC). Allele-specific PCR-RFLP was conducted for polymorphisms in MBL2 exon 1 (codon 52, 54, and 57) and IL-8 -251 T > A. IL-8 levels in gastric mucosal tissues and serum MBL levels were measured by enzyme-linked immunosorbent assay. RESULTS: MBL2 exon 1 polymorphic variants were found only in codon 54, and the allele frequencies did not differ significantly between the control and disease groups. Although serum MBL levels in codon 54 A/A mutants were markedly low, it did not influence susceptibility to H. pylori infection or the risk of gastroduodenal diseases. IL-8 levels were significantly different between T/T wild type, T/A heterozygote, and A/A mutant genotypes. IL-8 -251 A allele carriers (A/A + T/A) showed increased IL-8 levels, and were significantly associated with the risk of severe AG and GC. CONCLUSIONS: We suggest that a combination of H. pylori infection and the IL-8 -251 T > A polymorphism might increase the risk of severe AG and GC in a Korean population.


Assuntos
Infecções por Helicobacter/genética , Interleucina-8/genética , Lectina de Ligação a Manose/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , República da Coreia , Fatores de Risco , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
14.
Scand J Gastroenterol ; 52(9): 1029-1036, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28562104

RESUMO

OBJECTIVES: Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy. METHODS: The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3). RESULTS: The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93-75.01, p < .001), alcohol consumption (HR 3.84, 95% C.I. 1.99-7.39, p < .001), and older age (HR 1.06, 95% C.I. 1.01-1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314). CONCLUSIONS: LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Cirrose Hepática/fisiopatologia , Neoplasias Hepáticas/epidemiologia , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/efeitos adversos , Ascite/etiologia , Varizes Esofágicas e Gástricas/etiologia , Feminino , Humanos , Hipertensão Portal/etiologia , Incidência , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Medição de Risco
15.
Gut Liver ; 10(6): 962-968, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27282260

RESUMO

BACKGROUND/AIMS: The benefit of oral antiviral therapy in preventing hepatocellular carcinoma (HCC) in the general population is not well understood. We used a novel prediction method to estimate the risk of HCC in the Korean population based on various treatment guidelines. METHODS: The 5-year risk of HCC following antiviral therapy was calculated using an HCC risk prediction model. A virtual cohort that represented Koreans (>40 years old) with chronic hepatitis B virus (HBV) infection was established using the fifth National Health and Nutrition Examination Survey. The antiviral indications tested were the Korean National Health Insurance (NHI) and European Association for the Study of the Liver (EASL) guidelines as well as a new extended indication (serum HBV DNA >2,000 IU/mL regardless of serum aminotransferase level). RESULTS: A total of 993,872 subjects were infected with HBV in the general Korean population. Over a 5-year period, 2,725 HCC cases were predicted per 100,000 persons (0.55%/yr). When the cohort was treated based on the Korean NHI, the EASL, and the newly extended indications, HCC risks decreased to 2,531 (-7.1%), 2,089 (-23.3%), and 1,122 (-58.8%) cases per 100,000 persons, respectively (p<0.0001). CONCLUSIONS: Simulated risk prediction suggests that extending of oral antiviral indication may reduce the HCC risk in the general population.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/virologia , Hepatite B Crônica/tratamento farmacológico , Neoplasias Hepáticas/virologia , Medição de Risco/métodos , Adulto , DNA Viral/sangue , Feminino , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Valor Preditivo dos Testes , República da Coreia , Fatores de Risco , Transaminases/sangue
16.
J Pharmacol Exp Ther ; 357(1): 157-66, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26907620

RESUMO

Urate-lowering therapy is indispensable for the treatment of gout, but available drugs do not control serum urate levels tightly enough. Although the uricosurics benzbromarone and probenecid inhibit a urate reabsorption transporter known as renal urate transporter 1 (URAT1) and thus lower serum urate levels, they also inhibit other transporters responsible for secretion of urate into urine, which suggests that inhibiting URAT1 selectively would lower serum urate more effectively. We identified a novel potent and selective URAT1 inhibitor, UR-1102, and compared its efficacy with benzbromarone in vitro and in vivo. In human embryonic kidney (HEK)293 cells overexpressing URAT1, organic anion transporter 1 (OAT1), and OAT3, benzbromarone inhibited all transporters similarly, whereas UR-1102 inhibited URAT1 comparably to benzbromarone but inhibited OAT1 and OAT3 quite modestly. UR-1102 at 3-30 mg/kg or benzbromarone at 3-100 mg/kg was administered orally once a day for 3 consecutive days to tufted capuchin monkeys, whose low uricase activity causes a high plasma urate level. When compared with the same dosage of benzbromarone, UR-1102 showed a better pharmacokinetic profile, increased the fractional excretion of urinary uric acid, and reduced plasma uric acid more effectively. Moreover, the maximum efficacy of UR-1102 was twice that of benzbromarone, suggesting that selective inhibition of URAT1 is effective. Additionally UR-1102 showed lower in vitro potential for mechanisms causing the hepatotoxicity induced by benzbromarone. These results indicate that UR-1102 achieves strong uricosuric effects by selectively inhibiting URAT1 over OAT1 and OAT3 in monkeys, and could be a novel therapeutic option for patients with gout or hyperuricemia.


Assuntos
Benzobromarona/farmacologia , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Oxazinas/farmacologia , Piridinas/farmacologia , Uricosúricos/farmacologia , Animais , Cebus , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Feminino , Células HEK293 , Humanos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/biossíntese , Proteína 1 Transportadora de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos Sódio-Independentes/biossíntese , Transportadores de Ânions Orgânicos Sódio-Independentes/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Ligação Proteica , Ácido Úrico/sangue , Uricosúricos/efeitos adversos
17.
Intest Res ; 13(3): 242-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26130999

RESUMO

BACKGROUND/AIMS: Emerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-α) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-α. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans. METHODS: Genotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Heterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively). CONCLUSIONS: Our results suggest that the T507C SNP in PRKCDBP, a TNF-α-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans.

18.
Dig Dis Sci ; 59(12): 2947-57, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25052149

RESUMO

BACKGROUND: Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a putative tumor suppressor that is downregulated in many human cancers. Recently, PRKCDBP was identified to be activated by nuclear factor-κB in response to tumor necrosis factor (TNF)-α. AIMS: To explore the potential of PRKCDBP as a diagnostic or prognostic marker for inflammatory bowel disease, the possible correlation between its expression status and TNF-α signaling was evaluated in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy. METHODS: In total, 31 IFX therapy-naïve patients (13 females; median age, 41 years) with moderate-to-severe UC who had been scheduled for IFX treatment were included. Immunohistochemical analysis of TNF-α and PRKCDBP expression was performed in rectal biopsies. RESULTS: A significant correlation was observed in immunoreactivity between TNF-α and PRKCDBP. IFX therapy reduced immunohistochemical expression of PRKCDBP and TNF-α (P < 0.001 and P = 0.005, respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2%, and that of TNF-α decreased from 54.5 to 36.2%. The immunohistochemical expression pre- and post-PRKCDBP therapy correlated significantly with TNF-α levels pre- and post-therapy (Spearman's rank correlation test; P = 0.005 and P = 0.001, respectively). CONCLUSIONS: These results demonstrate that mucosal expression of PRKCDBP correlated strongly with TNF-α expression in UC patients and that IFX therapy resulted in profound reductions in both PRKCDBP and TNF-α. Thus, these findings support that PRKCDBP expression is tightly controlled by TNF-α, and the anti-inflammatory effect of IFX may in part stem from blockade of the TNF-α-PRKCDBP signaling pathway.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Colite Ulcerativa/metabolismo , Feminino , Humanos , Infliximab , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/genética , Adulto Jovem
19.
J Gastroenterol Hepatol ; 29(9): 1699-705, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24730702

RESUMO

BACKGROUND AND AIMS: Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. METHODS: A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. RESULTS: The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. CONCLUSIONS: In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB.


Assuntos
Antivirais/administração & dosagem , Arabinofuranosiluracila/análogos & derivados , Guanina/análogos & derivados , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Lamivudina/administração & dosagem , alfa-Fetoproteínas/análise , Administração Oral , Adulto , Idoso , Arabinofuranosiluracila/administração & dosagem , Biomarcadores/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/etiologia , Feminino , Guanina/administração & dosagem , Hepatite B Crônica/complicações , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Fatores de Tempo
20.
J Environ Radioact ; 132: 57-64, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24556176

RESUMO

Pot experiments were performed in a greenhouse to investigate the soil-to-soybean transfer of (99)Tc in two different upland soils labeled with (99)TcO4(-) in two contrasting ways. One was to mix the soil with a (99)TcO4(-) solution 26 d before sowing (pre-sowing deposition: PSD), and the other was to apply the solution onto the soil surface 44 d after sowing (growing-period deposition: GPD). The soil-to-plant transfer was quantified with the transfer factor (TF, ratio of the plant concentration to the average of at-planting and at-harvest soil concentrations) or the aggregated transfer factor (TFag, ratio of the plant concentration to the deposition density). For both the depositions, the transfer of (99)Tc to aerial parts decreased in the order of leaf > stem > pod > seed. TF values (dimensionless) from the PSD were 0.22 and 0.27 (no statistically significant difference) for mature dry seeds in the respective soils, whereas a 600-fold higher value occurred for dry leaves. The post-harvest concentrations of the PSD (99)Tc in the top 20 cm soils as a whole were about half the initial concentrations. Around 25% of the total applied activity remained in the GPD soils after the harvest. The post-harvest depth profiles of the GPD (99)Tc in the two soils showed similar patterns of logarithmic activity decrease with increasing soil depths. Only 1.5-4.3% of the total applied activity was removed through the harvested biomass (seeds, pods and stems), and it was estimated that a great part of the total pant uptake returned to the soil through the fallen leaves. TFag values (m(2) kg(-1)) were about 2-4 times higher for the GPD than for the PSD. This finding and generally high root uptake of Tc may indicate that the use of empirical deposition time-dependent TFag data is particularly important for predicting the plant concentrations of Tc after its growing-period deposition.


Assuntos
Contaminação Radioativa de Alimentos/análise , Glycine max/efeitos da radiação , Radioisótopos/análise , Poluentes Radioativos do Solo/análise , Tecnécio/análise , Poluição Ambiental , Concentração de Íons de Hidrogênio , Folhas de Planta/efeitos da radiação , Raízes de Plantas/efeitos da radiação , Caules de Planta/efeitos da radiação , Monitoramento de Radiação/métodos , Resíduos Radioativos , República da Coreia , Sementes/efeitos da radiação , Solo , Poluentes do Solo
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