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2.
Clin Ther ; 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38704294

RESUMO

PURPOSE: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy. METHODS: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography. FINDINGS: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study. IMPLICATIONS: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302).

3.
Artif Cells Nanomed Biotechnol ; 52(1): 278-290, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38733373

RESUMO

Type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD), obesity (OB) and hypertension (HT) are categorized as metabolic disorders (MDs), which develop independently without distinct borders. Herein, we examined the gut microbiota (GM) and Saururus chinensis (SC) to confirm their therapeutic effects via integrated pharmacology. The overlapping targets from the four diseases were determined to be key protein coding genes. The protein-protein interaction (PPI) networks, and the SC, GM, signalling pathway, target and metabolite (SGSTM) networks were analysed via RPackage. Additionally, molecular docking tests (MDTs) and density functional theory (DFT) analysis were conducted to determine the affinity and stability of the conformer(s). TNF was the main target in the PPI analysis, and equol derived from Lactobacillus paracasei JS1 was the most effective agent for the formation of the TNF complex. The SC agonism (PPAR signalling pathway), and antagonism (neurotrophin signalling pathway) by SC were identified as agonistic bioactives (aromadendrane, stigmasta-5,22-dien-3-ol, 3,6,6-trimethyl-3,4,5,7,8,9-hexahydro-1H-2-benzoxepine, 4α-5α-epoxycholestane and kinic acid), and antagonistic bioactives (STK734327 and piclamilast), respectively, via MDT. Finally, STK734327-MAPK1 was the most favourable conformer according to DFT. Overall, the seven bioactives from SC and equol that can be produced by Lactobacillus paracasei JS1 can exert synergistic effects on these four diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hipertensão , Hepatopatia Gordurosa não Alcoólica , Obesidade , Saururaceae , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/microbiologia , Obesidade/metabolismo , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipertensão/microbiologia , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Animais , Saururaceae/química , Saururaceae/metabolismo , Simulação de Acoplamento Molecular , Humanos , Mapas de Interação de Proteínas
4.
Coron Artery Dis ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38595079

RESUMO

BACKGROUND: Cilostazol has a vasodilatory function that may be beneficial for patients with vasospastic angina (VSA). We conducted a randomized, open-label, controlled trial to compare the efficacy and safety of long-acting cilostazol and isosorbide mononitrate (ISMN) for VSA. METHODS: The study included patients with confirmed VSA between September 2019 and May 2021. Participants were randomly assigned to receive long-acting cilostazol (test group, 200 mg once daily) or conventional ISMN therapy (control group, 20 mg twice daily) for 4 weeks. The clinical efficacy and safety were evaluated using weekly questionnaires. RESULTS: Forty patients were enrolled in the study (long-acting cilostazol, n = 20; ISMN, n = 20). Baseline characteristics were balanced between the two groups. Long acting cilostazol showed better angina symptom control within the first week compared to ISMN [reduction of pain intensity score, 6.0 (4.0-8.0) vs. 4.0 (1.0-5.0), P = 0.005; frequency of angina symptom, 0 (0-2.0) vs. 2.0 (0-3.0), P = 0.027, respectively]. The rate of neurological adverse reactions was lower in the cilostazol group than in the ISMN group (headache or dizziness, 40 vs. 85%, P = 0.009; headache, 30 vs. 70%, P = 0.027). CONCLUSION: Long-acting cilostazol provided comparable control of angina and fewer adverse neurologic reactions within 4 weeks compared to ISMN. Long-acting cilostazol provides more intensive control of angina within 1 week, suggesting that it may be an initial choice for the treatment of VSA.

6.
Med Eng Phys ; 124: 104098, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38418027

RESUMO

The surface topography of implant tools has indicated an interfacial contact in degradation still being discovered; however, the glossy texture of a tiny magnesium wire is important for absorbable medical devices. This paper investigated the alterations of surface quality by a magnetic abrasive polishing method using a rotational magnetic field-assisted system with input parameters of revolution, abrasive media, magnetic pole, flux density, vibration, and amplitude that could noticeably enhance asperities along a sample. Furthermore, the blood flow simulation is used to analyze flow within blood vessels while maintaining the surface roughness conditions of the guide wire. The results are compared and discussed. Magnetic field simulation is employed to investigate the magnetic field strength in the polishing zone. Scanning Electron Microscopy (SEM) provides visual aids for recognizing the differences between pre-and post-workpieces of magnesium wire. The experimental results reveal that a wire diameter of 0.50 mm predominantly achieves surface morphology from the initial roughness of 0.22 µm to 0.05 µm. The results corroborate that the distribution of blood in the circulatory system was relatively stable. Hence, this study establishes a crucial benchmark for the precision polishing of ultra-thin magnesium wires, which is vital for their use as high-precision biodegradable medical devices.


Assuntos
Materiais Biocompatíveis , Magnésio , Propriedades de Superfície , Microscopia Eletrônica de Varredura , Catéteres
7.
Korean Circ J ; 53(4): 254-267, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37161684

RESUMO

BACKGROUND AND OBJECTIVES: Although the shortage of donor is a common problem worldwide, a significant portion of unutilized hearts are classified as marginal donor (MD) hearts. However, research on the correlation between the MD and the prognosis of heart transplantation (HTx) is lacking. This study was conducted to investigate the clinical impact of MD in HTx. METHODS: Consecutive 73 HTxs during 2014 and 2021 in a tertiary hospital were analyzed. MD was defined as follows; a donor age >55 years, left ventricular ejection fraction <50%, cold ischemic time >240 minutes, or significant cardiac structural problems. Preoperative characteristics and postoperative hemodynamic data, primary graft dysfunction (PGD), and the survival rate were analyzed. Risk stratification by Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score was performed to examine the outcomes according to the recipient state. Each group was sub-divided into 2 risk groups according to the IMPACT score (low <10 vs. high ≥10). RESULTS: A total of 32 (43.8%) patients received an organ from MDs. Extracorporeal membrane oxygenation was more frequent in the non-MD group (34.4% vs. 70.7, p=0.007) There was no significant difference in PGD, 30-day mortality and long-term survival between groups. In the subgroup analysis, early outcomes did not differ between low- and high-risk groups. However, the long-term survival was better in the low-risk group (p=0.01). CONCLUSIONS: The outcomes of MD group were not significantly different from non-MD group. Particularly, in low-risk recipient, the MD group showed excellent early and long-term outcomes. These results suggest the usability of selected MD hearts without increasing adverse events.

8.
Int J Heart Fail ; 5(2): 91-99, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37180560

RESUMO

Background and Objectives: Recently, approximately 40% of all heart transplantation (HTx) in South Korea are performed using the direct extracorporeal membrane oxygenation (ECMO) bridging method. We conducted a study to examine the clinical outcome of direct ECMO-bridged HTx and to investigate the impact of multi-organ failure (MOF). Methods: From June 2014 to September 2022, a total of 96 adult patients who underwent isolated HTx at a single tertiary hospital were included in the study. The patients were sub-grouped into ECMO (n=48) and non-ECMO group (n=48), and the ECMO group was subdivided into awake (n=22) and non-awake (n=26) groups based on mechanical ventilator (MV) dependency. Baseline characteristics, 30-day, and 1-year mortality were analyzed retrospectively. Results: The 1-year survival rate was significantly lower in the ECMO group (72.9% vs. 95.8%, p=0.002). There was a significant difference in the 30-day survival rate between the awake and non-awake ECMO groups (81.8% vs. 65.4%, p=0.032). In the univariate analysis of logistic regression for 1-year mortality, the odds ratio was 8.5 for ECMO bridged HTx compared to the non-ECMO group, 12.3 in patients who required MV (p=0.003), and 23 with additional hemodialysis (p<0.001). Conclusions: Patients who required MV in ECMO bridged HTx showed higher preoperative MOF rates and early mortality than those extubated. When considering ECMO bridged HTx, the severity of MOF should be thoroughly investigated, and careful patient selection is necessary.

9.
Drug Des Devel Ther ; 17: 1047-1062, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051292

RESUMO

Purpose: This study aimed to assess the effectiveness and safety of a fixed-dose combination of rosuvastatin and valsartan (Rovatitan®) in Korean patients with concomitant hypertension and hyperlipidemia. Patients and Methods: A total of 1008 eligible patients with concomitant hypertension and hyperlipidemia were enrolled and treated for 12 weeks. Both upward and downward drug dose titrations were allowed based on the investigator's discretion. This study evaluated the effectiveness of the study drug, defined by the percentage of patients achieving the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) treatment targets. Additionally, regression analyses were conducted to evaluate the factors associated with the effectiveness and safety of the study drug. Of the 1008 patients enrolled in the study, 911 were analyzed for clinical effectiveness. Results: At 12 weeks, 84.6% and 75.9% of patients treated with the study drug achieved their BP and LDL-C targets, respectively, and 64.8% of patients achieved both targets simultaneously. Furthermore, the percentage of patients who achieved their BP and LDL-C treatment targets demonstrated a trend across the respective risk groups; the higher the risk group, the lower the success of attaining the respective target. This trend was also observed regardless of the prior antihypertensive and/or lipid-lowering treatments. According to regression analysis, poor metabolic profiles, including a higher body mass index (BMI) and higher BP and LDL-C levels at baseline, were significantly associated with treatment failure for BP. Among the 1005 patients included in the safety analysis, 17 patients (1.7%) experienced serious adverse events; however, none were considered related to the study drug. Conclusion: The study drug used for the treatment of concomitant hypertension and hyperlipidemia in a real-world setting was effective and was well tolerated. Therefore, the study drug is suggested as a good alternative to increase patient convenience and compliance, particularly in those taking multiple medications.


Assuntos
Hiperlipidemias , Hipertensão , Humanos , Rosuvastatina Cálcica/efeitos adversos , Valsartana/uso terapêutico , LDL-Colesterol , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/induzido quimicamente , Resultado do Tratamento
10.
BMC Cardiovasc Disord ; 23(1): 182, 2023 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016321

RESUMO

BACKGROUND: Evidence and guidelines for Non-vitamin K antagonist oral anticoagulants (NOACs) use when prescribing concurrent rifampin for tuberculosis treatment in patients with non-valvular atrial fibrillation (NVAF) are limited. METHODS: Using the Korean National Health Insurance Service database from January 2009 to December 2018, we performed a population-based retrospective cohort study to assess the net adverse clinical events (NACE), a composite of ischemic stroke or systemic embolism and major bleeding, of NOACs compared with warfarin among NVAF patients taking concurrent rifampin administration for tuberculosis treatment. After a propensity matching score (PSM) analysis, Cox proportional hazards regression was performed in matched cohorts to investigate the clinical outcomes. RESULTS: Of the 735 consecutive patients selected, 465 (63.3%) received warfarin and 270 (36.7%) received NOACs. Among 254 pairs of patients after PSM, the crude incidence rate of NACE was 25.6 in NOAC group and 32.8 per 100 person-years in warfarin group. There was no significant difference between NOAC and warfarin use in NACE (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.48-1.14; P = 0.172). Major bleeding was the main driver of NACE, and NOAC use was associated with a statistically significantly lower risk of major bleeding than that with warfarin use (HR, 0.63; 95% CI, 0.40-1.00; P = 0.0499). CONCLUSIONS: In our population-based study, there was no statically significant difference in the occurrence of NACE between NOAC and warfarin use. NOAC use may be associated with a lower risk of major bleeding than that with warfarin use.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tuberculose , Humanos , Anticoagulantes , Varfarina , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Rifampina/efeitos adversos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Tuberculose/induzido quimicamente , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Rivaroxabana/efeitos adversos
11.
Medicine (Baltimore) ; 101(36): e30477, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086714

RESUMO

Myocardial computed tomography perfusion (CTP) imaging is a noninvasive method for detecting myocardial ischemia. This study aimed to compare the diagnostic performance of dynamic and static adenosine-stress CTPs for detecting hemodynamically significant coronary stenosis. We prospectively enrolled 42 patients (mean age, 59.7 ± 8.8 years; 31 males) with ≥40% coronary artery stenosis. All patients underwent dynamic CTP for adenosine stress. The static CTP was simulated by choosing the seventh dynamic dataset after the initiation of the contrast injection. Diagnostic performance was compared with invasive fractional flow reserve (FFR) <0.8 as the reference. Of the 125 coronary vessels in 42 patients, 20 (16.0%) in 16 (38.1%) patients were categorized as hemodynamically significant. Dynamic and static CTP yielded similar diagnostic accuracy (90.4% vs 88.8% using visual analysis, P = .558; 77.6% vs 80.8% using quantitative analysis, P = .534; 78.4% vs 82.4% using combined visual and quantitative analyses, P = .426). The diagnostic accuracy of combined coronary computed tomography angiography (CCTA) and dynamic CTP (89.6% using visual analysis, P = .011; 88.8% using quantitative analysis, P = .018; 89.6% using combined visual and quantitative analyses, P = .011) and that of combined CCTA and static CTP (88.8% using visual analysis, P = .018; 90.4% using quantitative analysis, P = .006; 91.2% using combined visual and quantitative analyses, P = .003) were significantly higher than that of CCTA alone (77.6%). Dynamic CTP and static CTP showed similar diagnostic performance in the detection of hemodynamically significant stenosis.


Assuntos
Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Imagem de Perfusão do Miocárdio , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Adenosina , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Perfusão , Estudos Prospectivos , Tomografia Computadorizada por Raios X/métodos
12.
BMC Cardiovasc Disord ; 22(1): 207, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35538419

RESUMO

BACKGROUND: Compared to simple percutaneous coronary intervention (PCI), complex PCI is associated with higher bleeding and thrombotic risk. No previous study has evaluated the use of protamine after PCI with contemporary technologies. This study aimed to evaluate the safety and efficacy of manual compression with and without protamine after transfemoral complex PCI. METHODS: We retrospectively analyzed 160 patients (protamine group, n = 92; non-protamine group, n = 68) who underwent complex PCI via the femoral artery. The primary outcome was a composite of in-hospital death, myocardial infarction, stent thrombosis, stroke/systemic embolism, bleeding requiring blood transfusion, and vascular access complications. RESULTS: The primary outcome was significantly lower in the protamine group than in the non-protamine group (4.3% vs. 17.6%; p = 0.006). This was driven mainly by the lower incidences of hematoma in the protamine group (3.3% vs. 13.2%, p = 0.020). Furthermore, the protamine group had a significantly shorter hospital stay than the non-protamine group (4.8 ± 3.7 days vs. 8.4 ± 8.3 days, p = 0.001). While > 90% of the patients had acute coronary syndrome, there were no incidences of myocardial infarction or stent thrombosis in either group. CONCLUSIONS: Among patients who underwent complex PCI via transfemoral access, immediate protamine administration was associated with a significantly lower rate of vascular access complications, especially hematoma, and shorter hospital stay than no protamine administration.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombose , Anticoagulantes/efeitos adversos , Hematoma/complicações , Hemorragia/etiologia , Heparina/efeitos adversos , Mortalidade Hospitalar , Humanos , Infarto do Miocárdio/complicações , Intervenção Coronária Percutânea/efeitos adversos , Protaminas/efeitos adversos , Estudos Retrospectivos , Trombose/complicações , Resultado do Tratamento
13.
Clin Ther ; 44(4): 508-528, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35410753

RESUMO

PURPOSE: Renexin® is a combination pill of cilostazol and Ginkgo biloba leaf extract that is used for the improvement of ischemic symptoms associated with peripheral arterial disease (PAD). SID142 is a controlled-release tablet of cilostazol (200 mg) and G biloba leaf extract (160 mg) that was developed to address the limitation of BID administration with Renexin. This study aimed to verify that SID142 was not inferior to Renexin in the treatment of patients with PAD. METHODS: This was a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase III clinical trial. Study subjects were randomized to receive SID142 once daily or Renexin twice a day for 12 weeks. The primary end point was a change in the patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. If the lower limit of the two-sided 95% CI was greater than -10, the study drug was declared noninferior to the reference drug. Secondary efficacy end points included cold sensation, ankle-brachial index, ankle systolic pressure, maximum walking distance, pain-free walking distance, and investigator's global assessment. Study group results were compared 4, 8, and 12 weeks after treatment. Adverse events were assessed as a safety end point. FINDINGS: In total, 344 subjects from 19 medical centers were screened, and a total of 170 subjects were randomly assigned to either the SID142 (n = 86) or the Renexin (n = 84) group. Analysis of the change in lower extremity pain at 12 weeks compared with baseline revealed that SID142 was not inferior to Renexin (21.44 [19.23] vs 22.30 [17.75]; 95% CI, -7.70 to 5.97; P = 0.5942). No significant differences were found between groups in any secondary efficacy end point. However, the incidence of adverse reactions was significantly lower in the SID142 group (22.35% vs 39.29%; P = 0.0171). IMPLICATIONS: SID142 once daily was not inferior to Renexin twice a day for efficacy in patients with PAD. SID142 had a favorable safety profile. CLINICALTRIALS: gov identifier: NCT03318276.


Assuntos
Doença Arterial Periférica , Cilostazol , Método Duplo-Cego , Humanos , Dor , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Extratos Vegetais/efeitos adversos , Resultado do Tratamento
14.
Materials (Basel) ; 15(3)2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35161171

RESUMO

Ceramics are advanced engineering materials in which have been broadly used in numerous industries due to their superior mechanical and physical properties. For application, the industries require that the ceramic products have high-quality surface finishes, high dimensional accuracy, and clean surfaces to prevent and minimize thermal contact, adhesion, friction, and wear. Ceramics have been classified as difficult-to-machine materials owing to their high hardness, and brittleness. Thus, it is extremely difficult to process them with conventional finishing processes. In this review, trends in the development of non-conventional finishing processes for the surface finishing of difficult-to-machine ceramics are discussed and compared to better comprehend the key finishing capabilities and limitations of each process on improvements in terms of surface roughness. In addition, the future direction of non-conventional finishing processes is introduced. This review will be helpful to many researchers and academicians for carrying out additional research related to the surface finishing techniques of ceramics for applications in various fields.

15.
Nutrients ; 14(2)2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35057457

RESUMO

Osteoporosis is a major health concern in aging populations, where 54% of the U.S. population aged 50 and older have low bone mineral density (BMD). Increases in inflammation and oxidative stress play a major role in the development of osteoporosis. Men are at a greater risk of mortality due to osteoporosis-related fractures. Our earlier findings in rodent male and female models of osteoporosis, as well as postmenopausal women strongly suggest the efficacy of prunes (dried plum) in reducing inflammation and preventing/reversing bone loss. The objective of this study was to examine the effects of two doses of prunes, daily, on biomarkers of inflammation and bone metabolism in men with some degree of bone loss (BMD; t-score between -0.1 and -2.5 SD), for three months. Thirty-five men between the ages of 55 and 80 years were randomized into one of three groups: 100 g prunes, 50 g prunes, or control. Consumption of 100 g prunes led to a significant decrease in serum osteocalcin (p < 0.001). Consumption of 50 g prunes led to significant decreases in serum osteoprotegerin (OPG) (p = 0.003) and serum osteocalcin (p = 0.040), and an increase in the OPG:RANKL ratio (p = 0.041). Regular consumption of either 100 g or 50 g prunes for three months may positively affect bone turnover.


Assuntos
Densidade Óssea/fisiologia , Osso e Ossos/metabolismo , Osteoporose/sangue , Fitoterapia/métodos , Prunus domestica , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Composição Corporal , Remodelação Óssea , Exercício Físico , Humanos , Inflamação/sangue , Inflamação/prevenção & controle , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Osteoprotegerina/sangue , Ligante RANK/sangue
16.
Mol Cell Endocrinol ; 535: 111391, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34245847

RESUMO

Muscle mass is important for health. Decreased testicular androgen production (hypogonadism) contributes to the loss of muscle mass, with loss of limb muscle being particularly debilitating. Androgen replacement is the only pharmacological treatment, which may not be feasible for everyone. Prior work showed that markers of reactive oxygen species and markers of mitochondrial degradation pathways were higher in the limb muscle following castration. Therefore, we tested whether an antioxidant preserved limb muscle mass in male mice subjected to a castration surgery. Subsets of castrated mice were treated with resveratrol (a general antioxidant) or MitoQ (a mitochondria targeted antioxidant). Relative to the non-castrated control mice, lean mass, limb muscle mass, and grip strength were partially preserved only in castrated mice treated with MitoQ. Independent of treatment, markers of mitochondrial degradation pathways remained elevated in all castrated mice. Therefore, a mitochondrial targeted antioxidant may partially preserve limb muscle mass in response to hypogonadism.


Assuntos
Antioxidantes/administração & dosagem , Hipogonadismo/tratamento farmacológico , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/fisiologia , Compostos Organofosforados/administração & dosagem , Resveratrol/administração & dosagem , Ubiquinona/análogos & derivados , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Força da Mão , Hipogonadismo/etiologia , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Orquiectomia/efeitos adversos , Compostos Organofosforados/farmacologia , Resveratrol/farmacologia , Ubiquinona/administração & dosagem , Ubiquinona/farmacologia
18.
Commun Biol ; 4(1): 5, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398110

RESUMO

Previous work has revealed that progerin-lamin A binding inhibitor (JH4) can ameliorate pathological features of Hutchinson-Gilford progeria syndrome (HGPS) such as nuclear deformation, growth suppression in patient's cells, and very short life span in an in vivo mouse model. Despite its favorable effects, JH4 is rapidly eliminated in in vivo pharmacokinetic (PK) analysis. Thus, we improved its property through chemical modification and obtained an optimized drug candidate, Progerinin (SLC-D011). This chemical can extend the life span of LmnaG609G/G609G mouse for about 10 weeks and increase its body weight. Progerinin can also extend the life span of LmnaG609G/+ mouse for about 14 weeks via oral administration, whereas treatment with lonafarnib (farnesyl-transferase inhibitor) can only extend the life span of LmnaG609G/+ mouse for about two weeks. In addition, progerinin can induce histological and physiological improvement in LmnaG609G/+ mouse. These results indicate that progerinin is a strong drug candidate for HGPS.


Assuntos
Progéria/tratamento farmacológico , Adolescente , Animais , Criança , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Células HEK293 , Humanos , Lamina Tipo A/antagonistas & inibidores , Masculino , Camundongos , Cultura Primária de Células
19.
Thromb Haemost ; 121(10): 1376-1386, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33401330

RESUMO

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Plaquetas/efeitos dos fármacos , Redução da Medicação , Hemorragia/prevenção & controle , Inibidores da Agregação Plaquetária/administração & dosagem , Cloridrato de Prasugrel/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/etnologia , Idoso , Povo Asiático , Plaquetas/metabolismo , Monitoramento de Medicamentos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Testes de Função Plaquetária , Cloridrato de Prasugrel/efeitos adversos , Prevalência , Estudos Prospectivos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , República da Coreia/epidemiologia , Fatores de Tempo , Resultado do Tratamento
20.
Lab Med ; 52(1): 74-79, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-32700736

RESUMO

OBJECTIVE: Transplantations may require massive transfusion of blood products. Therefore, blood banks need to predict, prepare, and supply the required amount of blood products. METHODS: We measured the volume of transfused blood components as red blood cells, fresh frozen plasma, platelets, and cryoprecipitate in 54 and 89 patients who received heart and lung transplantation, respectively, in our hospital between January 2012 and December 2019. RESULTS: Platelets were the most frequently transfused blood component. Transfusion volumes during heart and lung transplantation surgeries differed: red blood cells, 7.83 units vs 14.84 units; fresh frozen plasma, 2.67 units vs 12.29 units; platelets, 13.13 units vs 23.63 units; and cryoprecipitate, 1.74 units vs 2.57 units; respectively. The average transfusion volume of transplants was different each year. CONCLUSION: Periodic evaluation of transfusion requirements will facilitate the efficient management of blood products at the time of transplantation and help blood banks predict changes in blood requirements.


Assuntos
Transfusão de Sangue/estatística & dados numéricos , Transplante de Coração/estatística & dados numéricos , Transplante de Pulmão/estatística & dados numéricos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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