Geometrical characteristics of eggs from 3 poultry species.

We studied the correlations between egg geometrical parameters (i.e., egg shape index, sphericity, geometric mean diameter, surface area, and volume) and eggshell qualities, or the organic matrix in eggshell. Eggs were collected from 5 poultry breeds belonging to 3 species (commercial Hy-line Brown Chicken, Shaoxing Duck, Jinding Duck, Taihu Goose, and Zhedong White Goose). The geometrical parameters showed high variation among 3 species of poultry, and even between breeds in the same species. The five geometrical parameters were grouped into 2 sets, one contained shape index and sphericity, the other comprised geometric mean diameter, surface area, and volume. The parameters in the same set can be perfectly fitted to one another. Egg weight, shell membrane weight, and calcified shell weight were significantly correlated with geometric mean diameter, surface area, and volume. In accordance with false discovery rate-adjusted P value, both shell membrane relative weight and calcified shell thickness showed no significant correlations with any of the geometrical parameters. However, the correlations between geometrical parameters and other shell variables (calcified shell weight, shell relative weight, calcified shell thickness uniformity, and eggshell breaking strength) depend on breed. Both constitutive proportions and percentage contents of 3 eggshell matrix components (acid-insoluble, water-insoluble, and both acid and water facultative-soluble matrix) had no effects on egg shape and size. The correlations between the amounts of various shell matrix, egg shape and size depend on breed or species. This study provides a methodology and the correlation between geometrical parameters and eggshell qualities, and between geometrical parameters and organic matrix components in calcified shells.

Tizoxanide mitigates inflammatory response in LPS-induced neuroinflammation in microglia via restraining p38/MAPK pathway.

OBJECTIVE: Traumatic brain injury (TBI) induced neuroinflammation is featured as excessive glial inflammatory activation and violent neurologic destruction and dysfunction. Massive microglia activation in situ and disrupt of blood-brain barrier contribute to severely collapsed nervous system. Tizoxanide (TIZ), a synthetic thiazolide derivative agent possessing a broad-spectrum anti-infective effect, currently shows a potential resistance against pathogens like bacteria, virus and parasites, while its underlying role in neuroinflammation is elusive. The study aimed to explore the effect of TIZ on neuroinflammation in vitro microglia. MATERIALS AND METHODS: Primary microglia were accepted to neuroinflammatory activation via lipopolysaccharide (LPS) administration. TIZ was conducted to pretreatment of microglia. Cell viability, inflammatory cytokines, chemotaxis, nitric oxide release, inflammation-related enzymes, and mitogen-activated protein kinase (MAPK) pathway activation in microglia were investigated respectively. RESULTS: We demonstrated that TIZ administration attenuates inflammatory cytokines and chemokines through quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) of medium supernatant. In addition, TIZ reduces pro-inflammatory mediators and nitric oxide release in microglia. Furtherly, TIZ inhibits the level of p38/MAPK pathway in LPS stimuli, indicating that TIZ negatively regulates neuroinflammation via inhibiting p38/MAPK pathway. CONCLUSIONS: TIZ is verified to be an anti-inflammation effect on neuroinflammation in microglia via downregulation of p38/MAPK pathway, which restrains inflammation by reduced inflammatory cytokines, chemokines and mediators and decreased nitric oxide release. To summarize, TIZ is considered to be a promising reagent to alleviate neuroinflammation targeting microglia in nervous system injury.

Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019.

OBJECTIVE: The Coronavirus disease 2019 (COVID-19) which outbroke in December 2019 is highly contagious with a low cure rate. In view of this, there is an urgent need to find a more appropriate therapeutic scheme against COVID-19. The study aimed to investigate whether lopinavir/ritonavir (LPV/r) in combination with other pneumonia-associated adjuvant drugs has a better therapeutic effect on COVID-19. PATIENTS AND METHODS: Totally 47 patients with COVID-19 infection who were admitted to Rui'an People's Hospital between January 22 and January 29, 2020 were collected. The patients were divided into the test group and the control group according to whether they had been treated with LPV/r or not during hospitalization. Patients in the test group were treated with LPV/r combined with adjuvant medicine, while those in the control group were just treated with adjuvant medicine. The changes of body temperature, blood routine and blood biochemistry between the two groups were observed and compared. RESULTS: Both groups achieved good therapeutic effect with the body temperature of patients decreased gradually from admission to the 10th day of treatment. But the body temperature of patients in the test group decreased faster than that of the control group. Blood routine indexes showed that compared with the control group, the abnormal proportion of white blood cells, lymphocytes and C-reactive protein of the test group could be reduced to some extent. Blood biochemical indexes exhibited that the proportion of patients with abnormal alanine aminotransferase and aspartate aminotransferase in the test group were lower than the control group. The number of days for nCoV-RNA turning negative after treatment was significantly decreased in the test group than that in the control group. CONCLUSIONS: Compared with the treatment of pneumonia-associated adjuvant drugs alone, the combination treatment with LPV/r and adjuvant drugs has a more evident therapeutic effect in lowering the body temperature and restoring normal physiological mechanisms with no evident toxic and side effects. In view of these conclusions, we suggested that the use of LPV/r combined with pneumonia-associated adjuvant drugs in the clinical treatment for patients with COVID-19 should be promoted.

[Optimized AAV package and experimental application of recombinant AAV8/hFâ § for gene therapy on hemophilia A mice].

Objective: To evaluate the effects of adeno-associated virus (AAV) carrying hFⅧ by serotype 8 (AAV8/hFⅧ) on hemophilia A (HA) mice by gene therapy strategy. Methods: pAAV-CB-EGFP, pH22 (serotype 2) and pfΔ6 (adenovirus helper) were used to package AAV into HEK-293 cells in different conditions (ratios of cells to plasmids). The efficiency of transfection and infection were evaluated using immunofluorescence microscope to seek an optimized package condition. pAAV-TTR-hFⅧ, pH 28 (serotype 8) and pfΔ6 were applied to package AAV8/hFⅧ in HEK-293 cells using the optimized package condition. The purified AAV8/hFⅧ were intravenously injected into HA mice and the effects of gene therapy were estimated. Results: The efficiency of package was evaluated according to the amount and intensity of enhanced green fluorescent protein (EGFP) under immunofluorescence microscope. Four package conditions including 10 cm-dish to transfect 10 µg plasmids, 20 cm-dish to 20 µg, 30 µg and 40 µg plasmids were employed, and the condition of 20 cm-dish to transfect 20 µg plasmids reached the highest transfection efficiency at 24 h, 48 h and 72 h after transfection. The small scale AAV-EGFP was packaged using the optimized condition and an AAV crude extract was harvested by a freeze-thaw method. HEK-293 and 16095 cells were infected by the AAV crude extract, and the preferential infection efficiency was recognized in 16095 cells under immunofluorescence microscope. Then, AAV8/hFⅧ was packaged and purified based on the optimized transfection condition, and the high purity of AAV8/hFⅧ was detected by Western blot. Fractions of AAV8/hFⅧ at the dose of 8×10(12) vg/kg were injected into HA mice through tail vein, an eye-bleeding was performed at every two weeks, and the activity of FⅧ was measured by aPTT assay. Results showed that the activity of FⅧ maintained at the therapeutic level and lasted up to 12 weeks after injection. Conclusion: The purified AAV8/hFⅧ based on the optimized package condition could play a role in HA mice gene therapy, and the long-term therapeutic effects of AAV8/hFⅧ were observed in vivo.

ILC3 cells promote the proliferation and invasion of pancreatic cancer cells through IL-22/AKT signaling.

PURPOSE: Type 3 innate lymphocytes (ILC3s) are reported to be involved in lung cancer, possibly by producing interleukin-22 (IL-22). However, whether ILC3s and their secreted IL-22 molecules contribute to the pathogenesis of pancreatic cancer (PC) remains unclear. To this end, in this study, we investigated the effects and possible mechanisms of ILC3s on PC pathogenesis. METHOD: The IL-22 and IL-2i2R levels and the ILC3s' frequency in cancer tissues from PC patients and in peripheral blood from PC patients and healthy controls were analyzed by flow cytometry, immunochemistry, or immunofluorescence. The effects of IL-22-induced AKT signaling on the proliferation, invasion, and migration of PC cells were examined by co-culturing PC cell lines with ILC3s isolated from PC tissues, with or without the addition of neutralizing IL-22 antibody, IL-22R antibody or AKT inhibitor. RESULTS: Our results showed that IL-22 and ILC3s were significantly upregulated in the PBMCs and cancer tissues of PC patients, and the IL-22R level was increased in PC cells. The increased frequency of ILC3s was positively correlated with the clinical features of PC patients. Co-culture experiments indicated that ILC3s promoted the proliferation, invasion, and migration of PC cell lines by secreting IL-22 to activate AKT signaling because IL-22/IL-22R or AKT blockage markedly counteracted such effects on PC cells. CONCLUSION: Our data demonstrated that ILC3s may promote PC pathogenesis through IL-22/IL-22R-AKT signaling, suggesting a potential intervention target for PC treatment in the future.

Association between rs12742784 polymorphism and hip fracture, bone mineral density, and EPHB2 mRNA expression levels in elderly Chinese women.

Objective: This study aimed to determine the association between rs12742784 polymorphism in the non-coding area and hip fracture, bone mineral density (BMD), and EPHB2 mRNA expression levels in elderly Chinese women.Methods: We investigated 250 Chinese women (mean age: 63.5 ± 8.3 years) including 123 hip fracture patients and 127 non-fracture controls. All participants underwent clinical examination to meet the inclusion criteria. Lumbar and hip BMD were detected by dual-energy X-ray absorptiometry. rs12742784 polymorphism was determined by restriction fragment length polymorphism and EPHB2 mRNA expression levels were measured by real-time polymerase chain reaction.Results: Distribution of rs12742784 genotypes agreed with Hardy-Weinberg equilibrium. The frequency of the CT + TT genotype was significantly associated with decreased risk of hip fracture (adjusted odds ratio = 0.57, p < 0.01) after adjusting for age and body mass index, and with increased BMD and EPHB2 mRNA expression levels. The T allele of the rs12742784 single nucleotide polymorphism (SNP) was a protective factor for hip fracture (adjusted odds ratio = 0.56, p < 0.01).Conclusion: rs12742784 polymorphism was associated with EPHB2 mRNA expression levels, BMD, and hip fracture in Chinese women. The T allele of the rs12742784 SNP was a protective factor for osteoporosis and hip fracture.

Effect of miR-497 on myocardial cell apoptosis in rats with myocardial ischemia/reperfusion through the MAPK/ERK signaling pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-497 on myocardial cell apoptosis in rats with myocardial ischemia/reperfusion (I/R) through the mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase (ERK) signaling pathway. MATERIALS AND METHODS: A rat model of myocardial I/R was established, myocardial cells were extracted, and miR-497 was inhibited by inhibitors and overexpressed using miRNA mimics. The cell apoptosis rate was detected by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The interaction between miR-497 and ERK was determined by dual-luciferase reporter gene assay. The change in the protein level was measured via Western blotting (WB). RESULTS: Up-regulation of miR-497 promoted myocardial cell apoptosis, and the 3'-untranslated region (3'-UTR) of ERK was highly conserved to combine with miR-497. The luciferase reporter gene assay showed that the transfection of miR-497 could significantly inhibit the relative luciferase activity in cells. CONCLUSIONS: MiR-497 overexpression significantly down-regulated the ERK expression at messenger RNA (mRNA) and protein levels in cells. MiR-497 plays an important role in regulating I/R injury-induced myocardial cell apoptosis by targeting the ERK-induced apoptosis pathway.

Nicotinamide protects chronic hypoxic myocardial cells through regulating mTOR pathway and inducing autophagy.

OBJECTIVE: To determine the protective effect of nicotinamide on chronic hypoxic myocardial cells and its underlying mechanism. MATERIALS AND METHODS: The H9C2 cell lines were taken as objects of study, and were divided into blank group, hypoxia group and nicotinamide treatment group. The cell viability, apoptosis level, autophagy level and mammalian target of rapamycin (mTOR) pathway activity in each group were detected via Cell Counting Kit-8 (CCK8) assay, Hoechst staining, immunofluorescence staining, Polymerase Chain Reaction (PCR) and Western blotting, respectively. RESULTS: Nicotinamide could protect the viability of normoxic and chronic hypoxic myocardial cells. Besides, it could also inhibit the expression of caspase3 messenger ribonucleic acid (mRNA) in chronic hypoxic myocardial cells, and reduce the expression of apoptosis-related proteins. Furthermore, it could induce the mRNA expression of autophagy-associated gene 5 (ATG5) and increase the expression of autophagy-related proteins. Further study on the mechanism of nicotinamide showed that nicotinamide could inhibit the activity of the mTOR pathway, thus regulating the autophagy. CONCLUSIONS: Nicotinamide induces the autophagy of chronic hypoxic myocardial cells by regulating the mTOR pathway, thereby protecting cells from apoptosis.

HOTAIR promotes inflammatory response after acute myocardium infarction by upregulating RAGE.

OBJECTIVE: The aim of this study was to explore the role of HOTAIR in inflammatory response after acute myocardium infarction (AMI) and to investigate its underlying mechanism. MATERIALS AND METHODS: The AMI model was first constructed in rats, and heart tissues were harvested. Expression levels of HOTAIR and receptor of advanced glycation end-products (RAGE) in rat heart were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The protein expression level of pEKR in rat heart was detected by Western blot. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in rats were determined by enzyme-linked immunosorbent assay (ELISA). The hypoxia-induced H9C2 cells were used to construct the MI model in vitro. Meanwhile, the expression levels of HOTAIR and RAGE in H9C2 cells were detected. The levels of TNF-α and IL-6 in the culture medium were determined by ELISA. Rescue experiments were conducted by co-transfecting pcDNA-HOTAIR and si-RAGE in H9C2 cells. Subsequently, the levels of pERK, TNF-α, and IL-6 were detected. RESULTS: The mRNA expression levels of HOTAIR and RAGE in the AMI group were significantly higher than those of the control group. Western blot showed remarkably higher protein levels of RAGE and pERK in AMI rats when compared with those of controls. Similarly, results of ELISA indicated that the levels of TNF-α and IL-6 in AMI rats were significantly higher than those of controls. Meanwhile, overexpression of HOTAIR in H9C2 cells remarkably elevated the expression levels of HOTAIR and RAGE. In addition, upregulated pERK, TNF-α, and IL-6 were observed in H9C2 cells overexpressing HOTAIR, which could be reversed by RAGE knockdown. CONCLUSIONS: HOTAIR promotes inflammatory response after AMI by upregulating RAGE expression.

20-Hydroxyecdysone-upregulated proteases involved in Bombyx larval fat body destruction.

During insect larval-pupal metamorphosis, the obsolete larval organs and tissues undergo histolysis and programmed cell death to recycle cellular materials. It has been demonstrated that some cathepsins are essential for histolysis in larval tissues, but the process of tissue destruction is not well documented. Fat body, the homologous organ to mammalian liver and adipose tissue, goes through a distinct destruction process during larval-pupal transition. Herein, we found that most of the Bombyx proteases - including Bombyx cathepsin B (BmCatB) (BmCatLL-2), Bombyx cathepsin D (BmCatD), Bombyx cathepsin L like-1 (BmCatLL-1) and -2(BmCatLL-2), Bombyx fibroinase (BmBcp), Bombyx matrix metalloprotease (BmMmp), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs 1 (BmAdamTS-1), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs like (BmAdamTS L) and Bombyx cysteine protease inhibitor (Bmbcpi)- were expressed highly in fat body during feeding and metamorphosis, with a peak occurring during the nonfeeding moulting or prepupal stage, as well as being responsive to 20-hydroxyecdysone (20E). The aforementioned protease genes expression was upregulated by injection of 20E into the feeding larvae, while blocking 20E signalling transduction led to downregulation. Western blotting and immunofluorescent staining of BmCatB and BmBcp confirmed the coincident variation of their messenger RNA (mRNA) and protein level during the development and after the treatments. Moreover, BmCatB, BmBcp, BmMmp and BmAdamTS-1 RNA interference all led to blockage of larval fat body destruction. Taken together, we conclude that 20E regulates larval fat body destruction by upregulating related protease gene expression and protein levels during larval-pupal transition.

Tetramethylpyrazine (TMPZ) triggers S-phase arrest and mitochondria-dependent apoptosis in lung cancer cells.

Tetramethylpyrazine (TMPZ) is one of the active compounds extracted from the traditional Chinese herb Chuanxiong. Several studies have shown its anti-cancer properties. However, its functions in lung cancer and the underlying cellular mechanisms are relatively unknown. Our present study aimed to investigate the effects of TMPZ on A549 and 95D cells. The MTT assay showed that TMPZ decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that TMPZ strongly suppressed colony formation ability in A549 and 95D cells. Flow cytometric analysis revealed that TMPZ induced S phase arrest in lung cancer cells. In addition, TMPZ induced apoptosis, as shown by the results of propidium iodide/Annexin V double-staining. Furthermore, TMPZ decreased mitochondrial membrane potential (∆Ψm) in a dose-dependent manner. Finally, western blot analysis of TMPZ-treated cells revealed the activation of Caspase-3 and the increase of the ratio of Bax/Bcl-2. These results demonstrated that TMPZ could suppress carcinogenesis of lung cancer cells through blocking cell cycle and inducing mitochondria-dependent apoptosis by regulating Caspase-3 and Bax/Bcl-2, suggesting that TMPZ may be a promising drug to treat lung cancer.

DNA methylation and expression of imprinted genes are associated with the viability of different sexual cloned buffaloes.

The DNA methylation of imprinted genes is an important way to regulate epigenetic reprogramming of donor cells in somatic cell nuclear transfer (SCNT). However, the effects of sexual distinction on the DNA methylation of imprinted genes in cloned animals have seldom been reported. In this study, we analysed the DNA methylation status of three imprinted genes (Xist, IGF2 and H19) from liveborn cloned buffaloes (L group, three female and three male), stillborn cloned buffaloes (S group, three female and three male) and natural reproduction buffaloes (N group, three female and three male), using bisulphite sequencing polymerase chain reaction (BS-PCR). The expression levels of these imprinted genes were also investigated by quantitative real-time PCR (QRT-PCR). The DNA methylation levels of H19 were not significantly different among the groups. However, the Xist in female and IGF2 in male of the S group were found to be significantly hypomethylated in comparison with the same sexual buffaloes in L group and N group (p < .05). Furthermore, the expression levels of Xist, IGF2 and H19 in the stillborn female cloned buffaloes of S group were significantly higher than that of the female buffaloes in the L group and N group (p < .05). The expression levels of IGF2 and H19 in the stillborn male cloned buffaloes in the S group were significantly higher than that of the male buffaloes in the L group and N group (p < .05). These results indicate that Xist may be associated with the viability of female cloned buffaloes, and IGF2 may also be related to the viability of male cloned buffaloes.

[Rapid determination of volatile organic compounds in workplace air by protable gas chromatography-mass spectrometer].

Objective: To establish a method for rapid determination of 47 volatile organic compounds in the air of workplace using portable gas chromatography-mass spectrometer(GC-MS). Methods: The mixed standard gas with different concentration levels was made by using the static gas distribution method with the high purity nitrogen as dilution gas. The samples were injected into the GC-MS by a hand-held probe. Retention time and characteristic ion were used for qualitative analysis,and the internal standard method was usd for quantitation. Results: The 47 poisonous substances were separated and determined well. The linear range of this method was 0.2-16.0 mg/m(3),and the relative standard deviation of 45 volatile ovganic compounds was 3.8%-15.8%. The average recovery was 79.3%-119.0%. Conclusion: The method is simple,accurate,sensitive,has good separation effect,short analysis period, can be used for qualitative and quantitative analysis of volatile organic compounds in the workplace, and also supports the rapid identification and detection of occupational hazards.

[Effect of Notch1, 2, 3 genes silencing on Notch and nuclear factor-κB signaling pathway of macrophages derived from patients with coronary artery disease].

Objective: To investigate the effects of Notch1, 2, 3 genes silencing by siRNA on Notch signaling pathway (Delta-like 4(DLL4), Jagged 1(JAG1)) and nuclear factor-κB (NF-κB) signaling pathway (IκBα, P52) of macrophages derived from patients with coronary artery disease (CAD), thus to explore the potential genetic treatment perspectives for CAD. Methods: Peripheral blood mononuclear cells of CAD patients were isolated by density gradient centrifugation and transformed by phorbol-12-myristate-13-acetate (PMA) to macrophages. Macrophages were then transfected with Notch1-small interference RNA (siRNA, Notch1-siRNA group), Notch2-siRNA (Notch2-siRNA group), Notch3-siRNA (Notch3-siRNA group), negative control siRNA (NC group) and none siRNA (control group) respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were applied to assess the mRNA and protein expression levels of DLL4, JAG1, IκBα and p52, respectively. Electrophoretic mobility shift assay (EMSA) was used to observe the NF-κB DNA binding activity. Subcellular distributions of NF-κB/p52 were detected through immunofluorescence. Results: (1) The mRNA and protein expressions of DLL4, JAG1 and p52 in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group were significantly downregulated, while the mRNA and protein expression of IκBα was significantly upregulated compared with NC group and control group(P<0.05 or 0.01). The mRNA and protein expressions of DLL4, JAG1 and p52 in Notch1-siRNA group were significantly downregulated, while the mRNA and protein expression of IκBα was significantly upregulated compared with Notch2-siRNA group and Notch3-siRNA group(P<0.05 or 0.01). The mRNA and protein expressions of DLL4, JAG1, IκBα and p52 were similar between NC group and control group (all P>0.05). (2) The binding activity of NF-κB DNA was significantly lower in Notch1-siRNA group (613±57), Notch2-siRNA group (1 169±85) and Notch3-siRNA group (1 454±90) compared with control group (2 643±115) and NC group (2 407±100) (all P<0.01), which was also significantly lower in Notch1-siRNA group compared to Notch2-siRNA group and Notch3-siRNA group (P<0.01); was significantly lower in Notch2-siRNA group compared with Notch3-siRNA group (P<0.01) and was similar between control group and NC group (P>0.05). (3) The fluorescence intensity of NF-κB/p52 was significantly lower both in the nucleus and cytoplasm in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group compared with NC group and control group (all P<0.01), and the decrease was more obviously in the nucleus than in cytoplasm in Notch1-siRNA group, Notch2-siRNA group and Notch3-siRNA group (P<0.05 or 0.01). The fluorescence intensity of NF-κB/p52 was similar between control group and NC group (P>0.05). Conclusion: There is a positive regulation between Notch and NF-κB pathway in macrophages derived from CAD patients, the regulation power on NF-κB signaling pathway of Notch1 is stronger than that of Notch2 and Notch 3.

Dual antiplatelet therapy after stroke or transient ischaemic attack - how long to treat? The duration of aspirin plus clopidogrel in stroke or transient ischaemic attack: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel for 90 days was recommended as the secondary prevention of minor ischaemic strokes or transient ischaemic attacks (TIAs) in 2014. However, whether the duration of 90 days is optimal for each patient remains unclear. Therefore, the efficacy and safety of short-term (≤3 months) and prolonged (≥1 year) DAPT after stroke or TIA were assessed via a systematic review and meta-analysis. METHODS: The Cochrane Library, Clinical Trials.gov and PubMed were searched up to December 2014 and nine randomized controlled trials were included involving 21 923 patients. RESULTS: Short-term DAPT significantly reduced the risk of ischaemic stroke recurrence by 41% and major vascular events by 30%, without increasing the risk of intracranial haemorrhage. Prolonged DAPT reduced the risk of ischaemic stroke recurrence by 12% and major vascular events by 10%. However, the risk of major bleeding and intracranial haemorrhage increased. CONCLUSIONS: Short-term DAPT appears to be superior to prolonged DAPT. However, the difference in efficacy outcome needs to be carefully explained and confirmed by further well-designed randomized controlled trials.

Dose Proportionality and Pharmacokinetics of Eplerenone in Healthy Chinese Subjects.

BACKGROUND: Eplerenone (CAS 107724-20-9) is the first highly selective aldosterone receptor blocker and is used worldwide for treatment of hypertension and heart failure. OBJECTIVE: The objective of this study was to investigate the eplerenone pharmacokinetics in healthy Chinese subjects and assess the dose proportionality over the therapeutic dose range. METHODS: A single-dose, randomized, 6-sequence, 3-treatment, 3-period crossover, open label study was conducted in 12 healthy Chinese subjects, who received 3 doses of eplerenone in random order (25, 50, 100 mg). The power model was used to evaluate the dose proportionality of eplerenone. The pharmacokinetic study of multiple-dose of eplerenone was also conducted. RESULTS: After single-dose oral administration, the mean C max value increased from 489 to 1 641 ng/mL, and the mean AUC 0-t value increased from 3 030 to 10 893 ng/mL·h with an increase in dose from 25 to 100 mg, respectively. The mean value for terminal T 1/2 was approximate 3 h with no significant differences among different dose groups. Though dose proportionality of eplerenone was inconclusive in Chinese subjects over the dose range of 25-100 mg, the maximal proportionality dose range (ρ1) was 2.06 based on power model. Steady state could achieve within at least 4 days and no accumulation was observed after multiple-dose of eplerenone. CONCLUSION: Dose proportionality was inconclusive in over the dose range of 25-100 mg; however, linear pharmacokinetics could be considered when dose ratio is no more than 2.06.