Pharmacokinetics and bioequivalence evaluation of acamprosate calcium tablets in healthy Chinese volunteers

AbstractBackgroundFew pharmacokinetic data of acamprosate were available in Chinese population and no medication is approved for alcohol dependence in China.Purpose1. Investigate the pharmacokinetic properties of acamprosate calcium in healthy Chinese male volunteers on single- and multiple-dose administration. 2. Compare the bioequivalence of two formulations of acamprosate calcium tablets both under fasting and fed conditions.MethodsThis open-label, randomized study included 3 stages. In each stage, a 2-way crossover bioequivalence study was conducted to study the pharmacokinetic properties and bioequivalence of acamprosate calcium tablets on multiple dosing after standardized meals, single dosing under fasting conditions and fed conditions, respectively. The washout period between each treatment in a stage and between each stage was 1week. Plasma acamprosate calcium was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG, and laboratory tests.ResultsTotally, 36 male subjects were enrolled in the study and all of them completed the whole 3 study stages. Main pharmacokinetic parameters of test and reference formulations were as follows: multiple dosing, Tmax 9.94±6.59 and 9.47±5.47h, Cmax 435.74±348.10 and 346.54±155.66ng·mL−1, AUC0-t 8600.52±5264.77 and 9315.10±6820.03ng·mL−1·h, AUC0–∞ 8845.38±5838.18 and 9669.24±7326.53ng·mL−1·h, t1/2 10.06±8.83 and 9.87±10.35h; single dosing under fasting conditions, Tmax 7.29±4.87 and 6.57±1.85h, Cmax 247.85±110.05 and 244.64±132.43ng·mL−1, AUC0-t 3385.41±1418.92 and 3496.24±1767.29ng·mL−1·h, AUC0–∞ 3781.53±1556.96 and 3829.56±1981.25ng·mL−1·h, t1/2 13.07±17.24 and 10.26±7.78h; single dosing under fed conditions, Tmax 17.72±9.42 and 19.50±9.84h, Cmax 183.90±74.52 and 168.14±60.67ng·mL−1, AUC0-t 3181.71±1368.24 and 3575.11±1416.39ng·mL−1·h, AUC0–∞3442.39±2002.53 and 3624.44±1418.12ng·mL−1·h, t1/2 8.76±12.28 and 6.67±4.84h, respectively. In all three stages, 90% CIs for the test/reference ratio of AUC0–t and AUC0–∞ were located within 80%–125%, 90% CI for Cmax was within 70%–143%.ConclusionsSimilar pharmacokinetic results of acamprosate calcium tablets in healthy Chinese volunteers were found as those in Caucasic population. In all three stages, the two formulations met the regulatory criteria for bioequivalence.Chictr.org identifier: ChiCTR-TTRCC-14004853

Spotlight on 3-K For All: New York Citys 3-K for All Supports Mothers Labor Force Participation

New York City's 3-K for All program was first introduced to a few districts beginning in 2017 and was gradually made available to all districts by 2021. The rollout prioritized the highest-need districts for prekindergarten services. This report focuses on the role of New York City's 3-K in supporting mothers' labor force participation and employment.Using data from the Early Childhood Poverty Tracker, which repeatedly surveyed the same New York City families with young children from 2017 to 2021, the report investigates whether 3-K availability was associated with increased labor force participation and employment among mothers of preschool-age children in New York City

Scutellarin regulates microglia-mediated TNC1 astrocytic reaction and astrogliosis in cerebral ischemia in the adult rats

Additional file 1: (A). Scutellarin at 0.54 mM did not elicit a noticeable reaction of GFAP/iNOS in TNC1. (B). iNOS mRNA expression in TNC1 astrocytes remained relatively unchanged at all time-points following treatment with BM, BM + L and CM; however, when incubated with CM + L for various time points, TNC1 showed a remarkable increase in iNOS peaking at 24 h. (C). Confocal images showing iNOS (C1-3) expression in TNC1 astrocytes incubated with different medium for 24 h. Compared with cells incubated in BM (C1) and BM + L (C2), TNC1 astrocytes incubated with CM + L (C3) were hypertrophic and showed a marked increase in iNOS immunofluorescence. Scale bars: 20 μm. DAPI—blue

NaoXinTong Inhibits the Development of Diabetic Retinopathy in d

Buchang NaoXinTong capsule (NXT) is a Chinese Materia Medica standardized product extracted from 16 Chinese traditional medical herbs and widely used for treatment of patients with cerebrovascular and cardiovascular diseases in China. Formation of microaneurysms plays an important role in the development of diabetic retinopathy. In this study, we investigated if  NXT can protect diabetic mice against the development of diabetic retinopathy. The db/db mice (~6 weeks old), a diabetic animal model, were divided into two groups and fed normal chow or plus NXT for 14 weeks. During the treatment, fasting blood glucose levels were monthly determined. After treatment, retinas were collected to determine retinal thickness, accumulation of carbohydrate macromolecules, and caspase-3 (CAS-3) expression. Our results demonstrate that administration of NXT decreased fasting blood glucose levels. Associated with the decreased glucose levels, NXT blocked the diabetes-induced shrink of multiple layers, such as photoreceptor layer and outer nuclear/plexiform layers, in the retina. NXT also inhibited the diabetes-induced expression of CAS-3 protein and mRNA, MMP-2/9 and TNFα mRNA, accumulation of carbohydrate macromolecules, and formation of acellular capillaries in the retina. Taken together, our study shows that NXT can inhibit the development of diabetic retinopathy and suggests a new potential application of NXT in clinic

Beat frequency quartz-enhanced photoacoustic spectroscopy for fast and calibration-free continuous trace-gas monitoring

Quartz-enhanced photoacoustic spectroscopy (QEPAS) is a sensitive gas detection technique which requires frequent calibration and has a long response time. Here we report beat frequency (BF) QEPAS that can be used for ultra-sensitive calibration-free trace-gas detection and fast spectral scan applications. The resonance frequency and Q-factor of the quartz tuning fork (QTF) as well as the trace-gas concentration can be obtained simultaneously by detecting the beat frequency signal generated when the transient response signal of the QTF is demodulated at its non-resonance frequency. Hence, BF-QEPAS avoids a calibration process and permits continuous monitoring of a targeted trace gas. Three semiconductor lasers were selected as the excitation source to verify the performance of the BF-QEPAS technique. The BF-QEPAS method is capable of measuring lower trace-gas concentration levels with shorter averaging times as compared to conventional PAS and QEPAS techniques and determines the electrical QTF parameters precisely

The Structural Characterization and Antigenicity of the S Protein of SARS-CoV

The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets

Fabrication of the carbon fiber reinforced plastic (CFRP) cone tube through the laboratory-scale 3-axis winding machine

Filament winding process is one of the composite fabrication methods, which has relative lower manufacturing costs, higher efficiency and automation. It is commonly used to manufacture axisymmetric composite products, such as tubes, vessels, and domes, which is mainly used in aerospace, military and defense technology. However, it is a challenging task to fabricate a composite cone structure with the high winding angle through a laboratory-scale 3-axis winding machine. This paper aims to design and fabricate the carbon fiber reinforced plastic (CFRP) cone tube by using a low-cost filament winding machine. The cone mandrel was designed and prepared using additive printing technique. Dry and wet winding processes were conducted with yarn and 3K carbon fiber tow, respectively. The CFRP cone tube was successfully designed and fabricated with a winding angle of 75.11°±0.12°. It can be concluded that the wet winding process provides better winding quality and higher surface smoothness compared to the dry winding process. Moreover, the compressive modulus was 1.62 GPa, and the maximum compressive stress was 16.29 MPa under quasi-static compression loading

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia

ObjectiveThe aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ).MethodsPatients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons.ResultsSixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group (p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores (r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume (r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)].ConclusionOxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes