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1.
J Environ Manage ; 355: 120440, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38437740

RESUMO

The best solution to address environmental pollution caused by arsenic-containing hazardous waste is to prepare high-purity elemental arsenic from such waste. The key to this approach lies in the efficient separation of arsenic from various impurities. This paper presents a viable solution for producing high-purity elemental arsenic from arsenic-alkali slag, and the keylies in utilizing the selective precipitation of magnesium ammonium arsenate (MgNH4AsO4) to achieve efficient separation of arsenic from alkali, antimony, and other impurities. Thermodynamic analysis and hydrometallurgical condition experiments indicate that in complex alkaline arsenic-containing solutions, over 90% of arsenic components can selectively precipitate in the form of MgNH4AsO4. The content of arsenic in the resulting precipitate reaches approximately 30%, while the content of antimony is below 0.1%. This achieves efficient enrichment of arsenic and preliminary separation of impurities in complex arsenic-alkali slag. Thermodynamic analysis and pyrometallurgical condition experiments demonstrate that the precipitate of MgNH4AsO4 can be reduced to elemental arsenic with an arsenic content reaching 99.85%, and an antimony content as low as 0.05%. This achieves a profound separation of arsenic from impurities. Based on the research presented in this paper, a production line was established that enables the deep resource utilization of arsenic-alkali slag.


Assuntos
Arsênio , Arsênio/análise , Antimônio , Álcalis , Resíduos Industriais/análise
2.
J Environ Sci (China) ; 139: 293-307, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38105056

RESUMO

Iron sulfide (FeS) is a promising material for separating copper and arsenic from strongly acidic wastewater due to its S2- slow-release effect. However, uncertainties arise because of the constant changes in wastewater composition, affecting the selection of operating parameters and FeS types. In this study, the aging method was first used to prepare various controllable FeS nanoparticles to weaken the arsenic removal ability without affecting the copper removal. Orthogonal experiments were conducted, and the results identified the Cu/As ratio, H2SO4 concentration, and FeS dosage as the three main factors influencing the separation efficiency. The backpropagation artificial neural network (BP-ANN) model was established to determine the relationship between the influencing factors and the separation efficiency. The correlation coefficient (R) of overall model was 0.9923 after optimizing using genetic algorithm (GA). The BP-GA model was also solved using GA under specific constraints, predicting the best solution for the separation process in real-time. The predicted results show that the high temperature and long aging time of FeS were necessary to gain high separation efficiency, and the maximum separation factor can reached 1,400. This study provides a suitable sulfurizing material and a set of methods and models with robust flexibility that can successfully predict the separation efficiency of copper and arsenic from highly acidic environments.


Assuntos
Arsênio , Cobre , Águas Residuárias , Inteligência Artificial
3.
Drug Des Devel Ther ; 17: 2303-2313, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554228

RESUMO

Background: Meloxicam is a selective cyclooxygenase-2 inhibitor used for pain relief, but its poor solubility limits its clinical applications. QP001 is a novel intravenous formulation of meloxicam developed with PEG and pH regulator to improve its solubility. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of QP001 in Chinese healthy subjects. Methods: The trial consisted of three parts. Part I was a two-period crossover study to evaluate bioavailability, in which 10 healthy were either intravenously infused with 15mg QP001 (test) or orally given 15mg MobicⓇ (reference). Part II was a single-arm design to assess the pharmacokinetic (PK) characteristics after 30 mg single- and multiple-dose QP001 in 10 subjects. In part III, we investigated the PKs and tolerability of QP001 at a high dose (60 mg) in another 10 subjects. The PK parameters and treatment-emergent adverse events (TEAEs) were evaluated. Results: A total of 30 subjects were enrolled in the study. QP001 was well tolerated and safe without significant TEAEs in all three study parts. The PK characteristics of QP001 were linear following a single-dose range of 15-60 mg (Cmax and AUC0-t were 5.82-17.66 µg/mL and 58.08-251.17 µg∙h/mL, respectively). After five consecutive daily 30 mg doses, the accumulation index was around 1.98, which indicated a minimal accumulation of QP001. Compared to the tablet dosage form, the relative bioavailability of QP001 reached 116.85%. Additionally, the PK profile of QP001 showed no gender difference. Conclusion: QP001 was well tolerated in healthy Chinese subjects after single ascending doses up to 60 mg and multiple-dose of 30 mg. Based on the PK and safety results, QP001 is a promising once-daily intravenous COX-2 inhibitor candidate for managing pain. Trial Registration: The trial is registered at chinadrugtrials.org.cn (ChiCTR2100047884).


Assuntos
População do Leste Asiático , Dor , Humanos , Área Sob a Curva , Estudos Cross-Over , Relação Dose-Resposta a Droga , Voluntários Saudáveis , Meloxicam
4.
Eur J Pharm Sci ; 190: 106536, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490973

RESUMO

OBJECTIVE: In patients with renal impairment, we studied apatinib and its major metabolites (M1-1, M1-2, M1-6, and M9-2) for pharmacokinetics. METHODS: Subjects with different renal functions were given a single oral dose of apatinib mesylate tablets of 250 mg. Pharmacokinetic samples were collected at 1 hour before dosing,0.25, 0.5, 1, 2, 3, 4, 6, 8, 24, 48, 72, and 96 h after dosing. The pharmacokinetic parameters of apatinib and its major metabolites were calculated by noncompartmental analysis. RESULTS: Comparing PK parameters of the mild or moderate renal impairment group with the healthy group: the geometric mean ratios of maximum observed drug concentration (Cmax), the area under the plasma drug concentration-time curve from time 0 to the final quantifiable time (AUC0-t), and the area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-inf) were all about one. No significant effect of mild and moderate renal impairment on apatinib pharmacokinetics was observed. Mild and moderate renal impairment was also not observed to have a significant effect on the pharmacokinetics of metabolites M1-1, M1-2, and M1-6. However, mild and moderate renal impairment had a certain increase in exposure to the metabolite M9-2. Considering that M9-2 has no inhibitory effect on protein tyrosine kinase, it has no clinical significance. In addition, the proportion of cumulative excretion of apatinib and its major metabolites was small and almost negligible in all three groups of subjects. CONCLUSION: Patients with mild and moderate renal impairment do not need to adjust the dose of apatinib when using low dose (250 mg) apatinib.


Assuntos
Hepatopatias , Humanos , Piridinas/metabolismo , Rim/metabolismo , Área Sob a Curva
5.
J Orthop Surg (Hong Kong) ; 31(2): 10225536231181706, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37268597

RESUMO

BACKGROUND: The medial plantar artery perforator (MPAP) flap is widely used to reconstruct the weight-bearing area of the foot. Traditionally, its donor site is closed using a skin graft, which is associated with several complications, including walking disability. This study aimed to examine our experience with using a super-thin anterolateral thigh (ALT) flap to reconstruct the MPAP flap donor site. METHODS: We examined 10 patients who underwent reconstruction of the MPAP flap donor site using a super-thin ALT flap between August 2019 and March 2021. The vascular pedicle was anastomosed to the proximal end of the medial plantar vessels or the end of the posterior tibial vessels. RESULTS: All reconstruction flaps survived and all patients were satisfied with the aesthetic appearance. No blisters, ulcerations, hyperpigmentation, or contractures occurred. All patients gained protective sensation in the super-thin ALT flap. The average visual analog scale score for the aesthetic appearance of the reconstructed foot was 8.5 ± 0.7 (range, 8-10). All patients were able to ambulate without aids and could wear regular shoes. The average revised Foot Function Index score was 26.4 ± 4.1 (range, 22-34). CONCLUSION: Reconstruction of the MPAP flap donor site using a super-thin ALT flap is reliable and provides satisfactory functional recovery, aesthetic appearance, and protective sensation while minimizing postoperative morbidity.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Humanos , Coxa da Perna/cirurgia , Retalho Perfurante/irrigação sanguínea , Transplante de Pele , Artérias/cirurgia , Resultado do Tratamento
6.
J Environ Manage ; 344: 118462, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37384991

RESUMO

Extensive research has been conducted on the separation and recovery of heavy metals from wastewater through the targeted precipitation of metal sulfides. It is necessary to integrate various factors to establish the internal correlation between sulfide precipitation and selective separation. This study provides a comprehensive review of the selective precipitation of metal sulfides, considering sulfur source types, operating factors, and particle aggregation. The controllable release of H2S from insoluble metal sulfides has garnered research interest due to its potential for development. The pH value and sulfide ion supersaturation are identified as key operational factors influencing selectivity precipitation. Effective adjustment of sulfide concentration and feeding rate can reduce local supersaturation and improve separation accuracy. The particle surface potential and hydrophilic/hydrophobic properties are crucial factors affecting particle aggregation, and methods to enhance particle settling and filtration performance are summarized. The regulation of pH and sulfur ion saturation also controls the zeta potential and hydrophilic/hydrophobic properties on the particles surface, thereby affecting particle aggregation. Insoluble sulfides can decrease sulfur ion supersaturation and improve separation accuracy, but they can also promote particle nucleation and growth by acting as growth platforms and reducing energy barriers. The combined influence of sulfur source and regulation factors is vital for achieving precise separation of metal ions and particle aggregation. Finally, suggestions and prospects are proposed for the development of agents, kinetic optimization, and product utilization to promote the industrial application of selective precipitation of metal sulfides in a better, safer, and more efficient way.


Assuntos
Metais Pesados , Águas Residuárias , Sulfetos/química , Enxofre , Precipitação Química
7.
Opt Express ; 30(15): 26676-26689, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-36236855

RESUMO

Heterogeneous integration of nitrides on Si (100) is expected to open the door to the new possibilities for this material system in the fields of high-speed integrated photonics and information processing. In this work, GaN epitaxial layer grown on the patterned sapphire substrate is transferred onto Si (100) by a combination of wafer bonding, laser lift-off and chemical mechanical polishing (CMP) processes. The GaN epilayer transferred is uniformly thinned down to 800 nm with a root mean square surface roughness as low as 2.33 Å. The residual stress within the InGaN quantum wells transferred is mitigated by 79.4% after the CMP process. Accordingly, its emission wavelength exhibits a blue shift of 8.8 nm, revealing an alleviated quantum-confined Stark effect. Based on this platform, an array of microcavities with diverse geometrics and sizes are fabricated, by which optically-pumped green lasing at ∼505.8 nm is achieved with a linewidth of ∼0.48 nm from ∼12 µm microdisks. A spontaneous emission coupling factor of around 10-4 is roughly estimated based on the light output characteristics with increasing the pumping densities. Lasing behaviors beyond the threshold suggest that the microdisk suffers less thermal effects as compared to its undercut counterparts. The electrically-injected microdisks are also fabricated, with a turn-on voltage of ∼2.0 V and a leakage current as low as ∼2.4 pA at -5 V. Being compatible with traditional semiconductor processing techniques, this work provides a feasible solution to fabricate large-area heterogeneously integrated optoelectronic devices based on nitrides.

8.
Chemosphere ; 307(Pt 3): 135992, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35964730

RESUMO

The alkaline leaching process of arsenic-containing solid waste discharged during nonferrous metal smelting affords typical high-salinity alkaline arsenic-containing wastewater (HSAW). In this study, for the first time, Me (Ca2+ and Mg2+)-AsO43--OH--H2O and Me (Ca2+ and Mg2+)-AsO43--CO32--H2O systems are studied based on a thermodynamic equilibrium diagram and an arsenic removal experiment, proving that the removal of arsenic using single metal ions in the presence of CO32- is infeasible because of carbonate coprecipitation. Based on this observation, a new method that uses magnesium ammonium complex salts (MACSs) for HSAW treatment is proposed. Based on the thermodynamic calculations of the Mg2+-AsO43--NH4+-CO32--H2O system and the arsenic removal experiment, carbonate and arsenate can be selectively separated by the formation of magnesium ammonium arsenate (NH4MgAsO4·6H2O). In an arsenic solution containing 150-g/L Na2CO3, the arsenic removal rate and the arsenic grade of the precipitation product reach 90.16% and 27.13%, respectively, when the molar ratios of Mg2+/NH4+:As(V) are 1.8:1 and 2:1, respectively. The proposed method is successfully employed for treating a leaching solution of alkaline arsenic slag discharged during antimony smelting. The findings of this study will broaden the basic theory of HSAW treatment and lay a foundation for the resource treatment of arsenic-containing solid waste.


Assuntos
Compostos de Amônio , Arsênio , Antimônio , Arseniatos , Carbonatos , Magnésio , Salinidade , Sais , Resíduos Sólidos , Águas Residuárias
9.
Front Pharmacol ; 13: 871492, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35668951

RESUMO

Background: The present study evaluated the safety, pharmacokinetics/pharmacodynamics (PK/PD), and absolute bioavailability (Fabs) of Dex nasal spray in healthy adult subjects, which serves as a bridge for the subsequent study in children. Methods: Part 1: a double-blind, placebo-controlled, single ascending dose study was performed on 48 subjects. For 20-/40-µg groups, every 6/2 subjects received either Dex/placebo nasal spray or Dex/placebo injection in two periods. In total, 12/4 subjects each received 100 µg Dex/placebo nasal spray. Part 2: a randomized, double-blind, placebo-controlled study; 12/4 subjects received 150 µg Dex/placebo nasal spray. Part 3: a randomized, open, self-crossover study; 12 subjects received 20 µg and 100 µg Dex nasal spray in two periods alternately. The method of administration was optimized in Part 2 and Part 3. Results: In part 1, Dex nasal spray was well tolerated up to the maximum dose of 100 µg, whereas the Fabs was tolerated to only 28.9%-32.3%. In Part 2 and Part 3, the optimized nasal spray method was adopted to promote the Fabs of Dex nasal spray to 74.1%-89.0%. A severe adverse event was found in Part 2. In Part 3 (100 µg), the Ramsay score increased the most and lasted the longest, whereas the BIS score decreased most significantly. Conclusion: Using the optimized nasal spray method, a single dose of 20/100 µg of the test drug was safe and tolerable, and 100 µg may have approached or reached the plateau of sedation. In addition, it is found that the optimized method can greatly improve the bioavailability of the test drug, leading to its higher reference value.

10.
J Orthop Surg (Hong Kong) ; 30(1): 10225536221094258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35404723

RESUMO

PURPOSE: To evaluate the clinical efficacy of using free tissue flap combined with contralateral instep thick plantar skin in reconstructing complex plantar forefoot defects. METHODS: During the past 8 years, 15 patients, aged 25-60 years, with defects in the soft-tissue and composite bone of the forefoot were treated. Their defects were caused by trauma. These defects were all located on the plantar forefoot. The free tissue flaps transposed to reconstruct defects were anterolateral thigh flaps, groin flaps, and latissimus dorsi flaps. Flap size varied in width 4-cm and length (6-16 cm). The mean size of flaps was 80.3 cm2. The follow-up period ranged from 12 to 90 months (mean, 25.5 months). RESULTS: Partial flap loss was observed in one anterolateral thigh flap and one latissimus dorsi flap. One patient showed skin graft loss at the defect site, and the wound was re-epithelialized by changing dressings. Hyperkeratosis was not observed in any of the cases. All patients were able to walk near-normally within 2.5 months after surgery, and there was no recurrence of ulceration. CONCLUSION: We advocate using a free tissue flap combined with contralateral instep thick plantar skin for reconstruction of moderate or large complex plantar forefoot defects.


Assuntos
Traumatismos do Pé , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , , Traumatismos do Pé/cirurgia , Retalhos de Tecido Biológico/transplante , Humanos , Transplante de Pele , Resultado do Tratamento
11.
Neurol Ther ; 11(2): 621-632, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35129802

RESUMO

INTRODUCTION: Buccal midazolam treatment is licensed in the European Union for prolonged acute convulsive seizures in children and adolescents, but the buccal pathway is often hampered by jaw clenching, hypersalivation, or uncontrolled swallowing. Midazolam formulations that are more secure, reliable, and faster for use are needed in the acute setting. Pharmacokinetics and comparative bioavailability of intranasally administered midazolam and two midazolam intravenous solutions administered buccally or intravenously in healthy adults were evaluated. METHODS: In this phase 1, open-label, randomized, single-dose, three-period, three-sequence crossover study, 12 healthy adults (19-41 years) were randomly assigned to receive 2.5 mg midazolam intranasally; 2.5 mg midazolam intravenously; 2.5 mg midazolam buccally. Blood samples were collected for 10 h post dose to determine pharmacokinetic profiles. Adverse events and vital signs were recorded. RESULTS: Intranasal administration of 2.5 mg midazolam demonstrated a more rapid median time to Cmax compared to buccal administration of midazolam (Tmax, 12.6 min vs. 45 min; Cmax, 38.33 ng/ml vs. 24.97 ng/ml). The antiepileptic effect of intranasal and buccal midazolam treatment lasted less than 4 h and generally did not differ from intravenously administered midazolam. No serious adverse events or deaths were reported, and no treatment-emergent adverse events led to study discontinuation. CONCLUSION: Intranasal administration of midazolam may be a preferable alternative to the currently approve buccal midazolam treatment for prolonged acute convulsive seizures in children and adolescents. TRIAL REGISTRATION: This study is registered at the Chinese Clinical Trial [ http://www.chictr.org.cn ] (ChiCTR2000032595) on 3 May, 2020.

12.
Opt Express ; 29(15): 24552-24560, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34614697

RESUMO

Phosphor-converted blue laser diodes are regarded as the next-generation high-brightness solid-state lighting sources. However, it is difficult to obtain white light with high angular color uniformity due to the Gaussian distribution of the laser light sources. Meanwhile, laser excitation power density of the light source is high, which would bring serious heating effects to the phosphor layers. In this study, a strategy has been proposed to solve the problem by using remote sediment phosphor plates. In detail, we have compared the effects of remote sediment/non-sediment phosphor plates to the phosphor-converted blue laser diodes on the overall light output characteristics, angular optical distribution properties, as well as their thermal performance. The emission from sediment phosphor samples has been found more divergent, and angular deviation in the correlated color temperature of the emitted light could be greatly reduced from 1486 to 294 K, yet with only 5% luminous flux loss, as compared to non-sediment phosphor samples. Most importantly, the sediment phosphor sample pushes the power damage threshold up to 588.1 W/cm2 (non-sediment sample: 512.3 W/cm2). Our work has demonstrated the sediment phosphor plates would ameliorate the angular color uniformity for the laser-based lighting source, while extending its lifespan with improved thermal stability.

13.
Med Sci Monit ; 27: e931471, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34446688

RESUMO

BACKGROUND The demand for plasma and plasma products has increased in China, which has a short supply. Compared with whole blood donors, plasma donors and their donation behavior have received less attention. This study aimed to investigate the demographic characteristics and lifestyle habits of Chinese plasma donors. MATERIAL AND METHODS During 2018-2019, information on plasma donors was collected from blood product companies using a 25-item questionnaire, including sex, age, height, weight, blood group, donation frequency, occupation, smoking and drinking, and sleeping and dietary habits. RESULTS Among 15 497 plasma donors, 70.5% were women and 78.5% were aged 46-55 years. Among 4847 plasma donors, the average height of men was 169.5±6.2 cm and the average height of women was 157.0±4.6 cm. In addition, the average weight of men was 67.0±10.4 kg and the average weight of women was 60.0±8.3 kg. The prevalence of obesity (body mass index ≥30.0 kg/m²) of all donors was 14.8%; 14.7% of men were obese, and 15% of women were obese. Among all plasma donors, 88.8% were farmers and 60% were frequent donors with a donation history of at least 5 years. Among all donors, 84.0% did not smoke, 67.3% did not drink, and 95.1% reported good sleep quality. All respondents reported healthy dietary habits. CONCLUSIONS Healthy lifestyle habits considerably affect the health of plasma donors and the quality of source plasma. Chinese plasma donors in this study demonstrated imbalances in terms of characteristics, which became more marked with age.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Doadores de Sangue/estatística & dados numéricos , Índice de Massa Corporal , Comportamento Alimentar , Estilo de Vida , Fumar/epidemiologia , Adolescente , Adulto , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
14.
J Environ Manage ; 287: 112348, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33735678

RESUMO

Leaching arsenic from solid waste selectively and removing arsenic from alkaline leachate efficiently are two key points in alkali treatment of copper smelter dust, and the latter is challenging. In this study, composite salt precipitation of magnesium ammonium arsenate (NH4MgAsO4·6H2O), similar to magnesium ammonium phosphate (NH4MgPO4·6H2O), was proposed to solve the difficult problem of separation arsenic from alkali. Based on the thermodynamic analysis, the selective leaching of arsenic from copper smelting dust was carried out in the NaOH-Na2S system. In the alkali leaching system, more than 80% arsenic can be leached out from the dust with the diffusion-controlled type in the Avrami model, while the leaching rates of valuable metals are less than 0.5%. For the strong alkaline leachate containing arsenic obtained by alkali leaching, the selective removal of arsenic was achieved by adding magnesium salt and ammonium salt. With the change of the amount of magnesium salt and ammonium salt, the sedimentation performance and composition of the arsenic slag changed accordingly. At the mole ratio of NH4+: As = 8:1 and Mg2+: As = 1.5:1, 96.38% of arsenic was removed, and the content of arsenic in the arsenic slag composed of MgNH4AsO4·6H2O reached 28.96%. On this basis, the circulating alkali leaching of copper smelter dust based on arsenic-alkali separation was successfully carried out. The whole scheme is not only economical and safe, but also achieves the reuse of wastewater without secondary pollution, which provides an alternative solution for the treatment of arsenic containing solid waste.


Assuntos
Arsênio , Álcalis , Cobre , Poeira
15.
Invest New Drugs ; 39(3): 796-802, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33420642

RESUMO

Purpose To assess the pharmacokinetic (PK) effect of proton pump inhibitors on the novel poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor fluzoparib, and observe the safety of its co-administration with omeprazole. Patients and methods Sixteen male healthy volunteers (HVs) were enrolled in a single-center, single-arm, open-label, fixed-sequence study. HVs took fluzoparib (100 mg, p.o.) after meal consumption on day-1, took omeprazole 40 mg (p.o.) under a fasting condition from day-5 to day-9, and took fluzoparib (100 mg, p.o.) after meal consumption on day-9. Blood samples were collected at predetermined timepoints for PK analyses. Safety was assessed via clinical laboratory tests. The study was registered with the Clinical Trials Registry on 30 September 2019 (NCT04108676). Results The peak plasma concentrations (Cmax) after fluzoparib administration was 2395.17 ± 418.27 ng/mL, the area under the curve (AUC) within 72 h (AUC0 - 72 h) was 26669.09 ± 7320.12 h·ng/mL, and AUC0-∞ was 26897.44 ± 7573.61 h·ng/mL. The Cmax after co-administration of fluzoparib and omeprazole was 2489.43 ± 423.72 ng·mL, AUC0 - 72 h was 30300.49 ± 8350.08 h·ng/mL, and AUC0-∞ was 30678.74 ± 8595.55 h·ng/mL. The geometric mean ratio of Cmax, AUC0 - 72 h and AUC0-∞ was 104.0% (90%CI: 94.8-114.0%), 113.6% (104.2-123.9%) and 104.1% (104.5-124.6%). The number of HVs with adverse reactions was identical (eight) for administration of fluzoparib and co-administration of fluzoparib and omeprazole. Conclusions The proton pump inhibitor omeprazole did not have a significant influence on the PK behavior of fluzoparib, and its safety profile was good upon co-administration with omeprazole. (NCT04108676, 30 September 2019).


Assuntos
Antineoplásicos , Omeprazol , Ftalazinas , Inibidores de Poli(ADP-Ribose) Polimerases , Inibidores da Bomba de Prótons , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Administração Oral , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Voluntários Saudáveis , Omeprazol/efeitos adversos , Omeprazol/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacocinética , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacologia , Ftalazinas/efeitos adversos , Ftalazinas/farmacocinética
16.
Clin Pharmacol Drug Dev ; 10(6): 598-606, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33241616

RESUMO

The current study compared the safety, tolerability, and pharmacokinetics of the new compound pharmaceutical preparation tazarotene clindamycin cream, and 2 single pharmaceutical preparations, tazarotene cream and clindamycin phosphate gel. Twelve healthy volunteers were enrolled in this single-center, single-blind, 3-treatment, 3-period crossover, single-dose randomized study. An 800-cm2 area on volunteers' backs was evenly smeared with 1.6 g of the test preparation to form a film. Blood samples were collected at predetermined time points for pharmacokinetic analysis. Safety and tolerability were assessed via skin reaction evaluation and clinical laboratory tests. The incidences of skin reactions were 18.2% for tazarotene clindamycin cream, 25.0% for tazarotene cream, and 18.2% for clindamycin phosphate gel. There were no significant differences in safety or tolerability among the 3 groups. Erythema, desquamation, and pruritus occurred in 7 volunteers, but no burning or tingling occurred. All adverse events were mild and resolved spontaneously, and there were no severe adverse events. The respective maximum plasma concentrations of tazarotenic acid after local administration of tazarotene clindamycin cream and tazarotene cream were 11 ± 5 pg/mL and 18 ± 12 pg/mL, and the areas under the curve within 72 hours were 444 ± 341 pg · h/mL and 692 ± 462 pg · h/mL.


Assuntos
Antibacterianos/administração & dosagem , Clindamicina/análogos & derivados , Fármacos Dermatológicos/administração & dosagem , Ácidos Nicotínicos/administração & dosagem , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Área Sob a Curva , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Clindamicina/farmacocinética , Estudos Cross-Over , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/farmacocinética , Combinação de Medicamentos , Feminino , Humanos , Masculino , Ácidos Nicotínicos/efeitos adversos , Ácidos Nicotínicos/farmacocinética , Método Simples-Cego , Adulto Jovem
17.
Arch Orthop Trauma Surg ; 140(11): 1775-1782, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32712822

RESUMO

BACKGROUND: The Krackow technique has the advantage of high strength, though it is not minimally invasive. The "Locking Block Modified Krackow" (LBMK) peri-tendon fixation technique was designed for minimally invasive surgery. This study aimed to compare the biomechanics of LBMK with Kessler and Percutaneous Achilles Repair System (PARS) techniques using a simulated early rehabilitation program. MATERIALS AND METHODS: Thirty-fresh bovine Achilles tendon specimens were randomly assigned to the LBMK, Kessler, and PARS groups (n = 10). In LBMK group, the main suture configuration was the LBMK technique, and the transverse suture was used as the secondary suture configuration. The Kessler group employed three suture configurations, two sagittal, one coronal plane. In the PARS group, two transverse and one locking sutures were placed at either end of the tendon. Each repaired specimen underwent two cyclic loading protocols (20-100 N, 20-190 N), 500 cycles, followed by measurement of the gap between the tendon ends. All specimens underwent a load-to-failure test at a 25 mm/s stretching rate. RESULTS: After the first loading cycle, the average gaps of the LBMK, Kessler and PARS groups were 0.76 ± 0.44 mm, 1.80 ± 0.82 mm, and 2.66 ± 1.04 mm, respectively. The LBMK group had a significantly reduced gap than the other groups (p < 0.01). The LBMK group gaps were all within 2 mm. The Kessler and PARS groups had six, and two specimens within 2 mm, respectively. After the second loading cycle, the average end gaps of the LBMK, Kessler, and PARS groups were 3.68 ± 1.08 mm, 5.70 ± 0.89 mm and 7.59 ± 1.26 mm, respectively. The LBMK group had a significantly reduced average gap than the other groups (p < 0.01). The maximum load-to-failure was highest 732.8 ± 138 N in the LBMK than the other groups (p < 0.01). CONCLUSION: The biomechanical strength of the LBMK suture was significantly greater than Kessler and PARS. The reduced gap in the LBMK group suggests superior resistance to gap formation, which may occur during early postoperative rehabilitation.


Assuntos
Tendão do Calcâneo/cirurgia , Técnicas de Sutura , Tendão do Calcâneo/lesões , Animais , Fenômenos Biomecânicos/fisiologia , Bovinos , Suturas
18.
Br J Clin Pharmacol ; 86(8): 1528-1536, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32069516

RESUMO

AIMS: Hetrombopag olamine is a novel small-molecule, nonpeptide thrombopoietin receptor agonist developed for immune thrombocytopenia treatment. This study aims to determine the safety and the effect of fasting duration after administration of hetrombopag on pharmacokinetics and pharmacodynamics in Chinese healthy subjects. METHODS: A randomized, open-label, single-dose, 3-period crossover, self-control trial was conducted. 15 eligible subjects were enrolled and received hetrombopag 7.5 mg at day 1 of each period followed by a standard meal 4 hours postdose (treatment A/fasting condition), or a high-calorie, high-fat meal 1 hour postdose (treatment B), or a high-calorie, high-fat meal 2 hours postdose (treatment C). The plasma concentrations of hetrombopag were determined by validated liquid chromatography-tandem mass spectrometry, platelet counts were quantified by blood test. Analysis was performed using a mixed model, including treatment, period as fixed effects and participant as a random effect. RESULTS: Compared with treatment A, peak concentration and area under concentration-time curve extrapolated to infinity decreased by 56 and 74.6%, and 44 and 61% in treatments B and C, respectively. The mean platelet number on day 6 increased by 15.8, 6.96 and 10.26%, respectively, in treatments A, B and C in comparison with baseline platelet level. No severe adverse events happened in any of the 3 treatments. CONCLUSION: Hetrombopag was well tolerated in healthy male subjects under fasted/fed conditions. The shorter fasting duration resulted in lower hetrombopag exposure, corresponding to a lower level of platelet elevation. Therefore, we recommended oral administration of hetrombopag on an empty stomach (fasting condition) or at least 2 hours before a meal to achieve maximum bioavailability.


Assuntos
Jejum , Interações Alimento-Droga , Hidrazonas/administração & dosagem , Pirazolonas/administração & dosagem , Administração Oral , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Meia-Vida , Voluntários Saudáveis , Humanos , Hidrazonas/farmacocinética , Masculino , Pirazolonas/farmacocinética
19.
Pulm Pharmacol Ther ; 61: 101902, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045673

RESUMO

BACKGROUND: Indacaterol is one of the long-acting beta2-adrenergic agonists, referred as first-line monotherapy for Chronic obstructive pulmonary disease since 2011. Generic products are encouraged to benefit the large COPD patients in China, in which can provide more choices association with reduced cost and improve the quality of patient life. OBJECTIVE: The three-part study consists of two independent cohorts of thirty-six subjects, aimed to evaluate the bioequivalence (BE) of two indacaterol formulations in gastrointestinal (GI) absorption charcoal-block or non-block conditions. One pilot study performed in six healthy subjects to determine the blocking effect of a new charcoal-based regimen on GI absorption after orally inhalation of indacaterol. METHODS: Two BE studies were conducted with a randomized, open-label, 2-period crossover design in two independent 36-healthy-subject cohorts, equivalence in systemic and lung deposition was assessed after inhalation of a single dose of 150 µg indacaterol (test or reference formulation) alone or concomitant administration of charcoal. The charcoal-based regimen was improved by optimizing the dose and number of doses, and its blocking efficacy against GI absorption was assessed in a pilot study. Six healthy subjects received 9 g charcoal 10 min before, immediately after and 2 h after indacaterol (3 g/100 ml water × 3 times). Blood collected at predetermined time points up to 72 h. Plasma indacaterol concentrations were determined using HPLC-MS/MS. Pharmacokinetics parameters were calculated with non-compartment analysis. Equivalences were concluded if the 90% confidence interval (CI) for test: reference of Cmax and AUC0-t fell within the limits of 0.8-1.25. RESULTS: Indacaterol was undetectable in plasma samples in pilot study. The T/R ratio of the geometric mean Cmax and AUC0-t was 109.9% (90% CI, 106.1-113.8%) and 104.8% (90% CI, 101.5-108.1%) for charcoal-block subjects and 105.4% (90% CI, 99.8% ~ 111.3%), and 101.0% (90% CI, 97.7%-104.4%) for non-block subjects. No serious adverse events were reported. CONCLUSIONS: The results showed that 150 µg indacaterol (+/- 9 g charcoal) was well tolerated in all subjects. The two formulations are bioequivalent in terms of the rate and absorption both in charcoal-block and non-block conditions. The improved charcoal-based regimen demonstrated to be effective and fully blockade of GI absorption of indacaterol.


Assuntos
Carvão Vegetal/uso terapêutico , Indanos/administração & dosagem , Indanos/farmacocinética , Quinolonas/administração & dosagem , Quinolonas/farmacocinética , Administração por Inalação , Adulto , Povo Asiático , Estudos Cross-Over , Composição de Medicamentos , Feminino , Humanos , Indanos/efeitos adversos , Masculino , Maleatos , Pessoa de Meia-Idade , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Quinolonas/efeitos adversos , Equivalência Terapêutica , Adulto Jovem
20.
Sci Total Environ ; 705: 135816, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31972947

RESUMO

Pyrrhotite is a potential source of S2- for the sulfide precipitation of nonferrous metal ions in hydrometallurgy and waste water treatment. In this study, different pyrrhotite crystals were prepared using zero-valent iron and sulfur to determine the effects of the pyrrhotite's structure on the sulfide precipitation of copper ions. The results indicate that the sulfide precipitation of copper ions highly depends on the crystal structure and crystallinity of pyrrhotite. Monoclinic pyrrhotite was found to be the most effective for copper sulfide precipitation, which can be used for the selective precipitation of copper ions from arsenic wastewater. More than 96% copper ions were removed with little loss of arsenic, contributing to a copper product of 20.2% Cu and 0.7% As, which can serve as raw materials of copper metallurgy. X-ray diffraction analysis showed the presence of CuS and (CuxFe1-x)S, indicating that most copper ions precipitated as CuS and some copper ions entered the FeS lattice by a lattice substitution reaction. Therefore, monoclinic pyrrhotite may provide an alternative solution for the selective precipitation of copper from arsenic wastewater.

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