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1.
Chemosphere ; 287(Pt 4): 132418, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34600927

RESUMO

Water pollution produced by various contaminants is presently a major worldwide issue, posing a significant challenge to the development of novel materials for water treatment. Herein, robust and recyclable biochar-graphene oxide (BC-GO) composite monoliths were prepared utilizing lignin precursor as a carbon source in a one-pot hydrothermal process free of hazardous chemicals. Characterization results indicated the BC-GO composite monolith had abundant microchannels, nanopores, and a large specific surface area, thereby exhibiting a high adsorption capacity of 796.8 mg g-1 to doxycycline in water, which was superior to conventional adsorbents. Furthermore, by annealing the BC-GO composite monolith, it could be transformed to hydrophobic (CA = 140°). The annealed BC-GO composite monolith retained a pronounced porous structure with a larger surface area and showed exceptional absorption capabilities of 55-130 g g-1 toward various oils and solvents, which were higher/comparable to previously reported graphene-based materials. In addition, both BC-GO composite monoliths were highly stable and could be reused for a number of cycles of pollutants removal. The simplicity, environmental friendliness, and effectiveness of our approach to building BC-GO composite monoliths may pave the way for their future applications in the field of water purification.

2.
Eur J Pharmacol ; : 174484, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34508752

RESUMO

Treprostinil palmitil (TP) is a long-acting inhaled pulmonary vasodilator prodrug of treprostinil (TRE). In this study, TP was delivered by inhalation (treprostinil palmitil inhalation suspension, TPIS) in a rat sugen 5416 (Su)/hypoxia (Hx) model of pulmonary arterial hypertension (PAH) to evaluate its effects on hemodynamics, pulmonary vascular remodeling, and cardiac performance and histopathology. Male Sprague-Dawley rats received Su (20 mg/kg, s.c), three weeks of Hx (10% O2) and 5 or 10 weeks of normoxia (Nx). TPIS was given during the 5-10 week NX period after the Su/Hx challenge. Su/Hx increased the mean pulmonary arterial blood pressure (mPAP) and right heart size (Fulton index), reduced cardiac output (CO), stroke volume (SV) and heart rate (HR), and increased the thickness and muscularization of the pulmonary arteries along with obliteration of small pulmonary vessels. In both the 8- and 13-week experiments, TPIS at inhaled doses ranging from 39.6 to 134.1 µg/kg, QD, dose-dependently improved pulmonary vascular hemodynamics, reduced the increase in right heart size, enhanced cardiac performance, and attenuated most of the histological changes induced by the Su/Hx challenge. The PDE5 inhibitor sildenafil, administered at an oral dose of 50 mg/kg, BID for 10 weeks, was not as effective as TPIS. These results in Su/Hx challenged rats demonstrate that inhaled TPIS may have superior effects to oral sildenafil. We speculate that the improvement of the pathobiology in this PAH model induced by TPIS involves effects on pulmonary vascular remodeling due to the local effects of TRE in the lungs.

3.
Phys Rev Lett ; 127(8): 083901, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477417

RESUMO

We theoretically reveal the link between two types of self-acceleration mechanisms widely emerging in wave dynamics and experimentally demonstrate such a connection via pulse interactions in nonlinear optical fibers. We find that, in order to realize a pulse pair subjected to a diametric drive acceleration, one of the two components can be directly obtained from a self-accelerating Airy-like pulse under appropriate conditions. Such a form of synchronized acceleration cannot be achieved by approaches previously used to generate diametric drive acceleration. Our results generalize the fundamental concept of diametric drive acceleration and may bring about unconventional approaches to control self-accelerating waves.

4.
J Hazard Mater ; 423(Pt A): 127107, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34523501

RESUMO

A new strategy for co-immobilization of laccase (Lac) and mediator 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) on geopolymer microspheres (GM) was reported in this work, which was promoted by pre-embedded homologous amino acids, i.e., histidine (His) and cysteine (Cys). The GM-H2C1 produced with a His/Cys ratio of 2:1 was highly efficient in co-immobilizing Lac and ABTS. The as-prepared composite biocatalyst (Lac-ABTS@GM-H2C1) exhibited the highest degradation rate (94.78%) to the model pollutant (Congo Red, CR), which was superior to free Lac-ABTS (79.23%) and Lac@GM-H2C1 (53.82%). The enhanced degradation efficiency of CR by the Lac-ABTS@GM-H2C1 was due to the promoted electron transfer and shortened mass transfer distance. Moreover, Lac-ABTS@GM-H2C1 demonstrated good pH resistance, competitive storage stability, and good reusability during ten cycles of CR degradation.

5.
Clin Infect Dis ; 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34453527

RESUMO

Using detailed exposure information on COVID-19 cases, we estimated the mean latent period to be 5.5 days (95% confidence interval: 5.1-5.9 days), shorter than the mean incubation period (6.9 days). Laboratory testing may allow shorter quarantines since 95% of COVID-19 cases shed virus within 10.6 days (95%CI: 9.6-11.6) of infection.

6.
Medicine (Baltimore) ; 100(33): e26944, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414955

RESUMO

BACKGROUND: To explore the diagnostic value of computed tomography (CT) imaging for duodenal lipoma and the potential clinical significance of the findings. METHODS: Clinicopathological and CT data from 57 patients, who were diagnosed with duodenal lipoma at the first affiliated Hospital of Zhengzhou University (Zhengzhou, China) between June 2014 and March 2019, were retrospectively reviewed. Data collected included location and size of the tumor, morphological manifestations (shape, density, boundary), concomitant diseases, pathology and gastroscopy results, and follow-up. Follow-up was performed via telephone, and surgical patients were followed-up for recurrence, metastasis and tumor size, and morphological changes. The follow-up period was up to January 2019. RESULTS: Of the 57 patients with duodenal lipoma, contrast-enhanced scanning was performed in 7 cases. The tumor was located in the descending duodenum in 33 cases, the ascending in 4 cases, the horizontal in 16 cases, and the bulb in 4 cases. Mean tumor size was 13.0 ±â€Š5.8 mm. CT morphological features of the tumor were as follows: tumor shape, round, quasi-round, or oval (n = 42); long strip (n = 3); nodular (n = 2); triangular (n = 1); and irregular lobulated (n = 9). Among the 57 patients, tumor density was homogeneous in 52 cases, inhomogeneous in 4 cases, and nodular with calcification in 1 case. The tumor boundary was classified as clear and with no capsule. Diseases concomitant with the tumor were as follows: gastritis (n = 23), gastric adenocarcinoma (n = 1), and gastric lymphoma (n = 1). Esophageal disease was found in 16 cases, including reflux esophagitis (n = 12) and esophageal cancer (n = 4). There were 13 cases of gallbladder and biliary disease, including cholecystolithiasis and cholecystitis (n = 9), common bile duct disease (n = 2), colorectal cancer (n = 4), lung cancer (n = 2), duodenal carcinoma with obstruction (n = 1), and ureteral space narrowing (n = 1). CONCLUSION: CT was an effective, non-invasive method for diagnosis of duodenal lipoma. CT imaging could clearly discern location, size, shape, and nature of duodenal lipomas. Duodenal lipoma can be associated with digestive tract inflammatory diseases and tumors in different locations, and its diagnosis is potentially valuable for their prevention and treatment.


Assuntos
Neoplasias Duodenais/diagnóstico por imagem , Lipoma/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/patologia , Duodeno/diagnóstico por imagem , Duodeno/patologia , Feminino , Humanos , Lipoma/diagnóstico , Lipoma/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
7.
Emerg Infect Dis ; 27(9): 2288-2293, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34423766

RESUMO

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23-February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient's onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.


Assuntos
COVID-19 , SARS-CoV-2 , Adolescente , Criança , China/epidemiologia , Humanos , Incidência , Modelos Logísticos
8.
Eur J Pharm Biopharm ; 166: 10-18, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34082122

RESUMO

The purpose of these studies was to understand the effect on product performance of batch-to-batch variability in both the amikacin liposome inhalation suspension (ALIS) formulation and its delivery device, the Lamira® nebulizer system, designed and manufactured by PARI (PARI Pharma GmbH, Munich, Germany). Three batches of ALIS spanning a range of lipid concentrations (43, 48 and 54 mg/mL) were tested with nine PARI inhalation devices that varied within the production process of the vibrating membrane with respect to hole geometry. Three hole geometry clusters were built including a geometry close to the mean geometry (median) and two geometries deviating from the mean geometry with smaller (smaller) and larger (larger) holes. The output parameters included the nebulization rate, the aerosol droplet size distribution, the liposome vesicle size post-nebulization, and the fraction of amikacin that remained encapsulated post-nebulization. Across the 27 experimental combinations of three formulation batches and nine devices, the nebulization time varied between 12 and 15 min with the fastest nebulization rate occurring with the combination of low lipid concentration and larger hole geometry (0.68 g/min) and the slowest nebulization rate occurring with the combination of high lipid concentration and the smaller hole geometry (0.59 g/min). The mean liposome vesicle size post-nebulization ranged from 269 to 296 nm across all experimental combinations which was unchanged from the control samples (276-292 nm). While all three batches contained > 99% encapsulated amikacin prior to nebulization, the nebulization process resulted in a consistent generation of ~ 35% unencapsulated amikacin (range: 33.8% to 37.6%). There was no statistically significant difference in the generated aerosol particle size distributions. The mass median aerodynamic diameters (MMAD) ranged from 4.78 µm to 4.98 µm, the geometric standard deviations (GSD) ranged from 1.61 to 1.66, and the aerosol fine particle fraction (FPF < 5 µm) ranged from 50.3 to 53.5%. The emitted dose (ED) of amikacin ranged from 473 to 523 mg (80.2 to 89.3% of loaded dose (LD)) and the fine particle dose (FPD < 5 µm) ranged from 244 to 278 mg (41.4 to 47.1% of label claim (LC)). In conclusion, while variations in the lipid concentration of the ALIS formulation and the device hole geometry had a small but significant impact on nebulization time, the critical aerosol performance parameters were maintained and remained within acceptable limits.

9.
Analyst ; 146(13): 4261-4267, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34105527

RESUMO

Glycosylation of proteins plays important roles in the occurrence and development of chronic diseases. In this study, we report an enrichment method of intact N-glycopeptides using a magnetic polyaniline nanomaterial (Fe3O4@PANI). Under the synergistic effect of hydrogen bonding and electrostatic adsorption, Fe3O4@PANI can rapidly and easily enrich N-glycopeptides derived from standard protein (bovine fetuin and transferrin) tryptic digests and serum haptoglobin tryptic digests. Finally we have detected 63 glycopeptides in the glycosylation sites of both N204 and N211 from the serum haptoglobin beta chain using MALDI FTICR MS. Compared with non-magnetic materials, Fe3O4@PANI can achieve complete separation from complex biological samples, meeting the requirement of the high purity of samples for mass spectrometric detection. Overall, Fe3O4@PANI exhibits great application potential in the highly efficient enrichment of intact N-glycopeptides due to its stability and convenient preparation.


Assuntos
Glicopeptídeos , Nanoestruturas , Compostos de Anilina , Animais , Bovinos , Interações Hidrofóbicas e Hidrofílicas , Fenômenos Magnéticos
10.
Antimicrob Agents Chemother ; 65(7): e0031621, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-33941518

RESUMO

Chronic pulmonary methicillin-resistant Staphylococcus aureus (MRSA) disease in cystic fibrosis (CF) has a high probability of recurrence following treatment with standard-of-care antibiotics and represents an area of unmet need associated with reduced life expectancy. We developed a lipoglycopeptide therapy customized for pulmonary delivery that not only demonstrates potent activity against planktonic MRSA, but also against protected colonies of MRSA in biofilms and within cells, the latter of which have been linked to clinical antibiotic failure. A library of next-generation potent lipoglycopeptides was synthesized with an emphasis on attaining superior pharmacokinetics (PK) and pharmacodynamics to similar compounds of their class. Our strategy focused on hydrophobic modification of vancomycin, where ester and amide functionality were included with carbonyl configuration and alkyl length as key variables. Candidates representative of each carbonyl attachment chemistry demonstrated potent activity in vitro, with several compounds being 30 to 60 times more potent than vancomycin. Selected compounds were advanced into in vivo nose-only inhalation PK evaluations in rats, where RV94, a potent lipoglycopeptide that utilizes an inverted amide linker to attach a 10-carbon chain to vancomycin, demonstrated the most favorable lung residence time after inhalation. Further in vitro evaluation of RV94 showed superior activity to vancomycin against an expanded panel of Gram-positive organisms, cellular accumulation and efficacy against intracellular MRSA, and MRSA biofilm killing. Moreover, in vivo efficacy of inhaled nebulized RV94 in a 48 h acute model of pulmonary MRSA (USA300) infection in neutropenic rats demonstrated statistically significant antibacterial activity that was superior to inhaled vancomycin.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/uso terapêutico , Lipoglicopeptídeos , Pulmão , Testes de Sensibilidade Microbiana , Ratos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina
11.
Ultrasound Med Biol ; 47(8): 2404-2415, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34052063

RESUMO

This study aims to investigate the feasibility of quantitative ultrasonic backscatter in evaluating human cortical and trabecular bone densities in vivo based on a head-down-tilt bed rest study, with 36 participants tested through 90 d of bed rest and 180 d of recovery. Backscatter measurements were performed using an ultrasonic backscatter bone diagnostic instrument. Backscatter parameters were calculated with a dynamic signal-of-interest method, which was proposed to ensure the same ultrasonic interrogated volume in cortical and trabecular bones. The backscatter parameters exhibited significant correlations with site-matched bone densities provided by high-resolution peripheral quantitative computed tomography (0.33 < |R| < 0.72, p < 0.05). Some bone densities and backscatter parameters exhibited significant changes after the 90-d bed rest. The proposed method can be used to characterize bone densities, and the portable ultrasonic backscatter bone diagnostic device might be used to non-invasively reveal mean bone loss (across a group of people) after long-term bed rest and microgravity conditions of spaceflight missions.


Assuntos
Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Espalhamento de Radiação , Ondas Ultrassônicas , Adulto , Repouso em Cama , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Masculino
12.
Clin Chim Acta ; 519: 276-284, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33989614

RESUMO

BACKGROUND AND AIMS: Early diagnosis is key to improving the prognosis of gastric cancer. Altered phospholipid metabolism has been observed in different types of cancer. This study assessed serum phospholipid levels of patients with gastric cancer to explore biomarkers for its early diagnosis. MATERIALS AND METHODS: A total of 199 participants were enrolled, including patients with early gastric cancer or precancerous gastric lesions and healthy controls. Serum phospholipids were extracted and identified using mass spectrometry. The relative abundances of these phospholipids were compared among patients at different disease stages. Twenty-four patients with early gastric cancer were followed up, and their serum phospholipid levels were compared beween before and after resection. RESULTS: Fifty-four phospholipids were identified. Phosphatidylethanolamine (36:3), phosphatidylethanolamine (36:2), phosphatidylcholine (32:0), and sphingomyelin (d18:0/18:1(9Z)) were more abundant in patients with early gastric cancer than in healthy controls. The area under the receiver operating curve of sphingomyelin (d18:0/18:1(9Z)) reached 0.883 in the training set (sensitivity 81.08%, specificity 78.82%) and 0.874 in the validation set. The levels of phosphatidylethanolamine (36:2), phosphatidylcholine (32:0), and sphingomyelin (d18:0/18:1(9Z)) significantly declined after the cancerous lesions were resected. CONCLUSION: Serum phospholipids can serve as potential biomarkers for the early diagnosis of gastric cancer.


Assuntos
Fosfolipídeos , Neoplasias Gástricas , Biomarcadores , Detecção Precoce de Câncer , Humanos , Esfingomielinas , Neoplasias Gástricas/diagnóstico
13.
Ying Yong Sheng Tai Xue Bao ; 32(4): 1230-1240, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33899391

RESUMO

In this study, desert grassland, grassland edge, shrubland edge, shrubland were selec-ted as four transition sites in a nearly 30 years typical desert grassland-shrubland mosaic formed by anthropogenic shrub introduction. Soil properties and soil microbial characteristics under vegetation patches and bare interspace in each site were investigated to examine the responses of soil nitrogen to the desert grassland-shrubland state transition. It was shown that the aboveground biomass increased with transition from desert grassland to shrubland. Annual herbs increased largely with the introduction of shrubs. Soil moisture, microbial biomass and total nitrogen and carbon decreased with the transition. The abundance of microogranisms was lower in grassland edge and shrubland edge, and then increased in shrubland, which was slightly higher than that of desert grassland. With respect to nitrogen, nitrate content reached the highest level of 28.45 mg N·kg-1 and ammonium reached the lowest level of 4.81 mg N·kg-1 in shrubland, which were significantly increased by 52.3% and decreased by 10.4% compared with desert grassland. In addition, soil moisture and microbial biomass nitrogen was positively correlated across all sites. The relationship between mine-ralized nitrogen and soil moisture was non-linear, as they were positively correlated in desert grassland and grassland edge, but negatively correlated in shrubland edge and shrubland. During the 30-year transition from desert grassland to shrubland, our results showed that soil total nitrogen and microbial biomass nitrogen were significantly decreased, but mineralized nitrogen, especially for nitrate, significantly increased over time, indicating that soil nitrification was inhibited in desert grassland but accelerated in shrubland.


Assuntos
Nitrogênio , Solo , Carbono/análise , China , Ecossistema , Pradaria , Nitrogênio/análise
14.
Clin Infect Dis ; 73(6): e1314-e1320, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-33772573

RESUMO

BACKGROUND: The relative contributions of asymptomatic, presymptomatic, and symptomatic transmission of severe acute respiratory syndrome coronavirus 2 have not been clearly measured, although control measures may differ in response to the risk of spread posed by different types of cases. METHODS: We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from 4 provinces and 1 municipality in China. We estimated the variation in risk of transmission over time and the severity of secondary infections by symptomatic status of the infector. RESULTS: There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included in the study. The secondary attack rates among close contacts of symptomatic and asymptomatic index cases were 4.1% (128 of 3136) and 1.1% (12 of 1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (odds ratio, 3.79; 95% confidence interval, 2.06-6.95). Approximately 25% (32 of 128) and 50% (6 of 12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. CONCLUSIONS: Asymptomatic and presymptomatic transmissions play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.


Assuntos
COVID-19 , SARS-CoV-2 , China/epidemiologia , Busca de Comunicante , Humanos , Incidência
15.
Acupunct Med ; 39(6): 656-662, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33715459

RESUMO

BACKGROUND: Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. METHODS: Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at -30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. RESULTS: Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased (p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment (p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group (p < 0.05). CONCLUSIONS: These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

16.
Inflamm Res ; 70(4): 445-457, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33609142

RESUMO

OBJECTIVE AND DESIGN: Diabetic retinopathy (DR) is one of the most serious microvascular complications of diabetes mellitus (DM). MicroRNAs (miRNAs) have been discovered to play a crucial role in DR, but the mechanisms underlying the effects of miR-301a-3p on DR are poorly understood. This paper was designed to explore the possible role of miR-301a-3p in DR. METHODS: The diabetic rat model was established by a single intraperitoneal injection of streptozotocin (STZ). The effects of miR-301a-3p on the biological functions of HRECs were determined through a series of experiments in vitro/vivo. RESULTS: The results revealed that interference with miR-301a-3p could decrease the expressions of inflammatory factors and apoptosis in the retinal tissue of DR. Furthermore, it can alleviate the oxidative stress in DR serum, reduce VEGF expression, increase endothelial cell marker expression, and inhibit (High Glucose) HG-induced apoptosis of HRECs. Six-transmembrane epithelial antigen of prostate 4 (STEAP4) was the target of miR-301a-3p. All the effects of miR-301a-3p in DR model were reversed by STEAP4 inhibitor. CONCLUSION: miR-301a-3p promotes diabetic retinopathy via regulation of STEAP4. The findings in this study may provide a vital reference for the drug research and development in DR treatment.

17.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430435

RESUMO

Treprostinil palmitil (TP) is a prodrug of treprostinil (TRE), a pulmonary vasodilator that has been previously formulated for inhaled administration via a nebulizer. TP demonstrates a sustained presence in the lungs with reduced systemic exposure and prolonged inhibition of hypoxia-induced pulmonary vasoconstriction in vivo. Here, we report on re-formulation efforts to develop a more convenient solution-based metered-dose inhaler (MDI) formulation of TP, a treprostinil palmitil inhalation aerosol (TPIA) that matches the pharmacokinetic (PK) and efficacy profile of a nebulized TP formulation, treprostinil palmitil inhalation suspension (TPIS). MDI canisters were manufactured using a two-stage filling method. Aerosol performance, formulation solubility, and chemical stability assays were utilized for in vitro evaluation. For in vivo studies, TPIA formulations were delivered to rodents using an inhalation tower modified for MDI delivery. Using an iterative process involving evaluation of formulation performance in vitro (TP and excipient solubility, chemical stability, physical stability, and aerosol properties) and confirmatory testing in vivo (rat PK and efficacy, guinea pig cough), a promising formulation was identified. The optimized formulation, TPIA-W, demonstrates uniform in vitro drug delivery, a PK profile suitable for a once-daily administration, efficacy lasting at least 12 h in a hypoxic challenge model, and a significantly higher cough threshold than the parent drug treprostinil.


Assuntos
Aerossóis/farmacologia , Epoprostenol/análogos & derivados , Pró-Fármacos/farmacologia , Hipertensão Arterial Pulmonar/tratamento farmacológico , Administração por Inalação , Animais , Modelos Animais de Doenças , Composição de Medicamentos , Epoprostenol/química , Epoprostenol/farmacologia , Cobaias , Humanos , Nanopartículas/química , Pró-Fármacos/química , Hipertensão Arterial Pulmonar/patologia , Ratos , Vasoconstrição/efeitos dos fármacos , Vasodilatadores/química , Vasodilatadores/farmacologia
18.
Influenza Other Respir Viruses ; 15(1): 19-26, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32767657

RESUMO

BACKGROUND: Between mid-January and early February, provinces of mainland China outside the epicentre in Hubei province were on high alert for importations and transmission of COVID-19. Many properties of COVID-19 infection and transmission were still not yet established. METHODS: We collated and analysed data on 449 of the earliest COVID-19 cases detected outside Hubei province to make inferences about transmission dynamics and severity of infection. We analysed 64 clusters to make inferences on serial interval and potential role of pre-symptomatic transmission. RESULTS: We estimated an epidemic doubling time of 5.3 days (95% confidence interval (CI): 4.3, 6.7) and a median incubation period of 4.6 days (95% CI: 4.0, 5.2). We estimated a serial interval distribution with mean 5.7 days (95% CI: 4.7, 6.8) and standard deviation 3.5 days, and effective reproductive number was 1.98 (95% CI: 1.68, 2.35). We estimated that 32/80 (40%) of transmission events were likely to have occurred prior to symptoms onset in primary cases. Secondary cases in clusters had less severe illness on average than cluster primary cases. CONCLUSIONS: The majority of transmissions are occurring around illness onset in an infected person, and pre-symptomatic transmission does play a role. Detection of milder infections among the secondary cases may be more reflective of true disease severity.


Assuntos
COVID-19/transmissão , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Eur Arch Otorhinolaryngol ; 278(3): 683-688, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32556783

RESUMO

PURPOSE: This study aimed to report the occurrence of benign paroxysmal positional vertigo (BPPV) in a 90-day head-down bed rest experiment and evaluate the potential relationship between BPPV-related seizures and bone metabolic changes. METHODS AND DESIGN: Five cases of lateral semicircular canal (LSC) BPPV were diagnosed during a 90-day head-down bed rest experiment. Five age-matched subjects who participated in this experiment and never felt dizziness or vertigo were assigned as controls. The differences between the BPPV and the controls in lumbar bone mineral density, 25-hydroxyvitamin D level, corrected serum calcium, potassium, sodium, phosphorus, iron, uric acid and N-terminal osteocalcin were analyzed to determine the cause of LSC-BPPV. RESULTS: BPPV occurred from Day 17 to Day 42 during head-down bed rest. The occurrences of BPPV were related to low 25-hydroxyvitamin D level (BPPV:20.70 ± 1.95 ng/L vs. control: 30.59 ± 2.75 ng/L at Day 30 during HDBR, p < 0.05). The relatively longer duration in the prone posture at 6° head down in this experiment may have a potential role in the involvement of the LSC. The maneuver used in the experiment effectively alleviated the acute symptoms of LSC-BPPV. CONCLUSION: The cases of LSC-BPPV in the early period of 90-day of head-down bed rest were related to the low 25-hydroxyvitamin D level and the 6° head-down posture. These results suggest that the potential role of unloading-induced bone loss on BPPV-related seizures deserves attention in future studies of long-term bed rest.


Assuntos
Repouso em Cama , Vertigem Posicional Paroxística Benigna , Vertigem Posicional Paroxística Benigna/diagnóstico , Vertigem Posicional Paroxística Benigna/etiologia , Calcifediol , Humanos , Postura , Canais Semicirculares
20.
J Vet Pharmacol Ther ; 44(3): 359-366, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33270918

RESUMO

Tilmicosin (TMS) is a semisynthetic macrolide antibiotic restricted to veterinary use but is only partially soluble in aqueous solutions, which limits its administration in treatments. We developed a strategy to enhance the supersaturated solubility of TMS using amorphous solid dispersion (SD). The dissolution profile shown that the dissolution rate of TMS-SD was obviously faster than TMS. The pharmacokinetics of tilmicosin (TMS) and tilmicosin solid dispersion (TMS-SD) in pigs after oral administration at a single dose of 50 mg/kg b.w were investigated. The tmax of TMS-SD (2.50 hr) was 1.80 times faster than TMS (4.50 hr) (p < .05). There were no significant differences in the other PK parameters (Cmax , t1/2ß , V/F, CL/F, MRT, and AUC0-inf ) (p > .05). The mean relative bioavailability of TMS-SD compared with TMS was 140.39%, according to the AUC0-inf values. These results demonstrated that the solid dispersion technique enhanced the bioavailability of TMS and the new formulation administered to animals via drinking water may be used as a therapeutic alternative for clinical treatments.

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