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1.
Cureus ; 16(4): e57661, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38707059

RESUMO

BACKGROUND:  Although an increasing number of network meta-analyses have been conducted on the effectiveness of conservative therapy for knee osteoarthritis, these may have been poorly planned and executed.We aimed to review the qualities of a comprehensive set of network meta-analyses on rehabilitation therapies for knee osteoarthritis and provide an overview of the effectiveness of each therapy. METHODS: The eligibility criteria were as follows: (i) conservative rehabilitation was the primary treatment in the intervention group, (ii) included patients were diagnosed with knee osteoarthritis, and (iii) patient groups were aged ≤75 years, and rehabilitation interventions comprised exercise, orthotic, or physical therapies or patient education. Two independent reviewers screened the titles and abstracts of the identified records and selected the eligible reviews; their full texts were further assessed for eligibility. Then, a checklist derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension statement for the reporting of systematic reviews incorporating network meta-analyses of healthcare Interventions was used to validate the completeness of the reporting of each network meta-analysis. Furthermore, the statistical and outcome data regarding the quality of life, knee joint function and pain, adverse events, and physical functions were extracted using a customized spreadsheet. RESULTS: Overall, 2701 titles and abstracts were screened, and eight network meta-analyses were ultimately selected. Nearly all reviews adequately addressed the PRISMA extension checklist, and the completeness of reporting was adequate; therefore, all expected information could be extracted. However, the methodology used to confirm the transitivity assumption was insufficient in many reviews. The following interventions were effective in reducing pain and improving physical function: (i) strengthening, flexibility, aerobic, and mind-body exercises, (ii) pulsed ultrasound, (iii) focused and radial extracorporeal shockwave therapy, and (iv) continuous ultrasound. The following interventions were effective in improving the quality of life: (i) strengthening, (ii) mixed, and (iii) mind-body exercises. CONCLUSIONS: Our results suggested that exercise therapies, including muscle-strengthening, aerobic, flexibility, and mind-body exercises, are likely to be effective for pain relief and functional improvement in knee osteoarthritis. This may be the first review to provide a comprehensive perspective for considering priorities for future rehabilitation interventions for knee osteoarthritis.

2.
Odontology ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502470

RESUMO

The research exploiting the ability of dental materials to induce or prevent secondary caries (SC) development still seems inconclusive. Controlling bacterial adhesion by releasing bacteriostatic ions and improving the surface structure has been suggested to reduce the occurrence of SC. This paper analyses the impact of five distinctively composed dental materials on cariogenic biofilm formation. Forty-five specimens of three composites (CeramX Spectra ST, Admira Fusion, Beautifil II) and two glass-ionomers (Fuji II LC, Caredyne Restore), respectively, were incubated in bacterial suspension composed of Streptococcus mutans, Lactobacillus acidophilus, Streptococcus mitis, Streptococcus sanguinis, and Streptococcus salivarius at pH 7.0 and 5.5. Coverslips were used as a control. Adhered bacteria were collected after 2, 4, 6, 12, 24, and 48 h and analyzed using quantitative polymerase chain reaction (qPCR). Fluoride leakage was measured at each collection. The specimens' surface topography was assessed using interferometry. In the present study, surface roughness seemed to have a partial role in bacterial adhesion and biofilm formation, together with chemical composition of the materials tested. Despite differences in fluoride leakage, biofilm accumulation was similar across materials, but the number of adhered bacteria differed significantly. A release of other ions may also affect adhesion. These variations suggest that certain materials may be more prone to initiating secondary caries.

3.
Chem Commun (Camb) ; 60(12): 1611-1614, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38230531

RESUMO

An efficient method to prepare dibenzothiophene S-oxides is disclosed. Suzuki-Miyaura cross-coupling of 2-bromoaryl sulfinate esters with arylboronic acids selectively at the bromo group followed by electrophilic cyclization of the resulting sulfinate ester moiety provides diverse dibenzothiophene S-oxides. Further transformations including Pummerer-type C-H propargylation and aryne reactions realize to synthesize highly functionalized dibenzothiophene derivatives.

4.
Photochem Photobiol ; 100(1): 146-158, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37477119

RESUMO

The effect of terahertz (THz) radiation has been studied in medicine. However, there is a lack of scientific information regarding its possible mutagenicity. Therefore, the present study aimed to assess the mutagenicity of 1.6 THz laser irradiation. The Ames test was conducted using five bacterial tester strains. The bacteria were subjected to (i) 1.6 THz laser irradiation at 3.8 mW/cm2 for 60 min using a tabletop THz pulse laser system, (ii) ultraviolet irradiation, (iii) treatment with positive control chemicals (positive control) or (iv) treatment with the solvent used in the positive control (negative control). After treatment, the bacterial suspensions were cultured on minimal glucose agar to determine the number of revertant colonies. In addition, the comet assay was performed using fibroblasts (V79) to assess possible DNA damage caused by the THz laser irradiation. The Ames test demonstrated that the THz laser irradiation did not increase the number of revertant colonies compared to that in the negative control group, whereas the ultraviolet irradiation and positive control treatment increased the number of revertant colonies. Thus, 1.6 THz laser irradiation is unlikely to be mutagenic. The comet assay additionally suggests that the THz laser irradiation unlikely induce cellular DNA damage.


Assuntos
Dano ao DNA , Mutagênicos , Mutagênicos/toxicidade , Ensaio Cometa , Mutagênese , Fibroblastos/efeitos da radiação , Testes de Mutagenicidade
5.
Anal Bioanal Chem ; 416(2): 407-417, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37968382

RESUMO

A polystyrene (PS) certified reference material (CRM) for the analysis of decabromodiphenyl ether (BDE 209) was issued. PS disk was prepared by injection molding of the mixture of versine PS and BDE 209. The certification of the PS CRM was conducted by two analytical methods with different sample preparation methods using isotope dilution mass spectrometry (IDMS). The certified value, wCRM, was 978 mg/kg, and this value coincided with the regulation value of BDE 209 in the Restriction of Hazardous Substances directive (1000 mg/kg). The uncertainties related to certification, uwmean, inhomogeneity, uhom, and long- and short-term instability, usts and ults, respectively, were evaluated based on the mass fraction of BDE 209. The uwmean, uhom, usts, and ults were 0.0265, 0.0046, 0.0061, and 0.0099 (relative), respectively, and the expanded uncertainty for this CRM was determined as 57 mg/kg (coverage factor is 2). Additionally, the quantitative capability of the thermal desorption-gas chromatography/mass spectrometry (TD-GC/MS) method was evaluated. In TD-GC/MS, the analytical values of the developed CRM obtained by the external and internal standard methods with matrix-free calibrants were out of the range of the wCRM (almost 10% larger or smaller), whereas those with matrix-matched calibrants agreed with the wCRM. In contrast to these results, the analytical values obtained by TD-GC/MS using IDMS were consistent with the wCRM no matter if matrix-free or matrix-matched calibrants were used. These results indicated that, for quantification of BDE 209 in PS, the trueness and precision of TD-GC/MS can be enhanced by applying IDMS without matrix-matched calibrants.

6.
J Pestic Sci ; 48(4): 137-148, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38090219

RESUMO

A method of quantifying glyphosate (Gly) in human urine by means of MonoSpin TiO extraction and 9-fluorenylmethoxycarbonyl chloride (FMOC-Cl) derivatization with isotope dilution mass spectrometry (IDMS) was investigated and optimized. The method's quantification limit under optimized conditions was 0.3 µg/kg for FMOC-Gly, which was comparable to or lower than those described in previous studies. When a spike test using human urine samples was carried out with optimized analytical conditions, the trueness for FMOC-Gly was as follows: 101.6-104.9% for a spike level of 0.5 µg/kg and 99.2-101.0% for a spike level of 30 µg/kg. The intra-day repeatability and inter-day reproducibility were <6.5%. The spike test results for validation between the "with" and "without" derivatization methods were comparable at 1 µg/kg. Our results indicate that using MonoSpin TiO extraction and FMOC-Cl derivatization with IDMS is an accurate method for analyzing Gly in human urine.

7.
Int J Mol Sci ; 24(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37958612

RESUMO

In recent decades, phage therapy has been overshadowed by the widespread use of antibiotics in Western countries. However, it has been revitalized as a powerful approach due to the increasing prevalence of antimicrobial-resistant bacteria. Although bacterial resistance to phages has been reported in clinical cases, recent studies on the fitness trade-offs between phage and antibiotic resistance have revealed new avenues in the field of phage therapy. This strategy aims to restore the antibiotic susceptibility of antimicrobial-resistant bacteria, even if phage-resistant variants develop. Here, we summarize the basic virological properties of phages and their applications within the context of antimicrobial resistance. In addition, we review the occurrence of phage resistance in clinical cases, and examine fitness trade-offs between phage and antibiotic sensitivity, exploring the potential of an evolutionary fitness cost as a countermeasure against phage resistance in therapy. Finally, we discuss future strategies and directions for phage-based therapy from the aspect of fitness trade-offs. This approach is expected to provide robust options when combined with antibiotics in this era of phage 're'-discovery.


Assuntos
Infecções Bacterianas , Bacteriófagos , Terapia por Fagos , Humanos , Bacteriófagos/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Terapia por Fagos/métodos , Infecções Bacterianas/terapia , Bactérias
8.
Nanoscale ; 15(46): 18939, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37970868

RESUMO

Expression of concern for 'Versatile plasmonic-effects at the interface of inverted perovskite solar cells' by Ahmed Esmail Shalan, et al., Nanoscale, 2017, 9, 1229-1236, https://doi.org/10.1039/C6NR06741G.

9.
JACS Au ; 3(10): 2692-2697, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37885589

RESUMO

Developing a method for creating a novel catalysis of organic molecules is essential because of the growing interest in organocatalysis. In this study, we found that cyclic carbonates immobilized on a nonporous or mesoporous silica support showed catalytic activity for hydrosilylation, which was not observed for the free cyclic carbonates, silica supports, or their physical mixture. Analysis of the effects of linker lengths and pore sizes on the catalytic activity and carbonate C=O stretching frequency revealed that the proximity of carbonates and surface silanols was crucial for synergistic hydrosilylation catalysis. A carbonate and silanol concertedly activated the silane and aldehyde for efficient hydride transfer. Density functional theory calculations on a model reaction system demonstrated that both the carbonate and silanol contributed to the stabilization of the transition state of hydride transfer, which resulted in a reasonable barrier height of 16.8 kcal mol-1. Furthermore, SiO2/carbonate(C4) enabled the hydrosilylation of an aldehyde with an amino group without catalyst poisoning, owing to the weak acidity of surface silanols, in sharp contrast to previously developed acid catalysts. This study demonstrates that immobilization on a solid support can convert inactive organic molecules into active and heterogeneous organocatalysts.

10.
J Mech Behav Biomed Mater ; 146: 106067, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37567065

RESUMO

Monolithic dental prostheses made of 3-6 mol% yttria-stabilized zirconia (3-6YSZ) have gained popularity owing to their improved material properties and semi-automated fabrication processes. In this study, we aimed to evaluate the influence of mechanical surface treatments, such as polishing, grinding, and sandblasting, on the residual stress of 3-6YSZ used for monolithic prostheses in association with crystalline phase transformation. Plate specimens were prepared from five dental zirconia blocks: Aadva Zirconia ST (3YSZ), Aadva Zirconia NT (6YSZ), Katana HT (4YSZ), Katana STML (5YSZ), and Katana UTML (6YSZ). The specimens were either polished using 1, 3, or 9 µm diamond suspensions, ground using 15, 35, or 55 µm diamond discs, or sandblasted at 0.2, 0.3, or 0.4 MPa. The residual stress, crystalline phase, and hardness were analyzed using the cosα method, X-ray diffraction (XRD), and Vickers hardness test, respectively. Additionally, we analyzed the residual stress on the surfaces of monolithic zirconia crowns (MZCs) made of 4YSZ, 5YSZ, and 6YSZ, which were processed using clinically relevant procedures, including manual grinding, followed by polishing using a dental electric motor on the external surface, and sandblasting on the internal surface. Residual stress analysis demonstrated that grinding and sandblasting, particularly the latter, resulted in the generation of compressive residual stress on the surfaces of the plate specimens. XRD revealed that the ground and sandblasted specimens contained a larger amount of the rhombohedral phase than that of the polished specimens, which may be a cause of the residual stress. Sandblasting significantly increased the Vickers hardness compared to polishing, which may possibly be due to the generation of compressive residual stress. In the case of MZCs, compressive residual stress was detected not only on the sandblasted surface, but also on the polished surface. The difference in the residual stress between the plate and crown specimens may be related to the force applied during the automated and manual grinding and polishing procedures. Further studies are required to elucidate the effects of the compressive residual stress on the clinical performance of MZCs.


Assuntos
Ítrio , Zircônio , Teste de Materiais , Propriedades de Superfície , Zircônio/química , Ítrio/química , Cerâmica/química , Diamante , Materiais Dentários , Polimento Dentário , Estresse Mecânico
11.
Org Biomol Chem ; 21(34): 6886-6891, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37602371

RESUMO

A practical method to synthesize sulfinate esters from aryl iodides is disclosed. Direct oxidation of thioesters prepared by copper-catalyzed C-S formation of aryl iodides realized the efficient synthesis of sulfinate esters. Due to the good accessibility of aryl iodides, a wide variety of sulfinate esters were prepared from easily available starting materials such as carboxylic acids and anilines.

12.
J AOAC Int ; 106(6): 1532-1541, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37439707

RESUMO

BACKGROUND: Supercritical fluid extraction (SFE) is a fast, versatile, and solvent-efficient automatic extraction method. Despite its advantages, the results of our proficiency tests imply that the applicability assessments of SFE for pesticide residues were insufficient. OBJECTIVE: In this study, as analytical method using SFE was optimized and validated by testing the incurred and fortified brown rice samples with organophosphorus (OP), pyrethroid (PYR), and dithiolane (DIT) pesticides. METHOD: A validation study using the incurred sample with etofenprox, fenitrothion, and isoprothiolane was performed by comparing the analytical results obtained using the SFE and solid-liquid extraction with homogenization (SLE), which is a well-validated official multi-residue extraction method. The tests on the fortified samples were also performed for seven pesticide residues, chlorpyrifos, diazinon, O-ethyl O-4-nitrophenyl phenylphosphonothioate (EPN), etofenprox, fenitrothion, isoxathion, and isoprothiolane, at three fortification levels, 0.001, 0.01, and 0.1 mg/kg. RESULTS: In the test on the incurred samples, optimized SFE-to-SLE analytical values (CSFE/CSLE) were 99.2-100.1%, with RSD lower than 3%. In contrast, the analytical-to-spiked concentrations in the tests on the fortified samples were 96.4-105.0%, with RSD lower than 8.8%. CONCLUSIONS: These results indicate that the proposed SFE method, which is well validated with the incurred brown rice sample, is useful for determining OP, PYR, and DIT pesticide residues in brown rice. HIGHLIGHTS: The proposed SFE method satisfies EU and Japanese maximum residue limits (MRLs). The consumption of solvent can be reduced to one-fourth of that of SLE using the proposed SFE method.


Assuntos
Cromatografia com Fluido Supercrítico , Oryza , Resíduos de Praguicidas , Piretrinas , Resíduos de Praguicidas/análise , Cromatografia com Fluido Supercrítico/métodos , Espectrometria de Massas em Tandem , Fenitrotion/análise , Piretrinas/análise , Cromatografia Líquida/métodos , Solventes/química
13.
Opt Express ; 31(12): 20274-20285, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381426

RESUMO

We have realized a comb system with a 30 GHz mode spacing, 62 % available wavelength coverage in the visible region, and nearly 40 dB spectral contrast by combining a robust erbium-doped-fiber-based femtosecond laser, mode filtering with newly designed optical cavities, and broadband-visible-range comb generation using a chirped periodically-poled LiNbO3 ridge waveguide. Furthermore, it is suggested that this system produces a spectrum with little change over 29 months. These features of our comb will contribute to fields requiring broad-mode-spacing combs, including astronomical observations, such as exoplanet exploration and the verification of the cosmic accelerating expansion.

14.
Nat Commun ; 14(1): 1696, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973291

RESUMO

Synthetic composite hydrogels comprising supramolecular fibers and covalent polymers have attracted considerable attention because their properties are similar to biological connective tissues. However, an in-depth analysis of the network structures has not been performed. In this study, we discovered the composite network can be categorized into four distinct patterns regarding morphology and colocalization of the components using in situ, real-time confocal imaging. Time-lapse imaging of the network formation process reveals that the patterns are governed by two factors, the order of the network formation and the interactions between the two different fibers. Additionally, the imaging studies revealed a unique composite hydrogel undergoing dynamic network remodeling on the scale of a hundred micrometers to more than one millimeter. Such dynamic properties allow for fracture-induced artificial patterning of a network three dimensionally. This study introduces a valuable guideline to the design of hierarchical composite soft materials.

15.
Clin Oral Investig ; 27(2): 739-750, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36484848

RESUMO

OBJECTIVES: An antimicrobial technique utilizing hydroxyl radicals generated by the photolysis of 3% H2O2 has been developed recently. The present study aimed to evaluate the effect of H2O2 photolysis treatment on tooth demineralization caused by Streptococcus mutans biofilm. MATERIALS AND METHODS: To induce tooth demineralization, S. mutans biofilm was allowed to form on the maxillary first molars collected from Wistar rats via 24-h culturing. The samples were immersed in 3% H2O2 and irradiated with 365-nm LED (H2O2 photolysis treatment). Viable bacterial counts in the biofilm were evaluated immediately after treatment and after an additional 30-h culturing by colony counting. The acidogenicity of the biofilm, re-established 30 h after treatment, was assessed by measuring the pH. The effect of H2O2 photolysis treatment on tooth demineralization was assessed by measuring the depth of the radiolucent layer in micro-CT images. RESULTS: H2O2 photolysis significantly reduced viable bacterial counts in the biofilm to 3.7 log colony forming units (CFU)/sample, while the untreated group had 7.9 log CFU/sample. The pH of the biofilm re-established after treatment (6.6) was higher than that of the untreated group (5.3). In line with the pH measurement, the treatment group had a significantly lower depth of radiolucent layer in dentin than the untreated group. CONCLUSIONS: H2O2 photolysis treatment was effective not only in killing the biofilm-forming S. mutans but also in lowering the acidogenicity of the biofilm. Thus, this technique could inhibit tooth demineralization. CLINICAL RELEVANCE: H2O2 photolysis can be applicable as a new dental caries treatment.


Assuntos
Anti-Infecciosos , Cárie Dentária , Desmineralização do Dente , Animais , Ratos , Peróxido de Hidrogênio/farmacologia , Cárie Dentária/microbiologia , Streptococcus mutans , Fotólise , Ratos Wistar , Desmineralização do Dente/tratamento farmacológico , Desmineralização do Dente/prevenção & controle , Anti-Infecciosos/farmacologia , Biofilmes
16.
Drug Discov Ther ; 16(6): 309-312, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36529485

RESUMO

Community pharmacies are required to play a role in maintaining the health of local residents. Since September 2015, a national policy in Japan has allowed saliva tests to be used for oral health check-ups at community pharmacies. In the present study, we aimed to reveal dentists' perceptions and expectations for oral health check-ups provided at community pharmacies. A questionnaire survey was administered to dentists at 1,000 randomly selected dental clinics in Tokyo, Japan; 257 responses (25.7%) were included in the analysis and 85.2% of respondents approved of oral health check-ups at community pharmacies. Most respondents who approved of oral health check-ups expected that community pharmacists would recommend that local residents visit a dental clinic (85.8%) and provide a report to dentists (60.3%) after the check-up. Furthermore, 79.0% of respondents desired collaboration with community pharmacies. These findings suggested the potential for oral health check-ups to facilitate collaboration between community pharmacies and dental clinics aimed at maintaining and improving oral health of local residents.


Assuntos
Saúde Bucal , Farmácias , Humanos , Farmacêuticos , Japão , Odontólogos
17.
Sci Rep ; 12(1): 21297, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494564

RESUMO

Staphylococcus virus ΦSA012 has a wide host range and efficient lytic activity. Here, we assessed the biological stability of ΦSA012 against temperature, freeze-thawing, and pH to clinically apply the phage. In addition, inoculation of ΦSA012 through i.p. and i.v. injections into mice revealed that phages were reached the limit of detection in serum and accumulated notably spleens without inflammation at 48 h post-inoculation. Furthermore, inoculation of ΦSA012 through s.c. injections in mice significantly induced IgG, which possesses neutralizing activity against ΦSA012 and other Staphylococcus viruses, ΦSA039 and ΦMR003, but not Pseudomonas viruses ΦS12-3 and ΦR18 or Escherichia viruses T1, T4, and T7 in vitro. Immunoelectron microscopic analysis showed that purified anti-phage IgG recognizes the long-tail fiber of staphylococcus viruses. Although S. aureus inoculation resulted in a 25% survival rate in a mouse i.p. model, ΦSA012 inoculation (i.p.) improved the survival rate to 75%; however, the survival rate of ΦSA012-immunized mice decreased to less than non-immunized mice with phage i.v. injection at a MOI of 100. These results indicated that ΦSA012 possesses promise for use against staphylococcal infections but we should carefully address the appropriate dose and periods of phage administration. Our findings facilitate understandings of staphylococcus viruses for phage therapy.


Assuntos
Terapia por Fagos , Infecções Estafilocócicas , Camundongos , Animais , Terapia por Fagos/métodos , Fagos de Staphylococcus/ultraestrutura , Staphylococcus aureus , Staphylococcus , Infecções Estafilocócicas/terapia , Myoviridae/ultraestrutura , Imunoglobulina G
18.
Kyobu Geka ; 75(9): 700-704, 2022 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-36156521

RESUMO

Coronary artery fistula (CAF) is a relatively rare disease, many of which are asymptomatic and are not indicated for surgery. However, CAF's patients with angina, heart failure due to shunt, and fistula hemangiomas are usually indicated for surgical treatment. A 49-year-old woman with severe congestive heart failure was found to have a fistula from the main trunk of the left coronary artery to the left atrium, and a fistula aneurysm. This patient had heart failure due to shunt blood flow, and also had a fistula aneurysm, so surgical treatment was indicated. During surgery, the fistula aneurysm was incised and the origin and opening of the fistula were closed without any problems. The postoperative course is good, and as of three years after the operation, the patient is being followed up at an outpatient clinic without recurrence of shunt flow and heart failure.


Assuntos
Aneurisma Coronário , Doença da Artéria Coronariana , Fístula , Cardiopatias Congênitas , Insuficiência Cardíaca , Fístula Vascular , Aneurisma Coronário/cirurgia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/cirurgia , Dilatação , Feminino , Fístula/complicações , Fístula/diagnóstico por imagem , Fístula/cirurgia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Humanos , Pessoa de Meia-Idade , Fístula Vascular/complicações , Fístula Vascular/diagnóstico por imagem , Fístula Vascular/cirurgia
19.
Clin Transl Sci ; 15(11): 2697-2708, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36053806

RESUMO

Molnupiravir (MK-4482) is an oral prodrug of the antiviral ribonucleoside analog, N-hydroxycytidine (NHC), which has activity against RNA viruses, including severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We conducted a phase I safety and pharmacokinetic study of molnupiravir in healthy Japanese adult participants. A sample size larger than typically used in pharmacokinetic studies was implemented to collect additional safety data in the Japanese population to support special approval for emergency use in Japan. Single doses of molnupiravir up to 1600 mg and multiple doses of 400 and 800 mg administered every 12 h (q12h) for 5.5 days were generally well-tolerated. NHC appeared rapidly in plasma and reached maximum concentration (Cmax ), with a median time to Cmax (Tmax ) between 1.00 and 2.00 h. Area under the concentration versus time curve from zero to infinity (AUC0-inf ), area under the concentration versus time curve from zero to 12 h (AUC0-12 ), and Cmax of plasma NHC increased approximately dose proportionally. With q12h dosing, the geometric mean (GM) accumulation ratios for NHC AUC0-12 and Cmax were ~1 for 400 and 800 mg. Pharmacokinetics of NHC triphosphate (NHC-TP), the active metabolite of NHC was assessed in peripheral blood mononuclear cells and also demonstrated roughly dose proportional pharmacokinetics. The GM accumulation ratios for NHC-TP AUC0-12 and Cmax were ~2.5 for 400 and 800 mg. Following administration with food, only a modest reduction (24%) in plasma NHC Cmax with comparable AUC0-inf was seen, supporting administration without regard to food.


Assuntos
Tratamento Farmacológico da COVID-19 , Adulto , Humanos , Japão/epidemiologia , Leucócitos Mononucleares , SARS-CoV-2 , Voluntários Saudáveis
20.
Curr Issues Mol Biol ; 44(3): 1353-1375, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35723314

RESUMO

The beneficial effects of polyphenols on metabolic disorders have been extensively reported. The interaction of these compounds with the gut microbiota has been the focus of recent studies. In this review, we explored the fundamental mechanisms underlying the beneficial effects of polyphenols in relation to the gut microbiota in murine models of metabolic disorders. We analyzed the effects of polyphenols on three murine models of metabolic disorders, namely, models of a high-fat diet (HFD)-induced metabolic disorder, dextran sulfate sodium (DSS)-induced colitis, and a metabolic disorder not associated with HFD or DSS. Regardless of the model, polyphenols ameliorated the effects of metabolic disorders by alleviating intestinal oxidative stress, improving inflammatory status, and improving intestinal barrier function, as well as by modulating gut microbiota, for example, by increasing the abundance of short-chain fatty acid-producing bacteria. Consequently, polyphenols reduce circulating lipopolysaccharide levels, thereby improving inflammatory status and alleviating oxidative imbalance at the lesion sites. In conclusion, polyphenols likely act by regulating intestinal functions, including the gut microbiota, and may be a safe and suitable therapeutic agent for various metabolic disorders.

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