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Background Acute lung injury is a severe respiratory disorder characterized by overwhelming lung inflammation. Dipalmitoylphosphatidylcholine (DPPC) is the major lipid component of pulmonary surfactant, which here acts as a carrier delivery system for drugs, while also preserving surface tension in the lung. The clinical development of naringenin (NG) is limited by its low solubility and bioavailability. Methods Novel NG-loaded DPPC phytosomes for dry powder inhalation (NPDPIs) were prepared by solvent evaporation and a freeze-drying method. The particle size, electric potential, in vitro release, and lung deposition were characterized. A rat model of acute lung injury was established and used for pharmacodynamic evaluations. Results A mixture of NG/DPPC 12 (w/w) formed stable phytosomes with the addition of appropriate ethanol. The phytosomes had high complexation efficiency (92.1% ± 1.87%) with NG, a small mean size (150.8 ± 6.9 nm), and a high zeta potential (20.97 ± 0.55 mV). NPDPIs composed of mannitol/DPPC/NG (421, w/w/w) presented a satisfactory appearance, good fluidity, quick reconstitution to naringenin phytosomes (NGPs), and small (167.2 nm) reconstituted NGPs. The aerodynamic diameter (12.48 μm) and fine particle fraction (23.90%) were suitable for pulmonary delivery by inhalation. The in vivo NPDPIs demonstrated efficacy in a rat model of acute lung injury. NPDPIs significantly inhibited the phosphorylation of P38 in the mitogen-activated protein kinase pathway and suppressed oxidative stress. Surprisingly, the DPPC vehicle exhibited potential effects against acute lung injury by protecting respiratory function. Conclusions NPDPIs were developed for sustained drug release, promoting pulmonary bioavailability of drug and protecting against acid-induced acute lung injury in rats by pulmonary delivery. NPDPIs are a promising dry powder inhaler for clinical application in acute lung injury.Background Unhealthy alcohol use is a public health issue, prioritized by the World Health Organization (WHO) for prevention and reduction. Ukraine falls in the highest WHO category of "years of life lost" due to alcohol use. Objective To investigate perceptions of alcohol consumption in a sample of youth and adults in western Ukraine. Methods In-depth semi-structured interviews were conducted with 38 adult stakeholders (aged 21-63 years), and 81 adolescents and young adults (aged 12-21 years) completed paper-and-pencil open-ended questions. A combined deductive-inductive thematic analysis of these qualitative data resulted in an initial coding scheme for both parts of the data. These initial codes were organized into patterns, which were further condensed to four themes. Results The four themes that were developed are (1) The general historical, socio-economic-political situation and its relation to alcohol use, (2) Alcohol in the home and daily environment, (3) Alcohol use, related feelings, peers, family, and burden to health, and (4) Perceptions of the consequences of alcohol (mis)use. Conclusions Respondents indicated awareness that daily consumption, also in youth, as well as binge drinking and childhood sipping constitute a risk to health. These risks were described in the context of easy availability, low pricing, and peer pressure. The respondents mentioned awareness that alcohol dependence (AD) of parents affected families with the risk of disadvantageous child development. Interventions may include targeting current norms, stigmatizing beliefs and supporting subjects in developing coping skills.Insulin resistance is one of the critical pathogeneses of type 2 diabetes mellitus (T2DM). Elevated levels of plasma branched-chain amino acids (BCAAs) are associated with insulin resistance. Recent studies have demonstrated the role of Porphyromonas gingivalis in the development of insulin resistance. However, the mechanisms by which P. gingivalis induces insulin resistance are still unclear. https://www.selleckchem.com/products/Phlorizin(Phloridzin).html The purpose of this study was to investigate whether P. gingivalis induces insulin resistance through BCAA biosynthesis. We established a murine model of periodontitis by infecting mice with P. gingivalis. Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs were measured. A P. gingivalis BCAA aminotransferase-deficient strain (∆bcat) was constructed, and its kinetic growth, biofilm formation, and in vivo colonization were compared with its wild-type strain. Alveolar bone loss, insulin sensitivity, and the plasma level of BCAAs of the mice infected with either wild-type strain or ∆bcat strain were further measured. We found that periodontal infection with P. gingivalis significantly upregulated the plasma level of BCAAs and aggravated the high-fat diet (HFD)-induced insulin resistance. Bcat deletion did not alter the growth, biofilm formation, and in vivo colonization of P. gingivalis. More important, the ∆bcat strain was unable to upregulate the plasma level of BCAAs and induce insulin resistance in HFD-fed mice. These findings suggest that the BCAA biosynthesis of P. gingivalis plays a critical role in the development of insulin resistance in the HFD-fed mice. The BCAA biosynthesis pathways may provide a potential target for the disruption of linkage between periodontitis and T2DM.Background There have been two methods of gaining retrospective self-report estimates of alcohol consumption, quantity frequency (QF) and retrospective diary (RD), offering distinct advantages and disadvantages. The typical and atypical drinking diary (TADD) was developed to benefit from each method's advantages. Objectives To compare estimates obtained from the TADD with corresponding estimates obtained from a QF measure (Khavari alcohol test; KAT) and an RD measure, the timeline follow-back (TLFB). It was hypothesized that the TADD's alcohol consumption estimates would correlate strongly with those obtained from the TLFB; and the strength of the TADD-TLFB correlation would be significantly stronger than the KAT-TLFB correlation. Method One hundred and sixty-eight (168) undergraduates (73% female) estimated their alcohol consumption for the preceding 12 weeks using all three measures. Results The TADD (r = 0.83, p less then .001) and the KAT (r = 0.066, p less then .001) produced estimates of total alcohol consumption that correlated very strongly and strongly, respectively, with the TLFB.
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