PLGA Nanoparticles Containing Natural Flavanones for Ocular Inflammation.

Flavanones are natural compounds that display anti-inflammatory activity. The aim of this work was to prepare PLGA nanoparticles (NPs) containing natural flavanones I ((2S)-5,7-dihydroxy-6-methyl-8-(3-methyl-2-buten-1-il)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one) and II (2S)-5,7-dihydroxy-2-(4'-methoxyphenyl)-6-methyl-8-(3-methyl-2-buten-1-yl)-2,3-dihydro-4H-1-Benzopyran-4-one) (NP I and NP II, respectively) so as to evaluate their potential for topical anti-inflammatory ocular therapy. An in silico study was carried out using the Molinspiration® and PASS Online web platforms before evaluating the in vitro release study and the ex vivo porcine cornea and sclera permeation. The HPLC analytical method was also established and validated. Finally, the in vitro anti-inflammatory efficacy of NPs was studied in the HCE-2 model. The flavanones I and II could be released following a kinetic hyperbolic model. Neither of the two NPs was able to permeate through the tissues. NP I and NP II were found to be respectful of any changes in the tissues' morphology, as evidenced by histological studies. In HCE-2 cells, NP I and NP II were not cytotoxic at concentrations up to 25 µM. NP I showed higher anti-inflammatory activity than NP II, being able to significantly reduce IL-8 production in LPS-treated HCE-2 cells. In summary, ocular treatment with NP I and NP II could be used as a promising therapy for the inhibition of ocular inflammation.

In Vitro Approaches to Explore the Anticancer Potential of One Natural Flavanone and Four Derivatives Loaded in Biopolymeric Nanoparticles for Application in Topical Delivery Treatments.

The increasing number of skin cancer cases worldwide and the adverse side effects of current treatments have led to the search for new anticancer agents. In this present work, the anticancer potential of the natural flavanone 1, extracted from Eysenhardtia platycarpa, and four flavanone derivatives 1a-d obtained by different reactions from 1 was investigated by an in silico study and through cytotoxicity assays in melanoma (M21), cervical cancer (HeLa) cell lines and in a non-tumor cell line (HEK-293). The free compounds and compounds loaded in biopolymeric nanoparticles (PLGA NPs 1, 1a-d) were assayed. A structure-activity study (SAR) was performed to establish the main physicochemical characteristics that most contribute to cytotoxicity. Finally, ex vivo permeation studies were performed to assess the suitability of the flavanones for topical administration. Results revealed that most of the studied flavanones and their respective PLGA NPs inhibited cell growth depending on the concentration; 1b should be highlighted. The descriptors of the energetic factor were those that played a more important role in cellular activity. PLGA NPs demonstrated their ability to penetrate (Qp of 17.84-118.29 µg) and be retained (Qr of 0.01-1.44 g/gskin/cm2) in the skin and to exert their action for longer. The results of the study suggest that flavanones could offer many opportunities as a future anticancer topical adjuvant treatment.

Screening Anti-Inflammatory Effects of Flavanones Solutions.

There are a large number of remedies in traditional medicine focused on relieving pain and inflammation. Flavanones have been a potential source in the search for leading compounds and biologically active components, and they have been the focus of much research and development in recent years. Eysenhardtia platycarpa is used in traditional medicine for the treatment of kidney diseases, bladder infections, and diabetes mellitus. Many compounds have been isolated from this plant, such as flavones, flavanones, phenolic compounds, triterpenoid acids, chalcones, sugars, and fatty acids, among others. In this paper, natural flavanone 1 (extracted from Eysenhardtia platycarpa) as lead compound and flavanones 1a-1d as its structural analogues were screened for anti-inflammatory activity using Molinspiration® and PASS Online in a computational study. The hydro alcoholic solutions (FS) of flavanones 1, 1a-1d (FS1, FS1a-FS1d) were also assayed to investigate their in vivo anti-inflammatory cutaneous effect using two experimental models, a rat ear edema induced by arachidonic acid (AA) and a mouse ear edema induced by 12-O-tetradecanoylphorbol acetate (TPA). Histological studies and analysis of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were also assessed in AA-inflamed rat ear tissue. The results showed that the flavanone hydro alcoholic solutions (FS) caused edema inhibition in both evaluated models. This study suggests that the evaluated flavanones will be effective when used in the future in skin pathologies with inflammation, with the results showing 1b and 1d to be the best.

Biopharmaceutic study and in vivo efficacy of natural and derivatives flavanones formulations.

Aim: The development and characterization of nanostructured flavanone formulations (FF) of 1 extracted from Eysenhardtia platycarpa and 1a, 1b, 1c and 1d derivatives by structural modification of 1 as anti-inflammatory candidates for topical treatment of local inflammation. Materials & methods: The FF were physicochemical characterized and the behavior release, skin permeation and, in vivo anti-inflammatory efficacy in the rat model were studied. Results: The FF revealed sustained drug release and showed slow drug penetration in human skin. The FF reduced inflammation in comparison with the standard formulation. Conclusion: The FF could be effective systems for the delivery and controlled release of flavanones on the skin, and the chemical modification of lead molecule 1 improved the efficacy.

Quantification of One Prenylated Flavanone from Eysenhardtia platycarpa and Four Derivatives in Ex Vivo Human Skin Permeation Samples Applying a Validated HPLC Method.

Prenylated flavanones are polyphenols that have diverse biological properties. The present paper focuses on a HPLC method validation for the quantification of prenylated flavanones (2S)-5,7-dihydroxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1Benzopyran-4-one 1 and derivatives (2S)-5,7-bis(acetyloxy)-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one A; (2S)-5-hydroxy-7-methoxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one B; (8S)-5-hydroxy-2,2-dimethyl-8-phenyl-3,4,7,8-tetrahydro-2H,6H-Benzo[1,2-b:5,4-b']dipyran-6-one C; and (8S)-5-hydroxy-2,2-dimethyl-8-phenyl-7,8-dihydro-2H,6H-Benzo[1,2-b:5,4-b']dipyran-6-one D applied in biopharmaceutic studies. The linear relationships are proven with significant correlation coefficients (R2 ˃ 0.999) in the range of 1.56 to 200 µg/mL with low limits of detection and quantification, on average of 0.4 µg/mL and 1.2 µg/mL, respectively. The validation method used in this work is highly accurate and precise, with values lower than 15%. The relative standard deviation values of repeatability of the instrumental system are demonstrated with less than 0.6% for all studied flavanones. Therefore, the applicability method of the quantification of the prenylated flavanones was established using the permeation of human skin in the Franz cell system. During the method previously described, there was no interference observed from human skin components in ex vivo permeation studies.

Disability-Disaggregated Data Collection: Hospital-Based Application of the Washington Group Questions in an Eye Hospital in Paraguay.

Disability-disaggregated data are increasingly considered important to monitor progress in Universal Eye Health Care. Hospital-based data are still elusive because of the cultural ambiguities of the term disability, especially in under-resourced Health Information Systems in low-and middle-income countries. The aim of this study was to estimate the hospital-based rate of disability in patients presenting at an eye department of a rural hospital in Paraguay and to discuss implications for the management of access barriers. Therefore, we introduced two standardized sets of the Washington Group (WG) Questions as a pilot project. In total, 999 patients answered the self-report WG short set (WG-SS) questionnaire with six functional domains, and 501 of these patients answered an extended set, which included additional domains for "anxiety" and "depression" (WG-ES3). Overall, 27.7% (95% Confidence Interval (CI) 24.9-30.3) were categorized as having a disability. A total of 9.6% (95% CI 7.9-11.6) were categorized as having a disability because of communication difficulties, which was second only to visual difficulties. The odds ratio for disability for patients aged 70 years and older was 8.5 (95% CI 5.0-14.4) and for male patients, it was 0.83 (95% CI 0.62-1.1). Of those patients who answered the WG-ES3, 3.4% were categorized as having a disability because of being worried, nervous or anxious and 1.4% because of feeling depressed. An analysis of the questions of the "depression" domain was impeded by a high rate of measurement errors. The results of the different domains can now be used to inform the identification and mitigation of potential access barriers to eye health services for different types of impairments.

Avaliação da capacidade de contração dos músculos do assoalho pélvico em atletas de voleibol do sexo feminino / Evaluation of pelvic floor muscle contraction capacity in female volleyball athletes

O número de mulheres que vêm adentrando o campo esportivo cresce consideravelmente. Entretanto, vale ressaltar que tal prática pode ser considerada de risco ao sistema reprodutivo feminino e aos músculos do assoalho pélvico. O objetivo do estudo foi comparar a CCAP em atletas praticantes da modalidade voleibol do sexo feminino e de mulheres sedentárias. Foi realizado um estudo com 20 mulheres, sendo 10 atletas de voleibol (GA) e 10 mulheres sedentárias (GS), do tipo transversal prospectivo quantitativo, no qual avaliou-se a capacidade de contração dos músculos do assoalho pélvico (CCAP) dessas mulheres e comparouse a CCAP entre os grupos GA e GS. A avaliação da CCAP foi realizada através do perineômetro. Após a avaliação não foi observada diferença estatisticamente significativa com relação a CCAP entre os grupos GA e GS, porém no GA a média da CCAP foi inferior a do GS. (AU)

The number of women who practice sports, among them volleyball has grown considerably, however, the modality may bring a special risk to these athletes, due to negative effects on the reproductive system. A cross-sectional prospective quantitative study was conducted with 20 women, including 10 volleyball players (GA) and 10 sedentary women (GS), in which we evaluated the ability of contraction of the pelvic floor muscles (CPFM) in volleyball athletes women and compared with CPFM in sedentary women. The evaluation of CPFM was done using the perineometer developed by the researcher. After the evaluation there was no statistically significant difference related to CPFM between the GA and GS groups, but the GA's average of CPFM was inferior to the GS's. (AU)

High plasma adenosine levels in overweight/obese pregnant women.

We aim to investigate whether overweight/obese pregnant women have elevated plasma levels of adenosine associated with increased consumption of high-calorie food. Sixty women were included. They were divided into lean (n = 23 and n = 12) or overweight/obese (n = 7 and n = 18) non-pregnant and pregnant women, respectively. Clinical records and maternal blood samples were collected after informed consent. A self-reported dietary questionnaire was also completed. Plasma adenosine levels were determined with high-performance liquid chromatography. Biochemical parameters, including glucose, total protein, and lipid profile, were determined using standard colorimetric assays. Adenosine levels were higher in pregnant women than in non-pregnant women (18.7 ± 1.6 vs 10.8 ± 1.3 nM/µg protein, respectively, p < 0.0001). Overweight/obese pregnant women (21.9 ± 2.5 nM/µg protein) exhibited higher adenosine levels than lean pregnant (14.5 ± 1.0 nM/µg protein, p = 0.04) or non-pregnant women (11.7 ± 1.5 nM/µg protein, p = 0.0005). Also, pregnant women with elevated weight gain exhibited higher (26.2 ± 3.7 nM/µg protein) adenosine levels than those with adequate weight gain (14.9 ± 1.4 nM/µg protein, p = 0.03). These differences were not statistically significant compared with those of pregnant women with reduced weight gain (17.4 ± 2.1 nM/µg protein, p = 0.053). Body mass index and adenosine only in pregnant women were positively correlated (r = 0.39, p = 0.02). While, polyunsaturated fatty acid (PUFA) consumption was negatively correlated with plasma adenosine levels only in non-pregnant women (r = -0.33, p = 0.03). Pregnancy is associated with high plasma adenosine levels, which are further elevated in pregnant women who are overweight/obese. High PUFA intake might reduce plasma adenosine levels in non-pregnant women.