Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients.

BACKGROUND: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. METHODS: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. RESULTS: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29-68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of -0.8kPa in non-RPV-exposed patients (p=0.254) and -1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, -2.8kPa [p<0.001]; non-RPV-exposed, -1.1kPa [p=0.22]). CONCLUSION: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.

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.

Efficacy of Apremilast Gels in Mouse Model of Imiquimod-Induced Psoriasis Skin Inflammation.

Apremilast (APM) is a novel drug for the treatment of psoriasis and psoriatic arthritis. APM is a phosphodiesterase 4 (PDE4) inhibitor, raising intracellular cAMP levels and thereby decreasing the inflammatory response by modulating the expression of TNF-α, IL-17, IL-23, and other inflammatory cytokines. The goal of this study is to develop APM gels as a new pharmaceutical formulation for the treatment of topical psoriasis. APM was solubilized in Transcutol-P and incorporated into Pluronic F127, Sepigel, and carbomer bases at different proportions. All formulations were characterized physiochemically. A biopharmaceutical study (release profile) was performed, and ex vivo permeation was evaluated using a human skin model. A toxicity assay was carried out on the HaCaT cell line. A mouse model of imiquimod-induced psoriasis skin inflammation was carried out to determine its efficacy by histological analysis, RNA extraction, and RT-qPCR assays. APM gel formulations showed good physicochemical characteristics and a sustained release profile. There was no permeation of any gel measured through human skin, indicating a high retained amount of APM on the skin. Cell viability was greater than 80% at most dilution concentrations. APM gels treated the psoriasis mouse model, and it shows a reduction in the proinflammatory cytokines (IL-8, IL-17A, IL-17F, and IL-23). APM gels could be a new approach for the treatment of topical psoriasis.

Wearables for Stress Management: A Scoping Review.

In recent years, wearable devices have been increasingly used to monitor people's health. This has helped healthcare professionals provide timely interventions to support their patients. In this study, we investigated how wearables help people manage stress. We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) standard to address this question. We searched studies in Scopus, IEEE Explore, and Pubmed databases. We included studies reporting user evaluations of wearable-based strategies, reporting their impact on health or usability outcomes. A total of 6259 studies were identified, of which 40 met the inclusion criteria. Based on our findings, we identified that 21 studies report using commercial wearable devices; the most common are smartwatches and smart bands. Thirty-one studies report significant stress reduction using different interventions and interaction modalities. Finally, we identified that the interventions are designed with the following aims: (1) to self-regulate during stress episodes, (2) to support self-regulation therapies for long-term goals, and (3) to provide stress awareness for prevention, consisting of people's ability to recall, recognize and understand their stress.

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.

Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients / Beneficios de la rilpivirina para la rigidez hepática en pacientes con coinfección por VIH/VHC

Background: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. Methods: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. Results: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29–68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of −0.8kPa in non-RPV-exposed patients (p=0.254) and −1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, −2.8kPa [p<0.001]; non-RPV-exposed, −1.1kPa [p=0.22]). Conclusion: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.(AU)

Antecedentes: La rilpivirina (RPV) es un fármaco antirretroviral caracterizado por una buena tolerabilidad y un perfil de seguridad hepática favorable. Las últimas investigaciones han mostrado que la RPV mejora la fibrosis hepática en modelos animales de varias enfermedades hepáticas crónicas. Nuestro estudio tenía como objetivo analizar el efecto de la RPV en la fibrosis hepática mediante la evaluación de cambios en la rigidez hepática utilizando una elastografía transitoria. Métodos: Estudio de cohortes retrospectivo de pacientes infectados por VIH expuestos y no expuestos a RPV. Se analizó el cambio en la rigidez hepática durante el período entre dos mediciones mediante elastografía transitoria y se comparó entre pacientes expuestos y no expuestos a RPV. Resultados: Seleccionamos a 118 pacientes infectados por VIH expuestos a RPV y 118 pacientes infectados por VIH no expuestos a RPV. La mediana del tiempo entre las mediciones mediante elastografía transitoria (ET) fue de 50 (29-68) meses. Un modelo lineal general de medidas repetidas basado en las principales características clínicas reveló una reducción significativa en el valor de ET, −0,8kPa en el grupo de pacientes no expuestos a RPV (p=0,254) y de −1,6kPa en el grupo de pacientes expuestos a RPV (p<0,001). El análisis de subgrupos mostró una reducción significativa en el valor de ET solo en pacientes curados de hepatitis C (expuestos a RPV, −2,8kPa [p<0,001]; no expuestos a RPV, −1,1kPa [p=0,22]). Conclusión: Las pautas antirretrovirales basadas en RPV redujeron significativamente la rigidez hepática, evaluada por las mediciones de ET, en los pacientes que se habían curado de hepatitis C crónica.(AU)

ECG Standards and Formats for Interoperability between mHealth and Healthcare Information Systems: A Scoping Review.

Interoperability is defined as the ability of a system or device to communicate between different technologies and software applications. This allows the exchange and use of data in an efficient, precise, and robust way. The present article gives researchers and healthcare information systems developers a qualitative and quantitative synthesis of the state of knowledge related to data formats and data standards proposed for mHealth devices interoperability in healthcare information systems that retrieve and store ECG data. We carry out a scoping review to answer to following questions: (1) What digital data formats or data standards have been proposed for the interoperability of electrocardiograph data between traditional healthcare information systems and mobile healthcare information systems? (2) What are the advantages and disadvantages of these data formats or data standards? The scoping review was conducted in four databases in accordance with the JBI methodology for scoping reviews, and in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A total of 4018 studies were identified of which 30 studies met the inclusion criteria. Based on our findings, we identify four standards and nine formats for capturing and storing streaming ECG data in mobile health applications. The standards used were HL7, SCP-ECG, x73-PHD, and PDF/A. Formats include CSV, PDF-ECG, and seven XML-based formats. These are ECG-XML, HL7-XML, mPCG-XML, mECGML, JSON, SaECG, and CDA R2.

Synthesis, Biological Evaluation, and Molecular Docking Study of 3-Amino and 3-Hydroxy-seco A Derivatives of α-Amyrin and 3-Epilupeol as Inhibitors of COX-2 Activity and NF-kB Activation.

In this study, a series of novel 3-seco-A derivatives of the natural triterpenes α-amyrin (1) and 3-epilupeol (2) were synthesized by a one-pot radical scission-oxidation procedure and evaluated in vitro and in vivo for their capacity to inhibit the inflammatory process. For the in vitro studies, the trans-4-hydroxy-l-proline methyl ester derivatives (1f and 2f) were consistently effective in inhibiting NO, IL-6, and TNF-α secretion, as well as inhibition of NF-κB activation, in RAW cells stimulated by LPS. The further in vivo anti-inflammatory study revealed that the trans-4-hydroxy-l-proline methyl ester derivatives (1f and 2f), together with 1g, were the most effective in inhibiting TPA-induced edema. Interestingly, the α-amyrin derivatives were the most potent inhibitors of COX-2, but inhibited COX-1 only to some extent. The hydroxyl derivative (1c) was selective for COX-2 inhibition (66.3 ± 1.1% at 17.5 µM) without affecting the COX-1 isoform and did not present toxicity. Molecular docking studies revealed that these compounds bind with their polar region in the cavity over Arg-120, and their lipophilic part is orientated to the HEM cofactor similarly to the natural substrate arachidonic acid in the catalytic site of COX-2. These results indicated that seco-A ursane derivatives could be considered promising candidates for the future development of selective NF-κB and COX-2 inhibitors.

Polymeric Nanoparticles and Chitosan Gel Loading Ketorolac Tromethamine to Alleviate Pain Associated with Condyloma Acuminata during the Pre- and Post-Ablation.

This study describes the preparation and evaluation of two formulations, a hydrogel and a nanostructured system, containing ketorolac tromethamine as an anti-inflammatory agent for the local therapy against the inflammatory process derived from the surgical excision of Condyloma acuminata. Both formulations were physicochemically characterized. In vitro release profiles show that the nanoparticles release 92% ± 2.3 of the total ketorolac tromethamine encapsulated, while the chitosan gel releases 18.6% ± 0.2. The ex vivo permeation and distribution through human skin were also assayed and was observed how the main amount of ketorolac tromethamine is retained in the epidermis. In vivo studies were accomplished to evaluate the anti-inflammatory efficacy in mice which also involved the histological analysis to confirm the in vivo results. The nanoparticles present a significantly higher anti-inflammatory efficacy than chitosan gel. The tolerability of developed formulations was assessed by monitoring the biomechanical properties of the skin before and after application of both formulations. No statistical differences in trans-epidermal water loss and skin hydration with respect to the basal values were observed and the formulations exhibited higher anti-inflammatory activity compared to a reference ketotorlac tromethamine solution. Therefore, it can be concluded that both formulations can be proposed as outstanding candidates for offering a local anti-inflammatory therapeutical tool with potential clinical application.

Efficacy, Safety, and Durability of Long-Acting Cabotegravir and Rilpivirine in Adults With Human Immunodeficiency Virus Type 1 Infection: 5-Year Results From the LATTE-2 Study.

BACKGROUND: In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years. METHODS: After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs). RESULTS: At week 256, 186 of 230 (81%) participants in randomized Q8W/Q4W groups and 41 of 44 (93%) participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after week 48. Injection wsite reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant. CONCLUSIONS: Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection.Clinical Trials Registration. NCT02120352.

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.

Psoriasis and Liver Damage in HIV-Infected Patients.

Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with psoriasis. Methods: We performed a retrospective observational study. Steatosis was defined as indicative abdominal ultrasound findings, CAP (controlled attenuated parameter by transient elastography) > 238 dB/m, and/or triglyceride and glucose index (TyG) > 8.38. Significant (fibrosis ≥ 2) and advanced liver fibrosis (fibrosis ≤ F3) were studied by transient elastography (TE) and/or FIB-4 using standard cutoff points. FIB-4 (Fibrosis 4 score) results were adjusted for hepatitis C (HCV)-coinfected patients. Results: We identified 80 patients with psoriasis (prevalence, 1.5%; 95% CI, 1.1-1.8). Psoriasis was severe (PASI > 10 and/or psoriatic arthritis) in 27.5% of cases. The prevalence of steatosis was 72.5% (95% CI, 65-85). Severe psoriasis was an independent risk factor for steatosis (OR, 12; 95% CI, 1.2-120; p = 0.03). Significant liver fibrosis (p < 0.05) was associated with HCV coinfection (OR 3.4; 95% CI, 1.1-10.6), total CD4 (OR 0.99; 95% CI, 0.99-1), and time of efavirenz exposure (OR 1.2; 95% CI, 1.0-1.3). Conclusions: The prevalence of psoriasis in HIV-infected patients was similar to that of the general population. Steatosis is highly prevalent, and severe psoriasis is an independent risk factor for steatosis in HIV-infected patients.

Topical Mucoadhesive Alginate-Based Hydrogel Loading Ketorolac for Pain Management after Pharmacotherapy, Ablation, or Surgical Removal in Condyloma Acuminata.

Condyloma acuminata is an infectious disease caused by the human papilloma virus (HPV) and one of the most common sexually transmitted infections. It is manifested as warts that frequently cause pain, pruritus, burning, and occasional bleeding. Treatment (physical, chemical, or surgical) can result in erosion, scars, or ulcers, implying inflammatory processes causing pain. In this work, a biocompatible topical hydrogel containing 2% ketorolac tromethamine was developed to manage the painful inflammatory processes occurring upon the removal of anogenital condylomas. The hydrogel was physically, mechanically, and morphologically characterized: it showed adequate characteristics for a topical formulation. Up to 73% of ketorolac in the gel can be released following a one-phase exponential model. Upon application on human skin and vaginal mucosa, ketorolac can permeate through both of these and it can be retained within both tissues, particularly on vaginal mucosa. Another advantage is that no systemic side effects should be expected after application of the gel. The hydrogel showed itself to be well tolerated in vivo when applied on humans, and it did not cause any visible irritation. Finally, ketorolac hydrogel showed 53% anti-inflammatory activity, suggesting that it is a stable and suitable formulation for the treatment of inflammatory processes, such as those occurring upon chemical or surgical removal of anogenital warts.

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.

Pacientes con hepatitis C perdidos en el sistema: aspectos éticos-legales y resultados de su búsqueda / No disponible

INTRODUCCIÓN: se conoce la existencia de pacientes con hepatitis C perdidos en el sistema, pero se desconocen su prevalencia y características. Además, su identificación colisiona con la barrera de la protección de datos. MÉTODOS: se presentó un protocolo de identificación y contacto al Comité de Ética Asistencial. Se obtendrían las serologías anti-VHC+ de Microbiología entre 2010-18. Se analizaría su situación en la base de datos hospitalaria y regional. Se clasificarían: a) hepatitis C crónica, si última determinación de ARN-VHC+; b) hepatitis C curada, si última determinación de ARN-VHC- tras 12 semanas de tratamiento; c) hepatitis C posible, si anti-VHC+ sin determinación de ARN-VHC. Se considerarían perdidos aquellos con hepatitis C crónica o posible sin seguimiento en Digestivo o Medicina Interna. Se contactaría con ellos mediante correo postal y, posteriormente, por teléfono para ofrecerles tratamiento. RESULTADOS: el Comité de Ética consideró que el protocolo cumplía los principios bioéticos de autonomía, beneficencia, no maleficencia y justicia, y que el contacto era éticamente deseable. Sobre 4.816 serologías anti-VHC+ identificamos 677 pacientes perdidos (14,06 %; IC 95 %: 13,2-15,2): edad 54 años, 61 % hombres, 12 % extranjeros y 95 % monoinfectados. Se consumieron 1,3 minutos en el estudio de cada serología. Un 25 % de las perdidas habían sido solicitadas por Digestivo o Medicina Interna. De los 677 perdidos, 228 (33,7 %) tenían también ARN-VHC+ y 449 (66,3 %) solo tenían solicitada la serología. CONCLUSIÓN: un número importante de pacientes con hepatitis C se encuentran perdidos en el sistema. Su búsqueda y contacto es posible desde el punto de vista ético-legal

No disponible

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.

Patients with hepatitis C lost to follow-up: ethical-legal aspects and search results.

INTRODUCTION: data on the prevalence and characteristics of hepatitis C patients lost to follow-up are lacking. In addition, the identification of this population clashes with data protection regulations. METHODS: the identification and contact protocol was submitted to the Health Care Ethics Committee. The protocol was based on anti-HCV serology test results for 2010-2018, which were obtained from the Microbiology Department. In addition, the situation of the patients in the hospital and regional database was analyzed, based on the following classification: a) chronic hepatitis C, if the last HCV RNA determination was positive; b) cured hepatitis C, if the last HCV RNA determination was negative after 12 weeks of treatment; and c) possible hepatitis C, if anti-HCV antibodies were positive with no result for HCV RNA. Lost patients were defined as those with chronic or possible hepatitis C and no follow-up in the Digestive Diseases or Internal Medicine Departments. The patients were contacted by postal mail and then by telephone, so that they could be offered treatment. RESULTS: the Ethics Committee considered that the protocol fulfilled the bioethical principles of autonomy, beneficence, non-maleficence and justice and that contact was ethically desirable. From 4,816 positive anti-HCV serology results, 677 patients were identified who were lost to follow-up (14.06 %; 95 % CI, 13.2-15.2). The mean age was 54 years, 61 % were male, 12 % were foreign born and 95 % were mono-infected. The study of each serology result took 1.3 minutes. One-quarter (25 %) of the losses corresponded to the Digestive Diseases and Internal Medicine Departments. Of the 677 losses, serology testing had only been ordered for 449 patients (66.3 %) and the remaining 228 (33.7 %) also had a positive HCV RNA result. CONCLUSION: a large number of patients with hepatitis C are lost to follow-up. Searching for and contacting these patients is legally and ethically viable.

Nanostructured supramolecular hydrogels: Towards the topical treatment of Psoriasis and other skin diseases.

Supramolecular hydrogels were synthesized using a bis-imidazolium based amphiphile, and incorporating chemically diverse drugs, such as the cytostatics gemcitabine hydrochloride and methotrexate sodium salt, the immunosuppressive drug tacrolimus, as well as the corticoid drugs betamethasone 17-valerate and triamcinolone acetonide, and their potential as drug delivery agents in the dermal treatment of Psoriasis was evaluated. The rheological behavior of gels was studied, showing in all cases suitable viscoelastic properties for topical drug delivery. Scanning electron microscopy (SEM) shows that the drugs included have a great influence on the gel morphology at the microscopic level, as the incorporation of gemcitabine hydrochloride leads to slightly thicker fibers, the incorporation of tacrolimus induces flocculation and spherical precipitates, and the incorporation of methotrexate forms curled fibers. 1H NMR spectroscopy experiments show that these drugs not only remain dissolved at the interstitial space, but up to 72% of either gemcitabine or methotrexate, and up to 38% of tacrolimus, is retained within the gel fibers in gels formed with a 1:1 gelator:drug molar ratio. This unique fiber incorporation not only protects the drug from degradation, but also importantly induces a Two Phase Exponential drug release, where the first phase corresponds to the drug dissolved in the interstitial space, while the second phase corresponds to the drug exiting from the gel fibers, and where the speed in each phase is in accordance with the physicochemical properties of the drugs, opening perspectives for controlled delivery. Skin permeation ex vivo tests show how these gels successfully promote the drug permeation and retention inside the skin for reaching their therapeutic target, while in vivo experiments demonstrate that they decrease the hyperplasia and reduce the macroscopic tissue damage typically observed in psoriatic skin, significantly more than the drugs in solution. All these characteristics, beside the spontaneous and easy preparation (room temperature and soft stirring), make these gels a good alternative to other routes of administration for Psoriasis treatment, increasing the drug concentration at the target tissue, and minimizing side effects.

IgG4-related disease in a patient with HIV infection.

A 47-year-old HIV-positive man with good immune and virological status presented with chronic multiple enlarged lymph nodes, lung disease and eosinophilia. Radiologic tests showed enlarged cervical, thoracic and axillary lymph nodes, with interstitial lung damage. After several non-specific histologic studies, an elevated serum IgG4 level led us to request immunohistochemistry of a lymph node sample. The test confirmed the diagnosis of IgG4-related disease.

Cytotoxic Evaluation of (2S)-5,7-Dihydroxy-6-prenylflavanone Derivatives Loaded PLGA Nanoparticles against MiaPaCa-2 Cells.

The search for new alternatives for the prevention and treatment of cancer is extremely important to minimize human mortality. Natural products are an alternative to chemical drugs, since they are a source of many potential compounds with anticancer properties. In the present study, the (2S)-5,7-dihydroxy-6-prenylflavanone (semi-systematic name), also called (2S)-5,7-dihydroxy-6-(3-methyl-2-buten-1-yl)-2-phenyl-2,3-dihydro-4H-1-Benzopyran-4-one (CAS Name registered) (1) was isolated from Eysenhardtia platycarpa leaves. This flavanone 1 was considered as the lead compound to generate new cytotoxic derivatives 1a, 1b, 1c and 1d. These compounds 1, 1a, 1b, 1c, and 1d were then loaded in nanosized drug delivery systems such as polymeric nanoparticles (NPs). Small homogeneous spherical shaped NPs were obtained. Cytotoxic activity of free compounds 1, 1a, 1b, 1c, and 1d and encapsulated in polymeric NPs (NPs1, NPs1a, NPs1b, NPs1c and NPs1d) were evaluated against the pancreatic cancer cell line MiaPaCa-2. The obtained results demonstrated that NPs1a and NPs1b exhibited optimal cytotoxicity, and an even higher improvement of the cytotoxic efficacy was exhibited with the encapsulation of 1a. Based on these results, NPs1a were proposed as promising anticancer agent candidates.