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1.
Rev Esp Enferm Dig ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767015

RESUMEN

BACKGROUND: Obesity affects many patients with inflammatory bowel disease (IBD). Glucagon-like peptide (GLP)-1 agonists are a promising therapy for obese patients. However, there is a lack of evidence of the use of these drugs in IBD populations. We investigated the efficacy and safety of GLP-1 agonists in a cohort of obese patients with IBD. METHODS: We analyzed a cohort of consecutive IBD patients who received GLP-1 agonists indicated for treating obesity between 2019 and 2021. The GLP-1 agonists included were semaglutide 1.0 mg or liraglutide 3.0 mg. The coprimary endpoints were the percentage of change in body weight from baseline to 6 months and a weight reduction of 5% or more at 6 months. In addition, we reviewed the safety profile of GLP-1 agonist therapy and its impact on the IBD course. RESULTS: We included 16 obese patients with IBD (9 CD and 7 UC). The median body mass index at baseline was 35 (32-37). The percentage of change in body weight was -6.2% (-3.4-(-8.5)) at 6 months, and a 5% or more weight reduction was achieved in 58.3% (7/12) of patients at 6 months. The most common side effect was nausea (13.3%), and one patient withdrew for diarrhea. IBD activity score did not change significantly during follow-up. CONCLUSION: Our results showed that GLP-1 agonists were effective and had a good safety profile in IBD patients. Most adverse effects were mild, and the IBD activity had no significant changes.

2.
Int J Mol Sci ; 24(2)2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36675312

RESUMEN

The genetic polymorphisms rs2395185 and rs2097432 in HLA genes have been associated with the response to anti-TNF treatment in inflammatory bowel disease (IBD). The aim was to analyze the association between these variants and the long-term response to anti-TNF drugs in pediatric IBD. We performed an observational, multicenter, ambispective study in which we selected 340 IBD patients under 18 years of age diagnosed with IBD and treated with anti-TNF drugs from a network of Spanish hospitals. Genotypes and failure of anti-TNF drugs were analyzed using Kaplan-Meier curves and Cox logistic regression. The homozygous G allele of rs2395185 and the C allele of rs2097432 were associated with impaired long-term response to anti-TNF drugs in children with IBD after 3 and 9 years of follow-up. Being a carrier of both polymorphisms increased the risk of anti-TNF failure. The SNP rs2395185 but not rs2097432 was associated with response to infliximab in adults with CD treated with infliximab but not in children after 3 or 9 years of follow-up. Conclusions: SNPs rs2395185 and rs2097432 were associated with a long-term response to anti-TNFs in IBD in Spanish children. Differences between adults and children were observed in patients diagnosed with CD and treated with infliximab.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Inhibidores del Factor de Necrosis Tumoral , Adulto , Humanos , Niño , Adolescente , Infliximab/uso terapéutico , Adalimumab/farmacología , Adalimumab/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/genética , Polimorfismo de Nucleótido Simple , ADN/uso terapéutico , Estudios Retrospectivos
3.
Gastroenterol Hepatol ; 46(10): 784-794, 2023 Dec.
Artículo en Inglés, Español | MEDLINE | ID: mdl-36803681

RESUMEN

BACKGROUND AND OBJECTIVE: Ulcerative colitis (UC) clinical guidelines include the best available evidence, although not all clinical situations are answered, so their management can be controversial. The aim of this study is to identify the situations of mild to moderate UC susceptible to controversy and to evaluate the degree of agreement or disagreement with specific proposals. METHODS: Inflammatory bowel disease (IBD) expert discussion meetings were used to identify criteria, attitudes and opinions regarding the management of UC. A Delphi questionnaire was then developed with 60 items regarding antibiotics, salicylates and probiotics; local, systemic and topical corticosteroids; and immunosuppressants. RESULTS: Consensus was reached in 44 statements (73.3%); 32 in agreement (53.3%) and 12 in disagreement (20.0%). Some of them were: it is not necessary the systematic use of antibiotics despite the severity of the outbreak, being reserved when there is suspicion of infection or systemic toxicity; when faced with a mild-moderate outbreak of UC and in patients who do not respond to aminosalicylates, it is appropriate to use a dose of beclomethasone of 10mg/day for one month and 5mg/day for another month; it is advised that the dose of azathioprine be administered in a single dose. CONCLUSIONS: IBD experts agree on most of the proposals identified for managing mild to moderate UC and there is a need for scientific evidence in some specific situations where expert opinion may be helpful.


Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Consenso , Técnica Delphi , Antibacterianos/uso terapéutico
4.
Photosynth Res ; 151(3): 251-263, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34807429

RESUMEN

Sulphide is proposed to have influenced the evolution of primary stages of oxygenic photosynthesis in cyanobacteria. However, sulphide is toxic to most of the species of this phylum, except for some sulphide-tolerant species showing various sulphide-resistance mechanisms. In a previous study, we found that this tolerance can be induced by environmental sulphidic conditions, in which two experimentally derived strains with an enhanced tolerance to sulphide were obtained from Microcystis aeruginosa, a sensitive species, and Oscillatoria, a sulphide-tolerant genus. We have now analysed the photosynthetic performance of the wild-type and derived strains in the presence of sulphide to shed light on the characteristics underlying the increased tolerance. We checked whether the sulphide tolerance was a result of higher PSII sulphide resistance and/or the induction of sulphide-dependent anoxygenic photosynthesis. We observed that growth, maximum quantum yield, maximum electron transport rate and photosynthetic efficiency in the presence of sulphide were less affected in the derived strains compared to their wild-type counterparts. Nevertheless, in 14C photoincoporation assays, neither Oscillatoria nor M. aeruginosa exhibited anoxygenic photosynthesis using sulphide as an electron donor. On the other hand, the content of photosynthetic pigments in the derived strains was different to that observed in the wild-type strains. Thus, an enhanced PSII sulphide resistance appears to be behind the increased sulphide tolerance displayed by the experimentally derived strains, as observed in most natural sulphide-tolerant cyanobacterial strains. However, other changes in the photosynthetic machinery cannot be excluded.


Asunto(s)
Cianobacterias , Microcystis , Cianobacterias/genética , Transporte de Electrón , Fotosíntesis , Sulfuros
5.
Bioorg Chem ; 119: 105551, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34915284

RESUMEN

Oxidative stress is linked to several invasive diseases which causes significant clinical and economic impact, therefore, there is a need to develop new antioxidants. The natural products could play an important role in overcoming the current need. In the present work, the antioxidant bioassay-guided fractionation of the ethanolic extract of Inula viscosa leaves (Asteraceae) was performed using DPPH and ABTS assays affording three known compounds, which were successfully characterized as ilicic acid (1), taxifolin (2) and quercetin (3) based on 1D, 2D NMR. Compounds 2 and 3 were identified as the most active, displaying similar or higher potency against ABTS (value 41.27 for quercetin and 142.58 for taxifolin) and similar activity against DPPH (value 41.27 for quercetin and 142.58 for taxifolin) than the well-known reference, ascorbic acid (value 65.36 for quercetin and 58.43 for taxifolin) but less potency than the standard gallic acid. The discussion of SAR of the antioxidant potential revealed that the type of natural product is crucial for the activity and the substitution pattern on the flavonoid skeleton modulate the antioxidant profile. Our findings show that I. viscosa leaves may be a natural source of antioxidants and once again the role of flavonoids health benefits is more strongly endorsed.


Asunto(s)
Antioxidantes/farmacología , Inula/química , Extractos Vegetales/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Benzotiazoles/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta/química , Relación Estructura-Actividad , Ácidos Sulfónicos/antagonistas & inhibidores
6.
Aquac Nutr ; 2022: 6992682, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36860445

RESUMEN

Macroalgae have been recently described as a potential ingredient for aquafeeds, exerting several physiological benefits. Grass carp (Ctenopharyngodon idella) is a freshwater species, which has been the major fish species produced in the world in the last years. In order to determine the potential use of macroalgal wracks in fish feeding, C. idella juveniles were fed with an extruded commercial diet (CD) or the CD supplemented with 7% of a wind dried-powder (1 mm) from either a multispecific macroalgal wrack (CD + MU7) or a monospecific macroalgal wrack (CD + MO7) obtained from Gran Canaria island (Spain) coasts. After 100 days of feeding, survival, fish weight, and body indexes were determined, and muscle, liver, and digestive tract samples were collected. The total antioxidant capacity of macroalgal wracks was analyzed by assesing the antioxidant defense response and digestive enzymes activity in fish. Finally, muscle proximate composition, lipid classes (LC), and fatty acid (FA) profiles were also studied. Our results suggest that dietary inclusion of macroalgal wracks does not have negative effects on growth, proximate, and lipid composition, antioxidative status, or digestive capacity of C. idella. In fact, both macroalgal wracks caused a general lower fat deposition, and the multispecific wrack enhanced catalase activity in the liver.

7.
Gastroenterol Hepatol ; 45(3): 165-176, 2022 Mar.
Artículo en Inglés, Español | MEDLINE | ID: mdl-34051313

RESUMEN

OBJECTIVE: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD. PATIENTS AND METHODS: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. RESULTS: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001). CONCLUSION: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.


Asunto(s)
Adalimumab/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Calidad de Vida , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Adulto , Anciano , Biomarcadores/sangre , Enfermedad de Crohn/sangre , Fatiga/tratamiento farmacológico , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión , Índice de Severidad de la Enfermedad , España , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
8.
J Mammary Gland Biol Neoplasia ; 26(4): 341-355, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34813005

RESUMEN

Breast cancer (BC) is the leading cause of cancer-related death in women in the world. Since tumor cells employ autophagy as a survival pathway, it has been proposed that autophagy inhibition could be beneficial for cancer treatment. There are several onging clinical trials where autophagy is being inhibited (using chloroquine, CQ or hydroxychloroquine, HCQ) along with chemotherapy with promising results. However, there is also in vitro evidence in which autophagy inhibition can induce epithelial to mesenchymal transition (EMT) in cancer cells, indicating that, at least in some cases, this strategy could be detrimental for cancer patients. In this study, we found that the genetic inhibition of autophagy primed cells for EMT by inducing a decrease in E-cadherin protein levels, while CQ treatment decreased E-cadherin levels, induced morphological changes related to EMT, increased EMT-related transcription factor (EMT-TF) expression and migration in estrogen receptor positive (ER +) BC cell lines. Importantly, CQ treatment increased intracellular reactive oxygen species (ROS) which induced the secretion of macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine related to malignancy. Both ROS production and MIF secretion were responsible for the mesenchymal morphology and increased migratory capacity induced by CQ. Our results indicate that CQ treatment increased malignancy by inducing ROS production, MIF secretion and EMT and suggest that autophagy inhibition in ER + BC patients might have detrimental effects. Our data indicates that a careful selection of patients should be performed in order to determine who will benefit the most from autophagy inhibition with available pharmacological agents for the treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama , Factores Inhibidores de la Migración de Macrófagos , Neoplasias de la Mama/tratamiento farmacológico , Cadherinas , Línea Celular , Línea Celular Tumoral , Cloroquina/farmacología , Transición Epitelial-Mesenquimal , Femenino , Humanos , Hidroxicloroquina/farmacología , Factores Inhibidores de la Migración de Macrófagos/farmacología , Especies Reactivas de Oxígeno/metabolismo
9.
Artículo en Inglés | MEDLINE | ID: mdl-33753334

RESUMEN

Leishmaniasis and Chagas are among the most significant neglected tropical diseases. Due to several drawbacks with the current chemotherapy, developing new antikinetoplastid drugs has become an urgent issue. In the present work, a bioassay-guided investigation of the root bark of Maytenus chiapensis on Leishmania amazonensis and Trypanosoma cruzi led to the identification of two D:A-friedo-nor-oleanane triterpenoids (celastroloids), 20ß-hydroxy-tingenone (celastroloid 5) and 3-O-methyl-6-oxo-tingenol (celastroloid 8), as promising antikinetoplastid leads. They displayed higher potency on L. amazonensis promastigotes (50% inhibitory concentrations [IC50s], 0.44 and 1.12 µM, respectively), intracellular amastigotes (IC50s, 0.83 and 1.91 µM, respectively), and T. cruzi epimastigote stage (IC50s, 2.61 and 3.41 µM, respectively) than reference drugs miltefosine and benznidazole. This potency was coupled with an excellent selectivity index on murine macrophages. Mechanism of action studies, including mitochondrial membrane potential (Δψm) and ATP-level analysis, revealed that celastroloids could induce apoptotic cell death in L. amazonensis triggered by the mitochondria. In addition, the structure-activity relationship is discussed. These findings strongly underline the potential of celastroloids as lead compounds to develop novel antikinetoplastid drugs.


Asunto(s)
Antiprotozoarios , Leishmania mexicana , Leishmaniasis , Maytenus , Trypanosoma cruzi , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Leishmaniasis/tratamiento farmacológico , Ratones
10.
J Nat Prod ; 84(10): 2717-2726, 2021 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-34549952

RESUMEN

The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 µM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.


Asunto(s)
Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , Physalis/química , Replicación Viral/efectos de los fármacos , Witanólidos/farmacología , Línea Celular , El Salvador , VIH-1/fisiología , Humanos , Estructura Molecular , Componentes Aéreos de las Plantas/química
11.
Parasitol Res ; 120(8): 3001-3005, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34251514

RESUMEN

Efficacious treatments against Acanthamoeba Keratitis (AK) is challenging, often ineffective and linked to the intragenotype variation in the drug efficacy. Increased oxygen can facilitate host response and can inhibit some organisms. Herein, we report the effect of increased oxygen concentrations on Acanthamoeba spp. growth and its effect on ROS (reactive oxygen species) production. The exposition to pure oxygen could reduce cell growth by at least 60% for Acanthamoeba castellanii Neff, Acanthamoeba polyphaga, and Acanthamoeba griffini. The increase in ROS production confirming that oxygen cell's growth inhibition was due to oxidative stress. Further studies are needed to determine oxygen saturation level, time of oxygen exposition, and number of sessions needed to eliminate the parasite.


Asunto(s)
Acanthamoeba castellanii , Estrés Oxidativo , Oxígeno , Acanthamoeba castellanii/crecimiento & desarrollo , Oxígeno/farmacología , Especies Reactivas de Oxígeno
12.
Molecules ; 26(14)2021 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-34299627

RESUMEN

Despite intensified efforts to develop an effective antibiotic, S. aureus is still a major cause of mortality and morbidity worldwide. The multidrug resistance of bacteria has considerably increased the difficulties of scientific research and the concomitant emergence of resistance is to be expected. In this study we have investigated the in vitro activity of 15 ethanol extracts prepared from Moroccan medicinal plants traditionally used for treatment of skin infections. Among the tested species I. viscosa, C. oxyacantha, R. tinctorum, A. herba alba, and B. hispanica showed moderate anti-staphylococcal activity. However, R. alaternus showed promising growth-inhibitory effects against specific pathogenic bacteria especially methicillin-susceptible Staphylococcus aureus Panton-Valentine leucocidin positive (MSSA-PVL) and methicillin-resistant S. aureus (MRSA). The bioguided fractionation of this plant using successive chromatographic separations followed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) including EIMS and HREIMS analysis yielded the emodin (1) and kaempferol (2). Emodin being the most active with MICs ranging between 15.62 and 1.95 µg/mL and showing higher activity against the tested strains in comparison with the crude extract, its mechanism of action and the structure-activity relationship were interestingly discussed. The active compound has not displayed toxicity toward murine macrophage cells. The results obtained in the current study support the traditional uses of R. alaternus and suggest that this species could be a good source for the development of new anti-staphylococcal agents.


Asunto(s)
Antibacterianos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Fitoquímicos , Rhamnus/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Toxinas Bacterianas , Exotoxinas , Leucocidinas , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología
13.
Rev Esp Enferm Dig ; 113(3): 170-178, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33213166

RESUMEN

PURPOSE: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naïve, IBD patients in the real life clinical practice. METHODS: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naïve patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naïve patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. RESULTS: two hundred and thirty-nine IBD biologic-naïve patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn's disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. CONCLUSIONS: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.


Asunto(s)
Biosimilares Farmacéuticos , Colitis Ulcerosa , Enfermedad de Crohn , Humanos , Biosimilares Farmacéuticos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Enfermedad de Crohn/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Infliximab/uso terapéutico , Estudios Retrospectivos , España , Resultado del Tratamiento
14.
J Clin Rheumatol ; 27(1): 25-30, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31356399

RESUMEN

BACKGROUND: Patients' experience with health care is becoming a key component for the provision of a patient-centered health care model. The aim of this study was to assess the experience with health care of patients with inflammatory arthritis and patient- and health care-related factors. METHODS: Patients responded to an anonymous survey provided by their treating clinical teams. The survey comprised the validated 12-item IEXPAC (Instrument to Evaluate the EXperience of PAtients with Chronic diseases) tool and demographic variables and health care-related characteristics that may affect patients' experience. RESULTS: A total of 359 of 625 surveys were returned (response rate, 57.4%). Overall, patient responses were positive (>60% gave "always/mostly" answers) for statements assessing the interaction between patients and health care professionals or patient self-management following health care professional guidance. However, positive patient responses for items regarding patient interaction with the health care system via the internet or with other patients were less than 13%. Only 25.6% of patients who had been hospitalized reported receiving a follow-up call or visit following discharge. In the bivariate analysis, experience scores were higher (better experience) in men, those seen by fewer specialists or by the same physician, and in patients treated with a fewer number of drugs or with subcutaneous/intravenous drugs. Multivariate analyses identified regular follow-up by the same physician and treatment with subcutaneous/intravenous drugs as variables associated with a better patient experience. CONCLUSIONS: This study identifies areas of care for patients with inflammatory arthritis with the potential to improve patients' experience and highlights the importance of patient-physician relationships and comprehensive patient care.


Asunto(s)
Artritis , Prioridad del Paciente , Medición de Resultados Informados por el Paciente , Mejoramiento de la Calidad/organización & administración , Artritis/psicología , Artritis/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Manejo de Atención al Paciente/métodos , Relaciones Médico-Paciente , Investigación Cualitativa , España , Encuestas y Cuestionarios
15.
Telemed J E Health ; 26(1): 80-88, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-30848700

RESUMEN

Objectives: Mobile apps are useful tools in e-health and self-management strategies in disease monitoring. We evaluated the Harvey-Bradshaw index (HBI) mobile app self-administered by the patient to see if its results agreed with HBI in-clinic assessed by a physician. Methods: Patients were enrolled in a 4-month prospective study with clinical assessments at months 1 and 4. Patients completed mobile app HBI and within 48 h, HBI was performed by a physician (gold standard). HBI scores characterized Crohn's disease (CD) as remission <5 or active ≥5. We determined agreement per item and total HBI score and intraclass correlation coefficients (ICCs). Bland-Altman plot was performed. HBI changes in disease activity from month 1 to month 4 were determined. Results: A total of 219 patients were enrolled. All scheduled assessments (385 pairs of the HBI questionnaire) showed a high percentage of agreement for remission/activity (92.4%, κ = 0.796), positive predictive value (PPV) for remission of 98.2%, and negative predictive value of 76.7%. High agreement was also found at month 1 (93.15%, κ = 0.82) and month 4 (91.5%, κ = 0.75). Bland-Altman plot was more uniform when the HBI mean values were <5 (remission). ICC values were 0.82, 0.897, and 0.879 in all scheduled assessments, 1 and 4 months, respectively. Conclusions: We found a high percentage of agreement between patients' self-administered mobile app HBI and in-clinic physician assessment to detect CD activity with a remarkably high PPV for remission. The mobile app HBI might allow a strict control of inflammation by remote monitoring and flexible follow-up of CD patients. Reduction of sanitary costs could be possible.


Asunto(s)
Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/terapia , Aplicaciones Móviles , Automanejo , Adulto , Anciano , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Telemedicina
16.
Int J Mol Sci ; 21(2)2020 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-31968593

RESUMEN

The Th17 immune response plays a key role in autoimmune diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Expression of Th17-related genes in inflamed tissues has been reported in autoimmune diseases. However, values are frequently obtained using invasive methods. We aimed to identify biomarkers of MS in an accessible sample, such as blood, by quantifying the relative expression of 91 Th17-related genes in CD4+ T lymphocytes from patients with MS during a relapse or during a remitting phase. We also compared our findings with those of healthy controls. After confirmation in a validation cohort, expression of SMAD7 and S1PR1 mRNAs was decreased in remitting disease (-2.3-fold and -1.3-fold, respectively) and relapsing disease (-2.2-fold and -1.3-fold, respectively). No differential expression was observed for other SMAD7-related genes, namely, SMAD2, SMAD3, and SMAD4. Under-regulation of SMAD7 and S1PR1 was also observed in another autoimmune disease, Crohn's disease (CD) (-4.6-fold, -1.6-fold, respectively), suggesting the presence of common markers for autoimmune diseases. In addition, expression of TNF, SMAD2, SMAD3, and SMAD4 were also decreased in CD (-2.2-fold, -1.4-fold, -1.6-fold, and -1.6-fold, respectively). Our study suggests that expression of SMAD7 and S1PR1 mRNA in blood samples are markers for MS and CD, and TNF, SMAD2, SMAD3, and SMAD4 for CD. These genes could prove useful as markers of autoimmune diseases, thus obviating the need for invasive methods.


Asunto(s)
Biomarcadores/análisis , Enfermedad de Crohn/inmunología , Esclerosis Múltiple/inmunología , Transducción de Señal , Receptores de Esfingosina-1-Fosfato/genética , Linfocitos T CD4-Positivos , Humanos , Proteína Smad2/genética , Proteína smad3/genética , Proteína Smad4/genética , Proteína smad7/genética , Células Th17/inmunología , Factor de Crecimiento Transformador beta/genética
17.
Molecules ; 25(23)2020 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-33291428

RESUMEN

Leukemia is a blood or bone marrow cancer with increasing incidence in developed regions of the world. Currently, there is an ongoing need for novel and safe anti-leukemic agents, as no fully effective chemotherapy is available to treat this life-threatening disease. Herein, are reported the isolation, structural elucidation, and anti-leukemic evaluation of twenty-nine withanolide-type steroids (1-29) from Withania aristata. Among them, the new isolated withanolides, withaperoxidins A-D (1-4) have an unusual six-membered cyclic peroxide moiety on the withasteroid skeleton as a structural novelty. Their structures have been elucidated by means of spectroscopic analyses, including 2D NMR experiments. In addition, extensive structure-activity relationships and in silico ADME studies were employed to understand the pharmacophore and pharmacokinetic properties of this series of withasteroids. Compounds 15, 16, and 22 together with withaferin A (14) were identified as having improved antiproliferative effect (IC50 ranging from 0.2 to 0.7 µM) on human leukemia HL-60 cell lines compared with the reference drug, etoposide. This cytotoxic potency was also coupled with good selectivity index (SI 33.0-9.2) on non-tumoral Vero cell line and in silico drug likeness. These findings revealed that these natural withasteroids are potential candidates as chemotherapeutic agents in the treatment of leukemia.


Asunto(s)
Antineoplásicos/farmacología , Leucemia/tratamiento farmacológico , Esteroides/farmacología , Withania/química , Witanólidos/farmacología , Animales , Línea Celular , Línea Celular Tumoral , Chlorocebus aethiops , Células HL-60 , Humanos , Relación Estructura-Actividad , Células Vero
18.
Gastroenterol Hepatol ; 43(7): 408-413, 2020.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32419715

RESUMEN

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was described in China in late 2019. There are currently more than three million diagnosed cases, constituting a pandemic which has caused a worldwide crisis. The devastating effects of this infection are due to its highly contagious nature and although mild forms predominate, in absolute values, the rates for severe forms and mortality are very high. The information on the characteristics of the infection in inflammatory bowel disease is of special interest, as these patients have higher attendance at health centres, which may increase their risk of infection. Furthermore, the treatments used to control the inflammatory activity may modify the disease course of COVID-19. The Spanish Working Group on Crohn's Disease and Ulcerative Colitis and the Spanish Nurses Working Group on Inflammatory Bowel Disease have prepared this document as a practical response to some common questions about the treatment of these patients.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Enfermedades Inflamatorias del Intestino/epidemiología , Pandemias , Neumonía Viral/epidemiología , Ansiedad/etiología , Productos Biológicos/efectos adversos , Productos Biológicos/uso terapéutico , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Comorbilidad , Contraindicaciones de los Medicamentos , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Diarrea/etiología , Susceptibilidad a Enfermedades , Interacciones Farmacológicas , Endoscopía Gastrointestinal/efectos adversos , Composición Familiar , Miedo , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Profesionales/prevención & control , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , Cuarentena , Riesgo , SARS-CoV-2 , España/epidemiología , Vitamina B 12/administración & dosificación , Deficiencia de Vitamina B 12/tratamiento farmacológico , Deficiencia de Vitamina B 12/etiología , Lugar de Trabajo , Tratamiento Farmacológico de COVID-19
19.
Gastroenterol Hepatol ; 43(2): 97-105, 2020 Feb.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31839219

RESUMEN

Although most patients with ulcerative colitis should be given topical treatment, different studies have shown that they are underused in clinical practice. The purpose of this article is to answer 10 specific questions about which drugs are available for topical use in the treatment of ulcerative colitis, and their characteristics in terms of formulation, dosage, presentation, application and proximal distribution of rectal-administered drugs. The efficacy of available topical drugs and the benefits of combining different formulations and routes of administration, and their usefulness during disease remission are evaluated. Finally, a series of recommendations addressed to patients are given on the correct application of topical treatment.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Colitis Ulcerosa/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Mesalamina/administración & dosificación , Administración Tópica , Humanos
20.
Gastroenterol Hepatol ; 43(10): 649-658, 2020 Dec.
Artículo en Inglés, Español | MEDLINE | ID: mdl-32600917

RESUMEN

Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment.


Asunto(s)
Antibacterianos/uso terapéutico , Colitis Ulcerosa/cirugía , Complicaciones Posoperatorias/terapia , Reservoritis/terapia , Probióticos/uso terapéutico , Enfermedad Aguda , Comités Consultivos , Algoritmos , Productos Biológicos/uso terapéutico , Budesonida/uso terapéutico , Enfermedad Crónica , Ciprofloxacina/uso terapéutico , Enfermedad de Crohn , Resistencia a Medicamentos , Enema/métodos , Humanos , Ileostomía/métodos , Inmunosupresores/uso terapéutico , Metronidazol/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Reservoritis/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Prevención Secundaria/métodos , España
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