ABSTRACT
Deep eutectic solvents (DESs) have emerged as a greener alternative to other more polluting traditional solvents and have attracted a lot of interest in the last two decades. The DESs are less toxic dissolvents and have a lower environmental footprint. This paper presents an alternative synthesis method to the classical heating-stirring method. The ultrasound method is one of the most promising synthesis methods for DESs in terms of yield and energy efficiency. Therefore, the ultrasound synthesis method was studied to obtain hydrophobic (Aliquat 336:L-Menthol (3:7); Lidocaine:Decanoic acid (1:2)) and hydrophilic DESs based on choline chloride, urea, ethylene glycol and oxalic acid. The physical characterization of DESs via comparison of Fourier transform infrared (FTIR) spectra showed no difference between the DESs obtained by heating-stirring and ultrasound synthesis methods. The study and comparison of all the prepared DESs were carried out via nuclear magnetic resonance spectroscopy (NMR). The density and viscosity properties of DESs were evaluated. The density values were similar for both synthesis methods. However, differences in viscosity values were detected due to the presence of some water in hygroscopic DESs.
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Objective: The purpose of this research was to design and psychometrically validate a new instrument (the Biobehavioural Pain and Movement Questionnaire/BioPMovQ), which assesses the relationship between pain and various factors related to motor behaviour from a biobehavioural perspective. Methods: A mixed-method design combining a qualitative study with an observational and cross-sectional study was employed to develop (content validity) and psychometrically validate (construct validity, reliability and concurrent/discriminant validity) a new instrument. A total of 200 patients with chronic musculoskeletal pain were recruited. Results: According to the exploratory factor analysis, the final version of the BioPMovQ consists of 16 items distributed across 4 subscales (1, disability, 2, self-efficacy for physical activity; 3, movement avoidance behaviours; and 4, self-perceived functional ability), all with an eigen value greater than 1, explaining 55.79% of the variance. The BioPMovQ showed high internal consistency (Cronbach's α = 0.82; McDonald's ω = 0.83). The intraclass correlation coefficient was 0.86 (95% confidence interval 0.76 to 0.91), which was considered to demonstrate excellent test-retest reliability. The standard error of measurement and minimal detectable change were 3.43 and 8.04 points, respectively. No floor or ceiling effects were identified. There was a positive, significant and moderate magnitude correlation with the Graded Chronic Pain Scale (r = 0.54), kinesiophobia (r = 0.60), pain catastrophising (r = 0.44) and chronic pain self-efficacy (r = -0.31). Conclusion: The BioPMovQ showed good psychometric properties. Based on the findings of this study, the BioPMovQ can be used in research and clinical practice to assess patients with chronic musculoskeletal pain.
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AIMS: The aim of the study is to evaluate the clinical and biochemical response of inflammatory bowel disease patients treated with vedolizumab, 16 weeks after transitioning from intravenous (iv) to subcutaneous (sc). METHODS: An observational, prospective, single-center cohort study was performed. Patients with inflammatory bowel disease and maintenance treatment with vedolizumab, stable for at least 4 months, were offered to switch to sc formulation. At the same time of treatment administration a blood test was performed, with vedolizumab levels and fecal calprotectin. RESULTS: Forty-three patients were included, 12 of them (27.9%) chose to transition to sc formulation. All included patients remained in remission during follow-up. At week 16 no significant differences were found in terms of calprotectin levels in patients on iv treatment (mean 146.6±SD 45.9) vs. sc (159.26±53.9) (p=0.9). Vedolizumab serum levels at week 16 were higher in the sc group (22,364.3±5141.6) vs. iv (11,425.9±1514.2) (p=0.009). At week 16, 9 (75%) of the patients in the sc group were highly satisfied with the medication and 11 (91.7%) considered it easy to administer. Four patients (12.9%) in the iv group and 2 (16.6%) in the sc group presented mild adverse effects. The 2 cases (100%) of the sc group the adverse event was local inflammation at the injection site. CONCLUSION: In our experience, vedolizumab sc is a convenient alternative to iv administration. Vedolizumab serum levels in patients who transitioned to sc were higher than iv formulation.
ABSTRACT
Arthropod herbivory poses a serious threat to crop yield, prompting plants to employ intricate defense mechanisms against pest feeding. The generalist pest 2-spotted spider mite (Tetranychus urticae) inflicts rapid damage and remains challenging due to its broad target range. In this study, we explored the Arabidopsis (Arabidopsis thaliana) response to T. urticae infestation, revealing the induction of abscisic acid (ABA), a hormone typically associated with abiotic stress adaptation, and stomatal closure during water stress. Leveraging a Forster resonance energy transfer (FRET)-based ABA biosensor (nlsABACUS2-400n), we observed elevated ABA levels in various leaf cell types postmite feeding. While ABA's role in pest resistance or susceptibility has been debated, an ABA-deficient mutant exhibited increased mite infestation alongside intact canonical biotic stress signaling, indicating an independent function of ABA in mite defense. We established that ABA-triggered stomatal closure effectively hinders mite feeding and minimizes leaf cell damage through genetic and pharmacological interventions targeting ABA levels, ABA signaling, stomatal aperture, and density. This study underscores the critical interplay between biotic and abiotic stresses in plants, highlighting how the vulnerability to mite infestation arising from open stomata, crucial for transpiration and photosynthesis, reinforces the intricate relationship between these stress types.
Subject(s)
Abscisic Acid , Arabidopsis , Herbivory , Plant Stomata , Tetranychidae , Animals , Abscisic Acid/metabolism , Tetranychidae/physiology , Plant Stomata/physiology , Arabidopsis/physiology , Arabidopsis/genetics , Arabidopsis/parasitology , Signal Transduction , Plant Leaves/parasitology , Plant Leaves/physiology , Plant Leaves/metabolismABSTRACT
A 62-year-old woman, originally from Peru, with rheumatoid arthritis under treatment with anti-tumor necrosis factor (anti-TNF) therapy, was admitted due to constitutional syndrome and suspicion of neoplasia. Computed tomography (CT) scan revealed involvement of three segments of the colon, ascites, and likely peritoneal implants. Ascitic fluid analysis showed elevated adenosine deaminase (ADA) levels and lymphocytosis. The patient presented with hematemesis and hematochezia with hemodynamic instability. Upper gastrointestinal endoscopy identified an extensive ulcer in the middle esophagus with a granular base, elevated and defined edges, indeterminate for malignancy and without blood residues. Colonoscopy also revealed multiple extensive ulcers in the transverse colon, with whitish bases and thickened and necrotic-looking surrounding mucosal edges. Histology showed granulomas and yeast-like fungal structures with methenamine silver staining in both tissues, consistent with disseminated histoplasmosis. Antifungal treatment was initiated with good clinical evolution.
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BACKGROUND: The role of ustekinumab (UST) and vedolizumab (VDZ) in the extraintestinal joint manifestations of inflammatory bowel disease (IBD) remain unclear, and most existing studies are retrospective. The aim of this prospective study was to analyze the incidence of new-onset joint disease or the worsening of pre-existing IBD-associated joint disease in patients treated with UST and VDZ. METHODS: The study population comprised IBD patients with previous spondyloarthritis (SpA) or new-onset arthropathy undergoing treatment with VDZ or UST. RESULTS: Eighty patients were referred to rheumatology because of previous SpA or onset of symptoms. Most patients (90%) were anti-TNF experienced. Two patients with previous SpA (2/22; 9%) experienced a flare-up (one with UST and one with VDZ), and two patients with VDZ developed SpA during follow-up (2/58; 3%). Only one of these four patients did not have gastrointestinal symptoms, and VDZ was discontinued because of joint symptoms. The other three patients had concomitant intestinal activity, and treatment was not discontinued. CONCLUSION: Our experience shows that treatment with UST and VDZ did not worsen joint disease in patients with SpA. Most remained stable or improved. In addition, poor control of IBD in patients with joint flare-ups could be the main cause of worsening SpA.
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CONTEXT: There are no available questionnaires in Spanish that assess the function and performance of shoulder and elbow in overhead sports. The Kerlan-Jobe Orthopaedic Clinic (KJOC) score is a reference tool for this purpose. We aimed to cross-culturally adapt and investigate its measurement properties in Spanish overhead athletes. DESIGN: Cross-cultural adaptation followed the steps of direct translation, back translation, comprehensibility analysis, and review by the Committee of Experts. Then, symptomatic and asymptomatic overhead athletes were invited to complete an electronic version of the Spanish adaptation (KJOC-Sp). The structural validity was evaluated through an exploratory factor analysis with principal axis factoring. Hypotheses were tested for known-groups and convergent validity, studying the correlation with the Shoulder Pain and Disability Index and the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaires in symptomatic athletes. Cronbach alpha was calculated for internal consistency and intraclass correlation coefficient (ICC)2,1 for test-retest reliability. Floor and ceiling effects and time to completion were also calculated. RESULTS: The KJOC-Sp maintained the content of the original version and was adapted to the new population. One hundred participants (41 females and 59 males) with a mean age of 22.4 (5.9) years participated in the study of measurement properties. The factor analysis revealed a 1-factor solution. Symptomatic participants scored significantly lower than asymptomatic, with a large effect size (P < .001; r = .67). Correlations were of -.60 (P < .05) with the Shoulder and Pain Disability Index questionnaire and -0.66 (P < .05) with the Disabilities of the Arm, Shoulder, and Hand Sports Module questionnaire. Cronbach alpha was .98 (95% confidence interval, .97-.98) and the ICC2,1 was .96 (95% confidence interval .93-.98). No floor or ceiling effects were observed among the symptomatic athletes, while mean time to completion was 121 seconds. CONCLUSION: The KJOC-Sp is equivalent to the original score, aside from valid and reliable, without floor or ceiling effects in symptomatic athletes and with a low time consumption.
Subject(s)
Orthopedics , Shoulder Injuries , Male , Female , Humans , Young Adult , Adult , Shoulder , Elbow , Reproducibility of Results , Cross-Cultural Comparison , Shoulder Pain/diagnosis , Surveys and QuestionnairesABSTRACT
The interaction between plants and phytophagous arthropods encompasses a complex network of molecules, signals, and pathways to overcome defences generated by each interacting organism. Although most of the elements and modulators involved in this interplay are still unidentified, plant redox homeostasis and signalling are essential for the establishment of defence responses. Here, focusing on the response of Arabidopsis thaliana to the spider mite Tetranychus urticae, we demonstrate the involvement in plant defence of the thioredoxin TRXh5, a small redox protein whose expression is induced by mite infestation. TRXh5 is localized in the cell membrane system and cytoplasm and is associated with alterations in the content of reactive oxygen and nitrogen species. Protein S-nitrosylation signal in TRXh5 over-expression lines is decreased and alteration in TRXh5 level produces changes in the JA/SA hormonal crosstalk of infested plants. Moreover, TRXh5 interacts and likely regulates the redox state of an uncharacterized receptor-like kinase, named THIOREDOXIN INTERACTING RECEPTOR KINASE (TIRK), also induced by mite herbivory. Feeding bioassays performed withTRXh5 over-expression plants result in lower leaf damage and reduced egg accumulation after T. urticae infestation than in wild-type (WT) plants. In contrast, mites cause a more severe injury in trxh5 mutant lines where a greater number of eggs accumulates. Likewise, analysis of TIRK-gain and -loss-of-function lines demonstrate the defence role of this receptor in Arabidopsis against T. urticae. Altogether, our findings demonstrate the interaction between TRXh5 and TIRK and highlight the importance of TRXh5 and TIRK in the establishment of effective Arabidopsis defences against spider mite herbivory.
Subject(s)
Arabidopsis , Tetranychidae , Animals , Arabidopsis/genetics , Tetranychidae/genetics , Plants , Thioredoxins/genetics , HomeostasisABSTRACT
The purpose of this study is to present the development and analysis of the factorial structure and psychometric properties of a new self-administered questionnaire (Dizziness Fear-Avoidance Behaviours and Beliefs Inventory (D-FABBI)) designed to measure fear-avoidance behaviors and cognitions related to dizziness disability. A mixed-method design combining a qualitative study with an observational and cross-sectional study was employed to develop (content validity) and psychometrically validate (construct validity, reliability, and convergent/discriminant validity) a new instrument. A total of 198 patients with vestibular disorders (acute vestibular syndrome (AVS), 23.2%; chronic vestibular syndrome (CVS), 35.4%; and episodic vestibular syndrome (EVS) 41.4%) were recruited. Sociodemographic characteristics, the Dizziness Handicap Inventory (DHI) and the Hospital Anxiety and Depression Scale (HADS) and D-FABBI were evaluated. The final version of the D-FABBI consists of 17 items distributed across two subscales: activities of daily living fear-avoidance and movement fear-avoidance. The D-FABBI showed high internal consistency (Cronbach α = 0.932; 95% CI [0.91-0.94]) and so did the subscales (Cronbach α > 0.8). The exploratory structural equation model and confirmatory factor analysis provided better fit results, with a comparative fit index and root mean square error of approximation values of 0.907 to 0.081. No floor or ceiling effects were identified. There was a positive, significant, and moderate-strong magnitude correlation with the total DHI (r = 0.62) and low-moderate with respect to the HADS depression (r = 0.35) and HADS anxiety subscales (r = 0.26). The patients with CVS had a higher D-FABBI score than those with AVS or EVS. The D-FABBI appears to be a valid and reliable instrument for measuring the fear-avoidance behaviors and cognition related to dizziness disability of patients with vestibular disorders.
Subject(s)
Dizziness , Vestibular Diseases , Humans , Activities of Daily Living , Avoidance Learning , Cross-Sectional Studies , Dizziness/diagnosis , Fear , Reproducibility of Results , Vertigo , Vestibular Diseases/diagnosisABSTRACT
Jasmonates are essential modulators of plant defences but the role of JA-derivatives has been scarcely studied, particularly in the plant-pest interplay. To deepen into the JA catabolism and its impact on plant responses to spider mite infestation, we selected the Arabidopsis JAO2 gene as a key element involved in the first step of the JA-catabolic route. JAO2 is responsible for the hydroxylation of JA into 12-OH-JA, contributes to attenuate JA and JA-Ile content and consequently, determines the formation of other JA-catabolites. JAO2 was up-regulated in Arabidopsis by mite infestation. Mites also induced JA-derivative accumulation in plants. In jao2 mutant lines, and in the triple mutant jaoT (jao2-1, jao3-1, jao4-2), mite feeding produced less leaf damage, minor callose deposition and lower mite fecundity rates than in Col-0 plants. The impairment of JA oxidation in jao2 lines not only diminished the 12-OH-JA levels but turned off further sulfation as shown the significant reduction of 12-HSO4-JA form. Thus, JAO2 acts as a negative modulator of defences to spider mites mediated by changes in the generation of JA catabolic molecules, and the consequent production of defensive metabolites such as glucosinolates or camalexin.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Mite Infestations , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cyclopentanes/metabolism , Oxylipins/metabolismABSTRACT
Endothelin (ET) is found to be increased in kidney disease secondary to hyperglycaemia, hypertension, acidosis, and the presence of insulin or proinflammatory cytokines. In this context, ET, via the endothelin receptor type A (ETA) activation, causes sustained vasoconstriction of the afferent arterioles that produces deleterious effects such as hyperfiltration, podocyte damage, proteinuria and, eventually, GFR decline. Therefore, endothelin receptor antagonists (ERAs) have been proposed as a therapeutic strategy to reduce proteinuria and slow the progression of kidney disease. Preclinical and clinical evidence has revealed that the administration of ERAs reduces kidney fibrosis, inflammation and proteinuria. Currently, the efficacy of many ERAs to treat kidney disease is being tested in randomized controlled trials; however, some of these, such as avosentan and atrasentan, were not commercialized due to the adverse events related to their use. Therefore, to take advantage of the protective properties of the ERAs, the use of ETA receptor-specific antagonists and/or combining them with sodium-glucose cotransporter 2 inhibitors (SGLT2i) has been proposed to prevent oedemas, the main ERAs-related deleterious effect. The use of a dual angiotensin-II type 1/endothelin receptor blocker (sparsentan) is also being evaluated to treat kidney disease. Here, we reviewed the main ERAs developed and the preclinical and clinical evidence of their kidney-protective effects. Additionally, we provided an overview of new strategies that have been proposed to integrate ERAs in kidney disease treatment.
Subject(s)
Endothelin Receptor Antagonists , Kidney Diseases , Humans , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Endothelin A Receptor Antagonists , Endothelin-1 , Endothelins , Kidney , Kidney Diseases/drug therapy , Proteinuria/drug therapy , Receptor, Endothelin AABSTRACT
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have proven to delay diabetic kidney disease (DKD) progression on top of the standard of care with the renin-angiotensin system (RAS) blockade. The molecular mechanisms underlying the synergistic effect of SGLT2i and RAS blockers is poorly understood. We gave a SGLT2i (empagliflozin), an angiotensin-converting enzyme inhibitor (ramipril), or a combination of both drugs for 8 weeks to diabetic (db/db) mice. Vehicle-treated db/db and db/m mice were used as controls. At the end of the experiment, mice were killed, and the kidneys were saved to perform a differential high-throughput proteomic analysis by mass spectrometry using isobaric tandem mass tags (TMT labeling) that allow relative quantification of the identified proteins. The differential proteomic analysis revealed 203 proteins differentially expressed in one or more experimental groups (false discovery rate < 0.05 and Log2 fold change ≥ ±1). Fourteen were differentially expressed in the kidneys from the db/db mice treated with empagliflozin with ramipril. Among them, MAP17 was up-regulated. These findings were subsequently validated by Western blot. The combined therapy of empagliflozin and ramipril up-regulated MAP17 in the kidney of a diabetic mice model. MAP17 is a major scaffolding protein of the proximal tubular cells that places transporters together, namely SGLT2 and NHE3. Our results suggest that SGLT2i on top of RAS blockade may protect the kidney by boosting the inactivation of NHE3 via the up-regulation of key scaffolder proteins such as MAP17.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Mice , Animals , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Renin-Angiotensin System , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Ramipril/pharmacology , Ramipril/therapeutic use , Proteomics , Sodium-Hydrogen Exchanger 3/metabolismABSTRACT
CASE REPORT A 86-year-old man with a recent history of stent placement for infrarenal aortic aneurysm arrives to the emergency department with abdominal pain. Computed tomography (CT) is performed to rule out complications of the endovascular procedure. The CT showed a loop of ileum with decreased caliber, fat trabeculation and hypervascularity causing proximal dilatation. No signs of ischemia or complications related to the prosthesis were observed. He was admitted to our service due to findings of non-specific ileitis. An intestinal ultrasound was performed and revealed a short segment of proximal ileum with pathological wall thickening with an intraluminal birefringent filamentary hyperechoic material (foreign body), which crossed all the layers of the wall. In the following days serial ultrasounds were performed showing that the foreign body remained in the same location and it was decided to perform surgery. During surgery the foreign body turned out to be a blister which conditioned an ileitis. Finally, intestinal resection was performed and the patient presented good clinical evolution. DISCUSSION The most validated technique for the diagnosis of foreign bodies is CT (1). However, intestinal ultrasound could help in its identification, especially for the non-radiopaque ingested material. On the other hand, it is especially useful in the pediatric age, where exposure to ionizing radiation should be avoided (2,3). In our case, it allowed not only to establish the diagnosis immediately but also to evaluate the evolutionary behavior of the same in terms of its mobilization or detection of local complications.
Subject(s)
Foreign Bodies , Ileitis , Aged, 80 and over , Humans , Male , Diagnosis, Differential , Foreign Bodies/diagnostic imaging , Foreign Bodies/surgery , Foreign Bodies/complications , Ileitis/diagnostic imaging , Ileum/diagnostic imaging , Ileum/surgery , Stents , Tomography, X-Ray ComputedABSTRACT
Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin-dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK-counteracting phosphatase whose function in mammals remains obscure. Lack of the two CDC14 family members, CDC14A and CDC14B, results in deficient development of the neural system in the mouse and impairs neural differentiation from embryonic stem cells (ESCs). Mechanistically, CDC14 directly dephosphorylates specific proline-directed Ser/Thr residues of undifferentiated embryonic transcription Factor 1 (UTF1) during the exit from stemness, triggering its proteasome-dependent degradation. Multiomic single-cell analysis of transcription and chromatin accessibility in differentiating ESCs suggests that increased UTF1 levels in the absence of CDC14 prevent the proper firing of bivalent promoters required for differentiation. CDC14 phosphatases are dispensable for mitotic exit, suggesting that CDC14 phosphatases have evolved to control stemness rather than cell cycle exit and establish the CDK-CDC14 axis as a critical molecular switch for linking cell cycle regulation and self-renewal.
Subject(s)
Cell Cycle Proteins , Saccharomyces cerevisiae Proteins , Animals , Mice , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Protein Tyrosine Phosphatases/genetics , Protein Tyrosine Phosphatases/metabolism , Cyclin-Dependent Kinases/metabolism , Cell Cycle , Phosphorylation/physiology , Mitosis , Saccharomyces cerevisiae Proteins/metabolism , MammalsABSTRACT
A 76-year-old man with multiple cardiovascular risk factors (hypertension, DM2, LD, smoker) and severe peripheral arterial disease (iliofemoral bypass, supracondylar amputation) came to the emergency with coffee ground emesis and mild anemia. Urgent gastroscopy showed diffuse circumferential black mucosa covered by fibrin affecting the middle and distal esophageal third. Acute esophageal necrosis is a rare cause of gastrointestinal bleeding that should be suspected in patients with cardiovascular risk factors with an image of a black esophagus that is abruptly interrupted at the EGJ.
Subject(s)
Esophageal Diseases , Male , Humans , Aged , Necrosis/complications , Esophageal Diseases/diagnostic imaging , Esophageal Diseases/surgery , Esophageal Diseases/complications , Hematemesis , Gastrointestinal Hemorrhage/etiology , Acute DiseaseABSTRACT
INTRODUCTION: Chronic immune-mediated diseases, including inflammatory bowel disease (IBD), present an increased risk of developing early atherosclerosis and cardiovascular events (CVE) at early age. OBJECTIVE: To describe the baseline and 1-year cardiovascular profile of patients with IBD according to the biologic treatment received, taking into account the inflammatory activity. PATIENTS AND METHODS: It is a retrospective, observational study that included 374 patients. Cardiovascular risk factors (CVRF) and CVE were collected at the baseline visit and at one-year follow-up to describe the cardiovascular risk according to the biological treatment received, also assessing clinical and biological remission. RESULTS: A total of 374 patients were included: 146 (38.73%) were treated with Infliximab, 128 (33.95%) with adalimumab, 61 (16.18%) with ustekinumab and 42 (11.14%) with vedolizumab. The changes in blood glucose levels are [86.31mg/dL (84.57-88.06) vs. 89.25mg/dL (87.54-90.96), P=.001] for those treated with antiTNFα and [86.52mg/dL (83.48-89.55) vs. 89.44mg/dL (85.77-93.11), P=.11] in the other group. In the group treated with antiTNFα total cholesterol values at baseline visit are [169.40mg/dL (164.97-173.83) vs. 177.40mg/dL (172.75-182.05) at one year of treatment, P=<.001], those of HDL [50.22mg/dL (48.39-52.04) vs. 54.26mg/dL (52.46-56.07), P=<.001] and those of triglycerides [114.77mg/dL (106.36-123.18) vs. 121.83mg/dL (112.11-131.54), P=.054]. Regarding weight, an increase was observed, both in those patients treated with antiTNFα [71.39kg (69.53-73.25) vs. 72.87kg (71.05-74.70), P<.001], and in the group treated with ustekinumab and vedolizumab [67.59kg (64.10-71.08) vs. 69.43kg (65.65-73.04), P=.003]. Concerning CVE, no significant differences were observed neither according to the drug used (p=0.36), nor according to personal history of CVE (P=.23) nor according to inflammatory activity (P=.46). CONCLUSIONS: Our results on a real cohort of patients with IBD treated with biologic drugs show a better control of certain cardiovascular parameters such as CRP or HDL, but a worsening of others such as total cholesterol or triglycerides, regardless of the treatment. Therefore, it is possibly the disease control and not the therapeutic target used, the one that affect the cardiovascular risk of these patients.
Subject(s)
Cardiovascular Diseases , Inflammatory Bowel Diseases , Humans , Ustekinumab/adverse effects , Retrospective Studies , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Risk Factors , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Infliximab/adverse effects , Biological Therapy/adverse effects , Triglycerides , Cholesterol , Heart Disease Risk FactorsSubject(s)
Humans , Male , Aged , Esophageal Diseases/diagnostic imaging , Esophageal Diseases/drug therapy , NecrosisABSTRACT
Treatments with sodium-glucose 2 cotransporter inhibitors (SGLT2i) or endothelin receptor antagonists (ERA) have shown cardiorenal protective effects. The present study aimed to evaluate the cardiorenal beneficial effects of the combination of SGLT2i and ERA on top of renin-angiotensin system (RAS) blockade. Type 2 diabetic mice (db/db) were treated with different combinations of an SGLT2i (empagliflozin), an ERA (atrasentan), and an angiotensin-converting enzyme inhibitor (ramipril) for 8 weeks. Vehicle-treated diabetic mice and non-diabetic mice were included as controls. Weight, blood glucose, blood pressure, and kidney and heart function were monitored during the study. Kidneys and heart were collected for histological examination and to study the intrarenal RAS. Treatment with empagliflozin alone or combined significantly decreased blood glucose compared to vehicle-treated db/db. The dual and triple therapies achieved significantly greater reductions in diastolic blood pressure than ramipril alone. Compared to vehicle-treated db/db, empagliflozin combined with ramipril or in triple therapy significantly prevented GFR increase, but only the triple combination exerted greater protection against podocyte loss. In the heart, empagliflozin alone or combined reduced cardiac isovolumetric relaxation time (IVRT) and left atrium (LA) diameter as compared to vehicle-treated db/db. However, only the triple therapy was able to reduce cardiomyocyte area. Importantly, the add-on triple therapy further enhanced the intrarenal ACE2/Ang(1-7)/Mas protective arm of the RAS. These data suggest that triple therapy with empagliflozin, atrasentan and ramipril show synergistic cardiorenal protective effects in a type 2 diabetic mouse model.
Subject(s)
Diabetes Mellitus, Type 2 , Renin-Angiotensin System , Mice , Animals , Sodium-Glucose Transporter 2 , Atrasentan/pharmacology , Endothelin Receptor Antagonists/pharmacology , Blood Glucose , Ramipril/pharmacology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Receptors, EndothelinABSTRACT
The frequency of a high Central Sensitization Inventory (CSI) total score and the prevalence of pain have already been established among breast cancer survivors (BCS). However, the psychological factors' influence based on the clinical features of pain is still unknown, as well as BCS characteristics with no pain. Thus, our main aim was to evaluate the presence of a high CSI total score in BCS with pain and compare it with BCS without pain and to evaluate the influence of psychosocial factors. A cross-sectional comparative study was designed to compare BCS with nociceptive pain (n = 19), pain with neuropathic features (n = 19) or no pain (n = 19), classified by the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS). CSI, pain catastrophizing, fear of movement, anxiety and depression symptoms were analyzed and compared among the three groups. The CSI total score was higher in both BCS pain groups compared to BCS without pain, but there were no statistical differences between the pain groups. The same observation was made when comparing pain catastrophizing. The neuropathic feature group showed greater levels of fear of movement, anxiety and depression compared to the no pain group. Thus, CS-psychosocial associated comorbidities and pain-catastrophizing thoughts were more prevalent among BCS with pain, regardless of the clinical features of pain. BCS with neuropathic pain features showed greater psychological disturbances.