ABSTRACT
Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. Diagnosing MM presents considerable challenges, involving the identification of plasma cells in cytology examinations on hematological slides. At present, this is still a time-consuming manual task and has high labor costs. These challenges have adverse implications, which rely heavily on medical professionals' expertise and experience. To tackle these challenges, we present an investigation using Artificial Intelligence, specifically a Machine Learning analysis of hematological slides with a Deep Neural Network (DNN), to support specialists during the process of diagnosing MM. In this sense, the contribution of this study is twofold: in addition to the trained model to diagnose MM, we also make available to the community a fully-curated hematological slide dataset with thousands of images of plasma cells. Taken together, the setup we established here is a framework that researchers and hospitals with limited resources can promptly use. Our contributions provide practical results that have been directly applied in the public health system in Brazil. Given the open-source nature of the project, we anticipate it will be used and extended to diagnose other malignancies.
Subject(s)
Multiple Myeloma , Humans , Bone Marrow/pathology , Brazil , Hematology/methods , Machine Learning , Multiple Myeloma/diagnosis , Multiple Myeloma/pathology , Neural Networks, Computer , Plasma Cells/pathologyABSTRACT
PURPOSE: Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. METHODS: We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. RESULTS: We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). CONCLUSION: In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.
Subject(s)
Anticoagulants , Atrial Fibrillation , Randomized Controlled Trials as Topic , Renal Dialysis , Vitamin K , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Vitamin K/antagonists & inhibitors , Administration, Oral , Anticoagulants/therapeutic use , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/complicationsABSTRACT
In current systems, the fermentation spontaneous process produces fermented beans of heterogeneous quality due to the fermentation time. This study demonstrated that the fermentation time should be reduced. For this purpose, the physicochemical parameters, antioxidant profile, and volatile compounds were characterized in two types of fermentation (spontaneous and starter culture) for 168 h in cocoa from three altitude levels. Multivariate analysis (cluster and PCA) was used to discriminate the fermentation stages. We found three stages in all fermentations, where the first two stages (0 h to 96 h) were characterized by a higher antioxidant potential of the cocoa bean and the presence of desirable volatile compounds such as acids, alcohols, aldehydes, ketones, and esters, which are precursors of cocoa aroma; however, prolonged fermentation times affected the antioxidant profile of the bean. In addition, the use of a starter culture facilitates the release of compounds in a shorter time (especially alcohols and esters). It is concluded that it is necessary to reduce the fermentation time under these conditions in the region of Amazonas.
ABSTRACT
Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.
Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Humans , Cancer-Associated Fibroblasts/pathology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Fibroblasts/pathology , Immune Tolerance , Immunosuppression Therapy , Tumor Microenvironment , Cell Proliferation , Receptors, Interleukin-1 Type I/geneticsABSTRACT
Brazil has the second-highest COVID-19 death rate worldwide, and Rio de Janeiro is among the states with the highest rate in the country. Although vaccine coverage has been achieved, it is anticipated that COVID-19 will transition into an endemic disease. It is concerning that the molecular mechanisms underlying clinical evolution from mild to severe disease, as well as the mechanisms leading to long COVID-19, are not yet fully understood. NMR and MS-based metabolomics were used to identify metabolites associated with COVID-19 pathophysiology and disease outcome. Severe COVID-19 cases (n = 35) were enrolled in two reference centers in Rio de Janeiro within 72 h of ICU admission, alongside 12 non-infected control subjects. COVID-19 patients were grouped into survivors (n = 18) and non-survivors (n = 17). Choline-related metabolites, serine, glycine, and betaine, were reduced in severe COVID-19, indicating dysregulation in methyl donors. Non-survivors had higher levels of creatine/creatinine, 4-hydroxyproline, gluconic acid, and N-acetylserine, indicating liver and kidney dysfunction. Several changes were greater in women; thus, patients' sex should be considered in pandemic surveillance to achieve better disease stratification and improve outcomes. These metabolic alterations may be useful to monitor organ (dys) function and to understand the pathophysiology of acute and possibly post-acute COVID-19 syndromes.
ABSTRACT
Intramural ventricular arrhythmias are challenging to treat. Adjunctive techniques such as bipolar ablation, ethanol injection, use of a needle catheter, or surgery have been described. These are often not readily available. This is a case report of a patient with refractory intramural ventricular arrhythmia that was ablated by incorporating electrodes of a mapping catheter into the ablation circuit. The results of ex vivo experiments to determine the characteristics of multipolar ablation lesions using different ablation settings are reported. The feasibility of generating transmural lesions with multipolar ablation in vivo in a porcine model was tested.
Subject(s)
Catheter Ablation , Tachycardia, Ventricular , Animals , Swine , Arrhythmias, Cardiac/surgery , Electrodes , Ethanol , Catheter Ablation/methodsABSTRACT
BACKGROUND: Predictors of in-hospital mortality after myocardial infarction (MI) have been reported dichotomously: survival vs death. Predictors of time from admission to death have not been reported. METHODS: A total of 7335 patients were enrolled in a prospective multicentre registry of acute MI. In-hospital mortality was classified by time from admission as acute (≤ 2 days), subacute (3 to 7 days), late (8 to 14 days), and very late (≥ 15 days) to identify factors associated with time to death in patients who died before discharge. Patient and MI characteristics, in-hospital interventions, and electrocardiographic findings were screened for differences in time to in-hospital death. RESULTS: In-hospital death affected 351 patients (4.8%). Mean age was 72.0 ± 12.4 years, and 40.5% were female patients. Median survival was 5 days (interquartile range: 2-12), and 41% of in-hospital deaths occurred after 1 week. Cardiac biomarkers and ejection fraction were not related to time to in-hospital death. Previous MI, systolic blood pressure, pharmacologic therapy, and interventional treatments were different among the 4 groups. The factors associated with late in-hospital death were coronary artery bypass graft surgery (CABG), new-onset atrial fibrillation or flutter, heart failure or pulmonary edema, bleeding, and lung disease. Acute and subacute in-hospital death was associated with ST-elevation MI, lower systolic blood pressure, and cardiac arrest on admission. CABG was performed in 12% of post-MI patients who died in hospital. CONCLUSIONS: Clinical risk factors for in-hospital mortality evolve over time immediately after acute MI. Understanding the time-dependent risk factors may allow for the development of new approaches to curtail the "later" in-hospital mortality.
Subject(s)
Myocardial Infarction , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , Hospital Mortality , Prospective Studies , Coronary Artery Bypass/adverse effects , RegistriesABSTRACT
Transcatheter aortic valve replacement (TAVR) is well-established for severe symptomatic aortic stenosis (AS), but its use in rheumatic heart disease (RHD) has been limited. We systematically review the use of TAVR for severe symptomatic AS in RHD. Pubmed, Embase, and Scopus were searched for TAVR for symptomatic severe AS and proven or suspected RHD. Procedure characteristics, efficacy, and safety endpoints were collected and all definitions were based on the Valve Academic Research Consortium-2 (VARC-2) criteria. We included 3 case series and 12 case reports, with a total of 43 patients. Mean age was 76 years, 75% were female, and 85% had NYHA class III-IV symptoms. Follow up ranged from 1 to 29 months. Patients were moderate to high risk, with Society of Thoracic Surgery score ranging from 6.1% to 17.6%. The approach was transfemoral in 30 (83%) cases. Procedural success occurred in 37 (86%) patients. Of the 7 patients with periprocedural complications, 4 had valve dislodgement, 1 deployment failure, 1 unplanned cardiopulmonary bypass, and 1 moderate aortic regurgitation. Paravalvular leak was reported in 5 (11.6%) patients. Only 1 patient had heart block requiring pacemaker. Among 13 studies (23 patients), 30-day mortality was 0%. One case series with 19 patients had a 30-day, 1-year, 2-year, and 5-year mortality of 5%, 11%, 31%, and 48%, respectively. TAVR appears feasible for selected patients with rheumatic severe AS, albeit our results indicate a 14% incidence of device failure. Future randomized clinical trials may clarify the role of TAVR in this group.
Subject(s)
Aortic Valve Stenosis , Heart Valve Prosthesis , Rheumatic Heart Disease , Transcatheter Aortic Valve Replacement , Aged , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Female , Humans , Male , Rheumatic Heart Disease/complications , Rheumatic Heart Disease/surgery , Risk Factors , Severity of Illness Index , Time Factors , Transcatheter Aortic Valve Replacement/methods , Treatment OutcomeABSTRACT
The use of yeasts as starter cultures is a promising alternative to produce fermented cacao with particular characteristics regarding the quality of aromas and physical and chemical characteristics that are accepted by the chocolate market. This study aimed to evaluate the physical and chemical transformations of cocoa beans during fermentation after inoculation with starter cultures of yeast species Pichia manshurica (PF) and Saccharomyces cerevisiae (SF), both previously isolated in cocoa bean fermentations in the Brazilian Amazon, in comparison with a fermentation without the inoculum addition (CF). During the fermentation time, which was carried out on a cocoa farm in Igarapé-Miri (Amazon biome, Pará, Brazil), the contents of phenolic compounds (catechin and epicatechin), sugars (glucose, fructose, and sucrose), acetic acid, and ethanol were monitored by HPLC, and the volatile compounds profiles were assessed by GC-MS. The starter culture of P. manshurica was able to produce fermented cocoa beans with highly desirable characteristics for the production of good quality chocolate: low acidity, a broad variety of aromatic compounds with floral, fruity, and sweet characteristics, in addition to showing high contents of catechin and epicatechin, which are known by their antioxidant properties. Therefore, the use of starter cultures with species of yeasts isolated in the Amazon region, during cocoa fermentation, is an alternative to obtain fermented seeds with high quality favoring the commercial agreements in the chocolate market by cocoa producers. PRACTICAL APPLICATION: The addition of starter cultures was able to produce cocoa beans with good quality. Yeasts species isolated and identified in Amazonian cocoa fermentation can improve the profiles of aromatic compounds. Catechin and epicatechin contents are higher in inoculated cocoa beans fermentations.
Subject(s)
Cacao , Catechin , Antioxidants , Cacao/chemistry , Ecosystem , Ethanol , Fermentation , Fructose , Glucose , Pichia , Saccharomyces cerevisiae , Sucrose , SugarsABSTRACT
OBJECTIVES: Evaluation of the anti-Leishmanial activity of imidazoquinoline-based TLR7/8 agonists. METHODS: TLR7/8-active imidazoquinolines (2 and 3) were synthesized and assessed for activity against Leishmania amazonensis-intracellular amastigotes using mouse peritoneal macrophages. The production of reactive oxygen species (ROS), nitric oxide (NO) and cytokines was determined in infected and non-infected macrophages. KEY FINDINGS: The imidazoquinolines, 2 and 3, were primarily agonists of TLR7 with compound 3 also showing modest TLR8 activity. Docking studies showed them to occupy the same binding pocket on TLR7 and 8 as the known agonists, imiquimod and resiquimod. Compounds 2 and 3 inhibited the growth of L. amazonensis-intracellular amastigotes with the most potent compound (3, IC50 = 5.93 µM) having an IC50 value close to miltefosine (IC50 = 4.05 µM), a known anti-Leishmanial drug. Compound 3 induced macrophages to produce ROS, NO and inflammatory cytokines that likely explain the anti-Leishmanial effects. CONCLUSIONS: This study shows that activating TLR7 using compounds 2 or 3 induces anti-Leishmanial activity associated with induction of free radicals and inflammatory cytokines able to kill the parasites. While 2 and 3 had a very narrow cytotoxicity window for macrophages, this identifies the possibility to further develop this chemical scaffold to less cytotoxic TLR7/8 agonist for potential use as anti-Leishmanial drug.
Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Macrophages, Peritoneal/drug effects , Toll-Like Receptor 7/agonists , Toll-Like Receptor 8/agonists , Animals , Antiprotozoal Agents/chemical synthesis , Cytokines/metabolism , Female , Humans , Imidazoles , Imiquimod , Inflammation/metabolism , Leishmaniasis/parasitology , Macrophages, Peritoneal/parasitology , Mice, Inbred BALB C , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolismABSTRACT
BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated. OBJECTIVE: The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF. METHODS: We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD). RESULTS: We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53-67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69-0.95; P = .008) and the "SCD" component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54-0.97; P = .03) compared with control. There was no significant difference in incident VA or the "cardiac arrest" SCD component between groups. CONCLUSION: SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect.
Subject(s)
Death, Sudden, Cardiac/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Heart Failure/drug therapy , Randomized Controlled Trials as Topic , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Diabetes Mellitus, Type 2/complications , Global Health , Heart Failure/complications , Humans , IncidenceABSTRACT
Gold nanoparticles (AuNP) modified with antibody and rifampicin (RP) were tested against Mycobacterium bovis Bacillus Calmette-Guérin (BCG), which previously generated in vitro infection of macrophages from mice. Such a drug delivery system works as nanocarrier for RP and presented lower toxicity for macrophages cells than each separated component. Surface-enhanced Raman scattering (SERS) spectroscopy and fluorescence microscopy were used as analytical tools for the characterization of the internalization of gold nanocarriers into macrophage cells. The effective antibiotic action of RP, when combined with gold nanocarrier, was confirmed by dead-live assay of BCG bacteria lysed from macrophages after incubation. Such results indicate the delivery of RP to BCG bacteria, which were infecting macrophages, occurred with remarkable efficiency. It was rationalized based on the strategy used for the adsorption of antibody molecules on gold surface.
Subject(s)
Metal Nanoparticles , Mycobacterium bovis , Animals , Drug Delivery Systems , Gold , Macrophages , Mice , Spectrum Analysis, RamanABSTRACT
BACKGROUND: Leukotrienes (LTs) participate in the process of tissue damage in periodontal disease by leukocyte chemotaxis and osteoclastic activation. The activation of Cysteinyl-LT receptor is associated with increased expression of proinflammatory molecules and osteoclastogenesis. However, its implications on periodontal disease progression have not been studied. The present study evaluated the effect of the cysteinyl-LT receptor antagonist (montelukast [MT]) on ligature-induced experimental periodontitis (EP) in rats. METHODS: Adult male Wistar rats were subjected to bilateral ligature-induced periodontitis and orally treated with MT (at doses of 10 or 30 mg/kg/d, MT10, and MT30, respectively). Sham animals had the ligatures immediately removed and received placebo treatment. Sets of animals were euthanized 7, 14, or 21 days after ligature placement and the mandibles were removed for macroscopic evaluation of alveolar bone loss (ABL). In addition, histological analysis of periodontal tissues, myeloperoxidase (MPO) activity of gingival tissues, and periodontal tissue expression of collagen type I, RUNX2, RANK, RANKL, OPG, BLT1, Cys-LTR1, LTA4H, and LTC4S were also analyzed. RESULTS: MT significantly reduced ABL at 14 (MT10 and MT30) and 21 days (MT10) (P < 0.05), gingival MPO at 7 (MT10) and 14 days (MT30) (P < 0.05), LTA4H, BLT1 and LTC4S gene expression on day 14 day (MT30, P < 0.05) and increased RUNX2 expression on day 14 (MT30, P < 0.05). CONCLUSION: Systemic therapy with MT decreases periodontal inflammation and ABL in ligature-induced periodontitis in rats.
Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/prevention & control , Animals , Inflammation , Leukotriene Antagonists , Male , Periodontitis/drug therapy , Rats , Rats, WistarABSTRACT
BACKGROUND: Angiotensin receptor-neprilysin inhibitor (ARNI) therapy has been associated with improved survival for patients with symptomatic heart failure and reduced ejection fraction (HFrEF). OBJECTIVES: We performed a meta-analysis of arrhythmia endpoints from studies comparing ARNI with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with HFrEF to assess for incremental benefit. METHODS: We searched PubMed, Embase, and ClinicalTrials.gov. Baseline study characteristics were collected and outcomes were sustained ventricular arrhythmias, atrial arrhythmias, appropriate implantable cardioverter-defibrillator (ICD) therapy, sudden cardiac death (SCD), and biventricular (BiV) pacing rate. RESULTS: We included 9 studies, 4 randomized trials, and 5 observational studies (5589 patients on ARNI vs 5615 on ACEIs/ARBs). Follow-up ranged from 2 to 51 months. The mean age was 65.4 ± 9.8 years, with 77.3% male patients and a mean ejection fraction of 29.0% ± 7.6%. Ischemic cardiomyopathy was present in 62% of patients. In the ARNI group, there were less SCD (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63-0.96; P = .02), ventricular arrhythmias (OR 0.45, 95% CI 0.25-0.79; P = .005), and appropriate ICD therapy (OR 0.39, 95% CI 0.21-0.74; P = .004). Higher rates of BiV pacing were seen (mean difference 3.13, 95% CI 2.58-3.68; P < .00001) when compared with ACEIs/ARBs. No difference in atrial arrhythmias was seen. CONCLUSION: ARNI therapy provides incremental benefit with respect to ventricular tachyarrhythmias/SCD, which may, in part, explain improved outcomes in patients with HFrEF compared to ACEIs/ARBs. There was increased BiV pacing and decreased ICD therapy in the ARNI group.
ABSTRACT
INTRODUCTION: Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP), and RVP for advanced AVB in patients with normal or mildly reduced EF. METHODS AND RESULTS: MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, Scopus, and Web of Science were searched. Outcomes were all-cause death, heart failure hospitalizations (HFH), EF, left ventricular volumes, 6-minute walk test, and QRS duration. HBP or BiVP was compared with RVP. Subsequently, network meta-analysis compared the three pacing options. Our protocol was registered in PROSPERO (CRD42018094132). Six studies compared BiVP and RVP (704 vs 614 patients) and four compared HBP and RVP (463 vs 568 patients). Follow-up was 6 months to 5 years. There was significantly lower mortality and HFH with HBP or BiVP as compared with RVP (odds ratio [OR], 0.66, [0.51-0.85], P = .002; OR, 0.61 [0.45-0.82], P < .001, respectively]. HBP or BiVP also showed significant increase in EF and decrease in QRS duration (mean difference [MD], 5.27 [3.86-6.69], P < .001; MD -42.2 [-51.2 to -33.3], P < .001, respectively). In network meta-analysis, HBP and BiVP were associated with significantly improved survival compared to RVP, with surface under the cumulative ranking curve (SUCRA) probability of 79.4%, 69.4%, and 1.2% for HBP, BiVP, and RVP, respectively. For HFH, SUCRA probability was 91.5%, 57.2%, and 1.3%, respectively. CONCLUSION: HBP or BiVP were the superior strategies to reduce all-cause death and HFH for advanced AVB with normal or mildly reduced EF, with no significant difference between BiVP and HBP.
Subject(s)
Atrioventricular Block/surgery , Bundle of His/physiopathology , Cardiac Pacing, Artificial , Ventricular Function, Left , Ventricular Function, Right , Action Potentials , Atrioventricular Block/diagnosis , Atrioventricular Block/mortality , Atrioventricular Block/physiopathology , Cardiac Pacing, Artificial/adverse effects , Cardiac Pacing, Artificial/mortality , Cardiac Resynchronization Therapy , Heart Rate , Humans , Network Meta-Analysis , Risk Assessment , Risk Factors , Stroke Volume , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Desipramine is a tricyclic antidepressant with immune-modulatory activity, whose effects on ligature-induced periodontitis are yet to be investigated. Hence, its actions on alveolar bone resorption, gingival collagen content and key inflammatory mediators were herewith analyzed. METHODS: A total of 60 male Wistar rats were randomly assigned into three groups: 1) control: rats without ligature treated with vehicle (saline); 2) ligature: rats with ligature-induced periodontitis treated with vehicle; 3) ligature + desipramine: rats with ligature-induced periodontitis treated with desipramine (20 mg/kg/d in vehicle). Mandibles and gingival tissues were collected 3 or 15 days after ligature insertion (or no ligature insertion for controls) and treatments. Alveolar bone resorption and gingival collagen fibers were histologically analyzed using either HE or picrosirius red staining. Gingival mRNA expressions of interleukin (IL)-1ß, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 were obtained through reverse transcription polymerase chain reaction. MMP-9 activity was analyzed by zymography. RESULTS: Alveolar bone loss was significantly reduced in the ligature + desipramine group (P < 0.05), whereas gingival collagen degradation was like the ligature group (P > 0.05). Desipramine administration downregulated mRNA expressions of IL-1ß, iNOS, COX-2, and TIMP-1 when compared to vehicle alone in the ligature group (P < 0.05). MMP-9 expression and MMP-9/TIMP-1 ratio were similar among rats with ligature-induced periodontitis (P > 0.05); however, MMP-9 activity was lower in the group treated with desipramine (P < 0.05). CONCLUSION: Desipramine administration reduced alveolar bone loss as histologically observed, and modulated key bone remodeling and inflammatory mediators in rats with ligature-induced periodontitis.
Subject(s)
Alveolar Bone Loss , Periodontitis , Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/prevention & control , Animals , Desipramine/pharmacology , Desipramine/therapeutic use , Disease Models, Animal , Gingiva , Male , Periodontitis/drug therapy , Rats , Rats, WistarABSTRACT
BACKGROUND: Data on heart failure (HF) epidemiology in less developed areas of Brazil are scarce. OBJECTIVE: Our aim was to determine the HF morbidity and mortality in Paraiba and Brazil and its 10-year trends. METHODS: A retrospective search was conducted from 2008 to 2017 using the DATASUS database and included patients ≥ 15 years old with a primary diagnosis of HF. Data on in-hospital and population morbidity and mortality were collected and stratified by year, gender and age. Pearson correlation and linear-by-linear association test for trends were calculated, with a level of significance of 5%. RESULTS: From 2008 to 2017, HF admissions decreased 62% (p = 0.004) in Paraiba and 34% (p = 0.004) in Brazil. The in-hospital mortality rate increased in Paraiba and Brazil [65.1% (p = 0.006) and 30.1% (p = 0.003), respectively], but the absolute in-hospital mortality had a significant decrease only in Paraiba [37.5% (p = 0.013)], which was maintained after age stratification, except for groups 15-19, 60-69 and > 80 years. It was observed an increase in the hospital stay [44% (p = 0.004) in Paraiba and 12.3% (p = 0.004) in Brazil]. From 2008 to 2015, mortality rate for HF in the population decreased 10.7% (p = 0.047) in Paraiba and 7.7% (p = 0.017) in Brazil. CONCLUSIONS: Although HF mortality rate has been decreasing in Paraiba and Brazil, an increase in the in-hospital mortality rate and length of stay for HF has been observed. Hospital-based clinical studies should be performed to identify the causes for these trends of increase.