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Europium ions (Eu3+) are gaining attention in the field of regenerative medicine due to increasing evidence of their osteogenic properties. However, inflammatory and oxidative environments present in many bone diseases, such as osteoporosis or rheumatoid arthritis, are known to hinder this regenerative process. Herein, we describe a straightforward synthetic procedure to prepare Eu3+-tannic acid nanocomplexes (EuTA NCs) with modulable physicochemical characteristics, as well as antioxidant, anti-inflammatory, and osteogenic properties. EuTA NCs were rationally synthesized to present different contents of Eu3+ on their structure to evaluate the effect of the cation on the biological properties of the formulations. In all the cases, EuTA NCs were stable in distilled water at physiological pH, had a highly negative surface charge (ζ ≈ -25.4 mV), and controllable size (80 < Dh < 160 nm). In vitro antioxidant tests revealed that Eu3+ complexation did not significantly alter the total radical scavenging activity (RSA) of TA but enhanced its ability to scavenge H2O2 and ferrous ions, thus improving its overall antioxidant potential. At the cellular level, EuTA NCs reduced the instantaneous toxicity of high concentrations of free TA, resulting in better antioxidant (13.3% increase of RSA vs. TA) and anti-inflammatory responses (17.6% reduction of nitric oxide production vs. TA) on cultures of H2O2- and LPS-stimulated macrophages, respectively. Furthermore, the short-term treatment of osteoblasts with EuTA NCs was found to increase their alkaline phosphatase activity and their matrix mineralization capacity. Overall, this simple and tunable platform is a potential candidate to promote bone growth in complex environments by simultaneously targeting multiple pathophysiological mechanisms of disease.
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Regeneração Óssea , Európio , Taninos , Európio/química , Európio/farmacologia , Regeneração Óssea/efeitos dos fármacos , Camundongos , Animais , Células RAW 264.7 , Taninos/química , Taninos/farmacologia , Inflamação/tratamento farmacológico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/síntese química , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Tamanho da Partícula , Propriedades de Superfície , Osteogênese/efeitos dos fármacos , PolifenóisRESUMO
BACKGROUND: Idiopathic hypereosinophilic syndrome (IHES) is a disorder characterized by abnormal and persistent peripheral blood hypereosinophilia (eosinophil count ≥ 1.5 × 109/L and ≥10% eosinophils) with duration ≥ 6 months, associated organ damage, and/or dysfunction attributable to tissue eosinophilic infiltrate of unknown cause. IHES affects different organs such as the heart, lungs, nervous system, and skin, with renal involvement being rare in this condition. CASE PRESENTATION: We present a case of a young patient with IHES and immune complex-mediated membranoproliferative glomerulonephritis with nephrotic syndrome, as a rare renal manifestation. We discuss the clinical, analytical, and histopathologic renal and hematologic features, comparing them with other reported cases in the literature.
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Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when looking at them using electron microscopy. This disease is associated with certain genetic diseases or is secondary to drugs or toxins. Drug-induced phospholipidosis encompasses many types of pharmaceuticals, most notably chloroquine, amiodarone or ciprofloxacin. Clinically and histologically, renal involvement can be highly variable, with the diagnosis not being made until the zebra bodies are seen under an electron microscope. These findings may require genetic testing to discount Fabry disease, as its histological findings are indistinguishable. Most of the chemicals responsible are cationic amphiphilic drugs, and several mechanisms have been hypothesized for the formation of zebra bodies and their pathogenic significance. However, the relationship between drug toxicity and phospholipid accumulation, zebra bodies and organ dysfunction remains enigmatic, as do the renal consequences of drug withdrawal. We present, to our knowledge, the first case report of acute renal injury with a monoclonal gammopathy of renal significance, lesions, and sclerodermiform syndrome, with zebra bodies that were associated with the initiation of a hydroxychloroquine and amiodarone treatment, as an example of drug-induced-phospholipidosis.
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Amiodarona , Hidroxicloroquina , Fosfolipídeos , Humanos , Injúria Renal Aguda/induzido quimicamente , Amiodarona/efeitos adversos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Lipidoses/induzido quimicamente , Paraproteinemias/induzido quimicamente , Feminino , IdosoRESUMO
INTRODUCTION: The percutaneous kidney biopsy (PKB) is an essential tool in nephrology; small kidney size has been a relative contraindication to PKB and there is limited data on the safety and utility of performing PKB in this setting. Our aim was to describe the complications of PKB in small kidneys and to assess if kidney biopsy results have an impact on medical decisions and outcomes. METHODS: This was a retrospective, descriptive, and observational study. Patients older than 16 years of age with a decreased kidney size (≤8 cm) and undergoing PKB of native kidneys from July 2019 to December 2022 were included. RESULTS: Twenty-five patients were included, 19 women and 6 men. The mean age was 42.3 ± 18.04. The mean kidney length was 7.56 ± 0.33 and the mean width was 4.2 cm. All patients received only 1 puncture, obtaining an average of 12 glomeruli. The mean blood urea nitrogen and serum creatinine were 36 mg/dL and 1.94 mg/dL, respectively and the mean Hgb (hemoglobin) was 12.87 ± 2.81 g/dL. Minor complications occurred in 5 patients, perirenal hematoma in 3 patients, hematuria in 1 patient, and hematoma plus hematuria in 1 patient. Histological examination showed FSGS, lupus nephritis, other Glomerular disease, crescentic glomerulonephritis, and tubulointerstitial nephritis in 36%, 20%, 16%, 16%, and 12% of the cases, respectively. Biopsy resulted in management modification in 64% of cases. In a bivariate analysis, kidney size was not associated with higher complication rates. CONCLUSIONS: PKB in small kidneys is a feasible and safe procedure when properly planned, providing an adequate sample in all cases, with an insignificant number of minor complications, and that is clinically relevant.
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Estudos de Viabilidade , Rim , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Rim/patologia , Pessoa de Meia-Idade , Biópsia/efeitos adversos , Biópsia/métodos , Nefropatias/patologia , Tamanho do Órgão , IdosoRESUMO
Aim: Understanding barriers and facilitators to pharmacogenomics (PGx) implementation and how to structure a clinical program with the Veterans Health Administration (VA). Materials & methods: Healthcare provider (HCP) survey at 20 VA facilities assessing PGx knowledge/acceptance and qualitative interviews to understand how best to design and sustain a national program. Results: 186 (12% response rate) surveyed believed PGx informs drug efficacy (74.7%) and adverse events (71.0%). Low confidence in knowledge (43.0%) and ability to implement (35.4-43.5%). 23 (60.5% response rate) interviewees supported a nationally program to oversee VA education, consultation and IT resources. Prescribing HCPs should be directing local activities. Conclusion: HCPs recognize PGx value but are not prepared to implement. Healthcare systems should build system-wide programs for implementation education and support.
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Farmacogenética , Saúde dos Veteranos , Humanos , Farmacogenética/educação , Atenção à Saúde , Inquéritos e Questionários , Pessoal de SaúdeRESUMO
Non-valvular atrial fibrillation (NVAF) is the most common cardiac arrhythmia in the general population, and its prevalence increases among patients with chronic kidney disease (CKD) undergoing hemodialysis. This population presents high risk of both hemorrhagic and thrombotic events, with little evidence regarding the use of oral anticoagulation treatment (OAT) and multiple complications arising from it; however, stroke prevention with percutaneous left atrial appendage closure (LAAC) is an alternative to be considered. We retrospectively describe the safety and efficacy of percutaneous LAAC in eight patients with NVAF and CKD on hemodialysis during a 12-month follow-up. The mean age was 78.8 years (range 64-86; SD ± 6.7), and seven patients were male. The mean CHA2DS2-VASC and HAS-BLED scores were high, 4.8 (SD ± 1.5) and 3.8 (SD ± 1.3), respectively. Seventy-five percent of the patients were referred for this intervention due to a history of major bleeding, with gastrointestinal bleeding being the most common type, while the remaining twenty-five percent of the patients were referred because of a high risk of bleeding. The percutaneous LAAC procedure was successfully completed in 100% of the patients, with complete exclusion of the appendage without complications or leaks exceeding 5 mm. There was one death not related to the procedure four days after the intervention. Among the other seven patients, no deaths, cardioembolic events or major bleeding were reported during the follow-up period. In our sample, percutaneous LAAC appears to be a safe and effective alternative to anticoagulation in patients with NVAF and CKD on hemodialysis.
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Apêndice Atrial , Fibrilação Atrial , Falência Renal Crônica , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Fibrilação Atrial/complicações , Fibrilação Atrial/cirurgia , Oclusão do Apêndice Atrial Esquerdo , Estudos Retrospectivos , Resultado do Tratamento , Hemorragia/complicações , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/complicações , Anticoagulantes/uso terapêutico , Diálise Renal/efeitos adversos , Apêndice Atrial/cirurgiaRESUMO
Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and dissolve upon reheating. They can induce small-vessel vasculitis with renal involvement. Cryoglobulinemic glomerulonephritis is a rare manifestation that occurs in patients with monoclonal gammopathy, specifically Waldenström's macroglobulinemia. We present the case of a 52-year-old patient with a history of cutaneous vasculitis and hypothyroidism, who presented with generalized edema, moderate anemia, hypercholesterolemia, nephrotic range proteinuria of 12.69 g/day, microhematuria, arterial hypertension, and hypocomplementemia via the classical pathway, without acute kidney injury and with negative serological studies and positive cryoglobulins in the second determination. Serum and urine protein electrophoresis and immunofixation studies showed a monoclonal band of IgM and kappa light chain. Renal biopsy was consistent with cryoglobulinemic glomerulonephritis. In the context of dysproteinemia and cryoglobulinemic glomerulonephritis, bone-marrow aspiration and biopsy were performed, leading to the diagnosis of Waldenström's macroglobulinemia. Monoclonal gammopathies have been described in association with type I cryoglobulinemias. This described association is uncommon, which is why we present this case, along with a review of the literature.
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Glomerulonefrite , Gamopatia Monoclonal de Significância Indeterminada , Paraproteinemias , Macroglobulinemia de Waldenstrom , Humanos , Pessoa de Meia-Idade , Crioglobulinas , Glomerulonefrite/complicações , Glomerulonefrite/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/complicações , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Paraproteinemias/complicações , Paraproteinemias/diagnóstico , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnósticoRESUMO
BACKGROUND: Monoclonal immunoglobulin deposition disease (MIDD) includes three entities: light chain deposition disease (LCDD), heavy chain deposition disease (HCDD) and light and heavy chain deposition disease (LHCDD). The renal presentation can manifest with varying degrees of proteinuria and/or nephrotic syndrome, microhematuria, and often leads to end-stage renal disease. Given the rarity of LHCDD, therapeutic approaches for this condition remain inconclusive, as clinical trials are limited. CASE PRESENTATION: We report two male patients with underlying monoclonal gammopathy of renal significance (MGRS) associated with LHCDD lesions. Both cases had non-nephrotic proteinuria, moderately impaired renal function, and normal levels of C3 and C4. Light microscopy of the renal biopsies in both patients did not show lesions of nodular glomerulosclerosis. Immunofluorescence showed a staining pattern with interrupted linear IgA-κ in patient #1 and IgA-λ in patient #2 only along the glomerular basement membrane (GBM). Electron microscopy of patient #1 revealed electrodense deposits in the subendothelial and mesangial areas only along the GBM. DISCUSSION: In this case series, we discuss the clinical, analytical, and histopathological findings of two rare cases of LHCDD. Both patients exhibited IgA monoclonality and were diagnosed with monoclonal gammopathy of undetermined significance (MGUS) by the hematology department at the time of renal biopsy. Treatment with steroids and cytotoxic agents targeting the clone cells responsible for the deposition disease resulted in a favorable renal and hematologic response.
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Introduction: Cryoglobulinemia refers to the presence of cryoglobulins (CGs) in the serum, encompassing a group of diseases caused by the type of circulating GC. Cryoglobulinemic glomerulonephritis (CryoGN) is the principal manifestation of renal involvement. The diagnosis may be challenging because the hallmark of cryoglobulinemia is the detection of CG in the serum. However, cases of CryoGN without serological evidence of CGs are not uncommon in clinical practice, often diagnosed by anatomopathological findings in the renal biopsy. Case Presentation: We report the case of an 86-year-old male who developed renal impairment, nephritic syndrome, and nephrotic-range proteinuria, without serological evidence of CGs, associated with staphylococcal bacteremia without apparent focus. Renal biopsy and pathological examination showed a membranoproliferative glomerulonephritis pattern with CD61-negative pseudothrombi. Immunofluorescence microscopy showed atypical IgA-dominant deposits. Electron microscopy revealed amorphous subendothelial and mesangial deposits and organized electrodense deposits within capillary loops (pseudothrombi) with microtubular substructure measuring 20-40 nm in thickness. These findings were consistent with seronegative CryoGN and microtubular organized atypical IgA-dominant deposits. Discussion: In this report, we discuss the clinical, analytical, and histopathological findings of a rare case of CryoGN without serological evidence of CGs. Regarding the etiology that triggered the glomerular disease in our patient, we conducted an exhaustive study in order to determine the underlying cause of CryoGN. At the time of biopsy, the patient had an active staphylococcal bacteremia. There are reports that postulate that staphylococcal antigens drive activation of immune system and in consequence, could cause this rare form of IgA-dominant glomerulonephritis with cryoglobulinemic features. After ruling out other causes of cryoglobulinemia, we discuss a plausible causal relationship of the staphylococcal infection in the pathogenesis of CryoGN in our patient.
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SGLT-2i are the new standard of care for diabetic kidney disease (DKD), but previous studies have not included patients on kidney replacement therapy (KRT). Due to their high risk of cardiovascular, renal complications, and mortality, these patients would benefit the most from this therapy. Residual kidney function (RKF) conveys a survival benefit and cardiovascular health among hemodialysis (HD) patients, especially those on incremental hemodialysis (iHD). We retrospectively describe the safety and efficacy of SGLT2i regarding RKF preservation in seven diabetic patients with different clinical backgrounds who underwent iHD (one or two sessions per week) during a 12-month follow-up. All patients preserved RKF, measured as residual kidney urea clearance (KrU) in 24 h after the introduction of SGLT2i. KrU levels improved significantly from 4.91 ± 1.14 mL/min to 7.28 ± 1.68 mL/min at 12 months (p = 0.028). Pre-hemodialysis blood pressure improved 9.95% in mean systolic blood pressure (SBP) (p = 0.015) and 10.95% in mean diastolic blood pressure (DBP) (p = 0.041); as a result, antihypertensive medication was modified. Improvements in blood uric acid, hemoglobin A1c, urine albumin/creatinine ratio (UACR), and 24 h proteinuria were also significant. Regarding side effects, two patients developed uncomplicated urinary tract infections that were resolved. No other complications were reported. The use of SGLT2i in our sample of DKD patients starting iHD on a 1-2 weekly regimen appears to be safe and effective in preserving RKF.
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Methotrexate (MTX) administration is the gold standard treatment for rheumatoid arthritis (RA), but its effects are limited to preventing the progression of the disease. Therefore, effective regenerative therapies for damaged tissues are still to be developed. In this regard, MTX complexes of general molecular formula M(MTX)·xH2O, where M = Sr, Zn, or Mg, were synthesized and physicochemically characterized by TGA, XRD, NMR, ATR-FTIR, and EDAX spectroscopies. Characterization results demonstrated the coordination between the different cations and MTX via two monodentate bonds with the carboxylate groups of MTX. Cation complexation provided MTX with new bioactive properties such as increasing the deposition of glycosaminoglycans (GAGs) and alternative anti-inflammatory capacities, without compromising the immunosuppressant properties of MTX on macrophages. Lastly, these new complexes were loaded into spray-dried chitosan microparticles as a proof of concept that they can be encapsulated and further delivered in situ in RA-affected joints, envisioning them as a suitable alternative to oral MTX therapy.
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Antirreumáticos , Artrite Reumatoide , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Humanos , Macrófagos , Metotrexato/farmacologia , Metotrexato/uso terapêuticoRESUMO
CONTEXT: Lipolysis is one of the most important pathways for energy management, its control in the adipose tissue (AT) is a potential therapeutic target for metabolic diseases. Adenosine Mono Phosphate-activated Protein Kinase (AMPK) is a key regulatory enzyme in lipids metabolism and a potential target for diabetes and obesity treatment. OBJECTIVE: The aim of this work is to analyse the existing information on the relationship of AMPK and lipolysis in the AT. METHODS: A thorough search of bibliography was performed in the databases Scopus and Web of Knowledge using the terms lipolysis, adipose tissue, and AMPK, the unrelated publications were excluded, and the documents were analysed. RESULTS: Sixty-three works were found and classified in 3 categories: inhibitory effects, stimulatory effect, and diverse relationships; remarkably, the newest researches support an upregulating relationship of AMPK over lipolysis. CONCLUSION: The most probable reality is that the relationship AMPK-lipolysis depends on the experimental conditions.
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Proteínas Quinases Ativadas por AMP , Lipólise , Proteínas Quinases Ativadas por AMP/metabolismo , Monofosfato de Adenosina/metabolismo , Tecido Adiposo/metabolismo , FosforilaçãoRESUMO
Fungal peritonitis secondary to non-albicans Candida is reported less frequently. There are uncertainties regarding the treatment of non-albicans Candida infection (i.e., preferred route or initial drug). The objective of this study is to determine the clinical characteristics and treatment used in cases of peritoneal dialysis associated fungal peritonitis secondary to non-albicans Candida. We report four cases with different clinical characteristics and different routes of administration of the antifungal drug, with no deaths. In all four patients, there were risk factors similar to those reported worldwide, without presenting the route of administration of the antifungal drug as a risk factor, suggesting that the mainstay of treatment is early initiation of the antifungal drug and early removal of the catheter.
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The prevalence of metabolic syndrome and cardiovascular disease has increased and continues to be the leading cause of mortality worldwide. The etiology of these diseases includes a complex phenotype derived from interactions between genetic, environmental, and nutritional factors. In this regard, it is common to observe vitamin deficiencies in the general population and even more in patients with cardiometabolic diseases due to different factors. Vitamins are essential micronutrients for cellular metabolism and their deficiencies result in diseases. In addition to its role in nutritional functions, increasingly, vitamins are being recognized as modulators of genetics expression and signals transduction, when consumed at pharmacological concentrations. Numerous randomized preclinical and clinical trials have evaluated the use of vitamin supplementation in the prevention and treatment of metabolic syndrome and cardiovascular disease. However, it is controversy regarding its efficacy in the treatment and prevention of these diseases. In this review, we investigated chemical basics, physiological effect and recommended daily intake, problems with deficiency and overdose, preclinical and clinical studies, and mechanisms of action of vitamin supplementation in the treatment and prevention of metabolic syndrome and cardiovascular disease.
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Doenças Cardiovasculares/dietoterapia , Síndrome Metabólica/dietoterapia , Vitaminas/uso terapêutico , Animais , HumanosRESUMO
The development of new drugs for musculoskeletal regeneration purposes has attracted much attention in the last decades. In this work, we present three novel vitamin B9 (folic acid)-derivatives bearing divalent cations (ZnFO, MgFO and MnFO), providing their synthesis mechanism and physicochemical characterization. In addition, a strong emphasis has been placed on evaluating their biological properties (along with our previously reported SrFO) using human mesenchymal stem cells (hMSC). In all the cases, pure folate derivatives (MFOs) with a bidentate coordination mode between the metal and the folate anion, and a 1:1 stoichiometry, were obtained in high yields. A non-cytotoxic dose of all the MFOs (50 µg/mL) was demonstrated to modulate by their own the mRNA profiles towards osteogenic-like or fibrocartilaginous-like phenotypes in basal conditions. Moreover, ZnFO increased the alkaline phosphatase activity in basal conditions, while both ZnFO and MnFO increased the matrix mineralization degree in osteoinductive conditions. Thus, we have demonstrated the bioactivity of these novel compounds and the suitability to further studied them in vivo for musculoskeletal regeneration applications.
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Materiais Biocompatíveis/química , Ácido Fólico/química , Células-Tronco Mesenquimais/citologia , Sistema Musculoesquelético/citologia , Engenharia Tecidual , Materiais Biocompatíveis/síntese química , Cátions/síntese química , Cátions/química , Células Cultivadas , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Ácido Fólico/síntese química , HumanosRESUMO
Plant-based pigments are widely present in nature, they are classified depending on their chemical structure as tetrapyrroles, carotenoids, polyphenolic compounds, and alkaloids and are extensively used in medicine, food industry, clothes, and others. Recently they have been investigated due to their role in the areas of food processing, food safety and quality, packaging, and nutrition. Many studies indicate a relationship between bioactive pigments and Non-Communicable Diseases derived from oxidative stress. Their biological applications can help in preventing oxidative injuries in the cell caused by oxygen and nitrogen reactive species. Those pigments are easily degraded by light, oxygen, temperature, pH conditions, among others. Nanotechnology offers the possibility to protect bioactive ingredients and increase its bioavailability after oral administration. Safety to humans (mainly evaluated from toxicity data) is the first concern for these products. In the present work, we present a comprehensive outlook of the most important plant-based pigments used as food colorants, the principal nanotechnology systems prepared with them, and the relationship of these compounds with the oxidative stress and related Non-Communicable Disease.
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Nanotecnologia , Estresse Oxidativo , Pigmentos Biológicos/química , Plantas/química , Estrutura MolecularRESUMO
: Bacterial, protozoan and other microbial infections share an accelerated metabolic rate. In order to ensure a proper functioning of cell replication and proteins and nucleic acids synthesis processes, folate metabolism rate is also increased in these cases. For this reason, folic acid antagonists have been used since their discovery to treat different kinds of microbial infections, taking advantage of this metabolic difference when compared with human cells. However, resistances to these compounds have emerged since then and only combined therapies are currently used in clinic. In addition, some of these compounds have been found to have an immunomodulatory behavior that allows clinicians using them as anti-inflammatory or immunosuppressive drugs. Therefore, the aim of this review is to provide an updated state-of-the-art on the use of antifolates as antibacterial and immunomodulating agents in the clinical setting, as well as to present their action mechanisms and currently investigated biomedical applications.
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Anti-Infecciosos/farmacologia , Antagonistas do Ácido Fólico/farmacologia , Fatores Imunológicos/farmacologia , Animais , Anti-Infecciosos/química , Resistência a Medicamentos , Antagonistas do Ácido Fólico/química , Humanos , Fatores Imunológicos/química , Imunomodulação/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
B-vitamins are a group of soluble vitamins which are cofactors of some of the enzymes involved in the metabolic pathways of carbohydrates, fats and proteins. These compounds participate in a number of functions as cardiovascular, brain or nervous systems. Folic acid is described as an accessible and multifunctional niche component that can be used safely, even combined with other compounds, which gives it high versatility. Also, due to its non-toxicity and great stability, folic acid has attracted much attention from researchers in the biomedical and bioengineering area, with an increasing number of works directed at using folic acid and its derivatives in tissue engineering therapies as well as regenerative medicine. Thus, this review provides an updated discussion about the most relevant advances achieved during the last five years, where folic acid and other vitamins B have been used as key bioactive compounds for enhancing the effectiveness of biomaterials' performance and biological functions for the regeneration of tissues and organs.
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Ácido Fólico/farmacologia , Medicina Regenerativa , Engenharia Tecidual , Complexo Vitamínico B/farmacologia , Animais , Ácido Fólico/análogos & derivados , Ácido Fólico/uso terapêutico , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Complexo Vitamínico B/química , Complexo Vitamínico B/uso terapêuticoRESUMO
Several studies have shown that pharmacological concentrations of biotin decrease hyperlipidemia. The molecular mechanisms by which pharmacological concentrations of biotin modify lipid metabolism are largely unknown. Adipose tissue plays a central role in lipid homeostasis. In the present study, we analyzed the effects of biotin supplementation in adipose tissue on signaling pathways and critical proteins that regulate lipid metabolism, as well as on lipolysis. In addition, we assessed serum fatty acid concentrations. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (control: 1.76 mg biotin/kg; supplemented: 97.7 mg biotin/kg diet) over 8 weeks postweaning. Compared with the control group, biotin-supplemented mice showed an increase in the levels of adipose guanosine 3',5'-cyclic monophosphate (cGMP) (control: 30.3±3.27 pmol/g wet tissue; supplemented: 49.5±3.44 pmol/g wet tissue) and of phosphorylated forms of adenosine 5'-monophosphate-activated protein kinase (AMPK; 65.2%±1.06%), acetyl-coenzyme A (CoA), carboxylase-1 (196%±68%), and acetyl-CoA carboxylase-2 (78.1%±18%). Serum fatty acid concentrations were decreased (control: 1.12±0.04 mM; supplemented: 0.91±0.03 mM), and no change in lipolysis was found (control: 0.29±0.05 µmol/mL; supplemented: 0.33±0.08 µmol/mL). In conclusion, 8 weeks of dietary biotin supplementation increased adipose tissue cGMP content and protein expression of the active form of AMPK and of the inactive forms of acetyl-CoA carboxylase-1 and acetyl-CoA carboxylase-2. Serum fatty acid levels fell, and no change in lipolysis was observed. These findings provide insight into the effects of biotin supplementation on adipose tissue and support its use in the treatment of dyslipidemia.
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Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/química , Tecido Adiposo/metabolismo , Biotina/administração & dosagem , GMP Cíclico/análise , Ácidos Graxos não Esterificados/sangue , Acetil-CoA Carboxilase/análise , Acetil-CoA Carboxilase/metabolismo , Tecido Adiposo/efeitos dos fármacos , Animais , Suplementos Nutricionais , Ativação Enzimática/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , FosforilaçãoRESUMO
Between May 2003 and July 2006, we carried out percutaneous patent ductus arteriosus closure using a Nit-Occlud device in 28 patients, who had a median age of 1.8 years (range 0.5-21 years) and a median weight of 10.9 kg (range 5.9-64 kg). The ductus arteriosus had several different morphologic forms, and there was one postsurgical recanalization of the ductus arteriosus. The median minimum ductal diameter was 1.8 mm and the median maximum aortic ampulla diameter was 6.5 mm. The occlusion rate immediately after intervention was 53.5%, which increased to 95.2% by 12 months and to 100% by 18 months. The median follow-up time was 20.5 months. The Nit-Occlud device provided an effective and safe means of patent ductus arteriosus closure, irrespective of ductus morphology.