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1.
J Pediatr (Rio J) ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38522478

RESUMO

OBJECTIVE: Complications of ascariasis are a significant cause of abdominal pain in pediatric emergencies, especially where it is endemic. A literature review was conducted with the aim of improving diagnostic and therapeutic approaches for these patients. DATA SOURCES: A PubMed search was conducted using the key terms "ascariasis complications" and "hepatobiliary ascariasis". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, case reports, and reviews published up to December 2023. SUMMARY OF FINDINGS: Obstruction of the small bowel is the most common complication. Others that are, rarer and more difficult to properly identify and treat, such as biliary, hepatic, and pancreatic complications, acute appendicitis, Meckel's diverticulitis, or peritoneal granulomas. Hepatic and pancreatic complications are rarer and more serious in children than in adults. While plain radiography is usually the only option in cases of intestinal obstruction, ultrasonography is the examination of choice in cases of hepatobiliary, pancreatic, and appendicular ascariasis complications in childhood. The treatment is clinical and conservative in most patients. Surgical treatment is indicated if conservative therapy fails, or if there are signs of complications. Laparoscopy has been used as an excellent technical alternative in adults with hepatobiliary complications of ascariasis, but further studies on its use in children are still needed. CONCLUSION: The creation of protocols and greater debate on this subject should be encouraged for a better understanding of the disease and to establish an early diagnosis and adequate treatment for children with complications resulting from massive infestation by Ascaris lumbricoides.

2.
Int J Mol Sci ; 25(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38396866

RESUMO

Vitamin D3 (VitD3) plays a crucial role in various cellular functions through its receptor interaction. The biological activity of Vitamin D3 can vary based on its solubility and stability. Thus, the challenge lies in maximizing its biological effects through its complexation within cyclodextrin (ßNS-CDI 1:4) nanosponges (NS) (defined as VitD3NS). Therefore, its activity has been evaluated on two different gut-brain axes (healthy gut/degenerative brain and inflammatory bowel syndrome gut/degenerative brain axis). At the gut level, VitD3-NS mitigated liposaccharide-induced damage (100 ng/mL; for 48 h), restoring viability, integrity, and activity of tight junctions and reducing ROS production, lipid peroxidation, and cytokines levels. Following intestinal transit, VitD3-NS improved the neurodegenerative condition in the healthy axis and the IBS model, suggesting the ability of VitD3-NS to preserve efficacy and beneficial effects even in IBS conditions. In conclusion, this study demonstrates the ability of this novel form of VitD3, named VitD3-NS, to act on the gut-brain axis in healthy and damaged conditions, emphasizing enhanced biological activity through VitD3 complexation, as such complexation increases the beneficial effect of vitamin D3 in both the gut and brain by about 50%.


Assuntos
Colecalciferol , Síndrome do Intestino Irritável , Humanos , Colecalciferol/farmacologia , Colecalciferol/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Eixo Encéfalo-Intestino , Citocinas , Encéfalo , Vitamina D/farmacologia , Vitamina D/uso terapêutico
3.
Antioxid Redox Signal ; 40(7-9): 369-432, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38299513

RESUMO

Significance: Physiological levels of reactive oxygen and nitrogen species (ROS/RNS) function as fundamental messengers for many cellular and developmental processes in the cardiovascular system. ROS/RNS involved in cardiac redox-signaling originate from diverse sources, and their levels are tightly controlled by key endogenous antioxidant systems that counteract their accumulation. However, dysregulated redox-stress resulting from inefficient removal of ROS/RNS leads to inflammation, mitochondrial dysfunction, and cell death, contributing to the development and progression of cardiovascular disease (CVD). Recent Advances: Basic and clinical studies demonstrate the critical role of selenium (Se) and selenoproteins (unique proteins that incorporate Se into their active site in the form of the 21st proteinogenic amino acid selenocysteine [Sec]), including glutathione peroxidase and thioredoxin reductase, in cardiovascular redox homeostasis, representing a first-line enzymatic antioxidant defense of the heart. Increasing attention has been paid to emerging selenoproteins in the endoplasmic reticulum (ER) (i.e., a multifunctional intracellular organelle whose disruption triggers cardiac inflammation and oxidative stress, leading to multiple CVD), which are crucially involved in redox balance, antioxidant activity, and calcium and ER homeostasis. Critical Issues: This review focuses on endogenous antioxidant strategies with therapeutic potential, particularly selenoproteins, which are very promising but deserve more detailed and clinical studies. Future Directions: The importance of selective selenoproteins in embryonic development and the consequences of their mutations and inborn errors highlight the need to improve knowledge of their biological function in myocardial redox signaling. This could facilitate the development of personalized approaches for the diagnosis, prevention, and treatment of CVD. Antioxid. Redox Signal. 40, 369-432.


Assuntos
Doenças Cardiovasculares , Selênio , Humanos , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Selenoproteínas/metabolismo , Selênio/metabolismo , Inflamação
4.
Curr Probl Cardiol ; 49(3): 102229, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154703

RESUMO

In recent years, important advances have been made in the field of Cardio-Oncology. The 2022 ESC Guidelines on Cardio-Oncology proposed a baseline cardiovascular risk stratification for cancer patients and preventive strategies in patients at high and very-high risk of cardiotoxicity. Cardiovascular toxic effects of anti-cancer drugs are being extensively studied; surveillance programs have been proposed, based on the baseline cardiovascular risk. On the other hand, there is little data on Cardio-Oncological management of patients at high and very-high cardiovascular risk with previous cardiovascular diseases. For example, little is known about management of cancer patients with heart failure with reduced ejection fraction (HFrEF), patients with a recent myocardial infarction or other cardiovascular diseases; when to resume anti-cancer drugs after a cardiovascular toxic event. Collaboration between Cardiologists and Oncologists and multidisciplinary team evaluations are certainly essential to decide the best therapeutic strategy for cancer patients, to treat cancer while saving the heart. Therefore, in the present review, we attempt to provide a useful guide to clinicians in treating patients with high and very-high risk of cardiotoxicity by enucleating main questions and answering them based on the evidence available as well as expert opinion and our clinical experience.


Assuntos
Antineoplásicos , Insuficiência Cardíaca , Neoplasias , Disfunção Ventricular Esquerda , Humanos , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Volume Sistólico , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Antineoplásicos/efeitos adversos , Disfunção Ventricular Esquerda/induzido quimicamente
5.
Int J Mol Sci ; 24(15)2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37569855

RESUMO

Ischemia is the underlying mechanism in a wide variety of acute and persistent pathologies. As such, understanding the fine intracellular events occurring during (and after) the restriction of blood supply is pivotal to improving the outcomes in clinical settings. Among others, gaseous signaling molecules constitutively produced by mammalian cells (gasotransmitters) have been shown to be of potential interest for clinical treatment of ischemia/reperfusion injury. Nitric oxide (NO and its sibling, HNO), hydrogen sulfide (H2S), and carbon monoxide (CO) have long been proven to be cytoprotective in basic science experiments, and they are now awaiting confirmation with clinical trials. The aim of this work is to review the literature and the clinical trials database to address the state of development of potential therapeutic applications for NO, H2S, and CO and the clinical scenarios where they are more promising.


Assuntos
Sistema Cardiovascular , Gasotransmissores , Sulfeto de Hidrogênio , Animais , Óxido Nítrico , Transdução de Sinais , Monóxido de Carbono/uso terapêutico , Mamíferos
6.
Antioxidants (Basel) ; 12(7)2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37507935

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. Calcium overload, altered oxygen levels, and mitochondrial ROS are also involved in these MIRI processes, resulting in the irreversible opening of the mitochondrial permeability transition pore (mPTP). These mechanisms and processes are associated with NLRP3 inflammasome priming and activation, which can also induce cell death by pyroptosis through the up-regulation of the caspase-1 pathway and IL-18 release. In addition, endothelial dysfunction, both in the presence and absence of MIRI, is also accompanied by altered oxygen levels, decreased nitric oxide production, and ROS overproduction, resulting in the expression of adhesion molecules and leukocyte infiltration in which the NLRP3 inflammasome plays a central role, thus contributing, through endothelial dysfunction, to the alteration of coronary flow, typical of ischemic heart disease. Given the intricate interrelationship between ROS and NLRP3, ROS inhibitors can reduce NLRP3 inflammasome activation, while NLRP3 inhibitors can reduce oxidative stress and inflammation. NLRP3 inhibitors have been intensively studied as anti-inflammatory agents in basic cardiovascular sciences. In this review, we analyze the interrelation between ROS and NLRP3 in ischemic heart disease and the effects of some NLRP3 inhibitors as possible therapeutic agents in this disease condition. All compounds considered in this review need larger studies to confirm their appropriate use in clinical scenarios as anti-ischemic drugs.

7.
Eur J Med Chem ; 257: 115542, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37290185

RESUMO

Inspired by the recent advancements in understanding the binding mode of sulfonylurea-based NLRP3 inhibitors to the NLRP3 sensor protein, we developed new NLRP3 inhibitors by replacing the central sulfonylurea moiety with different heterocycles. Computational studies evidenced that some of the designed compounds were able to maintain important interaction within the NACHT domain of the target protein similarly to the most active sulfonylurea-based NLRP3 inhibitors. Among the studied compounds, the 1,3,4-oxadiazol-2-one derivative 5 (INF200) showed the most promising results being able to prevent NLRP3-dependent pyroptosis triggered by LPS/ATP and LPS/MSU by 66.3 ± 6.6% and 61.6 ± 11.5% and to reduce IL-1ß release (35.5 ± 8.8% µM) at 10 µM in human macrophages. The selected compound INF200 (20 mg/kg/day) was then tested in an in vivo rat model of high-fat diet (HFD)-induced metaflammation to evaluate its beneficial cardiometabolic effects. INF200 significantly counteracted HFD-dependent "anthropometric" changes, improved glucose and lipid profiles, and attenuated systemic inflammation and biomarkers of cardiac dysfunction (particularly BNP). Hemodynamic evaluation on Langendorff model indicate that INF200 limited myocardial damage-dependent ischemia/reperfusion injury (IRI) by improving post-ischemic systolic recovery and attenuating cardiac contracture, infarct size, and LDH release, thus reversing the exacerbation of obesity-associated damage. Mechanistically, in post-ischemic hearts, IFN200 reduced IRI-dependent NLRP3 activation, inflammation, and oxidative stress. These results highlight the potential of the novel NLRP3 inhibitor, INF200, and its ability to reverse the unfavorable cardio-metabolic dysfunction associated with obesity.


Assuntos
Traumatismo por Reperfusão Miocárdica , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Animais , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos , Lipopolissacarídeos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Teóricos
8.
Int J Mol Sci ; 24(12)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37373223

RESUMO

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure.


Assuntos
Soluções Cardioplégicas , Parada Cardíaca , Humanos , Soluções Cardioplégicas/farmacologia , Soluções Cardioplégicas/uso terapêutico , Oxigênio/farmacologia , Coração , Miocárdio , Parada Cardíaca/tratamento farmacológico
9.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047079

RESUMO

Nitric oxide (NO) and carbon monoxide (CO) represent a pair of biologically active gases with an increasingly well-defined range of effects on circulating platelets. These gases interact with platelets and cells in the vessels and heart and exert fundamentally similar biological effects, albeit through different mechanisms and with some peculiarity. Within the cardiovascular system, for example, the gases are predominantly vasodilators and exert antiaggregatory effects, and are protective against damage in myocardial ischemia-reperfusion injury. Indeed, NO is an important vasodilator acting on vascular smooth muscle and is able to inhibit platelet activation. NO reacts with superoxide anion (O2(-•)) to form peroxynitrite (ONOO(-)), a nitrosating agent capable of inducing oxidative/nitrative signaling and stress both at cardiovascular, platelet, and plasma levels. CO reduces platelet reactivity, therefore it is an anticoagulant, but it also has some cardioprotective and procoagulant properties. This review article summarizes current knowledge on the platelets and roles of gas mediators (NO, and CO) in cardioprotection. In particular, we aim to examine the link and interactions between platelets, NO, and CO and cardioprotective pathways.


Assuntos
Gasotransmissores , Traumatismo por Reperfusão Miocárdica , Humanos , Óxido Nítrico/metabolismo , Óxidos , Gasotransmissores/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Gases , Vasodilatadores
10.
Int J Mol Sci ; 24(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36982396

RESUMO

Vitamin D plays an important role in numerous cellular functions due to the ability to bind the Vitamin D receptor (VDR), which is present in different tissues. Several human diseases depend on low vitamin D3 (human isoform) serum level, and supplementation is necessary. However, vitamin D3 has poor bioavailability, and several strategies are tested to increase its absorption. In this work, the complexation of vitamin D3 in Cyclodextrin-based nanosponge (CD-NS, in particular, ßNS-CDI 1:4) was carried out to study the possible enhancement of bioactivity. The ßNS-CDI 1:4 was synthesized by mechanochemistry, and the complex was confirmed using FTIR-ATR and TGA. TGA demonstrated higher thermostability of the complexed form. Subsequently, in vitro experiments were performed to evaluate the biological activity of Vitamin D3 complexed in the nanosponges on intestinal cells and assess its bioavailability without cytotoxic effect. The Vitamin D3 complexes enhance cellular activity at the intestinal level and improve its bioavailability. In conclusion, this study demonstrates for the first time the ability of CD-NS complexes to improve the chemical and biological function of Vitamin D3.


Assuntos
Antineoplásicos , Ciclodextrinas , Nanoestruturas , Humanos , Ciclodextrinas/farmacologia , Ciclodextrinas/química , Vitamina D/farmacologia , Nanoestruturas/química , Colecalciferol/farmacologia , Receptores de Calcitriol
11.
Biology (Basel) ; 12(2)2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36829584

RESUMO

Despite the development of cutting-edge treatments, coronary artery disease (CAD) morbidity and mortality rates remain present at high levels. Therefore, new cardioprotective approaches are crucial to improve the health of patients. To date, experimental investigations of acute ischemia-reperfusion injury (IRI) have generally demonstrated the efficacy of local ischemic preconditioning and postconditioning cardioprotection techniques as well as of remote conditioning. However, application in clinical settings is still highly controversial and debated. Currently, remote ischemic conditioning (RIC) seems to be the most promising method for heart repair. Protective factors are released into the bloodstream, and protection can be transferred within and across species. For a long time, the cross-function and cross-transmission mechanisms of cardioprotection were largely unknown. Recently, it has been shown that small, anuclear, bilayered lipid membrane particles, known as extracellular vesicles (EVs), are the drivers of signal transduction in cardiac IRI and RIC. EVs are related to the pathophysiological processes of cardiovascular diseases (CVDs), according to compelling evidence. In this review, we will first review the current state of knowledge on myocardial IRI and cardioprotective strategies explored over the past 37 years. Second, we will briefly discuss the role of EVs in CVD and the most recent improvements on EVs as prognostic biomarkers, diagnostic, and therapeutic agents. We will discuss how EVs can be used as a new drug delivery mechanism and how they can be employed in cardiac treatment, also from a perspective of overcoming the impasse that results from neglecting confounding factors.

13.
Vascul Pharmacol ; 145: 107001, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35623548

RESUMO

Experimentally, many strong cardioprotective treatments have been identified in different animal models of acute ischaemia/reperfusion injury (IRI) and coronary artery disease (CAD). However, the translation of these cardioprotective therapies for the benefit of the patients into the clinical scenario has been very disappointing. The reasons for this lack are certainly multiple. Indeed, many confounding factors we must deal in clinical reality, such as aging, sex and inflammatory processes are neglected in many experiments. Due to the pivotal role of aging, sex and inflammation in determining cardiac ischaemic disease, in this review, we take into account age as a modifier of tolerance to IRI in the two sexes, dissecting aging and myocardial reperfusion injury mechanisms and the sex differences in tolerance to IRI. Then we focus on the role of the gut microbiota and the NLRP3 inflammasome in myocardial IRI and on the possibility to consider NLRP3 inflammasome as a potential target in the treatment of CAD in relationship with age and sex. Finally, we consider the cardioprotective mechanisms and cardioprotective treatments during aging in the two sexes.


Assuntos
Inflamassomos , Traumatismo por Reperfusão Miocárdica , Envelhecimento , Animais , Feminino , Isquemia , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Proteína 3 que Contém Domínio de Pirina da Família NLR
14.
Int J Mol Sci ; 23(7)2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35409162

RESUMO

BACKGROUND: Hypercholesterolemia is a major cause of cardiovascular disease and statins, the HMGCoA inhibitors, are the most prescribed drugs. Statins reduce the production of hepatic cholesterol, leading to greater expression of the LDL receptor and greater absorption of circulating LDL, reducing peripheral LDL levels. Unfortunately, statins are believed to induce myopathy and other severe diseases. To overcome this problem, safe nutraceuticals with the same activity as statins could hold great promise in the prevention and treatment of hypercholesterolemia. In this study, the anti-cholesterol efficacy of a new nutraceutical, called Esterol10®, was evaluated. METHODS: HepG2 cells were used to study the biological mechanisms exerted by Esterol10® analyzing different processes involved in cholesterol metabolism, also comparing data with Atorvastatin. RESULTS: Our results indicate that Esterol10® leads to a reduction in total hepatocyte cholesterol and an improvement in the biosynthesis of free cholesterol and bile acids. Furthermore, the anti-cholesterol activity of Esterol10® was also confirmed by the modulation of the LDL receptor and by the accumulation of lipids, as well as by the main intracellular pathways involved in the metabolism of cholesterol. CONCLUSIONS: Esterol10® is safe and effective with anti-cholesterol activity, potentially providing an alternative therapy to those based on statins for hypercholesterolemia disease.


Assuntos
Anticolesterolemiantes , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Colesterol/farmacologia , LDL-Colesterol/farmacologia , Homeostase , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Receptores de LDL
15.
Vascul Pharmacol ; 144: 106995, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35470102

RESUMO

Since coronary reperfusion was introduced into clinical practice in the late 1970s, the further translation of several successful animal experiments on cardioprotection into clinical practice has been disappointing to date. Animal experiments are often performed on young, healthy animals lacking the risk factors, co-morbidities and co-medications characteristic of acute myocardial infarction patients. Many hopes were kindled in 1986 when ischemic preconditioning was discovered. However, it is not yet known how long ischemia can last and what is the best modality for additional cardioprotection through conditioning to obtain benefits. There is a lack of experimental studies on the long-term effects of additional cardioprotection, in addition to the reduction in infarct size; in particular, there is a lack of studies on vessel protection, repair, inflammation, remodeling, and mortality. The reproducibility and robustness of experimental studies are often limited by species differences, the role of co-morbidities, vascular damage, inflammatory processes, and co-medications, which are not adequately considered. In particular, inflammatory processes, including NLRP3 inflammasome, play an important role in the long-term effects. Future studies should focus on interventions/agents with robust preclinical data and should recruit patients who truly have the potential to benefit from further cardioprotection. Here we focus on the main mechanisms and targets of cardioprotection during remote conditioning and their alteration by one of the most common co-morbidities, namely diabetes, in which microvascular lesions and inflammatory processes play extremely important roles.


Assuntos
Precondicionamento Isquêmico Miocárdico , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Humanos , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Reprodutibilidade dos Testes , Fatores de Risco
16.
Biology (Basel) ; 11(1)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35053144

RESUMO

BACKGROUND: Treatment of myocardial ischemia/reperfusion (IR) injury is still an unmet clinical need. A large variability of remote ischemic conditioning (RIC) protection has been reported; however, no studies have considered the temperature of the ischemic limb. We analyzed the effects of temperature on RIC protection. METHODS: Left hind-limbs of anesthetized male mice were immersed in warm (40 °C, warm-RIC) or cold (20 °C, cold-RIC) water and subjected to a RIC protocol (4 × 5 min limb ischemia/reperfusion). In the control groups (warm-CTR or cold-CTR), the limbs underwent thermic conditions only. Isolated hearts underwent 30 min ischemia and 60 min reperfusion. A PI3K-inhibitor, LY294002 (5 µM), was infused in warm-RIC hearts before the IR protocol (warm-RIC LY). Infarct size was evaluated by nitro blue tetrazolium staining and expressed as the percent of risk area. RESULTS: While cold-RIC did not reduce the infarct size compared to cold-CTR (51 ± 1.62% vs. 54 ± 1.07% of risk area, p =NS), warm-RIC (44 ± 1.13%) significantly reduced the infarct size with respect to either cold-RIC (p <0.001) or warm-CTR (58 ± 1.41%, p <0.0001). LY294002 infusion revealed the PI3K/Akt involvement in the warm-RIC protection. Infarct size reduction was abrogated by LY294002 pretreatment (warm-RIC: 44 ± 1.13% vs. warm-CTR 58 ± 1.41% p <0.0001; vs. warm-RIC LY 54 ± 1.69% p =0.0002). CONCLUSION: our study shows a remarkable difference between warm-RIC and cold-RIC in terms of infarct size reduction, supporting a pivotal role for limb temperature in RIC-induced cardioprotection.

17.
Curr Pharm Des ; 28(6): 468-470, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34751111

RESUMO

In the case of serious cardiovascular diseases, such as refractory heart failure, heart transplantation is the only possible intervention. Currently, the modes of organ transport in hypothermic cardioplegic solution do not allow the implantation of the heart beyond 4-5 hours from the explant. The heart being an organ with a greater consumption of oxygen and high metabolism than the brain, its transport in hypothermic cardioplegic solutions presents critical issues in terms of time and conservation. An ambitious goal of many researchers and clinicians is to minimize the hypoxia of the explanted heart and extend the permanence time in cardioplegic solution without damage from hypoxia. Adequately oxygenating the explanted organs may extend the usability time of the explanted organ. This challenge has been pursued for years with approaches that are often expensive, risky, and/or difficult to use. We propose to consider oxygenated nanocarriers releasing oxygen for a long time. In this way, it will also be possible to use organs from distant countries with respect to the recipient, thus exceeding the canonical 4-5 hours tolerated up to now. In addition to the lack of oxygen, the transplanted organ can undergo the accumulation of catabolites due to the lack of perfusion during transport. Therefore, nanocarriers can also be perfused in adequate solution during organ transportation. A better oxygenation improving the postoperative recovery of the transplanted heart will improve the recipient's quality of life.


Assuntos
Transplante de Coração , Oxigênio , Soluções Cardioplégicas/metabolismo , Soluções Cardioplégicas/uso terapêutico , Coração , Humanos , Miocárdio/metabolismo , Preservação de Órgãos/métodos , Qualidade de Vida
18.
J Cardiovasc Med (Hagerstown) ; 23(1): 1-11, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34091532

RESUMO

2020 marked the 20th anniversary of the discovery of the angiotensin-converting enzyme 2 (ACE2). This major event that changed the way we see the renin-angiotensin system today could have passed quietly. Instead, the discovery that ACE2 is a major player in the severe acute respiratory syndrome coronavirus 2 pandemic has blown up the literature regarding this enzyme. ACE2 connects the classical arm renin-angiotensin system, consisting mainly of angiotensin II peptide and its AT1 receptor, with a protective arm, consisting mainly of the angiotensin 1-7 peptide and its Mas receptor. In this brief article, we have reviewed the literature to describe how ACE2 is a key protective arm enzyme in the function of many organs, particularly in the context of brain and cardiovascular function, as well as in renal, pulmonary and digestive homeostasis. We also very briefly review and refer to recent literature to present an insight into the role of ACE2 in determining the course of coronavirus diseases 2019.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Sistema Renina-Angiotensina/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Angiotensinas/fisiologia , Animais , COVID-19/complicações , COVID-19/metabolismo , COVID-19/virologia , Humanos , Camundongos , Especificidade de Órgãos , Ratos , Receptores de Angiotensina/fisiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , SARS-CoV-2/metabolismo
19.
J Matern Fetal Neonatal Med ; 35(25): 7200-7206, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34219602

RESUMO

BACKGROUND: Toxoplasmosis is one of the main preventable congenital infections in Brazil. This manuscript aims to describe antenatal factors possibly associated with congenital toxoplasmosis (CT). METHODS: This is a case-control study, with data collected from medical records, from infants admitted under one year of age at the Infectious Diseases Clinic of Instituto de Puericultura e Pediatria Martagão Gesteira, reference center from Rio de Janeiro, exposed to toxoplasmosis during their antenatal period. Patients diagnosed with CT were classified as cases and those exposed without infection as controls. RESULTS: A total of 289 patients were followed up in 10 years. CT was confirmed in 43 (14.9%) of which six (14%) were asymptomatic, five (12%) had the classic triad (retinochoroiditis, hydrocephalus and intracranial calcifications), 27/42 (64.3%) had reactive IgM. Even after adjusted for prematurity, cases were born with lower weight (OR 0.49 - IC95% 0.33-0.73). There was a 13% increase in chance of CT per gestational week of the maternal diagnosis. Maternal fever, consumption of poorly washed vegetables during pregnancy, and diagnosis in the third trimester were associated with CT (OR: 6.43, 6.55, and 2.16, respectively). CONCLUSION: Fever during pregnancy, consumption of poorly washed vegetables and diagnosis in the third trimester were associated with CT. Infants with diagnosis of CT were born with lower weight than the controls.


Assuntos
Complicações Infecciosas na Gravidez , Toxoplasma , Toxoplasmose Congênita , Toxoplasmose , Lactente , Humanos , Feminino , Gravidez , Toxoplasmose Congênita/epidemiologia , Brasil/epidemiologia , Estudos de Casos e Controles , Complicações Infecciosas na Gravidez/diagnóstico
20.
Physis (Rio J.) ; 32(2): e320221, 2022.
Artigo em Português | LILACS | ID: biblio-1386839

RESUMO

Resumo Estudo qualitativo com abordagem de História Oral Temática, com o objetivo de compreender a atenção à saúde da mulher na visão de mulheres sem filhos, considerando as políticas públicas em saúde. Utilizou-se a técnica de snowball para definição das 19 mulheres participantes, sem filhos, idade entre 18 e 90 anos, que conheçam ou utilizem políticas públicas de saúde. As narrativas foram recolhidas por meio de entrevistas, com um roteiro semiestruturado, e submetidas ao método de análise de narrativas. Dentre os achados, encontram-se os discursos e as representações da maternidade, produzidos e veiculados nas políticas públicas de saúde, nas quais estão implícitas as características biológicas femininas na fragmentação do corpo feminino em útero e peito. Destaca-se ainda a percepção das mulheres sem filhos de que os programas e políticas de saúde, ao se concentrarem nos aspectos reprodutivos, reafirmam o ideal feminino de mulher-mãe, negligenciando outros aspectos e desconsiderando a mulher que escolhe a não maternidade. As representações do feminino concentram-se no corpo, alvo do poder, vinculando a condição de ser mulher à maternidade, baseado num determinismo biológico. Faz-se necessário reelaborar essas políticas, considerando as transformações no papel feminino e a liberdade de escolha da mulher na contemporaneidade.


Abstract Qualitative study with a Thematic Oral History approach, aiming to understand women's health care from the point of view of childless women, considering public health policies. The snowball technique was used to define the 19 participating women, without children, aged between 18 and 90 years, who know or use public health policies. The narratives were collected through interviews, with a semi-structured script, and submitted to the narrative analysis method. Among the findings, there are the discourses and representations of motherhood, produced and conveyed in public health policies, in which the biological characteristics of women are implicit in the fragmentation of the female body into uterus and breast. Also noteworthy is the perception of childless women that health programs and policies, by focusing on reproductive aspects, reaffirming the female ideal of a woman-mother, neglecting other aspects and disregarding the woman who chooses no maternity. The representations of the feminine focus on the body, the target of power, linking the condition of being a woman to motherhood, based on biological determinism. It is necessary to re-elaborate these policies, considering the transformations in the female role and women's freedom of choice in contemporary times.


Assuntos
Humanos , Feminino , Gravidez , Saúde da Mulher/legislação & jurisprudência , Assistência Integral à Saúde/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Útero , Sistema Único de Saúde , Brasil , Mama
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