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1.
Eur J Clin Invest ; 54(7): e14224, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634717

RESUMO

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of end-stage liver disease associated with increased mortality and cardiovascular disease. Obesity and diabetes are the most important risk factors of MASLD. It is well-established that obesity-associated insulin resistance leads to a situation of tissue lipotoxicity characterized by an accumulation of excess fat in non-fat tissues such as the liver, promoting the development of MASLD, and its progression into metabolic dysfunction-associated steatohepatitis. METHODS: Here, we aimed to review the impact of disrupted intestinal permeability, antimicrobial proteins and bacterial endotoxin in the development and progression of MASLD. RESULTS AND CONCLUSION: Recent studies demonstrated that obesity- and obesogenic diets-associated alterations of intestinal microbiota along with the disruption of intestinal barrier integrity, the alteration in antimicrobial proteins and, in consequence, an enhanced translocation of bacterial endotoxin into bloodstream might contribute to this pathological process through to impacting liver metabolism and inflammation.


Assuntos
Endotoxinas , Microbioma Gastrointestinal , Obesidade , Animais , Humanos , Peptídeos Catiônicos Antimicrobianos/metabolismo , Translocação Bacteriana , Endotoxinas/metabolismo , Fígado Gorduroso/metabolismo , Microbioma Gastrointestinal/fisiologia , Resistência à Insulina/fisiologia , Mucosa Intestinal/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/metabolismo , Obesidade/complicações , Função da Barreira Intestinal
2.
Emerg Infect Dis ; 29(12): 2553-2556, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37916983

RESUMO

We report a massive mortality of 5,224 sea lions (Otaria flavescens) in Peru that seemed to be associated with highly pathogenic avian influenza A(H5N1) virus infection. The transmission pathway may have been through the close contact of sea lions with infected wild birds. We recommend evaluating potential virus transmission among sea lions.


Assuntos
Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Leões-Marinhos , Animais , Animais Selvagens
3.
Pharmacol Res ; 187: 106562, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36410673

RESUMO

Lipopolysaccharide binding protein (LBP) knockout mice models are protected against the deleterious effects of major acute inflammation but its possible physiological role has been less well studied. We aimed to evaluate the impact of liver LBP downregulation (using nanoparticles containing siRNA- Lbp) on liver steatosis, inflammation and fibrosis during a standard chow diet (STD), and in pathological non-obesogenic conditions, under a methionine and choline deficient diet (MCD, 5 weeks). Under STD, liver Lbp gene knockdown led to a significant increase in gene expression markers of liver inflammation (Itgax, Tlr4, Ccr2, Ccl2 and Tnf), liver injury (Krt18 and Crp), fibrosis (Col4a1, Col1a2 and Tgfb1), endoplasmic reticulum (ER) stress (Atf6, Hspa5 and Eif2ak3) and protein carbonyl levels. As expected, the MCD increased hepatocyte vacuolation, liver inflammation and fibrosis markers, also increasing liver Lbp mRNA. In this model, liver Lbp gene knockdown resulted in a pronounced worsening of the markers of liver inflammation (also including CD68 and MPO activity), fibrosis, ER stress and protein carbonyl levels, all indicative of non-alcoholic steatohepatitis (NASH) progression. At cellular level, Lbp gene knockdown also increased expression of the proinflammatory mediators (Il6, Ccl2), and markers of fibrosis (Col1a1, Tgfb1) and protein carbonyl levels. In agreement with these findings, liver LBP mRNA in humans positively correlated with markers of liver damage (circulating hsCRP, ALT activity, liver CRP and KRT18 gene expression), and with a network of genes involved in liver inflammation, innate and adaptive immune system, endoplasmic reticulum stress and neutrophil degranulation (all with q-value<0.05). In conclusion, current findings suggest that a significant downregulation in liver LBP levels promotes liver oxidative stress and inflammation, aggravating NASH progression, in physiological and pathological non-obesogenic conditions.


Assuntos
Cirrose Hepática , Fígado , Hepatopatia Gordurosa não Alcoólica , Animais , Humanos , Camundongos , Modelos Animais de Doenças , Inflamação/genética , Cirrose Hepática/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/genética , RNA Mensageiro/metabolismo
4.
MMWR Morb Mortal Wkly Rep ; 72(32): 871-876, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37561674

RESUMO

Persons receiving maintenance dialysis are at increased risk for SARS-CoV-2 infection and its severe outcomes, including death. However, rates of SARS-CoV-2 infection and COVID-19-related deaths in this population are not well described. Since November 2020, CDC's National Healthcare Safety Network (NHSN) has collected weekly data monitoring incidence of SARS-CoV-2 infections (defined as a positive SARS-CoV-2 test result) and COVID-19-related deaths (defined as the death of a patient who had not fully recovered from a SARS-CoV-2 infection) among maintenance dialysis patients. This analysis used NHSN dialysis facility COVID-19 data reported during June 30, 2021-September 27, 2022, to describe rates of SARS-CoV-2 infection and COVID-19-related death among maintenance dialysis patients. The overall infection rate was 30.47 per 10,000 patient-weeks (39.64 among unvaccinated patients and 27.24 among patients who had completed a primary COVID-19 vaccination series). The overall death rate was 1.74 per 10,000 patient-weeks. Implementing recommended infection control measures in dialysis facilities and ensuring patients and staff members are up to date with recommended COVID-19 vaccination is critical to limiting COVID-19-associated morbidity and mortality.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Humanos , Centers for Disease Control and Prevention, U.S. , COVID-19/diagnóstico , COVID-19/mortalidade , Vacinas contra COVID-19 , Diálise Renal , SARS-CoV-2 , Estados Unidos/epidemiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia
5.
Faraday Discuss ; 245(0): 352-367, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37317671

RESUMO

Several small Polycyclic Aromatic Hydrocarbons (PAHs) have been identified recently in the Taurus Molecular Cloud (TMC-1) using radio telescope observations. Reproducing the observed abundances of these molecules has been a challenge for astrochemical models. Rapid radiative cooling of PAHs by Recurrent Fluorescence (RF), the emission of optical photons from thermally populated electronically excited states, has been shown to efficiently stabilize small PAHs following ionization, augmenting their resilience in astronomical environments and helping to rationalize their observed high abundances. Here, we use a novel method to experimentally determine the radiative cooling rate of the cation of 1-cyanonaphthalene (C10H7CN, 1-CNN), the neutral species of which has been identified in TMC-1. Laser-induced dissociation rates and kinetic energy release distributions of 1-CNN cations isolated in a cryogenic electrostatic ion-beam storage ring are analysed to track the time evolution of the vibrational energy distribution of the initially hot ion ensemble as it cools. The measured cooling rate is in good agreement with the previously calculated RF rate coefficient. Improved measurements and models of the RF mechanism are needed to interpret astronomical observations and refine predictions of the stabilities of interstellar PAHs.

6.
Semin Dial ; 36(1): 24-28, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35384078

RESUMO

BACKGROUND: Hemodialysis solutions typically contain a high alkali concentration designed to counter interdialytic acidosis, but this could result in persistent alkalosis in some patients. The prevalence and significance of persistent alkalosis were therefore examined at four outpatient centers over a 10-year period. METHODS: Alkalosis was defined as a pre-dialysis serum [HCO3 ] ≥ 26 meq/L in >6 months of a 12-month period and was persistent if present in a majority of months thereafter. Control patients had a serum [HCO3 ] of 19-23 meq/L > 6 of every 12 months. Standard, citrate-containing dialysate was used in all patients without adjustment of bicarbonate concentration. RESULTS: 444 of 1271 patients had alkalosis that persisted in 73. Compared to control patients, persistently alkalotic patients were older, but gender, race, starting weight, comorbidities, and mortality did not differ. Dialysis dose was 7% greater, protein catabolic rate was 11% lower, and interdialytic weight gain was 29% lower, all p < 0.001. Persistently alkalotic patients had double the incidence of cardiac arrhythmias (p = 0.07) and a 20% greater intradialytic blood pressure decrease (p < 0.001). CONCLUSIONS: Alkalosis is common in hemodialysis patients and can be persistent, likely due to decreased protein catabolic rate and increased dialysis dose, and may have detrimental cardiovascular effects.


Assuntos
Alcalose , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Estudos Prospectivos , Soluções para Diálise , Soluções para Hemodiálise , Alcalose/epidemiologia , Alcalose/etiologia , Bicarbonatos/metabolismo
7.
Phys Chem Chem Phys ; 25(15): 10726-10740, 2023 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-37000595

RESUMO

We have measured recurrent fluorescence (RF) cooling rates of internally hot tetracene cations, C18H12+, as functions of their storage times and internal energies in two different electrostatic ion-beam storage rings - the cryogenic ring DESIREE with a circumference of 8.6 meters in Stockholm and the much smaller room temperature ring Mini-Ring in Lyon, which has a circumference of 0.71 meters. The RF rates were measured to be as high as 150 to 1000 s-1 for internal energies in the 7 to 9.4 eV energy range, where we have probed the time evolution of the internal energy distribution with nanosecond laser pulses with a 1 kHz repetition rate. These RF rates are found to be significantly higher than those of previously investigated smaller PAHs such as e.g. anthracene and naphthalene, for which the lowest non-forbidden electronic excited state, the D2 state, is populated with a smaller probability by inverse internal conversion. Furthermore, the D2-D0 transition rate is smaller for these smaller molecules than for tetracene. The complementary features of the two storage rings allow for RF rate measurements in a broader internal energy range than has been possible before. The smaller sampling period of about 6 µs in Mini-Ring is ideal to study the cooling dynamics of the hotter ions that decay fast, whereas DESIREE with a sampling period of about 60 µs is better suited to study the colder ions that decay on longer timescales ranging up to hundreds of milliseconds. The excellent agreement between the two series of measurements in the region where they overlap demonstrates the complementarity of the two electrostatic ion-beam storage rings.

8.
J Chem Phys ; 158(24)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37347125

RESUMO

Polycyclic aromatic hydrocarbons have widely been conjectured to be ubiquitous in space, as supported by the recent discovery of two isomers of cyanonaphthalene, indene, and 2-cyanoindene in the Taurus molecular cloud-1 using radioastronomy. Here, the photoionization dynamics of 1-cyanonaphthalene (1-CNN) are investigated using synchrotron radiation over the hν = 9.0-19.5 eV range, revealing that prompt autoionization from the plasmon resonance dominates the photophysics for hν = 11.5-16.0 eV. Minimal photo-induced dissociation, whether originating from an excited state impulsive bond rupture or through internal conversion followed by a statistical bond cleavage process, occurs over the microsecond timescale (as limited by the experimental setup). The direct photoionization cross section and photoelectron angular distributions are simulated using an ezDyson model combining Dyson orbitals with Coulomb wave photoejection. When considering these data in conjunction with recent radiative cooling measurements on 1-CNN+, which showed that cations formed with up to 5 eV of internal energy efficiently stabilize through recurrent fluorescence, we conclude that the organic backbone of 1-CNN is resilient to photodestruction by VUV and soft XUV radiation. These dynamics may prove to be a common feature for the survival of small polycyclic aromatic hydrocarbons in space, provided that the cations have a suitable electronic structure to support recurrent fluorescence.


Assuntos
Temperatura Baixa , Hidrocarbonetos Policíclicos Aromáticos , Fluorescência , Isomerismo , Transição de Fase
9.
J Chem Phys ; 158(17)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37125715

RESUMO

Naphthalene and azulene are isomeric polycyclic aromatic hydrocarbons (PAHs) and are topical in the context of astrochemistry due to the recent discovery of substituted naphthalenes in the Taurus Molecular Cloud-1 (TMC-1). Here, the thermal- and photo-induced isomerization, dissociation, and radiative cooling dynamics of energized (vibrationally hot) naphthalene (Np+) and azulene (Az+) radical cations, occurring over the microsecond to seconds timescale, are investigated using a cryogenic electrostatic ion storage ring, affording "molecular cloud in a box" conditions. Measurement of the cooling dynamics and kinetic energy release distributions for neutrals formed through dissociation, until several seconds after hot ion formation, are consistent with the establishment of a rapid (sub-microsecond) Np+ ⇌ Az+ quasi-equilibrium. Consequently, dissociation by C2H2-elimination proceeds predominantly through common Az+ decomposition pathways. Simulation of the isomerization, dissociation, recurrent fluorescence, and infrared cooling dynamics using a coupled master equation combined with high-level potential energy surface calculations [CCSD(T)/cc-pVTZ], reproduce the trends in the measurements. The data show that radiative cooling via recurrent fluorescence, predominately through the Np+ D0 ← D2 transition, efficiently quenches dissociation for vibrational energies up to ≈1 eV above dissociation thresholds. Our measurements support the suggestion that small cations, such as naphthalene, may be more abundant in space than previously thought. The strategy presented in this work could be extended to fingerprint the cooling dynamics of other PAH ions for which isomerization is predicted to precede dissociation.

10.
Int J Mol Sci ; 24(5)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36902180

RESUMO

Excess iron is known to trigger adipose tissue dysfunction and insulin resistance. Circulating markers of iron status have been associated with obesity and adipose tissue in cross-sectional studies. We aimed to evaluate whether iron status is linked to changes in abdominal adipose tissue longitudinally. Subcutaneous abdominal tissue (SAT) and visceral adipose tissue (VAT) and its quotient (pSAT) were assessed using magnetic resonance imaging (MRI), at baseline and after one year of follow-up, in 131 (79 in follow-up) apparently healthy subjects, with and without obesity. Insulin sensitivity (euglycemic- hyperinsulinemic clamp) and markers of iron status were also evaluated. Baseline serum hepcidin (p = 0.005 and p = 0.002) and ferritin (p = 0.02 and p = 0.01)) were associated with an increase in VAT and SAT over one year in all subjects, while serum transferrin (p = 0.01 and p = 0.03) and total iron-binding capacity (p = 0.02 and p = 0.04) were negatively associated. These associations were mainly observed in women and in subjects without obesity, and were independent of insulin sensitivity. After controlling for age and sex, serum hepcidin was significantly associated with changes in subcutaneous abdominal tissue index (iSAT) (ß = 0.406, p = 0.007) and visceral adipose tissue index (iVAT) (ß = 0.306, p = 0.04), while changes in insulin sensitivity (ß = 0.287, p = 0.03) and fasting triglycerides (ß = -0.285, p = 0.03) were associated with changes in pSAT. These data indicated that serum hepcidin are associated with longitudinal changes in SAT and VAT, independently of insulin sensitivity. This would be the first prospective study evaluating the redistribution of fat according to iron status and chronic inflammation.


Assuntos
Resistência à Insulina , Gordura Intra-Abdominal , Ferro , Feminino , Humanos , Tecido Adiposo , Estudos Transversais , Hepcidinas , Ferro/metabolismo , Obesidade/complicações , Estudos Prospectivos , Gordura Subcutânea
11.
Eur J Clin Invest ; 52(2): e13685, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34582564

RESUMO

BACKGROUND: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. AIM: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). MATERIALS AND METHODS: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. RESULTS: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. CONCLUSION: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Gordura Intra-Abdominal/metabolismo , Leucócitos Mononucleares/metabolismo , Obesidade/genética , Receptores de Coronavírus/genética , Gordura Subcutânea/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Enzima de Conversão de Angiotensina 2/metabolismo , Cirurgia Bariátrica , COVID-19 , Metilação de DNA , Dieta Cetogênica , Dieta Redutora , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Obesidade/terapia , Obesidade Mórbida/genética , Obesidade Mórbida/metabolismo , Obesidade Mórbida/terapia , Receptores de Coronavírus/metabolismo , SARS-CoV-2 , Redução de Peso
12.
J Chem Phys ; 157(17): 174308, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36347688

RESUMO

Time-dependent photodetachment action spectra for the linear hydrocarbon anions C4H- and C6H- are investigated using the cryogenic Double ElectroStatic Ion Ring ExpEriment. The radiative cooling characteristics of these ions on the millisecond to seconds timescale are characterized by monitoring changes in their spectra as the ions cool by spontaneous infrared (IR) emission. The average cooling rates, extracted using Non-negative Matrix Factorization, are fit with 1/e lifetimes of 19 ± 2 and 3.0 ± 0.2 s for C4H- and C6H-, respectively. The cooling rates are successfully reproduced using a simple harmonic cascade model of IR emission. The ultraslow radiative cooling dynamics determined in this work provide important data for understanding the thermal cooling properties of linear hydrocarbon anions and for refining models of the formation and destruction mechanisms of these anions in astrochemical environments.

13.
Semin Cell Dev Biol ; 85: 164-172, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29107169

RESUMO

The relationship among chronic low-grade inflammation, insulin resistance and other obesity-associated metabolic disturbances is increasingly recognized. The possible mechanisms that trigger these immunologic alterations remain to be fully understood. The complement system is a crucial element of immune defense system, being important in the activation of innate and adaptative immune response, promoting the clearance of apoptotic and damaged endogenous cells and participating in processes of tissue development, degeneration, and regeneration. Circulating components of the complement system appear to be dysregulated in obesity-associated metabolic disturbances. The activation of the complement system is also evident in adipose tissue from obese subjects, in association with subclinical inflammation and alterations in glucose metabolism. The possible contribution of some components of the complement system in the development of insulin resistance and obesity-associated metabolic disturbances, and the possible role of complement system in adipose tissue physiology is reviewed here. The modulation of the complement system could constitute a potential target in the pathophysiology and therapy of obesity and associated metabolic disease.


Assuntos
Tecido Adiposo/metabolismo , Proteínas do Sistema Complemento/metabolismo , Resistência à Insulina , Doenças Metabólicas/sangue , Doenças Metabólicas/metabolismo , Obesidade/sangue , Obesidade/metabolismo , Complemento C3/metabolismo , Humanos , Inflamação/metabolismo
14.
Int J Obes (Lond) ; 45(2): 415-426, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33040077

RESUMO

BACKGROUND AND OBJECTIVES: The importance of hydrogen sulfide is increasingly recognized in the pathophysiology of obesity and type 2 diabetes in animal models. Very few studies have evaluated circulating sulfides in humans, with discrepant results. Here, we aimed to investigate serum sulfide levels according to obesity. SUBJECTS AND METHODS: Serum sulfide levels were analyzed, using a selective fluorescent probe, in two independent cohorts [cross-sectionally in discovery (n = 139) and validation (n = 71) cohorts, and longitudinally in 82 participants from discovery cohort]. In the validation cohort, blood gene expression of enzymes contributing to H2S generation and consumption were also measured. RESULTS: In the discovery cohort, serum sulfide concentration was significantly increased in subjects with morbid obesity at baseline and follow-up, and positively correlated with BMI and fat mass, but negatively with total cholesterol, haemoglobin, serum ferritin, iron and bilirubin after adjusting by age, gender and fat mass. Fat mass (ß = 0.51, t = 3.67, p < 0.0001) contributed independently to age-, gender-, insulin sensitivity- and BMI-adjusted serum sulfide concentration variance. Importantly, receiver operating characteristic analysis demonstrated the relevance of fat mass predicting serum sulfide levels, which was replicated in the validation cohort. In addition, serum sulfide concentration was decreased in morbidly obese subjects with impaired compared to those with normal fasting glucose. Longitudinally, weight gain resulted in increased serum sulfide concentration, whereas weight loss had opposite effects, being the percent change in serum sulfide positively correlated with the percent change in BMI and waist circumference, but negatively with bilirubin. Whole blood CBS, CTH, MPST, SQOR, TST and MPO gene expression was not associated to obesity or serum sulfide concentration. CONCLUSIONS: Altogether these data indicated that serum sulfide concentrations were increased in subjects with morbid obesity in proportion to fat mass and inversely associated with circulating markers of haem degradation.


Assuntos
Tecido Adiposo/fisiologia , Obesidade Mórbida , Sulfetos/sangue , Adulto , Estudos Transversais , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/fisiopatologia , Adulto Jovem
15.
Curr Opin Cardiol ; 36(4): 420-428, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34059610

RESUMO

PURPOSE OF REVIEW: Controlling hypertension to the desired target is commonly unsuccessful and requires multi-drug regimen, which can lead to undesirable side effects. Resistant hypertension (RH) is more cumbersome to deal with and has robust morbidity and mortality burden even with current multiple medical options. Herein, we review the literature for the potential role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as a treatment option for hypertension and RH. RECENT FINDINGS: With more recent randomized controlled trials (RCTs), SGLT2i have gained more recognition for their renal and cardiovascular protection as well as mortality benefit that are believed to be medication class-related effects. Multiple RCTs have evaluated blood pressure (BP) lowering properties of SGLT2i, as a primary or secondary end point, in diabetic and nondiabetic patients, yet trials are scarce in studying SGLT2i as first-line antihypertensives, or as add-on agents for treating RH. SUMMARY: Finding the right medical therapy in treating hypertension, especially RH, is commonly onerous when it comes to achieving BP targets, avoiding medication side effects, and aiming for the best outcomes. Utilizing existing drugs like SGLT2i or exploring other novel agents with more RCTs for these purposes will be beneficial. The addition of SGLT2i to the therapeutic armamentarium in patients with RH should be considered as a target for upcoming RCTs.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Humanos , Hipertensão/tratamento farmacológico , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
16.
Am J Nephrol ; 52(3): 190-198, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33827078

RESUMO

BACKGROUND: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. METHODS: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. RESULTS: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). CONCLUSION: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , COVID-19/mortalidade , Falência Renal Crônica/complicações , Idoso , COVID-19/sangue , COVID-19/complicações , COVID-19/etnologia , Feminino , Georgia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tromboembolia/virologia
17.
Pharmacol Res ; 166: 105486, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33556481

RESUMO

Chronic systemic low-level inflammation in metabolic disease is known to affect adipose tissue biology. Lysozyme (LYZ) is a major innate immune protein but its role in adipose tissue has not been investigated. Here, we aimed to investigate LYZ in human and rodents fat depots, and its possible role in obesity-associated adipose tissue dysfunction. LYZ mRNA and protein were identified to be highly expressed in adipose tissue from subjects with obesity and linked to systemic chronic-low grade inflammation, adipose tissue inflammation and metabolic disturbances, including hyperglycemia, dyslipidemia and decreased markers of adipose tissue adipogenesis. These findings were confirmed in experimental models after a high-fat diet in mice and rats and also in ob/ob mice. Importantly, specific inguinal and perigonadal white adipose tissue lysozyme (Lyz2) gene knockdown in high-fat diet-fed mice resulted in improved adipose tissue inflammation in parallel to reduced lysozyme activity. Of note, Lyz2 gene knockdown restored adipogenesis and reduced weight gain in this model. In conclusion, altogether these observations point to lysozyme as a new actor in obesity-associated adipose tissue dysfunction. The therapeutic targeting of lysozyme production might contribute to improve adipose tissue metabolic homeostasis.


Assuntos
Adipogenia , Dieta Hiperlipídica/efeitos adversos , Inflamação/genética , Muramidase/genética , Tecido Adiposo/metabolismo , Animais , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/genética , Ratos Wistar
18.
Arterioscler Thromb Vasc Biol ; 40(5): 1413-1419, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32078340

RESUMO

OBJECTIVE: Warfarin is associated with medial arterial calcification in humans, but the magnitude and specificity of this effect and the role of other risk factors are unknown. Using serial mammograms, progression of arterial calcification was compared in women receiving no anticoagulants, warfarin, or other anticoagulants, and before, during, and after warfarin use. Approach and Results: Warfarin users with mammograms were identified by computerized searches of medical records that included renal function and diabetes mellitus. Lengths of calcified arterial segments were measured, with progression expressed as millimeters per breast per year and presented as medians and interquartile range (IQR). In women with normal renal function (estimated glomerular filtration rate >60 mL/minute per 1.73 m2), progression was 3.9-fold greater in warfarin users: 9.9 (3.8-16) versus 2.5 (0.7-6.7) in controls, P=0.0003, but not increased in users of other anticoagulants. In longitudinal analyses, progression increased from 2.1 (IQR, 0.3-3.9) to 13.8 (IQR, 7.8-38.7; P=0.011) after starting warfarin (n=11) and decreased from 8.8 (IQR, 1.1-10) to 1.9 (IQR, -10 to 6.7; P=0.024) after discontinuation of warfarin (n=13). Progression of calcification was similar in warfarin users with chronic kidney disease (7.3 [IQR, 3.6-17], n=29) but markedly accelerated in warfarin users with end-stage renal disease (47 [IQR, 31-183], n=11; P=0.0002). Progression was similar in diabetic and nondiabetic warfarin users (10.1 [IQR, 3.8-24] versus 7.8 [IQR, 3.6-15]) and did not correlate with age (r=0.09) or duration of warfarin therapy (r=0.12). CONCLUSIONS: Warfarin significantly accelerates medial arterial calcification in humans. This effect is markedly augmented in end-stage renal disease.


Assuntos
Anticoagulantes/efeitos adversos , Mama/irrigação sanguínea , Doença Arterial Periférica/induzido quimicamente , Calcificação Vascular/induzido quimicamente , Varfarina/efeitos adversos , Idoso , Estudos de Casos e Controles , Progressão da Doença , Feminino , Humanos , Falência Renal Crônica/complicações , Mamografia , Doença Arterial Periférica/diagnóstico por imagem , Medição de Risco , Fatores de Risco , Calcificação Vascular/diagnóstico por imagem
19.
Dig Surg ; 38(3): 237-246, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33906192

RESUMO

INTRODUCTION: Obesity is usually considered a risk factor for surgical complications. Laparoscopic adrenalectomy has replaced open adrenalectomy as the standard operation for adrenal tumors. OBJECTIVE: To compare the safety of laparoscopic adrenalectomy to treat adrenal tumors in obese versus nonobese patients. METHODS: This observational cohort study analyzed consecutive patients who underwent laparoscopic adrenalectomy with a lateral transperitoneal approach at a single center (2003-2020). Data and outcomes of obese (body mass index ≥30 kg/m2) and nonobese patients were compared. To analyze the association between operative time and other variables, we used simple and multivariate linear regression. RESULTS: N = 160 (90 obese/70 nonobese) patients underwent laparoscopic adrenalectomy. Cushing syndrome and pheochromocytoma were the most frequent indications. Obese patients were older (58 vs. 52 years, p < 0.001). A greater proportion of obese patients were ASA grade III + IV (71.1 vs. 48.6%, p = 0.004). Obesity was associated with a longer operative time (72.5 vs. 60 min, p < 0.001) and greater blood loss (40 vs. 20 mL, p = 0.022). There were no differences in conversion, morbidity, or hospital stay. After adjustment for confounding factors, operative time was positively correlated with BMI ≥30 kg/m2, learning curve, estimated blood loss, 2D laparoscopy, and specimen size. CONCLUSION: Lateral transperitoneal laparoscopic adrenalectomy is safe in patients with a BMI 30-35 kg/m2, so these patients also benefit from this minimally invasive surgery.


Assuntos
Adenoma/cirurgia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia , Obesidade/complicações , Feocromocitoma/cirurgia , Adenoma/complicações , Adolescente , Neoplasias das Glândulas Suprarrenais/complicações , Adulto , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Feocromocitoma/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
BMC Nephrol ; 22(1): 81, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33676397

RESUMO

BACKGROUND: Emory Dialysis serves an urban and predominantly African American population at its four outpatient dialysis facilities. We describe COVID-19 infection control measures implemented and clinical characteristics of patients with COVID-19 in the Emory Dialysis facilities. METHODS: Implementation of COVID-19 infection procedures commenced in February 2020. Subsequently, COVID-19 preparedness assessments were conducted at each facility. Patients with COVID-19 from March 1-May 31, 2020 were included; with a follow-up period spanning March-June 30, 2020. Percentages of patients diagnosed with COVID-19 were calculated, and characteristics of COVID-19 patients were summarized as medians or percentage. Baseline characteristics of all patients receiving care at Emory Dialysis (i.e. Emory general dialysis population) were presented as medians and percentages. RESULTS: Of 751 dialysis patients, 23 (3.1%) were diagnosed with COVID-19. The median age was 67.0 years and 13 patients (56.6%) were female. Eleven patients (47.8%) were residents of nursing homes. Nineteen patients (82.6%) required hospitalization and 6 patients (26.1%) died; the average number of days from a positive SARS-CoV-2 (COVID) test to death was 16.8 days (range 1-34). Two patients dialyzing at adjacent dialysis stations and a dialysis staff who cared for them, were diagnosed with COVID-19 in a time frame that may suggest transmission in the dialysis facility. In response, universal masking in the facility was implemented (prior to national guidelines recommending universal masking), infection control audits and re-trainings of PPE were also done to bolster infection control practices. CONCLUSION: We successfully implemented recommended COVID-19 infection control measures aimed at mitigating the spread of SARS-CoV-2. Most of the patients with COVID-19 required hospitalizations. Dialysis facilities should remain vigilant and monitor for possible transmission of COVID-19 in the facility.


Assuntos
Instituições de Assistência Ambulatorial/normas , Negro ou Afro-Americano , COVID-19/prevenção & controle , Controle de Infecções/métodos , Diálise Renal/normas , Populações Vulneráveis/etnologia , Idoso , COVID-19/diagnóstico , COVID-19/etnologia , Teste de Ácido Nucleico para COVID-19 , Suscetibilidade a Doenças , Feminino , Georgia , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Telemedicina , População Urbana
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