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1.
Diabetes ; 73(6): 964-976, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38530908

RESUMO

Adiponectin has vascular anti-inflammatory and protective effects. Although adiponectin protects against the development of albuminuria, historically, the focus has been on podocyte protection within the glomerular filtration barrier (GFB). The first barrier to albumin in the GFB is the endothelial glycocalyx (eGlx), a surface gel-like barrier covering glomerular endothelial cells (GEnCs). In diabetes, eGlx dysfunction occurs before podocyte damage; hence, we hypothesized that adiponectin could protect from eGlx damage to prevent early vascular damage in diabetic kidney disease (DKD). Globular adiponectin (gAd) activated AMPK signaling in human GEnCs through AdipoR1. It significantly reduced eGlx shedding and the tumor necrosis factor-α (TNF-α)-mediated increase in syndecan-4 (SDC4) and MMP2 mRNA expression in GEnCs in vitro. It protected against increased TNF-α mRNA expression in glomeruli isolated from db/db mice and against expression of genes associated with glycocalyx shedding (namely, SDC4, MMP2, and MMP9). In addition, gAd protected against increased glomerular albumin permeability (Ps'alb) in glomeruli isolated from db/db mice when administered intraperitoneally and when applied directly to glomeruli (ex vivo). Ps'alb was inversely correlated with eGlx depth in vivo. In summary, adiponectin restored eGlx depth, which was correlated with improved glomerular barrier function, in diabetes.


Assuntos
Adiponectina , Diabetes Mellitus Tipo 2 , Glicocálix , Glomérulos Renais , Animais , Glicocálix/metabolismo , Glicocálix/efeitos dos fármacos , Adiponectina/metabolismo , Adiponectina/genética , Camundongos , Diabetes Mellitus Tipo 2/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Glomérulos Renais/efeitos dos fármacos , Humanos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Masculino , Barreira de Filtração Glomerular/metabolismo , Barreira de Filtração Glomerular/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Sindecana-4/metabolismo , Sindecana-4/genética , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
2.
Am J Case Rep ; 22: e929537, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33782375

RESUMO

BACKGROUND Leclercia adecarboxylata is a gram-negative rod, which is normally found in water and food. It is an emerging pathogen that affects immunocompromised patients, including patients with hematological malignancies or those receiving chemotherapy. Generally, L. adecarboxylata is considered a low-virulence pathogen with an excellent susceptibility profile, but some strains may be resistant to multiple antibiotics, such as b-lactams. Moreover, L. adecarboxylata is usually isolated as a part of polymicrobial cultures in immunocompetent individuals, but there have been cases where it was the only isolate. CASE REPORT A 74-year-old woman who was non-immunosuppressed and had multiple comorbidities was admitted with acute decompensated heart failure due to pneumonia. She was treated with multiple courses of antibiotics including amoxicillin-clavulanate and ciprofloxacin for pneumonia, but her infection worsened, and she had cardiopulmonary arrest. After resuscitation, she was stable for several days but suddenly became confused and hypotensive. The septic screen showed L. adecarboxylata bacteremia without a clear source, which was treated successfully with meropenem for 14 days. After the meropenem course, the patient developed diarrhea and was found to have severe Clostridium difficile infection. She did not respond to oral vancomycin and intravenous metronidazole and died. CONCLUSIONS This case illustrated an infection in a non-immunosuppressed individual by an organism that is considered an opportunistic pathogen, mainly affecting immunocompromised patients. The patient's blood culture grew L. adecarboxylata, which was sensitive to all antibiotics but resolved with meropenem treatment. Owing to increasing L. adecarboxylata infections, we recommend further studies to understand the organism's pathogenesis, risk factors, and resistance pattern.


Assuntos
Bacteriemia , Infecções por Enterobacteriaceae , Idoso , Antibacterianos/uso terapêutico , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Enterobacteriaceae , Feminino , Humanos , Hospedeiro Imunocomprometido
3.
Am J Case Rep ; 20: 1902-1906, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31857571

RESUMO

BACKGROUND Synthetic cannabinoids have a higher affinity for the cannabinoid receptors CB1 and CB2 than natural cannabinoids. Their use can be associated with cardiovascular disease and neurological complications. A case is reported of status epilepticus and stress cardiomyopathy following the recreational use of the synthetic cannabinoid, UR-144. CASE REPORT A 19-year-old woman presented to the emergency department in status epilepticus after smoking the synthetic cannabinoid known as 'space'. Recurring seizure activity was controlled after three hours. On hospital day 3, the patient developed severe biventricular failure. Cardiac magnetic resonance imaging (MRI) confirmed the diagnosis of stress cardiomyopathy. A comprehensive urine drug screen was performed using gas chromatography-mass spectrometry (GC-MS), which was positive for UR-144, or (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)-methanone, and negative for all other illicit recreational drugs. The patient improved at one week following admission, with a left ventricular ejection fraction (LVEF) of 40%. She was discharged home on hospital day 10. CONCLUSIONS The use of the synthetic cannabinoid, UR-144, may be associated with prolonged status epilepticus and stress cardiomyopathy. Physicians should be aware of these potentially lethal complications associated with the recreational use of this and other illicit synthetic cannabinoids.


Assuntos
Canabinoides/efeitos adversos , Overdose de Drogas/complicações , Fumar/efeitos adversos , Estado Epiléptico/induzido quimicamente , Cardiomiopatia de Takotsubo/induzido quimicamente , Bisoprolol/uso terapêutico , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Indóis/urina , Lisinopril/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Detecção do Abuso de Substâncias , Cardiomiopatia de Takotsubo/tratamento farmacológico , Adulto Jovem
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