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1.
Physiol Rep ; 12(13): e16127, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38960895

RESUMO

BACKGROUND AND AIMS: High tissue sodium accumulation and intermuscular adipose tissue (IMAT) are associated with aging, type 2 diabetes, and chronic kidney disease. In this study, we aim to investigate whether high lower-extremity tissue sodium accumulation relates to IMAT quantity and whether systemic inflammatory mediators and adipocytokines contribute to such association. METHODS: Tissue sodium content and IMAT accumulation (percentage of IMAT area to muscle area) were measured in 83 healthy individuals using sodium imaging (23Na-MRI) and proton (1H-MRI) imaging of the calf. Insulin sensitivity was assessed by glucose disposal rate (GDR) measured with the hyperinsulinemic-euglycemic clamp. RESULTS: Median (interquartile range) muscle and skin sodium contents were 16.6 (14.9, 19.0) and 12.6 (10.9, 16.7) mmol/L, respectively. Median IMAT was 3.69 (2.80, 5.37) %. In models adjusted for age, sex, BMI, GDR, adiponectin, and high-sensitivity C-reactive protein, increasing tissue sodium content was significantly associated with higher IMAT quantity (p = 0.018 and 0.032 for muscle and skin tissue sodium, respectively). In subgroup analysis stratified by sex, skin sodium was significantly associated with IMAT only among men. In interaction analysis, the association between skin sodium and IMAT was greater with increasing levels of high-sensitivity C-reactive protein and interleukin-6 (p for interaction = 0.022 and 0.006, respectively). CONCLUSIONS: Leg muscle and skin sodium are associated with IMAT quantity among healthy individuals. The relationship between skin sodium and IMAT may be mediated by systemic inflammation.


Assuntos
Tecido Adiposo , Músculo Esquelético , Sódio , Humanos , Masculino , Feminino , Tecido Adiposo/metabolismo , Tecido Adiposo/diagnóstico por imagem , Adulto , Sódio/metabolismo , Músculo Esquelético/metabolismo , Pessoa de Meia-Idade , Pele/metabolismo , Resistência à Insulina , Imageamento por Ressonância Magnética/métodos
3.
BMC Med ; 22(1): 249, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886716

RESUMO

BACKGROUND: Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). METHODS: The SCCS is a prospective cohort of primarily low-income adults aged 40-79, enrolled from the southeastern United States during 2002-2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. RESULTS: Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P < 0.05/3 except for cancer mortality after comprehensive adjustment). The standard risk factors explained < 40% of the variations in NDI/RSI/SVI and mediated < 70% of their associations with mortality. Among 1110 circulating metabolites measured in 1688 participants, 134 and 27 metabolites were associated with NDI and RSI (all FDR < 0.05) and mediated 61.7% and 21.2% of the NDI/RSI-mortality association, respectively. Adding those metabolites to standard risk factors increased the mediation proportion from 38.4 to 87.9% and 25.8 to 42.6% for the NDI/RSI-mortality association, respectively. CONCLUSIONS: Among low-income Black/African American adults and non-Hispanic White adults living in the southeastern United States, a disadvantaged neighborhood sociodemographic environment was associated with increased all-cause and CVD and cancer-specific mortality beyond standard risk factors. Circulating metabolites may unveil biological pathways underlying the health effect of neighborhood sociodemographic environment. More public health efforts should be devoted to reducing neighborhood environment-related health disparities, especially for low-income individuals.


Assuntos
População Branca , Humanos , Sudeste dos Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Adulto , Estudos Prospectivos , População Branca/estatística & dados numéricos , Doenças Cardiovasculares/mortalidade , Características de Residência , Neoplasias/mortalidade , Neoplasias/sangue , Negro ou Afro-Americano/estatística & dados numéricos , Características da Vizinhança , Pobreza , Mortalidade/tendências , Fatores Socioeconômicos
4.
Hypertension ; 81(3): 516-529, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37675576

RESUMO

BACKGROUND: The mechanisms by which salt increases blood pressure in people with salt sensitivity remain unclear. Our previous studies found that high sodium enters antigen-presenting cells (APCs) via the epithelial sodium channel and leads to the production of isolevuglandins and hypertension. In the current mechanistic clinical study, we hypothesized that epithelial sodium channel-dependent isolevuglandin-adduct formation in APCs is regulated by epoxyeicosatrienoic acids (EETs) and leads to salt-sensitive hypertension in humans. METHODS: Salt sensitivity was assessed in 19 hypertensive subjects using an inpatient salt loading and depletion protocol. Isolevuglandin-adduct accumulation in APCs was analyzed using flow cytometry. Gene expression in APCs was analyzed using cellular indexing of transcriptomes and epitopes by sequencing analysis of blood mononuclear cells. Plasma and urine EETs were measured using liquid chromatography-mass spectrometry. RESULTS: Baseline isolevuglandin+ APCs correlated with higher salt-sensitivity index. Isolevuglandin+ APCs significantly decreased from salt loading to depletion with an increasing salt-sensitivity index. We observed that human APCs express the epithelial sodium channel δ subunit, SGK1 (salt-sensing kinase serum/glucocorticoid kinase 1), and cytochrome P450 2S1. We found a direct correlation between baseline urinary 14,15 EET and salt-sensitivity index, whereas changes in urinary 14,15 EET negatively correlated with isolevuglandin+ monocytes from salt loading to depletion. Coincubation with 14,15 EET inhibited high-salt-induced increase in isolevuglandin+ APC. CONCLUSIONS: Isolevuglandin formation in APCs responds to acute changes in salt intake in salt-sensitive but not salt-resistant people with hypertension, and this may be regulated by renal 14,15 EET. Baseline levels of isolevuglandin+ APCs or urinary 14,15 EET may provide diagnostic tools for salt sensitivity without a protocol of salt loading.


Assuntos
Hipertensão , Lipídeos , Cloreto de Sódio na Dieta , Humanos , Cloreto de Sódio na Dieta/metabolismo , Canais Epiteliais de Sódio/metabolismo , Cloreto de Sódio/metabolismo , Eicosanoides , Pressão Sanguínea/fisiologia
5.
Nutr Metab Cardiovasc Dis ; 33(7): 1398-1406, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37156670

RESUMO

BACKGROUND AND AIMS: High sodium intake is associated with obesity and insulin resistance, and high extracellular sodium content may induce systemic inflammation, leading to cardiovascular disease. In this study, we aim to investigate whether high tissue sodium accumulation relates with obesity-related insulin resistance and whether the pro-inflammatory effects of excess tissue sodium accumulation may contribute to such association. METHODS AND RESULTS: In a cross-sectional study of 30 obese and 53 non-obese subjects, we measured insulin sensitivity determined as glucose disposal rate (GDR) using hyperinsulinemic euglycemic clamp, and tissue sodium content using 23Na magnetic resonance imaging. Median age was 48 years, 68% were female and 41% were African American. Median (interquartile range) BMI was 33 (31.5, 36.3) and 25 (23.5, 27.2) kg/m2 in the obese and non-obese individuals, respectively. In obese individuals, insulin sensitivity negatively correlated with muscle (r = -0.45, p = 0.01) and skin sodium (r = -0.46, p = 0.01). In interaction analysis among obese individuals, tissue sodium had a greater effect on insulin sensitivity at higher levels of high-sensitivity C-reactive protein (p-interaction = 0.03 and 0.01 for muscle and skin Na+, respectively) and interleukin-6 (p-interaction = 0.024 and 0.003 for muscle and skin Na+, respectively). In interaction analysis of the entire cohort, the association between muscle sodium and insulin sensitivity was stronger with increasing levels of serum leptin (p-interaction = 0.01). CONCLUSIONS: Higher muscle and skin sodium are associated with insulin resistance in obese patients. Whether high tissue sodium accumulation has a mechanistic role in the development of obesity-related insulin resistance through systemic inflammation and leptin dysregulation remains to be examined in future studies. CLINICALTRIALS: gov registration: NCT02236520.


Assuntos
Resistência à Insulina , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Leptina , Glicemia/metabolismo , Insulina , Estudos Transversais , Obesidade , Inflamação/diagnóstico , Sódio
6.
Circ Res ; 131(4): 328-344, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35862128

RESUMO

BACKGROUND: Salt sensitivity of blood pressure is an independent predictor of cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure and cardiovascular risk is unknown. We previously found that sodium entry into antigen-presenting cells (APCs) via the amiloride-sensitive epithelial sodium channel EnaC (epithelial sodium channel) leads to the formation of IsoLGs (isolevuglandins) and release of proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension. In the current study, we hypothesized that ENaC-dependent entry of sodium into APCs activates the NLRP3 (NOD [nucleotide-binding and oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome via IsoLG formation leading to salt-sensitive hypertension. METHODS: We performed RNA sequencing on human monocytes treated with elevated sodium in vitro and Cellular Indexing of Transcriptomes and Epitopes by Sequencing analysis of peripheral blood mononuclear cells from participants rigorously phenotyped for salt sensitivity of blood pressure using an established inpatient protocol. To determine mechanisms, we analyzed inflammasome activation in mouse models of deoxycorticosterone acetate salt-induced hypertension as well as salt-sensitive mice with ENaC inhibition or expression, IsoLG scavenging, and adoptive transfer of wild-type dendritic cells into NLRP3 deficient mice. RESULTS: We found that high levels of salt exposure upregulates the NLRP3 inflammasome, pyroptotic and apoptotic caspases, and IL (interleukin)-1ß transcription in human monocytes. Cellular Indexing of Transcriptomes and Epitopes by Sequencing revealed that components of the NLRP3 inflammasome and activation marker IL-1ß dynamically vary with changes in salt loading/depletion. Mechanistically, we found that sodium-induced activation of the NLRP3 inflammasome is ENaC and IsoLG dependent. NLRP3 deficient mice develop a blunted hypertensive response to elevated sodium, and this is restored by the adoptive transfer of NLRP3 replete APCs. CONCLUSIONS: These findings reveal a mechanistic link between ENaC, inflammation, and salt-sensitive hypertension involving NLRP3 inflammasome activation in APCs. APC activation via the NLRP3 inflammasome can serve as a potential diagnostic biomarker for salt sensitivity of blood pressure.


Assuntos
Hipertensão , Inflamassomos , Animais , Canais Epiteliais de Sódio/genética , Epitopos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/genética , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sódio/metabolismo , Cloreto de Sódio/metabolismo , Cloreto de Sódio na Dieta/efeitos adversos
7.
J Am Heart Assoc ; 11(8): e022723, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35435017

RESUMO

Background Sodium (Na+) stored in skin and muscle tissue is associated with essential hypertension. Sodium magnetic resonance imaging is a validated method of quantifying tissue stores of Na+. In this study, we evaluated tissue Na+ in patients with elevated blood pressure or stage I hypertension in response to diuretic therapy or low Na+ diet. Methods and Results In a double-blinded, placebo-controlled trial, patients with systolic blood pressure 120 to 139 mm Hg were randomized to low sodium diet (<2 g of sodium), chlorthalidone, spironolactone, or placebo for 8 weeks. Muscle and skin Na+ using sodium magnetic resonance imaging and pulse wave velocity were assessed at the beginning and end of the study. Ninety-eight patients were enrolled to undergo baseline measurements and 54 completed randomization. Median baseline muscle and skin Na+ in 98 patients were 16.4 mmol/L (14.9, 18.9) and 13.1 mmol/L (11.1, 16.1), respectively. After 8 weeks, muscle Na+ increased in the diet and chlorthalidone arms compared with placebo. Skin sodium was decreased only in the diet arm compared with placebo. These associations remained significant after adjustment for age, sex, body mass index, systolic blood pressure, and urinary sodium. No changes were observed in pulse wave velocity among the different groups when compared with placebo. Conclusions Diuretic therapy for 8 weeks did not decrease muscle or skin sodium or improve pulse wave velocity in patients with elevated blood pressure or stage I hypertension. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02236520.


Assuntos
Hipertensão , Sódio , Pressão Sanguínea , Clortalidona , Diuréticos , Método Duplo-Cego , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Análise de Onda de Pulso
8.
Blood Adv ; 6(7): 1981-1990, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35130338

RESUMO

Cancer survivors are at increased risk of type 2 diabetes, which usually develops from obesity and insulin resistance. Whether diabetes susceptibility is due to shared risk factors for cancer and insulin resistance or directly related to cancer and its treatment is unknown. We investigated effect modification between malignancy and body mass index (BMI) as determinants of insulin sensitivity in patients with hematologic malignancies and controls without cancer. In a cross-sectional study of 43 individuals without diabetes (20 patients with treated hematologic malignancies; 23 controls without malignancies), we measured insulin-stimulated whole-body glucose use (M) by hyperinsulinemic euglycemic clamp. Insulin sensitivity index (ISI) was calculated by dividing M over steady-state plasma insulin. Inflammatory cytokines were measured in plasma. Controls were more obese and included more non-White individuals and women vs patients with hematologic malignancies. Patients with cancer exhibited greater insulin sensitivity (median ISI, 42.4 mg/kg/min/[µU/mL]; interquartile range [IQR], 33.9-67.2 vs 23.4 mg/kg/min/[µU/mL]; IQR, 12.9-29.2; P < .001) and higher interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) concentrations vs controls. Patients with cancer demonstrated greater reduction in ISI with increasing BMI vs controls, which remained significant after adjustment for sex and race (ß = -2.6 units; 95% confidence interval, -4.8 to -0.4; P interaction = .024). This interaction also remained significant after adjusting for log IL-6 (P interaction = .048) and log MCP-1 (P interaction = .021). Cancer survivors had disproportionately greater insulin resistance with increasing BMI vs controls without malignancies. Effect modification between cancer and BMI in determining insulin sensitivity implicated cancer-specific etiologies in glucose dysregulation and could partially explain excess diabetes diagnoses among oncology patients.


Assuntos
Sobreviventes de Câncer , Diabetes Mellitus Tipo 2 , Neoplasias Hematológicas , Resistência à Insulina , Glicemia , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Glucose , Neoplasias Hematológicas/complicações , Humanos , Insulina , Resistência à Insulina/fisiologia , Interleucina-6 , Masculino , Obesidade
9.
Kidney Int Rep ; 6(11): 2811-2820, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34805633

RESUMO

INTRODUCTION: Insulin resistance and obesity are prevalent in chronic kidney disease (CKD) patients. The interaction of body mass index (BMI) and kidney function across the continuum of estimated glomerular filtration rate (eGFR) is unknown. METHODS: In a cross-sectional study of 139 patients, 52 with CKD stages 3 and 4 and 87 patients with normal eGFR, we measured the insulin sensitivity index (ISI) using the hyperinsulinemic euglycemic clamp and homeostasis model assessment of insulin resistance (HOMA-IR). We investigated the interaction between eGFR and BMI in their association with ISI and HOMA-IR using linear models with robust standard errors. RESULTS: Median age was 56 (42, 66) years, 50.4% were female, and 36% were African American. Patients with low eGFR (∼30 ml/min per 1.73 m2) had low ISI (2.3 mg/min per µU/ml) regardless of BMI. Among patients with preserved eGFR (>90 ml/min per 1.73m2), BMI had a greater effect on ISI (6.3 mg/min per µU/ml at a BMI of 20 kg/m2 vs. 4.6 mg/min per µU/ml at a BMI of 30 kg/m2) (P for interaction = 0.046). In models adjusted for demographics, and log transformed interleukin-6, high-sensitivity C-reactive protein, leptin, and adiponectin, a 1-SD (28 ml/min per 1.73 m2) lower eGFR was associated with a statistically significant 1.14-unit decrease in ISI (95% confidence interval = -1.80, -0.48) among nonobese patients. Among obese patients, the effect estimate was -0.25 (95% confidence interval = -0.88, 0.39). The association between BMI and HOMA-IR was stronger in patients with lower eGFR (P for interaction = 0.005). CONCLUSION: Both eGFR and BMI are independently associated with insulin sensitivity, but the strength of the association between BMI and insulin sensitivity varies significantly across eGFR.

10.
Pak J Pharm Sci ; 34(3): 1011-1017, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602426

RESUMO

In this study, antibacterial, antifungal, antihyaluronidase, anticollagenase and antielastase activity of Hypericum bithynicum, Malva neglecta, Morus alba, Rubus discolor, Sambucus ebulus and Smilax excelsa were investigated. Methanol extracts of M. neglecta and R. discolor and all extracts of H. bithynicum were more active against Staphylococcus epidermidis. Similarly, water extracts of M. alba and S. ebulus were more active against Streptococcus pneumonia. Additionally, S. ebulus and S. excelsa had prominent antifungal activity on Candida albicans. Besides, methanol extract of M. neglecta and n-hexane extract of H. bithynicum were determined to have significant antihyaluronidase activity. Only R. discolor showed significant antielastase effect.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Colagenases , Escherichia coli/efeitos dos fármacos , Hialuronoglucosaminidase/antagonistas & inibidores , Hypericum , Klebsiella pneumoniae/efeitos dos fármacos , Malva , Inibidores de Metaloproteinases de Matriz/farmacologia , Morus , Elastase Pancreática/antagonistas & inibidores , Pseudomonas aeruginosa/efeitos dos fármacos , Rubus , Sambucus , Smilax , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Turquia
11.
Antioxid Redox Signal ; 35(18): 1477-1493, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34569287

RESUMO

Significance: Salt sensitivity of blood pressure (SSBP) is an independent risk factor for mortality and morbidity due to cardiovascular disease, and disproportionately affects blacks and women. Several mechanisms have been proposed, including exaggerated activation of sodium transporters in the kidney leading to salt retention and water. Recent Advances: Recent studies have found that in addition to the renal epithelium, myeloid immune cells can sense sodium via the epithelial Na+ channel (ENaC), which leads to activation of the nicotinamide adenine dinucleotide phosphate oxidase enzyme complex, increased fatty acid oxidation, and production of isolevuglandins (IsoLGs). IsoLGs are immunogenic and contribute to salt-induced hypertension. In addition, aldosterone-mediated activation of ENaC has been attributed to the increased SSBP in women. The goal of this review is to highlight mechanisms contributing to SSBP in blacks and women, including, but not limited to increased activation of ENaC, fatty acid oxidation, and inflammation. Critical Issues: A critical barrier to progress in management of SSBP is that its diagnosis is not feasible in the clinic and is limited to expensive and laborious research protocols, which makes it difficult to investigate. Yet without understanding the underlying mechanisms, this important risk factor remains without treatment. Future Directions: Further studies are needed to understand the mechanisms that contribute to differential blood pressure responses to dietary salt and find feasible diagnostic tools. This is extremely important and may go a long way in mitigating the racial and sex disparities in cardiovascular outcomes. Antioxid. Redox Signal. 35, 1477-1493.


Assuntos
Hipertensão , Cloreto de Sódio na Dieta , Negro ou Afro-Americano , Pressão Sanguínea , Feminino , Humanos , Hipertensão/etiologia , Inflamação/complicações , Estresse Oxidativo , Sódio
12.
Artigo em Inglês | MEDLINE | ID: mdl-33351140

RESUMO

BACKGROUND: Tissue sodium content in patients on maintenance hemodialysis (MHD) and peritoneal dialysis (PD) were previously explored using 23Sodium magnetic resonance imaging (23NaMRI). Larger studies would provide a better understanding of sodium stores in patients on dialysis as well as the factors influencing this sodium accumulation. METHODS: In this cross-sectional study, we quantified the calf muscle and skin sodium content in 162 subjects (10 PD, 33 MHD patients, and 119 controls) using 23NaMRI. Plasma levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured to assess systemic inflammation. Sixty-four subjects had repeat 23NaMRI scans that were analyzed to assess the repeatability of the 23NaMRI measurements. RESULTS: Patients on MHD and PD exhibited significantly higher muscle and skin sodium accumulation compared to controls. African American patients on dialysis exhibited greater muscle and skin sodium content compared to non-African Americans. Multivariable analysis showed that older age was associated with both higher muscle and skin sodium. Male sex was also associated with increased skin sodium deposition. Greater ultrafiltration was associated with lower skin sodium in patients on PD (Spearman's rho=-0.68, P = 0.035). Higher plasma IL-6 and hsCRP levels correlated with increased muscle and skin sodium content in the overall study population. Patients with higher baseline tissue sodium content exhibited greater variability in tissue sodium stores on repeat measurements. CONCLUSIONS: Our findings highlight greater muscle and skin sodium content in dialysis patients compared to controls without kidney disease. Tissue sodium deposition and systemic inflammation seen in dialysis patients might influence one another bidirectionally.

13.
Curr Hypertens Rep ; 22(10): 79, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880753

RESUMO

PURPOSE OF REVIEW: Salt sensitivity of blood pressure (SSBP) is an independent predictor of death due to cardiovascular events and affects nearly 50% of the hypertensive and 25% of the normotensive population. Strong evidence indicates that reducing sodium (Na+) intake decreases blood pressure (BP) and cardiovascular events. The precise mechanisms of how dietary Na+ contributes to elevation and cardiovascular disease remain unclear. The goal of this review is to discuss mechanisms of salt-induced cardiovascular disease and how the microbiome may play a role. RECENT FINDINGS: The innate and adaptive immune systems are involved in the genesis of salt-induced hypertension. Mice fed a high-salt diet exhibit increased inflammation with a marked increase in dendritic cell (DC) production of interleukin (IL)-6 and formation of isolevuglandins (IsoLG)-protein adducts, which drive interferon-gamma (IFN-γ) and IL-17A production by T cells. While prior studies have mainly focused on the brain, kidney, and vasculature as playing a role in salt-induced hypertension, the gut is the first and largest location for Na+ absorption. Research from our group and others strongly suggests that the gut microbiome contributes to salt-induced inflammation and hypertension. Recent studies suggest that alterations in the gut microbiome contribute to salt-induced hypertension. However, the contribution of the microbiome to SSBP and its underlying mechanisms are not known. Targeting the microbiota and the associated immune cell activation could conceivably provide the much-needed therapy for SSBP.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Animais , Pressão Sanguínea , Humanos , Hipertensão/etiologia , Inflamação , Camundongos , Cloreto de Sódio na Dieta/efeitos adversos
15.
Pak J Pharm Sci ; 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30473520

RESUMO

In this study, antibacterial, antifungal, antihyaluronidase, anticollagenase and antielastase activity of Hypericum bithynicum, Malva neglecta, Morus alba, Rubus discolor, Sambucus ebulus and Smilax excelsa were investigated. Methanol extracts of M. neglecta and R. discolor and all extracts of H. bithynicum were more active against Staphylococcus epidermidis. Similarly, water extracts of M. alba and S. ebulus were more active against Streptococcus pneumonia. Additionally, S. ebulus and S. excelsa had prominent antifungal activity on Candida albicans. Besides, methanol extract of M. neglecta and n-hexane extract of H. bithynicum were determined to have significant anti-hyaluronidase activity. Only R. discolor showed significant anti-elastase effect.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29610677

RESUMO

BACKGROUND: Juvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome. CASE PRESENTATION: A previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation. CONCLUSIONS: This is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.

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