Immunohistochemistry of aldosterone synthase leads the way to the pathogenesis of primary aldosteronism.

Our group previously purified human and rat aldosterone synthase (CYP11B2 and Cyp11b2, respectively) from their adrenals and verified that it is distinct from steroid 11β-hydroxylase (CYP11B1 or Cyp11b1), the cortisol- or corticosterone-synthesizing enzyme. We now describe their distributions immunohistochemically with specific antibodies. In rats, there is layered functional zonation with the Cyp11b2-positive zona glomerulosa (ZG), Cyp11b1-positive zona fasciculata (ZF), and Cyp11b2/Cyp11b1-negative undifferentiated zone between the ZG and ZF.

Somatic KCNJ5 mutation occurring early in adrenal development may cause a novel form of juvenile primary aldosteronism.

We report a case of non-familial juvenile primary aldosteronism (PA). Super-selective adrenal venous sampling identified less aldosterone production in the right inferior adrenal segment than others. Bilateral adrenalectomy sparing the segment normalized blood pressure and improved PA.

Disorganized Steroidogenesis in Adrenocortical Carcinoma, a Case Study.

Most adrenocortical carcinomas (ACCs) produce excessive amounts of steroid hormones including aldosterone, cortisol, and steroid precursors. However, aldosterone- and cortisol-producing cells in ACCs have not yet been immunohistochemically described. We present a case of ACC causing mild primary aldosteronism and subclinical Cushing's syndrome.

Pre-Implementation Review of Contracts, Prompts, and Reinforcement in SUD Continuing Care.

The Contracts, Prompts, and Reinforcement (CPR) intervention has demonstrated an ability to increase the duration of continuing care participation following substance use disorder (SUD) treatment, resulting in improved treatment outcome. The current project was a qualitative pre-implementation study aimed at identifying barriers and facilitators to implementation of CPR using an evidence-based quality improvement (EBQI) approach. Formative evaluations were conducted with staff from residential SUD treatment programs across three VA sites, and key informant interviews were completed with opinion and program leaders.

Spirituality, Religiosity, and Weight Management Among African American Adolescent Males: The Jackson Heart KIDS Pilot Study.

Spirituality and religion have been identified as important determinants of health for adults; however, the impact of faith-oriented factors on health behaviors and outcomes among African American adolescent males has not been well studied. The purpose of this study is to examine the relationship between religiosity and spirituality and obesity-related behaviors among 12-19 year old African American males (N = 105) in the Jackson Heart KIDS Pilot Study. Key variables of interest are church attendance, prayer, daily spirituality, weight status, attempts to lose weight, nutrition, physical activity, and stress.

Temporal and spatial distribution of mast cells and steroidogenic enzymes in the human fetal adrenal.

Mast cells are present in the human adult adrenal with a potential role in the regulation of aldosterone secretion in both normal cortex and adrenocortical adenomas. We have investigated the human developing adrenal gland for the presence of mast cells in parallel with steroidogenic enzymes profile and serotonin signaling pathway. RT-QPCR and immunohistochemical studies were performed on adrenals at 16-41 weeks of gestation (WG).

Examination of the Relationship Between PTSD and Distress Tolerance in a Sample of Male Veterans With Comorbid Substance Use Disorders.

Distress tolerance (DT), the perceived or actual ability to tolerate negative emotional or physical states, is inversely related to posttraumatic stress disorder (PTSD) symptoms in civilian, community samples. No studies to date have examined the relationship between DT and PTSD in clinical samples of veterans with a comorbid diagnosis of PTSD and a substance use disorder (SUD). Thus, the present study examined the relationship between DT and PTSD in a sample of predominately African American, male veterans ( = 75) diagnosed with comorbid PTSD and SUD (according to a structured clinical interview).

Activating mutations in CTNNB1 in aldosterone producing adenomas.

Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5-10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs.

Condom Breakage Among Young Black Men Who Have Sex With Men: An In-Depth Investigation Including Men Living With HIV/AIDS.

Correlates of condom breakage (reported by 19% of 398 young black who have sex with men) for anal insertive sex included the following: condoms drying out (P = 0.018), erection loss during application (P = 0.03), and using erection-enhancing drugs (P = 0.

Development of a novel cell based androgen screening model.

The androgen receptor (AR) mediates the majority of androgen effects on target cells. The DNA cis-regulatory elements that respond to AR share sequence similarity with cis-regulatory elements for glucocorticoid, mineralocorticoid and progesterone receptors (GR, MR and PR, respectively). As a result, many of the current AR screening models are complicated by inaccurate activation of reporters by one of these receptor pathways.

Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis.

Background: In obesity, the excessive synthesis of aldosterone contributes to the development and progression of metabolic and cardiovascular dysfunctions. Obesity-induced hyperaldosteronism is independent of the known regulators of aldosterone secretion, but reliant on unidentified adipocyte-derived factors. We hypothesized that the adipokine leptin is a direct regulator of aldosterone synthase (CYP11B2) expression and aldosterone release and promotes cardiovascular dysfunction via aldosterone-dependent mechanisms.

Different Somatic Mutations in Multinodular Adrenals With Aldosterone-Producing Adenoma.

Primary aldosteronism is the most common form of secondary hypertension. Somatic mutations in KCNJ5, ATP1A1, ATP2B3, and CACNA1D are found in aldosterone-producing adenoma. In addition, adrenals with aldosterone-producing adenomas show cortical remodeling and frequently multiple secondary nodules.

Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands.

Primary aldosteronism (PA) represents the most common cause of secondary hypertension, but little is known regarding its adrenal cellular origins. Recently, aldosterone-producing cell clusters (APCCs) with high expression of aldosterone synthase (CYP11B2) were found in both normal and PA adrenal tissue. PA-causing aldosterone-producing adenomas (APAs) harbor mutations in genes encoding ion channels/pumps that alter intracellular calcium homeostasis and cause renin-independent aldosterone production through increased CYP11B2 expression.

Role of Nongenomic Signaling Pathways Activated by Aldosterone During Cardiac Reperfusion Injury.

Aldosterone (Aldo) activates both genomic and nongenomic signaling pathways in the cardiovascular system. Activation of genomic signaling pathways contributes to the adverse cardiac actions of Aldo during reperfusion injury; however, the extent nongenomic signaling pathways contribute has been difficult to identify due to lack of a specific ligand that activates only nongenomic signaling pathways. Using a pegylated aldosterone analog, aldosterone-3-carboxymethoxylamine-TFP ester conjugated to methoxypegylated amine (Aldo-PEG), we are able for the first time to distinguish between nongenomic and genomic cardiac actions of Aldo.

Immunohistochemical, genetic and clinical characterization of sporadic aldosterone-producing adenomas.

Adrenal glands removed for unilateral primary aldosteronism (PA) display marked histological heterogeneity. Recently reported somatic mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D can partially account for these differences. In this study we aimed at combining phenotypic and genotypic characteristics, integrating genetic and immunohistochemistry correlates in sporadic PA.

Weight Loss, the Obesity Paradox, and the Risk of Death in Rheumatoid Arthritis.

Objective: In contrast to what is observed in the general population, a low body mass index (BMI) has been associated with accelerated mortality in patients with rheumatoid arthritis (RA). The aim of this study was to assess whether weight loss might explain these seemingly paradoxical observations.

Methods: Our study included patients identified from the Veterans Affairs (VA) RA Registry.

Association of hospitalization with long-term cognitive and brain MRI changes in the ARIC cohort.

Objective: To determine whether hospitalization is associated with subsequent cognitive decline or changes on brain MRI in a community-based cohort.

Methods: Baseline and follow-up cognitive testing (n = 2,386) and MRI scans with standardized assessments (n = 885) were available from a subset of white and black participants in the Atherosclerosis Risk in Communities study. Cognitive tests included the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT).

Adrenal vein sampling in primary aldosteronism: towards a standardised protocol.

Primary aldosteronism comprises subtypes that need different therapeutic strategies. Adrenal vein sampling is recognised by Endocrine Society guidelines as the only reliable way to correctly diagnose the subtype of primary aldosteronism. Unfortunately, despite being the gold-standard procedure, no standardised procedure exists either in terms of performance or interpretation criteria.

Quality of life and outcomes in African Americans with CKD.

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies.

Autoimmune mechanisms activating the angiotensin AT1 receptor in 'primary' aldosteronism.

Context: The mechanisms causing excessive aldosterone production and hypertension in primary aldosteronism (PA) are complex and often incompletely recognized. Autoantibodies to the angiotensin AT1 receptor (AT1R) have been reported in some PA patients with an aldosterone-producing adenoma but not with idiopathic adrenal hyperplasia.

Objective: We investigated whether these autoantibodies will activate AT1R and thereby potentially contribute to the pathophysiology of PA.