Renal denervation represents an emerging treatment for resistant hypertension in patients with end-stage renal disease, but data about the anatomic substrate of this treatment are lacking. Therefore, ...the aim of this study was to investigate the morphological basis of sympathetic hyperactivity in the setting of hemodialysis patients to identify an anatomical substrate that could warrant the use of this new therapeutic approach.
The distribution of sympathetic nerves was evaluated in the adventitia of 38 renal arteries that were collected at autopsy or during surgery from 25 patients: 9 with end-stage renal disease on dialysis (DIAL group) and 16 age-matched control nondialysis patients (CTRL group). Patients in the DIAL group showed a significant increase in nerve density in the internal area of the peri-adventitial tissue (within the first 0.5 mm of the beginning of the adventitia) compared with the CTRL group (4.01±0.30 versus 2.87±0.28×mm(2), P=0.01). Regardless of dialysis, hypertensive patients with signs of severe arteriolar damage had a greater number of nerve endings in the most internal adventitia, and this number was significantly higher than in patients without hypertensive arteriolar damage (3.90±0.36 versus 2.87±0.41×mm(2), P=0.04), showing a correlation with hypertensive arteriolar damage rather than with hypertensive clinical history.
The findings from this study provide a morphological basis underlying sympathetic hyperactivity in patients with end-stage renal disease and might offer useful information to improve the use of renal denervation in this group of patients.
Osteopontin, an extracellular matrix protein involved in bone remodeling, tissue repair and inflammation, has previously been associated with increased inflammation and neurodegeneration in multiple ...sclerosis (MS), promoting a worse disease course. Osteopontin is also likely involved in acute MS relapses.
In 47 patients with relapsing-remitting MS, we explored the correlation between the time elapsed between the last clinical relapse and lumbar puncture, and the cerebrospinal fluid (CSF) levels of osteopontin and a group of inflammatory cytokines and adipokines such as resistin, plasminogen activator inhibitor-1, osteoprotegerin, interleukin (IL)-1β, IL-2, IL-6 and IL-1 receptor antagonist (IL-1ra). We also analyzed the correlations between CSF levels of osteopontin and the other CSF molecules considered.
Osteopontin CSF concentrations were higher in patients with a shorter time interval between the last clinical relapse and CSF withdrawal. In addition, CSF levels of osteopontin were positively correlated with the proinflammatory cytokines IL-2 and IL-6 and negatively correlated with the anti-inflammatory molecule IL-1ra.
Our results further suggest the role of osteopontin in acute MS relapses showing that, in proximity to relapses, osteopontin expression in CSF may be increased along with other proinflammatory mediators and correlated with decreased concentrations of anti-inflammatory molecules.
Erythrocyte glutathione transferase (e-GST) displays increased activity in patients with renal damage and positive correlation with homocysteine (Hcy) in patients under maintenance hemodialysis. ...Here, we determined e-GST, Hcy, and erythrocyte catalase (e-CAT) in 328 patients affected by type 2 diabetes mellitus (T2DM), 61 diabetic non-nephropathic patients and 267 affected by diabetes and by chronic kidney disease (CKD) under conservative therapy subdivided into four stages according to K-DOQI lines. e-GST activity was significantly higher in all T2DM patients compared to the control group (7.90 ± 0.26 vs. 5.6 ± 0.4 U/g
Hb
), and we observed an enhanced activity in all subgroups of CKD diabetic patients. No significant correlation or increase has been found for e-CAT in all patients tested. Mean Hcy in diabetic patients is higher than that in healthy subjects (33.42 ± 1.23 vs. 13.6 ± 0.8 μM), and Hcy increases in relation to the CKD stage. As expected, a significant correlation was found between e-GST and Hcy levels. These findings suggest that e-GST hyperactivity is not caused directly by diabetes but by its consequent renal damage. e-GST, as well as Hcy, may represent an early biomarker of renal failure.
Metabolic diseases are chronic disorders correlated to a greater risk of cardiovascular event and death. Recently, many data have sustained the biological link between microvascular dysfunction, ...oxidative stress, vascular inflammation, and metabolic diseases. The determination of new and specific blood biomarkers of vascular inflammation associated with obesity-related metabolic syndrome (MetS) and diabetes such as lipoprotein-associated phospholipase A2 (Lp-PLA2) could be useful to identify subject with high risk of cardiovascular events. Lp-PLA2 participates by a crucial role in microvascular dysfunction and oxidative stress showing positive association with metabolic disorders. In this review, we will argue the evolving role of Lp-PLA2 in predicting cardiovascular events in metabolic disease patients.
OBJECTIVE:--Obesity is associated with chronic inflammation due to overproduction of proinflammatory cytokines, including tumor necrosis factor (TNF)-α. We assessed the effects of TNF-α ...neutralization by infliximab on vascular reactivity during hyperinsulinemia in obesity-related metabolic syndrome. RESEARCH DESIGN AND METHODS--Vascular responses to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in patients with metabolic syndrome, before and after administration of infliximab. RESULTS:--Patients had blunted vasodilator responses to ACh and SNP during hyperinsulinemia compared with control subjects; a potentiation of the responsiveness to both ACh and SNP, however, was observed in patients following infliximab. The antioxidant vitamin C improved the vasodilator response to ACh in patients with metabolic syndrome, but its effect was not further enhanced by concurrent administration of infliximab. CONCLUSIONS:--TNF-α neutralization ameliorates vascular reactivity in metabolic syndrome during hyperinsulinemia, likely in relation to decreased oxidative stress, thereby suggesting an involvement of inflammatory cytokines in vascular dysfunction of these patients.
Adrenocortical oncocytomas are rare and mostly nonfunctioning neoplasms. We report the case of a 27-year-old woman diagnosed with an ACTH-independent Cushing’s syndrome due to left adrenal ...oncocytoma. She underwent laparoscopic adrenalectomy. Histopathological examination revealed an oncocytoma of uncertain malignant potential with a low Ki-67 proliferation index, inhibin A positivity, and chromogranin A negativity. Electron micrographs confirmed adrenal oncocytoma cells, characterized by the presence of a large amount of mitochondria. The postoperative course was uneventful, and the patient experienced a progressive regression of Cushing-related symptoms. Periodical follow-ups with MRI and cortisol dosage are required due to the neoplasm’s uncertain malignant potential. Considerations on the diagnosis, pathology findings, clinical remarks, and interventions are made.
Background
CV risk exponentially increases as the number of damaged organs increases The Systemic Hemodynamic Atherosclerotic Syndrome (SHATS) represents a novel conceptualization of the CV continuum ...focusing on simultaneous multi-organ alteration. This is the first study operationally defining SHATS and aimed at identifying its determinants.
Methods
Left Ventricular Hypertrophy (echocardiography), Common Carotid Artery plaque and increased thickness (ultrasound), and Chronic Kidney Disease (estimated Glomerular Filtration Rate) indexed selective target organ damage. SHATS was operationally defined as their simultaneous presence in a patient. PWV was measured by Sphygmocor® and BP variability by 24 h ABPM.
Results
SHATS affected 19.9% of the 367 studied subjects. Subjects with SHATS had a similar prevalence in diabetes mellitus, but a greater prevalence of very stiff artery (84.9 vs 64.3 %, p < 0.01) and use of antihypertensive medications. In the presence of similar office BP, SHATS was associated with higher 24 h SBP and lower 24 h DBP (a greater pulsatile pressure!), reduced nighttime SBP fall, and a twofold greater prevalence of reverse dipper status (48.2 vs 20.2 %, p < 0.001). BMI (positive correlation) and DBP (negative correlation) were the only traditional CV risk factors significantly associated with the odds of having SHATS. Very stiff artery and BP variability were significant independent determinants of SHATS, with highly predictive accuracy.
Conclusion
SHATS, the simultaneous damage of multiple target organs, may easily operationally defined. Very stiff artery and BP variability represent key factors for SHATS. The present results support the hypothesis of SHATS as a systemic condition, needing further characterization.
Brown tumour represents a serious complication of hyperparathyroidism. Differential diagnosis, based on histological examination, is only presumptive and clinical, radiological and laboratory data ...are necessary for definitive diagnosis. Here we describe a case of a brown tumour localised in the maxilla due to secondary hyperparathyroidism in a young women with chronic renal failure. Hemodialysis and pharmacological treatment were unsuccessful in controlling secondary hyperparathyroidism making it necessary to proceed with a subtotal parathyroidectomy. The proper timing of the parathyroidectomy and its favourable effect on regression of the brown tumor made it possible to avoid a potentially disfiguring surgical removal of the brown tumor.
Obesity represents one of the most complex public health challenges and has recently reached epidemic proportions. Obesity is also considered to be primarily responsible for the rising prevalence of ...metabolic syndrome, defined as the coexistence in the same individual of several risk factors for atherosclerosis, including dyslipidemia, hypertension and hyperglycemia, as well as for cancer. Additionally, the presence of three of the five risk factors (abdominal obesity, low high-density lipoprotein cholesterol, high triglycerides, high fasting glucose and high blood pressure) characterizes metabolic syndrome, which has serious clinical consequences. The current study was conducted in order to identify metabolic differences in visceral adipose tissue (VAT) collected from obese (body mass index 43-48) human subjects who were diagnosed with metabolic syndrome, obese individuals who were metabolically healthy and nonobese healthy controls. Extensive gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS/MS) analyses were used to obtain the untargeted VAT metabolomic profiles of 481 metabolites belonging to all biochemical pathways. Our results indicated consistent increases in oxidative stress markers from the pathologically obese samples in addition to subtle markers of elevated glucose levels that may be consistent with metabolic syndrome. In the tissue derived from the pathologically obese subjects, there were significantly elevated levels of plasmalogens, which may be increased in response to oxidative changes in addition to changes in glycerolphosphorylcholine, glycerolphosphorylethanolamine glycerolphosphorylserine, ceramides and sphingolipids. These data could be potentially helpful for recognizing new pathways that underlie the metabolic-vascular complications of obesity and may lead to the development of innovative targeted therapies.
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