Skin lesions and vancomycin use in a hemodialysis patient.

Vancomycin is a widely used antibiotic in hemodialysis patients. The main complications include renal toxicity and skin lesions. Herein, we report the case of a 29-year-old hemodialysis patient who presented a bullous pruriginous dermatosis after vancomycin treatment. A skin biopsy revealed a linear IgA bullous dermatosis (LABD). This is a rare form of dermatosis and is either idiopathic or more likely vancomycin-induced. Similarities in the molecular structure of vancomycin and epidermal basement membrane glycoproteins could explain the auto-immune response. The overall prognosis after drug discontinuation and dermocorticoid treatment was good.

The measured glomerular filtration rate (mGFR) before and 6 months after bariatric surgery: A pilot study.

INTRODUCTION: Over the last few decades, the prevalence of obesity has increased dramatically. This increase has been mirrored by a rise in the risk of a number of health conditions, including hypertension, diabetes and chronic kidney disease. Although the weight loss following bariatric surgery has been shown to relieve the severity of diabetes and reduce hypertension, the effect on renal function has been less extensively evaluated. OBJECTIVE: The aims of the present study were to: (i) compare the estimated glomerular filtration rate (eGFR, using the MDRD and CKD-EPI equations) and the calculated glomerular filtration rate (using the 24-hour urine volume) with the measured glomerular filtration rate (mGFR) assessed with the plasma iohexol clearance method in severely obese patients, and (ii) evaluate the effect of weight loss on the mGFR 6 months after bariatric surgery. METHODS: Before and six months after bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy), eligible patients for bariatric surgery were admitted as day cases to the nephrology unit, where they underwent a plasma iohexol clearance test. The GFR was also estimated using the MDRD and CKDEPI equations and the 24-hour urine method. Changes in eGFR and mGFR were compared using a Wilcoxon test for paired data. RESULTS: Data from 16 patients with severe obesity (mean ± standard deviation of Body Mass Index [BMI]: 43.9 ± 7.3 kg/m2) were analyzed. At baseline, 12 (75%) presented with hypertension and 10 (63%) presented with diabetes. The median [range] iohexol clearance rate was 109 [57-194] mL/min. The plasma iohexol clearance test evidenced hyperfiltration (mGFR>120 mL/min) in 7 patients. In contrast, the eGFR values generated by the MDRD equation, the CKDEPI equation and the GFR MFR calculated with the 24-hour urine method only identified hyperfiltration in 1, 0 and 5 patients, respectively. Six months after surgery, the mean BMI had fallen significantly (P<0.0012), and the severity of diabetes (according to the HbA1c level) had decreased significantly from 6.6 [6.0-9.8] % to 5.7 [5.2-8.6] % (P=0.025). The iohexol clearance rate increased slightly after bariatric surgery. Changes in BMI after surgery do not seem to be correlated with the changes in iohexol clearance. In patients displaying hyperfiltration at baseline, the mGFR fell significantly (n=7; P=0.01) and returned to near normal values. No significant changes in the eGFR were observed. CONCLUSION: Our results suggest that MDRD and CKD-EPI equations do not provide accurate estimates of the true GFR in severely obese patients (particularly in those with hyperfiltration). Iohexol clearance or other methods for determining mGFR should constitute the gold standard for the accurate evaluation of renal function in this context. Renal function (as evaluated by the mGFR) improved 6 months after bariatric surgery in severely obese individuals particularly in patients displaying hyperfiltration at baseline. However, these observations must be confirmed in a larger study with a longer follow-up period.

Relationship of brown adipose tissue perfusion and function: a study through ß2-adrenoreceptor stimulation.

Brown adipose tissue (BAT) activation increases glucose and lipid consumption; as such, it is been considered as a potential therapy to decrease obesity. BAT is highly vascularized and its activation is associated with a necessary increase in blood flow. However, whether increasing BAT blood flow per se increases BAT activity is unknown. To examine this hypothesis, we investigated whether an isolated increase in BAT blood flow obtained by ß2-adrenoreceptor (ß2-AR) stimulation with salbutamol increased BAT activity. BAT blood flow was estimated in vivo in mice using contrast-enhanced ultrasound. The absence of direct effect of salbutamol on the function of isolated brown adipocytes was assessed by measuring oxygen consumption. The effect of salbutamol on BAT activity was investigated by measuring BAT glucose uptake in vivo. BAT blood flow increased by 2.3 ± 0.6-fold during ß2-AR stimulation using salbutamol infusion in mice (P= 0.003). ß2-AR gene expression was detectable in BAT but was extremely low in isolated brown adipocytes. Oxygen consumption of isolated brown adipocytes did not change with salbutamol exposure, confirming the absence of a direct effect of ß2-AR agonist on brown adipocytes. Finally, ß2-AR stimulation by salbutamol increased BAT glucose uptake in vivo (991 ± 358 vs. 135 ± 49 ng glucose/mg tissue/45 min in salbutamol vs. saline injected mice, respectively,P= 0.046). In conclusion, an increase in BAT blood flow without direct stimulation of the brown adipocytes is associated with increased BAT metabolic activity. Increasing BAT blood flow might represent a new therapeutic target in obesity.

Brown adipose tissue blood flow and mass in obesity: a contrast ultrasound study in mice.

BACKGROUND: When activated by the sympathetic nervous system, brown adipose tissue (BAT) increases energy expenditure to produce heat. Augmenting BAT mass or increasing BAT activation could potentially be used to decrease obesity. Noninvasive methods to detect and monitor BAT mass are needed. Contrast ultrasound can estimate BAT blood flow and is able to measure the perfused volume of an organ and thus its mass. The objective of this study was to evaluate whether contrast ultrasound could characterize BAT mass in two mouse models of obesity: wild-type mice fed a high-fat diet and mutant db/db mice. METHODS: Contrast ultrasound of BAT (Definity 2 µL/min; 14-MHz linear probe) was performed before and after stimulation of BAT with norepinephrine (NE). BAT replenishment curves were obtained, and blood flow was estimated by the product of the curve's plateau and slope. Additionally, consecutive two-dimensional images of perfused BAT were acquired at 1-mm intervals after stimulation with NE and used to assess BAT volume and mass. RESULTS: BAT blood flow increased after NE infusion in all mice studied. Blood flow response to NE was similar in wild-type mice fed either a low-fat diet or a high-fat diet. BAT blood flow was lower in db/db mice than in wild-type mice (P = .02). Contrast ultrasound-derived BAT mass was correlated with BAT mass obtained at necropsy (R(2) = 0.83, P < .001). BAT mass was higher in mice fed a high-fat diet than in those fed a low-fat diet. CONCLUSIONS: Contrast ultrasound can be used to estimate BAT mass in mice when BAT vascularization is not significantly impaired. This noninvasive technique may potentially allow the serial evaluation of therapies designed to augment BAT mass.

Soluble guanylate cyclase α1-deficient mice: a novel murine model for primary open angle glaucoma.

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1-deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and ß1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG.

In vivo noninvasive characterization of brown adipose tissue blood flow by contrast ultrasound in mice.

BACKGROUND: Interventions to increase brown adipose tissue (BAT) volume and activation are being extensively investigated as therapies to decrease the body weight in obese subjects. Noninvasive methods to monitor these therapies in animal models and humans are rare. We investigated whether contrast ultrasound (CU) performed in mice could detect BAT and measure its activation by monitoring BAT blood flow. After validation, CU was used to study the role of uncoupling protein 1 and nitric oxide synthases in the acute regulation of BAT blood flow. METHODS AND RESULTS: Blood flow of interscapular BAT was assessed in mice (n=64) with CU by measuring the signal intensity of continuously infused contrast microbubbles. Blood flow of BAT estimated by CU was 0.5±0.1 (mean±SEM) dB/s at baseline and increased 15-fold during BAT stimulation by norepinephrine (1 µg·kg(-1)·min(-1)). Assessment of BAT blood flow using CU was correlated to that performed with fluorescent microspheres (R(2)=0.86, P<0.001). To evaluate whether intact BAT activation is required to increase BAT blood flow, CU was performed in uncoupling protein 1-deficient mice with impaired BAT activation. Norepinephrine infusion induced a smaller increase in BAT blood flow in uncoupling protein 1-deficient mice than in wild-type mice. Finally, we investigated whether nitric oxide synthases played a role in acute norepinephrine-induced changes of BAT blood flow. Genetic and pharmacologic inhibition of nitric oxide synthase 3 attenuated the norepinephrine-induced increase in BAT blood flow. CONCLUSIONS: These results indicate that CU can detect BAT in mice and estimate BAT blood flow in mice with functional differences in BAT.