l-Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia.

BACKGROUND AND PURPOSE: Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with l-citrulline in Dahl salt-sensitive rats, a model of superimposed preeclampsia. EXPERIMENTAL APPROACH: Parental Dahl salt-sensitive rats were treated with l-citrulline (2.5 g·L-1 in drinking water) from the day of mating to the end of lactation period. Blood pressure was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant Dahl salt-sensitive rats was assessed by wire myograph. KEY RESULTS: In Dahl salt-sensitive rats, l-citrulline supplementation significantly reduced maternal blood pressure, proteinuria and levels of circulating soluble fms-like tyrosine kinase 1. l-Citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium-derived hyperpolarizing factor-mediated vasorelaxation in resistance arteries. l-Citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, l-citrulline down-regulated genes involved in the TLR4 and NF-κB signalling pathways. CONCLUSION AND IMPLICATIONS: This study shows that l-citrulline supplementation reduced gestational hypertension and improved placentation and fetal growth in a rat model of superimposed preeclampsia. l-Citrulline supplementation may provide an effective and safe therapeutic strategy for preeclampsia that benefits both the mother and the fetus.

A Rare Case of Addison's Disease Presenting With Intermittent Pancytopenia and Cardiac Tamponade.

OBJECTIVE: To report the first case, to our knowledge, of intermittent pancytopenia and cardiac tamponade occurring together in association with Autoimmune Addison's Disease (AAD). METHODS: A 21 year-old woman presented on three different occasions with multiple complaints. Her evaluation was significant for intermittent pancytopenia (white blood cell, 1.3-3.0 × 103/µL [normal 4.5-11 × 103]; hemoglobin, 8.8-9.6 g/dL [11-16]; and platelets, 102-117 × 103/µL [150-400 × 103/µL]) and pericardial effusion with cardiac tamponade. Further investigation including a morning serum cortisol level of 0.6 µg/dL (5.27-22.45 µg/dL), adrenocorticotropic hormone level of 1027 pg/mL (normal 6-50 pg/mL), and positive 21-hydroxylase antibodies confirmed the diagnosis of primary adrenal insufficiency due to AAD. Treatment with steroids resulted in prompt hemodynamic recovery with normalization of all blood cell lines. RESULTS: The diagnosis of AAD is often delayed or overlooked. Pancytopenia occurring in AAD is most likely due to either marrow suppression in the setting of acute illness and exacerbated by hypoadrenalism or possibly an autoimmune-mediated marrow reaction. Pericarditis with cardiac tamponade has been described in AAD occurring in the setting of polyglandular autoimmune syndrome type II. The pathogenesis involves autoimmune inflammation of the pericardium, which precipitates an acute inflammatory reaction and rapid fluid accumulation. CONCLUSION: Pericarditis with cardiac tamponade and intermittent neutropenia may be rare manifestations of an Addisonian crisis.

Association of MEP1A gene variants with insulin metabolism in central European women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) shows not only hyperandrogenemia, hirsutism and fertility problems, but also metabolic disturbances including obesity, cardiovascular events and type-2 diabetes. Accumulating evidence suggests some degree of inflammation associated with prominent aspects of PCOS. We aimed to investigate the association of genetic variants 3'UTR rs17468190 (G/T) of the inflammation-associated gene MEP1A (GenBank ID: NM_005588.2) with metabolic disturbances in PCOS and healthy control women. Genetic variants rs17468190 (G/T) of MEP1A gene were analyzed in 576 PCOS women and 206 controls by using the Taqman fluorogenic 5'-exonuclease assay. This polymorphism was tested for association with anthropometric, metabolic, hormonal, and functional parameters of PCOS. There was a borderline significant difference in genotype distribution between PCOS and control women (p=0.046). In overweight/obese PCOS patients, the variants rs17468190 (G/T) in the MEP1A gene are associated with glucose and insulin metabolism. In a dominant model, the GG genotype of the MEP1A gene was more strongly associated with insulin metabolism in overweight/obese PCOS women (body mass index, BMI>25 kg/m(2)), than in GT+TT genotypes. The MEP1A GG-carriers showed a significantly increased homeostatic model assessment - insulin resistance (HOMA-IR) (p=0.003), elevation of fasting insulin (p=0.004) and stimulated insulin (30 min, p<0.001; 60 min, p=0.009; 120 min, p=0.009) as well as triglyceride (p=0.032) levels. MEP1A is a possible target gene for disease modification in PCOS. It might contribute to the abnormalities of glucose metabolism and insulin sensitivity and serve as a diagnostic or therapeutic target gene for PCOS.

(18)F-FDG PET in the evaluation of acuity of deep vein thrombosis.

PURPOSE: F-FDG PET has been used for vascular disease, but its role in deep vein thrombosis (DVT) remains prospectively unexplored. PATIENTS AND METHODS: Whole-body F-FDG PET/CT scans were performed in patients 1 to 10 weeks after onset of symptomatic DVT (n = 12) and in control subjects without DVT (n = 24). The metabolic activity (SUVmax) of thrombosed and contralateral nonthrombosed vein segments was determined. The sensitivity and specificity of F-FDG PET/CT for the diagnosis of DVT were determined by receiver operating characteristic curve analyses. In 2 patients with DVT, changes in the metabolic activity of thrombosed vein segments in serial F-FDG PET scans. RESULTS: The metabolic activity in thrombosed veins [SUVmax, 2.41 (0.75)] was visually appreciable and significantly higher than in nonthrombosed veins in either the contralateral extremity of patients with DVT [SUVmax, 1.09 (0.25), P = 0.007] or control subjects [1.21 (0.22), P < 0.001]. The area under the receiver operating characteristic curve for SUVmax was 0.9773 (P < 0.001), indicating excellent accuracy. An SUVmax threshold of greater than 1.645 was 87.5% sensitive and 100% specific for DVT. Metabolic activity in thrombosed veins correlated significantly with time from DVT symptom onset (decrease in SUVmax of 0.02/d, P < 0.05). Best-fit-line analyses suggested that approximately 84 to 91 days after acute DVT, the maximum metabolic activity of thrombosed veins would return to normal levels. CONCLUSIONS: F-FDG PET/CT is accurate for detecting acute symptomatic, proximal DVT. Metabolic activity in thrombosed veins decreases with time, suggesting that F-FDG PET may be helpful in assessing the age of the clot.

Colloid normalizes resuscitation ratio in pediatric burns.

Fluid resuscitation of burned children is challenging because of their small size and intolerance to over- or underresuscitation. Our American Burn Association-verified regional burn center has used colloid "rescue" as part of our pediatric resuscitation protocol. With Institutional Review Board approval, the authors reviewed children with ≥15% TBSA burns admitted from January 1, 2004, to May 1, 2009. Resuscitation was based on the Parkland formula, which was adjusted to maintain urine output. Patients requiring progressive increases in crystalloid were placed on a colloid protocol. Results were expressed as an hourly resuscitation ratio (I/O ratio) of fluid infusion (ml/kg/%TBSA/hr) to urine output (ml/kg/hr). We reviewed 53 patients; 29 completed resuscitation using crystalloid alone (lactated Ringer's solution [LR]), and 24 received colloid supplementation albumin (ALB). Groups were comparable in age, gender, weight, and time from injury to admission. ALB patients had more inhalation injuries and larger total and full-thickness burns. LR patients maintained a median I/O of 0.17 (range, 0.08-0.31), whereas ALB patients demonstrated escalating ratios until the institution of albumin produced a precipitous return of I/O comparable with that of the LR group. Hospital stay was lower for LR patients than ALB patients (0.59 vs 1.06 days/%TBSA, P = .033). Twelve patients required extremity or torso escharotomy, but this did not differ between groups. There were no decompressive laparotomies. The median resuscitation volume for ALB group was greater than LR group (9.7 vs 6.2 ml/kg/%TBSA, P = .004). Measuring hourly I/O is a helpful means of evaluating fluid demands during burn shock resuscitation. The addition of colloid restores normal I/O in pediatric patients.