The influence of uric acid treatments on liver glutathione system prevent oxidative damages in experimental autoimmune encephalomyelitis mice

Recently we reported that antioxidant system in brain and spinal cord in experimental autoimmune encephalomyelitis (EAE) mice is mainly affected at early stages of the disease [M. Zargari, A. Allameh, M.H. Sanati, T. Tiraihi, S.H. Lavasani, O. Emadyan, Relationship between the clinical scoring and demyelination in central nervous system with total antioxidant capacity of plasma during experimental autoimmune encephalomyelitis development in mice, Neurosci. Lett. 412 (2007), 24–28]. The aim of the present study was to investigate the role of uric acid (UA) on antioxidant system in liver and plasma of EAE mice. EAE was induced in C57/BL6 mice (n = 60), followed by i.p. administration of UA (10 mg/kg BW) in 30 mice at three distinct clinical stages (A: prior to onset, B: after onset, C: after development of EAE). Livers were removed and processed for measurement of lipid peroxidation products, reduced glutathione (GSH), and glutathione S-transferase (GST) and total antioxidant capacity of plasma (FRAP). The results showed that lipid peroxidation products in liver of EAE mice was increased significantly (∼85%) as compared to normal. UA administration to EAE mice caused a significant suppression of liver lipid peroxidation products (∼45%) at early stages (A and B). There was an inverse relationship between lipid peroxidation and cellular GSH in liver. GSH was significantly depleted in mice liver during the EAE progression, but it was recovered (∼29%) when UA was injected before the onset of the disease (groups A and B). Plasma total antioxidant capacity was significantly decreased during the development of EAE, however it was subsided in mice treated with UA as compared to the corresponding controls (21%) in groups A and B. Elevated liver GST as a result of EAE induction was reversed in mice treated with UA particularly in groups A and B. These results indicate that hepatic glutathione system, particularly GST plays a major role in modulation of oxidative damages to central nervous system (CNS) during EAE induction. The positive response of antioxidant system to UA administration in EAE mice was corroborated with improvement of clinical manifestation of the animals.     

Lipopolysaccharides,but not Angiotensin ll,lnduces Direct Pro‐lnflammatory Effects in Cultured Mouse Arteries and Human Endothelial and Vascular Smooth Muscle Cells

Angiotensin II (Ang II) might induce pro‐inflammatory effects directly in the vascular wall independently of its haemodynamic effects. The aim of our study was to investigate the putative direct pro‐inflammatory and vasomotor effects of Ang II and compare to those of lipopolysaccharides (LPS) in mouse isolated mesenteric resistance‐sized arteries (MRA) supported by experiments in cultured human primary endothelial and vascular smooth muscle cells. Results showed that 24‐hr organ culture of mouse MRA with 10 nM Ang II had, unlike 100 ng/mL LPS, no effects on IL‐6 or MCP‐1 secretion, VCAM1 mRNA expression or endothelial function, while Ang II significantly decreased maximal vasomotor responses to phenylephrine. In support, 24‐hr organ culture of mouse MRA significantly suppressed Agtr1a mRNA and augmented Tlr4 mRNA along with attenuated vasomotor responses to Ang II. Moreover, contrary to LPS and TNF‐α, Ang II and [Sar1]‐Ang II had no concentration‐ or time‐dependent effects on IL‐6 and MCP‐1 secretion in human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC). AGTR1 or AGTR2 mRNA expression was undetectable in HUVEC, whereas HASMC expressed only AGTR1 mRNA. In summary, contrary to previous studies and the observed effects of LPS, we could not demonstrate direct vascular pro‐inflammatory effects of Ang II ex vivo or in vitro. As indicated by our results, down‐regulation or desensitization of AT₁R during culture may explain our findings.     

Plasma leptin levels in patients with floppy eyelid syndrome

PURPOSE: To determine the range of plasma leptin levels in patients with floppy eyelid syndrome (FES). METHODS: This was a retrospective, noninterventional case series of 11 patients with FES. Charts were reviewed for patient age, sex, plasma leptin level, body mass index (BMI), presence or absence of obstructive sleep apnea (OSA) and diabetes mellitus, and any treatments for OSA. RESULTS: Charts of 11 patients were reviewed (10 male, 1 female). Plasma leptin levels were elevated in 7 of 11 patients (64%). Mean plasma leptin concentration was 49.5 ng/ml in male patients (range, 5 to 120 ng/ml) compared with a normal range of 1 to 35 ng/ml. Plasma leptin level in the female patient was 180 ng/ml (normal range, 4 to 72 ng/ml). Five patients had a known diagnosis of OSA. Four of these patients received continuous positive airway pressure during leptin level measurement. Plasma leptin levels averaged 110.0 ng/ml in the continuous positive airway pressure group. Average BMI was 37.4 kg/m (range, 24.9 to 57.1 kg/m). All patients with elevated leptin levels had a high BMI. CONCLUSIONS: Patients with FES demonstrate elevated plasma leptin levels, which correlate with BMI. Hyperleptinemia may play a role in the pathogenesis of FES.     

Juvenile dermatomyositis presenting with periorbital edema

Juvenile dermatomyositis is a rare disease that affects the skin and muscles. It often presents with a classic heliotrope eyelid rash. We present a case of juvenile dermatomyositis presenting with significant bilateral periorbital edema, with its complete resolution after systemic antiinflammatory therapy.     

Optic disc coloboma and localized chorioretinal defects in constitutional partial trisomy 8 mosaicism

Constitutional partial trisomy 8 mosaicism is a rare chromosomal multisystem disorder with systemic and ophthalmologic manifestations. We report the case of a 15-year-old female mosaic for trisomy 8 who has unilateral colobomatous microphthalmia and multiple chorioretinal defects. These congenital anomalies have not been previously reported in association with constitutional partial trisomy 8 mosaicism.     

Ultrasonographic visualization of lower eyelid structures and dynamic motion analysis

AIM

To define the ultrasonographic structure of normal lower eyelid anatomic compartments and their spacial relationship in dynamic motion.

METHODS

High resolution ultrasound (15MHz) was performed on the lower eyelids of 7 normal subjects. Movements of the lower eyelid and its compartments were visualized with ultrasound. In addition, the maximal excursion area of the lower eyelid fat compartments and retractor motions was measured before and after motion.

RESULTS

The orbicularis muscle could be seen as an echolucent structure between the dermis and the echodence fat pads. Lower eyelid fat pad seems to be divided into 2 compartments as range of motion and direction of movement of each of them varies. It seems that these compartments have also different behavior. The measured profile area of the visible normal lower eyelid fat pads during movement of globe from up-gaze to down-gaze decreased by 50%. Order of movement of lower eyelid structures seems to be as follows: after globe movement fist we see retractor movement, anterior orbital fat pad, then skin and septum, and finally movement of inferior fat pad.

CONCLUSION

Ultrasound represents a noninvasive tool for the visualization of lower eyelid morphology. Expanding its application could help us understand the compartmental changes in physiological eyelid movement, in aging and diseased study populations, as well as assess operative outcomes.     

Association of persistent hyperglycemia with outcome of severe traumatic brain injury in pediatric population

Purpose

Hyperglycemia is a common secondary insult associated with an increased risk of mortality and poor outcome in traumatic brain injury (TBI), but the effect of hyperglycemia on outcomes of severe TBI in children and adolescents is less apparent. The aim of this study was to evaluate the association of hyperglycemia with mortality in pediatric patients with severe TBI.

Methods

In this cross-sectional study, data of all children and adolescents with severe TBI admitted to Poursina Hospital in Rasht, including age, gender, Glasgow Coma Scale (GCS) upon admission, mortality rate, hospital length of stay, and serial blood glucose during the first three consecutive ICU days following admission, were reviewed from April 2007 to May 2011. After univariate analysis and adjustment for related covariates, logistic regression model was established to determine the association between persistent hyperglycemia and outcome.

Results

One-hundred and twenty-two children were included with a median admission GCS of 6 (interquartile range (IQR) 5–7) and a median age of 13?years (IQR 7.75–17). Among them, 91 were boys (74.6?%) and 31 were girls (26.6?%); the overall mortality was 40.2?% (n?=?49). Patients who died had a significantly greater blood glucose levels than survivors for the first 3?days of admission (P?=?0.003, P?P?=?0.001, respectively). Moreover, persistent hyperglycemia during the first 3?days of admission had an adjusted odds ratio of 11.11 for mortality (P?Conclusion Early hyperglycemia is associated with poor outcome, and persistent hyperglycemia is a powerful and independent predictor of mortality in children and adolescents with severe TBI.     

Importance of Mean Platelet Volume in Predicting Cardiac Mechanics Parameters and Carotid‐Intima Media Thickness in Children With End‐Stage Renal Disease and Comparison With Healthy Children

Cardiovascular disease (CVD) is the major cause of death in children with ESRD. Echocardiography and Doppler ultrasound are useful devices for diagnosing cardiovascular abnormalities in such patients. However, they are expensive, difficult to perform as a routine, and not available in many centers. Therefore, finding a more accessible and inexpensive method for CVD evaluation biomarkers is needed. The aim of this study was to evaluate the relationship between mean platelet volume (MPV) as a routine hematological parameter with cardiac mechanics characteristics in children with ESRD. Forty‐two children under dialysis and 60 age‐ and sex‐matched healthy subjects as control group were enrolled in the study. Carotid‐intima media thickness (CIMT) and echocardiographic parameters were measured in both groups. In addition, hematological and biochemical variables were evaluated in blood samples of participants. MPV was significantly higher in patients than in controls. CIMT, left ventricular mass index (LVMI), end diastolic diameter, strain rate, and global longitudinal strain were significantly different between the two groups. MPV was positively correlated with LVMI and inversely with ejection fraction. In receiver operating characteristic (ROC) curve analysis, the area under the ROC curve (AUC) values for MPV in predicting left ventricular hypertrophy (LVH) and abnormal CIMT were 0.65 (P = 0.07) and 0.53 (P = 0.74), respectively. MPV was correlated with some cardiac abnormalities in children with ESRD. However, it could not show appropriate predictive values in diagnosing LVH and subclinical atherosclerosis. Further studies with prospective design could shed more light in this topic.