Evidence that membrane-bound G protein-coupled melatonin receptors MT1 and MT2 are not involved in the neuroprotective effects of melatonin in focal cerebral ischemia

Melatonin is synthesized and released by the pineal gland in a circadian rhythm, and many of its peripheral actions are mediated via membrane MT1 and MT2 receptors. Apart from its metabolic functions, melatonin is a potent neuroprotective molecule owing to its antioxidative actions. The roles of MT1 and MT2 in the neuroprotective effects of melatonin and cell signaling after cerebral ischemia remain unknown. With the use of MT1 and MT2 knockout (mt1/2(-/-) ) mice treated with melatonin, we evaluated brain injury, edema formation, inducible nitric oxide synthase (iNOS) activity, and signaling pathways, including CREB, ATF-1, p21, Jun kinase (JNK)1/2, p38 phosphorylation, resulting from ischemia/reperfusion injury. We show that the infarct volume and brain edema do not differ between mt1/2(-/-) and wild-type (WT) animals, but melatonin treatment decreases infarct volume in both groups and brain edema in WT animals after middle cerebral artery occlusion. Notably, melatonin's neuroprotective effect was even more pronounced in mt1/2(-/-) animals compared to that in WT animals. We also demonstrate that melatonin treatment decreased CREB, ATF-1, and p38 phosphorylation in both mt1/2(-/-) and WT mice, while p21 and JNK1/2 were reduced only in melatonin-treated WT animals in the ischemic hemisphere. Furthermore, melatonin treatment lowered iNOS activity only in WT animals. We provide evidence that the absence of MT1 and MT2 has no unfavorable effect on ischemic brain injury. In addition, the neuroprotective effects of melatonin appear to be mediated through a mechanism independent of its membrane receptors. The underlying mechanism(s) should be further studied using selective melatonin receptor agonists and antagonists.     

Efficacy of closed reduction for nasal fractures in children

The aim of this study was to evaluate the efficacy of closed reduction and the effects of the time of intervention on young patients’ satisfaction. Patients older than 16 years and those with additional maxillofacial fractures were excluded. All patients were treated by closed reduction and external fixation. The patients and parents were asked about their satisfaction in a survey 6 months’ postoperatively. They were divided into groups according to the time of intervention, and the results. Twenty-four patients, age range 4–16 years, with isolated nasal fractures were included in the study. The mean (SD) time before intervention was 5.5 (1.8) days. The first group comprised 16 patients whose fractures were reduced between days 1 and 5 after the injury, and the second the 8 whose fractures were reduced between days 6 and 10. At 6 months 15 of the 24 were satisfied with the result, and 9 were not. In the group treated between days 1–5, 12/16 were happy with the result, and in the group treated between days 6–10, 3/8 were satisfied. Closed reduction gives good results in the treatment of nasal fractures in children. Early intervention increases the rate of satisfaction.     

Bilateral Lower Limb Edema Caused by Compression of the Retrohepatic Inferior Vena Cava by a Giant Hepatic Hemangioma

Hemangiomas are the most common benign primary tumors of the liver and their prevalence ranges from 0.4% to 20%. Approximately 85% of hemangiomas are clinically asymptomatic and are incidentally detected in imaging studies performed for other causes. In a very small minority of patients, nausea, vomiting, abdominal pain, distension, palpable mass, obstructive jaundice, bleeding, and signs and symptoms of Budd-Chiari syndrome may develop due to compression of bile duct, hepatic vein, portal vein, and adjacent organs. Occasionally, external compression of inferior vena cava may lead to edema and/or indirect symptoms such as deep vein thrombosis of the lower limbs. In this report, we present a case of giant hepatic hemangioma that completely filled the right lobe of the liver. The patient presented with bilateral lower limb edema and pain. A computed tomography scan detected a 9 × 11 × 12 cm mass indicative of a hemangioma in the right lobe of the liver that compressed the inferior vena cava. The patient refused treatment initially but returned 6 months later presenting with the same symptoms. At that time, the mass had increased in size and a hepatectomy was performed, preserving the middle hepatic vein. By postoperative month 13, the swelling in the lower extremities had decreased significantly and the inferior vena cava appeared normal.     

Cord blood nesfatin-1 and apelin-36 levels in gestational diabetes mellitus

To assess maternal serum and cord blood apelin-36 and nesfatin-1 concentrations in pregnant women with and without gestational diabetes mellitus (GDM). Thirty pregnant women with GDM and 30 gestational age matched healthy pregnant subjects participated to the study. Maternal serum and cord blood nesfatin-1 and apelin-36 levels were measured with ELISA, at the time of birth. The relationships between maternal serum and cord blood nesfatin-1 and apelin-36 levels, anthropometric and metabolic parameters were also assessed. Maternal serum apelin-36 levels were found higher (13.5?±?8.3 vs. 9.6?±?5.9?ng/ml, P?=?0.001) and nesfatin-1 levels were found lower (5.5?±?8.1 vs. 8.1?±?23.9?ng/ml, P?=?0.001) in patients with GDM compared with control pregnant women. However, the cord blood apelin-36 levels (8.8?±?4.3 and 8.2?±?1.9?ng/ml, P?=?0.618) and nesfatin-1 levels (5.4?±?4.0 and 6.2?±?10.3?ng/ml, P?=?0.688) were similar in the GDM and control groups, respectively. Maternal serum apelin-36 and nesfatin-1 levels correlated positively with their respective cord blood levels. Maternal serum and cord blood apelin-36 levels correlated negatively with the gestational age and birth weight. Similarly maternal serum and cord blood nesfatin-1 levels correlated negatively with the gestational age, but there was no correlation with the birth weight. We did not find a correlation between maternal serum apelin-36 and nesfatin-1 levels, maternal age, BMI, fasting glucose, fasting insulin, and HOMA-IR. Also cord blood apelin-36 and nesfatin-1 levels did not correlate with the maternal age, BMI, HOMA-IR, cord blood glucose, and cord blood insulin levels. Our results indicate that apelin-36 concentrations increase and nesfatin-1 concentrations decrease in maternal serum of women with GDM.     

Acute presentation of autoimmune hepatitis in a patient with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder

Myasthenia gravis is an antibody-mediated autoimmune disease at the neuromuscular junctions. It can be associated with many other autoimmune diseases. We report a case of acute presentation of autoimmune hepatitis with myasthenia gravis, thymoma, Hashimoto thyroiditis and connective tissue disorder.