Crocin improved amyloid beta induced long‐term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats

Extracellular beta‐amyloid (Aβ) accumulation and deposition is the main factor, which causes synaptic loss and eventually cells death in Alzheimer's disease (AD). Memory loss and long‐term potentiation (LTP) dysfunction in the hippocampus are involved in the AD. The involvement of crocin, as the main and active constituent of saffron extract in learning and memory processes, has been proposed. Here we investigated the probable therapeutic effect of crocin on memory, LTP, and neuronal apoptosis using in vivo Aβ models of the AD. The Aβ peptide (1–42) was bilaterally administered into the frontal‐cortex using stereotaxic apparatus. Five hours after surgery, rats were given intraperitoneal crocin (30 mg/kg) daily, which repeated for 12 days. Barnes maze results showed that administration of crocin significantly improves spatial memory indicators such as latency time to achieving the target hole and the number of errors when compared to Aβ‐group. Passive avoidance test revealed that crocin significantly increased the step‐through‐latency compared to Aβ‐treated alone. These learning deficits in Aβ‐treated animals correlated with a reduction of LTP in hippocampal CA1 synapses in freely moving rats, which crocin improved population spike amplitude and mean field excitatory postsynaptic potentials (fEPSP) slope reduction induced by Aβ. Neuronal apoptosis was detected by TUNEL assay and the expression levels of c‐Fos proteins were examined by Western blotting. Crocin significantly reduced the number of TUNEL‐positive cells in the CA1 region and decreased c‐Fos in the hippocampus compared to Aβ‐group. In vivo Aβ treatment altered significantly the electrophysiological properties of CA1 neurons and crocin further confirmed a neuroprotective action against Aβ toxicity.     

Langerhans Cell Histiocytosis of the Lung and Thyroid, Co-Existing with Papillary Thyroid Cancer

A 24-year-old man presented to our center with a huge goiter compressing his airway. He had a previous diagnosis of Langerhans cell histiocytosis (LCH) of the lung. Core needle biopsy was consistent with histiocytosis. Thyroidectomy was performed. A very invasive mass was encountered at the time of surgery. Histopathology result was consistent with an invasive papillary cancer of thyroid co-occurring with LCH. Although association of LCH with different malignancies has been reported, co-existing invasive papillary thyroid cancer and LCH is a rare combination.     

Electroencephalogram complexity analysis in children with attention-deficit/hyperactivity disorder during a visual cognitive task

Objective: The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Method: Thirty 7–12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders–Fifth Edition (DSM–5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel–Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. Results: The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Conclusion: Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.     

A novel splice site mutation in the SPG7 gene causing widespread fiber damage in homozygous and heterozygous subjects

Hereditary spastic paraplegias (HSP) are genetically and clinically heterogeneous neurodegenerative disorders. The purpose of this study was to assess the genotype and phenotype in a family with a complicated form of autosomal recessive hereditary spastic paraplegia (ARHSP). Neurological and neuropsychological evaluation, neurophysiologic studies, fiberoptic endoscopic evaluation of swallowing (FEES), neuroimaging analysis including diffusion tensor imaging (DTI), and mutation analysis of SPG4 and SPG7 gene were performed. The index case (mother) was affected by an adult‐onset form of complicated ARHSP due to the homozygous splice site mutation c.1552+1 G>T in the SPG7 gene. This mutation leads to an abnormally spliced mRNA lacking exon 11. Additional clinical features were bilateral ptosis and subtle deficits in executive function. All three asymptomatic daughters carried the sequence variation c.1552+1 G>T in heterozygous state. DTI of the mother revealed disturbance of white matter (WM) integrity in the left frontal lobe, the left corticospinal tract and both sides of the brainstem. DTI of the daughters showed subtle WM alteration in the frontal corpus callosum. The novel mutation is the first splice site mutation found in the SPG7 gene. It removes part of the AAA domain of paraplegin protein, probably leading to a loss‐of‐function of the paraplegin‐AFG3L2 complex in the mitochondrial inner membrane. The pattern of WM damage in the homozygote index case may be specific for SPG7‐HSP. The detection of cerebral WM alterations in the corpus callosum of asymptomatic heterozygote carriers confirms this brain region as the most prominent and early location of fiber damage in ARHSP. © 2010 Movement Disorder Society     

Intermediate follow-up of a composite stentless porcine valved conduit of bovine pericardium in the pulmonary circulation

BACKGROUND: In the pediatric population, glutaraldehyde-preserved bovine pericardium conduit containing a stentless porcine valve has been proposed as an alternative to homografts for right ventricular outflow tract reconstruction. METHODS: Between June 1996 and March 2000, a total of 55 patients, 20 with truncus arteriosus, 21 with pulmonary atresia with ventricular septal defect, and 14 with miscellaneous defects, received this conduit. Median age at implantation was 3.4 months (range, 3 days to 19 years), and 27 patients (50%) were less than 3 months old. Clinical outcome, echocardiographic data, and pathologic analysis were recorded. End points for conduit failure were conduit replacement or dilation. A mean follow-up of 27 months (range, 2 to 46 months) was available for 47 survivors. RESULTS: Procedure for conduit obstruction was required in 13 patients. The most common procedure was operation, and all but 3 patients had an unsuccessful balloon angioplasty before reoperation. Actuarial freedom from conduit dilation or reoperation was 93.6% (95% confidence limits, 82% to 99%), 81.9% (95% confidence limits, 64% to 91%), 77.8% (95% confidence limits, 39% to 78%), and 64.3% (95% confidence limits, 26% to 73%) at 1, 2, 3, and 4 postoperative years, respectively. Univariate analysis identified small conduit size as a risk factor for conduit obstruction. CONCLUSIONS: Although this new conduit was not free from progressive obstruction, our clinical results (easy to work and good valvular function) and the availability in small sizes encouraged us to use it as an alternative to small-size homografts when those were not available.     

Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels

Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage-gated neuronal sodium channels at very low concentrations (about 0.1 microM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch-clamp technique, we applied riluzole on recombinant voltage-gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage-gated skeletal muscle sodium channels, shifting the midpoint of the steady-state inactivation curve to more negative potentials, but only in comparatively high concentrations (> or = 0.1 mM). At these concentrations, riluzole also caused an open-channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage-gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 microM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole.     

2,6 di-tert-butylphenol, a nonanesthetic propofol analog, modulates alpha1beta glycine receptor function in a manner distinct from propofol

The anesthetic propofol (2,6 diisopropylphenol) mediates some of its effects by activating inhibitory chloride currents in the lower brainstem and spinal cord. The effects comprise direct activation of gamma-aminobutyric acid-A and glycine receptors in the absence of the natural agonist, as well as potentiation of the effect of submaximal agonist concentrations. Replacement of propofol's isopropyl groups by di-tert-butyl groups yields a compound without in vivo anesthetic effects. We have studied the effects of propofol and 2,6 di-tert-butylphenol on chloride inward currents via rat alpha1beta glycine receptors heterologously expressed in human embryonic kidney cells. Propofol, but not 2,6 di-tert-butylphenol, directly activated glycine receptors; half-maximal current activation was observed with propofol 114 +/- 27 microM. Both compounds potentiated the effect of a submaximal glycine concentration (10 microM) to a maximum value of 136% +/- 71% (propofol) and 279% +/- 109% (2,6 di-tert-butylphenol) of the response to glycine 10 microM. The 50% effective concentration for this effect was 12.5 +/- 6.4 microM and 9.4 +/- 10.2 microM for propofol and 2,6 di-tert-butylphenol, respectively. Propofol and its nonanesthetic structural analog do not differ in their ability to coactivate the glycine receptor but differ in their ability to directly activate the receptor in the absence of the natural agonist.     

Is surgical intervention still indicated in recurrent aortic arch obstruction?

BACKGROUND: Introduction of balloon dilatation has become the standard treatment for recurrent aortic arch obstruction and has changed the therapeutic approach to patients with this disorder. OBJECTIVES: Whether all patients with recurrent aortic arch obstruction are candidates for balloon dilatation remains unanswered. In addition, only few reports have tried to compare the results between patients undergoing balloon dilatation or redo operations. METHODS: Since 1983, 97 patients underwent reintervention for recurrent aortic arch obstruction (42 dilations and 55 reoperations). Eight had immediate unsuccessful dilatation and were shifted to the surgical group (n = 63). The median age at reintervention was 21.7 months (10 days-45 years), and the median delay was 13.6 months (7 days-17 years). Anatomy of the aortic arch oriented the surgical approach to treat arch hypoplasia. It could be performed through a left thoracotomy in 52 patients, with extended end-to-end anastomosis in 34 patients, subclavian flap repair in 9 patients, conduit insertion in 6 patients, and patch enlargement in 3 patients. More recently, an anterior approach with cardiopulmonary bypass without circulatory arrest was applied to enlarge the patch in all the aortic arches. RESULTS: There was one early death in the surgical intervention group and 2 late deaths in the dilation group. Major complications and recurrence were higher in the dilated group (4 vs 0, P <.01, and 14 vs 5, P <.0004, respectively). At a mean follow-up of 11.8 +/- 4.1 years in the surgical intervention group and 7.5 +/- 2.5 years in the dilated group, systemic hypertension was normalized in all but 5 patients in the surgical intervention group and 6 patients in the dilated group. CONCLUSION: Reoperation for recurrent aortic arch obstruction can be performed safely, with low rates of mortality and morbidity. This approach should be considered versus balloon angioplasty, especially in patients older than 4 years and in the presence of aortic arch hypoplasia.     

Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial [ISRCTN64132371]

Background  

Attention-deficit hyperactivity disorder is an early-onset, clinically heterogenous disorder of inattention, hyperactivity, and impulsiveness. The diagnosis and treatment of attention-deficit hyperactivity disorder continues to raise controversy, and, there is also an increase in treatment options. In this 6-week double blind, placebo controlled-trial, we assessed the effects of zinc plus methylphenidate in the treatment of children with attention deficit hyperactivity disorder. To the best of our knowledge, this study is the first double blind and placebo controlled clinical trial assessing the adjunctive role of zinc in ADHD.