Prediction of scoliosis progression with serial three-dimensional spinal curves and the artificial progression surface technique

Adolescent idiopathic scoliosis (AIS) progression is clinically monitored by a series of full spinal X-rays. To decrease radiation exposure, an artificial progression surface (APS) is proposed to predict progression. Fifty-six acquisitions (posteroanterior radiographs, 0° and 20°) were obtained from 11 AIS patients (29.8 ± 9.6° Cobb angle). Three-dimensional curves were constructed through vertebral pedicle centers. Three previous serial spinal curves (6-month intervals) were used to construct an APS with a Non-uniform Rational B-Spline surfacing technique. Future progression was achieved by aligning the curves on the APS using the generalized cross-validation extrapolation technique. With three and four previous serial spinal curves, the prediction accuracies of future progression at the next 6-month interval were 4.1 ± 3.3° for Cobb angles and 3.6 ± 3.5 mm for apex lateral deviations. Apex locations and Cobb regions varied within one vertebral level. The proposed technique shows potential as an accurate three-dimensional prediction method for AIS progression and could help pediatricians make decisions about treatment. However, it could only be applied once before more radiographic data would be needed.     

Estrogen-BDNF interactions: implications for neurodegenerative diseases

Since its' discovery over 20 years ago, BDNF has been shown to play a key role in neuronal survival, in promoting neuronal regeneration following injury, regulating transmitter systems and attenuating neural-immune responses. Estrogen's actions in the young and mature brain, and its role in neurodegenerative diseases in many cases overlaps with those observed for BDNF. Reduced estrogen and BDNF are observed in patients with Parkinson's disease and Alzheimer's disease, while high estrogen levels are a risk factor for development of multiple sclerosis. Estrogen receptors, which transduce the actions of estrogen, colocalize to cells that express BDNF and its receptor trkB, and estrogen further regulates the expression of this neurotrophin system. This review describes the distribution of BDNF and trkB expressing cells in the forebrain, and the roles of estrogen and the BDNF-trkB neurotrophin system in Parkinson's disease, Alzheimer's disease and multiple sclerosis.     

Antibiotic resistance determinants of multidrug-resistant Acinetobacter baumannii clinical isolates in Algeria

Antibiotic susceptibility testing was performed on 71 Acinetobacter baumannii clinical isolates, and presence of antibiotic resistance genes was screened for by PCR amplification and sequencing. Resistance rates were very high for aminoglycosides (22–80%), fluoroquinolones (>90%), and cephalosporins (>90%) but remained low for rifampin (2.8%) or null for colistin. Antibiotic resistance encoding genes detected were as follows: bla_TEM-128 gene (74.6%), aph(3′)-VI (50.7 %), aadA (63.4%), ant(2″)-I (14.1%), aac(3)-Ia (91.1%), aac(6′)-Ib (4.2%), mutation Ser83Leu in gyrA (94.4%), double mutations Ser83Leu and Ser80Leu (or Ser84Leu) in gyrA and parC (69.0%), and mutation I581N in RRDR of the rpoB gene.     

Interaction Between αCaMKII and GluN2B Controls ERK-Dependent Plasticity

Understanding how brief synaptic events can lead to sustained changes in synaptic structure and strength is a necessary step in solving the rules governing learning and memory. Activation of ERK1/2 (extracellular signal regulated protein kinase 1/2) plays a key role in the control of functional and structural synaptic plasticity. One of the triggering events that activates ERK1/2 cascade is an NMDA receptor (NMDAR)-dependent rise in free intracellular Ca(2+) concentration. However the mechanism by which a short-lasting rise in Ca(2+) concentration is transduced into long-lasting ERK1/2-dependent plasticity remains unknown. Here we demonstrate that although synaptic activation in mouse cultured cortical neurons induces intracellular Ca(2+) elevation via both GluN2A and GluN2B-containing NMDARs, only GluN2B-containing NMDAR activation leads to a long-lasting ERK1/2 phosphorylation. We show that αCaMKII, but not βCaMKII, is critically involved in this GluN2B-dependent activation of ERK1/2 signaling, through a direct interaction between GluN2B and αCaMKII. We then show that interfering with GluN2B/αCaMKII interaction prevents synaptic activity from inducing ERK-dependent increases in synaptic AMPA receptors and spine volume. Thus, in a developing circuit model, the brief activity of synaptic GluN2B-containing receptors and the interaction between GluN2B and αCaMKII have a role in long-term plasticity via the control of ERK1/2 signaling. Our findings suggest that the roles that these major molecular elements have in learning and memory may operate through a common pathway.     

Detailed mapping of germline deletions of the von Hippel--Lindau disease tumour suppressor gene

Von Hlppel-Llndau disease is a domlnantly Inherited familialcancer syndrome characterised by the development of retinalangiomatosis, cerebellar and spinal hemangloblastoma, renalcell carcinoma, phaeochromocytoma and pancreatic tumours. AcDNA (g7) which detects frequent genomic rearrangements in VHLdisease patients on Southern analysis, and contains the partialcoding sequence of the VHL gene has been isolated recently.To characterise the nature of the genomic rearrangements inVHL disease we initially screened 116 patients with VHL diseaseand identified 22 patients (19%) with abnormal fragments InEcoR1 digested DNA probed with g7. We then established thatthe coding sequence contained within g7 is represented in 3exons, and designed exon specific probes to investigate the22 patients with genomic rearrangements. All 22 patients weredemonstrated to have germline deletions, but the deletions wereheterogeneous with 7 patients having deletions confined to the5' exon 1, and 8 with non-overlapping deletions of exon 3. In7 unrelated patients, including 2 new mutations, the germilnedeletions were similar in size and position. There was no relationshipbetween the clinical phenotype and the deletion of individualexons. Although phaeochromocytoma was less frequent in kindredswith germllne deletions than those without detectable deletions,the difference was not statistically significant (1/19 versus16/72 respectively, x² = 1.84 p<0.1).     

Oleuropein and hydroxytyrosol inhibit the <Emphasis Type="Italic">N</Emphasis>-formyl-methionyl-leucyl-phenylalanine-induced neutrophil degranulation and chemotaxis via AKT,p38, and ERK1/2 MAP-Kinase inhibition

Purpose

Oleuropein and hydroxytyrosol are polyphenols that are extracted from olives and are major biological active components of olives and olive oil. Oleuropein and hydroxytyrosol exhibit interesting pharmacological effects on cells, and have been shown to have many health benefits such as anti-inflammatory effects. These effects were mainly attributed to their ability to scavenge the reactive oxygen species (ROS) produced by phagocytes such as neutrophils. The aim of this study was to investigate the effect of oleuropein and hydroxytyrosol on other neutrophil functions.

Methods

Human neutrophils were isolated from healthy donors. ROS production was measured by luminol-amplified chemiluminescence. Degranulation was assessed by measuring myeloperoxidase activity and Western blots. Chemotaxis was assessed by the under-agarose chemotaxis assay. Phosphorylated proteins were assessed by gel electrophoresis and Western blots.

Results

We show that in addition to their ROS scavenging effect, oleuropein and hydroxytyrosol significantly inhibited the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF)-induced degranulation of azurophilic and specific granules as measured by myeloperoxidase and lactoferrin release, respectively. We also show that oleuropein and hydroxytyrosol reduced fMLF-induced neutrophil chemotaxis. Interestingly, both agents impaired the fMLF-induced AKT, p38MAPKinase, and ERK1/2 phosphorylation, signaling molecules that are involved in pathways regulating neutrophil functions.

Conclusion

Our data suggest that the anti-inflammatory properties of oleuropein and hydroxytyrosol are not only restricted to their ROS scavenging effect, but also involve the inhibition of two other major pro-inflammatory neutrophil functions.

     

beta-Adrenoceptor blockers protect against staurosporine-induced apoptosis in SH-SY5Y neuroblastoma cells

The beta-adrenoceptor blockers exhibit a well-characterized anti-apoptotic property in the heart and kidney while less is known about the effect of this class of drugs on neuronal apoptosis. We studied the effects of three beta-adrenoceptor blockers propranolol (1-(isoproplyamino)-3-(naphthalene-1-yloxy)propan-2-ol), atenolol (2-[4-[2-hydroxy-3-(1-methylethylamino)propoxyl]phenyl]ehanamide), and ICI 118551 (1-[2,3-(dihydro-7-methyl-1H-iden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), against staurosporine-induced apoptosis in SH-SY5Y human neuroblastoma cells. Staurosporine increased caspase 3-like activity, DNA fragmentation, PARP cleavage, and the number of TUNEL positive cells consistent with the induction of apoptosis. Propranolol and ICI 118551, but not atenolol, demonstrated a concentration-dependent inhibition of caspase 3-like activity. Propranolol and ICI 118551 directly inhibited the enzymatic activity of recombinant caspase 9 while atenolol did not; however, none of the beta-adrenoceptor blockers that were examined directly blocked caspases 2 or 3 activity. In isolated mitochondria, propranolol and ICI 118551 inhibited staurosporine-induced cytochrome c release while atenolol did not. We conclude that propranolol and ICI 118551 protect SH-SY5Y cells against staurosporine-induced apoptosis through a dual action on the mitochondria and on caspase 9 in a cell type and an apoptotic paradigm where the conventional inhibitors of mitochondrial permeability transition such as cyclosporin A and bongkrekic acid demonstrate no protection.     

Clinical Review: Familial Mediterranean Fever—An Overview of Pathogenesis,Symptoms, Ocular Manifestations,and Treatment

Familial Mediterranean fever is an autoinflammatory multisystem disease, which most commonly affects patients from the Mediterranean basin. This review discusses the common polymorphisms in the MEFV gene as well as the role of pyrin in disease pathogenesis. Patients with familial Mediterranean fever typically develop peritonitis, pleuritis, arthritis, and fever. In addition, a number of authors have reported ophthalmic features. These case reports and series are further explored in this review. Colchicine has transformed the prognosis for patients with familial Mediterranean fever. The rationale for the use of colchicine, as well as the evidence for newer biologic agents is also covered.