Acute Outcomes of Cervical Spine Injuries in the Elderly: Atlantaxial vs Subaxial Injuries

Abstract

Background/Objective: Recent studies have reported on the outcomes of spinal cord injuries in the elderly. Our aim was to identify acute survival differences between elderly patients with atlantoaxial injuries relative to subaxial injuries at our institution and to determine whether operative treatment is associated with improved survival rates in either population.

Study Design: Retrospective database review of all traumatic cervical spine injuries in patients at least 65 years of age at a single tertiary care center.

Methods: A total of 193 consecutive patients at least 65 years of age treated at a single tertiary care center over a 12-year period were identified. Initial hospitalization records were reviewed. Patients were divided by anatomic level of injury: atlantoaxial (C1 or C2) and subaxial (C3 or below). Demographics, mechanism, and mortality rates were compared. Each group was further divided by treatment (operative or nonoperative), and inpatient survival rates were compared.

Results: Statistically similar survival rates were observed among patients with atlantoaxial and subaxial injuries (P= 0.10). Patients with nonoperatively treated subaxial injuries died at significantly higher rates than did their operatively treated peers (P < 0.05).

Conclusions: In this large comprehensive series of elderly patients with cervical spine injuries, survival rates were comparable regardless of anatomic level of injury. The operative treatment of subaxial injuries was associated with an improved acute survival rate vs nonoperative management. Further prospective study is needed to better assess this relationship.     

Chronic antidepressant-like effect of EMD386088, a partial 5-HT6 receptor agonist,in olfactory bulbectomy model may be connected with BDNF and/or CREB signalling pathway

Background

The removal of the olfactory bulbs has been attributed to behavioral changes and neuroplasticity manifesting themselves among others like increases in brain neurotrophin expression and neurogenesis. Earlier data presented that EMD386088, a 5-HT₆ receptor partial agonist, exerts antidepressant-like properties after chronic administration in olfactory bulbectomy (OB) model as was it compared with amitriptyline (AMI). The aim of this study was to compare acute and chronic biochemical effects of EMD386088, administered in its antidepressant active (2.5 mg/kg) and non-active (1.25 mg/kg) doses, found in the open field test in OB rats, with those of AMI (10 mg/kg). The levels of 5-HT₆ receptor protein and selected neurotrophins in prefrontal cortex (PFC) and hippocampus (Hp) of rats have been examined.

Assessment of metabolic changes within normal appearing gray and white matter in children with growth hormone deficiency: Magnetic resonance spectroscopy and hormonal correlation

Objective: The pathogenesis of idiopathic growth hormone deficiency (GHD) in children, including possible cerebral metabolic alterations, remains unclear. The aim of the study was to evaluate metabolic changes within the normal appearing brain in children with GHD using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations and with pituitary gland size. Methods: Seventy children with GHD (mean age 7.8 yrs) and 11 healthy controls (mean age 8.4 yrs) were enrolled in the study. The MRS examinations were performed on a 1.5T scanner. Voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, Cho/Cr and mI/Cr ratios were analyzed. The metabolite ratios, pituitary gland size and hormonal concentrations: growth hormone (GH) in two stimulation tests and GH during the night, as well as IGF-1 (insulin-like growth factor) and IGFBP3 (insulin-like growth factor-binding protein) levels were also correlated. Results: There was a significant (p < 0.05) decrease of the NAA/Cr ratios in PCG and PWM in children with GHD compared to the normal subjects. Other metabolite ratios showed no significant differences. We also found significant positive correlations between NAA/Cr ratio in PWM and IGFBP3 level, as well as with GH concentration in a stimulation test with glucagon. Conclusions: The reduction of NAA/Cr ratios may suggest loss of neuronal activity within normal appearing gray and white matters in children with GHD. MRS could be a sensitive marker of cerebral metabolic disturbances associated with GHD and maybe used as an additional indicator for therapy with recombinant GH.     

Comprehensive morphometry of subcortical grey matter structures in early‐stage Parkinson's disease

Previous imaging studies that investigated morphometric group differences of subcortical regions outside the substantia nigra between non‐demented Parkinson's patients and controls either did not find any significant differences, or reported contradictory results. Here, we performed a comprehensive morphometric analysis of 20 cognitively normal, early‐stage PD patients and 19 matched control subjects. In addition to relatively standard analyses of whole‐brain grey matter volume and overall regional volumes, we examined subtle localized surface shape differences in striatal and limbic grey matter structures and tested their utility as a diagnostic marker. Voxel‐based morphometry and volumetric comparisons did not reveal significant group differences. Shape analysis, on the other hand, demonstrated significant between‐group shape differences for the right pallidum. Careful diffusion tractography analysis showed that the affected parts of the pallidum are connected subcortically with the subthalamic nucleus, the pedunculopontine nucleus, and the thalamus and cortically with the frontal lobe. Additionally, microstructural measurements along these pathways, but not along other pallidal connections, were significantly different between the two groups. Vertex‐wise linear discriminant analysis, however, revealed limited accuracy of pallidal shape for the discrimination between patients and controls. We conclude that localized disease‐related changes in the right pallidum in early Parkinson's disease, undetectable using standard voxel‐based morphometry or volumetry, are evident using sensitive shape analysis. However, the subtle nature of these changes makes it unlikely that shape analysis alone will be useful for early diagnosis. Hum Brain Mapp 35:1681–1690, 2014. © 2013 Wiley Periodicals, Inc.     

The dose-dependent release of histamine from placental mast cells after administration of atrial natriuretic peptide

Inflammation Research -     

Antibacterial,antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs

Context: Crataegus monogyna L. (Rosaceae) (CM), Equisetum telmateia L. (Equisataceae) (ET), Geranium purpureum Vil. (Geraniaceae) (GP), Mentha suaveolens Ehrh. (Lamiaceae) (MS), and Lavandula stoechas L. spp. luisieri (Lamiaceae) (LS) are all medicinal.

Objective: To evaluate the antioxidant, antiproliferative and antimicrobial activities of plant extracts and quantify individual phenolics and zinc.

Material and methods: Aerial part extracts were prepared with water (W), ethanol (E) and an 80% mixture (80EW). Antioxidant activity was measured with TAA, FRAP and RP methods. Phenolics were quantified with a HPLC. Zinc was quantified using voltammetry. Antibacterial activity (after 48?h) was tested using Enterococcus faecalis, Bacillus cereus, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Listeria monocytogenes. Antiproliferative activity (after 24?h) was tested using HEP G2 cells and fibroblasts.

Results: Solvents influenced results; the best were E and 80EW. GP had the highest antioxidant activity (TAA and FRAP of 536.90?mg AAE/g dw and 783.48?mg TE/g dw, respectively). CM had the highest zinc concentration (37.21?mg/kg) and phenolic variety, with neochlorogenic acid as the most abundant (92.91?mg/100?g dw). LS was rich in rosmarinic acid (301.71?mg/100?g dw). GP and LS inhibited the most microorganisms: B. cereus, E. coli and S. aureus. GP also inhibited E. faecalis. CM had the lowest MIC: 5830?μg/mL. The antibacterial activity is explained by the phenolics present. LS and CM showed the most significant anti-proliferative activity, which is explained by their zinc content.

Conclusion: The most promising plants for further studies are CM, LS and GP.     

Coronatin-1 isolated from entomopathogenic fungus Conidiobolus coronatus kills Galleria mellonella hemocytes in vitro and forms potassium channels in planar lipid membrane

Entomopathogenic fungi are important natural regulatory factors of insect populations and have potential as biological control agents of insect pests. The cosmopolitan soil fungus Conidiobolus coronatus (Entomopthorales) easily attacks Galleria mellonella (Lepidoptera) larvae. Prompt death of invaded insects is attributed to the action of toxic metabolites released by the invader. Effect of fungal metabolites on hemocytes, insect blood cells involved in innate defense response, remains underexplored to date.C. coronatus isolate 3491 inducing 100% mortality of G. mellonella last instar larvae exposed to sporulating colonies, was cultivated at 20 °C in minimal medium. Post-incubation filtrates were used as a source of fungal metabolites. A two-step HPLC (1 step: Shodex KW-803 column eluted with 50 mM KH₂PO₄ supplemented with 0.1 M KCl, pH 6.5; 2 step: ProteinPak™ CM 8HR column equilibrated with 5 mM KH₂PO₄, pH 6.5, proteins eluted with a linear gradient of 0.5 M KCl) allowed the isolation of coronatin-1, an insecticidal 36 kDa protein showing both elastolytic and chitinolytic activities.Addition of coronatin-1 into primary in vitro cultures of G. mellonella hemocytes resulted in rapid disintegration of spherulocytes freely floating in culture medium and shrinkage of plasmatocytes adhering to the bottom of culture well. Coronatin-1 stimulated pseudopodia atrophy and, in consequence, disintegration of nets formed by cultured hemocytes.After incorporation of coronatin-1 into planar lipid membrane (PLM) ion channels selective for K⁺ ions in 50/450 mM KCl solutions were observed. Potassium current flows were recorded in nearly 70% of experiments with conductance from 300 pS up to 1 nS. All observed channels were active at both positive and negative membrane potentials. Under experimental conditions incorporated coronatin-1 exhibited a zero current potential (E_rev) of 47.7 mV, which indicates K⁺-selectivity of this protein.The success of the purification of coronatin-1 will allow further characterization of the mode of action of this molecule, including ability of coronatin-1 to form potassium channels in immunocompetent hemocytes.     

Mitochondria as a pharmacological target

Mitochondria play a central role in energy metabolism within the cell. Mitochondrial dysfunctions lead to various neurodegenerative disorders and to the so-called "mitochondrial diseases". A vast amount of evidence points to the implication of mitochondria in such complex processes as apoptosis and cardioprotection. The purpose of this review is to present a recent state of our knowledge and understanding of the action of various therapeutically applied substances on mitochondria. These include antitumor, immunosuppressant, and antiviral drugs, potassium channel openers, sulfonylureas, and anesthetics. Some of these substances are specifically designed to affect mitochondrial functions. In other cases, drugs with primary targets in other cellular locations may modify mitochondrial functions as side effects. In any case, identification of mitochondria as primary or secondary targets of a drug may help us to better understand the drug's mechanism of action and open new perspectives for its application. As far as possible, the molecular mechanisms of the interference of particular drugs in the mitochondrial metabolism will be described. In some cases, metabolic routes in which the drugs interfere will also be briefly outlined.     

Effect of chronic imipramine or electroconvulsive shock on the expression of mGluR1a and mGluR5a immunoreactivity in rat brain hippocampus

Previous studies showed that chronic electroconvulsive shock (ECS) or imipramine treatment induced a subsensitivity of group I metabotropic glutamate receptors (mGluR) in hippocampus. In the present study effects of antidepressant treatment on the expression of mGluR1a and mGluR5a, belonging to the group I mGluR, were investigated in rat brain hippocampus using immunohistochemical and Western blot methods, respectively. Male Wistar rats were treated singly or chronically for 21 days with imipramine, 10 mg/kg, twice daily; with ECS (90 mA, 50 Hz, 0.5 s) every second day; or with haloperidol, 1.2 mg/kg, once daily. Appropriate controls were injected with saline. Rats were sacrificed 24 h after the last treatment and their hippocampi were taken out for analysis.

It was found that the mGluR1a-immunoreactivity expression increased significantly in Ammon’s horn (CA) regions after chronic ECS. The most pronounced effect was observed in the CA3. No significant effects were found after single treatment or after haloperidol. The expression of mGluR5a increased significantly after chronic imipramine in the CA1 and after chronic ECS in the CA3 region.

The results obtained indicate an influence of antidepressant treatment on group I mGluR. This increase in the receptor protein level may be a compensatory mechanism developing after chronic treatment.     

Interaction of zinc with antidepressants in the forced swimming test in mice

Recent preclinical data have suggested that glutamate NMDA receptor may be involved in the mechanism of action of antidepressant treatments. Functional antagonists of the NMDA receptor complex exhibit an antidepressant-like effect in animal tests that predict antidepressant activity and in animal models of depression. Zinc, a very potent inhibitor of the NMDA receptor, is active in the forced swimming test in rats and mice. The present study investigated the interaction of zinc with antidepressants in the forced swimming test in mice. Mice were injected with imipramine or citalopram alone and in combination with zinc. Low, ineffective per se doses of imipramine and citalopram administered together with low, ineffective doses of zinc were active in this test. The present data support the notion that inhibition of the NMDA receptor participates in an antidepressant action, and further demonstrate particular role of zinc in this activity.