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Brad Wilson C.,Louisiana State University | McLaughlin L.D.,Louisiana State University | Ebenezer P.J.,Louisiana State University | Nair A.R.,Louisiana State University | And 6 more authors.
Frontiers in Behavioral Neuroscience | Year: 2014

Serotonin (5-HT), norepinephrine (NE), and other neurotransmitters are modulated in post-traumatic stress disorder (PTSD). In addition, pro-inflammatory cytokines (PIC) are elevated during the progression of the disorder. Currently, the only approved pharmacologic treatments for PTSD are the selective-serotonin reuptake inhibitors (SSRI) sertraline and paroxetine, but their efficacy in treating PTSD is marginal at best. In combat-related PTSD, SSRIs are of limited effectiveness. Thus, this study sought to analyze the effects of the SSRI sertraline on inflammation and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. We hypothesized that sertraline would diminish inflammatory components and increase 5-HT but might also affect levels of other neurotransmitters, particularly NE. PTSD-like effects were induced in male Sprague-Dawley rats (n = 6/group × 4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1 h on days 1 and 11 of a 31-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, treatment group animals were injected intraperitoneally (i.p.) with sertraline HCl at 10 mg/kg for 7 consecutive days, while controls received i.p. vehicle. The animals were subsequently sacrificed on day 8. Sertraline attenuated inflammatory markers and normalized 5-HT levels in the central nervous system (CNS). In contrast, sertraline produced elevations in NE in the CNS and systemic circulation of SSRI treated PTSD and control groups. This increase in NE suggests SSRIs produce a heightened noradrenergic response, which might elevate anxiety in a clinical setting. © 2014 Wilson, McLaughlin, Ebenezer, Nair, Dange, Harre, Shaak, Diamond and Francis.


Bashore T.M.,The American College | Barac A.,The American College | Byrne J.G.,Society of Thoracic Surgeons Representative | Cavendish J.J.,The American College | And 12 more authors.
Journal of the American College of Cardiology | Year: 2012

The last expert consensus document on cardiac catheterization laboratory standards was published in 2001 (1). Since then, many changes have occurred as the setting has evolved from being primarily diagnostic based into a therapeutic environment. Technology has changed both the imaging and reporting systems. The lower risk of invasive procedures has seen the expansion of cardiac catheterization laboratories to sites without onsite cardiovascular surgery backup and even to community hospitals where primary percutaneous coronary intervention (PCI) is now being performed. This has increased the importance of quality assurance (QA) and quality improvement (QI) initiatives. At the same time, the laboratory has become a multipurpose suite with both diagnostic procedures to investigate pulmonary hypertension and coronary flow and with therapeutic procedures that now include intervention into the cerebral and peripheral vascular systems as well as in structural heart disease. These new procedures have impacted both the adult and pediatric catheterization laboratories. The approaches now available allow for the treatment of even very complex heart disease and have led to the development of hybrid cardiac catheterization laboratories where a team of physicians (including invasive cardiologists, cardiovascular surgeons, noninvasive cardiologists, and anesthesiologists) is required. © 2012 by the American College of Cardiology Foundation.


Yang K.,University of Maryland, Baltimore | Yang K.,PLA Fourth Military Medical University | Ma H.,Clinical Force
Neuroscience | Year: 2011

Metabotropic GABA type B (GABA B) receptors are abundantly expressed in the rat spinal dorsal horn. Activation of GABA B receptors by exogenous agonists inhibits synaptic transmission, which is believed to underlie the GABA B receptor-mediated analgesia. However, little effort has been made to test whether endogenous GABA might also mediate inhibition by acting on GABA B receptors. In this study, whole-cell recording techniques were employed to study the effect of endogenous GABA on GABA B receptors in substantia gelatinosa (SG) neurons in adult rat spinal cord slices. In current-clamp mode, blockade of GABA B receptors by their selective antagonist 3-[[[(3,4-dichlorophenyl)methyl]amino]propyl] (diethoxy-methyl) phosphinic acid (CGP 52432) facilitated presynaptic stimulation-induced action potential discharge and increased amplitude of postsynaptic potentials (PSPs), meaning a GABA B receptor-mediated inhibition of SG neuron excitability. In voltage-clamp mode, blockade of GABA B receptors increased the amplitude of evoked excitatory postsynaptic currents (eEPSCs) and decreased paired-pulse ratio, indicating a presynaptic CGP 52432 action. Primary afferent Aδ or C fiber-evoked EPSCs were also facilitated by CGP 52432 application. Amplitudes of evoked GABAergic and glycinergic inhibitory postsynaptic currents (eIPSCs) were enhanced by GABA B receptor blockade. The facilitation of amplitude persisted in the presence of a specific GABA transporter 1 (GAT-1) blocker, tiagabine, or GAT-2/3 blocker SNAP5114. However, blockade of GABA B receptors had no effect on action potential-independent miniature EPSCs (mEPSCs), miniature IPSCs (mIPSCs), or membrane conductance. Taken together, these results suggest that endogenous GABA modulates evoked synaptic transmission in SG neurons by acting on GABA B receptors. This GABA B receptor-mediated homeostatic regulation of neuronal excitability and neurotransmitter release might contribute to modulation of nociception in spinal dorsal horn. © 2011 IBRO.


Moghissi E.S.,Clinical Force | Moghissi E.S.,University of California at Los Angeles
American Journal of Health-System Pharmacy | Year: 2010

Purpose. To review the risks of hyperglycemia in hospitalized patients, data supporting the benefits of treating hyperglycemia, and recommendations from the 2009 American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on the management of inpatient hyperglycemia. Summary. Inpatient hyperglycemia is common, costly, and associated with poor clinical outcomes in many disease states. Despite inconsistencies in clinical trial results, good glucose management in the hospital remains important. Target blood glucose concentrations (BGs) were recently modified to somewhat higher values with the expectation that the benefit of treatment will persist with a lower risk of hypoglycemia, which is itself another marker of poor outcome in critically and noncritically ill patients. In the intensive care unit (ICU), the threshold to start treatment is a BG of ≤180 mg/dL. I.V. insulin is the treatment of choice in critically ill patients because of its rapid onset and offset of action. Once i.v. insulin is started, the BG should be maintained between 140 and 180 mg/dL; a lower BG target (110-140 mg/dL) may be appropriate in selected patients. Targets of <110 mg/dL or >180 mg/dL are no longer recommended. In noncritically ill patients, premeal BG targets are <140 mg/dL; random BGs of <180 mg/dL are recommended. Scheduled subcutaneous insulin is the treatment of choice for hyperglycemia in noncritically ill patients; use of sliding-scale insulin is strongly discouraged. To avoid hypoglycemia, insulin regimens should be reassessed if BG falls to <100 mg/dL. Conclusion. Poor glycemic control in the hospital setting is a quality-of-care, safety, and cost issue. Safe and effective strategies to implement optimal glycemic control require multidisciplinary involvement. Insulin given i.v. in the ICU or subcutaneously on an as-scheduled regimen in other parts of the hospital is the treatment of choice. Copyright © 2010, American Society of Health-System Pharmacists, Inc. All rights reserved.


Ma Y.L.,Clinical Force
Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology | Year: 2010

The aim of this study was to investigate the effect of Celastrol on induction of HL-60 cell apoptosis and its possible mechanism. The proliferative activity of HL-60 cells treated with 0.25 - 8.0 μmol/L of Celastrol for 24 - 72 hours was assayed by MTT method, the effects of Celastrol on apoptosis and cell cycle of HL-60 were detected by TUNEL staining and flow cytometry with Annexin V-FITC/PI double labeling, the expression of pAkt and cyclin D1 at protein and gene level in HL-60 cells treated with Celastrol were measured by Western blot and RT-PCR. The results showed that the Celastrol could obviously inhibit the proliferation of HL-60 cells in concentration-and time-dependent manners, the IC value of Celastrol for 24 hours was 6.21 ± 0.242 μmol/L. The Celastrol concentration-dependently induced the apoptosis of HL-60 cells, accompanying with morphological changes of apoptotic cells, which may be related with arrest of cells in G/G phase. The Celastrol suppressed the expression of pAkt and Cyclin D1 in HL-60 cells to a varying degree which showed obvious concentration-and time-dependent manners. It is concluded that the Celastrol inhibits the proliferation and induced the apoptosis of HL-60 cells. Its mechanism may be related with down-regulation of p-Act and cyclin D1 expressions.


Xu X.,Clinical Force
Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology, head, and neck surgery | Year: 2012

To comparatively analyze the disease data of nasal sinus between helicopter and (strike) fighter pilots under flying qualification, and then to provide references for aeromedical support as a significant part of new logistics service union in army, The CT data of nasal sinus in 138 pilots who accepted physical examination for change to new-type aircraft, were collected included 46 cases of helicopter pilots and 92 cases of (strike)fighter pilots). The incidence of chronic sinusitis and cyst of nasal sinus were computed respectively in helicopter pilots and (strike)fighter pilots. (1) Fourteen cases suffered from chronic sinusitis (6 cases of maxillary sinusitis, 4 cases of ethmoiditis and 4 cases of maxillary sinusitis and ethmoiditis) in helicopter pilots whose incidence rate of chronic sinusitis was 30.4% (14/46). Of which, 3 cases of antracele were treated. Twelve cases suffered from chronic sinusitis (8 cases of maxillary sinusitis, 1 case of ethmoiditis, 3 cases of maxillary sinusitis and ethmoiditis) in (strike)fighter pilots whose incidence of chronic sinusitis was 13.0% (12/92). Of which, 1 case of antracele was treated. The incidence of chronic sinusitis was higher in helicopter pilots than (strike) fighters pilots (Chi2 = 6.07, P < 0.05). (2) Four cases suffered from unilateral mucosa cysts in maxillary sinus in helicopter pilots whose incidence of cyst of nasal sinus was 8.7% (4/46). Ten cases suffered from mucosa cysts in maxillary sinus (unilateral 8 cases and bilateral 2 cases) in (strike) fighters pilots whose incidence of cyst of nasal sinus was 10.87% (10/92). The difference of the incidence of cyst of nasal sinus was not statistically significant between the helicopter pilots and(strike)fighters pilots. The cysts of nasal sinus did not need treatment in 14 cases of this group data. The incidence of symptomless chronic sinusitis and cyst of nasal sinus are high in pilots. It is related with repeatedly changes of atmosphere pressure during flying. But most chronic sinusitis and cyst of nasal sinus do not need treatment. The incidence of chronic sinusitis is higher in helicopter pilots than(strike)fighter pilots. It may be related with the environment of helicopter which have unclosed cockpit and load other aircrew.


Objective: The construction of suicide plasmid vector could be used to make mutation of pgm gene which attenuates the virulent of Brucella melitensis strain 16, the research may lay a foundation for the development of novel live attenuated vaccines. Methods: Sucrose sensitive gene as forward screening sign and fusion sequences of kanamycin resistance gene were constructed based on plasmid puc19; pucS1.6K suicide plasmid vector was established by modifying pgm gene with fusion sequences of kanamycin resistance gene (insertion mutation); pgm gene mutation of Brucella melitensis strain 16 was obtained by electro transformation and mutation was confirmed by PCR amplification. Results: The results showed that the identified Brucella melitensis strain 16 pgm gene was inactivated after insertion of kanamycin resistance gene, and the mutant pgm gene DNA fragment length was approximately 3525 bp, in line with expectations, Brucella pgm gene mutant melitensis strain 16 was successfully constructed. Conclusions: The construction of suicide plasmid vector and precise mutation of Brucella melitensis strain 16 is successful, the study is not only provided an effective technology platform for constructing mutants of Brucella but also lays a foundation for the development of novel live attenuated vaccines.


Petalas K.,Clinical Force | Durham S.R.,Imperial College London
Rhinology | Year: 2013

Allergic rhinitis, a risk factor for bronchial asthma, is a global health problem that impairs patients' physical and social activity and consequently their quality of life. Specific Immunotherapy (SIT) involves the administration, subcutaneously or sublingually, of increasing doses of the causative allergen, in order to induce clinical and immunologic tolerance. SIT has been shown to be effective in those with a poor response to conventional drug therapy. Immunotherapy has been shown to have disease-modifying effects and result in long term remission of allergic symptoms and reduces the risk of progression from rhinitis to asthma, as well as the chances of developing new sensitizations to allergens. Injection immunotherapy is a safe treatment for allergic rhinitis with/without mild controlled asthma, provided that it is performed in the context of a harmonious interaction between trained medical personnel and appropriately selected patients. Immunotherapy suppresses early and late responses to allergen exposure by modifying both T-cell and B-cell responses to inhaled allergens. Immune deviation of allergen-specific T cell responses in favour of Th1 and/or the induction of regulatory T cells is crucial in achieving immune tolerance. Increased understanding of the mechanisms of immunotherapy has identified potential biomarkers of the response to treatment and highlighted new therapeutic pathways with potential for even more effective future standardized vaccines.


Petalas K.,Clinical Force
Rhinology | Year: 2013

Allergic rhinitis, a risk factor for bronchial asthma, is a global health problem that impairs patients` physical and social activity and consequently their quality of life. Specific Immunotherapy (SIT) involves the administration, subcutaneously or sublingually, of increasing doses of the causative allergen, in order to induce clinical and immunologic tolerance. SIT has been shown to be effective in those with a poor response to conventional drug therapy. Immunotherapy has been shown to have disease-modifying effects and result in long term remission of allergic symptoms and reduces the risk of progression from rhinitis to asthma, as well as the chances of developing new sensitizations to allergens. Injection immunotherapy is a safe treatment for allergic rhinitis with/without mild controlled asthma, provided that it is performed in the context of a harmonious interaction between trained medical personnel and appropriately selected patients. Immunotherapy suppresses early and late responses to allergen exposure by modifying both T-cell and B-cell responses to inhaled allergens. Immune deviation of allergen-specific T cell responses in favour of Th1 and/or the induction of regulatory T cells is crucial in achieving immune tolerance. Increased understanding of the mechanisms of immunotherapy has identified potential biomarkers of the response to treatment and highlighted new therapeutic pathways with potential for even more effective future standardized vaccines.


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