7 research outputs found
The routine use of pediatric airway exchange catheter after extubation of adult patients who have undergone maxillofacial or major neck surgery: a clinical observational study
No full textFirst international paired exchange kidney transplantations of Turkey
No full textObjective. We estimated that many patients on the waiting list for kidney transplantation in Turkey have immunologicaly incompatible suitable living donors. Paired exchange kidney transplantation (PETx) is superior to desensitization for patients with incompatible donors. Recently we decided to begin an international PETx program. Methods. We report three international living related paired kidney transplantations which occurred between May 14,2013, and March 7, 2014. The international donor and recipient operations were performed at Medical Park Hospital, Antalya, Turkey. All pairs were living related and written proofs were obtained according to Turkish laws. As with the donor procedures, the transplantation procedures were performed at the same time. Results. The uniqueness of these transplantations was that they are the first international exchange kidney transplantations between Turkey and Kirghizia. Currently all recipients are alive with wel-functioning grafts. Conclusion. In our institute, a 5% increase was obtained in living-related kidney transplantations by the help of PETx on a national basis. We believe that international PETx may also have the potential to expand the donor pool
Inhibition of phosphatase activity facilitates the formation and maintenance of NMDA-induced calcium/calmodulin-dependent protein kinase ii clusters in hippocampal neurons
No full textAuthor Posting. © The Authors, 2004. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Neuroscience 130 (2005), doi:10.1016/j.neuroscience.2004.10.008.The majority of hippocampal neurons in dissociated cultures and in intact brain exhibit clustering of CaMKII into spherical structures with an average diameter of 110 nm when subjected to conditions that mimic ischemia and excitotoxicity (Tao-Cheng et al., 2001). Because clustering of CaMKII would reduce its effective concentration within the neuron, it may represent a cellular strategy to prevent excessive CaMKII-mediated phosphorylation during episodes of Ca2+ overload. Here we employ a relatively mild excitatory stimulus to promote sub-maximal clustering for the purpose of studying the conditions for the formation and disappearance of CaMKII clusters. Treatment with 30 µM NMDA for 2 min produced CaMKII clustering in ~15 percent of dissociated hippocampal neurons in culture, as observed by pre-embedding immunogold electron microscopy. These CaMKII clusters could be labeled with antibodies specific to the phospho form (Thr286) of CaMKII, suggesting that at least some of the CaMKII molecules in clusters are autophosphorylated. To test whether phosphorylation is involved in the formation and maintenance of CaMKII clusters, the phosphatase inhibitors calyculin A (5 nM) or okadaic acid (1 µM) were included in the incubation medium. With inhibitors more neurons exhibited CaMKII clusters in response to 2 min NMDA treatment. Furthermore, 5 min after the removal of NMDA and Ca2+, CaMKII clusters remained and could still be labeled with the phospho-specific antibody. In contrast, in the absence of phosphatase inhibitors, no clusters were detected 5 min after the removal of NMDA and Ca2+ from the medium. These results suggest that phosphatases type 1 and/or 2A regulate the formation and disappearance of CaMKII clusters.Supported by NINDS intramural funds and National Science Foundation grant 9817317 to A. D
Distribution of postsynaptic density (PSD)-95 and Ca2+/calmodulin-dependent protein kinase II at the PSD
No full textAuthor Posting. © Society for Neuroscience, 2003. This article is posted here by permission of Society for Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Neuroscience 23 (2003): 11270-11278.Postsynaptic densities (PSDs) contain proteins that regulate synaptic transmission. We determined the positions of calcium/calmodulin-dependent protein kinase II (CaMKII) and PSD-95 within the three-dimensional structure of isolated PSDs using immunogold labeling, rotary shadowing, and electron microscopic tomography. The results show that all PSDs contain a central mesh immediately underlying the postsynaptic membrane. Label for PSD-95 is found on both the cytoplasmic and cleft sides of this mesh, averaging 12 nm from the cleft side. All PSDs label for PSD-95. The properties of CaMKII labeling are quite different. Label is virtually absent on the cleft sides of PSDs, but can be heavy on the cytoplasmic side at a mean distance of 25 nm from the cleft. In tomograms, CaMKII holoenzymes can be visualized directly, appearing as labeled, tower-like structures reflecting the 20 nm diameter of the holoenzyme. These towers protrude from the cytoplasmic side of the central mesh. There appears to be a local organization of CaMKII, as judged by fact that the nearest-neighbor distances are nearly invariant over a wide range of labeling density for CaMKII. The average density of CaMKII holoenzymes is highly variable, ranging from zero to values approaching a tightly packed state. This variability is significantly higher than that for PSD-95 and is consistent with an information storage role for CaMKII.This work was supported by National Institute of Neurological Disorders and Stroke Grants RO1 NS-27337 and
RO1 NS-35083 (J.L.)
Persistent accumulation of calcium/calmodulin-dependent protein kinase II in dendritic spines after induction of NMDA receptor-dependent chemical long-term potentiation
No full textAuthor Posting. © Society for Neuroscience, 2004. This article is posted here by permission of Society for Neuroscience for personal use, not for redistribution. The definitive version was published in Journal of Neuroscience 24 (2004): 9324-9331, doi:10.1523/JNEUROSCI.2350-04.2004.Calcium/calmodulin-dependent protein kinase II (CaMKII) is a leading candidate for a synaptic memory molecule because it is persistently activated after long-term potentiation (LTP) induction and because mutations that block this persistent activity prevent LTP and learning. Previous work showed that synaptic stimulation causes a rapidly reversible translocation of CaMKII to the synaptic region. We have now measured green fluorescent protein (GFP)-CaMKIIα translocation into synaptic spines during NMDA receptor-dependent chemical LTP (cLTP) and find that under these conditions, translocation is persistent. Using red fluorescent protein as a cell morphology marker, we found that there are two components of the persistent accumulation. cLTP produces a persistent increase in spine volume, and some of the increase in GFP-CaMKIIα is secondary to this volume change. In addition, cLTP results in a dramatic increase in the bound fraction of GFP-CaMKIIα in spines. To further study the bound pool, immunogold electron microscopy was used to measure CaMKIIα in the postsynaptic density (PSD), an important regulator of synaptic function. cLTP produced a persistent increase in the PSD-associated pool of CaMKIIα. These results are consistent with the hypothesis that CaMKIIα accumulation at synapses is a memory trace of past synaptic activity.This work was supported by Grant R01 NS-27337 from the National Institutes of Health/National Institute of
Neurological Disorders and Stroke
The use of mobile phones and the risk of brain tumors among children and adolescents
No full textMobile phones experienced a steep rise in popularity among children and adolescents during the last decade. The increase in popularity has been reflected in both increased ownership and increased usage of mobile phones. Most children start to use mobile phones when they are around 9–10 years old, but usage before school age is not uncommon. The increase in mobile phone use has raised concerns about possible adverse health effects. Brain tumors have been a main concern because the brain absorbs most of the radio frequency energy emitted by mobile phones during calls. In addition, it has been hypothesized that children may be more vulnerable to radio frequency electromagnetic fields (RF-EMFs) because their nervous system is developing, their brain tissue is more conductive than that of adults, and RF-EMFs penetrate in to regions that are deeper in their brains. Radio frequency radiation emitted by mobile phones has insufficient energy to directly damage the DNA and the only known effect of RF-EMFs is heating of the tissue. Studies about mobile phone use and brain tumor risk among adults have shown no increased risk for regular users but have been inconclusive regarding long-term (≥10 years) and heavy mobile phone use. The largest case-control study so far, INTERPHONE, found an increased risk for glioma among heavy users (≥1640 lifetime calls). Another study from a Swedish research group reported a five-fold increased risk for astrocytoma for adults who first used mobile phones before the age of 20. No study has addressed the association between mobile phone use and brain tumor risk among children and adolescents so far. The goal of this thesis was to assess whether there is a relationship between mobile phone use and brain tumor risk among children and adolescents or not. In 2006, we set up CEFALO, an international case-control study about the relationship between mobile phone use and brain tumor risk in children and adolescents aged 7–19 years. CEFALO was performed in Denmark, Sweden, Norway, and Switzerland. The study period ranged from 2004 through 2008. Children and adolescents of age 7–19 years who were diagnosed during the study period with a primary brain tumor were eligible. For each case patient, we selected two healthy controls matched by age, sex and geographical region of residence using population registries. Exposure data was collected by face to face interviews with the study participants accompanied by at least one parent. Risk estimates for brain tumors were calculated for various exposure surrogates. We also examined the gender and age-adjusted brain tumor incidence rates among Swedish children and adolescents aged 5–19 years from 1990 to 2008 including hypothetical incidence rate trends based on the risk estimates found in our analyses. Lastly, we compared the self-reported amount of mobile phone use with objectively recorded data by network operators. Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with non-regular users (OR=1.36, 95%-CI: 0.92 to 2.02). No clear exposure-response relationship was observed for any exposure surrogate. Moreover, no exposure-response relationship was seen in terms of localization of the tumor. For the study participants for whom operator-recorded data were available, we found a statistically significantly increased risk among users with more than 2.8 years since the start of the first subscription (OR=2.15). The odds ratio for brain tumor risk among ipsilateral regular users of mobile phones was not higher than the odds ratio of contralateral regular users. The risk estimate of 2.15 after 3 years of regular mobile phone use is incompatible with the stable (or even downward) incidence trends observed among Swedish children and adolescents aged 5–19 years from 1990 to 2008. This indicates that short-term use of mobile phones does not cause brain tumors in children and adolescents. In the validation study, cases overestimated their cumulative number of calls by 9% on average and controls by 34%. Cases also overestimated their cumulative duration of calls by 52% on average and controls by 163%. We found little evidence for differential recall errors. CEFALO is the first study to investigate the relationship between mobile phone use and brain tumor risk in children and adolescents. We found no consistent evidence for a causal association between short-term mobile phone use and brain tumor risk among children and adolescents. The lack of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal relationship. These findings are corroborated by the fact that brain tumor incidence rates among children and adolescents have not increased in many countries in recent times. We cannot, however, exclude the possibility of a small increase in brain tumor risk due to mobile phone use. As we found that self-reported mobile phone use is affected with large random and some systematic recall errors, we emphasize the importance of future studies with objective exposure assessment or the use of prospectively collected exposure data. We also recommend the monitoring of time trends in brain tumor incidence rates as increased risks should be reflected in future brain tumor incidence rate trends
Cannabinoids for the control of experimental multiple sclerosis
No full textPhDThere have been numerous studies reporting that cannabinoids, both exogenous
and endogenous, have a potential beneficial function during incidences of
neurological damage. Using gene knockout mice and cannabinoid-selective agents,
this study demonstrates the diverse actions of cannabinoids with a particular focus
on experimental autoimmune encephalomyelitis, an animal model of multiple
sclerosis. The results presented here report on the action of stimulators of
cannabinoid receptors in the nervous system (CNS) on; immune function, as a
mechanism of suppressing autoimmune attack of the central nervous system, as
agents to suppress neurodegenerative events leading to disease progression and as
agents that can control signs of disease that occur as the consequences of
autoimmune neurodegeneration such as spasticity. Tetrahydrocannabinol the
psychoactive component in cannabis and the CB1 cannabinoid receptor appears to
be central to many of the therapeutic actions of cannabis but also to the side-effect
potential of cannabinoid drugs. This study reports on methods to avoid
psychoactive side-effects of conventional brain-penetrant CB1 receptor agonists
whilst exploiting the therapeutic potential of the cannabinoid system in order to
control spasticity. This was achieved by targeting mechanisms of endocannabinoid
degradation, particularly using fatty acid amide hydrolase inhibitors. Furthermore,
this study also reports the development of novel cannabinoid compounds that are
excluded from the brain and inhibit spasticity and also demonstrates the
mechanism of exclusion of CNS-excluded cannabinoid CB1 receptor agonists. This
study provides further evidence for the efficacy of cannabinoid compounds during
an ongoing CNS disease and also their efficacy for treating the consequences of
CNS autoimmune disease, which hopefully, will give additional impetus for further
clinical investigations of cannabinoid agents in not only multiple sclerosis but also
other neurodegenerative diseases of the CNS
