preparation-synaptic-plasma-membrane-postsynaptic-density-proteins

Preparation of Synaptic Plasma Membrane and Postsynaptic Density Proteins Using a Discontinuous Sucrose Gradient

Neuronal subcellular fractionation techniques allow the quantification of proteins that are trafficked to and from the synapse. As originally described in ...

University of Toronto

The aim of this case-control study was to assess the risk of developing multiple sclerosis (MS) associated with certain lifestyle factors (cigarette smoking and coffee and alcohol consumption). The study groups consisted of 210 cases with clinically proven and/or laboratory-confirmed MS (Poser's criteria) and an identical number of sex- and age-matched hospital controls. In the MS patients, cigarette smoking was significantly more frequent than in the controls (OR = 1.6, p = 0.021). A dose-response relationship between the risk of MS and both duration (years) of smoking (p = 0.027) and number of cigarettes smoked daily (p = 0.021) was observed. Coffee consumption was significantly more frequent in the MS group (OR = 1.7, p = 0.047), with dose-response relationships. The analysis of alcohol drinking showed a significant association between consumption of hard liquor per day and risk of MS (OR = 6.7, p = 0.026). In multivariate logistic regression analysis, smoking was detected to be a significant independent risk factor for MS (OR = 2.4, p = 0.004).

Lifestyle factors and multiple sclerosis: A case-control study in Belgrade.

Cytoreductive surgery and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) significantly improves patients survival with peritoneal carcinomatosis especially in low-grade tumor e.g. ovarian and appendiceal adenocarcinoma, peritoneal pseudomyxoma and grade I gastric and colorectal cancer.

Hemodynamic and cardiovascular problems during modified hyperthermic intraperitoneal perioperative chemotherapy.

NMDA receptors are key regulators of synaptic plasticity, and their hypofunction is thought to contribute to the pathophysiology of CNS disorders. Furthermore, NMDA receptors participate in the formation, maintenance, and elimination of synapses. The consequences of NMDA receptor hypofunction on synapse biology were explored in a genetic mouse model, in which the levels of NMDA receptors are reduced to 10% of normal levels (i.e., NR1-knockdown mice). In these mice, synapse number is reduced in an age-dependent manner; reductions are observed at the postpubertal age of 6 wk, but normal at 2 wk of age. Efforts to uncover the biochemical underpinnings of this phenomenon reveal synapse-specific reductions in 14-3-3ε protein and in Disrupted in Schizophrenia-1 (DISC1), two schizophrenia susceptibility factors that have been implicated in the regulation of spine density. Subchronic administration of MK-801, an NMDA receptor antagonist, produces similar synaptic reductions in both spine density and DISC1, indicating that synaptic levels of DISC1 are regulated by NMDA receptor function. The synaptic reduction of DISC1 and 14-3-3ε is developmentally correlated with the age-dependent decrease in striatal spine density.

Impaired NMDA receptor transmission alters striatal synapses and DISC1 protein in an age-dependent manner.

Recent studies have shown that biological treatments for rheumatoid arthritis can change the course of rheumatoid arthritis and improve functional ability of patients with rheumatoid arthritis. In spite of this fact, use of biological therapy is still limited by high prices of these medicines, especially in countries in socioeconomic transition. The aim of our study was to compare cost-effectiveness of a combination of tocilizumab and methotrexate with methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic transition.

Cost-effectiveness analysis of tocilizumab in combination with methotrexate for rheumatoid arthritis: a Markov model based on data from Serbia, country in socioeconomic transition.

Chronic N-methyl-d-aspartate receptor (NMDAR) hypofunction has been proposed as a contributing factor to symptoms of schizophrenia. However, it is unclear how sustained NMDAR hypofunction throughout development affects other neurotransmitter systems that have been implicated in the disease. Dopamine neuron biochemistry and activity were examined to determine whether sustained NMDAR hypofunction causes a state of hyperdopaminergia. We report that a global, genetic reduction in NMDARs led to a remodeling of dopamine neurons, substantially affecting two key regulators of dopamine homeostasis, i.e. tyrosine hydroxylase and the dopamine transporter. In NR1 knockdown mice, dopamine synthesis and release were attenuated, and dopamine clearance was increased. Although these changes would have the effect of reducing dopamine transmission, we demonstrated that a state of hyperdopaminergia existed in these mice because dopamine D2 autoreceptors were desensitized. In support of this conclusion, NR1 knockdown dopamine neurons have higher tonic firing rates. Although the tonic firing rates are higher, phasic signaling is impaired, and dopamine overflow cannot be achieved with exogenous high-frequency stimulation that models phasic firing. Through the examination of several parameters of dopamine neurotransmission, we provide evidence that chronic NMDAR hypofunction leads to a state of elevated synaptic dopamine. Compensatory mechanisms to attenuate hyperdopaminergia also impact the ability to generate dopamine surges through phasic firing.

Article	Year
Lifestyle factors and multiple sclerosis: A case-control study in Belgrade. Neuroepidemiology\| PubMed ID: 17095875	2006
Hemodynamic and cardiovascular problems during modified hyperthermic intraperitoneal perioperative chemotherapy. Hepato-gastroenterology\| PubMed ID: 17523275	2007
Impaired NMDA receptor transmission alters striatal synapses and DISC1 protein in an age-dependent manner. Proceedings of the National Academy of Sciences of the United States of America\| PubMed ID: 21436042	2011
Cost-effectiveness analysis of tocilizumab in combination with methotrexate for rheumatoid arthritis: a Markov model based on data from Serbia, country in socioeconomic transition. Vojnosanitetski pregled. Military-medical and pharmaceutical review\| PubMed ID: 24665571	2014
Sustained N-methyl-d-aspartate receptor hypofunction remodels the dopamine system and impairs phasic signaling. The European journal of neuroscience\| PubMed ID: 24754704	2014

Marija Milenkovic

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