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PubMed: bipolar AND (free fu...
NCBI: db=PubMed; Term=bipolar
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Brain-Derived Neurotrophic Factor Val/Met Polymorphism and Bipolar Disorder. Association of the Met Allele with Suicidal Behavior of Bipolar Patients.
Neuropsychobiology. 2008 Oct 9;58(2):97-103
Authors: Kim B, Kim CY, Hong JP, Kim SY, Lee C, Joo YH
Background/Aims: The substitution of valine by methionine in the brain-derived neurotrophic factor (BDNF Val/Met) gene alters the intracellular trafficking and regulated secretion of BDNF. This study tested whether the BDNF Val/Met polymorphism is associated with bipolar disorder in Korean subjects, and whether clinical features vary according to genotype. Methods: The allelic and genotypic distributions of BDNF Val/Met were determined in a population of 169 bipolar patients and 251 normal controls. Between-genotype comparisons of clinical features were performed without a priori knowledge of the genotype of individual patients. Results: Allelic distributions did not differ significantly between bipolar patients and controls (chi(2) = 0.400, p = 0.821). However, the rate of suicide attempts among the Val/Val (11.3%), Val/Met (28.8%) and Met/Met (38.9%) genotype groups were significantly different (chi(2) = 9.879, p = 0.007). Relative to patients with the Val/Val genotype, those with the Met/Met genotype had a 4.9-fold higher risk of suicide attempts (95% CI, 1.7-14.7). Conclusions: These findings suggest that BDNF Val/Met is related to the suicidal behavior of bipolar patients, and may have clinical relevance as a biological indicator of bipolar patients at risk of suicide.
PMID: 18843195 [PubMed - as supplied by publisher]
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Targeting of RGS7/Gbeta5 to the dendritic tips of ON-bipolar cells is independent of its association with membrane anchor R7BP.
J Neurosci. 2008 Oct 8;28(41):10443-9
Authors: Cao Y, Song H, Okawa H, Sampath AP, Sokolov M, Martemyanov KA
Complexes of regulator of G-protein signaling (RGS) proteins with G-protein beta5 (Gbeta5) subunits are essential components of signaling pathways that regulate the temporal characteristics of light-evoked responses in vertebrate retinal photoreceptors and ON-bipolar cells. Recent studies have found that RGS/Gbeta5 complexes bind to a new family of adapter proteins, R9AP (RGS9 anchor protein) and R7 family binding protein (R7BP), that in case of the RGS9/Gbeta5 complex were shown to determine its precise subcellular targeting to either the outer segment of photoreceptors or postsynaptic structures of striatal neurons, respectively. In this study, we establish that another trimeric complex consisting of RGS7, Gbeta5, and R7BP subunits is specifically targeted to the dendritic tips of retinal bipolar cells. However, examination of the mechanisms of complex targeting in vivo surprisingly revealed that the delivery of RGS7/Gbeta5 to the dendrites of ON-bipolar cells occurs independently of its association with R7BP. These findings provide a new mechanism for adapter-independent targeting of RGS/Gbeta5 complexes.
PMID: 18842904 [PubMed - in process]
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Two Calretinin-Positive GABAergic Cell Types in Layer 2/3 of the Mouse Neocortex Provide Different Forms of Inhibition.
Cereb Cortex. 2008 Oct 8;
Authors: Caputi A, Rozov A, Blatow M, Monyer H
Calretinin (CR)-positive GABAergic (gamma-aminobutyric acidergic) interneurons have been suggested to target preferentially other GABAergic cells in the neocortex. To systematically study this cell population in the cortex, we generated transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the CR promoter and characterized EGFP/CR-positive cells at the cellular and network level. Based on anatomical and electrophysiological characteristics, 2 types of EGFP/CR-positive cells could be distinguished that we termed bipolar (BCR) and multipolar (MCR) CR cells. Both cell types share the feature of preferential interneuron targeting but differ in most other characteristics, including firing pattern, biochemical markers, neurite arborization, and synaptic plasticity. Like many other GABAergic interneurons, BCR cells but not MCR cells exhibit restricted cell type-specific gap junction coupling. Notably, MCR cells are electrically coupled in an asymmetric fashion with GABAergic interneurons of another subtype, the parvalbumin-positive multipolar bursting (MB) cells. Most importantly, the strength of electrical coupling between MCR and MB cells underlies their synchronous activation during carbachol-induced oscillations.
PMID: 18842664 [PubMed - as supplied by publisher]
Vestibulospinal responses in motor incomplete spinal cord injury.
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Vestibulospinal responses in motor incomplete spinal cord injury.
Clin Neurophysiol. 2008 Oct 6;
Authors: Liechti M, Müller R, Lam T, Curt A
OBJECTIVE: Postural instability limits ambulatory capacity in patients with spinal cord injury (SCI). Galvanic vestibular stimulation (GVS) was used to investigate the integrity of vestibulospinal pathways and related changes in postural responses in SCI. METHODS: Binaural bipolar galvanic stimuli of 400ms duration and 3mA intensity were applied in 8 motor incomplete SCI and 8 control subjects who stood facing towards the left. EMG responses were recorded from the right soleus muscle and the trajectory of the centre of pressure (CoP) was measured with a force plate. RESULTS: There was no difference in excitability and amplitude of the responses between the groups. However, the latency and duration of the medium latency EMG response and all CoP responses were significantly longer in the SCI group. Additionally, postural stability was reduced in the SCI group, as shown by a greater tendency to fall due to GVS. CONCLUSIONS: Despite early EMG responses proving the basic connectivity of the direct vestibulospinal pathways, the delayed GVS responses suggest a vestibulospinal deficit in the SCI subjects. SIGNIFICANCE: GVS can be applied in incomplete SCI to supplement the neurological examination by revealing changes in vestibulospinal responses and impairment of postural stability.
PMID: 18842452 [PubMed - as supplied by publisher]
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Evaluation of plasma antioxidant levels during different phases of illness in adult patients with bipolar disorder.
J Biol Regul Homeost Agents. 2008 Jul-Sep;22(3):195-200
Authors: De Berardis D, Conti CM, Campanella D, Carano A, Di Giuseppe B, Valchera A, Tancredi L, Serroni N, Pizzorno AM, Fulcheri M, Gambi F, Sepede G, Moschetta FS, Salerno RM, Ferro FM
The aim of the present study is to evaluate role of plasma antioxidants (albumin, bilirubin and uric acid) in patients suffering from type I Bipolar Disorder (BD-I) during different phases of illness: acute mania, euthymia and bipolar depression. Medical records of consecutive 110 BD-I patients (38 patients with acute mania, 35 in euthymic state, full remission, and 37 in depressive phase) were reviewed to evaluate plasma antioxidant levels. Laboratory data of 40 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. Serum uric acid levels were higher in acute mania than other patient subgroups and healthy controls. Serum uric acid levels directly correlated with BRMRS and YMRS scores. No differences were found between clinical groups during different phases and healthy controls concerning albumin and bilirubin. In conclusion, the results of the present study support the notion that serum uric acid levels may be higher in patients with BP-I (especially during manic phases) which may suggest a dysregulation of the purinergic system. However, limitations should be considered and further studies are needed.
PMID: 18842173 [PubMed - in process]
[Antiepileptic drugs as mood stabilizers: what did we learn from the epileptology?]
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[Antiepileptic drugs as mood stabilizers: what did we learn from the epileptology?]
Ideggyogy Sz. 2008 Sep 30;61(9-10):305-16
Authors: Rajna P
Author summarizes the practical aspects of psychiatric application of mood stabilizing antiepileptic drugs. He observes how to transfer experiences taken from the "epileptological" practice into the psychiatric care of bipolar patients. He shortly demonstrates the relevant information on the mechanisms of action, controversies and possible clinical effects influenced by the seizure inhibiting effect of the concerning molecules. By the opinion of the author the clinical importance of pharmacokinetic parameters are underestimated in the psychiatric practice. Therefore--as an original approach in the literature--he summarizes the detailed clinical indications of serum level measurements of antiepileptic drugs applied in psychiatry as mood stabilizers. The therapeutic experiences in epilepsy added a lot of practices for the most effective dosing, building, tapering and exchange of the mood stabilizer antiepileptics. Drug interactions (appear among the psychotropic drugs or with the commonly used medicines). As in any chronic therapies the main condition of patient's compliance is the lacking or very mild presence of the applied therapy. The paper discusses the most frequently occurring and drug-specific side effects in table forms. Using the term of "relative therapeutic potential" the need of balance between the efficacy (influenced by the choice and dosing) and the tolerance are pointed. Rules of application can change significantly in special populations like in pregnancy, obesity, chronic diseases or in chronic comorbide states and in case of polytherapy. As for the special therapeutic effects, the experiences are not completed even in group of antiepileptics: we have larger and more favorable knowledge on the traditional drugs (carbamazepine and valproates) and on lamotrigine (from the newer generation) but promising but not enough information exists on the newest antiepileptic molecules. Further targeted studies are needed for the identification and positioning of antiepileptic drugs in the palette of mood stabilizing pharmacotherapy and for the definition of evidence based, individually tailored and lifelong applied highly effective combinations of the mood stabilizing pharmacotherapy containing antiepileptic agents.
PMID: 18841650 [PubMed - in process]
Reliability and validity of the Korean version of UKU-SERS-Pat in patients with bipolar disorder.
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Reliability and validity of the Korean version of UKU-SERS-Pat in patients with bipolar disorder.
Nord J Psychiatry. 2008 Oct 7;:1-17
Authors: Kim JH, Choi SW, Joe SH, Ha TH, Yoo HJ, Choi JE, Cha B, Ha K
Poor drug compliance caused by side effects is an important factor affecting clinical outcomes. Thus reliable and valid rating scales to accurately evaluate the side effects of medications in their early stages are needed. This study aimed to develop the Korean version of the Udvalg for Kliniske Undersøgelser (UKU) Side Effects Rating Scale for Patients (K-UKU-SERS-Pat) to comprehensively measure side effects of psychotropic medications by the self-report method and to examine reliability and validity in patients with bipolar disorder (BD). Ninety-three patients diagnosed with BD by DSM-IV criteria were recruited in this study. The patients completed the K-UKU-SERS-Pat. The Side Effects Rating Scale for Clinicians was administered simultaneously. In 19 patients, the K-UKU-SERS-Pat was conducted twice on a 3-day interval to examine the test-retest reliability. Depressive symptoms were evaluated with the Hamilton Depression Rating Scale-17 and (hypo)manic symptoms with the Young Mania Rating Scale. The test-retest reliability (rho = 0.89, P<0.01) and the concurrent validity (rho = 0.80, P<0.01) of K-UKU-SERS-Pat were good. However, patients had a tendency to report their side effects more frequently and severely than clinicians. The K-UKU-SERS-Pat is proved to be a reliable and valid tool to comprehensively and practically monitor the side effects of psychotropics.
PMID: 18841509 [PubMed - as supplied by publisher]
Evolutionary analysis of PHLPP1 gene in humans and non-human primates.
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Evolutionary analysis of PHLPP1 gene in humans and non-human primates.
Bioinformation. 2008;2(10):471-4
Authors: Anbazhagan P, Purushottam M, Kumar HB, Kubendran S, Mukherjee O, Brahmachari SK, Jain S, Sowdhamini R
The chromosome 18q22-23 region has been shown to be implicated in bipolar disorder (BPAD) by several studies. PHLPP1 gene, in the locus (chromosome 18q22-23), is involved in circadian pathways and bears modules like 'PH domain and leucine rich repeat protein phosphatase'. This gene also contains a polyglutamine (CAG or PolyQ) repeat motif at the carboxyl terminal end. A comparative analysis of the PolyQ repeats of the PHLPP1 gene in humans, non-human primates and other species has been attempted in order to investigate the possible significance of repeat length as seen in other triplet-repeat associated diseases. Sequencing of the CAG repeat in humans and in non-human primates revealed that the CAG repeat is not polymorphic in humans; whereas, in other species it shows an area of high variability, both in length and sequence composition. Despite the conservation of circadian clock components in different species, there is remarkable diversity in the protein structure, regulation and biochemical functions of the circadian orthologs. These can be due to specific adaptations in accordance with the physiology of the particular species providing a species-specific biological advantage.
PMID: 18841245 [PubMed - in process]
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Evolutionary analysis of WD40 super family proteins involved in spindle checkpoint and RNA export: Molecular evolution of spindle checkpoint.
Bioinformation. 2008;2(10):461-8
Authors: Reddy DM, Aspatwar A, Dholakia BB, Gupta VS
The spindle checkpoint delays sister chromatid separation until all chromosomes have undergone bipolar spindle attachment. Previous studies have revealed BUB3, as an essential spindle checkpoint protein and its extensive sequence similarity with Rae1 (Gle2), a highly conserved member of WD40 repeat protein family throughout their length which was first shown to be involved in mRNA export. However, the recent discovery of Rae1 as an essential mitotic checkpoint protein, based on the studies from mouse and drosophila, has renewed the interest in its function during cell division. Study of evolution of proteins involved in checkpoint might throw light on evolution of eukaryotic cell cycle regulation. Here we report the evolutionary relationships between these two WD40 repeat family proteins. Amino acid sequences of BUB3 and Rae1 homologs were retrieved from various databases and phylogenetic analysis was performed with the MEGA program. Multiple sequence alignments of these two protein homologues with the ClustalX software revealed specific amino acid signatures corresponding to the protein function and also few amino acids, which are conserved in BUB3 and Rae1 indicating some common overlapping function. Data indicated a common ancestral origin of these two important proteins and further suggest that, BUB3 mediated cell cycle checkpoint might have evolved with compartmentalization of genetic material into the nucleus in eukaryotes.
PMID: 18841243 [PubMed - in process]
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Treatment of fluoride containing drinking water by electrocoagulation using monopolar and bipolar electrode connections.
Chemosphere. 2008 Oct 5;
Authors: Ghosh D, Medhi CR, Purkait MK
Electrocoagulation was investigated for the effective removal of fluoride from drinking water. Different initial concentrations (2-10mgL(-1)) of fluoride were considered for the experiment. Two different electrode connections (monopolar and bipolar) were examined for choosing the better alternative in order to intensify the performance of the process. It was observed that the removal of fluoride was better for bipolar connection than for monopolar connection. The final recommendable limit of fluoride (1mgL(-1)) was obtained in 30min at 625Am(-2) using bipolar connection. The corrosion of electrodes as well as the sludge formed during the process was estimated for the bipolar connection. Thickness of film generated on the electrode surfaces in bipolar connection was also estimated at different current densities as well as for different initial fluoride concentrations. By-products obtained from the electrocoagulation bath were analyzed using SEM, EDAX, FTIR and XRD and explained. Comparative cost estimation for both electrode connections was adopted and presented as well. Total operating costs for monopolar and bipolar connections were 0.38 and 0.62US$m(-3), respectively, for the initial fluoride concentration of 10mgL(-1). These findings might be useful in order to treat the fluoride contaminated water for drinking.
PMID: 18840387 [PubMed - as supplied by publisher]
[A rat model for cochlear implant research]
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[A rat model for cochlear implant research]
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2008 Jul;22(13):603-5
Authors: Lu W, Xu J, Shepherd RK
OBJECTIVE: To introduce a rat model for use in cochlear implant related research. METHOD: Five deafened Hooded-Wistar rats were implanted with a scala tympani electrode array using a new surgical method. Electrically evoked brainstem responses (EABRs) using bipolar stimulation were recorded and cochlear histogy was assessed. RESULT: Electrically evoked brainstem responses with normal configuration confirmed the functional status of the cochlear implantation. There was no evidence of severe insertion-induced damage of intra-cochlear structure. CONCLUSION: The surgical method established in the rat model is a safe and effective procedure for acute or chronic cochlear implantation.
PMID: 18839880 [PubMed - in process]
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Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances.
Mol Psychiatry. 2008 Aug;13(8):786-99, 741
Authors: Wang SS, Kamphuis W, Huitinga I, Zhou JN, Swaab DF
Hyperactivity of corticotropin-releasing factor (CRF) neurons in the paraventricular nucleus (PVN) of the hypothalamus is a prominent feature in depression and may be important in the etiology of this disease. The activity of the CRF neurons in the stress response is modulated by a number of factors that stimulate or inhibit CRF expression, including (1) corticosteroid receptors and their chaperones, heat shock proteins 70 and 90, (2) sex hormone receptors, (3) CRF receptors 1 (CRFR1) and 2, (4) cytokines interleukin 1-beta and tumor necrosis factor-alpha, (5) neuropeptides and receptors, vasopressin (AVP), AVP receptor 1a (AVPR1A) and oxytocin and (6) transcription factor cAMP-response element-binding protein. We hypothesized that, in depression, the transcript levels of those genes that are involved in the activation of the hypothalamo-pituitary-adrenal (HPA) axis are upregulated, whereas the transcript levels of the genes involved in the inhibition of the HPA axis are downregulated. We performed laser microdissection and real-time PCR in the PVN and as a control in the supraoptic nucleus. Snap-frozen post-mortem hypothalami of seven depressed and seven matched controls were used. We found significantly increased CRF mRNA levels in the PVN of the depressed patients. This was accompanied by a significantly increased expression of four genes that are involved in the activation of CRF neurons, that is, CRFR1, estrogen receptor-alpha, AVPR1A and mineralocorticoid receptor, while the expression of the androgen receptor mRNA involved in the inhibition of CRF neurons was decreased significantly. These findings raise the possibility that a disturbed balance in the production of receptors may contribute to the activation of the HPA axis in depression.
PMID: 18427561 [PubMed - indexed for MEDLINE]
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Sustained low-efficiency dialysis with filtration (SLEDD-f) in the management of acute sodium valproate intoxication.
Hemodial Int. 2008 Apr;12(2):211-4
Authors: Khan E, Huggan P, Celi L, MacGinley R, Schollum J, Walker R
Hemodialysis is only infrequently used in drug overdosage situations. The efficacy of hemodialysis to remove the drug depends upon the pharmacokinetics and pharmacodynamics of the drug. At normal therapeutic concentrations, valproic acid is predominantly protein bound and therefore removal by hemodialysis is limited. In an overdose situation, protein binding is rapidly saturated and therefore the substantially larger quantities of the free drug can rapidly cause toxicity. Slow low-efficient daily diafiltration (SLEDD) has not previously been utilized in a drug overdose situation. We report the effective use of SLEDD to remove high toxic concentrations of valproic acid in an overdose situation. Slow low-efficient daily diafiltration also prevented the rebound phenomenon that can occur as the excess drug is released from its protein-bound stores. Hybrid dialysis therapies deserve further evaluation in the management of other poisonings where extra-corporeal therapy is indicated.
PMID: 18394052 [PubMed - indexed for MEDLINE]
