Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

Genome characterization of a new strain of peanut chlorotic streak virus causing chlorotic vein banding disease of groundnut (Arachis hypogaea L.) in India

The double-stranded DNA of the chlorotic vein banding isolate of peanut chlorotic streak caulimovirus (PC1SV-CVB), isolated from purified virus, resolved into circular and linear molecules similar to those of other caulimoviruses. A physical map of viral DNA was constructed, which showed the PCLSV-CVB DNA to be circular and composed of approximately 8.2 kbp. A number of restriction sites were found to be shared with a similar caulimovirus, PCLSV. Nevertheless, several differences between physical maps of the 2 viruses suggested that PCLSV-CVB should be considered as a distinct strain of PCLSV. Bam HI-cleaved PCLSV-CVB DNA was cloned into pUC 118 and was infectious when cleaved from the cloning vector and inoculated onto Vigna unguiculata [cowpeas]

Shell occupancy of the intertidal hermit crab Clibanarius erythropus (Decapoda, Diogenidae) on São Miguel (Azores).

Copyright © 2000 Kluwer Academic Publishers. Printed in the Netherlands.The intertidal hermit crab Clibanarius erythropus was collected at three sites on São Miguel (Azores) during low spring tides. Shells occupied were identified and measured. Crab sizes ranged from 1.78 to 13.67 mm (cephalothoracic shield length), with an average size of 4.40 +- 1.44 mm. Of the 19 different shells utilised, the most frequent were Littorina striata (23.8%), Nassarius incrassatus (22.5%) and Mitra sp. (22.0%). At Fenais da Luz. L. strita was most frequently occupied, while at Água de Alto it was N. incrassatus and, at Caloura, Mitra sp. shells were most frequently used. Shell selection appears to be determined by respective sizes of hermit crab and shell species. Small size-class crabs occupy more shell species than larger crabs. The smallest crab was found at Fenais da Luz occupying a small Bittium sp., whereas the largest crab was found at Caloura inhabiting Stramonita haemastoma

Transgene integration - an analysis in autotransgenic Labeo rohita Hamilton (Pisces: Cyprinidae)

Transgenic Labeo rohita founder population was analyzed for the presence of autotransgene having histone 3 promoter and growth hormone (GH) cDNA (LRH3-GHcDNA) or total GH gene (LRH3-GH2.8) by PCR with transgene specific primers. Transgene specific amplification was seen with LRH3-GHcDNA in five out of seven individuals and all three fishes with LRH3-GH2.8, indicating their transgenic nature. Transgene integration was also studied by Southern hybridization of DNA isolated from blood of the transgenic fishes with two different probes (histone 3 promoter and cDNA of L. rohita). Autotransgene integration was confirmed in all PCR positive transgenic individuals. The site of integration of the transgene in the genome of the four transgenic fish could be determined by inverse PCR. Two individuals showed integration at the same site whereas in the remaining two individuals the integration sites were different

Mucinous cystic neoplasm of the pancreas in a male patient

Mucinous cystic neoplasms (MCNs) make up a morphologic family of similar appearing tumors arising in the ovary and various extraovarian organs such as pancreas, hepatobiliary tract and mesentery. MCNs of the pancreas occur almost exclusively in women. Here, we report a rare case of MCN in a male patient. A 39-year-old man was admitted to our hospital with the chief complaint of back pain. Abdominal computed tomography revealed a multilocular cyctic mass 6.3 cm in diameter in the pancreatic tail. In addition, the outer wall and septae with calcification were demonstrated in the cystic lesion. On magnetic resonance imaging , the cystic fluid had low intensity on T1-weighted imaging and high intensity on T2-weighted imaging. Endoscopic retrograde cholangio-pancreatography (ERCP) showed neither communication between the cystic lesion and the main pancreatic duct nor encasement of the main pancreatic duct. Endoscopic ultrasonography revealed neither solid component nor thickness of the septae in the cystic lesion. Consequently, we performed distal pancreatectomy with splenectomy under the diagnosis of cystic neoplasia of the pancreas. Histopathologically, the cystic lesion showed two distinct component: an inner epithelial layer and an outer densely cellular ovarian-type stromal layer. Based on these findings, the cystic lesion was diagnosed as MCN

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Hydroimidazolone Modification of the Conserved Arg12 in Small Heat Shock Proteins: Studies on the Structure and Chaperone Function Using Mutant Mimics

Methylglyoxal (MGO) is an α-dicarbonyl compound present ubiquitously in the human body. MGO reacts with arginine residues in proteins and forms adducts such as hydroimidazolone and argpyrimidine in vivo. Previously, we showed that MGO-mediated modification of αA-crystallin increased its chaperone function. We identified MGO-modified arginine residues in αA-crystallin and found that replacing such arginine residues with alanine residues mimicked the effects of MGO on the chaperone function. Arginine 12 (R12) is a conserved amino acid residue in Hsp27 as well as αA- and αB-crystallin. When treated with MGO at or near physiological concentrations (2–10 µM), R12 was modified to hydroimidazolone in all three small heat shock proteins. In this study, we determined the effect of arginine substitution with alanine at position 12 (R12A to mimic MGO modification) on the structure and chaperone function of these proteins. Among the three proteins, the R12A mutation improved the chaperone function of only αA-crystallin. This enhancement in the chaperone function was accompanied by subtle changes in the tertiary structure, which increased the thermodynamic stability of αA-crystallin. This mutation induced the exposure of additional client protein binding sites on αA-crystallin. Altogether, our data suggest that MGO-modification of the conserved R12 in αA-crystallin to hydroimidazolone may play an important role in reducing protein aggregation in the lens during aging and cataract formation

Galectin-9/TIM-3 Interaction Regulates Virus-Specific Primary and Memory CD8+ T Cell Response

In this communication, we demonstrate that galectin (Gal)-9 acts to constrain CD8+ T cell immunity to Herpes Simplex Virus (HSV) infection. In support of this, we show that animals unable to produce Gal-9, because of gene knockout, develop acute and memory responses to HSV that are of greater magnitude and better quality than those that occur in normal infected animals. Interestingly, infusion of normal infected mice with α-lactose, the sugar that binds to the carbohydrate-binding domain of Gal-9 limiting its engagement of T cell immunoglobulin and mucin (TIM-3) receptors, also caused a more elevated and higher quality CD8+ T cell response to HSV particularly in the acute phase. Such sugar treated infected mice also had expanded populations of effector as well as memory CD8+ T cells. The increased effector T cell responses led to significantly more efficient virus control. The mechanisms responsible for the outcome of the Gal-9/TIM-3 interaction in normal infected mice involved direct inhibitory effects on TIM-3+ CD8+ T effector cells as well as the promotion of Foxp3+ regulatory T cell activity. Our results indicate that manipulating galectin signals, as can be achieved using appropriate sugars, may represent a convenient and inexpensive approach to enhance acute and memory responses to a virus infection

Expression profile analysis of the inflammatory response regulated by hepatocyte nuclear factor 4α

<p>Abstract</p> <p>Background</p> <p>Hepatocyte nuclear factor 4α (HNF4α), a liver-specific transcription factor, plays a significant role in liver-specific functions. However, its functions are poorly understood in the regulation of the inflammatory response. In order to obtain a genomic view of HNF4α in this context, microarray analysis was used to probe the expression profile of an inflammatory response induced by cytokine stimulation in a model of HNF4α knock-down in HepG2 cells.</p> <p>Results</p> <p>The expression of over five thousand genes in HepG2 cells is significantly changed with the dramatic reduction of HNF4α concentration compared to the cells with native levels of HNF4α. Over two thirds (71%) of genes that exhibit differential expression in response to cytokine treatment also reveal differential expression in response to HNF4α knock-down. In addition, we found that a number of HNF4α target genes may be indirectly mediated by an ETS-domain transcription factor ELK1, a nuclear target of mitogen-activated protein kinase (MAPK).</p> <p>Conclusion</p> <p>The results indicate that HNF4α has an extensive impact on the regulation of a large number of the liver-specific genes. HNF4α may play a role in regulating the cytokine-induced inflammatory response. This study presents a novel function for HNF4α, acting not only as a global player in many cellular processes, but also as one of the components of inflammatory response in the liver.</p

Sequential surgical resection of hepatic and pulmonary metastases from colorectal cancer

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Resection of isolated hepatic or pulmonary metastases from colorectal cancer is widely accepted and associated with a 5-year survival rate of 25–40%. The value of aggressive surgical management in patients with both hepatic and pulmonary metastases still remains a controversial area. Materials and methods A retrospective review of 1,497 patients with colorectal carcinoma (CRC) was analysed. Of 73 patients identified with resection of CRC and, at some point in time, both liver and lung metastases, 17 patients underwent metastasectomy (resection group). The remaining 56 patients comprised the non-resection group. Primary tumour, hepatic and pulmonary metastases of all patients were surgically treated in our department of surgery, and the results are that of a single institution. Results The resection group had a 3-year survival of 77%, a 5-year survival of 55 % and a 10-year survival of 18%; median survival was 98 months. The longest overall survival was 136 months; six patients are still alive. In the resection group, overall survival was significantly higher than in the non-resection group (p&lt;0.01). Independent from the chronology of metastasectomy, 5-year survival was 55 % with respect to the primary resection, 28 % with respect to the first metastasectomy and 14 % with respect t