Histamine and Histamine H4 Receptor Promotes Osteoclastogenesis in Rheumatoid Arthritis.

Histamine H4 receptor (H4R) has immune-modulatory and chemotaxic effects in various immune cells. This study aimed to determine the osteoclastogenic role of H4R in rheumatoid arthritis (RA). The concentration of histamine in synovial fluid (SF) and sera in patients with RA was measured using ELISA. After RA SF and peripheral blood (PB) CD14+ monocytes were treated with histamine, IL-17, IL-21 and IL-22, and a H4R antagonist (JNJ7777120), the gene expression H4R and RANKL was determined by real-time PCR. Osteoclastogenesis was assessed by counting TRAP-positive multinucleated cells in PB CD14+ monocytes cultured with histamine, Th17 cytokines and JNJ7777120. SF and serum concentration of histamine was higher in RA, compared with osteoarthritis and healthy controls. The expression of H4R was increased in PB monocytes in RA patients. Histamine, IL-6, IL-17, IL-21 and IL-22 induced the expression of H4R in monocytes. Histamine, IL-17, and IL-22 stimulated RANKL expression in RA monocytes and JNJ7777120 reduced the RANKL expression. Histamine and Th17 cytokines induced the osteoclast differentiation from monocytes and JNJ7777120 decreased the osteoclastogenesis. H4R mediates RANKL expression and osteoclast differentiation induced by histamine and Th17 cytokines. The blockage of H4R could be a new therapeutic modality for prevention of bone destruction in RA

Benserazide, the first allosteric inhibitor of Coxsackievirus B3 3C protease

AbstractCoxsackievirus B3 is the main cause of human viral myocarditis and cardiomyopathy. Virally encoded Coxsackievirus 3C protease (3Cpro) plays an essential role in viral proliferation. Here, benserazide was discovered as a novel inhibitor from a drug library screen targeting Coxsackievirus 3Cpro using a FRET-based enzyme assay. Benserazide, whose chemical structure has no electrophilic functional groups, was characterized as a non-competitive inhibitor by enzyme kinetic studies. A molecular docking study with benserazide and its analogs indicated that a novel putative allosteric binding site was involved. Specifically, a 2,3,4-trihydroxybenzyl moiety was determined to be a key pharmacophore for the enzyme’s inhibitory activity. We suggest that the putative allosteric binding site may be a novel target for future therapeutic strategies

Pulsed Corona Discharge for Oxidation of Gaseous Elemental Mercury

Positive pulsed corona discharge has been applied for the oxidation of gaseous elemental mercury (Hg0) from a simulated flue gas. The oxidation of Hg0 to HgO and HgCl2 can significantly enhance the mercury removal from flue gas. At a gas condition of O2 (10%), H2O (3%), and N2 (balance), Hg0 oxidation efficiency of 84% was achieved at an input energy density of 45 J/l. The presence of NO, however, hinders Hg0 oxidation due to the preferential reaction of NO with O and O3. On the contrary, SO2 shows little effect on Hg0 oxidation due to its preferential reaction with OH. It has been also observed that the HCl in gas stream can be dissociated to Cl and Cl2 and can induce additional Hg0 oxidation to HgCl2

Mediastinal lymphoma in a young Turkish Angora cat

An 8-month old intact male Turkish Angora cat was referred to the Veterinary Medical Teaching Hospital (VMTH), Seoul National University, for an evaluation of anorexia and severe dyspnea. The thoracic radiographs revealed significant pleural effusion. A cytology evaluation of the pleural fluid strongly suggested a lymphoma containing variable sized lymphocytes with frequent mitotic figures and prominent nucleoli. The feline leukemia virus and feline immunodeficiency virus tests were negative. The cat was euthanized at his owner's request and a necropsy was performed. A mass was detected on the mediastinum and lung lobes. A histopathology evaluation confirmed the mass to be a lymphoma. Immunohistochemistry revealed the mass to be CD3 positive. In conclusion, the cat was diagnosed as a T-cell mediastinal lymphoma

Novel LMNA Gene Mutation in a Patient With Atypical Werner's Syndrome

Hutchinson-Gilford progeria syndrome (HGPS) and Werner's syndrome are representative types of progeroid syndrome. LMNA (Lamin A/C) gene mutation with atypical Werner's syndrome have recently been reported. Atypical Werner's syndrome with the severe metabolic complications, the extent of the lipodystrophy is associated with A133L mutation in the LMNA gene and these patients present with phenotypically heterogeneous disorders. We experienced a 15-yr-old Korean female with progeroid features, generalized lipodystrophy, hypertriglyceridemia, fatty liver, steatohepatitis, and type 2 diabetes mellitus. Skin fibroblasts from the patient showed marked abnormal nuclear morphology, compared with that from normal persons. Gene analysis revealed that this patient had T506del of exon 2 in the LMNA gene. We report here the first case of atypical Werner's syndrome with frameshift mutation that was caused by T506del

Involvement of Heme Oxygenase-1 Induction in the Cytoprotective and Immunomodulatory Activities of Viola patrinii in Murine Hippocampal and Microglia Cells

A number of diseases that lead to injury of the central nervous system are caused by oxidative stress and inflammation in the brain. In this study, NNMBS275, consisting of the ethanol extract of Viola patrinii, showed potent antioxidative and anti-inflammatory activity in murine hippocampal HT22 cells and BV2 microglia. NNMBS275 increased cellular resistance to oxidative injury caused by glutamate-induced neurotoxicity and reactive oxygen species generation in HT22 cells. In addition, the anti-inflammatory effects of NNMBS275 were demonstrated by the suppression of proinflammatory mediators, including proinflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β). Furthermore, we found that the neuroprotective and anti-inflammatory effects of NNMBS275 were linked to the upregulation of nuclear transcription factor-E2-related factor 2-dependent expression of heme oxygenase-1 in HT22 and BV2 cells. These results suggest that NNMBS275 possesses therapeutic potential against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation

Corticospinal Tract Integrity and Long-Term Hand Function Prognosis in Patients With Stroke

Background: The restoration of hand function is an important goal for patients with stroke. This study investigated the relationship between corticospinal tract (CST) integrity and the functional status of the hand in patients with stroke 6 months after onset and evaluated which of the following values would be useful for predicting hand function: fiber number (FN), fractional anisotropy (FA) at the mid-pons, and FA at the pontomedullary junction.Methods: The present retrospective cross-sectional observational study assessed 44 patients with stroke who were able to walk without using a walking aid or orthosis. The final hand function results were classified into three groups: no recovery (unable to grasp), partial recovery (able to grasp, unable to oppose), and full recovery (able to grasp and oppose). All subjects underwent diffusion tensor imaging (DTI) at 6 months after stroke onset. Values for FA at the mid-pons and pontomedullary junction and CST FN were measured. The normalization ratio for FN and FA was calculated using the following formula: data for affected hand/data for non-affected hand.Results: The normalized FN, FA (mid-pons), and FA (pontomedullary junction) DTI values differed significantly. The FA (mid-pons) value for the full recovery group was higher than those for the other groups. The FA (mid-pons) value for the partial recovery group was higher than that for the no recovery group. The normalized FA (mid-pons) value differed significantly among all three groups.Conclusions: The present study showed that CST integrity (at 6 months after onset) in patients with chronic stroke was related to functional hand status. In addition, the mid-pons FA value was more predictive of functional restoration of the hand than the FN or FA value at the pontomedullary junction. These results may be useful in predicting the functional restoration of the hand and understanding the functional prognosis of stroke