New Universality Class of Quantum Criticality in Ce- and Yb-based Heavy Fermions

A new universality class of quantum criticality emerging in itinerant electron systems with strong local electron correlations is discussed. The quantum criticality of a Ce- or Yb-valence transition gives us a unified explanation for unconventional criticality commonly observed in heavy fermion metals such as YbRh2Si2 and \beta-YbAlB4, YbCu5-xAlx, and CeIrIn5. The key origin is due to the locality of the critical valence fluctuation mode emerging near the quantum critical end point of the first-order valence transition, which is caused by strong electron correlations for f electrons. Wider relevance of this new criticality and important future measurements to uncover its origin are also discussed.Comment: 20 pages, 4 figure

Regulation of interleukin-1Β–induced chemokine production and matrix metalloproteinase 2 activation by epigallocatechin-3-gallate in rheumatoid arthritis synovial fibroblasts

Objective To evaluate the efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating interleukin-1Β (IL-1Β)–induced production of the chemokines RANTES (CCL5), monocyte chemoattractant protein 1 (MCP-1/CCL2), epithelial neutrophil–activating peptide 78 (ENA-78/CXCL5), growth-regulated oncogene Α (GROΑ/CXCL1), and matrix metalloproteinase 2 (MMP-2) activity in rheumatoid arthritis (RA) synovial fibroblasts. Methods Fibroblasts obtained from RA synovium were grown, and conditioned medium was obtained. Cell viability was determined by MTT assay. RANTES, MCP-1, ENA-78, and GROΑ produced in culture supernatants were measured by enzyme-linked immunosorbent assay. MMP-2 activity was analyzed by gelatin zymography. Western blotting was used to study the phosphorylation of protein kinase C (PKC) isoforms and nuclear translocation of NF-ΚB. Results EGCG was nontoxic to RA synovial fibroblasts. Treatment with EGCG at 10 Μ M or 20 Μ M significantly inhibited IL-1Β–induced ENA-78, RANTES, and GROΑ, but not MCP-1 production in a concentration-dependent manner. EGCG at 50 Μ M caused a complete block of IL-1Β–induced production of RANTES, ENA-78, and GROΑ, and reduced production of MCP-1 by 48% ( P < 0.05). Zymography showed that EGCG blocked constitutive, IL-1Β–induced, and chemokine-mediated MMP-2 activity. Evaluation of signaling events revealed that EGCG preferentially blocked the phosphorylation of PKCΔ and inhibited the activation and nuclear translocation of NF-ΚB in IL-1Β–treated RA synovial fibroblasts. Conclusion These results suggest that EGCG may be of potential therapeutic value in inhibiting joint destruction in RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55807/1/22023_ftp.pd

Relaxin: Review of Biology and Potential Role in Treating Heart Failure

Relaxin is a naturally occurring human peptide initially identified as a reproductive hormone. More recently, relaxin has been shown to play a key role in the maternal hemodynamic and renal adjustments that accommodate pregnancy. An understanding of these physiologic effects has led to the evaluation of relaxin as a pharmacologic agent for the treatment of patients with acute heart failure. Preliminary results have been encouraging. In addition, the other known biologic properties of relaxin, including anti-inflammatory effects, extracellular matrix remodeling effects, and angiogenic and anti-ischemic effects, all may play a role in potential benefits of relaxin therapy. Ongoing, large-scale clinical testing will provide additional insights into the potential role of relaxin in the treatment of heart failure

Anti-angiogenic action of hyperthermia by suppressing gene expression and production of tumour-derived vascular endothelial growth factor in vivo and in vitro

Vascular endothelial growth factor is an important angiogenic factor for tumour progression because it increases endothelial-cell proliferation and remodels extracellular matrix in blood vessels. We demonstrated that hyperthermia at 42°C, termed heat shock, suppressed the gene expression and production of vascular endothelial growth factor in human fibrosarcoma HT-1080 cells and inhibited its in vitro angiogenic action on human umbilical vein endothelial cells. The gene expression of alternative splicing variants for vascular endothelial growth factor, VEGF121, VEGF165 and VEGF189, was constitutively detected in HT-1080 cells, but the VEGF189 transcript was less abundant than VEGF121 and VEGF165. When HT-1080 cells were treated with heat shock at 42°C for 4 h and then maintained at 37°C for another 24 h, the gene expression of all vascular endothelial growth factor variants was suppressed. In addition, HT-1080 cells were found to produce abundant VEGF165, but much less VEGF121, both of which were inhibited by heat shock. Furthermore, the level of vascular endothelial growth factor in sera from six cancer patients was significantly diminished 2–3 weeks after completion of whole-body hyperthermia at 42°C (49.9±36.5 pg ml−1, P<0.01) as compared with that prior to the treatment (177.0±77.5 pg ml−1). On the other hand, HT-1080 cell-conditioned medium showed vascular endothelial growth factor-dependent cell proliferative activity and the augmentation of pro-matrix metalloproteinase-1 production in human umbilical vein endothelial cells. The augmentation of endothelial-cell proliferation and pro-matrix metalloproteinase-1 production was poor when human umbilical vein endothelial cells were treated with conditioned medium from heat-shocked HT-1080 cells. These results suggest that hyperthermia acts as an anti-angiogenic strategy by suppressing the expression of tumour-derived vascular endothelial growth factor production and thereby inhibiting endothelial-cell proliferation and extracellular matrix remodelling in blood vessels

Regulation of human endometrial function: mechanisms relevant to uterine bleeding

This review focuses on the complex events that occur in the endometrium after progesterone is withdrawn (or blocked) and menstrual bleeding ensues. A detailed understanding of these local mechanisms will enhance our knowledge of disturbed endometrial/uterine function – including problems with excessively heavy menstrual bleeding, endometriosis and breakthrough bleeding with progestin only contraception. The development of novel strategies to manage these clinically significant problems depends on such new understanding as does the development of new contraceptives which avoid the endometrial side effect of breakthrough bleeding

Vasodilators in the treatment of acute heart failure: what we know, what we don’t

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebo-controlled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. Unfortunately, most of this discussion is only partially evidence based due to lack of appropriate clinical trials. In general, we believe that vasodilators should be administered early to AHF patients with normal or high blood pressure (BP) at presentation. They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients’ outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1–2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice

Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis

Objective. Evaluation of the efficacy of green tea extract (GTE) in regulating chemokine production and chemokine receptor expression in human RA synovial fibroblasts and rat adjuvant-induced arthritis (AIA). Methods. Fibroblasts isolated from human RA synovium were used in the study. Regulated upon activation normal T cell expressed and secreted (RANTES)/CCL5, monocyte chemoattractant protein (MCP)-1/CCL2, growth-regulated oncogene (GRO)a/CXCL1 and IL-8/CXCL8 production was measured by ELISA. Western blotting was used to study the phosphorylation of protein kinase C (PKC)d and c-Jun N-terminal kinases (JNK). Chemokine and chemokine receptor expression was determined by quantitative RT–PCR. The benefit of GTE administration in rat AIA was determined. Results. GTE (2.5–40 mg/ml) inhibited IL-1b-induced MCP-1/CCL2 (10 ng/ml), RANTES/CCL5, GROa/CXCL1 and IL-8/CXCL8 production in human RA synovial fibroblasts (P<0.05). However, GTE inhibited MCP-1/CCL2 and GROa/CXCL1 mRNA synthesis in RA synovial fibroblasts. Furthermore, GTE also inhibited IL-1b-induced phosphorylation of PKCd, the signalling pathway mediating IL-1b-induced chemokine production. Interestingly, GTE preincubation enhanced constitutive and IL-1b-induced CCR1, CCR2b, CCR5, CXCR1 and CXCR2 receptor expression. GTE administration (200 mg/kg/day p.o.) modestly ameliorated rat AIA, which was accompanied by a decrease in MCP-1/CCL2 and GROa/CXCL1 levels and enhanced CCR-1, -2, -5 and CXCR1 receptor expression in the joints of GTE administered rats. Conclusions. Chemokine receptor overexpression with reduced chemokine production by GTE may be one potential mechanism to limit the overall inflammation and joint destruction in RA.NIHPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77485/1/Marotte, et al. Green tea extract...Rheumatology 2010.pdf-