Because these intranuclear structures do not have a membrane, the components of nuclear bodies and nuclear structures can rapidly interact. Many components of nuclear bodies change quickly, and an increased retention time of each component at a place represents foci.[27, 51] Therefore, the interaction should be regulated temporally and rapid dissociation depends

on the circumstance. Finally, we examine the possibility that TDP-43 directly contributes to the formation of Gems. In TDP-43-depleted cells, selleck chemicals llc a substantial number of Gems were still observed, whereas TDP-43 was not detected in the nucleus or Gems.[34] In addition, not all Gems include TDP-43 in cultured cells and normal spinal motor neurons.[34] Moreover, the size of each Gem was similar between control and ALS cells.[34] These results clearly indicate that TDP-43 is not a necessary component for all types of Gems. Thus, we propose two possibilities regarding the contribution of TDP-43 in the formation of Gems: (i) TDP-43 contributes to the formation of Gems only at a specific stage during their maturation (Fig. 2a); or (ii)

TDP-43 is associated with only a subtype of Gems, but not all Gems (Fig. 2b). Interestingly, the overexpression of TDP-43 also decreased the number of Gems in the cultured cells,[34] indicating that the proper amount of each component is important for maintaining the number of Gems. One outcome of a decrease in the number of Gems can be speculated based on the molecular mechanism underlying spinal muscular LDK378 in vitro atrophy. Gems are the sites of assembly and maturation of snRNP.[29, 31, 52] In the assembly of snRNP, SMN first forms a dimer and directly binds to Gemin 2, 3 and 8 and indirectly binds to Gemin 4, 5, 6 and 7 and unrip.[53] This SMN complex then binds to the Sm complex and U snRNA and transports them into the nucleus.[47] At the Gems, additional proteins are assembled to snRNPs and U snRNAs are modified, consequently forming a spliceosome, which functions for pre-mRNA splicing. In addition, Gems accumulate at most U snRNA genes.[30] These findings suggest that the Gems may regulate the quality

as well as the quantity of the U Protein kinase N1 snRNA. Therefore, researchers have speculated that the depletion of SMN or Gems may result in decreasing amounts of SMN complex, snRNPs and U snRNAs. Indeed, Gemin 2, 3 and 8 are decreased in SMN-depleted cells and tissues.[54, 55] In addition, the assembly of snRNP is also disrupted in these cells and tissues. Furthermore, a subset of U snRNA is decreased in the affected tissues in spinal muscular atrophy.[47, 54] The U snRNAs are involved in the splicing machinery, the spliceosome, and are categorized into major and minor classes depending on the consensus sequences of the donor and acceptor splice sites of the introns.[56] Most of the splicing is regulated by major spliceosomes, whereas less than 1% is regulated by minor spliceosomes.

[31] In good agreement with these findings, the down-regulation of NLRP3 and procaspase-1 gene transcription using ROS-inhibitors suggests that ROS in our experiment is a mediator of the priming of NLRP3

inflammasome. Our results showed that RWE treatment in the presence of NADPH enhanced procaspase-1 and IL-1β protein levels in THP-1 macrophages. This effect was dependent on the presence of exogenously added NADPH, implying the role of pollen NADPH oxidases in these effects. While using an immunoblotting technique, the RWE treatment in the presence of NADPH further increased caspase-1 processing (Fig. 4f), this did not result in significantly increased caspase-1 activity (see Fig. 4e). These results appear to be contradictory, MK0683 supplier however, it should be taken into account that the selleck immunoblotting technique detects the processed caspase-1 independent of its activity, and it has been demonstrated that caspase-1 is rapidly inactivated in THP-1 cells (with a half-life of 9 min) leading to the accumulation of processed but inactive

caspase-1.[32] It should be noted that despite intensive studies on NLRP3 inflammasome and IL-1β production, the molecular and biochemical details of the protein expression, half-life and degradation of NLRP3 and caspase-1 are far from being understood. Post-translational modification, enhanced protein inactivation and degradation may strongly deviate the actual protein levels and activity from those that could be predicted from the gene expression patterns alone. Various signal pathways have been shown to be involved in LPS-mediated NLRP3 inflammasome component

up-regulation.[33, 34] Based on our studies, RWE induces p38 and JNK phosphorylation in an NADPH-dependent manner; however, this does not lead to elevated pro-IL-1β, NLRP3 and procaspase-1 transcription. Nevertheless, co-treatment of the THP-1 macrophages with LPS and RWE in the presence of NADPH resulted in a substantially more intensive phosphorylation of these proteins, presumably leading to the observed gene expression induction. Unlike LPS, RWE and NADPH did not significantly activate the nuclear factor-κB signalling pathway. Signals triggering activation of nuclear factor-κB pathways like that of LPS ligating TLR4, induce Casein kinase 1 strong expression of pro-IL-1β because its promoter region contains multiple nuclear factor-κB responsive elements.[35] On the other hand, p38 and JNK pathways are typically induced by stress stimuli like ROS. Cross-talk between signalling pathways like phosphorylation of cytosolic elements of the pathway or transcriptional regulators by JNK and p38 kinase may result in the formation of more stable enhancer complexes, as described previously.[36] Our results show that LPS-induced p38 and JNK phosphorylation, also the activation of AP-1 (c-Fos and c-Jun) and subsequent gene expressions are enhanced by RWE and NADPH.

In this study, we describe three young Chinese patients

with MELAS/LS overlap syndrome who carried the m.13513G>A mutation. Clinical and MRI features were characteristic of both MELAS and LS. Interestingly, the clinical presentation of this overlap syndrome could be variable depending on the degree of relative contribution of MELAS and LS, that find more is, MELAS as the initial presenting syndrome, LS as the predominant syndrome, or both MELAS and LS appearing at the same time. The final brain MRI showed findings characteristic of both MELAS and LS, with asymmetrical lesions in the cortex and subcortical white matter of the occipital, temporal, and frontal lobes (MELAS), and bilateral and symmetrical lesions in the basal ganglia and brainstem (LS). Brain autopsy in one case revealed infarct-like lesions in the cerebral cortex, basal ganglia and brainstem, providing further insight into the distribution of the pathological lesions in MELAS/LS overlap syndrome. This is the first report of the brain pathological changes in a patient with m.13513G>A mutation. The spatial MK-8669 nmr distribution of infarct-like lesions in the brain could explain the symptoms in MELAS/LS overlap syndrome. “
“Peripheral primitive neuroectodermal

tumor/Ewing’s sarcoma (ES) (pPNET/ES) of intracranial origin are very rare. These tumors are characterized by specific translocations involving a gene on chromosome 22q12, the most common being t(11;22) (q24;q12). We report a case of 37-year-old man with pPNET/ES arising in the meninges and bearing the rare translocation t(21;22) (q22;q12). The tumor was composed of sheets and nests of monotonous small cells with round to oval nuclei, finely dispersed chromatin, small nucleolus

and scant cytoplasm. We discuss the importance of the differential Janus kinase (JAK) diagnosis with central primitive neuroectodermal tumors (cPNET). “
“F. Geser, J. A. Malunda, H. I. Hurtig, J. E. Duda, G. K. Wenning, S. Gilman, P. A. Low, V. M.-Y. Lee and J. Q. Trojanowski (2011) Neuropathology and Applied Neurobiology37, 358–365 TDP-43 pathology occurs infrequently in multiple system atrophy Aims and Methods: The α-synucleinopathy multiple system atrophy (MSA) and diseases defined by pathological 43-kDa transactive response DNA-binding protein (TDP-43) or fused in sarcoma (FUS) aggregates such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration show overlapping clinico-pathological features. Consequently, we examined MSA for evidence of TDP-43 or FUS pathology utilizing immunohistochemical studies in autopsy material from 29 MSA patients. Results: TDP-43 pathology was generally rare, and there were no FUS lesions.

f (TWHF) which has been applied extensively for treatment of patients with early diabetic nephropathy (DN) in China. Despite this, therapeutic mechanisms remain unclear. Increasing evidences demonstrate renal inflammation is

a determinant during glomerular injurious progress under high-glucose condition. Among them, p38MAPK signaling activity and its related inflammatory factors play pivotal roles respectively. This study aimed to investigate effects and mechanisms in vivo of TP on inflammatory and sclerotic lesions in glomeruli by regulating p38MAPK signaling activity and inflammatory factor expression. Methods: Rats were randomly divided into Ibrutinib 3 groups, Sham-operated group, TP-treated group, and Vehicle given group, and sacrificed at weeks 8 after induction of DN induced by 2 consecutive intraperitoneal injections of streptozotocin (STZ) at 30 mg/kg dose with an interval of 1 week following unilateral nephrectomy. Daily oral administration of TP (0.5 mg/kg/d) and vehicle (saline) was started after the second injection of STZ until sacrifice. Urinary albumin (UAlb), biochemical indicators, glomerular morphology, glomerular macrophage infiltration and protein expressions of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, p38MAPK, phosphorylated p38MAPK (p-p38MAPK) and TGF-beta1 in kidneys were examined, respectively.

Results: Characterizations of glomerular inflammatory damage in DN model rats involved glomerular macrophages (ED1+ cell) infiltration, IL-1beta and TNF-alpha R428 concentration proteins over-expression and p38MAPK signaling molecules activation, especially p-p38MAPK and TGF-beta1 in kidneys,

accompanied by the exasperation of glomerulosclerosis (GS). TP could not only improve the DN model rats’ general state including body weight (BW), kidney weight (KW) and KW/BW, but also attenuate UAlb, GS, glomerular ED1+ cell infiltration and protein over-expressions of IL-1beta, TNF-alpha, p-p38MAPK and TGF-beta1 in kidneys. Cell press Conclusion: By means of these DN model rats, we demonstrated that activation of p38MAPK signaling pathway promotes glomerular damage, and that TP, as a natural regulator in vivo, could ameliorate renal inflammation and GS via down-regulating protein over-expressions of p-p38MAPK and TGF-beta1 in p38MAPK signaling pathway. TP may be exploited for therapeutic intervention of DN patients at early stage. TERAMI NAOTO, OGAWA DAISUKE, TACHIBANA HIROMI, HATANAKA TAKASHI, SUGIYAMA HITOSHI, SHIKATA KENICHI, MAKINO HIROFUMI Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Trefoil factor (TFF) peptides are coexpressed with mucins in the gastrointestinal tract stomach, colon and are also expressed in kidney tubules. Serum levels of TFF3 have been reported a possible biomarker of gastric cancer.

The predictive capacity is further improved to distinguish mutant epitopes from the non-mutated epitopes if the peptide–TCR interface is integrated into the computing simulation programme. Specific CD8 T-lymphocyte responses are important in recovery from respiratory syncytial virus (RSV) infection1–3 as well as for protection against heterotypic influenza viruses.4–6 Formalin-inactivated vaccines are not formulated to prime for MHC class I-restricted CD8 T-lymphocyte responses.7,8 MK-8669 nmr Similar to inactivated vaccines, purified protein antigens are not effective at activation of CD8 T-lymphocyte responses despite the presence of adjuvants.9–11 Complications of adjuvant formulations often enhance

one arm of immune effectors but inhibit another.11 Immunisation with synthetic peptide vaccines is a promising approach to protection against viral infections

via the induction of specific CD8 T-lymphocyte responses.12–15 Hence, identification of protective epitopes is a priority in the development of synthetic peptide vaccines.12,16 In particular, the identification of immunodominant epitopes is indispensable for the prevention of mutable viruses16,17 even if the non-immunodominant epitope provides partial protection against influenza virus infection.14 CD8 T lymphocytes recognise peptides presented by MHC class I molecules.18 MHC class I-restricted peptides contain 8–12 amino acids.19–26 Since procedures selleck chemicals of peptide–MHC class I binding experiments are becoming complicated, many immunoinformatical programmes have been developed to predict epitopes, even prior to any laboratory experiments.19,27–32 Bioinformatical programmes can be

classified into sequence-based,19,27,33,34 integrative29 and structure-based approaches,35,36 which are not integrated with the recognition interface between Clomifene peptide–MHC class I molecules and T-cell receptors (TCR) for immunological purposes. An increasing number of MHC class I–peptide–TCR structures were analysed by X-ray diffraction, so the structure-based simulation approach has been exploited in this research to provide insights in the structure with the aim of developing an immunoinformatical programme for a further demonstration of the recognition mechanism found in our laboratory experiments. For the research described here, we attempt to clarify the impact of TCR contact residues on the TCR recognition mechanism as well as on the prediction accuracy on CD8 T-lymphocyte epitopes from protein sequences by immunoinformatical programmes for the rational design of T-lymphocyte epitope vaccines. Peptides were synthesized with Fmoc chemistry (Iris Biotech GmbH Co., Germany & Mission Biotech Co., Taiwan). Synthesized peptides were purified with HPLC and confirmed with mass spectrometry for 95% purity. Variant peptides were synthesized with amino acid substitutions at either anchor motifs (P2 or P9) or TCR contact sites (P6 or P8). Peptide sequences are presented in Table 1.

Previous work in animal models indicates that the development of many human autoimmune diseases might be caused

by impairment of the FcR regulatory system [13]. It has been shown that FcγR triggering determination of APC behaviour is an important step in developing a Th2 response and subsequent allergic inflammation. An asthma model using Fc receptor gamma chain (FcRγ)-deficient mice has demonstrated that expression of FcRγ on APCs is important EPZ-6438 cost for the development of allergic airway inflammation and AHR [23]. Deletion of FcRγ results in the deficiency of activating-type FcRs, including FcγRI, FcγRIII and FcεRI, which play important roles as activating Fc receptors, but does not affect the expression or inhibitory function of FcγRIIb. Regnault et al. reported that DCs derived from FcRγ-deficient mice failed to mature normally or promote efficient antigen presentation of peptides from exogenous IgG-complexed antigens [24]. Conversely, a recent report has shown the inhibitory mechanisms of FcγRIIb on CD11c+ APCs in allergic airway inflammation [25]. In this study, FcγRIIb on DCs reportedly controls the cellular maturation state. DCs derived from FcγRIIb-deficient mice showed proliferation BMN 673 supplier of antigen-specific T cells

in vitro and in vivo[26]. These reports indicate that signalling through both activating and inhibitory FcRs regulates the activity of APCs in the immune system in the pathogenesis of asthma. In bronchial asthma, IgE and FcεRI are generally considered to be important and logical therapeutic targets. Omalizmab is available as anti-IgE therapy and binds to free IgE; this results in the reduction of FcεRI on mast cells and basophils Protein kinase N1 [27]. It has been reported that cross-linking of FcεRI with FcγRIIb on mast cells and basophils inhibits the degranulation and release of potent inflammatory mediators [19]. In the alum–OVA model used in this study, development of allergic airway inflammation is not dependent upon the existence of B cells or IgE, but instead on CD4+

T cells [28,29]. These facts suggest that allergic airway inflammation with a Th2 response can be regulated by the FcγRIIb-mediated inhibitory pathway on DCs independently of IgE-FcεRI binding. However, there are a few cases of refractory asthma whose pathogenesis seems to be independent of IgE. To modify the function of lung DCs via FcγRIIb might be one of the additional therapeutic strategies in refractory asthma. For the management of bronchial asthma, it is necessary to approach the pathogenesis with sensitivity to multiple allergens. In one possible candidate for treatment of allergic airway inflammation, Sehra et al. showed that specific allergen–IgG interactions repressed inflammatory responses triggered by bystander allergen, thus suggesting that allergen-specific IgG suppress the immune response induced by other allergens [11].

“
“Please cite this paper as: Bonacasa, Siow and Mann (2011). Impact of Dietary Soy Isoflavones in Pregnancy on Fetal Programming of Endothelial Function in Offspring. Microcirculation 18(4), 270–285. Epidemiological evidence suggests that soy-based diets containing phytoestrogens (isoflavones) afford protection against cardiovascular diseases (CVDs); however, supplementation

trials have largely reported only marginal health benefits. The molecular mechanisms by which the isoflavones genistein, daidzein, and equol afford protection against oxidative stress find more remain to be investigated in large scale clinical trials. Isoflavones are transferred across the placenta in both rodents and humans, yet there is limited information on their actions in pregnancy

and the developmental origins of disease. Our studies established that feeding a soy isoflavone-rich diet https://www.selleckchem.com/products/PD-0325901.html during pregnancy, weaning, and postweaning affords cardiovascular protection in aged male rats. Notably, rats exposed to a soy isoflavone-deficient diet throughout pregnancy and adult life exhibited increased oxidative stress, diminished antioxidant enzyme and eNOS levels, endothelial dysfunction, and elevated blood pressure in vivo. The beneficial effects of refeeding isoflavones to isoflavone-deficient rats include an increased production of nitric oxide and EDHF, an upregulation of antioxidant defense enzymes and lowering of blood pressure in vivo. This review focuses on the role that isoflavones in the fetal circulation may play during

fetal development in affording protection against CVD in the offspring via their ability to activate eNOS, EDHF, and redox-sensitive gene expression. “
“Please cite this paper as: Schneider M, Broillet A, Tardy I, Pochon S, Bussat P, Bettinger T, Helbert A, Costa M, Tranquart F. Use of intravital microscopy to study the microvascular behavior of microbubble-based ultrasound contrast agents. Microcirculation19: 245–259, 2012. Purpose:  The study describes the use of intravital microscopy (IVM) to assess Interleukin-3 receptor the behavior of ultrasound contrast agents (UCAs), including targeted UCAs, in the microcirculation of rodents. Materials and Methods:  IVM was performed on various exteriorized organs: hamster cheek pouch, rat mesentery, liver, spinotrapezius muscle, and mouse cremaster muscle. A dorsal skin-fold chamber with MatBIII tumor cells was also implanted in rats. Nontargeted UCAs (SonoVue® and BR14) and targeted UCAs (BR55 and P-selectin targeted microbubbles) were tested. IVM was used to measure microbubble size, determine their persistence, and observe their behavior in the blood circulation.

Use of this cryptic splice site led mostly to an insertion of 132 bp that introduced 44 amino acids and a premature stop codon between exons 56 and 57 (p.Gly2898GlyfsX36). In

addition, the presence of another putative AG dinucleotide splice acceptor site upstream to the cryptic Erlotinib cost donor splice site, led to an additional alternative frameshift insertion of 32 nucleotides, also leading to a premature stop codon (p.Gly2898AspfsX54) (Figure 7a). However, no truncated proteins were detected on Western blot analysis, suggesting either instability of the cryptic transcripts as a result of a nonsense-mediated mRNA decay process or an early degradation of the truncated proteins as a result of an unfolded protein response. The residual physiological splicing allowed the production of a low amount of wild-type RyR1

(22 ± 12%) in the muscle of the patient (Figure 6). Patient 7 was p.[Pro3202Leu] + p.[Arg4179His] compound heterozygous. The maternal p.Pro3202Leu (c.9605C>T, exon 65) variant was recurrent in this study (patient 4). The paternal p.Arg4179His (c.12536G>A, exon 90) variant affected a highly conserved arginyl residue that mapped to a cytoplasmic domain of the protein close to the p.Glu4181Lys variant identified in patient 2. We have identified a cohort of seven patients with congenital myopathy and a peculiar morphological pattern in muscle biopsies associated with recessive mutations Navitoclax in the gene encoding the skeletal muscle ryanodine receptor (RYR1). All the patients showed early onset of the disease, ophthalmoparesis of variable severity and presence of early disabling contractures, next especially in the masticators. Rigid spine syndrome was also present in two patients. Otherwise clinical presentation was similar to most congenital myopathies, showing hypotonia of variable severity, delay in the acquisition of developmental motor milestones, axial and proximal limb weakness and restrictive respiratory syndrome. Cardiac and cognitive functions were invariably spared. Our data enlarges the histological phenotype associated with RYR1 mutations. Indeed,

the areas of sarcomeric/myofibrillar disorganization are distinguishable from typical cores. On oxidative stains, these areas are large, diffuse and poorly delimited. Ultrastructurally, they are broader than cores in transverse sections, as they frequently cover extensive cross-sectional areas of the fibre, often reaching the sarcolemma. They are also shorter than cores, as in longitudinal sections they extend along a relatively small number of sarcomeres. In contrast with cores the presence of mitochondria within the lesions accounts for the excessive oxidative staining in some fibres. On the other hand, ‘purple dusty areas’ corresponding to foci of Z line rearrangements are not usually seen in muscle biopsies of patients with classical core myopathies.

The thermal hyperemia elicited by each chamber is thus reduced to a series of average flow values, separated by time intervals of one minute (as Selleck Kinase Inhibitor Library scans are repeated at a rate of 1/minute). The PF4001 laser-Doppler flowmeter generates analog DC output voltages proportional to the detected flow, which were digitized at a sampling frequency of 40 Hz and stored on computer disk, using the Powerlab 8/35 hardware and the Labchart V5.0 software by ADInstruments (Spechbach, Germany). These signals were then

time-averaged over successive, contiguous periods of one minute. In this fashion, whether evaluated with LDI or LDF, all thermal hyperemias were expressed in time series of identical format. The last step in data reduction was then the calculation of the following variables: baseline flow (average of five values corresponding to the five minutes preceding the rise in local temperature), early peak response (maximal flow during the 10 minutes following the rise in temperature, minus baseline flow), nadir response (minimal flow from the time of early peak to the 15th minute of recording, minus baseline flow), and plateau response (mean of the last five flow values, recorded from 25th to 30th minute following the rise in temperature minus baseline flow). As measurements obtained

with the two laser-Doppler techniques are not in the same units (i.e., volts vs PU), statistical analysis was carried out separately for LDI and for LDF data. Baseline flow, early peak response, nadir response, and plateau response were tested with analysis of variance for repeated measures. The model included time (T0 Selleck Atezolizumab or T2), chamber type (custom, commercial), and their interaction as repeated factors. The alpha level of all tests was set at 0.05. Data are presented as the mean and SD, unless specified otherwise. The 28 subjects were healthy men, aged 19–32 years. Fifteen of them were lean (BMI <25 kg/m2) and the others were overweight, but not obese (BMI 25–29 kg/m2). The mean skin temperature measured in the immediate vicinity of sites A, B, C, and D was 32.8 ± 0.8°C.

Between T0 +30 and T2 +30 minutes, HR did not change (65 ± 8 vs 64 ± 9 beats/minute), but the mean 3-mercaptopyruvate sulfurtransferase BP slightly increased (from 80 ± 7 to 87 ± 6 mmHg, p < 0.001), a difference that may be explained by the discomfort induced by lasting bilateral arm immobilization, as expressed by several subjects. Figure 2 shows the mean time courses of SkBF responses to local heating, observed in the four experimental conditions. As expected, the general shape was biphasic with an early peak of SkBF occurring between 0 and 5 minutes after the onset of local heating, followed by a nadir during about five minutes and later a secondary progressive increase, which stabilized between 25 and 30 minutes (plateau). The most obvious feature is a decrease in the plateau SkBF contrasting with a slight increase in the early peak, from T0 to T2.

Further studies are needed to reveal the underlying ICG-001 solubility dmso mechanisms. MORI DAISUKE1, INOUE KAZUNORI1, HAMANO TAKAYUKI2, MATSUI ISAO1, SHIMOMURA AKIHIRO1, KUSUNOKI YASUO1, NAKANO CHIKAKO1, OBI YOSHITSUGU1, TSUBAKIHARA YOSHIHARU2, ISAKA YOSHITAKA1, RAKUGI HIROMI1 1Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine; 2Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine Introduction: Left ventricular

hypertrophy (LVH) and a resultant heart failure are the leading causes of death in patients with chronic kidney disease (CKD). Therefore, it is important to establish novel strategies to prevent LVH in CKD. Studies on vitamin D receptor knockout mice have revealed that active vitamin D may be one of the promising agents that ameliorate LVH. Therefore, in the current study, we examined preventive Bafilomycin A1 concentration effects of maxacalcitol (22-oxacalcitriol (OCT)), a clinically used less calcemic analogue of active vitamin D, on LVH in hemi-nephrectomized rats. Methods: Six-week-old male Wister rats were subjected to heminephrectomy and then divided into four groups; normal saline + vehicle (N+V), normal saline + OCT (N+O), angiotensin II (Ang II) + vehicle (A+V), and Ang II + OCT (A+O). Vehicle or OCT at a dose of 0.15 μg/kg BW was administered subcutaneously twice a day. We also

examined the effects of OCT on hypertrophy using cultured neonatal rat ventricular tetracosactide myocytes (NRVM). Results: In comparison with groups N+V and N+O, group A+V had increased heart weight, cross sectional area of cardiomyocytes, and LVH-associated genes. Because it is well established that an activation of calcineurin A

(CnA)-NFAT pathway in cardiomyocyte causes pathological LVH, we examined the status of this pathway in these rats. In comparison with groups N+V and N+O, group A+V had higher activity of CnA. Elevated expression of moderately calcineurin interacting protein 1 (MCIP-1), a down-stream component of CnA-NFAT pathway, in group A+V also confirmed the activation of CnA-NFAT pathway in group A+V. All of these changes were suppressed in group A+O in a blood-pressure-independent manner. To understand the underlying mechanism more precisely how OCT suppressed LVH, we performed in vitro examinations using NRVM. An overexpression of constitutive-active form CnA in the NRVM induced MCIP-1 expression and hypertrophy. OCT suppressed these changes in a dose dependent manner. Conclusion: Our findings may provide a novel approach for the suppression of pathological LVH in CKD. HAN SEUNG SEOK1, PARK JAE YOON1, KIM MYOUNGHEE2, JOO KWON WOOK1, KIM YON SU1, KIM DONG KI1 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; 2Department of Dental Hygiene, College of Health Science, Eulji University, Gyeonggi-do, Korea Introduction: The elderly constitutes a substantial proportion of patients suffering from the end-stage renal disease.