2B). Since by using other combinations of inbred mouse strains we previously identified a locus quantitatively controlling thymic Treg-cell development on chromosome 17 [14], we assessed if the same locus was involved in the quantitative regulation of Treg-cell

differentiation in NOD mice. To address this question, we first analyzed the proportion of thymic CD25high CD4SP Treg cells in the congenic mouse strains NOD.B10-H2b and NOD.B6-H2b. These two congenic lines, that carry the B10- or B6-derived H2 locus of H-2b haplotype on an NOD genetic background, respectively, showed a ‘low’ (B6-like) percentage of Treg cells (data not shown). This observation indicated a major influence of an H2-linked locus on this website the quantitative development of Treg cells. To better define the region of interest, we analyzed other recombinant NOD.B6 congenic

mouse strains [17]. NOD.B6-R76 (R76) mice carry a <20 Mbp B6-derived chromosomal region centromeric to the H2 locus. These mice displayed low (B6-like) proportions of thymic Foxp3+ CD4SP Treg cells. In contrast, thymocytes from the NOD.B6-R156 (R156) strain, carrying a distinct PD0325901 mouse B6-derived region centromeric to H2, had high (NOD-like) proportions and numbers of Foxp3+ CD4SP Treg cells (Fig. 3A and B). Peripheral percentages and numbers of Treg cells were comparable in all the strains analyzed (Supporting Information Fig. 1). In conclusion, a ≤20 Mbp long region centromeric to the H2 complex on mouse chromosome 17 harbors a gene (or multiple genes) that quantitatively controls Treg-cell development. Interestingly, the Trd1 locus contains the diabetes susceptibility locus Idd16. The locus on chromosome 17 controlling Treg-cell development previously reported by us was located telomeric of

H2 and is therefore clearly distinct from the one we report here [14]. It was previously shown that R76 congenic mice develop diabetes with delayed kinetics when compared with those of NOD animals [17]. Ibrutinib price To analyze whether changes in Treg-cell development may somehow be linked to diabetes by influencing Treg-cell function in the periphery, we compared NOD and R76 Treg-cell suppressive activity in vitro. We purified NOD and R76 CD4+CD25high CD127− splenic Treg cells and analyzed their capacity to inhibit proliferation of CD4+CD25−CD127+ splenic Tconv cells induced with plate-bound anti-CD3ε antibody. As shown in Supporting Information Fig. 2, NOD and R76 Treg cells inhibited proliferation of NOD and R76 Tconv cells with similar efficiency. Together, these data show that the intrinsic suppressive function of Treg cells and the sensitivity of Tconv cells to Treg-cell–mediated suppression are similar in NOD and R76 mice.

In an in vitro study, a M1 state of macrophage activation induced by C.

parvum antigen that was shown to have a protective role in vivo was enhanced by co-culture with Vismodegib neutrophils [44]. However, an inability of neonatal IFN-γ−/− mice to clear infection was associated with a pronounced increase in numbers of neutrophils, but not macrophages in the small intestine [25]. These findings may suggest that a protective role for neutrophils requires interaction with macrophages in an appropriate cytokine microenvironment. However, results of studies of the effect on infection of neutrophil depletion in neonatal animals do not support a major protective role for these cells. Antibody-mediated prevention of neutrophil recruitment in the intestine of piglets had no significant effect on levels of C. parvum infection, villous atrophy or faecal output [46]. Neonatal mice with neutropaenia induced by the mAb NIMP-R14 had a similar course of infection compared with control mice except that in the

latter stages of the patent infection low levels of oocyst excretion selleck chemicals llc could be detected for a few days longer in the neutrophil-deficient mice (D.S. Korbel and V. McDonald, unpublished data). Clearly, the role of neutrophils in immunity needs to be better defined. As the target for infection by cryptosporidia in vivo, epithelial cells might be expected to play a central role in innate immunity. Investigations suggest that in response to infection the epithelium activates mechanisms that help to maintain structural integrity, establish an inflammatory response and contribute to parasite killing. One potential protective measure against parasite replication is epithelial cell apoptosis. Infection of epithelial cells alters expression of hundreds of hosts cell genes, many of them associated with apoptosis [47]. In studies with epithelial cell lines a proportion of cells

was shown to undergo apoptosis soon after invasion by sporozoites [47]. Within a few hours, however, the infected cells upregulated anti-apoptotic genes, allowing the parasite time to complete the first generation of merogony [47]. NF-κB activation in infected cells has been shown to be important for inhibition Progesterone of apoptosis [48]. In infected cell monolayers, uninfected cells also underwent apoptosis due in part to secretion of FasL by infected cells [49]. If this effect occurred in vivo the resulting disruption of the epithelial barrier providing luminal bacteria access to lamina propria myeloid cells could play an important part in immunopathogenesis. However, a recent study of C. parvum infection of piglets that show similar pathological features to those in infected humans indicated that during heavy infection causing villous atrophy, apoptosis was repressed in the intestinal epithelium [50].

Moreover, the onset in most cases is several months or even years after the inciting delivery, so it is often misrecognized selleckchem and not adequately treated. Hyponatremi and hypoglicemi that have been rarely reported in the literature. Case Report: A 47-year-old woman, a housewife, was admitted because disturbed consciousness. She had a history of postpartum hemorrhage which had occurred 15 years previous. Amenorrhea and failure to lactate developed thereafter. Fatigue and dry skin were also found. Physical examination revealed a chronically ill looking. She was drowsy, her fluid status was euvolemic, and her conjunctiva appeared anemic. Laboratory data were as follows:

hemoglobin 7, 8 g/dl, the random blood glucose 40 g/dl and the serum sodium 108 meq/L with low serum osmolality and elevated urine sodium. Moreover, the investigations also showed a low of FSH, LH and prolactin. Magnetic Resonance Imaging

of the brain showed an “empty sella” appearance. Thus, a diagnosis of Sheehan MEK inhibitor syndrome was made. Hyponatremia and hypoglycemia that was improved after replacement with glucocorticoids. Conclusions: This case illustrates that Sheehan’s syndrome whose first presentation was with hyponatraemia and hypoglycaemia that have been rarely reported in the literature. Early diagnosis and appropriate treatment are necessary to reduce the morbidity and mortality of patients. Key words: Sheehan Syndrome, Hyponatremia and Hypoglycemia, Empty sella. 283 MILD PERSISTENT HYPERKALEMIA: AN IMPORTANT DIAGNOSTIC CLUE IN SHORT STATURE S CAMPBELL, A WALKER, J KAUSMAN, C QUINLAN Royal Children’s Hospital – Nephrology Department, Melbourne, Australia Aim: The case is of a 10-year-old female who presented

as a diagnostic dilemma to multiple paediatric physicians with key features short stature & hyperkalemia. Background: She initially presented with Perthes disease of both hips was then noted to have a height on the 3rd centile, with mid-parental height expectation of a 10th centile. She was found to be normotensive (50th centile), and without dysmorphic features. Investigations revealed a persistent hyperkalemia (average = 6.2 (3.5–5.5 mmol/L)), in the presence of low/normal aldosterone level (55U/L), and low renin ≤0.2 (1.0–4.0). Sitaxentan Plasma creatinine was normal (36 mmol/L) as was urinary potassium excretion (91 mmol/L). A venous gas demonstrated a mild metabolic acidosis (pH 7.32, BE = −4). Methods: A diagnostic trial of hydrochlorothiazide was successful in resolving her hyperkalemia. Results: The clinical & biochemical picture is consistent with that of Type II pseudohypoaldosteronism (PHAII), specifically Spitzer-Weinstein syndrome. Conclusions: A rare disorder, inherited in an autosomal dominant manner involving the WNK1 and WNK4 genes. WNK kinases are named so due to a lack of lysine in the ATP binding cassette of the catalytic region.

13 ± 2.43 cmH2O, but the difference is not statistically significant.3 At 14 days, the leak point pressure of the cell-implantation group, 17.82 ± 1.31 cmH2O, is significantly higher than that of the control group, 11.78 ± 3.23 cmH2O (P < 0.05). We do not yet know the leak point pressures of healthy rabbits, and whether or not the cell-implanted rabbits have voluntary control of the restored sphincters. Clinically,

while less than 60–65 cmH2O of (abdominal) leak point pressure is one of the indexes of human stress urinary incontinence, it is not sufficient to diagnose it. Nevertheless, it is clear that increased or a high leak point pressure is helpful to inhibit urine leakage that can occur during physical activity. Therefore, check details cell therapy using bone

marrow-derived cells could have a great potential to reduce urinary incontinence and improve quality of life. At 7 and 14 days after cell-implantation and cell-free Selleck Acalabrutinib control injection, the urethral sphincters are analyzed by histology, cytology, and immunohistochemistry to determine if the improvement of leak point pressures is related to the recovery of muscle layers.3 At 7 days after cell-free control injection, there are few striated muscle cells, and a few clusters composed of smooth muscle cells. Among the cells that are present, few express immunohistochemically detectable levels of myoglobin or SMA (Fig. 3a,b). In contrast, at 7 days after cell SPTBN5 implantation, there are developing muscle layers composed of striated and clusters composed of smooth muscle cells, many of which express readily detectable levels of myoglobin and SMA (Fig. 3c,d). Seven days after implantation, myoglobin- and SMA-expressing cells account for 15 ± 3 and 7 ± 1% respectively

of the histological fields. This is significantly higher than in the cell-free injected areas, 2 ± 0.1 and 2 ± 0.2%, respectively (P < 0.01 for each). At 14 days after control cell-free injection, the regional composition of cells is similar to the 7-day control regions with relatively few cells expressing myoglobin (Fig. 3e) or SMA (Fig. 3f). In contrast, at 14 days after cell implantation, the regions have distinctly regenerated muscle layers composed of numerous striated and smooth muscle cells that are similar to the intact urethral sphincters. Many of the cells express myoglobin and form distinct striated muscle layers (Fig. 3g). These regions also have larger clusters of SMA-positive cells that are organized into smooth muscle layers (Fig. 3h) similar to the intact urethral sphincters. Fourteen days after implantation, myoglobin- and SMA-expressing cells account for 12 ± 1 and 25 ± 5% respectively of the histological fields. This is significantly higher than in the cell-free injected areas, 4 ± 1 and 6 ± 1%, respectively (P < 0.01 for each). Bone marrow-derived cells can produce cytokines and growth factors that accelerate healing in damaged tissues.

1). However, little is known of their mode of action on microglia in disease and, in view of their phenotypic spectrum, it would seem relevant to define and monitor specific windows of therapeutic opportunity. While PET imaging of microglia ligands has afforded meaningful insights into the evolution of microglial activation in neurodegenerative diseases in vivo, further studies are needed to define markers of increased specificity for microglial activation states

that would enable monitoring of drugs that affect microglial activation in the CNS. We gratefully acknowledge the financial support of the Italian MS Foundation, the Italian Ministry of Health, the Italian Ministry of the University and Scientific Research, the Liguria Region and the CARIGE Foundation. The authors have no financial disclosures or competing interests. “
“Chronic Maraviroc price granulomatous disease (CGD) is a rare inherited disorder selleckchem of the innate immune system caused by a defect in NADPH oxidase, leaving the granulocytes unable to kill invading microorganisms. CGD is caused by mutation in one of the five components gp91phox, p22phox, p47phox, p67phox and p40phox, encoded by the X-linked CYBB gene and the autosomal CYBA, NCF1, NCF2 and NCF4 genes respectively. We have collected samples from all Danish patients with known CGD followed in the clinic or newly diagnosed during a 5-year period, a cohort of 27 patients, and characterized

them genetically. The cohort includes 10 male patients with X-linked CGD and one female with extremely lyonized expression of a defective CYBB allele. Six patients had mutation in CYBA. Seven of 10 patients with a defect in NCF1 were homozygous for the common GT deletion, one was compound heterozygous for the GT deletion and a splice-site tuclazepam mutation, and two patients were homozygous for a nonsense mutation in exon 7. Three novel mutations were detected, a deletion of exon 6 in CYBA, a duplication of exon

8–13 in CYBB and a splice site mutation in intron 7 of NCF1. Chronic granulomatous disease (CGD) is a rare inherited disorder of the innate immune system characterized by severe recurrent bacterial and fungal infections at the body surfaces, e.g. the skin, the airways, the gut as well as the lymph nodes [1]. The major clinical manifestations of CGD are pyoderma, pneumonia, inflammation of the gastrointestinal tract, lymphadenitis, liver abscess and osteomyelitis [1, 2]. The underlying mechanism is a defect of NADPH oxidase activity in phagocytic cells, i.e. neutrophils, monocytes, macrophages and eosinophils. The activity of this NADPH oxidase is markedly diminished or completely absent, resulting in very low or no production of superoxide and thereby of its toxic derivates important for the killing of invading microorganisms [3, 4]. The incidence of CGD is between 1/200,000 and 1/250,000 live births in Caucasians [2, 5].

Pseudallescheria boydii and S. aurantiacum were the PF-562271 cost second most found species in symptomatic patients; but interestingly P. boydii is rare in samples from the environment and therefore over-represented in clinical samples.11 Immunocompromised persons generally bear an increased risk for infections with Pseudallescheria and Scedosporium.2,12,13 In immunocompetent individuals, two entry routes for Pseudallescheria and Scedosporium are relevant: first, the aspiration of contaminated water followed by a comatose period14,15 as a result of a near-drowning event; second, a traumatic inoculation of infectious material.16

As soon as the central nervous system (CNS) is affected by fungal invasion, case fatality is high for both immunocompromised and immunocompetent patients.17,18 In an animal model, infection by P. apiosperma or P. boydii killed 20% of immunocompetent mice and even 100% of immunosuppressed animals. Similarly, S. dehoogii caused the death of even 70% of the immunocompetent mice.19 This high fatality rate highlights the urgent need to clarify the pathogenic mechanisms and subsequently to develop new therapeutic approaches. Two prerequisites enable the invading fungus to survive in the infected host and thus represent FG-4592 in vitro interesting targets for antifungal intervention: the capacity to gain nutrients from the host, and the effective execution of immune

evasion processes. The production and secretion of proteases could encounter both challenges. Digestion of proteins into peptides or free amino acids allows the acquisition of nutrients such as nitrogen and carbon out of proteins, as well as the sourcing of iron by degradation of

transferrin that binds free iron in blood and bodily fluids.20,21 Furthermore, secreted fungal proteases might target complement proteins which represent a major immune shield in the CNS.22,23 Whereas microglia and astrocytes have to undergo a long-standing multistep activation process before exerting antimicrobial activities in the brain, the complement cascade can start within seconds Forskolin nmr after contact with immune complexes (classical pathway), of microbial carbohydrates (lectin pathway) or activator surfaces (alternative pathway) (Fig. 1). The broad spectrum of antimicrobial functions not only include cell lysis of many invading pathogens via formation of the membrane attack complex (MAC), but also the deposition of complement fragments on microbial surfaces (opsonisation) to target them for phagocytosis. Additional complement effects are the attraction of phagocytes to the site of infection and the activation of different cell types via intracellular signal transduction pathways.23 The spectrum of secreted proteases depends on the genetic background of the fungi as well as on the regulatory mechanisms driven by the available nutrients in the environment.

1). Splenic lymphocytes from mice

immunized with AMH formulated selleck chemicals with adjuvants DDA and BCG PSN secreted high levels of IFN-γ upon stimulation with Ag85B, HspX, Mpt64190–198 and PPD (Fig. 2). Splenic lymphocytes from mice immunized with AMH produced higher level of IFN-γ than those immunized with Ag85B, AMM, BCG and PBS with the stimulation of HspX, Mpt64190–198 and PPD. When stimulated with antigen Ag85B, the level of IFN-γ induced by AMH vaccine was lower than that by AMM (P < 0.05) and Ag85B (P > 0.05) vaccines, but was still higher than that receiving BCG (P < 0.05). With the aid of adjuvant DDA + BCG PSN, AMH induced higher levels of antigen-specific IgG1 and IgG2a than Ag85B and AMM (Table 1). Ag85B-specific IgG2a and HspX-specific IgG1 and IgG2a from AMH group were the highest among all groups. PPD-specific IgG1 and IgG2a from the mice immunized with AMH were higher than Ag85B and BCG group. The ratio of Ag85B-specific IgG2a/IgG1 from AMH group was lower than that of BCG group but higher than that of AMM and Ag85B groups. The ratio of HspX-specific IgG2a/IgG1 from AMH group was the highest among all groups. High IgG2a/IgG1 ratio reflects Th1 activity which produces IFN-γ to promote intracellular killing activity by activating

macrophages and cytotoxic T cells [17]. Cell-mediated immune responses in mice primed with BCG and boosted by AMH, AMM, or AMM + AMH were analysed with the stimulation of Ag85B and PPD. The results showed that there were higher levels of IFN-γ SB-3CT production PLX4032 cell line in mice boosted with AMH, AMM and AMM + AMH vaccines than the group of BCG (Fig. 3). It

indicated that Ag85B-, PPD-specific cell-mediated immunity were highly induced by AMH, AMM and AMM + AMH boosting. Unlike the fusion proteins, single-protein Ag85B boosting did not significantly induce high cell-mediated immunity compared with BCG alone. There was no significant difference among AMM, AMH and AMM + AMH groups. The boost with subunit vaccines induced a higher humoral immune response against Ag85B (data not shown). PBS control did not produce antibodies. The titres of IgG1 and IgG2a against Ag85B from mice immunized with BCG and boosted with subunit vaccines were higher than that primed with BCG alone (P < 0.05), whereas there were no significant differences among boosting groups. Protective efficacy was evaluated by CFU count in mice boosted with different protein vaccines followed by challenging with virulent M. tuberculosis H37Rv. The CFUs from the lungs of mice boosted with the subunit vaccines AMM + AMH and AMM were significantly lower than PBS injection, although AMH subunit vaccine boosting did not lead to a significant decrease in CFUs. The bacilli were effectively inhibited in the lungs of mice boosted by AMM + AMH in DDA-BCG PSN, which even induced significantly lower CFU than BCG group (P < 0.05) (Fig. 4).

The culture supernatants were serially diluted in minimal essential medium containing 1% bovine serum albumin supplemented with penicillin and streptomycin. DENV-2 was added to the diluted supernatant and incubated at 4° for 1 hr. The virus and supernatant mixture was added to the Vero cells to achieve a multiplicity of infection of 0·2. Each dilution

was assayed in duplicate. The plates were incubated at 37° in 5% CO2 for 1 hr. One millilitre of minimum essential medium containing 5% fetal bovine serum was added to each well, and the plates were incubated at 37° in 5% CO2 for 24 hr. Each well was washed with 1 ml PBS. Plates were incubated see more with 0·2 ml trypsin/well at 37° for 5 min and washed with1 ml PBS containing 10% fetal bovine serum. The cells were pipetted to break up any clumps and centrifuged at 1000 g for 5 min. Cells were permeabilized using Cytofix/Cytoperm and stained with a 1 : 100 dilution of DENV-specific antibody 2H2 (Millipore, Billerica, MA) followed by 1 : 200 dilution of FITC-conjugated anti-mouse IgG as a secondary antibody (Sigma). Approximately 20 000 cells were analysed for

each sample. The per cent neutralization in the number of infected cells was calculated for each dilution using the formula: 100 – [(Frequency of infected cells in the presence of antibody × 100)/Frequency of infected cells in the absence of antibody]. All statistical calculations were performed using graph pad prism version 5 (Graph Pad software, La Jolla, CA). Mann–Whitney U-tests (two-tailed) were performed to determine statistically significant Selleck GS 1101 differences between median values of each data set. P-values < 0.05 were considered significant. The BLT-NSG mice were implanted with HLA-A2-positive or -negative human fetal thymus and liver under the kidney capsule. CD34+ cells isolated from autologous fetal liver were injected intravenously as a source of HSC. BLT-NSG mice were validated for levels of human haematopoietic engraftment at 12 weeks by flow cytometry of peripheral blood, spleen and bone marrow as described previously.14 We found that BLT-NSG mice had high-level engraftment of

multiple human T-cell and B-cell populations in their bone marrow and spleen, which was superior to reconstitution in cord blood-engrafted mice (Fig. 1). The total percentages of human CD45+ ranged between 13 and 75% (median 50%, n = 16) in the spleen and 16–84% GBA3 (median 53%, n = 16) in the bone marrow (Fig. 1b). Similarly high percentages of human CD45+ CD3+ T cells and CD19+ CD20+ human B cells were detected in the periphery of the BLT-NSG mice (Fig. 1c,d). To determine whether BLT-NSG mice could be infected with DENV, immunization was carried out with laboratory and vaccine strains of DENV-2 by the subcutaneous route. We monitored infected mice for signs of illness. More than 50% of mice experienced weight loss by day 13 and had ruffled fur and hunched back posture, suggesting that BLT-NSG mice exhibited clinical signs of DENV infection.

Why fibrocytes

are induced to infiltrate kidneys following unilateral ureteral obstruction, but are relatively rare in renal tissues from similarly manipulated severe combined immunodeficiency Fostamatinib supplier (SCID) mice, might be attributable to the absence of lymphocytes in immunodeficient animals. A recent study by Pilling et al. [15] has examined the markers that might be useful in distinguishing human fibrocytes from fibroblasts. In their remarkably detailed and exhaustive study, the authors found that among the cell types examined, only fibrocytes express the combination of CD45RO, 25F9 and S100A8/A9. They included in their study fibroblasts, macrophages and peripheral blood monocytes. Importantly, Selleck Buparlisib they concluded that CD34, CD68 and collagen fail to discriminate among these four cell types. Several cytokines, including IFN-γ, IL-4, IL-12, IL-13 and serum amyloid P, differentially affect the display of CD32, CD163, CD172a and CD206 in fibrocytes and macrophages [15]. Human fibrocytes express a diverse array of cytokines, including TNF-α, IL-1β, IL-10, monocyte chemoattractant protein (MCP), macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, platelet-derived growth factor (PDGF)-A, TGF-β1 and macrophage colony-stimulating factor (M-CSF). Moreover, treatment

of fibrocytes with exogenous IL-1β induced IL-6, IL-8, IL-10, MCP-1, MIP-1α and MIP-1β. Thus the array of cytokines produced by fibrocytes, either under basal conditions or following activation by Baricitinib IL-1β, appears to be very similar to that found in fibroblasts originating from a variety of tissues. Regulation of fibrocyte trafficking to sites of injury and tissue repair apparently derives from a network of chemokines and chemoattractants. CXCR4 represents the principal chemokine receptor displayed on human fibrocytes. Its cognate ligand, CXCL12, is generated by several cell types. CXCL12 has been shown in several

models to exert powerful chemotactic influence by fibrocytes and represents a major determinant for their infiltration of target tissues. In addition, CCR3, CCR5 and CCR7 are also expressed on the human fibrocyte surface [16,17]. A slightly different profile of receptors is found on animal fibrocytes. For instance, mouse fibrocytes display CXCR4, CCR2 and CCR7. PDGF, insulin-like growth factor (IGF) and epidermal growth factor (EGF) can induce CXCR4 mRNA [18]. Growth factor and hypoxia-driven CXCR4 display is mediated through the PI3 kinase/mTor pathway and can be inhibited by rapamycin, which substantially diminished the accumulation of fibrocytes in targeted tissues. In the last few years, more attention has been focused upon the study of human fibrocytes and their potential abnormalities in disease.

TOMIOKA SATORU, KUBO EIJI, KOBAYASHI KANA, ARAI SHIGEYUKI, TAMURA YOSHIFURU, KURIBAYASHI EMIKO, CHANG WENXIU, UCHIDA selleck chemicals SHUNYA Department of Internal Medicine, Faculty of Medicine, Teikyo University, Tokyo, Japan Introduction: When to start hemdialysis remains a matter of debate. Too early or too late is neither optimal. Serum creatinine (Cr) is the only numerical indicator for the

start of hemodialysis decided by the committee of the Ministry of Health, Labour and Welfare of Japan. In this study, the appropriate start point for hemodialysis was investigated not only by serum Cr but also by other parameters including patients’ symptoms. Methods: Out of the 333 patients started on hemodialysis in our hospital between 2001 and 2006, we selected patients who received outpatient treatment for more than six months and whose serum Cr trends were linearly regressive. Patients with increased serum CRP were excluded. Finally, 78 patients were enrolled in the analysis. First, the two sets of data were prepared; one was the data at the start of hemodialysis and another date was one month previously. Logistic regression analysis was applied to reveal predictors. Results: In all cases, serum Cr was extracted as the most influencial predictor followed by serum sodium (Na) and serum β2 microglobulin (β2MG) for judging the

start point for hemodialysis. The discriminating ability by these three factors increased to 75% from 66% by serum Cr alone. In the sex-based analysis, only serum KU-57788 cost Cr was significant in male while the serum

Na and β2MG levels were significant when serum Cr was excluded in female. Conclusion: Serum Cr is an appropriate parameter when to start hemodialysis. In addition, serum β2MG and serum Na are also influencial learn more factors especially in female. The optimal start point of hemodialysis may be determined by concidering multiple predictors rather than serum Cr alone, leading to more appropriate judgment. ARDHANY ARDITYO RAHMAT1,2,3, THAHA MOCHAMMAD1,2, YOGIANTORO MOHAMMAD1, YASUHIKO TOMINO3 1Nephrology and Hypertension Division, Department of Internal Medicine Faculty of Medicine Airlangga University, Dr. Soetomo Teaching Hospital Surabaya, Indonesia; 2Institute of Tropical Disease, Airlangga University, Surabaya, Indonesia; 3Division of Nephrology, Juntendo School of Medicine, Tokyo, Japan Introduction: The prevalence of hyperhomocysteinaemia in hemodialysis patients reaches 90–95%. Hyperhomocysteinaemia increased cardiovascular risk. Various therapies by supraphysiologic dose of folic acid, vitamin B6, and B12 failed to normalize the homocysteine level, especially in hemodialysis patients. Oral dose of 1200 mg N-Acetylcysteine (NAC) has been shown to reduce plasma level of homocysteine. However, its effect in the form of capsule has not been investigated. Capsule dosage form is expected to reduce the strong smell of NAC and gastritis experienced by patients who take the effervescent tablet.