A pacemaker infection was diagnosed in 19 (9 4%) patients There

A pacemaker infection was diagnosed in 19 (9.4%) patients. There were 34 (16.8%) mechanical valves and 112 (55.4%) bioprosthetic valves implanted. Valvular plasties were performed in selleck catalog 66 patients (32.7%). One patient (0.5%) had a concomitant coronary artery bypass graft, and fourteen (6.9%) underwent ascending aorta replacement using a prosthetic tube. Median duration of extracorporeal circulation was 118 (85 to 163) minutes, and median duration of aortic cross-clamping was 89 (65 to 121) minutes. Circulatory arrest was necessary in five (2.5%) patients. A second operation (or more) was necessary in 29 (14.4%) patients. The main reasons were: tamponnade (n = 12, 41.4%), valve dysfunction (n = 6, 20.7%) and mediastinitis (n = 4, 13.8%).MicrobiologyThe causative pathogens are presented in Table 2.

The three most frequently involved species were: streptococci (n = 84, 41.6%), staphylococci (n = 56, 27.8%) and enterococci (n = 18, 8.9%). Blood cultures were positive in 155 (76.7%) patients.Table 2MicrobiologyRenal function and prognosisSixty-five patients (32.2%) presented with AKI before surgery, and 137(67.8%) had normal renal function before surgery. Of the 65 patients with pre-operative AKI, 52 (80%) were in AKIN stage 1, 9 (13.8%) in stage 2 and 4 (6.2%) in stage 3. A flow chart depicting the evaluation of renal function throughout the peri-operative period is provided in Figure 1. The evolution of serum creatinine in the peri-operative period is separately described in Figure 2.Figure 1Flow chart of patients. AKI, acute kidney injury.

Figure 2Evolution of serum creatinine during the peri-operative period. AKI, acute kidney injury.A total of 120 (59.4%) patients met the criteria for AKI in the post-operative period: 64 (46.7%) of the 137 patients without pre-operative AKI and 56 (86.1%) of the 65 patients with pre-operative AKI. Among the 65 patients with pre-operative AKI, 9 (13.8%) recovered during the 7 days following surgery, 29 (44.6%) had no AKI progression, and 27 (41.6%) experienced AKI progression (that is, worsening in their AKI stage).A total of 20 patients (9.9%) required RRT during the post-operative ICU stay. The delay between ICU admission and the initiation of RRT was 1.5 (1 to 3) days.Association between acute kidney injury and patients�� outcomesThirty patients (14.8%) died during their hospital stay.

Mortality was associated with the presence/absence of AKI. The association was not statistically significant when considering pre-operative AKI only: 16 (11.7%) patients Batimastat without pre-operative AKI died versus 14 (21.5%) patients with pre-operative AKI (P = 0.09 for univariate analysis). However, the association between post-operative AKI and mortality was statistically significant: 2 (2.4%) patients without post-operative AKI died, and 28 (23.3%) patients with post-operative AKI died during their hospital stay (P <0.001 for univariate analysis). AKI stage was also associated with mortality: 18 (52.

Endotoxin levels bound to PBMC and in plasmaThe levels of endotox

Endotoxin levels bound to PBMC and in plasmaThe levels of endotoxin in lysates of PBMC are presented in Figure Figure3.3. LPS was detected in PBMC lysates of 71.4% of AAS patients, with levels significantly higher than apply for it in CAS patients. Highest levels of LPS were observed after blood reperfusion (T4) in AAS patients and decreased progressively at POD1 and POD2. On the other hand, the CAS group showed no significant presence of LPS in their PBMC during the observational period. Plasma levels of LPS were also measured in AAS patients. Only 57.1% of the plasmas were positive and the detected levels were much lower than those found in PBMC (data not shown).Figure 3Assessment of endotoxin (LPS) associated with circulating peripheral blood mononuclear cells (PBMC) in AAS and CAS patients.

Endotoxin associated with patients’ PBMC was measured using a Limulus amebocyte assay. T1 (before anesthesia), T2 (before incision), …Comparison of the reliability of the assays for the detection of NOD2 agonist and endotoxinIn order to examine the reliability of detection of the NOD2 agonist and endotoxin tests, we compared the positive responses to the tests based on the detection limits. The detection limits of the LAL test in PBMC and plasma were 5 pg/ml and 1.6 pg/ml, respectively. The natural structure derived from PGN following translocation is unknown and may be different from that resulting from enzymatic digestion and purification performed in vitro. We avoided extrapolating the levels of luciferase activity to a standard curve of biochemically purified PGN.

Our test was expressed as fold increase as compared with the plasma before surgery, each patient being his own control. The detection limit of the NOD2 agonist test showed a 1.57-fold increase in luciferase activity as compared with the value at T1 (before anesthesia). This detection limit was calculated on the basis of the mean �� 2SD of the fold increase at T2 in control patients. For reference, the mean �� SEM and median fold increase for various PGN (5.0 ��g/ml) incubated in healthy plasma were 1.76 �� 0.19 and 1.68, respectively (Figure (Figure1b1b).In all AAS and CAS patients, we compared the detection reliability for the NOD2 agonist test in plasma with the endotoxin test in PBMC. In AAS patients, 90.5% (19 out of 21 patients) were positive in the NOD2 agonist test, and 71.4% (15 out of 21 patients) were positive in the LAL test (PBMC-associated LPS). In CAS patients, 23.8% (5 out of 21 patients) were positive in the NOD2 agonist test, and 19% (4 out of 21 patients) in the LAL test (Figure (Figure4).4). From Entinostat this result, we can conclude that the NOD2 agonist detection test was more reliable than the endotoxin test.

Also, the umbilical access is a well-known and standardized site

Also, the umbilical access is a well-known and standardized site for access Calcitriol vitamin d to the abdominal cavity for laparoscopic procedures [13]. However, many authors have described an SPA appendectomy as a step toward less invasive surgical procedures [14]. According to surgeon’s experience, umbilical access does not add new risks, and it makes the operating view the same as in standard laparoscopic appendectomy. In this study no differences were found comparing the trocar placement time of each group, and all the trocars were placed under direct vision. Once the pneumoperitoneum is performed, both techniques can allow making an intraoperative differential diagnosis with other pathologies [15]. In our series, examination of distal ileum, female genital organs including the tubes and the ovary, and other organs situated in pelvic area can be accomplished without difficulties.

We had to reconvert to an open surgery approach in a cecal carcinoma misdiagnosed preoperatively. When the fascia is exposed, it is possible to enter the abdominal cavity with various devices such as 10mm trocar and two 5mm trocars. The single-port technique allows easy use of a 10-mm instrument if needed without the burden of having to work with a 5mm and a 10mm port so close together. Due to the vicinity of the ports at the fascial plane in the umbilicus, the operative technique can be more difficult. In some cases the crossing of the instruments (or specially designed instruments) makes the procedure more challenging and initiating new learning curve for surgeon.

It has not been defined yet the number of cases needed to gain good experience in SPAA. But it seems that 10 cases should be the number in order to perform a correct learning curve with previous experience in laparoscopic surgery [16]. In our opinion appendectomy is relatively easy operation performed in a relatively safe abdominal area (no much vital organs). This novel approach should probably be the first one to be considered before beginning SPA cholecystectomies, which are more demanding. When drain is required, right side placement is suitable and can be placed under direct vision. A very important issue is to consider the conversion from single-incision (SPAA) technique to standard laparoscopic technique. Fear from intraoperative complications is due to inadequate visualization or mobilization of the appendix.

For this reason, we consider that a two-port or three-port conversion should not be considered a failure or complication. This concept is very important and is absolutely mandatory in emergency surgeries. An optimum safe view must be achieved. If this is not achieved then the addition of ports is recommended. Batimastat The opinion of the authors concerning the visualization in this series was not as optimal as with typical laparoscopy.

3)) Still, other investigations such as plain film X-ray and ult

3)). Still, other investigations such as plain film X-ray and ultrasound have been used to help make the diagnosis. The classic triad of abdominal pain, bloody stools, and a palpable mass is rarely seen in these cases of intussusception, and therefore, it is important to take a multimodality selleck compound approach. The combined use of clinical history, physical exam, and radiographic images increases the sensitivity significantly and helps to plan the surgery in a more suitable time frame [8]. Figure 1 (a) Illustration of intussusception. (b) Target sign: it indicates hyperemia of mucosa, muscularis, and serosa with submucosal edema. The high attenuation of mucosa, muscularis, and serosa is due to contrast enhancement, while the low attenuation of submucosa …

Figure 2 (a) Axial view of the CT scan showing intussusception with fat and blood vessels within the lumen of intestine (white arrow��target sign and pneumatosis). (b) Coronal view of the CT scan showing intussusception (white arrow��sausage-shaped … Figure 3 Sagittal view of the CT scan showing intussusception (white arrow��site of intussusception). Although our ability to detect and treat intussusception following gastric bypass surgery has improved, its etiology remains somewhat unclear. Most people still believe that intussusception is related to dysmotility, which develops secondary to the development of ectopic pacemakers. Other proposed mechanisms include development of new lead points such as sutures or staple lines and focal nodal hyperplasia. However, in the vast majority of cases, no identifiable lead points or aberrations in anatomy are detected [7, 9, 10].

2. Material and Methods A comprehensive search was conducted to identify the literature published worldwide including articles, reviews, case reports, and series and abstracts describing intussusception after gastric bypass surgery. We also included patients from our own clinical experience. We included all patients who underwent gastric bypass surgery for weight loss��both open and laparoscopic, confirmed diagnosis of intussusception��either preoperative or postoperative based on pathology. Patients with gastric bypass surgery for reasons other than weight loss, intussusception not associated with weight loss surgery, and diagnosis of intestinal obstruction due to causes other than intussusception were excluded in this review.

The data was extracted using a structured form that included information regarding demographic profile, medical history, weight loss, clinical presentation, radiographic imaging, diagnosis, management, and posttreatment course in these patients (Table 1). Table 1 Summary of patient profile. 3. Results Seventy one patients were identified including seven patients from our own series, in 29 studies published worldwide between the years 1991 and 2011. The majority of patients identified were females (n = 70, 98.6%), with the median age of 35.5 years (range, 20�C60 years). Sixty nine patients Batimastat (97.

29 days versus laparoscopic = 5 01 days; P < 0 001) resulting in

29 days versus laparoscopic = 5.01 days; P < 0.001) resulting in lower hospital costs (open = $24, 060 versus laparoscopic = $12, 451;P < 0.001). Improved outcomes Tipifarnib clinical were also observed in patients ��80 years with respect to LOS (open = 11.91 versus laparoscopic = 6.77; P < 0.001) and hospital costs (open = $26, 342 versus laparoscopic = $15, 030;P < 0.001). In addition, among patients aged ��80 years, there was a significant increase in these patients being successfully discharged home directly from the hospital (open = 37.0% versus laparoscopic = 63.2%; P < 0.001). 4. Discussion Gallstone disease is the most common indication for abdominal surgery in the United States. Prevalence of gallstone disease is known to increase with age.

An increasing life expectancy means that, over the next several decades, the proportion of the population aged over 65 years is expected to rise from 12% to 20% resulting in more patients presenting with gallstone disease requiring surgery [1]. Evaluating national trends to decipher the optimum surgical approach for these patients is important. This large cross-sectional study of hospitalized patients undergoing cholecystectomy found a steady increase in the adoption of laparoscopic cholecystectomy from 1999 to 2006 among all age groups. Although older patients clearly benefited from laparoscopic cholecystectomy than open cholecystectomy, they are significantly less likely than younger patients to undergo laparoscopic cholecystectomy. However, there was an increasing trend among elderly patients (65�C79 years and ��80 years) undergoing toward laparoscopic cholecystectomy over the study period.

Compared to younger patients, elderly patients experienced more adverse outcomes overall, but this was reduced with the adoption of laparoscopic surgery. This is important given that elderly patients tend to present with more complex biliary disease and multiple diagnoses that may increase their surgical risk [3]. Elderly patients are also more likely to require further procedures such as cholecystostomy decompression, endoscopic retrograde cholangiopancreatography (ERCP), common bile duct exploration, and intraoperative cholangiogram [3, 4]. Among the elderly, laparoscopic cholecystectomy, compared with open cholecystectomy, is associated with lower mortality rates, surgical complications, LOS, hospital costs, and better discharge deposition overall, supporting laparoscopic cholecystectomy as the procedure of choice in this population.

In previous studies, the mortality rates in elderly patients undergoing laparoscopic Batimastat cholecystectomy are reported between 0 and 1% [6�C8]. However, these studies defined elderly as patients between the ages of 65 to 79 years only. In direct comparison, we observed a comparable mortality rate of 0.9% in the same age group. In our study cohort of patients aged ��80 years, the mortality rate was 2.


selleck chemicals llc Metastasis is the major obstacle in the treatment of malig nant cancer and it accounts for more than 90% of cancer related mortality. Since gastric cancer is the second most lethal cancer worldwide, the underlying molecu lar mechanisms responsible for gastric cancer metastasis need to be elucidated. Nuclear factor ��B is a family of signal responsive transcription factors that includes RelA p65, RelB, c Rel, NF ��B1 p50 and NF ��B2 p52. NF ��B exists in an in active form in the cytoplasm because of its interaction with the inhibitory protein, I��B. After activation of I��B kinases, I��Bs become phosphorylated, ubi quitinated and degradaded by proteasomes, which allows NF ��B to translocate to the nucleus, where it can activate or repress target genes.

With respect to gastric cancer, NF ��B is one of the most well studied transcription fac tors, and is known to be activated by various factors, including cytokines, growth factors, Toll like receptor signaling and many other pathways of microbial recognition. NF ��B activation has been frequently observed in both gastric cancer cells and tumor infiltrating lymphocytes. In addition, down regulation of NF ��B has been shown to suppress cell migration and invasion in gastric cancer cells in vitro. Thus, modulation of the NF ��B pathway might be a promising therapeutic target for gastric cancer metas tasis. However, the downstream mediators of NF ��B induced metastasis in gastric cancer cells remain unclear. Signal transducers and activators of transcription 3 belongs to the STAT family of signal responsive transcription factors.

The inactive form of STAT3 in the cytoplasm of non stimulated cells is activated by cytokines, growth factors and oncogenic proteins through sequential phosphorylation of tyrosine 705 and serine 727. Like NF ��B, constitutive activation of STAT3 has been shown to contribute to the progression of gastric can cer, including proliferation, apoptosis, angiogenesis and metastasis. However, STAT3 showed differential roles in gastric cancer cell metastasis depending on the upstream regulator of STAT3 activation. Previously, NF ��B activation in human cancers has been reported to be positively or negatively correlated with STAT3 activation in the control of tumorigenesis, tumor growth and angiogenesis. STAT3 activation increased NF ��B activation and tumor growth derived from cervical cancer cells or glioblastoma cells.

STAT3 also maintains NF ��B activation and reten tion in the nucleus in melanoma cells and prostate cancer cells. In addition, NF ��B activation increased STAT3 activation through up regulation of interleukin 6 in melanoma cells. On the other hand, a positive crosstalk between NF ��B and STAT3 was found in GSK-3 B cell lymphoma, which increased cell proliferation and decreased apoptosis.

Here, we will only be concerned with true canonical labels, but i

Here, we will only be concerned with true canonical labels, but in the case of either a canonical or pseudo canonical labeling algorithm, the algorithm must be called only once for each chemical species EMD 1214063 graph repre senting a newly generated reaction product. An algo rithm assigning canonical labels can thus be used to determine graph isomorphism efficiently, as string com parisons are much more efficient than graph compari sons. In practice, if there are a large number of graphs that need to be compared to one another, it is efficient to assign canonical labels using an algorithm such as Nauty to each graph and then to compare the graphs using their labels. Although hierarchical graphs are currently only pro posed here for annotation purposes, such graphs could in principle be incorporated into models as formal ele ments.

To enable the incorporation of hierarchical graphs into executable models, we describe a generaliza tion of the Nauty algorithm, which takes as input hierarchical graphs and assigns them canonical labels. Results Hierarchical Graphs for Annotating Rule based Models Definitions We give exact definitions of hierarchical graphs before discussing how hierarchical graphs can be used to repre sent particular proteins with hierarchical substructures. A hierarchical graph is a graph together with an acyclic parent function p, The parent function defines the hierarchy, the parent of a vertex is the next level up in the hierarchy. While the function p must be acyclic we do allow vertices to be their own parents, the assignment p v is permissible.

It is common to represent the hier archy as a directed tree. A labeled hierarchi cal graph is a hierarchical graph with a labeling of the vertices as above. Although many pro teins do indeed have a hierarchical substructure, the above definition may be too strict in some cases. An example of such a case is provided by overlapping linear motifs, because amino acid residues in the region of overlap cannot be considered to have a unique parent in a hier archical graph. We will call such hierarchies pseudo hierarchies and define a pseudo hierarchical graph to be a directed acyclic graph. Although individual nodes in pseudo hierarchical graphs may not have a unique par ent, the acyclicity of the hierarchy ensures there is still a top down structure to the graph.

In models, we will want to essentially use both hier archical graphs and the conven tional flat graphs of BNGL at the same time, the first type of graph to show the structural relationships between molecular components and the second type of graph to show bonds between molecular components. Thus, we will use graphs with two edge types, the Carfilzomib first type will represent the hierarchy and will be directed, the second type will represent bonds and will be undirected. The vertices of the graphs in BNGL are not only labeled but are also attributed.

The plates were incubated, and culture supernatants were harveste

The plates were incubated, and culture supernatants were harvested 24 hours later. The IFN�� concentration in this media was determined by ELISA. IL 18 bioactivity was determined based on the difference in IFN�� levels bet ween cultures with and those without mouse anti IL 18 monoclonal selleck bio antibody. Immunofluorescence staining RA synovial fibroblasts were plated in 8 well Labtek chamber slides and processed as described previously. Briefly, cells were untreated or stimulated with TNF for 48 hours with or without preincubation with PD98059 or AG490 for 2 hours. After 48 hours, cells were washed, fi ed, permeabilized, and blocked. IL 18 primary antibody, which reacts with both immature and mature IL 18 forms, was used after washing in combination with Ale a Fluor conjugated goat anti rabbit antibody.

After washing, nuclei were stained with 4,6 diamidino 2 phenylindole. Slides were dehydrated, mounted, and coverslipped. Immuno fluorescence staining was detected using an Olympus FV 500 microscope. Statistical analysis Statistically significant differences between groups were calculated using Students t test. P values less than 0. 05 were considered significant. All statistical data are e pressed as the mean standard error of the mean. Results TNF induced functional caspase 1 in RA synovial fibroblasts To determine whether pro IL 18 was potentially cleaved by active caspase 1 to the IL 18 active form, we e a mined caspase 1 e pression in cell lysates and IL 18 e pression in cell lysates and conditioned media at the protein level, without or with TNF stimulation.

TNF induced caspase 1 at the protein level in cell lysates in a time dependent manner and the mature IL 18 secretion in the conditioned media assessed by western blot and ELISA. The pro IL 18 level in cell lysates did not change over time, suggesting that pro IL 18 is cleaved to IL 18 and then secreted. These data indicate that TNF induced functional caspase 1 to cleave pro IL 18. Role of the JAK pathway in TNF induced caspase 1 To identify signaling events that are critical for TNF induced caspase 1, RA synovial fibroblasts were in cubated with chemical signaling inhibitors for 2 hours, followed by TNF stimulation. Only JAK pathway inhibition significantly decreased TNF induced caspase 1 at the transcriptional level in RA synovial fibroblasts.

TNF induced caspase 1 protein e pression was markedly re duced when the JAK pathway was blocked in RA synovial fibroblasts. Anacetrapib According to our blot, this reduction is due mainly to a reduction of pro caspase 1 e pression. At the end, we assessed the functional activity of capsase 1. Blocking the JAK pathway strongly reduced TNF induced caspase 1 activity. Furthermore, blocking the JNK pathway already slightly decreased the TNF induced caspase 1 activity. These data indicate that the JAK pathway is a critical pathway for TNF induced caspase 1 and IL 18 bioactivity.

However, the acetylation

However, the acetylation concerning site in Smad4 which directly interacts with SIRT1 remains unknown. We generated a flag tagged Smad4 WT, Smad4 K37R, and Smad4 K428R mutant OECM1 cells, and analyzed their acetylation levels. After immunopurifying ectopically e pressed Flag tagged Smad4 proteins from OECM1 mutants after knock down of SIRT1, we found that the acetylation mimetic mutant Smad4K37R had a signifi cantly decreased level of acetylation compared to the wild type Smad4. Whereas K428R substitution greatly increased acetylation to levels similar to those observed in wild type Smad4. Together, these obser vations indicated that TGF B stimulation increased Smad4 and MMP7 e pression, and SIRT1 deacetylated Smad4 in vivo. additionally, K37 was the primary target of SIRT1, resulting in decreased MMP7 e pression and activity.

Thus, SIRT1 participates in regulation of MMP7 activity and e pression by deacetylating K37 of Smad4, and repressing the effect of TGF B signaling in oral cancer. Overe pression of SIRT1 inhibits lung metastasis of OSCC cells Our results showed that SIRT1 inhibits the EMT process in cancer by deacetylating Smad4 and repressing the effect of TGF B signaling on MMP7. We therefore pos tulated that overe pression of SIRT1 may suppress can cer cell metastasis in vivo. We used a floor of the mouth murine model in SCID mice to determine whether SIRT1 inhibits cancer cell metastasis in vivo. OECM1 cells were stably transfected with the vector alone or a vector inducing overe pression of SIRT1. Ten SCID mice used in the floor of the mouth model were injected with OECM1 cells.

Two mice were injected with PBS, four were injected with control vector, and four with SIRT1 overe pressing OECM1 cells. As shown in Figure 8, With the e ception of PBS control mice, all mice grew similar tumors in the floor of the mouth. Upon dissection, the tumors showed multiple foci and poorly differentiated SCCs with prominent lymphovascu lar invasion at the orthotopic injection site. Among mice injected with vector alone 75% showed lung metastasis, while 25% of mice injected with SIRT1 overe pressing vector showed lung metastasis. These results showed that stable overe pression of SIRT1 significantly suppressed lung metastasis of OECM1 cells, resulting in fewer metastatic foci and smaller nodules in the lung.

We also e amined the tumor region of the e tracted tissue by ICH with anti Smad4 polyclonal antibody, and found higher levels of Smad4 e pression in the lung tissue e tracted from Dacomitinib mice in the vector only control group. The results indi cated that overe pression of SIRT1 in OECM1 cells led to significantly suppressed lung metastasis in the floor of the mouth murine model. Discussion In this study, we demonstrated that SIRT1 suppresses the EMT process in oral squamous cell carcinoma cells by deacetylating Smad4 and repressing MMP7 e pression.

Although the physiologi cal role of this process is not well unde

Although the physiologi cal role of this process is not well understood, it is likely that CCR2 down regulation may be involved in restricting the reverse migration of differentiated monocytes back into the blood stream. This in turn facilitates the retention of differentiated monocytes within Erlotinib inflamed tissues. Thus, by improving our understanding of the regulatory mecha nisms that govern CCR2 e pression on monocyte lineage cells, we can better appreciate how monocyte recruitment and activation is controlled during chronic inflammatory pathologies such as atherosclerosis. Background Elevated levels of plasma homocysteine are associated with chronic kidney disease and end stage renal disease irrespective of the underlying aetiol ogy.

However, the pathophysiological consequences of hyperhomocysteinemia remain controversial because, although Hhcy has consistently been associated with morbidity and mortality, recent epidemiologic stud ies have produced conflicting results. In a prospective community based study of persons without kidney dis ease at study inception, over a 5 year period, chronic kid ney disease risk was found to increase in association with escalating Hcy levels in both men and women. The converse has been also reported. that is, chronic kidney disease is a direct cause of Hhcy. Hcy levels rises in direct relationship to reduction in glomerular filtration rates. Given the e istence of these inconsistent observations, the role of Hcy in progressive kidney disease is unresolved and continues to be the focus of ongoing clinical and basic investigations.

Notwithstanding contradictory observations, studies have identified an association between Hcy and inflammation. For instance, in subject aged 65 years, IL 6 and IL 1ra cytokines were independent predictors of plasmatic Hcy concentrations. Similarly, in another study, serum Hcy levels and C reactive protein levels were significantly higher in patients with stage 3 chronic kidney disease compared to those with stage 1 disorder. In this regard, the potential consequences of Hhcy on inflamma tion in the kidney have been studied by assessing the impact of Hcy on monocyte chemoattractant protein 1 e pression by glomerular mesangial cells. Hcy induced MCP 1 protein and mRNA levels in glomerular MC via nuclear factor kappa B activation, a process found to be mediated by generation of o idative stress.

In a related study, the same investigators observed that in methionine induced Hhcy rats, MCP 1 protein and mRNA levels were increased in kidneys Cilengitide and that this increase was dependent on NF ?B. The authors surmised that these observations link Hcy induced inflammatory response to kidney injury and progressive kidney disease. We have demonstrated that Hcy induces DNA damage and apoptosis in MC. These adverse effects were depend ent on Hcy induced o idative stress and p38 MAPK activa tion.