Given that Parkinson's disease broadly affects frontostriatal circuitry, it is not surprising that the disorder is associated with a reduction of working memory. We tested whether this reduction is due to diminished storage capacity or impaired ability to exclude task-irrelevant items. Twenty-one medication-withdrawn patients and 28 age-matched control subjects performed a visuospatial memory task while their electroencephalograms were recorded. The task required them to remember the orientations of red rectangles within the half of the screen that was cued while ignoring all green rectangles. Behavioural and electroencephalogram measures indicated that patients with Parkinson's disease were impaired at filtering out distracters, and that they were able to hold fewer items in memory than control subjects. The results support recent suggestions that the basal ganglia help control access to working memory.
Parkinson's disease; visual working memory; event-related potentials; selective attention; dopamine
Negative regulation of osteoclastogenesis is important for bone homeostasis and prevention of excessive bone resorption in inflammatory and other diseases. Mechanisms that directly suppress osteoclastogenesis are not well understood. In this study we investigated regulation of osteoclast differentiation by the β2 integrin CD11b/CD18 that is expressed on myeloid lineage osteoclast precursors. CD11b-deficient mice exhibited decreased bone mass that was associated with increased osteoclast numbers and decreased bone formation. Accordingly, CD11b and β2 integrin signaling suppressed osteoclast differentiation by preventing RANKL-induced induction of the master regulator of osteoclastogenesis NFATc1 and of downstream osteoclast-related NFATc1 target genes. CD11b suppressed induction of NFATc1 by the complementary mechanisms of downregulation of RANK expression and induction of recruitment of the transcriptional repressor BCL6 to the NFATC1 gene. These findings identify CD11b as a negative regulator of the earliest stages of osteoclast differentiation, and provide an inducible mechanism by which environmental cues suppress osteoclastogenesis by activating a transcriptional repressor that makes genes refractory to osteoclastogenic signaling.
osteoclast; signaling; integrin; CD11b; BCL6
Aim. To compare two creatinine-based estimated glomerular filtration rate (eGFR) equations, the chronic kidney disease epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD), for predicting the risk of CKD progression in type 2 diabetic patients with nephropathy. Methods. A total of 707 type 2 diabetic patients with 24 hr urinary albumin excretion of more than 30 mg/day were retrospectively recruited and traced until doubling of baseline serum creatinine (SCr) levels was noted. Results. During the follow-up period (median, 2.4 years), the CKD-EPI equation reclassified 10.9% of all MDRD-estimated subjects: 9.1% to an earlier stage of CKD and 1.8% to a later stage of CKD. Overall, the prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was lowered from 54% to 51.6% by applying the CKD-EPI equation. On Cox-regression analysis, both equations exhibited significant associations with an increased risk for doubling of SCr. However, only the CKD-EPI equation maintained a significant hazard ratio for doubling of SCr in earlier-stage CKD (eGFR ≥ 45 mL/min/1.73 m2), when compared to stage 1 CKD (eGFR ≥ 90 mL/min/1.73 m2). Conclusion. In regard to CKD progression, these results suggest that the CKD-EPI equation might more accurately stratify earlier-stage CKD among type 2 diabetic patients with nephropathy than the MDRD study equation.
Maintenance dialysis is made decreased the death rate of patients with end-stage renal disease; however, mortality is still high. The aim of this study was to identify the association between clinical parameters at the start of hemodialysis with survival and compare these findings with data from patients who underwent hemodialysis about 15 years ago at the same dialysis center.
We reviewed 117 patients who started hemodialysis between 2000 and 2004. We analyzed medical histories, laboratory findings, and clinical outcomes, and compared them with patients who started hemodialysis 15 years ago at the same center.
The proportion of elderly patients and those with diabetes increased from 17% and 18% in the previous study to 33% and 49% in this study, respectively. Elderly and patients with diabetes had much higher mortalities than their counterparts. Nevertheless, the overall survival rate (66% vs. 71% at 5 years) and survival of patients with diabetes improved (55% vs. 75% at 1.5 years). Common causes of death were infection and cardiovascular disease in the present study; however, inadequate dialysis accounted for 25% of deaths in the previous study.
The overall survival rate of patients undergoing hemodialysis has improved over the 15-year interval, even with an increased proportion of elderly patients and patients with diabetes. Adequate dialysis and further medical improvements could ameliorate mortality in patients undergoing dialysis.
Renal dialysis; Mortality; Survival analysis
Gram-positive bacteria naturally produce extracellular vesicles. However, little is known regarding the functions of Gram-positive bacterial extracellular vesicles, especially in the bacterial community. Here, we investigated the role of Staphylococcus aureus extracellular vesicles in interbacterial communication to cope with antibiotic stress. We found that S. aureus liberated BlaZ, a β-lactamase protein, via extracellular vesicles. These extracellular vesicles enabled other ampicillin-susceptible Gram-negative and Gram-positive bacteria to survive in the presence of ampicillin. However, S. aureus extracellular vesicles did not mediate the survival of tetracycline-, chloramphenicol-, or kanamycin-susceptible bacteria. Moreover, S. aureus extracellular vesicles did not contain the blaZ gene. In addition, the heat-treated S. aureus extracellular vesicles did not mediate the survival of ampicillin-susceptible bacteria. The β-lactamase activities of S. aureus soluble and extracellular vesicle-associated BlaZ were similar, but only the extracellular vesicle-associated BlaZ was resistant to protease digestion, which suggests that the enzymatic activity of BlaZ in extracellular vesicles is largely protected by the vesicle structure. Our observations provide evidence of the important role of S. aureus extracellular vesicles in antibiotic resistance, which allows the polymicrobial community to continue to evolve and prosper against antibiotics.
Interferon (IFN)-gamma is an important component of the immune response to viral infections that can have a role both in controlling virus replication and inducing inflammatory damage. To determine the role of IFN-gamma in fatal alphavirus encephalitis, we have compared the responses of wild type C57BL/6 (WTB6) mice with mice deficient in either IFN-gamma (GKO) or the alpha-chain of the IFN-gamma receptor (GRKO) after intranasal infection with a neuroadapted strain of sindbis virus. Mortalities of GKO and GRKO mice were similar to WTB6 mice. Both GKO and GRKO mice had delayed virus clearance from the brain and spinal cord, more infiltrating perforin+ cells and lower levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 mRNAs than WTB6 mice. However, inflammation was more intense in GRKO mice than WTB6 or GKO mice with more infiltrating CD3+ T cells, greater expression of major histocompatibility complex-II and higher levels of interleukin-17A mRNA. Fibroblasts from GRKO embryos did not develop an antiviral response after treatment with IFN-gamma, but showed increases in TNF-alpha, IL-6, CXCL9 and CXCL10 mRNAs although these increases developed more slowly and were less intense than those of WTB6 fibroblasts. These data indicate that both GKO and GRKO mice fail to develop an IFN-gamma-mediated antiviral response, but differ in regulation of the inflammatory response to infection. Therefore, GKO and GRKO cannot be considered equivalent when assessing the role of IFN-gamma in CNS viral infections.
We examined whether high flux membranes (HF) may induce a greater loss of amino acids compared to low flux membranes (LF). Ten hemodialysis patients participated in this study. Pre- and post-hemodialysis plasma amino acid profiles were measured by reverse-phase high pressure liquid chromatography for both HF and LF. We measured the dialysate amino acid losses during hemodialysis. The reduction difference for plasma total amino acid (TAA), essential amino acid (EAA), and branch chained amino acid (BCAA) was not significantly different in comparisons between the two membranes. (HF vs. LF; TAA 66.85±30.56 vs. 53.78±41.28, p=0.12; EAA 14.79±17.16 vs. 17.97±28.69, p=0.12; BCAA 2.21±6.08 vs. 4.16±10.98 mg/L, p=0.13). For the HF, the reduction in plasma amino acid levels for TAA and EAA were statistically significant. Although it was not statistically significant, the dialysate losses of BCAA were greater than the reduction in plasma (plasma reduction vs. dialysate loss; HF 2.21±6.08 vs. 6.58±4.32, LF 4.16±10.98 vs. 7.96±3.25 mg/L). HF with large pores and a sieving coefficient do not influence dialysate amino acid losses. Hemodialysis itself may influence the dialysate amino acid losses and may have an effect on protein metabolism.
Amino Acid; High Flux Membrane; Low Flux Membrane
To determine the loading and maintenance dosage of glutathione (GSH) for patients suffering from reactive oxygen species (ROS) injury such as acute paraquat intoxication, a kinetic study of reduced GSH was performed in synchrony with that of cysteine (Cys), cystine (Cys2), and methionine (Met). Human subject's porticipitation was voluntary. The effective dose of Cys, Cys2, and Met against ROS in fibroblast cells generated by paraquat was assessed using laser scanning confocal microscopy. Both Cys and Met suppressed ROS in a dose-dependent manner at concentrations of 1-1,000 µM; the concentration required to suppress ROS by 50% was 10 µM for Cys and 50 µM for Met. Using metabolite kinetics with the assumption that Cys and Met are the metabolites of GSH, expected concentrations of Cys and Met of above 20 and 50 µM were estimated when GSH was administered at 50 mg/kg body weights every 205.4 min for Cys and 427.4 min for Met.
Cysteine; Cystine; Glutathione; Methionine; Paraquat; Reactive Oxygen Species; Pharmacokinetics
The proteasome is a key regulator of cellular protein homeostasis and is a clinically validated anticancer target. The immunoproteasome, a subtype of proteasome expressed mainly in hematopoietic cells, was initially recognized for its role in antigen presentation during the immune response. Recently, the immunoproteasome has been implicated in several disease conditions including cancer and autoimmune disorders, but many of the factors contributing to these pathological processes remain unknown. In particular, the codon 60 polymorphism of the PSMB9 gene encoding the β1i immunoproteasome catalytic subunit has been investigated in the context of a variety of diseases. Despite this, previous studies have so far reported inconsistent findings regarding the impact of this polymorphism on proteasome activity. Thus, we set out to investigate the impact of the PSMB9 codon 60 polymorphism on the expression and activity of the β1i immunoproteasome subunit in a panel of human cancer cell lines. The β1i-selective fluorogenic substrate Acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin was used to specifically measure β1i catalytic activity. Our results indicate that the codon 60 Arg/His polymorphism does not significantly alter the expression and activity of β1i among the cell lines tested. Additionally, we also examined the expression of β1i in clinical samples from colon and pancreatic cancer patients. Our immunohistochemical analyses showed that ∼70% of clinical colon cancer samples and ∼53% of pancreatic cancer samples have detectable β1i expression. Taken together, our results indicate that the β1i subunit of the immunoproteasome is frequently expressed in colon and pancreatic cancers but that the codon 60 genetic variants of β1i display similar catalytic activities and are unlikely to contribute to the significant inter-cell-line and inter-individual variabilities in the immunoproteasome activity.
Tofacitinib, a novel Janus kinase inhibitor, may prevent structural damage in rheumatoid arthritis (RA). In this cohort study, we compared radiographic progression of hand joints between 21 RA patients who took tofacitinb for 18 months in a phase IIb and its extension study and 42 patients who took conventional disease modifying antirheumatic drugs (DMARDs), using simple erosion narrowing score. For tofacitinib group, changes before and after the treatment were also compared. The changes of erosion and sum scores were significantly less in tofacitinib than DMARDs group (for erosion, -0.60 ± 1.83 vs 0.51 ± 1.77, P = 0.038; for sum, -0.50 ± 1.72 vs 1.57 ± 4.13, P = 0.012). Joint space narrowing score (JSN) was also less in tofacitinib group (0.095 ± 0.58 vs 1.06 ± 2.60, P = 0.055). In tofacitinib group, yearly rates of both erosion and JSN were significantly decreased after administration of tofacitinib (For erosion, 0.62 ± 0.93 to -0.14 ± 0.48, P = 0.009; for JSN, 0.47 ± 0.64 to 0.03 ± 0.40, P = 0.032), as was change of sum score (1.09 ± 1.27 to -0.10 ± 0.63, P < 0.001). In conclusion, tofacitinib may prevent structural damage caused by RA.
Arthritis, Rheumatoid; Radiographic Progression; Tofacitinib
We have encountered numerous cases of rhabdomyolysis associated with acute pesticide intoxication; however, the cause, incidence, and treatment outcomes of rhabdomyolysis have not been studied. The current study involved 2,125 patients hospitalized with acute chemical poisoning. Based on clinical and laboratory parameters and treatment outcomes, we found that overall incidence of rhabdomyolysis in our hospital was 0.06% (93 of 143,830 patients admitted), but the incidence associated with acute pesticide intoxication was 1.8% (33 of 1,793 cases). The incidence of rhabdomyolysis after pesticide intoxication was significantly higher in men than in women (P = 0.010). The amount of pesticide ingested was significantly higher in rhabdomyolysis patients than that in those who did not develop rhabdomyolysis (mean ± SD, 114.1 ± 79.5 mL vs 74.1 ± 94.2 mL, P = 0.010). Our results show that pesticide intoxication is a frequent cause of rhabdomyolysis and is more common among men than women. The volume of pesticide ingested, and not the degree of human toxicity, is the main factor influencing the incidence of rhabdomyolysis.
Acute Kidney Injury; Intoxication; Pesticides; Rhabdomyolysis; Surfactant
Individuals being treated with tumor necrosis factor (TNF)-α inhibitors are at increased risk of developing tuberculosis (TB). We determined the clinical characteristics and treatment response of patients who developed TB after using TNF-α inhibitors.
Patients with TB detected within 12 months of the initiation of TNF-α inhibitor treatment were included, if seen from January 1, 2000 to August 31, 2011. We retrospectively reviewed the clinical records, results of bacteriological examinations, and radiographs of the included patients and the response to anti-TB treatment.
We indentified seven cases of TB in 457 patients treated with TNF-α inhibitors during the study period. TB developed a median of 123 days (range, 48 to 331) after the first dose of TNF-α inhibitor. Pulmonary TB, including TB pleuritis, was diagnosed in three patients and extrapulmonary TB in four. Favorable treatment outcomes were achieved in six of seven patients.
Among the TNF-α inhibitor users who contracted TB, extrapulmonary sites were common and the treatment response was satisfactory.
Tumor necrosis factor-alpha; Tuberculosis; Mycobacterium
Although magnetic resonance imaging (MRI) is a good visual modality for the evaluation of pituitary lesions, it has limited value in the diagnosis of mixed nodules and some cystic lesions. We evaluated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) for patients with pituitary lesions.
18F-FDG PET and MRI were performed simultaneously in 32 consecutive patients with pituitary lesions. The relationships between FDG uptake patterns in PET and MRI findings were analyzed.
Of 24 patients with piuitary adenomas, 19 (79.2%) showed increased uptake of 18F-FDG in the pituitary gland on PET scans. All patients with pituitary macroadenomas showed increased 18F-FDG uptake on PET scans. Meanwhile, only five (50%) of the 10 patients with pituitary microadenomas showed positive PET scans. Interestingly, of two patients with no abnormal MRI findings, one showed increased 18F-FDG uptake on PET. For positive 18F-FDG uptake, maximum standardized uptake values (SUVmax) > 2.4 had 94.7% sensitivity and 100% specificity. In addition, SUVmax increased in proportion to the size of pituitary adenomas. Most cystic lesions did not show 18F-FDG uptake on PET scans.
About 80% of pituitary adenomas showed positivity on PET scans, and SUVmax was related to the size of the adenomas. PET may be used as an ancillary tool for detection and differentiation of pituitary lesions.
Pituitary; Positron-emission tomography; Magnetic resonance imaging
Although peroxisome proliferator receptor (PPAR)-α and PPAR-γ agonist have been developed as chemical tools to uncover biological roles for the PPARs such as lipid and carbohydrate metabolism, PPAR-δ has not been fully investigated. In this study, we examined the effects of the PPAR-δ agonist GW0742 on fatty liver changes and inflammatory markers. We investigated the effects of PPAR-δ agonist GW0742 on fatty liver changes in OLETF rats. Intrahepatic triglyceride contents and expression of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemo-attractant protein-1 (MCP-1) and also, PPAR-γ coactivator (PGC)-1α gene were evaluated in liver tissues of OLETF rats and HepG2 cells after GW0742 treatment. The level of TNF-α and MCP-1 was also examined in supernatant of Raw264. 7 cell culture. To address the effects of GW0742 on insulin signaling, we performed in vitro study with AML12 mouse hepatocytes. Rats treated with GW0742 (10 mg/kg/day) from 26 to 36 weeks showed improvement in fatty infiltration of the liver. In liver tissues, mRNA expressions of TNF-α, MCP-1, and PGC-1α were significantly decreased in diabetic rats treated with GW0742 compared to diabetic control rats. We also observed that GW0742 had inhibitory effects on palmitic acid-induced fatty accumulation and inflammatory markers in HepG2 and Raw264.7 cells. The expression level of Akt and IRS-1 was significantly increased by treatment with GW0742. The PPAR-δ agonist may attenuate hepatic fat accumulation through anti-inflammatory mechanism, reducing hepatic PGC-1α gene expression, and improvement of insulin signaling.
diabetes mellitus; fatty liver; GW0742; inflammation; monocyte chemo-attractant protein-1; PPAR δ; PPARGC1A protein, human; tumor necrosis factor-α
Infection by microorganisms may cause fatally erroneous interpretations in the biologic researches based on cell culture. The contamination by microorganism in the cell culture is quite frequent (5% to 35%). However, current approaches to identify the presence of contamination have many limitations such as high cost of time and labor, and difficulty in interpreting the result. In this paper, we propose a model to predict cell infection, using a microarray technique which gives an overview of the whole genome profile. By analysis of 62 microarray expression profiles under various experimental conditions altering cell type, source of infection and collection time, we discovered 5 marker genes, NM_005298, NM_016408, NM_014588, S76389, and NM_001853. In addition, we discovered two of these genes, S76389, and NM_001853, are involved in a Mycolplasma-specific infection process. We also suggest models to predict the source of infection, cell type or time after infection. We implemented a web based prediction tool in microarray data, named Prediction of Microbial Infection (http://www.snubi.org/software/PMI).
Prediction Model; Microbial Infection; DNA Microarray; Mycoplasma
Statins, hydroxymethylglutaryl-coenzyme A reductase inhibitors, have been reported to have antiinflammatory and/or immunomodulatory effects and prophylactic and therapeutic effects in collagen-induced arthritis, an experimental model of rheumatoid arthritis (RA). The authors undertook to determine the effect of atorvastatin on the expressions of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs), to identify the mechanisms responsible for these effects, and to determine whether the statin inhibits osteoclastogenesis.
FLSs isolated from five RA patients were cultured in the presence of 20 ng/ml of tumor necrosis factor-α (TNF-α) with or without atorvastatin. RANKL expressions were assayed with Western blotting and enzyme-linked immunosorbent assay. RANKL, RANK, and OPG expression were assayed with reverse transcription-polymerase chain reaction (RT-PCR). Osteoclast formation was assayed by counting cells after staining for tartrate-resistant acid phosphatase in cocultures of peripheral blood mononuclear cells (PBMCs) and RA FLSs.
Atorvastatin inhibited the expression of RANKL in RA FLSs in a dose-dependent manner, and the suppression of RANKL was prevented by mevalonate. However, OPG expression was not affected by atorvastatin in RA FLSs, and atorvastatin did not affect RANK expression in CD14+ cells. Conversely, atorvastatin suppressed TNF-α-induced p38 phosphorylation in RA FLSs and significantly reduced TRAP-positive multinucleated osteoclast formation in the coculture of PBMCs and RA FLSs.
These results suggest that atorvastatin inhibits osteoclastogenesis and bone destruction in RA patients.
In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However, multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection. In this study, we determined the usefulness of plasma exchange (PE) for removing anti-A/B antibodies that cause hyperacute/acute humoral graft rejection in patients undergoing ABO-incompatible kidney transplantation.
In our study, 12 patients underwent ABO-incompatible kidney transplantation. All recipients received pre-transplantation conditioning by PE or intravenous immunoglobulin (IVIG) administration. After pre-transplantation conditioning, anti-A/B antibody titers were evaluated, and transplantation was performed when the titer was below 1:8. To assess the transplantation outcome, anti-A/B antibody titers, creatinine level, estimated glomerular filtration rate (eGFR), and proteinuria levels were measured.
Anti-A/B antibody titers were below 1:8 in all patients at the time of transplantation. eGFR measured on post-transplant day 14 showed that 10 patients had immediate recovery of graft function, while 2 patients had slow recovery of graft function. Short-term outcomes of ABO-incompatible kidney transplantation (measured as creatinine levels) after reducing anti-A/B antibody titers were similar to those of ABO-compatible kidney transplantation. After transplantation, the anti-A/B antibody titers were below 1:8 in 7 patients, but the remaining 5 patients required post-transplantation PE and IVIG treatment to prevent antigen-antibody reactions.
With the increasing demand for kidney donations, interest in overcoming the ABO incompatibility barrier has increased. PE may be an important breakthrough in increasing the availability of kidneys for transplantation.
Plasma exchange; ABO blood-group system; Blood group incompatibility; Kidney transplantation
The elastin metabolism in systemic sclerosis (SSc) has been known to be abnormal. The authors investigated relationship between the clinical manifestations of systemic sclerosis (SSc) and serum levels of soluble elastin-derived peptide (S-EDP) and anti-elastin antibodies. Serum samples were obtained from 79 patients with SSc and 79 age- and sex-matched healthy controls. Concentrations of serum S-EDP and anti-elastin antibodies were measured by ELISA. The serum concentrations of S-EDP in SSc patients were significantly higher than in healthy controls (median, 144.44 ng/mL vs 79.59 ng/mL, P < 0.001). Serum EDP concentrations were found to be correlated with disease duration in SSc (P = 0.002) and particularly in diffuse cutaneous SSc (P = 0.005). Levels of anti-elastin antibodies were found to be more elevated in SSc patients than in healthy controls (median, 0.222 U vs 0.191 U, P = 0.049), more increased in diffuse cutaneous SSc than limited cutaneous SSc (median, 0.368 U vs 0.204 U, P = 0.031). In addition, levels of anti-elastin antibodies were also found to be negatively associated with presence of anti-centromere antibody (P = 0.023). The S-EDP levels were not found to be correlated with levels of anti-elastin antibodies. The increased S-EDP and anti-elastin antibody levels and association with clinical and laboratory characteristics may reflect the abnormal metabolism in SSc.
Elastin; Elastin-Derived Peptide; Systemic Sclerosis
Malignant melanoma has a very high propensity to metastasize to the heart. However, melanoma may sometimes present as a metastatic lesion in the absence of a primary lesion, which are called melanomas of unknown primary origin. We report a case in which a patient presented with a metastatic maligant melanoma in the right atrium with pericardial effusion and without a primary origin.
Melanoma; Neoplasma, unknown primary; Unknown primary; Heart neoplasms
Cancer vaccines with optimal tumor-associated antigens show promise for anti-tumor immunotherapy. Recently, nano-sized vesicles, such as exosomes derived from tumors, were suggested as potential antigen candidates, although the total yield of exosomes is not sufficient for clinical applications. In the present study, we developed a new vaccine strategy based on nano-sized vesicles derived from primary autologous tumors. Through homogenization and sonication of tumor tissues, we achieved high yields of vesicle-bound antigens. These nanovesicles were enriched with antigenic membrane targets but lacked nuclear autoantigens. Furthermore, these nanovesicles together with adjuvant activated dendritic cells in vitro, and induced effective anti-tumor immune responses in both primary and metastatic melanoma mouse models. Therefore, autologous tumor-derived nanovesicles may represent a novel source of antigens with high-level immunogenicity for use in acellular vaccines without compromising safety. Our strategy is cost-effective and can be applied to patient-specific cancer therapeutic vaccination.
Chloracetanilide herbicides (alachlor, butachlor, metachlor) are used widely. Although there are much data about chronic low dose exposure to chloracetanilide in humans and animals, there are few data about acute chloracetanilide poisoning in humans. This study investigated the clinical feature of patients following acute oral exposure to chloracetanilide. We retrospectively reviewed the data on the patients who were admitted to two university hospitals from January 2006 to December 2010. Thirty-five patients were enrolled. Among them, 28, 5, and 2 cases of acute alachlor, metachlor, butachlor poisoning were included. The mean age was 49.8 ± 15.4 yr. The poison severity score (PSS) was 17 (48.6%), 10 (28.6%), 5 (14.3%), 2 (5.7%), and 1 (2.9%) patients with a PSS of 0, 1, 2, 3, and 4, respectively. The age was higher for the symptomatic patients (1-4 PSS) than that for the asymptomatic patients (0 PSS) (43.6 ± 15.2 vs 55.7 ± 13.5). The arterial blood HCO3 ¯ was lower in the symptomatic patients (1-4 PSS) than that in the asymptomatic patients (0 PSS). Three patients were a comatous. One patient died 24 hr after the exposure. In conclusion, although chloracetanilide poisoning is usually of low toxicity, elder patients with central nervous system symptoms should be closely monitored and cared after oral exposure.
Alachlor; Butachlor; Metachlor; Herbicides; Poisoning
The cellular toxicities of surfactants, a solvent, and an antifreeze that are included in herbicide formulations were assessed by measuring their effects on membrane integrity, metabolic activity, mitochondrial activity, and total protein synthesis rate in a cell culture. Polyethylene glycol, propylene glycol, and monoethylene glycol exhibited no cellular toxicity even at a high concentration of 100 mM. Sodium lauryl ether sulfate and polyoxyethylene lauryl ether significantly damaged the membrane, disturbed cellular metabolic activity, and decreased mitochondrial activity and the protein synthesis rate; however, their toxicity was far below those of the severely toxic chemicals at comparable concentrations. The severely toxic category included polyoxypropylene glycol block copolymer, polyoxyethylene tallow amine, and polyoxyethylene lauryl amine ether. These surfactants were cytotoxic between 3.125 µM and 100 µM in a dose-dependent manner. However, the toxicity graph of concentration vs toxicity had a point of inflection at 25 µM. The slope of the toxicity graph was gentle when the concentration was below 25 µM and steep when the concentration was greater than 25 µM. In conclusion, our results suggest that the toxicity of surfactants be taken care of pertinent treatment of acute herbicide intoxication.
Acute Poisoning; Herbicide; Surfactant; Cytotoxicity
Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.
diabetes mellitus, experimental; diabetic nephropathies; ferulic acid; inflammation; oxidative stress
Although nursing students experience a high level of stress during their training, there has been limited research on stress and its impact on the student's physical responses, such as gastrointestinal symptoms. The aims of this study are to assess the prevalence of GI symptoms in nursing students in Korea and to examine the association between the perceived stress and GI symptoms.
A cross-sectional descriptive study design was used. A total of 715 students of a three-year associate degree nursing program in a Korean college participated. The Perceived Stress Scale and a GI Symptoms Questionnaire were administered through a self-reported system. Chi-square tests, Fisher's exact test, and logistic regression analysis were performed using SPSS 17.0.
Sixty-five percent of the nursing students experienced more than one GI symptom, with 31.1% of students reporting more than three GI symptoms. Most of the nursing students complained of upper dysmotility and bowel symptoms. In addition, students who reported higher perceived stress were significantly more likely to complain of GI symptoms. Compared to nursing students with the lowest perceived stress level, the adjusted odds ratio (OR) for GI symptoms in students with the highest perceived stress level was 3.52 times higher (95% CI = 2.05-6.06).
GI symptoms that are highly prevalent among nursing students are significantly associated with the perceived stress level. High perceived stress should be considered a risk factor for GI symptoms. To reduce perceived stress, stress management programs including cognitive reappraisal training are needed in nursing curriculum.