The effects of nonyl phenoxypolyethoxyl ethanol on cell damage pathway gene expression in SK-NSH cells

BACKGROUND/AIMS: Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways. METHODS: The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line. RESULTS: The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N-SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold). CONCLUSIONS: NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene.

A Case of Favorable Responses after Gefitinib in a Patient with EGFR Mutated Adenosquamous Lung Carcinoma

In patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) mutations, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as first treatment option. Because adenosquamous carcinoma (ASC) is a rare histologic subtype, evidences about EGFR-TKIs as first treatment option for advanced ASC are lacking. We report a case of an advanced ASC patient with the EGFR mutation, who showed good responses during 4-month treatment with gefitinib. And we will review about a necessity of EGFR mutation test and efficacy of EGFR-TKIs in ASC patients from the recent studies.

A Case of Systemic Amyloidosis Found by Goiter in Crohn's Disease

Secondary amyloidosis is characterized by accumulation of insoluble, fibrous amyloid proteins in various tissues and organs, accompanied by infectious or inflammatory diseases. Amyloidosis may involve the thyroid, gastrointestinal tract, kidneys, liver, or bone marrow. Amyloidosis as a complication of Crohn's disease is rare but serious, and may worsen the prognosis. We have experienced a case of amyloid goiter and gastrointestinal amyloidosis secondary to Crohn's disease. A 74-year-old female patient with Crohn's disease was admitted to Soonchunhyang University Hospital with general weakness and poor oral intake. Anterior-neck diffuse goiter and tenderness around the navel were found. Amyloid goiter and gastrointestinal amyloidosis diagnosed by sonoguided needle biopsy of the thyroid and endoscopic biopsies of the stomach and duodenum.

A case of scrub typhus requiring maintenance hemodialysis

Renal failure caused by scrub typhus is known to be reversible. In most cases, renal function is almost fully restored after appropriate antibiotic treatment. A 71-year-old man was diagnosed with scrub typhus complicated by renal failure. A renal biopsy revealed histopathologic findings consistent with acute tubulointerstitial nephritis. Renal function did not improve 18 months after discharge and the patient required continuous hemodialysis. Although severe renal failure requiring dialysis is a rare complication of scrub typhus, we describe a case of scrub typhus requiring maintenance hemodialysis. To the best of our knowledge, this is the first such report.

Risk Factors for Mortality in Patients with Candidemia and the Usefulness of a Candida Score / 대한의진균학회지

BACKGROUND: Although effective antifungal agents for the treatment of candidemia have recently been introduced, the mortality rate attributed to candidemia remains high (19~49%). OBJECTIVE: This study aimed at evaluating the risk factors for mortality in patients with candidemia and at assessing the usefulness of a Candida Score in these patients. METHODS: A cohort of patients with positive blood cultures for Candida species was retrospectively analyzed at Soonchunhyang University Hospital, a 750-bed teaching hospital, from May 2003 to February 2012. The Candida Score was calculated by assigning 1 point to any of total parenteral nutrition (TPN), surgery, or multifocal Candida species colonization, and 2 points to severe sepsis. RESULTS: Sixty patients (68.3% men; mean age (standard deviation [SD]), 61.8 [18.9] years) with blood cultures positive for Candida species were identified. Most patients had been admitted to an intensive care unit (48 [80%]), were receiving broad-spectrum antibiotics (37 [61.7%]), had TPN (29 [48.3%]), had diabetes mellitus (23 [38.3%]), and were receiving hemodialysis (10 [16.7%]). The mean (SD) Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 19.60 (8.8). Twenty-three patients (38.3%) had a Candida Score >2.5. The Candida species causing infection included C. albicans (41 [68.3%]), C. tropicalis (7 [11.7%]), C. parapsilosis (4 [6.7%]), C. krusei (3 [5%]), C. glabrata (3 [5%]), C. guilliermondii (1 [1.7%]), and C. catenulata (1 [1.7%]). Only 32 patients (53.3%) received adequate antifungal treatment. The candidemia-related mortality rate was 61.7% (n = 37 patients). Multivariate logistic regression analysis demonstrated that a high APACHE II score (adjusted odds ratio [aOR], 1.2; 95% confidence interval [95% CI], 1.0~1.3; p = 0.01), presence of a malignancy (aOR, 14.8; 95% CI, 2.5~88.0; p = 0.003), and treatment with an antifungal agent (aOR, 0.2; 95% CI, 0.0~1.0; p = 0.048) were associated with disease-related mortality. CONCLUSION: The risk factors for mortality in patients with candidemia are a high APACHE II scores and presence of a malignancy. However, the sensitivity of the Candida Score was not high (38.3%). New methods to rapidly identify candidemia and avoid delays in treatment with appropriate antifungal therapy are needed.

Acute Fulminant Myocarditis Following Scrub Typhus Infection / 대한내과학회지

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi that is characterized by focal or disseminated vasculitis and perivasculitis. Scrub typhus can have fatal complications, such as acute respiratory distress syndrome, septic shock, and acute kidney injury. However, there are few reports of fatal myocarditis caused by scrub typhus. We present a case of acute fatal myocarditis combined with acute kidney injury complicating scrub typhus.