Effect of MDR1 gene polymorphisms on mortality in paraquat intoxicated patients.

Paraquat is a fatal herbicide following acute exposure. Previous studies have suggested that multidrug resistance protein 1 (MDR1) might help remove paraquat from the lungs and the kidney. MDR1 single-nucleotide polymorphisms (SNPs) are involved in the pharmacokinetics of many drugs. The purpose of this study was to determine whether MDR1 SNPs were associated with the mortality in paraquat intoxicated patients. We recruited 109 patients admitted with acute paraquat poisoning. They were genotyped for C1236T, G2677T/A, and C3435T single-nucleotide polymorphisms (SNPs) of MDR1 gene. Their effects on mortality of paraquat intoxicated patients were evaluated. Overall mortality rate was 66.1%. Regarding the C1236T of the MDR1 gene polymorphism, 21 (19.3%) had the wild type MDR1 while 88 (80.7%) had homozygous mutation. Regarding the C3435T MDR1 gene polymorphism, 37(33.9%) patients had the wild type, 23 (21.1%) had heterozygous mutation, and 49 (45.0%) had homozygous mutation. Regarding the G2677T/A MDR1 gene polymorphism, 38 (34.9%) patients had the wild type, 57 (52.3%) had heterozygous mutation, and 14 (12.8%) had homozygous mutation. None of the individual mutations or combination of mutations (two or three) of MDR1 SNP genotypes altered the morality rate. The mortality rate was not significantly different among SNP groups of patients with <4.0 µg/mL paraquat. In conclusion, MDR1 SNPs have no effect on the mortality rate of paraquat intoxicated patients.

The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication.

Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

Changes in serum magnesium concentration after use of a proton pump inhibitor in patients undergoing percutaneous coronary intervention.

BACKGROUND: Although cross-sectional studies have suggested a relationship between proton pump inhibitor (PPI) use and hypomagnesemia, no large-scale cohort study has been conducted to date. Here, we examined the changes in serum magnesium levels in response to PPI use. We hypothesized that PPI use might change the serum magnesium concentration. METHODS: Of the 2,892 patients hospitalized for percutaneous coronary intervention between January 2007 and May 2012, 1,076 patients with normal baseline (1.6-2.5 mg/dL) and follow-up serum magnesium concentrations were enrolled. These patients were divided into two groups: the PPI group and the control group. RESULTS: The mean follow-up period was 9.51 ± 2.94 months. The incidence of hypomagnesemia (< 1.6 mg/dL) was 0.4% (3/834) in the PPI group and 0.4% (1/242) in the control group (P = 0.904). The change in magnesium levels did not differ between the two groups, and this result was maintained in the analysis of covariance after adjusting for confounding factors (P = 0.381). Moreover, magnesium levels did not significantly differ between the long-term (duration of use ≥ 12 months, n = 71) and short-term PPI groups (duration of use < 12 months, n = 763), and the control group (n = 242; P = 0.620). The effect of PPI use on change in serum magnesium concentration was affected by the use of multiple diuretics (-0.01 ± 0.25 mg/dL; P = 0.025), although a single diuretic use with PPI did not alter the change in magnesium level (0.12 ± 0.27 mg/dL). CONCLUSION: Changes in magnesium levels might be subtle after PPI use in patients with normal baseline magnesium values.

P-Glycoprotein Induction Ameliorates Colistin Induced Nephrotoxicity in Cultured Human Proximal Tubular Cells.

The pathogenesis of colistin induced nephrotoxicity is poorly understood. Currently there are no effective therapeutic or prophylactic agents available. This study was aimed to determine the mechanism of colistin induced nephrotoxicity and to determine whether P-glycoprotein (P-gp) induction could prevent colistin induced nephrotoxicity. Colistin induced cell toxicity in cultured human proximal tubular cells in both dose and time dependent manner. Colistin provoked ROS in a dose dependent manner as measured by DCF-DA. To investigate apoptosis, caspase 3/7 activity was determined. Caspase 3/7 activity was increased dose dependently (25, 50, 100 µg/ml) at 6 h. Autophagosome formation was assessed by measuring LC3- II/LC3-I ratio. The ratio of LC3-II to LC3- I was increased at 2 h (25 µg/ml). Suppression of autophagosome formation increased colistin induced nephrotoxicity. The expression of P-gp and the cell toxicity was determined in colistin with or without dexamethasone (P-gp inducer) and verapamil (selective P-gp inhibitor). Colistin itself suppressed the expression of P-gp. P-gp expression and activity decreased colistin induced nephrotoxicity with dexamethasone treatment. In addition induced P-gp transporter was shown to improve the efflux effect on colistin treated HK2 cell line, which was demonstrated by calcein-AM fluorescence accumulation assay. The increased activity could be blocked by N-acetylcysteine. In conclusion, colistin induces nephrotoxicity by suppressing P-gp. Induction of P-gp could ameliorate colistin induced nephrotoxicity by decreasing apoptosis.

Indolent metastatic squamous cell carcinoma of unknown primary in the intrathoracic lymph node: a case report and review of the literatures.

Metastatic squamous cell carcinoma from a cancer of unknown primary (CUP) affecting the intrathoracic lymph node is very rare. We reported a case of metastatic squamous cell carcinoma in the hilar and interlobar lymph node from a patient with CUP and reviewed the associated literature. Abnormal mass in the right hilar area was incidentally detected. A chest computed tomography scan showed a 2.5-cm diameter mass in the right hilum that had changed little in size for 3 years. The patient underwent a right pneumonectomy and mediastinal lymph node dissection. A metastatic squamous cell carcinoma in the hilar and interlobar lymph nodes without a primary lung or other lesion was diagnosed. The patient received adjuvant chemotherapy for a diagnosis of T0N1M0 lung cancer.