Sepsis - which is a severe life-threatening infection with organ dysfunction - initiates a complex interplay of host pro-inflammatory and anti-inflammatory processes. Sepsis can be considered a race to the death between the pathogens and the host immune system, and it is the proper balance between the often competing pro- and anti-inflammatory pathways that determines the fate of the individual. Although the field of sepsis research has witnessed the failure of many highly touted clinical trials, a better understanding of the pathophysiological basis of the disorder and the mechanisms responsible for the associated pro- and anti-inflammatory responses provides a novel approach for treating this highly lethal condition. Biomarker-guided immunotherapy that is administered to patients at the proper immune phase of sepsis is potentially a major advance in the treatment of sepsis and in the field of infectious disease.

/pdf/sepsis-induced-immunosuppression-from-cellular-dysfunctions-425knwqbvv.pdf

Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy

Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications

Sepsis: Current Dogma and New Perspectives

Toll-like receptors in immunity and inflammatory diseases: Past, present, and future.

Objective
To determine whether persistent lymphopenia on the fourth day following the diagnosis of sepsis predicts mortality.

/pdf/persistent-lymphopenia-after-diagnosis-of-sepsis-predicts-4bob4zpukg.pdf

Persistent lymphopenia after diagnosis of sepsis predicts mortality.

Objective:To investigate the immunological changes caused by severe sepsis in elderly patients.Design:One-year, prospective observational study.Setting:Emergency department and intensive care unit of a single university hospital.Patients:Seventy-three patients with severe sepsis and 72 healthy donor

Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly.

A 59-year-old man was found dead in his house, where three sachets containing herbal blends were found on a table. The sachet contents were analyzed by gas chromatography–mass spectrometry and found to contain [1-(5-fluoropentyl)-1H-indol-3-yl](4-methyl-1-naphthalenyl)methanone (MAM-2201). The deceased was subjected to forensic autopsy. There were neither external injuries nor endogenous diseases judged by macroscopic and microscopic observations. Liquid chromatography–electrospray ionization–tandem mass spectrometry was used to quantitate the concentrations of MAM-2201 in postmortem samples using deuterated MAM-2201 as internal standard. The MAM-2201 concentrations were: 12.4 ng/ml in whole blood; 18.1 ng/g in the liver; 11.2 ng/g in the kidney; 4.3 ng/g in the brain; and 1,535 ng/g in the adipose tissue. We concluded that the man’s death was caused by acute intoxication with MAM-2201. In addition, we propose that the adipose tissue is the specimen of choice to detect MAM-2201 in the unchanged form. To our knowledge, this is the first report of a fatal MAM-2201 poisoning case. In addition, this report is also the first to describe the distribution of the drug in postmortem human tissues and blood.

A fatal case of MAM-2201 poisoning

A rapid and specific method for simultaneous quantitation of organophosphates [fenitrothion (MEP), malathion (MAL), and phenthoate (PAP)], glyphosate (GLYP), and glufosinate (GLUF) in human serum and urine by gas chromatography–mass spectrometry (GC–MS) was validated. All targeted compounds, together with the internal standards [fenitrothion-d
 6 (MEP-d
 6) and dl-2-amino-3-phosphonopropionic acid (APPA)], were extracted from the serum and urine with a mixed-mode C–C18 monolithic spin column. Extracted samples were derivatized with N-methyl-N-(tert-butyldimethylsilyl) trifluoroacetamide (MTBSTFA) containing 1% tert-butyldimethylchlorosilane (TBDMCS). Linear calibration curves for serum and urine spanned the ranges of 0.1–10.0 μg/ml for organophosphates, 10–100.0 μg/ml for GLYP, and 5–100.0 μg/ml for GLUF. Detection limits for serum and urine were 10 and 5 μg/ml for GLYP and GLUF, respectively, and quantitation limits for serum and urine were 10 and 5 μg/ml for GLYP and GLUF, respectively. Both detection and quantitation limits for serum and urine were 0.1 μg/ml for organophosphates. The intra-assay and interassay accuracy and precision (expressed as relative standard deviation, %RSD) evaluated for all compounds were within 96.5–109.5% and 5.9–13.1%, respectively. The recovery of organophosphates from serum and urine, spiked at concentrations of 0.1, 1.5, 5, and 9 μg/ml, ranged from 58.8 to 90.8%. Recovery of GLYP and GLUF from serum and urine, spiked at concentrations of 10 (serum) or 5 (urine), 15, 50, and 90 μg/ml, ranged from 2.6 to 6.9%. This method had a chromatographic run time of 16.0 min. The validated method was successfully applied to a clinical case of GLYP poisoning.

Mixed-mode C–C18 monolithic spin-column extraction and GC–MS for simultaneous assay of organophosphorus compounds, glyphosate, and glufosinate in human serum and urine

Background Antipsychotic/Antidepressant use is a risk factor for QT interval (QT) prolongation and sudden cardiac death. However, it is unclear which drugs are risk factors for QT prolongation and torsades de pointes in cases of psychotropic drug overdose. Methods After correction of QT data by Bazett formula (QTc), QTc was classified into 3 categories (QTc Results A total of 649 patients were enrolled in the study. The independent risk factors for QTc prolongation were therapeutic and toxic range of phenotiazine antipsychotic drug (therapeutic range: odds ratio [OR], 1.56 [ P = .039]; toxic range: OR, 3.85 [ P P = .018). In addition, toxic range of phenotiazine antipsychotic drug (OR, 3.87; P = .012) and tricyclic antidepressants (OR, 4.94; P Conclusions The possibility of QT prolongation and torsades de pointes due to overdose of phenotiazine antipsychotic drug or tricyclic antidepressants requires particular consideration.

Risk factors for QT prolongation associated with acute psychotropic drug overdose

Organophosphates and carbamates are pesticides whose acute toxicities are caused by inhibition of acetylcholinesterase. A liquid chromatography–mass spectrometry/mass spectrometry method was developed and validated for the quantification of 16 organophosphate and carbamate insecticides in human serum. Nonpolar and polar pesticides were simultaneously extracted from serum samples using a simple and fast monolithic spin column procedure using mixed-mode C-C18 cartridges. Recovery was achieved in the range 11.9–99.2 %. Chromatography was carried out on an InertSustain® C18 HP 3 μm analytical column with gradient elution. Mass spectrometric analysis was performed using an Agilent 6410 Triple Quad Tandem mass spectrometer coupled with an electrospray ionization source in the positive ion mode. The assay was validated over a large concentration range and the limits of detection for all compounds ranged from 0.1 to 50 ng mL−1. The precision for both intra- and inter-day determination of all analytes was found to be acceptable (< 12.9 %) and no significant matrix effect was observed. The developed method was effectively applied to clinical samples from patients presenting at hospital with symptoms of acute intentional organophosphate or carbamate poisoning, demonstrating its applicability to diagnostic applications.

Naoya Miura

Papers

Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly.

A fatal case of MAM-2201 poisoning

Mixed-mode C–C18 monolithic spin-column extraction and GC–MS for simultaneous assay of organophosphorus compounds, glyphosate, and glufosinate in human serum and urine

Risk factors for QT prolongation associated with acute psychotropic drug overdose

Rapid Determination of Polar and Non-Polar Pesticides in Human Serum, Using Mixed-Mode C-C 18 Monolithic Spin Column Extraction and LC–MS/MS