Search

The article offers information on a study related to the cleaning methods and devices used for crushing drugs in geriatric units. Topics discussed include association of swallowing dysfunction with neurological diseases in old patients; development of recommendations for crushing drugs and their impact on clinical practice; and efficiency of different cleaning methods used in geriatric units and quality of mortar used.

Bacteriophages have been shown to be effective for treating acute infections of the respiratory tract caused by antibiotic-resistant bacteria in animal models, but no evidence has yet been presented of their activity against pathogens in complex biological samples from chronically infected patients. We assessed the efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa following its addition to 58 sputum samples from cystic fibrosis ( CF) patients collected at three different hospitals. Ten samples that did not contain P. aeruginosa were not analysed further. In the remaining 48 samples, the addition of bacteriophages led to a significant decrease in the levels of P. aeruginosa strains, as shown by comparison with controls, taking two variables (time and bacteriophages) into account (p = 0.024). In 45.8% of these samples, this decrease was accompanied by an increase in the number of bacteriophages. We also tested each of the ten bacteriophages individually against 20 colonies from each of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of the samples. An analysis of the clinical data revealed no correlation between patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment, FEV1 (forced expiratory volume in the first second) and the efficacy of bacteriophages. The demonstration that bacteriophages infect their bacterial hosts in the sputum environment, regardless of the clinical characteristics of the patients, represents a major step towards the development of bacteriophage therapy to treat chronic lung infections. [ABSTRACT FROM AUTHOR]

Abstract: Due to the non-polar nature and the absence of an ionizable group on the cannabinoids, the ionization efficiency in electrospray is low and leads to poor limits of detection (LOD). The reaction of chloride dabsyl with the phenolic OH group of cannabinoids results in a product containing a tertiary amine, which is easily protonated in positive electrospray mode and can significantly improve the cannabinoids LOD. A rapid, selective and sensitive LC/MS-MS method was developed for quantitative determination of Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH–THC), 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC–COOH), cannabinol (CBN) and cannabidiol (CBD), in micro volume blood samples following dabsyl derivatization to enhance signal intensity. The method comprised protein precipitation followed by derivatization with dabsyl chloride and subsequent analysis using liquid chromatography–tandem mass spectrometry (LC/MS-MS). Chromatographic separation was achieved using a 150mm×2.1mm C18 analytical column maintained at 65°C and eluted with a gradient of water and acetonitrile, both containing 0.2% formic acid. The run time was 8min. The assay was successfully validated using the approach based on the accuracy profile. Lower limits of quantification (LOQ) were 0.25ng/mL for THC and THC–COOH, 0.30ng/mL for 11-OH–THC, 0.40ng/mL for CBN and 0.80ng/mL for CBD. A comparative study of cannabinoids in blood and plasma, as determined by the developed LC/MS-MS method or the in-house GC/MS-MS technique, demonstrated an excellent correlation between the two methods. Dabsylation was also tested on-line with a spiral of peek tubing placed in the LC/MS-MS column heater at 65°C before the analytical column. The results obtained with on-line dabsyl derivatization were similar to those observed off-line. [Copyright &y& Elsevier]

Abstract: A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC–MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and −20°C for up to 6 months. Illicit drugs seemed to be much more stabled at −20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs. [Copyright &y& Elsevier]

The article focuses on a study which developed a method using online extraction coupled to liquid chromatography-tandem mass spectrometry (LC-MS-MS) to determine cyanide (CN) in blood. The method involved the use of cyanide isotope 13C15N as internal standard (IS) for quantification in MS-MS, and derivatization step with naphtalene-2,3-dicarboxyaldehyde (NDA) and taurine. The study showed that the method is suitable for CN identification in blood and in forensic toxicology.

Abstract: Over the past decade great progress has been made in metals and metalloids analysis. This analysis is a basic stage in toxicity assessment and is indispensable in achieving a realistic evaluation of substance toxicity. A recently introduced technique, inductively coupled plasma mass spectrometry (ICP-MS) is progressively replacing atomic absorption. This analysis permits multi-elementary determinations, approximately 30 elements, with an optimal gain in sensitivity in many biological matrices: i.e. whole blood, plasma, urine, hair, nail, biopsy samples. Moreover, this method allows semiquantitative determination with an additional 30 supplementary elements, which enables the toxicologist to sufficiently estimate the toxic levels and metal exposure. The authors demonstrate that the ICP-MS could be very useful for a wide range of clinical applications. Furthermore, this procedure offers new exploration possibilities in various fields such as clinical toxicology, forensic toxicology as well as work place testing or environmental exposure and permits epidemiologic studies. This analytical method in fact also provides a new scientific approach. To our knowledge we are the first to propose: the metallic profile. [Copyright &y& Elsevier]

The article focuses on a study concerning the application of inductively coupled plasma mass spectrometry (ICP-MS) to multielement analysis in fingernail and toenail that will serve as biological indices for metal exposure. It notes that the application of ICP-MS to multielement analysis provides great noninvasive control of domestic, environmental, or domestic exposure and is very helpful for epidemiological studies. Methods involved in the study, as well as the results and findings obtained are also discussed.

Abstract: Nephrogenic systemic fibrosis (NSF) is a rare acquired disorder affecting renal insufficiency patients. There is a growing recognition of the association between the rapid rise in the use of gadolinium (Gd)-containing contrast agents for magnetic resonance imaging (MRI), and the occurrence of acute nephrogenic systemic fibrosis. This case report concerns a 62-year-old woman with chronic renal insufficiency who underwent numerous MRI examinations using Gd-based contrast agents. For the first time, to our knowledge, Gd was performed in the NSF patient''s blood, as well as in hair and in fingernails by inductively plasma coupled mass spectrometry. Gd contents in blood, hair and in fingernails were initially 300 to 1000 times higher compared to controls. These results are a new illustration of the strong association between the frequent use of Gd-based contrast media and NSF in patients with kidney diseases. Gd quantitative determination could be of major interest for patients with renal failure who are required to undergo repeated gadolinium-enhanced MRI examinations. [Copyright &y& Elsevier]

Summary: Mutations in cystic fibrosis transmembrane conductance regulator gene, CFTR, are responsible for cystic fibrosis, CF, a channelopathie. CFTR protein is a multifunctional protein with a main function of Cl− channel. CFTR is expressed in epithelia (upper airways, intestine, pancreas etc.). In the first part of this revue, we describe the main properties of CFTR underlying that it is not only a Cl− channel protein but also a multifunctional protein. We present a hypothesis which postulates that CFTR is a hub protein interacting with more than 140 proteins, and through these interactions regulates a number of functions which are abnormal in CF (ion transport, inflammation etc.). In the second part of the revue we briefly present a selection of other epithelial channelopathies due to mutations in genes of other Cl− or cation channels. Of note, these channels either interacts with CFTR or are considered as alternative channels in CF, and, as such, are targets for pharmacotherapies. We want to leave the reader with a message that to investigate channalopathies, to dissect the molecular mechanisms underlying channels’activity, allow not only to better understand basic mechanisms of channel regulation but in fine, to propose new targets for pharmacotherapies. [Copyright &y& Elsevier]

Abstract: Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (CrVI), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically CrVI reactive intermediates and reactive oxygen species. After CrVI has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of CrVI to CrIII reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of CrVI is cleared in urine as CrIII. We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49days. During this period Cr decreased respectively from 2088μg/L to 5μg/L, 631μg/L to 129μg/L and 3512μg/g to 10μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells. [Copyright &y& Elsevier]

Abstract: Intoxications by chromium (Cr) compounds are very life threatening and often lethal. After oral ingestion of 2 or 3g of hexavalent Cr (CrVI), gastrointestinal injury, but also hepatic and renal failure, often occurs which each leads to a fatal outcome in most patients. Cellular toxicity is associated with mitochondrial and lysosomal injury by biologically CrVI reactive intermediates and reactive oxygen species. After CrVI has been absorbed, there is not much that can be done except to control the main complications as the treatment is only symptomatic. The biotransformation of CrVI to CrIII reduces the toxicity because the trivalent form does not cross cellular membranes as rapidly. In fact, more than 80% of CrVI is cleared in urine as CrIII. We report the case of a 58-year-old male patient who was admitted to hospital after accidental oral ingestion of a 30g/L potassium dichromate (the estimated amount of ingested Cr is about 3g). ICP-MS equipped with a collision/reaction cell (CRC) and validated methods were used to monitor plasma (P), red blood cells (RBCs), urine (U) and hair chromium. For urine the results were expressed per gram of creatinine. After 7days in the intensive care unit, the patient was discharged without renal or liver failure. P, RBC and U were monitored during 49days. During this period Cr decreased respectively from 2088μg/L to 5μg/L, 631μg/L to 129μg/L and 3512μg/g to 10μg/g. The half-life was much shorter in P than in RBC as the poison was more quickly cleared from the P than from the RBC, suggesting a cellular trapping of the metal. Hair was collected 2months after the intoxication. We report a very rare case of survival after accidental Cr poisoning which has an extremely poor prognosis and usually leads to rapid death. For the first time, this toxicokinetic study highlights a sequestration of chromium in the RBC and probably in all the cells. [Copyright &y& Elsevier]