A Validated Reversed-Phase HPLC Method for the Determination of Atorvastatin Calcium in Tablets

A Reversed-Phase Liquid Chromatographic (RP-LC) assay method was developed for the quantitative determination of atorvastatin calcium in the presence of its degradation products. The assay involved an isocratic elution of atorvastatin calcium in a LiChroCARTR 250*4 mm HPLC Cartridge LiChrospherR 100 RP-18 (5 μm) column using a mobile phase consisting of 0.1% acetic acid solution: acetonitrile (45:55, v/v), pH = 3.8. The flow rate was 0.8 mL/min and the analytes monitored at 246 nm. The assay method was found to be linear from 8.13 to 23.77 μg/mL. All the validation parameters were within the acceptance range. The developed method was successfully applied to estimate the amount of atorvastatin calcium in tablets.Fil: Simionato, Laura Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Ferello, L.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Stamer. S.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Repetto, M. F.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Zubata, P. D.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; ArgentinaFil: Segall, Adriana Ines. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

PLoS Genet.

The Helicobacter pylori cag pathogenicity island (cagPAI) encodes a type IV secretion system. Humans infected with cagPAI-carrying H. pylori are at increased risk for sequelae such as gastric cancer. Housekeeping genes in H. pylori show considerable genetic diversity; but the diversity of virulence factors such as the cagPAI, which transports the bacterial oncogene CagA into host cells, has not been systematically investigated. Here we compared the complete cagPAI sequences for 38 representative isolates from all known H. pylori biogeographic populations. Their gene content and gene order were highly conserved. The phylogeny of most cagPAI genes was similar to that of housekeeping genes, indicating that the cagPAI was probably acquired only once by H. pylori, and its genetic diversity reflects the isolation by distance that has shaped this bacterial species since modern humans migrated out of Africa. Most isolates induced IL-8 release in gastric epithelial cells, indicating that the function of the Cag secretion system has been conserved despite some genetic rearrangements. More than one third of cagPAI genes, in particular those encoding cell-surface exposed proteins, showed signatures of diversifying (Darwinian) selection at more than 5% of codons. Several unknown gene products predicted to be under Darwinian selection are also likely to be secreted proteins (e.g. HP0522, HP0535). One of these, HP0535, is predicted to code for either a new secreted candidate effector protein or a protein which interacts with CagA because it contains two genetic lineages, similar to cagA. Our study provides a resource that can guide future research on the biological roles and host interactions of cagPAI proteins, including several whose function is still unknown

Spread, Behavior, and Ecosystem Consequences of Conventional Munitions Compounds in Coastal Marine Waters

Coastal marine environments are contaminated globally with a vast quantity of unexploded ordnance and munitions from intentional disposal. These munitions contain organic explosive compounds as well as a variety of metals, and represent point sources of chemical pollution to marine waters. Most underwater munitions originate from World Wars at the beginning of the twentieth century, and metal munitions housings have been impacted by extensive corrosion over the course of the following decades. As a result, the risk of munitions-related contaminant release to the water column is increasing. The behavior of munitions compounds is well-characterized in terrestrial systems and groundwater, but is only poorly understood in marine systems. Organic explosive compounds, primarily nitroaromatics and nitramines, can be degraded or transformed by a variety of biotic and abiotic mechanisms. These reaction products exhibit a range in biogeochemical characteristics such as sorption by particles and sediments, and variable environmental behavior as a result. The reaction products often exhibit increased toxicity to biological receptors and geochemical controls like sorption can limit this exposure. Environmental samples typically show low concentrations of munitions compounds in water and sediments (on the order of ng/L and μg/kg, respectively), and ecological risk appears generally low. Nonetheless, recent work demonstrates the possibility of sub-lethal genetic and metabolic effects. This review evaluates the state of knowledge on the occurrence, fate, and effect of munition-related chemical contaminants in the marine environment. There remain a number of knowledge gaps that limit our understanding of munitions-related contaminant spread and effect, and the need for additional work is made all the more urgent by increasing risk of release to the environment

Water quality in the central Nebraska basins, Nebraska, 1992-95

This report is intended to summarize major findings that emerged between 1992 and 1995 from the water-quality assessment of the Central Nebraska Basins Study Unit and to relate these findings to water-quality issues of regional and national concern. The information is primarily intended for those who are involved in waterresource management. Indeed, this report addresses many of the concerns raised by regulators, water-utility managers, industry representatives, and other scientists, engineers, public officials, and members of stakeholder groups who provided advice and input to the USGS during this NAWQA Study-Unit investigation. Yet, the information contained here may also interest those who simply wish to know more about the quality of water in the rivers and aquifers in the area where they live. Land use in central Nebraska appears to affect water quality significantly; streams in rangelands generally had fewer occurrences and smaller concentrations of pesticides than did streams in croplands where corn and soybeans were planted extensively. Subbasins with greater proportions of rangeland, such as the Dismal River, had negligible herbicide concentrations. The largest pesticide concentrations were in storm runoff following pesticide applications. Because some pesticide concentrations may exceed the U.S. Environmental Protection Agency’s (USEPA) drinking-water Maximum Contaminant Levels (MCLs) in storm runoff, the timing and intensity of rainfall has implications for drinking-water supplies. Pesticides in streams from storm runoff may enter alluvial aquifers as a consequence of ground-water withdrawals. Sites with degraded water chemistry commonly had degraded physical habitats as well. Streamflow regulation of the Platte River has affected water quality through habitat alterations that are deleterious to native species. The combination of degraded physical and chemical environments commonly resulted in structurally simple fish communities. CONTENTS National Water-Quality Assessment Program .. 1 Summary of major issues and findings... 2 Environmental setting and hydrologic conditions.... 4 Major issues and findings ... 6 Nitrate content in water is related to agricultural land management 6 Agricultural activities potentially affect the management of public water supplies . 8 Water quality in the Platte River alluvial aquifer may be affected by surface-water quality in areas of ground-water withdrawals .. 10 Aquatic environments potentially are altered by human activities... 12 Aquatic and migratory species are affected directly by changes in the physical characteristics of the Platte River .. 14 Water-quality conditions in anational context ... 16 Study design and data collection .. 20 Summary of compound detections and concentrations ... 22 References . 28 Glossary 3

In situ measurements of explosive compound dissolution fluxes from exposed munition material in the Baltic Sea

Underwater munitions containing millions of tons of toxic explosives are present worldwide in coastal marine waters as a result of unexploded ordnance and intentional dumping. Dissolution flux of solid explosives following corrosion of metal munition housings controls exposure of biological receptors to toxic munition compounds (MC; including TNT: 2,4,6-Trinitrotoluene, RDX: 1,3,5-Trinitro-1,3,5-triazinane, and DNB: 1,3-Dinitrobenzene). Very little is known about the dissolution behavior of MC in the marine environment. In this work, we exploit a unique marine study site in the Baltic Sea with exposed solid explosives to quantify in situ MC dissolution fluxes using dissolved MC gradients near the exposed explosive surface, as well as benthic chamber incubations. The gradient method gave dissolution fluxes that ranged between 0.001 and 3.2, 0.0001 and 0.04, and 0.003 and 1.7 mg cm-2 d-1 for TNT, RDX, and DNB, respectively. Benthic chamber incubations indicated dissolution fluxes of 0.0047-0.277, 0-0.11, and 0.00047-1.45 mg cm-2 d-1 for TNT, RDX, and DNB, respectively. In situ dissolution fluxes estimated in the current study were lower than most dissolution rates reported for laboratory experiments, but clearly demonstrated that MC are released from underwater munitions to the water column in the Baltic Sea

Quantification of munition compounds in the marine environment by solid phase extraction – ultra high performance liquid chromatography with detection by electrospray ionisation – mass spectrometry

Highlights • High resolution mass spectrometry used to detect munition compounds. • Isotope dilution used for accurate quantification of TNT. • Seven explosives and metabolites detected in seawater at ng L−1 concentrations. • Ten explosives and metabolites detected in marine biota from a contaminated site. Abstract As a consequence of World War II, large amounts of munition have been deposited in coastal waters. Deterioration of the mines and bombs is resulting in a release of munition compounds (MCs) like trinitrotoluene to the surrounding marine environment, with potential implications to ecosystems. Analytical methods have thus far been unable to detect these compounds reliably in seawater. We present a highly sensitive method for the analysis of MCs in the marine environment. We combine preconcentration and sample clean up by solid phase extraction with separation and detection by ultra-high performance liquid chromatography – electrospray ionisation – mass spectrometry (UHPLC-ESI-MS) for the detection of MCs dissolved in filtered (< 0.2 µm) seawater. For biota, dried and ground samples were extracted in acetonitrile and analysed after simple dilution. Eleven MCs were detected by UHPLC-ESI-MS with limits of detection between 0.01 and 25 pg. For the first time, we used heavy isotopes of trinitroluene and dinitrobenzene to improve quantification in environmental samples. We detected 7 MCs in waters sampled at a known munition disposal site in the Baltic Sea after a 1000-fold preconcentration and using an injection volume of 25 µL. Trinitrotoluene and dinitrobenzene were the most abundant MCs, occurring at concentrations between 0.1 and 11.8 ng L−1. We observed 10 MCs at concentrations up to 24 µg g−1 dry weight in benthic organisms sampled from the site. The enhanced sensitivity of our method allowed us to detect MCs at concentrations relevant for assessment and management of munitions disposal sites in the marine environment

Ethical procedures and patient consent differ in Europe

BACKGROUND: Research ethics approvals, procedures and requirements for institutional research ethics committees vary considerably by country and by type of organisation. OBJECTIVE: To evaluate the requirements and procedures of research ethics committees, details of patient information and informed consent based on a multicentre European trial. DESIGN: Survey of European hospitals participating in the prospective observational study on chronic postsurgical pain (euCPSP) using electronic questionnaires. SETTING: Twenty-four hospitals in 11 European countries. PARTICIPANTS: From the 24 hospitals, 23 local investigators responded; 23 answers were analysed. OUTCOME MEASURES: Comparison of research ethics procedures and committee requirements from the perspective of clinical researchers. Comparison of the institutions' procedures regarding patient information and consent. Description of further details such as costs and the duration of the approval process. RESULTS: The approval process lasted from less than 2 weeks up to more than 2 months with financial fees varying between 0 and 575 €. In 20 hospitals, a patient information sheet of variable length (half page up to two pages) was provided. Requirements for patients' informed consent differed. Written informed consent was mandatory at 12, oral at 10 and no form of consent at one hospital. Details such as enough time for consideration, possibility for withdrawal and risks/benefits of participation were provided in 25 to 30% of the institutions. CONCLUSION: There is a considerable variation in the administrative requirements for approval procedures by research ethics committees in Europe. This results in variation of the extent of information and consent procedures for the patients involved

Pain Management in Patients with Cancer: Focus on Opioid Analgesics

Cancer pain is generally treated with pharmacological measures, relying on using opioids alone or in combination with adjuvant analgesics. Weak opioids are used for mild-to-moderate pain as monotherapy or in a combination with nonopioids. For patients with moderate-to-severe pain, strong opioids are recommended as initial therapy rather than beginning treatment with weak opioids. Adjunctive therapy plays an important role in the treatment of cancer pain not fully responsive to opioids administered alone (ie, neuropathic, bone, and visceral colicky pain). Supportive drugs should be used wisely to prevent and treat opioids’ adverse effects. Understanding the pharmacokinetics, pharmacodynamics, interactions, and cautions with commonly used opioids can help determine appropriate opioid selection for individual cancer patients