Total selenium and selenomethionine in pharmaceutical yeast tablets: assessment of the state of the art of measurement capabilities through international intercomparison CCQM-P86.

Results of an international intercomparison study (CCQM-P86) to assess the analytical capabilities of national metrology institutes (NMIs) and selected expert laboratories worldwide to accurately quantitate the mass fraction of selenomethionine (SeMet) and total Se in pharmaceutical tablets of selenised-yeast supplements (produced by Pharma Nord, Denmark) are presented. The study, jointly coordinated by LGC Ltd., UK, and the Institute for National Measurement Standards, National Research Council of Canada (NRCC), was conducted under the auspices of the Comité Consultatif pour la Quantité de Matière (CCQM) Inorganic Analysis Working Group and involved 15 laboratories (from 12 countries), of which ten were NMIs. Apart from a protocol for determination of moisture content and the provision of the certified reference material (CRM) SELM-1 to be used as the quality control sample, no sample preparation/extraction method was prescribed. A variety of approaches was thus used, including single-step and multiple-step enzymatic hydrolysis, enzymatic probe sonication and hydrolysis with methanesulfonic acid for SeMet, as well as microwave-assisted acid digestion and enzymatic probe sonication for total Se. For total Se, detection techniques included inductively coupled plasma (ICP) mass spectrometry (MS) with external calibration, standard additions or isotope dilution MS (IDMS), inductively coupled plasma optical emission spectrometry , flame atomic absorption spectrometry and instrumental neutron activation analysis. For determination of SeMet in the tablets, five NMIs and three academic/institute laboratories (of a total of five) relied upon measurements using IDMS. For species-specific IDMS measurements, an isotopically enriched standard of SeMet (76Se-enriched SeMet) was made available. A novel aspect of this study relies on the approach used to distinguish any errors which arise during analysis of a SeMet calibration solution from those which occur during analysis of the matrix. To help those participants undertaking SeMet analysis to do this, a blind sample in the form of a standard solution of natural abundance SeMet in 0.1 M HCl (with an expected value of 956 mg kg(-1) SeMet) was provided. Both high-performance liquid chromatography (HPLC)-ICP-MS or gas chromatography (GC)-ICP-MS and GC-MS techniques were used for quantitation of SeMet. Several advances in analytical methods for determination of SeMet were identified, including the combined use of double IDMS with HPLC-ICP-MS following extraction with methanesulfonic acid and simplified two-step enzymatic hydrolysis with protease/lipase/driselase followed by HPLC-ICP-IDMS, both using a species-specific IDMS approach. Overall, satisfactory agreement amongst participants was achieved; results averaged 337.6 mg kg(-1) (n = 13, with a standard deviation of 9.7 mg kg(-1)) and 561.5 mg kg(-1) (n = 11, with a standard deviation of 44.3 mg kg(-1)) with median values of 337.6 and 575.0 mg kg(-1) for total Se and SeMet, respectively. Recovery of SeMet from SELM-1 averaged 95.0% (n = 9). The ability of NMIs and expert laboratories worldwide to deliver accurate results for total Se and SeMet in such materials (selensied-yeast tablets containing approximately 300 mg kg(-1) Se) with 10% expanded uncertainty was demonstrated. The problems addressed in achieving accurate quantitation of SeMet in this product are representative of those encountered with a wide range of organometallic species in a number of common matrices.

Comparison between the accumulation capacity of four lichen species transplanted to a urban site.

The capacity to accumulate trace elements from the atmosphere of the lichens Hypogymnia physodes, Parmelia sulcata, Pseudevernia furfuracea and Usnea gr. hirta transplanted to an urban site of N Italy was compared. Twenty-nine elements (Al, As, Br, Ca, Cd, Ce, Cl, Co, Cr, Cs, Cu, Fe, Hg, I, K, La, Mg, Mn, Ni, Pb, Rb, Sb, Sc, Se, Sm, Th, Ti, V, Zn) were analyzed by Instrumental Neutron Activation Analysis (INAA) and Electro-Thermal Atomic Absorption Spectroscopy (ET-AAS). The ratio between the concentrations of each element in exposed samples to that of control samples (exposed-to-control ratio and EC ratio) was used to investigate the accumulation rates of lichen thalli. The results showed that in general elements did not exhibit well defined trends, but rather showed fluctuations, and indicated that H. physodes, P. furfuracea and U. gr. hirta have a similar accumulation capacity, while that of P. sulcata is lower.

A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease.

In many parkinsonian syndromes, neuromelanin (NM)-containing dopaminergic neurons of the substantia nigra (SN) are selectively targeted by the noxius pathogens. Studies of the constitutional and functional features of human NM allow the formulation of a logical hypothesis on its role in parkinsonian syndromes. In the early stages, NM synthesis and iron-chelating properties may act as a powerful protective mechanism, delaying symptom appearance and/or slowing disease progression. Once these systems have been exhausted, the pathogenic mechanisms affecting cytoplasmic organelles other than NM destroy NM-harboring neurons, with consequent pouring out of NM granules. These in turn activate microglia, causing release of nitric oxide, interleukin-6 and tumor necrosis factor-alpha, thus becoming an important determinant of disease aggravation. Neuromelanin appears to be a suitable target for devising chemical agents that might modify the course of these diseases.

Neuromelanin and iron in human locus coeruleus and substantia nigra during aging: consequences for neuronal vulnerability.

In this study a comparative analysis of iron molecules during aging was performed in locus coeruleus (LC) and substantia nigra (SN), known targets of Parkinson's Disease (PD) and related disorders. LC and SN neurons, especially the SN pars compacta, degenerate in PD and other forms of parkinsonism. Iron and its major molecular forms, such as ferritin and neuromelanin (NM), were measured in LC and SN of normal subjects at various ages. Iron levels were lower, H-ferritin/iron ratio was higher and the iron content in NM was lower in LC than in SN. Iron deposits were abundant in SN tissue, very scarse in LC tissue and completely absent in pigmented neurons of both SN and LC. In both regions H- and L-ferritins were present only in glia. This suggests that in LC neurons iron mobilization and toxicity is lower than that in SN and is efficiently buffered by NM. Ferritins accomplish the same buffering function in glial cells.

Determination of baseline element composition of lichens using samples from high elevations.

The results of a survey aimed at providing baseline element composition of lichens from unpolluted or very low polluted areas are reported. Lichen samples collected at high elevation areas in Himalayas (Nepal), Mt. Kenya (Kenya) and the Alps (Italy) were analyzed for their trace element content, mostly by INAA, allowing for a multi-element analysis. The elemental composition of lichen samples was essentially influenced by natural occurrence, mainly airborne soil dust. However, also anthropogenic input determined by long-distance atmospheric transport of pollutants was involved for some highly volatile elements such as Br, Cd and Sb. To avoid the influence of soil contamination and air pollution, and obtain baseline concentrations to be used as reference (the "natural" elemental composition of lichens), the average of the lowest concentrations is suggested.

Determination of trace elements and evaluation of their enrichment factors in Himalayan lichens.

Within the framework of the Ev-K2-CNR research program of the Italian National Research Council a specific task project has been initiated for the identification of trace elements in lichens in remote high altitude areas. This is to evaluate the possibility of using lichens as biomonitors of trace elements of atmospheric pollution. In this preliminary study, more than 20 elements have been determined in some species of lichens collected at different altitudes (from 1300 to 5000 m) in the region of the Sagarmatha National Park (Nepal). Samples of superficial soils were also collected and analyzed to calculate the trace element enrichment factors (EF) using scandium as a normalizing element. Most of the trace elements were determined by instrumental neutron activation analysis (INAA), while lead and cadmium measurements were carried out with electrothermal atomic absorption spectroscopy (ET-AAS). The EF values as well as the elemental concentrations are reported and discussed.

Trace elements determination in lichens and in the airborne particular matter for the evaluation of the atmospheric pollution in a region of northern Italy.

Lichens as biomonitors and neutron activation analysis as analytical technique have been employed to study the distribution of trace elements (TE) in a mountain region of north Italy (Biella) characterized by settlements of wool industry. Samples of airborne particulate matter collected onto filters, different species of lichens and samples of soils have been analyzed for the calculation of the enrichment factors (EFs) of more than 25 TE. By comparison of the corresponding EFs, the most suitable lichen species (Parmelia caperata) was selected as specific TE biomonitor of the area investigated. Samples of this lichen were collected and analyzed for the evaluation of the TE distribution in four different locations. The results obtained from the analysis of the lichens gave information about the predominant direction of pollutants transportation, while those related to the concentrations found in the air particulate allowed the evaluation of the degree of the local TE atmospheric pollution.

Preconcentration and preseparation procedure for platinum determination at trace levels by neutron activation analysis.

A procedure that simultaneously allows both preconcentration and preseparation of platinum for its determination by neutron activation analysis at trace levels (<0.1 microg x g(-1)) in environmental related matrixes is developed. The method is mainly based on a two-step chemical procedure: (i) a preirradiation concentration/separation based on a column chromatography separation where the platinum is previously retained and subsequently separated from Au, Ca, Na, Br, and P; (ii) a postirradiation separation/purification of the 199Au at 158.4 keV used for the platinum determination via [198Pt (n,gamma)-->199Pt (beta-)-->199Au]. The method eliminates the following radionuclides with the gamma lines in the region of 158 keV: 47Sc (daughter of Ca) at 159.3 keV; 199Au (produced by double neutron capture onto the natural 197Au) at 158.4 keV; 123m Te at 158.8 keV. In addition, the background activity deriving from 24Na, 32p, and 82Br is drastically reduced. The method was tested by the analysis of certified rock material and then applied for platinum determination in airborne particulate matter.

Trace metals in oral mucosa in relation to the lichen ruberplanus pathology. A preliminary study carried out by neutron activation analysis.

Lichen ruberplanus, contact allergy and hypersensitivity can be linked to oral exposure to metals released from metal alloys commonly used in dentistry. In this context neutron activation analysis was developed for the microdetermination of 36 elements in oral mucosa biopsies of two patients affected by lichen ruber planus and of five subjects as control group. In order to minimise metal contamination during sample collection, biopsies were taken by laser bistoury technique and then submitted to radiochemical neutron activation analysis (RNAA). Among the metals analysed, chromium showed obvious high concentration in gingival biopsies of the two pathological subjects compared to the corresponding tissues of control group. Cobalt and nickel were also determined in higher concentrations, but only in one of the oral mucosa of the two patients. The present findings way support the hypothesis concerning a potential link of lichen ruber planus condition with the exposure to Cr, Co and Ni as released into oral cavity from prosthodontic alloys.

Some analytical problems encountered for trace elements determination in the airborne particulate matter of urban and rural areas.

The determination of trace elements (TE) in airborne particulate matter collected onto filters requires an accurate evaluation of the entire analytical procedure. Since many elements have to be determined at a few milligrams of air dust at nanogram levels, possible sources of error can arise from uncontrolled parameters such as blank of the filters, sample homogeneity, pre-analytical treatment, primary and comparator standards. These potential critical points are presented here and discussed on the basis of the experience developed in our laboratory in previous studies where several TE monitoring campaigns have been performed for air particulate matter collected in urban as well as in rural residential areas of north Italy. Instrumental neutron activation analysis (INAA) and electrothermal atomic absorption spectroscopy (ET-AAS) have been used for the investigation of more than 30 trace elements.

Trace elements total content and particle sizes distribution in the air particulate matter of a rural-residential area in north Italy investigated by instrumental neutron activation analysis.

The concentrations (ng/m3) of more than 30 trace elements have been determined in the total air particulate of a rural-residential area in north Italy. By collecting the aerosols with multistage impactors the distribution of the trace elements in the different size-fractionated particles has been also investigated. The fine 'inhalable' fraction with particles of less than 10 microns in equivalent aerodynamic diameter (PM10) as well as the subsequent finest 'respirable' fractions with particles of 0-1.1 microns (alveolar), 1.1-4.6 microns (bronchial) and 4.6-9 microns (tracheo-pharynx) have been analyzed and evaluated. Apart from Pb, Cd and, in some cases, Ni and Cu which have been determined by ETAAS (electrothermal atomic absorption spectroscopy), all measurements have been carried out by instrumental neutron activation analysis (INAA).

Content of trace elements in the respirable fractions of the air particulate of urban and rural areas monitored by neutron activation analysis.

The concentrations (ng/m3) of more than 30 trace elements have been determined in the total air particulate matter and in the size-segregated fractions collected in urban, industrialized, and rural residential areas in northern Italy by means of a multistage inertial impactor with the PM10 inlet. All measurements have been carried out by instrumental neutron activation analysis, except for Pb and Cd, which have been determined by electrothermal atomic absorption spectroscopy. Analytical quality assurance procedures have been developed with special regard to blanks, reagents, and sampling. Total concentrations and the granulometric distribution found in the different locations are reported and compared.

Rectal methadone in cancer patients with pain. A preliminary clinical and pharmacokinetic study.

BACKGROUND: Cancer pain can be treated in most cases with oral analgesics. However, during their clinical history, 53% to 70% of patients will need alternative routes of opioid administration. The rectal administration of opioids is a simple alternative route for many patients. There are no data in the literature regarding the pharmacodynamics and pharmacokinetics of rectal methadone. PATIENTS AND METHODS: We evaluated the analgesia, tolerability and absorption profile of methadone hydrochloride in six opioid-naive cancer patients with pain. A blood sample was collected before administration of a single dose of drug (10 mg) and then again after fixed times. At these fixed times the patients were asked about pain, nausea and drowsiness by means of a visual analogue scale of 0-100 mm (VAS). RESULTS: Pain relief was statistically significant as early as 30 minutes and up to eight hours after methadone administration. None of the patients reported significant side effects. The pharmacokinetics of rectal methadone showed rapid and extensive distribution phases followed by a slow elimination phase. CONCLUSIONS: Rectal methadone can be considered an effective analgesic therapy for patients with cancer pain for whom oral and/or parenteral opioids are not indicated or available.

Gallium distribution in several human brain areas.

Gallium is an element of increasing biological interest: It is involved in problems related to environmental pollution (Ga compounds are used in electronics industry) and to clinical treatments (Ga radionuclides are employed to detect neoplastic lesions). Moreover, since its chemical behavior is similar to that of aluminum, gallium could play a role in the health effects attributed to this element. Data on naturally occurring Ga levels in human samples from healthy subjects are scanty; regarding the brain, the only reliable values available in the literature were published by Hamilton in 1972/73. In this work, the gallium distribution in several human brain areas, evaluated by radiochemical neutron activation analysis (RNAA), was found to be dishomogeneous. The element concentration determined in dry samples was, in any case, lower than the ppb level.