Molar Units Research Articles

Effect of vascular endothelial growth factor on nasal vascular permeability

One of the major functions of vascular endothelial growth factor (VEGF) is increasing vascular permeability. We previously reported that VEGF is present in nasal secretions in rhinosinusitis, particularly in allergic rhinitis, and is hyperproduced immediately after antigen provocation. However, its function in nasal mucosa has not yet been investigated. This study was designed to estimate the increased vascular permeability by VEGF in nasal mucosa and to discuss its possible role in allergic rhinitis. Prospective animal experiment. Hartley guinea pigs were used. Ethyl carbamate was injected into the abdomen for anesthesia, followed by intravenous injection of Evans blue into the femoral vein. Phosphate buffered saline, histamine, or VEGF was then applied to nasal cavities. Nasal mucosa was harvested after saline reflux from heart with phlebotomy by amputating the abdominal aorta. Tissue samples were soaked in formamide for 12 hours at 63 degrees C to extract dye exudates from nasal mucosa. To analyze vascular permeability, dye was quantified by colorimetry. VEGF increased vascular permeability in nasal mucosa, and was more than 1 x 10(6) times more potent than histamine on the basis of molar units. Although increased vascular permeability by VEGF was not inhibited by histamine 1 receptor antagonist, it was markedly inhibited by anti-VEGF receptor antibodies. VEGF increased vascular permeability to a greater degree than histamine in nasal mucosa via a different pathway. Regulating VEGF may be a new therapeutic option for persistent nasal symptoms in allergic rhinitis.

A Single ClpS Monomer Is Sufficient to Direct the Activity of the ClpA Hexamer

ClpS is an adaptor protein that interacts with ClpA and promotes degradation of proteins with N-end rule degradation motifs (N-degrons) by ClpAP while blocking degradation of substrates with other motifs. Although monomeric ClpS forms a 1:1 complex with an isolated N-domain of ClpA, only one molecule of ClpS binds with high affinity to ClpA hexamers (ClpA(6)). One or two additional molecules per hexamer bind with lower affinity. Tightly bound ClpS dissociates slowly from ClpA(6) with a t((1/2)) of approximately 3 min at 37 degrees C. Maximum activation of degradation of the N-end rule substrate, LR-GFP(Venus), occurs with a single ClpS bound per ClpA(6); one ClpS is also sufficient to inhibit degradation of proteins without N-degrons. ClpS competitively inhibits degradation of unfolded substrates that interact with ClpA N-domains and is a non-competitive inhibitor with substrates that depend on internal binding sites in ClpA. ClpS inhibition of substrate binding is dependent on the order of addition. When added first, ClpS blocks binding of both high and low affinity substrates; however, when substrates first form committed complexes with ClpA(6), ClpS cannot displace them or block their degradation by ClpP. We propose that the first molecule of ClpS binds to the N-domain and to an additional functional binding site, sterically blocking binding of non-N-end rule substrates as well as additional ClpS molecules to ClpA(6). Limiting ClpS-mediated substrate delivery to one per ClpA(6) avoids congestion at the axial channel and allows facile transfer of proteins to the unfolding and translocation apparatus.

The availability of toxicological analyses for poisoned patients in Ireland

Background. The National Poisons Information Service and the Association of Clinical Biochemists in the United Kingdom published guidelines on laboratory analyses for poisoned patients in 2002. In 2003, U.S. guidelines were prepared by an expert panel of analytical toxicologists and emergency department (ED) physicians. Some professional associations in different countries quote these guidelines but there are no data to support adherence to these recommendations in the medical literature. Objective. To analyze the availability of 15 quantitative laboratory analyses, specifically relating to the management of the poisoned patient, in Ireland. Methods. A questionnaire relating to the provision of toxicological analyses was compiled and distributed to 39 acute care hospital laboratories in Ireland. The availability of 15 quantitative analyses (carbamazepine, carboxyhemoglobin, digoxin, ethanol, ethylene glycol, iron, lithium, methemoglobin, methanol, paracetamol, paraquat, phenobarbital, salicylate, theophylline, and valproic acid), specifically relating to the management of the poisoned patient, was analyzed. The reporting units for these analyses were also collected. The acute care hospitals were sorted into groups according to their number of ED attendances: A) <20,000, B) 20,000–30,000, C) 30,000–40,000, D) 40,000–50,000, and E) >50,000 based on ED activity data for 2008. The median number of assays provided by each hospital group was calculated. Results. The response rate was 100%, allowing complete national data to be ascertained. Hospital laboratories provided a more comprehensive testing service when ED attendances exceeded 30,000 per annum. Sixteen hospital laboratories (41.0%) performed at least 10 of the 15 toxicological investigations. The most widely available assay was paracetamol (74.4%, n = 29) and the least widely available assays were methanol, ethylene glycol, and paraquat (2.6%, n = 1). Only one hospital laboratory provided all 15 analyses. Hospital laboratories in groups A and B carried out a median number of 3/15 assays (range 0–8) and 4/15 assays (range 0–10), respectively. Hospital laboratories where ED attendances exceeded 30,000 per annum carried out a median number of 11/15 toxicological assays (range 1–15). There was a lack of consistency in the reporting units with both molar and mass units used. Conclusion. There is wide availability of toxicological analyses among hospital laboratories in Ireland. Most analyses were provided with 24-h availability. Hospitals with ED attendances in excess of 30,000 provided a more comprehensive laboratory service with respect to the number of analyses performed. The lack of consistency with units used by Irish hospital laboratories could present challenges with the reporting and interpretation of quantitative results. This study could be carried out in other countries to establish what analyses are available for the treatment of poisoned patients.

Mechanisms of Activity-dependent Plasticity in Cellular Nitric Oxide-cGMP Signaling

Cellular responsiveness to nitric oxide (NO) is shaped by past history of NO exposure. The mechanisms behind this plasticity were explored using rat platelets in vitro, specifically to determine the relative contributions made by desensitization of NO receptors, which couple to cGMP formation, and by phosphodiesterase-5 (PDE5), which is activated by cGMP and also hydrolyzes it. Repeated delivery of brief NO pulses (50 nm peak) at 1-min intervals resulted in a progressive loss of the associated cGMP responses, which was the combined consequence of receptor desensitization and PDE5 activation, with the former dominating. Delivery of pulses of differing amplitude showed that NO stimulated and desensitized receptors with similar potency (EC50 = 10–20 nm). PDE5 activation was highly sensitive to NO, with a single pulse peaking at 2 nm being sufficient to evoke a 50% loss of response to a subsequent near-maximal NO pulse. However, the activated state of the PDE subsided quickly after removal of NO, the half-time for recovery being 25 s. In contrast, receptor desensitization reverted much more slowly, the half-time being 16 min. Accordingly, with long (20-min) exposures, NO concentrations as low as 600 pm provoked significant desensitization. The results indicate that PDE5 activation and receptor desensitization subserve distinct short term and longer term roles as mediators of plasticity in NO-cGMP signaling. A kinetic model explicitly describing the complex interplay between NO concentration, cGMP synthesis, PDE5 activation, and the resulting cGMP accumulation successfully simulated the present and previous data.

Electrical Conductance — A Versatile Guide in Freshwater Science

Abstract Attention is directed to the many potential uses of specific electrical conductance (‘conductivity’) in the study of inland waters. Its measurement is capable of a precision useful in the detection of differences in a standing or flowing water-mass, but cannot be translated into measures of chemical concentration with equivalent absolute accuracy. Reasons — not infrequently neglected — include approximations in temperature correction, in allowance for a depression effect at higher ionic strength (salinity), and especially in the differences of specific conductance of chemically different ions. The last can be reduced by treating ionic concentration in chemical equivalents (e.g. meq L-1) rather than the usual units of mass (e.g. mg L-1) or molarity (e.g. mmol L-1); also by making allowance for the exceptionally high equivalent conductance of H+and OH- ions of significance in markedly acid and alkaline waters. Measurement in the field has been helped by the development of small portable instruments...

Interaction of Tim23 with Tim50 Is Essential for Protein Translocation by the Mitochondrial TIM23 Complex

The TIM23 complex is the major translocase of the mitochondrial inner membrane responsible for the import of essentially all matrix proteins and a number of inner membrane proteins. Tim23 and Tim50, two essential proteins of the complex, expose conserved domains into the intermembrane space that interact with each other. Here, we describe in vitro reconstitution of this interaction using recombinantly expressed and purified intermembrane space domains of Tim50 and Tim23. We established two independent methods, chemical cross-linking and surface plasmon resonance, to track their interaction. In addition, we identified mutations in Tim23 that abolish its interaction with Tim50 in vitro. These mutations also destabilized the interaction between the two proteins in vivo, leading to defective import of preproteins via the TIM23 complex and to cell death at higher temperatures. This is the first study to describe the reconstitution of the Tim50-Tim23 interaction in vitro and to identify specific residues of Tim23 that are vital for the interaction with Tim50.

Ethylation of arabinoxylan from Ispaghula ( Plantago ovata) seed husk

The ethylation of arabinoxylan, isolated from Ispaghula seed husk by alkali extraction, was carried out heterogeneously with ethyl iodide in the presence of aqueous sodium hydroxide (25%). The reaction parameters were varied in terms of molar ratio anhydrosugar unit:reagent, slurry medium, and temperature. In order to determine the total degree of substitution of ethyl groups (DS Et), 1H NMR spectroscopic investigations of ethyl arabinoxylans (EAX) after peracetylation with acetyl chloride in N,N-dimethyl formamide were carried out. Structural elucidation of the peracetylated EAX was conducted by means of 1H, 1H COSY- and HSQC-DEPT NMR experiments. DS values for EAX as high as 0.61 were achieved. Samples were soluble in dimethyl sulfoxide at 80 °C. The intrinsic viscosity [ η] of EAX samples depends on reaction conditions applied. The highest [ η] obtained was 518 mL/g for a sample synthesized at 40 °C in methanol as slurry medium using a molar ratio arabinoxylan:ethyl iodide of 1:18.

Human chorionic gonadotropin isoforms and their epitopes: diagnostic utility in pregnancy and cancer

Clinical management of pregnancy, pregnancy-related disorders and trophoblastic tumors is dependent on immunoassay measurements of the complex analyte human chorionic gonadotropin (hCG). Differences in hCG results using different methods affect clinical interpretation with potentially adverse consequences for patient care. Objectives/method: To provide an overview of factors contributing to method-related differences in hCG measurements and how to overcome these drawbacks. Six recently established highly purified and molar unit calibrated World Health Organization Reference Reagents for important hCG variants provide means for in-depth characterization of diagnostic immunoassays for hCG. For different clinical applications in pregnancy and cancer, appropriate epitopes and specificities of pairs of monoclonal antibodies against hCG in immunoassays have been clearly defined. This led to the conclusion that in routine clinical situations assays are preferred that measure all relevant hCG variants. The adoption of new nomenclature unambiguously describing what is being measured and the anticipated introduction of a new highly pure international standard for hCG represent significant progress towards improved analytical reliability and comparability of diagnostic hCG results.

The application of macroalga Pithophora varia Wille enriched with microelements by biosorption as biological feed supplement for livestock

AbstractBACKGROUND: The paper discusses biosorption of microelements by a freshwater macroalga Pithophora varia Wille to produce biological feed supplement for livestock. The biomass was enriched with microelements recommended by feeding standards in a single and a multi‐metal system.RESULTS: The equilibrium of biosorption was described by using a Langmuir model and the following values of the maximum biosorption capacity in the single‐metal system were obtained: Zn(II), 61.1 mg g−1; Co(II), 52.3 mg g−1; Cu(II), 55.7 mg g−1; and Mn(II), 38.3 mg g−1. The average value of maximum biosorption capacity expressed in molar units for all the cations was equal 1.7 ± 0.2 meq g−1, suggesting chemical rather than physical biosorption. It was also found that the mechanism of biosorption was due to cation exchange of alkali and alkaline earth metals with microelements. The biomass was also enriched with microelements in multi‐metal system. The total metal ion binding capacity in the multi‐metal system was two‐fold lower than in the single‐metal system and was 0.90 meq g−1 in the preparation for laying hens and 0.95 meq g−1 in the supplement for swine.CONCLUSION: Finally, the level of supplementation of livestock feed (with enriched single‐ and multi‐metal system macroalga), to cover 25% of total requirements for microelements, according to feeding standards, was provided. Copyright © 2008 Society of Chemical Industry

Efficient allylation of cellulose in dimethyl sulfoxide/tetrabutylammonium fluoride trihydrate

The cellulose solvent dimethyl sulfoxide (DMSO)/tetrabutylammonium fluoride trihydrate (TBAF) was successfully applied as reaction medium for the synthesis of allyl cellulose by conversion of the polymer with allyl chloride in the presence of solid NaOH. Samples with degree of substitution from 0.50 to 2.98 were accessible by varying the molar ratio anhydroglucose unit:allyl chloride:NaOH and reaction time. DMSO/TBAF was found to be an efficient reaction medium for the preparation of highly functionalized samples from spruce sulfite pulp with degree of polymerization of about 500 even in a scale of 50 g. The allyl cellulose samples were characterized by means of FTIR- and NMR spectroscopy. Size exclusion chromatography revealed negligible polymer degradation during synthesis and purification of the samples.

Limited Mitochondrial Permeabilization Is an Early Manifestation of Palmitate-induced Lipotoxicity in Pancreatic β-Cells

Involvement of the mitochondrial permeability transition (MPT) pore in early stages of lipotoxic stress in the pancreatic beta-cell lines MIN6 and INS-1 was the focus of this study. Both long term (indirect) and acute (direct) effects of fatty acid (FA) application on beta-cell susceptibility to Ca(2+)-induced MPT induction were examined using both permeabilized and intact beta-cells. Long term exposure to moderate (i.e. below cytotoxic) levels of the saturated FA palmitate sensitized beta-cell mitochondria to MPT induced by Ca(2+). Long term exposure to palmitate was significantly a more efficient inducer of MPT than the unsaturated FA oleate, although upon acute application both caused similar MPT activation. Application of antioxidants, inhibitors of the ceramide pathway, or modifiers of membrane fluidity did not protect beta-cell mitochondria from FA exposure. However, significant protection was provided by co-application of the unsaturated FA oleate in a phosphatidylinositol 3-kinase-dependent manner. Characterization of MPT pore opening in response to moderate palmitate treatment revealed the opening of a unique form of MPT in beta-cells as it encompassed features of both low and high conductance MPT states. Specifically, this MPT showed solute selectivity, characteristic of a low conductance MPT; however, it affected mitochondrial respiration and membrane potential in a way typical of a high conductance MPT. Activation of the full-size/high conductance form of MPT required application of high levels of FA that reduced growth and initiated apoptosis. These findings suggest that in the beta-cell, MPTs can act as both initiators of cell death and as versatile modulators of cell metabolism, depending on the mode of the MPT pore induced.

An electrospray technique for hyperquenched glass calorimetry studies: Propylene glycol and di- n-butyl phthalate

We describe an electrospray technique for in situ preparation, for differential scanning calorimetry study, of samples of molecular liquids quenched into the glassy state on extremely short time scales (hyperquenched). We study the cases of a hydrogen-bonded liquid, propylene glycol, PG and a Van der Waals liquid, di- n-butyl phthalate DBP. Using a fictive temperature method of obtaining the temperature dependence of enthalpy relaxation, we show that the electrospray method yields quenching rates of ∼10 5 K/s, while the more common method, dropping a sealed pan of sample into liquid nitrogen, yields only 120 K/s. These hyperquenched samples start to relax, exothermically, far below the glass temperature, at a temperature (0.75 T g) where the thermal energy permits escape from the shallow traps in which the system becomes localized during hyperquenching. This permits estimation of the trap depths, which are then compared with the activation energy estimated from the fictive temperature of the glass and the relaxation time at the fictive temperature. The trap depth in molar energy units is compared with the ‘height of the landscape’ for PG, the quasi-lattice energy of the liquid based on the enthalpy of vaporization, and the single molecule activation energy for diffusion in crystals. The findings are consistent with the mechanism of relaxation invoked in a current model of relaxation in glassforming liquids. In the case of di- n-butyl phthalate we investigate the additional question of sub- T g annealing effects. We find the ‘shadow’ glass transition, (an annealing prepeak) seen previously only in multicomponent mineral and metallic glasses. The phenomenon is important for understanding microheterogeneities in viscous liquid structures.

Hybridized ruthenium(II) complexes with high molar extinction coefficient unit: Effect of energy band and adsorption on photovoltatic performances

Two hybridized Ru(II) complexes cis-Ru(dcbpy) 2(PNI-phen)(NCS) 2 and cis-Ru(dcbpy) 2(PERY-phen)(NCS) 2, coded as RuPBS and RuPPS containing naphthalimide or perylene imide unit, were synthesized and utilized in dye-sensitized TiO 2 solar cells (DSCs). Their absorption spectra, electrochemical and photovoltatic properties were studied. Both complexes, especially for RuPPS, have wide absorption bands with high molar extinction coefficient in the visible spectrum region. The effects of the energy band of the incorporated ligand and adsorption on TiO 2 were extensively discussed. The complexes are served to enhance our knowledge regarding manipulation of new sensitizers for DSCs, providing a powerful strategy for prediction of photovoltatic performances.

Structure and properties of the polyelectrolyte complex of chitosan with poly(methacrylic acid)

AbstractThe structure and properties of the polyelectrolyte complex composed of chitosan (CS) and poly(methacrylic acid) (PMAA) were studied in aqueous solutions using UV‐visible transmittance measurements, a fluorescence probe technique, and transmission electron microscopy. The thermal properties of the solid complex were measured using differential scanning calorimetry. The results showed that the complex optimum molar ratio (in monomer unit) of CS to PMAA is 1:4 at pH = 4.0, that is, there is an optimum complex between CS and PMAA when the feed ratio (in molar monomer unit) of CS to PMAA is 1:4 and an ionic bond between the amino ion group and carboxylate group can be formed on average every four carboxylate (or carboxyl) groups. The conformation of PMAA changed from a hypercoiled to a loose coil on complexation, and the pH‐ and salt‐sensitive range of the polyelectrolyte complex was obviously different from that of CS or PMAA. The formation process of the complex under various external conditions is discussed in detail. Transmission electron microscopy revealed that the sizes of CS–PMAA complex particles increased with increasing pH or salt concentration, and a change in morphology of the complex was observed. Thermal analysis further revealed that there was a change of structure and properties on blending in aqueous solutions. Copyright © 2007 Society of Chemical Industry

Starch Derivatives of High Degree of Functionalization. 13. Novel Amphiphilic Starch Products

AbstractAmphiphilic starch derivatives of high degree of substitution (DS) were prepared by benzylation of pea, potato and waxy maize starch followed by the introduction of hydroxypropyltrimethylammonium and carboxymethyl moieties. The conversions were carried out under heterogeneous conditions leading to products with a total DS of up to 1.8. The starch composition regarding amylose and amylopectin influences the DS value.The structure of the products was characterized by means of elemental analysis, FTIR and NMR spectroscopy, and, in case of benzyl carboxymethyl starch by means of HPLC after complete chain degradation. The tensioactive properties depend on the DS values of hydrophilic and lipophilic groups and can be adjusted by controlling the molar ratio anhydroglucose unit to reagent during the synthesis. Surface tensions as low as 48.6 mN/m were found for benzyl hydroxypropyltrimethylammonium starch and 38.6 mN/m for benzyl carboxymethyl starch. The lowest critical micelle concentration determined is 2.1 mmol/L.

Distribution of bioactive trace metals (Fe, Co, Ni, Cu, Zn and Cd) in the Sulu Sea and its adjacent seas

Abstract Here we present the first vertical distribution of dissolved (D) and acid-dissolvable (AD) bioactive trace metals (Fe, Co, Ni, Cu, Zn and Cd) in the Sulu Sea and the South China Sea, together with those observed previously by the same method in the western North Pacific. At a depth of 50–75 m, concentration minima of some trace metals were observed in the Sulu Sea (D-Zn, Cu and Fe) and the South China Sea (D-Zn), which coincided with the Chl a maximum, indicating scavenging of these metals including biological uptake. Above 150 m in the South China Sea, elevated concentrations of D-Co and Cu were observed, which could result from fluvial/coastal waters and/or shelf-sedimentary sources. In the surface mixed layer in the Sulu Sea, D-Fe concentrations were high (2 nM), presumably due to the flowing of waters across the Philippine Archipelago. Except for Fe, concentrations of D and AD species at each corresponding depth were not significantly different. Concentrations of AD-Fe (6.8–17 nM), below 500 m in the Sulu Sea were much higher than those of D-Fe (0.2–1.7 nM), indicating that particulate Fe is abundant in the basin, probably coming from nearby sedimentary sources. The vertical distributions of D-Ni, Cu, Zn and Cd in the South China Sea were nutrient-like and deviated slightly from those in the western North Pacific. This is caused by a rapid flushing of waters from the Philippine Sea coupled with vertical mixing within the South China Sea. The distribution of these metals in the Sulu Sea was more uniform below 500 m. The average concentrations of D-Ni, Cu, Zn and Cd in the deep water of the Sulu Sea were 6.1, 1.5, 3.3 and 0.5 nM, significantly lower than those of the western North Pacific (9.6, 2.8, 10.1 and 1.0 nM, respectively). We also found lower D-Cd/PO4, Ni/PO4 and Zn/Si(OH)4 ratios in the Sulu Sea than those of the Pacific. The depletion of these concentrations and the D-Cd/PO4 and Ni/PO4 ratios in the Sulu Sea is probably because the deep water of the basin is rapidly exchanged with shallow waters but isolated from nutrient-rich deep waters derived from the North Pacific, due to the surrounding topographic barriers including the islands and the shallow sills ( While subsurface waters were flowing along density surfaces (sigma-T values of ∼26) from the South China Sea to the Sulu Sea, the concentrations of macronutrients, D-Ni, Cu, Zn and Cd increased due to the regeneration from biogenic particles. The increases in the concentrations of bioactive elements relative to that of PO4 were N : P : Si : Ni : Cu : Zn : Cd=15 : 1 : 40 : 2.4×10−3 : 0.6×10−3 : 2.7×10−3 : 0.03×10−3 in a molar unit.

Cadmium, lead and mercury biosorption on waste fungal biomass issued from fermentation industry. I. Equilibrium studies

Two kinds of waste biomass ( Penicillium oxalicum var. Armeniaca, Tolypocladium sp.) used in fermentation industry were submitted to different treatments and were tested as biosorbents of cadmium, lead and mercury. The study was initially focused on the evaluation of the impact of pH on the sorption of selected metals and continued with the sorption isotherms determination. The sorption capacities for the target metals can be ranked according to Hg ≫ Pb > Cd for P. oxalicum sorbent and Hg ≫ Cd > Pb for Tolypocladium sp. sorbent. P. oxalicum shows greater sorption capacities (based on sorption capacities in molar units) than Tolypocladium sp. Maximum sorption capacity as high as 270 mg Hg g −1 (initial pH 5, equilibrium pH close to 6.2) has been obtained for Penicillium derived biosorbent. The Langmuir isotherm equation fits significantly better experimental data than the Freundlich isotherm equation. FT-IR spectra and elemental analysis of the biosorbents have shown significant changes in their composition according to the treatment.

A surface adsorption/reaction mechanism for gold oxidation by copper(II) in ammoniacal thiosulfate solutions

Literature data for gold dissolution in ammoniacal copper(II) thiosulfate solutions is reinterpreted on the basis of adsorption and mixed potential theory. The dissolution reaction appears to take place via the adsorption of copper(II)–ammonia–thiosulfate onto the gold surface, forming the adsorbed species ⊢Au(S 2O 3) n Cu(NH 3) −(2 n−2) p . Equilibrium constants for the formation of these species from Cu(NH 3) 2+ m are in the range K ads = 172 – 510 (molar units) for m = 4 , n = 1 or 2, and p = 2 or 3. These complexes decompose with a rate constant of k Au = 1.7 × 10 −4 mol m −2 s −1 , to produce Au(S 2O 3) 3− 2 and Cu(NH 3) + 3 or Cu(NH 3) + 2, where the copper(I) complexes in solution are re-equilibrated to the more stable species Cu(S 2O 3) 3− 2 and Cu(S 2O 3) 5− 3.

Factors Influencing Isoprotein Dependency of Polyclonal Apolipoprotein(a) Assays

Hyperbolic relationships can be expected when comparing data obtained by apolipoprotein(a) [apo(a)] isoprotein-sensitive assays against data obtained by an isoprotein-independent assay ( x axis), and almost all polyclonal antibody-based apo(a) assays are isoprotein sensitive (1). We have developed a dual polyclonal antibody ELISA for quantification of plasma apo(a) and attempted to standardize it with regard to its accuracy in nmol/L while calibrating on the IFCC PRM2 calibrator. We also followed the traditional approach and compared the results with other established methods that express the results in mass or molar units. We found that our assay gave linear relationships with two other assays, of which at least one was isoprotein-independent. We confirmed the apo(a) isoprotein dependency by testing the IFCC PRM-2 calibrator and material differing in apo(a) molecular weight. Our results suggest that polyclonal antibody-based apo(a) assays a priori are not isoprotein-dependent. The work also gives insight into the suitability and comparativity of three different calibrators with target values in molar or mass units. Here we discuss our experiences in the hope that they are helpful for others who also want to standardize apo(a) assays. apo(a) is a glycoprotein bound to LDLs; a small amount may also circulate in free form (1)(2). There is no doubt that the standardization of total apo(a) measurements in routine laboratories world-wide needs improvement (1). The main problem in standardization is the specificity of the detecting …

The Irrationality of the Present Use of the Osmole Gap

The present clinical use of serum osmometry is erroneous in two respects. The first, and the most important, is the incorrect assumption that serum behaves as a dilute 'ideal' solution and that the osmotic activity of a substance depends solely on the number of solute particles. The amount of variance from ideal behaviour of serum containing an exogenous substance is expressed by the osmotic coefficient (phi). We have calculated the osmotic coefficient for serum containing ethanol (alcohol) and recommend that the osmotic coefficient for serum containing other low molecular weight substances such as methanol (methyl alcohol), isopropyl alcohol and ethylene glycol also be calculated. This is necessary for the accurate calculation of the contribution of these substances to the serum osmolality.Secondly, the practice of subtracting the calculated serum molarity from measured serum osmolality is not valid since it represents a mathematically improper expression. The units of these two terms are different. The 'osmole gap' (OG) is typically viewed as the difference between serum osmolality determined by an osmometer and the estimated total molarity of solute in serum by directly measuring the concentration of several substances and then substituting them into a published formula. Some authors call this sum the calculated or estimated osmolarity but, because the concentrations are measured directly and not with an osmometer, the calculated term represents molarity. The units of osmolality are mmol/kg of H2O and the units of molarity are mmol/L. Therefore, the practice of subtracting calculated serum molarity from measured serum osmolality is not mathematically sound and is an oversimplification for ease of application. This mathematical transgression necessarily adds an error to the incorrectly calculated OG. Despite this, the OG is commonly used in clinical medicine. Serum osmolality can be converted to molarity provided the weight percentage and the density of the solution are known and thus, we recommend that this conversion be done prior to calculation of the gap. We recommend that the gap between measured serum osmolarity and calculated serum molarity be called the 'osmolar gap'. After having corrected for non-ideality for serum and for inconsistency of units, the standard value and reference range for this gap must be determined in an adequate number of patient populations and in a variety of clinical settings. An example of this determination, using data from a group of ethanol-poisoned patients is given. This correction should be applied before the evaluation of the osmolar gap as a screening test for other low molecular weight substances proceeds.