Polycarboxylate ethers: The key towards non-toxic TiO2 nanoparticle stabilisation in physiological solutions.

Stable, non-agglomerated TiO2 nanoparticle (NP) dispersions are a crucial requirement for an accurate NP dosing in in vitro and in vivo experiments. In this study self-synthesised TiO2 NPs were stabilised in three different cell culture media (DMEM, RPMI, BEGM) with the help of stabilising agents. Cell culture tested stabilisers (bovine serum albumin, fetal bovine serum) were compared to non-tested commercial products which are commonly utilized in the cement industry (Melflux(®) 4930 F, Melpers(®) 4343, Sika(®) ViscoCrete(®)-10110178). For a quantitative evaluation and comparison of the degree of stabilisation, a sedimentation study using UV absorbance spectroscopy was carried out and the agglomerate size was measured via dynamic light scattering. The cytotoxicity of the novel surfactants and stabilised NPs was examined in a head and neck squamous cell carcinoma-derived FaDu cell line and in human mesenchymal stem cells. We successfully stabilised TiO2 NPs with Melflux(®) 4930 F in each cell culture medium, achieving perfect stability over at least one day and agglomerate sizes of less than 100nm, while the cytotoxicity of the NPs was not affected.

Mechanochemical surface functionalisation of superparamagnetic microparticles with in situ formed crystalline metal-complexes: a fast novel core-shell particle formation method.

An innovative mechanochemical method is reported for the in situ formation of crystalline metal-complexes on the surface of superparamagnetic nanocomposite microparticles. The process is demonstrated for coating Fe3O4 multicore-silica matrix particles with the 1,2,4-1H-triazole complex [ZnCl2(TzH)2]. The use of mechanochemistry demonstrates a flexible process to obtain functional shells on magnetic particle cores without the need for complicated surface-functionalisation reactions in solution. Simple mixing of the desired shell-precursors ZnCl2 and 1,2,4-1H-triazole (TzH) with the magnetic particles in a ball mill is sufficient to tailor the particle surfaces with novel functionalities while retaining the superparamagnetic behaviour.

Surfactant free superparamagnetic iron oxide nanoparticles for stable ferrofluids in physiological solutions.

A process is reported to obtain a nanoparticle sol from co-precipitated iron oxide particles without using any surfactant. The sol - a true ferrofluid - is not only stable over a wide range of pH but also in physiological solutions. This is a decisive step towards biomedical applications where nanoparticle agglomeration could so far only be prevented by using unwanted surfactants.

Light echoes reveal an unexpectedly cool η Carinae during its nineteenth-century Great Eruption.

η Carinae is one of the most massive binary stars in the Milky Way. It became the second-brightest star in our sky during its mid-nineteenth-century 'Great Eruption', but then faded from view (with only naked-eye estimates of brightness). Its eruption is unique in that it exceeded the Eddington luminosity limit for ten years. Because it is only 2.3 kiloparsecs away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that during its nineteenth-century eruption, η Car ejected more than ten solar masses in an event that released ten per cent of the energy of a typical core-collapse supernova, without destroying the star. Here we report observations of light echoes of η Carinae from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km s(-1), in good agreement with predicted expansion speeds. The light-echo spectra correlate best with those of G2-to-G5 supergiants, which have effective temperatures of around 5,000 kelvin. In contrast to the class of extragalactic outbursts assumed to be analogues of the Great Eruption of η Carinae, the effective temperature of its outburst is significantly lower than that allowed by standard opaque wind models. This indicates that other physical mechanisms such as an energetic blast wave may have triggered and influenced the eruption.

Survey of laxative use by adults with self-defined constipation in South America and Asia: a comparison of six countries.

BACKGROUND: In contrast to the US and Europe, prevalence and laxative use for self-defined constipation among adults was previously reported to be unassociated with age among adults in South Korea and Brazil. AIM: To determine whether observations in South Korea and Brazil are reflective of other Asian and South American countries. METHODS: A total of 8100 adults from Argentina, Colombia, Indonesia and China completed a questionnaire identical to that previously used in South Korea and Brazil. RESULTS: Prevalence of constipation was similar to that reported for Brazil and South Korea and was 2.17-fold (95% CI: 1.71-2.64) higher amongst women than amongst men. Prevalence increased with age amongst all adults in Argentina and China and only among men in Colombia and Brazil. With the exception of Indonesia, the majority of those with constipation had symptoms at least once weekly, and for < or =3 years. Less than one-third of adults reported using laxatives to treat constipation. Laxative use was not associated with gender and increased with age in Argentina and Colombia. CONCLUSIONS: No clear geographical or cultural tendencies were observed in the prevalence of constipation and laxative use among the South American and Asian countries studied in this survey.

A multinational survey of prevalence and patterns of laxative use among adults with self-defined constipation.

BACKGROUND: While numerous studies report prevalence of constipation, use of laxatives is poorly understood. AIM: To conduct a survey in seven countries evaluating prevalence of constipation and laxative use in its treatment. METHODS: Thirteen thousand eight hundred seventy-nine adults [approximately 2000 each from US, UK, Germany (GE), France (FR), Italy (IT), Brazil (BR) and South Korea (SK)] completed questionnaires assessing occurrence, frequency, duration and laxative use for treating constipation. RESULTS: Overall, 12.3% of adults had constipation [range: 5% (GE) to 18% (US)] in the prior year. A greater percent of women from all countries and elderly from all except SK and BR reported constipation; odds ratios for constipation among women and elderly were 2.43 (95% CI: 2.18-2.71) and 1.5 (95% CI: 1.25-1.73) vs. men and young subjects. Among those with constipation, 16% (SK) to 40% (US) used laxatives. Laxative use was generally associated with increasing age, symptom frequency and lower income and education. A similar percentage of men and women with constipation reported using laxatives; a greater percentage of women used laxatives for a longer time. CONCLUSIONS: Prevalence of self-defined constipation and laxative use varies among countries. Prevalence is generally related to gender and age, whereas laxative use is related to age, but not to gender.

Noncompaction of the myocardium associated with Roifman syndrome.

Noncompaction of the ventricular myocardium, sometimes referred to as "spongy myocardium", appears as excessive and prominent trabeculations and deep intratrabecular recesses within the ventricular wall, usually involving the left ventricle, although the right ventricle and interventricular septum can also be affected. It may occur with or without additional heart malformations. Roifman syndrome is a constellation of antibody deficiency, spondyloepiphyseal dysplasia, facial dysmorphism, growth retardation, and retinal dystrophy. We report a patient with Roifman syndrome who presented with noncompaction of the left ventricular myocardium. Our findings expand the spectrum of diseases associated with noncompaction. The recognition of noncompaction among patients with Roifman syndrome is important, as the immune deficiencies may be subtle and undiagnosed until adulthood. Thus, some patients may first present with cardiac failure.

Review article: alginate-raft formulations in the treatment of heartburn and acid reflux.

Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate-based raft-forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate-based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH-neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro-oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate-based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents. The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate-containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate-based raft-forming formulations can additionally provide longer-lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms. Alginate-based, raft-forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate-rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non-systemic mechanism of action provides rapid and long-duration relief of heartburn and acid reflux symptoms.

Fatty acid-mediated gastroprotection does not correlate with prostaglandin elevation in rats exposed to various chemical insults.

This study involved a comparison of activity of several long-chain fatty acids (arachidonic acid, dihomo-[gamma]-linolenic acid, linoleic acid, and oleic acid) for protection against gastric mucosal damage elicited by taurocholic acid, acidified aspirin, and ethanol in rats. Each damaging agent induced gastric mucosal lesions in the corpus. Mucosal damage was induced by all agents, and all fatty acids protected the gastric mucosa; however, ethanol and arachidonic acid were the most potent damaging and protecting agents, respectively. Maximally protective doses for prevention of taurocholic acid-induced damage by arachidonic, dihomo-[gamma]-linolenic, linoleic, and oleic acids were 50, 200, 100, and 200 mg/kg, respectively; however, 10 mg/kg arachidonic acid reduced lesion length by > 50%, whereas minimally effective doses of the other fatty acids were > or = 50 mg/kg. Similar potency differences were observed for fatty acid protection against acidified aspirin-induced gastric damage. Although all the fatty acids reduced macroscopic damage, histologic studies showed they did not totally eliminate surface mucosal damage. Microscopic analysis showed that treatment with dihomo-[gamma]-linolenic acid or oleic acid attenuated depletion of neutral and acidic glycoproteins from the mucus neck cells of the gastric mucosa in response to exposure to taurocholic acid. Despite having similar gastroprotective activity, arachidonic, dihomo-[gamma]-linolenic, linoleic, and oleic acids had very dissimilar abilities to elevate gastric mucosal E-series prostaglandins. Both arachidonic and dihomo-[gamma]-linolenic acids elevated E-series prostaglandins, but arachidonic acid had 2-5-fold greater gastroprotective potency. Furthermore, oleic and linoleic acids, which had protective potency similar to that dihomo-[gamma]-linolenic acid, did not significantly elevate prostaglandins. These studies failed to demonstrate an absolute correlation between prostaglandin elevation and gastroprotection. The results of this investigation suggest that prostaglandin elevation, although associated with gastroprotection, does not appear to be the sole mechanism for fatty acid-mediated protection of rat gastric mucosa.

Comparison of monoclonal antibody methods and a ribosomal ribonucleic acid probe test for Neisseria gonorrhoeae culture confirmation.

Recently, a chemiluminescent nucleic acid probe test that specifically detects the ribosomal ribonucleic acid of Neisseria gonorrhoeae has been released for clinical laboratory use (AccuProbe Neisseria gonorrhoeae). In this study, three coagglutination tests (GonoGen I, Meritec GC, and GC Omni), the GonoGen II immunofiltration method and the Micro Trak Neisseria gonorrhoeae fluorescent monoclonal antibody test were compared with AccuProbe for identification of gonococci. Strains tested (n = 376) included 194 Neisseria gonorrhoeae, 82 Neisseria meningitidis, 32 Neisseria lactamica, 32 Neisseria species, 32 Moraxella catarrhalis, 2 Moraxella spp. and 2 Kingella denitrificans. The GonoGen I, Meritec GC and GC Omni coagglutination tests produced clearly positive results for 93.8%, 92.3% and 95.9% of the gonococci, respectively. The GonoGen II unequivocally identified 91.8% and the MicroTrak fluorescent antibody test identified 90.7% with 2+ or greater fluorescence. AccuProbe identified 100% of the gonococci tested. GonoGen I and GonoGen II were 98% specific, Meritec GC was 99% specific and the specificity of the GC Omni, MicroTrak fluorescent antibody and AccuProbe tests was 100%. While antibody-based tests were reliable when results were clearly interpretable, the AccuProbe was the only confirmatory test that was 100% accurate. Serotyping studies indicate that an array of beta-lactamase positive and negative gonococcal serotypes fail to react with the monoclonal antibody-based tests in general and with the fluorescent antibody test in particular.

Neurokinin3 receptor regulation of acetylcholine release from myenteric plexus.

This study sought to characterize the action of neurokinin B (NKB) and senktide, a selective synthetic agonist for NK3 receptors, on the myenteric plexus of the guinea pig small intestine. Both peptides stimulated a dose-dependent release of [3H]-acetylcholine (ACh). The mean effective dose values were 1 x 10(-9) for NKB and 3 x 10(-11) M for senktide. The action of these two neurokinins was blocked by the removal of Ca2+ and was sensitive to tetrodotoxin. The release of [3H]ACh was antagonized by omega-conotoxin GVIA, implying the involvement of N-type voltage-sensitive calcium channels. Senktide-evoked ACh release was also insensitive to nifedipine or flunarizine but was blocked by diltiazem. Treatment with protein kinase C (PKC) inhibitors (H-7 and polymyxin B) or activators (12-tetradecanoylphorbol 13-acetate and SC-9) failed to alter the NK3 receptor-mediated ACh output. Our data did not support an action mediated via PKC upon the activation of NK3 receptors on myenteric cholinergic neurons.

Effect of mebeverine hydrochloride on jejunal motility and epithelial transport in the anesthetized ferret.

Previous in vitro and in vivo studies demonstrate that mebeverine, administered to isolated smooth muscle preparations or given intravenously, (i.v.), acts as an antispasmodic agent and may be useful in treating intestinal hypermotility. Whether mebeverine affects intestinal mucosal transport is, however, unknown. The aim of the present study was to characterize the effect of mebeverine on both small intestinal motor activity and electrogenic epithelial transport in the urethane anesthetized ferret. The effects of mebeverine were compared following i.v. and intrajejunal (i.j.) administration. Following both routes of drug administration mebeverine dose dependently inhibited jejunal motility, with the i.j. route being more potent. However, when administered i.v. but not i.j., the doses of mebeverine that inhibited jejunal motility also significantly reduced heart rate and arterial blood pressure. Mebeverine (0.1-10 mg/kg) administered i.v. had no significant effect on epithelial transport as measured by a change in transmural potential difference. However, when dosed i.j., mebeverine (0.1-10 mg/kg) induced a decrease in potential difference towards lower lumen negativity, which was suggestive of a decrease in fluid secretion or enhancement of absorption. In conclusion, the results confirm in vivo the antispasmodic effect of mebeverine and suggested that mebeverine can influence epithelial transport, probably in the direction of enhanced intestinal absorption.

Irradiation of pigmented melanoma cells with high intensity pulsed radiation generates acoustic waves and kills cells.

Photokilling of pigmented mouse melanoma cells (B-16) was investigated using pulsed high intensity visible radiation. Melanin acts as an endogenous chromophore, and 694 nm radiation with 40 nsec pulse duration and 0.5-3 X 10(7)w/cm2 intensity causes cell death. Irradiation of non-pigmented human melanoma cells (U1) or human squamous carcinoma cells (FaDu) under similar conditions did not kill the cells. Also, irradiation of B-16 cells with 300 microsec laser pulses (10(3)W/cm2) or with continuous wave (CW) radiation (10(-3)W/cm2) did not kill the cells. These data indicate that pigmented cell killing is due to absorption of radiation by melanin and that the pulsewidth and intensity of radiation play important roles in cell killing. The generation of acoustic waves due to absorption of the pulsed radiation by pigmented cells and by isolated melanosomes was demonstrated at 532 and 625 nm and 8.5 nsec pulse duration (10(7)-10(8) W/cm2); the amplitudes of the acoustic signals were approximately 2.5-3.0-fold higher at 532 nm compared with 625 nm, and they increased with increasing fluence. In contrast, irradiation of U1 or FaDu cells with comparable fluences and intensities did not generate acoustic waves. A possible correlation between the generation of photoacoustic waves and pigment cell death is proposed. Since the thermal relaxation time of melanosomes is 0.5-1.0 microsec, the mechanism proposed is that thermal confinement of high intensity, short-pulse visible radiation generates acoustic waves by thermal expansion, leading to mechanical damage to the cells.

In vivo assessment of precursor induced prostaglandin release within the rat gastric lumen.

Gastroprotection associated with the intragastric administration of prostaglandin (PG) precursor fatty acids such as linoleic (LA), gamma-linolenic (GLA), and arachidonic acid (AA) has been reported to be mediated via their conversion to PGs. This report examines the relationship between gastroprotection and the extent/rate of PG-release in rats intragastrically administered PG biosynthetic precursors: LA, AA, dihomo-gamma-linolenic acid (DHGL) or oleic acid (OA, a nonprecursor fatty acid). At various times following intragastric administration of a fatty acid, gastric fluid was collected, extracted, chromatographed, and assayed for PGE1 or PGE2 by specific radioimmunoassay. AA and DHGL dose dependently elevated gastric PGE2 and PGE1 levels, respectively. Maximal PGE elevation, 200-400 ng/stomach, was over 400-fold above basal values, and observed within 5-10 minutes of administration. Conversely, OA and LA elicited only a minor (2-10 fold) stimulation of PGE release. In contrast to effects on PG release, all four fatty acids protected the gastric mucosa against macroscopic damage induced by ethanol. The apparent rank order of potency was AA greater than DHGL = LA greater than OA (the difference in potency between DHGL or LA and OA was not significant). Since LA and OA (a nonprecursor) only marginally elevated lumenal PGs relative to DHGL or AA, yet were equally efficacious in the gastroprotection assay, it is likely that other fatty acid-related mechanisms play an important role in protecting the stomach against ethanol-induced injury.

Inhibition of ATP levels by quinidine in a human colonic epithelial cell line.

The influence of quinidine, a putative K+ channel blocker, on Cl- secretion induced by vasoactive intestinal polypeptide (VIP) was investigated. Quinidine inhibited Cl- secretion induced by VIP in T84 cell monolayers. A similar inhibitory effect of quinidine on Cl- secretion was observed in an isolated human colon. However, in the isolated human colon, which absorbs Na+ avidly, inhibition of Na+ absorption predominated. In the T84 cell, the half-maximal inhibition by quinidine occurred at 60 microM, while 300 microM almost completely inhibited the VIP-induced Cl- secretion. Mucosal addition of quinidine was at least equally effective compared with serosal addition, suggesting that quinidine acts on the apical membrane or intracellularly. Quinidine had little or no effect on VIP-stimulated Cl- efflux in the first 15 min after its addition, suggesting that blockage of the Cl- exit pathway on the apical membrane is an unlikely mechanism. Similarly, quinidine did not inhibit the K+-recycling mechanism on the basolateral membrane in the first 15 min after its addition. The initial inhibitory action of quinidine corresponded better with its ability to decrease cellular ATP levels. Our study suggests that the depletion of cellular ATP levels may explain the initial inhibitory action of quinidine on electrolyte transport in the intestine, while the late effect is multifactorial.

Ba2+ inhibition of VIP- and A23187-stimulated Cl- secretion by T84 cell monolayers.

Addition of either 10(-8) M vasoactive intestinal polypeptide (VIP) or 10(-6) M A23187 to T84 cell monolayers, grown on permeable supports and mounted in Ussing chambers, stimulated net Cl- secretion. The effect of 10(-6) M A23187 on Cl- flux was consistently smaller than that observed with 10(-8) M VIP. In both cases the increase in net Cl- secretion accounted for the entire change in the observed short-circuit current (Isc). Since Cl- enters the cells through a basolaterally localized Na+-K+-Cl(-)-cotransport system (J. Clin. Invest. 75: 462, 1985), the fate of K+, which is cotransported with Cl- during VIP, and A23187-mediated Cl- secretion was explored. Unidirectional and net transepithelial 42K+ flux rates were negligible compared with 36Cl- flux rates (less than 4% of Cl- flux), indicating that little K+ was secreted along with Cl-. K+ recycling across the basolateral membrane was suggested from experiments in which 86Rb+ efflux (as a tracer for K+) was measured across the apical and basolateral membranes of 86Rb+ -preloaded monolayers under voltage-clamped conditions. In the absence of secretagogues, 86Rb+ efflux was 10-fold higher across the basolateral membrane than across the apical membrane. 86Rb+ efflux across the basolateral membrane was accelerated two- to threefold by addition of either VIP or A23187. In each case accelerated efflux was inhibited by 5 mM Ba2+. Cl- secretion induced by VIP or A23187 was also inhibited by serosal addition of Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of a cyclic AMP-activated Cl-transport pathway in the apical membrane of a human colonic epithelial cell line.

This report describes a Cl- transport pathway in confluent monolayer cultures of the T84 human colonic carcinoma cell line which is: 1) activated by vasoactive intestinal polypeptide, or other agents which induce or mimic cAMP; 2) independent of extracellular Na+ or K+; 3) refractory to inhibition by 0.1 mM bumetanide and 1 mM 4-acetamido-4'-isothiocyanostilbene-2,-2'-disulfonic acid; 4) competitively inhibited by NO3-, I-, SCN-, and Br-; 5) inhibited in a noncompetitive-complex manner by the putative Cl- channel-blocking agent, N-phenylanthranilic acid; and 6) localized to the apical membrane of confluent monolayers. This Cl- transport system is, therefore, distinct from the bumetanide-sensitive, basolateral membrane-localized, Na+, K+, Cl- cotransport system previously described in these cells (Dharmsathaphorn, K., Mandel, K., Masui, H., and McRoberts, J.A. (1985) J. Clin. Invest. 75, 462-471). Kinetic studies revealed that Cl- transport by this pathway fit simple Michaelis-Menten kinetics with an apparent Km for Cl- of about 6 mM. Activation by vasoactive intestinal polypeptide increased the Vmax but did not alter the apparent Km. We discuss the possibility that this transport system is a Cl- channel which is intimately involved in hormonally mediated, electrogenic Cl- secretion across T84 cell monolayers.