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Talc granulomatosis in the rat. Involvement of bone in the acute-phase response.

We investigated the dynamics of the acute-phase response (APR) and osteoblast trabecular surface in rats with subcutaneous inflammation provoked by magnesium silicate (talc). The first visible indicator of the APR was a rapid and profound hypozincemia, paralleled by a decrease in metaphyseal trabecular surfaces covered with osteoblasts in long bones. Both the intensity of serum APR and the decrease in osteoblast trabecular surface were directly proportional to the number of granulomas. Alterations in bone metabolism were specific for the inflammation, whereas mild hypozincemia and decrease in mononuclear and increase in polymorphonuclear peripheral white blood cell fractions developed in animals pair-fed with rats bearing two or four granulomas. Rats with talc granulomatosis had high serum ACTH and corticosterone levels, but neither adrenalectomy nor high doses of hydrocortisone could revert bone alterations in talc-injected animals. Glucocorticoids were necessary for the development of hypozincemia and hypercupremia seen in talc granulomatosis, as well as for normal bone metabolism. Inhibition of prostaglandin synthesis had no effect on bone alterations and serum APR in rats bearing talc-induced granulomas. We conclude that the decrease in bone formation constitutes an important aspect of the host acute-phase response in a rat model of talc granulomatosis.

Acute-Phase Reaction↗

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis.

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that they may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.

Acute-Phase Reaction↗

The effect of stool consistency on rectal and neorectal emptying.

Although stool consistency is considered to be an important component of anorectal continence, its effect on rectal emptying has never been quantitated. In 12 healthy volunteers and 12 patients after ileal pouch-anal anastomosis (IPAA) (46 +/- 5 months after the operation; mean +/- SEM), perfused anal manometry was performed; movements of the anorectal angle were quantitated scintigraphically; and rectal capacity and compliance were measured by air insufflation of an intrarectal balloon at three infusion rates. The efficiency of rectal evacuation of three consistencies (5 percent, liquid; 7.5 percent semisolid gel; 11.25 percent solid gel; w/w) of Tc99m labeled artificial stool (aluminum magnesium silicate gel) was quantitated by gamma camera imaging. No abnormalities of pelvic floor function were demonstrated in either controls or patients. The mean neorectal capacity and compliance of patients with IPAA did not differ from control, (capacity; IPAA: 215 +/- 22 ml vs. control; 245 +/- 29 ml; compliance; IPAA: 5.5 +/- 0.7 ml/cm H2O vs. control; 6.6 +/- 0.7 ml/cm H2O; P greater than 0.05). In controls, the percentage of the 7.5 percent consistency evacuated (81 +/- 5 percent, mean +/- SEM) was significantly more than the percentage evacuation of either the 5 percent consistency (67 +/- 7 percent) or the 11.25 percent consistency (77 +/- 2 percent) (P less than 0.05). After IPAA, the mean overall percent evacuation of the three stool consistencies was significantly less than control (52 +/- 6 percent after IPAA; 75 +/- 5 percent control, P less than 0.05). However, there was no significant difference in neorectal emptying between the liquid, the semisolid gel and the solid gel (56 +/- 6, 55 +/- 6, 51 +/- 9 percent, respectively, P greater than 0.1). We concluded that in healthy subjects but not in patients after IPAA, stool consistency affected the efficiency of evacuation of enteric content.

Adult↗

Acute zinc deficiency and trabecular bone loss in rats with talc granulomatosis.

Subcutaneous inflammation induced by magnesium silicate (talc) leads to the suppression of bone elongation, osteoblast insufficiency, and subsequent bone loss in rats. Since bone and immunological changes in talc granulomatosis are similar to those observed in zinc deficiency, we investigated the kinetics of zinc tissue distribution and the effects of zinc supplementation on the development of bone loss in rats with talc-induced inflammation. Decrease in serum zinc concentration was observed between 5 and 15 h in rats with talc granulomatosis. It was paralleled by the accumulation of zinc in the liver and rapid disappearance of osteoblasts from the trabecular bone surfaces. However, talc-injected rats supplemented parenterally and orally with zinc sulfate exhibited a decrease in osteoblast trabecular surface comparable to that of unsupplemented rats bearing granulomas despite normalized serum zinc concentrations. Zinc supplementation slightly increased osteoblast trabecular surface in all supplemented groups, but this effect was not significant. We conclude that zinc is the earliest indicator of the acute-phase response in rats with talc granulomatosis. Although zinc appears to be important for the normal function of bone cells, there is no causative relationship between acute zinc deficiency and decreased osteoblast number and activity in rats with talc granulomatosis.

Acute-Phase Reaction↗

Determination of biogenic halogenated methyl-phenyl ethers (halogenated anisoles) in the picogram m(-3) range in air.

Halogenated anisoles (methyl-phenyl ethers) appear to be ubiquitous organic trace compounds in the environment. An analytical method is presented for analyzing the altogether 134 congeners of chloro-, bromo- and mixed bromochloro-anisoles on an isomer-specific basis in air. High volume sampling (20 m(3) per hour) is carried out by adsorption, using a mixture of silica gel 60 and ENVI-Carb. The preseparation of the anisoles is achieved by NP-LC on Florisil (a magnesium silicate). The interference by volatile n-alkyl nitrates in the electron-capture detection can be avoided by a LC-preseparation on a carboneous phase. The isomer-specific separation and detection is performed by HRGC-ECD and HRGC-MS-SIM. A structure-specific systematic numbering of the 134 congeners of the chloro-, bromo- and bromochloro-anisoles is suggested. The retention data are given of 16 chloroanisoles, 10 bromoanisoles and 27 bromo-chloroanisoles on three stationary phases with different polarity.

Journal Article↗

A sonication extraction method for the analysis of pyrethroid, organophosphate, and organochlorine pesticides from sediment by gas chromatography with electron-capture detection.

A method was developed for the simultaneous determination of 5 pyrethroid, 1 organophosphate, and 20 organochlorine pesticides in sediment. Pesticide residues were extracted using sonication with acetone-methylene chloride (1:1 vol/vol) and the extracts were subsequently cleaned with deactivated Florisil (magnesium silicate; U.S. Silica, Berkeley Springs, West Virginia). Gas chromatography with an electroncapture detector was used for analyte determination, and two columns were used for confirmation of the analytes. Four control sediments from different sources were spiked with a pesticide mix and analyzed for method validation. The method detection limits ranged from 0.22 to 0.85 microg/kg dry sediment. Recoveries for spiked samples at four concentrations (1, 5, 20, and 400 microg/kg dry sediment) were 71.9% to 129.8% with relative standard deviations (RSDs) < 11%. Taking the matrix effect into account, 1 microg/kg was chosen for the threshold of detection, but 0.5 microg/kg of spiked control sediment still provided good recoveries and RSDs. This method was validated using field-collected sediment taken from agricultural areas of Fresno County, California.

Chemistry Techniques, Analytical↗

Pulmonary toxicity of inhaled and intravenous talc.

Talc (magnesium silicate) is a widely used, generally considered benign substance. It is principally used as an inert filler material in drug tablets or as a drying ingredient in baby powders. However, in both cases inappropriate use can lead to severe pulmonary toxicological responses. On the one hand, intravenous injection of 'solubilized', CNS active pills can produce microemboli in small pulmonary vessels. This can lead to various degrees of granuloma formation, compromised pulmonary function, or death. Overzealous application of baby powder can also produce severe pulmonary complications if the infant inspires the powder. Although the data are relatively scarce, a number of reports suggest the existence of a chronic problem in this area.

Granuloma↗

Liver pathology in fatal drug addiction.

Liver sections from 273 drug addicts submitted to medicolegal autopsy at the Institute of Forensic Medicine in Copenhagen in the period 1975-1979 were studied. In 65% of the cases non-specific portal inflammation only was found. Birefringent material--identified as the mineral talc (magnesium silicate) was observed in 38% of the cases; in these cases non-specific portal inflammation was always present. Changes compatible with acute or chronic persistent hepatitis or hepatitis sequelae were observed in 8% of the cases; cirrhosis in 3%. HBs-antigens were detected in 4%. In 22% fatty infiltration was present; in 4% as the only abnormal finding. Finally no pathological changes were found in 6%. The results were related to anamnestic information of kind and duration of drug abuse and to the cause of death. Furthermore a comparison was performed between the groups with and without birefringent material. The data suggest that the birefringent material may be of importance to the pathogenesis of the non-specific portal inflammation.

Adolescent↗

Proliferation and osteoblastic differentiation of human bone marrow-derived stromal cells on akermanite-bioactive ceramics.

In the present study, the effects of a calcium magnesium silicate bioactive ceramic (akermanite) on proliferation and osteoblastic differentiation of human bone marrow stromal cells (hBMSC) have been investigated and compared with the classical ceramic (beta-tricalcium phosphate, beta-TCP). Akermanite and beta-TCP disks were seeded with hBMSC and kept in growth medium or osteogenic medium for 10 days. Proliferation and osteoblastic differentiation were evaluated on day 1, 4, 7 and 10. The data from the Alamar Blue assay and lactic acid production assay showed that hBMSC proliferated more significantly on akermanite than on beta-TCP. The analysis of osteoblast-related genes, including alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), indicated that akermanite ceramics enhanced the expression of osteoblast-related genes, but type I collagen (COL I) showed no noticeable difference among akermanite and beta-TCP ceramics. Furthermore, this stimulatory effect was observed not only in osteogenic medium, but also in normal growth medium without osteogenic reagents such as l-ascorbic acid, glycerophosphate and dexamethasone. This result suggests that akermanite can promote osteoblastic differentiation of hBMSC in vitro even without osteogenic reagents, and may be used as a bioactive material for bone regeneration and tissue engineering applications.

Adult↗

Interfacial-chemistry mediated behavior of colloidal talc dispersions.

Interfacial chemistry and rheological behavior of talc suspensions as a function of pH, talc solid content, and type and concentration of ions have been investigated using electrokinetic measurements, rheology, settling behavior, and solution analysis. Zeta potential measurements show a strong dependence on the pH history of the talc suspension that only occurs when the surface area (solid content) of the talc is high. Particle interactions measured through dispersion yield stress measurements show a similar dependence. Talc is a magnesium silicate mineral and the dependence seen in the electrokinetic properties in this study has been attributed to Mg(II) dissolution at low pH, and has been confirmed by solution analysis. At high solid content (>20 wt%), pronounced Mg(II) ion dissolution occurs at low pH values. Formation and adsorption of electropositive Mg(II) hydrolysis products occurs at high pH (>9), and these lead to zeta potential reduction and, at high solid contents, charge reversal. Particle interactions reflect the surface chemistry behavior. Consequently, for a freshly prepared suspension at high pH, the yield stress is lower compared to after the pH has been taken to 5 and subsequently increased.

Journal Article↗

Some features associated with organosilane groups grafted by the sol-gel process onto synthetic talc-like phyllosilicate.

Two new lamellar inorganic-organic magnesium silicates have been successfully synthesized by using sol-gel based processes under mild temperature conditions. The talc-organosilicates derived using two silylating agents as the silicon source, (i) 3-chloropropyltrimethoxysilane, and (ii) from the attachment of 5-amino-1,3,4-thiadiazole-2-thiol molecule to this precursor agent, yielded PhMg-Cl and PhMg-Tz phyllosilicates. These organoclays were characterized through elemental analyses, infrared spectroscopy, X-ray diffractometry, surface area, thermogravimetry, and carbon and silicon solid state nuclear magnetic resonance spectroscopy. The results confirmed the presence of organic moieties covalently bonded to the inorganic silicon sheet network of the 2:1 class of phyllosilicates, with a density of organic molecules of 6.6+/-0.1 and 2.7+/-0.2 mmol g(-1) anchored on the inorganic layer and with interlayer distances of 1158 and 1628 pm, respectively. The nuclear magnetic resonances results in the solid state are in agreement with the sequence of carbons distributed in the pendant chains of the original silylating agents and the silicon bonded to oxygen atoms or carbon atoms of the inorganic sheets, as expected for the organically functionalized phyllosilicates. The enhanced potential of the new compound PhMg-Tz as a multi property material was explored in adsorbing cations from aqueous solution. The basic sulfur and nitrogen centers attached to the pendant chains inside the lamellar cavity can coordinate mercury, by presenting an isotherm saturated at 0.19 mmol g(-1) of this heavy metal. The functionality of this organoclay-like material expresses its potential for heavy cation removal from an ecosystem.

Journal Article↗

Measurement of effective Knudsen diffusion coefficients for powder beds used in heterogeneous uptake experiments.

The effective Knudsen diffusion coefficients for characteristic oxide powder beds used in heterogeneous uptake experiments have been measured using countercurrent diffusion and transient pressure drop techniques. Room-temperature thermal-velocity-normalized effective Knudsen diffusion coefficients are found to lie in the 0.15 to 0.35 microm range for magnesium silicate, aluminum oxide, and iron oxide powder beds. Measured values are compared with theoretical estimates and are consistent with low bed tortuosities (below 3) expected for media with open porosity above 0.5. The impact of uncertainties in effective diffusion coefficients on corrections of measured uptake coefficients is discussed. The value of careful uptake measurements in both the low and high sample mass limits is reinforced, as this allows uptake corrections independent of explicitly measured or estimated diffusion coefficient values. It is suggested that correction procedures requiring tortuosity values greater than 3 are suspect.

Journal Article↗

Seismic detection of folded, subducted lithosphere at the core-mantle boundary.

Seismic tomography has been used to infer that some descending slabs of oceanic lithosphere plunge deep into the Earth's lower mantle. The fate of these slabs has remained unresolved, but it has been postulated that their ultimate destination is the lowermost few hundred kilometres of the mantle, known as the D'' region. Relatively cold slab material may account for high seismic velocities imaged in D'' beneath areas of long-lived plate subduction, and for reflections from a seismic velocity discontinuity just above the anomalously high wave speed regions. The D'' discontinuity itself is probably the result of a phase change in relatively low-temperature magnesium silicate perovskite. Here, we present images of the D'' region beneath the Cocos plate using Kirchhoff migration of horizontally polarized shear waves, and find a 100-km vertical step occurring over less than 100 km laterally in an otherwise flat D'' shear velocity discontinuity. Folding and piling of a cold slab that has reached the core-mantle boundary, as observed in numerical and experimental models, can account for the step by a 100-km elevation of the post-perovskite phase boundary due to a 700 degrees C lateral temperature reduction in the folded slab. We detect localized low velocities at the edge of the slab material, which may result from upwellings caused by the slab laterally displacing a thin hot thermal boundary layer.

Journal Article↗

Olive oil and its main phenolic micronutrient (oleuropein) prevent inflammation-induced bone loss in the ovariectomised rat.

The present study was designed to evaluate the effect of olive oil and its main polyphenol (oleuropein) in ovariectomised rats with or without inflammation. Rats (6 months old) were ovariectomised or sham-operated as control. Ovariectomised rats were separated into three groups receiving different diets for 3 months: a control diet with 25 g peanut oil and 25 g rapeseed oil/kg (OVX), the control diet with 50 g olive oil/kg or the control diet with 0.15 g oleuropein/kg. The sham-operated group was given the same control diet as OVX. Inflammation was induced 3 weeks before the end of the experiment by subcutaneous injections of talc (magnesium silicate) in one-half of each group. The success of ovariectomy was verified at necropsy by the atrophy of uterine horns. Inflammation, oleuropein or olive oil intakes did not have any uterotrophic activity, as they had had no effect on uterus weight. The plasma concentration of alpha-1-acid glycoprotein (an indicator of inflammation) was increased in OVX rats with inflammation. With regard to bone variables, osteopenia in OVX was exacerbated by inflammation, as shown by a decrease in metaphyseal and total femoral mineral density. Both oleuropein and olive oil prevented this bone loss in OVX rats with inflammation. At necropsy, oleuropein and olive oil consumption had had no effect on plasma osteocalcin concentrations (marker of bone formation) or on urinary deoxypyridinoline excretion (marker of bone resorption). In conclusion, oleuropein and olive-oil feeding can prevent inflammation-induced osteopenia in OVX rats.

Animals↗

Calibration study on subchronic inhalation toxicity of man-made vitreous fibers in rats.

This 3-mo inhalation study investigated the biological effects of a special-purpose glass microfiber (E-glass microfiber), the stone wool fiber MMVF21, and a new high-temperature application fiber (calcium-magnesium-silicate fiber, CMS) in Wistar rats. Rats were exposed 6 h/day, 5 days/wk for 3 mo to fiber aerosol concentrations of approximately 15, 50, and 150 fibers/ml (fiber length >20 microm) for E-glass microfiber and MMVF21. For the CMS fiber only the highest exposure concentration was used. During a 3-mo postexposure period, recovery effects were studied. In the highest exposure concentration groups, gravimetric concentrations were 17.2 mg/m3 for E-glass microfiber, 37 mg/m3 for MMVF21, and 49.5 mg/m3 for the CMS fiber. After 3 mo of exposure, lung retention of fibers longer than 20 micro m per lung was 17 x 10(6) for E-glass microfiber, 5.7 x 10(6) for MMVF21, and 0.88 x 10(6) for CMS. After 3 mo of recovery the concentration of the long fiber fraction was decreased to 38.4%, 63.9%, and 3.0% compared to original lung burden for the E-glass microfiber, MMVF21, and CMS, respectively. Biological effects measured included inflammatory and proliferative potential, histopathology lesions, and the persistence of these effects over a recovery period of 3 mo. Generally, observed effects were higher for E-glass microfiber when compared to MMVF21. The following clear dose-dependent effects on E-glass microfiber and MMVF21 exposure were observed as main findings of the study: increase in lung weight, in measured biochemical parameters and polymorphonuclear leukocytes (PMN) in the bronchoalveolar lavage fluid (BALF), in cell proliferation (BrdU-response) of terminal bronchiolar epithelium, and in interstitial fibrosis. The values observed in the proliferation assay on the carcinogenic E-glass microfiber indicate that this assay has an important predictive value with regards to potential carcinogenicity. Surprisingly, for the biosoluble CMS fiber, fibrogenic potential was detected in this study. The results of the CMS exposure group indicate that effects may be dominated by the presence of nonfibrous particles and that fibrosis may not be a predictor of carcinogenic activity of fiber samples, if the fiber preparation contains a significant fraction of nonfibrous particles. In summary, this study demonstrates the importance of fiber dust contamination by granular components. For future subchronic studies a longer posttreatment observation period would be advisable.

Administration, Inhalation↗

Parametrization of perovskite structures: an ab initio study.

An overview of the pressure, temperature and chemical composition dependence of the lattice distortion in orthorhombic ABO(3) perovskite structures is presented. Within the framework of the so-called global parametrization method (GPM) [Thomas (1998). Acta Cryst. B54, 585--599] an improved description for the position of the A cation in terms of the AO(12) and BO(6) polyhedral volume ratio is proposed. The relationship is derived from an extensive ab initio study based on the density functional theory. The applicability of the improved GPM in combination with ab initio total energy calculations in the prediction of changes in the structural distortion under increasing hydrostatic pressure is investigated. Test calculations are performed for the geophysically important magnesium silicate perovskite and the results are compared with the available theoretical and experimental data.

Journal Article↗

Laue orientation imaging.

Advantage was taken of the highly focused X-ray beam (10-30 microm) and the broad white spectrum of synchrotron X-rays at the ESRF for automatic recording of Laue patterns from polycrystals and extraction of orientation information. The procedure used is similar to that applied for electron-backscattering patterns in the scanning electron microscope and provides data for local orientation mapping used in texture analysis. Laue patterns are obtained from a thin slice of material in transmission and recorded with a CCD detector. The Laue geometry is converted into a gnomonic projection in which co-zonal reflections lie on straight lines. On applying the Hough transform these lines are merged into a single point, which is recognized by the computer and assigned zone indices [uvw] by comparison with a table of interzonal angles. From the angular positions of several [uvw] the crystal orientation is calculated. The method is illustrated for the orthorhombic magnesium silicate olivine.

Journal Article↗

Symptomatic efficacy of beidellitic montmorillonite in irritable bowel syndrome: a randomized, controlled trial.

BACKGROUND: Beidellitic montmorillonite is a purified clay containing a double aluminium and magnesium silicate. AIM: To assess the efficacy and the safety of beidellitic montmorillonite (3 g, t.d. for 8 weeks) in patients with irritable bowel syndrome (IBS). METHODS: A multicentre, double-blind, placebo-controlled, randomized study with parallel groups, was performed in IBS patients selected according to ROME I criteria. Patients were included after a 1-week washout period to confirm that abdominal pain and/or discomfort was rated at least 2 on a 0-4 graded Likert scale. Patients were then randomized and stratified according to their predominant bowel habit profile into three groups. The use of rescue medication was allowed: polyethylene glycol 4000 (10-20 g/day) as a laxative agent in case of stool absence for three consecutive days, phloroglucinol (80 to a maximum of 320 mg/day) as a spasmolytic agent for no more than 8 days. The main end-point was the improvement of abdominal pain and/or discomfort by at least 1 point on the Likert scale. RESULTS: A total of 524 patients constituted the overall intent-to-treat population (ITT), 263 were assessed in the beidellitic montmorillonite group, i.e. 93 diarrhoea-predominant IBS (D-IBS), 83 constipation-predominant IBS (C-IBS), 87 alternating constipation/diarrhoea-IBS (A-IBS); 261 in the placebo group, i.e. 81 D-IBS, 92 C-IBS and 88 A-IBS. Initial analysis in the ITT population demonstrated a higher rate of success with beidellitic montmorillonite (51.7%) when compared with the placebo group (45.2%); however, the difference was not statistically significant. Improvement was significant in C-IBS both in ITT (beidellitic montmorillonite group = 49.4%, placebo group = 31.5%, P < 0.016) and per protocol populations (59.4% vs. 37.8%) (P < 0.01). The time to improvement of abdominal pain and/or discomfort (log Rank test) was also significantly in favour of beidellitic montmorillonite, (P < 0.04). The average number of stools per day was not different from baseline, either in all patients or in C-IBS patients. Spasmolytic and laxative agent intakes were not different between the two groups. Subjective evaluation by patients of treatment efficacy and visual analogue scale test of treatment efficacy by investigators were significantly better in the beidellitic montmorillonite group (P < 0.05). Tolerance of beidellitic montmorillonite was considered optimal without any significant adverse event. CONCLUSIONS: Although pain or discomfort was not significantly improved in the entire IBS population treated with beidellitic montmorillonite in comparison with placebo, this study demonstrates that beidellitic montmorillonite is efficient for C-IBS patients (P < 0.016). This effect of beidellitic montmorillonite on pain cannot be explained by changes in bowel habits. The efficacy of this well-tolerated therapy warrants further confirmatory therapeutic trials in C-IBS patients.

Abdominal Pain↗