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PubMed2004

Ethanol recovery from corn fiber hydrolysate fermentations by pervaporation.

Corn fiber, a byproduct of corn wet milling, is an attractive feedstock for biomass ethanol production. Corn fiber was hydrolyzed by dilute sulfuric acid and neutralized by one of two methods: conventional lime treatment or neutralization by strongly basic anion exchange. The anion exchange neutralized (AEN) hydrolysate contained substantially lower levels of the inhibiting compounds furfural, 5-hydroxymethylfurfural, and acetic acid compared to the lime neutralized hydrolysate. In batch fermentations the ethanol yields and final ethanol concentration of the two hydrolysates were similar at 0.32-0.43 g/g and 29-44 g/l, respectively. Sugar consumption in the AEN fermentations was superior. Coupling of a membrane pervaporation unit to a fed-batch fermentation of AEN hydrolysate maintained the ethanol concentration below 25 g/l with complete sugar utilization for approximately 5 days. A concentrated ethanol stream of 17 wt.% ethanol was produced by the pervaporation unit.

Calcium Compounds↗

PubMed1999

Reconstruction of bone using calcium phosphate bone cements: a critical review.

The calcium phosphate cements (CPCs) are rapidly emerging as a new technology in craniofacial surgery and will soon impact many areas of orthopedic and maxillofacial reconstructive surgery as well. These materials are, in many ways, substantially different from the previously marketed dense, crystalline, hydroxyapatite (HA) ceramic materials of the 1980s. The CPCs are blends of amorphous and crystalline calcium phosphate compounds and set to produce HA. These materials 1) have x-ray diffraction spectra similar to the mineral phase of bone, 2) set endothermically at body temperature, 3) are capable of being injected into fractures or bone defects, 4) have compressive strengths equal to or greater than bone, 5) form chemical bonds to the host bone, and 6) may exhibit osteoconductive properties. This review provides an overall commentary on the different types of CPCs, emphasizing those materials currently on the market or soon to emerge in the marketplace.

Animals↗

PubMed1994

Closed-circuit anesthesia with sevoflurane in humans. Effects on renal and hepatic function and concentrations of breakdown products with soda lime in the circuit.

BACKGROUND: Sevoflurane reacts with CO2 absorbents, resulting in the generation of breakdown products. The concentrations of sevoflurane breakdown products in a low-flow system within 5 h have been reported, but concentrations in low-flow anesthesia exceeding 5 h or in closed-circuit anesthesia have not. In this study, the breakdown products of sevoflurane in closed-circuit anesthesia exceeding 5 h were examined. METHODS: Closed-circuit sevoflurane anesthesia was administered to ten patients. Laboratory tests of hepatic and renal function were performed before and after anesthesia. Gas samples were obtained from the inspiratory limb of the anesthesia circuit, and breakdown products were analyzed by gas chromatography. The temperature of the soda lime was measured during anesthesia. RESULTS: Among the breakdown products of sevoflurane, two products, CF2 = C(CF3)-O-CH2F (compound A) and CH3OCF2CH(CF3)OCH2F (compound B), were detected. Compound A was detected in all measurements, and its concentration reached 19.5 +/- 5.4 ppm 1 h after anesthesia and decreased after 5 h. The highest concentration observed for compound A was 30.0 ppm. Compound B was detected in seven of the ten patients; its concentration was 0.17 +/- 0.37 ppm after 0.5 h of anesthesia and remained at similar concentrations thereafter. The highest mean temperature of the soda lime was 46.0 +/- 1.7 degrees C. Postanesthetic clinical laboratory tests showed no abnormalities in hepatic or renal function associated with anesthesia. CONCLUSIONS: Two breakdown products were detected in the patients anesthetized with sevoflurane using a closed-circuit technique. No abnormalities were observed during anesthesia, and no evidence of hepatic or renal dysfunction was noted in postoperative laboratory tests.

Adult↗

PubMed2004

2-APB inhibits volume-regulated anion channels independently from intracellular calcium signaling modulation.

It has previously been suggested that volume-regulated anion channels (VRACs) and store-operated channels (SOCs) interact with each other according to their expected colocalization in the plasma membrane of LNCaP cells. In order to study interactions between these two channels, we used 2-aminoethoxydiphenyl borate (2-APB) as a regular SOC inhibitor. Surprisingly 2-APB reduced VRAC activity in a dose-dependent manner (IC(50)=122.8 microM), but not 2,2-diphenyltetrahydrofuran (a structural analog of 2-APB). This effect was also present in keratinocytes. We conclude that 2-APB is an inhibitor of the VRAC family, and is also a potent tool to study the SOC-VRAC interaction in LNCaP cells.

Boron Compounds↗

PubMed2005

Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.

Glucagon, secreted from pancreatic alpha-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10(-9) M, suppressed low-glucose-induced intracellular calcium ion ([Ca2+]i) oscillations in alpha-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified alpha-cells indicate that 17beta-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the G alpha i- and G alpha o-protein inhibitor pertussis toxin, by the guanylate cyclase-specific inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3',5'-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic alpha-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.

Animals↗

PubMed1988

Influence of steroid ovarian hormones and calcium on drug-induced contractions of the isolated immature uterine muscle of mouse. An analysis of histamine receptor system.

1. Through the relative responsiveness (rho) determined for histamine (Hist), oxytocin (Oxy) and acetylcholine (Ach) in prepuberal untreated, estrogen, and estrogen plus progesterone dominated uteri of mouse, it was possible to measure the capability of each receptor system, which mediates responses induced by these agonists. 2. In all cases values of rho for Hist were lower than those for Ach and Oxy independently of hormone treatment and calcium concentrations used (0.2 or 2.0 mM), suggesting that the ability of histamine receptor system to promote contraction of mouse uterus is less effective than those mediating responses induced by other agonists studied here. 3. A comparison between the present data with those previously reported for dog uterus showed marked differences in the abilities of the histamine receptor system to mediate histaminergic stimulus in myometrium of two different animal species. 4. The author suggests that genetic characteristics controlling the development of a given receptor system can play a role regulating physio-pharmacological actions of drugs in the myometrium.

Acetylcholine↗

PubMed1999

Subcellular compartmentalization of activation and desensitization of responses mediated by NK2 neurokinin receptors.

A functional fluorescent neurokinin NK2 receptor was constructed by joining enhanced green fluorescent protein to the amino-terminal end of the rat NK2 receptor and was expressed in human embryonic kidney cells. On cell suspensions, the binding of fluorescent Bodipy-labeled neurokinin A results in a saturatable and reversible decrease of NK2 receptor fluorescence via fluorescence resonance energy transfer. This can be quantified for nM to microM agonist concentrations and monitored in parallel with intracellular calcium responses. On single cells, receptor site occupancy and local agonist concentration can be determined in real time from the decrease in receptor fluorescence. Simultaneous measurement of intracellular calcium responses and agonist binding reveals that partial receptor site occupancy is sufficient to desensitize cellular response to a second agonist application to the same membrane area. Subsequent stimulation of a distal membrane area leads to a second response to agonist, provided that it had not been exposed to agonist during the first application. Together with persistent translocation of fluorescent protein kinase C to the membrane area exposed to agonist, the present data support that not only homologous desensitization but also heterologous desensitization of NK2 receptors is compartmentalized to discrete membrane domains.

Animals↗

PubMed2004

Integrated, long term, sustainable, cost effective biosolids management at a large Canadian wastewater treatment facility.

The Greater Moncton Sewerage Commission's 115,000 m3/d advanced, chemically assisted primary wastewater treatment facility located in New Brunswick, Canada, has developed an integrated, long term, sustainable, cost effective programme for the management and beneficial utilization of biosolids from lime stabilized raw sludge. The paper overviews biosolids production, lime stabilization, conveyance, and odour control followed by an indepth discussion of the wastewater sludge as a resource programme, namely: composting, mine site reclamation, landfill cover, land application for agricultural use, tree farming, sod farm base as a soil enrichment, topsoil manufacturing. The paper also addresses the issues of metals, pathogens, organic compounds, the quality control program along with the regulatory requirements. Biosolids capital and operating costs are presented. Research results on removal of metals from primary sludge using a unique biological process known as BIOSOL as developed by the University of Toronto, Canada to remove metals and destroy pathogens are presented. The paper also discusses an ongoing cooperative research project with the Université de Moncton where various mixtures of plant biosolids are composted with low quality soil. Integration, approach to sustainability and "cumulative effects" as part of the overall biosolids management strategy are also discussed.

Calcium Compounds↗

PubMed1994

Dual effects of angiotensin II on calcium currents in neonatal rat nodose neurons.

Angiotensin II (AII) reversibly modulates calcium current in isolated neonatal rat nodose ganglion cells by two different pathways. A maximum inhibitory effect of 43 +/- 6% (n = 25) of the peak calcium current at -10 mV was observed at 10 nM AII. The IC50 of the inhibitory response was 100 pM. Losartan, a specific antagonist for the AT1 type of AII receptor, abolished the AII-induced inhibition, as did preincubation with pertussis toxin (PTX). When omega-conotoxin GVIA (CTX) was added to the bath solution, AII produced no inhibition of the remaining calcium current, indicating that the AII inhibition was mediated through CTX-sensitive calcium channels. Reversible facilitation of calcium current was seen more rarely. The AII-induced facilitation was unaffected by losartan and PTX, indicating that the effect is mediated by a non-AT1 receptor and does not depend upon a PTX-sensitive G-protein. The facilitation is present when the CTX-sensitive current has been blocked and involves activation of a reserve pool of dihydropyridine (DHP)-sensitive channels. In general, a particular neuron exhibited either inhibition or facilitation. However, in some neurons both inhibition and facilitation could be demonstrated in the presence of the appropriate blocking agents.

Angiotensin II↗

PubMed1997

[Causes for the reaction between dry soda lime and halogenated inhalation anesthetics].

All volatile anesthetics undergo chemical breakdown to multiple, partly identified degradation products in the presence of dry soda lime. These chemical reactions are highly exothermic, ranging from 100 degrees C for halothane to 120 degrees C for sevoflurane. The increase in temperature correlates with the moisture content of the soda lime, being maximal below 5%. Sevoflurane and isoflurane were exposed to dry soda lime in a circle system. The anaesthetic gas was condensed in a series of cold temperature traps and the degradation products of the volatile anesthetics were analysed using GC/MS. Surprisingly, neither sevoflurane nor its degradation products could be measured in the gas-flow emerging from the soda lime during the first 15-20 min of exposure. After 20 minutes, larger quantities of methanol, compounds C and D as well as compounds A and B were detected. After 40-60 min of exposure, sevoflurane's degradation markedly decreased and unaltered sevoflurane emerged from the soda lime canister. Additionally, using isoflurane in the same experimental set-up resulted in various degradation products due to its reaction with dry soda lime. Obviously, all volatile anesthetics are prone to such a reaction. In conclusion, sevoflurane and isoflurane react with dry soda lime. These reactions are caused by the presence of two components of soda lime, sodium hydroxide and potassium hydroxide. A modification of soda lime to prevent its reaction with volatile anaesthetics is discussed.

Anesthetics, Inhalation↗

PubMed1993

Substance P-evoked calcium mobilization and ionic current activation in the human astrocytoma cell line U 373 MG: pharmacological characterization.

In the human astrocytoma cell line U 373 MG, application of substance P (SP) leads to a transient increase in cytosolic calcium concentration and to a biphasic current response in voltage-clamped cells. Using these two functional assays we have characterized pharmacologically the SP response in U 373 MG cells. SP and [L-Pro9]SP displayed high potencies in both assays with EC50 values of 2.5 x 10(-9) M and 1 x 10(-9) M on calcium responses and 1 x 10(-9) M and 5 x 10(-9) M on ion current responses, respectively. The high potency of SP and [L-Pro9]SP as well as the low potency of [Lys5,MeLeu9,N-Leu10]neurokinin A(4-10) and the inactivity of senktide demonstrate the NK1-type pharmacology of these responses. Furthermore, the NK1 antagonists (+/-)-CP 96,345, its chloro analogue, (+/-)-cis-3-(2-chlorobenzylamino)-2-benzhydrylquinuclidine, and RP 67580 were potent antagonists of both SP responses. For the calcium mobilization induced by SP (10(-7) M), the IC50 values for the three antagonists were 4 x 10(-10) M, 4 x 10(-9) M, and 9 x 10(-9) M, respectively, whereas on the current response evoked by SP (10(-8) M), the IC50 values were 8 x 10(-9) M, 2.4 x 10(-8) M, and 1.2 x 10(-7) M, respectively. Despite differences in the absolute IC50 values obtained with both techniques, the relative potencies of the three antagonists correlate fairly well.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma↗

PubMed1988

Histologic localization of lipid in the articular tissues in calcium pyrophosphate dihydrate crystal deposition disease.

We demonstrated the histologic localization of lipid in the articular cartilage, meniscus, and synovium in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, by staining with Sudan III. Almost all the sites of tophus-like deposits of CPPD crystals and the degenerated matrix containing low concentrations of scattered CPPD crystals stained strongly with Sudan III. Transmission electron microscopy demonstrated round or oval lipid droplets in more than half of the chondrocytes around the crystals in each of these tissues. Small lipid droplets were also seen on or around the crystals. These findings suggest that lipids are abundant at the site of CPPD crystal deposition and may be involved in CPPD crystal formation.

Aged↗

PubMed2006

Meta-analysis of biochemical and patient-level effects of calcimimetic therapy.

BACKGROUND: Many randomized trials have now evaluated the effects of calcimimetics in patients with chronic kidney disease and secondary hyperparathyroidism (SHPT) on standard therapy with vitamin D and/or phosphate binders. We conducted a meta-analysis to evaluate outcomes of therapy with these novel agents. METHODS: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and conference proceedings were searched for randomized controlled trials evaluating any calcimimetic against placebo or another agent in predialysis or dialysis patients with chronic kidney disease. Data were extracted for all relevant patient-centered and surrogate outcomes. Analysis was by means of a random-effects model, and results are expressed as relative risk or weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: Eight trials (1,429 patients) were identified that compared a calcimimetic agent plus standard therapy with placebo plus standard therapy. End-of-treatment values for parathyroid hormone (4 trials; 1,278 patients; WMD, -290.49 pg/mL; 95% CI, -359.91 to -221.07), serum calcium (3 trials; 1,201 patients; WMD, -0.85 mg/dL; 95% CI, -1.14 to -0.56), serum phosphorus (3 trials; 1,195 patients; WMD, -0.29 mg/dL; 95% CI, -0.50 to -0.08), and calcium x phosphorus product (3 trials; 1,194 patients; WMD, -7.90 mg2/dL2; 95% CI, -10.25 to -5.54) were significantly lower with calcimimetic therapy compared with placebo. No significant effects on patient-based end points were shown. CONCLUSION: Calcimimetic treatment of patients with SHPT leads to significant improvements in biochemical parameters that observational studies have associated with increased mortality, cardiovascular risk, and osteitis fibrosa, but patient-based benefits have not yet been shown. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until additional randomized trials become available.

Aniline Compounds↗

PubMed1987

In vitro infection and disinfection of dentinal tubules.

An in vitro model for dentinal tubule infection of root canals was developed. Cylindrical dentin specimens, 4 mm high with a diameter of 6 mm and a canal 2.3 mm wide, were prepared from freshly extracted bovine incisors. The cementum was removed from all dentin blocks. The tubules were opened by four-minute treatments with 17% EDTA and 5.25% NaOCl before being infected with Enterococcus faecalis ATCC 29212 in yeast extract-glucose broth. Bacteria rapidly invaded the tubules. After three weeks of incubation, a heavy infection was found 400 micron from the canal lumen, and the front of the infection reached 1000 micron in some blocks. Camphorated paramonochlorophenol (CMCP) and a calcium hydroxide compound, Calasept, were tested for their disinfecting efficacy toward E. faecalis-infected dentin. Liquid CMCP rapidly and completely disinfected the dentinal tubules, whereas CMCP in gaseous form disinfected tubules less rapidly. Calasept failed to eliminate, even superficially, E. faecalis in the tubules. The method used in bacteriological sampling allowed for sequential removal of 100-micron-thick zones of dentin from the central canal toward the periphery. Control specimens were uniformly infected and yielded growth in bur samples up to some 500 microns from the surface. The model proved quite sensitive and seems suitable for in vitro testing of root canal medicaments.

Animals↗

PubMed2002

The synthesis and structure-activity relationships of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones: a new class of calcium-dependent, large conductance, potassium (maxi-K) channel opener targeted for urge urinary incontinence.

A series of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones was prepared and shown by electrophysiological analysis to activate a cloned maxi-K channel mSlo (or hSlo) expressed in Xenopus laevis oocytes. The effects of these structurally novel maxi-K channel openers on bladder contractile function were studied in vitro using isolated rat bladder strips pre-contracted with carbachol. Several 1,3-diaryl 1,2,4-(4H)-triazol-5-one derivatives were found to be potent smooth muscle relaxants but this activity did not completely correlate with maxi-K channel opening.

Animals↗

PubMed2001

GABA(B) receptors in anterior pituitary cells. Mechanism of action coupled to endocrine effects.

The activation of pituitary GABA(B) receptors by the specific agonist baclofen inhibits pituitary hormone secretion in vitro. Here we studied the mechanism of action of GABA(B) receptors in rat adenohypophysis. Anterior pituitary cells were obtained by trypsinization and were either plated for hormonal studies and cAMP determination or incubated in FURA 2AM for calcium measurements. Baclofen (BACL: 1 x 10(-5) M) significantly inhibited basal and thyrotropic releasing hormone (TRH)-stimulated (1 x 10(-7) M) PRL secretion in anterior pituitary cells from proestrous rats. In the presence of pertussis toxin (PTX: 150 ng/ml, 20 h), which leads to the uncoupling of the G(i/o)-protein from the receptor, both effects of BACL were abolished while the effect of dopamine (DA: 1 x 10(-8) M), used as an inhibitory control, was reduced from 70 to 25%. PTX also reversed BACL-induced inhibition of gonadotropin-releasing hormone (GnRH)-elicited luteinizing hormone (LH) secretion in anterior pituitary cells from 15-day-old female rats. In addition, though working in a pituitary mixed cell population, in which only some cell types possess GABA(B) receptors, BACL (1 x 10(-5) M) attenuated the forskolin-induced (0.5 microM) increase in cAMP. This effect was prevented by co-incubation with the antagonist 2 hydroxysaclofen and by preincubation with PTX. BACL (5 x 10(-5) M) and DA (5 x 10(-7) M) inhibited basal intracellular calcium concentrations ([Ca(2+)](i)) in pituitary cells and the effect of the latter was significantly stronger. The effect of BACL on [Ca(2+)](i) was abolished after preincubation with PTX. In the presence of the potassium channel blocking agents barium (200 microM and 1 mM) and tetraethylammonium (10 mM), BACL was still able to inhibit [Ca(2+)](i). Blockade of voltage-sensitive calcium channels (VSCC) with either verapamil (5 x 10(-6) M) or nifedipine (1 x 10(-6) M) completely abolished the effect of BACL on [Ca(2+)](i). In the presence of 12.5 mM potassium concentration baclofen significantly inhibited [Ca(2+)](i). In conclusion, our results describe the negative coupling of adenohypophyseal GABA(B) receptors to VSCC through PTX-sensitive G-proteins. These characteristics suggest a resemblance of these receptors to the typical presynaptic GABA(B) sites described in the central nervous system.

Animals↗

PubMed1986

The effect of nass use and smoking on the risk of oral leukoplakia.

The results of a survey of a population with a high incidence of oral cancer are presented in this paper. A remarkably high proportion (41%) of the men surveyed used nass, which is a mixture of tobacco, lime, ash, and cotton oil. The prevalence of oral leukoplakia, lesions thought to be a precursor of oral cancer, was high in persons who used nass (12%) and who smoked cigarettes (15%), and highest among those men who both used nass and smoked (21%). It has been shown that nass use increases the frequency of micronucleated cells in the exfoliated sublingual cells. The clastogenic and genotoxic effect of nass revealed in the study could be attributed to the presence of tobacco-specific N-nitroso compounds. However, the results of chemical analysis, which has shown that nass contains relatively low levels of these compounds, suggest that the relatively strong genotoxic activity of nass could primarily be associated with other chemicals, possibly oxidized phenolics. Despite the uncertainty as to which of the chemicals contained in nass are involved in the etiology of oral cancer and what exactly are the mechanisms of nass-induced carcinogenesis, the results of this study suggest that in populations where nass is widely used, oral leukoplakia and, most probably, oral cancer are conditions that could be prevented by the elimination of nass use and cigarette smoking.

Aged↗

PubMed2001

2-Aminoethoxydiphenyl borate directly inhibits store-operated calcium entry channels in human platelets.

In this study, we examined 2-aminoethoxydiphenyl borate (2APB) as an inhibitor of Ca(2+) influx in human platelets. 2APB was found to inhibit thrombin-mediated intracellular Ca(2+) mobilization rapidly in platelets incubated in the absence of extracellular Ca(2+). This result supports an intracellular action of 2APB on inositol 1,4,5-trisphosphate (IP(3))-receptor Ca(2+) channels. 2APB was without effect on the ability of thapsigargin to mobilize intracellular Ca(2+). This result suggests that the efflux of Ca(2+) from the endoplasmic reticulum mediated by thapsigargin is not via IP(3) Ca(2+) channels. However, 2APB was able to prevent the entry of Ca(2+) and Sr(2+) through thapsigargin-activated, store-operated Ca(2+) channels (SOCC). This result supports a direct inhibitory effect of 2APB on SOCC. 2APB was also able to block the entry of Sr(2+), Ba(2+), and Mn(2+) entry into unstimulated platelets, which suggests that 2APB was inhibiting the Ca(2+) influx channels directly. The capacity of 2APB to prevent Ca(2+) influx and Sr(2+) influx was rapid because it occurred immediately upon addition to the platelets. The inhibition of Ca(2+) and Sr(2+) influx by 2APB was similar to that seen with the cell-impermeable nonselective Ca(2+)-channel blocker La(3+) or the Ca(2+) chelator EGTA. Diphenylboronic anhydride and 2,2-diphenyltetrahydrofuran, two compounds that are structurally similar to 2APB, also inhibited Ca(2+) influx. It was concluded that 2APB was a rapid and effective direct inhibitor of SOCC in human platelets; as such, it cannot be used to support the involvement of IP(3) receptors in the activation of SOCC.

Barium↗