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PubMed1989

Effects of enteric neural stimulation on chloride transport in human left colon in vitro.

Nonpathological segments of muscle-stripped left colon from patients undergoing surgery for carcinoma, diverticulitis, or other causes were set up in flux chambers in order to determine the influence of intrinsic neurons on ion transport. In the basal state, both sodium and chloride were actively absorbed, and there was no significant residual ion flux. Electrical field stimulation of the intrinsic mucosal innervation evoked an increase in short-circuit current that was dependent on stimulus frequency and strength. The response was mimicked by scorpion venom, which is known to depolarize neurons, and was nearly abolished by tetrodotoxin, which prevents neurotransmitter release. Atropine reduced, but did not abolish, the response to neural stimulation. Carbachol, aminophylline, and theophylline significantly increased short-circuit current above basal levels. Electrical field stimulation evoked an increase in short-circuit current that could be accounted for by a decrease in net chloride absorption without any significant effect on sodium absorption or residual ion flux. These results suggest that ion transport in the human left colon is regulated by intrinsic submucosal cholinergic neurons as well as other neuronal types, and activation of these nerves could provide the basis for certain diarrheal disorders.

Aged↗
PubMed1972

The depolarizing action of acetylcholine or carbachol in intestinal smooth muscle.

1. The membrane potential of the longitudinal muscle of the guinea-pig ileum was recorded intracellularly with glass micro-electrodes.2. Acetylcholine or carbachol depolarized the membrane. The depolarization produced by 1.4 x 10(-6)M carbachol was only 3.6 mV less than that produced by 5.5 x 10(-5)M.3. When the change in size of the electrotonic potential was used to estimate the increase in membrane conductance produced by different concentrations of carbachol, the increase in conductance was about tenfold at 1.4 x 10(-6)M and about 100-fold at 5.5 x 10(-5)M. There was a significant (P < 0.025) regression of the change in size of the electrotonic potential on the logarithm of the concentration of carbachol over this dose range. This and other observations suggest that it is not the availability of receptors which curtails the depolarization produced by concentrations of carbachol in excess of 1.4 x 10(-6)M.4. Reducing the external sodium concentration shifted the level of peak depolarization produced by carbachol negatively, and increasing the external sodium concentration shifted it positively.5. Reducing the external chloride from 134 to 13 mM had no significant effect on the level of peak depolarization produced by carbachol. Reducing the external chloride to 7 mM shifted the level of peak depolarization 3.1 mV in a positive direction.6. Increasing the external potassium concentration had little effect on the level of peak depolarization produced by carbachol, and decreasing the external potassium shifted the level of peak depolarization positively.7. It was possible to account for the observed relationship between membrane potential and membrane conductance if the assumption was made that carbachol opens additional ion channels in the membrane which have an equilibrium potential of about -9 mV. It is suggested therefore that the depolarizing action of carbachol on this smooth muscle is limited by its equilibrium potential, and that the equilibrium potential and the membrane potential in the presence of large concentrations of carbachol (e.g. 5.5 x 10(-5)M) are very close. Hence changes in the level of peak depolarization produced by varying the ionic composition of the external solution probably reflect changes in the equilibrium potential fairly closely.8. A simple model in which carbachol opens conductances to sodium, potassium and chloride ions and in which these conductances are independent of external ion concentrations (and voltage) could account for the effects on the equilibrium potential of varying [Na(+)](0) and [Cl(-)](0) but not [K(+)](0).9. It is suggested that carbachol increases the conductance to sodium, potassium and possibly other cations, and that, if it increases chloride conductance, then the increase produced is small relative to the increase in conductance to cations.

Acetylcholine↗
PubMed1981

Transsynovial distribution of ibuprofen in arthritic patients.

Free and total ibuprofen levels in serum and synovial fluid (SF) were determined in one male and 14 female arthritic patients (mean age 56 yr, range 19 to 77) after 400 mg three times daily for 2 days. Free drug was separated by ultrafiltration and assayed by a new highly sensitive and precise gas chromatographic-mass spectrometric technique. Total protein and albumin were assayed by automatic analyzer, and the routine serum biochemical profile obtained. Serum and SF nonesterified fatty acids (NEFAs) were methylated and assayed by gas chromatography. While both total protein and albumin levels were lower (P less than 0.01) in SF, NEFA levels did not differ (p greater than 0.05). Ibuprofen readily partitions into and binds strongly to joint fluid, the total level being about half that in serum. The ratio of total ibuprofen in SF to that in serum (x = 0.41 +/- 0.17) correlated with the albumin concentration ratio (r = 0.886) indicating that albumin binding is an important determinant of ibuprofen transsynovial distribution. A low total ibuprofen SF/serum ratio, apparent for three patients on concomitant aspirin therapy, is consistent with reports of an ibuprofen-salicylate interaction. Free ibuprofen in SF (0.192 +/- 0.086 microgram ml-1) did not differ (p greater than 0.05) from serum free levels (x = 0.251 +/- 0.139 microgram ml-1), supporting the concept of the synovial cavity as a compartment readily accessible to unbound drug species. Multiple regression analyses revealed relative independence of free concentration on total levels, and the small positive and negative influences of NEFAs and albumin concentrations. Bilirubin, uric acid, cholesterol, triglycerides, and chloride ion did not correlate with serum free concentration.

Adult↗
PubMed2005

Highly-functionalised difluorinated cyclohexane polyols via the Diels-Alder reaction: regiochemical control via the phenylsulfonyl group.

A difluorinated dienophile underwent cycloaddition reactions with a range of furans to afford cycloadducts which could be processed regio- and stereoselectively via episulfonium ions, generated by the reaction between their alkenyl groups and phenylsulfenyl chloride. The oxabicyclic products were oxidised to the phenylsulfonyl level and ring opened via E1(C)B or reductive desulfonative pathways to afford, ultimately, difluorinated cyclohexene or cyclohexane polyols.

Journal Article↗
PubMed2002

Myeloperoxidase-mediated protein oxidation: its possible biological functions.

Oxidation of proteins occurs both as a side-effect of aerobic energy metabolism and as an effect of specific metabolism of phagocytic polymorphonuclear granulocytes producing O2- and H2O2. In contrast to other cells, which control their H2O2 level by degrading it to O2 and H2O, polymorphonuclear neutrophilic leukocytes (PMN) use H2O2 as a substrate for oxidizing chloride ions to HOCl which rapidly react with all neighboring thiol, disulfide and amino residues. Chloramines, which are the most abundant HOCl reaction products, react with proteins, modifying only certain exposed methionine and cysteine residues. This may account for selective inactivation of a number of enzymes, carrier proteins and peptide mediators, including the alpha1-proteinase inhibitor, alpha2-macroglobulin and plasminogen activator inhibitor. Inactivaton of plasma proteinase inhibitors protects PMN elastase, collagenase, cathepsin G and other serine proteases in the inflammatory foci. This promotes proteolytic degradation of damaged tissue, removal of bacterial debris and wound healing, as well as tissue remodeling related to the inflammatory processes. Oxidative control of protease-anti-protease balance affects the development of the inflammatory processes. Moreover, inactivation of plasma proteinase inhibitors facilitates primary antigen processing, upregulates lymphocyte proliferative response and activates the local immune response. Oxidation produces a specific protein tagging which attracts and stimulates immune active cells. Therefore, humoral response against oxidatively modified proteins occurs more effectively than that of the native proteins. The effect is dose-dependent with respect to the amount of oxidant employed. Glycol aldehyde, which is the serine chloramine spontaneous decay product, in mice immunized with glycol aldehyde-modified egg-white albumin, yields specific IgG production manifold higher than that in mice immunized with native albumin. Immunopotentiation is produced by proliferation expansion of the same immunocompetent clones. Oxidative tagging of proteins may also affect the autoimmune-type reaction. Thus, a growing body of data suggest that the specific role of protein oxidation by activated PMN is oxidative protein tagging facilitating further development of the immune reaction.

Animals↗
PubMed1998

Bioaccumulation of mercury in pelagic freshwater food webs.

Current paradigms regarding the bioaccumulation of mercury are rooted in observations that monomethyl mercury (meHg) biomagnifies along pelagic food chains. However, mechanisms regulating the formation of meHg, its initial incorporation at the base of pelagic food chains, and its subsequent trophic transfer remain controversial. Here we use field data from 15 northern Wisconsin lakes, equilibrium aqueous speciation modeling, and statistical modeling to revisit several hypotheses about the uptake, distribution, and fate of inorganic Hg (HgII) and meHg in aquatic biota. Our field data comprise determinations of total Hg (HgT) and meHg in surface waters, sediments, microseston, zooplankton, and small fish in each of the study lakes. For these lake waters, strong positive correlations between DOC and aqueous concentrations of mercury along with negative correlations between DOC and the seston-water partitioning of mercury indicate that organic ligands bind HgII and meHg strongly enough to dominate their apparent aqueous speciation. In the microseston, zooplankton and fish, meHg concentrations and bioaccumulation factors (BAFs) increased with increasing trophic level while biotic concentrations of HgII decreased--indicating that meHg was indeed the biomagnified species of mercury. For all trophic levels, meHg concentrations varied positively with the calculated aqueous concentration of meHg+ (free ion), especially when coupled with pH, or meHgOH (hydroxide) species but not with meHgCl0, the neutral chloride complex. These findings suggest that: (1) the passive uptake of meHg does not control bioaccumulation at the base of aquatic food webs in nature (i.e. phyto- and bacterioplankton); (2) correlation with pH and DOC largely reflect the supply and bioavailability of meHg to lower trophic levels; and (3) meHg concentrations at higher trophic levels reflect uptake at low trophic levels and other factors, such as diet and growth. Low concentrations of meHg in surficial sediments indicate that the fates of biotic HgII and meHg are different. Most biotic meHg is demethylated rather than buried in lake sediments.

Animals↗
PubMed1997

Early interactions of hepatitis A virus with cultured cells: viral elution and the effect of pH and calcium ions.

Hepatitis A virus (HAV) is less well-characterized than other picornaviruses due to its slow and inefficient replication. In order to gain a greater understanding of HAV-receptor interactions we have used the recovery of cell-bound, infectious virus particles to measure the effects of temperature, pH and divalent cations on the binding of HAV to susceptible cells. Viral attachment to cultured cells proceeded at similar rates between 4 degrees C and 37 degrees C, with a slight increase in the total amount of virus attached at 4 degrees C. In contrast, both acidic pH and the presence of calcium ions independently caused greater than 20-fold increases in the cell attachment of infectious HAV diluted in buffered sodium chloride solutions, to a level approaching that of binding in culture medium, whereas magnesium led to a slight enhancement and zinc had no effect. The increased levels of binding observed with low temperature, low pH and the presence of calcium coincided with reduced rates of virus elution under similar conditions, suggesting that these conditions lead to a strengthening of the virus-receptor binding. The addition of calcium to highly purified HAV in buffered sodium chloride reduced the stability of virus during protracted incubation at 37 degrees C, as measured by immunoblotting of capsid proteins. The results suggest that the major effect of calcium in promoting HAV-receptor interactions is through a direct effect on the conformation of the viral capsid.

Animals↗
PubMed1980

The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain.

myo-Inositol-1-phosphatase has been partially purified from bovine brain. The enzyme has a molecular weight of about 58,000. Both L-myo-inositol 1-phosphate and D-myo-inositol 1-phosphate are hydrolyzed by the enzyme as well as (-)-chiro-inositol 3-phosphate and 2'-AMP. Triphosphoinositide is not a substrate. The phosphatase is completely dependent on Mg2+, which has a Km of 1 mM. Calcium and manganese ions are competitive inhibitors of Mg2+ binding with Ki values of 18 microM and 2 microM, respectively. Lithium chloride inhibits the hydrolysis of both L- and D-myo-inositol 1-phosphate to the extent of 50% at a concentration of 0.8 mM. The phosphatase from testis is similarly inhibited by lithium. Lithium ion is a noncompetitive inhibitor of Mg2+ binding and an uncompetitive inhibitor of myo-inositol 1-phosphate binding. Because lithium chloride administration elicits both an increase in the levels of myo-inositol 1-phosphate and a decrease in the levels of myo-inositol in rat brain (Allison, 1978), and because these actions are blocked by anticholinergic agents, we examined the effects of cholinergic agonists and antagonists on the enzyme and found none. The possibility that the inhibition of this enzyme by lithium ion is related to the pharmacological actions of lithium is discussed.

Animals↗
PubMed1975

Alterations in the metabolism of fats and phosphatides in rat liver induced by halide ions.

The effects of halide ions on several pathways of lipid metabolism have been investigated in rat liver slices. Through the use of carboxyl-14-C-labeled acetate and palmitate and U-14-C-labeled glycine, striking differences were found when the effects of the four halide ions on the labeling of the lipids were compared. Both fluoride and iodide dpressed [14-C]acetate incorporation into phosphatide and triglyceride fractions. The effects of the halide ions on the labeling from the effects observed when [14-C]acetate was the precursor of the lipid molecule. In contrast with the phospholipid fractions, the level of radioactivity from [14-C]palmitate incorporated into the triglycerides was lower with fluoride than with chloride. The incorporation of [14-C]glycine into the phospholipids was also greatly depressed by fluoride. The effects of halide ions on acetoacetate formation, on 14-CO2 production and on the acetylcoenzyme A synthetase of rat liver were also investigated. Decreasing [I-14-C]-acetate conversion to acetoacetate iodide had an opposite effect on 14-CO2 production from the same labeled substrate. The effects of the four halide ions and the differences observed with the three labeled substrates on several pathways related to lipid metabolism are discussed.

Acetates↗
PubMed2005

Chemical characterization of extractable water soluble matter associated with PM10 from Mexico City during 2000.

We report the chemical composition of PM10-associated water-soluble species in Mexico City during the second semester of 2000. PM10 samples were collected at four ambient air quality monitoring sites in Mexico City. We determined soluble ions (chloride, nitrate, sulfate, ammonium, sodium, potassium), ionizable transition metals (Zn, Fe, Ti, Pb, Mn, V, Ni, Cr, Cu) and soluble protein. The higher PM(10) levels were observed in Xalostoc (45-174 microg m(-3)) and the lowest in Pedregal (19-54 microg m(-3)). The highest SO2 average concentrations were observed in Tlalnepantla, NO2 in Merced and O3 and NO(x) in Pedregal. The concentration range of soluble sulfate was 6.7-7.9 and 19-25.5 microg m(-3) for ammonium, and 14.8-29.19 for soluble V and 3.2-7.7 ng m(-3) for Ni, suggesting a higher contribution of combustion sources. PM-associated soluble protein levels varied between 0.038 and 0.169 mg m(-3), representing a readily inhalable constituent that could contribute to adverse outcomes. The higher levels for most parameters studied were observed during the cold dry season, particularly in December. A richer content of soluble metals was observed when they were expressed by mass/mass units rather than by air volume units. Significant correlations between Ni-V, Ni-SO4(-2), V-SO4(-2), V-SO2, Ni-SO2 suggest the same type of emission source. The variable soluble metal and ion concentrations were strongly influenced by the seasonal meteoclimatic conditions and the differential contribution of emission sources. Our data support the idea that PM10 mass concentration by itself does not provide a clear understanding of a local PM air pollution problem.

Air Pollutants↗
PubMed1980

The role of albumin conformation in the binding of diazepam to human serum albumin.

The effect of hydrogen, chloride and calcium ions on the binding of diazepam to human serum albumin has been studied by circular dichroism and equilibrium dialysis. In all cases the molar ellipticity of the diazepam-albumin complex increases with pH over the pH range 5 to 9. Under these conditions the free concentration of diazepam at a constant low drug to protein ratio decreases with pH. This free concentration is higher in the presence of chloride and calcium ions. With a two state conformational model for albumin it was shown, that the pH dependences of molar ellipticity of the diazepam-albumin complex and of the free concentration of diazepam are linked. It was demonstrated that the N-B transition of albumin is involved in the pH dependent binding of diazepam. The consequences of these findings for equilibrium dialysis procedures in determining free plasma levels of diazepam are discussed.

Calcium↗
PubMed1976

Studies on gamma-glutamyl transpeptidase of human urine.

A simple and rapid method suitable for clinical laboratories, for the removal of the inhibitors in urine of gamma-glutamyl transpeptidase activity, using an ion-retardation resin, is described. Gel chromatography of urine resulted in appreciable loss of the enzyme activity. Freezing at -5 degrees C and thawing, did not affect the activity of the enzyme. Dimethyl sulfoxide and polyvinyl pyrrolidone up to a creatinine and NaCl at levels found in normal urine did not inhibit the transpeptidase.

Chlorides↗
PubMed1975

Analysis of vinyl chloride by mass fragmentography.

Vinyl chloride is analyzed by mass fragmentography by simultaneously recording its m/e 62 and 64 ions. The minimum quantity necessary for detection is 8.7 X 10(-12) g/10 ml injection. At this level the coefficient of variation is 8.51%.

Chromatography, Gas↗
PubMed1988

Kinetic analysis of acetylcholine-induced chloride current in isolated Aplysia neurones.

(1) Kinetics of activation and desensitization phases of the ACh-induced chloride current (ICl) were studied in isolated single neurones of Aplysia kurodai, using the 'concentration clamp' technique which combines internal perfusion and rapid exchange of the external solution within a few milliseconds (2) The dose-response curve for the peak ICl gave a dissociation constant of 6.7 X 10(-6) M and a Hill coefficient of 1.7. (3) The current-voltage relationship was linear in the voltage range examined (-70 to +30 mV). The reversal potential (EACh) was -7.1 +/- 1.8 mV (n = 14). The value was close to the calculated equilibrium potential for chloride ions (ECl). (4) The activation phase of the ICl was single exponential and the desensitization proceeded double exponentially to a steady state level. The time constants of both phases decreased with increasing concentrations of ACh but showed no potential dependency. The desensitizing component of the ICl was generated by activation of a single population of the receptor-channel complex. (5) The recovery from desensitization of the ICl induced by 6 X 10(-6) M ACh proceeded double exponentially, with time constants of 6.5 and 43 s at a holding potential of -30 mV. (6) Noise analysis performed on the steady state of ICl induced by low concentrations of ACh (3 X 10(-7) M to 3 X 10(-6) M) showed that the steady ICl was due to activation of a single population of the receptor-channel complex with a single channel conductance of 23.3 +/- 4.3 pS (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1989

Some properties of Streptococcus faecalis subsp. liquefaciens isolated from cheese with special reference to production of bitterness.

Streptococcus faecalis subsp. liquefaciens was examined for proteolysis and development of bitterness in sterile buffaloes' skim milk with and without some additives. Cell population and the pH of milk were the most important factors in the breakdown of casein and development of bitterness. Sodium chloride level, altering the final concentration of bacteria in milk, had a direct role in the production of bitter peptides. Calcium ions up to 5 mM did not affect proteolysis whereas higher concentrations were inhibitory. Electrophoretic analysis of proteose-peptone formed in sterile skim milk with and without NaCl revealed the presence of 3 peptides, 2 of which were probably associated with bitterness. S. faecalis subsp. liquefaciens produced acidity slowly, but was the most acid producer (1.25% after 72 h) of the streptococci. However, milk coagulated enzymatically and the curd shrinkage was related to salt-dependent acidity. Strains of the organism coagulated fresh citrated human plasma within 21 h at 30 degrees C, but without any visible fibrinolysis. The strains also were all alpha-haemolytic with occasionally a very few beta-haemolytic variants on sheep blood agar. On human blood agar, a weak alpha-reaction was given.

Animals↗
PubMed1988

Mitochondria-rich cells and carbonic anhydrase content of toad skin epithelium.

The density and carbonic anhydrase (CA) content of the mitochondria-rich cells (MRCs) in the skin epithelium of the toad, Bufo viridis, were studied under conditions of acclimation to various chlorinities. Long-term (days to weeks) acclimation to chloride-free solutions induced a great increase in the MRC density and the area occupied by the apical portion of these cells on the surface of the epithelium. The CA content of the epithelium, and individual MR cells, showed a 5- to 10-fold reduction after acclimation to solutions containing high chloride levels. The MRC density and their relative apical surface area correlated with the chloride permeability of the skin in acclimated (long-term) toads. It is concluded that the MRCs are the principal site of chloride permeability across the amphibian skin, and they respond in an adaptive manner to long-term changes in environmental chloride levels.

Animals↗