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PubMed2005

Oxidative degradation of ethers promoted by strontium and barium tetraphenylimidodiphosphinates.

The novel M[(OPPh2)2N]2.nTHF (M = Sr (2), Ba (3)) complexes were prepared and characterized. Upon exposure to atmospheric oxygen, 2 and 3 were transformed to the dinuclear species Sr2-[(OPPh2)2N]4.2C3H6O3 (4) and Ba(2)[(OPPh2)2N]4.2C4H8O3 (5), respectively. Compounds 4 and 5 contain coordinated carboxylic acids obtained from the oxidative degradation of DME and THF, respectively, which were used as solvents for crystallization.

Journal Article↗
PubMedDate not supplied

Isolation, purification, and partial characterization of prunellin, an anti-HIV component from aqueous extracts of Prunella vulgaris.

Prunellin, an anti-HIV active compound, was isolated from aqueous extracts of the Chinese medicinal herb, Prunella vulgaris, and purified to chromatographic homogeneity. Infrared and NMR spectroscopy identified prunellin as a polysaccharide. Elemental analyses, precipitation with calcium(II), barium(II), or 9-aminoacridine suggest a sulfated polysaccharide. Paper chromatography of the exhaustively hydrolyzed material indicates the presence of glucose, galactose, xylose, gluconic acid, galactonic acid and galactosamine as the constituent monosaccharides. The molecular size of prunellin, as determined by gel permeation chromatography and the Squire method on Sephadex G-75, is about 10 kDa.

Antiviral Agents↗
PubMed2004

Synthesis and evaluation of in vivo activity of diphenylhydantoin basic derivatives.

During the search for antiarrhythmic agents among amide derivatives of phenytoin, compound 7 {3-ethyl-1-[2-hydroxy-3-(4-phenyl-piperazin-1-yl)-propyl]-2,4-dioxo-5,5-diphenyl-imidazolidine} was selected as it showed antiarrhythmic as well as antihypertensive activity. Treating this compound as a lead, new derivatives 8-19 were synthesised, differing in piperazine phenyl ring substitution (2-, 3-, 4-Cl, 2-CH3O) as well as in hydantoin N3 alkyl chain (ethyl, ethyl acetate or ethyl 2-propionate). The obtained compounds in form of hydrochlorides 7a-19a were examined for prophylactic antiarrhythmic and antihypertensive properties. Compounds containing ethyl 2-propionate moiety (17a, 18a) exhibited the highest antihypertensive properties. Water-soluble compounds, containing 2-methoxyphenylpiperazine group (11a, 19a), showed strong antiarrhythmic properties in adrenaline-induced arrhythmia; compound 9a {1-[3-(4-(3-chloro-phenyl)-piperazin-1-yl)- 2-hydroxy-propyl]- 3-ethyl-2,4-dioxo-5,5-diphenyl-imidazolidine hydrochloride} exhibited the highest antiarrhythmic activity in barium chloride arrhythmia model.

Animals↗
PubMed2003

Understanding the formation of new clusters of alkali and alkaline Earth metals: a new synthetic approach, single-crystal structures, and theoretical calculations.

A new synthetic approach, reacting alkaline earth metal iodides with butyllithium, lithium hydroxide, and/or lithium butoxide under salt elimination, is presented, giving access to some interesting clusters of calcium, strontium, and barium, partially in combination with lithium. The so far largest calcium cluster Li[[Ca(7)(mu(3)-OH)(8)I(6)(thf)(12)](2)(mu(2)-I)].3THF, 4, and the new strontium compound [Sr(3)I(3)(OH)(2)(thf)(9)]I, 5, are shown to feature common building blocks of OH-capped M(3) triangles. On the basis of mainly electrostatic interactions, these clusters are not volatile. By introducing LiO(t)Bu, the two clusters [IM(O(t)Bu)(4)[Li(thf)](4)(OH)] (6, M = Sr; 7, M = Ba) are prepared, 7 exhibiting volatility as an important physical property, which makes it a potential precursor for chemical vapor deposition. The structural relationship between 4, 5, 6, and 7 and their respective starting materials is shown, and possible reaction mechanisms are proposed. Exhibiting surprising and new structural motifs, the bonding modes of these clusters are investigated by the electron localization function as well as by ab initio calculations.

Journal Article↗
PubMedDate not supplied

The effect of chromatographically pure sample of adenosine 5'-tetraphosphate on sheep and rabbit blood platelets.

1. The commercially available trisodium salt of adenosine 5'-tetraphosphate (ATetraP) (Sigma) was found to be contaminated with ATP, ADP and AMP, and therefore unsuitable for use in platelet studies. 2. The more stable barium salt of ATetraP was converted to the ammonium salt and found to be chromatographically homogeneous. This sample was tested for its influence on sheep blood platelets in citrated-rich plasma by the photometric method. 3. The ammonium salt of ATetraP (5-105 mumol.1(-1)) induced platelet aggregation which showed no tendency towards disaggregation. 4. The log dose-response lines for ATetraP and for adenosine diphosphate were parallel. On a molar basis, the tetraphosphate and only 1.5% of the aggregating activity of ADP. 5. The initial rate of aggregation induced by the tetraphosphate was inhibited by adenosine 5'-monophosphate analogues which are selective ADP-antagonists. These compounds also dispersed aggregates produced by ATetraP. 6. Platelets made refractory to ADP were also refractory to ATetraP. 7. Like ADP, ATetraP induced the change in shape of rabbit platelets and in this respect had only 3.4% the activity of ADP. 8. It is concluded that ATetraP per se can induced platelet aggregation and platelet shape change, and appears to exert its effect at the same site on the platelet surface as does ADP.

Adenine Nucleotides↗
PubMed1990

A transient outward current in NG108-15 neuroblastoma x glioma hybrid cells.

Outward currents were recorded from voltage-clamped NG108-15 mouse neuroblastoma X rat glioma hybrid cells, differentiated with prostaglandin E1. Depolarising voltage steps from -70 mV, evoked a transient outward current from a threshold of -30 mV. The outward current showed complete inactivation at potentials positive to -10 mV. Inactivation was removed by hyperpolarisation with half-inactivation at -53 mV. The time course of the inactivation could be best fitted by two exponentials with mean time constants of 280 ms and 1.6 s at +80 mV. Tail current measurements showed a shift in the reversal potential with changes in external K+ concentration, consistent with K+ as the current-carrying ion. The outward current amplitude was reversibly reduced by 4-aminopyridine, and the time course of inactivation modified. In the presence of other K+ channel blockers (tetraethylammonium, barium and tetrahydroaminoacridine) the amplitude of the outward current was also reversibly reduced, but with a negligible effect on its time course. The current was unaffected by dendrotoxin, d-tubocurarine, apamin, Cd2+ and Ni2+, and by replacing external Ca2+ with Co2+ or Mg2+. In current clamp, action potential duration was greatly increased by 4-aminopyridine. The findings show that the NG108-15 cell line displays a transient outward current that resembles IK(A) but with a higher than usual threshold and relatively slow inactivation, and that this current is likely to be important for action potential repolarisation.

4-Aminopyridine↗
PubMed1988

Adrenaline depolarization in paravertebral sympathetic neurones of bullfrogs.

Responses to adrenaline (Ad) and their ionic mechanisms were analysed using intracellular recording and voltage-clamp methods in neurones of bullfrog sympathetic ganglia. Ad (5 microM-1 mM) applied directly to sympathetic neurones by pressure ejection through a micropipette produced three types of depolarizing responses (2-20 mV). Under voltage-clamp conditions, Ad (100 microM) produced fast, slow and mixed types of inward currents (AdIs) with amplitude of 2.9 +/- 1.3 nA. beta-Adrenoceptors may be responsible for the generation of these AdDs. The slow AdI which lasted for 1-5 min was associated with a decreased membrane conductance. The slow AdI decreased at hyperpolarized potential level and eventually nullified at -70 mV. No reversal of the slow AdI polarity was observed in the Ringer solution. Injection of Cs2+ into the ganglion cells produced a marked depression of the amplitude of the slow AdI. The slow AdI was blocked by bath-applied Ba2+ but not by TEA. Ad reduced the slow current relaxation, the M current, associated with voltage jumps in the membrane potential range -35 to -55 mV. The fast Ad response was associated with an increase in membrane conductance. When the membrane was depolarized, the fast AdI decreased and reversed its polarity at -36 +/- 8.3 mV. Removal of Cl ion from superfusing solution depressed the fast AdI, suggesting that activation of Cl- conductances may be involved in the generation of the fast AdI. The mixed type of Ad response exhibited characteristics of both the fast and slow Ad responses. The results suggest that Ad increases the excitability of neurones in bullfrog sympathetic ganglia.

Animals↗
PubMed1986

Intraepithelial current flow in rat pancreatic secretory epithelia.

To assess the importance for transepithelial salt secretion of current flow across the baso-lateral membrane, we studied the effects of ouabain (1 mmol/l), Ba (3 mmol/l) and tetraethylammonium (TEA: 10 mmol/l) on secretion by the acinar (caerulein stimulated) and ductal (secretin stimulated) epithelia of the perfused rat pancreas. Within 10 min, ouabain caused a 79% inhibition of acinar secretion which was resolvable into two exponentials with half-times, respectively, of 0.24 min +/- 0.19 (S.D.) and 6.40 +/- 0.46 min. In contrast, it caused only a monoexponential inhibition of ductal secretion (61% in 10 min) with a half-time of 5.08 +/- 0.26 min. Ba caused a monoexponential inhibition of acinar secretion (70% in 10 min) with a half-time of 1.82 +/- 0.27 min, but it had no inhibitory effect on ductal secretion. The action of TEA was similar to that of Ba: it caused monoexponential inhibition of acinar secretion (26% in 10 min) with a half-time of 1.82 +/- 0.03 min, and it too had no effect on ductal secretion. For comparison, we also studied the effect of these drugs on the more rapidly secreting rat mandibular gland (stimulated with acetylcholine). All three drugs were strongly inhibitory: within 10 min, ouabain caused a 95%, Ba an 89% and TEA an 83% inhibition. The decay curves appeared to be monoexponential with half-times, respectively, of 1.49 +/- 0.12, 0.51 +/- 0.3 and 0.56 +/- 0.02 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1990

An electrophysiological technique to measure change in hepatocyte water volume.

We have applied an electrophysiologic technique (Reuss, L. (1985) Proc. Natl. Acad. Sci. USA 82, 6014) to measure changes in steady-state hepatocyte volume during osmotic stress. Hepatocytes in mouse liver slices were loaded with tetramethylammonium ion (TMA+) during transient exposure of cells to nystatin. Intracellular TMA+ activity (alpha 1TMA) was measured with TMA(+)-sensitive, double-barrelled microelectrodes. Loading hepatocytes with TMA+ did not change their membrane potential (Vm), and under steady-state conditions alpha iTMA remained constant over 4 min in a single impalement. Hyperosmotic solutions (50, 100 and 150 mM sucrose added to media) and hyposmotic solutions (sucrose in media reduced by 50 and 100 mM) increased and decreased alpha iTMA, respectively, which demonstrated transmembrane water movements. The slope of the plot of change in steady-state cell water volume, [(alpha iTMA)0/(alpha iTMA)4min] -1, on the relative osmolality of media, (experimental mosmol/control mosmol) -1, was less predicted for a perfect osmometer. Corresponding measurements of Vm showed that its magnitude increased with hyposmolality and decreased with hyperosmolality. When Ba2+ (2 mM) was present during hyposmotic stress of 0.66 X 286 mosmol (control), cell water volume increased by a factor of 1.44 +/- 0.02 compared with that of hyposmotic stress alone, which increased cell water volume by a factor of only 1.12 +/- 0.02, P less than 0.001. Ba2+ also decreased the hyperpolarization of hyposmotic stress from a factor of 1.62 +/- 0.04 to 1.24 +/- 0.09, P less than 0.01. We conclude that hepatocytes partially regulate their steady-state volume during hypo- and hyperosmotic stress. However, volume regulation during hyposmotic stress diminished along with hyperpolarization of Vm in the presence of K(+)-channel blocker, Ba2+. This shows that variation in Vm during osmotic stress provides an intercurrent, electromotive force for hepatocyte volume regulation.

Amphotericin B↗
PubMed1991

The effect of K(+)-conductance-blocking substances on the occurrence of retinal spreading depression.

Retinal spreading depression (SD) has been thought to be generated by an abnormal increase in [K+]o in the inner plexiform layer. When a retina isolated from bullfrog was immersed in a medium conditioned for SD (low Cl- Ringer's solution), spontaneous SDs periodically occurred at a fixed interval in the dark. The effect of K(+)-conductance blocking substances (Ba2+, Cs+, TEA and 4-AP) on the occurrence of SD was studied using the concomitant changes in the field potential (spreading depression potential; SDP) as an index. These substances increased the frequency of occurrence and decreased the amplitude of the potential. According to the Müller cell theory of SDP, an increase in [K+]o depolarizes the Müller cells and the resulting extracellular current generates the potential change. Since the small amplitude of the SDP reflects the decreased K+ current, it may be said that the K(+)-buffering capacity of the Müller cells was partially reduced by the substances and that the frequency of the SD occurrence consequently increased in order to clear accumulating [K+]o from neurons with the decreased buffering capacity. The present results lend a good support to the current Müller cell theory for the occurrence of SDP.

4-Aminopyridine↗
PubMed1994

A comparative trial of magnesium citrate (Citramag) and Picolax for barium enema bowel preparation.

It has previously been suggested that a single dose of magnesium citrate produces adequate cleansing of the bowel for barium enema examination. To determine whether such a regimen has any advantage over the widely used two doses of Picolax, a prospective randomized blinded trial was performed with over 100 patients allocated to each of the bowel preparation regimens. Radiographs were assessed for quality of mucosal coating, faecal residue and overall quality of bowel preparation. Patient compliance was good with both regimens. Normal daily activities were inconvenienced significantly more by the Picolax (P < 0.001), whereas the magnesium citrate (Citramag) caused more interruption of sleep (P < 0.01). Mucosal coating was similar with both regimens. There was more faecal residue and poorer overall bowel preparation with Citramag (P < 0.001), although diagnostic accuracy was only infrequently felt to be compromised as a result. Citramag may offer an alternative to Picolax in patients where minimal disruption to daily activities is desirable and where the detection of polyps is not critical.

Activities of Daily Living↗
PubMed1976

Pyridoxal phosphate. 5. 2-Formylethynylphosphonic acid and 2-formylethylphosphonic acid, potent inhibitors of pyridoxal phosphate binding and probes of enzyme topography.

The title compounds (17 and 21) were prepared in good yield by synthesis of the phosphonate diester acetals (14 and 19), deesterification with chloro- or bromotrimethylsilane, hydrolysis of the acetal group, and formation of the characterized barium salts. The 3-carbon aldehydrophosphonic acids (17 and 21) were potent inhibitors (Ki = 2 X 10(-6)) of pyridoxal phosphate (PPal) binding to apoaspartate aminotransferase (AAT) and are believed to span between and bind to the enzymic functional groups which bind the aldehyde and phosphate groups of PPal.

Apoenzymes↗
PubMed1991

Whole-cell clamp of dissociated photoreceptors from the eye of Lima scabra.

Voltage-dependent membrane currents were investigated in enzymatically dissociated photoreceptors of Lima scabra using the whole-cell clamp technique. Depolarizing steps to voltages more positive than -10 mV elicit a transient inward current followed by a delayed, sustained outward current. The outward current is insensitive to replacement of a large fraction of extracellular Cl- with the impermeant anion glucuronate. Superfusion with tetraethylammonium and 4-aminopyridine reversibly abolishes the outward current, and internal perfusion with cesium also suppresses it, indicating that it is mediated by potassium channels. Isolation of the inward current reveals a fast activation kinetics, the peak amplitude occurring as early as 4-5 ms after stimulus onset, and a relatively rapid, though incomplete inactivation. Within the range of voltages examined, spanning up to +90 mV, reversal was not observed. The inward current is not sensitive to tetrodotoxin at concentrations up to 10 microM, and survives replacement of extracellular Na with tetramethylammonium. On the other hand, it is completely eliminated by calcium removal from the perfusing solution, and it is partially blocked by submillimolar concentrations of cadmium, suggesting that it is entirely due to voltage-dependent calcium channels. Analysis of the kinetics and voltage dependence of the isolated calcium current indicates the presence of two components, possibly reflecting the existence of separate populations of channels. Barium and strontium can pass through these channels, though less easily than calcium. Both the activation and the inactivation become significantly more sluggish when these ions serve as the charge carrier. A large fraction of the outward current is activated by preceding calcium influx. Suppression of this calcium-dependent potassium current shows a small residual component resembling the delayed rectifier. In addition, a transient outward current sensitive to 4-aminopyridine (Ia) could also be identified. The relevance of such conductance mechanisms in the generation of the light response in Lima photoreceptors is discussed.

4-Aminopyridine↗
PubMed1996

HM-PAO-labeled leukocyte scintigraphy in pediatric patients with inflammatory bowel disease.

Leukocyte scintigraphy (LS) was performed in 20 pediatric patients with inflammatory bowel disease (IBD: 10 with ulcerative colitis, 2 with indeterminate colitis, and 8 with Crohn disease) in different stages of clinical activity. Leukocytes were separated from 15 to 60 ml venous blood and were labeled in vitro with [99mTc]HM-PAO. The segmental extent (small intestine; ascending, transverse, and descending colon; and recto-sigmoideum) of the process was determined by LS. The uptake of each bowel segment was scored in relation to the bone marrow uptake. The scintigraphic activity, calculated by summing the segment scores, was compared with laboratory parameters. The mean labeling efficacy was 76% (60-86%). The segmental extent of the process determined by LS was compared with the results of barium enema or colonoscopy with regard to 32 bowel segments. The sensitivity, specificity, and accuracy of LS were 93, 88, and 91%, respectively. Two extraintestinal manifestations (abdominal abscess and joint involvement) were also detected by LS. These lesions were verified by computed tomography (CT) (abscess) and on the basis of the clinical outcome (arthritis). The scintigraphic activity correlated with the C-reactive protein (CRP) level (r = 0.82, p < 0.001), the alpha 2-globulin level (r = 0.63, p < 0.02), the sedimentation rate (r = 0.51, p < 0.05), and the fS iron level (r = -0.66, p < 0.005). LS is applicable in pediatric patients. The method is an excellent technique for assessment of the extent of IBD in children. Extraintestinal manifestations of IBD can also be investigated by LS. The scintigraphic activity is a useful parameter for determination of the activity of IBD in children.

Adolescent↗