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  • 1995-1999  (37)
  • 1955-1959  (8)
  • Chemistry  (38)
  • Analytical Chemistry and Spectroscopy  (3)
  • Altitude acclimatization  (2)
  • Biochemistry and Biotechnology  (2)
  • Canine  (2)
  • Computational Chemistry and Molecular Modeling
  • United States
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Year
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  • 1
    Electronic Resource
    Electronic Resource
    Effects of cromakalim or glibenclamide on arrhythmias and dispersion of refractoriness in chronically infarcted anesthetized dogs (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 222-228 
    Details
    ISSN: 1432-1912
    Keywords: Dispersion ; Refractoriness ; ATP-sensitive potassium channel ; Canine ; Programmed electrical stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The proarrhythmic effects of the ATP-sensitive potassium channel modulators cromakalim (n = 10; 0.01 to 0.3 mg/kg i.v.), glibenclamide (n = 10; 0.3 to 10 mg/kg i.v.) or volume equivalents of vehicle (n = 10) were evaluated in post-infarcted anaesthetised dogs. Dogs were anaesthetised, subjected to an anterior-apical myocardial infarction, and allowed to recover. At 7.4 ± 0.7 days post infarction, animals were anaesthetised again, electrophysiologic measurements (effective refractory periods, QT-intervals and ventricular fibrillation thresholds) were taken, and animals were tested for arrhythmias using a programmed electrical stimulation protocol. Only animals that did not have programmed electrical stimulation-inducible arrhythmias were used. Ventricular fibrillation thresholds were determined twice, once before the first dose then after the last dose of drug. At the end of the experiment, animals were subjected to ligation of the left circumflex coronary artery and survival was measured over the next two hours. Cromakalim significantly increased heart rate and decreased blood pressure. Although cromakalim significantly reduced effective refractory periods, it neither increased electrical dispersion, as determined by the standard deviation or coefficient of variance of the effective refractory period, nor did it enhance inducibility (0 out of 10 in both vehicle and cromakalim treated animals), change ventricular fibrillation thresholds, or reduce sudden death survival relative to vehicle. Glibenclamide did not increase electrical dispersion, but slightly increased the incidence of programmed electrical stimulation-induced arrhythmias (3 out of 10), and lowered ventricular fibrillation thresholds values. However, these changes were not statistically significant. Glibenclamide did not significantly affect survival relative to vehicle. Infarct sizes of the left ventricle were not statistically different among groups. In conclusion, cromakalim and glibenclamide did not affect dispersion of refractoriness. Glibenclamide did demonstrate a propensity towards proarrhythmic activity. However, the doses needed to observe proarrhythmic activity with glibenclamide were significantly higher than those needed for clinical treatment of hyperglycemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176778
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of cromakalim or glibenclamide on arrhythmias and dispersion of refractoriness in chronically infarcted anesthetized dogs (1995)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 352 (1995), S. 222-228 
    Details
    ISSN: 1432-1912
    Keywords: Key words Dispersion ; Refractoriness ; ATP-sensitive potassium channel ; Canine ; Programmed electrical stimulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The proarrhythmic effects of the ATP-sensitive potassium channel modulators cromakalim (n=10; 0.01 to 0.3 mg/kg i.v.), glibenclamide (n=10; 0.3 to 10 mg/kg i.v.) or volume equivalents of vehicle (n=10) were evaluated in post-infarcted anaesthetised dogs. Dogs were anaesthetised, subjected to an anterior-apical myocardial infarction, and allowed to recover. At 7.4±0.7 days post infarction, animals were anaesthetised again, electrophysiologic measurements (effective refractory periods, QT-intervals and ventricular fibrillation thresholds) were taken, and animals were tested for arrhythmias using a programmed electrical stimulation protocol. Only animals that did not have programmed electrical stimulation-inducible arrhythmias were used. Ventricular fibrillation thresholds were determined twice, once before the first dose then after the last dose of drug. At the end of the experiment, animals were subjected to ligation of the left circumflex coronary artery and survival was measured over the next two hours. Cromakalim significantly increased heart rate and decreased blood pressure. Although cromakalim significantly reduced effective refractory periods, it neither increased electrical dispersion, as determined by the standard deviation or coefficient of variance of the effective refractory period, nor did it enhance inducibility (0 out of 10 in both vehicle and cromakalim treated animals), change ventricular fibrillation thresholds, or reduce sudden death survival relative to vehicle. Glibenclamide did not increase electrical dispersion, but slightly increased the incidence of programmed electrical stimulation-induced arrhythmias (3 out of 10), and lowered ventricular fibrillation thresholds values. However, these changes were not statistically significant. Glibenclamide did not significantly affect survival relative to vehicle. Infarct sizes of the left ventricle were not statistically different among groups. In conclusion, cromakalim and glibenclamide did not affect dispersion of refractoriness. Glibenclamide did demonstrate a propensity towards proarrhythmic activity. However, the doses needed to observe proarrhythmic activity with glibenclamide were significantly higher than those needed for clinical treatment of hyperglycemia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00176778
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  • 3
    Electronic Resource
    Electronic Resource
    Hypoxic ventilatory response during rest and exercise after a Himalayan expedition (1996)
    Springer
    European journal of applied physiology 73 (1996), S. 202-209 
    Details
    ISSN: 1439-6327
    Keywords: Peripheral chemoreceptors ; Hypoxic ventilatory response ; Altitude acclimatization ; High altitude
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Hypoxic ventilatory response (HVR) was examined before and after acclimatization to high altitude. Transient hyperoxic switches according to Dejours's technique were used to examine the contribution of HVR to the hyperpnoea of increasing exercise intensities. Ten mountaineers were exposed to hypoxia (oxygen fraction in inspired gas,F 1O2 = 0.11, 79 mmHg) before the expedition and after return from altitude (56 days, 30 days at 4900 m or higher). After 25-min breathing hypoxic gas, the subjects performed a maximal cycle ergometer test (increments 50 W per 5 min). Respired gases and ventilation $$(\dot V_E )$$ were analysed breath-by-breath, partial pressure of oxygen (PO2) and oxygen saturation (SO2) were measured in capillary blood. The HVR was tested by switching two breaths to anF 1O2 of 1.0. The nadir of $$\dot V_E $$ after the switch was measured (decrease in ventilation, D $$\dot V_E $$ ). The HVR was expressed as the D $$\dot V_E $$ at a PO2 of 40 mmHg (D $$\dot V_{E40} $$ ) and the D $$\dot V_E $$ versus decrease ofSO2 (D $$\dot V_E $$ /[100 −SO2]). The HVR estimated by D $$\dot V_{E40} $$ increased from 19.9 to 28.01 · min−1 (median,P = 0.013). The HVR expressed as D $$\dot V_E $$ /(100 −SO2) at rest was no different before and after acclimatization (0.89 and 0.86 l · min−1 · %−1, respectively) and during exercise it did not change before the expedition (0.831 · min−1 %−1). However, D $$\dot V_E $$ /(100 −SO2) increased significantly with exercise intensity after the expedition (1.61 l · min−1 · %−1 at 200 W). The changes of D $$\dot V_E $$ versusSO2 as well as of D $$\dot V_E $$ versus $$\dot V_E $$ were steeper after the expedition than before. In summary, after return from 30 day at high altitude, an increased HVR was observed. The augmentation of HVR was evident at higher exercise intensities and we suggest that this reflects a change in sensitivity of the peripheral chemoreflex loop.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02425477
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  • 4
    Electronic Resource
    Electronic Resource
    Lung diffusion capacity, oxygen uptake, cardiac output and oxygen transport during exercise before and after an Himalayan expedition (1996)
    Springer
    European journal of applied physiology 74 (1996), S. 187-193 
    Details
    ISSN: 1439-6327
    Keywords: Hypoxia ; Exercise ; Rebreathing Alveolar-arterial difference ; Altitude acclimatization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Studies were made of pulmonary diffusion capacity and oxygen transport before and after an expedition to altitudes at and above 4900 m. Maximum power (P max) and maximal oxygen uptake (VO 2max) were measured in 11 mountaineers in an incremental cycle ergometer test (25W · min−1) before and after return from basecamp (30 days at 4900 m or higher). In a second test, cardiac output (Q c) and lung diffusion capacity of carbon monoxide (D L,CO) were measured by acetylene and CO rebreathing at rest and during exercise at low, medium and submaximal intensities. After acclimatization, VO2max and P max decreased by 5.1% [from 61.0 (SD 6.2) to 57.9 (SD 10.2) ml·kg−1, n.s.] and 9.9% [from 5.13 (SD 0.66) to 4.62 (SD 0.42) W·kg−1, n.s.], respectively. The maximal cardiac index and DL,co decreased significantly by 15.6% [14.1 (SD 1.41) 1·min−1 · m−2 to 11.9 (SD 1.44)1·min−1 m−2, P〈0.05] and 14.3% [85.9 (SD 4.36)ml·mmHg−1 min−t to 73.6 (SD 15.2) ml · mmHg−1 -min−1, P〈0.05], respectively. The expedition to high altitude led to a decrease in maximal Q c, oxygen uptake and DL,CO. A decrease in muscle mass and capillarity may have been responsible for the decrease in maximal Qc which may have resulted in a decrease of D L,CO and an increase in alveolar-arterial oxygen difference. The decrease in D L,CO especially at lower exercise intensities after the expedition may have been due to a ventilation-perfusion mismatch and changes in blood capacitance. At higher exercise intensities diffusion limitation due to reduced pulmonary capillary contact time may also have occurred.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00376512
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  • 5
    Electronic Resource
    Electronic Resource
    Diet and risk of colon cancer in a large prospective study of older women: an analysis stratified on family history (Iowa, United States) (1998)
    Springer
    Cancer causes & control 9 (1998), S. 357-367 
    Details
    ISSN: 1573-7225
    Keywords: Colon cancer ; diet ; family history ; United States ; women
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective: The purpose was to investigate whether dietary associations with risk of colon cancer in women differ by family history of the disease. Methods: Data were analyzed from a prospective cohort study of 35,216 Iowa (United States) women aged 55 to 69 years at baseline. Through 31 December 1995, 241 colon cancers were identified through record linkage with the State Health Registry. The cohort was stratified on family history of colon cancer in first-degree relatives; nutrient intakes were divided into tertiles. Results: Analyses using Cox regression revealed that the association of most dietary components with colon cancer incidence were similar for individuals with and without a family history. However, total calcium intake was associated inversely with colon cancer among women with a negative family history (relative risk [RR]=0.50 for upper cf lower tertile, P 〈 0.001), but was unrelated to incidence for women with a positive family history (RR=1.1 for upper cf lower tertile, P=0.69). Similarly, total vitamin E intake was associated with lower risk among women with a negative family history (RR=0.67 for upper cf lower tertile, P=0.04), but not among women with a positive family history (RR=0.87 for upper cf lower tertile, P=0.67). High intakes of fiber, fruits, and vegetables were each weakly inversely associated with risk among family-history negative women, but not among family-history positive women. Conclusions: These data, if corroborated, suggest that dietary factors typically associated with lower risk may be less effective risk-reduction interventions against colon cancer for individuals with a family history of colon cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008886715597
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  • 6
    Electronic Resource
    Electronic Resource
    Early body size and subsequent weight again as predictors of breast cancer incidence (Iowa, United States) (1995)
    Springer
    Cancer causes & control 6 (1995), S. 112-118 
    Details
    ISSN: 1573-7225
    Keywords: Breast cancer ; body mass index ; females ; United States ; weight gain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: We examined whether associations of adult weight gain with the risk of postmenopausal breast cancer vary by stature, waist-hip ratio (WHR), and early adult size in a cohort of 37,105 Iowa (United States) women. Both low body mass index (kg/m2) (BMI) at age 18 and high subsequent weight-gain were associated independently with increased risk of incident postmenopausal breast cancer. After stratifying on BMI at age 18, high weight gain was associated with increased risk irrespective of whether early BMI was low (relative risk [RR]=1.92, 95 percent confidence interval [CI]=1.45–2.53) or high (RR=1.59, Ci=1.19–2.12). Women with lower BMI at 18 were at a higher risk at all levels of weight change, but having low BMI at age 18 and low subsequent weight gain conferred no significantly excess risk over those with high BMI at 18 and low gain. An inconsistent increase in risk was associated with taller stature; there was no additional risk associated with high WHR. Part of the observed risk from lower early size may reflect greater weight gain by lighter women. Limiting adult weight gain thus may be a feasible method to avoid increasing an individual's risk of breast cancer. Reasons for different effects of early cf late weight gain are not established, but benefits of a greater size at age 18 are likely to be offset by increased risks of other weight-related diseases at older ages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00052771
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  • 7
    Electronic Resource
    Electronic Resource
    Metal Complexes with Macrocyclic Ligands. Part XLIVPart XLIII:[1] Kinetics of the Cu2+ incorporation into a macrocyclic ligand conjugated to proteins: Model studies for the d‘post-labeling’ technique (1997)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 80 (1997), S. 934-947 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The kinetics of the Cu2+ complexation by macrocycles 1 (4-[(l,4,8,11-tetraazacyclotetradec-1-yl)methyl]-benzoic acid) and 2 (N-propyl-4-[(1,4,8,11-tetraazacyclotetradec-1-yl)methyl]-benzamide) as well as by macrocycle 1 conjugated to bovine serum albumin (bsa) and to ribonuclease A (rnase) were studied by stopped flow techniques. For 1 and 2, the kinetics were followed in the mM range monitoring the d-d* absorption band of the Cu2+ complex. From the pH dependence of kobs, the rate law is v = [Cu2+] (kLH[LH] + kLH2[LH2]), where kLH and kLK2 are the bimolecular rate constants for Cu2+ with the diprotonated (LH2) and monoprotonated (LH1) form of the ligand, respectively. The values are kLH2 = 1.7(1) M-1s-1 and kLH = 2.3(1) 105 M-1s-1 for 1, and kLH2, = 0.28(9) M-1s-1 and kLH = 2.0(1) 105 M-1s-1 for 2. The kinetics of the Cu2+ incorporation into 1,2 and 1 conjugated to bsa and rnase, i.e., 3 and 4, respectively, were also followed using nitroso-R salt as a metal indicator in the μM range, i.e., under conditions typical for the ‘post-labeling’ technique to give radiolabeled monoclonal antibodies. In these cases, the reaction takes place between the 1:1 complex of Cu2+ with nitroso-R-salt and the macrocycle. At pH 6.5, the rates are very similar to each other indicating that the complexation properties of the macrocycle attached to a protein are not very different from those of the free ligand under comparable conditions.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19970800325
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  • 8
    Electronic Resource
    Electronic Resource
    Metal Complexes with Macrocyclic Ligands. Part XXXVIIIPart XXXVII: [1].. Steric effects in the copper(II) and nickel(II) complexes with tetra-N-alkylated 1,4,8,11-tetraazacyclotetradecanes (1995)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 78 (1995), S. 505-513 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A series of tetra-N-alkylated 1,4,8,11-tetraazacyclotetradecanes have been synthesized and their complexation potential towards Ni2+ and Cu2+ studied. In the case of sterically demanding alkyl substituents, such as i-Pr, PhCH2, or 2-MeC6H4CH2, no metal complexes are formed, whereas for substituents such as Me, Et, and Pr, the metal ion is incorporated into the macrocycle. The spectroscopic properties of the Ni2+ and Cu2+ complexes in aqueous solution indicate that, depending on the sterical hindrance of the N-substituents, the complexes are either square planar or pentacoordinated. All these Ni2+ and Cu2+ complexes react with N3- to give ternary species, the stability of which have been determined by spectrophotometric titrations. The tendency to bind N3- decreases with increasing steric hindrance of the alkyl substituents. The X-ray studies of the Ni2+ complex with the macrocycle 11, substituted by two Me and two Pr groups, and that of the Cu2+ complex with the tetraethyl derivative 8 show that in the solid state, the metal ions exhibit square planar coordination with a small distortion towards tetrahedral geometry.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19950780220
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  • 9
    Electronic Resource
    Electronic Resource
    Metal Complexes with Macrocyclic Ligands. Part XLIIIPart XLII [1]. Tetraazamacrocyclic nickel(II) and copper(II) complexes with aliphatic methylthio- and methoxy-substituted pendant chains (1997)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 80 (1997), S. 241-252 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The 14-membered tetraazamacrocyclic Ni2+ and Cu2+ complexes of 4 (1, 4, 8-trimethyl-11-[(2-methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), 5. (1, 4-dimethyl-8, 11-bis[2-(methylthio)ethyl]-l, 4, 8, 11-tetraazacyclotetradecane), and 7 (1, 4, 8, ll-tetrakis[2-(methylthio)ethyl]-1, 4, 8, 11-tetraazacyclotetradecane), with pne, two, and four methylthio-substituted pendant chains, respectively, and the Ni2+ complex of 6 (1, 4-dimethyl-8, 11-bis (2-methoxyethyl)-1, 4, 8, 11-tetraazacyclotetradecane), with two methoxy-substituted pendant chains, were synthesized and their chemistry studied with regard to modelling F430. Solution spectra in H2O, MeCN, and DMF indicate participation of the side chain in metal coordination when the donor group is a thioether, whereas no coordination with the metal ion is observed with the ether group. Similarly the X-ray structures of the thioether-containing compounds [Ni(5)](ClO4)2, [Cu(5)](ClO4)2, and [Cu(7)](ClO4)2 show a coordination number of 5, whereas that of [Ni(6)](ClO4)2 with ether pendant chains, shows a coordination number of 4. Cyclic voltammetry of these complexes in MeCN reveals that Ni2+ is reversibly reduced to Ni+ between -0.64 and -0.77 V vs. SCE, the potential being influenced by the nature and number of the pendant chains. At more negative potentials, the thioether is cleaved, whereby a thiol is formed; the thiol is then oxidized at ca. + 0.8 V vs. SCE, when a glassy carbon electrode is used, or at ca. 0 V vs. SCE at a dropping Hg electrode. No cleavage of the ether bond in [Ni(6)](ClO4)2 is observed under similar conditions.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19970800122
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  • 10
    Electronic Resource
    Electronic Resource
    Metal Complexes with Macrocyclic Ligands. PartXLVPart XLIV: [1] Axial coordination tendency in reinforced tetraazamacrocyclic complexes (1997)
    New York, NY : Wiley-Blackwell
    Helvetica Chimica Acta 80 (1997), S. 948-959 
    Details
    ISSN: 0018-019X
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The Cu2+ and Ni2+ complexes of three reinforced tetraazamacrocycles, containing a piperazine subunit and one or two alkyl substituents at the other two N-atoms have been prepared and their structural properties studied. In solution, the Ni2+ complexes are square-planar and show no tendency to axially coordinate a solvent molecule or an N3- ion. In contrast, the Cu2+ complexes change their geometry depending upon the donor properties of the solvent, being square-planar in MeNO2 and pentacoordinate in DMF. They also easily react in aqueous solution with N3- to give ternary species with pentacoordinate geometry, the stabilities of which have been determined. In the solid state, the X-ray crystal structures of three Cu2+ complexes also show both geometrical arrangements, two having a square-planar, the other one a distorted square pyramidal geometry. The difference behavior of Ni2+ and Cu2+ stems from the fact that the structural change from square-planar to square-pyramidal can easily be accomplished for Cu2+, whereas, for Ni2+, it is accompanied by an electronic rearrangement from the low-spin to the high-spin configuration. The relatively rigid ligands cannot Adapt to the somewhat larger high-spin Ni2+ion.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/hlca.19970800326
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