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  • 1
    Electronic Resource
    Electronic Resource
    Abnormal regulation of cell membrane fluidity in diabetic nephropathy (1998)
    Springer
    Diabetologia 41 (1998), S. 337-342 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Diabetic nephropathy ; fluidity ; anisotropy ; N-ethylmaleimide ; erythrocyte ; insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An abnormality of the physical properties of the cell membrane may underlie the defect that unites the clinical and biochemical abnormalities found in subjects with diabetic nephropathy. The cell membrane is linked both structurally and functionally with the cytoskeleton. The fluorescence anisotropy, a measure of membrane fluidity, was studied at baseline and after modulation of cytoskeletal proteins by thiol group alkylation with N-ethylmaleimide (NEM). 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess anisotropy in the deep hydrophobic regions of the lipid bilayer and trimethylammonium-diphenylhexatriene (TMA-DPH) was used to assess the superficial, relatively hydrophilic regions. We compared 17 subjects with insulin-dependent diabetes mellitus (IDDM) and nephropathy with 17 control subjects with IDDM and 24 non-diabetic control subjects. Median TMA-DPH anisotropy (0.271 (0.239–0.332) vs 0.269 (0.258–0.281) vs 0.275 (0.246–0.287)) and DPH anisotropy (0.221 (0.193–0.261) vs 0.227 (0.197–0.253) vs 0.226 (0.193–0.245)) were similar in erythrocytes from the three groups. However after alkylation of protein thiol groups with NEM clear differences emerged. In the control subjects with and without IDDM there was a significant fall in TMA-DPH anisotropy compared to the subjects with diabetic nephropathy in whom the addition of NEM had no effect (ΔTMA-DPH anisotropy –0.005 (–0.020– + 0.006) vs –0.005 (–0.011– + 0.016) vs + 0.002 (–0.010 – + 0.008) p 〈 0.001). This finding was confirmed when the deep regions of the lipid bilayer were assessed using DPH (ΔDPH anisotropy –0.017 (–0.029 –– 0.007.) vs –0.015 (–0.029 – + 0.001) vs + 0.003 (–0.021 – + 0.018) p 〈 0.001). We conclude that cytoskeletal modulation of the physical properties of the cell membrane lipids by proteins is abnormal in subjects with diabetic nephropathy. Such an abnormality could explain some of the clinical and metabolic abnormalities found in this condition. [Diabetologia (1998) 41: 337–342]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050912
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  • 2
    Electronic Resource
    Electronic Resource
    Thiol group modulation of sodium-lithium countertransport kinetics in diabetic nephropathy (1997)
    Springer
    Diabetologia 40 (1997), S. 1079-1084 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Diabetic nephropathy ; sodium-lithium countertransport ; thiol group ; N-ethylmaleimide ; erythrocyte ; insulin-dependent diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Abnormal erythrocyte sodium-lithium countertransport (Na-Li CT) activity, traditionally measured at a single sodium concentration of 140 mmol · l–1 (V140), may represent an inherited risk marker for diabetic nephropathy. The membrane defect underlying this association is poorly understood, though modulation by key protein thiol groups appears to be important in essential hypertension. To improve understanding of this abnormality, Na-Li CT kinetics in untreated erythrocytes and after thiol group alkylation with N-ethylmaleimide were investigated in 18 subjects with diabetic nephropathy, 20 normoalbuminuric insulin-dependent diabetic (IDDM) subjects and 18 non-diabetic individuals. Using the traditional assay, V140 was similar in subjects with diabetic nephropathy compared to IDDM control subjects vs 0.311 (0.152–0.475) (0.247 (0.111–0.498) mmol Li · h–1· l erythrocytes–1). Kinetic parameters were abnormal in subjects with diabetic nephropathy compared with diabetic and non-diabetic control subjects, with both Vmax (maximal Na-Li CT activity) (0.454 (0.257–0.963) vs 0.338 (0.183–0.972) vs 0.332 (0.213–0.603) mmol Li · h–1· l erythrocytes–1, p 〈 0.05), and Vmax/Km(So) ratio, reflecting ion association (6.03 (2.3–9.6) vs 4.73 (2.0–10.4) vs 4.48 (1.5–7.1), p 〈 0.01), significantly higher. N-ethylmaleimide decreased Km(So) and Vmax abolishing differences in Vmax/Km(So) ratio between groups (2.45 (1.18–4.21) vs 2.23 (0.96–4.3) vs 2.44 (1.4–3.7), but enhancing the differences in Vmax (0.186 (0.090–0.315) vs 0.120 (0.051–0.256) vs 0.128 (0.080–0.206) mmol Li · h–1· l erythrocytes–1, p 〈 0.0001). Of subjects with diabetic nephropathy, 78 % were outside the 75th percentile of the non-diabetic control subjects when Vmax and Vmax/Km(So) ratio were combined, compared to 20 % of the normoalbuminuric control subjects. We conclude that the traditional assay, V140, is poor at detecting individuals with diabetic nephropathy. Study of the kinetic parameters of the transporter, including thiol group modulation, suggests that increased ion association, Vmax/Km(So) ratio may represent the inherited defect and improves identification of subjects with diabetic nephropathy. [Diabetologia (1997) 40: 1079–1084]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050790
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  • 3
    Electronic Resource
    Electronic Resource
    The toxicity of alkyllead compounds to Scrobicularia plana (Da Costa) (1988)
    New York, NY [u.a.] : Wiley-Blackwell
    Applied Organometallic Chemistry 2 (1988), S. 143-149 
    Details
    ISSN: 0268-2605
    Keywords: Scrobicularia ; alkyllead compounds ; toxicity ; inhalent siphon ; bivalves ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Conventional (whole animal) toxicity tests were made with Scrobicularia plana (Da Costa), an infaunal estuarine bivalve, and compared with the responses recorded from siphonal preparations. Exposure of Scrobicularia to low concentrations of triethyllead chloride and trimethyllead chloride, for 35 and 60 days respectively, produced typical response curves. However, mortality had not become asymptotic with time at lower concentrations, suggesting further mortality with increased exposure time. An approximate incipient lethal concentration was predicted.A siphonal preparation technique with isolated and in-situ inhalent siphons of Scrobicularia was used to estimate the lowest effect concentrations of alkyllead compounds. Response to alkyllead was indicated by contraction of the siphon, recorded via an isotonic transducer. Trialkyllead compounds were more toxic than the respective dialkylleads and inorganic lead. Toxicity of trialklleads and inorganic lead. Toxicity of trialkylleads increased with alkyl chain length. Pure tetraethyllead did not cause any siphonal contraction even when applied directly to the preparation. It was concluded that tetraethyllead has a low toxicity or is non-toxic in pure form.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aoc.590020208
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  • 4
    Electronic Resource
    Electronic Resource
    The effects of organolead compounds on a freshwater and a marine alga (1987)
    New York, NY [u.a.] : Wiley-Blackwell
    Applied Organometallic Chemistry 1 (1987), S. 29-38 
    Details
    ISSN: 0268-2605
    Keywords: Algae ; alkyllead compounds ; toxicity ; alkyl chain length ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: There are conflicting reports concerning the toxicity of tetraalkyllead (TAL) compounds to algae. A number of groups have found the TAL's to be comparable in toxicity with the trialkyllead compounds (R3Pb+), whereas in a recent report it is suggested that the TAL's themselves are completely non-toxic and any apparent toxicity is due to R3Pb+ breakdown products.With the object of identifying the toxic agent, the effect of Et4Pb (TEL) on two algal species was re-examined. Analyses were carried out during the course of the incubations to establish the nature and concentrations of organoleads present in both media and algae, and hence evaluate their relative contributions to total toxicity.Algae were also cultured in the presence of Me4Pb (TML), Me3PbCl, Et3PbCl, Bu3PbCl and Et2PbCl2 to assess relationships between alkyl chain length and degree of substitution around the lead on algal activity. Additions of selenide and sulphide were made to the Et3Pb+ and Et2Pb2+ systems to see if these environmentally abundant species reduced or enhanced organolead toxicity. Problems were encountered in the analysis of the heterogeneous TEL containing media. Regardless of the analytical problems, the results confirm the previous findings that TAL's are non-toxic to algae and it is the R3Pb+ breakdown products which are responsible for the apparent toxicity of the TAL's. The trialkylleads were the most toxic of the several alkyllead species studied, and within the trialkyl series toxicity increased with alkyl chain length. Neither selenide or sulphide had any significant ameliorative effect on alkyllead toxicity. It was found that the ionic organoleads were complexed on the TAL's and this complexing led to a number of unexpected results.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/aoc.590010106
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