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1. Synthesis and In vitro evaluation of bichalcones as novel anti-toxoplasma agents

Author

Flaminia Mazzone, Moritz K. T. Klischan, Julian Greb, Sander H. J. Smits, Jörg Pietruszka, and Klaus Pfeffer

Subjects
Toxoplasma gondii, bichalcones, anti-infective, anti-toxoplasma, stereoisomers, biaryl, Chemistry, QD1-999
Abstract

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world’s human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa—1bg and axially chiral A-A′-connected bichalcones 2aa—2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (Ra)-enantiomer (Ra)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs.

Published
2024
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3. Synthesis and In vitro evaluation of bichalcones as novel anti-toxoplasma agents.

Author

Mazzone, Flaminia, Klischan, Moritz K. T., Greb, Julian, Smits, Sander H. J., Pietruszka, Jörg, Pfeffer, Klaus, Shaik, Afzal Basha, and Kasireddy, Sudarsan (Sudarshan)

Subjects
*TOXOPLASMA gondii, *STEREOISOMERS, *ISOMERISM, *BIOACTIVE compounds, *ANTI-infective agents
Abstract

Toxoplasmosis is a zoonotic disease caused by Toxoplasma gondii, an apicomplexan parasite that infects approximately a third of the world's human population. This disease can cause serious complications during pregnancy and can be fatal in immunocompromised hosts. The current treatment options for toxoplasmosis face several limitations. Thus, to address the urgent medical need for the discovery of novel anti-toxoplasma potential drug candidates, our research focused on exploring a series of monomeric and dimeric chalcones, polyphenolic molecules belonging to the class of flavonoids. Chalcones 1aa-1bg and axially chiral A-A'-connected bichalcones 2aa-2bg were evaluated in vitro against the proliferation of the parasite in a cell-based assay. A comparison of the efficacy demonstrated that, in several cases, bichalcones exhibited increased bioactivity compared to their corresponding monomeric counterparts. Among these compounds, a bichalcone with a phenyl substituent and a methyl moiety 2ab showed the most potent and selective inhibitory activity in the nanomolar range. Both enantiomers of this bichalcone were synthesized using an axially chiral biphenol building block. The biaryl bond was forged using Suzuki cross-coupling in water under micellar catalysis conditions. Separation of the atropisomers of this biphenol building block was conducted by chiral HPLC on a preparative scale. The biological evaluation of the enantiomers revealed that the (Ra)-enantiomer (Ra)-2ab is the eutomer. These studies suggest that bichalcones may be important drug candidates for further in vivo evaluations for the discovery of anti-toxoplasma drugs. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Success Factors for Strategic Partnerships in the Biotechnology Sector

Author

Kehrel, U, Klischan, K, Sick, N, Kehrel, U, Klischan, K, and Sick, N

Abstract

Over half of all research-oriented partnerships in the biotechnology industry fail due to problems in inter-organizational relationships. The analysis of factors that determine the success of strategic partnerships can help companies reduce the high failure rates. Based on the resourceoriented and relationship-oriented approach, this chapter examines the influence of three structural factors and three dynamic factors on the success of strategic, research-oriented partnerships in the biotechnology industry. In the empirical analysis, data from 48 research collaborations by 28 companies were collected and analyzed. The results confirm the significant influence of the factors “complementary resources”, “operational compatibility”, “bilateral exchange of information”, and “opportunistic behavior”. On the basis of these findings, companies can identify approaches to influence the success of their own research collaborations. In particular, appropriate recommendations for action can be derived in the context of the structural design of partnerships and the dynamic exchange process.

Published
2019

8. Protein intake and urinary albumin excretion rates in the EURODIAB IDDM Complications Study

Author

Toeller, M, Buyken, A, Heitkamp, G, Brämswig, S, Mann, J, Milne, R, Gries, F. A, Keen, H, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Klischan, A, Forst, T, Schumacher, W, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, Mitchell, DAVID ROSS, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Djs, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, Manuel, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, Sivieri, P., R, Carta, Q, Petraroli, G, Papazoglu, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Henio, Ev, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Vrhovac, V., Toeller, M, Buyken, A, Heitkamp, G, Bramswig, S, Mann, J, Milne, R, Gries, Fa, Keen, H, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Klischan, A, Forst, T, Schumacher, W, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Dj, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglu, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, and Vrhovac, V

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Urinary system, Physiology, Albuminuria, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Dietary Proteins, Europe, Female, Humans, Middle Aged, Nephropathy, Protein intake, urinary albumin, Diabetic nephropathy, Excretion, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Internal Medicine, Medicine, Proteinuria, business.industry, medicine.disease, Endocrinology, Blood pressure, medicine.symptom, business, Type 1, Kidney disease
Abstract

For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection. Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20 % of total food energy intake, mean AER was below 20 μg/min. In those in whom protein intake constituted more than 20 %, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83). These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20 % of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 μg/min (approximately 30 mg/24 h), especially when arterial pressure is raised and/or diabetic control is poor. [Diabetologia (1997) 40: 1219–1226]

Published
1997

9. Why Research Partnerships Fail in the Biotechnology Sector-An Empirical Analysis of Strategic Partnerships

Author

Kehrel, U, Klischan, K, Sick, N, Kehrel, U, Klischan, K, and Sick, N

Abstract

Over half of all research-oriented partnerships in the biotechnology industry fail due to problems in inter-organizational relationships. The analysis of factors that determine the success of strategic partnerships can help companies to reduce the high failure rates. Based on the resource-oriented and relationship-oriented approach, this study examines the influence of three structural factors and three dynamic factors on the success of strategic, research-oriented partnerships in the biotechnology industry. In the empirical study, data of 48 research collaborations by 28 companies were collected and analyzed. The results confirm the significant influence of the factors "complementary resources", "operational compatibility", "bilateral exchange of information" and "opportunistic behavior". On the basis of these findings, companies can find approaches to influence the success of their own research collaborations. In particular, appropriate recommendations for action can be formulated in the areas of the structural design of partnerships and the dynamic exchange process.

Published
2016

11. Why Research Partnerships Fail in the Biotechnology Sector — An Empirical Analysis of Strategic Partnerships

Author

Nathalie Sick, Kai Klischan, and Uwe Kehrel

Subjects
Empirical research, Exchange of information, Strategic partnership, Management of Technology and Innovation, 0502 economics and business, 05 social sciences, 050211 marketing, Business, Marketing, 050203 business & management, Industrial organization, Biotechnology industry
Abstract

Over half of all research-oriented partnerships in the biotechnology industry fail due to problems in inter-organizational relationships. The analysis of factors that determine the success of strategic partnerships can help companies to reduce the high failure rates. Based on the resource-oriented and relationship-oriented approach, this study examines the influence of three structural factors and three dynamic factors on the success of strategic, research-oriented partnerships in the biotechnology industry. In the empirical study, data of 48 research collaborations by 28 companies were collected and analyzed. The results confirm the significant influence of the factors “complementary resources”, “operational compatibility”, “bilateral exchange of information” and “opportunistic behavior”. On the basis of these findings, companies can find approaches to influence the success of their own research collaborations. In particular, appropriate recommendations for action can be formulated in the areas of the structural design of partnerships and the dynamic exchange process.

Published
2016

12. Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study

Author

Greaves, M, Malia, Rg, Goodfellow, K, Mattock, M, Stevens, Lk, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Segato, T, Midena, E, Cipollina, Mr, Fedele, D, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Navelesi, R, Sjolie, Ak, Viberti, Gc, Ward, J, Partridge, T, John, Wg, Collins, A, Dredge, A, Sharp, R, Kohner, E, Aldington, S, Cockley, S., Greaves, M, Malia, Rg, Goodfellow, K, Mattock, M, Stevens, Lk, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Dj, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Francesco, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Segato, T, Midena, E, Cipollina, Mr, Fedele, D, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Navelesi, R, Sjolie, Ak, Viberti, Gc, Ward, J, Partridge, T, John, Wg, Collins, A, Dredge, A, Sharp, R, Kohner, E, Aldington, S, and Cockley, S.

Subjects
Blood Glucose, Male, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, Blood lipids, Blood Pressure, Fibrinogen, Body Mass Index, Risk Factors, biology, Smoking, von Willebrand factor, fibrinogen, The EURODIAB IDDM Study, Europe, Cholesterol, Cardiovascular Diseases, Female, medicine.symptom, medicine.drug, Type 1, Adult, medicine.medical_specialty, HDL, LDL, Von Willebrand factor, Internal medicine, Diabetes mellitus, von Willebrand Factor, Internal Medicine, medicine, Diabetes Mellitus, Humans, Albuminuria, Cholesterol, HDL, Cholesterol, LDL, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Diabetic Angiopathies, Triglycerides, Glycated Hemoglobin, business.industry, Vascular disease, medicine.disease, Blood pressure, Endocrinology, biology.protein, Microalbuminuria, business
Abstract

The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 European countries: the EURODIAB IDDM Complications study. The anticipated significant relationships between both plasma fibrinogen and plasma von Willebrand factor concentrations and age and glycaemic control, and between fibrinogen and body mass index, were noted. Fibrinogen, adjusted for age and glycated haemoglobin concentration, was also related to smoking habits and was higher in the quartiles with highest systolic and diastolic blood pressures. There was a clustering of vascular risk factors, with a positive relationship between plasma fibrinogen and serum triglyceride concentrations in both genders and between fibrinogen and total cholesterol in males. An inverse relationship between fibrinogen and high density lipoprotein cholesterol was also apparent in males. A prominent feature was a positive relationship between both fibrinogen and von Willebrand factor and albumin excretion rate (p < 0.001 and p < 0.003 respectively) in those with retinopathy but not in these without this complication. In view of previous observations on blood pressure and albuminuria in these subjects the findings are consistent with the hypothesis that microalbuminuria and increased plasma von Willebrand factor are due to endothelial cell perturbation in response to mildly raised blood pressure in subjects with retinopathy. Fibrinogen may also contribute to microvascular disease and its relationships to lipid vascular risk factors suggest a possible pathogenic role in arterial disease in diabetes.

Published
1997

13. Nutritional intake of 2868 IDDM patients from 30 centres in Europe

Author

Toeller, M, Klischan, A, Heitkamp, G, Schumacher, W, Milne, R, Buyken, A, Karamanos, B, Gries, Fa, Fuller, Jh, Keen, H, Krans, Hmj, Navalesi, R, Sjolie, Ak, Stephenson, Jm, Viberti, Gc, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Forst, T, Wagener, W, Venhaus, A, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Lemkes, Hhpj, Janse, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Alfonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Djs, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Bourgeois, Md, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z., Toeller, M, Klischan, A, Heitkamp, G, Schumacher, W, Milne, R, Buyken, A, Karamanos, B, Gries, Fa, Fuller, Jh, Keen, H, Krans, Hmj, Navalesi, R, Sjolie, Ak, Stephenson, Jm, Viberti, Gc, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Forst, T, Wagener, W, Venhaus, A, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Lemkes, Hhpj, Janse, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Alfonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Dj, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Francesco, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Bourgeois, Md, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
medicine.medical_specialty, education.field_of_study, Cross-sectional study, business.industry, Endocrinology, Diabetes and Metabolism, Saturated fat, Population, Nutritional intake, IDDM patients, medicine.disease, Diet Records, Endocrinology, Internal medicine, Diabetes mellitus, Cohort, Internal Medicine, medicine, Population study, education, business, Cohort study
Abstract

The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme.

Published
1996

14. Cardiovascular disease and its risk factors in IDDM in Europe

Author

Koivisto VA, Stevens LK, Mattock M, Ebeling P, Muggeo M, Stephenson J, IdziorWalus B, Karamanos B, Tountas C, Kofinis A, Petrou K, Katsilambros N, Cignarelli M, Giorgino R, DeGeco ML, Ramunni I, IonescuTirgoviste C, Iosif CM, Pitei C, Buligescu S, Tamas G, Kerenyi Z, Ahmed AM, Toth J, Kempler P, Muntoni S, Songini M, Stabilini M, Fossarello M, Pintus S, Ferris B, Cronin CC, Toeller M, Klischan A, Forst T, Gries FA, Wagener W, Rottiers R, Priem H, Sinisalo M, Solnica B, SzopinskaCiba L, Solnica K, Krans M, Lemkes HHPJ, Jansen JJ, NunesCorrea J, Rogado C, Boavida JM, Correia LG, Michel G, Wirion R, Boulton AJM, Ashe H, Fernando DJS, Pozza G, Slaviero G, Comi B, Fattor F, Janka HU, Nuber A, Mehnert H, BenSoussan D, Fallas MC, Fallas P, Jepson E, McHardyYoung S, Fuller JH, Betteridge DJ, Milne M, Crepaldi C, Nosadini R, Cathelineau G, Cathelineau BV, Jellal M, Grodner N, Feiss PG, Santeusanio F, Rosi G, Cagini C, Marino C, Navalesi R, Penno G, Miccoli R, Nannipieri M, Stefano M, Ghirlanda G, Controneo P, Manto A, Teodonio C, Minnella A, Ward JD, Tesfaye S, Mody C, Rudd C, Molinatti GM, Vitelli F, Porta M, Pagano GF, Estivi P, Sivieri R, Carta Q, Petraroli G, Papazoglou N, Manes G, Triantaphyllou G, Ioannides A, Cacciatori V, Bellavere F, Galante P, Gemma ML, Irsigler K, Abrahamian H, Gurdet C, Hornlein B, Willinger C, Walford S, Wardle EV, Roglic G, Resman Z, Metelko Z, Skrabalo Z, Keen H, Sjolie AK, Viberti GC, Ward J, John G, Collins A, Sharp R., BANDELLO , FRANCESCO, Koivisto, Va, Stevens, Lk, Mattock, M, Ebeling, P, Muggeo, M, Stephenson, J, Idziorwalus, B, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, C, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferris, B, Cronin, Cc, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, R, Priem, H, Sinisalo, M, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, M, Lemkes, Hhpj, Jansen, Jj, Nunescorrea, J, Rogado, C, Boavida, Jm, Correia, Lg, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Dj, Pozza, G, Slaviero, G, Comi, B, Fattor, F, Bandello, Francesco, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Crepaldi, C, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Stefano, M, Ghirlanda, G, Controneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Sjolie, Ak, Viberti, Gc, Ward, J, John, G, Collins, A, and Sharp, R.

Subjects
medicine.medical_specialty, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Cardiovascular disease, EURODIAB IDDM study, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Risk factor, education, Advanced and Specialized Nursing, education.field_of_study, business.industry, medicine.disease, 3. Good health, Endocrinology, Blood pressure, Albuminuria, Metabolic syndrome, medicine.symptom, business
Abstract

OBJECTIVE To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean ± SD duration of diabetes was 14.7 ± 9.3 years. RESULTS The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15–29 years old to 25% in patients 45–59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS The overall prevalence of CVD in these IDDM patients was ∼ 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

Published
1996

15. BLOOD-PRESSURE, RETINOPATHY AND URINARY ALBUMIN EXCRETION IN IDDM - THE EURODIAB IDDM COMPLICATIONS STUDY

Author

Stephenson, Jm, Fuller, Jh, Viberti, Gc, Sjolie, Ak, Navalesi, R, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, M, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Mehnert, H, Nuber, A, Janka, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
Adult, Male, medicine.medical_specialty, THE EURODIAB IDDM COMPLICATIONS STUDY, Endocrinology, Diabetes and Metabolism, Urology, Blood Pressure, Nephropathy, Diabetic nephropathy, Diastole, Reference Values, Risk Factors, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Confidence Intervals, Prevalence, Albuminuria, Humans, Age of Onset, Proteinuria, Diabetic Retinopathy, business.industry, Diabetic retinopathy, medicine.disease, Europe, Endocrinology, Blood pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, medicine.symptom, business, Retinopathy
Abstract

Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (20 micrograms/min) below median diastolic pressure (75 mmHg) and increased steeply (p0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk.

Published
1995

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