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2. Effects of Manidipine and Delapril in Hypertensive Patients With Type 2 Diabetes Mellitus

Author

Ruggenenti, P, Lauria, G, Iliev, IP, Fassi, A, Ilieva, AP, Rota, S, Chiurchiu, C, Barlovic, DP, Sghirlanzoni, A, Lombardi, R, Penza, P, CAVALETTI, GUIDO ANGELO, Piatti, ML, Frigeni, B, Filipponi, M, Rubis, N, Noris, G, Motterlini, N, Ene Iordache, B, Gaspari, F, Perna, A, Zaletel, J, Bossi, A, Dodesini, AR, TREVISAN, ROBERTO, Remuzzi, G, DEMAND Study Investigators, Parvanova, IA, Petrov, II, Yakymchuk, S, Arnoldi, F, Prandini, S, Kocijancic, A, Pongrac, D, Prezelj, J, Gala, T, Kersnik, M, Trevisan, G, Lepore, G, Mondo, E, Inversi, F, Mangili, R, Bruno, S, Brusegan, V, Lecchi, V, Belviso, A, Genovese, S, Pareyson, D, Camozzi, F, Cavaletti, G, Marzorati, L, MARMIROLI, PAOLA LORENA, Mattavelli, L, Tadini, S, Gherardi, G, Calini, W, Diadei, O, Rossoni, D, Villa, D, Carminati, S, Agus, E, Remuzzi, A, Giuliano, GA, Ganeva, M, Cannata, AN, Carrara, F, Cella, C, Centemeri, E, Ferrari, S, Petrò, C, Savoldelli, E, Stucchi, N, Boccardo, P, Perico, N, Peracchi, S, Gelmi, S, Mecca, G, Imbimbo, B, Alberici, M, Gardini, F, Lauria, G., Ruggenenti, P, Lauria, G, Iliev, I, Fassi, A, Ilieva, A, Rota, S, Chiurchiu, C, Barlovic, D, Sghirlanzoni, A, Lombardi, R, Penza, P, Cavaletti, G, Piatti, M, Frigeni, B, Filipponi, M, Rubis, N, Noris, G, Motterlini, N, Ene Iordache, B, Gaspari, F, Perna, A, Zaletel, J, Bossi, A, Dodesini, A, Trevisan, R, Remuzzi, G, DEMAND Study, I, Parvanova, I, Petrov, I, Yakymchuk, S, Arnoldi, F, Prandini, S, Kocijancic, A, Pongrac, D, Prezelj, J, Gala, T, Kersnik, M, Trevisan, G, Lepore, G, Mondo, E, Inversi, F, Mangili, R, Bruno, S, Brusegan, V, Lecchi, V, Belviso, A, Genovese, S, Pareyson, D, Camozzi, F, Marzorati, L, Marmiroli, P, Mattavelli, L, Tadini, S, Gherardi, G, Calini, W, Diadei, O, Rossoni, D, Villa, D, Carminati, S, Agus, E, Remuzzi, A, Giuliano, G, Ganeva, M, Cannata, A, Carrara, F, Cella, C, Centemeri, E, Ferrari, S, Petrò, C, Savoldelli, E, Stucchi, N, Boccardo, P, Perico, N, Peracchi, S, Gelmi, S, Mecca, G, Imbimbo, B, Alberici, M, and Gardini, F

Subjects
Adult, Blood Glucose, Male, Dihydropyridines, medicine.medical_specialty, Diabetic neuropathy, Urology, Renal function, Delapril, Angiotensin-Converting Enzyme Inhibitors, Kidney Function Tests, Placebo, Risk Assessment, Severity of Illness Index, Drug Administration Schedule, Piperazines, Body Mass Index, Manidipine, Double-Blind Method, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Diabetic Nephropathies, Nitrobenzenes, Aged, Dose-Response Relationship, Drug, diabetes, business.industry, Hazard ratio, Middle Aged, Calcium Channel Blockers, Prognosis, medicine.disease, Survival Rate, Treatment Outcome, Endocrinology, Diabetes Mellitus, Type 2, Hypertension, Indans, Albuminuria, Drug Therapy, Combination, Female, medicine.symptom, business, medicine.drug
Abstract

To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria 2 (IQR: 0.16–0.50 mL/min per 1.73 m 2 ) on combined therapy, 0.36 mL/min per 1.73 m 2 (IQR: 0.18–0.53 mL/min per 1.73 m 2 ) on delapril, and 0.30 mL/min per 1.73 m 2 (IQR: 0.12–0.50 mL/min per 1.73 m 2 ) on placebo ( P =0.87 and P =0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04–0.78; P =0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07–0.99; P =0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24–0.87; P =0.017) and 0.52 (0.27–0.99; P =0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo ( P =0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline but safely ameliorated cardiovascular disease, retinopathy, and neuropathy and stabilized insulin sensitivity.

Published
2011

3. Effects of Manidipine and Delapril in Hypertensive Patients With Type 2 Diabetes Mellitus: The Delapril and Manidipine for Nephroprotection in Diabetes (DEMAND) Randomized Clinical Trial

Author

Ruggenenti, P, Lauria, G, Iliev, I, Fassi, A, Ilieva, A, Rota, S, Chiurchiu, C, Barlovic, D, Sghirlanzoni, A, Lombardi, R, Penza, P, Cavaletti, G, Piatti, M, Frigeni, B, Filipponi, M, Rubis, N, Noris, G, Motterlini, N, Ene Iordache, B, Gaspari, F, Perna, A, Zaletel, J, Bossi, A, Dodesini, A, Trevisan, R, Remuzzi, G, DEMAND Study, I, Parvanova, I, Petrov, I, Yakymchuk, S, Arnoldi, F, Prandini, S, Kocijancic, A, Pongrac, D, Prezelj, J, Gala, T, Kersnik, M, Trevisan, G, Lepore, G, Mondo, E, Inversi, F, Mangili, R, Bruno, S, Brusegan, V, Lecchi, V, Belviso, A, Genovese, S, Pareyson, D, Camozzi, F, Marzorati, L, Marmiroli, P, Mattavelli, L, Tadini, S, Gherardi, G, Calini, W, Diadei, O, Rossoni, D, Villa, D, Carminati, S, Agus, E, Remuzzi, A, Giuliano, G, Ganeva, M, Cannata, A, Carrara, F, Cella, C, Centemeri, E, Ferrari, S, Petrò, C, Savoldelli, E, Stucchi, N, Boccardo, P, Perico, N, Peracchi, S, Gelmi, S, Mecca, G, Imbimbo, B, Alberici, M, Gardini, F, Iliev, IP, Ilieva, AP, Barlovic, DP, CAVALETTI, GUIDO ANGELO, Piatti, ML, Dodesini, AR, TREVISAN, ROBERTO, DEMAND Study Investigators, Parvanova, IA, Petrov, II, MARMIROLI, PAOLA LORENA, Giuliano, GA, Cannata, AN, Lauria, G., Ruggenenti, P, Lauria, G, Iliev, I, Fassi, A, Ilieva, A, Rota, S, Chiurchiu, C, Barlovic, D, Sghirlanzoni, A, Lombardi, R, Penza, P, Cavaletti, G, Piatti, M, Frigeni, B, Filipponi, M, Rubis, N, Noris, G, Motterlini, N, Ene Iordache, B, Gaspari, F, Perna, A, Zaletel, J, Bossi, A, Dodesini, A, Trevisan, R, Remuzzi, G, DEMAND Study, I, Parvanova, I, Petrov, I, Yakymchuk, S, Arnoldi, F, Prandini, S, Kocijancic, A, Pongrac, D, Prezelj, J, Gala, T, Kersnik, M, Trevisan, G, Lepore, G, Mondo, E, Inversi, F, Mangili, R, Bruno, S, Brusegan, V, Lecchi, V, Belviso, A, Genovese, S, Pareyson, D, Camozzi, F, Marzorati, L, Marmiroli, P, Mattavelli, L, Tadini, S, Gherardi, G, Calini, W, Diadei, O, Rossoni, D, Villa, D, Carminati, S, Agus, E, Remuzzi, A, Giuliano, G, Ganeva, M, Cannata, A, Carrara, F, Cella, C, Centemeri, E, Ferrari, S, Petrò, C, Savoldelli, E, Stucchi, N, Boccardo, P, Perico, N, Peracchi, S, Gelmi, S, Mecca, G, Imbimbo, B, Alberici, M, Gardini, F, Iliev, IP, Ilieva, AP, Barlovic, DP, CAVALETTI, GUIDO ANGELO, Piatti, ML, Dodesini, AR, TREVISAN, ROBERTO, DEMAND Study Investigators, Parvanova, IA, Petrov, II, MARMIROLI, PAOLA LORENA, Giuliano, GA, Cannata, AN, and Lauria, G.

Abstract

To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127). GFR was centrally measured by iohexol plasma clearance. Median monthly GFR decline (interquartile range [IQR]) was 0.32 mL/min per 1.73 m(2) (IQR: 0.16-0.50 mL/min per 1.73 m(2)) on combined therapy, 0.36 mL/min per 1.73 m(2) (IQR: 0.18-0.53 mL/min per 1.73 m(2)) on delapril, and 0.30 mL/min per 1.73 m(2) (IQR: 0.12-0.50 mL/min per 1.73 m(2)) on placebo (P=0.87 and P=0.53 versus combined therapy or delapril, respectively). Similar findings were observed when baseline GFR values were not considered for slope analyses. Albuminuria was stable in the 3 treatment groups. The hazard ratio (95% CI) for major cardiovascular events between combined therapy and placebo was 0.17 (0.04-0.78; P=0.023). Among 192 subjects without retinopathy at inclusion, the hazard ratio for developing retinopathy between combined therapy and placebo was 0.27 (0.07-0.99; P=0.048). Among 200 subjects with centralized neurological evaluation, the odds ratios for peripheral neuropathy at 3 years between combined therapy or delapril and placebo were 0.45 (0.24-0.87; P=0.017) and 0.52 (0.27-0.99; P=0.048), respectively. Glucose disposal rate decreased from 5.8±2.4 to 5.3±1.9 mg/kg per min on placebo (P=0.03) but did not change on combined or delapril therapy. Treatment was well tolerated. In hypertensive type 2 diabetic patients, combined manidipine and delapril therapy failed to slow GFR decline bu

Published
2011

5. Meperidine in detoxification of hospitalized heroin addicts.

Author

Besana C, Memoli M, Salvioni PM, Finazzi RA, Inversi F, and Rugarli C

Subjects
Administration, Oral, Adolescent, Adult, Combined Modality Therapy, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Heroin Dependence psychology, Humans, Male, Middle Aged, Patient Dropouts psychology, Substance Abuse, Intravenous rehabilitation, Heroin Dependence rehabilitation, Hospitalization, Meperidine administration & dosage
Abstract

Forty-six heroin abusers were hospitalized and treated with meperidine either alone or in association with clonidine. Meperidine was given orally in rapidly decreasing doses according to three different schedules. The majority of patients (87%) successfully completed the detoxification program. The best meperidine starting posology was 200 mg four times daily, which allowed stoppage of the opioid treatment after gradual reduction of the daily dose in a mean time of 9.5 days. Association with clonidine was not proven to be useful. This study shows that meperidine can be effectively used in rapidly decreasing doses in the pharmacological detoxification treatment of hospitalized heroin addicts.

Published
1991
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6. Evidence for adenosine adenosinedeaminase lymphocyte system impairment in ageing.

Author

Crosti F, Ciboddo GF, Barbieri MC, Inversi F, Pavoni D, Quarenghi S, Navone P, Vezzoni P, and Rugarli C

Subjects
Aged, Aging metabolism, Concanavalin A, Humans, Middle Aged, Adenosine pharmacology, Adenosine Deaminase metabolism, Aging immunology, Lymphocyte Activation drug effects, Lymphocytes enzymology, Nucleoside Deaminases metabolism
Abstract

Age related immune disfunctions are the result of humoral and cellular changes of the immune system and reflect major alterations of T cell subpopulations which concern cyclic nucleotides and their precursors. There are now many reports showing that adenosine can affect some phenotypic and functional lymphocyte characteristics. We have found that a short preincubation (30') with adenosine can inhibit proliferative responses of peripheral blood lymphocytes to polyclonal mitogen Concanavalin A in young healthy controls (p less than 0.05) but not in aged healthy subjects. These data led us to the hypothesis that an impairment of the adenosine-adenosinedeaminase system could play an important role in the age-associated decline of immune responses. Our results show a highly significant reduction (16.45 +/- 3.56 vs 24.42 +/- 9.5 p less than 0.001) of adenosinedeaminase activity in peripheral lymphocytes of aged humans (mean age 75.5 +/- 6.7 range 23-30). Preliminary studies suggest that this alteration could be responsible to some extent, for the decreased mitogenic response of lymphocytes reported in ageing.

Published
1987

7. [Lyme borreliosis].

Author

Arlotta B, Inversi F, Chekikian G, Gorla E, and Besana C

Subjects
Anti-Bacterial Agents therapeutic use, Diagnosis, Differential, Humans, Lyme Disease diagnosis, Lyme Disease therapy
Published
1988

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