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4. Atazanavir and darunavir in pregnant women with HIV: evaluation of laboratory and clinical outcomes from an observational national study

Author

Floridia, M., Masuelli, G., Ravizza, M., Tassis, B., Cetin, I., Sansone, M., Antoni, A. D., Simonazzi, G., Maccabruni, A., Francisci, D., Frisina, V., Liuzzi, G., Dalzero, S., Tamburrini, E., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., S. Mercurio V., Zanaboni, D., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Antoni, A. M. D., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Maso, G., Rizzante, E., Belcaro, C., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., Bordonivicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Crupano, F. M., Calabretti, D., Cervi, F., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Tiso, G. C., Genovese, O., Cafforio, C., Pinnetti, C., Casadei, A. M., Cavaliere, A. F., Cellini, M., Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Parazzini, F., Vella, S., Floridia, M., Masuelli, G., Ravizza, M., Tassis, B., Cetin, I., Sansone, M., Antoni, A. Degli, Simonazzi, G., Maccabruni, A., Francisci, D., Frisina, V., Liuzzi, G., Dalzero, S., Tamburrini, E., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., S.Mercurio, V., Zanaboni, D., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Antoni, A.M. Degli, Molinari, A., Crisalli, M.P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Maso, G., Rizzante, E., Belcaro, C., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., BordoniVicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Crupano, F.M., Calabretti, D., Cervi, F., Margarito, E., Capretti, M.G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G.M., Tibaldi, C., Trentini, L., Todros, T., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Tiso, G.C., Genovese, O., Cafforio, C., Pinnetti, C., Casadei, A.M., Cavaliere, A.F., Cellini, M., Marconi, A.M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M.F., Amici, R., Galluzzo, C.M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Parazzini, F., and Vella, S.

Subjects
Male, 0301 basic medicine, medicine.medical_treatment, HIV Infections, 0302 clinical medicine, Pregnancy, Pharmacology (medical), 030212 general & internal medicine, Pregnancy Complications, Infectious, Darunavir, medicine.diagnostic_test, Obstetrics, Pregnancy Outcome, virus diseases, Alanine Transaminase, Viral Load, Cholesterol, Treatment Outcome, Infectious Diseases, Premature birth, Gestation, Female, Drugs in pregnancy, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Anti-HIV Agents, Atazanavir Sulfate, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, pharmacology, pharmacology (medical), infectious diseases, medicine, Humans, Caesarean section, Triglycerides, Pharmacology, business.industry, Infant, Newborn, Infant, Bilirubin, medicine.disease, 030112 virology, Atazanavir, azatanavir sulfate, Lipid profile, business
Abstract

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Published
2017

7. Structural domains involved in substrate selectivity in two neutral amino acid transporters

Author

Soragna, Andrea, Anna Mari, Stefania, Pisani, Rossana, Peres, Antonio, Castagna, Michela, Sacchi, V. Franca, and Bossi, Elena

Subjects
Amino acid metabolism, Epithelium, Larvae, Biological sciences
Abstract

The ability of the two highly homologous [Na.sup.+]/[Cl.sup.-]-dependent neutral amino acid transporters KAAT1 and CAATCH1, cloned from the midgut epithelium of the larva Manduca sexta, to transport different amino acids depends on the cotransported ion, on pH, and on the membrane voltage. Different organic substrates give rise to transport-associated currents with their own characteristics, which are notably distinct between the two proteins. Differences in amplitude, kinetics, and voltage dependence of the transport-associated currents have been observed, as well as different substrate selectivity patterns measured by radioactive amino acid uptake assays. These diversities represent useful tools to investigate the structural determinants involved in the substrate selectivity. To identify these regions, we built four chimeric proteins between the two transporters. These proteins, heterologously expressed in Xenopus laevis oocytes, were analyzed by two-electrode voltage clamp and uptake measurements. Initially, we exchanged the first three domains, obtaining the chimeras C3K9 and K3C9 (where numbers indicate the transmembrane domains and letters represent the original proteins), which showed electrophysiological and [[sup.3]H]amino acid uptake characteristics resembling those of KAAT1 and CAATCH1, respectively. Subsequent substitution of the last four domains in C3K9 and K3C9 gave the proteins C3K5C4 and K3C5K4, which showed the same behavior as KAAT1 and CAATCH1 in electrophysiological and transport determinations. These results suggest that in KAAT1 and CAATCH1, only the central transmembrane domains (from 4 to 8) of the protein are responsible for substrate selectivity. structure and function; Manduca sexta

Published
2004

9. Glutamate 59 is critical for transport function of the amino acid cotransporter KAAT1

Author

Sacchi, V. Franca, Castagna, Michela, Mari, Stefania A., Perego, Carla, Bossi, Elena, and Peres, Antonio

Subjects
Amino acids -- Research, Biological sciences
Abstract

KAAT1 is a neutral amino acid transporter activated by [K.sup.+] or by [Na.sup.+] (9). The protein shows significant homology with members of the [Na.sup.+]/[Cl.sup.-] -dependent neurotransmitter transporter super family. E59G KAAT1, expressed in Xenopus oocytes, exhibited a reduced leucine uptake [20-30% of wild-type (WT)], and kinetic analysis indicated that the loss of activity was due to reduction of [V.sub.max] and apparent affinity for substrates. Electrophysiological analysis revealed that E59G KAAT1 has presteady-state and uncoupled currents larger than WT but no leucine-induced currents. Site-directed mutagenesis analysis showed the requirement of a negative charge in position 59 of KAAT1. The analysis of permeant and impermeant methanethiosulfonate reagent effects confirmed the intracellular localization of glutamate 59. Because the 2-aminoethyl methanethiosulfonate hydrobromid inhibition was not prevented by the presence of [Na.sup.+] or leucine, we concluded that E59 is not directly involved in the binding of substrates. N-ethylmaleimide inhibition was qualitatively and quantitatively different in the two transporters, WT and E59G KAAT1, having the same cysteine residues. This indicates an altered accessibility of native cysteine residues due to a modified spatial organization of E59G KAAT1. The arginine modifier phenylglyoxal effect supports this hypothesis: not only cysteine but also arginine residues become more accessible to the modifying reagents in the mutant E59G. In conclusion, the results presented indicate that glutamate 59 plays a critical role in the three-dimensional organization of KAAT1. amino acid transport; structure/function; amino acid modifiers; Manduca sexta

Published
2003

10. Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series

Author

Floridia M, Masuelli G, Meloni A, Cetin I, Tamburrini E, Cavaliere AF, Dalzero S, Sansone M, Alberico S, Guerra B, Spinillo A, Chiadò Fiorio Tin M, Ravizza M, Mori F, Ortolani P, Dalle Nogare ER, Di Lorenzo F, Sterrantino G, Meli M, Polemi S, Nocentini J, Baldini M, Montorzi G, Mazzetti M, Rogasi P, Borchi B, Vichi F, Del Pin B, Pinter E, Anzalone E, Marocco R, Mastroianni C, Mercurio VS, Carocci A, Grilli E, Maccabruni A, Zaramella M, Mariani B, Natalini Raponi G, Guaraldi G, Nardini G, Stentarelli C, Beghetto B, Degli Antoni AM, Molinari A, Crisalli MP, Donisi A, Piepoli M, Cerri V, Zuccotti G, Giacomet V, Coletto S, Di Nello F, Madia C, Placido G, Vivarelli A, Castelli P, Savalli F, Portelli V, Sabbatini F, Francisci D, Bernini L, Grossi P, Rizzi L, Maso G, Airoud M, Soppelsa G, Dedoni M, Cuboni C, Ortu F, Piano P, Citernesi A, Bordoni Vicini I, Luzi K, Roccio M, Vimercati A, Miccolis A, De Gennaro A, Cervi F, Simonazzi G, Margarito E, Capretti MG, Marsico C, Faldella G, Martinelli P, Agangi A, Capone A, Maruotti GM, Tibaldi C, Trentini L, Todros T, Frisina V, Brambilla T, Savasi V, Personeni C, Giaquinto C, Fiscon M, Rubino E, Bucceri A, Matrone R, Scaravelli G, Genovese O, Cafforio C, Pinnetti C, Liuzzi G, Tozzi V, Massetti P, Casadei AM, Cellini M, Castelli Gattinara G, Marconi AM, Sacchi V, Ierardi M, Polizzi C, Mattei A, Pirillo MF, Amici R, Galluzzo CM, Donnini S, Baroncelli S, Villani P, Cusato M, Cerioli A, De Martino M, Mastroiacovo P, Parazzini F, Vella S., Floridia M, Masuelli G, Meloni A, Cetin I, Tamburrini E, Cavaliere AF, Dalzero S, Sansone M, Alberico S, Guerra B, Spinillo A, Chiadò Fiorio Tin M, Ravizza M, and Mori F, Ortolani P, Dalle Nogare ER, Di Lorenzo F, Sterrantino G, Meli M, Polemi S, Nocentini J, Baldini M, Montorzi G, Mazzetti M, Rogasi P, Borchi B, Vichi F, Del Pin B, Pinter E, Anzalone E, Marocco R, Mastroianni C, Mercurio VS, Carocci A, Grilli E, Maccabruni A, Zaramella M, Mariani B, Natalini Raponi G, Guaraldi G, Nardini G, Stentarelli C, Beghetto B, Degli Antoni AM, Molinari A, Crisalli MP, Donisi A, Piepoli M, Cerri V, Zuccotti G, Giacomet V, Coletto S, Di Nello F, Madia C, Placido G, Vivarelli A, Castelli P, Savalli F, Portelli V, Sabbatini F, Francisci D, Bernini L, Grossi P, Rizzi L, Maso G, Airoud M, Soppelsa G, Dedoni M, Cuboni C, Ortu F, Piano P, Citernesi A, Bordoni Vicini I, Luzi K, Roccio M, Vimercati A, Miccolis A, De Gennaro A, Cervi F, Simonazzi G, Margarito E, Capretti MG, Marsico C, Faldella G, Martinelli P, Agangi A, Capone A, Maruotti GM, Tibaldi C, Trentini L, Todros T, Frisina V, Brambilla T, Savasi V, Personeni C, Giaquinto C, Fiscon M, Rubino E, Bucceri A, Matrone R, Scaravelli G, Genovese O, Cafforio C, Pinnetti C, Liuzzi G, Tozzi V, Massetti P, Casadei AM, Cellini M, Castelli Gattinara G, Marconi AM, Sacchi V, Ierardi M, Polizzi C, Mattei A, Pirillo MF, Amici R, Galluzzo CM, Donnini S, Baroncelli S, Villani P, Cusato M, Cerioli A, De Martino M, Mastroiacovo P, Parazzini F, Vella S.

Subjects
Infectious Disease Transmission, Prenatal diagnosis, HIV Infections, 0302 clinical medicine, Birth defect, Pregnancy, Odds Ratio, Vertical, Medicine, 030212 general & internal medicine, Pregnancy Complications, Infectious, education.field_of_study, Amniocentesi, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Obstetrics, Infectious, Obstetrics and Gynecology, Amniocentesis, birth defects, chorionic villus sampling, HIV, invasive testing, mother-to child HIV transmission, pregnancy, prenatal diagnosis, Birth defects, Chorionic villus sampling, Invasive testing, Mother-to child HIV transmission, Anti-Retroviral Agents, Chorionic Villi Sampling, Female, Adult, medicine.medical_specialty, Prenatal diagnosi, Population, Settore MED/17 - MALATTIE INFETTIVE, 03 medical and health sciences, Humans, education, Fetal Death, Analysis of Variance, Chi-Square Distribution, business.industry, Infectious Disease Transmission, Vertical, Odds ratio, medicine.disease, Confidence interval, Pregnancy Complications, business, Chi-squared distribution
Abstract

Objectives To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. Design Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. Setting University and hospital clinics. Population Pregnant women with HIV. Methods Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. Main outcome measures Rate of invasive testing, intrauterine death, HIV transmission. Results Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011–2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. Conclusions The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. Tweetable abstract No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens.

Published
2016

13. Abacavir/Lamivudine and Tenofovir/Emtricitabine in Pregnant Women with Hiv: Laboratory and Clinical Outcomes in an Observational National Study

Author

Floridia, M., Pinnetti, C., Ravizza, M., Masuelli, G., Personeni, C., Sansone, M., Antoni, A. D., Guaraldi, G., Spinillo, A., Tassis, B., Dalzero, S., Liuzzi, G., Tamburrini, E., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., Mercurio, V. S., Maccabruni, A., Zaramella, M., Mariani, B., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Papalini, C., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Maso, G., Rizzante, E., Belcaro, C., Meloni, A., Dedoni, M., Ortu, F., Piano, P., Citernesi, A., Vicini, I. B., Luzi, K., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Badolato, R., Tiso, G. C., Genovese, O., Cafforio, C., Casadei, A. M., Cavaliere, A. F., Cellini, M., Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., and Baroncelli, S.

Subjects
0301 basic medicine, HIV Infections, Hemoglobins, 0302 clinical medicine, Abacavir, Anemia, Cholesterol, Emtricitabine, HIV-RNA, Lamivudine, Low birthweight, Pregnancy, Preterm delivery, Tenofovir, immune system diseases, Antiretroviral Therapy, Highly Active, Pharmacology (medical), 030212 general & internal medicine, Pregnancy Outcome, virus diseases, Lipoproteins, LDL, Drug Combinations, Infectious Diseases, Hypertension, RNA, Viral, Female, medicine.drug, Adult, medicine.medical_specialty, Anti-HIV Agents, Pregnancy Trimester, Third, 03 medical and health sciences, Internal medicine, medicine, Humans, AIDS-Associated Nephropathy, Cesarean Section, business.industry, Abacavir/Lamivudine, medicine.disease, 030112 virology, Dideoxynucleosides, CD4 Lymphocyte Count, Pregnancy Complications, HIV-1, Observational study, business
Abstract

Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study.Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, hemoglobin, and alanine transferase) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, and pregnancy complications) were compared after prenatal exposure to ABC/3TC or TDF/FTC.The study evaluated 913 pregnancies (ABC/3TC: 252; TDF/FTC: 661). At entry in pregnancy, women on TDF/FTC were older (33.6 vs. 32.4 years, P = 0.005), less frequently on treatment (66.9% vs. 80.2%, P0.001), and had lower CD4 counts (475/mm vs. 533/mm, P = 0.003) and higher plasma HIV-RNA levels (2.48 vs. 2.22 log10 copies/mL, P = 0.003). Women on ABC/3TC had more commonly hypertension/nephropathy (5.2% vs. 2.0%, P = 0.013). No major differences were observed in the main pregnancy outcomes and in rates of undetectable HIV-RNA at third trimester. In a subgroup analysis that evaluated at third trimester only cases with regular 3-drug treatment during pregnancy, women on TDF/FTC had lower hemoglobin levels (median: 11.1 vs. 11.8 g/dL, P = 0.002) and women on ABC/3TC had higher levels of total cholesterol (median: 230 vs. 216 mg/dL, P = 0.023) and low-density lipoprotein-cholesterol (133 vs. 111 mg/dL, P = 0.030).In this study, use of TDF/FTC and ABC/3TC in pregnancy was associated with similar pregnancy outcomes and with some differences in laboratory measures that might guide physicians' prescriptions in mothers with hematologic or metabolic risk factors.

Published
2018

14. VEGF dose regulates vascular stabilization through Semaphorin3A and the Neuropilin-1+ monocyte/TGF- 1 paracrine axis

Author

Groppa E., Brkic S., Bovo E., Reginato S., Sacchi V., Di Maggio N., Muraro M. G., Calabrese D., Heberer M., Gianni-Barrera R., and Banfi A.

Abstract

VEGF is widely investigated for therapeutic angiogenesis but while short term delivery is desirable for safety it is insufficient for new vessel persistence jeopardizing efficacy. Here we investigated whether and how VEGF dose regulates nascent vessel stabilization to identify novel therapeutic targets. Monoclonal populations of transduced myoblasts were used to homogeneously express specific VEGF doses in SCID mouse muscles. VEGF was abrogated after 10 and 17 days by Aflibercept treatment. Vascular stabilization was fastest with low VEGF but delayed or prevented by higher doses without affecting pericyte coverage. Rather VEGF dose dependently inhibited endothelial Semaphorin3A expression thereby impairing recruitment of Neuropilin 1 expressing monocytes (NEM) and decreasing TGF ß1 and endothelial SMAD2/3 activation. TGF ß1 further initiated a feedback loop stimulating endothelial Semaphorin3A expression thereby amplifying the stabilizing signals. Blocking experiments showed that NEM recruitment required endogenous Semaphorin3A and that TGF ß1 was necessary to start the Semaphorin3A/NEM axis. Conversely Semaphorin3A treatment promoted NEM recruitment and vessel stabilization despite high VEGF doses or transient adenoviral delivery. Therefore VEGF inhibits the endothelial Semaphorin3A/NEM/TGF ß1 paracrine axis and Semaphorin3A treatment accelerates stabilization of VEGF induced angiogenesis.

Published
2015
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15. Pregnant with HIV before age 25: Data from a large national study in Italy, 2001-2016

Author

Floridia, M., Masuelli, G., Tamburrini, E., Cetin, I., Liuzzi, G., Martinelli, Paolo, Guaraldi, G., Spinillo, A., Vimercati, A., Maso, G., Pinnetti, C., Frisina, V., Dalzero, S., Ravizza, M., Di Lorenzo, F., Sterrantino, G., Meli, M., Campolmi, I., Vichi, F., Del Pin, B., Marocco, R., Mastroianni, C., Mercurio, V. S., Maccabruni, A., Zaramella, M., Mariani, Bianca, Nardini, G., Stentarelli, C., Beghetto, B., Antoni, A. M. Degli, Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Milini, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Angeli, G., Bernini, L., Grossi, P., Rizzi, L., Bernardon, M., Rizzante, E., Belcaro, C., Meloni, Antonio, Dedoni, M., Ortu, F., Piano, Pierluigi, Citernesi, A., Vicini, I. Bordoni, Luzi, K., Roccio, M., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, Filippo, Simonazzi, G., Margarito, E., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Agangi, A., Capone, A., Maruotti, G. M., Tibaldi, C., Trentini, L., Todros, T., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Franceschetti, L., Tassis, B., Genovese, O., Cafforio, C., Casadei, A. M., Cavaliere, A. F., Cellini, Matteo, Marconi, A. M., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Cerioli, A., DE MARTINO, MARIA CRISTINA, Parazzini, F., and Vella, S.

Subjects
Antiretroviral treatment, HIV diagnosis, HIV testing, pregnancy, women's health, medicine.medical_specialty, Pediatrics, Longitudinal study, Adolescent, Epidemiology, Short Report, HIV Infections, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pregnancy, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Young adult, 030219 obstetrics & reproductive medicine, business.industry, Odds ratio, medicine.disease, Female, Italy, Infectious Diseases, Confidence interval, Family planning, business, Cohort study
Abstract

SUMMARYYoung pregnant women with HIV may be at significant risk of unplanned pregnancy, lower treatment coverage, and other adverse pregnancy outcomes. In a large cohort of pregnant women with HIV in Italy, among 2979 pregnancies followed in 2001–2016, 9·0% were in women P< 0·001). Younger women had a lower rate of planned pregnancy (23·2%vs.37·7%, odds ratio (OR) 0·50, 95% confidence interval (CI) 0·36–0·69), were more frequently diagnosed with HIV in pregnancy (46·5%vs.20·9%, OR 3·29, 95% CI 2·54–4·25), and, if already diagnosed with HIV before pregnancy, were less frequently on antiretroviral treatment at conception (vs.99·3%), with no differences in rate of HIV viral suppression at third trimester and adverse pregnancy outcomes. The data show that young women represent a growing proportion of pregnant women with HIV, and are significantly more likely to have unplanned pregnancy, undiagnosed HIV infection, and lower treatment coverage at conception. During pregnancy, antiretroviral treatment, HIV suppression, and pregnancy outcomes are similar compared with older women. Earlier intervention strategies may provide additional benefits in the quality of care for women with HIV.

Published
2017

16. Pregnancy outcomes and cytomegalovirus DNAaemia in HIV-infected pregnant women with CMV

Author

Ravizza, M., Tamburrini, E., Mori, F., Ortolani, P., dalle Nogare, E.R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V.S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A.M., Molinari, A., Crisalli, M.P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Spinillo, A., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Guerra, B., Cervi, F., Simonazzi, G., Margarito, E., Capretti, M.G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Capone, A., Maruotti, G.M., Tibaldi, C., Trentini, L., Todros, T., Masuelli, G., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Genovese, O., Cafforio, C., Pinnetti, C., Liuzzi, G., Tozzi, V., Massetti, P., Casadei, A.M., Cavaliere, A.F., Cellini, M., Castelli Gattinara, G., Marconi, A.M., Dalzero, S., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M.F., Amici, R., Galluzzo, C.M., Donnini, S., Baroncelli, S., Floridia, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Parazzini, F., Vella, S., and Degli Antoni, A.

Published
2016
Full Text
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18. European palliative care guidelines

Author

Sampson, E.L., van der Steen, J.T., Pautex, S., Svartzman, P., Sacchi, V., Block, L., Den Noortgate, N., Family Medicine and Chronic Care, End-of-life Care Research Group, General practice, and EMGO - Quality of care

Subjects
Health Services Needs and Demand, Cognition Disorders/psychology, Research Support, Non-U.S. Gov't, Dementia/psychology, Palliative Care, Health Services Needs and Demand/standards, Pain management, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Europe, terminal care, Palliative Care/psychology/standards, delirium, Surveys and Questionnaires, mental disorders, Practice Guidelines as Topic, Delirium/psychology, Humans, Pain Measurement/methods/standards, Terminal Care/psychology/standards, Cognition Disorders, Pain Management/psychology/standards, ddc:613, dementia, Pain Measurement
Abstract

Item does not contain fulltext OBJECTIVE: Numbers of people dying with cognitive impairment (intellectual disability (ID), dementia or delirium) are increasing. We aimed to examine a range of European national palliative care guidelines to determine if, and how well, pain detection and management for people dying with impaired cognition are covered. METHODS: Questionnaires were sent to 14 country representatives of the European Pain and Impaired Cognition (PAIC) network who identified key national palliative care guidelines. Data was collected on guideline content: inclusion of advice on pain management, whether cognitively impaired populations were mentioned, assessment tools and management strategies recommended. Quality of guideline development was assessed with the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. RESULTS: 11 countries identified palliative care guidelines, 10 of which mentioned pain management in general. Of these, seven mentioned cognitive impairment (3 dementia, 2 ID and 4 delirium). Half of guidelines recommended the use of pain tools for people with cognitive impairment; recommended tools were not all validated for the target populations. Guidelines from the UK, the Netherlands and Finland included most information on pain management and detection in impaired cognition. Guidelines from Iceland, Norway and Spain scored most highly on AGREE rating in terms of developmental quality. CONCLUSIONS: European national palliative care guidelines may not meet the needs of the growing population of people dying with cognitive impairment. New guidelines should consider suggesting the use of observational pain tools for people with cognitive impairment. Better recognition of their needs in palliative care guidelines may drive improvements in care.

Published
2015

19. Good prenatal detection rate of major birth defects in HIV-infected pregnant women in Italy

Author

Floridia, M, Mastroiacovo, P., Ravizza, M., Todros, T., Chiadò Fiorio Tin, M., Marconi, A. M., Cetin, I., Maruotti, G. M., Liuzzi, G., Pinnetti, C., Degli Antoni, A., Spinillo, A., Guerra, B., Tamburrini, E., Floridia, M., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Nardini, G., Stentarelli, C., Beghetto, B., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Coletto, S., Di Nello, F., Madia, C., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, Daniela, Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Roccio, M., Vimercati, A., Miccolis, A., De Gennaro, A., Cervi, F., Puccetti, C., Margarito, E., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Capone, A., Tibaldi, C., Trentini, L., Masuelli, G., Frisina, V., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Fiscon, M., Rinaldi, R., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Fundarò, C., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Dalzero, S., Sacchi, V., Ierardi, M., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Parazzini, F., and Vella, S.

Subjects
Adult, Infectious, Obstetrics and Gynecology, HIV Infections, Congenital Abnormalities, Pregnancy Complications, Italy, Pregnancy, Humans, Female, Pregnancy Complications, Infectious, Genetics (clinical)
Published
2015

20. Atazanavir and lopinavir profile in pregnant women with HIV: tolerability, activity and pregnancy outcomes in an observational national study

Author

Floridia, M., Ravizza, M., Masuelli, G., Giacomet, V., Martinelli, P., Degli Antoni, A., Spinillo, A., Fiscon, M., Francisci, D., Liuzzi, G., Pinnetti, C., Marconi, A. M., Tamburrini, E., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Del Pin, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, Giovanni, Nardini, Giulia, Stentarelli, Chiara, Beghetto, Barbara, Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Fabiano, V., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Bernini, L., Grossi, P., Rizzi, L., Alberico, S., Maso, G., Airoud, M., Soppelsa, G., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Bordoni Vicini, I., Luzi, K., Roccio, M., Vimercati, A., Miccolis, A., Bassi, E., Guerra, B., Cervi, F., Puccetti, C., Murano, P., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Agangi, A., Tibaldi, C., Trentini, L., Todros, T., Frisina, V., Cetin, I., Brambilla, T., Savasi, V., Personeni, C., Giaquinto, C., Rinaldi, R., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Fundaro, C., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Dalzero, S., Sacchi, V., De Pirro, A., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Regazzi, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Moroni, M., Parazzini, F., Vella, S., Floridia, M, Ravizza, M, Masuelli, G, Giacomet, V, Martinelli, Pasquale, Degli Antoni, A, Spinillo, A, Fiscon, M, Francisci, D, Liuzzi, G, Pinnetti, C, Marconi, Am, Tamburrini, E, on behalf of The Italian Group on Surveillance on Antiretroviral Treatment in, Pregnancy, Floridia, M1, Italian Group on Surveillance on Antiretroviral Treatment in, P. r. e. g. n. a. n. c. y., Marco Floridia, Marina Ravizza, Giulia Masuelli, Vania Giacomet, Pasquale Martinelli, Anna Degli Antoni, Arsenio Spinillo, Marta Fiscon, Daniela Francisci, Giuseppina Liuzzi, Carmela Pinnetti, Anna Maria Marconi, Enrica Tamburrini, on behalf of The Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy [.., Capretti, M.G., Marsico, C., Faldella, G., and ].

Subjects
Pyridines, Pyridine, HIV Infections, Triglyceride, Lopinavir, Liver Function Tests, Pregnancy, HIV Infection, Pharmacology (medical), Viral, Pregnancy Complications, Infectious, triglycerides, pre-term delivery, medicine.diagnostic_test, Liver Function Test, Obstetrics, Medicine (all), Pregnancy Outcome, Infectious, virus diseases, HIV, pregnancy, RNA, Lipid, Viral Load, Lipids, Infectious Diseases, Tolerability, Oligopeptide, Population study, RNA, Viral, Female, medicine.symptom, bilirubin, Viral load, Oligopeptides, Human, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, HIV RNA, Anti-HIV Agents, Atazanavir Sulfate, Infectious Disease, Bilirubin, Cholesterol, Pre-term delivery, Triglycerides, Pharmacology, cholesterol, Settore MED/17 - MALATTIE INFETTIVE, medicine, Humans, business.industry, Anti-HIV Agent, medicine.disease, Atazanavir, CD4 Lymphocyte Count, Pregnancy Complications, Immunology, Pregnancy Complications, Infectiou, business, Liver function tests, Weight gain
Abstract

BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options.

Published
2014

21. Fisiologia, Molecole, cellule e sistemi

Author

Angioy A. M., Bardoni R., Biella G., Bigiani A., Bossi E., Brunelli M., Catacuzzeno L., Contestabile A., D'Angelo E., Fesce R., Fioretti B., Franciolini F., Fugassa E., Fulle S., Galimberti S., Ghirardelli R., Giovannardi S., Levi R., Lionetto M. G., Lombardi V., Macchi E., Negrini D., Paggi P., Palmero S., Peres A., perin P., Piccolino M., Poggesi C., Rispoli G., Rossi P., Sacchi V. F., Schettino T., Serio R., Valenti G., Vellani V., Zaza A., CRISPINO, MARIANNA, GIUDITTA, ANTONIO, D'Angelo E., Peres A., Angioy, A. M., Bardoni, R., Biella, G., Bigiani, A., Bossi, E., Brunelli, M., Catacuzzeno, L., Contestabile, A., Crispino, Marianna, D'Angelo, E., Fesce, R., Fioretti, B., Franciolini, F., Fugassa, E., Fulle, S., Galimberti, S., Ghirardelli, R., Giovannardi, S., Giuditta, Antonio, Levi, R., Lionetto, M. G., Lombardi, V., Macchi, E., Negrini, D., Paggi, P., Palmero, S., Peres, A., Perin, P., Piccolino, M., Poggesi, C., Rispoli, G., Rossi, P., Sacchi, V. F., Schettino, T., Serio, R., Valenti, G., Vellani, V., Zaza, A., and D'Angelo E, Peres A

Published
2007

22. Pregnancy outcomes and cytomegalovirus DNAaemia in HIV-infected pregnant women with CMV

Author

Floridia, M., primary, Pirillo, M.F., additional, Degli Antoni, A., additional, Molinari, A., additional, Tamburrini, E., additional, Pinnetti, C., additional, Guaraldi, G., additional, Nardini, G., additional, Masuelli, G., additional, Dalzero, S., additional, Cetin, I., additional, Sansone, M., additional, Amici, R., additional, Ravizza, M., additional, Mori, F., additional, Ortolani, P., additional, dalle Nogare, E.R., additional, Di Lorenzo, F., additional, Sterrantino, G., additional, Meli, M., additional, Polemi, S., additional, Nocentini, J., additional, Baldini, M., additional, Montorzi, G., additional, Mazzetti, M., additional, Rogasi, P., additional, Borchi, B., additional, Vichi, F., additional, Del Pin, B., additional, Pinter, E., additional, Anzalone, E., additional, Marocco, R., additional, Mastroianni, C., additional, Mercurio, V.S., additional, Carocci, A., additional, Grilli, E., additional, Maccabruni, A., additional, Zaramella, M., additional, Mariani, B., additional, Natalini Raponi, G., additional, Stentarelli, C., additional, Beghetto, B., additional, Degli Antoni, A.M., additional, Crisalli, M.P., additional, Donisi, A., additional, Piepoli, M., additional, Cerri, V., additional, Zuccotti, G., additional, Giacomet, V., additional, Coletto, S., additional, Di Nello, F., additional, Madia, C., additional, Placido, G., additional, Vivarelli, A., additional, Castelli, P., additional, Savalli, F., additional, Portelli, V., additional, Sabbatini, F., additional, Francisci, D., additional, Bernini, L., additional, Grossi, P., additional, Rizzi, L., additional, Alberico, S., additional, Maso, G., additional, Airoud, M., additional, Soppelsa, G., additional, Meloni, A., additional, Dedoni, M., additional, Cuboni, C., additional, Ortu, F., additional, Piano, P., additional, Citernesi, A., additional, Bordoni Vicini, I., additional, Luzi, K., additional, Spinillo, A., additional, Roccio, M., additional, Vimercati, A., additional, Miccolis, A., additional, De Gennaro, A., additional, Guerra, B., additional, Cervi, F., additional, Simonazzi, G., additional, Margarito, E., additional, Capretti, M.G., additional, Marsico, C., additional, Faldella, G., additional, Martinelli, P., additional, Agangi, A., additional, Capone, A., additional, Maruotti, G.M., additional, Tibaldi, C., additional, Trentini, L., additional, Todros, T., additional, Frisina, V., additional, Brambilla, T., additional, Savasi, V., additional, Personeni, C., additional, Giaquinto, C., additional, Fiscon, M., additional, Rubino, E., additional, Bucceri, A., additional, Matrone, R., additional, Scaravelli, G., additional, Genovese, O., additional, Cafforio, C., additional, Liuzzi, G., additional, Tozzi, V., additional, Massetti, P., additional, Casadei, A.M., additional, Cavaliere, A.F., additional, Cellini, M., additional, Castelli Gattinara, G., additional, Marconi, A.M., additional, Sacchi, V., additional, Ierardi, M., additional, Polizzi, C., additional, Mattei, A., additional, Galluzzo, C.M., additional, Donnini, S., additional, Baroncelli, S., additional, Floridia, M., additional, Villani, P., additional, Cusato, M., additional, Cerioli, A., additional, De Martino, M., additional, Mastroiacovo, P., additional, Parazzini, F., additional, and Vella, S., additional

Published
2016
Full Text
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23. European palliative care guidelines: how well do they meet the needs of people with impaired cognition?

Author

Sampson, E.L., Steen, J.T. van der, Pautex, S., Svartzman, P., Sacchi, V., Block, L. Van den, Noortgate, N. Van Den, Sampson, E.L., Steen, J.T. van der, Pautex, S., Svartzman, P., Sacchi, V., Block, L. Van den, and Noortgate, N. Van Den

Abstract

Item does not contain fulltext, OBJECTIVE: Numbers of people dying with cognitive impairment (intellectual disability (ID), dementia or delirium) are increasing. We aimed to examine a range of European national palliative care guidelines to determine if, and how well, pain detection and management for people dying with impaired cognition are covered. METHODS: Questionnaires were sent to 14 country representatives of the European Pain and Impaired Cognition (PAIC) network who identified key national palliative care guidelines. Data was collected on guideline content: inclusion of advice on pain management, whether cognitively impaired populations were mentioned, assessment tools and management strategies recommended. Quality of guideline development was assessed with the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. RESULTS: 11 countries identified palliative care guidelines, 10 of which mentioned pain management in general. Of these, seven mentioned cognitive impairment (3 dementia, 2 ID and 4 delirium). Half of guidelines recommended the use of pain tools for people with cognitive impairment; recommended tools were not all validated for the target populations. Guidelines from the UK, the Netherlands and Finland included most information on pain management and detection in impaired cognition. Guidelines from Iceland, Norway and Spain scored most highly on AGREE rating in terms of developmental quality. CONCLUSIONS: European national palliative care guidelines may not meet the needs of the growing population of people dying with cognitive impairment. New guidelines should consider suggesting the use of observational pain tools for people with cognitive impairment. Better recognition of their needs in palliative care guidelines may drive improvements in care.

Published
2015

24. Tools to Assess Pain or Lack of Comfort in Dementia: A Content Analysis

Author

Steen, J.T. van der, Sampson, E.L., Block, L. Van den, Lord, K., Vankova, H., Pautex, S., Vandervoort, A., Radbruch, L., Shvartzman, P., Sacchi, V., Vet, H.C. de, Noortgate, N.J. Van Den, Steen, J.T. van der, Sampson, E.L., Block, L. Van den, Lord, K., Vankova, H., Pautex, S., Vandervoort, A., Radbruch, L., Shvartzman, P., Sacchi, V., Vet, H.C. de, and Noortgate, N.J. Van Den

Abstract

Item does not contain fulltext, CONTEXT: There is need for tools to help detect pain or lack of comfort in persons unable to communicate. However, pain and (dis)comfort tools have not been compared, and it is unclear to what extent they discriminate between pain and other possible sources of discomfort, or even if items differ. OBJECTIVES: To map and compare items in tools that assess pain and the broader notion of discomfort or comfort in people with severe dementia or at the end of life. METHODS: Using qualitative content analysis with six classifications, we categorized each item of four thoroughly tested observational pain tools (Pain Assessment in Advanced Dementia [PAINAD], Pain Assessment Checklist for Seniors with Limited Ability to Communicate [PACSLAC], Doloplus-2, and draft Pain Assessment in Impaired Cognition [PAIC]), and four discomfort tools (including distress, comfort, and quality of life in severe dementia or at the end of life; Discomfort Scale-Dementia Alzheimer Type [DS-DAT], Disability Distress Assessment Tool [DisDAT], End-of-Life in Dementia-Comfort Assessment in Dying with Dementia [EOLD-CAD], and Quality of Life in Late-Stage Dementia [QUALID] scale). We calculated median proportions to compare distributions of categories of pain and discomfort tools. RESULTS: We found that, despite variable content across tools, items from pain and discomfort tools overlapped considerably. For example, positive elements such as smiling and spiritual items were more often included in discomfort tools but were not unique to these. Pain tools comprised more "mostly descriptive" (median 0.63 vs. 0.44) and fewer "highly subjective" items (0.06 vs. 0.18); some used time inconsistently, mixing present and past observations. CONCLUSION: This analysis may inform a more rigorous theoretical underpinning and (re)development of pain and discomfort tools and calls for empirical testing of a broad item pool for sensitivity and specificity in detecting and discriminating pain from other sources of disc

Published
2015

25. Pain control with ultrasound-guided inguinal field block compared with spinal anesthesia after hernia surgery: A randomized trial

Author

Mokini, Z, Vitale, G, Aletti, G, Sacchi, V, Mauri, T, Colombo, V, Fumagalli, R, Pesenti, A, MOKINI, ZHIRAJR, MAURI, TOMMASO, COLOMBO, VALENTINA, FUMAGALLI, ROBERTO, PESENTI, ANTONIO MARIA, Mokini, Z, Vitale, G, Aletti, G, Sacchi, V, Mauri, T, Colombo, V, Fumagalli, R, Pesenti, A, MOKINI, ZHIRAJR, MAURI, TOMMASO, COLOMBO, VALENTINA, FUMAGALLI, ROBERTO, and PESENTI, ANTONIO MARIA

Abstract

Background Inguinal field block (IFB) is a recommended technique for pain control after inguinal hernia repair but is also underused by surgeons. Currently, there is no decisive evidence on which technique, IFB or spinal anesthesia block (SAB), provides better pain control during the first day after hernia repair. In this study, we compared ultrasound-guided IFB performed by anesthesiologists and SAB for pain control during the first day after hernia repair. Methods We compared static and dynamic pain scores measured with a numerical rating scale in 86 male patients scheduled for elective unilateral inguinal hernia repair with either ultrasound-guided IFB (n = 42) or SAB (n = 44). Results Dynamic and static pain at 4 hours (P <.01, r > 0.34, "large effect size"), and dynamic pain the morning after operation (P =.04, r > 0.20, "medium effect size") were less in the field block group compared with the SAB group. Postoperative analgesic consumption was reduced during hospital stay (P =.005, r > 0.34, "large effect size") and for 7 postoperative days in the field block group (P =.03, r > 0.20, "medium effect size"). Conclusion In this study, ultrasound-guided IFB provided lesser dynamic pain scores during the first postoperative day and reduced use of analgesics for 1 week compared with spinal anesthesia after inguinal hernia repair. Our technique could become a substitute performed by anesthesiologists in settings in which IFB is not performed routinely by surgeons.

Published
2015

27. Body Mass Index and Weight Gain in Pregnant Women With HIV: A National Study in Italy

Author

Floridia, M., Ravizza, M., Masuelli, G., Dalzero, S., Pinnetti, C., Cetin, I., Meloni, A., Spinillo, A., Rubino, E., Francisci, D., Tamburrini, E., Mori, F., Ortolani, P., Dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Vichi, F., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, Claudio Maria, Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Luzi, K., Nardini, G., Stentarelli, C., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Fabiano, V., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Bernini, L., Alberico, S., Maso, G., Tropea, M., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Vicini, I., Roccio, M., Vimercati, A., Miccolis, A., Bassi, E., Guerra, B., Cervi, F., Puccetti, C., Murano, P., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Sansone, M., Martinelli, P., Agangi, A., Tibaldi, C., Trentini, L., Todros, T., Garetto, S., Brambilla, T., Savasi, V., Crepaldi, A., Giaquinto, C., Fiscon, M., Rinaldi, R., Bucceri, A., Matrone, R., Scaravelli, G., Fundaro, C., Genovese, O., Cafforio, C., Liuzzi, G., Tozzi, V., Massetti, Anna Paola, Anceschi, M., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Marconi, A. M., Sacchi, V., De Pirro, A., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Mastroiacovo, P., Moroni, M., Parazzini, F., Vella, S., Floridia, M, Ravizza, M, Masuelli, G, Dalzero, S, Pinnetti, C, Cetin, I, Meloni, A, Spinillo, A, Rubino, E, Francisci, D, Tamburrini, E, Italian Group on Surveillance on Antiretroviral Treatment in, Pregnancy, Martinelli, Pasquale, Floridia M, Ravizza M, Masuelli G, Dalzero S, Pinnetti C, Cetin I, Meloni A, Spinillo A, Rubino E, Francisci D, Tamburrini E, Faldella G, Guerra B, and for the Italian Group on Surveillance on Antiretroviral Treatment in Pregnancy

Subjects
Microbiology (medical), medicine.medical_specialty, antiretroviral therapy, MEDLINE, Human immunodeficiency virus (HIV), HIV Infections, body mass index, medicine.disease_cause, Settore MED/17 - MALATTIE INFETTIVE, Body Mass Index, BMI, weight gain, HIV-1, Pregnancy, Medicine, Humans, HIV infection, pregnancy, Pregnancy Complications, Infectious, business.industry, Obstetrics, Cesarean Section, Infectious, Pregnancy Outcome, HIV, medicine.disease, Pregnancy Complications, Infectious Diseases, Italy, National study, Female, medicine.symptom, business, Weight gain, Body mass index
Abstract

Although most of the women (69.4%) had a normal BMI at start of pregnancy, only 37% had an adequate weight gain during pregnancy. Inadequate body weight gain was more common (44.8%) than excessive weight gain (18.2%), but 40% of overweight women and 50% of obese women had an excessive weight gain in pregnancy, with about 9% of the women in these categories gaining >18 kg during pregnancy (Table 1). Only 1.9% of the women had a vaginal delivery; elective and nonelective cesarean deliveries accounted for 81.3% and 16.7% of deliveries, respectively. Compared to underweight/normal women, overweight/obese women had similar occurrences of preterm delivery (23.4% vs 22.7%, P = .871), significantly lower rates of low birthweight (14.2% vs 24.2%, P = .007) and nonelective cesarean deliveries (11.7% vs 18.3%, P = .042), and a significantly higher occurrence of fasting plasma glucose >92 mg/dL at 20–28 weeks (12.1% vs 6.6%, P = .027), hypertension during pregnancy (6.4% vs 2.7%, P = .019), and gestational age–adjusted birthweight >90th percentile (15.5% vs 5.0%, P < .001). Complications of delivery, major birth defects, and HIV transmission were similar between the 2 groups (7.3% vs 7.6%, P = .881; 2.6% vs 3.5%, P = .589; and 0.8% vs 0.5%, P = .661, respectively). An inadequate weight gain during pregnancy was associated with an increased risk of nonelective cesarean delivery (OR, 1.589 [95% CI, 1.077–2.346], P = .020). Excessive weight gain during pregnancy was not associated with either hypertension (OR, 1.364 [95% CI, .537–3.465], P = .514) or 20–28 week glucose level of >92 mg/dL (OR, 0.841 [95% CI, .399–1.772], P = .648), but was significantly associated with birthweight >90th percentile (OR, 2.271 [95% CI, 1.229–4.195], P = .009), and appeared to be protective against low birthweight (OR, 0.544 [95% CI, .323–.918], P = .023) and birthweight

Published
2013

28. Body Mass Index and Weight Gain in Pregnant Women With HIV: A National Study in Italy

Author

Floridia, M, Ravizza, M, Masuelli, G, Dalzero, S, Pinnetti, C, Cetin, I, Meloni, A, Spinillo, A, Rubino, E, Francisci Dtamburrini, E, Mori, F, Ortolani, P, Dalle Nogare Er, Di Lorenzo, F, Sterrantino, G, Meli, M, Polemi, S, Nocentini, J, Baldini, M, Montorzi, G, Mazzetti, M, Rogasi, P, Borchi, B, Vichi, F, Pinter, E, Anzalone, E, Marocco, R, Mastroianni, C, Mercurio, Vs, Carocci, A, Grilli, E, Maccabruni, A, Zaramella, M, Mariani, B, Natalini Raponi, G, Guaraldi, G, Luzi, K, Nardini, G, Stentarelli, C, Degli Antoni Am, Molinari, A, Crisalli, Mp, Donisi, A, Piepoli, M, Cerri, V, Zuccotti, G, Giacomet, V, Fabiano, V, Placido, G, Vivarelli, A, Castelli, P, Savalli, F, Portelli, V, Sabbatini, F, Francisci, D, Bernini, L, Alberico, S, Maso, G, Tropea, M, Dedoni, M, Cuboni, C, Ortu, F, Piano, P, Citernesi, A, Vicini, I, Roccio, M, Vimercati, A, Miccolis, A, Bassi, E, Guerra, B, Cervi, F, Puccetti, C, Murano, P, Contoli, M, Capretti, Mg, Marsico, C, Faldella, G, Sansone, M, Martinelli, P, Agangi, A, Tibaldi, C, Trentini, L, Todros, T, Garetto, S, Brambilla, T, Savasi, V, Crepaldi, A, Giaquinto, C, Fiscon, M, Rinaldi, R, Bucceri, A, Matrone, R, Scaravelli, G, Fundarò, C, Genovese, O, Cafforio, C, Liuzzi, G, Tozzi, V, Massetti, P, Anceschi, M, Casadei, Am, Cavaliere, Af, Finelli, V, Cellini, M, Castelli Gattinara, G, Marconi, Am, Sacchi, V, De Pirro, A, Polizzi, C, Mattei, A, Pirillo, Mf, Amici, R, Galluzzo, Cm, Donnini, S, Baroncelli, S, Villani, P, Cusato, M, Cerioli, A, De Martino, Maurizio, Mastroiacovo, P, Moroni, M, Parazzini, F, Tamburrini, E, Vella, S, and Martinelli, P.

Subjects
HIV
Published
2013

29. Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001-2011

Author

Floridia, M., Mastroiacovo, P., Tamburrini, E., Tibaldi, C., Todros, T., Crepaldi, A., Sansone, M., Fiscon, M., Liuzzi, G., Guerra, B., Vimercati, A., Vichi, F., Vicini, I., Pinnetti, C., Marconi, A. M., Ravizza, M., Mori, F., Ortolani, P., dalle Nogare, E. R., Di Lorenzo, F., Sterrantino, G., Meli, M., Polemi, S., Nocentini, J., Baldini, M., Montorzi, G., Mazzetti, M., Rogasi, P., Borchi, B., Pinter, E., Anzalone, E., Marocco, R., Mastroianni, C., Mercurio, V. S., Carocci, A., Grilli, E., Maccabruni, A., Zaramella, M., Mariani, B., Natalini Raponi, G., Guaraldi, G., Luzi, K., Nardini, G., Stentarelli, C., Degli Antoni, A. M., Molinari, A., Crisalli, M. P., Donisi, A., Piepoli, M., Cerri, V., Zuccotti, G., Giacomet, V., Fabiano, V., Coletto, S., Placido, G., Vivarelli, A., Castelli, P., Savalli, F., Portelli, V., Sabbatini, F., Francisci, D., Bernini, L., Alberico, S., Maso, G., Tropea, M., Meloni, A., Dedoni, M., Cuboni, C., Ortu, F., Piano, P., Citernesi, A., Spinillo, A., Roccio, M., Miccolis, A., Bassi, E., Cervi, F., Puccetti, C., Murano, P., Contoli, M., Capretti, M. G., Marsico, C., Faldella, G., Martinelli, P., Agangi, A., Trentini, L., Masuelli, G., Garetto, S., Cetin, I., Brambilla, T., Savasi, V., Giaquinto, C., Rinaldi, R., Rubino, E., Bucceri, A., Matrone, R., Scaravelli, G., Fundaro, C., Genovese, O., Cafforio, C., Tozzi, V., Massetti, P., Anceschi, M., Casadei, A. M., Cavaliere, A. F., Finelli, V., Cellini, M., Castelli Gattinara, G., Dalzero, S., Sacchi, V., De Pirro, A., Polizzi, C., Mattei, A., Pirillo, M. F., Amici, R., Galluzzo, C. M., Donnini, S., Baroncelli, S., Regazzi, M., Villani, P., Cusato, M., Cerioli, A., De Martino, M., Moroni, M., Parazzini, F., Vella, S., Floridia, M, Mastroiacovo, P, Tamburrini, E, Tibaldi, C, Todros, T, Crepaldi, A, Sansone, M, Fiscon, M, Liuzzi, G, Guerra, B, Vimercati, A, Vichi, F, Vicini, I, Pinnetti, C, Marconi, A, Ravizza, M, Martinelli, Pasquale, and The Italian Group on Surveillance on Antiretroviral Treatment in, Pregnancy

Subjects
Male, HIV Infections, transcriptase inhibitors, Cohort Studies, chemistry.chemical_compound, Pregnancy, Prevalence, Birth Weight, Young adult, Pregnancy Complications, Infectious, education.field_of_study, Obstetrics, Coinfection, Antiretroviral therapy, birth defects, efavirenz, HIV, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, pregnancy, protease inhibitors, women, Obstetrics and Gynecology, Abnormalities, Drug-Induced, Middle Aged, Italy, Maternal Exposure, Reverse Transcriptase Inhibitors, Female, Cohort study, Adult, medicine.medical_specialty, Efavirenz, Adolescent, Anti-HIV Agents, Birth weight, Population, Antiretroviral Therapy, Birth defects, HIV-1, Young Adult, Hepatitis B, Chronic, medicine, Humans, education, business.industry, Infant, Newborn, Odds ratio, Hepatitis C, Chronic, medicine.disease, Infectious Disease Transmission, Vertical, Surgery, Pregnancy Trimester, First, chemistry, business
Abstract

Objective We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. Design Observational study. Setting University and hospital clinics. Population Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. Methods The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. Main outcome measures Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. Results A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9–4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9–4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51–1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51–1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56–2.55; protease inhibitors, OR 0.92, 95% CI 0.43–1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). Conclusions This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities.

Published
2013

31. HCV–HIV coinfected pregnant women: data from a multicentre study in Italy

Author

Baroncelli, S., primary, Pirillo, M. F., additional, Amici, R., additional, Tamburrini, E., additional, Genovese, O., additional, Ravizza, M., additional, Maccabruni, A., additional, Masuelli, G., additional, Guaraldi, G., additional, Liuzzi, G., additional, Pinnetti, C., additional, Giacomet, V., additional, Degli Antoni, A., additional, Vimercati, A., additional, Dalzero, S., additional, Sacchi, V., additional, and Floridia, Marco, additional

Published
2015
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32. Fisiologia: molecole, cellule e sistemi

Author

Angioy, A. M., Bardoni, Rita, Bigiani, Albertino, Brunelli, M., Contestabile, A., Crispino, M., D'Angelo, E., Franciolini, F., Fugassa, E., Fulle, S., Giuditta, A., Levi, R., Lionetto, M. G., Lombardi, V., Macchi, E., Negrini, D., Paggi, P., Palmero, S., Peres, A., Piccolino, M., Poggesi, C., Rispoli, G., Rossi, P., Sacchi, V. F., Schettino, T., Serio, R., Valenti, G., Vellani, Vittorio, and Zaza, A.

Subjects
fisiologia generale, Fisiologia cellulare, fisiologia dei sistemi
Published
2006

35. Intraperitoneal nebulization of ropivacaine for pain control after laparoscopic cholecystectomy: A double-blind, randomized, placebo-controlled trial

Author

Ingelmo, P, Bucciero, M, Somaini, M, Sahillioglu, E, Garbagnati, A, Charton, A, Rossini, V, Sacchi, V, Scardilli, M, Lometti, A, Joshi, G, Fumagalli, R, Diemunsch, P, INGELMO, PABLO MAURICIO, BUCCIERO, MARIO PAOLO, SOMAINI, MARTA, SAHILLIOGLU, EMRE, GARBAGNATI, ANDREA, FUMAGALLI, ROBERTO, Diemunsch, P., Ingelmo, P, Bucciero, M, Somaini, M, Sahillioglu, E, Garbagnati, A, Charton, A, Rossini, V, Sacchi, V, Scardilli, M, Lometti, A, Joshi, G, Fumagalli, R, Diemunsch, P, INGELMO, PABLO MAURICIO, BUCCIERO, MARIO PAOLO, SOMAINI, MARTA, SAHILLIOGLU, EMRE, GARBAGNATI, ANDREA, FUMAGALLI, ROBERTO, and Diemunsch, P.

Abstract

BackgroundIntraperitoneal local anaesthetic nebulization is a relatively novel approach to pain management after laparoscopic surgery. This randomized, double-blind, placebo-controlled trial evaluated the effects of intraperitoneal ropivacaine nebulization on pain control after laparoscopic cholecystectomy. MethodsPatients undergoing laparoscopic cholecystectomy were randomized to receive intraperitoneal nebulization of ropivacaine 1% (3 ml) before surgical dissection and normal saline 3 ml at the end of surgery (preoperative nebulization group); intraperitoneal nebulization of normal saline 3 ml before surgical dissection and ropivacaine 1% (3 ml) at the end of surgery (postoperative nebulization group); or intraperitoneal nebulization of normal saline 3 ml before surgical dissection and at the end of surgery (placebo group). Intraperitoneal nebulization of ropivacaine or saline was performed using the Aeroneb Pro® device. Anaesthetic and surgical techniques were standardized. The degree of pain on deep breath or movement, incidence of shoulder pain, morphine consumption, and postoperative nausea and vomiting were collected in the post-anaesthesia care unit and at 6, 24, and 48 h after surgery.ResultsCompared with placebo, ropivacaine nebulization significantly reduced postoperative pain (-33%; Cohen's d 0.64), referred shoulder pain (absolute reduction -98%), morphine requirements (-41% to -56% Cohen's d 1.16), and time to unassisted walking (up to -44% Cohen's d 0.9) (P<0.01). There were no differences in pain scores between ropivacaine nebulization groups.ConclusionsRopivacaine nebulization before or after surgery reduced postoperative pain and referred shoulder pain after laparoscopic cholecystectomy. Furthermore, ropivacaine nebulization reduced morphine requirements and allowed earlier mobility. © 2013 Author.

Published
2013

36. The k+-driven amino-acid cotransporter of the larval midgut of lepidoptera - is na+ an alternative substrate

Author

HANOZET, GIORGIO MARIA, BONFANTI, PATRIZIA, Sacchi, V, Nedergaard, S, Magagnin, S, Giordana, B., Hanozet, G, Sacchi, V, Nedergaard, S, Bonfanti, P, Magagnin, S, and Giordana, B

Subjects
aminoacid transport, Brush border membrane vescicles, BIO/06 - ANATOMIA COMPARATA E CITOLOGIA
Abstract

Amino acid accumulation within brush-border membrane vesicles (BBMV) from the larval midgut of Lepidoptera is driven by a K+ gradient. However, it can also be driven by a Na+ gradient, although with reduced efficiency. To examine the possibility that sodium and potassium ions are handled by the same amino acid transporter, glycine uptake into BBMV from Philosamia cynthia Drury was measured in the presence of a pH gradient and of a transmembrane electrical potential difference, i.e. in simulated 'physiological' conditions. The kinetics of glycine uptake at extravesicular saturating Na+ or K+ concentrations discloses a higher affinity of the cotransporter for the amino acid in the presence of Na+ but a maximum transport rate with K+. Glycine uptake at a fixed concentration as a function of external Na+ or K+ concentration yields curves that show saturation but do not fit a rectangular hyperbola, with Hill coefficients less than 1 with Na+ and greater than 1 with K+. These coefficients vary according to glycine concentration. Increasing the concentration of extravesicular Na+ at a saturating external K+ concentration reduced glycine uptake to 70% of the control value. This inhibition curve is compatible with competition between the two cations for the same cotransporter and with the presence of different kinetic constants with Na+ or K+. The data are consistent with a steady-state random two-substrate mechanism for glycine transport, with Na+ and K+ as alternative substrates.

Published
1992

38. The Glial Glutamate Transporter 1 (GLT1) Is Expressed by Pancreatic β-Cells and Prevents Glutamate-induced β-Cell Death

Author

Di Cairano, Eliana S., primary, Davalli, Alberto M., additional, Perego, Lucia, additional, Sala, Silvia, additional, Sacchi, V. Franca, additional, La Rosa, Stefano, additional, Finzi, Giovanna, additional, Placidi, Claudia, additional, Capella, Carlo, additional, Conti, Paola, additional, Centonze, Victoria E., additional, Casiraghi, Francesca, additional, Bertuzzi, Federico, additional, Folli, Franco, additional, and Perego, Carla, additional

Published
2011
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46. Interaction between na+ and the k+-dependent amino-acid-transport in midgut brush-border membrane-vesicles from philosamia-cynthia larvae

Author

Sacchi, V, Parenti, P, Perego, C, Giordana, B, Sacchi, VF, Giordana, B., PARENTI, PAOLO, Sacchi, V, Parenti, P, Perego, C, Giordana, B, Sacchi, VF, Giordana, B., and PARENTI, PAOLO

Abstract

Both sodium and potassium can drive leucine uptake into brush-border membrane vesicles from Pholosamia cynthia midgut, but the effects of these cations are not additive. 2mM sodium reduces leucine uptake at saturating potassium concentration, which indicates that these cations interact with the same transporter. The mixed type inhibition of sodium was explained in terms of different kinetic parameters of the co-transporter when this cation binds to the transport protein instead potassium. At 0.2 mM leucine, the affinity of sodium for the transporter was about 18 times that of potassium, whereas leucine Vmax was 2.5 times higher with potassium. Kinetic experiments performed to characterize Na+-dependent leucine uptake showed that the leucine kinetics at different sodium concentrations did not follow Michaelis-Menten kinetics and that the effect of sodium was mainly to increase the affinity of the amino acid for the co-transporter. Na+-activation curves, as fixed leucine concentrations, showed that the Vmax increased with leucine concentration. Since both cations are present in the midgut lumen of P. cynthia larva (200 mM potassium and 1mM sodium), the interaction between sodium and the K+-dependent co-transporter was observed by measuring leucine uptake as a function of potassium concentration at different fixed sodium concentrations. In accordance with the kinetic parameters that characterize the co-transport in the presence of either Na+ or K+, sodium reduces leucine uptake at high potassium concentrations and increases leucine uptake at low potassium concentrations. Assuming that the translocation is the rate limiting step of the process, we present a model for two alternative drivers (Na+ and K+) and for leucine translocation in the absence of any cation. The derived velocity equation adequately describes the experiments reported here and previously. The physiological meaning of this transport mechanism, probably evolved from a more primative Na+-dependent co-tra

Published
1994

48. Theoretical analysis of cotransport: Its use in alanine uptake in plasma membrane vesicles

Author

Leonardi, M, Andrietti, F, Bonfanti, P, Sacchi, V, Leonardi, MG, BONFANTI, PATRIZIA, Sacchi, VF, Leonardi, M, Andrietti, F, Bonfanti, P, Sacchi, V, Leonardi, MG, BONFANTI, PATRIZIA, and Sacchi, VF

Abstract

A theoretical model of a cotransport system in plasma membrane vesicles has been utilized for the analysis of the Na(+)-dependent L-alanine transport into plasma membrane vesicles purified from Yoshida ascites hepatoma (AH 130) cells in the exponential and stationary phases of growth. The analysis was performed by comparing the experimental curves with computer simulations. In particular we considered the differences in alanine uptake observed in the two preparations and we tried to ascribe them to changes of some parameters of the transport model. The simulations indicate that sodium, alanine or water passive permeability changes cannot explain the experimental data which are consistent, on the contrary, with a relevant enhancement of the Vmax of the transport agency. The involvement of the membrane electrical potential difference is also discussed.

Published
1993

49. Sodium and potassium interaction on the leucine cotransporter

Author

Sacchi, V, Martino, P, Dassi, M, Perego, C, Parenti, P, Giordana, B, Sacchi, VF, Giordana, B., PARENTI, PAOLO, Sacchi, V, Martino, P, Dassi, M, Perego, C, Parenti, P, Giordana, B, Sacchi, VF, Giordana, B., and PARENTI, PAOLO

Published
1993

50. The k+-driven amino-acid cotransporter of the larval midgut of lepidoptera - is na+ an alternative substrate

Author

Hanozet, G, Sacchi, V, Nedergaard, S, Bonfanti, P, Magagnin, S, Giordana, B, HANOZET, GIORGIO MARIA, BONFANTI, PATRIZIA, Giordana, B., Hanozet, G, Sacchi, V, Nedergaard, S, Bonfanti, P, Magagnin, S, Giordana, B, HANOZET, GIORGIO MARIA, BONFANTI, PATRIZIA, and Giordana, B.

Abstract

Amino acid accumulation within brush-border membrane vesicles (BBMV) from the larval midgut of Lepidoptera is driven by a K+ gradient. However, it can also be driven by a Na+ gradient, although with reduced efficiency. To examine the possibility that sodium and potassium ions are handled by the same amino acid transporter, glycine uptake into BBMV from Philosamia cynthia Drury was measured in the presence of a pH gradient and of a transmembrane electrical potential difference, i.e. in simulated 'physiological' conditions. The kinetics of glycine uptake at extravesicular saturating Na+ or K+ concentrations discloses a higher affinity of the cotransporter for the amino acid in the presence of Na+ but a maximum transport rate with K+. Glycine uptake at a fixed concentration as a function of external Na+ or K+ concentration yields curves that show saturation but do not fit a rectangular hyperbola, with Hill coefficients less than 1 with Na+ and greater than 1 with K+. These coefficients vary according to glycine concentration. Increasing the concentration of extravesicular Na+ at a saturating external K+ concentration reduced glycine uptake to 70% of the control value. This inhibition curve is compatible with competition between the two cations for the same cotransporter and with the presence of different kinetic constants with Na+ or K+. The data are consistent with a steady-state random two-substrate mechanism for glycine transport, with Na+ and K+ as alternative substrates.

Published
1992

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