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2. Šećerna bolest tip 1 u trudnoći: visoka incidencija novorođenčadi velike za gestacijsku dob unatoč adekvatnoj kontroli glikemije i niskoj glikemijskoj varijabilnosti

Author

G, Leksic, M, Baretic, L, Gudelj, M, Radic, and M, Ivanisevic

Subjects
šećerna bolest tip 1, trudnoća, novorođenčad velika za gestacijsku dob
Abstract

Background Pregnancy with type 1 diabetes mellitus (T1DM) carries risks for many adverse outcomes ; the most common are large-for-gestational-age neonates (LGA). Proper glycemic control reduces the risk for LGA. However, it occurs in almost 40% of T1DM pregnancies despite of achieving almost normoglycemia. Some studies suggested the contributing role of maternal body mass index (BMI) and glucovariability, but the effect on development of LGA still remains unclear. Objectives The aim of this study was to analyse incidence of LGA in planned and well- controlled T1DM pregnancies. Methods This prospective study included 42 patients with T1DM who were using continuous glucose monitoring (CGM) from preconception to delivery. Including criteria were preconception counselling, CGM at least 3 months prior to the study, duration of T1DM for at least 1 year, HbA1c ! 7.5%, BMI !25 kg/m2. Excluding criteria were HbA1c O7.5% and maternal weight gain O 20 kg in the 2nd and 3rd trimester. Patients used intermittently scanned CGM and data was analysed once in every trimester. Statistical analysis was performed with IBM SPSS software and data was defined as mean and standard deviation. Results In the first, second and third trimester time in range was 54.3G14.3, 62.4G 10.6, 67.5G11.7% respectively. Glucose management indicator was 6.5G0.5, 6.0G 0.4, 5.9G0.4% and %coefficient of variation 41.2G7.5, 38.6G5.9, 34.1G6.5% in the first, second and third trimester, respectively. Neonatal birth weight was 3594.3G632.2 grams, birth weight percentile 72.1G28.6 and 45% of neonates were LGA. Conclusions In this study we observed improved glycaemic control and decrease of glycemic variability from the first to the third trimester as a result of structured preconception counselling and strict follow-up. However, there was high incidence of LGA despite adequate glycemic control, low glycemic variability and normal BMI. Further studies for defining LGA aetiology in T1DM pregnancies are needed.

Published
2022

4. Significant liver fibrosis, as assessed by fibroscan, is independently associated with chronic vascular complications of type 2 diabetes: A multicenter study

Author

Giovanni Targher, H. Jerkic, T. Matic, V Domislović, Ivana Mikolašević, Zeljko Krznaric, Marko Martinović, Delfa Radić-Krišto, M. Medjimurec, Goran Hauser, Dario Rahelić, A. Ruzic, T. Filipec Kanizaj, T. Turk-Wensween, and M. Radic

Subjects
Liver Cirrhosis, nonalcoholic fatty liver disease, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Gastroenterology, Diabetic complications, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Non-alcoholic Fatty Liver Disease, Internal medicine, Diabetes mellitus, Nonalcoholic fatty liver disease, Internal Medicine, medicine, diabetic complications, Humans, 030212 general & internal medicine, Myocardial infarction, Liver stiffness measurement, liver stiffness measurement, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, business.industry, General Medicine, medicine.disease, controlled attenuation parameter, type 2 diabetes, Diabetes Mellitus, Type 2, Liver, Cardiovascular Diseases, Controlled attenuation parameter, Elasticity Imaging Techniques, Transient elastography, business, Polyneuropathy, Retinopathy, Kidney disease
Abstract

Aims The aim of this study was to investigate whether controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as assessed by vibration-controlled transient elastography (VCTE), are associated with chronic vascular complications of diabetes mellitus type 2 (T2DM). Methods We studied 442 outpatients with established T2DM, and who underwent VCTE and extensive assessment of chronic vascular complications of diabetes. Results A quarter of analyzed patients had a previous history of myocardial infarction and/or ischemic stroke, and about half of them had at least one microvascular complication (chronic kidney disease (CKD), retinopathy or polyneuropathy). The prevalence of liver steatosis (i.e., CAP ≥ 238 dB/m) and significant liver fibrosis (i.e., LSM ≥ 7.0/6.2 kPa) was 84.2% and 46.6%, respectively. Significant liver fibrosis was associated with an increased likelihood of having myocardial infarction (adjusted-odds ratio 6.61, 95%CI 1.66–37.4), peripheral polyneuropathy (adjusted-OR 4.55, 95%CI 1.25–16.6), CKD (adjusted-OR 4.54, 95%CI 1.24–16.6) or retinopathy (adjusted-OR 1.81, 95%CI 1.62–1.97), independently of cardiometabolic risk factors, diabetes-related variables, and other potential confounders. Liver steatosis was not independently associated with any macro-/microvascular diabetic complications. Conclusions Significant liver fibrosis is strongly associated with the presence of macro-/microvascular complications in patients with T2DM. These results offer a new perspective on the follow-up of people with T2DM.

Published
2021

5. PS6:116 Diet habits in patients with systemic lupus erythematosus

Author

M Petric, M Radic, D Perkovic, J Bozic, D Marasovic Krstulovic, K Boric, I Bozic, I Erceg, and D Martinovic Kaliterna

Subjects
medicine.medical_specialty, Proteinuria, Calorie, business.industry, Disease duration, food and beverages, Normal values, Complement components, Diet habits, Internal medicine, medicine, In patient, medicine.symptom, business, Serum complement
Abstract

Objective Many patients with systemic lupus erythematosus (SLE) are interested in diet advices. We wanted to investigate which diet habits are most common in our patients, and which of them are in correlation with laboratory parameters that are related to disease remission, such as normal values of serum complement and 24 hour proteinuria. Methods We included 76 patient with SLE in remission, in age between 21 and 75. They fulfilled 23-item questionnaire about weekly diet habits. Basic anthropometric data, disease duration, levels of C3 and C4 complement components and 24 hour proteinuria were recorded and analysed in correlation with diet habits. Results Majority of our patients had normal BMI (between 18.5 and 25 kg/m2), prefered to eat healthy food and did regular weekly workout. Milk, meat, fruits, vegetables, pasta, rice and bread were the most abundant food. Lower serum values of C3 were found in 34 (44.7%) cases, and lower values of C4 were found in 28 (36.8%) cases. Only 5 (6.6%) patients had significant 24 hour proteinuria higher than 3.5 g and another 7 (9.2%) had proteinuria higher than 1 g. Lower values of C3 were found in patients who often consumed meat (p=0.015) and fast food (p=0.060), and those patients who more often consumed fast food or fried food had lower levels of C4 (p=0.043 and p=0.051). Conclusions There is an evidence that food rich in proteins and calories can lower serum complement levels. As clinicians, we should always advice our SLE patients to eat a lot of fish, fruits and fresh vegetables, although there is no strong support for that. More studies with dietary interventions have to be done before final recommendations can be made.

Published
2018

6. Are inherited prothrombotic gene polymorphisms associated with lesion location in pediatric arterial ischemic stroke?

Author

J. Lenicek Krleza, D. Coen Herak, Vlasta Djuranovic, Andrea Čeri, Renata Zadro, Ivana Horvat, Nina Barišić, and M. Radic Antolic

Subjects
medicine.medical_specialty, business.industry, General Medicine, Arterial Ischemic Stroke, Lesion, pediatric, stroke, localization, thrombophilia, polymorphisms, Internal medicine, Pediatrics, Perinatology and Child Health, Cardiology, medicine, Neurology (clinical), medicine.symptom, business, Gene
Abstract

Pediatric arterial ischemic stroke (AIS) is a relatively rare disorder with multifactorial etiology. A variety of incompletely investigated genetic polymorphisms may cause hypercoagulability and lead to ischemic lesion formation in different parts of brain. As correlation between neuroimaging finding and genetic risk factors might be helpful for further therapeutic decisions, we investigated the significance of inherited prothrombotic gene polymorphisms in different pediatric AIS subtypes according to time of onset and lesion location. Eleven polymorphisms (FV Leiden, FV HR2, FII G20210A, β-fibrinogen −455G>A, FXIII-A Val34Leu, PAI-1 4G/5G, HPA-1, MTHFR C677T, MTHFR A1298C, ACE I/D, apoE ε2-4) were genotyped using a multilocus CVD Strip assay (ViennaLab, Austria) in DNA extracted from blood samples of 112 children (46 girls, 66 boys) with perinatal (N = 51) and childhood AIS (N = 61), and 110 sex- and age-matched controls. FV Leiden (OR: 4.24 ; 95% CI: 1.16–15.46, p = 0.015) and ACE I/D (OR: 1.90 ; 95% CI: 1.01–3.55, p = 0.044) were found to be associated with AIS. Stroke localization data collected from patient medical records and magnetic resonance imaging results indicated cortical stroke in 69 children (39 with perinatal ; 30 with childhood AIS) and subcortical stroke in 43 children, being more frequent in childhood (N = 31), compared to perinatal AIS (N = 12). Cortical and subcortical strokes differed in β- fibrinogen −455G>A genotype distributions (p = 0.026), −455AA genotype was identified in cortical stroke only. Difference in PAI-1 4G/5G genotype distributions was found between childhood and perinatal subcortical stroke (p = 0.028), yielding to a 4.80-fold increased risk for childhood subcortical stroke (95% CI: 1.16– 19.92). Obtained results corroborate previously reported FV Leiden association with AIS (Coen Herak et al. Clin Appl Thromb/Hemost, in press) with additional ACE I/D association. Exclusive associations of β-fibrinogen −455AA genotype with cortical stroke and PAI-1 4G/5G with childhood subcortical stroke support the assumption that specific polymorphisms may contribute to location dependant lesion formation.

Published
2017

7. Pathophysiology and clinical studies in CKD 5D

Author

J. G. Raimann, F. Gotch, M. Keen, P. Kotanko, N. W. Levin, A. Pierratos, R. Lindsay, G. Severova-Andreevska, L. Trajceska, S. Gelev, G. Selim, A. Sikole, S. Y. Yoon, S. D. Hwang, D. K. Cho, Y. H. Cho, S. J. Moon, W. Ribitsch, P. J. Schreiner, M. Uhlmann, G. Schilcher, V. Stadlbauer, J. H. Horina, A. R. Rosenkranz, D. Schneditz, I. Kiss, L. Kerkovits, C. Ambrus, I. Kulcsar, J. Szegedi, A. Benke, B. Borbas, S. Ferenczi, M. Hengsperger, S. Kazup, L. Nagy, J. Nemeth, A. Rozinka, T. Szabo, T. Szelestei, E. Toth, G. Varga, G. Wagner, G. Zakar, L. Gergely, A. Tisler, Z. Kiss, S. Sasaki, M. Miyamato, A. Nomura, K. Koitabashi, H. Nishiwaki, T. Suzuki, D. Uchida, H. Kawarazaki, Y. Shibagaki, K. Kimura, C. Libetta, C. Martinelli, E. Margiotta, I. Borettaz, M. Canevari, P. Esposito, V. Sepe, A. Dal Canton, P. Pateinakis, C. Dimitriadis, A. Papagianni, S. Douma, G. Efstratiadis, D. Memmos, C. L. Nelson, P. J. Dunstan, R. Zwiech, Y. Hasuike, K. Yanase, S. Hamahata, T. Nagai, M. Yahiro, S. Kaibe, A. Kida, Y. Nagasawa, T. Kuragano, T. Nakanishi, J. S. Kim, J. W. Yang, S. O. Choi, B. G. Han, J. H. Chang, A. J. Kim, H. S. Kim, H. Ro, J. Y. Jung, H. H. Lee, W. Chung, H. Tanaka, T. Kita, K. Okamoto, M. Mikami, R. Sakai, E. Lojacono, B. Votta, T. Rampino, M. Gregorini, A. Amore, R. Coppo, M. M. S. ElSharkawy, M. Kamel, M. Elhamamsy, S. Allam, J.-H. Ryu, S. Lee, S. C. Hong, S.-J. Kim, D.-H. Kang, D.-R. Ryu, K. B. Choi, T. Kiraz, A. Yalcin, M. Akay, G. Sahin, A. Musmul, Y. Kamijo, H. Horiuchi, H. Iida, K. Saito, R. Furutera, Y. Ishibashi, M. Sidiropoulou, S. Patsialas, M. Angelopoulos, M. Torreggiani, N. Serpieri, M. Arazzi, V. Esposito, M. Calatroni, E. La Porta, D. Catucci, G. Montagna, L. Semeraro, E. Efficace, V. Piazza, L. Picardi, G. Villa, C. Esposito, J. C. Kim, E. Hwang, K. Park, H. Karakizlis, K. Bohl, B. Kortus-Goetze, R. Dodel, J. Hoyer, A. Cinar, R. Kazancioglu, A. T. Isik, E. Aydemir, B. Gorcin, J. Radic, D. Ljutic, M. Radic, V. Kovacic, M. Sain, K. Dodig Curkovic, A. E. Grzegorzewska, L. Niepolski, J. Sikora, P. Jagodzinski, A. Sowinska, V. Sirolli, C. Rossi, A. Di Castelnuovo, P. Felaco, L. Amoroso, M. Zucchelli, D. Ciavardelli, P. Sacchetta, A. Urbani, A. Arduini, M. Bonomini, T. Inoue, K. Okano, Y. Tsuruta, K. Tsuchiya, T. Akiba, K. Nitta, and D. Pajzderski

Subjects
Transplantation, Nephrology
Published
2013

8. [Benefit Assessment and Price Negotiation Under AMNOG: Calculable Process or Unfair Poker Game?]

Author

D, Radic, S, Haugk, and M, Radic

Subjects
Drug Industry, Negotiating, Germany, Commerce, Costs and Cost Analysis, Humans, Drug Costs
Abstract

Ever since the introduction of the Market Restructuring Act, the evaluation and price negotiations of drugs have been controversial. While the Federal Joint Committee considers that the process is transparent and in accordance with clear evidence-based criteria, representatives of pharmaceutical companies are particularly critical of the fact that the central association of statutory health insurance is involved in both the determination of added therapeutic benefit of drugs as well as in the subsequent price negotiation. In this study, we investigate these 2 contradictory assessments empirically. For this purpose, we model the benefit assessment and price negotiation processes under AMNOG and analyze their relationship. We show that the number of patients in the target population, and the annual cost of therapy for the appropriate comparator therapy have a negative influence on the determination of the added benefit of the new therapy. The added value itself has a positive (negative) effect on the mark-up for the appropriate comparator therapy (price discount), while the annual treatment costs of the new therapy (which appropriate comparator therapy) have a positive (negative) influence. We find clues, but no significant evidence for the hypothesis that the decisions on the added value of new medicines and the subsequent price negotiations are interdependent.Die Nutzenbewertung und Preisverhandlung unter dem Arzneimittelmarktneuordnungsgesetz wird seit seiner Einführung kontrovers diskutiert. Während der Gemeinsame Bundesausschuss die Meinung vertritt, dass das Verfahren transparent und nach klaren evidenzbasierten Kriterien abläuft, wird von Vertretern von Pharmaunternehmen insbesondere die Tatsache kritisiert, dass mit dem Spitzenverband der gesetzlichen Krankenversicherungen eine Partei sowohl bei der Feststellung des Zusatznutzens als auch bei der anschließenden Preisverhandlung involviert ist. In der Arbeit wollen wir diese beiden sich widersprechenden Einschätzungen empirisch überprüfen. Dazu modellieren wir die Nutzenbewertungs- und Preisverhandlungsprozesse unter AMNOG und analysieren deren Zusammenhang. Wir können zeigen, dass die Anzahl an Patienten in der Zielpopulation und die Jahrestherapiekosten für die zweckmäßige Vergleichstherapie einen negativen Einfluss auf die Feststellung des Zusatznutzens der neuen Therapie haben. Der Zusatznutzen selbst hat einen positiven (negativen) Einfluss auf den Zuschlag zur zweckmäßigen Vergleichstherapie (Rabatt auf Ausgabepreis), während die Jahrestherapiekosten der neuen Therapie (der zweckmäßigen Vergleichstherapie) einen positiven (negativen) Einfluss haben. Wir finden Hinweise, aber keine signifikante Evidenz für die These, dass die Beschlüsse über den Zusatznutzen von neuen Medikamenten und die anschließenden Preisverhandlungen interdependent ablaufen.

Published
2016

9. Epidemiology and outcome research in CKD 5D

Author

L. Coentrao, C. Ribeiro, C. Santos-Araujo, R. Neto, M. Pestana, W. Kleophas, A. Karaboyas, Y. LI, J. Bommer, R. Pisoni, B. Robinson, F. Port, G. Celik, B. Burcak Annagur, M. Yilmaz, T. Demir, F. Kara, K. Trigka, P. Dousdampanis, N. Vaitsis, S. Aggelakou-Vaitsi, K. Turkmen, I. Guney, F. Turgut, L. Altintepe, H. Z. Tonbul, E. Abdel-Rahman, P. Sclauzero, G. Galli, G. Barbati, M. Carraro, G. O. Panzetta, M. Van Diepen, M. Schroijen, O. Dekkers, F. Dekker, A. Sikole, G. Severova- Andreevska, L. Trajceska, S. Gelev, V. Amitov, S. Pavleska- Kuzmanovska, H. Rayner, R. Vanholder, M. Hecking, B. Jung, M. Leung, F. Huynh, T. Chung, S. Marchuk, M. Kiaii, L. Er, R. Werb, C. Chan-Yan, M. Beaulieu, P. Malindretos, P. Makri, G. Zagkotsis, G. Koutroumbas, G. Loukas, E. Nikolaou, M. Pavlou, E. Gourgoulianni, M. Paparizou, M. Markou, E. Syrgani, C. Syrganis, J. Raimann, L. A. Usvyat, V. Bhalani, N. W. Levin, P. Kotanko, X. Huang, P. Stenvinkel, A. R. Qureshi, U. Riserus, T. Cederholm, P. Barany, O. Heimburger, B. Lindholm, J. J. Carrero, J. H. Chang, J. Y. Sung, J. Y. Jung, H. H. Lee, W. Chung, S. Kim, J. S. Han, K. Y. Na, A. Fragoso, A. Pinho, A. Malho, A. P. Silva, E. Morgado, P. Leao Neves, N. Joki, Y. Tanaka, M. Iwasaki, S. Kubo, T. Hayashi, Y. Takahashi, K. Hirahata, Y. Imamura, H. Hase, C. Castledine, J. Gilg, C. Rogers, Y. Ben-Shlomo, F. Caskey, J. S. Sandhu, G. S. Bajwa, S. Kansal, J. Sandhu, A. Jayanti, M. Nikam, L. Ebah, A. Summers, S. Mitra, J. Agar, A. Perkins, R. Simmonds, A. Tjipto, S. Amet, V. Launay-Vacher, M. Laville, A. Tricotel, C. Frances, B. Stengel, J.-Y. Gauvrit, N. Grenier, G. Reinhardt, O. Clement, N. Janus, L. Rouillon, G. Choukroun, G. Deray, A. Bernasconi, R. Waisman, A. P. Montoya, A. A. Liste, R. Hermes, G. Muguerza, R. Heguilen, E. L. Iliescu, V. Martina, M. A. Rizzo, P. Magenta, L. Lubatti, G. Rombola, M. Gallieni, C. Loirat, H. Mellerio, M. Labeguerie, B. Andriss, E. Savoye, M. Lassale, C. Jacquelinet, C. Alberti, Y. Aggarwal, J. Baharani, S. Tabrizian, S. Ossareh, M. Zebarjadi, P. Azevedo, F. Travassos, I. Frade, M. Almeida, J. Queiros, F. Silva, A. Cabrita, R. Rodrigues, C. Couchoud, J. Kitty, S. Benedicte, C. Fergus, C. Cecile, B. Sahar, V. Emmanuel, J. Christian, E. Rene, H. Barahimi, M. Mahdavi-Mazdeh, M. Nafar, M. Petruzzi, M. De Benedittis, M. Sciancalepore, L. Gargano, P. Natale, M. C. Vecchio, V. Saglimbene, F. Pellegrini, G. Gentile, P. Stroumza, L. Frantzen, M. Leal, M. Torok, A. Bednarek, J. Dulawa, E. Celia, R. Gelfman, J. Hegbrant, C. Wollheim, S. Palmer, D. W. Johnson, P. J. Ford, J. C. Craig, G. F. Strippoli, M. Ruospo, B. El Hayek, B. Hayek, E. Baamonde, E. Bosch, J. I. Ramirez, G. Perez, A. Ramirez, A. Toledo, M. M. Lago, C. Garcia-Canton, M. D. Checa, B. Canaud, B. Lantz, A. Granger-Vallee, P. Lertdumrongluk, N. Molinari, J. Ethier, M. Jadoul, B. Gillespie, C. Bond, S. Wang, T. Alfieri, P. Braunhofer, B. Newsome, M. Wang, B. Bieber, M. Guidinger, L. Zuo, X. Yu, X. Yang, J. Qian, N. Chen, J. Albert, Y. Yan, S. Ramirez, M. Beresan, A. Lapidus, M. Canteli, A. Tong, B. Manns, J. Craig, G. Strippoli, M. Mortazavi, B. Vahdatpour, S. Shahidi, A. Ghasempour, D. Taheri, S. Dolatkhah, A. Emami Naieni, M. Ghassami, M. Khan, K. Abdulnabi, P. Pai, M. Vecchio, M. A. Muqueet, M. J. Hasan, M. A. Kashem, P. K. Dutta, F. X. Liu, L. Noe, T. Quock, N. Neil, G. Inglese, M. Motamed Najjar, B. Bahmani, A. Shafiabadi, J. Helve, M. Haapio, P.-H. Groop, C. Gronhagen-Riska, P. Finne, R. Sund, M. Cai, S. Baweja, A. Clements, A. Kent, R. Reilly, N. Taylor, S. Holt, L. Mcmahon, M. Carter, F. M. Van der Sande, J. Kooman, R. Malhotra, G. Ouellet, E. L. Penne, S. Thijssen, M. Etter, A. Tashman, A. Guinsburg, A. Grassmann, C. Barth, C. Marelli, D. Marcelli, G. Von Gersdorff, I. Bayh, L. Scatizzi, M. Lam, M. Schaller, T. Toffelmire, Y. Wang, P. Sheppard, L. Neri, V. A. Andreucci, L. A. Rocca-Rey, S. V. Bertoli, D. Brancaccio, G. De Berardis, G. Lucisano, D. Johnson, A. Nicolucci, C. Bonifati, S. D. Navaneethan, V. Montinaro, M. Zsom, A. Bednarek-Skublewska, G. Graziano, J. N. Ferrari, A. Santoro, A. Zucchelli, G. Triolo, S. Maffei, S. De Cosmo, V. M. Manfreda, L. Juillard, A. Rousset, F. Butel, S. Girardot-Seguin, T. Hannedouche, M. Isnard, Y. Berland, P. Vanhille, J.-P. Ortiz, G. Janin, P. Nicoud, M. Touam, E. Bruce, B. Grace, P. Clayton, A. Cass, S. Mcdonald, Y. Furumatsu, T. Kitamura, N. Fujii, S. Ogata, H. Nakamoto, K. Iseki, Y. Tsubakihara, C.-C. Chien, J.-J. Wang, J.-C. Hwang, H.-Y. Wang, W.-C. Kan, N. Kuster, L. Patrier, A.-S. Bargnoux, M. Morena, A.-M. Dupuy, S. Badiou, J.-P. Cristol, J.-M. Desmet, V. Fernandes, F. Collart, N. Spinogatti, J.-M. Pochet, M. Dratwa, E. Goffin, J. Nortier, D. S. Zilisteanu, M. Voiculescu, E. Rusu, C. Achim, R. Bobeica, S. Balanica, T. Atasie, S. Florence, S. Anne-Marie, L. Michel, C. Cyrille, A. Strakosha, N. Pasko, S. Kodra, N. Thereska, A. Lowney, E. Lowney, R. Grant, M. Murphy, L. Casserly, T. O' Brien, W. D. Plant, J. Radic, D. Ljutic, V. Kovacic, M. Radic, K. Dodig-Curkovic, M. Sain, I. Jelicic, T. Hamano, C. Nakano, S. Yonemoto, A. Okuno, M. Katayama, Y. Isaka, M. Nordio, A. Limido, M. Postorino, M. Nichelatti, M. Khil, I. Dudar, V. Khil, I. Shifris, M. Momtaz, A. R. Soliman, M. I. El Lawindi, P. Dzekova-Vidimliski, S. Pavleska-Kuzmanovska, I. Nikolov, G. Selim, T. Shoji, R. Kakiya, N. Tatsumi-Shimomura, Y. Tsujimoto, T. Tabata, H. Shima, K. Mori, S. Fukumoto, H. Tahara, H. Koyama, M. Emoto, E. Ishimura, Y. Nishizawa, and M. Inaba

Subjects
Transplantation, medicine.medical_specialty, Nephrology, business.industry, Epidemiology, Medicine, business, Intensive care medicine, Outcome (game theory)
Published
2012

10. Thematic stream: systemic autoimmune diseases (PP32-PP58): PP32. Trace Element Levels in Patients with Familial Mediterranean Fever as Compared to Healthy Controls

Author

K. Yildirim, H. Uzkeser, A. Uyanik, S. Karatay, A. Kiziltunc, M. Keles, M. D. Kaya, C. O. Serdal, S. Emire, K. Fatih, Y. Ayla, T. Hasan, Y. Hasan, M. Radic, J. Radic, D. M. Kaliterna, S. Ugurlu, A. Engin, G. Ozgon, G. Hatemi, E. Akyayla, M. Bakir, H. Ozdogan, Y. Ozguler, S. Masatlioglu, S. Celik, H. Kilic, M. Cengiz, V. Hamuryudan, Y. Ozyazgan, E. Seyahi, S. Yurdakul, H. Yazici, C. Mat, K. Tascilar, Y. Demirel, S. Calli, S. Yildirim, M. Batumlu, D. Cevirgen, O. Alpaslan, M. Balli, F. Sametoglu, D. Doganyilmaz, T. F. Cermik, M. O. Erdede, B. Y. Yesilada, M. Yilmaz, M. Saglam, B. Pinar, T. Figen, K. Seher, O. Muyesser, G. Emel, E. Meral, A. Karakuzu, M. H. Uyanik, M. Atasoy, F. Gundogdu, B. Aktan, F. Alper, A. M. Kantarci, X. Agrogianni, I. Lintzeris, A. Lintzeri, K. Nas, Z. Demircan, M. Karakoc, U. Yuksel, R. Cevik, T. T. Sumer, I. Zagar, N. Gaspersic, H. Rafa, O. Medjeber, M. Belkhelfa, D. Hakem, C. Touil-Boukoffa, E. Aydogdu, S. Donmez, G. E. Pamuk, O. N. Pamuk, N. Cakir, N. S. Shahril, E. Mageswaren, L. M. Isa, S. Rajalingam, F. Abdullah, M. R. Kaslan, A. T. Samsudin, A. Arbi, H. Hussein, M. Brandao, A. R. Caldas, A. Marinho, A. M. da Silva, F. Farinha, C. Vasconcelos, C.-B. Choi, S.-R. Park, K. Wha Lee, S.-C. Bae, S. Beg, J. Popovich, S. Sessoms, T. Dimitroulas, G. Giannakoulas, K. Papadopoulou, H. Karvounis, H. Dimitroula, G. Koliakos, T. Karamitsos, D. Parcharidou, L. Settas, A. C. Nandagudi, S. Ziaj, G. M. Dabrera, T. Kim, K. Kim, and C. Kang

Subjects
business.industry, Trace element, chemistry.chemical_element, Serum copper, Familial Mediterranean fever, Inflammation, Systemic scleroderma, medicine.disease, Rheumatology, chemistry, Immunology, Medicine, Pharmacology (medical), In patient, medicine.symptom, business, Selenium
Published
2011

11. Gene frequencies of platelet-specific antigens in Croatian population

Author

Marina Pavić, D. Coen Herak, Renata Zadro, M. Radic Antolic, and Slavica Dodig

Subjects
Adult, Male, endocrine system, Adolescent, Genotype, Croatia, Platelet disorder, Population, Population genetics, Platelet Membrane Glycoproteins, Biology, Platelet membrane glycoprotein, Young Adult, trombocitni antigeni, polimorfizam, dijete, Gene Frequency, Antigen, Polymorphism (computer science), Humans, Antigens, Human Platelet, Child, education, Allele frequency, Alleles, Aged, Genetics, education.field_of_study, Infant, Hematology, Middle Aged, Europe, Phenotype, Child, Preschool, Immunology, Female, hormones, hormone substitutes, and hormone antagonists
Abstract

The human platelet antigens (HPA) are genetically defined polymorphisms expressed on platelet membrane glycoproteins. As platelet antigens are very important in several clinical situations and in population genetics, we used the polymerase chain reaction with sequence-specific primers (PCR-SSP) to investigate HPA-1, -2, -3 and -5 allele frequencies in the Croatian population. The HPA frequencies obtained in 219 Croatians were: 1a-0.854, 1b-0.146, 2a-0.890, 2b-0.110, 3a-0.575, 3b-0.425, 5a-0.895 and 5b-0.105. These data are similar to the frequencies reported in most European studies with some significant differences in HPA-2 when compared with the Dutch and German population, in HPA-3 when compared with the Swiss population and in HPA-5 when compared with the Finnish population. The three most common condensed HPA genotypes in the Croatian population were: HPA-1a/a, -2a/a, -3a/b, -5-a/a (0.283), HPA-1a/a, -2a/a, -3a/a, -5-a/a (0.137) and HPA-1a/b, -2a/a, -3a/b, -5-a/a (0.087). Data obtained in this study can be used for better understanding and treatment of immune-mediated platelet disorders in our population.

Published
2010

12. C0326: Polymorphisms in Coagulation Factor Genes and Enzymes of Homocysteine Metabolism in Croatian Children with Arterial Ischemic Stroke

Author

J. Lenicek Krleza, R. Zrinski-Topic, M. Radic Antolic, Renata Zadro, D. Coen Herak, Vlasta Djuranovic, and Ivana Horvat

Subjects
Croatian, chemistry.chemical_classification, medicine.medical_specialty, business.industry, Hematology, Arterial Ischemic Stroke, language.human_language, Endocrinology, Enzyme, Coagulation, chemistry, Internal medicine, medicine, language, Homocysteine metabolism, business, Gene
Published
2014

16. Low-molecular weight hyaluronic acid for the treatment of vulvovaginal atrophy: an innovative clinical practice

Author

V. Prestia, E. Bertozzi, and M. Radice

Subjects
low-molecular weight hyaluronic acid, quality of life, vulvovaginal atrophy, radiofrequency, genitourinary syndrome of menopause, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Objective: Vulvovaginal Atrophy / Genitourinary Syndrome of Menopause (VVA/GSM) is a clinical manifestation of symptoms at vaginal level, associated to menopause, as dryness, burning, and itching, or impairment of sexual life. Physicians have several options that can be adopted to improve patient health. The clinical use of Low Molecular Weight Hyaluronic Acid (LMWHA) represents one of the most interesting approach for these patients. The aim of this work is to evaluate the ability of LMWHA to improve VVA/GSM symptoms on menopausal women. Patients and Methods: 50 menopausal women reporting dryness, itching, burning and dyspareunia, were enrolled. Vaginal and oral administrations of LMWHA were performed in association with radiofrequency (RF) and poration (PO) treatment sessions. For the first five weeks, one oral tablet with 100 mg of LMWHA was administered everyday while, at vaginal level, one suppository for day, containing 5 mg of LMWHA, 1 mg of Vitamin A and 1 mg of Vitamin E, was administered in the two days preceding RF. One RF/PO session for week was performed, during the first five weeks. When RF was interrupted, LMWHA treatment was continued with daily administrations of one suppository for two weeks and one tablet for ten months. At baseline (T0), and after 5 weeks (T1), 6 months (T2) and 12 months (T3) all patients have reported symptoms perception. Primary and secondary outcomes of this study were improvements of vaginal dryness and of all other symptoms respectively. Results: A rapid improvement of vaginal dryness was reported when compared to T0, with reductions of 80.28%, 79.77% and 67.91% at T1, T2 and T3, respectively. In a similar way, also all other symptoms were resulted improved, and the result has remained stable over time. Conclusions: Considering data obtained, LMWHA administration represents an innovative solution to improve symptomatology of VVA/GSM patients.

Published
2020
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17. Reactive Sintering of Diamond-Titanium System under High Pressure

Author

Momčilo M. Ristić, I. Kushtalova, I. Krstanovic, S. M. Radic, and I. Stasyuk

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Titanium carbide, Toroid, Materials science, Metallurgy, technology, industry, and agriculture, Diamond, Sintering, chemistry.chemical_element, engineering.material, equipment and supplies, Pressure vessel, chemistry.chemical_compound, chemistry, hemic and lymphatic diseases, High pressure, parasitic diseases, Superhard material, engineering, Titanium
Abstract

The reactive sintering of diamond with titanium was studied. The experiments were carried out at pressures of 4.3 and 7.0 GPa in a “TOROID” type pressure chamber. Under these conditions it was possible to investigate reactive sintering at temperatures up to 1973°K without graphitization of diamond.

Published
1984

18. Caracterización fenotípica y genotípica de la resistencia a imipenem en Pseudomonas aeruginosa aisladas en un hospital de Buenos Aires Phenotypic and genotypic characterization of imipenem-resistant Pseudomonas aeruginosa isolated in Buenos Aires

Author

D. Cejas, M. Almuzara, G. Santella, A. Tuduri, S. Palombarani, S. Figueroa, G. Gutkind, and M. Radice

Subjects
Carbapenemasas, Metalo-beta-lactamasas, Resistencia a carbapenemes, Carbapenemases, Metallo-beta-lactamases, Carbapenem resistance, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

En el presente estudio, que tuvo por objeto analizar los mecanismos involucrados en la resistencia a carbapenemes, se incluyeron 129 aislamientos de Pseudomonas aeruginosa recuperados durante el año 2006 en el Hospital "Eva Perón" de la Provincia de Buenos Aires. La caracterización fenotípica y genotípica de la resistencia permitió reconocer la presencia de metalo-beta-lactamasas (MBL) en el 14% de esos aislamientos. En todos ellos se identificó la presencia de la enzima IMP-13; sin embargo, algunos aislamientos resultaron sensibles a carbapenemes de acuerdo con los puntos de corte establecidos por el CLSI e incluso con las sugerencias de la Subcomisión de Antimicrobianos de SADEBAC, AAM. El ensayo de detección fenotípica de MBL de sinergia con doble disco resultó útil en este estudio. Sólo aquellos aislamientos productores de IMP-13 que a su vez presentaron alteraciones en las proteínas de membrana externa resultaron completamente resistentes a imipenem. Los aislamientos productores de MBL correspondieron a varios tipos clonales, lo cual sugiere no sólo la diseminación de una cepa resistente, sino también la diseminación horizontal de este mecanismo de resistencia entre clones diferentes.From 129 P. aeruginosa isolated at a health care centre located in Buenos Aires (Hospital "Eva Perón"), 14% produced IMP-13. Although 18 isolates were metallo-beta-lactamases (MBL) producers, only those isolates that displayed altered outer membrane protein profiles correlated with the resistant category according to CLSI or even Subcomisión de Antimicrobianos, SADEBAC, AAM. Phenotypic screening of metallo-beta-lactamases proved to be appropriate for detecting MBL producing isolates. IMP-13 producing isolates corresponded to at least five different clonal types, which not only suggests the dissemination of the resistant strain but also of the resistant marker.

Published
2008

30. Comparación de diferentes métodos para identificar las especies del género Proteus Comparison of different methods in order to identify Proteus spp

Author

S. T. Castro, C. R. Rodríguez, B. E. Perazzi, M. Radice, M. Paz Sticotti, H. Muzio, J. Juárez, G. Gutkind, A. M. R. Famiglietti, P. I. Santini, and C. A. Vay

Subjects
género Proteus, identificación, genus Proteus, identification, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Los objetivos de este trabajo fueron: a) identificar a nivel de especie aislamientos de Proteus siguiendo la combinación de los esquemas de Farmer y O'Hara; b) determinar la utilidad del sistema comercial API 20E y de un esquema reducido de pruebas (agar TSI y agar MIO: movilidad, indol y ornitina), comparar estos procedimientos con la metodología convencional y evaluar su sensibilidad y especificidad, y c) evaluar la utilidad del perfil proteico en la identificación de las distintas especies. Se estudiaron 205 aislamientos de Proteus spp. aislados en el período comprendido entre enero de 1998 y setiembre de 2004, recuperados de distintos materiales clínicos correspondientes a pacientes hospitalizados y ambulatorios atendidos en el Hospital de Clínicas. Los organismos fueron identificados mediante la metodología convencional, por el sistema API 20E y con un esquema reducido de pruebas; 48 de ellos fueron sometidos a un SDS-PAGE. API 20E identificó 79 de 87 aislamientos de P. mirabilis (90,8%), 103/103 del complejo P. vulgaris y 15/15 de P. penneri. Ocho aislamientos identificados como Proteus spp. resultaron ser P. mirabilis, al incluir una prueba adicional (maltosa). En la identificación, el esquema reducido coincidió en un 100% con la metodología convencional. A diferencia del sistema API 20E, el esquema reducido alcanza la correcta identificación de todas las especies en laboratorios de baja complejidad, sin la necesidad de pruebas adicionales. El perfil proteico permitió la correcta diferenciación de las tres especies, independientemente de las diferentes atipias de P. mirabilis.The objectives were: a) to identify Proteus strains to species level, following Farmer's and O'Hara's conventional biochemical reactions; b) to evaluate the sensitivity and specificity of both the API 20E method and a schema of reduced reactions (TSI and MIO agar: motility, indole and ornithine) comparing them with conventional methodology, and c) to evaluate the utility of SDS-PAGE (total proteins) in order to identify Proteus strains to species level. Two hundred and five Proteus spp. clinical isolates, were collected between January 1998 and September 2004, from inpatients and outpatients at Hospital de Clínicas. Strains were identified by means of conventional methodology, the API 20E method, and a schema of reduced reactions. SDS-PAGE (total proteins) was used in 48 out of the 205 strains. The API 20E method identified 79 out of 87 (90.8%) strains of P. mirabilis, 103 out of 103 P. vulgaris complex, and 15 out of 15 P. penneri. Eight strains of P. mirabilis were identified as Proteus spp., the acid production from maltose being necessary to identify them to species level. The schema of reduced reactions identified 205 out of 205 (100%) strains, that is, this schema of reduced reactions identified all the strains to species level without any additional tests, in marked contrast to the API 20E method. The SDS-PAGE (total proteins) identified the three species of the genus, even if the strains of P. mirabilis showed different biochemical reactions.

Published
2006

31. Entorno genético de CTX-M-2 en aislamientos de Klebsiella pneumoniae provenientes de pacientes hospitalizados en Uruguay Genetic environment of CTX-M-2 in Klebsiella pneumoniae isolates from hospitalized patients in Uruguay

Author

R. Vignoli, N. Cordeiro, V. Seija, F. Schelotto, M. Radice, J. Ayala, P. Power, and G. Gutkind

Subjects
orf513, integrón de clase 1, beta-lactamasas de espectro extendido, blaCTX-M-2, class 1 integron, extended-spectrum beta-lactamases, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Se estudiaron las cepas de Klebsiella pneumoniae K96005 y K13, productoras de la beta-lactamasa de espectro extendido CTX-M-2, aisladas durante 1996 y 2003, respectivamente, de pacientes hospitalizados en Uruguay. Se realizó la caracterización del entorno génico del gen blaCTX-M-2 mediante mapeo por PCR y secuenciación de los amplicones. Los resultados revelan que en ambos aislamientos el gen codificante de dicha enzima se encuentra en un integrón complejo de clase 1, asociado a la presencia de orf513. El integrón identificado, cuyo arreglo de genes es aac(6')-Ib, blaOXA-2, orfD, asociados a orf513-blaCTX-M-2, parece estar ampliamente diseminado en la región del Río de la Plata.We studied two CTX-M-2-producing Klebsiella pneumoniae clinical strains, K96005 and K13, isolated from hospitalized patients in Uruguay, during 1996 and 2003, respectively. The genomic surroundings of blaCTX-M-2 were characterized by PCR-mapping and DNA sequencing. Our results show that blaCTX-M-2 is included in a complex class-1 integron (InK13), associated with an orf513 in both isolates. The genetic array of the integron, aac(6')-Ib, blaCTX-M-2, orfD (gene cassette region), associated with an orf513-blaCTX-M-2, seems to be widely disseminated over the Río de la Plata region.

Published
2006

32. Prevalencia de metalo-β-lactamasas en Pseudomonas aeruginosa resistentes a carbapenemes en un Hospital Universitario de Buenos Aires Prevalence of metallo-β-lactamase in carbapenem resistant Pseudomonas aeruginosa at an University Hospital of Buenos Aires City

Author

G. Pagniez, M. Radice, A. Cuirolo, O. Rodríguez, H. Rodríguez, C. Vay, A. Famiglietti, and G. Gutkind

Subjects
metalo-β-lactamasas, resistencia a carbapenemes, carbapenemasas, metallo-undefined-lactamases, carbapenem resistance, carbapenemases, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Se estudiaron 91 aislamientos de Pseudomonas aeruginosa resistentes a carbapenemes con el objetivo de conocer la prevalencia de metalo-β-lactamasas y evaluar la habilidad del ensayo de inhibición empleando discos de EDTA (1 µmol) en su detección. Se determinó la presencia de carbapenemasas en 10 (11%) de los aislamientos recuperados. La sensibilidad a aztreonam en los aislamientos resistentes a ambos carbapenemes resultó un buen predictor de la presencia de estas enzimas. Dichas carbapenemasas correspondieron a la enzima VIM-2 en tres de ellos y a VIM-11 en otros siete. En todos los casos los genes codificantes de estas enzimas se encontraron localizados en integrones de clase 1 seguidos corriente abajo de genes codificantes de enzimas acetilantes de antibióticos aminoglucosídicos. El ensayo de detección fenotípica de metalo-β-lactamasas empleando discos de EDTA mostró un 100% de especificidad y sensibilidad en la detección de estas enzimas en la población de Pseudomonas aeruginosa analizadas.The present study was conducted to estimate the prevalence of metallo-β-lactamases in 91 consecutive carbapenem resistant Pseudomonas aeruginosa isolates, recovered from inpatients at Hospital de Clínicas in Buenos Aires. Both, phenotypic and genotypic methods detected the presence of carbapenemases in 10 (11%) isolates, corresponding to VIM-11 in 7/10 and VIM-2 in the others. Codifying genes were all included in class 1 integrons, upstream genes coding for aminoglycoside modifying enzymes. One hundred percent sensitivity and specificity was achieved by the metallo-β-lactamases phenotypic screening method using EDTA (1 µmol) disks in the Pseudomonas aeruginosa isolates included in this study. Sensitivity to aztreonam in carbapenem resistant isolates was suspicious of the presence of these enzymes.

Published
2006

33. Caracterización fenotípica y genotípica de la resistencia enzimática a las cefalosporinas de tercera generación en Enterobacter spp. Phenotypic and genotypic characterization of resistance to third-generation cephalosporins in Enterobacter spp.

Author

E. Bertona, M. Radice, C. H. Rodríguez, C. Barberis, C. Vay, A. Famiglietti, and G. Gutkind

Subjects
Enterobacter spp., b-lactamasas de espectro extendido, cefepima, expanded-spectrum beta-lactamases, cefepime, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Enterobacter spp. es un patógeno intrahospitalario que presenta múltiples mecanismos de resistencia a los antibióticos b-lactámicos. Se caracterizaron fenotípica y genotípicamente las diferentes b-lactamasas presentes en 27 aislamientos consecutivos e ininterrumpidos de Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes). También se evaluó la habilidad de diferentes métodos fenotípicos para detectar b-lactamasas de espectro extendido (BLEE) en estos microorganismos. En 15/27 aislamientos (63%) se observó resistencia a las cefalosporinas de tercera generación. En 12 de los aislamientos resistentes se detectó un alto nivel de producción de cefalosporinasa cromosómica, siendo 6 de ellos también productores de PER-2. Dicha resistencia en los 3 aislamientos restantes se debió exclusivamente a la presencia de BLEE, PER-2 en 2 de ellos y CTX-M-2 en un caso. Sólo CTX-M-2 se detectó con todas las cefalosporinas probadas en los ensayos de sinergia, utilizando el método de difusión, mientras que cefepima mejoró la detección de PER-2 en 7/8 aislamientos productores de esta BLEE, 4/8 utilizando la prueba de doble disco y 7/8 comparando discos de cefepima con y sin el agregado de ácido clavulánico. El método de dilución empleado solo detectó 1/9 BLEE al comparar las cefalosporinas con y sin el agregado de inhibidor.Enterobacter spp. are becoming increasingly frequent nosocomial pathogens with multiple resistance mechanism to b-lactam antibiotics. We carried out the phenotypic and genotypic characterization of beta-lactamases in 27 Enterobacter spp. (25 Enterobacter cloacae y 2 Enterobacter aerogenes), as well as the ability of different extended spectrum b-lactamase (ESBL) screening methods. Resistance to third generation cephalosporins was observed in 15/27 (63%) isolates. Twelve resistant isolates produced high level chromosomal encoded AmpC b-lactamase; 6 of them were also producers of PER-2. Resistance to third generation cephalosporins in the remaining 3 isolates was due to the presence of ESBLs, PER-2 in 2 cases, and CTX-M-2 in the other. Only CTX-M-2 production was detected with all tested cephalosporins using difusion synergy tests, while cefepime improved ESBLs detection in 7/8 PER-2 producers, 4/8 in the inhibitor aproximation test and 7/8 with double disk test using cefepime containing disk with and without clavulanic acid. Dilution method, including cephalosporins with and without the inhibitor detected 1/9 ESBLs producers.

Published
2005

34. Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae Consensus for antimicrobial susceptibility testing for Enterobacteriaceae

Author

A. Famiglietti, M. Quinteros, M. Vázquez, M. Marín, F. Nicola, M. Radice, M. Galas, F. Pasterán, C. Bantar, J. M. Casellas, J. Kovensky Pupko, E. Couto, M. Goldberg, H. Lopardo, G. Gutkind, and R. Soloaga

Subjects
Enterobacteriaceae, Pruebas de sensibilidad, Antimicrobianos, Resistencia, beta-lactamasas, Susceptibility testing, Antimicrobial, Resistance, beta-lactamases, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

En este documento se elaboraron una serie de recomendaciones para el ensayo, lectura, interpretación e informe de las pruebas de sensibilidad a los antimicrobianos para las enterobacterias aisladas con mayor frecuencia de especímenes clínicos. Se adoptaron como base las recomendaciones del National Committee for Clinical Laboratory Standards (NCCLS) de los EEUU, los de la subcomisión de Antimicrobianos, de la Sociedad Argentina de Bacteriología Clínica (SADEBAC), división de la Asociación Argentina de Microbiología (AAM) y de un grupo de expertos invitados. En él se indican las resistencias naturales de los diferentes miembros que integran la familia Enterobacteriaceae y se analiza la actividad de las diferentes beta-lactamasas cromosómicas, propias de cada especie, sobre las penicilinas, cefalosporinas y carbapenemes. Se recomiendan los antimicrobianos que se deberían ensayar, ubicados estratégicamente, para detectar los mecanismos de resistencia más frecuentes y cuales se deberían informar de acuerdo a la especie aislada, el sitio de infección y el origen de la cepa (intra o extrahospitalario). Se detallan los métodos de "screening" y de confirmación fenotipíca para detectar beta-lactamasas de espectro extendido (BLEE) que son más adecuados a nuestra realidad. Por último, se mencionan patrones infrecuentes de sensibilidad/resistencia que deberían verificarse y los perfiles de sensibilidad que pueden hallarse en las distintas enterobacterias en relación con los probables mecanismos de resistencia. Se debe resaltar que el contenido de este documento debe ser considerado como recomendaciones realizadas por expertos argentinos basadas en una revisión de la literatura y datos personales.Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

Published
2005

35. Prevalencia de metalo-β-lactamasas en Pseudomonas aeruginosa resistentes a carbapenemes en un Hospital Universitario de Buenos Aires

Author

G. Pagniez, M. Radice, A. Cuirolo, O. Rodríguez, H. Rodríguez, C. Vay, A. Famiglietti, and G. Gutkind

Subjects
metalo-β-lactamasas, resistencia a carbapenemes, carbapenemasas, Infectious and parasitic diseases, RC109-216, Microbiology, QR1-502
Abstract

Se estudiaron 91 aislamientos de Pseudomonas aeruginosa resistentes a carbapenemes con el objetivo de conocer la prevalencia de metalo-β-lactamasas y evaluar la habilidad del ensayo de inhibición empleando discos de EDTA (1 µmol) en su detección. Se determinó la presencia de carbapenemasas en 10 (11%) de los aislamientos recuperados. La sensibilidad a aztreonam en los aislamientos resistentes a ambos carbapenemes resultó un buen predictor de la presencia de estas enzimas. Dichas carbapenemasas correspondieron a la enzima VIM-2 en tres de ellos y a VIM-11 en otros siete. En todos los casos los genes codificantes de estas enzimas se encontraron localizados en integrones de clase 1 seguidos corriente abajo de genes codificantes de enzimas acetilantes de antibióticos aminoglucosídicos. El ensayo de detección fenotípica de metalo-β-lactamasas empleando discos de EDTA mostró un 100% de especificidad y sensibilidad en la detección de estas enzimas en la población de Pseudomonas aeruginosa analizadas.

36. Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma.

Author

Vesna M Coric, Tatjana P Simic, Tatjana D Pekmezovic, Gordana M Basta-Jovanovic, Ana R Savic Radojevic, Sanja M Radojevic-Skodric, Marija G Matic, Dejan P Dragicevic, Tanja M Radic, Ljiljana M Bogdanovic, Zoran M Dzamic, and Marija S Pljesa-Ercegovac

Subjects
Medicine, Science
Abstract

The aim of this study was to evaluate specific glutathione S-transferase (GST) gene variants as determinants of risk in patients with clear cell renal cell carcinoma (cRCC), independently or simultaneously with established RCC risk factors, as well as to discern whether phenotype changes reflect genotype-associated risk. GSTA1, GSTM1, GSTP1 and GSTT1 genotypes were determined in 199 cRCC patients and 274 matched controls. Benzo(a)pyrene diolepoxide (BPDE)-DNA adducts were determined in DNA samples obtained from cRCC patients by ELISA method. Significant association between GST genotype and risk of cRCC development was found for the GSTM1-null and GSTP1-variant genotype (p = 0.02 and p

Published
2016
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37. Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with survival in muscle invasive bladder cancer patients.

Author

Tatjana I Djukic, Ana R Savic-Radojevic, Tatjana D Pekmezovic, Marija G Matic, Marija S Pljesa-Ercegovac, Vesna M Coric, Tanja M Radic, Sonja R Suvakov, Biljana N Krivic, Dejan P Dragicevic, and Tatjana P Simic

Subjects
Medicine, Science
Abstract

OBJECTIVE: To examine the association of six glutathione transferase (GST) gene polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1, GSTA1/rs3957357) with the survival of patients with muscle invasive bladder cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A total of 105 patients with muscle invasive bladder cancer were included in the study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on predicting mortality was analyzed by the Cox proportional hazard models, while Kaplan-Meier analysis was performed to assess differences in survival. RESULTS: GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P = 0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively) and significantly influenced the overall survival. There was no association between GSTP1, GSTM1 and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a significant effect on the survival in the subgroup of patients who received chemotherapy (P = 0.006). CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in patients with muscle invasive bladder cancer.

Published
2013
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38. Analysis of progression-free and overall survival in ovarian cancer: Bevacizumab treatment outcomes using historical cohort.

Author

Conic I, Nedovic B, Zivadinovic R, Zivadinovic R, Petric A, Stojnev S, Petkovic I, Krtinic D, and Radic M

Subjects
Humans, Female, Middle Aged, Aged, Cohort Studies, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Agents, Immunological therapeutic use, Serbia epidemiology, Treatment Outcome, Kaplan-Meier Estimate, Retrospective Studies, Survival Rate, Aged, 80 and over, Bevacizumab therapeutic use, Bevacizumab administration & dosage, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Ovarian Neoplasms mortality, Progression-Free Survival, Carcinoma, Ovarian Epithelial drug therapy, Carcinoma, Ovarian Epithelial mortality, Carcinoma, Ovarian Epithelial pathology
Abstract

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

Published
2024
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39. Comparison of pharmacotherapeutic analgesic response and safety profile of tapentadol with other opioids.

Author

Krtinic D, Rankovic GN, Cvetanovic A, Conic I, Mitic MT, Radic M, Prokin AL, and Cevrljakovic M

Subjects
Humans, Drug Interactions, Phenols adverse effects, Phenols administration & dosage, Delayed-Action Preparations, Chronic Pain drug therapy, Animals, Pain drug therapy, Tapentadol administration & dosage, Analgesics, Opioid adverse effects, Analgesics, Opioid administration & dosage
Abstract

Tapentadol is a unique opioid analgesic due to its dual mechanism of action. Compared to other opioids with a classical mechanism of action, its analgesic potential is not far behind them, and its advantages are: a better safety profile in terms of a lower potential for drug-drug interactions and a lower potential for causing adverse events, and it is safe to use in sensitive populations. Tapentadol in the form of a immediate release formulation is an adequate drug of choice for achieving a pharmacotherapeutic analgesic response in acute pain conditions, while in the form of a extended release formulation it is an adequate pharmacotherapeutic analgesic solution for chronic pain syndromes of various etiology. Due to the specificity of the mechanism of action, tapentadol adequately relieves both pain components - nociceptive and neuropathic, and has an indication area for mixed pain syndrome as well. Based on this, the need for the use of co-analgesics is reduced, and thus the incidence of possible interactions and adverse events is reduced.

Published
2024
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40. Enthesitis in IBD Patients.

Author

Akrapovic Olic I, Vukovic J, Radic M, and Sundov Z

Abstract

Inflammatory bowel disease (IBD) is marked by chronic inflammation of the gastrointestinal tract and encompasses two major subtypes, Crohn's disease (CD) and ulcerative colitis (UC). IBD is frequently accompanied by extraintestinal manifestations (EIMs), with axial and peripheral spondyloarthritis (SpA) being the most common. Enthesitis, an inflammation of the bone insertions of capsules, ligaments, and tendons, represents an initial lesion in SpA. However, enthesitis remains an underestimated and often obscured EIM. The early detection of subclinical entheseal involvement in IBD patients using ultrasound (US) could provide an opportunity for timely intervention. US is a more feasible and affordable approach than magnetic resonance imaging (MRI). While previous meta-analyses have reported on the incidence and prevalence of SpA in IBD, specific attention to enthesitis has been lacking. Therefore, this narrative review aims to assess the current knowledge on existing IBD-SpA cohorts, focusing specifically on enthesitis.

Published
2024
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41. DN4 questionnaire as a useful tool for evaluating the pharmacotherapeutic response to opioid pharmacotherapy in malignant neuropathy.

Author

Krtinic D, Rankovic GN, Petkovic I, Cvetanovic A, Conic I, Mitic MT, Radic M, Cevrljakovic M, Golubovic ST, Binic I, Apostolovic MA, Jovanovic H, Trajkovic H, Milijasevic D, Mladenovic N, and Lukic R

Subjects
Humans, Female, Middle Aged, Surveys and Questionnaires, Aged, Cancer Pain drug therapy, Adult, Bone Neoplasms secondary, Bone Neoplasms drug therapy, Bone Neoplasms complications, Palliative Care methods, Pain Measurement, Follow-Up Studies, Tapentadol administration & dosage, Analgesics, Opioid administration & dosage, Analgesics, Opioid therapeutic use, Neuralgia drug therapy, Phenols administration & dosage, Breast Neoplasms drug therapy, Breast Neoplasms pathology
Abstract

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Published
2024
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42. The Association of Death Receptors and TGF-β1 Expression in Urothelial Bladder Cancer and Their Prognostic Significance.

Author

Stojnev S, Conic I, Ristic Petrovic A, Petkovic I, Radic M, Krstic M, and Jankovic Velickovic L

Abstract

Death receptor signalization that triggers the extrinsic apoptotic pathway and TGF-β1 have important roles in urothelial carcinogenesis, with a complex interplay between them. The aim of this research was to assess the association of death receptors DR4, DR5, and FAS as well as TGF-β1 immunohistochemical expression with the clinicopathological characteristics of urothelial bladder cancer (UBC) and to evaluate their prognostic significance. The decrease or loss of death receptors' expression was significantly associated with muscle-invasive tumors, while non-invasive UBC often retains the expression of death receptors, which are mutually strongly linked. High DR4 expression is a marker of low-grade tumors and UBC associated with exposition to known carcinogens. Conversely, TGF-β1 was significantly associated with high tumor grade and advanced stage. High expression of DR4 and FAS indicates longer overall survival. High TGF-β1 signifies an inferior outcome and is an independent predictor of adverse prognosis in UBC patients. This study reveals the expression profile of death receptors in UBC and their possible interconnection with TGF-β1 and indicates independent prognostic significance of high FAS and TGF-β1 expression in UBC, which may contribute to deciphering the enigma of UBC heterogeneity in light of the rapid development of novel and effective therapeutic approaches, including targeting of the TRAIL-induced apoptotic pathway.

Published
2024
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43. SARS-CoV-2 and Influenza Co-Infection: Fair Competition or Sinister Combination?

Author

Teluguakula N, Chow VTK, Pandareesh MD, Dasegowda V, Kurrapotula V, Gopegowda SM, and Radic M

Subjects
Humans, Animals, Virus Replication, Coinfection virology, Influenza, Human virology, SARS-CoV-2 physiology, COVID-19 virology, COVID-19 complications, Lung virology
Abstract

The COVID-19 pandemic remains a serious public health problem globally. During winter influenza seasons, more aggressive SARS-CoV-2 infections and fatalities have been documented, indicating that influenza co-infections may significantly impact the disease outcome of COVID-19. Both influenza and SARS-CoV-2 viruses share many similarities in their transmission and their cellular tropism for replication in the human respiratory tract. However, the complex intricacies and multi-faceted dynamics of how the two pathogens interact to ensure their survival in the same lung microenvironment are still unclear. In addition, clinical studies on influenza co-infections in COVID-19 patients do not provide conclusive evidence of how influenza co-infection mechanistically modifies disease outcomes of COVID-19. This review discusses various viral as well as host factors that potentially influence the survival or synergism of these two respiratory pathogens in the infected lung microenvironment.

Published
2024
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44. Phenotypic and Molecular Characterization of a Hospital Outbreak Clonal Lineage of Salmonella enterica Subspecies enterica serovar Mikawasima Containing bla TEM-1B and bla SHV-2 That Emerged on a Neonatal Ward, During the COVID-19 Pandemic.

Author

Novak A, Dzelalija M, Goic-Barisic I, Kovacic A, Pirija M, Maravic A, Radic M, Marinovic J, Rubic Z, Carev M, and Tonkic M

Subjects
Infant, Newborn, Humans, Anti-Bacterial Agents pharmacology, Serogroup, Pandemics, Microbial Sensitivity Tests, Salmonella, beta-Lactamases genetics, Drug Resistance, Multiple, Bacterial genetics, Hospitals, Salmonella enterica genetics, COVID-19 epidemiology
Abstract

Nontyphoid salmonella can cause severe infections in newborns and is therefore declared a pathogen of major health significance at this age. The aim of the study was molecular and antimicrobial characterization of β-lactamase-producing Salmonella Mikawasima outbreak clone on a Neonatal ward, University Hospital of Split (UHS), Croatia during the COVID-19 pandemic. From April 2020, until April 2023, 75 nonrepetitive strains of Salmonella Mikawasima were isolated from stool specimens and tested for antimicrobial resistance. All 75 isolates were resistant to ampicillin and gentamicin, while 98% of isolates were resistant to amoxicillin/clavulanic acid. A high level of resistance was observed to third-generation cephalosporins (36% to ceftriaxone and 47% to ceftazidime). Extended-spectrum β-lactamase production was phenotypically detected by double-disk synergy test in 40% of isolates. Moderate resistance to quinolones was detected; 7% of isolates were resistant to pefloxacin and ciprofloxacin. All isolates were susceptible to carbapenems, chloramphenicol, and co-trimoxazole. Fourteen representative isolates, from 2020, 2021, 2022, and 2023, were analyzed with PFGE and all of them belong to the same clone. Whole-genome sequencing (WGS) analysis of three outbreak-related strains (SM1 and SM2 from 2020 and SM3 from 2023) confirmed that these strains share the same serotype (Mikawasima), multilocus sequence typing profile (ST2030), resistance genes [ bla TEM-1B, aac(6')-Iaa, aac(6')-Im, and aph(2'')-Ib) ] and carry incompatibility group C (IncC) plasmid. Furthermore, the gene bla SHV-2 was detected in SM1 and SM2. In summary, WGS analysis of three representative strains clearly demonstrates the persistence of β-lactamase-producing Salmonella Mikawasima in UHS during the 4-year period.

Published
2024
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45. A quantitative and T-pattern analysis of anxiety-like behavior in male GAERS, NEC, and Wistar rats bred under the same conditions, against a commercially available Wistar control group in the hole board and elevated plus maze tests.

Author

Casarrubea M, Radic M, Morais TP, Mifsud E, Cuboni E, Aiello S, Crescimanno G, Crunelli V, and Di Giovanni G

Subjects
Humans, Rats, Male, Animals, Rats, Wistar, Elevated Plus Maze Test, Control Groups, Electroencephalography, Anxiety, Disease Models, Animal, Epilepsy, Absence genetics
Abstract

Aim: The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbred polygenic model of childhood absence epilepsy (CAE), which, as their non-epileptic control (NEC) rats, are derived from Wistar rats. While the validity of GAERS in reproducing absence seizures is well established, its use as a model for CAE psychiatric comorbidities has been subject to conflicting findings. Differences in colonies, experimental procedures, and the use of diverse controls from different breeders may account for these disparities. Therefore, in this study, we compared GAERS, NEC, and Wistar bred in the same animal facility with commercially available Wistar (Cm Wistar) as a third control., Methods: We performed hole board (HB) and elevated plus maze (EPM) tests that were analyzed with standard quantitative and T-pattern analysis in male, age-matched Cm Wistar and GAERS, NEC, and Wistar, bred under the same conditions, to rule out the influence of different housing factors and provide extra information on the structure of anxiety-like behavior of GAERS rats., Results: Quantitative analysis showed that GAERS and NEC had similar low anxiety-like behavior when compared to Cm Wistar but not to Wistar rats, although a higher hole-focused exploration was revealed in NEC. T-pattern analysis showed that GAERS, NEC, and Wistar had a similar anxiety status, whereas GAERS and NEC exhibited major differences with Cm Wistar but not Wistar rats. EPM results indicated that GAERS and NEC also have similar low anxiety compared to Cm Wistar and/or Wistar rats. Nevertheless, the analysis of the T-pattern containing open-arm entry showed GAERS and Wistar to be less anxious than NEC and Cm Wistar rats., Conclusion: To summarize, comorbid anxiety may not be present in male GAERS rats. This study also highlighted the importance of including a control Wistar group bred under the same conditions when evaluating their behavior, as using Wistar rats from commercial breeders can lead to misleading results., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Published
2024
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46. scaRNA20 promotes pseudouridylatory modification of small nuclear snRNA U12 and improves cardiomyogenesis.

Author

Perales S, Sigamani V, Rajasingh S, Gurusamy N, Bittel D, Czirok A, Radic M, and Rajasingh J

Subjects
Humans, Alternative Splicing, Hypoxia, Myocytes, Cardiac, RNA, Small Nuclear genetics, RNA
Abstract

Non-coding RNAs, particularly small Cajal-body associated RNAs (scaRNAs), play a significant role in spliceosomal RNA modifications. While their involvement in ischemic myocardium regeneration is known, their role in cardiac development is unexplored. We investigated scaRNA20's role in iPSC differentiation into cardiomyocytes (iCMCs) via overexpression and knockdown assays. We measured scaRNA20-OE-iCMCs and scaRNA20-KD-iCMCs contractility using Particle Image Velocimetry (PIV), comparing them to control iCMCs. We explored scaRNA20's impact on alternative splicing via pseudouridylation (Ψ) of snRNA U12, analyzing its functional consequences in cardiac differentiation. scaRNA20-OE-iPSC differentiation increased beating colonies, upregulated cardiac-specific genes, activated TP53 and STAT3, and preserved contractility under hypoxia. Conversely, scaRNA20-KD-iCMCs exhibited poor differentiation and contractility. STAT3 inhibition in scaRNA20-OE-iPSCs hindered cardiac differentiation. RNA immunoprecipitation revealed increased Ψ at the 28th uridine of U12 RNA in scaRNA20-OE iCMCs. U12-KD iCMCs had reduced cardiac differentiation, which improved upon U12 RNA introduction. In summary, scaRNA20-OE in iPSCs enhances cardiomyogenesis, preserves iCMC function under hypoxia, and may have implications for ischemic myocardium regeneration., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rajasingh Johnson reports financial support was provided by National Heart Lung and Blood Institute. Johnson Rajasingh reports financial support was provided by American Heart Association. Selene Perales reports financial support was provided by American Heart Association. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare no potential conflict of interest relevant to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
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47. Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID.

Author

Narasaraju T, Neeli I, Criswell SL, Krishnappa A, Meng W, Silva V, Bila G, Vovk V, Serhiy Z, Bowlin GL, Meyer N, Luning Prak ET, Radic M, and Bilyy R

Subjects
Humans, Post-Acute COVID-19 Syndrome, Lung metabolism, Elastin, Collagen metabolism, Extracellular Matrix Proteins metabolism, Endopeptidases, Extracellular Matrix metabolism, Fibrosis, Neutrophils metabolism, COVID-19 metabolism
Abstract

Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.

Published
2024
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48. Evaluation of Reporting Quality of Glaucoma Randomized Controlled Trial Abstracts: Current Status and Future Perspectives.

Author

Vucinovic A, Bukic J, Rusic D, Leskur D, Seselja Perisin A, Radic M, Grahovac M, and Modun D

Abstract

The aim of this study was to explore adherence to the Consolidated Standards of Reporting Trials (CONSORT) reporting standards in abstracts of randomized controlled trials on glaucoma. A cross-sectional observational study was conducted on the aforementioned abstracts, indexed in MEDLINE/PubMed between the years 2017 and 2021. In total, 302 abstracts met the inclusion criteria and were further analyzed. The median score of CONSORT-A items was 8 (interquartile range, 7-10) out of 17 (47.0%). Most analyzed studies were conducted in a single center (80.5%) and the abstracts were predominantly structured (95.0%). Only 20.5% of the abstracts adequately described the trial design, while randomization and funding were described by 6.0% of the abstracts. Higher overall scores were associated with structured abstracts, a multicenter setting, statistically significant results, funding by industry, a higher number of participants, and having been published in journals with impact factors above four ( p < 0.001, respectively). The results of this study indicate a suboptimal adherence to CONSORT-A reporting standards, especially in particular items such as randomization and funding. Since these factors could contribute to the overall quality of the trials and further translation of trial results into clinical practice, an improvement in glaucoma research reporting transparency is needed.

Published
2024
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49. The role of tapentadol in cancer pain pharmacotherapy in patients with metastatic malignant disease.

Author

Krtinic D, Nedin Rankovic G, Petkovic I, Cvetanovic A, Conic I, Todorovic Mitic M, Radic M, Milijasevic B, Lucic Prokin A, Djordjevic V, Jovanovic H, Trajkovic H, Andjelkovic Apostolovic M, Milijasevic D, Zdravkovic R, and Binic I

Subjects
Humans, Female, Tapentadol, Prospective Studies, Phenols therapeutic use, Delayed-Action Preparations, Analgesics, Opioid therapeutic use, Cancer Pain drug therapy, Low Back Pain diagnosis, Neuralgia drug therapy, Breast Neoplasms complications, Breast Neoplasms drug therapy, Breast Neoplasms chemically induced, Chronic Pain drug therapy
Abstract

Objective: The aim of this study was to establish the effects of prolonged formulation of tapentadol in combination with palliative radiotherapy on bone metastatic changes in oncology patients with primary breast cancer and proven bone metastases., Patients and Methods: The research was conducted as a prospective study at the Clinic for Oncology, University Clinical Center Nis, Nis, Serbia, during a three-month interval of monitoring the patients. The first group comprised 30 patients with mentioned malignancy for which tapentadol was prescribed, and they underwent palliative radiotherapy for bone metastatic changes. The second group comprised 30 patients with the same disease treated only with pain relief radiotherapy to metastatic changes. All the patients were interviewed using the Pain Detect questionnaire., Results: Significantly more patients from the first group had severe pain in comparison to patients from the control group (χ2=16.596; p<0.001) at the second measurement and also at the third measurement (χ2=15.357; p<0.001). At the third measurement, pain with a neuropathic component was significantly more present in patients from the control group (χ2=8.541; p=0.014). There was a significant pain reduction in both groups - Tapentadol group (χ2=59.513; p<0.001) and control group (χ2=60.000; p<0.001) - and also a significant reduction of neuropathic pain component: Tapentadol group (χ2=56.267; p<0.001) and control group (χ2=60,000; p<0.001). There was a statistically significant positive correlation between tapentadol dose and pain intensity according to the numerical pain scale at all three measurements., Conclusions: Tapentadol prolonged-release formulation is an effective pharmacotherapy solution, along with palliative radiotherapy, for pain relief in patients with skeletal metastatic breast cancer. Palliative radiotherapy in these patients does not provide adequate neuropathic pain component relief.

Published
2023
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50. Neutrophil attachment via Mac-1 ( α M β 2 ; CD11b/CD18; CR3) integrins induces PAD4 deimination of profilin and histone H3.

Author

Neeli I, Moarefian M, Kuseladass J, Dwivedi N, Jones C, and Radic M

Subjects
Humans, Citrullination, Profilins metabolism, Integrins metabolism, Manganese metabolism, Macrophage-1 Antigen genetics, Macrophage-1 Antigen metabolism, Inflammation metabolism, Histones metabolism, Neutrophils
Abstract

Neutrophil adhesion to endothelia, entry into tissues and chemotaxis constitute essential steps in the immune response to infections that drive inflammation. Neutrophils bind to other cells and migrate via adhesion receptors, notably the α M β 2 integrin dimer (also called Mac-1, CR3 or CD11b/CD18). Here, the response of neutrophils to integrin engagement was examined by monitoring the activity of peptidylarginine deiminase 4 (PAD4). Histone H3 deimination was strongly stimulated by manganese, an integrin-activating divalent cation, even in the absence of additional inflammatory stimuli. Manganese-induced cell attachment resulted in neutrophil swarm formation that paralleled histone deimination, whereas antibodies that impair integrin binding prevented both cell adhesion and histone deimination. Manganese treatment led to putative deimination of profilin, a protein that functions as an actin-organizing hub, as detected by two-dimensional gel electrophoresis and citrulline immunoblotting. Cl-amidine, a covalent inhibitor of PAD4, and GSK484, a specific PAD4 inhibitor, blocked profilin deimination. Neutrophil migration toward leukotriene B4 and toward synovial fluid from a rheumatoid arthritis patient were inhibited by chloramidine, thus supporting the contribution of deimination to chemotaxis. The data, based on a simplified system for integrin activation, imply a mechanism whereby integrin attachment coordinates neutrophil responses to inflammation and orchestrates deimination of nuclear and cytoskeletal proteins. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.

Published
2023
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