<p>Dijabetesna retinopatija je među vodećim uzročnicima stečenog slepila, kako u razvijenim zemljama, tako i zemljama u razvoju. Dijabetesna retinopatija je jedna od<br />najče&scaron;ćih komplikacija Dijabetes Mellitus-a. U sklopu dijabetesne retinopatije jedan od najranijih razloga koji dovodi do pada vidne o&scaron;trine je dijabetični makularni edem (DME). Pad vidne o&scaron;trine kod pacijenata sa dijabetesom naru&scaron;ava njihov kvalitet života i umanjuje radnu sposobnost. Dosada&scaron;nji oblik lečenja laserfotokoaguacijom makule, nije dao zadovoljavajuće rezultate. U novije vreme sve vi&scaron;e je zastupljeno farmakolo&scaron;ko lečenje edema koje podrazumeva intrvitrealnu aplikaciju lekova iz grupe inhibitora vaskularnog endotelnog faktora rasta (VEGF inhibitori), koji dovodi do stabilizacije zidova krvnih sudova.&nbsp;<br />Cilj ove studije je da se ispita efikasnost lečenja DME uz pomoć intravitrealno aplikovanih lekova iz grupe inhibitora vaskularnog endotelnog faktora rasta u odnosu na konvencionalno do sada priznato lečenje laserfotokogulacijom makule.&nbsp;<br />Efikasnost lečenja je procenjivana na dva načina: anatomski, na osnovu smanjenja centralne makularne debljine izražene u &mu;m, merene metodom optičke koherentne tomografije, i funkcionalno, na osnovu pobolj&scaron;anja vidne o&scaron;trine koja je izražavana u log MAR jedinicama. U ovoj prospektivnoj, randomiziranoj kliničkoj studiji sa minimumom praćenja od 6 meseci, u eksperimentalnoj grupi tretiran je 51 pacijent,<br />odnosno 84 oka aplikacijom bevacizumaba (anti VEGF agens) u dozi od 1,25 mg, sa ili bez dodatnog laser tretmana.&nbsp;<br />Uz prosečno 2,46 inekcije postignuta je prosečna redukcija centralne makularne debljine od 139,15 &mu;m.&nbsp; Dobijene vrednosti su nakon svake aplikovane doze su značajno bolje u odnosu na početnu. Edemi sa većom centralnom makularnom debljinom su zahtevali tretman sa većim brojem inekcija. Kod većih edema je postignuta i veća redukcija centralne makularne debljine. U odnosu na vidnu o&scaron;trinu u eksperimentalnoj grupi postignuto je pobolj&scaron;anje od 0,135 log MAR jedinica. Efekat lasera kao samostalne terapije u kontrolnoj grupi (50 pacijenata, 92 oka) nije bio<br />značajan ni u pogledu smanjenja centralne makularne debljine kao ni na osnovu pobolj&scaron;nja vidne o&scaron;trine. Tretman bevacizumabom samostalno ili u kombinaciji sa laserom je efikasniji u tretmanu DME u odnosu na konvencionalni tretman laserfotokoaguacijom koji potvrđeno dovodi do stabilizacije stanja. Značaj ove studije je potvrda efikasnosti i bezbednosti jednog novog oblika lečenja koji samostalno ili u kombinaciji sa laser tretmanom predstavlja novi protokol lečenja dijabetičnog makularnog edema.</p> / <p>Diabetic retinopathy is among the leading causes of acquired blindness in developed countries, as well as in developing countries. Diabetic retinopathy is one of the most frequent Diabetes Mellitus complications. Within diabetic retinopathy, diabetic macular edema (DME) is one of the earliest causes of the loss of visual acuity. Impaired vision causes decline in life quality in diabetic patients and it decreases their<br />working ability. Up to this date, laser photocoagulation treatment has not given<br />satisfactory results. Recently, new promising treatment forms have emerged, including the intravitreal application of vascular endothelium growth factor (VEGF inhibitors), which lead to stabilization of the vessel wall. The aim of this study is to evaluate the efficacy of DME treatment consisting of intravitreal&nbsp; VEGF inhibitor application alone or as a part of combined treatment (intravitreal VEGF inhibitor plus laser photocoagulation) compared with conventional laser treatment alone. The effect of treatment was evaluated according to morphological parameters by measuring central macular thickness (CMT) in &mu;m with optical coherence tomography, and according to functional parameter by visual acuity in log MAR scale. In this prospective randomized clinical trial, with minimum follow up of 6 months, in experimental group 51 patient, or 84 eyes were treated with bevacizumab (VEGF inhibitor) in 1.25 mg dosage, alone or in combination with laser. The mean reduction in was 139.15 &mu;m, which was achieved with 2.46 doses on average. The difference between the final and initial CMT values after each dos age was tatistically significant.<br />Edemas with high central macular thickness required high number of intraviteal<br />aplicatons and the reduction was higher. In our study, mean visual acuity improved significantly in 0.135 log MAR. In control group (50 patient, 92 eyes) treated with laserphotocolagulation alone, the effect on visual acuity and central acular thickness was not statistically significant. The treatment with bevacizumab alone or in combined<br />treatment is more effective in treating DME than conventional macular laser treatment alone, from both - anatomical and functional perspective. The importance of this study is confirmation of the efficacy and safety of a new form of treatment and the introduction of a new protocol for the treatment of diabetic macular edema.</p>

<p>Uvod: Reumatoidni artritis (RA) je bolest koja dovodi do ireverzibilnog o&scaron;tećenja zglobova usled čega je neophodno pri postavljanju dijagnoze započeti lečenje. TNF-alfa inhibitori predstavljaju revolucionarno otkriće u lečenju RA, pri čemu su najče&scaron;će kori&scaron;ćeni Etanercept i Adalimumab. Oni nisu efikasni kod svih pacijenata kod kojih se primene, a mehanizmi gubitka odgovora nisu jasni. Cilj rada je odrediti uticaj Etanercepta i Adalimumaba na aktivnost bolesti (merenjem DAS28 SE i DAS28 CRP skora) i funkcionalni status pacijenata (merenjem HAQ-DI upitnika), broj bolnih i otečnih zglobova pre i tokom godinu dana primene ovih lekova, kao i utvrditi povezanost koncentracije Etanercepta i Adalimumaba u krvi sa vrednostima DAS28 SE u momentu odreĎivanja koncentracije leka. Praćena je i učestalost neželjenih efekata kod pacijenata lečenih sa ova dva leka. Ispitan je i uticaj primene Metotreksata na nivoe lekova u krvi, kao i doza Metotreksata pre i 6 meseci nakon uvoĎenja Etanercepta ili Adalimumaba. Metode: Studija je sprovedena u Specijalnoj bolnici za reumatske bolesti i Klinici za nefrologiju i kliničku imunologiju, Kliničkog centra Vojvodine u Novom Sadu i obuhvatila je 88 pacijenata kod kojih je postavljena dijagnoza RA, od kojih je 49 bilo lečeno Etanerceptom, a 39 Adalimumabom. Analizirana je medicinska dokumentacija, a nakon početka primene TNF-alfa inhibitora svim ispitanicima je u toku godinu dana svaka tri meseca raĎena kontrola koja je podrazumevala anamnezu i fizički pregled, analizu biohemijskih nalaza krvi, merena je aktivnost bolesti merenjem indeksa aktivnosti bolesti DAS28 SE i DAS28 CRP i raĎena procena funkcionalnog statusa tako &scaron;to je pacijent popunjavao HAQ-DI upitnik. Rezultati: Aktivnost RA merena DAS28 SE i DAS28 CRP indeksima, funkcionalni status meren HAQ-DI upitnikom, broj bolnih i otečenih zglobova i vrednosti reaktanata akutne faze značajno su veći pre početka terapije Etanerceptom i Adalimumabom i smanjuje se tokom prvih 6 meseci lečenja ovim lekovima i potom se taj efekat terapije održava do kraja perioda praćenja. Nema statistički značajne razlike u poreĎenju Etanercepta i Adalimumaba u odnosu na učestalost neželjenih dejstava. Doza Metotreksata je statistički značajno manja 6 meseci nakon upotrebe biolo&scaron;kog leka Etanercept i Adalimumab. Pacijenti lečeni Metotreksatom uz Adalimumab imali su statistički značajno veće nivoe leka, nego oni koji ga nisu koristili. Zaključak: TNF-alfa inhibitori ne dovode do zaustavljanja bolesti kod svih pacijenata kod kojih se primene. Mehanizam gubitka odgovora na terapiju TNF-alfa inhibitorima nije jasan. Kako bi se donela najbolja odluka za pacijenta, neophodno je odrediti nivo leka u krvi, kao i nivo antitela na lek prilikom svake promene stanja pacijenta. Za sada nema dovoljno studija koje ukazuju da li postoji veza izmeĎu ekspresije TNF-alfa gena i nivoa TNF-alfa u krvi, te da li bi se merenjem TNF-alfa u krvi mogla korigovati terapija i doza TNF-alfa inhibitora &scaron;to će verovatno biti predmet budućih istraživanja.</p> / <p>Rheumatoid Arthritis (RA) is a disease that leads to irreversible joint damage, which makes necessary to start treatment when the diagnosis is set. TNF-alpha inhibitors represent a revolutionary discovery in the treatment of RA, and the most commonly used are Etanercept and Adalimumab. They are not effective in all patients, and the mechanisms of loss of response are not clear. The aim of this study is to determine the effect of Etanercept and Adalimumab on disease activity (by measuring DAS28 SE and DAS28 CRP score) and the functional status of patients (by measuring the HAQ-DI questionnaire), the number of painful and swollen joints before and during the first year of administration of these drugs. Also, it was determined a correlation between the concentration of Etanercept and Adalimumab in blood and the values of DAS28 SE at the moment of drug concentration measurement. The incidence of adverse effects in patients treated with these two drugs was also observed. It was examined the effect of Methotrexate on drug levels in the blood as well as the dose of Methotrexate before and 6 months after the introduction of Etanercept or Adalimumab. Methods: The study was conducted at the Special Hospital for Rheumatic Diseases and the Clinic of Nephrology and Clinical Immunology, Clinical Center of Vojvodina in Novi Sad. It included 88 patients with RA, 49 were treated with Etanercept and 39 with Adalimumab. Medical documentation was analyzed, and during the first year of TNF-alpha inhibitor administration, every three months were done anamnesis and physical examination, analysis of blood biochemical findings, measurements of the disease activity with DAS28 SE and DAS28 CRP score and a functional status assessment with the HAQ-DI questionnaire. Results: Disease activity measured by DAS28 SE and DAS28 CRP scores, functional status measured with HAQ-DI questionnaire, number of painful and swollen joints and acute phase reactant values are significantly higher before Etanercept and Adalimumab therapy and decreased during the first 6 months of treatment with these drugs and then this effect of therapy is maintained until the end of the monitoring period. There is no statistically significant difference in the comparison of Etanercept and Adalimumab with respect to the frequency of adverse events. The dose of Methotrexate was statistically significantly lower for 6 months after the use of Etanercept and Adalimumab. Patients treated with Methotrexate and Adalimumab had statistically significantly higher drug levels than those who did not use it. Conclusion: TNF-alpha inhibitors are not effective in all patients who used them. The mechanism of loss of response to TNF-alpha inhibitors is not clear. In order to make the best decision for the patient, it is necessary to determine the drug level in the blood as well as the level of antibodies to the drug in each change in the patient&#39;s condition. For now, there are not enough studies to indicate whether there is a link between expression of the TNF-alpha gene and the level of TNF-alpha in the blood, and whether the measurement of the TNF-alpha in blood could be used for therapy correction and change of dose of TNF-alpha inhibitor, which is likely to be the subject of the future research.</p>

University of Macau / Institute of Chinese Medical Sciences

Human immunodeficiency type 1 (HIV-1) is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years’ infection and as a result, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that a moderate protection is possible, which may correlate with antibody dependent cellular cytotoxicity (ADCC) activity. Previous studies in the Lu lab demonstrated that in an HIV-1 vaccine phase I trial, DP6-001, a polyvalent Env DNA prime-protein boost formulation, could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities along with multiple Fc mediated effector functions. I developed a protocol for the production and analysis of HIV-1 Env-specific human monoclonal antibodies (mAbs) isolated from these DP6-001 vaccinees. By utilizing a labeled gp120 bait to isolate Env specific B cells, paired heavy and light chain immunoglobulin (Ig) genes were cloned and allowed for the production of monoclonal antibodies with specificity for gp120. By using this protocol, 13 isolated mAbs from four DP6-001 vaccinees showed broad binding activities to gp120 proteins of diverse subtypes, both autologous and heterologous to vaccine immunogens, with mostly conformational epitopes and a few V3 and C5 specific mAbs. Equally cross-reactive Fc-mediated functional activities, including ADCC and antibody dependent cellular phagocytosis (ADCP), were present with both immune sera and isolated mAbs, confirming the induction of non-neutralizing functional antibodies by the DNA prime- protein boost vaccination. Elicitation of broadly reactive mAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV-1 vaccine design.