REZISTENŢA LA INRT LA PACIENŢII MULTIPLU EXPERIMENTAŢI DIN CONSTANŢA: IMPLICAŢII TERAPEUTICE

Obiective. Identificarea prevalenţei rezistenţei dobândite la INRT (inhibitorii non-nucleozidici de reverstranscriptază) şi al profilelor de rezistenţă la un lot de pacienţi cu multiple scheme de terapie antiretrovirală din Constanţa şi evaluarea opţiunilor terapeutice remanente. Material şi metode. Studiu retrospectiv ce a inclus 144 pacienţi seropozitivi HIV, multiplu experimentaţi terapeutic, aflaţi în eşec virusologic. Tulpinile izolate de la aceşti pacienţi au fost analizate în Laboratorul de Genetică Moleculară al Institutului Naţional de Boli Infecţioase „Matei Balş“ din Bucureşti, secvenţele rezultate fiind salvate în format Fasta. Subtiparea HIV-1 s-a efectuat pe baza algoritmului „REGA HIV-1&2 Automated subtyping tool version 2.0“. Pentru determinarea opţiunile terapeutice s-a utilizat „Stanford HIVdb Program version 8.4“. Datele au fost prelucrate statistic cu programul R-Project. Reprezentările grafice au fost realizate cu programul GNUPLOT. Rezultate. Prevalenţa rezistenţei dobândite a fost de 92,36%. Cea mai frecventă mutaţie a fost la nivelul codonului 184. Calea TAM-2 a fost mai frecvent selectată decât TAM-1, existând şi asociaţii între cele douăcăi; în schimb, mutaţia K65R a fost rar întâlnită. Concluzii. Prevalenţa rezistenţei dobândite la INRT a fost crescută. Opţiunea terapeutică cea mai valoroasă în clasa INRT a ramas tenofovirul, datorită profilului mutaţional selectat, mai ales din cauza neutilizării lui şi a folosirii extensive anterioare a analogilor timidinici

Antiangiogenic cytokines as potential new therapeutic targets for resveratrol in diabetic retinopathy

Mihaela Popescu,1 Cătălina Bogdan,2 Adela Pintea,3 Dumitriţa Rugină,3 Corina Ionescu1 1Department of Biochemistry, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania; 2Department of Dermopharmacy and Cosmetics, University of Medicine and Pharmacy “Iuliu Haţieganu”, Cluj-Napoca, Romania; 3Department of Biochemistry, University of Agriculture Sciences and Veterinary Medicine, Cluj-Napoca, Romania Abstract: Diabetes mellitus (DM) affects >350 million people worldwide. With many complications that can reduce the patient’s quality of life, vision loss is one of the most debilitating disorders it can cause. Active research in the field of diabetes includes microvascular complications in diabetic retinopathy (DR). Disturbances in the balance of pro-angiogenesis and anti-angiogenesis factors can lead to the progression of DR. The retinal pigment epithelium (RPE) is the outermost layer of the retina, and it is essential in maintaining the visual function. The RPE produces and secretes growth factors as well as protective agents which maintain structural integrity of the retina. Small natural molecules, such as resveratrol, may influence neurotrophic factors of the retina. The pigment epithelium-derived factor (PEDF) and thrombospondin-1 (TSP-1) are secreted by RPE cells. These two proteins inhibit angiogenesis and inflammation in RPE cells. An alteration of their production contributes to various eye diseases. There is a critical balance between two important factors secreted on opposite sides of the RPE: at the basal side, vascular endothelial growth factor (VEGF; acts on the choroidal endothelium) and, on the apical side, PEDF (acts on neurons and photoreceptors). Resveratrol inhibits VEGF expression in human adult RPE cells and limits the development of proliferative vitreoretinopathy, by attenuating transforming growth factor-β2-induced wound closure and cell migration. Possible new mechanisms could include PEDF and TSP-1 expression alterations under physiological and pathological conditions. Resveratrol is currently of interest due to its capacity to influence the cell’s secretory activity. Some limitations arise from its low bioavailability. Several drug delivery systems are currently tested, promising to improve tissue concentrations. This article reviews biological pathways involved in the pathogenesis of DR that could be influenced by resveratrol. A study of these pathways could identify new potential targets for the reduction of diabetic complications. Keywords: diabetes, retinal secretome, diabetic microvascular complications, phytoalexi

Chemopreventive Effects of Propolis in the MNU-Induced Rat Mammary Tumor Model

Currently, one of the central problems in cancer management is the relapse of disease following conventional treatments, yet few therapeutic agents targeting resistance and tolerance exist. Propolis is known as a healing agent since ancient times. Therefore, over time, its curative properties have kept the interest of scientists, thus leading permanently to investigations of its other possible undiscovered effects. In this context, current experiments were performed to establish the chemopreventive potential of propolis extract (PE) (1.05 mg/kg BW/day) in N-methyl-N-nitrosourea- (MNU-) induced rat mammary tumors. MNU-inoculated/PE-treated rats had tumors of different physical attributes compared with control rats MNU-inoculated. The number of developed tumors (mean 49% versus 100%), incidence (mean 49% versus 100%), multiplicity (1.8 versus 3.7 (p<0.001)), tumor volume (mean 10 cm3 versus 16 cm3 (p<0.001)), and weight of the tumor mass (mean 7.42 g versus 9.00 g (p<0.05)) were noted. The numbers of grade I tumors recorded for MNU-inoculated rats were 24 (Group 1) and 7 (Group 2) for MNU-induced/PE-treated rats. In the serum of rats MNU-inoculated/PE-treated were found higher levels of antioxidative enzymes (SOD, CAT, and GPx) than in MNU-induced. Taken together, these data indicate that propolis could be a chemopreventive agent against MNU-induced mammary carcinogenesis