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POLYMORPHISMS IN GENES FOR ENDOTHELIN 1, ENDOTHELIN RECEPTORS AND NITRIC OXIDE SYNTHASE 3 IN PATIENTS WITH DIABETIC RETINOPATHY AND DIABETES MELLITUS TYPE 2 : DISSERTATION
Dejan Bregar, 2018, doctoral dissertation

Abstract: The major causes of Diabetes Mellitus Type 2 (T2DM) are multi-factorial consequences of complex interactions between environmental, social and genetic factors. We investigated the genetic risk factors in Slovene patients with T2DM on a model of microvascular complication – Diabetic Retinopathy (DR). Retrospective case-control study includes a T2DM Slovene population with clinical risk factors for T2DM and DR. Only some of the candidate genes with selected single nucleotid polymorphisms (SNPs) were included: (EDN1 (rs5370, rs3087459, rs1476046), EDNRA (rs5335, rs1801708), EDNRB (rs10507875, rs4885493), NOS3 (rs869109213). By genotyping with either real-time polymerase chain reaction or standard polymerase chain reaction (PCR) we successfully identified the contribution of variable number of tandem repeats rs869109213 in DR progression (Proliferative Diabetic Retinopathy (PDR)) in Slovene patients with T2DM. The joint effect of individual genotypes of rs10507875 in EDNRB and rs869109213 in NOS3 on DR onset (DR) and DR progression (PDR) was demonstrated as well. The joint effect of the two polymorphisms on DR onset (DR) and DR progression (PDR) was greater than the individual effect of each polymorphism separately in the analyzed genetic models. Despite genetic research contributions in DR, linkage studies, and Genome-wide association studies the identification of susceptible loci through candidate gene approaches still remains in its early stages. The frequent approach with an ultimate focus on SNP associations with phenotype is likely to underestimate the roles of genetics in human diseases by disregarding not only the joint effect of multiple loci but the complex interaction network between them. By identifying polymorphisms in genetic disorders in a more systematic way, we will be able to deepen our understanding of the regulatory mechanisms and disease etiology which should lead to a more effective development of mechanism-based therapies as well.
Keywords: endothelin 1, EDN1, endothelin receptor A, EDNRA, endothelin receptor B, EDNRB, nitric oxide synthase 3, NOS3, diabetic retinopathy, DR, diabetes mellitus type 2, T2DM, polymorphism, SNP, genetic model
Published in RUNG: 07.09.2018; Views: 3599; Downloads: 178
.pdf Full text (3,06 MB)

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Diagnostic and prognostic markers in canine inflammatory and neoplastic head and neck conditions : dissertation
Ana Rejec, 2015, doctoral dissertation

Abstract: Several different types of conditions with inflammatory and neoplastic background affect the anatomical localities of the head and neck in a dog. It is a well-recognized fact that these conditions affect the quality of life, as they are associated with various degree of regional dysfunction, have systemic effects and can be direct or indirect cause of death. Unfortunately, many dogs with both inflammatory and neoplastic head and neck conditions are presented at an advanced stage of the disease which can have significant impact on treatment strategies. The identification of biomarkers is advisable to enhance effective staging, grading and prognostication, which will in turn more accurately direct recommendations for therapy. These biomarkers can theoretically help to distinguish between inflammatory and neoplastic conditions, justify the management of patients more accurately and potentially predict the prognosis and the survival of patients. It was our interest to investigate the diagnostic and prognostic value of complete blood count parameters and indices in dogs with head and neck conditions of inflammatory and neoplastic origin, regulatory T cells in dogs with periodontal disease, immunohistochemical (Ki-67 and VEGFR-2) and histopathological biomarkers in dogs with inflammatory and neoplastic head and neck conditions and to evaluate the effectiveness of an accelerated radiotherapy protocol for the treatment of advanced canine HNSCC. We have proved that the parameters investigated might serve as important supportive diagnostic and/or prognostic biomarkers which might help to improve the treatment strategies of both inflammatory and neoplastic head and neck conditions in dogs and that the accelerated chemoradiotherapy protocol represents an effective alternative treatment option for dogs with advanced HNSCC.
Keywords: biomarkers, dogs, periodontal disease, regulatory T cells, head and neck tumours, complete blood count, radiotherapy, vascular endothelial growth factor receptor 2
Published in RUNG: 26.11.2015; Views: 5990; Downloads: 120
.pdf Full text (59,54 MB)

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