Programa de Pós-Graduação em Ciências Farmacêuticas

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  • Master Thesis
    Parâmetros inflamatórios e fisiopatológicos do envenenamento induzido pelo escorpião Tityus stigmurus em camundongos
    (Universidade Federal do Rio Grande do Norte, 2016-03-01) Pinheiro, Ilanna Tainá Medeiros Gurgel; Pedrosa, Matheus de Freitas Fernandes; http://lattes.cnpq.br/2929963416385218; http://lattes.cnpq.br/2410445649667950; Freitas, Janaina Cristiana de Oliveira Crispim; https://orcid.org/0000-0002-1344-0078; http://lattes.cnpq.br/2644540835478572; Salvador, Daniela Priscila Marchi; http://lattes.cnpq.br/2247233142415132
    Scorpion bites are responsible for significant morbidity and pediatric mortality in many parts of the world and represents a public health problem in Brazil. Tityus stigmurus is a scorpion specie of medical importance that occur in the Brazilian Northeast. In this context, this work proposed to analized the inflammatory and pathophysiological parameters after Tityus stigmurus scorpion envenoming in vivo by intraperitoneal injection of 375 µg/kg of venom in BALB/c mice to evaluate its local and systemic effects. For this purpose, the total and differential leukocyte number, myeloperoxidase activity, nitrite levels and total protein were quantified in peritoneal exsudate, as well as, serum biochemical parameters and cytokine (TNF-α and IL-10) levels were analyzed. Alterations in relative organs weight of the experimental animals were also assessed. The results showed that the venom was not able to induce the migration of cells into the peritoneum of experimental animals. However, significant biochemical abnormalities were observed as the increase in CK, CK-MB, AST, ALT, creatinine, amylase, and uric acid. Moreover, it was observed lesions in organs such as heart, liver, kidney and pancreas. It was also demonstrated edema response that was characterized by rapid onset, lasting up to 1 hour. This is the first time that partial characterization of the envenoming induced by T. stigmurus in mice was carried out.
  • Master Thesis
    Avaliação das atividades anti-inflamatória, cicatrizante e antiofídica de um gel contendo extrato hidroetanólico das folhas de Jatropha mollissima (Pohl) Baill
    (Universidade Federal do Rio Grande do Norte, 2019-03-29) Passos, Júlia Gabriela Ramos; Pedrosa, Matheus de Freitas Fernandes; Silva, Juliana Félix da; https://orcid.org/0000-0003-3131-9025; http://lattes.cnpq.br/7927574480239375; http://lattes.cnpq.br/2929963416385218; http://lattes.cnpq.br/1969453327313987; Guerra, Gerlane Coelho Bernardo; http://lattes.cnpq.br/5677318431530876; Luna, Karla Patrícia de Oliveira
    Accidents caused by snakes are considered a major public health problem in several regions of the world. Bothrops are responsible for the vast majority of ophidic accidents in Brazil. It is known that, currently, the only specific treatment available for the bite of these snakes is the bothropic antivenom, but it has some limitations, such as not combat local effects effectively, difficult access in some regions, and high cost. Plants of the genus Jatropha (Euphorbiaceae) are often indicated by traditional medicine, in some regions of Brazil, to reverse the damage caused by snake bites and also with anti-inflammatory function. In this view, the objective of this work was to evaluate the anti-inflammatory, healing and antiophidic potential against the venom of the snake Bothrops jararaca of the hydroethanolic extract of the leaves of Jatropha mollissima (Pohl) Baill. incorporated into a formulation developed for topical application. Tests were performed to evaluate the topical anti-inflammatory activity of this species in carrageenan-induced paw edema and ear edema induced by single application (acute inflammation) or multiple applications (chronic inflammation) of chroton oil. Tests were also performed to evaluate the healing activity of the formulation, while the skin irritation test was conducted to analyze safety during topical use of the formulations developed. It was possible to observe that the gel had anti-inflammatory action in acute inflammation models induced by carrageenan, and in acute and chronic inflammation models by chroton oil. chroton oil. It was also observed that the gel has cicatrizant activity, since it significantly decreased the size of the wound in relation to the placebo group. The gel did not cause skin irritation in mice, proving to be safe for topical use. The efficacy of the gel containing the hydroethanolic extract of the leaves of J. mollissima alone and in association with the commercial polyvalent antibothropic-crotalic commercial antivenom in relation to its antiophidic potential against the local effects of B. jararaca envenoming were evaluated in the paw edema and muscle hemorrhagic models and it was seen that the venom-induced edematogenic and hemorrhagic activities were inhibited, both by the gel alone and by the association with the antiophidic antivenom, since these treatments reduced edema (the gel treatment containing the extract in association with the antiophidic antivenom had an inhibition of approximately 90% after four hours of the envenoming), in addition to significantly reducing the concentration of hemoglobin in the evaluated tissues, consequently having a significant anti-hemorrhagic potential. In conclusion, the results show that the gel containing the hydroethanolic extract of the leaves of J. mollissima shows potential anti-inflammatory, healing and antiophidic activity, acting on the local effects of the bite, suggesting that this formulation of topical use has an important antiophidic potential as a complementary alternative to the treatment of local effects caused by bothropic envenoming, besides acting as healing potential and topical antiinflammatory for the treatment of various skin diseases.
  • Master Thesis
    Estudo da associação dos genes TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 e IL18 com o desenvolvimento da nefropatia em pacientes com diabetes mellitus tipo 1
    (Universidade Federal do Rio Grande do Norte, 2014-06-30) Melo, Thamara Rodrigues de; Silbiger, Vivian Nogueira; Rezende, Adriana Augusto de; ; http://lattes.cnpq.br/4245215108740331; ; http://lattes.cnpq.br/6121935907512568; ; http://lattes.cnpq.br/4034812397526187; Chaves, Guilherme Maranhão; ; http://lattes.cnpq.br/1463249528959656; Freitas, Maria Cristina Foss; ; http://lattes.cnpq.br/9072914722827985
    Inflammation has been described as an important development factor for chronic diseases, such as diabetes and the condition of hyperglycemia would be responsible for activation of toll-like receptors (TLRs) and cytokines and consequently the induction of local and systemic inflammation. In this sense, the objective of this study was to evaluate the association of the mRNA expression of TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 and IL18 genes in peripheral blood mononuclear cells of children, adolescents and young adults with type 1 diabetes with pro-inflammatory state of Diabetes mellitus type 1 (DM1) and abnormal renal function. 49 normoglycemic individuals (NG) and 49 patients with DM1, between 6 and 20 years were studied. Diabetic patients were analyzed as a whole (group DM1), and subdivided into two groups according to glycemic control: offset diabetics (DM1C group) and diabetic uncompensated (DM1NC group). We evaluated fasting glucose, glycated hemoglobin, urea, serum creatinine, total protein fractions and albumin/creatinine ratio (ACR) urinary individuals studied. mRNA expression of TLR2, TLR4, MYD88, NFKB, MCP1/CCL2 and IL18 genes was also determined using the technique of real time PCR (Taqman ®). Most individuals with DM1 (65.3%) had poor glycemic control (glycated hemoglobin >8%). With respect to renal function, we observed a significant increase in the values of ACR groups DM1(p=0.006) and DM1NC(p=0.008) compared to NG. Regarding the biochemical markers such as total protein fractions (p=0.044) and an increase in serum concentrations of total protein in DM1 group, and concentrations of globulins in DM1(p<0.001), DM1C(p<0.001) and DM1NC (p<0.001) group when compared to the NG group. In the molecular analysis, significant increase in the expression of TLR2 (p = 0.003), TLR4 (p = 0.006), MYD88 (p = 0.015) and NFKB (p = 0.035) for DM1 group compared to NG were observed. A significantly increased expression of TLR2 (p=0.017) e NFKB (p=0.035) to DM1NC group compared to NG was also observed. No significant differences were observed in expression of IL18 and MCP1/CCL2 between groups and subgroups. These results suggest that poor glycemic control, together with the presence of risk factors and the inflammatory state associated with hyperglycemia may be mediated by activation of TLR-2 and TLR-4, which may contribute to the development of future complications, such as diabetic nephropathy.
  • Master Thesis
    Commiphora leptophloeos (Mart.) J.B. Gillett (Burseraceae): estudo fitoquímico, toxicidade e avaliação do potencial antiinflamatório e antimicrobiano
    (Universidade Federal do Rio Grande do Norte, 2019-03-28) Medeiros, Renato Dantas de; Langassner, Silvana Maria Zucolotto; Silva, Juliana Félix da; Ferreira, Leandro de Santis
    The specie Commiphora leptophloeos (Burseraceae) is a native plant from Brazil, belongs to caatinga biome and is known popularly as “imburana-de-espinho” and “imburana-decambão”. The ethnopharmacology studies mention the use of this specie in the treatment of inflammations and infections. In this context, the present study aimed to evaluate the toxicity, anti-inflammatory and antimicrobial activity in non-clinical in vitro and in vivo assays of leaf and stem bark extracts, and to isolate, identify and quantify chemical markers. In the phytochemical study, the hydroethanolic extract was prepared by maceration and the fractionation was performaded by liquid-liquid partition (dichloromethane, ethyl acetateAcOEt and n-buthanol-BuOH fractions). Isolation, structural elucidation and characterization of the extracts were performed by CPC, LC-MS, FIA-ESI-IT-MS/MS and 1H NMR and quantification of the content of markers in the extracts was made by HPLC-DAD and HPLCELSD. The toxicity of both extracts was evaluated by MTT and flow cytometry assays and in vivo by the acute toxicity test. The in vitro anti-inflammatory activity was evaluated using LPS-induced nitric oxide assay and in viv by carrageenan-induced paw edema and oral zymosan induced air pocket models. The antimicrobial activity was measured by the determination of minimum inhibitory concentration (MIC) and virtual screening of the isolated compounds was performed by in silico studies. From leaves extract, 2 flavonoids were isolated by CPC and 16 compounds were characterized by Mass spectrometry such as phenolic acids, glycosylated flavonoids derivatives of quercetin, luteolin and apigenin, and condensed tannins derivatives of catechin. From the stem bark extract, 2 tannins were isolated by CPC and 8 compounds were characterized as phenolic acids and procyanidins. The leaves extract at 200 µg/mL and stem bark extract at concentrations of 1, 10, 100 and 200 µg/mL demonstrated in vitro anti-inflammatory effect in the LPS-induced nitric oxide assay. In the carrageenan-induced paw edema of model, the extracts of leaves and stem bark at the doses of 100, 200 and 400 mg/kg, by oral route, significantly reduced the edema followed by reduction of myeloperoxidase (MPO) and in the zymosan-induced model of pouch-air, at doses tested, significantly reducing (p < 0.001), cell migration, total protein concentration, myeloperoxidase (MPO), and malondialdehyde (MDA) and the proinflammatory cytokine TNF-α and increased the production of the anti-inflammatory cytokine IL-10. In the evaluation of the antimicrobial activity, the extracts of the barks and the AcOET and BuOH fractions at concentrations of 20 to 100 μg/mL demonstrated a fungistatic and bactericidal effect. The in silico study indicated possible ligands of type B dimeric procyanidin and isovitexin related to anti-inflammatory and antimicrobial activity. The results obtained are unprecedent for the specie, justify its use in folk medicine and reveals that extracts of leaves and stem bark have a therapeutic potential for the development of herbal products with antiinflammatory and antimicrobial properties.
  • Master Thesis
    Avaliação da atividade anti-inflamatória de géis a base de extratos vegetais de plantas do nordeste brasileiro: Jatropha gossypiifolia e Ipomoea pes-caprae
    (2018-12-19) Santos, Jacinthia Beatriz Xavier dos; Pedrosa, Matheus de Freitas Fernandes; Silva, Juliana Félix da; ; ; ; Araújo, Aurigena Antunes de; ; Soares, Luiz Alberto Lira;
    The inflammatory process is a physiological event, whose events generated in this process are caused by the release of inflammatory mediators, aiming to restore homeostasis. Anti-inflammatory drugs are used for the treatment of inflammations, however, prolonged therapy leads to the appearance of adverse reactions that may be harmful to the patient, and the search for new, safer and more effective alternatives becomes relevant. In this context, medicinal plants, such as the plant species Jatropha gossypiifolia (Jg) and Ipomoea pes-caprae (Ipc) can be highlighted as strong candidates, since in traditional medicine they are popularly used for a wide range of curative purposes, including inflammatory conditions. In this sense, in the present study the obtain of gels containing the vegetal extracts of these species and the evaluation of their topical antiinflammatory activity were carried out, using the models of ear edema induced by single application of crton oil and paw edema induced by carrageenan (acute inflammation) and ear edema induced by multiple application of chrotonic oil (chronic inflammation). The gels presented adequate physico-chemical characteristics and were stable during 30 days of observation, showing no change in color, odor or appearance. The gels had pH similar to the cutaneous pH, thus minimizing the appearance of irritation or cutaneous alteration, results that corroborated with the in vivo skin irritation test, where the gels showed no clinical signs of toxicity between the 14 days of observation, indicating product safety developed for topical use. Jg gels demonstrated significant acute antiinflammatory activity in ear edema, and this activity was significantly increased when equivalent amounts of the extract were applied incorporated into the developed gels, and also reduced the levels of edema, nitrite and MPO enzyme in the gels. ears of mice, with intensity similar to dexamethasone (anti-inflammatory pattern). The Ipc extract showed no activity in the acute ear edema model, even after gel incorporation, however, it significantly inhibited paw edema throughout the duration of the dexamethasone-like experiment. Gels of 1.0% and Ipc 5% also showed a significant anti-inflammatory effect in the chronic inflammation test, reducing edema (also observed in the histopathological analysis) and oxidative (lipid peroxidation and reduced glutathione depletion) dexamethasone. Thus, this study demonstrated the anti-inflammatory potential of the gels with the extracts of the species J. gossypiifolia and I. pes-caprae, and can serve as starting point for the development of herbal products for the treatment of inflammatory processes.
  • Master Thesis
    Estudo fitoquímico e avaliação da toxicidade e do efeito antiinflamatório do extrato da casca de castanha de cajú (Anacardium occientale) no modelo de artrite aguda e crônica em ratos
    (2018-02-28) Santos, Ariane Teixeira dos; Langassner, Silvana Maria Zucolotto; Guerra, Gerlane Coelho Bernardo; ; ; ; Soares, Juliana Késsia Barbosa; ; Ferreira, Leandro de Santis;
    Rheumatoid arthritis is an autoimmune disease, its progression is accompanied by pain, edema and bone degeneration. Oil extracted from cashew nuts (Anacardium occidentale) has been the subject of recent researchs motivated by its potential biological effect. Preclinical studies have already demonstrated evidence of several activities, which highlights its antioxidant, anti-inflammatory and anti-tumor effects. Therefore, the goal of this work was to isolate and identify the main markers of the extract, as well as to evaluate the anti-inflammatory effect in the acute and chronic in vivo model and the toxicity of this extract. From the extract of the oil of the chestnut bark of A. occidentale, it was possible to isolate three substances, being characterized as 6- [8 (Z), 11 (Z), 14-pentadecatrienyl] salicylic acid, 6- [8 ), 11 (Z) - pentadecadienyl] salicylic acid and 6- [8 (Z) -pentadecenyl] acid. Pretreatment with the M3 extract (50 and 100 mg / kg, ρ <0.001) revealed a significant reduction of edema in zymosan-induced arthritis, with consequent decrease in leukocyte influx. In addition, M3 extract (50 and 100 mg / kg, ρ <0.001l) caused a significant reduction of myeloperoxidase. In mice, oral administration of the M3 extract (25, 50 and 100 mg / kg, ρ <0.001) showed a significant anti-inflammatory activity in the zymosan-induced air pocket model, evidenced by the reduction in leukocyte influx and oxidative stress markers myeloperoxidase and malonaldehyde. The results also showed a significant decrease in the release of IL-1β. Post-treatment of the extract M3 (25, 50 and 100 mg/kg, ρ <0.001) revealed a significant reduction of paw edema in chronic arthritis induced by CFA. However, only doses of 50 and 100 mg/kg were able to significantly reduce MPO and MDA enzyme levels, as well as cytokines TNF-α and IL-1β ρ <0.001. Acute toxicity of M3 extract (2000 mg/kg, oral) did not produce any behavioral changes in the biochemical and hematological parameters. The biochemical and hematological analyzes of the subchronic toxicity test (50 and 100 mg / kg, orally) did not indicate any change from supplementation with the M3 extract. The results demonstrate that the extract M3 exhibits anti-inflammatory effect in acute and chronic model and this effect may be related to the inhibition of proinflammatory cytokines and the migration of neutrophils.
  • Master Thesis
    Avaliação do HLA-G solúvel e do perfil de citocinas como potenciais biomarcadores plasmáticos do carcinoma papilífero da tireoide
    (2018-04-05) Araújo, Jéssica Nayara Góes de; Silbiger, Vivian Nogueira; Luchessi, André Ducati; ; ; ; Rezende, Adriana Augusto de; ; Wastowski, Isabela Jubé; ; Genre, Julieta;
    Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Limitations in diagnosis and prognosis determination still represent a great challenge for clinical management of PTC. Thus, the search for new targets for minimally invasive diagnosis became crucial. Considering the recognized association between PTC and chronic inflammation, the aim of the present study was to investigate plasma levels of cytokines and soluble HLA-G as potential biomarkers for diagnosis and/or prognosis of CPT. We studied PTC patients before (n = 85) and after thyroidectomy (n = 77), and 80 controls. Plasma levels of 13 cytokines were measured by flow cytometry beadbased assays, and soluble HLA-G was measured by ELISA. Data were evaluated using univariate and multivariate analyses, and ROC curves. Compared to prethyroidectomy, IL-4, IL-10, TNF, IFN-α and TGF-β1 levels were increased in postthyroidectomy. Compared to controls: i) sHLA-G levels were decreased after thyroidectomy, ii) IL-6 levels were increased, while IL-1β, IFN-α and TGF-β1 levels were decreased in pre-thyroidectomy, iii) IL-5 and IL-6 levels were increased, while IFN-α and TGF-β1 were decreased in post-thyroidectomy. IFN-α and TGF-β1 discriminated patients from controls after multiple logistic regression analysis, and IFNα presented the best diagnostic performance. Increased IL-1β and decreased IL-12p70 levels presented independent associations with larger tumors (>2.0 cm), while decreased sHLA-G levels were associated with invasion. Patients presenting biochemical/structural incomplete response presented higher IL-5 and IFN-α levels when compared to patients with excellent/indeterminate response. In conclusion, a differential cytokine profile was observed in plasma before and after thyroidectomy, and IFN-α and TGF-β1 levels seems to be potential biomarkers candidates for PTC diagnosis. Cytokines were associated with factors of poor prognosis (IL-1β e IL-12p70) and unsatisfactory response to treatment (IFN-α e IL-5). However, further studies are needed to confirm the clinical relevance of these molecules for PTC.
  • Master Thesis
    A influência da perda de peso no perfil inflamatório de mulheres com síndrome dos ovários policísticos
    (Universidade Federal do Rio Grande do Norte, 2015-03-27) Santos, Ana Celly Souza dos; Lemos, Telma Maria Araújo Moura; ; http://lattes.cnpq.br/4311626091295357; ; http://lattes.cnpq.br/4226802684575669; Rezende, Adriana Augusto de; ; http://lattes.cnpq.br/4245215108740331; Souza Júnior, José Edvan de; ; http://lattes.cnpq.br/8649739086762968
    The polycystic ovary syndrome (PCOS) is considered the most common endocrine disorder in reproductive age women, with a prevalence ranging from 15 to 20%. In addition to hormonal and reproductive changes, it is common in PCOS the presence of risk factors for developing cardiovascular disease (CVD) and diabetes mellitus, insulin resistance (IR), visceral obesity, chronic low-grade inflammation and dyslipidemia. Due to the high frequency of obesity associated with PCOS, weight loss is considered as the first-line treatment for the syndrome by improving metabolic and normalizes serum androgens, restoring reproductive function of these patients. Objectives: To evaluate the inflammatory markers and IR in women with PCOS and healthy ovulatory with different nutritional status and how these parameters are displayed after weight loss through caloric restriction in with Down syndrome. Methods: Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) were assessed in serum samples from 40 women of childbearing age. The volunteers were divided into four groups: Group I (not eutrophic with PCOS, n = 12); Group II (not eutrophic without PCOS, n = 10), Group III (eutrophic with PCOS, n = 08) and Group IV (eutrophic without PCOS, n = 10). The categorization of groups was performed by body mass index (BMI), according to the World Health Organization (WHO) does not eutrophic, overweight and obesity (BMI> 25 kg / m²) and normal weight (BMI <24.9 kg / m²). IR was determined by HOMA-IR index. In the second phase of the study a controlled dietary intervention was performed and inflammatory parameters were evaluated in 21 overweight and obese women with PCOS, before and after weight loss. All patients received a low-calorie diet with reduction of 500 kcal / day of regular consumption with standard concentrations of macronutrients. Results: Phase 1: PCOS patients showed increased levels of CRP (p <0.01) and HOMAIR (p <0.01). When divided by BMI, both not eutrophic group with PCOS (I) as eutrophic with PCOS (III) showed increased levels of CRP (I = 2.35 ± 0,55mg / L and 2.63 ± III = 0,65mg / L; p <0.01) and HOMA-IR (I = 2.16 ± 2.54 and III = 1.07 ± 0.55; p <0.01). There were no differences in TNF-α and IL-6 between groups. Step 2: After the weight loss of 5% of the initial weight was reduced in all of the components of serum assessed inflammatory profile, PCR (154.75 ± 19:33) vs (78.06 ± 8.9) TNF α (10.89 ± 5.09) vs (6:39 ± 1:41) and IL6 (154.75 ± 19:33) vs (78.06 ± 08.09) (p <0:00) in association with improvement some hormonal parameters evaluated. Conclusion: PCOS contributed to the development of chronic inflammation and changes in glucose metabolism by increasing CRP, insulin and HOMA-IR, independent of nutritional status. The weight loss, caloric restriction has improved the inflammatory condition and hormonal status of the evaluated patients.
  • Master Thesis
    Associação do receptor toll-like 2 com o estado pró-inflamatório do diabetes tipo 1
    (Universidade Federal do Rio Grande do Norte, 2009-03-30) Ururahy, Marcela Abbott Galvão; Rezende, Adriana Augusto de; ; http://lattes.cnpq.br/4245215108740331; ; http://lattes.cnpq.br/8016222352823817; Sales, Valéria Soraya de Farias; ; http://lattes.cnpq.br/8525532896559374; Hirata, Mario Hiroyuki; ; http://lattes.cnpq.br/8551642748793896
    Inflammation has been pointed out as an important factor in development of chronic diseases, as diabetes. Hyperglycemia condition would be responsible by toll-like receptors, TLR2 and TLR4, and, consequently by local and systemic inflammation induction. Thus, the objective of present study was to evaluate type 1 Diabetes mellitus (T1DM) pro-inflammatory state through mRNA expression of TLRs 2 and 4 and proinflammatory cytokines IL-1β, IL-6 and TNF-α correlating to diabetic nephropathy. In order to achieve this objective, 76 T1DM patients and 100 normoglycemic (NG) subjects aged between 6 and 20 years were evaluated. T1DM subjects were evaluated as a total group DM1, and considering glycemic control (good glycemic control DM1G, and poor glycemic control DM1P) and considering time of diagnosis (before achieving 5 years of diagnosis DM1< 5yrs, and after achieving 5 years of diagnosis DM1 <5yrs). Metabolic control was evaluated by glucose and glycated hemoglobin concentrations; to assess renal function serum urea, creatinine, albumin, total protein and urinary albumin-to-creatinine ratio were determined and to evaluate hepatic function, AST and ALT serum activities were measured. Pro-inflammatory status was assessed by mRNA expression of TLRs 2 and 4 and the inflammatory cytokines IL-1β, IL-6 and TNF-α. Except for DM1G group (18.4%), DM1NC patients (81.6%) showed a poor glycemic control, with glycated hemoglobin (11,2%) and serum glucose (225,5 md/dL) concentrations significantly increased in relation to NG group (glucose: 76,5mg/dL and glycated hemoglobin: 6,9%). Significantly enhanced values of urea (20%) and ACR (20,8%) and diminished concentrations of albumin (5,7%) and total protein (13,6%) were found in T1DM patients, mainly associated to a poor glycemic control (DM1P increased values of urea: 20% and ACR:49%, and diminished of albumin: 13,6% and total protein:13,6%) and longer disease duration (DM1 <5yrs - increased values of urea: 20% and ACR:20,8%, and diminished of albumin: 14,3% and total protein:13,6%). As regarding pro-inflammatory status evaluation, significantly increased mRNA expressions were presented for TLR2 (37,5%), IL-1β (43%), IL-6 (44,4%) and TNF-α (15,6%) in T1DM patients in comparison to NG, mainly associated to DM1P (poor glycemic control TLR2: 82%, IL-1β: 36,8% increase) and DM1 <5yrs (longer time of diagnosis TLR2: 85,4%, IL-1β: 46,5% increased) groups. Results support the existence of an inflammatory state mediated by an increased expression of TLR2 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in T1DM