El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objectives: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. Methods: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. Results: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. Conclusion: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT.

This study examined the precision of central fiber growth in a subpopulation of dorsal root ganglion neurons in developing mouse spinal cord. Immunohistochemical techniques using a monospecific, polyclonal antiserum to mouse adenosine deaminase (ADA) were utilized to label a population of primary sensory afferents that have been found to exclusively innervate laminae I and II of the dorsal horn in adult mice. Initial growth of ADA-immunoreactive (ADA-IR) primary afferents occurred very early in development, embryonic day 10 (E10), a time coincident with the earliest settling time of dorsal root ganglion neurons. Adenosine deaminase immunoreactive primary afferents were observed throughout the cross-sectional area of the primordial dorsal funiculus (DF) as early as E10. Immunostained fibers remained quiescent in the DF during its growth and separation into the tract of Lissauer and dorsal column pathway. By E15, the two pathways had formed and ADA-IR fibers were observed exclusively in the tract of Lissauer. This segregation of fibers remained throughout development and reflected the adult pattern. Growth was reinitiated at E16 when the fibers advanced into the dorsal horn and proceeded directly to laminae I and II mimicking their adult distribution. Exuberant fiber growth was not detected throughout their development. These results strongly suggest that ADA-IR fibers exhibit precise fiber guidance to a preferred pathway, the tract of Lissauer, and accurate laminar innervation of the dorsal horn.

Extracellular adenosine has the potential to influence many aspects of target cell metabolism. The present study has determined the endogenous levels of adenosine in the pregnant mouse uterus and developing embryodecidual unit with respect to the expression of two key enzymes of adenosine metabolism, 5′‐nucleotidase (5′‐NT; EC 3.1.3.5) and adenosine deaminase (ADA; EC 3.5.4.4). To measure adenosine levels, nucleoside extracts were etheno‐derivatized and quantitated by high‐performance liquid chromatography‐fluorescence detection (0.03 pmol/mg protein sensitivity). Adenosine levels were determined to be 0.18 nmol/mg protein in the nonpregnant uterus; however, two statistically significant changes were identified in the pregnant uterus: (1) a periimplantation surge between day 3 (0.24 nmol/mg protein) and day 5 (0.59 nmol/mg protein) of gestation (plug day 0; implantation day 4); and (2) an early postimplantation decline between day 6 (0.54 nmol/mg protein) and day 7 (0.10 nmol/mg protein). The periimplantation adenosine surge coincided with uterine expression of 5′‐NT, an enzyme which catalyzes the irreversible dephos‐phorylation of 5′‐AMP to adenosine. 5′‐NT expression was shown by Northern blot analysis to peak in the embryo‐decidual unit on day 5 of gestation and then to decline through day 9; transcripts remained elevated in the placenta between day 9 and day 13 (the latest day examined in this study). By use of specific enzyme histochemistry, most 5′‐NT activity was localized to the primary decidual zone on day 5. This expression subsequently declined during regression of the primary decidua; however, 5′‐NT appeared on giant trophoblast (days 7–13) and the metrial gland (days 11–13). Other purine catabolic enzymes degrading AMP (adenylate deaminase) or generating adenosine (S‐adenosylhomocysteine hydrolase) were not detected in the embryo‐decidual unit suggesting that the net flux of utero‐placental AMP catabolism proceeds with adenosine as an intermediate, this being the major pathway of adenosine formation. The sharp drop in adenosine levels between day 6 and day 7 coincided with a rise in the activity and mRNA expression of ADA, an enzyme which catalyzes the irreversible deamination of adenosine to inosine. ADA was previously localized to the secondary decidual zone (days 6–11), secondary giant cells (days 7–13), and spongiotrophoblasts (days 8–13) in the mouse (Knudsen et al., 1991). Results of developmental Northern blot analysis demonstrated a direct correlation of relative 5′‐NT/ADA mRNA band intensity to adenosine content between day 4 and day 9 of gestation, suggesting that the local availability of adenosine in the antimesometrium is dependent upon the distribution of these enzymatic activities. Purine nucleoside phosphorylase and xanthine oxidase, which are two catabolic enzymes acting subsequent to 5′‐NT and ADA in the sequential degradation of AMP to xanthine, remained low and constant in the tissues examined suggesting that the catabolic pathway is geared toward regulation of adenosine levels. These results suggest the establishment of an adenosine gradient across the developing antimesometrium. It is proposed that the source of adenosine is AMP released during uterine cell death, and that adenosine, in turn, serves as a regulatory signal to coordinate early postimplantation morphogenetic events with the progression of cell death at the uterine‐embryo interface.

A novel method for the immobilization of ribonucleosides to polysaccharides, namely to agarose, is presented, and the immobilized nucleosides are used for the purification of nucleoside-converting enzymes, such as adenosine deaminase, guanase OMP-decarboxylase and xanthine oxidase.

Spinal tuberculosis (TB) is associated with serious neurologic morbidity. It commonly presents as back pain, with or without systemic symptoms. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging modality for spinal TB. The diagnosis of spinal TB is made with tissue biopsy and acid-fast bacilli (AFB) culture; however, tissue AFB smear and tissue TB deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) can influence early clinical decision making. Ancillary tests such as the purified protein derivative (PPD) skin test, QuantiFERON®-TB Gold (QFT) or pleural adenosine deaminase (ADA) can be used in conjunction with radiology and clinical findings to initiate treatment while AFB tissue cultures are pending. Spinal TB responds well to early medical management and surgery is reserved for cases with neurologic complications.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23796号 / 医博第4842号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森信 暁雄, 教授 椛島 健治, 教授 杉田 昌彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Na Anemia Falciforme em situações de baixa tensão de oxigênio, a hemoglobina mutante S (HbS) sofre polimerização promovendo a falcização das hemácias, que podem aderir ao endotélio vascular, causando a oclusão de vasos (VO) e isquemia tecidual (crises dolorosas) que caracterizam o quadro clínico da doença. Além disso, os pacientes falciformes apresentam outras manifestações clínicas como o priapismo, alterações ósseas, certas complicações pulmonares entre outros. Além das células eritróides, células endoteliais, leucócitos e plaquetas também desempenham um papel fundamental na fisiopatologia da anemia falciforme. A hidroxiuréia (HU), na anemia falciforme, aumenta a produção de hemoglobina fetal (HbF) em células eritróides, reduzindo a polimerização da HbS, diminuindo os sintomas clínicos dos pacientes. O aumento da HbF, no entanto, não implica necessariamente na melhora clínica, indicando desta forma a potencial ação da HU sobre outros processos. Estudos recentes vêm relacionando priapismo e asma com elevados níveis de adenosina. Devido a esta importância da adenosina relacionada a patologias comuns a AF, tivemos como objetivo identificar polimorfismos em genes de receptores de adenosina e na adenosina deaminase e verificar a possível associação entre as manifestações clínicas, além de investigar o papel da HU na modulação de marcadores envolvido na síntese e degradação da adenosina. Foram analisados diversos sítios polimórficos nos genes que codificam ADORA1, ADORA 2b, ADORA 3 e ADA, seguindo com a genotipagem em pacientes com AF, comparando afetados e não afetados. Em adição foi avaliada a expressão diferencial de mRNA de ADA pela HU em monócitos destes pacientes, comparando tratados e não tratados e também avaliamos por citometria de fluxo a modulação de marcadores de superfície CD39, CD73 e CD26, pela HU. As análises estatísticas foram realizadas utilizando os softwares GenePop 3.4 para análises de associação, cálculo do HWE, GraphPad Prism 5, Arlequin para identificação de desequilíbrio de ligação, haplótipos, heterozigozidade e SAS 9.13 para associação dos haplótipos as características. Os resultados mostraram que os pacientes sob tratamento com HU apresentaram um aumento da expressão de mRNA de ADA, aumento da expressão de CD26 em monócitos e diminuição de CD39 em linfócitos. Sem alterações significativas em relação a CD73. Encontramos também um aumento da freqüência do alelo T do SNP (rs1685103) presente no gene de ADORA 1 associado com pacientes afetados com síndrome torácica aguda. Apesar de não ter sido estatisticamente significante, concorda com dados da literatura. No gene ADORA 2B, verificamos associação do SNP 1007 C>T no desenvolvimento de STA indicando o alelo T como fator de risco e o alelo C para alterações ósseas. Para o SNP 968 G>T houve associação com alterações ósseas. Na análise haplotípica entre os SNPs 968 G>T e 1007 C>T encontramos associação dos haplótipos ht2 e ht3 com STA, como fator de risco, ht2 para hipertensão pulmonar. ht1 para priapismo, alterações ósseas e estenose/AVC. Os haplótipos formados pelos três SNPs 968 G>T, 1007 C>T e rs16851030, encontramos associação entre ht1, ht3 e ht4 entre os afetados com priapismo, caracterizando-o como haplótipo de risco e também ht1 e ht6 associados à estenose/AVC. Concluímos, que a hidroxiuréia participa na modulação da expressão da adenosina deaminase, de CD26 em monócitos e CD39 em linfócitos. Além disso, mostrou-se a importância de sítios polimórfico presente no gene ADORA 2B e ADORA1 envolvido na fisiopatologia das manifestações clínicas da doença falciforme. Associações dos SNPs em ADORA 1 e ADA, devem ser melhor estudados em um número maior de pacientes. A determinação destes polimorfismos associados com diferentes características clínicas pode levar a um melhor entendimento dos processos fisiopatológicos da anemia falciforme, levando à identificação de pacientes de risco, possibilitando um manejamento racional dos mesmos, em termos de cuidados específicos, ou mesmo à determinação de alvos para o desenvolvimento de terapias alternativas. / In sickle cell disease in low oxygen tension, mutant hemoglobin S (HbS) undergoes polymerization promoting sickling of red blood cells that can adhere to vascular endothelium, causing vessel occlusion (VO) and tissue ischemia (painful crises) that characterize the clinical disease. In addition, sickle cell patients have other clinical manifestations such as priapism, bone disorders, certain pulmonary complications among others. In addition to the erythroid cells, endothelial cells, white cells and platelets also play a key role in the pathophysiology of sickle cell anemia. Hydroxyurea (HU) in sickle cell anemia, increases the production of fetal hemoglobin (HbF) in erythroid cells, reducing the HbS polymerization, reducing the clinical symptoms of patients. The increase in HbF, however, does not necessarily imply clinical improvement, thus indicating the potential effects of HU on other processes. Recent studies relating asthma and priapism with high levels of adenosine. Due to this importance of adenosine-related pathologies common to AF, we aimed to identify gene polymorphisms in adenosine receptors and adenosine deaminase and verify the possible association between clinical manifestations, and to investigate the role of HU in the modulation of markers involved synthesis and degradation of adenosine. We analyzed several polymorphic sites in genes that encode ADORA1, ADORA 2b, 3 and ADORA ADA, according to the genotype in patients with AF, comparing affected and unaffected. In addition we assessed the differential expression of ADA mRNA by HU in monocytes of these patients, comparing treated and untreated, and also evaluated by flow cytometry modulation of surface markers CD39, CD73 and CD26 by HU. Statistical analysis was performed using the software GenePop 3.4 for association analysis, calculation of HWE, GraphPad Prism 5, Arlequin for identification of linkage disequilibrium, haplotypes, heterozygosity and SAS 9.13 for association of haplotypes features. The results showed that patients treated with HU showed an increase in mRNA expression of ADA, increased expression of CD26 on monocytes and decreased CD39 on lymphocytes. No significant changes in relation to CD73. We also found an increased frequency of allele T (SNP rs1685103) present in a gene associated with ADORA affected patients with acute chest syndrome. Although not statistically significant, agrees with literature data. ADORA 2B gene, we found association of the SNP 1007 C> T in the development of STA indicating the T allele as a risk factor for the C allele and bone changes. For the SNP 968 G> T was associated with bone disorders. In haplotype analysis between SNPs 968 G> T and 1007 C> T found association of haplotypes ht2 and HT3 with STA as a risk factor for pulmonary hypertension ht2. ht1 for priapism, stenosis and bone disorders / stroke. The three haplotypes formed by SNPs 968 G> T, 1007 C> T and rs16851030, we found association between ht1, HT3 and HT4 among those affected with priapism, characterizing it as a risk haplotype and also ht1 ht6 associated with renal and / AVC. We conclude that hydroxyurea participates in modulating the expression of adenosine deaminase of CD26 on monocytes and CD39 on lymphocytes. Moreover, he showed the importance of polymorphic sites in this gene and ADORA 2B ADORA1 involved in the pathophysiology of clinical manifestations of sickle cell disease. Associations of SNPs in ADORA 1 and ADA should be better studied in a larger number of patients. The determination of these polymorphisms associated with different clinical characteristics can lead to a better understanding of the pathophysiological processes of sickle cell anemia, leading to the identification of patients at risk, enabling a rational handling of the same in terms of specific care, or even the determination of targets for the development of alternative therapies.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Neonatal hypoxic-ischemic injury (HI) is the direct complication to severe choking and may cause brain damage. HI may be found in different stages and clinical manifestations contributing to neonatal morbidity and mortality. The neuropathology of neonatal HI insult is multi-factorial and complex. Hypoxic-ischemic brain damage begins during the insult and extends during the recovery period after reperfusion, thus, it is an evolutionary process. Adenosine deaminase (ADA) is an aminohidrolase actively involved in the metabolism of purines catalyzing irreversibly adenosine and 2'desoxiadenosine into inosine and 2'desoxinosine, respectively. The objectives of this study were to evaluate the activity of ADA in the cortex of rats subjected to neonatal HI at different post-insult time points. Effects of thiobarbituric acid reactive species (TBARS) levels were also assessed in cortex. The histological analysis was evaluated using hematoxylin eosin (HE) and glial fibrillary acidic protein (GFAP) in the cortex of these animals. The ADA activity was significantly increased 8 days after the insult in the left hemisphere in the cortex. In this period, TBARS levels were significantly increased in the cortex of these animals. HE revealed the presence of ischemic area in the cerebral cortex 8 days after HI. A moderate lymphocytic infiltration was also evidenced in the cortex during this period. A proliferation and an increase in the expression of GFAP in the periphery of the ischemic area was observed, resulting in astrocytosis in the cortex of these animals. In conclusion, an activation of the immune system was observed due to the inflammatory process caused by the HI insult that may be correlated with astrocytosis and lymphocytic infiltration observed in the cerebral cortex of animals that suffered insult 8 days after neonatal HI. / A lesão hipóxico-isquêmica (HI) neonatal é a complicação imediata à asfixia grave e pode causar dano cerebral. A HI pode apresentar-se em diferentes estágios e manifestações clínicas contribuindo assim intensamente na morbidade e mortalidade neonatal. A neuropatologia do insulto HI neonatal é multi-fatorial e complexa. O dano cerebral hipóxicoisquêmico inicia durante o insulto e estende-se no período de recuperação após a reperfusão, portanto é um processo evolutivo. A adenosina deaminase (ADA) é uma aminohidrolase que participa ativamente do metabolismo das purinas catalisando irreversivelmente a adenosina e 2 desoxiadenosina em inosina e 2 desoxinosina, respectivamente. Os objetivos deste estudo foram avaliar em ratos submetidos à HI neonatal a atividade da ADA no córtex destes animais em diferentes tempos pós-insulto. Também foram avaliados em córtex os efeitos dos níveis de espécies reativas ao ácido tiobarbitúrico (TBARS). A análise histológica foi avaliada através da hematoxilina eosina (HE) e proteína glial fibrilar ácida (GFAP) no córtex destes animais. A atividade da ADA aumentou significativamente 8 dias após o insulto no hemisfério esquerdo no córtex. Neste período os níveis de TBARS mostraram-se significativamente aumentados no córtex destes animais. A HE revelou presença de área isquêmica no córtex cerebral 8 dias após a HI. Também evidenciou uma moderada infiltração linfocitária no córtex neste período. Houve proliferação e aumento na expressão da GFAP na periferia da área isquêmica, resultando em astrocitose no córtex dos animais submetidos à HI. Conclui-se que houve uma ativação do sistema imune em decorrência do processo inflamatório causado pelo insulto HI que pode estar correlacionada com a astrocitose e a infiltração linfocitária observada no córtex cerebral dos animais que sofreram o insulto 8 dias após a HI neonatal.

Diabetes mellitus (DM) is a metabolic disorder of multiple etiology characterized by chronic hyperglycemia resulting from deficiency of insulin production and/or action. This state of hyperglycemia may cause a variety of cardiovascular, renal, neurological and eye complications. Adenosine deaminase (ADA) is an important enzyme responsible for regulation the levels of adenosine (ado) an important component of the system purinergic nucleoside. Changes in ADA activity has been demonstrated in several diseases, including DM. The Rutin (RT) is an abundant polyphenolic flavonoid found in food that exhibits multiple pharmacological activities including antibacterial, antitumoural, vasodilator and hepatoprotective activities. The objective of this study was to investigate the effect of RT on the activity of ADA in serum, tissues and biochemical parameters in models of diabetes induced by streptozotocin (STZ). Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ). RT (100 mg/kg/day) and glibenclamide (10mg/kg/day) were administered for 30 days, except for control groups (non diabetic and diabetic). Six groups of rats were used in the study and grouped based on fasting blood glucose levels after diabetes induction. The results showed an increase in ADA activity in serum and liver of diabetic rats, like transaminases (AST, ALT), -glutamyltransferase (-GT) and glucose. The RT at a concentration of 100 mg/kg was able to reduce the ADA activity in serum and liver tissue when compared with the diabetic control. The protective effect of RT was also observed increases the activity of enzymes ALT and -GT. Significant reductions were also observed in total cholesterol and LDL-cholesterol as well as in blood glucose levels in the diabetic group treated with RT. The results suggest that RT can improve hyperglycemia and hyperlipidemia, and restoring damaged liver function, as well as prevents the increase in ADA activity in serum and liver tissue on diabetic rats treated with this flavonoid. / O Diabetes mellitus (DM) é uma disfunção metabólica de múltipla etiologia caracterizado por hiperglicemia crônica resultante da deficiência da produção e/ou ação da insulina. Esse estado de hiperglicemia pode provocar uma série de complicações cardiovasculares, renais, neurológicas e oculares. A Adenosina deaminase (ADA) é uma importante enzima responsável por regular os níveis de adenosina (ado), um importante nucleosídeo componente do sistema purinérgico. Alterações na atividade da ADA têm sido demonstradas em várias doenças, incluindo o DM. A rutina (RT) é um flavonoide polifenólico abundante nos alimentos que exibe múltiplas atividades farmacológicas como atividade antibacteriana, antitumoral, vasodilatadora e hepatoprotetora. O objetivo deste estudo foi verificar o efeito da RT sobre a atividade da ADA sérica e tecidual e parâmetros bioquímicos em modelos de diabetes induzidos por estreptozotocina (STZ). O diabetes foi induzido através de injeção única intraperitoneal (i.p.) de 55 mg/kg de STZ. A RT (100 mg / kg / dia) e a glibenclamida (10mg/kg/dia) foram administradas durante 30 dias, com exceção dos grupos controles (não diabéticos e diabéticos). Seis grupos de ratos foram utilizados no estudo e agrupados com base nos níveis de glicose em jejum após a indução de diabetes. Os resultados demonstraram um aumento na atividade da ADA no soro e no fígado de ratos diabéticos, assim como das transaminases (AST, ALT), -glutamiltransferase (-GT) e glicose. A RT na concentração de 100 mg/kg foi capaz de reduzir a atividade sérica e em tecido hepático da ADA quando comparado com o controle. O efeito protetor da RT também foi observado sobe a atividade das enzimas ALT e -GT. Reduções significativas foram observadas no colesterol total e LDL-colesterol, bem como, na concentração sérica de glicose no grupo diabético tratado com RT. Os resultados sugerem que a RT pode melhorar a hiperglicemia e dislipidemia, restabelecer danos à função hepática, bem como é capaz de prevenir o aumento da atividade da ADA no soro e no fígado de ratos diabéticos tratados com este flavonoide.

Made available in DSpace on 2014-06-11T19:26:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-18Bitstream added on 2014-06-13T19:12:50Z : No. of bitstreams: 1 domingos_acb_me_sjrp.pdf: 2339356 bytes, checksum: a0674e0784be91957c9249d57f61d341 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O diabetes melito (DM) é um grupo heterogêneo de alterações metabólicas, caracterizado por hiperglicemia crônica, com alterações do metabolismo de carboidratos, ácidos graxos e proteínas. O diabetes melito tipo 2 (DMT2) é a forma mais comum dessa doença, acomentendo aproximadamente 90% dos indivíduos que apresentam DM. Caracteriza-se principalmente por modificações da ação e secreção de insulina, embora sua etiologia, genética e fisiopatologia específicas ainda não estejam completamente determinadas. Os pacientes com DMT2 apresentam maior risco de desenvolvimento de complicações macro e microvasculares. Estudos revelaram que a enzima conversora de angiotensina (ECA) e a adenosina deaminase (ADA) podem estar relacionadas ao desenvolvimento de DMT2 ou de suas complicações. Com base nesses dados, foram estudados os polimorfismos I/D do gene ECA e TaqI do gene ADA em 162 indivíduos com DMT2, e 160 indivíduos saudáveis. Segundo a Associação Americana de Diabetes, os indivíduos diabéticos que apresentam HDLc abaixo de 40mg/dl ou LDLc acima de 100 mg/dl ou triglicerídeos acima de 150 mg/dl apresentam maior risco de desenvolvimento de doenças cardiovasculares. Por isso, foram selecionados 81 indivíduos com essas características para compor o grupo de estudo de pacientes diabéticos com “risco de doença cardiovascular”. Os polimorfismos foram avaliados por PCR e PCR-RFLP para os genes da ECA e ADA respectivamente. As frequências obtidas para o polimorfismo do gene ECA foram: pacientes diabéticos: I/I (19,1%); I/D (52,5%); D/D (28,4%); grupo controle I/I (12,5%); I/D (55,6%); D/D (31,9%) e grupo de diabéticos com riscos de doença cardiovascular I/I (16%); I/D (59,3%); D/D (24,7%). E para o gene ADA: em pacientes diabéticos ADA*1/*1 (89,31%); ADA*1/*2 (10,06%); ADA*2/*2 (0,63%); grupo controle ADA*1/*1 (91,25%); ADA*1/*2 (7,50%); ADA*2/*2 (1,25%); pacientes... / Diabetes mellitus (DM) is a heterogeneous group of metabolic disorders characterized by chronic hyperglycemia, with changes in the carbohydrates, fatty acids and proteins metabolism. Diabetes mellitus type 2 (DMT2) is the most common form of this disease, that affect approximately 90% of people who have DM. It is characterized mainly by changes in the action and insulin secretion, although the etiology, genetics and specific pathophysiology of the disease is not yet completely determined. DMT2 patients have a higher risk of developing macro and microvascular complications. Studies have shown that angiotensin-converting enzyme (ACE) and adenosine deaminase (ADA) may be related to the development of DMT2 or its complications. Based on these data, we studied the polymorphisms I / D of the ACE gene and the polymorphism TaqI in the ADA gene, in 162 patients with DMT2, and 160 blood donors. According to the American Diabetes Association, people with diabetes who have HDL-C below 40 mg / dL or LDL-C above 100 mg / dl or triglycerides above 150 mg / dl are at increased risk of developing cardiovascular disease. Therefore, we selected 81 individuals with these characteristics to compose the study group of diabetic patients named “risk of cardiovascular disease . The polymorphisms are evaluated by PCR for ACE gene and PCR-RFLP for the ADA Gene. The frequencies obtained for the ACE gene polymorphism were: diabetic patients: I / I (19.1%), I / D (52.5%) and D / D (28.4%), control group: I / I ( 12.5%) I / D (55.6%) and D / D (31.9%) and group of patients with cardiovascular disease risk: I / I (16%) I / D (59.3% ), D / D (24.7%). And for the ADA gene polymorphism: in diabetic patients: ADA * 1 / * 1 (89.31%); ADA * 1 / * 2 (10.06%), ADA * 2 / * 2 (0.63%); control group: ADA * 1 / * 1 (91.25%); ADA * 1 / * 2 (7.50%); ADA * 2 / * 2 (1.25%), and patients with cardiovascular risk:... (Complete abstract click electronic access below)