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ABSTRACT: Despite the evidences showing the relevance of regulatory immune-mediated mechanisms to guarantee the stable graft function in renal transplanted patients, studies focusing on the immune response observed over a long-term period after renal transplantation are still limited. Several efforts have been done to establish novel biomarkers with relevant predictive values that could be used as prognostic laboratorial tools to monitor the complex network triggered through time after kidney transplantation. In this study, we have evaluated the pro-inflammatory and regulatory patterns of plasma cytokines in a group of 120 renal transplanted patients with stable graft function ranging from 1 to 160months. Our data demonstrated an overall predominance of regulatory cytokines short-term after renal transplantation (1-24months) with peaks of IL-4, IL-5 and IL-10. Moreover, a slight peak of TNF-α was observed 25-60months after renal transplantation. Following a gap of stable cytokine profile (61-120months), peaks of pro-inflammatory cytokines IL-8, IL-6, IL1β, TNF-α and IL-12 were observed later on (>120months) after renal transplantation. Additionally, the categorical analysis of "low" or "high" cytokine producers re-enforce the occurrence of an overall regulatory status early-after stable renal graft function with a predominant pro-inflammatory pattern later on long-term renal transplantation. Taken together, our data suggest that IL-5 is a good biomarker associated with short-term stable renal function, whereas IL-12 seems to be a relevant pro-inflammatory element in long-term renal transplanted patients.
Cytokine 04/2013; · 3.02 Impact Factor
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ABSTRACT: BACKGROUND: Parvovirus B19 presents tropism for human erythroid progenitor cells, causing chronic anemia in organ transplant recipients, due to their suppressed humoral and cellular responses. Diagnosis may be achieved through serological tests for detection of anti-B19 antibodies. However, renal transplant recipients are not routinely tested for parvovirus B19 infection, since there is scanty data or consensus on screening for B19 infection, as well as for treatment or preventive management of transplanted patients. CASE PRESENTATION: Herein we report a kidney transplant recipient, who was unresponsive to treatment of severe anemia, and presented hypocellular hematopoietic marrow, megaloblastosis and hypoplasia of erythroid lineage with larger cells with clear nuclei chromatin and eosinophilic nuclear inclusions. This patient was seropositive for Epstein-Barr and Cytomegalovirus infections and negative for anti-parvovirus B19 IgM and IgG antibodies, although symptoms were suggestive of parvoviruses infection. A qualitative polymerase chain reaction testing for B19 in serum sample revealed positive results for B19 virus DNA. CONCLUSION: This case report suggests that the diagnostic process for parvovirus B19 in renal transplant recipients should include a polymerase chain reaction assay to detect B19-DNA, since specific serological tests may be unreliable given their impaired humoral responses. These results also indicate the importance of considering parvovirus B19 infection in the differential diagnosis of persistent anemia in transplanted patients.
BMC Research Notes 01/2013; 6(1):28.
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ABSTRACT: Preeclampsia (PE) is a multifactorial pregnancy-specific syndrome which represents one of the leading causes of maternal mortality worldwide. Inherited thrombophilia have been investigated as risk factor for the development of PE and it is currently known that ABO blood group may impact haemostatic balance, having the non-O blood groups (A, B or AB) subjects increased risk for thrombus formation, as compared to those of group O. We performed a systematic review of the literature for published studies investigating whether ABO blood groups could influence PE developing. A sensitive search of four databases identified 45 unique titles. The retrieved papers were assessed independently by authors and a rigorous process of selection and data extract was conduct. Methodological quality of the included studies was also evaluated. Two studies met eligibility criteria. As a main finding of our systematic review, an association between the AB blood group and the occurrence of PE was detected based on two original studies. Considering the role of ABO blood groups on the hemostatic process and thrombus formation, special attention should be given to pregnant patients carrying the AB blood group in order to prevent the syndrome and improve prognosis.
Molecular Biology Reports 11/2012; · 2.93 Impact Factor
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ABSTRACT: Diabetic nephropathy is the leading cause of end stage renal disease (ESRD) and an important risk factor for cardiovascular disease. Recent studies have shown that increased plasma levels of Von Willebrand factor (VWF) and reduced plasma levels of enzyme ADAMTS13 are associated with diabetic nephropathy and an increased risk of developing cardiovascular disease, suggesting that these markers of hypercoagulability may contribute to an increased risk of cardiovascular disease in diabetic patients with impaired renal function.However, it is still not clear whether VWF and ADAMTS13 are only markers of cardiovascular events or whether they play an active role in the development of these events. It is also unclear how renal injury may affect ADAMTS13 levels, leading consequently to hypercoagulability. The association of diabetic nephropathy,atherosclerotic cardiovascular disease and these hypercoagulability markers is discussed in this review. Insights on the role that renal dysfunction and other possible mechanisms may have in ADAMTS13 metabolism, leading to reduced levels of this enzyme and increased hypercoagulability are also presented.
Clinica chimica acta; international journal of clinical chemistry 11/2012; · 2.54 Impact Factor
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ABSTRACT: BACKGROUND: There may be a relationship between endothelial dysfunction, coagulation activation and nitric oxide (NO) synthesis in women with mild and severe preeclampsia (PE). METHODS: Plasma thrombomodulin (TM), D-Dimer (D-Di), cyclic guanosine monophosphate (cGMP) and placental nitric oxide synthase activity (NOS) were investigated in 21 normotensive pregnant women (G1), 22 pregnant women with mild PE (G2) and 20 pregnant women with severe PE (G3). RESULTS: TM and D-Di were significantly increased in G3 compared to G1 (P=0.001 and P=0.006, respectively) and G2 (P=0.001, in both cases). However, there was no significant difference when G1 was compared to G2. For total NOS, calcium independent NOS, calcium dependent NOS no significant difference was observed among the groups studied. CONCLUSIONS: TM and D-Di levels are raised in women with severe PE compared to normotensive pregnant women and women with mild PE. While increased TM levels may reflect endothelial dysfunction, raised D-Di levels indicate a hypercoagulable state. NO assessed by 2 indirect methods did not show any significant difference among the groups studied. Due to current limitations with in vitro NO measurements and interferences associated with NO bioavailability, particularly in PE, such findings should not be over-interpreted.
Clinica chimica acta; international journal of clinical chemistry 10/2012; · 2.54 Impact Factor
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ABSTRACT: Preeclampsia (PE) is a multi-system disorder of human pregnancy, whose etiology remains poorly understood. Preeclamptic women are known to have an increased hypercoagulable state that result in excess fibrin deposition in several organs, which compromises their function. Tissue factor (TF) is the main physiological initiator of blood coagulation and its activity is regulated by a specific inhibitor known as Tissue factor pathway inhibitor (TFPI). Based on the important role of TF and TFPI in hemostasis, we hypothesize that their levels may change in the severe PE contributing to exacerbate hypercoagulable state. Some studies have assessed the balance between TF and TFPI in preeclamptic women, but results are inconsistent. Therefore, the aim of this study was to examine these inconsistencies and to assess TF and TFPI plasma levels in three groups of age matched women; pregnant with severe PE (n = 60), normotensive pregnant (n = 50) and normotensive non-pregnant women (n = 50). There was not significantly different among the three groups for TF plasma levels; severe PE women: 338.4 pg/mL (248.1-457.6), normotensive pregnant women: 301.5 pg/mL (216.4-442.9) and normotensive non-pregnant women 393 pg/mL (310.3-522.9). TFPI plasma levels were higher in severe PE comparing to normotensive pregnant women and normotensive non-pregnant women, 115.8 ng/mL (75-149.8); 80.3 ng/mL (59.6-99.7) and 74.5 ng/mL (47.1-98.0), respectively No difference was found between normotensive pregnant women and normotensive non-pregnant women. As for gestational age, a significant difference in TFPI levels was found between severe PE and normotensive pregnant women up to the 33rd week of pregnancy (p = 0.001), and severe PE and non-pregnant women up to the 34th (p = 0.01). In summary, our results indicated that TF plasma levels did not vary in the studied groups, while TFPI plasma levels were significantly increased in severe PE compared to normotensive pregnant and normotensive non-pregnant women. So, our data do not explain the exacerbated hypercoagulability state observed in severe PE. Further studies evaluating genes expression, TF activity and antigen, total and free TFPI and TFPI-2, both in plasma and obstetric tissues, throughout the pregnancy in PE (mild and severe forms) are required.
Journal of Thrombosis and Thrombolysis 03/2012; 34(1):1-6. · 1.48 Impact Factor
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Daniela Amorim Melgaço Guimarães,
Mariana Silva dos Santos, Karina Braga Gomes,
Johanna G van der Bom,
Danyelle Romana Rios,
Jarbas Cardoso,
Romerson Martins Franco,
George da Silva Teixeira,
Luci Maria Sant'Ana Dusse,
Maria das Graças Carvalho,
Ana Paula Fernandes
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ABSTRACT: The aim of this study was to investigate the effect of postmenopausal hormone therapy on coagulation and whether this effect differs according to ABO blood groups.
This was a prospective observational study to evaluate factor VIII (FVIII) activity, factor von Willebrand (vWF), and D-dimer (D-Di) levels and ABO blood groups in 61 postmenopausal women using oral estrogen plus progestogen therapy (EPT; 2 mg estradiol + 1 mg norethisterone acetate) for 3 months and in 101 women not using EPT. After 3 months, all eligible women who had completed the treatment scheme proposed for the EPT group or those who opted to participate but had not undergone EPT had a blood sample collected for analysis.
Significant differences were observed in FVIII activity and vWF levels in the control group between those carrying group O and non-group O blood. For EPT users, significant differences were observed for FVIII activity, vWF, and D-Di levels. After a multivariate regression analysis, FVIII activity and ABO blood groups were independently associated with vWF levels, whereas interaction between ABO blood groups and EPT were independently associated with FVIII activity. Besides diabetes, the ABO × EPT interaction was also noted to be independently associated with D-Di levels.
These findings suggest an interactive effect between oral EPT and non-O blood groups, contributing to the mechanism by which estrogen triggers the hypercoagulability state and increased risk for venous thrombosis in women undergoing oral EPT.
Menopause (New York, N.Y.) 11/2011; 19(3):339-45. · 3.08 Impact Factor
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ABSTRACT: Evidence suggests that giardiasis is a zoonotic disease. The present work aimed to evaluate the genetic identity of Giardia duodenalis isolated from human and dog fecal samples from Belo Horizonte.
Human and dog fecal samples were cultured for isolation of G. duodenalis. To determine the genotype of the isolates, primers that amplify a specific region in rRNA of the protozoan were used.
Two G. duodenalis isolates were obtained, which belong to the subgroup A genotype.
These findings suggest that the transmission of giardiasis follows a zoonotic pattern.
Revista da Sociedade Brasileira de Medicina Tropical 08/2011; 44(4):508-10. · 0.68 Impact Factor
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Lillian Harboe Gonçalves,
Luci Maria Sant'ana Dusse,
Ana Paula Fernandes, Karina Braga Gomes,
Mirelle Oliveira Sóter,
Michelle Teodoro Alves,
Kathryna Fontana Rodrigues,
Fernanda Rocha Freitas,
Flavia Komatsuzaki,
Marinez Oliveira Sousa,
Adriana Aparecida Bosco,
Gérson Antônio Pianett,
Maria das Graças Carvalho
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ABSTRACT: Diabetic patients commonly present an increased risk for cardiovascular events, for which aspirin is the most frequently used medication for primary prevention. Urinary 11-dehydro thromboxane (11-dhTXB₂) concentrations assess the effect of aspirin on platelets and identify patients who are at risk of cardiovascular events. The present study investigated whether or not type 2 diabetic patients who took a daily dose of 100mg of aspirin had a significant reduction in urinary 11-dhTXB₂ concentrations and whether these results were associated with clinical and laboratory variables.
Eighty-one type 2 diabetic patients were enrolled in the study. Laboratory tests included the determination of lipidic profile, glycated hemoglobin, platelets count, molecular analysis for both GPIIbIIIa and COX-1 polymorphisms, and urinary 11-dhTXB₂.
Patients' median value for urinary 11-dhTXB₂ before aspirin intake was 179 pg/mg of creatinine. After 15days taking aspirin, the patients presented median of 51 pg/mg of creatinine, thus revealing a significant difference between medians (p=0.00). A reduction of 95% in urinary 11-dhTXB₂ concentrations could only be identified in 4 patients (5%). A BMI of ≥ 26 presented a significant association with a reduction of urinary 11-dhTXB₂ concentrations (p=0.010), as shown by the multiple logistic regression model. Other clinical and laboratory variables showed no association.
Regardless of the mechanisms related to aspirin non-responsiveness, most patients enrolled in the present study also presented a reduced or minimal response to low-dose aspirin therapy, thereby indicating a clear variability related to aspirin effectiveness. Moreover, BMI appears to be independently associated to the reduction of urinary 11-dhTXB₂ concentrations in type 2 diabetic patients taking aspirin.
Clinica chimica acta; international journal of clinical chemistry 07/2011; 412(15-16):1366-70. · 2.54 Impact Factor
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ABSTRACT: Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic variations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated.
To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals without the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals.
The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the 'Time-resolved fluorometer' technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III).
The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect against the disease.The DQA1 label proved to be able to differentiate between 71.13% of the diabetic and non-diabetic individuals.This value increased to 82.47% when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups.
The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles.
Arquivos brasileiros de endocrinologia e metabologia 05/2009; 53(3):368-73. · 0.68 Impact Factor
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ABSTRACT: Congenital Generalized Lipodystrophy (CGL) or Berardinelli-Seip Syndrome (BSCL) is a rare autosomal recessive disease characterized by complete absence of adipose tissue and by several metabolic alterations in carbohydrate (diabetes mellitus) and lipid metabolism and involvement of heart, bone and ovaries. Mental retardation and psychiatric disturbances are present in a variable proportion of affected patients. In the present review, the major advances in clinical, molecular and genetic characterization of BSCL affected subjects are recorded and discussed.
Clinica chimica acta; international journal of clinical chemistry 02/2009; 402(1-2):1-6. · 2.54 Impact Factor
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ABSTRACT: Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by a near total congenital absence of fat and predisposition to develop diabetes mellitus. In this study, we investigated the presence of mutations in the Seipin and 1-acylglycerol phosphate acyltransferase 2 (AGPAT2) genes in 32 affected subjects with BSCL from 17 consanguineous pedigrees living in two separate geographical regions, the northeastern and southeastern regions, of Brazil. All, except one, of the 22 BSCL subjects from 15 families living in the northeastern region were found to have a homozygous 669insA mutation in the Seipin gene. In contrast, all 10 BSCL subjects from two families living in the southeastern region were found to a have a homozygous 1036-bp deletion including exons 3 and 4 of AGPAT2. These results support genetic heterogeneity among BSCL patients in Brazil. Our finding of a single mutation in the Seipin and AGPAT2 genes in the pedigrees from the northeastern and southeastern regions, respectively, will be useful in genetic counseling of subjects from these large pedigrees from Brazil.
Journal of Clinical Endocrinology & Metabolism 02/2004; 89(1):357-61. · 6.50 Impact Factor
