Effect of the glycemic control on intracellular cytokine production from peripheral blood mononuclear cells of type 1 and type 2 diabetic patients

Aims: To evaluate the intracellular production of tumor necrosis factor (TNF-alpha), interleukine-6 (IL-6), INF-gamma, IL-8 and IL-10 in peripheral blood lympbomononuclear cells from type 1 and type 2 diabetic patients, stratified according to the glycemic control. Methods: Thirty-five diabetic patients (17 type 1 and 18 type 2) and nine healthy individuals paired to patients in terms of sex and age were studied. Nine patients of each group were on inadequate glycemic controls. Intracellular cytokines were evaluated using flow cytometry. Cell cultures were stimulated with LPS to evaluate TNF-alpha and IL-6 or with PMA and lonomycin to evaluate IFN-gamma, IL-8 and IL-10 intracellular staining. Results: The percentages of CD33(+) cells bearing TNF-alpha and CD3(+) cells bearing IL-10 were increased in type 1 diabetic patients with inadequate glycemic control in relation to those with adequate control. In contrast, the percentage of CD3(+) cells bearing IL-8 was decreased in type 2 patients under inadequate glycemic control. Conclusions: The glycemic control is important for the detection of intracellular cytokines, and may contribute towards the susceptibility to infections in diabetic patients. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

HbA(1c) as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study

Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p < 0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

Antioxidant Effect of Thiamine on Acutely Alcoholized Rats and Lack of Efficacy Using Thiamine or Glucose to Reduce Blood Alcohol Content

Although there is no consensus about the use of glucose and thiamine for the treatment of acute ethanol intoxication, this is a routine practice in many countries. Our objective was to determine the efficacy of this treatment and the changes it causes in the antioxidant status of the liver. Male Wistar rats were intoxicated with an ethanol dose of 5 g/kg and divided into three groups: ethanol (EtOH; untreated), EtOH+G (treated with glucose), and EtOH+B1 (treated with thiamine). Blood and urinary ethanol as well as hepatic malondialdehyde, reduced glutathione and vitamin E were determined in all animals. Blood alcohol levels did not differ between groups, although urinary excretion was about four times higher in the group treated with thiamine (EtOH+B1). The malondialdehyde, reduced glutathione and vitamin E values used here as parameters of the antioxidant system of the liver showed improvement for the thiamine-treated group (EtOH+B1). Treatment with glucose or thiamine was ineffective in reducing blood alcohol levels in rats with acute ethanol intoxication. However, the beneficial effect of thiamine as an antioxidant for ethanol metabolism was demonstrated. Further investigations are necessary to clarify the urinary excretion of ethanol reported here for the first time and the possibility of using thiamine as an antioxidant in situations of chronic alcohol use.

A pilot case-control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions

Objective and study design: A case-control study was conducted on 42 Brazilian women presenting with human papilloma virus (HPV) infection and cervical lesion and 87 HPV-negative women to evaluate single nucleotide polymorphisms observed in TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma genes. Results and conclusion: No significant association was observed on the cytokine polymorphisms analyzed in this series. Larger studies using cytokine polymorphisms may be useful for providing further information regarding their influence or not in HPV-related cervical lesions. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Effects of periodontal therapy on glycemic control and inflammatory markers

Background: Periodontitis, a complication of diabetes mellitus (DM), can induce or perpetuate systemic conditions. This double-masked, placebo-controlled study evaluated the effects of periodontal therapy (scaling and root planing [SRP]) on the serum levels of glycated hemoglobin (HbA1c) and on inflammatory biomarkers. Methods: Thirty subjects with type 2 DM and periodontitis were treated with SRP + placebo (SRP; N = 15) or with SRP + doxycycline (SRP+Doxy; N = 15), 100 mg/day, for 14 days. Clinical and laboratory data were recorded at baseline and at 3 months after treatment. Results: After 3 months, the reduction in probing depth Was 0.8 mm for the SRP group (P <0.01) and 1.1 mm for the SRP+Doxy group (P <0.01) followed by a 0.9% (SRP; P = 0.17) and 1.5% (SRP+Doxy; P<0.01) reduction in HbA1c levels. A significant reduction in interleukin (IL)-6; interferon-inducible protein 10; soluble fas ligand; granulocyte colony-stimulating factor; RANTES; and IL-12 p70 serum levels were also verified (N = 30). To our knowledge, this is the first report on the effects of periodontal therapy on multiple systemic inflammatory markers in DM. Conclusions: Periodontal therapy may influence the systemic conditions of patients with type 2 DM, but no statistical difference was observed with the adjunctive systemic doxycycline therapy. Moreover, it is possible that the observed improvement in glycemic control and in the reduction of inflammatory markers could also be due to diet, which was not controlled in our study. Therefore, a confirmatory study with a larger sample size and controlled diet is necessary.

Frequency of HLA-B27 and its alleles in patients with Reiter syndrome: comparison with the frequency in other spondyloarthropathies and a healthy control population

This retrospective study analyzed the HLA-B*27 alleles in a group of 20 consecutive patients with the diagnosis of Reiter syndrome (RS) followed in a tertiary referral university hospital in Brazil, during the period 1990-2006, and compared the data with that observed in other patients with spondyloarthropathies followed at the same institution. Eight cases were associated to gastrointestinal infection, eight cases to previous urethritis, and four cases presented no established preceding infection. HLA-B*27 alleles were typed by polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes (HLA-B*2701 to HLA-B*2721). They were compared to a group of 108 patients with ankylosing spondylitis (AS), 40 with undifferentiated spondyloarthropathy (uSpA) and 111 healthy controls. Among the 20 patients, 17 were HLA-B*27 positive (85%). Two HLA-B*27 alleles were observed: HLA-B*2705 (65%) and HLA-B*2702 (35%). In the other spondyloarthropathies, the observed alleles were HLA-B*2705 (90% in AS and 92.5% in uSpA), HLA-B*2702 (8% in AS and 5% in uSpA), HLA-B*2704 (1% in AS and 2.5% in uSpA) and HLA-B*2713 (1% in AS). Among the 111 healthy controls, 80% presented HLA-B*2705, followed by HLA-B*2702 in 10%, HLA-B*2703 in 6%, HLA-B*2707 in 3% and HLA-B*2713 in 1%. Concluding, in the HLA-B*27 positive patients with RS in this study there was predominance of HLA-B*2705 allele, in a lower frequency than that observed in patients with other spondyloarthropathies and healthy controls.

Quality control of blood irradiation with a teletherapy unit: damage to stored red blood cells after cobalt-60 gamma irradiation

BACKGROUND: Previous publications have documented the damage caused to red blood cells (RBCs) irradiated with X-rays produced by a linear accelerator and with gamma rays derived from a Cs-137 source. The biologic effects on RBCs of gamma rays from a Co-60 source, however, have not been characterized. STUDY DESIGN AND METHODS: This study investigated the effect of 3000 and 4000 cGy on the in vitro properties of RBCs preserved with preservative solution and irradiated with a cobalt teletherapy unit. A thermal device equipped with a data acquisition system was used to maintain and monitor the blood temperature during irradiation. The device was rotated at 2 r.p.m. in the irradiation beam by means of an automated system. The spatial distribution of the absorbed dose over the irradiated volume was obtained with phantom and thermoluminescent dosimeters (TLDs). Levels of Hb, K+, and Cl- were assessed by spectrophotometric techniques over a period of 45 days. The change in the topology of the RBC membrane was investigated by flow cytometry. RESULTS: Irradiation caused significant changes in the extracellular levels of K+ and Hb and in the organizational structure of the phospholipid bilayer of the RBC membrane. Blood temperature ranged from 2 to 4 degrees C during irradiation. Rotation at 2 r.p.m. distributed the dose homogeneously (92%-104%) and did not damage the RBCs. CONCLUSIONS: The method used to store the blood bags during irradiation guaranteed that all damage caused to the cells was exclusively due to the action of radiation at the doses applied. It was demonstrated that prolonged storage of Co-60-irradiated RBCs results in loss of membrane phospholipids asymmetry, exposing phosphatidylserine (PS) on the cells` surface with a time and dose dependence, which can reduce the in vivo recovery of these cells. A time- and dose-dependence effect on the extracellular K+ and plasma-free Hb levels was also observed. The magnitude of all these effects, however, seems not to be clinically important and can support the storage of irradiated RBC units for at last 28 days.