Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis.

The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 µmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p < 0.001), tumor necrosis factor alpha (TNF-α, p < 0.001), TNF receptor 1 (TNFR1, p = 0.038), TNF receptor 2 (TNFR2, p < 0.001), and lower levels of PECAM (p = 0.001), ICAM (p < 0.001) and VCAM (p = 0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p < 0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.

CCR5Δ32 (rs333) polymorphism is associated with the susceptibility to systemic lupus erythematosus in female Brazilian patients.

The role of CCR5Δ32 (rs333) polymorphism in the pathogenesis of systemic lupus erythematosus (SLE) has been evaluated worldwide. The aim of this study was to determine the association between CCR5Δ32 polymorphism with the susceptibility to SLE and the activity of disease in female Southern Brazilian patients. The study enrolled 169 female SLE patients and 132 unrelated female healthy individuals. Baseline clinical, laboratorial characteristics, and the SLE activity (determined using the SLEDAI) were evaluated according to the CCR5Δ32 genotypes. The CCR5Δ32 polymorphism was determined from genomic DNA using a polymerase chain reaction. The frequencies of the genotypes CCR5/CCR5, CCR5/CCR5Δ32, and CCR5Δ32/CCR5Δ32 were 87.6, 11.8, and 0.6 %, respectively, among the patients and 96.2, 3.8, and 0.0 %, respectively, among the controls [CCR5/CCR5 vs. CCR5/CCR5Δ32 + CCR5Δ32/CCR5Δ32: p = 0.0081, odds ratio 3.604 (95 % confidence interval 1.321-9.4836)]. The frequencies of the CCR5 and the CCR5Δ32 alleles were 93.2 and 6.8 % among the patients, and 98.1 and 1.9 % among the controls, respectively (p = 0.0047, OR 3.758, 95 % CI 1.409-10.80). Patients carrying the genotypes with the CCR5Δ32 allele presented earlier age of onset of disease (p = 0.0293) and higher levels of anti-dsDNA (p = 0.0255) than those carrying the wild-type genotype. When the analysis was adjusted for ethnicity, only the age at onset of disease remained significant (p > 0.05). The results suggest that the CCR5Δ32 polymorphism might be associated with SLE genetic predisposition among female Brazilian patients and the age at onset of the disease; however, this genetic variant was not associated with the activity of SLE in this population.

Inflammatory and metabolic markers and short-time outcome in patients with acute ischemic stroke in relation to TOAST subtypes.

The aim of this study was to evaluate the association between inflammatory and metabolic markers and short-time outcome with acute ischemic stroke subtypes. A total of 121 patients was classified according to TOAST criteria, such as large artery atherosclerosis (LAAS), lacunar infarct (LAC), cardioembolic infarct (CEI), other determined etiology (ODE), and undetermined etiology (UDE). The functional impairment was evaluated within the first eight hours of stroke and the outcome after three-month follow-up using the modified Rankin Scale. Blood samples were obtained up to 24 h of stroke. Compared with 96 controls, patients with LAAS, CEI, and LAC subtypes showed higher levels of white blood cells, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), metalloproteinase 9 (MMP-9), glucose, and iron (p < 0.05); and lower high-density lipoprotein cholesterol (HDL-C) (p < 0.0001); platelets, insulin, insulin resistance, and homocysteine were higher in LAC (p < 0.0001); ferritin was higher in LAAS (p < 0.0001); and total cholesterol (TC) was lower in LAAS and CEI (p < 0.01). When stroke subtypes were compared, insulin was higher in LAAS vs. LAC and in LAC vs. CEI (p < 0.05); and TC was lower in LAAS vs. LAC (p < 0.05). Outcome and rate of mortality after three-month were higher in LAAS vs. LAC (p < 0.001 and p = 0.0391 respectively). The results underscored the important role of the inflammatory response and metabolic changes in the pathogenesis of ischemic stroke subtypes that might be considered on the initial evaluation of stroke patients to identify those that could benefit with individualized therapeutic strategies that taken into account these markers after acute ischemic event.

Tumor necrosis factor beta NcoI polymorphism (rs909253) is associated with inflammatory and metabolic markers in acute ischemic stroke.

Polymorphisms in genes coding for pro-inflammatory molecules represent important factors for the pathogenesis and outcome of stroke. The aim of this study was to evaluate the relationship between the tumor necrosis factor beta (TNF-ß) NcoI (rs909253) polymorphism with inflammatory and metabolic markers in acute ischemic stroke. Ninety-three patients and 134 controls were included. The TNF-ß polymorphism was determined using PCR-RFLP with NcoI restriction enzyme. Stroke subtypes and neurological deficit score were evaluated. White blood cell counts, erythrocyte sedimentation rate (ESR), plasma levels of IL-6 and TNF-α, serum high sensitivity C-reactive Protein (hsCRP), serum lipid profile, plasma levels of glucose and insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. Stroke patients presented higher white blood cell counts, hsCRP, ESR, glucose, insulin, and HOMA-IR, and lower HDL cholesterol than controls (p < 0.01). There was no difference in genotypic and allelic frequency of TNF-ß NcoI polymorphism among patients and controls (p > 0.05). However, stroke patients carrying the TNFB2/B2 genotype presented higher levels of TNF-α, white blood cell counts, total cholesterol, LDL cholesterol, glucose, insulin, and HOMA-IR than those with other genotypes (p < 0.05). White blood cells, IL-6, hsCRP, and ESR were positively correlated with the neurological deficit of the patients (p < 0.05). Taken together, TNF-ß NcoI polymorphism, by itself, was not associated with increased susceptibility for stroke development. However, the homozygous genotype for the allele TNFB2 was associated with higher expression of classical inflammatory and metabolic markers of development and outcome of stroke than other genotypes. The identification of variant alleles might allow both better prediction of susceptibility for stroke as well the identification of novel stroke mechanisms that could be target to new therapeutic approaches. Stroke patients carrying the TNFB2 variant allele could have a beneficial effect with the anti-inflammatory therapies in the early inflammatory phase of stroke.

Fish oil N-3 fatty acids increase adiponectin and decrease leptin levels in patients with systemic lupus erythematosus.

Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE.

Reduced-energy cranberry juice increases folic acid and adiponectin and reduces homocysteine and oxidative stress in patients with the metabolic syndrome.

The metabolic syndrome (MetS) comprises pathological conditions that include insulin resistance, arterial hypertension, visceral adiposity and dyslipidaemia, which favour the development of CVD. Some reports have shown that cranberry ingestion reduces cardiovascular risk factors. However, few studies have evaluated the effect of this fruit in subjects with the MetS. The objective of the present study was to assess the effect of reduced-energy cranberry juice consumption on metabolic and inflammatory biomarkers in patients with the MetS, and to verify the effects of cranberry juice concomitantly on homocysteine and adiponectin levels in patients with the MetS. For this purpose, fifty-six individuals with the MetS were selected and divided into two groups: control group (n 36) and cranberry-treated group (n 20). After consuming reduced-energy cranberry juice (0·7 litres/d) containing 0·4mg folic acid for 60 d, the cranberry-treated group showed an increase in adiponectin (P=0·010) and folic acid (P=0·033) and a decrease in homocysteine (P<0·001) in relation to baseline values and also in comparison with the controls (P<0·05). There was no significant change in the pro-inflammatory cytokines TNF-a, IL-1 and IL-6. In relation to oxidative stress measurements, decreased (P<0·05) lipoperoxidation and protein oxidation levels assessed by advanced oxidation protein products were found in the cranberry-treated group when compared with the control group. In conclusion, the consumption of cranberry juice for 60 d was able to improve some cardiovascular risk factors. The present data reinforce the importance of the inverse association between homocysteine and adiponectin and the need for more specifically designed studies on MetS patients.

Serum levels of high sensitive C reactive protein in healthy adults from southern Brazil.

BACKGROUND: With the emergence of more sensitive assay techniques, it has been shown that C reactive protein (CRP) is present at low levels in the serum of all the clinically healthy individuals. OBJECTIVE: To determine the interval values of high-sensitivity CRP (hs-CRP) in healthy adults. METHODS: Serum hs-CRP level was evaluated in 176 healthy blood donors. RESULTS: The serum hs-CRP level ranged from <0.175 to 48.7 mg/l (median 1.2 mg/l); 127 (72.2%) individuals exhibited values ≥0.175 and <3.0 mg/l and 31 (17.6%) showed values >3.0 and ≤10.0 mg. Higher hs-CRP level was observed among the female than male (P = 0.0001), and among the older than the younger individuals (P = 0.0180). Individuals with body mass index ≥25.0 kg/m(2) exhibited higher hs-CRP level than those with normal weight (18.5-24.9 kg/m(2) ; P < 0.0005). When the participants were stratified into gender and low (≤24.9 kg/m(2) ) and high (≥24.9 kg/m(2) ) body mass index (BMI) groups, the gender difference in hs-CRP levels remained (female with low BMI vs. male with low BMI, P = 0.0221; female with high BMI vs. male with high BMI, P = 0.0001). CONCLUSION: Gender, age, and BMI influence serum hs-CRP level in healthy individuals and these variables should be considered for the interpretation of hs-CRP values. The results reinforce the importance in evaluating whether these differences in hs-CRP levels could contribute to alter the cardiovascular risk criteria and clinical outcomes, and whether hs-CRP thresholds for cardiovascular risk assessment should be adjusted for different gender and body mass index groups.

Blood pressure decrease with ingestion of a soya product (kinako) or fish oil in women with the metabolic syndrome: role of adiponectin and nitric oxide.

The aim of the present study was to verify the effects of fish oil and a soya-based product on inflammatory markers and endothelial function measured by NO in women with the metabolic syndrome (MetS). A total of sixty-five women (mean age: 47·9 (SD 9·98) years) were studied in a 90-d parallel, randomised design. A control group maintained their usual diet; the second group received 29 g/d of soyabean (kinako); the third group received 3 g/d of fish oil n-3 fatty acids; and the fourth group received fish oil (3 g/d) and kinako (29 g/d). Anthropometric, blood pressure (BP), inflammatory markers, anti-inflammatory marker (adiponectin) and NO concentrations were evaluated. In relation to the baseline values, the group that received fish oil and kinako concomitantly presented a statistically significant decrease in systolic BP (SBP; P < 0·05), whereas there was a significant decrease in diastolic BP (DBP) in the control group (P < 0·05), kinako group (P < 0·01) and fish oil group (P < 0·01) after 90 d. There was a significant increase in adiponectin (P < 0·01) and NO values (P < 0·05) after 90 d in the kinako and fish oil groups. Differences between treatment groups verified a significant decrease (P < 0·05) in DBP in the kinako group after 90 d when compared to the results obtained from the fish oil and kinako groups. In conclusion, the findings of increased serum adiponectin and NO metabolite levels after 90 d, both in the fish oil and soya groups, reinforce the importance of the influence of adiponectin and NO levels on BP decrease in patients with the MetS.

Growth hormone directly favors hepatic ketogenesis in persons with prediabetes or type 2 diabetes mellitus treated with empagliflozin.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors increase glucagon secretion by pancreatic alpha cells and the susceptibility to ketoacidosis. On the other hand, growth hormone (GH) stimulates peripheral lipolysis and provides free fatty acids (FFA) for ketogenesis; however, it remains unresolved whether GH directly impacts hepatic ketogenesis. We aimed to investigate the role of physiologic GH levels in promoting ketogenesis in prediabetic or type 2 diabetic patients under empagliflozin treatment. METHODS: Sixteen patients (11 women, 5 men) with prediabetes or type 2 diabetes mellitus, aged 55.6 ± 4.7 years and with a mean BMI of 30.7 ± 4.8 kg/m2 and HbA1c 7.1 ± 1.6% (means ± SD), participated in this study. All of them were submitted to three mixed-meal tests: they received placebo at -60 min (test 1), and empagliflozin 25 mg (test 2, 21st day) and empagliflozin 25 mg plus pegvisomant 30 mg were administered subcutaneously 36 h before (test 3, 28th day). After test 1, all patients were instructed to take empagliflozin 25 mg daily. RESULTS: The empagliflozin treatment decreased the plasma concentrations of glucose by 14% (P < 0.01), FFA by 23% (P < 0.01), and the insulin/glucagon ratio by 26% (P < 0.01), and it increased ß-hydroxybutyrate by 44% (P < 0.05). The GH receptor block by pegvisomant restored the plasma ß-hydroxybutyrate to baseline levels. CONCLUSIONS: We conclude that GH has a direct effect on promoting the ketogenesis environment in patients treated with empagliflozin.

Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients.

BACKGROUND: The magnitude of lipoprotein level reduction during the acute-phase response may be associated with the severity and mortality of sepsis. However, it remains to be determined whether low lipoprotein levels can be considered a risk factor for developing sepsis. We aimed to investigate lipoprotein levels as risk factors for sepsis in hospitalized patients, and also describe sequential changes in lipoprotein and cholesterol ester transfer protein (CETP) levels during sepsis. DESIGN: This is a prospective cohort study and case-control analysis from selected hospitalized patients. Blood samples were collected at admission, and participants were monitored for severe sepsis. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein, and triglyceride levels were compared between sepsis cases and controls. Cholesterol, apolipoprotein, phospholipid and CETP concentrations were monitored in the case group. RESULTS: Of 1719 enrolled patients, 51 developed severe sepsis and were paired with 71 controls by age, gender, presence of infection at admission and chronic disease. HDL cholesterol level at admission was a risk factor for severe sepsis (OR = 0.969; 95% CI: 0.944-0.995). Mean CETP levels diminished between hospital admission and day 3 of sepsis. The magnitude of this variation (Delta CETP) was more pronounced in non-survivors (0.78 +/- 1.08 microg mL(-1)) than that in survivors (0.02 +/- 0.58 microg mL(-1), P = 0.01). CONCLUSIONS: HDL cholesterol may have a protective effect against sepsis. Each 1 mg dL(-1) increase in HDL decreased the odds of severe sepsis by 3% during hospitalization. The reduction of plasma CETP was associated with mortality.

Functional iron deficiency in patients on hemodialysis: prevalence, nutritional assessment, and biomarkers of oxidative stress and inflammation.

INTRODUCTION: Anemic patients with chronic kidney disease (CKD) can be divided into anemic patients without or with functional iron deficiency (FID). The increase in the number of cases of hemosiderosis in patients on hemodialysis (HD) attributed to excessive intravenous iron replacement has called for the investigation of the factors involved in the genesis of FID. OBJECTIVES: This study aimed to describe the prevalence of FID in patients with CKD on HD, characterize the included individuals in terms of clinical and workup parameters, and assess their nutritional, oxidative stress, and inflammation statuses. This cross-sectional study assembled a convenience sample of 183 patients with CKD on HD treated in Southern Brazil. Patients meeting the inclusion and exclusion criteria were divided into two groups, one with anemic subjects with FID and one with anemic patients without FID. Participants answered a questionnaire probing into socio-epidemiological factors, underwent anthropometric measurements, and were tested for markers of anemia, oxidative stress, inflammation, and nutrition. STATISTICAL ANALYSIS: The date sets were treated on software package GraphPad InStat version 3.1. Variables were tested with the Kolmogorov-Smirnov, chi-square, Student's t, and Mann-Whitney tests. Statistical significance was attributed to differences with a p < 0.05. RESULTS: Markers of inflammation were not statistically different between the two groups. Markers of anemia and nutrition were significantly lower in patients with FID. Patients with FID were prescribed higher doses of parenteral iron (p < 0,05). DISCUSSION: FID was associated with lower nutritional marker levels, but not to increased levels of markers of inflammation or oxidative stress, as reported in the literature. Additional studies on the subject are needed.

Epidemiological, immunological and virological characteristics, and disease progression of HIV-1/HCV-co-infected patients from a southern Brazilian population.

A cross-sectional study was carried out in order to describe the epidemiological, immunological and virological characteristics, and the disease progression of hepatitis C virus (HCV)/human immunodeficiency virus type 1 (HIV-1)- co-infected patients from a southern Brazilian population. Of 778 HIV-1-infected individuals enrolled in the study from September 2001 to December 2003, and followed up until June 2004, 757 were tested for anti-HCV antibodies. Of these, 159 (21.0%) showed positive results for anti-HCV. Males, individuals in the 25 to 34 year age range, and individuals of lower economic levels were more likely to be seropositive for both viruses [prevalence rate (PR), 2.04; 95% confidence interval (95% CI), 1.43-2.92; p<0.001]. The anti-HCV reactivity was also associated with blood routes of transmission (PR, 2.20; 95% CI, 1.28-3.77; p<0.001), intravenous drug use (PR, 5.79; 95% CI, 4.74-7.07; p<0.001), self-reported previous sexually transmitted diseases (PR, 1.55; 95% CI, 1.18-2.04; p=0.002), VDRL positivity (PR, 2.87; 95% CI, 2.40-3.43; p<0.001), and anti-HTLV I/II reactivity (PR, 5.09; 95% CI, 4.16-6.23; p<0.001). In the follow-up period, the HCV/HIV-1-co-infected patients showed a trend toward lower CD4+ T-cell counts, higher HIV-1 RNA plasma viral load and faster disease progression than patients infected only with HIV-1, but significant differences were not observed. Although there were proportionately more deaths in the HCV/HIV-1-co-infected group, the use of highly active antiretroviral therapy (HAART) was a string predictor of increased CD4+ T-cell counts and decreased HIV-1 RNA plasma levels, suggesting that HAART is more important to the immunological and virological outcomes in HIV-1 infection than is HCV co-infection status.

Frequency of CCR5-Delta32 deletion in human immunodeficiency virus type 1 (HIV-1) in healthy blood donors, HIV-1-exposed seronegative and HIV-1-seropositive individuals of southern Brazilian population.

The frequency of CCR5-Delta32 allele in human immunodeficiency virus type 1 (HIV-1) infection in the southern Brazilian population was determined in a cross-sectional study carried out from October 2001 to June 2004. Genomic DNA was extracted from peripheral blood cells of 134 healthy blood donors, 145 HIV-1-exposed seronegative individuals, 152 HIV-1-seropositive asymptomatic individuals, and 478 HIV-1-seropositive individuals with AIDS. A fragment with 225 base-pairs of the CCR5 gene was amplified by polymerase chain reaction. The CCR5-Delta32 homozygous deletion was observed in 2 (1.5%) blood donors and in 1 (0.7%) individual HIV-1-exposed seronegative, and was absent among all the HIV-1-seropositive individuals (Fisher's exact test, p=0.0242). The frequency of the homozygous CCR5-Delta32 deletion in the HIV-1-exposed did not differ when compared with that observed in the HIV-1 seronegative blood donors (Fisher's exact test, p=0.6093; OR: 2.18, 95% CI: 0.11-129.6). The wild-type genotype CCR5/CCR5 frequency was higher among the HIV-1-seropositive with AIDS compared to HIV-1 seropositive asymptomatic individuals (Chi-square test, p=0.0263; OR: 2.02, 95% CI: 1.03-3.97). The absence of the homozygous deletion of CCR5-Delta32 among HIV-1-seropositive individuals underscored that this genotype is an important genetic factor associated with the decreased susceptibility to HIV-1 infection. The higher frequency of heterozygosity for the CCR5-Delta32 and the CCR5-Delta32 allele in HIV-1 seropositive asymptomatic compared to HIV-seropositive with AIDS individuals also underscored that this deletion could be associated with the delay of the HIV-1 disease progression in this population. However, the low frequency of CCR5-Delta32 homozygosity observed among HIV-1-exposed seronegative individuals shows that the allele could not explain, by itself, the natural resistance to HIV-1 infection and different mechanisms of protection against HIV-1 infection that must be involved in this population.

CCR5-Delta32 genetic polymorphism associated with benign clinical course and magnetic resonance imaging findings in Brazilian patients with multiple sclerosis.

The CCR5 chemokine receptor has been implicated in the pathogenesis of multiple sclerosis (MS). This research was carried out to investigate the association between the CCR5-Delta32 deletion in 124 patients with MS from Southern Brazil. Ninety-eight (79.0%) patients presented with relapsing-remitting MS (RR-MS), 17 (13.7%) secondary progressive MS (SP-MS), 8 (6.5%) primary progressive MS (PP-MS) and one (0.8%) clinically isolated syndrome (CIS). The control group consisted of 127 healthy blood donors from the same geographic region. The disease severity was assessed clinically using the Expanded Disability Status Scale (EDSS). Genomic DNA was extracted from peripheral blood cells and the genetic polymorphism was evaluated by polymerase chain reaction. Of the MS patients, 85 (68.5%) were females (p=0.0093). The CCR5-Delta32 frequency among the controls was 5.5%, and did not differ from that observed among the MS patients (4.8%) (p=0.7337). The mean (+/-SD) age at disease onset among the carriers and non-carriers of the CCR5-Delta32 allele was 31.7 (+/-11.1) and 36.6 (+/-12.0) years, respectively (p=0.1312). The duration (+/-SD) of the disease was 11.2 (+/-12.9) and 7.7 (+/- 5.6) years among the CCR5-Delta32 heterozygous, and CCR5 wild type, respectively (p=0.396). The mean (+/-SD) EDSS among the MS patients carriers and non-carriers of the CCR5-Delta32 allele was 2.4+/-1.2 and 2.67+/-2.2, respectively (p=0.9796). The MRI findings in MS patients with the CCR5-Delta32 genotype exhibited lower positive gadolinium enhancing-imaging (p=0.0013) and lower brain atrophy (p=0.1333) than MS patients with the CCR5 wild-type genotype. Despite that the differences were not significant, the results suggested that the disease onset and progression to disability may be prolonged in MS carriers of CCR5-Delta32, and CCR5-Delta32 could be considered a favorable prognostic biomarker of MS. Further studies comprising larger numbers of individuals carrying non-wild-type haplotypes are needed to determine CCR5-Delta32 involvement in the specific process of MS pathology and pathogenesis.

Difficulties in the diagnosis of HTLV-2 infection in HIV/AIDS patients from Brazil: comparative performances of serologic and molecular assays, and detection of HTLV-2b subtype.

The current diagnosis of human T-lymphotropic virus type-2 (HTLV-2) infection is based on the search of specific antibodies; nevertheless, several studies conducted in Brazil pointed deficiencies of the commercially available kits in detecting HTLV-2, mostly in HIV/AIDS patients. This study searched for the presence of HTLV-1 and -2 in 758 HIV/AIDS patients from Londrina, Paraná, Brazil. Serum samples were screened for HTLV-1/2 antibodies using two EIA kits (Vironostika and Murex), and confirmed by WB (HTLV Blot 2.4, Genelabs). The results obtained by EIA disclosed 49 (6.5%) reactive sera: 43 positive by both EIA kits, and six with discordant results. WB confirmed HTLV-1 infection in seven samples (0.9%) and HTLV-2 in 21 sera (2.8%). Negative and indeterminate results were detected in four (0.5%) and 16 (2.1%) sera, respectively. Blood from 47 out of 49 HTLV seroreactive patients were collected and analyzed for the presence of env, LTR and tax genomic segments of HTLVs by PCR. PCR confirmed six cases of HTLV-1 and 37 cases of HTLV-2 infection (14 out of 16 that were found to be WB indeterminate). Restriction analysis of the env PCR products of HTLV-2 disclosed 36 isolates of HTLV-2a/c subtype, and one of HTLV-2b subtype. These results emphasize the need of improving serologic tests for detecting truly HTLV-2 infected patients from Brazil, and confirm the presence of HTLV-2b subtype in the South of this country.

Parkinson's Disease is Accompanied by Intertwined Alterations in Iron Metabolism and Activated Immune-inflammatory and Oxidative Stress Pathways.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a complex interplay between peripheral and central inflammatory and oxidative stress pathways. OBJECTIVE: To investigate immune-inflammatory and oxidative stress pathways in relation to iron metabolism in peripheral blood of PD patients and healthy controls. METHOD: We recruited 56 healthy individuals and 56 PD patients in stages 1-3 of Hoehn and Yahr Scale. Plasma haptoglobin (Hp), homocysteine, interleukin 6, soluble interleukin 6 receptor, iron (Fe), ferritin, total iron binding capacity, transferrin (Tf), soluble transferrin receptor (sTfR), malondialdehyde (MDA) and paraoxonase 1 (PON1) were measured. RESULTS: PD was associated with significant changes in Tf (lowered), sTfR, ferritin, Hp, interleukin 6 and MDA (all increased) levels, while there was a trend towards a negative association with PON1. Logistic regression showed that the most significant biomarkers of PD were MDA, sTfR, Hp and ferritin. Moreover, Fe levels were negatively associated with Hp and positively with PON1, total iron binding capacity and Tf, while ferritin and sTfR were positively associated with MDA levels. CONCLUSION: Our study indicates a state of systemic inflammation and oxidative stress in PD patients coupled with alterations in Fe metabolism. Chronic inflammation and oxidative pathways in PD may in part determine changes in iron metabolism. New drug treatments for PD should target inflammatory and oxidative stress pathways and iron metabolism as well.

Insulin resistance, atherogenicity, and iron metabolism in multiple sclerosis with and without depression: Associations with inflammatory and oxidative stress biomarkers and uric acid.

Depression is accompanied by metabolic disorders in iron metabolism, lipoproteins, and insulin resistance. We measured plasma levels of ferritin, iron, lipids, insulin, and glucose and computed the homeostasis model assessment (HOMA2IR) and atherogenic index of plasma (AIP) in MS patients with and without depression and healthy controls. Explanatory variables were serum uric acid, interleukin (IL)-6, lipid hydroperoxides (CL-LOOH), albumin, and C-reactive protein (CRP). Depression was assessed using the Hospital Anxiety and Depression Scale (HADS), neurological disability using the Expanded Disability Status Scale (EDSS), and disease progression using ∆EDSS over five years earlier. HOMA2IR and insulin were predicted by diagnosis (increased in MS), age and body mass index (BMI); AIP by diagnosis, sex, BMI, CRP, and uric acid; triglycerides by diagnosis (higher in MS without depression), age, BMI and uric acid; ferritin by diagnosis (higher in MS), sex, CRP, and albumin; and iron by albumin. The HADS score was significantly predicted by ∆EDSS, gastro-intestinal symptoms, iron (inverse), and age. MS is characterized by significantly increased insulin resistance, which is determined by increased insulin levels; and increased ferritin, a biomarker of inflammation. Depression in MS is not associated with increased insulin resistance and atherogenicity but with lowered iron.

Disease progression and oxidative stress are associated with higher serum ferritin levels in patients with multiple sclerosis.

Hyperferritinemia and oxidative stress have been implicated in the pathogenesis of multiple sclerosis (MS). The aim of the present study was to evaluate the serum levels of ferritin and to verify their association with oxidative stress markers and MS progression. This study included 164 MS patients, which were divided in two groups according to their levels of ferritin (cut off 125.6µg/L). Oxidative stress was evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), sulfhydryl groups of protein and total radical-trapping antioxidant parameter (TRAP). MS patients with elevated levels of ferritin showed higher disease progression (p=0.030), AOPP (p=0.001), and lower plasma NOx levels (p=0.031) and TRAP (p=0.006) than MS patients with lower ferritin levels. The multivariate binary logistic regression analysis showed that increased AOPP and progression of disease were significantly and positively associated with increase of ferritin. The combination of serum ferritin levels and oxidative stress markers were responsible for 13,9% in the disease progression. In conclusion, our results suggest that ferritin could aggravate oxidative stress in patients with MS and contribute to progression of disease.

Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná , Brazil.

A cross-sectional study was carried out among 996 volunteer blood donors enrolled from May 1999 to December 1999 to determine the seroprevalence of hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil, and to evaluate whether the rate of seroprevalence of IgG anti-HEV antibodies is associated with sociodemographic variables and with seropositivity for hepatitis A virus (HAV) infection. All participants answered the questionnaire regarding the sociodemographic characteristics. Serum samples were tested for IgG antibodies to HEV (anti-HEV) by an enzyme linked immunoassay (ELISA). All serum samples positive for anti-HEV IgG and 237 serum samples negative for anti-HEV were also assayed for IgG anti-HAV antibodies by ELISA. Anti-HEV IgG was confirmed in 23/996 samples, resulting in a seroprevalence of 2.3% for HEV infection, similar to previous results obtained in developed countries. No significant association was found between the presence of anti-HEV IgG antibodies and the sociodemographic variables including gender, age, educational level, rural or urban areas, source of water, and sewer system (p > 0.05). Also, no association with seropositivity for anti-HAV IgG antibodies was observed (p > 0.05). Although this study revealed a low seroprevalence of HEV infection in the population evaluated, the results showed that this virus is circulating among the population from Londrina, South Brazil, and point out the need of further studies to define the clinical and epidemiological importance of HEV infection and to identify additional risk factors involved in the epidemiology and pathogenesis of this infection in this population.