Association between Vitamin D Status, Oxidative Stress Biomarkers and Viral Load in Human Immunodeficiency Virus Type 1 Infection.

BACKGROUND: The role of vitamin D in the pathophysiology of human immunodeficiency virus type 1 (HIV-1) infection is still unclear. OBJECTIVE: To evaluate the associations between vitamin D and immunological, virological, and oxidative stress biomarkers in individuals with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: The serum levels of 25 hydroxyvitamin D [25(OH)D] were determined in 314 HIV-1- infected individuals and 127 controls and the values ≥30 ng/mL defined a vitamin D sufficient (VDS) status, and <30 ng/mL defined the presence of hypovitaminosis D (HD). Oxidative stress was evaluated with plasma levels of lipid hydroperoxides, advanced oxidation protein products (AOPP), carbonyl protein, nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP), and sulfhydryl groups of proteins. Plasma HIV-1 viral load and CD4+/CD8+ T cells were quantified. RESULTS: The 25(OH)D levels and vitamin D status did not differ between HIV-1-infected individuals and controls. Hydroperoxides and AOPP were higher (p<0.0001 and p=0.002, respectively), whereas TRAP, carbonyl protein, and NOx were lower in HIV-1-infected individuals than controls (p<0.0001). HIV-1-infected individuals with HD showed higher hydroperoxide levels than those with a VDS status (p=0.012) and controls (p=0.022), independent of ethnicity and antiretroviral therapy. A positive correlation between 25(OH)D ≥30 ng/mL and viral load was observed when expressed as the number of copies/mL (r=0.178, p=0.039), as well as log10 copies/mL (r=0.183, p=0.033). CONCLUSION: These results suggest the bimodal influence of vitamin D in the modulation of immune response in HIV-1 infection, considering its differential susceptibility to modulation of the various immune targets and pathways.

Vitamin D deficiency is associated with disability and disease progression in multiple sclerosis patients independently of oxidative and nitrosative stress.

The aim of this study was to assess vitamin D status in patients with multiple sclerosis (MS) and to evaluate whether it was associated with oxidative and nitrosative stress (O&NS) markers and disability. This study included 137 patients with MS and 218 healthy controls. The markers evaluated were serum levels of 25-hydroxyvitamin D, lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter TRAP/UA. Patients with 25(OH)D<20ng/mL showed higher EDSS (p=0.016), MSSS (p=0.005) and lower AOPP (p=0.046) than those with 25(OH)D≥20ng/mL. After the binary logistic regression analyses, EDSS and MSSS remained significantly associated with vitamin D deficiency. We showed that lower levels of 25(OH)D were associated with higher EDSS and MSSS independently of variables such as O&NS, age, sex, body mass index, ethnicity, MS therapy, use of interferon beta, and clinical forms of MS (odds ratio: 1.380, 95% confidence interval 1.030-1.843, p=0.031). Moreover, the study showed an association between serum levels of 25(OH)D and EDSS (r2=0.115, p=0.002), demonstrating that 25(OH)D may contribute with 11.5% of increase in EDSS. Our results suggest that vitamin D deficiency may be considered one of the predictors of the disability in MS patients, independently of their redox status and influence the progression of disability in MS.

Albumin and Protein Oxidation are Predictors that Differentiate Relapsing-Remitting from Progressive Clinical Forms of Multiple Sclerosis.

The aim of the present study was to evaluate inflammatory, oxidative, and nitrosative stress (IO&NS) blood markers as possible predictors of multiple sclerosis (MS) and its clinical forms. This study included 258 MS patients (175 with relapsing-remitting MS (RRMS) and 83 with progressive MS clinical forms) and 249 healthy individuals. Peripheral blood samples were obtained to determine serum levels of albumin, ferritin, C-reactive protein (CRP), total protein, lipid hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH), carbonyl protein content, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter (TRAP). MS patients showed higher ferritin (p < 0.001) and CL-LOOH (p < 0.001) and lower albumin (p = 0.001), TRAP (p < 0.001), AOPP (p = 0.013), and NOx values (p < 0.001) than controls. Difference was not observed in CRP, total protein, and carbonyl proteins between patients and controls. In the logistic regression age-adjusted, ferritin and CL-LOOH showed positive association with MS and were predictors of MS development (OR: 1.006, 95 % CI: 1.003-1.009, p < 0.001 and OR: 1.029, 95 % CI: 1.007-1.052, p = 0.009, respectively). Albumin, TRAP, AOPP, and NOx were negatively associated with MS (p = 0.019, p = 0.003, p = 0.001, and p = 0.003, respectively). Moreover, other logistic regression age-adjusted showed that MS patients with progressive clinical forms had lower albumin and higher AOPP than those with RRMS (p = 0.037). In conclusion, ferritin, albumin, and biomarkers of IO&NS, such as CL-LOOH, AOPP, TRAP, and NOx were predictors of MS diagnosis, whereas albumin and AOPP were predictors that differentiated RRMS from the progressive clinical forms of MS.

CCp5A Protein from Toxoplasma gondii as a Serological Marker of Oocyst-driven Infections in Humans and Domestic Animals.

Considering that the current immunoassays are not able to distinguish the infective forms that cause Toxoplasma gondii infection, the present study was carried out to evaluate the reactivity of two recombinant proteins (CCp5A and OWP1) from oocyst/sporozoite, in order to differentiate infections occurring by ingestion of oocysts or tissue cysts. The reactivity of the recombinant proteins was assessed against panels of serum samples from animals (chickens, pigs, and mice) that were naturally or experimentally infected by different infective stages of the parasite. Also, we tested sera from humans who have been infected by oocysts during a well-characterized toxoplasmosis outbreak, as well as sera from pregnant women tested IgM(+)/IgG(+) for T. gondii, which source of infection was unknown. Only the sporozoite-specific CCp5A protein was able to differentiate the parasite stage that infected chickens, pigs and mice, with specific reactivity for oocyst-infected animals. Furthermore, the CCp5A showed preferential reactivity for recent infection by oocyst/sporozoite in pigs and mice. In humans, CCp5A showed higher reactivity with serum samples from the outbreak, compared with serum from pregnant women. Altogether, these findings demonstrate the usefulness of the CCp5A protein as a new tool to identify the parasite stage of T. gondii infection, allowing its application for diagnosis and epidemiological investigations in animals and humans. The identification of parasite infective stage can help to design effective strategies to minimize severe complications in immunocompromised people and, particularly, in pregnant women to prevent congenital infection.

Role of metabolic syndrome and antiretroviral therapy in adiponectin levels and oxidative stress in HIV-1 infected patients.

OBJECTIVE: HIV-1 infection is accompanied by severe metabolic and immune dysfunction. The aim of this study was to evaluate the role of metabolic syndrome (MetS) and antiretroviral therapy (ART) utilization on the adiponectin levels and oxidative stress in patients infected with HIV-1. METHODS: We allocated 285 patients into four groups: group 1: patients without MetS who were not using ART; group 2: patients without MetS using ART; group 3: patients with MetS who were not using ART; and group 4: patients with MetS using ART. Biochemical, immunologic, and oxidative stress parameters were measured. RESULTS: Group 4 exhibited higher lipoperoxides when compared with group 1 (P < 0.0001) and higher advanced oxidation protein products (AOPP) compared with group 2 or group 1 (P < 0.0001). Group 3 also presented higher AOPP than group 2 (P < 0.05). Group 4 showed lower adiponectin levels compared with groups 1 or 2 (P < 0.0001). Similarly, group 3 presented lower adiponectin levels compared with group 2 (P < 0.05) or group 1 (P < 0.0001). Multivariate analysis showed that both an increase in AOPP and a decrease in total radical-trapping antioxidant parameter/uric acid were independently associated with MetS in HIV-1 patients. Regarding immunologic markers of HIV-1 disease progression and viral replication, group 4 exhibited significantly higher CD45(+), CD3(+), and CD4(+) T cells count compared with group 2 (P < 0.01). CONCLUSION: HIV-1-infected patients with MetS exhibited hypoadiponectinemia and increased oxidative stress, and these findings were not influenced by ART use. The findings of the present study allow the suggestion that MetS and inflammation might be mainly responsible for the aforementioned features. More studies are needed to verify whether drugs or food, which yield increased adiponectinemia and decreased oxidative stress, could reduce cardiovascular risk in HIV-infected patients.

Seroprevalence and risk factors for human T cell lymphotropic virus type 1 and 2 infection in human immunodeficiency virus-infected patients attending AIDS referral center health units in Londrina and other communities in Paraná, Brazil.

The municipality of Londrina ranks second in the number of AIDS cases in the state of Paraná, Brazil, with the Ministry of Health notified of 1070 cases from 1984 to 2002. The aim of this study was to determine the seroprevalence and risk factors for HTLV-1/2 infection in HIV-infected patients attending the AIDS Reference Center serving Londrina (and surrounding region), Paraná, Brazil. Data concerning sociodemographic conditions and risk factors were collected from 784 HIV-infected patients, using a questionnaire. Blood samples were obtained from 758 of the patients and subjected to serologic screening tests for the determination of HTLV-1/2, as well as hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis. Most patients were white (mean age, 35.9 years); 55.9% were males and 44.1% were females. The most frequent sexually transmitted disease was gonorrhea (28.5%), followed by syphilis (14.3%) and condyloma (12.2%). The major risk factors associated with the acquisition of retroviruses were sexual contact (84.8%) and intravenous drug use (IDU, 11.9%). The overall infection seroprevalence was 6.4% for HTLV-1/2, 37.2% for HBV, 21.0% for HCV, and 24.4% for syphilis. HTLV-1 and HTLV-2 infections were confirmed in 0.8 and 4.9% of patients, respectively. HIV/HTLV-1/2 coinfection was more frequent in IDUs (59.2% of cases) and was strongly associated with HCV (22.60 [95% CI, 10.35-49.35]). A weak association with HBV (2.09 [95% CI, 1.13-3.90]) and no association with syphilis were observed. The results showed that human retroviruses are circulating in southern Brazil, mainly among white people of both genders of low socioeconomic conditions and educational level. Although the sexual route was considered to be the major risk factor for HIV infection, HTLV-1/2 infection was strongly associated with IDU.

Caracterização, produção e indicação clínica dos principais hemocomponentes / Characterization, production and indication of the principal blood components

A prática da transfusão de sangue é uma ciência que cresce rapidamente, modifica-se continuamente e que apresenta uma grande perspectiva de desenvolvimento futuro. A rotina habitual dos serviços de hemoterapia requer o aperfeiçoamento de técnicas, pois o fracionamento do sangue coletado se faz necessário, uma vez que cada unidade doada pode beneficiar diversos pacientes e permitir que sejam transfundidas grandes quantidades de um determinado componente que o paciente necessite. O objetivo do presente trabalho foi revisar os procedimentos de coleta, produção, armazenamento e a indicação clínica dos principais hemocomponentes, como concentrado de hemácias, concentrado de hemácias lavadas, eritrócitos pobres em leucócitos, concentrado de plaquetas, concentrado de plaquetas por aférese, concentrado de granulócitos, plasma fresco congelado, plasma normal ou comum e crioprecipitado. Perspectivas futuras apontam para mudanças na terapia transfusional, e o maior foco será no aperfeiçoamento da segurança, havendo aumento de produtos manufaturados, desenvolvimento de produtos acelulares, tecnologias em aféreses, atenuação microbiana e proteínas recombinantes do plasma, que poderão substituir produtos derivados plasmáticos dentro de poucas décadas.