Deficiency of the human complement regulatory protein factor H associated with low levels of component C9

We identified a 4-year-old Brazilian boy from a family of Japanese descent and history of consanguinity, who suffered from severe recurrent pneumonia. He carries factor H (FH) deficiency associated with reduced levels of component C9 and low serum levels of C3 and factor B. His mother also presented low levels of these proteins and factor I, while his father and sister had only lower levels of FH. Western blot assays confirmed the complete absence of FH and FHL-1 polypeptides in this patient. Sequencing of the proband`s FH cDNA revealed a homozygous G453A substitution, encoding an Arg(127)His change. His mother, father and sister are heterozygous for this substitution. Despite the absence of FH in the plasma, this protein was detected in the patient`s fibroblasts, suggesting that Arg(127) may be important for FH secretion. Low concentrations of C9 were detected in the proband serum but no mutations in the patient`s C9 gene or promoter have been identified, suggesting that this is a consequence of uncontrolled complement activation and high C9 consumption.

Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey

OBJECTIVE— To determine the association between serum 25-hydroxyvitamin D (25OHD) and diabetes risk and whether it varies by ethnicity.
RESEARCH DESIGN AND METHODS— We performed an analysis of data from participants who attended the morning examination of the Third National Health and Nutrition Examination Survey (1988–1994), a cross-sectional survey of a nationally representative sample of the U.S. population. Serum levels of 25OHD, which reflect vitamin D status, were available from 6,228 people (2,766 non-Hispanic whites, 1,736 non-Hispanic blacks, and 1,726 Mexican Americans) aged ≥20 years with fasting and/or 2-h plasma glucose and serum insulin measurements.
RESULTS— Adjusting for sex, age, BMI, leisure activity, and quarter of year, ethnicityspecific odds ratios (ORs) for diabetes (fasting glucose ≥7.0 mmol/l) varied inversely across quartiles of 25OHD in a dose-dependent pattern (OR 0.25 [95% CI 0.11– 0.60] for non-Hispanic whites and 0.17 [0.08–0.37] for Mexican Americans) in the highest vitamin D quartile (25OHD ≥81.0 nmol/l) compared with the lowest 25OHD (≥43.9 nmol/l). This inverse association
was not observed in non-Hispanic blacks. Homeostasis model assessment of insulin resistance (loge) was inversely associated with serum 25OHD in Mexican Americans (P ≥ 0.0024) and non-Hispanic whites (P≥0.058) but not non-Hispanic blacks (P≥0.93), adjusting for confounders.
CONCLUSIONS— These results show an inverse association between vitamin D status and diabetes, possibly involving insulin resistance, in non-Hispanic whites and Mexican Americans. The lack of an inverse association in non-Hispanic blacks may reflect decreased sensitivity to vitamin D and/or related hormones such as the parathyroid hormone.

Evaluation of brief dietary questions to estimate vegetable and fruit consumption - using serum carotenoids and red-cell folate

Objective To evaluate responses to self-administered brief questions regarding consumption of vegetables and fruit by comparison with blood levels of serum carotenoids and red-cell folate.

Design A cross-sectional study in which participants reported their usual intake of fruit and vegetables in servings per day, and serum levels of five carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and lycopene) and red-cell folate were measured. Serum carotenoid levels were determined by high-performance liquid chromatography, and red-cell folate by an automated immunoassay system.

Settings and subjects Between October and December 2000, a sample of 1598 adults aged 25 years and over, from six randomly selected urban centres in Queensland, Australia, were examined as part of a national study conducted to determine the prevalence of diabetes and associated cardiovascular risk factors.

Results Statistically significant (P<0.01) associations with vegetable and fruit intake (categorised into groups: ≤1 serving, 2–3 servings and ≥4 servings per day) were observed for α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin and red-cell folate. The mean level of these carotenoids and of red-cell folate increased with increasing frequency of reported servings of vegetables and fruit, both before and after adjusting for potential confounding factors. A significant association with lycopene was observed only for vegetable intake before adjusting for confounders.

Conclusions These data indicate that brief questions may be a simple and valuable tool for monitoring vegetable and fruit intake in this population.

Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Blood serum components and serum protein test of Hybro-PG broilers of different ages

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Changes of metabolic and inflammatory markers in HIV infection: glucose, lipids, serum Hs-CRP and myeloperoxidase

Objective: HIV infection is exacerbated through additional pro-atherogenic mechanisms related to the processes of immune activation, inflammation, coagulation, and the modification of lipoproteins (e.g., particles of high density lipoprotein), contributing to increased cardiovascular risk. The aim of this study was to analyze the serum concentrations of myeloperoxidase (MPO) and other laboratory parameters in HIV-infected patients treated or not with antiretroviral drugs compared to non-infected individuals.Materials/Methods: The study included 154 volunteers: 47 non-infected individuals (control group - CON), 27 infected and untreated individuals (NTARv group) and 80 treated individuals (TARV group). We analyzed the counts of CD4+ lymphocytes and the viral load of the infected patients, along with the blood count, fasting glucose, total serum cholesterol (CHOL), HDL cholesterol, LDL cholesterol, triglycerides, MPO and high-sensitivity C-reactive protein (CRP) of all study participants.Results: There were significant increases in glucose, CHOL, LDL cholesterol, and triglycerides in the TARV group and significant reductions in the levels of HDL cholesterol for the TARV and NTARV groups. Significantly elevated levels of Hs-CRP were observed only in the TARV group, while levels of MPO were significantly higher in the TARV and NTARV groups compared to the control group. A correlation of MPO with Hs-CRP (r = 0.21, p = 0.032) was observed for HIV-infected patients, but MPO did not correlate significantly with the other analyzed parameters.Conclusions: The investigation of early biomarkers for cardiovascular risk evaluation, such as MPO, contributes to the clinical monitoring of HIV-infected individuals. The serum levels of MPO correlated with Hs-CRP and were high in HIV-infected individuals, indicating a possible predictor of cardiovascular events in these patients. (c) 2012 Elsevier B.V. All rights reserved.

Gonadal function arrest in fillies after birth, as reflected by steroid serum concentrations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Serum homocysteine and physical exercise in patients with Parkinson's disease

Background: Hyperhomocysteinemia is a major risk factor for cerebral and peripheral vascular diseases, as well as cortical and hippocampal injury, including an increased risk of dementia and cognitive impairment. Elevated serum homocysteine (Hcy) concentrations are common in patients with Parkinson's disease (PD) who have been treated with levodopa; however, physical exercises can help reduce Hcy concentrations. The aim of the present study was to compare serum Hcy levels in patients with PD who partook in regular physical exercises, sedentary PD patients, and healthy controls.Methods: Sixty individuals were enrolled in the present study across three groups: (i) 17 patients who did not partake of any type of exercise; (ii) 24 PD patients who exercised regularly; and (iii) 19 healthy individuals who did not exercise regularly. All participants were evaluated by Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab and England scale (measure daily functionality). The serum levels of Hcy were analyzed by blood samples collected of each participant. An analysis of variance and a Tukey's post hoc test were applied to compare and to verify differences between groups. Pearson's correlation and stepwise multiple regression analyses were used to consider the association between several variables.Results: Mean plasma Hcy concentrations in individuals who exercised regularly were similar to those in the healthy controls and significantly lower than those in the group that did not exercise at all (P = 0.000). In addition, patients who did not exercise were receiving significantly higher doses of levodopa than those patients who exercised regularly (P = 0.001). A positive relationship between levodopa dose and Hcy concentrations (R(2) = 0.27; P = 0.03) was observed in patients who did not exercise, but not in those patients who exercised regularly (R(2) = 0.023; P = 0.15).Conclusions: The results of the present study suggest that, even with regular levodopa therapy, Hcy concentrations in PD patients who exercise regularly are significantly lower than in patients who do not exercise and are similar Hcy concentrations in healthy controls.

INFLUENCE OF ENTERAL PARASITES ON THE BLOOD VITAMIN-A LEVELS IN PRESCHOOL-CHILDREN ORALLY SUPPLEMENTED WITH RETINOL AND OR ZINC

A sample of 471 pre-school children who frequented schools and creches in a poor district of Manaus (Amazonas), Brazil, were randomly submitted to faecal parasitological tests. Two-hundred-and-forty children from both sexes between the ages of 3 and 7 years with Ascaris lumbricoides and/or Giardia lamblia were selected. The objective of the study was to determine the possible influence of these two intestinal parasites and vitamin A and/or zinc supplementation on the serum retinol levels of primary school children. The children were submitted to clinical and anthropometric examinations, dietary interviews and biochemical examinations of retinol and carotene in the serum and of zinc in the hair. The parasitic incidence was 85.0% and about 54% of the children were polyparasitic. During the pretreatment phase, the retinol and carotene serum levels were 36% and 57%, respectively, below the normal levels. Using the Waterlow classification, the anthropometric analyses revealed that 88% of the children showed normal growth. A significant effect was observed of the anti-parasitic medicine on the serum retinol levels.

Interleukin-8 as a prognostic serum marker in canine mammary gland neoplasias

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Serum Vitamins in Adult Patients With Short Bowel Syndrome Receiving Intermittent Parenteral Nutrition

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Biochemical evaluation of glycemic levels of long-term tacrolimus therapy in rats

One of the more serious complications following transplantation is the development of post-transplantation diabetes mellitus (PTDM), which has a major impact on the quality of life, with effects ranging from the control of glycemia times to increased susceptibility to infections and cardiovascular complications. It has been suggested that immunosuppressive therapy, mainly tacrolimus therapy, may be an important factor in the development of PTDM. There is a lack of studies that explore the effects of long-term tacrolimus on PTDM in animal protocols. The objective of this study was therefore to evaluate the effects of long-term therapy with tacrolimus in rats. One group was treated with tacrolimus, injected subcutaneously, in a daily dose of 1 mg/kg of body weight. The chosen dose was sufficient to achieve therapeutic tacrolimus serum levels. The experimental periods were 60, 120, 180 and 240 days. One group was used as control and received daily subcutaneous injections of saline solution during all periods. A tendency towards increased glycemia levels during the initial periods (60 and 120 days) was observed. However, at 180 and 240 days, the glycemia levels were not statistically different from that of the control group of the same period. It may thus be concluded that the deleterious effects of tacrolimus therapy on glycemia may be a time-related side effect.

Experimental infection of commercial layers using a Salmonella enterica serovar Gallinarum strain: Leukogram and serum acute-phase protein concentrations

The aim of the present study was to evaluate white blood cell counts and serum protein profiles of commercial layers experimentally infected with Salmonella Gallinarum (SG) in order to better understand the pathophysiology of the disease caused by this bacterium. 180 five-day-old commercial layers were divided into 3 groups (G); G1 and G2 received 0.2 mL of inoculate containing 3.3x10 8 CFU or 3.3×10 5 CFU SG resistant to nalidix acid (Nal r)/mL, respectively, directly into their crops. G3 group did not receive the inoculum. Birds were sacrificed 24 hours before (T1) and 24 hours after the infection (T2), and three (T3), five (T4), seven (T5), and ten (T6) days after the administration of the inoculum. White blood cell counts were carried out in a Neubauer hemocytometer and in blood smears. Serum protein concentrations, including acute-phase proteins, were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Data were submitted to analysis of variance, and means were compared by Tukey's test (P <0.05). G1 and G2 groups presented higher leukocyte counts on T4 and T5, respectively, due to the increase of circulating lymphocytes and heterophils, with a significant difference relative to G3. In electrophoresis, an increase in the serum levels of ceruloplasmin, haptoglobin, and hemopexin and a decrease in transferrin, which are acute-phase proteins, was verified. IgA serum levels did not change; however, IgG concentration increased during the infection. In conclusion, the results provide information for the better understanding of the pathophysiology of fowl typhoid.

Compartmentalization of pro-inflammatory cytokine levels in renal-transplanted pregnant women

Objective: We evaluated whether chronic exposure to immunosuppression in transplant recipients modulate the placental inflammatory cytokine levels associated to gestational tolerance mechanisms. Methods: Serum samples were collected from 12 renal transplanted pregnant under immunosuppressive regimen treatment and 10 healthy women in second/third trimester of gestation. Term placental tissues (decidua and chorionic villi) were also obtained after elective caesarean. Serum IL-1β, IL-6, IL-8, IL-12p70 and TNF-α were measured, as also in placental homogenates, by Cytometric Bead Array (CBA) combined with flow cytometry and, TGF-β and IL-18 were measured by ELISA. Results: Serum levels of IL-6 (p=0.0001) and TNF-α (0.0112) were higher in the 2nd and 3rd trimesters and in decidua the spectrum of increased pro inflammatory cytokines was wider: IL-1β (p=0.0001), IL-6 (p=0.0001), IL-8 (p=0.0001), IL-12p70 (p=0.0001), TGF-β (p=0.0089) and TNF-α (p=0.0002). TGF-β1 was particularly increased in decidual compartment (p=0.001). In the chorionic villous, pro inflammatory profile also were maintained. High IL-1β (p=0.0001), IL-6 (p=0.0001), IL-8 (p=0.0001) and TNF-α (p=0.0001) levels establish a similar pattern to that seem in decidua. Conclusion: Immunosuppressors may impair the immune response, but when associated with pregnancy the cytokine levels seems to shift a proinflammatory profile in placental compartments, which might also impact on the gestational outcomes in transplanted mothers. © 2013 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.

Characterization of mannose-binding lectin plasma levels and genetic polymorphisms in HIV-1-infected individuals

INTRODUÇÃO: O presente estudo investigou a associação entre o polimorfismo no gene da lectina ligante de manose (MBL) e os níveis séricos da proteína com a infecção pelo HIV-1. MÉTODOS: As amostras de sangue (5mL) foram coletadas de 97 indivíduos infectados pelo HIV-1 residentes em Belém, Estado do Pará, Brasil, que frequentavam a Unidade de Referência Especial para Doenças Infecciosas e Parasitárias Especiais (URE-DIPE). Os níveis de linfócitos T CD4+ e da carga viral plasmática foram quantificados. Um fragmento de 349pb do exon 1 da MBL foi amplificado via PCR, utilizando DNA genômico extraído das amostras controles e dos indivíduos portadores do HIV-1, seguindo protocolos previamente estabelecidos. O nível plasmático de MBL nos pacientes foi quantificado usando kit de ensaio imunoenzimático. RESULTADOS: Dois alelos foram observados - MBL*O, com uma frequência de 26,3% em indivíduos infectados e o alelo selvagem MBL*A (73,7%). Frequências similares foram observadas no grupo controle (p > 0,05). As frequências genotípicas estavam em equilíbrio de Hardy-Weinberg em ambos os grupos. A média dos níveis plasmáticos MBL variou por genótipo, com diferenças significativas entre os genótipos AA e AO (p < 0,0001), e AA e OO (p < 0,001), mas não entre AO e OO (p=0,17). Além disso, os linfócitos T CD4+ e os níveis plasmáticos de carga viral não diferiram significativamente de acordo com o genótipo (p>0,05). CONCLUSÕES: Os resultados deste estudo não apoiam a hipótese de que o polimorfismo no gene MBL ou baixa concentração plasmática de MBL poderia ter uma influência direta sobre a infecção pelo HIV-1, embora um estudo com número maior de pacientes seja necessário.