Retinol-binding Protein Concentrations Research Articles

Renal Evaluation in Women with Preeclampsia

Background/Aims: Preeclampsia (PE) is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP) is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR) may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. Methods: Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group) by performing urinary tests. Results: Mean (±SD) age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001). Mean (±SD) urinary RBP (p = 0.017), albuminuria (p = 0.002), and urinary albumin concentration (UAC) ratio (p = 0.006) of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002), and 3,778.9 ± 4,296.6 mg/g (p = 0.006), respectively. Mean (±SD) urine PCR in the PE group was 6.7 ± 6.1 g/g (p < 0.001). No statistical differences were found between podocyturia in the CG and PE group (p = 0.258). Conclusions: Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE.

Improvement of Vitamin D Status via Daily Intake of Fortified Yogurt Drink Either with or without Extra Calcium Ameliorates Systemic Inflammatory Biomarkers, including Adipokines, in the Subjects with Type 2 Diabetes

Systemic inflammation is thought to have a central role in diabetic long-term complications. The aim of this study was to investigate the effects of vitamin D either with or without extra calcium on certain inflammatory biomarkers in the subjects with type 2 diabetes (T2D). This was a double-blind, randomized, controlled trial conducted over 12 wk in 90 T2D subjects aged 30-60 yr from both sexes. Subjects were randomly allocated to one of three groups to receive two 250-ml bottles a day of plain Persian yogurt drink or doogh (PD, containing 150 mg calcium and no detectable vitamin D(3)/250 ml), vitamin D-fortified doogh (DD, containing 500 IU vitamin D(3) and 150 mg calcium/250 ml), or calcium + vitamin D(3)-fortified doogh (CDD, containing 500 IU vitamin D(3) and 250 mg calcium/250 ml). The changes in inflammatory markers were evaluated. Compared to the baseline values, highly sensitive C-reactive protein, IL-1β, IL-6, fibrinogen, and retinol binding protein-4 concentrations significantly decreased in both the DD and CDD groups. Although the decrement in highly sensitive C-reactive protein and fibrinogen was more in CDD compared to DD (-4.0 ± 8.5 vs. -1.3 ± 2.8 mg/liter, and -0.40 ± 0.74 and -0.20 ± 0.52 mg/liter, respectively), the differences were not significant. There was a significant increase in serum adiponectin in both the DD and CDD groups (51.3 ± 65.3 vs. 57.1 ± 33.8 μg/liter; P < 0.05). Mean adiponectin changes in CDD were significantly higher than in PD (P = 0.021). Daily intake of vitamin D-fortified doogh improved inflammatory markers in T2D subjects, and extra calcium conferred additional benefit only for the antiinflammatory adipokine, i.e. adiponectin.

Are plasma levels of visfatin and retinol-binding protein 4 (RBP4) associated with body mass, metabolic and hormonal disturbances in women with polycystic ovary syndrome?

To analyze potential interactions of visfatin and retinol-binding protein 4 (RBP4) levels with body mass, metabolic, and hormonal status in normal weight and obese women with PCOS. Body composition was determined by bioimpedance in 83 women (44 obese) diagnosed with PCOS and in 67 women (36 obese) without PCOS. In addition, serum glucose, lipids, androgens, FSH, LH, SHBG, insulin, visfatin, and RBP4 were measured in a fasting state and the free androgen index (FAI) was calculated, as was insulin resistance using the HOMA-IR assessment. Plasma RBP4 levels were significantly higher in women of normal weight compared to obese subjects when both were diagnosed with PCOS (14.1 ± 4.6 vs.10.9 ± 4.5 ng/mL, p<0.001); while in non-PCOS subjects the opposite was found (10.8 ± 4.5 vs. 18.4 ± 11.6 ng/mL, p<0.01; respectively). Plasma visfatin levels were similar in PCOS and non-PCOS subjects. In non-PCOS subjects, positive correlations between RBP4 level and anthropometric parameters were observed. In PCOS, RBP4 levels inversely correlated with serum insulin levels and HOMA-IR values. No correlation was found between plasma visfatin levels and anthropometric parameters in all study groups. Similarly, no correlation was found in PCOS and non-PCOS subgroups. Additionally, there was an inverse correlation between RBP4 and LH concentrations and LH/FSH ratio in all study subjects. Plasma visfatin level is not a useful biomarker of insulin resistance and hyperandrogenism. RBP4 level reflects visceral body fat content in non-PCOS women. Decreasing RBP4 release along with increasing insulin resistance and hormonal disturbances may be a compensatory mechanism preventing deterioration in obese PCOS.

The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels

ObjectiveIt has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). MethodSerum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. ResultsThere was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06–11.52]ng/ml versus 10.50 [4.30–20.60]ng/ml, p=0.004) and adiponectin (mean±SD, 10.07±4.0μg/ml versus 20.66±8.12μg/ml, p<0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30–0.79]; p=0.004 and OR=0.74, CI [0.67–0.82]; p<0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. ConclusionsThe FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs’ increased risk of diabetes needs to be further elucidated.

Vitamin A deficiency associated with urinary retinol binding protein wasting in Dent’s disease

Three patients with Dent's disease presented with complaints of impaired night vision or xerophthalmia and were found to have severely decreased serum retinol concentrations. Retinol, bound to its carrier retinol-binding protein (RBP), is filtered at the glomerulus and reabsorbed at the proximal tubule. We hypothesized that urinary loss of retinol-RBP complex is responsible for decreased serum retinol. The study aim was to investigate vitamin A status and RBP in serum and urine of patients with genetically confirmed Dent's disease. Eight patients were studied, three boys had clinical vitamin A deficiency, three had asymptomatic deficiency, and two young men with Dent's disease and impaired renal function had normal retinol values. Serum RBP concentrations were low in patients with vitamin A deficiency and were correlated with vitamin A levels. Urinary RBP concentrations were increased in all patients (2,000-fold), regardless of vitamin A status. This was in contrast to patients with glomerular proteinuria who had only mildly increased urinary RBP with normal serum RBP and vitamin A, and patients with cystinosis with impaired renal function who had massive urinary RBP losses but without a decrease in serum RBP or vitamin A levels. Treatment with vitamin A supplements in patients with retinol deficiency resulted in rapid resolution of ocular symptoms and an increase in serum retinol concentrations. Vitamin A deficiency is common in patients with Dent's disease and preserved renal function. We therefore recommend screening these patients for retinol deficiency and treating them before visual symptoms develop.

Serum retinol binding protein 4 and bone metabolism in patients with type 2 diabetes

To determine the relation between serum concentration of retinol binding protein (RBP) 4 and markers of bone metabolism, bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). A total of 82 patients newly diagnosed with T2DM and 46 subjects with normal glucose tolerance (NGT) enrolled in the cross-sectional study. Subset analyses were performed, dividing subjects on the basis of gender into M-T2DM, F-T2DM, M-NGT, and F-NGT. The serum concentrions of RBP4, osteocalcin (OC) and C-terminal telopeptide of collagen type I (CTX) were measured with ELISA. The BMD was measured by dual-energy X-ray absorptiometry (DXA) with a Hologic QDR4500A device. In both the T2DM groups, lnRBP4 showed a positive relationship with lnCTX (M-T2DM, r=0.564, P<0.01; F-T2DM, r=0.386, P=0.018), but no association with lnOC. After adjusting for age, smoking, creatinine clearance rate (CCr), and waist-to-hip ratio (WHR), lnRBP4 still showed a strong association with lnCTX in the M-T2DM group (r'=0.536, P<0.01), but not in F-T2DM (r'=0.317, P=0.072). In the NGT group, there was no relation between lnRBP4 and lnCTX or lnOC. LnRBP4 showed no association with BMD in all groups. The level of serum RBP4 may be correlated with the bone metabolism in patients with T2DM.

Effects of Exercise Training on Circulating Retinol-Binding Protein 4 and Cardiovascular Disease Risk Factors in Obese Men

Introduction: The purpose of this study was to investigate the effects of 12-week exercise training on circulating retinol-binding protein 4 (RBP4) concentration and cardiovascular disease (CVD) risk factors in obese men. Methods: 29 obese men (age 48 ± 2 years; BMI 29.6 ± 0.7 kg/m²) participated in a 12-week exercise program (50–70% maximal heart rates; 3 times/week) without calorie restriction. Anthropometric parameters, CVD risk factors (total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides (TG), and quantitative insulin sensitivity check index), and circulating RBP4 and adipokine (adiponectin, leptin, and interleukin-6 (IL-6)) concentrations were measured. Results: Exercise training significantly improved in absolute peak oxygen consumption (p < 0.05), and CVD risk factors (p < 0.05), with the exception of HDLC. There was a significant decrease in circulating RBP4, leptin, and IL-6 concentrations (p < 0.05). Stepwise regression analysis revealed that changes in RBP4 concentration were independently related to the changes in TG concentration (β = 0.46, p < 0.05). Conclusion: These results demonstrate that exercise training without calorie restriction improves several CVD risk factors and circulating RBP4 and adipokine concentrations. Moreover, the change in circulating RBP4 may be more associated with the improvements in TG concentration in obese men.

Sepsis-Induced Adipokine Change with regard to Insulin Resistance

Background. Assessment of white adipose tissue has changed in recent years, with WAT now being considered as an active endocrine organ, secreting a large number of bioactive mediators, so-called adipokines. Besides other functions, these adipokines are involved in inflammatory response thereby exhibiting predominantly proinflammatory or anti-inflammatory properties and contribute to insulin resistance. Methods. Comprehensive review of the literature of the role of adipokines relevant to critical care medicine using PubMed search. Results. Adiponectin—the prototype of an anti-inflammatory and insulin-sensitizing adipokine—is diminished in sepsis, while resistin—a protein with proinflammatory properties—is elevated. Plasminogen activator inhibitor-1, interleukin (IL)-1, IL-6, IL-8, and IL-10, and tumor-necrosis-factor-alpha mediate insulin resistance and are elevated in sepsis, while retinol-binding protein-4 concentrations are significantly reduced in sepsis. Chemerin displays potent anti-inflammatory and insulin-resistance properties, while monocyte chemotactic protein-1—increased in sepsis—contributes to macrophage infiltration in adipose tissue and insulin resistance. Conclusions. The expression of adipokines in humans is altered as well in obese as in septic patients with elevated levels of proinflammatory adipokines. Changes in adipokine levels in acute sepsis could contribute to insulin resistance. Consequently, in critically ill patients, these alterations underline a possible contribution of adipokines in the development of hyperglycemia.

Serum Retinol-Binding Protein-4 Levels Are Increased in HIV-Infected Subjects with Metabolic Syndrome Receiving Highly Active Antiretroviral Therapy

Metabolic syndrome is an important long term complication in chronic asymptomatic HIV-infected subjects under highly active antiretroviral therapy (HAART), because it can contribute to morbidity and mortality via cardiovascular disease (CVD). Therefore, a predictive marker for early detection of metabolic syndrome may be necessary to prevent CVD in HIV-infected subjects. Retinol-binding protein-4 (RBP-4) has been shown to be associated with metabolic syndrome in various non-HIV-infected populations. We performed a cross-sectional study to evaluate whether serum RBP-4 levels are correlated with metabolic syndrome in HIV-infected subjects receiving HAART. In total, 98 HIV-infected Koreans who had been receiving HAART for at least 6 months were prospectively enrolled. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III criteria, and serum RBP-4 concentrations were measured using human RBP-4 sandwich enzyme-linked immunosorbent assay. Serum RBP-4 levels were significantly higher in HIV-infected subjects receiving HAART with metabolic syndrome (n=33, 33.9±7.7 µg/mL) than in those without it (n=65, 29.9±7.2 µg/mL) (p=0.012). In multivariate linear regression analysis, the number of components of metabolic syndrome presented and waist circumference were independently, significantly correlated with RBP-4 (p=0.018 and 0.030, respectively). In conclusion, we revealed a strong correlation between RBP-4 and the number of components of metabolic syndrome in HIV-infected subjects receiving HAART.

Alterations in systemic concentrations of progesterone during the early luteal phase affect RBP4 expression in the bovine uterus

Systemic progesterone affects the timing and duration of uterine endometrial gene and protein expression and has significant effects on conceptus development. The objective of the present study was to examine how changes in progesterone concentrations during the early luteal phase affect retinol-binding protein (RBP4) mRNA and protein concentrations in the uterus. Endometrial tissue and uterine flushings were recovered on Days 7 and 13 of the oestrous cycle in heifers with high, normal and low progesterone concentrations. RBP4 mRNA and protein concentrations were higher (P<0.05) on Day 13 compared with Day 7 in heifers with high and control progesterone concentrations. However, there was no difference in RBP4 protein concentrations between Days 7 and 13 in heifers with low progesterone (P>0.05). On Day 7, although heifers with low progesterone had lower RBP4 mRNA expression compared with controls (P<0.05) there was no difference in protein concentrations between treatment groups. On Day 13, RBP4 mRNA was 2-fold higher (P<0.001) in heifers with high and control progesterone compared with their low-progesterone counterparts and RBP4 protein concentrations were over 2-fold higher (P<0.001) in heifers with high compared to low progesterone. In conclusion, progesterone modulates uterine RBP4 mRNA and protein abundance in a time- and concentration-dependent manner.

Plasma Retinol-Binding Protein Predicts Plasma Retinol Concentration in Both Infected and Uninfected Cameroonian Women and Children

Variation in the relationship between plasma retinol-binding protein (RBP) and retinol (ROH) has implications for vitamin A (VA) status assessment using RBP. Our objectives were to identify factors affecting the RBP:ROH relationship and to derive and evaluate population-specific RBP cutoffs for VA deficiency (VAD) in Cameroon. Plasma RBP, C-reactive protein (CRP), a1-acid-glycoprotein (AGP), and ROH concentrations were compared in a subsample of women 15–49 y (n = 121) and children 12–59 mo (n = 123) included in a national survey conducted in 2009. Plasma RBP and ROH were highly correlated (r = 0.94 for women; r = 0.96 for children; P < 0.001). Pregnancy and lactation altered the RBP:ROH relationship in women, but obesity, elevated CRP and AGP, age, and VA status did not. Among children, age altered the RBP:ROH relationship, but sex, stunting, VA status, and elevated CRP and AGP did not. Cutoffs for VAD derived using regression analysis were <1.17 μmol RBP/L for women (corresponding to <1.05 μmol ROH/L) and <0.83 μmol RBP/L for children (corresponding to <0.70 μmol ROH/L). The sensitivity and specificity of derived cutoffs were 81.8 and 93.0% for women and 94.7 and 88.9% for children, respectively. The infection-adjusted prevalence of low VA status (<1.17 μmol RBP/L) was 21.9% (95% CI = 18.7–25.0%) among women. Among children, the infection-adjusted prevalence of VAD (<0.83 μmol RBP/L) was 35.0% (95% CI = 31.1–39.0%). In conclusion, VAD remains a public health problem in Cameroon. The RBP:ROH relationship should be considered in surveys using RBP to assess VA status, and use of population-specific cutoffs may be advisable.

Decreased concentrations of retinol-binding protein 4 in sera of epithelial ovarian cancer patients: A potential biomarker identified by proteomics

Ovarian cancer is the fifth leading cause of cancer death in women. Absence of a reliable biomarker precludes early diagnosis of the disease. To identify new proteins with potential diagnostic or prognostic value for the therapy of ovarian cancer we performed comparative proteomic analysis of sera from ovarian cancer patients and healthy women. We analyzed serum samples from 10 patients diagnosed with epithelial ovarian cancer and 10 age-matched healthy women. To decrease the extremely wide dynamic range of protein concentrations in serum we used combinatorial hexapeptide libraries. Serum samples were then subjected to proteomic 2-DE analysis. Three proteins with differential abundance were found and identified by mass spectrometry: α-1-antitrypsin, apolipoprotein A-IV and retinol-binding protein4. Identification of α-1-antitrypsin and apolipoprotein A-IV confirms previous studies but the identification of significantly decreased levels of RBP4 in ovarian cancer patients represents a novel observation. We verified the decrease of RBP4 levels in ovarian cancer patient sera by two independent methods and determined absolute RBP4 concentrations in patients and healthy women. We excluded possible non-cancer factors that could be responsible for the observed RBP4 decrease. We propose a connection of RBP4 with epithelial ovarian cancer and advocate the potential of RBP4 as a candidate diagnostic or prognostic biomarker.

Toll-like receptors 1–9 are elevated in livers with fructose-induced hepatic steatosis

Studies in animals and human subjects indicate that gut-derived bacterial endotoxins may play a critical role in the development of non-alcoholic fatty liver disease (NAFLD). In the present study, we investigated if the liver is also sensitised by other microbial components during the onset of fructose-induced steatosis in a mouse model. C57BL/6 mice were either fed with 30 % fructose solution or tap water (control) with or without antibiotics for 8 weeks. Expression of toll-like receptors (TLR)1-9, TNF-α, inducible NO synthase (iNOS), myeloid differentiation factor 88 (MyD88) and number of F4/80 positive cells in the liver were assessed. Occludin protein, DNA of microbiota in the small and large intestine and retinol binding protein 4 (RBP4) in plasma were analysed using Western blot, DNA fingerprinting and ELISA, respectively. F4/80 positive cells were determined by immunohistochemistry. The accumulation of TAG found in the livers of fructose-fed mice was associated with a significant induction of TLR 1-4 and 6-8. Plasma RBP4 concentration and hepatic mRNA expression levels of TNF-α, iNOS, MyD88 and number of F4/80 positive cells of fructose-fed animals were significantly higher than those of controls; however, these effects of fructose were attenuated in antibiotic-treated mice. Whereas protein concentration of occludin was lower in the duodenum of fructose-treated mice, no systematic alterations of microbiota were found in this part of the intestine. Taken together, these data support the hypothesis that (1) an increased intestinal translocation of microbial components and (2) an increased number of F4/80 positive cells and induction of several TLR and dependent pathways (e.g. MyD88 and iNOS) may be involved in the onset of fructose-induced NAFLD.

DDT, MALE REPRODUCTIVE HEALTH AND THYROID HOMEOSTASIS OF NON-OCCUPATIONALLY EXPOSED MEN FROM A MALARIA AREA IN LIMPOPO PROVINCE, SOUTH AFRICA

Background and Aims: The Persistent Organic Pollutant (POP), dichloro-diphenyl-trichloroethane (DDT), has been used for malaria vector control in Limpopo Province, South Africa, since 1945. POPs are noted for their toxicity, persistence and bio-accumulative characteristics. The Aim of the study was to investigate the association between DDT, as reflected in plasma concentrations, and seminal parameters, possible adverse effects on human sperm genetic integrity, and thyroid homeostasis, while considering related factors. Methods: A cross-sectional study, recruiting 546 young males from three communities in an endemic malaria area where DDT is sprayed annually, was conducted. Blood plasma DDT and its metabolite levels were measured. A semen analyses were performed and sperm chromatin structure assay and Aniline Blue test were used to assess sperm DNA/chromatin integrity in 209 participants. Dietary intake, serum retinol-binding protein (RBP), transthyretin (TTR) and albumin concentrations and liver- and thyroid function were compared between cases with evidence of a body burden of DDT in the circulation and controls. Results: The lipid adjusted DDT mean (+SD) and median concentrations were 109.2 (+106.6) and 83.9 µg/g, respectively; and the lipid adjusted DDE mean (+SD) and median concentrations were 246.2 (+218.5) and 177.8 µg/g, respectively. In additions to effects on seminal parameters, the results point to a weak association between DDT/DDE plasma concentration and the incidence of sperm with chromatin defects. Significantly lower thyroid hormone concentrations were in observed cases (p•0.01). A significant linear trend was observed for S-free T4 and T3 concentrations (p&lt;0.001) and relatively low RBP concentrations were associated with significantly higher DDT and DDE isomer concentrations, and a higher DDE/DDT ratio (p•0.01), which signifies long-term exposure. Conclusions: The results suggest that long-term non-occupational environmental DDT exposure may have a negative impact on seminal parameters, sperm chromatin integrity, and on thyroid function and related parameters of young South African males.

Effects of 1-year orlistat treatment compared to placebo on insulin resistance parameters in patients with type 2 diabetes

The behavioural approach is usually slow and not always sufficient to achieve optimal targets in weight and metabolic control in obese diabetic patients, and a pharmacological treatment is often necessary. The aim of this study was to compare the effects of orlistat and placebo on body weight, glycaemic and lipid profile and insulin resistance in patients with type 2 diabetes. Two hundred and fifty-four obese, diabetic patients were enrolled in this study and randomized to take orlistat 360mg or placebo for 1year. We evaluated at baseline and after 3, 6, 9 and 12months body weight, waist circumference (WC), body mass index (BMI), glycated haemoglobin (HbA(1c) ), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), lipid profile, retinol-binding protein-4 (RBP-4), resistin, visfatin and high-sensitivity C-reactive protein (Hs-CRP). We observed a significant reduction in body weight, WC, BMI, lipid profile, RBP-4 and visfatin in the orlistat group but not in control group. Faster improvements in HbA(1c) , PPG, FPI, HOMA-IR, resistin and Hs-CRP were recorded with orlistat than with placebo. A similar decrease in FPG was seen in the two groups. Significant predictors of change in insulin resistance (HOMA-IR) were RBP-4 and resistin concentration in the orlistat group (r=-0·53, P<0·05, and r=-0·59, P<0·01, respectively). To the best of our knowledge, this is the first study investigating the effect of orlistat on insulin resistance and markers of inflammation. Orlistat improved lipid profile and led to faster glycaemic control and insulin resistance parameters than the control, without any serious adverse event. Orlistat also improved RBP-4 and visfatin, effects not observed with placebo.

EFECTO DE UN PRODUCTO CÁRNICO MODIFICADO SOBRE EL ESTADO NUTRICIONAL DE ANCIANOS INSTITUCIONALIZADOS

Objective: To determine whether the inclusion of a new modified meat product as a dietary supplement has a positive influence on the nutritional status and blood lipid profile of institutionalized elderly subjects. Method: a sample population of elderly people living in institutions (9 men and 29 women aged 68-97 years) completed a crossover study with two dietary supplements. Nutritionally complete diets differed only in food supplementation, first, with a standard meat product and, subsequently, with a modified meat product. Venous blood samples were taken prior to each of the three phases of the study: the basal phase, during which participants followed their normal, controlled diet; a control phase (3 days per week for 3 weeks), during which the subjects’ normal diet was supplemented with 50 g of the standard product; and an experimental phase (3 days per week for 3 weeks), when the normal diet was supplemented with 50 g of the modified product. Results: Nutritional intervention did not influence hematological parameters or serum lipids. The modified meat product altered blood concentrations of urea, creatinine, GOT, transferrin, iron, and retinol-binding protein. Conclusions: Consumption of both the standard and the modified products contributes to maintaining the individuals’ nutritional status and equalizes nutritional status across the study population with no effect on blood lipid profiles. Despite the limitations of the experiment, the introduction of dietary supplements in meat products significantly increased plasma iron levels in this elderly sample.

The Positive Correlation between Cord Serum Retinol-Binding Protein 4 Concentrations and Fetal Growth

Background/Aims: Retinol-binding protein 4 (RBP4) has been shown to be associated with insulin resistance and fatty acid metabolism. We hypothesize that RBP4 might play a role in fetal growth and that cord serum RBP4 may act as a marker of fetal growth, independent of fetal insulin levels. Methods: Twenty-one women having fetuses in the top quartile (>75th percentile) of birth weights for gestational age were enrolled into the trial, along with 21 women having fetuses in the bottom quartile (<25th percentile) of birth weights for gestational age. Serum RBP4 and insulin levels were analyzed. Results: Cord serum RBP4 and insulin concentrations were significantly higher in the top quartile group (14.3 ± 3.7 ng/ml, 3.8 ± 5.2 µIU/ml) than in the bottom quartile group (11.3 ± 2.6 ng/ml, 0.9 ± 1.4 µIU/ml; p = 0.004, p = 0.017). Cord serum RBP4 and insulin as well as gestational age (r = 0.744, r² = 0.553, p < 0.001) were significantly correlated with fetal birth weights. Conclusion: Cord serum RBP4 concentrations were higher in subjects with top quartile fetuses than in those with bottom quartile fetuses. Cord serum RBP4 concentrations were significantly correlated with fetal birth weight. These findings may indicate that cord serum RBP4 plays a regulatory role in fetal growth.

Retinol-binding protein 4 in adipose and placental tissue of women with gestational diabetes

In the present study, we evaluated serum levels of retinol-binding protein 4 (RBP4) and the expression of RBP4, glucose transporter-4 (GLUT4) and peroxisome proliferator activated receptor gamma (PPARγ) mRNA (using quantitative real time-PCR) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes (GDM) and healthy pregnant women. Serum RBP4 concentrations and its expression in SAT were higher in the women with GDM than in the controls (p = 0.03). No association between serum or tissue RBP4 and the indices of insulin resistance was noted. In the GDM group serum RBP4 correlated with its mRNA expression in SAT (r = 0.67, p = 0.007). Stepwise regression analysis revealed that RBP4 mRNA expression in SAT was independently predicted by GLUT4 mRNA expression (β = 0.59, p = 0.003) and the presence of GDM (β = 0.46, p = 0.01), whereas RBP4 mRNA expression in VAT was related to PPARγ mRNA expression (β = 0.64, p = 0.0003) and the patient's age (β = −0.38, p = 0.03). In conclusion, our results suggest that the elevated expression of RBP4 in SAT may contribute to the increase in circulating RBP4 in GDM subjects.

Systemic pro- and anti-inflammatory responses in cachectic patients with gastric and colorectal cancer correlates with nutritional impairment, immune suppression, and poor prognosis.

e19709 Background: We have reported high levels of interleukin(IL)-6, one of pro-inflammatory cytokines, in cachectic patients with cancer. Compensatory anti-inflammatory response syndrome (CARS) frequently arises in patients under post-operative and other physiological types of stress such as severe infection or burns. The mechanisms of CARS are characterized by high serum levels of anti-inflammatory complexes such as soluble interleukin-2 (IL-2) receptor (sIL-2R), tumor necrosis factor (sTNF-R1) or IL-1 receptor antagonist (IL-1ra), that participate in the development of cachexia. Methods: We measured levels of these three factors using enzyme immunoassays in sera from 36 patients with gastric cancer, 66 with colorectal cancer, 34 with benign diseases and 10 healthy volunteers. We also measured the nutritional parameters of prealbumin, transferrin and retinol binding protein, and the immunological parameters of thymidine uptake by lymphocytes and surface markers of CD3, CD4. Results: Serum levels of sIL-2R, sTNF-R1 and IL-1ra increased with advancing disease, were the highest in patients with cachexia and were inversely correlated with serum concentrations of albumin, prealbumin, transferrin, retinol-binding protein and zinc (all p < 0.05). Serum levels of the three factors were also inversely correlated with markers of the immune response including thymidine incorporation by T cells and the ratio (%) of CD3(+) cells (both p < 0.05). Cachectic patients with gastric cancer survived longer if their sIL-2 and sTNF-R1 levels were >1000 U/ml or >1300 pg/ml, respectively, (both p < 0.05). Conclusions: As an underlying condition in cancer cachexia, CARS is apparently important for patient care. Furthermore, sIL-2R, sTNF-R1 and IL-1ra are useful markers of nutritional impairment and a poor prognosis. Patients with cancer-related cachexia might be helped by devising new treatment strategies that include immune system manipulation.

Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers

BackgroundAssociations of proteinuria with low-level urinary cadmium (Cd) are currently interpreted as the sign of renal dysfunction induced by Cd. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins.MethodsWe examined 184 healthy male workers (mean age, 39.5 years) from a zinc smelter (n = 132) or a blanket factory (n = 52). We measured the concentrations of Cd in blood (B-Cd) and the urinary excretion of Cd (U-Cd), retinol-binding protein (RBP), protein HC and albumin. Associations between biomarkers of metal exposure and urinary proteins were assessed by simple and multiple regression analyses.ResultsThe medians (interquartile range) of B-Cd (μg/l) and U-Cd (μg/g creatinine) were 0.80 (0.45-1.16) and 0.70 (0.40-1.3) in smelter workers and 0.66 (0.47-0.87) and 0.55 (0.40-0.90) in blanket factory workers, respectively. Occupation had no influence on these values, which varied mainly with smoking habits. In univariate analysis, concentrations of RBP and protein HC in urine were significantly correlated with both U-Cd and B-Cd but these associations were substantially weakened by the adjustment for current smoking and the residual influence of diuresis after correction for urinary creatinine. Albumin in urine did not correlate with B-Cd but was consistently associated with U-Cd through a relationship, which was unaffected by smoking or diuresis. Further analyses showed that RBP and albumin in urine mutually distort their associations with U-Cd and that the relationship between RBP and Cd in urine was almost the replicate of that linking RBP to albuminConclusionsAssociations between proteinuria and low-level urinary Cd should be interpreted with caution as they appear to be largely driven by diuresis, current smoking and probably also the co-excretion of Cd with plasma proteins.