The impact of olive mill wastewater on soil properties, nutrient and heavy metal availability - A study case from Syrian vertisols.

Olive oil mill wastewater (OMW) is an environmental concern in olive oil producers' regions due to its use in agricultural soils as an organic amendment. However, OMW can also be used as organic fertilizer due to their high organic matter and nutrient levels, but its use, when it occurs without environmental management, can cause serious environmental implications for soils and waters. This work evaluated the impact of different OMW levels on a set of physicochemical parameters from an agricultural vertisol where wheat grew (Triticum aestivum L var. Douma 1). A set of physicochemical parameters were conducted before adding different levels of OMW (0, 5, 10 and 15 L m-2) at two soil depths (0-30 and 30-60 cm) and for the two growing seasons to determine: i) the effect of OMW treatments on the studied physicochemical soil properties (bulk density, soil porosity, soil pH, electrical conductivity and organic matter), ii) available primary (N, P, K) and secondary macronutrients (Ca, Mg and Na), ii) micronutrients (Cu Fe, Mn and Zn), and iv) available heavy metals (Cd and Pb). The results indicated that soil physicochemical parameters were slightly improved, mainly due to improvement in organic matter, macro- and micronutrients, usually proportionally to the olive mill wastewater dose. Cadmium and Pb were within the permissible limits. The increased OMW had different behaviour on the soil nutritional balances of different elements, leading to nutrient imbalances, although in some cases, they were improved. However, the plant growth was not affected, and it was improved under 10 L m-2 and 15 L m-2 doses. The results offer valuable data about the use of OMW as organic fertilizer for crops and their potential impact on soil properties.

Ecotoxicological relevance of glyphosate and flazasulfuron to soil habitat and retention functions - Single vs combined exposures.

Glyphosate (GLY) and flazasulfuron (FLA) are two non-selective herbicides commonly applied together. However, research focused on their single and combined ecotoxicological impacts towards non-target organisms is still inconclusive. Therefore, this study aimed to test their single effects on soil's habitat and retention functions, and to unravel their combined impacts to earthworms and terrestrial plants. For this, ecotoxicological assays were performed with plants (Medicago sativa), oligochaetes (Eisenia fetida) and collembola (Folsomia candida). Soil elutriates were also prepared and tested in macrophytes (Lemna minor) and microalgae (Raphidocelis subcapitata). FLA (82-413 µg kg-1) reduced earthworms' and collembola's reproduction and severely impaired M. sativa growth, being much more toxic than GLY (up to 30 mg kg-1). In fact, the latter only affected plant growth (≥ 9 mg kg-1) and earthworms (≥ 13 mg kg-1), especially at high concentrations, with no effects on collembola. Moreover, only elutriates from FLA-contaminated soils significantly impacted L. minor and R. sucapitata. The experiments revealed that the co-exposure to GLY and FLA enhanced the toxic effects of contaminated soils not only on plants but also on earthworms'. However, such increase in toxicity was dependent on GLY residual concentrations in soils. Overall, this work underpins that herbicides risk assessment should consider herbicides co-exposures, since the evaluation of single exposures is not representative of current phytosanitary practices and of the potential effects under field conditions, where residues of different compounds may persist in soils.

Causative links between ER stress and oxidative damage in a yeast model of human N88S seipinopathy.

Seipin is encoded by the gene Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) and FLD1/SEI1 in yeast. The gain-of-function N88S mutation in the BSCL2 gene was identified in a cohort of autosomal dominant motor neuron diseases (MNDs) collectively known as seipinopathies. Previous work has shown that this mutation disrupts N-glycosylation, leading to the formation of inclusion bodies (IBs) and contributing to severe Endoplasmic Reticulum (ER) stress and cell death. In this work, we established a humanized yeast model of N88S seipinopathy that recapitulated the formation of IBs and activation of the unfolded protein response (UPR) observed in mammalian systems. Autophagy and the Hrd1-mediated endoplasmic reticulum-associated degradation (ERAD) were fully functional in cells expressing mutant homomers and WT-mutant heteromers of seipin, discarding the possibility that mutant seipin accumulate due to impaired protein quality control systems. Importantly, the N88S seipin form IBs that appear to induce changes in ER morphology, in association with Kar2 chaperone and the Hsp104 disaggregase. For the first time, we have determined that N88S homo-oligomers expressing cells present reduced viability, decreased antioxidant activity and increased oxidative damage associated with loss of mitochondrial membrane potential, higher reactive oxygen species (ROS) levels and lipid peroxidation. This was correlated with the activation of oxidative stress sensor Yap1. Moreover, activation of ERAD and UPR quality control mechanisms were essential for proper cell growth, and crucial to prevent excessive accumulation of ROS in cells expressing N88S homomers solely. Overall, this study provides new insights into the molecular underpinnings of these rare diseases and offers novel targets for potential pharmacological intervention.

The critical role of the dispersant agents in the preparation and ecotoxicity of nanomaterial suspensions.

This work reports the role of different dispersants, namely, polyethylene glycol (PEG 200 2%), ethylene glycol 5%, ethanol 2%, dimethyl sulfoxide (DMSO 5%), and polyvinyl alcohol (PVA 5%) in the toxicity profile of several commercial nanomaterials (NM), such as hydrophilic and hydrophobic TiO2, hydrophilic SiO2, SiO2 in aqueous suspension (aq), and ZnO towards the bioluminescent bacterium Aliivibrio fischeri. The majority of NM showed tendency to form agglomerates in the different dispersants. Although some particle agglomeration could be detected, DMSO at 5% was the best dispersant for hydrophobic TiO2 NM while PVA at 5% was the most effective dispersant for the other types of NM. Average size was not the most relevant aspect accounting for their toxicity. A remarkable reduction in average size was followed by a decrease in NM toxicity, as demonstrated for SiO2 aq. in PVA 5%. Contrarily, despite of high particle agglomeration, ZnO NM showed a higher toxicity to bacteria when compared with other tested NM. Independently of the average particle size or surface charge, the dispersant either enhanced the toxicity to bacteria or acted as physical barrier decreasing the NM harmful effect to A. fischeri.

Ecotoxicity to Freshwater Organisms and Cytotoxicity of Nanomaterials: Are We Generating Sufficient Data for Their Risk Assessment?

The aim of the present study was to investigate the eco-cytotoxicity of several forms of nanomaterials (NM), such as nano-CuO, nano-TiO2, nano-SiO2 and nano-ZnO, on different aquatic species (Raphidocelis subcapitata, Daphnia magna and Lemna minor) following standard protocols and on human cell lines (Caco-2, SV-80, HepG2 and HaCaT). Predicted no-effect concentrations (PNEC) or hazard concentrations for 5% of the species (HC5) were also estimated based on the compilation of data available in the literature. Most of the NM agglomerated strongly in the selected culture media. For the ecotoxicity assays, nano-CuO and nano-ZnO even in particle agglomeration state were the most toxic NM to the freshwater organisms compared to nano-TiO2 and nano-SiO2. Nano-ZnO was the most toxic NM to R. subcapitata and D. magna, while nano-CuO was found to be very toxic to L. minor. Nano-CuO was very toxic to Caco-2 and HepG2 cells, particularly at the highest tested concentrations, while the other NM showed no toxicity to the different cell lines. The HC5 and PNEC values are still highly protective, due to data limitations. However, the present study provides consistent evidence of the potential risks of both nano-CuO and nano-ZnO against aquatic organisms and also their effects on public health.

Inhibition of the Formation In Vitro of Putatively Carcinogenic Metabolites Derived from S. haematobium and O. viverrini by Combination of Drugs with Antioxidants.

Infections caused by Schistosoma haematobium and Opisthorchis viverrini are classified as carcinogenic. Although carcinogenesis might be a multifactorial process, it has been postulated that these helminth produce/excrete oxysterols and estrogen-like metabolites that might act as initiators of their infection-associated carcinogenesis. Current treatment and control of these infections rely on a single drug, praziquantel, that mainly targets the parasites and not the pathologies related to the infection including cancer. Thus, there is a need to search for novel therapeutic alternatives that might include combinations of drugs and drug repurposing. Based on these concepts, we propose a novel therapeutic strategy that combines drugs with molecule antioxidants. We evaluate the efficacy of a novel therapeutic strategy to prevent the formation of putative carcinogenic metabolites precursors and DNA adducts. Firstly, we used a methodology previously established to synthesize metabolites precursors and DNA adducts in the presence of CYP450. Then, we evaluated the inhibition of their formation induced by drugs and antioxidants alone or in combination. Drugs and resveratrol alone did not show a significant inhibitory effect while N-acetylcysteine inhibited the formation of most metabolite precursors and DNA adducts. Moreover, the combinations of classical drugs with antioxidants were more effective rather than compounds alone. This strategy might be a valuable tool to prevent the initiation of helminth infection-associated carcinogenesis.

Treatment of a textile effluent by adsorption with cork granules and titanium dioxide nanomaterial.

This study aimed to explore the efficiency of two adsorbents, cork granules with different granulometry and titanium dioxide nanomaterial, in the removal of chemical oxygen demand (COD), colour and toxicity from a textile effluent. The adsorption assays with cork were unsatisfactory in the removal of chemical parameters however they eliminated the acute toxicity of the raw effluent to Daphnia magna. The assay with TiO2 NM did not prove to be efficient in the removal of colour and COD even after 240 min of contact; nevertheless it also reduced the raw effluent toxicity. The best approach for complete remediation of the textile effluent has not yet been found however promising findings were achieved, which may be an asset in future adsorption assays.

Influence of the stabilizers on the toxicity of metallic nanomaterials in aquatic organisms and human cell lines.

In this study, following a systematic approach, we used aquatic species (bacteria Vibrio fischeri and microalgae Raphidocelis subcapitata) and different human cell lines (Caco-2, HepG2, SV-80 and HaCaT) representing different tissues and exposure pathways, to investigate how two organic stabilizers (PVA and DMSO) used for NMs dispersion influence their physicochemical properties, the persistence of metals in suspension and the toxicity/ecotoxicity of two metallic NMs (nano-Ag and nano-Cu). Although the stabilizers are expected to contribute to improve the dispersion and stability of NMs, the results obtained clearly showed that no similar changes in toxicity and morphological properties of the nano-Ag can be expected after its stabilization with PVA. Thus, regarding human cell lines, the reduction in the average size of the PVA-nano-Ag was followed by a reduction or maintenance of its toxicity, but the opposite was observed for the aquatic species tested since an increase in the average size enhanced its toxicity. As far as nano-Cu is considered DMSO contributed for a better dispersion of this nanomaterial, however this was not translated in a similar toxicity/ecotoxicity modification. In summary, even for nano-Cu, for which few or no data exists regarding its toxicity after stabilization with organic compounds, it was confirmed with consistent data, that the toxicity of metallic NMs is a complex combination of average size, chemical composition, solubilization or persistence in suspension of the metallic forms, interaction with test medium components and sensitivity of test species and cell lines. The combination of all of these factors makes the toxicity of metallic NMs unpredictable and points for the need of an extensive evaluation of each new formulation.

Oxidative stress and genotoxicity of an organic and an inorganic nanomaterial to Eisenia andrei: SDS/DDAB nano-vesicles and titanium silicon oxide.

In the past few years the number of studies on the toxic effects of nanomaterials (NMs) in the environment increased significantly. Nonetheless, the data is still scarce, since there is a large number of NMs and new ones are being developed each day. Soils are extremely important for life, and are easily exposed to the released NMs, thus enhanced efforts are needed to study the impacts on soil biota. The objective of the present work was to determine if different concentrations of two NMs, one inorganic (TiSiO4) and other organic (nano-vesicles of sodium sodecyl sulfate/ didodecyl dimethylammonium bromide - SDS/DDAB), are genotoxic to soil invertebrates. Additionally, it was intended to understand whether, in the event of occurring, genotoxicity was caused by the incapability of the cells to deal with the oxidative stress caused by these NMs. With that purpose, Eisenia andrei were exposed for 30 days to the artificial OECD soil contaminated with different concentrations of the NMs being tested. After the exposure, coelomocytes were extracted from earthworms and DNA damage was measured by the comet assay. The activity of antioxidant enzymes (e.g. glutathione peroxidase, glutathione reductase and glutathione-S-Transferase) and lipid peroxidation were also assessed. The results showed that both NMs were genotoxic, particularly TiSiO4 for which significant DNA damages were recorded for concentrations above 444mg of TiSiO4-NM/kg of soildw. Since no statistically significant differences were found in the tested antioxidant enzymes and in lipid peroxidation, the mechanism of genotoxicity of these NMs seemed to be unrelated with oxidative stress.

TiO2 nanoparticles for the remediation of eutrophic shallow freshwater systems: Efficiency and impacts on aquatic biota under a microcosm experiment.

The application of nanomaterials (NMs) in the remediation of eutrophic waters, particularly in the control of internal loading of nutrients, has been started, but limited investigations evaluated the effectiveness of these new treatment approaches and of their potential impacts on species from shallow freshwater lakes. The present work investigated, under a microcosm experiment, the application of a TiO2 nanomaterial both for reducing nutrient (mainly phosphorus and nitrogen forms) desorption and release from sediments (preventive treatment-PT) and for eliminating algal blooms (remediation treatment-RT). Furthermore, we also intended to assess the potential impacts of nano-TiO2 application on key freshwater species. The results showed the effectiveness of nano-TiO2 in controlling the release of phosphates from surface sediment and the subsequent reduction of total phosphorus in the water column. A reduction in total nitrogen was also observed. Such changes in nutrient dynamics contributed to a progressive inhibition of development of algae after the application of the NM in PT microcosms. Concerning the ability of nano-TiO2 to interact with algal cells, this interaction has likely occurred, mainly in RT, enhancing the formation of aggregates and their rapid settlement, thus reducing the algal bloom. Both treatments caused deleterious effects on freshwater species. In PT, Daphnia magna and Lemna minor showed a significant inhibition of several endpoints. Conversely, no inhibitory effect on the growth of Chironomus riparius was recorded. In opposite, C. riparius was the most affected species in RT microcosms. Such difference was probably caused by the formation of larger TiO2-algae aggregates in RT, under a high algal density, that rapidly settled in the sediment, becoming less available for pelagic species. In summary, despite the effectiveness of both treatments in controlling internal nutrient loading and in the mitigating algal bloom episodes, their negative effects on biota have to be seriously taken into account.

Toxicity of solid residues resulting from wastewater treatment with nanomaterials.

Nanomaterials (NMs) are widely recommended for wastewater treatments due to their unique properties. Several studies report the different advantages of nanotechnology in the remediation of wastewaters, but limited research has been directed toward the fate and potential impacts of the solid residues (SRs) produced after the application of such technologies. The present work aimed at investigating the ecotoxicity of SRs resulting from the treatment of three effluents (OOMW, kraft pulp mill, and mining drainage) with two NMs (TiO2 and Fe2O3). The invertebrate Chironomus riparius was selected as test organism and exposed to the residues. The effect on percentage of survival and growth was assessed. Results showed that the SRs from the treatments nano-TiO2(1.0gL(-1))/H2O2(0.5M) and nano-Fe2O3(1.0gL(-1))/H2O2(1.0M) from OOMW and nano-Fe2O3(0.75gL(-1))/H2O2(0.01M) from kraft pulp mill effluent exhibited lethal toxicity to C. riparius. Only the exposure to SRs resulting from the treatment with nano-Fe2O3(0.75gL(-1))/H2O2(0.01M) applied to the kraft pulp mill effluent significantly affected the growth rate based on the head capsule width. In terms of growth rate, based on the body length, it decreased significantly after exposure to the SRs from the treatments nano-TiO2 (1.0gL(-1)) and nano-Fe2O3(0.75gL(-1))/H2O2(0.01M) of kraft paper mill effluent and nano-Fe2O3(1.0gL(-1))/H2O2(1.0M) of OOMW. According to our study the SRs can promote negative effects on C. riparius. However, the effects are dependent on the type of effluent treated as well as on the organic and inorganic compounds attached to the NMs.

Prevalence of thyroid dysfunction in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) and thyroid dysfunction (TD) are the two most common endocrine disorders in clinical practice. The unrecognized TD may adversely affect the metabolic control and add more risk to an already predisposing scenario for cardiovascular diseases. The objective of this study was to investigate the prevalence of TD in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). METHODS: This is an observational cross-sectional study. Three hundred eighty-six (386) patients with T1DM or T2DM that regularly attended the outpatient clinic of the Diabetes unit, Hospital Universitário Pedro Ernesto, participated in the study. All patients underwent a clinical and laboratory evaluation. Thyroid dysfunction was classified as clinical hypothyroidism (C-Hypo) if TSH > 4.20 µUI/mL and FT4 < 0.93 ng/dL; Subclinical hypothyroidism (SC-Hypo) if TSH > 4.20 µUI/ml and FT4 ranged from 0.93 to 1.7 ng/dL; Subclinical hyperthyroidism (SC-Hyper) if TSH < 0.27 µUI/ml and FT4 in the normal range (0.93 and 1.7 ng/dL) and Clinical hyperthyroidism (C-Hyper) if TSH < 0.27 µUI/ml and FT4 > 1.7 µUI/mL. Autoimmunity were diagnosed when anti-TPO levels were greater than 34 IU/mL. The positive autoimmunity was not considered as a criterion of thyroid dysfunction. RESULTS: The prevalence of TD in all diabetic patients was 14,7%. In patients who had not or denied prior TD the frequency of TD was 13%. The most frequently TD was subclinical hypothyroidism, in 13% of patients with T1DM and in 12% of patients with T2DM. The prevalence of anti-TPO antibodies was 10.8%. Forty-four (11.2%) new cases of TD were diagnosed during the clinical evaluation. The forty-nine patients with prior TD, 50% with T1DM and 76% with T2DM were with normal TSH levels. CONCLUSIONS: We conclude that screening for thyroid disease among patients with diabetes mellitus should be routinely performed considering the prevalence of new cases diagnosed and the possible aggravation the classical risk factors such as hypertension and dyslipidemia, arising from an undiagnosed thyroid dysfunction.

Impact of organic and inorganic nanomaterials in the soil microbial community structure.

In this study the effect of organic and inorganic nanomaterials (NMs) on the structural diversity of the soil microbial community was investigated by Denaturing Gradient Gel Electrophoresis, after amplification with universal primers for the bacterial region V6-V8 of 16S rDNA. The polymers of carboxylmethyl-cellulose (CMC), of hydrophobically modified CMC (HM-CMC), and hydrophobically modified polyethylglycol (HM-PEG); the vesicles of sodium dodecyl sulphate/didodecyl dimethylammonium bromide (SDS/DDAB) and of monoolein/sodium oleate (Mo/NaO); titanium oxide (TiO(2)), titanium silicon oxide (TiSiO(4)), CdSe/ZnS quantum dots, gold nanorods, and Fe/Co magnetic fluid were the NMs tested. Soil samples were incubated, for a period of 30 days, after being spiked with NM suspensions previously characterized by Dynamic Light Scattering (DLS) or by an ultrahigh-resolution scanning electron microscope (SEM). The analysis of similarities (ANOSIM) of DGGE profiles showed that gold nanorods, TiO(2), CMC, HM-CMC, HM-PEG, and SDS/DDAB have significantly affected the structural diversity of the soil bacterial community.

Avaliação da secreção e resistência insulínica em indivíduos com diferentes graus de tolerância à glicose - do metabolismo normal ao diabetes mellitus / Insulin resistance and secretion assessment across a range of glucose tolerance from normal individuals through diabetes

OBJETIVO: Os principais objetivos são determinar a associação entre os parâmetros clínicos e demográficos e os diferentes índices de secreção e resistência insulínica em indivíduos aparentemente saudáveis, sem conhecimento prévio de seu grau de tolerância à glicose. PACIENTES E MÉTODOS: Submetemos ao teste oral de tolerância à glicose (TOTG), no período de fevereiro a agosto de 2003, 105 indivíduos com média de idade de 33,4 ± 1,4 anos, sendo 57,1 por cento do sexo feminino, subdividindo-os em 4 grupos: grupo 0 (normais): indivíduos com IMC < 25 e metabolismo glicídico normal, grupo 1 (obesos): IMC > 25 e metabolismo glicídico normal, grupo 2 (IFG): glicemia de jejum alterada e grupo 3 (IOG): intolerância oral à glicose. RESULTADOS: Encontramos diferença estatística para todas as variáveis analisadas durante o TOTG dentre os 4 grupos de indivíduos: glicemias de jejum e em 2 horas (p < 0,05; p < 0,05), valor de pico (p < 0,05), delta (p = 0,02), percentual de incremento (p = 0,047), área sob a curva (p < 0,05) e tempo de pico da glicose (p = 0,022). Não encontramos diferença para a velocidade de incremento da glicose, assim como para nenhuma variável da curva de insulina. Em relação aos índices de secreção insulínica, não houve significância estatística para os índices insulinogênico ou delta, porém estes tornaram-se significantes após correção da secreção pela resistência insulínica (p = 0,008). Quanto aos índices de resistência insulínica, os índices HOMA e QUICKI foram estatisticamente significativos (p = 0,005; p = 0,005, respectivamente), assim como a relação glicose/insulina em jejum (p = 0,053). CONCLUSÃO: Apesar do tamanho limitado da amostra, podemos inferir que indivíduos com intolerância à glicose em jejum e pós-prandial possivelmente estão em momentos diferentes da história natural da doença. Nossos dados demonstram que os melhores índices para a avaliação de resistência insulínica são o HOMA e o QUICKI, e que os...

AIM AND METHODS: Our main aim was to determine the association between clinical, demographical parameters and different insulin resistance and secretion indices in apparently healthy subjects, without previous knowledge of their own level of glucose tolerance. For that purpose, we evaluated 105 individuals from February to August 2003 by means of OGTT, aged 33.4 ± 1.4 years old, 57.1 percent female. We allocated them in four groups: group 0 (normal): individuals with BMI < 25 Kg/m² and normal glucose metabolism, group 1 (obese): BMI > 25 Kg/m² and normal glucose metabolism, group 2 (IFG): impaired fasting glucose and group 3 (IGT): impaired glucose tolerance. RESULTS: We have found statistical difference on all variables during OGTT between all groups: fasting glucose (p < 0.05), 2-hour glucose (p < 0.05), glucose peak value (p < 0.05), glucose delta (p = 0.02), glucose incremental percentage (p = 0.047), area under curve (p < 0.05), and glucose peak time (p = 0.022). We have not found difference on any variable in insulin curves or on glucose incremental velocity. Regarding insulin secretion indices there were no statistical significance in insulinogenic or delta indices, but they became significant after being corrected by insulin resistance (p = 0.008). When we evaluated insulin resistance alone, by using HOMA and QUICKI indices and the fasting glucose to insulin index, we have found statistical significance (p = 0.005; p = 0.005; p = 0.053). CONCLUSION: Although studying a small sample, we could suggest that individuals with impaired fasting glucose and impaired glucose tolerance are in different stages of diabetes natural history disease. We found out that the best indices of insulin resistance are both HOMA and QUICKI. We also suggest that pancreatic secretion indices should be corrected by the insulin resistance, which could best reflect type 2 diabetes natural history.

[Insulin resistance and secretion assessment across a range of glucose tolerance from normal individuals through diabetes]. / Avaliação da secreção e resistência insulínica em indivíduos com diferentes graus de tolerância à glicose--do metabolismo normal ao diabetes mellitus.

AIM AND METHODS: Our main aim was to determine the association between clinical, demographical parameters and different insulin resistance and secretion indices in apparently healthy subjects, without previous knowledge of their own level of glucose tolerance. For that purpose, we evaluated 105 individuals from February to August 2003 by means of OGTT, aged 33.4+/-1.4 years old, 57.1% female. We allocated them in four groups: group 0 (normal): individuals with BMI < 25 Kg/m(2) and normal glucose metabolism, group 1 (obese): BMI >or= 25 Kg/m(2) and normal glucose metabolism, group 2 (IFG): impaired fasting glucose and group 3 (IGT): impaired glucose tolerance. RESULTS: We have found statistical difference on all variables during OGTT between all groups: fasting glucose (p < 0.05), 2-hour glucose (p < 0.05), glucose peak value (p < 0.05), glucose delta (p = 0.02), glucose incremental percentage (p = 0.047), area under curve (p < 0.05), and glucose peak time (p = 0.022). We have not found difference on any variable in insulin curves or on glucose incremental velocity. Regarding insulin secretion indices there were no statistical significance in insulinogenic or delta indices, but they became significant after being corrected by insulin resistance (p = 0.008). When we evaluated insulin resistance alone, by using HOMA and QUICKI indices and the fasting glucose to insulin index, we have found statistical significance (p = 0.005; p = 0.005; p = 0.053). CONCLUSION: Although studying a small sample, we could suggest that individuals with impaired fasting glucose and impaired glucose tolerance are in different stages of diabetes natural history disease. We found out that the best indices of insulin resistance are both HOMA and QUICKI. We also suggest that pancreatic secretion indices should be corrected by the insulin resistance, which could best reflect type 2 diabetes natural history.

[Evaluation of microalbuminuria in non-diabetic individuals]. / Avaliação da microalbuminúria em indivíduos não diabéticos.

AIM: To evaluate the presence of microalbuminuria in non-diabetic subjects, associating it to the presence of cardiovascular risk factors like hypertension, smoking, dislipidemia and obesity. The urinary albumin excretion rate (UAE) was also evaluated regarding to insulin secretion and resistance indices. DESIGN AND METHODS: 105 subjects aged 33.4 +/- 1.4 years (57.1% women), received 75 g dextrose for an OGTT, and the following variables were evaluated for glucose and insulin curves: basal and 2 hours values, peak values (PV) and area under the curves (AUC). To evaluate insulin secretion and resistance, we used the insulinogenic, delta, HOMA, QUICKI, glucose to insulin ratio and the relation between insulinogenic and HOMA indices. A urine sample was collected overnight for albuminuria. Individuals were allocated in two groups: 1) normal, and 2) altered glucose metabolism. RESULTS: The two groups differed in age, BMI, BP, abdominal circumference (AC), WHR, cholesterol, triglycerides (TG), glycemias (basal and 2h), AUCg, HOMA and QUICKI indices and the relation between insulinogenic and HOMA. Mean UAE was 4.28 +/- 2.73 microg/mL, correlating to DBP, glycemias, AUCg, GPV, HOMA, 2h insulin, IPV e AUCi. By stepwise multiple-regression analysis, only AUCg was predictive of UAE. By comparing interquartile intervals of UAE, we found statistical significance between the 1st and 4th quartile for: BMI, SBP, DBP, AC, waist, 2h glucose, TG, LDL, AUCg, AUCi, GPV and HOMA and QUICKI indices. CONCLUSION: Although in the absence of microalbuminuric individuals, we found differences among UAE in individuals across a range of glucose tolerance and differences between clinical and laboratorial variables in the interquartile analysis. Our findings suggest that in non-diabetic individuals, UAE is associated to some characteristics of the metabolic syndrome, probably predisposing to greater atherogenic susceptibility.

Avaliação da microalbuminúria em indivíduos não diabéticos / Evaluation of microalbuminuria in non-diabetic individuals

OBJETIVO: Avaliar a presença de microalbuminúria em indivíduos não diabéticos, associando-a à presença de fatores de risco cardiovasculares como hipertensão arterial, tabagismo, dislipidemia e obesidade. A taxa de excreção urinária de albumina (EUA) foi avaliada em relação aos índices de secreção e resistência insulínica (RI). PACIENTES E MÉTODOS: 105 indivíduos com idade de 33,4 ± 1,4 anos (57,1 por cento mulheres) foram submetidos ao TOTG com 75 g de dextrose, sendo avaliadas as curvas de glicose e insulina: valores basais e em 2h, valores de pico e áreas sob a curva (ASC). Para a avaliação da secreção e RI, utilizamos os índices: insulinogênico, delta, HOMA, QUICKI, relação glicose/insulina e relação entre os índices insulinogênico e HOMA. As amostras para avaliação da albuminúria foram colhidas overnight. Os indivíduos foram divididos em dois grupos: 1) tolerância normal à glicose e 2) alteração do metabolismo glicídico. RESULTADOS: Houve diferença entre os 2 grupos para idade, IMC, PA, cintura, RCQ, colesterol, triglicerídeos (TG), glicemias (GJ e G2h), ASCg, índices HOMA e QUICKI, e relação entre os índices insulinogênico e HOMA. A EUA foi de 4,28 ± 2,73 æg/mL, apresentando correlação com PAD, GJ, G2h, ASCg, VPG, HOMA, I2h, VPI e ASCi. Após regressão em stepwise, apenas ASCg foi preditora de EUA. Na comparação da amostra estratificada em quartis de EUA, o 1° e o 4° quartis foram estatisticamente diferentes para IMC, PAS, PAD, cintura, quadril, G2h, TG, LDL, ASCg, ASCi, VPG e índices HOMA e QUICKI. CONCLUSÃO: Embora não houvesse nenhum indivíduo com microalbuminúria, encontramos diferença entre a EUA em indivíduos com diferentes graus de tolerância à glicose e diferenças entre as variáveis clínicas e laboratoriais entre o 1° e o 4° quartis de EUA. Nossos achados sugerem que em indivíduos não diabéticos o aumento da EUA está relacionado a algumas características da síndrome metabólica, o que pode conferir uma maior suscetibilidade aterogênica.

Acute-phase proteins and microalbuminuria among patients with type 2 diabetes.

OBJECTIVE: to determine the relationship between acute-phase proteins and microalbuminuria in type 2 diabetic patients without clinical evidence of macrovascular disease. RESEARCH DESIGN AND METHODS: We studied cross-sectionally 64 non-smoking outpatients with type 2 diabetes mellitus without clinical evidence of cardiovascular disease attended at Brazilian University General Hospital aged 59.5 +/- 8.1 years and with a known duration of diabetes of 11.5 +/- 8 years. Urinary albumin excretion rate (AER) was determined in timed overnight urine samples. Serum alpha(1)-acid glycoprotein (AGP) and plasma fibrinogen were determined by immunoturbidimetry assay and serum C-reactive protein (CRP) was measured by a high-sensitive immunonephelometry assay. RESULTS: A higher levels of AGP (P = 0.0000), CRP (P= 0.003) and fibrinogen ( P = 0.0001) were found in microalbuminuric (n = 26) than in normoalbuminuric patients ( n = 38). All the acute-phase proteins were correlated with each other and with AER, respectively (r = 0.67 for AGP; 0.35 for fibrinogen, and 0.41 for CRP, P < 0.01 for all). Stepwise multiple regression analysis showed that AGP was independently associated with AER along with systolic blood pressure (r2 = 0.49, P = 0.000). Logistic regression analysis showed that AGP was independently related to microalbuminuria with an odds ratio (95% CI) of 1.16 ((1.08-1.24), P = 0.000). CONCLUSIONS: According to our results acute-phase proteins a known markers of chronic inflammation were associated with microalbuminuria independently of clinical cardiovascular disease. The influence of AGP on AER and microalbuminuria needs to be confirmed in prospective studies. Intervention studies are necessary to assess whether anti-inflammatory treatment would have a beneficial effect on this chronic complication of diabetes.