No description available.

No description available.

The purpose of this study was to improve the melt extrusion processability of polyvinyl acetate phthalate (PVAP) and investigate its use as a stabilizing polymer for supersaturated solutions of itraconazole (ITZ) in neutral pH aqueous media and in the solid-state during storage over time. Polyvinyl pyrrolidone vinyl acetate (PVPVA) was incorporated into PVAP as a carrier matrix with the aim of lowering the melt viscosity and increasing the plasticity of PVAP while maintaining its high glass transition temperature (Tg). Amorphous solid dispersions of ITZ (40% w/w) in a 30:70% w/w PVAP:PVPVA mixture were produced by melt extrusion. Solid-state analyses of the composition were performed using differential scanning calorimetry and X-ray diffraction. Dissolution analysis was conducted using a pH-change method. Solid-state analyses demonstrated that the extruded composition was entirely amorphous and ITZ was largely distributed in PVAP- and PVPVA-rich portions of the ternary dispersion. Dissolution analysis revealed that PVAP functioned to prolong the release of supersaturated levels of ITZ from the dispersion following an acidic-to-neutral pH transition. In the solid state, ITZ remained in its amorphous form throughout 6 months of storage. The results of this study suggest that substantial improvements in melt extrusion with PVAP can be achieved by incorporating PVPVA and that the PVAP-PVPVA polymer combination can stabilize amorphous ITZ. / Pharmaceutical Sciences

As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The polymers used for the fabrication of this multilayered device consists of cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion property of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. After the initial characterization of the CAPP system, the device was specifically modified to achieve sequential release of drugs aimed at the treatment of periodontitis. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. To obtain different erosion times and achieve appropriate release profiles specific to the disease condition, the device was modified by increasing the number of layers or by inclusion of a slower eroding polymer layer. In all the cases, the device was able to release the four different drugs in the designed temporal sequence. Analysis of antibiotic and anti-inflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. Following extensive studies on the in vitro sequential drug release from these devices, the in vivo drug release profiles were investigated. The CAPP devices with different release rates and dosage formulations were implanted in a rat calvarial onlay model, and the in vivo drug release and erosion was compared with in vitro results. In vivo studies showed sequential release of drugs comparable to those measured in vitro, with some difference in drug release rates observed. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule.

Orientador: Rejane Maira Góes / Texto em português e inglês / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-24T19:26:40Z (GMT). No. of bitstreams: 1 Negrin_AnaCarolina_M.pdf: 3573186 bytes, checksum: 84ff9397d827717b776f6497a21bc510 (MD5) Previous issue date: 2014 / Resumo: Desreguladores endócrinos (DE), como o di-n-butil ftalato (DBP), podem alterar o panorama dos hormônios esteroides ou sua ação, comprometendo o desenvolvimento testicular e a capacidade reprodutiva na vida adulta. Estudos toxicológicos mostram que ratos adultos, quando expostos a altas doses de ftalatos durante a fase de diferenciação sexual, exibem diversas anomalias reprodutivas, como agenesia do epidídimo e redução na produção diária de espermatozoides. Dados mostram que exposições a 2mg/kg/dia de DBP durante a gestação e a lactação são suficientes para prejudicar o desenvolvimento das células germinativas. Além disso, há relatos de que DE contrinuem para o aumento da adipogênese por causar alterações na sinalização celular de adipócitos. É conhecido que a obesidade masculina pode afetar a qualidade do sêmen e aumenta as taxas de infertilidade. Considerando que os ftalatos podem se acumular no tecido adiposo, ficamos interessados em avaliar os efeitos da exposição prolongada a baixas doses de DBP a as possíveis interferências do excesso de lipídeos na dieta para a função testicular e os parâmetros espermáticos de gerbilos adultos. Gerbilos fêmeas adultas, alimentadas com dieta balanceada (4% de lipídeos) ou hiperlipídica (20% de lipídeos) por oito semanas, foram acasaladas com machos normais. A prole masculina foi dividida em grupos controle (C), di-n-butil ftalato (Ph), dieta hiperlipídica (HF) e hieta hiperlipídica mais di-n-butil ftalato (HFPh). DBP (5 mg/kg/dia) foi administrado na água de beber às mães durante a gravidez e lactação e aos filhotes do desmame até a idade adulta (14 semanas). A resposta do testículo foi avaliada por meio de análises microscópicas e esterológicas, da sensibilidade de suas principais populações celulares a andrógenos e estrógenos, e da produção espermática. Também foram examinados os efeitos sobre a reserva espermática, o tempo de trânsito dos espermatozoides pelo epidídimo e a motilidade espermática. Isoladamente, baixas doses de DBP resultaram em obesidade e dislipidemia nos animais adultos. Nenhuma alteração foi observada na estrutura testicular, mas a síntese de estrógeno pelo testículo foi reduzida, resultando em tendência a diminuição na eficiência espermática. A redução no estrógeno intratesticular, após exposição ao DBP, foi acompanhada de um aumento de ~70% na expressão de ER? nos testículos, que pode ser uma resposta adaptativa aos baixos níveis deste hormônio. A ingestão crônica de dieta hiperlipídica não induziu os gerbilos adultos à obesidade, mas causou uma leve queda na eficiência espermática. Esta redução não está relacionada a alterações na estrutura testicular ou na sua capacidade esteroidogênica, mas podem estar ligadas ao comprometimento da sinalização testicular, já que foi verificada uma redução no conteúdo de AR. A exposição combinada à dieta hiperlipídica e a baixas doses de DBP atuaram sinérgica e negativamente na síntese de testosterona intratesticular, prejudicando a eficiência espermática e aumentando o tempo de trânsito dos espermatozoides pelo epidídimo. A motilidade espermática não sofreu alteração frente as exposições isoladas ou combinadas. Este estudo demonstrou que o ambiente nutricional pode interferir na resposta dos testículos frente aos ftalatos e proporciona novas informações para o entendimento das consequências da exposição aos DE para a redução na reverva espermática e fertlidade humana / Abstract: Endocrine disrupting chemicals (EDC), as di-n-butyl phthalate (DBP), can alter the scenary of steroid hormones or their action, impairing the testicular development and reproductive capacity in adulthood. Toxicological studies show that adult rats, when exposed to high doses of phthalates during sexual differentiation, exhibit several reproductive anomalies, such as agenesis of the epididymis and reduction in daily sperm production. Data show that exposures to 2mg/kg/day of DBP during gestation and lactation periods are enough to impair the development of the male germ cells. Furthermore, there are reports that EDC contribute to the increase of the adipogenesis by altering cell signaling of adipocytes and lipid metabolism. It is known that the male obesity can affect semen quality and increases infertility rates. Whereas that phthalates can accumulate in adipose tissue, we were interested in evaluating the effects of prolonged exposure to low doses of DBP and possible interferences of excess dietary fat for testicular function and spermatic parameters of adult gerbils. Adult female gerbils, fed high-fat (20% fat) or balanced diet (4% fat) for eight weeks, were mated with normal males. The male offspring was divided into control (C), di-n-butyl phthalate (Ph), high-fat diet (HF) and high-fat diet plus di-n-butyl phthalate (HFPh) groups. DBP (5 mg/kg/day) was administered in drinking water to pregnant and breastfeeding mothers and to offspring from weaning up to adulthood (14-week-old). Testis response was evaluated by means of microscopic and stereological analyses, sensitivity of its major cell populations to androgens and estrogens, steroidogenic capacity and spermatic efficiency. We also examined the effects on sperm reserves, sperm transit time through the epididymis and sperm motility. Alone, low doses of DBP resulted in obesity and dislipidemy at adulthood. No histological change was observed in testicular structure of these animals, but there was reduction in intratesticular estrogen synthtesis, resulting in a tendency to decrease in sperm production. The decrease in intratesticular estrogen after lifetime DBP exposure was accompanied by a ~70% increment in ER? content in the testis, that might be an adaptative response to low estrogen levels. Chronic intake of high-fat diet did not induce obesity in aldult gerbils, but led to a slight decrease in spermatic efficiency. This decrease was not associated with changes in testicular structure or steroidogenic capacity, because serum or intratesticular testosterone and estrogen concentrations were not altered, but it can be linked to an unbalanced in androgen receptor signaling, since it was observed a decrease in AR content. The combined exposure to high-fat diet and to low doses of DBP acted synergical and negatively on intratesticular testosterone synthesis, impairing the spermatic efficiency and increasing the sperm transit time. The sperm motility was not changed in isolated or combined exposures. This study demonstrated that fat nutritional environment may adversely affect the response of testes to phthalates, and provide new informations for understanding the consequences of exposures to ECD in decreasing human sperm counts and fertility / Mestrado / Biologia Celular / Mestra em Biologia Celular e Estrutural

Orientador: Rejane Maira Góes / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-23T14:41:50Z (GMT). No. of bitstreams: 1 Jesus_MarianaMarcielode_M.pdf: 3839823 bytes, checksum: 5cdcc794169929d299d222355a85e2d1 (MD5) Previous issue date: 2013 / Resumo: O resumo poderá ser visualizado no texto completo da tese digital / Abstract: The abstract is available with the full electronic document / Mestrado / Biologia Celular / Mestra em Biologia Celular e Estrutural

Endocrine disrupting chemicals (EDCs) are emerging contaminants that can interfere with the hormone system and may cause cancers, birth defects and reproductive system disorders. Prevalence of endocrine-related dysfunction and disease has increased steadily over the past decades. Although accumulating data suggest that these diseases have fetal origins, associations of EDC exposure during pregnancy and adverse health effects on both mothers and fetuses have not been thoroughly evaluated, particularly at multiple points in time. We firstly developed an analytical method for quantification of 28 EDCs (9 phthalates, 8 bisphenols, 5 parabens, 5 benzophenones and triclosan) in urine samples using ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometer. The method was applied to measure targeted compounds in a total of 5220 urine samples collected from 951 pregnant women at three trimesters and 1501 pregnant women at one or two trimesters in Wuhan, China between 2014 and 2015. Based on the quantification results, exposure patterns and health risks of 28 EDCs on participants were evaluated and discussed in detail below. Among these samples, bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), 4-hydroxybenzophenone (4-OH-BP), 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3), triclosan, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethylhexyl) phthalate (MEHHP), monobenzyl phthalate (MBzP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP) were determined with detection rates exceeding 50%, in which BPA, BP-3, MeP and MnBP were the predominant compounds. We found the U-shaped trends of urinary concentrations of phthalate metabolites over trimesters. Parabens, benzophenones and triclosan displayed a downward trend over three visits. We also found the levels of targeted compounds varied by exposure-related factors, such as sampling seasons, physical activities, computer using time and decoration information. In addition, multiple EDCs were mostly determined at low doses over trimesters, indicating that real-world exposure of pollutants were dominated by low-dose mixtures. We then evaluated the combined health hazards induced by EDC exposure via calculating the estimated daily intakes on the basis of average urinary concentrations at three trimesters. It was found that 24.9% of participants had potential health risks caused by exposure to phthalate mixtures. The most frequency of cumulative risks occurred in women who were exposed to a high dose of one specific phthalate, di-n-butyl phthalate (DnBP) or di(2-ethylhexyl) phthalate (DEHP). We also evaluated the cumulative health risks of BPA and its alternatives and found that about 1.6% of participants were at risks induced by bisphenol exposure. Combined health hazards were mainly driven by one specific bisphenol (BPS or BPA). Our findings suggested that regional interventions of DnBP, DEHP, BPA and BPS in application and production should be tighten and/or taken. Considering the low-dose effects of BPA, we further investigated the associations of BPA and three major natural estrogens, including estrone (E1), estradiol (E2) and estriol (E3), at three trimesters of pregnancy. We observed non-monotonic dose-response relationships of BPA to E1, E2 and E3 over trimesters even when BPA concentrations were below the current safety thresholds. In the gender-stratified models, we found significant negative relationships (β < 0, p < 0.05) between BPA and E2 among mothers with male fetuses in the first trimester. However, we found that no significant relationship between BPA and E2 among mothers with female fetuses over three trimesters. Significant non-monotonic associations (from significant negative to positive associations) between BPA and E3 were observed among mothers with female fetuses in the second trimester. The above mentioned findings suggested the gender-specific and trimester-specific effects of BPA on estrogens. Our findings also indicated that the current tolerance daily intake value maybe not safe enough to evaluate the potential health risks induced by BPA exposure. We next investigated the effects of maternal exposure to phthalates on both mothers and fetuses. Associations of phthalate exposure with the risks of gestational diabetes mellitus (GDM) and plasma glucose levels were evaluated based on a nested case-control study design. It was found that the levels of phthalate metabolites in women with GDM were significantly higher than those without GDM. Meanwhile, positive associations between urinary concentrations of phthalate metabolites and the risks of GDM were obvious, indicating that phthalate exposure may be a risk factor for GDM. In addition, phthalate levels were related to the increased plasma glucose levels after 75 g oral glucose tolerance test. Our findings suggested that phthalates might disturb the glucose homeostasis and increase GDM risks. Furthermore, we assessed the trimester-specific and gender-specific effects of DEHP exposure on fetal growth, birth size and postnatal growth at 6, 12 and 24 months. We found that among male offspring, 1st-trimester DEHP was negatively related to fetal growth (β < 0, p < 0.05), but positively related to 24-month body mass index (BMI). 2nd-trimester DEHP was negatively related to fetal growth, birth weight and birth length, but positively related to the weight gain rates from birth to 12 months old. 3rd-trimester DEHP was positively (β > 0, p < 0.05) associated with birth weight, BMI at 6 and 12 months. However, among females, 1st-trimester DEHP was associated with increased birth length, while 2nd-trimester DEHP was negatively associated with BMI at 6 and 12 months. A negative association between DEHP and weight gain rates at 6 months was noted among females. Our findings indicated the second trimester maybe the sensitive window of DEHP exposure for offspring growth since 2nd-trimester DEHP levels were related to the decreased fetal growth, decreased birth size, but increased weight gain rates in early childhood age among male offspring. To investigate the mechanism underlying the associations of DEHP exposure with glucose and lipid metabolism, we investigated the biotransformation of DEHP and the disturbed metabolisms induced by MEHP, the putative toxic metabolite of DEHP, in human normal liver cell L02 using metabolomics and lipidomics. We found that MEHP was the major metabolite of DEHP. Decreased uptake of glucose and accumulation of glucose in liver cells were obvious after MEHP exposure. Phospholipid remodeling, incomplete fatty acid β-oxidation, inhibition of purine metabolism and glycolysis, and increased oxidative stress were noted in MEHP-exposed L02 cells, which were related to insulin resistance. In this work, we measured 28 EDCs in a total of 5220 urine samples provided by 951 pregnant women (three trimesters) and 1501 pregnant women (one or two trimesters) and then evaluated the exposure levels, exposure patterns (variations, variability and correlations), health risks and health effects of these compounds on pregnant women and fetuses. Our data suggested that participants had potential health risks induced by exposure to phthalates or bisphenols. Phthalate exposure was related with the increased plasma glucose levels and risks of GDM. Prenatal DEHP exposure may induce the intrauterine growth restriction and catch-up growth among males, which supported the evidence of fetal origin. To explore the underlying mechanisms of MEHP on glucose and lipid metabolic disorders, we exposed the human normal hepatic L02 cells with MEHP, and applied metabolomic and lipidomic approaches for finding potential biomarkers and disturbed pathways. We found that MEHP exposure inhibited glucose uptake, caused phospholipid remodeling and increased oxidative stress in L02. These findings suggest that the usage of products containing EDCs, particularly phthalates, in pregnant women should be limited in China, intervention of BPS should be considered, and threshold values of BPA are called for reevaluation.

El di(2-etilhexil) ftalat (DEHP) és un plastificant que s’afegeix als productes de clorur de polivinil (PVC) per a dotar-los de més flexibilitat. El material mèdic fet de PVC, i en particular els dispositius i bosses que s’utilitzen en les transfusions de sang, conté el DEHP com additiu. Així, el receptor d’una transfusió està altament exposat a aquest compost. L’objectiu de la tesi va ser estudiar els metabòlits del DEHP en orina com a possibles marcadors de la pràctica d’una transfusió de sang en l’esport. Es va desenvolupar i validar un mètode d’anàlisi per cromatografia líquida acoblada a espectrometria de masses en tàndem per a la quantificació dels principals metabòlits del DEHP en orina humana: mono-(2-etilhexil) ftalat (MEHP), mono-(2-etil-5-hidroxihexil) ftalat (MEHHP), mono-(2-etil-5-oxohexil) ftalat (MEOHP), mono-(2-carboximetilhexil) ftalat (2cx-MMHP) i mono-(2-etil-5-carboxipentil) ftalat (5cx-MEPP). El mètode es va aplicar a mostres procedents de voluntaris sans (grup control), de pacients hospitalitzats que havien rebut una transfusió de sang i de pacients hospitalitzats sotmesos a tractaments mèdics amb materials de PVC i no a transfusions. Es van obtenir diferències significatives en les concentracions dels tres metabòlits estudiats (MEHP, MEHHP, MEOHP) entre les mostres dels pacients transfosos respecte els altres dos grups de població. El mètode també es va aplicar a mostres d’orina de vint-i-cinc voluntaris sans que s’havien sotmès a un procediment d’autotransfusió. Els resultats van indicar concentracions elevades dels cinc metabòlits del DEHP en orina fins a les 48 hores després d’haver rebut la sang. Finalment, es van determinar les concentracions dels cinc metabòlits de DEHP en una població d’esportistes i es van calcular límits de referència que permetessin sospitar d’una transfusió. Així doncs, els resultats indiquen que la mesura dels metabòlits de DEHP en orina pot ser usada com una eina pel cribatge de l’ús de transfusions en l’esport. / The plasticizer di(2-ethylhexyl)phthalate (DEHP) is used in polyvinyl chloride products (PVC) to increase its flexibility. Medical devices made of PVC, especially blood bags used in blood transfusions, contain DEHP as additive. Therefore, subjects submitted to blood transfusion are widely exposed to this compound. The aim of the project was to evaluate DEHP metabolites in urine as possible markers of the use of a blood transfusion in sports. An analytical method was developed and validated to quantify the main DEHP metabolites mono-(2-ethylhexyl)phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl)phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl)phthalate (MEOHP), mono-(2-carboxymethylhexyl)phthalate (2cx-MMHP) and mono-(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP), in human urine by liquid chromatography tandem mass spectrometry. The methodology was applied to samples belonging to healthy volunteers (control group), hospitalized patients subjected to blood transfusions and hospitalized patients subjected to medical treatments involving plastic material different to blood transfusions. Significant differences were obtained in the concentrations of the three metabolites studied (MEHP, MEHHP, MEOHP) between transfused patients samples’ and the other two population groups. The method was also applied to urine samples from twenty-five healthy volunteers who were subjected to an autologous blood transfusion. The results indicated high concentrations of the five DEHP metabolites in urine up to 48 hours after the blood transfusion. Finally, the concentration of the five DEHP metabolites were evaluated in a sportsmen population and reference limits to allow suspicion of blood transfusion were calculated. Thus, the results indicate that the DEHP metabolites could be used as markers of blood transfusions in sports.

タンデトロン加速器質量分析計業績報告

<p>Uvod. Ftalati su endokrini disruptori, &scaron;iroko se koriste kao plastifikatori, rastvarači i aditivi u mnogim potro&scaron;ačkim proizvodima. Eksperimentalni podaci i humane studije sugeri&scaron;u na povezanost ftalata sa gojazno&scaron;ću i dijabetesom. Cilj. Utvrditi da li su i koji urinami metaboliti ftalata prisutni i da li postoje razlike u njihovim nivoima između bolesnika s tipom 2 &scaron;ećeme bolesti, gojaznih i kontrolne grupe zdravih osoba; da li postoji povezanost između metabolita ftalata i gojaznosti, lipida i lipoproteina seruma, glikemije, insulinemije i insulinske rezistencije.<br />Metode. Istraživanje je obuhvatilo 305 ispitanika, podeljenih u 3 grupe: gojazni (n=104), dijabetesni bolesnici tip 2 (n=101) i zdrave osobe (n=100), oba pola. U svih ispitanika su izvr&scaron;ena antropometrijska merenja (BMI i obim struka), određivanje serumskih lipida (ukupni holesterol, trigliceidi, HDL i LDL holesterol), te glikemija, insulinemija i izračunat indeks insulinske rezistencije (HOMA IRI). U jutarnjem uzorku urina meren je nivo 10 ftalatnih metabolita: mono-metil ftalat (MMP), mono-etil ftalat (MEP), mono-n-butil ftalat (MnBP), mono- benzil ftalat (MBzP), mono-cikloheksil ftalat (MCHP), mono-n-propil ftalat (MPP), mono-n-amil ftalat (MnAP), mono-izo-amil ftalat (MiAP), mono- n-oktil ftalat (MOP), mono-2-etilheksil ftalat (MEHP). U odnosu na prisustvo ftalata u urinu svaka grupa je podeljena u podgrupe na one sa prisutnim ftalatima i one bez ftalata u urinu, odnosno na podgrupe MEP pozitivne, MEP negativne, MEHP pozitivne i MEHP negativne. Rezultati. Kod polovine ispitanika registrovali smo prisustvo u urinu pojedinih metabolita ftalata. Najče&scaron;ći su bili MEHP i MEP. Najveća sličnost u nivou MEP-a i MEHP-a je bila između gojaznih i dijabetesnih ispitanika. U odnosu na antropometrij ske parametre uočena je pozitivna korelacija MEP-a sa BMI i obimom struka, a negativna korelacija MEHP-a sa BMI i obimom struka, ali su bile nesignifikantne. Samo kod MEHP pozitivnih kontrolne grupe uočena je statistički značajna pozitivna korelacija MEHP-a i obima struka. Utvrđena je statistički značajna negativna korelaciju MEP-a i HDL holesterola, a pozitivna korelacija MEP-a i triglicerida samo kod gojaznih. Samo u kontrolnoj grupi MEHP pozitivnih postojala je statistički značajna negativna korelacija sa HDL holesterolom. Postojala je pozitivna korelacija MEP-a i HOMA-IRI, a pozitivna korelacija MEHP-a sa glikemijom samo kod MEHP pozitivnih DM tip 2. Zaključak. Potvrđeno je da je kontaminacija ftalatima prisutna u na&scaron;oj populaciji, a najče&scaron;će su prisutni MEHP i MEP, ukazujući na ekspoziciju DEHP i DEP. Indirektno smo stekli uvid da povećana izloženost DEP i DEHP može doprineti nastanku izvesnih poremećaja lipida i lipoproteina, insulinskoj rezistenciji kao i razvoju gojaznosti.</p> / <p>Introduction. Phthalates are endocrine disruptors, widely used as plasticizers, solvents and additives in a wide range of consumer products. Experimental data and human studies suggest that phthalate exposure is linked with obesity and diabetes. Aim. To determine whether urinary phthalate metabolites are present, which ones are present, whether there are differences between their levels among the patients with type 2 diabetes, obesity patients and a control group of healthy individuals; whether there is a link between phthalate metabolites and obesity, lipids, serum lipoproteins, glycemia, insulinemia and insulin resistance. Methods. The research included 305 participants divided into three groups: obesity patients (n=104), type 2 diabetes patients (n=101) and healthy individuals (n=100) in both sexes. Anthropometric measurements were taken from all participants (BMI and waist circumference), as well as measurement of serum lipids (total cholesterol, triglycerides, HDL and LDL cholesterol), glycemia, insulinemia and a calculation of insulin resistance index (HOMA IRI). The levels of ten phthalate metabolites were<br />measured in a morning sample of urine: Mono-methyl phthalate (MMP), Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), Mono-benzyl phthalate (MBzP), Mono- cyclohexyl phthalate (MCHP), Mono-n-propyl phthalate (MPP), Mono-n-amyl phthalate (MnAP), Mono-iso-amyl phthalate (MiAP), Mono-n-octyl phthalate (MOP), Mono-2- ethylhexyl phthalate (MEHP). Regarding the presence of phthalates in urine, each group was divided into subgroups, containing phthalates and or not containing phthalates, i.e. subgroups MEP positive and MEP negative, MEHP positive and MEHP negative. Results. In a half of participants, we have registered the presence of certain phthalate metabolites in urine, most often MEHP and MEP. The highest similarity in the levels of MEHP and MEP was between obesity and diabetes participants. Regarding anthropometric measurements, positive correlation has been registered between MEP and BMI and waist circumference, while negative correlation has been registered between MEHP and BMI and waist circumference, but it was insignificant. Only in MEHP positive control group, statistically significant positive correlation between MEHP and waist circumference has been registered. Statistically significant negative correlation between MEP and HDL cholesterol has been registered, while positive correlation between MEP and triglycerides has been registered only in obesity patients group. Only in MEHP positive control group statistically significant negative correlation with HDL cholesterol has been registered. There has been a positive correlation between MEP and HOMA-IRI, while positive correlation between MEHP and glycemia has been registered only in MEHP positive DM type 2. Conclusion. It has been confirmed that our population is contaminated with phthalates, most commonly MEHP and MEP, indicating exposure to DEHP and DEP. Indirectly, we have realized that an increased exposure to DEHP and DEP can contribute to the development of certain lipid and lipoprotein disorders, insulin resistance, as well as the development of obesity.</p>