<p>Uvod. Kardiovaskularne bolesti kao deo grupe hroničnih nezaraznih bolesti predstavljale su i predstavljaju vodeći uzrok obolevanja i umiranja u svetu. Brojni naučni dokazi potvrđuju da je arterijska hipertenzija glavni kardiovaskularni faktor rizika, a da postignute vrednosti krvnog pritiska niže od 140/90mmHg značajno smanjuju kardiovaskularni rizik, odnosno pojavu kardiovaskularnih događaja, prvenstveno infarkta miokarda i moždanog udara. Arterijska hipertenzija je najzastupljenije stanje koje se viđa u ustanovama primarne zdravstvene za&scaron;tite, a mere prevencije, rano dijagnostikovanje, lečenje i kontrola arterijske hipertenzije predstavljaju javno-zdravstveni izazov u svim zemljama sveta. Ciljevi. Ciljevi istraživanja su utvrđivanje prevalencije arterijske hipertenzije koja je pod kontrolom; utvrđivanje prevalencije i povezanosti metaboličkih faktora sa ishodom u kontroli krvnog pritiska; utvrđivanje prevalencije i povezanosti nezdravih stilova života sa ishodom u kontroli krvnog pritiska; utvrđivanje prediktora lo&scaron;e kontrole krvnog pritiska i izračunavanje 10-godi&scaron;enjeg kardivaskularnog rizika. Metode. U studiju preseka (prevalencije) uključeno je 373 ispitanika oba pola starosti od 45 do 75 godina sa dijagnozom arterijske hipertenzije u kartonu koji su u periodu od oktobra 2015. godine do februara 2016. godine dolazili kod svog izabranog lekara. Prikupljanje podataka obavljeno je merenjem krvnog pritiska, antropometrijskim merenjima, biohemijskim analizama i anketiranjem popunjavanjem upitnika. Rezultati. Uzorak ispitanika je činilo 55% žena i 45% mu&scaron;karaca prosečne starosti 59&plusmn;6,3 godine. Utvrđena je niska učestalost arterijske hipertenzije pod kontrolom od 39,1%, a visoka učestalost metaboličkih faktora (44,5% predgojaznosti, 34% gojaznosti, 29% &scaron;ećerne bolesti, 88,2% povi&scaron;enih masnoća i 41,8% metaboličkog sindroma) kao i njihova povezanost sa ishodom u kontroli krvnog pritiska jer su ispitanici sa nekontrolisanim krvnim pritiskom najče&scaron;će imali dva faktora rizika (40,5%), dok su ispitanici sa kontrolisanim krvnim pritiskom najče&scaron;će imali jedan faktor rizika (45,9%). Utvrđeno je da su prosečne vrednosti sistolnog, dijastolnog pritiska i pulsa bile značajno (p&lt;0,001) niže u grupi sa kontrolisanim pritiskom kao i da su ispitanici sa nekontrolisanim pritiskom imali značajno veći obim struka (p=0,006), metabolički sindrom (p&lt;0,001) i značajno če&scaron;će pili veći broj lekova (p&lt;0,001). Utvrđena je visoka učestalost pu&scaron;enja (26,3%) i visoka učestalost sedentarnog načina života (76,7%) kao i da znanja, stavovi i pona&scaron;anja ispitanika u vezi faktora rizika (pu&scaron;enja, konzumiranja alkohola, fizičke neaktvnosti i prekomerne upotrebe soli) nisu na zadovoljavajućem nivou. Kao nezavisni prediktori arterijske hipertenzije koja nije pod kontrolom dobijeni su obim struka, telesna masa, indeks telesne mase, starost, vrednost pulsa, broj lekova koje ispitanici piju, pasivno pu&scaron;enje, nesvesnost o postojanju arterijske hipertenzije, neznanje o &scaron;tetnosti konzumiranja prekomerne količine alkohola, nepreležan infarkt miokarda i moždani udar. Izračunato je da je u visokom i veoma visokom riziku od neželjenih kardiovaskularnih događaja u desetogodi&scaron;njem periodu 2,7% ispitanika sa arterijskom hipertenzijom bez dijabetesa i 22,2% hipertenzivnih ispitanika sa dijabetesom. Zaključak. Potrebno je sprovođenje javno-zdravstveno vaspitnih i promotivnih aktivnosti u cilju povećanja znanja, promene stavova i pona&scaron;anja kod populacije sa arterijskom hipertenzijom usled lo&scaron;e kontrole krvnog pritiska i prisustva visoke učestalosti pridruženih faktora rizika koji utiču na njegovu kontrolu.</p> / <p>Introduction. Cardiovascular diseases, as part of a group of chronic noncommunicable diseases, have been and still are the leading cause of morbidity and mortality in the world. Numerous scientific proofs confirm that arterial hypertension is a major cardiovascular risk factor and that the achieved blood pressure values lower than 140/90mmHg significantly reduce cardio-vascular risk, or the appearance of cardio-vascular events, mainly myocardial infarction and stroke. Arterial hypertension is the most common condition that is seen in primary health care institutions and preventive measures, early diagnosis, treatment and control of arterial hypertension are a public health challenge in all countries of the world. Objectives. The objectives of the research were to determine the prevalence of arterial hypertension which is controlled; to determine the prevalence and correlation of the metabolic factors with the outcome in blood pressure control; to determine the prevalence and correlation of unhealthy lifestyles with the outcome in blood pressure control; to determine the predictors of poor blood pressure control and calculate a 10-year cardiovascular risk. Methods. The cross-sectional study (of prevalence) included 373 respondents of both sexes aged 45 to 75 years diagnosed with arterial hypertension who in the period from October 2015 to February 2016 visited their chosen doctor. Data collection was performed by measuring blood pressure, anthropometric measurements, biochemical analyses and surveying by filling out a questionnaire. Results. The sample consisted of 55% women and 45% men, of mean age of 59&plusmn;6.3 years. The results showed low incidence of arterial hypertension under control of 39.1%, and high incidence of metabolic factors (44.5% of overweight, 34% of obesity, 29% of diabetes mellitus, 88.2% of elevated fat and 41.8% of the metabolic syndrome) as well as their association with the outcome in blood pressure control as the respondents with uncontrolled blood pressure usually had two risk factors (40.5%), while the group with controlled blood pressure usually had one risk factor (45.9%). It was found that the average values of systolic, diastolic blood pressure and heart rate were significantly (p&lt;0.001) lower in the group with controlled blood pressure, as well as that the respondents with uncontrolled pressure had a significantly greater waist circumference (p=0.006), the metabolic syndrome (p&lt;0.001) and more often drunk greater number of medicines (p&lt;0.001). There was a high prevalence of smoking (26.3%) and a high incidence of sedentary lifestyle (76.7%) and it was found that knowledge, attitudes, and behaviors of the respondents related to risk factors (smoking, alcohol consumption, physical inactivity and excessive use of salt) were not satisfactory. As independent predictors of arterial hypertension which was not under the control, the study obtained waist circumference, body weight, body mass index, age, heart rate value, the number of medicines that the respondents drunk, second-hand smoking, unawareness of the existence of arterial hypertension, inexperience on the harmful effects of excessive amounts of alcohol, not overcome myocardial infarction and stroke. It was calculated that 22.2% of hypertensive respondents with diabetes and 2.7% of respondents with arterial hypertension without diabetes were in the high and very high risk of adverse&nbsp; Conclusion. It is necessary to implement public-health educational and promotional activities in order to increase the knowledge, changes in the attitudes and behavior of the population with arterial hypertension due to the poor control of blood pressure and the presence of the high incidence of associated risk factors affecting its control.</p>

INTRODUCTION Insomnia became an object of concern in Aristotelian times, when he wrote a monograph on sleep disorders (350 BC). Although community of science and medicine has been interested in sleep disorders for almost 2000 years, however, there are not much information about the prevalence of insomnia, especially among citizens of developing countries. Epidemiological information about prevalence of insomnia and sleep complaints varies in different countries [Roth et.al., 1996], because of diversity of methodology for data collection. According to data of research carried out in the United States of America, Europe and Australia, 10–49% of population are not satisfied with their sleep quality. [Walsh, Ustun, 1999]. According to data of lifestyle research in Lithuania (1996), insomnia was a problem for 22.5% of male (from 20 to 64 years old) and 29.3% of female [Grabauskas, Klumbienė, 1998]. Sleep complaints among Lithuanian citizens have not been researched up to now, although, as foreign scientists maintain, sleep disorder can accelerate development of many somatic as well as mental diseases, besides, after a few sleepless nights, follows irritability, decrease of efficiency, it is difficult to concentrate, considerably increases risk of traffic accidents or accidents at work [Balter, Uhlenhuth, 1992]. Supposedly, there is a connection among heart and vascular diseases, sleep disorders and depression [Mahowald et.al., 1989]. Research that was carried out abroad proved... [to full text]

Good health is a fundamental resource for social and economic development. Non-communicable chronic diseases (NCDs) such as cardiovascular diseases (CVD), cancer, chronic respiratory diseases and diabetes mellitus are reaching epidemic proportions worldwide. Over the last decades NCDs remain the main public health problem in Lithuania also. The leading NCD’s in the Lithuania are CVD and cancer. The key targets of the Health 21 policy for WHO European Region as well as of Lithuanian Health Programme are reduction of morbidity and mortality from CVD, cancer and other NCD’s. The leading strategy to tackle NCDs is control and prevention of risk factors. Common, modifiable risk factors underlie the major NCD’s. Seven risk factors are responsible for the majority of NCD in the European region: high blood pressure, tobacco, alcohol, high cholesterol, being overweight, low intake of fruits and vegetables, and physical inactivity. The lifestyle habits start to develop in childhood. Children and adolescents begin to smoke and use alcohol, adopt unhealthy nutrition habits and sedentary lifestyle. Harmful lifestyle choices lead to children’s overweight, increase of their blood pressure (BP), and metabolic disorders. Many epidemiological studies designed to assess the association between health indices in childhood and adulthood were conducted over the last years. However, the number of longitudinal, cohort studies that would follow people from childhood to middle age and would apply the... [to full text]

Tyrimo tikslas – įvertinti kraujospūdžio kitimo ir su sveikata susijusios gyvenimo kokybės sąsajas tarp vyrų ir moterų, kuriems nustatytas padidėjęs kraujospūdis, dalyvavimo profilaktinėse kraujospūdžio reguliavimo grupėse laikotarpiu. Naudota metodika: Gyvenimo kokybės – 100 klausimynas (WHOQOL-100). Profilaktinėse grupėse dalyvavo 110 terapinės apylinkės pacientų. Visus keturis užsiėmimus lankė atitinkamai 80 pacientų. Pacientai buvo prašomi užpildyti GK-100 klausimyną, siekiant nustatyti kraujospūdžio kitimus užsiėmimų metu ir sąsajas su pacientų gyvenimo kokybės ypatumais. Tiriamieji dalyvavo keturiuose vienos valandos užsiėmimuose, kurie vyko kartą per savaitę vakare. Visoms keturioms pacientų grupėms vedami tie patys užsiėmimai taikant modifikuotą progresyvios raumenų relaksacijos metodą, diskusiją gyvenimo būdo keitimo klausimais ir abiejų šių metodų (raumenų relaksacijos ir diskusijos) derinį. Tyrimo rezultatai parodė, jog moterų ir vyrų grupėse statistiškai reikšmingas kraujo spaudimo sumažėjimas stebimas užsiėmimo pabaigoje. Aukštesni statistiškai reikšmingi arterinio kraujo spaudimo rodikliai susiję su vyresnio amžiaus ir žemesnio išsilavinimo rodikliais vyrų ir moterų grupėse. Aukšti statistiškai reikšmingi arterinio kraujo spaudimo rodikliai susiję su blogesne gyvenimo kokybe, o mažesni - su geresne gyvenimo kokybe. / Purpose of the survey is to assess the relations between blood pressure changes and health-related quality of life in men and women with high blood pressure during the period of blood pressure regulation in preventive groups. Methodology used: The Quality of Life - 100 Questionnaire (WHOQOL-100). Preventive groups involved 110 patients in the therapeutic environs. 80 patients attended all four workshops. Patients were asked to fill in WHOQOL-100 questionnaire to determine the associations with health – related quality of life and blood pressure variations in workshops. Patients participated in four one-hour classes, held once a week in the evening. All four groups of patients were involved in workshops using the modified progressive muscle relaxation method, the discussion on the changing of lifestyle and the combination of both of these methods (progressive muscle relaxation and discussion). The study showed that statistically significant decreased blood pressure was observed in men and women groups at the end of each workshop. Higher statistically significant arterial blood pressure was related to the older age and lower level of education in men and women groups. Higher statistically significant arterial blood pressure was related to poorer health – related quality of life, as lower arterial blood pressure was associated with better health – related quality of life.

Moksliniais tyrimais nustatyta, kad širdies ir kraujagyslių sistemos ligų rizikos veiksniai atsiranda jau vaikystėje. Arterinė hipertenzija – vienas pagrindinių širdies ir kraujagyslių sistemos ligų rizikos veiksnių, neretai pasireiškia jau paauglystėje. Padidėjęs arterinis kraujo spaudimas, ilgainiui pažeidžia organus taikinius: kraujagysles, širdį, smegenis, inkstus, akis. Todėl nepavėluotam gydymui užtikrinti vis aktualesnė tampa ankstyva AH diagnostika, kuri leistų sumažinti ligos progresavimą, pailginti laiką iki komplikacijų pasireiškimo ir užtikrinti geresnę gyvenimo kokybę, nes sveikatos būklė vaikystėje turi įtakos sveikatos būklei suaugus. Pirmą kartą Lietuvoje kompleksiškai įvertinta sveikų ir sergančių pirmine arterine hipertenzija paauglių fizinė ir psichinė sveikata. Nustatėme, jog sergant pirmine arterine hipertenzija paauglystėje prasideda vidinės miego arterijos sienelės ankstyvi struktūriniai ir funkciniai pakitimai, kuriuos sukelia arterinė hipertenzija, rūkymas, alkoholio vartojimas bei uždegiminio proceso aktyvumas. Pirmą kartą vertinta paauglių arterinės hipertenzijos įtaka trombocitų agregacinei funkcijai, degranuliacijos reakcijai bei trombocitų ir monocitų adhezijai. Tyrime nustatyta, jog arterinė hipertenzija bei padidėjusi kūno masė veikia elgesio ir emocijų sutrikimus, gali padidinti širdies ir kraujagyslių ligų riziką. / Hypertension is one of the main causes of cardiovascular disease and the reason of early death in the world. Growing epidemiology data support a correlation between blood pressure at childhood and adolescence with the incidence of hypertension at adulthood. This is the first study in Lithuania presenting complex assessment of physical and mental health of healthy adolescents as well as of those with primary arterial hypertension. We found out that in case of primary arterial hypertension in adolescence development of early structural and functional changes of internal carotid artery takes place; these changes are determined by arterial hypertension, smoking, alcohol consumption and activity of inflammation process. The influence of arterial hypertension of the platelets aggregation function, reaction of degranulation and formation of platelets-monocytes complexes in adolescents was assessed for the first time. It was demonstrated in the study that arterial hypertension and increased body mass has an effect on behavioural and emotion disorders and may increase cardiovascular risk.

Moksliniais tyrimais nustatyta, kad širdies ir kraujagyslių sistemos ligų rizikos veiksniai atsiranda jau vaikystėje. Arterinė hipertenzija – vienas pagrindinių širdies ir kraujagyslių sistemos ligų rizikos veiksnių, neretai pasireiškia jau paauglystėje. Padidėjęs arterinis kraujo spaudimas, ilgainiui pažeidžia organus taikinius: kraujagysles, širdį, smegenis, inkstus, akis. Todėl nepavėluotam gydymui užtikrinti vis aktualesnė tampa ankstyva AH diagnostika, kuri leistų sumažinti ligos progresavimą, pailginti laiką iki komplikacijų pasireiškimo ir užtikrinti geresnę gyvenimo kokybę, nes sveikatos būklė vaikystėje turi įtakos sveikatos būklei suaugus. Pirmą kartą Lietuvoje kompleksiškai įvertinta sveikų ir sergančių pirmine arterine hipertenzija paauglių fizinė ir psichinė sveikata. Nustatėme, jog sergant pirmine arterine hipertenzija paauglystėje prasideda vidinės miego arterijos sienelės ankstyvi struktūriniai ir funkciniai pakitimai, kuriuos sukelia arterinė hipertenzija, rūkymas, alkoholio vartojimas bei uždegiminio proceso aktyvumas. Pirmą kartą vertinta paauglių arterinės hipertenzijos įtaka trombocitų agregacinei funkcijai, degranuliacijos reakcijai bei trombocitų ir monocitų adhezijai. Tyrime nustatyta, jog arterinė hipertenzija bei padidėjusi kūno masė veikia elgesio ir emocijų sutrikimus, gali padidinti širdies ir kraujagyslių ligų riziką. / Hypertension is one of the main causes of cardiovascular disease and the reason of early death in the world. Growing epidemiology data support a correlation between blood pressure at childhood and adolescence with the incidence of hypertension at adulthood. This is the first study in Lithuania presenting complex assessment of physical and mental health of healthy adolescents as well as of those with primary arterial hypertension. We found out that in case of primary arterial hypertension in adolescence development of early structural and functional changes of internal carotid artery takes place; these changes are determined by arterial hypertension, smoking, alcohol consumption and activity of inflammation process. The influence of arterial hypertension of the platelets aggregation function, reaction of degranulation and formation of platelets-monocytes complexes in adolescents was assessed for the first time. It was demonstrated in the study that arterial hypertension and increased body mass has an effect on behavioural and emotion disorders and may increase cardiovascular risk.

Darbo tikslas: Įvertinti Kaišiadorių rajono gyventojų mitybą ir jos ryšį su arterine hipertenzija. Uždaviniai: Nustatyti Kaišiadorių rajono 25-64 m. gyventojų paros maisto davinio sudėtį. Įvertinti Kaišiadorių rajono 25-64 m. gyventojų mitybą ir jos sąsajas su socialiniais veiksniais. Nustatyti Kaišiadorių gyventojų mitybos įpročių pokyčius nuo1999 m. iki 2007 m. Įvertinti arterinės hipertenzijos paplitimą tarp Kaišiadorių gyventojų bei jos kontrolės būklę 1999 m. ir 2007 m. Įvertinti gyventojų mitybos ryšį su arterine hipertenzija. Tyrimo metodika. Naudojant 24 val. mitybos apklausos metodą, 1999 m. buvo apklausti 326 atsitiktinai atrinkti 25-64 m. Kaišiadorių rajono gyventojai. Suskaičiuota paros maisto davinio energinė vertė ir maisto medžiagų kiekiai. 1999 m. ir 2007 m. (n=257) buvo atlikta dažnuminė mitybos apklausa. Sveikatos patikrinimų metu matuotas arterinis kraujospūdis. Statistinė duomenų analizė atlikta naudojant SPSS programos 12 versiją. Skirtumai tarp skirstinių vertinti, taikant Mann-Whitney ir Kruskal-Wallis testus. Vertinant hipertenzijos paplitimo skirtumus tarp grupių, taikytas Z ir χ2 kriterijus. Statistiškai reikšmingu laikytinas rezultatas, kai paklaidos tikimybė p<0,05. Rezultatai. Kaišiadorių rajono 25-64 m. gyventojai vartojo pakankamai baltymų, bet per daug riebalų ir per mažai angliavandenių. Vyrų ir moterų maisto davinyje buvo per didelis cholesterolio ir natrio kiekis bei nepakankamas maistinių skaidulų ir kalcio kiekis. Vyrai su maistu gavo... [toliau žr. visą tekstą] / Aim of the study: to evaluate nutrition habits of Kaišiadoris region population and to examine the association between diet and hypertension. Objectives: to examine daily energy and nutrient intake of population aged 25-64 in Kaišiadoris region in relation to social factors; to evaluate changes in nutrition habits between 1999 and 2007; to assess the prevalence of hypertension and control status; to examine the association between diet and hypertension. Methods: 24 hour dietary recall and food frequency questionnaire were used to examine nutrition of randomly selected people in Kaišiadoris region: 326 persons aged 25-64 years were examined in 1999 and 257 - in 2007. The daily energy and nutrient intake was calculated. Blood pressure was measured in both surveys. Statistical analyses were performed using statistical software package “SPSS 12”. The differences in the distributions of energy and nutrients between various groups were assessed by Mann-Whitney and Kruskal-Wallis tests. The differences in prevalence of hypertension were assessed by Z test and χ2 criterion. The difference was considered to be statistically significant when p<0.05. Results. The average total fat intake of population of Kaišiadoris region was above recommendations for healthy nutrition and the average intake of carbohydrates was insufficient. The intake of protein was sufficient. The diet of men and women contained too much cholesterol and sodium and lacked fibers and calcium. Daily energy and nutrient... [to full text]

<p>UVOD: Hipertenzivna oboljenja u trudnoći predstavljaju heterogenu grupu bolesti koja se javljaju kod 3-8% trudnica op&scaron;te populacije. Najteže forme ovih oboljenja preeklampsija, eklampsija i HELLP sindrom su vodeći uzročnici morbiditeta i mortaliteta majke i ploda u odnosu na sve druge komplikacije u trudnoći. Etiopatogeneza ovih oboljenja je jo&scaron; uvek nedovoljno razja&scaron;njena ali se smatra da placenta ima ključnu ulogu u nastanku ovih komplikacija, odnosno da placentalna insuficijencija, koja nastaje kao posledica nedovoljne adaptacije decidualnih i intramiometrijalnih delova spiralnih arterija već u prvih nekoliko nedelja trudnoće, dovodi do redukcije utero-placentalne cirkulacije i lokalne placentalne hipoksije, &scaron;to se nepovoljno održava i na majku i na plod. U cilju razja&scaron;njenja patofiziolo&scaron;kih mehanizama nastanka hipertenzivnih oboljenja u trudnoći i pronalaska dovoljno senzitivnih makera koji bi pomogli u ranom predviđanju nastanka najtežih formi ovih oboljenja, do sada su ispitivani brojni proteini koji učestvuju u procesima stvaranja i razvoja placentalne vaskularne mreže kao &scaron;to su vaskularni endotelni faktor rasta (VEGF-A), placentalni faktor rasta (PlGF) i solubilni receptor fms-like tirozin kinaza receptor (sFlt-1). CILJ: Uporediti serumske koncentracije (sFlt-1, PlGF, VEGF-A, PAPP-a, free&szlig;hCG, glukoze, ukupnog holesterola, HDL holesterola, LDL holesterola, triglicerida, apo-AI, apoB, AST, ALT, GGT, kreatinina, ureje, mokraćne kiseline, hsCRP, Na, K, Cl, P, Mg i Ca između grupe trudnica sa preeklampsijom, hroničnom i gestacijskom hipertenzijom i kontrolne grupe trudnica u prvom trimestru trudnoće između 11 i 14. nedelje gestacije. Ispitati da li se vrednosti odabranih laboratorijskih parametara (sFlt-1, VEGF-A i PLGF) kod ispitivanih trudnica statistički značajno razlikuju u odnosu na gestacijsku nedelju u trenutku porođaja, težinu i dužinu i APGAR skor bodovanja novorođenčeta. Ispitati da li se vrednosti angiogenih proteina:sFlt-1, VEGF-A, PlGF značajno razlikuju kod ispitivanih trudnica u odnosu na broj prethodnih trudnoća i starosti trudnica. MATERIJAL I METODE: Istraživanje je sprovedeno kao prospektivno analitička studija u Kliničkom centru Vojvodine, u periodu od juna 2012. do februara 2015. godine. U istraživanje je uključeno ukupno 143 trudnice starosti od 18 &ndash; 43 godine. Sve trudnice uključene u istraživanje podeljene su na dve ispitivane i jednu kontrolnu grupu. Prvu ispitivanu grupu činilo je 43 trudnice koje su po definisanim kriterijuma razvile preeklampsiju u aktuelnoj trudnoći. Drugu ispitivanu grupu činilo je 46 trudnica kojima je dijagnostikovana ili potvrđena hronična ili gestacijska hipertenzija u aktuelnoj trudnoći. Kontrolnu grupu činilo je 54 zdravih trudnica sa verifikovanim fiziolo&scaron;kim ishodom trudnoće u terminu, bez maternalnih i fetalnih komplikacija. Prilikom regrutovanja trudnica (između 11+0 i 13+6 nedelja gestacije) za uče&scaron;će u istraživanju, uzeti su anamnestički podaci o faktorima rizika za pojavu hipertenzivnih oboljenja u trudnoći, i u okviru kliničkog i aku&scaron;erskog pregleda urađena su antropometrijska merenja, merenje krvnog pritiska, i specijalizovani ultrazvučni pregled ploda radi utvrđivanja gestacijske starosti ploda i određivanja rizika za pojavu hromozomskih anomalija ploda. Trudnicama je nakon uzimanja anamnestičkih podataka i kliničkog i aku&scaron;erskog pregleda i potpisanog pisanog pristanka pacijenta o dobrovoljnom učestvovanju u istraživanju izvađena krv radi određivanja odabranih laboratorijskih parametara. Serumske koncentracije sFlt1, VEGF-A i PIGF određivane su kvantitativnom ELISA tehnikom (R&amp;D Systems Europe Ltd. Abingdon, UK), dok su: glukoza, ukupni holesterol, HDL holesterol, LDL holesterol, trigliceridi, apo-AI I apoB, AST, ALT, GGT, kreatinin, ureja, mokraćna kiselina, hsCRP, Na, K, Cl, Mg, P, Ca određivani na automatizovanim analizatorskim sistemima. Sve trudnice su kategorisane u 2 ispitivane i kontrolnu grupu na osnovu pojave ili isključenja hipertenzivnih oboljenja u aktuelnoj trudnoći. Statistička obrada podataka urađena je u statističkom programu STATISTICA 12 (StatSoft Inc.,Tulsa, OK, USA). Podaci su predstavljeni tabelarno i grafički, nivo statističe značajnosti p, je tumačen statistički značajnim ukoliko su vrednosti p&lt;0,05. REZULTATI: Vrednosti serumskih koncentracija sFlt-1 se statistički značajno razlikuju u sve tri grupe ispitanica i značajno su vi&scaron;e u grupama sa hipertenzivnim oboljenjima u odnosu na zdravu grupu ispitanica, p&lt;0,001. Serumske koncentracije VEGF-A su značajno niže u grupi trudnica sa preeklampsijom u odnosu na zdrave trudnice kontrolne grupe (p&lt;0,001), dok se nivoi serumskih koncentracija PlGF statistički značajno razlikuju između sve tri grupe trudnica tako da su najniže vrednosti uočene u grupi sa preeklampsijom (p&lt;0,001) u odnosu na preostale dve grupe ispitanica. Nije uočeno postojanje statistički značajne razlike u nivoima PAPP-A, biohemijskih parametara (glukoze, AST, ALT, GGT kreatinina, ureje, mokraćne kiseline), lipidskih parametara (uk. holesterol, LDL, apo A-I, apo B), parametara inflamatornog (kompletna krvna slika, fibrinogen), hemostaznog (D-dimer, vWF-antigen) i elektrolitskog statusa (Na, K, Cl, P, Mg), p&gt;0,05. Nivoi free &szlig;hCG i HDL holesterola su značajno niže, dok su vrednosti hsCRP i triglicerida značajno vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu bez hipertenzivnih poremećaja u trudnoći. Serumske koncentracije sFlt-1 preko 865 pg/ml imaju senzitivnost od 93% i specifičnost od 81,5% u predviđanju nastanka preeklampsije, dok serumske koncentracije PlGF ispod 60 pg/ml senzitivnost od 88,4% i specifičnost od 79,6% u predviđanju pojave preeklampsije. Serumske koncentracije sFlt-1, VEGF-A i PlGF ne pokazuju statistički značajnu razliku u odnosu na godine života trudnice i broja prethodnih trudnoća p&gt;0,05. Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na telesnu težinu novorođenčeta, tako da su niže vrednosti oba proteina detektovane u grupi novorođenčadi sa porođajnom težinom ispod 1500 gr. u odnosu na telesnu masu između 2800-3300 gr, p&lt;0,001. Takođe su nađene niže vrednosti sFlt-1 i PlGF u grupi trudnica koje su se porodile pre 33. nedelje gestacije u odnosu na nedelju gestacije u trenutku porođaja preko 37 nedelje gestacije, p&lt;0,001. Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na indeks telesne mase majke tako da su vi&scaron;e vrednosti sFlt-1 i niže vednosti PlGF nađene u grupi trudnica sa indeksom telesne mase ispod 25 u odnosu na grupu trudnica sa indeksom telesne mase preko 30 kg/m2, p&lt;0,001. Serumske koncentracije sFlt-1 u prvom trimestru trudnoće su značajno povezane sa parametrima inflamacije (hsCRP), vrednostima dijastolnog krvnog pritiska i nivoima free &szlig;hCG. Takođe se uočava značajna povezanost koncentracije PlGF sa indeksom telesne mase, vrednostima sistolnog krvnog pritiska i koncentracijom hsCRP u prvom trimestru trudnoće. ZAKLJUČAK: Nivoi antiangiogenog proteina sFlt-1 su vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu sa hroničnom i gestacijskom hipertenzijom i grupu trudnica bez hipertenzivnih poremećaja trudnoći. Nivoi proangiogenog proteina VEGF-A su značajno niže u grupi trudnica sa preeklampsijom i hroničnom i gestacijskom hipertenzijom u odnosu na grupu trudnica bez hipertenzivnih poremećaja u trudnoći. Serumske koncentracije proangiogenog proteina PlGF su niže u grupi trudnica sa preeklampsijom u odnosu na grupu sa hroničnom i gestacijskom hipertenzijom i grupu trudnica bez hipertenzivnih poremećaja trudnoći. Serumske koncentracije placentalnog proteina free &szlig;hCG i HDL holesterola su značajno niže, dok su vrednosti hsCRP i triglicerida značajno vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu bez hipertenzivnih poremećaja u trudnoći. Između trudnica sa hipertenzivnim poremećajima u trudnoći i zdravih trudnica nije uočeno postojanje značajne razlike u vrednostima placentalnog proteina PAPP-A, biohemijskih parametara (glukoze, AST, ALT, GGT kreatinina, ureje, mokraćne kiseline), lipidskih parametara (uk. holesterol, LDL, apo A-I, apo B), parametara inflamatornog (kompletna krvna slika, fibrinogen), hemostaznog (D-dimer, vWF-antigen) i elektrolitskog statusa (Na, K, Cl, P, Mg). Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na gestacijsku starost na porođaju i telesnu masu novorođenčeta i niže su kod trudnica koje su se prevremeno porodile kao i kod novorođenčati sa manjom porođajnom težinom. Serumske koncentracije sFlt-1 se značajno razlikuju u odnosu telesnu dužinu i APGAR skor novorođenčeta, tako da su vi&scaron;e vrednosti sFlt-1 udružene sa većom telesnom dužinom novorođenčeta i boljim APGAR skorom. Serumske koncentracije sFlt-1, VEGF-A i PlGF se ne razlikuju značajno u odnosu na godine života trudnice i broja prethodnih trudnoća. Nivoi proteina angiogeneze sFlt-1 i PlGF predstavljaju dobre prediktore u predviđanju nastanka preeklampsije u prvom trimestru trudnoće.</p> / <p>INTRODUCTION: Hypertensive disorders in pregnancy are a heterogeneous group of diseases that occur in 3-8% of all pregnancies. The most difficult forms of these diseases: preeclampsia, eclampsia and HELLP syndrome are the leading causes of maternal and fetal morbidity and mortality in relation to all other pregnancy complications. Etiopathogenesis of these diseases is still insufficiently understood but it is thought that the placenta plays a key role in the development of these complications, and that placental insufficiency, which occurs as a result of insufficient adaptation of decidual intramiometrial and parts of the spiral arteries in the first few weeks of pregnancy, leading to a reduction of utero- placental circulation and local placental hypoxia, which adversely affects the mother and the fetus. In order to elucidate the pathophysiological mechanisms of hypertensive disorders in pregnancy and to find sufficiently sensitive makers for early prediction of the most severe forms of these diseases, so far have been investigated a number of proteins involved in the processes of creation and development of placental vascular network such as vascular endothelial growth factor (VEGF-A), placental growth factor (PlGF) and soluble fms-like receptor tyrosine kinase receptor (sFlt-1). OBJECTIVE: The aim of the study was to compare serum concentration of sFlt-1, PlGF, VEGF-A, PAPP-A, free&szlig;hCG, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apo-AI, apo B, AST, ALT, GGT, creatinine, urea, uric acid, hsCRP, Na, K, Cl, P, Mg and Ca between the group of pregnant women with preeclampsia, chronic and gestational hypertension and the control group of pregnant women in the first trimester of pregnancy between 11 and 14 weeks gestation. Also the aim was to examine whether the value of selected laboratory parameters (sFlt-1, VEGF-A and PlGF) differ in relation to gestational week at the time of birth, weight, length and APGAR scoring system of newborns. The aim was to examine whether the value of angiogenic proteins: sFlt-1, VEGF-A and PlGF differ significantly in relation to the number of previous pregnancies and age of the pregnant woman. MATERIALS AND METHODS: The study was conducted as a prospective analytical study in the Clinical Center of Vojvodina, in the period from June 2012 to February 2015. The study included a total of 143 pregnant women aged 18 - 43 years. All pregnant women included in the study were divided into two study and one control group. The first study group consisted of 43 pregnant women who developed preeclampsia during the current pregnancy. The second study group consisted of 46 pregnant women who are newly diagnosed or confirmed chronic or gestational hypertension during the current pregnancy. The control group consisted of 54 healthy pregnant women with verified physiological outcome of pregnancy at term without maternal and fetal complications. Patients were included in the study between 11 + 0 and 13 + 6 weeks of gestation. All patients had data about risk factors for developing hypertensive disorders in pregnancy. After clinical and obstetric examination all patients underwent anthropometric measurements, measurement of blood pressure, and specialized ultrasound examination to determine precise gestational age of the fetus and to determine the risk for fetal chromosomal abnormalities. All patients signed a written consent of the patient&#39;s voluntary participation in the study. Serum levels of sFlt1, VEGF-A and PlGF were determined by quantitative ELISA (R &amp; D Systems Europe Ltd., Abingdon, UK), while glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apo-AI, apo B, AST, ALT, GGT, creatinine, urea, uric acid, hsCRP, Na, K, Cl, P, Mg, Ca were determined on automated analyzer systems. All pregnant women were categorized into 2 study and a control group on the basis of presence of hypertensive disorders in the current pregnancy. Statistical analysis was performed in 12 statistical program STATISTICA (StatSoft Inc., Tulsa, OK, USA). The data are presented in tables and graphs, the level of significance p is interpreted statistically significant if the p value was less than &lt;0.05. RESULTS: Serum concentrations of sFlt-1 are statistically significantly different in all study groups and significantly higher in the groups with hypertensive disorders compared to healthy subjects p &lt;0.001. Serum levels of VEGF-A are significantly lower in the preeclampsia group compared to healthy control group (p &lt;0.001), while the levels of serum concentration of PlGF statistically significantly different between all groups so that the lowest values are observed in the preeclampsia group (p &lt;0.001) compared to the other two study groups. There is no statistically significant differences in the levels of PAPP-A, biochemical parameters (glucose, AST, ALT, GGT creatinine, urea, uric acid), lipid parameters (total cholesterol, LDL, apo AI, apo B), inflammatory parameters (complete blood count, fibrinogen), hemostatic (D-dimer, vWF-antigen) and electrolyte status (Na, K, Cl, P, Mg, Ca), p&gt; 0.05. Levels of free &szlig;hCG and HDL cholesterol levels are significantly lower, while the value of hsCRP and triglycerides significantly higher in the group of women with preeclampsia compared to the healthy control group. Serum concentrations of sFlt-1 over 865 pg/ml have a sensitivity of 93% and specificity of 81.5% in predicting preeclampsia, while serum PlGF concentration below 60 pg/ml, a sensitivity of 88.4% and a specificity of 79.6% in predicting preeclampsia. Serum concentrations of sFlt-1, VEGF-A and PlGF do not show a statistically significant difference compared to the age of pregnant women and the number of previous pregnancies p&gt; 0.05. Serum concentrations of sFlt-1 and PlGF are significantly different in relation to the weight of the newborn, so that the lower values of both proteins are in the group of infants with birth weight below 1500 gr. in relation to the body weight between 2800-3300 gr., p &lt;0.001. There is also lower concentrations of sFlt-1 and PlGF in a group with deliveries before 33 weeks of gestation compared to the deliveries after 37 week of gestation, p &lt;0.001. Serum concentrations of sFlt-1 and PlGF are significantly different in relation to the mother&#39;s body mass index so that the lower values of sFlt-1 and PlGF are in the group of women with a body mass index below 25 in relation to a group with a body mass index over 30 kg/m2, p &lt;0.001. Serum concentrations of sFlt-1 in the first trimester of pregnancy were significantly associated with the parameters of inflammation (hsCRP), diastolic blood pressure and levels of free &szlig;hCG. It is also observed a significant correlation between PlGF with a body mass index, systolic blood pressure and hsCRP concentration in the first trimester of pregnancy. CONCLUSION: The levels of anti-angiogenic protein sFlt-1 are higher in the group of pregnant women with preeclampsia than in the group with chronic and gestational hypertension and the control healthy group. Levels of proangiogenic VEGF-A protein are significantly lower in the preeclampsia group and group with gestational and chronic hypertension compared to the control group. Serum levels of proangiogenic PlGF protein are significantly lower in the preeclampsia group than in the group with chronic and gestational hypertension and the control group. Serum concentrations of placental protein free &szlig;hCG and HDL cholesterol are significantly lower, while the value of hsCRP and triglycerides significantly higher in the preeclampsia group compared to the control group. Among pregnant women with hypertensive disorders in pregnancy and healthy pregnant women there are no significant differences in the values of placental PAPP-A protein, biochemical parameters (glucose, AST, ALT, GGT creatinine, urea, uric acid), lipid parameters (total cholesterol, LDL, apo AI, apo B), inflammatory parameters (complete blood count, fibrinogen), hemostatic (D-dimer, vWF-antigen) and electrolyte status (Na, K, Cl, P, Mg, Ca). Serum concentrations of sFlt-1 and PlGF are significantly different in relation to gestational age at delivery and newborn body weight and are lower in group with preterm delivery and newborns with lower birth weight. Serum concentrations of sFlt-1 are significantly different compared to body length and Apgar score, so that the higher values of sFlt-1 are associated with better outcome of newborns (greater body length and better APGAR score). Serum concentrations of sFlt-1, VEGF-A and PlGF are not different significantly with respect to age of pregnancy and the number of previous pregnancies. The levels of sFlt-1 and PlGF represents helpful markers in prediction of preeclampsia in the first trimester of pregnancy.</p>

<p>Cilj: Cilj ovog istraživanja bio je da se utvrde promene koje arterijska hipertenzija dvojakim mehanizmima (dnevno-noćnim ritmom i svojim trajanjem) ostavlja na funkciju i geometriju leve pretkomore i komore srca. Ispitanici i metode: u ovo istraživanje bilo je uključeno 180 ispitanika koji su bili podeljeni u ispitivane grupe u odnosu na dnevno-noćni ritam arterijskog krvnog pritiska tokom 24-časovnog monitoringa arterijskog krvnog pritiska i to na sledeći način: grupa ispitanika sa očuvanim dnevno-noćnim ritmom arterijskog krvnog pritiska sastojala se od ukupno 90 ispitanika, a grupu onih sa naru&scaron;enim dnevno-noćnim ritmom arterijskog krvnog pritiska takođe je činilo 90 ispitanika. U svakoj od ovih grupa izvr&scaron;ena je dodatna podela ispitanika prema dužini trajanja arterijske hipertenzije na one kod kojih je arterijska hipertenzija trajala do 5 godina, one kod kojih je trajala od 5 do 10 godina i na one sa trajanjem arterijske hipertenzije vi&scaron;e od 10 godina. Svim ispitanicima rađen je incijalno 24-časovni ambulantni monitoring arterijskog krvnog pritiska, a nakon toga i ehokardiografski pregled radi određivanja parametara morfologije leve pretkomore i komore, kao i dijastolne funkcije leve komore. Rezultati i diskusija: nakon statističke obrade podataka dobijeni su rezultati koji ukazuju da se dijastolna disfunkcija stepena većeg od I statistički značajno če&scaron;će (p=0,011) uočava kod onih ispitanika koji nemaju očuvan dnevno-noćni ritam arterijskog krvnog pritiska. Naru&scaron;en dnevno-noćni ritam arterijskog krvnog pritiska takođe dovodi do povećanja indeksirane mase miokarda leve komore prema povr&scaron;ini tela ispitanika (LVM/BSA) &ndash; p=0,001; do zadebljanja zidova leve komore (IVS/PLW) &ndash; p=0,025, kao i do smanjenja sistolne brzine miokarda na nivou septalnog dela mitralnog anulusa (s&rsquo;) - p&lt;0,0005. Pored ovoga, u grupi onih sa naru&scaron;enim dnevno-noćnim ritmom arterijskog krvnog pritiska primećeno je če&scaron;će prisustvo ekscentrične hipertrofije miokarda leve komore (p=0,027). U odnosu na geometriju i funkciju leve pretkomore, naru&scaron;en dnevno-noćni ritam arterijskog krvnog pritiska dovodi do promena u smislu povećanja antero-posteriornog dijametra leve pretkomore (LA)-p=0,003; maksimalnog volumena leve pretkomore u komorskoj sistoli (LAVs) &ndash;p=0,007; indeksiranog LAVs prema povr&scaron;ini tela ispitanika (LAVs/BSA)-p&lt;,0005; E/e&rsquo; odnosa &ndash;p=0,040; rezervoarnog strain-a leve pretkomore (PLAS)- p=0,004; krutosti leve pretkomore (stiffness)-p=0,047, kao i brzine propagacije talasa kroz mitralni otvor (Vp)-p=0,029. Sa povećanjem dužine trajanja arterijske hipertenzije takođe su pokazane promene u morfologiji i funkciji leve pretkomore i leve komore srca. Dijastolna disfunkcija stepena većeg od I retko je bila uočena u grupi onih koji su arterijsku hipertenziju lečili kraće od 5 godina, a njeno prisustvo u ispitivanim grupama trajanja od 5 do 10 godina i duže od 10 godina bilo je statistički značajno če&scaron;će (p&lt;0,0005). Takođe, sa trajanjem arterijske hipertenzije statistički značajno se menjaju i parametri leve komore za koje smo pokazali da su pogor&scaron;ani kada dnevno-noćni ritam arterijskog krvnog pritiska nije očuvan, s tim &scaron;to smo ovde uočili i značajne promene u smislu postojanja lo&scaron;ijih vrednosti strain-a leve komore (LVGS)-p&lt;0,0005. Na sličan način kao i u odnosu na dnevno-noćni ritam arterijskog krvnog pritiska, menjao se predominantni oblik hipertrofije miokarda leve komore, te je uočeno značajno če&scaron;će (p=0,017) prisustvo ekscentrične hipertrofije kod ispitanika koji su duže lečili arterijsku hipertenziju. Uz ove promene, sa trajanjem arterijske hipertenzije, uočene su i promene sledećih ehokardiografskih parametara leve pretkomore (p&lt;0,0005): LA, LAVs, LAVs/BSA, E/e&rsquo;, PLAS, stiffness, Vp. Na kraju, formiran je i model za dijagnostiku dijastolne disfunkcije stepena većeg od I koji je testiran na 30 novih ispitanika i koji se pokazao kao kvalitetan uz visoku senzitivnost i specifičnost. Zaključak: arterijska hipertenzija dnevno-noćnim oscilacijama (ritmom), ali i svojim trajanjem dovodi do promena u funkciji i geometriji leve pretkomore i komore srca. Noviji ehokardiografski parametri (PLAS, LVGS, stiffness) su dobri pokazatelji ranih promena na nivou leve pretkomore i komore srca kod pacijenata sa arterijskom hipertenzijom.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>Vukadin Milankov</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> 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<p>Uprkos op&scaron;te prihvaćenom stavu da u trudnoći lekove treba izbegavati, veliki broj trudnica tokom trudnoće uzima lekove sa manje ili vi&scaron;e opravdanja. Primena lekova u trudnoći zahteva dodatnu patnju, jer se mora voditi računa o zdravlju majke i zdravlju jo&scaron; nerođenog&nbsp; deteta. Većina lekova koji nalaze primenu u trudnoći, nisu ispitani u kontrolisanim studijama na trudnicama, već se njihov uticaj naljudski fetus, bazira na predpostavkama i kliničkim istraživanjima na životinjama. Odsustvo studija dovodi do toga da se trudnicama obično prepisuju lekovi u dozi za odrasle osobe, koje ne prate fiziolo&scaron;ke promene u trudnoći. Tokom trudnoće u telu trudnica dolazi do promena u funkciji organa i organskih sistema, a zbog nastalih promena menja se i sudbina leka u organizmu. Sistemske bolesti trudnice poput hipertenzije i dijabetesa dovode do hemodinamskih promena i utiču na nastanak patolo&scaron;kih promena posteljice, &scaron;to sve zajedno menja farmakokinetiku lekova i njihov transplacentrarni transport. Ukupno 75 trudnica je uključeno u studiju i podeljeno u tri grupe: zdrave trudnice-kontrolna grupa (n=31), trudnice sa hipertenzijom (n=30) i trudnice sa dijabetesom (n=14). Sve trudnice su u premedikaciji primile iste lekove koji su deo standardne kliničke&nbsp; procedure. Trudnice su primile jednu dozu diazepama intramuskularnom injekcijom (10mg/2ml), a intravenski su primile pojedinačne doze cefuroksima (1,5g), metoklopramida (10mg/2ml) i ranitidina (50mg/2ml). Od svakog para majka-dete ukupno je analizirano po 5 uzoraka. Uzorci krvi od majke uzimani su u tri vremenske tačke: nakon davanja leka, u momentu ekstrakcije deteta i nakon porođaja. Uzorci&nbsp; krvi&nbsp; deteta&nbsp; uzimani su&nbsp; nakon&nbsp; porođaja iz pupčane vene i arterije. Prikupljeni uzorci plazme analizirani su metodom tečne hromatografije visokih performansi (HPLC). Istraživanje je pokazalo da lekovi&nbsp; primenjeni u premedikaciji&nbsp; carskog reza prolaze transplacentarnu membranu i da se ni jedan&nbsp; od&nbsp; lekova&nbsp; primenjenih&nbsp; u studiji nije akumulirao u fetusu i nije imao neželjeno dejsvo na novorođenče. Cefuroksim, ranitidin i metoklopramid pokazali su nizak feto-maternalni transfer, dok je diazepam pokazao visok&nbsp; feto-maternalni transfer. Izmerene koncentracije cefuroksima u plazmi trudnica u momentu porođaja bile su &ge;8 &mu;g/ml, &scaron;to je koncentracija veća od MIC za većinu patogena odgovornih za nastavak infekcija u aku&scaron;erstvu. Koncentracije cefuroksima u fetalnoj plazmi bile su &ge;4&mu;g/ml &scaron;to je veće od&nbsp; MIC koncentracija za veliki broj patogena. Gestacijska starost trudnoće nije uticala na obim prolaska cefuroksima&nbsp; kroz placentu, koji je prolazi uglavnom pasivnom difuzijom. Farmakokinetski parametri cefuroksima razlikovali su se kod hipertenzivnih i dijabetičnih trudnica, u odnosu kontrolnu grupu, ali ove bolesti nisu imale značajan uticaj na smanjenje terapijske efikasnosti cefuroksima. Farmakokinetika cefuroksima kod hipertenzivnih&nbsp; trudnica&nbsp; ukazala je na bržu eliminaciju cefuroksima iz krvi majke i na veću distribuciju leka u okolna tkiva. U dijabetičnoj grupi trudnica i novorođenčadi koncentracije cefuroksima su bile vi&scaron;e u odnosu na druge ispitivane grupe, dok je feto-maternalni odnos bio niži, &scaron;to ukazuje na postojanje strukturalne i funkcionalne pomenu posteljice u dijabetesu. Hipertenzija i dijabetes trudnica nisu imali uticaj na prodor ranitidina kroz placentu. Hipertenzija i dijabetes trudnica nisu uticali na većinu farmakokinetskih parametara ranitidina, mada je zabeleženo smanjenje volumena distribucije u ovim grupama trudnica, &scaron;to bi moglo da ukazuje na njihovu hemodinamsku nestabilnost i povećanje slobodne frakcije ranitidina. Koncentracija metoklopramida bila veća u krvi majki u odnosu na krv fetusa. Transport metoklopramida iz fetusa ka majci bio je dominantniji, a naročito u hipertenzivnoj i dijabetičnoj grupi trudnica. Hipertenzija i dijabetes trudnica uticali su na zadržavanje metoklopramida u fetusu. Koncentracije dijazepama u majčinoj i fetalnoj krvi bile su vi&scaron;e u kontrolnoj i hipertenzivnoj grupi trudnica. Hipertenzija i dijabetes trudnica povećavaju&nbsp; transfer diazepama kroz placentu, povećanjem koncentracije slobodnih masnih kiselina, steroidnih hormona, smanjenjem vezivnog kapaciteta potencijalna opasnost od neželjenog dejstva diazepama i njegovih metabolita na fetus i novorođenče. Ova doktorska studija ukazuju na potrebu obimnijih farmakokinetskih istraživanja kako na zdravim tako i na bolesnim trudnicama, koja će dati zaključke utvrđene na dokazima i pomoći u individualnom terapijskom pristupu svakoj trudnici.</p> / <p>In spite of&nbsp; the widespread opinion&nbsp; that&nbsp; drugs should be avoided in pregnancy, a great number of&nbsp; pregnant&nbsp; women&nbsp; take drugs with more or less justification.&nbsp; Administration of drugs in pregnancy requires additional attention because the health of&nbsp; both the mother and&nbsp; her unborn child must be protected. Majority of drugs administered in pregnancy have not been tested&nbsp; within the controlled studies performed on pregnant women, but&nbsp; their effect on the human foetus is based on assumptions and clinical trials performed on animals. This absence of studies results in the situation that pregnant&nbsp; women are usually prescribed drugs in a dose&nbsp; for adults, which does not take into account the physiological changes happening in pregnancy. During pregnancy, the pregnant woman&rsquo;s body undergoes changes in the<br />functions of organs and organ systems. These changes further affect the destiny of a&nbsp; drug in the organism. In pregnant women, systemic diseases such as hypertension&nbsp;&nbsp; and diabetes mellitus lead to hemodynamic changes and cause pathological&nbsp; changes in placenta, thus changing the pharmacokinetics of drugs and their transplacental transport. The study sample consisted of 75 pregnant women, who were divided into three groups as follows: the control group included healthy pregnant&nbsp; women (n=31), a group of pregnant women&nbsp; with&nbsp; hypertension (n=30) and&nbsp; a group of&nbsp; those&nbsp; with&nbsp; diabetes mellitus (n=14). All of them were administered the same drugs as a part of standard clinical procedure in premedication. The pregnant women received a single dose of diazepam by intramuscular injection (10mg/ml), and individual doses of cefuroxime (1.5mg), metoclopramide (10mg/2ml) and ranitidine (50mg/2ml). Five samples taken from each mother-infant pair were analyzed. Blood samples were taken from the mother three times: after drug administration, at the moment of extraction of baby and after delivery. Baby&rsquo;s blood samples were taken from the umbilical cord vein and artery after delivery. Plasma samples were analyzed by the method of high-performance liquid chromatography (HPLC). The research has shown that drugs administered in premedication of caesarean section went through the transplacental membrane and that none of the tested drugs accumulated in the foetus and had an adverse effect on the newborn. Cefuroxime, ranitidine and metoclopramide were shown to have a low transfer between the mother and her foetus, whereas diazepam showed a high foetal-maternal transfer. Cefuroxime concentrations measured in the pregnant woman&rsquo;s and foetal plasma at the moment of delivery were &ge;8&mu;g/ml and &ge;4&mu;g/ml, respectively, that&nbsp; being above the minimum inhibitory concentration (MIC) for most pathogens responsible for the development of infection in obstetrics. Gestational age had no effect on the range of cefuroxime flow through the placenta, which happens mostly by&nbsp; passive diffusion. Pharmacokinetic parameters of cefuroxime differed in the pregnant&nbsp; women having hypertension and diabetes mellitus from the controls; however, these diseases did not significantly reduce the therapeutic efficacy of cefuroxime. Pharmacokinetics of cefuroxime indicated faster elimination of&nbsp; cefuroxime into the maternal blood and greater distribution of the drug into the surrounding tissues in the hypertensive pregnant women. In the group consisting of pregnant women and newborns having diabetes, the cefuroxime concentrations were higher than in other groups, whereas foetal-maternal relation was lower, which suggests the presence of structural and functional change in the placenta in diabetes. Hypertension and diabetes mellitus had no affect either on the flow of ranitidine through the placenta in the pregnant women or on&nbsp; the&nbsp; majority of pharmacokinetic parameters of ranitidine, although a certain reduction in the volume&nbsp; of distribution was recorded in these groups of pregnant women, which could suggest their hemodynamic instability and increased free fractions of ranitidine. The concentration of metocloporamide was higher in the maternal blood than in the&nbsp; foetal blood, and&nbsp; the transport of metocloporamide from the foetus towards the mother was more dominant, particularly in&nbsp; the&nbsp; group of&nbsp; hypertensive and diabetic&nbsp;&nbsp;&nbsp; pregnant women. Metoclopramide tended to retain in the foetuses of mothers having&nbsp; hypertension and diabetes. The concentrations of diazepam in maternal and foetal blood were higher in the controls&nbsp; and hypertensive&nbsp; pregnant&nbsp; women. Hypertension and diabetes in pregnant&nbsp; women increase the transfer of diazepam through the placenta by increasing the concentration of free fatty acids and steroid hormones and by reducing the binding capacity of carrier proteins and the concentration of plasma&nbsp;&nbsp; proteins, thus increasing the potential danger of adverse effects of diazepam and its metabolites on the foetus and the newborn. This doctoral study suggests the necessity for more extensive pharmacokinetic research including both healthy and affected pregnant women that would lead to conclusions based on evidence and help to develop individual therapeutic approach to each pregnant woman.</p>