Indicators of Preeclampsia in Correlation with Maternal Cytokines in Pregnancy

Aim: the purpose of the actual study was to evaluate, in the third trimester of pregnancy, the relationship between the formation of anti-inflammatory IL-10 cytokine and several indicators of moderate and severe preeclampsia. Materials and methods: in the third trimester of gestation, examination of the biochemical markers of preeclampsia (PE) and maternal IL-10 levels was conducted in 100 women with pregnancies complicated by varying degrees of preeclampsia and in 100 normotensive patients, hospitalized at the University Clinic of Gynecology and Obstetrics, Skopje, Republic of Macedonia. Patients with preeclampsia were categorized into moderate and severe preeclampsia groups according to the degree of preeclampsia. Logistic regression of the different parameters for the occurrence of severe preeclampsia analysis was used to determine the predictive value. Results: the regression analysis detected systolic blood pressure of 160 mmHg or higher, diastolic blood pressure of 100 mmHg or higher, persistent proteinuria in pregnancy, serum LDH concentration of 450 U/L or higher, and reduced serum concentrations of IL-10 as significant predictors of severe preeclampsia. Conclusion: significantly, lower IL-10 concentrations in maternal serum in patients with severe preeclampsia in comparison with respective concentrations in patients with moderate preeclampsia can be considered as major pathognomonic laboratory sign of severe form of preeclampsia

Улогата на некои инфламаторни маркери, цитокини и тумор маркери во дијагноза на ендометриозата

Endometriosis is a multifactorial disease which etiopathogenesis has not been elucidated. One of the theories of etiopathogenesis is the inflammatory theory. Aims of the study: To develop a practical non-invasive test for the diagnosis of endometriosis by examining some inflammatory markers and cytokines; to compare the highly sensitive C-reactive protein (hsCRP), cytokines (interleukin-6-IL-6 and tumor necrotizing factor alpha) and the tumor marker cancer antigen 125 (CA-125) among healthy patients and patients with endometriosis; to determine the sensitivity and specificity of each biomarker separately in the diagnosis of endometriosis and to determine their role in the diagnosis of endometriosis. Materials and methods: In a prospective study conducted at the University Clinic for Gynecology and Obstetrics, Ss. Cyril and Methodius University in Skopje, North Macedonia 138 patients were included of a reproductive age between 18-50 years (83 with diagnosis endometriosis operated laparoscopically or with laparotomy) and a control group of 55 healthy women, in a period between 01.09.2018 to 01.05.2021. Serum levels of IL-6, TNF-α, hs-CRP and tumor marker CA-125 were evaluated in both groups. Results: Serum levels of CA-125, IL-6 and TNF-α and hs-CRP were significantly higher in patients with endometriosis compared to the control group. The surface under the ROC curve (AUC) for IL-6, CA-125, hs-CRP, and TNF-α has shown that as individual markers they all have a discriminatory capacity to diagnose patients with endometriosis. Conclusions: Results obtained in our study showed statistically significantly higher serum concentrations of CA-125, IL-6 and TNF-α and hs-CRP in patients with endometriosis compared to the control group of patients. However, none of these biomarkers showed a high sensitivity for diagnosis of endometriosis. It is necessary to find a panel combination of biomarkers with a high sensitivity of about 100% that will enable early diagnosis of endometriosis.Ендометриозата е мултифакторно заболување, чија етиопатогенеза не е разјаснета. Една од теориите за етиопатогенезата е инфламаторната теорија. Цели на истражувањето: Да се развие практичен неинвазивен тест за дијагноза на ендометриозата со иследување нанекои инфламаторни маркери и цитокини; да се направи споредба на  високосензитивниот Ц-реактивен протеин  (hsCRP), цитокините (интерлеукин 6 –IL-6 и тумор-некротизирачки фактор алфа - TNF-α) и туморскиот маркер cancer antigen 125 (CA-125) кај здрави пациентки и пациентки со ендометриоза; да се утврди сензитивноста и специфичноста на секој биомаркер посебно во дијагнозата на ендометриозата и да се утврди нивната улога во дијагноза на ендометриозата. Материјал и методи: Во проспективна студија спроведена на Универзитетската клиника за гинекологија и акушерство, Универзитет „Св. Кирил и Методиј“ во Скопје, Северна Македонија беа вклучени 138 испитанички на репродуктивна возраст помеѓу 18-50 години (83 со дијагнозa ендометриоза, оперирани со лапароскопија или лапаротомија) и контролна група од 55 здрави жени, во период од 01.09.2018 година до 01.05.2021. Серумските вредности на интерлеукин 6 (IL-6), тумор-некротизирачки фактор алфа (TNF-α), високоспецифичен Ц-реактивен протеин (hsCRP) и туморскиот маркер CA-125 беа евалуирани во двете групи. Резултати: Серумските вредности на CA-125, IL-6 и TNF-α и hsCRP беа сигнификантно повисоки кај пациентките со ендометриоза во споредба со оние во контролната група. Површината под ROC кривата (AUC) за IL-6, CA-125, hs-CRP и TNF-α покажа дека како поединечни маркери сите имаат дискриминаторен капацитет за дијагноза на пациентки со ендометриоза. Заклучоци: Иследувањата во нашата студија покажаа статистички сигнификантно повисоки концентрации на CA-125, IL-6 и TNF-α и hs-CRP кај пациентките со ендометриоза во однос на контролната група пациентки. Меѓутоа, ниту еден од овие биомаркери не покажа висока сензитивност за дијагноза на ендометриозата. Потребно е да се најде панел комбинација на биомаркери со висока сензитивност од околу 100% кои ќе овозможат  рана дијагноза на ендометриозата

KONCENTRACIJA JODA U MOKRAĆI: PREDSKAZATELJ POROĐAJNE TEŽINE ILI BIOLOŠKI BILJEG ZA PROCJENU JODNOG STATUSA SAMO U ZDRAVIH TRUDNICA?

Introduction: This study determined urine iodine concentration (UIC) during gestation, assessed the maternal iodine nutrition status and correlated it with gestational age at birth (GAB) and birth weight (BW).The measurement of UIC provides the best single measurement of the iodine nutritional status in population. Objective: Determination of UIC in pregnant women in North Macedonia. Methods: This prospective study assessed the iodine nutrition status during the course of pregnancy with reference of median UIC among 364 healthy pregnant women in different gestational age (in trimester and 5-week intervals). Results: The overall and the 1st to the 3rd trimester median UIC were: 183.7, 207, 189.75 and 169.28 [μg/L], respectively. The median UIC (μg/L) results according to 5-week interval in advancing gestation were: 232.34, 200.13, 152.81, 194.39, 181.28, 160.28, 169.41 and 175.24, respectively. We detected 5.22% (19/364) and 74.72% (272/364) with the median UIC < 50 μg/L and UIC ≥ 100 μg/L, respectively. In multiple regression, the median UIC (β = 0.0000767, P = 0.929) had no statistically signifi cant prediction to the GAB. Disease prevalence results for mean UIC in detecting BW had no statistical signifi cance: area under curve (AUC) = 0.521, z-statistic (0.340), sensitivity (45.83%), specifi city (66.27%), predictive (6.59%) and P value (0.734). Conclusion: Iodine status of pregnant women in our study is generally suffi cient by World Health Organization recommendations. The median UIC in each trimester and 5-week interval has statistically insignifi cant decrease in accordance to the advancing gestation. The median UIC has no signifi cance in predicting GAB and BW.Uvod: Ova je studija utvrdila koncentraciju joda u mokraći (UIC) tijekom trudnoće, procijenila prehrambeni status joda kod majke i povezala ga s gestacijskom dobi pri rođenju (GAB) i porođajnom težinom (BW). Mjerenje UIC-a omogućava najbolje pojedinačno mjerenje prehrambenog statusa joda u populaciji. Cilj: Određivanje UIC-a trudnicama u sjevernoj Makedoniji. Metode: Ova prospektivna studija procjenjivala je prehrambeni status joda tijekom trudnoće, pozivajući se na medijan UIC 364 zdrave trudnice u različitoj gestacijskoj dobi (u intervalima tromjesečja i 5 tjedana). Rezultati: Ukupna i prosječna UIC od 1. do 3. tromjesečja bila su: 183,7, 207, 189,75 i 169,28 [μg / L]. Srednji rezultati UIC (μg / L) prema intervalu od 5 tjedana u napredovanju trudnoće bili su: 232,34, 200,13, 152,81, 194,39, 181,28, 160,28, 169,41 i 175,24. Otkrili smo 5,22 % (19/364) i 74,72 % (272/364) s medijanom UIC <50 μg / L, odnosno UIC ≥ 100 μg / L. U višestrukoj regresiji, medijan UIC (β = 0,0000767, P = 0,929) nije imao statistički značajno predviđanje za GAB. Rezultati prevalencije bolesti za srednji UIC u otkrivanju BW nisu imali statističku značajnost: područje ispod krivulje (AUC) = 0,521, z-statistika (0,340), osjetljivost (45,83 %), specifi čnost (66,27 %), prediktivna (6,59 %) i P vrijednost (0,734). Zaključak: Jodni status trudnica u našem istraživanju u pravilu je dovoljan prema preporukama Svjetske zdravstvene organizacije. Medijan UIC-a u svakom tromjesečju i intervalu od 5 tjedana statistički je beznačajno smanjen u skladu s napredovanjem trudnoće. Medijan UIC nema značenje u predviđanju GAB i BW

REPRODUCTIVE OUTCOME, DURATION OF PREGNANCY AND MODE OF DELIVERY AFTER HYSTEROSCOPIC METROPLASTY IN PATIENTS WITH INFERTILITY

Introduction: Reproductive outcome can be negatively affected in patients with congenital uterine anomalies (CUA), increasing the number of unsuccessful pregnancies and obstetric complications. Standard, safe and minimally invasive method for the treatment of correctible types of congenital uterine anomalies is hysteroscopic metroplasty (HM). The aim of the study was to analyze the reproductive outcome, duration of pregnancy and mode of delivery in group of patients with infertility after hysteroscopic metroplasty. Material and methods: We analyzed 48 patients with previous history of fetal loss (abortion) to whom hysteroscopy was done in the period of 01.11.2009 to 01.05.2013 year at the University Clinic of Obstetrics and Gynecology in Skopje. In patients who were diagnosed having CUA hysteroscopic metroplasty was done. Patients and their reproductive outcome were followed for a period of at least 2 years after the intervention. Reproductive outcome was followed considering pregnancy rate, fetal loss (abortion) up to 22 gestational week, rates of preterm and term deliveries, live births and mode of delivery. Statistical analysis was performed using computer software and value for the confidence interval (± 95% CI) was considered to be statistically significant with level of p<0.05. Results: After hysteroscopic metroplasty, there was a significant decrease of the abortion rate to 13.9%, and significant increase in pregnancy rates of 86.1%. Overall pregnancy rate was 75%, and term delivery was noted in 93,6 % of the patients, with spontaneus deliveries in 58,6 %. There were no complications during the hysteroscopic metroplasty, nor during the deliveries. Conclusion: Hysteroscopic metroplasty has a significant effect on the reproductive outcome, resulting in a large number of live births and no significant complication during consecutive pregnancy and delivery

Maternal cytokines and biochemical markers as indicators of moderate and severe preeclampsia

Preeclampsia is considered as a failure of body’s adaptive mechanisms. Maternal immune system is involved in maternal endothelial dysfunction and the subsequent systemic reaction seen in preeclampsia. Further arguments to support the idea of the involvement of the maternal immune system in the development of preeclampsia come from the primipaternity theory. This hypothesis holds that the risk of developing preeclampsia is highest in the first pregnancy, and a previous normal pregnancy is associated with a lowered incidence of preeclampsia in the subsequent pregnancy. Studying production of pro-inflammatory (IL-1β, IL- 8), anti-inflammatory (IL-10), CRP and TNF alpha in moderate and severe preeclampsia in third trimester of pregnancy

The role of human papillomavirus (HPV) testing in the follow-up of patients after treatment for cervical intraepithelial neoplasia (CIN)

<strong>Introduction:</strong> The aim of this study was to examine the role of human papillomavirus testing in the follow-up after treatment for CIN, as a prognostic sign for residual/recurrent cervical precancerous lesions.<br />Methods: A hospital-based analysis was performed on 460 patients previously treated for CIN with cold knife conization, at the University Clinic for Gynecology and Obstetrics and General Hospital Remedika, in Skopje, Republic of Macedonia, in a period of 3 years. The patients were followed-up with HPV testing in addition to cytology, colposcopy and/or biopsy. The first after treatment HPV testing was performed<br />8 months after cold knife conization, proceeded by follow-up within 24 months after treatment, at 4 months intervals.<br /><strong>Results:</strong> Among 460 treated patients, at the fi rst HPV and cytologic testing, 8 months after treat-ment, 69 (15%) were HPV+, and 391 (85%) HPV negative. From the 69 HPV+ patients, 41 (59.4%) were with<br />cytologic abnormalities and 28 (40.6%) without abnormalities. 12 months after treatment, the number of HPV+ patients developing cytologic abnormalities raised to 45/70 (64.29%). Within the 24 months after<br />treatment, the number of patients who had recurrent/ residual CIN from the HPV+ patients reached 50/71 (70.42%); which was 10.87% from all 460 treated patients.<br /><strong>Conclusion: </strong>Persistence or clearance of HPV especially 8 months after treatment even in patients with normal cytology, is an early valid prognostic marker of treatment failure, and is more accurate than cytology<br />at the same follow-up intervals

Antioxidant potential of selected supplements in vitro and the problem of its extrapolation for in vivo

<strong>Introduction</strong>: antioxidants, free radicals and oxidative stress have been studied extensively for quite some time but their role in diseases and their prevention has not been clearly determined. Because commercial<br />antioxidants do not need to pass clinical tests in order to be sold over the counter we have decided to test the antioxidant potential of different commercial preparations with the antioxidative properties.<br /><strong>Methods</strong>: pH, rH and oxidant-reduction potential of different preparations in aqueous solution was measured. Afterwards antioxidant potential using FormPlus® after adding the preparation to human blood as a more<br />complex environment with different homeostasis mechanisms was determined.<br /><strong>Results</strong>: all the results showed expected change compared to the control but the results in aqueous solution did not match the results obtained from the human blood, as was expected.<br /><strong>Conclusion</strong>: from the experiments it can be concluded that while the preparations did show antioxidant activity, it is very difficult and even wrong to predict the antioxidant potential of an antioxidant preparation<br />added to human blood, let alone in a living organism, based just on the results obtained in aqueous solution. Further possibilities for research include more extensive studies of antioxidant preparations in more complex environment and last but not least in test organisms or in human trials

Izolirana hipotiroksinemija majke i perinatalni ishod u Sjevernoj Makedoniji

Isolated maternal hypothyroxinemia (IMH) is defined as the presence of low maternal total thyroxine (TT4) level in conjunction with normal maternal thyroid-stimulating hormone (TSH) level. The aim was to investigate whether IMH is associated with adverse pregnancy outcome in North Macedonia. Dried blood spot samples were obtained from 359 pregnant women meeting the inclusion criteria and analyzed for TT4 and TSH. Postpartum data were entered from their medical histories. Out of 359 women, 131 (37.42%) belonged to IMH group. There were statistically significant differences in birth weight (p=0.043), intrauterine growth restriction (IUGR) (p=0.028), Apgar score at 1 min <7 (p=0.018) and cesarean section for dystocia/disproportion (p=0.024) between the IMH and normal thyroid function (NTF) groups. In regression analysis, TSH was a significant variable predicting Apgar score (βst=0.05597, p=0.047), body mass index predicting birth weight (βst=0.02338, p=0.045) and TT4 predicting small for gestational age/IUGR (βst=-0.089834, p=0.029) in IMH group. TT4 was a strong predictor of birth weight (βst=-0.004778, p=0.003) and premature delivery (βst=0.028112, p=0.004) in NTF group. The impact of IMH in pregnancy remains controversial. IMH was associated with an increased maternal BMI and higher birth weight of neonates. Overweight could be a potential risk factor for thyroid dysfunction in pregnant women, and specifically IMH. The worst fetal outcome was seen in IMH mothers examined in second trimester. We found TSH, TT4 and BMI to be strong predictors of perinatal outcomes.Izolirana hipotiroksinemija majke (IMH) je prisutnost niske koncentracije ukupnog tiroksina (TT4) u majke u kombinaciji s normalnim majčinim hormonom za stimulaciju štitnjače (TSH). Cilj naše studije bio je istražiti je li IMH povezan sa štetnim ishodom trudnoće u Sjevernoj Makedoniji. U 359 trudnica koje su zadovoljile kriterije uzeti su uzorci osušene kapi krvi koji su analizirani na TT4 i TSH. Podaci nakon porođaja uneseni su za svaku majku iz njihove povijesti bolesti. Od ukupno 359 žena 131 (37,42%) je pripadala skupini IMH. Utvrđene su statistički značajne razlike u porođajnoj težini (p=0,043), intrauterinom ograničenju rasta (IUGR) (p=0,028), Apgar zbroju u 1. minuti <7 (p=0,018) i carskom rezu zbog distocije/disproporcije (p=0,024) između skupina s IMH i s normalnom funkcijom štitnjače (NFŠ). U regresijskoj analizi TSH je bila značajna varijabla za predviđanje Apgar zbroja (βst=0,05597, p=0,047), indeks tjelesne mase (ITM) za predviđanje porođajne težine (βst=0,02338, p=0,045) i TT4 za predviđanje rođenja djeteta malog za gestacijsku dob/IUGR (βst=-0,089834, p=0,029) u skupini IMH. TT4 je bio snažni prediktor porođajne težine (βst=-0,004778, p=0,003) i prijevremenog porođaja (βst=0,028112, p=0,004) u skupini NTF. Učinak IMH u trudnoći i dalje je proturječan. IMH je bio povezan s povećanim ITM majke i većom težinom novorođenčeta. Prekomjerna težina može biti potencijalni čimbenik rizika za disfunkciju štitnjače u trudnica, osobito IMH. Najgori fetalni ishod bio je kod majki s IMH koje su ispitane u drugom tromjesečju. TSH, TT4 i ITM snažni su prediktori za perinatalni ishod

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia

Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypothyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy