Paraoxonase and arylesterase activity of paraoxonase 1 and oxidative stress parameters in cervical intraepithelial neoplasia.

Introduction: Paraoxonase 1 (PON1) is the enzyme that removes carcinogenic radicals from lipids. The aim of the study was to investigate the differences in PON1 activity and oxidation stress parameters between patients with cervical intraepithelial neoplasia (CIN) and healthy controls. Materials and methods: The study included 65 women with CIN and 109 healthy women. Lipid parameters were determined on Cobas Integra 400 plus (Roche, Mannheim, Germany). Tiols and reduced glutathione (GSH) were determined spectrophotometric using Eliman reagent. Activity of PON1 was assessed with two substrates, paraoxon and phenylacetate by spectrophotometric method. Malondialdehyde (MDA) was determined by high performance liquid chromatography (Shimadzu Corporation, Kyoto, Japan). Mann-Whitney-test, t-test, χ2-test, correlation and logistic regression was used in statistical analysis. P < 0.05 was considered statistically significant. Results: The basal (P = 0.929) and NaCl-stimulated (P = 0.985) PON1 activity and activities standardised on the concentration of high-density lipoprotein (HDL; P = 0.076; P = 0.065, respectively) and apolipoprotein AI (apo AI; P = 0.444; P = 0.499, respectively) as well as PON1 phenotypes (P = 0.842) did not differ significantly between the groups. The PON1 arylesterase activity (53±19 kU/L vs. 77±17 kU/L; P < 0.001) and HDL-standardized activity (37 (28-44) kU/mmol vs. 43 (37-50) kU/mmol; P < 0.001) and apoAI (29±11 kU/g vs. 44±11 kU/g; P < 0.001) was significantly reduced in the CIN group. The concentration of the thiol groups was similar (P = 0.519), of MDA was lower (0.39 (0.27-0.55) µmol/L vs. 0.76 (0.57-1.15) µmol/L; P < 0.001) and of GSH was higher (112.0 (66.0-129.6) µg/mL vs. 53.4 (34.8-134.4) µg/mL; P < 0.001) in the CIN group. Conclusion: Reduced PON1 arylesterase activity, lower MDA and higher GSH concentration were observed in CIN patients.

The effects of HPV oncoproteins on host communication networks: Therapeutic connotations.

Human papillomavirus (HPV) infections are a leading cause of viral-induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms. A comprehensive understanding of these molecular alterations is essential for the development of targeted therapies and strategies to combat HPV-induced premalignancies and prevent their progress to cancer. Furthermore, this review underscores the intricate interplay between HPV oncoproteins and some of the most important cellular signaling pathways: Notch, Wnt/ß-catenin, MAPK, JAK/STAT, and PI3K AKT/mTOR. The treatment efficacies of the currently available inhibitors on these pathways in an HPV-positive context are also discussed. This review also highlights the importance of continued research to advance our knowledge and enhance therapeutic interventions for HPV-associated diseases.

Effect of Alpha-Lipoic Acid Supplementation on Low-Grade Squamous Intraepithelial Lesions-Double-Blind, Randomized, Placebo-Controlled Trial.

Low-grade squamous intraepithelial lesion (SIL) is a cytologic diagnosis etiologically related to human papilloma virus (HPV) infection that leads to the release of inflammation mediators, the formation of reactive oxygen species (ROS) and decreased levels of antioxidants in tissues, which is why antioxidants might be considered effective against SIL progression. This randomized double-blind placebo-controlled study aimed to investigate the effectiveness of alpha-lipoic acid (ALA) supplementation (600 mg/day) on the regression of low-grade SIL in 100 patients. Low-grade SIL was determined after the cytological screening, colposcopic examination and targeted biopsy and histological confirmation of cytological−colposcopic diagnosis. Inflammation parameters and the presence of HPV were determined by standard laboratory methods. Dietary and lifestyle habits were investigated using a standardized and validated semi-quantitative food questionnaire (FFQ). ALA supplementation significantly reduced the proportion of patients with low-grade cytological abnormalities, in comparison to placebo. Given the obtained level of significance (p < 0.001), the presented results indicate that short-term ALA supplementation shows a clinically significant effect on cervical cytology. Future studies should focus on the use of innovative formulations of ALA that might induce bioavailability and therapeutic efficiency against HPV infection and the investigation of synergistic effects of concurrent dietary/lifestyle modification and ALA supplementation in both low-grade and high-grade SIL.

URETERAL TRIPLICATION ACCIDENTALLY FOUND DURING CERVICAL CARCINOMA OPERATION.

Ureteral triplication is a very rare anomaly found in the upper urinary tract. This condition can be connected with a higher incidence of congenital anomalies and predisposition for urinary infections. Operative procedure is considered in cases where symptoms reduce the patient's quality of life. The type of surgical treatment depends on symptom manifestation. The risk of renal failure is usually a deciding factor, which can be found in conditions such as vesicoureteral reflux, obstruction, ureteral ectopy and recurrent infections. Simultaneous treatment of upper and lower urinary tract can be performed. We report a case of a 38-year-old female patient diagnosed with cervical carcinoma, where ureteral triplication was detected incidentally during a radical operative procedure.

UTERINE RUPTURE IN THIRD TRIMESTER OF PREGNANCY FOLLOWING CORNUAL RESECTION DUE TO ECTOPIC PREGNANCY.

Uterine rupture during pregnancy is a critical obstetric complication associated with maternal and fetal mortality and morbidity. The risk is increased in patients with a history of previous uterine surgery including cesarean section, myomectomy, salpingectomy, as well as uterine and placental anomalies and polyhydramnios. It can also occur spontaneously. We present a case of uterine rupture in the early third trimester in a woman who had undergone previous laparoscopic removal of the left fallopian tube due to sactosalpinx and laparotomic removal of left uterine horn due to ectopic pregnancy.

The association of the decline in glomerular filtration rate with aggressive endometrial cancers.

PURPOSE: Most site-specific cancer incidence is increased with the decrease of glomerular filtration rate (GFR). We analyzed endometrial cancers depending on different type, staging, and histology grades. We hypothesized that patients with lower GFR levels have an increased risk for higher staging and histology grades of endometrial cancers. METHODS: Patients were divided into two subgroups regarding GFR; the first group with GFR < 60 ml/min and the second group with GFR > 60 ml/min and regarding different histology grades and cancer stages. Cancers were also divided by stages (1-4). Patients were followed up during 1 year through regular controls in the outpatient clinic and during that time cancer recurrence was recorded. RESULTS: GFR was the strongest predictor for higher cancer histology grade and higher cancer staging. Patients with reduced GFR had OR for higher histology grade and higher staging of 1.06 and 1.06. Traditional risk factors for endometrial cancer development were not associated with higher histology grade or higher cancer staging. CONCLUSION: Higher staging and histology grades in patients with endometrial cancers are associated with reduced GFR. Patients with mild-to-moderate CKD had significantly higher number of cancers with higher histology grades and higher stages than patients with mild or normal GFR category. Decline in GFR was independently associated with more aggressive cancers without other well-known risk factors for endometrial cancer development like age, menopause, diabetes, and obesity.

Spontaneous Rupture of Venae Gastricae Breves in Pregnancy: Case Report.

INTRODUCTION: Hemiperitoneum caused by venous bleeding from the hilum of the spleen is a rare cause of acute abdomen in the last trimester of pregnancy. MATERIAL AND METHODS: We are presenting a case of a twenty-nine-year-old primipara with the clinical picture of acute abdomen. CASE REPORT: Primipara in the 36th week of pregnancy presented with the clinical picture of acute abdomen with the ultrasound finding of free fluid in the abdominal cavity and foetal bradycardia. Considering the clinical picture of the mother and the risks for the foetus, it was decided to complete the pregnancy with an emergency caesarean section. During the procedure, exploration of the abdominal cavity found the bleeding site from the venae gastricae breves, and a surgeon stopped active bleeding. CONCLUSION: Non-obstetric bleedings are not common in pregnancy, but they are life-threatening both to the mother and the foetus. The exact cause is usually found during the surgical procedure. If a pregnant woman presents with a clinical picture of abdominal pain, and the signs of foetal distress or clinical instability of the mother are also present, an emergency surgical procedure is indicated. In this case, the indication was foetal bradycardia, and the child was born alive by a caesarean section, while an extended surgical procedure saved the mother's life.

Subcutaneous Dirofilariasis in Female Pubic Region - Case Report.

BACKGROUND: Number of reported cases of human dirofilariasis in the last couple of decades has been increasing. Dogs are the main reservoir hosts, while various mosquito species represent/serve as vectors. Human infections are caused by two different parasites: Dirofilaria immitis and Dirofilaria repens. Dirofilaria repens is currently considered to be one of the most rapidly-spreading human and animal parasite species in Europe. Clinical features are characterised by subcutaneous or ocular lesions which can persist for months without any symptoms. The disease is considered to be endemic in Mediterranean countries, central Asia, Israel, and Sri Lanka with increased incidence in Central and East Europe. Apart from the local population, tourists are also susceptible to this disease. Export of domestic animals can transfer parasites between different countries. This disease is rare in Croatia. CASE PRESENTATION: We are presenting a case of a 58-year-old female patient with dirofilariasis of the genital region caused by Dirofilaria repens, confirmed with PCR and sequencing. CONCLUSION: From the clinician point of view, subcutaneous dirofilariasis should be considered as a differential diagnosis in cases of long-lasting subcutaneous swellings.

TWENTY-YEAR EXPERIENCE WITH LARGE LOOP EXCISION OF THE TRANSFORMATION ZONE AT SESTRE MILOSRDNICE UNIVERSITY HOSPITAL CENTRE.

The 20-year experience with large loop excision of the transformation zone (LLETZ) at Gynecologic Oncology Unit, Department of Gynecology and Obstetrics, Sestre milosrdnice University Hospital Centre from Zagreb is presented. This retrospective observational study included 1407 women with cervical dysplasia treated by LLETZ technique during the 1995-2016 period. LLETZ was most commonly performed in the 25-35 age group (51%), followed by the 36-45 age group (22%), and least frequently in the >65 age group (2%). Histopathologic results lower than high-grade squamous intraepithelial lesion were found in 23% and high grade squamous intraepithelial lesion or worse findings in 77% of patients. Positive margin as a sign of possible residual dysplasia was found in 25% of cones, 80% of which included endocervical positive margin. Cervical canal biopsy result was positive in 18% of cases. Accurate colposcopy and its findings can help avoid overtreatment, the rate of which was higher than expected in our retrospective study. Long-term follow up is an imperative for proper assessment of the procedure success. This method is the best choice for complete disease removal without unnecessary overtreatment, but it requires continuous education and training of the whole team.

Spontaneous Rupture of Internal Iliac Artery in Pregnancy: Case Report.

Rupture of the internal iliac artery is a rare complication in pregnancy that is associated with maternal and fetal morbidity and mortality. We present a case of a 30-year-old primipara admitted to our department in 39th week of gestation after sudden onset of intense abdominal pain. On admission, the patient was pale, tachycardiac, but with normal blood pressure and afebrile. Symptoms of acute abdomen were clear and surgery was indicated. Diagnosis was confirmed during cesarean section. Enlarged gravid uterus compressed the ruptured artery and prevented heavier bleeding. Acute bleeding due to arterial rupture causes severe symptoms, predominantly abdominal pain. Changes in blood count become significant some time after the onset of rupture. As the gravid uterus compressed the arterial rupture, preoperative bleeding was by far less abundant than the bleeding after the baby had been delivered and the size of the uterus decreased. Any cause of acute abdomen during pregnancy (abruption of the placenta, spleen rupture, visceral artery thrombosis) requires urgent surgical treatment, as well as intraoperative and postoperative intensive treatment. Rupture of the internal iliac artery is a rare complication in pregnancy, but has to be considered as a differential diagnosis of abdominal pain.

Henoch-Schönlein purpura in the third trimester of pregnancy.

Henoch-Schönlein purpura (HSP) is an IgA-mediated small vessels' vasculitis that affects the skin, intestines and kidneys. Pregnancy has been reported as an exacerbating factor. We present the case of a 24-year-old primigravida with HSP that occurred in the third trimester and lasted up to the end of the successful delivery. She had pruritic maculopapular exanthema on her legs. Biopsy of a cutaneous lesion was performed for histopathologic features and direct immunofluorescence (DIF) for the presence of perivascular IgA deposition. Histopathology of the cutaneous lesion confirmed leukocytoclastic vasculitis. A DIF examination of the skin lesion confirmed deposits of fibrinogen in the small blood vessel walls. Six weeks following delivery, the skin lesions almost completely disappeared. Control laboratory findings were normal. This case of HSP might have been primarily associated with a preceding respiratory infection but this should first be carefully investigated due to a possible severe immunological disease in the patient's background requiring special attention since nephrotic symptoms may occur.

Obesity and hypercholesterolemia in patients with prolactinomas: Could DHEA-S and growth hormone be the missing link?

PURPOSE: Increasing evidence exists that hyperprolactinemia alters metabolic profile. The mechanism of this effect is unknown. We aimed to investigate the differences between the metabolic profile of patients with prolactinomas and nonfunctional pituitary adenomas and to evaluate the impact of other pituitary hormones on their metabolic profile. METHODS: Our retrospective study included 86 consecutive patients with prolactinomas and nonfunctional adenomas (29 prolactinomas and 57 adenomas). Body mass index (BMI), blood pressure, serum prolactin, growth hormone (GH), insulin-like growth factor I (IGF-I), adrenocorticotropic hormone (ACTH), cortisol, urinary free cortisol, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), dehydroepiandrosterone-sulfate (DHEA-S), testosterone in men, triglycerides, total cholesterol, HDL (high-density lipoprotein) cholesterol, LDL (Low-density lipoprotein) cholesterol, alanine-transaminase, aspartate-transaminase, fasting glucose, and C-reactive protein (CRP) were obtained for all patients. Regression analyses were performed on log-transformed data. RESULTS: After adjustment for age, gender, and tumor size, prolactinomas were associated with higher BMI (OR 5.61, 95%CI 1.70-9.51, p = 0.005), LDL cholesterol (OR 3.60, 95%CI 1.35-5.93, p = 0.015), DHEA-S (OR 1.97, 95%CI 1.23-3.72, p = 0.026), and lower GH levels (OR 0.43, 95%CI 0.03-0.84, p = 0.037). In a linear multivariate regression, the association between DHEA-S, GH, and prolactin remained significant even after adjustment for BMI. GH and IGF-I were associated with BMI and LDL cholesterol, but the association diminished after adjustment for serum prolactin. CONCLUSIONS: Prevalence of obesity is four times higher in patients with prolactinomas than in patients with nonfunctional adenomas. Higher DHEA-S and lower GH levels in patients with prolactinomas may have an important role in prolactin-induced metabolic effects. Further studies are needed.

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

AIMS: To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. STUDY DESIGN: This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). RESULTS: 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). CONCLUSION: Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta.

Coexistence of ruptured ectopic tubal pregnancy, dermoid and endometriotic cyst with tubo-ovarian abscess in the same adnexa: case report.

A 32-year-old pregnant woman presented to the hospital with abdominal pain and minimal vaginal bleeding. Transvaginal ultrasound revealed visible fluid in pelvic region with suspected tubal rupture, and subsequently laparoscopy was performed. During laparoscopy, additional gynecologic pathologies were noticed. Histopathologic finding showed dermoid and endometriotic cyst, as well as tubo-ovarian abscess in the same adnexa. This case report highlights the necessity of considering multiple diagnoses in the same organic system, which may be encountered by surgeon and histopathologist.

Paraoxonase 1 activity and phenotype distribution in premenopausal and postmenopausal women.

INTRODUCTION: Postmenopausal women have higher risk of cardiovascular disease. One of the contributing factors could be reduced activity of anti-atherogenic enzyme paraoxonase 1 (PON1). The aim of this study was to examine differences in the lipid status, paraoxonase and arylesterase PON1 activities and PON1 phenotype in women with regular menstrual cycle and in postmenopausal women. MATERIALS AND METHODS: The study included 51 women in reproductive age (25 in follicular and 26 in luteal phase of the menstrual cycle) and 23 women in postmenopause. Lipid parameters in sera were determined using original reagents and according to manufacturer protocol. PON1 activity in serum was assessed by spectrophotometric method with substrates: paraoxon and phenylacetate. PON1 phenotype was determined by double substrate method. RESULTS: Compared to the women in follicular and luteal phase, postmenopausal women have significantly higher concentration of triglyceride [0.9 (0.7-1.3), 0.7 (0.6-1.0) vs. 1.5 (0.9-1.7) mmol/L; P = 0.002], cholesterol [5.10 (4.78-6.10), 5.05 (4.70-5.40) vs. 6.30 (5.73-7.23) mmol/L; P < 0.001], LDL [3.00 (2.56-3.63), 3.00 (2.70-3.70) vs. 3.90 (3.23-4.50) mmol/L; P < 0.001], and apolipoprotein B [0.88 (0.75-1.00), 0.79 (0.68-1.00) vs. 1.07 (0.90-1.24) mmol/L; P = 0.002]. PON1 basal [104 (66-260), 106 (63-250) vs. 93 (71-165) U/L; P = 0.847] and salt-stimulated paraoxonase activity [210 (131-462), 211 (120-442) vs. 180 (139-296) U/L; P = 0.857] as well as arylesterase activity [74 (63-82), 70 (54-91) vs. 70 (60-81) kU/L; P = 0.906] and PON1 phenotype (P = 0.810) were not different in the study groups. CONCLUSION: There are no differences in PON1 activity and PON1 phenotype between women with regular menstrual cycle and postmenopausal women.

Biochemical screening of fetal aneuploidies and neural tube defects by "double-test" in Croatia: a 10 years' experience.

The aim of the study is to investigate the efficiency of the second-trimester biochemical screening, with maternal serum alpha-fetoprotein (MS-AFP) and free beta-subunit of human chorionic gonadotropin (free beta-hCG), during the ten-year period. The study included 11,292 of pregnant women between the 15th and 18th gestational week, who underwent screening from November 1996 to December 2006. The risk for trisomy 21 and trisomy 18 were calculated by computer software, based on a model which generated the final risk for fetal aneuploidies from the pregnant woman's a priori age risk and the likelihood ratio of the distribution of the biochemical markers, according to the second-trimester gestation. With the cut-off value of the final risk > or = 1:250, the detection rate for trisomy 21 was 75% (21/28). In women less than or equal to 35, the detection was 57.1% (8/14) and 92.9% (13/14) in those over 35 years, respectively. The detection rate of trisomy 18 was 50% (2/4). The results confirmed that the implementation of double-test, as non-invasive screening for fetal aneuploidies, should be accepted as a complementary method of antenatal care.