Effect of Interaction between Chromium(VI) with 17ß-Estradiol and Its Metabolites on Breast Cancer Cell Lines MCF-7/WT and MDA-MB-175-VII: Preliminary Study.

The number of factors initiating and stimulating the progression of breast cancer are constantly increasing. Estrogens are a risk factor for breast adenocarcinoma, the toxicity of which increases as a result of metabolism and interaction with other factors. Due to the presence of environmental exposure to estrogens and metalloestrogens, we investigated how interactions between estrogens and toxic chromium(VI)[Cr(VI)] affect breast cancer lines and investigated whether estrogens play a protective role. The aim of the study was to investigate the effect of 17ß-estradiol and its metabolites: 2-methoxyestradiol (2-MeOE2), 4-hydroxyestradiol (4-OHE2), and 16α-hydroxyestrone (16α-OHE1) in exposure to Cr(VI) on cell viability and DNA cell damage. Two estrogen-dependent breast cancer cell lines, MCF 7/WT and MDA-MB-175-VII, were examined. In addition, the expression of Cu-Zn superoxide dismutase (SOD1) was determined immunocytochemically to elucidate the mechanism of oxidative stress. The effects of single substances and their mixtures were tested in the model of simultaneous and 7-day estrogen pre-incubation. As a result, the viability of MCF-7 and MDA-MB-175-VII cells is lowered most by Cr(VI) and least by 17ß-E2. In the combined action of estrogens and metalloestrogens, we observed a protective effect mainly of 17ß-E2 against Cr(VI)-induced cytotoxicity. The highest expression of SOD1 was found in MCF-7/WT cells exposed to 17ß-E2. Moreover, high apoptosis was caused by both Cr(VI) itself and its interaction with 4-OHE2 and 2-MeOE2. The direction and dynamics of changes in viability are consistent for both lines.

The Influence of Interaction between Cadmium with 17ß-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone on Viability and p-Glycoprotein in Ovarian Cancer Cell Line.

Occupational and environmental exposure to xenoestrogens, a subgroup of endocrine disruptors (EDCs), can affect the endocrine system and increase the risk of cancer, primarily the hormone-dependent kind. This type of cancer includes ovarian cancer, which is the leading cause of death from gynecological tumors. The aim of this study was to assess the role of 17ß-estradiol and its metabolites: 2-MeOE2, 16α-OHE1 in exposure to the metalloestrogen cadmium. The effect of interactions of cadmium with estrogens on the viability of cells in malignant ovarian cancer cells SKOV-3 was investigated, both in simultaneous action and in the pre-incubation model. There are no known interactions between estrogens and cadmium in ovarian cancer cells. Due to the frequent occurrence of multidrug resistance (MDR) in ovarian cancer, the effects of estrogens and cadmium on MDR in SKOV-3, measured as P-glycoprotein (P-gp), were assessed. An interaction study showed that E2 had an antagonistic effect on cadmium-induced cell damage, while 2-MeOE2 showed less of a protective effect in combination with CdCl2 than E2. There were two types of interaction: toxic synergism and beneficial antagonism. E2 and cadmium increased P-gp expression in SKOV-3 cells, while 2-MeOE2 decreased P-gp expression to a potentially beneficial effect on MDR prevention. The obtained results constitute an interesting starting point for further research in the field of interactions between estrogens and xenoestrogens in ovarian cancer.

Effects of Different Timing of Alveolar Bone Graft on Craniofacial Morphology in Unilateral Cleft Lip and Palate.

OBJECTIVE: To evaluate the effect of the timing of secondary alveolar bone graft (SABG) on craniofacial morphology in patients with complete unilateral cleft lip and palate (UCLP). DESIGN: Single-center retrospective assessment of consecutively treated nonsyndromic patients with complete UCLP. PARTICIPANTS: One hundred sixty-seven patients (108 males, 59 females) with complete UCLP in whom the cleft was repaired with 1-stage method at approximately 8 months of age. The age of 128 patients at SABG varied from 1.4 to 11.5 years (SABG group), while 39 patients still awaited SABG at the moment of cephalometric evaluation (no-SABG group). METHODS: Craniofacial morphology was assessed on lateral cephalograms taken at 10 years of age (standard deviation = 0.8; range: 7.5-12.3) using linear and angular measurements. T tests and regression models were made to analyze data. RESULTS: Regression models demonstrated that the effect of SABG on the craniofacial morphology was limited-cephalometric variables which were statistically significantly different between SABG and no-SABG groups showed no association with the timing of SABG when (1) age of primary repair of the cleft, (2) age of cephalometric evaluation, (3) cleft side, (4) gender, and (5) operator were controlled for. Only the length of the maxilla (Condylion-point A) was affected-1-year delay of SABG corresponded with an increase in Co-point A distance by 0.52 mm. However, adjusted R2 of the model was 0.11. CONCLUSIONS: Our findings cautiously indicate that SABG performed before 8 years of age can have limited negative effect on craniofacial morphology. Nevertheless, our results should be confirmed by cleft centers practicing alternative surgical repairs of the cleft.

Effect of Interaction between 17ß-Estradiol, 2-Methoxyestradiol and 16α-Hydroxyestrone with Chromium (VI) on Ovary Cancer Line SKOV-3: Preliminary Study.

Ovarian cancer is the leading cause of death from gynecologic malignancies. Some estrogens, as well as xenoestrogens, such as chromium (VI) (Cr(VI)), are indicated as important pathogenic agents. The objective of this study was to evaluate the role of estradiol and some its metabolites upon exposure to the metalloestrogen Cr(VI) in an in vitro model. The changes in cell viability of malignant ovarian cancer cells (SKOV-3 resistant to cisplatin) exposed to 17ß-estradiol (E2) and its two metabolites, 2-methoxyestradiol (2-MeOE2) and 16α-hydroxyestrone (16α-OHE1), upon exposure to potassium chromate (VI) and its interactions were examined. The single and mixed models of action, during short and long times of incubation with estrogens, were applied. The different effects (synergism and antagonism) of estrogens on cell viability in the presence of Cr(VI) was observed. E2 and 16α-OHE1 caused a synergistic effect after exposure to Cr(VI). 2-MeOE2 showed an antagonistic effect on Cr(VI). The examined estrogens could be ranked according to the most protective effect or least toxicity in the order: 2-MeOE2 > E2 > 16α-OHE1. Early pre-incubation (24 h or 7 days) of cells with estrogens caused mostly an antagonistic effect-protective against the toxic action of Cr(VI). The beneficial action of estrogens on the toxic effect of Cr(VI), in the context of the risk of ovarian cancer, seems to be important and further studies are needed.

Estrogen Receptors in Cell Membranes: Regulation and Signaling.

Estrogens can stimulate the development, proliferation, migration, and survival of target cells. These biological effects are mediated through their action upon the plasma membrane estrogen receptors (ERs). ERs regulate transcriptional processes by nuclear translocation and binding to specific response elements, which leads to the regulation of gene expression. This effect is termed genomic or nuclear. However, estrogens may exert their biological activity also without direct binding to DNA and independently of gene transcription or protein synthesis. This action is called non-genomic or non-nuclear. Through non-genomic mechanisms, estrogens can modify regulatory cascades such as MAPK, P13K, and tyrosine cascade as well as membrane-associated molecules such as ion channels and G-protein-coupled receptors. The recent studies on the mechanisms of estrogen action provide an evidence that non-genomic and genomic effects converge. An example of such convergence is the potential possibility to modulate gene expression through these two independent pathways. The understanding of the plasma membrane estrogen receptors is crucial for the development of novel drugs and therapeutic protocols targeting specific receptor actions.

THE ESTROGENS / CHROMIUM INTERACTION IN THE NITRIC OXIDE GENERATION.

The interaction of estrogens with environmental toxins in free radicals generation: reactive oxygen species (ROS) or reactive nitrogen species (RNS) which participates in cancerogenesis is not yet recognized. Chromium(VI) is widely present in environment. One of its toxicity pathway is free radicals generation. Estrogens have the ability to scavenge free radicals, but may also act as prooxidants. Both chromium(VI) and estrogens are classified by International Agency for Research on Cancer (IARC) as carcinogens, so synergistic effect seems very dangerous. The interaction of chromium and estrogens in ROS generation are partly described but there are no reports on estrogen/chromium interaction on nitric oxide (NO) generation. The aim of the study was to examine the interaction of chromium(VI) and 17-p-estradiol (E2) on NO level in human blood as well as the role of E2 metabolites: 4-hydroxyestradiol (4-OHE2) and 16a-hydroxyestrone (16α-OHE1) in these processes. The NO level was estimated with the diagnostic kit (Nitric Oxide Colorimetric Detection Kit from Arbor Assays) in human blood in vitm. The results showed that Cr(VI) in used concentration (0.5; 1.0 and 5.0 gg/mL) decreases significantly NO level in blood, acting antagonistically to E2 and 4-OHE2. Estrogens (E2, 4-OHE2 and 16α-OHEI) do not protect against inhibiting effect of Cr(VI) on nitric oxide generation in blood because after combined exposure the decreased production of NO in blood was noted. In conclusion, presented results provide the information about the character of estrogen/Cr(VI) interaction in NO level in human blood. It is important knowledge for cardio protected effect e.g., hormone replacement therapy in environmental or occupational exposure to Cr(VI), chromium supplementation, also important for cancer risk evaluation.

Giant congenital melanocytic nevi: selected aspects of diagnostics and treatment.

BACKGROUND: Treatment of giant melanocytic nevi (GMN) remains a multidisciplinary challenge. We present analysis of diagnostics, treatment, and follow- up in children with GMN to establish obligatory procedures in these patients. MATERIAL/METHODS: In 24 children with GMN, we analyzed: localization, main nevus diameter, satellite nevi, brain MRI, catecholamines concentrations in 24-h urine collection, surgery stages number, and histological examinations. The t test was used to compare catecholamines concentrations in patient subgroups. RESULTS: Nine children had "bathing trunk" nevus, 7 had main nevus on the back, 6 on head/neck, and 2 on neck/shoulder and neck/thorax. Brain MRI revealed neurocutaneous melanosis (NCM) in 7/24 children (29.2%), symptomatic in 1. Among urine catecholamines levels from 20 patients (33 samples), dopamine concentration was elevated in 28/33, noradrenaline in 15, adrenaline in 11, and vanillylmandelic acid in 4. In 6 NCM children, all catecholamines concentrations were higher than in patients without NCM (statistically insignificant). In all patients, histological examination of excised nevi revealed compound nevus, with neurofibromatic component in 15 and melanoma in 2. They remain without recurrence/metastases at 8- and 3-year-follow-up. There were 4/7 NCM patients with more than 1 follow-up MRI; in 1 a new melanin deposit was found and in 3 there was no progression. CONCLUSIONS: Early excision with histological examination speeds the diagnosis of melanoma. Brain MRI is necessary to confirm/rule-out NCM. High urine dopamine concentration in GMN children, especially with NCM, is an unpublished finding that can indicate patients with more serious neurological disease. Treatment of GMN children should be tailored individually for each case with respect to all medical/psychological aspects.

[The role of oxidative stress in bladder cancer]. / Rola stresu oksydacyjnego w raku pecherza moczowego.

The review of the knowledge concerning the impact of oxidative and nitrosative stress on signaling pathways and transcription factors involved in the formation of bladder cancer was prepared. In the industrialized countries, bladder cancer is the fourth most frequently occurring malignant tumors. Recent studies indicate the involvement of oxidative and nitrosative stress in the formation and development of this disease. Red-ox disorders are characteristic for both, the initiation and progression of bladder cancer. There are observed changes in the activity of transcription factors, such as nuclear factor NF-kB; transcription factors: AP-1, Nrf2 and STAT3 and hypoxia-inducible factor HIF-1α. In addition, studies indicate a role for oxidative stress in the regulation of MAPK cascade and its involvement in carcinogenesis consisting bladder. Examples of kinases belonging to the MAPK family are ERK kinases, which expression is proportional to the severity and malignant of bladder cancer. Nitric oxide also plays an important role in tumor biology. Overproduction of NO can both inhibit and promote tumor growth, depending on its concentration, duration of action and tumor microenvironment. Numerous studies show that the bladder cancer is characterized by an intensified production of NO. Reactive forms of nitrogen, similar to oxygen free radicals, could cause oxidative and nitrosative damage to DNA and have capacity to post-translational modification of proteins. In contrast to the ROS, which overproduction result from exposure to carcinogenic xenobiotic, nitrogen oxide in high level is produced during inflammation. Sustained iNOS activity therefore plays an important role in carcinogenesis associated with the inflammatory response, characteristic also for bladder cancer.

Meconium ileus in newborns with cystic fibrosis - results of treatment in the group of patients operated on in the years 2000-2014.

AIM: Evaluation of diagnostic and treatment procedures in children with cystic fibrosis (CF) operated on because of meconium ileus (MI). MATERIAL AND METHODS: The authors retrospectively reviewed the documentation of 10 CF newborn patients operated on in the years 2000-2014 because of MI. In prenatal ultrasound (US) examinations, suspicion of bowel abnormalities was raised in 2 cases, even though all the 10 mothers had a minimum of 3 US examinations during pregnancy. The mean gestational age of the newborns was 39.2 weeks - 36-41 weeks), their mean birth weight 3472g (2560-4550 g). Family history of CF was positive in two patients. Genetic testing was performed in all the children operated on. RESULTS: In all the children operated on, mutations in both alleles of the CFTR gene were found. Five patients were F508del homozygotic, 4 were heterozygotic for this mutation, one had another mutation. Sweat tests were positive in all the children. Abdominal distention was observed in 9 patients, vomiting and retention of gastric contents in 5. In 8 children meconium was not passed at all. 2 children passed a small amount of viscid meconium. Before the operation, rectal saline washouts were done in 5 newborns. Five patients were operated on during the first day of life, four on the second day and one on the third day of life. Intra-operatively a simple form of MI was diagnosed in 8 cases, a complicated form in 2 cases. In patients with the simple form of MI, a Bishop-Koop stoma was created after the evacuation of meconium. Two of these children needed a resection of some centimetres of dilated terminal ileum with doubtful viability. In newborns with the complicated form of MI, the treatment was individualized, always with stoma formation. The time of postoperative meconium evacuation through enterostomy ranged from 6 to 15 days. Enteral feeding was started on average on the 9th day postoperatively. The mean hospital stay was 22.9 days. In 8 children the stoma was taken out at the mean age of 19.4 months, in one patient the stoma closed spontaneously. No disturbances in electrolyte balance or excessive fluid loss, nor any body weight deficits connected with the stoma were observed. There were no complications during stoma closure. All the patients are alive. The time of observation ranges from 7 to 146 months (average 95 months). All the patients currently present respiratory symptoms, have pancreatic insufficiency and need pancreatic enzyme supplementation. Seven do not, however, have body weight and height deficits. All the children with weight and height deficits have abnormal liver function tests. During observation two patients had MI equivalent symptoms, which was resolved by conservative treatment. CONCLUSIONS: 1. In every case of intra-operative diagnosis of MI, it is necessary to perform genetic testing and sweat tests to confirm or exclude CF. 2. Mechanical intra-operative decompression of the bowel from inspissated meconium with a temporary stoma, which makes the continuation of bowel decompression possible in the postoperative period, is an effective treatment in children with MI. 3. The Bishop-Koop stoma, permitting the passage through the whole gastrointestinal tract, is a safe option. In our material, no complications of this stoma, such as stoma care problems or dyselectrolithemia were observed. 4. The decision of stoma closure in children with MI and CF should be delayed until the moment of introducing a broadened diet and should be undertaken together with a pediatrician who is a specialist in CF therapy. .

Outcome of alveolar bone grafting in patients with unilateral cleft lip and palate operated by one-stage method.

UNLABELLED: The aim of the study was the assessment of outcome of alveolar bone grafting in patients with unilateral cleft lip and palate operated on by the one-stage surgical procedure. MATERIAL AND METHODS: The study concerned 108 patients (69 boys, 39 girls) with unilateral cleft of lip and palate operated by one stage method in the Surgical Department of Children and Adolescents IMC between 1994 and 2003. The reconstruction of alveolar process in these patients was carried out by autogenic bone graft at the age ranged from 1.5 to 16 years. The surgical procedure was the same regardless of age. The patients were divided into 3 groups according to age during this procedure: I- below 6 years, II - between 6 and 10 years, III - above 10 years. Evaluation of outcome of bone grafting was assessed on the base of Oslo classification and Chelsea scale. The relation between the patient's age at the time of bone grafting and the bone healing result was analyzed by the Spearman's rank correlation coefficient for the studied group as a whole, the age subgroups and the gender groups. RESULTS: Good results of treatment (I and II type) was obtained in 93 (86%) of patients, bad (III and IV type) in 15 patients according to Olso classification. According to Chelsea scale ultimate or satisfactory results (A, B, C) were obtained in 93 patients (86%) , unsatisfactory results (D, E, F) were obtained in 15 patients. Negative correlation between bone graft outcome and age of patients at the time of the procedure above 6 years was confirmed. No statistical significance in relation to sex of patients was found. CONCLUSIONS: According to two classifications (Oslo, Chelsea) good results of bone graft were obtained in 86% of patients. There was a relationship in outcome of bone grafting and the age of patients. The inter-gender correlation did not gain the statistical relevance.

Complete unilateral cleft lip and palate operated on by means of the one-stage method - own experience.

The study presents the surgical protocol of unilateral cleft lip and palate (UCLP) treatment based on the one-stage method. It is exemplified by the treatment course of a patient suffering from UCLP. The method was worked out and implemented at the Institute of Mother and Child in Warsaw. Its main advantage is the early establishment of the anatomical structures of the naso-oral cave and the facial part of the skull, before the development of speech. The complete closure of each part of the cleft - the soft and hard palate and the lip before the end of the first year of life, enables the quick implementation of the next stages of treatment, such as alveolar osteoplasty, which facilitates both orthodontic treatment and speech therapy.

Cephalic index in the evaluation of surgical treatment of children with sagittal synostosis. Preliminary report.

AIM OF THE STUDY: To analyze changes of the cephalic index (CI) values in patients with sagittal synostosis operated on in the Department of Surgery of Children and Adolescents of the Institute of Mother and Child in Warsaw. MATERIAL AND METHODS: The study group consisted of 14 consecutive cases (11 boys and 3 girls). In 8 patients younger than 3 months of age (1st subgroup) the modified reversed-pi technique (craniotomy in the shape of the reversed Greek π letter) was utilized. In 6 older infants and in patients with severe head deformity - the radical cranial vault reconstructions were performed (2nd subgroup). The statistical analysis of the preoperative (preop) and postoperative (postop) cephalic index (CI) values was done. RESULTS: For the entire study group the preop CI values ranged from 61 to 77 (mean 68.14, median 68.5) and postop CIs from 73 to 89 (mean 77.64, median 76). In the 1st subgroup the preop CIs ranged from 63 to 77 (mean 69.625, median 69) whereas the postop CIs from 69 to 89 (mean 78.125, median 76.5). In the 2nd subgroup the preop CI values ranged from 61 to 72 (mean 66.1667, median 66) and postop from 73 to 81 (mean 77, median 77). All the differences were statistically significant. CONCLUSION: The values of cephalic index increased after both types of procedures. It signifies the correction of dolichocephaly in both subgroups of the patients. However, because of the small number of operated children, further studies are necessary.

Surgical Treatment of Lip Pits in Van der Woude Syndrome: A Preliminary Retrospective Study of 24 Patients.

BACKGROUND: Van der Woude syndrome (VWS) is a rare congenital malformation characterized by lower lip pits among patients with a lip and/or palate cleft. It is transmitted by an autosomal dominant inheritance with variable expressivity. METHODS: The study group consisted of 24 consecutive patients (13 males and 11 females) with VWS operated on at a single center between 2009 and 2022. They suffered from: bilateral cleft lip and palate - 6 patients; unilateral cleft lip and palate - 9 patients; cleft lip - 1 patient; and isolated cleft palate - 8 patients. RESULTS: In 16 (66%) cases pits of lower lip occurred on both side of midline, while in 8 (34%) the pits were detected unilaterally. The primary cleft repairs were performed according to one-stage principle at the mean age of 8.6 months (SD 1.4, range 6-12). In all patients lower lip pits repairs were performed after the primary cleft repairs as a separate procedure at the mean age of 37 months (SD 11.3 range 14-85). The mean number of all primary repairs of the syndrome-both cleft defect and lower lip pits repairs-was 2.46. Nine patients (37.5%) required additional secondary corrections of the lower lip due to the poor aesthetic post-operative outcome. CONCLUSIONS: The frequent need for secondary corrections of residual lower lip deformities indicates the considerable difficulties in obtaining a satisfactory outcome of the repairs to lip pits caused by VWS. The average number of the primary surgical interventions in evaluated material remained low.

Prenatal ultrasound markers for prediction of complex gastroschisis-single-center retrospective cohort study.

OBJECTIVE: To evaluate prenatal ultrasound markers for distinguishing simple gastroschisis (sGS) from complex gastroschisis (cGS) and identifying fetuses at risk of complications. STUDY DESIGN: A retrospective cohort study analyzed 61 fetuses with isolated gastroschisis at a tertiary center from 2011 to 2021, utilizing serial ultrasounds from 14 to 35 weeks' gestation. A general linear model, quantile regression, and logistic regression assessed ultrasound markers, fetal weeks, and gastroschisis risk, yielding predictive models. RESULTS: IABL dilatation showed the highest PPV but low NPV. Non-free floating bowel loops (NFFBL) indicated the best PPV to NPV ratio. Combinations of markers yielded the highest predictive value for cGS. EABL collapsed and non-free floating bowel loops were significant, consistent risk factors. CONCLUSIONS: Prenatal ultrasounds can predict cGS risk, particularly using IABL dilatation and NFFBL as markers. Accurate assessment requires considering gestational age, qualitative symptoms, emphasizing experienced perinatologists' role and monitoring, particularly after 30 weeks of gestation.

The effects of coenzyme Q10 and baicalin in cisplatin-induced lipid peroxidation and nitrosative stress.

Cisplatin is the alkylating anticancer drug. These drugs show many side-effects including the damage of kidney. The nephrotoxicity of cisplatin is explained mainly by reactive oxygen species (ROS) generation. The increased level of lipids peroxidation was observed in patients treated with this drug. In the toxicity of cisplatin, are also involved reactive nitrogen species (RNS) such as nitric oxide (NO*) or peroxynitrite. The lack of cisplatin selectivity and its side effects tend to look for ways to reduce the toxicity in chemotherapy. Our previous studies demonstrated that oxidative stress caused by xenobiotics can sometimes be effectively inhibited by coenzyme Q10 and baicalin. The aim of our research was the evaluation of usefulness of two coenzyme Q10 forms: lipophilic, currently used (QA) and new, produced by nanotechnology, soluble in water, PureSorb-QTM40-P40 (QB). Also the utility of baicalin as free radicals scavenger in reducing the nephrotoxicity of cisplatin was examined. The study was performed on an in vitro model, human erythrocytes and serum. Oxidative stress was evaluated by the level of lipid peroxidation (TBARS method). The concentration of nitric oxide (NO*) and nitrate (NO3) was estimated in serum [Nitric Oxide Colorimetric Detection Kit (Cat. No. K023-H1) of Arbor Assays], based on reaction with Griess reagent. Cisplatin at concentration: 3.5, 10, 30 and 50 pg/mL significantly increased the level of TBARS in erythrocytes. All antioxidants: baicalin and two forms of coenzyme Q10 significantly inhibited TBARS compared to controls (p < 0.05). Both QA and QB studied in a wide range of concentrations (from 1.0 to 120.0 microg/mL) demonstrated their antioxidative effect. In all used doses they statistically significantly decreased TBARS level with the negative correlation (r = -0.751; p = 0.000). In the study of nitrosative stress, all doses of cisplatin increased NO* and NO3 level in serum (p < 0.05). Baicalin and QA showed no statistically significant influence on production of NO* and NO3 in serum, while QB unexpectedly increased these parameters. In joint exposure with cisplatin all three antioxidants, in the most of concentrations, decreased TBARS levels, elevated by cisplatin (p < 0.05). In nitrosative stress-induced by cisplatin, the most effective was QB, however, protective influence of all antioxidants varies and the results are ambiguous.

Speech and Burden of Secondary Surgical Interventions Following One-Stage Repair of Unilateral Cleft Lip and Palate and Alveolar Bone Grafting Performed at Different Timings.

A comprehensive assessment of the treatment outcome in cleft lip and palate involves evaluating speech and the impact of speech-correcting surgical interventions. This retrospective case-control study compared the speech outcomes of 37 boys and 19 girls with unilateral cleft lip and palate (UCLP) who underwent one-stage cleft repair at an average age of 8.1 months and alveolar bone grafting either before or after 6 years of age, with a non-cleft control group at an average age of 10 years. Two experienced speech and language pathologists conducted perceptual speech assessments using a specialized test of 27 sentences designed for Polish-speaking cleft patients. The results revealed that 5.3% had severe hypernasality, 1.8% had severely impaired speech intelligibility, 10.7% exhibited retracted compensatory articulations, and 7.1% displayed facial grimacing. Mild hyponasality was observed in 12.3% of patients, while 16.1% exhibited voice abnormalities. Additionally, 12.5% of patients required orofacial fistula repairs, 3.6% underwent pharyngoplasties, and 28.6% received ear ventilation tube insertions. The study indicates that speech abnormalities in UCLP patients were relatively infrequent and not highly severe, suggesting that the primary UCLP repair method presented effectively reduced the need for further surgical interventions, leading to positive speech outcomes.

The Effect of Metalloestrogens on the Effectiveness of Aromatase Inhibitors in a Hormone-Dependent Breast Cancer Cell Model.

Endocrine-disrupting compounds (EDC) play an important role in the increased incidence of breast cancer (BC). There are some 160 xenoestrogens that may be involved in the development of BC. Much less is known about the influence of xenoestrogens on the effectiveness of the treatment of BC. The aim of this study was to analyze the interaction of metalloestrogens (aluminum and chromium (III)) and drugs used in the treatment of hormone-dependent BC-aromatase inhibitors (AI)-letrozole and exemestane. A cell viability assay, a flow cytometer analysis of apoptosis and cell cycle phases, and protein activity of BAX and Bcl-2 were performed on two human breast cancer cell lines-MCF-7 and MCF-7/DOX. In MCF-7 cells, the lower concentration of exemestane and higher of letrozole, in combination with metalloestrogens, results in a decrease in the effectiveness of drugs. Additionally, in the MCF-7/DOX cell line, we observed that the combination of metalloestrogens and AI leads to a decrease in the drug's effectiveness due to an increase in the viability of breast cancer cells (both concentrations of letrozole and higher concentration of exemestane). In both cell lines, the reduction in the effectiveness of AI, in combination with metalloestrogens, is not related to the influence on the cell cycle. Our results confirm that exposure to metalloestrogens may negatively affect the effectiveness of hormone therapy with AI. Further studies are needed to fully explain the mechanism of these interactions.

Perinatal Outcomes of Neonates with Complex and Simple Gastroschisis after Planned Preterm Delivery-A Single-Centre Retrospective Cohort Study.

This research analysed early neonatal outcomes of complex and simple gastroschisis following planned elective preterm delivery in relation to prenatal ultrasound assessment of bowel conditions. A retrospective study of 61 neonates with prenatal gastroschisis diagnosis, birth, and management at a single tertiary centre from 2011 to 2021 showed a 96.72% survival rate with no intrauterine fatalities. Most cases (78.7%) were simple gastroschisis. Neonates with complex gastroschisis had longer hospital stays and time to full enteral feeding compared to those with simple gastroschisis-75.4 versus 35.1 days and 58.1 versus 24.1 days, respectively. A high concordance of 86.90% between the surgeon's and perinatologist's bowel condition assessments was achieved. The caesarean delivery protocol demonstrated safety, high survival rate, primary closure, and favourable outcomes compared to other reports. Prenatal ultrasound effectively evaluated bowel conditions and identified complex gastroschisis cases.

The impact of dietary nitrates and acrylamide intake on systemic redox status in healthy young adults.

OBJECTIVES: The nitrogen-containing xenobiotics, such as nitrates and acrylamide may potentially influence systemic redox status and contribute to the generation of oxidative stress (OS) in the human body, but there is still a lack of studies that would evaluate the various parameters assessing the oxidative-antioxidant balance. The aim of this study was to evaluate the exposure to nitrates and acrylamide derived from daily diet and to analyze the impact of these nitrate-containing xenobiotics on the parameters of systemic redox status in healthy young adults. MATERIAL AND METHODS: To assess nitrate and acrylamide intake in the study population, a semi-quantitative food frequency questionnaire was used. Systemic redox status was evaluated by measurement of a panel of biochemical parameters: enzymatic (glutathione S-transferase, glutathione reductase, glutathione peroxidase [GPx]) and non-enzymatic (uric acid, bilirubin and albumin), thiol/disulphide homeostasis parameters (total thiol, native thiol, and disulfide) and oxidative/ antioxidant balance indicators (total antioxidant status, total oxidant status, OS index). RESULTS: The average consumption of nitrates and acrylamide in the study population was 1.24 mg/kg b.w./day and 0.23 µg/kg b.w./day, respectively, which is within the normal value range. Of 12 measured parameters, significant differences were revealed for disulfide and total thiol levels, which were increased in the subgroup with the highest daily intake of nitrates compared to the subgroup with the lowest intake; for GPx, which was highest in the subgroup of the lowest daily intake of acrylamide; and for native thiols in the subgroup with the highest daily intake. CONCLUSIONS: The intake of nitrogen-containing xenobiotics within the range considered as normal does not markedly influence redox state parameters in healthy young adults. Some significant changes were revealed only for thiol/disulphide homeostasis parameters, which may be the first line of antioxidant defense, as well as for GPx activity. Compensative mechanisms in healthy young people are efficient enough to neutralize OS induced by slightly increased exposure to nitrogen-containing xenobiotics delivered with food. Int J Occup Med Environ Health. 2023;36(6):773-87.

Role of estradiol in chromium-induced oxidative stress.

This study investigated the role of 17beta-estradiol in chromium-generated oxidative stress in order to determine whether it has a detoxifying activity or increases the toxic effects of chromium compounds. Reduced glutathione (GSH) levels, membrane lipid peroxidation (levels of malondialdehyde -- MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities were measured in blood. Isolated mitochondria were used to investigate the MDA levels and hydroxyl radical (OHradical) generation. The results showed a varying influence of estradiol on the chromium-induced oxidative stress. This paper demonstrated, that 17beta-estradiol showed a positive effect when erythrocytes were exposed to moderate concentrations of CrVI and increased the levels of erythrocytal GSH. Estradiol did not show any interactions with chromium on the antioxidative enzymes (SOD in erythrocytes and GPx in whole blood) activity measurements. Additionally, estradiol played a generally positive role in the chromium-induced lipid peroxidation in erythrocytes. Unexpectedly, the interaction of estradiol with chromium was found in human mitochondria, where estradiol increased the MDA levels induced by both forms of chromium. Estradiol also increased the OHradical generation triggered with CrVI. It appeared that estradiol acted protectively on lipid peroxidation caused by chromium in erythrocytes but gave an interaction with Cr in mitochondria, which partially correlated with hydroxyl radical formation in this organelle.