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Introduction: Chronic kidney disease and end-stage renal disease have been found to be caused by diabetes. More recently, the renal tubulointerstitium has been increasingly assumed to play a role in the pathogenesis of diabetic nephropathy with prolonged exposure to a variety of metabolic and haemodynamic injuring factors associated with sustained hyperglycaemia as contributing factors. This study aimed to investigate whether maternal diabetes could be the factor affecting kidney function in a newborn with the use of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) - biomarkers of renal injury. Material and methods: The study included 138 full-term newborns: 50 newborns from diabetic pregnancies and 88 healthy newborns. The concentrations of NGAL and KIM-1 were determined in urine in the first or the second day of life with a commercially available ELISA kit. Results: Considerably higher urine level of NGAL (25.7 (11.8-40.8)) and NGAL/cr. (29.1 (19.1-47.4)) in babies from diabetic pregnancies has been found when compared to the reference group (16.74 (9.9-27.5)) and (21.9 (14.6-29.8)) (p = 0.01, p < 0.01) respectively. We also found a significantly higher urine level of NGAL (27.8 (13.6-44.2)), NGAL/cr. (31.9 (17.6-57.4)), and KIM-1/cr. (2.6 (1.6-5.5)) in babies of diabetic mothers treated with insulin when compared to the reference group (16.7 (9.9-27.5)), (21.9 (14.6-29.8)), (1.9 (0.8-3.2)), (p = 0.01, p = 0.02, p = 0.02), respectively. Conclusions: Based on the results of this study, we indicate for the first time that maternal diabetes mellitus during pregnancy may be considered as the cause of tubular kidney damage in newborns.
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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.
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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.
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Anomalías Múltiples , Labio Leporino , Fisura del Paladar , Labio , Humanos , Labio Leporino/cirugía , Femenino , Fisura del Paladar/cirugía , Masculino , Estudios Retrospectivos , Labio/anomalías , Labio/cirugía , Anomalías Múltiples/cirugía , Preescolar , Lactante , Niño , Resultado del Tratamiento , Procedimientos de Cirugía Plástica/métodos , Quistes/cirugíaRESUMEN
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.
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Acrilamida , Antioxidantes , Humanos , Adulto Joven , Adolescente , Antioxidantes/metabolismo , Nitratos , Estrés Oxidativo , Oxidación-Reducción , Compuestos de Sulfhidrilo , Disulfuros , NitrógenoRESUMEN
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.
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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.
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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.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Superóxido Dismutasa-1 , Células MCF-7 , Estradiol/farmacología , Estradiol/metabolismo , Estrógenos/farmacologíaRESUMEN
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.
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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.
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Cadmio , Neoplasias Ováricas , 2-Metoxiestradiol , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Cadmio/metabolismo , Carcinoma Epitelial de Ovario , Línea Celular , Estradiol/metabolismo , Estrógenos/metabolismo , Humanos , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
BACKGROUND: Large and giant congenital melanocytic nevi (CMN), benign naevomelanocytic proliferations derived from neural crests, with a projected adult size (PAS) ≥ 20 cm, are connected to a high risk of melanoma and neurocutaneous melanosis. Among several factors, genetic alterations seem to be involved in tumorigenesis. The aim of the present study was to analyse the mutation status of NRAS and BRAF genes in resection specimens from large or giant CMN in a group of Polish patients. MATERIAL AND METHODS: The formalin-fixed, paraffin-embedded resection specimens from 18 patients, fixed in the years of 2006 to 2017, were included in the study. The regions containing the highest load of melanocytes were macrodissected prior to DNA isolation. The NRAS and BRAF mutation status was evaluated using qPCR. RESULTS: We detected activating mutations in NRAS gene (codons: 12 and 61) in 7 out of the 18 (38.9%) patients. No BRAF mutations were found. CONCLUSION: Our study, the first molecular analysis of large/giant CMN in Polish patients, supports the hypothesis that NRAS mutation in codon 61 are frequent, recurrent mutations in large/giant CMN. Moreover, we show, for the first time, that NRAS mutations in codon 12 (p.Gly12Asp) can be also detected in giant CMN. The exact role of these genetic alterations in CMN formation remains to be elucidated.
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Nevo Pigmentado , Neoplasias Cutáneas , Adulto , Niño , Humanos , Recurrencia Local de Neoplasia , Nevo Pigmentado/genética , Polonia , Estudios Retrospectivos , Neoplasias Cutáneas/genéticaRESUMEN
This study was intended to evaluate the relationship between secondary alveolar bone grafting (SABG) timing and the alveolar volume in patients with unilateral cleft lip and palate (UCLP). The material consisted of CTs of 35 patients (17 males, 18 females) with UCLP who underwent a one-stage primary cleft repair at a mean age of 8.4 months and SABG at different timings ranges of 1.8-18.8 years. The mean age at CT was 17.2 years. The relative coefficient (ê¶) which was independent from factors such as individual maxillary size, gender or age at the CT was introduced in order to compare volumes of the cleft-side in relation to the non-cleft-side alveolus. Pearson correlation coefficient r between ê¶ coefficient and SABG timing was weak negative (r = -0.34, p = 0.045). The multiple regression analysis implied that the dependent variable-ê¶ coefficient was associated with independent variables (cleft repair and SABG timings and age at CT) with r2 = 0.228. Only patient's age at SABG explained the dependent variable (p = 0.003). The study cautiously indicates a tendency to larger alveolar volume following earlier timing of SABG. Nevertheless, the further research on a larger group of patients should be performed before formulating any clinical indications.
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The epidemiological studies confirm that the overproduction of free radical is an important factor of cancer induction as well as development, and loss of antioxidant systems efficiency is associated with an increased risk of carcinogenesis. While bladder cancer is the fourth most common type of cancer all over the world, there is little evidence of the advancing changes in oxidative/nitrative stress during the progression of bladder cancer. Our study aimed to investigate the plasma levels of typical markers of oxidative/nitrative stress depending on the clinical classification of bladder cancer differentiation and infiltration degree. We examined 40 patients with newly diagnosed bladder cancer and 20 healthy volunteers as a control group. We analysed the plasma levels of protein carbonyls, thiol groups, 3-nitrotyrosine, lipid peroxidation, as well as non-enzymatic plasma antioxidant capacity using DPPH· and ABTS·+ radicals. We confirmed that all analysed biomarkers are higher in enrolled BC patients than in healthy subjects. Furthermore, our findings demonstrate a positive correlation between the degree of bladder cancer progression and the level of oxidative stress, but no correlation in the case of NT-3. Based on obtained results, we might conclude that during carcinogenesis of the bladder increased oxidative damage of biomolecules is manifested. This indicates the participation of oxidative stress in the development of bladder cancer, and it is important the ensure the proper antioxidant protection.
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Biomarcadores/metabolismo , Estrés Oxidativo/fisiología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Adulto , Antioxidantes/metabolismo , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Radicales Libres/metabolismo , Humanos , Peroxidación de Lípido/fisiología , Masculino , Persona de Mediana Edad , Compuestos de Sulfhidrilo/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
The study aimed at comparing maxillofacial morphology and burden of surgical treatment in post-pubertal patients with unilateral cleft lip and palate (UCLP) following early vs. late secondary alveolar bone grafting (SABG). In this retrospective study maxillofacial morphology was assessed on lateral cephalograms of skeletally matured patients with UCLP operated on consecutively in one center by the same method of one-stage primary cleft repair followed by SABG. Cephalometric analysis comprised 8 angular and 7 linear measurements. Maxillary growth restriction was evaluated by measuring SNA angle and Co-A and PNS-A distances. Five linear regression models with SNA, SNB, ANB, Co-A, and MP/SN as dependent variables and age at primary cleft repair, age at SABG, age at taking cephalogram, surgeon, and total number of surgical interventions as independent variables were also created. 135 patients were included in the study - 70 patients (47 males and 23 females) had early SABG (E-SABG group) and 65 patients (40 males and 25 females) had late SABG (L-SABG group). Mean age at bone grafting procedure was 2.7 years (range 1.5-5.9, SD 1.1) and 10.3 years (range 6.1-18.8, SD 3.2) in E-SABG and LSABG group respectively. The variables describing the degree of maxillary growth restriction - SNA, Co-A, and PNS-A - were comparable in both groups (p = 0.707, 0.116, and 0.932, respectively). Regression models demonstrated that independent variables were not associated with the values of SNA angle, SNB angle, ANB angle, MP/SN angle, and Co-A distance (p = 0.761, 0.088, 0.249, 0.380, and 0.363, respectively). The percentages of oronasal fistula repair, VPI repair, repeated SABG, upper lip correction, rhinoplasty, orthognathic surgery were 22.9, 7.1, 15.7, 24.3, 42.9, 2.9 in E-SABG group and 27.7, 7.7, 9.2, 36.9, 47.7, 3.1 in L-SABG group respectively. Mean number of all surgical interventions was 3.2 in E-SABG and 3.4 in L-SABG group, respectively (p = 0.271). Considering the comparable maxillofacial morphology and burden of surgical care in matured patients after early and late SABG, the choice of timing of bone grafting surgery could be left to the discretion of the surgeon.
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Injerto de Hueso Alveolar , Labio Leporino , Fisura del Paladar , Cefalometría , Preescolar , Labio Leporino/cirugía , Fisura del Paladar/diagnóstico por imagen , Fisura del Paladar/cirugía , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION: Genotoxicity of chemical compounds is primarily associated with the interaction with DNA, formation of mutations, damage to chromosomes and initiating carcinogenesis processes. Currently, many compounds found in the environment are considered to be genotoxic agents, among them chromium: trivalent (III) and hexavalent (VI). The genotoxicity of hexavalent (VI) chromium has been proven in numerous epidemiological, in vitro and in vivo studies. The main source of Cr (VI) is environmental pollution associated with its use in various industries. On the other hand, the role of chromium (III) as a microelement is widely discussed. Due to its beneficial properties, associated with maintaining adequate blood glucose levels and supporting weight loss, it is widely used in the form of dietary supplements, often in doses exceeding the daily requirement. However, the safety of chromium compounds is disputable. Data about the mechanism of genotoxic effects are still incomplete. OBJECTIVE: The aim of this review is to present the current knowledge about the induction of genotoxicity from two forms of chromium: trivalent (III) and hexavalent (VI). STATE OF KNOWLEDGE: Chromium (VI) is a carcinogen with proven mutagenic and genotoxic effects, but this issue is still being investigated by scientists. In recent years, numerous studies have also been conducted on the genotoxic effect of chromium (III). CONCLUSIONS: Due to the still unexplained mechanism of the genotoxic action and incomplete knowledge about the transformation of chromium in the body, further research is needed, especially due to the growing popularity of Cr (III) compounds and their consumption in the form of dietary supplements and doubts as to the safety of its use, as well as environmental exposure to Cr (VI).
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Cromo/toxicidad , Daño del ADN/efectos de los fármacos , Mutágenos/toxicidad , Animales , Carcinógenos Ambientales/toxicidad , HumanosRESUMEN
During the last decade, a significant increase in the incidence of bladder cancer (BC) has been observed. Angiogenesis plays a key role in the process of tumor growth and metastasis. Additionally, the participation of oxidative stress and chronic inflammation in BC pathogenesis is indicated. The aim of the study was to evaluate the urinary levels of parameters of angiogenesis, stimulating angiogenin (ANG) and inhibiting angiostatin (ANGST), 8-iso-prostaglandin F2α (8-iso-PGF2α) as a marker of oxidative stress, É£-synuclein (SNCG) as a cancer progression parameter, and interleukin-13 (IL-13) as an anti-inflammatory immunomodulator. The levels of ANG, ANGST, 8-iso-PGF2α, SNCG, and IL-13 in the urine of BC patients and healthy controls were measured by the enzyme-linked immunosorbent assay. These parameters were examined in the whole group of BC patients and in subgroups depending on the clinical stage: nonmuscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC); histopathologic malignancy: low grade (LG) and high grade (HG) and in primary and recurrent BC. Significantly, higher urinary parameters were found in BC patients in comparison to controls. Levels of all parameters increased with the development of cancer, with the exception of 8-iso-prostaglandin F2α, in which the level was higher in the early stages of the disease, but these differences were not statistically significant. Some correlations have been demonstrated between parameters in BC patients. Based on the receiver operating characteristic curves, ANG and ANGST had the best diagnostic value for BC. The obtained results indicate the important role of the examined parameters of angiogenesis, oxidative stress, and inflammation in the pathogenesis and development of BC. It is reasonable to continue research in order to thoroughly assess the impact of various associated processes on the course of BC. It is also important to carry out similar tests in patients with other urological diseases.
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INTRODUCTION: Breast cancer is the most common cancer occurring in women and causing the highest number of deaths among them. The role of xenoestrogens has been the subject of many studies in the pathogenesis of breast cancer. Less is known about the impact of xenoestrogens on the effectiveness of hormone therapy used to treat breast cancer, and thus possible drug-xenostrogen interactions. OBJECTIVE: The aim of this review is to summarize the current state of knowledge and present perspectives for further research on the impact of xenoestrogens on the effectiveness of drugs used in the treatment of hormone-dependent breast cancer. CURRENT STATE OF KNOWLEDGE: Phytoestrogens, in particular flavonoid genistein, are the best studied group of xenoestrogens in terms of interaction with drugs used in the treatment of breast cancer, due to their frequent use, including their use in alleviating the adverse effects of hormone therapy. Analyzing the current state of knowledge, it seems that phytoestrogens intake should be avoided during conventional anti-cancer treatment. Of the other xenoestrogens, bisphenol A (BPA) is one of the best-tested compounds for interactions with drugs used to treat breast cancer. It has been shown that bisphenol A could reduced therapeutic effect of active tamoxifen metabolite and cytostatics used in breast cancer treatment. CONCLUSIONS: Confirmation in clinical trials of the results obtained in vitro and in vivo tests, would enable the creation of specific recommendations for patients undergoing breast cancer treatment, especially hormone therapy. An area requiring further research is the analysis of the effects of xenoestrogens other than phytoestrogens, e.g. metalloestrogens, on the effects of drugs used in the treatment of breast cancer.
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Antineoplásicos/farmacología , Compuestos de Bencidrilo/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Flavonoides/farmacología , Fenoles/farmacología , Fitoestrógenos/farmacología , Neoplasias de la Mama/inducido químicamente , Femenino , Hormonas/efectos adversos , HumanosRESUMEN
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.
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2-Metoxiestradiol/farmacología , Cromatos/farmacología , Cromo/farmacología , Estradiol/farmacología , Hidroxiestronas/farmacología , Neoplasias Ováricas/patología , Compuestos de Potasio/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Antagonismo de Drogas , Sinergismo Farmacológico , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
Objective/Purpose. Evaluation of efficacy and safety of autologous adipose-derived regenerative cells (ADRCs) treatment in autoimmune refractory epilepsy. Patients. Six patients with proven or probable autoimmune refractory epilepsy (2 with Rasmussen encephalitis, 2 with antineuronal autoantibodies in serum, and 2 with possible FIRES) were included in the project with approval of the Bioethics Committee. METHOD: Intrathecal injection of autologous ADRC acquired through liposuction followed by enzymatic isolation was performed. The procedure was repeated 3 times every 3 months with each patient. Neurological status, brain MRI, cognitive function, and antiepileptic effect were monitored during 12 months. RESULTS: Immediately after the procedure, all patients were in good condition. In some cases, transient mildly elevated body temperature, pain in regions of liposuction, and slight increasing number of seizures during 24 hours were observed. During the next months, some improvements in school, social functioning, and manual performance were observed in all patients. One patient has been seizure free up to the end of trial. In other patients, frequency of seizures was different: from reduced number to the lack of improvement (3-year follow-up). CONCLUSION: Autologous ADRC therapy may emerge as a promising option for some patients with autoimmune refractory epilepsy. Based on our trial and other clinical data, the therapy appears to be safe and feasible. Antiepileptic efficacy proved to be various; however, some abilities improved in all children. No signs of psychomotor regression were observed during the first year following the treatment.
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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.