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1.
Clin Transplant ; 38(1): e15192, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37975531

RESUMO

Xenotransplantation, transplanting animal organs into humans, may offer a solution to the shortage of organs for transplantation. This would increase the chances for scheduled, elective transplantation, even for patients currently ineligible for receiving a human organ. However, xenotransplantation raises specific ethical and philosophical issues, that is, a personal identification of the body parts with the soul and spirit, the relationships between humans and animals, and challenges related to issues of medical and social ethics. The three monotheistic religions have laws and perspectives pertaining to xenotransplantation. This scholarly review examines the theology and viewpoints of the three monotheistic religions and their concerns regarding xenotransplantation (interspecies) in terms of religious-legal rulings, the ethical considerations related to the procedure, through religious scriptures and rulings of scholars of the three faith communities. This review should be viewed as a continuation of an extensive investigation of these issues, as the field of transplantation advances toward clinical trials. It was found that there are no fundamental religious reasons presented by any of the three religions to prohibit the use of animal organs as a means of treating severe and life-threatening conditions. However, there are certain limitations prescribed by each religion relating to the treatment of the animals and the choice of organs to be transplanted.


Assuntos
Religião , Animais , Humanos , Transplante Heterólogo
2.
J Relig Health ; 62(5): 3215-3229, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37715869

RESUMO

The aim of the study was to investigate whether a Muslim woman with a child afflicted with a genetic disease who is living at home would perform more prenatal tests and pregnancy terminations as opposed to a woman with a normal child living at home, and what demographic characteristics, if any, influenced this decision. The study included 771 Muslim women; 37.1% lived with a child afflicted with a genetic disease; and 62.9% did not. Muslim women with a child affected with a genetic disease living at home will undergo more prenatal testing and more pregnancy terminations. Village dwellers were more religious and consulted further with a religious authority. More city dwellers underwent prenatal tests and pregnancy terminations and received more health care and genetic counseling. In the villages populated by Muslims, more genetic counselling must be given, accompanied by guidance from religious Muslim authorities.


Assuntos
Aborto Induzido , Islamismo , Gravidez , Humanos , Criança , Feminino , Israel , Encaminhamento e Consulta
3.
J Relig Health ; 62(5): 3204-3214, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36890359

RESUMO

Our goal was to determine if differences exist in the attitudes of religious Muslim women living in Israel toward prenatal testing and pregnancy termination after undergoing in vitro fertilization (IVF) compared to the secular Muslim women who had undergone IVF. Six hundred and ninety-nine Muslim women from cities and villages participated, 47% city-dwellers; 53% village-dwellers; 50%-secular; 50%-religious. Secular women who had undergone IVF performed more invasive tests and terminated more pregnancies due to an abnormal fetus than religious women. More genetic counseling must be provided explaining the different prenatal tests and the problems in raising an abnormal child.


Assuntos
Aborto Induzido , Islamismo , Gravidez , Criança , Humanos , Feminino , Islamismo/psicologia , Israel , Diagnóstico Pré-Natal , Fertilização in vitro
4.
Omega (Westport) ; : 302228231183191, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37311213

RESUMO

Evidence indicates that the religious beliefs of patients, potential donors, family members, and healthcare professionals play an important role in deciding to donate an organ. We aim to summarize the religious views of Christians, Muslims, and Jews on organ donation contributing to the decision-making process. Different approaches to this topic worldwide are presented, providing helpful information for medical professionals. A literature review was conducted regarding the view of Israel's leadership of the three largest religions on organ transplantation. This review revealed that all Israeli central religious leaders have a positive view on organ donation. However, various aspects of the transplantation process (such as consent, brain death, and respect for the dead body) must be carried out as each religion prescribes. Thus, understanding the different religious views and regulations on organ donations may help reduce religious concerns about transplantation and narrow the gap between the need and the availability of organ donations.

5.
Genes Dev ; 27(21): 2356-66, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24186980

RESUMO

Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers of cellular senescence. During embryonic development, ERVWE1-mediated cell fusion results in formation of the syncytiotrophoblast, which serves as the maternal/fetal interface at the placenta. Expression of ERVWE1 caused cell fusion in normal and cancer cells, leading to formation of hyperploid syncytia exhibiting features of cellular senescence. Infection by the measles virus, which leads to cell fusion, also induced cellular senescence in normal and cancer cells. The fused cells activated the main molecular pathways of senescence, the p53- and p16-pRb-dependent pathways; the senescence-associated secretory phenotype; and immune surveillance-related proteins. Thus, fusion-induced senescence might be needed for proper syncytiotrophoblast function during embryonic development, and reuse of this senescence program later in life protects against pathological expression of endogenous fusogens and fusogenic viral infections.


Assuntos
Senescência Celular/fisiologia , Produtos do Gene env/metabolismo , Vírus do Sarampo/fisiologia , Proteínas da Gravidez/metabolismo , Fusão Celular , Linhagem Celular , Linhagem Celular Tumoral , Senescência Celular/genética , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Fibroblastos/virologia , Regulação da Expressão Gênica , Produtos do Gene env/genética , Humanos , Sarampo/fisiopatologia , Placenta/citologia , Gravidez , Proteínas da Gravidez/genética , Trofoblastos/metabolismo
6.
J Assist Reprod Genet ; 35(1): 143-148, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28900814

RESUMO

PURPOSE: The purpose of this study was to evaluate telomere homeostasis in sub-fertile compared to fertile human sperm. METHODS: This observational, comparative study included 16 sub-fertile men who required intracytoplasmic sperm injection and 10 fertile men. At least 100 sperm cells from each participant were assessed. Main outcome measures were telomere length and telomere aggregates. Telomerase RNA component (TERC) copy number and telomere capture were assessed using fluorescence in situ hybridization technique and human telomerase reverse transcriptase (hTERT) using immunohistochemistry. RESULTS: Clinical backgrounds were similar. The percentage of sperm cells with shorter telomeres was higher among the sub-fertile compared to the fertile participants (3.3 ± 3.1 vs. 0.6 ± 1.2%, respectively; P < 0.005). The percentage of cells with telomere aggregates was significantly higher in the sub-fertile group (15.12 ± 3.73 vs. 4.73 ± 3.73%; P < 0.005). TERC gene copy number was similar between groups. The percentage of cells that were positive for hTERT was lower in the sub-fertile group (3.81 ± 1.27 vs. 8.42 ± 1.80%; P < 0.005). Telomere capture rates were higher among the sub-fertile sperm cells (P < 0.005). CONCLUSIONS: Sub-fertile sperm cells have short telomeres that are elongated by the alternative pathway of telomere capture. Dysfunctional telomeres may affect sperm fertilizability.


Assuntos
Infertilidade/patologia , Espermatozoides/fisiologia , Homeostase do Telômero , Telômero/patologia , Adulto , Humanos , Infertilidade/fisiopatologia , Masculino , RNA/metabolismo , Análise do Sêmen , Espermatozoides/patologia , Telomerase/metabolismo , Telômero/fisiologia
7.
Isr Med Assoc J ; 20(5): 295-299, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29761675

RESUMO

BACKGROUND: Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules. OBJECTIVES: To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology. METHODS: We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2-5, 6-10, and 11-15 telomeres, relative to the size of a single telomere. RESULTS: Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of > 5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group. CONCLUSIONS: While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.


Assuntos
Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Telômero/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Israel , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Telômero/metabolismo
8.
Cytogenet Genome Res ; 150(2): 93-99, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28006764

RESUMO

Nonalcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC) are considered preneoplastic conditions that might progress to hepatocellular carcinoma. We evaluated parameters of telomere dysfunction in these patient groups to study the correlation between telomere length and the progression of NAFLD. We analyzed peripheral lymphocytes from 22 patients with NAFLD, 20 patients with CC, and 20 healthy, age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization, and cellular senescence was evaluated by the percentage of cells with senescence-associated heterochromatin foci. The expression of telomerase reverse transcriptase (hTERT) mRNA was measured using polymerase chain reaction, and telomere capture (TC) was assessed with 2 Cytocell probes, 15qter and 13qter. Shorter telomere length and increased cellular senescence was demonstrated in patients with NAFLD, compared to the CC patients and healthy controls. While hTERT mRNA was significantly decreased, TC was increased in CC patients, compared to the NAFLD group and healthy individuals. Thus, there is a correlation between hTERT mRNA expression and telomere length in patients with NAFLD, which might be related to associated metabolic disorders and the risk of malignant transformation. Patients with CC, on the contrary, elongate their telomeres through the TC mechanism.


Assuntos
Cirrose Hepática/congênito , Hepatopatia Gordurosa não Alcoólica/genética , Telômero/genética , Idoso , Estudos de Casos e Controles , Senescência Celular/genética , Progressão da Doença , Feminino , Instabilidade Genômica , Humanos , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Mensageiro/genética , Telomerase/genética , Homeostase do Telômero/genética , Encurtamento do Telômero/genética
9.
Am J Obstet Gynecol ; 214(2): 283.e1-283.e7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26321036

RESUMO

BACKGROUND: Telomeres are nucleoprotein structures, essential for chromosome stability and cell survival. Telomeres are progressively shortened with each cell division and by environmental factors. Telomere loss has been linked to age and stress-induced premature senescence. Dysfunctional telomeres tend to form aggregates, which consist of the end-to-end fusion of telomeres. Telomere elongation is carried out by telomerase, which is a specific reverse transcriptase capable of adding telomeric repeats to chromosome termini. The TERC gene encodes the RNA template of the telomerase. Another compensatory mechanism that is enhanced in response to telomere shortening and senescence is the telomere capture (TC). Telomere shortening and elevated aggregate formation have been observed in trophoblasts from pregnancies complicated with preeclampsia (PE). OBJECTIVE: We opted to study mechanisms of telomere shortening in trophoblasts from pregnancies complicated with PE and to assess telomere length and homeostasis in fetal cord blood cells from PE pregnancies. STUDY DESIGN: Placental specimens and cord blood samples from uncomplicated pregnancies and from pregnancies complicated with PE were collected. Staining with 4',6-diamidino-2-phenylindole was used to assess nuclear fragmentation: senescence-associated heterochromatin foci (SAHF). Fluorescence in situ hybridization was used to evaluate TERC gene copy number and TC. Telomere length and aggregate formation were assessed in cord blood using quantitative fluorescence in situ hybridization. Nonparametric Kruskal-Wallis and Mann-Whitney U tests were applied to test the differences between the study groups. RESULTS: Nine samples from pregnant patients with PE without intrauterine growth restriction and 14 samples from uncomplicated pregnancies that served as controls were collected. In cord blood cells, no differences were observed in telomere length, aggregate formation, TERC copy number, TC, or SAHF between PE and controls. In PE trophoblasts the percentage of cells with SAHF was higher in PE trophoblasts compared to controls (56.8 SD = 10.5% vs 35.2 SD = 10.7%, P = .028). The percentage of cells with abnormal TERC copy number was increased in PE trophoblasts compared to controls (31 ± 3.6% vs 12.97 SD = 5%, P = .004) as well as the percentage of cells with TC (27.4 SD = 9.4% vs 16 SD = 4.67%, P = .028). CONCLUSION: We suggest that telomere shortening in PE trophoblasts is linked to cellular increased senescence. Alterations in telomere homeostasis mechanisms are present in such cases. These findings support the role of telomeres in the pathogenesis of trophoblastic dysfunction in PE. The lack of telomere shortening, modified telomere homeostasis mechanisms, and increased senescence in cord blood from pregnancies complicated with PE suggests that these processes are probably restricted primarily to the placenta.


Assuntos
Células Sanguíneas/metabolismo , Senescência Celular/genética , Sangue Fetal/metabolismo , Pré-Eclâmpsia/genética , RNA/genética , Telomerase/genética , Homeostase do Telômero/genética , Encurtamento do Telômero/genética , Trofoblastos/metabolismo , Adulto , Estudos de Casos e Controles , Feminino , Sangue Fetal/citologia , Dosagem de Genes , Humanos , Hibridização in Situ Fluorescente , Placenta/metabolismo , Gravidez , Estudos Prospectivos , Adulto Jovem
10.
Cytogenet Genome Res ; 145(1): 35-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25895441

RESUMO

Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are associated chronic inflammatory diseases with malignant potential. Loss of replication synchrony during the S-phase of the cell cycle has been shown to be linked to several malignant and premalignant states. This study evaluated temporal differences in replication timing between these diseases. The replication pattern of peripheral blood lymphocytes obtained from patients with PSC and IBD and healthy individuals was analyzed by fluorescence in situ hybridization (FISH) in 2 pairs of alleles, in 15qter and 13qter. Asynchrony was determined by the presence of 1 single and 1 set of double dots in the same cell. Samples from subjects with PSC showed significantly greater temporal differences in replication timing, in contrast to the high level of synchrony observed in samples from healthy individuals (p = 0.045). Samples from IBD patients exhibited a nonsignificant increase in replication asynchrony. We believe that these results reflect impairment in the replication control of structural homologous loci in PSC, and that this phenomenon may be correlated with the inflammation-induced malignant potential of this condition.


Assuntos
Colangite Esclerosante/genética , Replicação do DNA , Doenças Inflamatórias Intestinais/genética , Linfócitos/patologia , Divisão Celular/genética , Proliferação de Células , Células Cultivadas , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade
11.
Hepatogastroenterology ; 60(127): 1713-6, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24634940

RESUMO

BACKGROUND/AIMS: Shortened telomeres reflect genetic instability that might lead to increased aneuploidy and malignant transformations. Chronic hepatitis C (HCV) viral infection is considered a pre-neoplastic condition that might progress to hepatocellular carcinoma. We evaluated telomere length and elongation, in patients with different stages of HCV to study the correlation between telomere length and the progression of HCV. METHODOLOGY: We analyzed peripheral lymphocytes from 10 patients with chronic active HCV, 10 patients with HCV infection in a remission stage, and 10 healthy, age-matched patients, as controls. The expression of hTERT mRNA, which is correlated with elongation of telomeres was measured using RT-PCR and telomere length was analyzed using Q-FISH and a novel computerized technique. RESULTS: hTERT mRNA was significantly decreased in patients with active HCV and slightly decreased in patients who were in remission, compared to healthy individuals. Telomere length was shorter in patients with chronic active HCV and in patients in remission, compared to the healthy controls. CONCLUSIONS: There is a correlation between telomerase reverse transcriptase mRNA expression and telomere length in patients with different stages of HCV infection that might be related to the risk of malignant transformation.


Assuntos
Hepatite C Crônica/enzimologia , RNA Mensageiro/análise , Telomerase/genética , Encurtamento do Telômero , Adulto , Antivirais/uso terapêutico , Estudos de Casos e Controles , Células Cultivadas , Progressão da Doença , Hepatite C Crônica/sangue , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Humanos , Hibridização in Situ Fluorescente , Linfócitos/enzimologia , Pessoa de Meia-Idade , Indução de Remissão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Telomerase/sangue , Resultado do Tratamento
12.
Children (Basel) ; 10(9)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37761399

RESUMO

Deafness is the most common sensory disability in humans, influencing all aspects of life, However, early diagnosis of hearing impairment and initiating the rehabilitation process are of great importance to enable the development of language and communication as soon as possible. We examined the differences in attitudes towards performing prenatal invasive tests and pregnancy terminations in Jewish and Muslim women in Israel due to deafness. Overall, 953 Israeli women, aged 18-46 years with a mean age of 32.0 (SD = 7.12), were enrolled. Of those, 68.7% were city dwellers and 31.3% were village dwellers, and 60.2% were Muslim women and 39.8% were Jewish women. All participants had a child with a hearing impairment or deafness. The group with no genetic hearing loss performed more prenatal invasive tests and pregnancy terminations than those with genetic hearing loss in both ethnic groups. Jewish women performed more invasive prenatal tests and, consequently, a pregnancy termination. Secular Jewish women more frequently underwent pregnancy terminations due to fetal deafness. Further genetic counseling and information concerning IVF and PGD procedures should be provided to the Muslim population.

13.
Clin Exp Med ; 23(8): 4891-4899, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37658247

RESUMO

Coronavirus disease (COVID-19) is highly transmissible between human beings. We examined differences in the core families with COVID-19 severity and mortality and comorbidities between Arab and Jews and explored the factors associated with COVID-19 severity and mortality to find a genetic component. A cross-sectional study was conducted among 2240 COVID-19 patients (> 18 years of age) randomly selected by online panels and questionnaires in the native language (Hebrew or Arabic) during March 2021-June 2022. Multivariable linear regression models were used to assess correlations with COVID-19 disease severity and mortality. Overall, 1549 (69%) were Arabs and 691 (31%) were Jews. The proportion of participants who died from COVID-19 was higher among Arabs compared with Jews (66% vs. 59%), P < 0.001. The mean number of deaths from COVID-19 and patients with severe COVID-19 was higher in ultra-Orthodox Jewish, non-academic core families and those who lived in the city residence compared with secular, academic core families and who live in the village residence, P < 0.001. A multivariable linear regression model showed a significant association between metabolic, kidney, cardiovascular, and respiratory diseases with COVID-19 severity (B coefficient - 0.43, B coefficient - 0.53, B coefficient - 0.53, B coefficient - 0.42, respectively) and COVID-19 mortality (B coefficient - 0.51, B coefficient - 0.64, B coefficient - 0.67, B coefficient - 0.34, respectively), P < 0.001. COVID-19 severity and mortality were highly associated with comorbidities, ethnicity, social and environmental factors. Furthermore, we believe that genetic factors also contribute to the increase in COVID-19 severity and mortality and the differences rates of these between Arabs and Jews in Israel.


Assuntos
COVID-19 , Etnicidade , Humanos , Estudos Transversais , Israel/epidemiologia , Árabes , Judeus
14.
Reprod Sci ; 30(2): 487-493, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35608796

RESUMO

Preterm delivery complicates 5-12% of pregnancies and is the primary cause of neonatal morbidity and mortality. The pathophysiology of preterm labor and parturition is not fully known, although it is probably related to inflammation and placental senescence. Telomere shortening is related to senescence and galectin-3 (Gal-3) protein is involved in cell growth, differentiation, inflammation, and fibrosis. This study examined changes in Gal-3 expression and telomere homeostasis (which represent inflammatory and stress markers) in maternal blood and placental tissue of spontaneous preterm births (SPTB) and uncomplicated, spontaneous term pregnancies (NTP) during labor. Participants included 19 women with NTP and 11 with SPTB who were enrolled during admission for delivery. Maternal blood samples were obtained along with placental tissue for Gal-3 analysis and telomere length evaluation. Gal-3 protein expression in placental tissue was increased in SPTB compared to NTP (fold change: 1.89 ± 0.36, P < 0.05). Gal-3 immunohistochemistry demonstrated strong staining in placental extravillous trophoblast tissue from SPTB. Maternal blood levels of Gal-3 protein were elevated in SPTB compared to NTP (19.3 ± 1.3 ng/ml vs. 13.6 ± 1.07 ng/ml, P = 0.001). Placental samples from SPTB had a higher percentage of trophoblasts with short telomeres (47.6%) compared to NTP (15.6%, P < 0.0001). Aggregate formation was enhanced in SPTB (7.8%) compared to NTP (1.98%, P < 0.0001). Maternal blood and placental samples from SPTB had shorter telomeres and increased Gal-3 expression compared to NTP. These findings suggest that increased senescence and inflammation might be factors in the abnormal physiology of spontaneous preterm labor.


Assuntos
Trabalho de Parto Prematuro , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Nascimento Prematuro/metabolismo , Placenta/metabolismo , Encurtamento do Telômero , Galectina 3/metabolismo , Trabalho de Parto Prematuro/metabolismo , Inflamação/metabolismo
15.
Am J Reprod Immunol ; 88(4): e13598, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35976163

RESUMO

PROBLEM: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8%-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR. METHODS OF STUDY: In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery. RESULTS: NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples versus NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood. CONCLUSIONS: NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR.


Assuntos
Retardo do Crescimento Fetal , Pré-Eclâmpsia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Células Endoteliais/metabolismo , Feminino , Humanos , Recém-Nascido , Inflamassomos/metabolismo , Placenta/metabolismo , Gravidez , Estudos Prospectivos
16.
Am J Reprod Immunol ; 2022 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-35810355

RESUMO

PROBLEM: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8-10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome-dependent inflammation processes in placental tissue of women with PE and IUGR. METHODS OF STUDY: In this prospective cohort study, 14 women with PE, 15 with placental-related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery. RESULTS: NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples vs. NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood. CONCLUSIONS: NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR. This article is protected by copyright. All rights reserved.

17.
Pregnancy Hypertens ; 26: 95-101, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34700108

RESUMO

OBJECTIVES: Preeclampsia (PE) is a pregnancy-related syndrome characterized by the onset of hypertension and proteinuria that can lead to end-organ dysfunction. Galectin-3 (Gal-3) is involved in cell growth, differentiation, inflammation and fibrosis. Thioredoxin (TXN) acts as antioxidant enzyme in several cellular processes, regulating inflammation and inhibiting apoptosis. TXNIP is an endogenous inhibitor of TXN. We evaluated changes in the inflammatory response of Gal-3, TXN, and TXNIP at the level of maternal blood, placenta, and umbilical cord blood of women with PE. STUDY DESIGN: Ten women with PE and 20 with normal pregnancy (NP) were recruited during admission for delivery. Blood samples were obtained from parturients and umbilical cords, and placental tissue for analysis. RESULTS: Gal-3 and TXNIP mRNA expression were higher in maternal plasma in PE group compared to NP and were lower in cord blood plasma and placentas in the PE group. In the PE group, TXN/TXNIP mRNA ratio was higher in cord blood plasma (2.07) compared to maternal plasma (1.09). TXN/TXNIP placental protein ratio was similar between PE (0.89) and NP (0.79). ELISA demonstrated that Gal-3 levels in maternal serum were significantly higher in the PE vs. the NP group. CONCLUSIONS: Pro-inflammatory changes were expressed by high Gal-3 and TXNIP mRNA in maternal blood of PE women, but not in their placental and cord blood samples. These findings may imply that the placenta has a role in protecting the fetus from the damages of inflammatory response, which is more common in PE than in NP.


Assuntos
Galectina 3/sangue , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Adulto , Biomarcadores/sangue , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Feminino , Sangue Fetal , Humanos , Gravidez , Estudos Prospectivos , Tiorredoxinas/metabolismo
18.
Am J Obstet Gynecol ; 202(4): 381.e1-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20350645

RESUMO

OBJECTIVE: Telomeres shorten and aggregate with cellular senescence and oxidative stress. Telomerase and its catalytic component human telomerase reverse-transcriptase regulate telomere length. The pathogenesis of preeclampsia and intrauterine growth restriction involves hypoxic stress. We aimed to assess telomere length in trophoblasts from pregnancies with those complications. STUDY DESIGN: Placental specimens from 4 groups of patients were studied: severe preeclampsia, intrauterine growth restriction, preeclampsia combined with intrauterine growth restriction, and uncomplicated (control). Telomere length and human telomerase reverse-transcriptase expression were assessed by using quantitative fluorescence-in-situ protocol and immunohistochemistry. RESULTS: Telomere length was significantly lower in preeclampsia, intrauterine growth restriction, and preeclampsia plus intrauterine growth restriction placentas. More aggregates were found in preeclampsia, but not in intrauterine growth restriction placentas. Human telomerase reverse-transcriptase was significantly higher in the controls compared with the other groups. CONCLUSION: Telomeres are shorter in placentas from preeclampsia and intrauterine growth restriction pregnancies. Increased telomere aggregate formation in preeclampsia but not in intrauterine growth restriction pregnancies, implies different placental stress-related mechanisms in preeclampsia with or without intrauterine growth restriction.


Assuntos
Senescência Celular/genética , Retardo do Crescimento Fetal/genética , Doenças Placentárias/genética , Pré-Eclâmpsia/genética , Telômero/patologia , Biópsia , Feminino , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/patologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Estresse Oxidativo , Placenta/patologia , Placenta/fisiopatologia , Doenças Placentárias/metabolismo , Doenças Placentárias/patologia , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Gravidez , Terceiro Trimestre da Gravidez , Telomerase/genética , Telomerase/metabolismo , Telômero/metabolismo
19.
Hereditas ; 147(2): 90-3, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20536547

RESUMO

Telomeres are TTAGGG repetitions at the ends of chromosomes. Functioning telomeres are essential for normal segregation and maintenance of chromosomes during mitotic and meiotic divisions. Dysfunctional telomeres support the survival of aneuploid cells, a characteristic of many human malignancies. In contrast to the non-overlapping nature of telomeres in normal nuclei, telomeres of tumor nuclei tend to form aggregates. In this study, our objective was to evaluate the number of telomere aggregates (TAs) in karyotype-balanced structural rearrangements. This is an additional parameter of genetic instability, which might suggest a possible increased risk for diseases related to genomic instability, such as cancer. Twenty-six amniotic fluid cell cultures were established following genetic amniocentesis. Telomere FISH protocol was applied to the samples. Telomere aggregates were counted using a 2D microscope. The results were statistically tested by analysis of variance (ANOVA) and Kruskal-Wallis tests. More telomere aggregates in the structural balanced rearrangements were found in both study groups (balanced translocations and inversions) compared to the control group (P < 0.05). The persistence of TAs in cells is probably related to Breakage-Bridge-Fusion (BBF) cycles, a mechanism of TAs described by Muller and McClintock, resulting in end-to-end fusion that contributes to the onset of genomic instability. BBF cycles contribute to deletions, gene amplification, non-reciprocal translocations, and overall genetic changes associated with tumor genesis. According to our studies, the individuals who are carriers of balanced structural chromosomal rearrangements show some of the genetic instability parameters that appear in other circumstances, such as premalignant and malignant conditions.


Assuntos
Líquido Amniótico/metabolismo , Aberrações Cromossômicas , Telômero , Hibridização in Situ Fluorescente , Cariotipagem
20.
Hum Fertil (Camb) ; 23(4): 282-288, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30773064

RESUMO

Telomeres are a specific base sequence of DNA, responsible for chromosome stability and DNA protection. We aimed to investigate the association between telomere systems and IVF outcomes according to patients' BMI. For all telomere characteristics, there was a distinct trend towards shorter telomeres and activation of telomere shortening compensatory mechanisms in the BMI group >25 kg/m2, reaching statistical significance for senescence only (r = 0.7, p value <0.01). There was a trend towards a relationship between telomere length and number of oocytes between telomere length and fertilization rate, but these did not reach a statistical significance. For pregnancy outcome, all telomere characteristics were better for the patients who achieved a pregnancy. While there is paucity of data in the literature concerning the association between telomere characteristics and infertility, telomeres might contribute to the association between obesity and sub-optimal IVF results.


Assuntos
Índice de Massa Corporal , Fertilização in vitro/estatística & dados numéricos , Homeostase do Telômero , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Gravidez , Adulto Jovem
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