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Recent studies have shown that programmed cell death 4 (PDCD4) modulates distinct signal transduction pathways in different pathological conditions. Despite acute and chronic immune responses elicited by ischemia contributing to the functional deterioration of the kidney, the contributions and mechanisms of PDCD4 in acute kidney injury (AKI) have remained unclear. Using two murine AKI models including renal ischemia/reperfusion injury (IRI) and cisplatin-induced AKI, we found that PDCD4 deficiency markedly ameliorated renal dysfunction and inflammatory responses in AKI mice. Consistently, upregulation of PDCD4 was also confirmed in the kidneys from patients with biopsy confirmed acute tubular necrosis from a retrospective cohort study. Moreover, we found that overexpression of
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Background: Low birth weight is a socio, economic, cultural and community based health issue which reflects responsibility and commitment of local and national administrative authorities. It continues to be a cause of short and long term adverse perinatal outcome with a bearing on adult non communicable health risks.Methods: This is a prospective observational and analytic study to know the prevalence, risk factors and perinatal outcome of LBW, from July 2017 to December 2018 in department of Obstetrics and Gynecology, MIMS Medical College, Andhra Pradesh, India. Maternal risk factors and outcomes associated with LBW were defined through risk ratios.Results: 721 infants including 116 LBW and 605 NBW born during study period were included in the study. Prevalence of LBW was 16%. Preterm birth accounted for 35%, FGR for 13.8% and SGA for 51.2% of them. Maternal factors like age <20 years and >35years, social status II to IV, below higher secondary education, house maker, primi gravida, grand multi para, BMI <18.5kg/M2 or >24.9kg/M2, Hb<11 gm% were having higher RR for LBW. LBW infants showed frequent association with oligo or polyhydramnious and hemorrhagic or turbid amniotic fluid. They had higher risks for non reassuring fetal heart rate changes, for induced delivery or an elective caesarean section. More often they needed NICU care for longer duration and showed a higher risk for malformations and neonatal mortality. Overall perinatal mortality was 5.54 per 1000 live birth.Conclusions: LBW is a risk factor for neonatal morbidity and mortality; which can be minimised by institutional delivery. High prevalence PTB (35%) warrants obstetricians to be more vigilant about indentifying the risk factors and adequate management planning. Constitutionally small baby at birth probably needs redefining normal birth weight for different ethnicity.
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Background: This study was aimed to evaluate the effect of sildenafil citrate on Doppler velocity indices in patients with fetal growth restriction (FGR) associated with impaired placental circulation.Methods: A double-blinded, parallel group randomized clinical trial (clinicaltrials.gov NCT02590536) was conducted in Ain Shams Maternity Hospital, in the period between October 2015 and June 2017. Ninety pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were randomized to either sildenafil citrate 25 mg orally every 8 hours or placebo visually-identical placebo tablets with the same regimen. The primary outcome of the study was the change in umbilical artery and fetal middle cerebral artery indices.Results: There was a significant improvement in umbilical and middle cerebral artery indices after sildenafil administration p<0.001. Present study observed that, sildenafil group, in comparison to placebo, has a significantly higher mean neonatal birth weight. 1783±241g vs 1570±455g (p<0.001). There was a significantly higher mean gestational age at delivery in women in sildenafil group 35.3±1.67 weeks, whereas it was lower in the placebo group 33.5±1.7 weeks. The side effects as headache, palpitation and facial flushing were significantly higher in sildenafil group compared to placebo group.Conclusions: The use sildenafil citrate in pregnancies with fetal growth restriction (FGR) improved the feto-placental Doppler indices (pulsatility index of umbilical artery and middle cerebral artery) and improved neonatal outcomes.
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Objective To initially screen the genes associated with chemotherapeutic resistance in esophageal cancer cells, verify the correlation of the genes to the poor prognosis of patients with esophageal cancer, and predict the possible regulatory mechanism of esophageal cancer resistance. Methods The drug sensitivity data of esophageal cancer cell lines were analyzed from GDSC database to screen the cell lines that were relatively sensitive or resistant to both cisplatin and docetaxel. In order to obtain differentially expressed genes, the transcriptome data of the two groups of cell lines were analyzed by the edgeR package according to the following screening criteria: the log2 (fold change) more than –1 or less than1 and P value <0.05. The enrichment cluster analysis of GO biological process was performed in the relatively highly expressed genes of drug-resistant group to identify possible signaling pathways related with drug resistance, and the target genes related to chemotherapeutic resistance were identified based on previous studies. The associations between the expression level of target gene and the clinical pathological features and prognosis of patients were verified in the tissue transcriptome data of esophageal cancer patients. Finally, the proteins interacting with the target gene encoded protein were predicted online using the STRING database, and its possible mechanism of action was analyzed. Results Five cell lines with resistance to both cisplatin and docetaxel and 5 sensitive cell lines were obtained. According to the transcriptome data of the two groups of cell lines, 1097 differentially expressed genes were finally obtained, including 532 highly expressed and 565 low expressed genes in the drug resistant group. The results of GO enrichment analysis for the highly expressed genes indicated that the receptor protein tyrosine kinase pathway was obviously enriched. The expression level of FGR involved in this pathway was significantly correlated with tumor T stage (P=0.021), clinical stage (P=0.007) and prognosis (P=0.0021) of patients with esophageal cancer. In addition, protein interaction analysis indicated that FGR interacted directly or indirectly with multiple proteins, mainly in the form of kinase. Conclusions The receptor protein tyrosine kinase pathway is the most significant signaling pathway associated with chemotherapeutic resistance in esophageal cancer cells. The expression level of FGR in this signaling pathway is significantly correlated with the pathological stage and prognosis of patients with esophageal cancer. FGR may regulate the drug resistance of esophageal cancer cells by phosphorylating downstream target proteins.
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Introdução: O uso da ultrassonografia tem sido importante no âmbito da obstetrícia e a introdução da Dopplervelocimetria angariou vantagens no auxílio da avaliação da vitalidade fetal. O uso do Doppler da artéria umbilical tem apresentado melhores resultados perinatais, especialmente em fetos com RCF (restrição de crescimento fetal). A vigilância fetal em casos de RCF é indispensável na determinação do momento ideal para a interrupção da gestação, a fim de se minimizar o risco tanto de uma interrupção excessivamente prematura quanto o de um óbito fetal potencialmente evitável. Objetivo: Realizar uma revisão da literatura, a fim de avaliar o melhor momento da interrupção da gestação em fetos com RCF com Doppler da artéria umbilical alterado. Metodologia: Foi utilizada como fonte de pesquisa a base de dados eletrônica PubMed/Medline. Foram incluídos estudos randomizados que avaliaram especificamente o Doppler da artéria umbilical como método diagnóstico na decisão quanto ao momento da interrupção da gestação em situações de RCF. Foram localizados 89 resultados com a estratégia de busca, dentre os quais 22 foram considerados potencialmente elegíveis e revisados integralmente, e apenas 2 foram definitivamente elegíveis, ambos referentes a um único estudo. Resultados: Os dois artigos selecionados são estudos clínicos multicêntricos randomizados controlados, sendo que um revela os resultados a curto prazo, com 548 gestantes entre 24 e 36 semanas de gestação, e o outro, os resultados após 2 anos de acompanhamento, com 588 crianças que desenvolveram RCF durante a gestação. Os desfechos avaliados em ambos os estudos (óbito fetal ou neonatal e comprometimento neurológico no longo prazo) não foram significativamente diferentes entre grupos em que, após o diagnóstico de diástole umbilical comprometida, se realizou a interrupção precoce após corticoterapia versus vigilância com interrupção mais tardia, mediante piora no padrão do Doppler umbilical. Conclusão: Não é possível utilizar apenas o Doppler da artéria umbilical para indicar a interrupção da gestação em fetos com RCF, devendo-se associar outros métodos para a avaliação da vitalidade fetal. Mais ensaios clínicos randomizados são necessários para elucidar esta questão.(AU)
Introduction: The use of ultrassonography has been an important development in the field of obstetrics, and the introduction of Doppler assessment has gathered many advantages in the evaluation of fetal well-being. Umbilical artery Doppler has demonstrated the best perinatal results, especially in fetal growth restriction (FGR). Fetal surveillance, in these scenarios, is invaluable in determining the ideal moment for delivery, avoiding both an excessively and unnecessarily premature interruption, and a preventable intrauterine fetal demise due to an inappropriately delayed delivery. Objective: To perform a review of the literature, with the objective to evaluate the best moment of interruption of gestation in fetuses with FGR and an abnormal umbilical artery Doppler. Methodology: Electronic database PubMed/ MEDLINE was used to search and locate the studies. Randomized trials which specifically studied umbilical artery Doppler as a decision-making diagnostic study among fetuses with growth restriction were considered for inclusion in this review. There were 89 results retrieved with the search strategy, among which 22 were selected as potentially eligible, and only 2 were definitely included (both from a single study). Results: Both included papers are multicentric randomized controlled trials, the first reporting short term outcomes of 548 pregnancies between 24 and 36 weeks, and the second one reporting long-term outcomes of 588 children who had FGR, after two years of follow-up. Both short term outcomes (fetal or neonatal death) and long-term outcomes (death or disability) were not significantly different when, after diagnosing compromised umbilical end diastolic flow, immediate delivery was compared with expectant management and delayed delivery after worsening of the umbilical Doppler pattern. Conclusion: It is not possible to use only umbilical artery Doppler to decide whether to deliver a FGR or not, and that other fetal assessment methods should be associated. More randomized trials are needed to definitely answer this question.(AU)
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Humans , Female , Pregnancy , Umbilical Arteries/diagnostic imaging , Ultrasonography, Doppler , Fetal Growth Retardation/diagnostic imaging , Pregnancy Complications/diagnostic imaging , Prenatal Care/methods , Randomized Controlled Trials as Topic , Databases, Bibliographic , Abortion, Legal , Fetal DistressABSTRACT
The objective of the study is to earlier diagnose the cases of FGR (Fetal growth restriction) and to identify the possible causes and management option to prevent further damage and to study the fetomaternal outcome and improve fetomaternal outcome in FGR cases. Methods: This is an analytical study of 50 cases of FGR pregnancies done during the period of 1st April 2013 to 31st March 2014. Data was collected from the OPD books and indoor case papers of patients attending routine antenatal care and emergency services provided by obstetrics and gynaecology department of our institute. Results: 50 cases of FGR were studied. Various possible etiological factors were studied like presence of anaemia, hypoproteinemia and PIH, maternal pre-pregnancy weight, and average weight gain during pregnancy. Among them, malnutrition (64%) was the commonest aetiology of FGR followed by PIH (44%). Ante partum surveillance was done by serial fundal height measurement, maternal weight gain monitoring and serial ultrasound. 40% patients were having severe oligoamnios and 30% were having altered Doppler waveforms. Operative interference was required in 44% cases. 30 babies out of 50 were admitted to NICU. And perinatal mortality was 13.72%. Conclusion: Timely diagnosis, proper management at all levels in well-equipped centre can definitely prevent morbidity and mortality from FGR. Improving pre-pregnancy health, ensuring better antenatal care, effective use of contraception, preventing teenage pregnancies, stop smoking are some preventive measures.
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O hiperparatireoidismo secundário desenvolve-se cedo no curso da doença renal crônica como um mecanismo compensatório para controlar os níveisséricos de cálcio, fósforo e vitamina D. Seu controle inadequado está associado a conseqüências clínicas importantes, como calcificação vascular, e a umimpacto negativo na sobrevida do paciente renal crônico. O conhecimento de sua patogênese é importante para uma escolha terapêutica adequada.Recentemente, a descoberta do receptor de cálcio e das fosfatoninas acrescentou significativos avanços acerca do assunto. Nessa revisão, os mecanismosfisiopatológicos do hiperparatireoidismo secundário são examinados em tópicos: papel do cálcio e do seu receptor, do fósforo, da vitamina D e daresistência óssea ao PTH. Além disso, o papel do fator de crescimento de fibroblastos23 também é discutido. Embora abordados separadamente, estesfatores estão inter-relacionados podendo um ou mais deles predominar de acordo com o tipo e a fase da doença renal crônica.
Secondary hyperparathyroidism (SHPT) occurs early in the course of chronic kidney disease (CKD) as an adaptive mechanism to control the serum levelsof calcium, phosphorus and vitamin D. If not treated adequately, it is associated with serious complications, like vascular calcification, with a negative impacton survival of CKD patients. A better understanding of its pathogenesis can help clinicians as to an appropriate therapeutic choice for SHPT. In this regard, the recent identification of both the calcium sensing receptor and the phosphatonins have shed some light to the field. In the present review, thepathophysiologic pathway of the SHPT is discussed in topics: role of calcium and calcium sensing receptor, role of phosphorus, and role of vitamin D andbone resistance to PTH. Furthermore, the role of fibroblast growth factor-23 is also discussed. Although analyzed separately, these factors are inter-related and according to the etiology and phase of CKD one or more of them may prevail.
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Humans , Calcium/analysis , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/metabolism , Phosphorus/metabolism , Hyperparathyroidism, Secondary/physiopathology , Vitamin D/analysisABSTRACT
To investigate the effect of magnesium sulfate on the fetal rats of FGR and the expression of caspase-3 in the placenta of maternal rat; To explore the mechanism of using magnesium sulfate to cure the FGR. Establish model of FGR by a way of passive smoking: giving the maternal rats different agent of magnesium sulfate by subcutaneous injection: low agent group (300 mg/kg),high agent group (600 mg/kg). Concentration of magnesium sulfate was monitored. The expres sion of caspase-3 was measured by RT-PCR and immunohistochemistry technology. Both of the concentrations of magnesium sulfate in high and low agents group are higher than the FGR group (P＜0. 01); the weight of the placenta and fetal rat in high agent group are higher than the FGR group (P＜0.05 and P＜0.01); the expression of mRNA and protein of caspase-3 in the two agent group is higher than the FGR group (P＜0.05 respectively); concentration of magnesium sulfate in the maternal rat blood correlate to the weight of fetal rat (r=0. 899, P=0. 038) and the expression of caspase-3 in the placenta of maternal rat (r= 0.747, P 0.033; r=-0. 915, P=0.001).The research suggests that the weight of fetal rat could be increased by treatment of magnesium sulfate. Because it would imfrmove the placental function by depressing the expression of caspase-3.