Maternal Adverse Outcomes in Hypertensive Disorders of Pregnancy and Their Association with Serum Adiponectin and Redox Markers.

Background: Premature termination of pregnancy because of unmanageable maternal complications in hypertensive disorders of pregnancy (HDP) results in adverse neonatal outcome. Identification of biochemical derangements associated with maternal complications may help in the better medical management of the mother resulting in better neonatal outcomes. Method: Healthy pregnant women (C); pregnant women with gestational hypertension (GH), and preeclampsia (late [LP] and early [EP] onset) were studied. Maternal serum redox markers and adipokines were evaluated for their association with maternal complications. Results: Adiponectin levels were significantly raised in preeclampsia groups when compared with control and GH groups. Univariate and multivariate analysis confirmed that malondialdehyde (MDA) and total antioxidant status (TAS) were associated with eclampsia; adiponectin and TAS with HELLP syndrome; adiponectin, MDA and TAS with severe preeclampsia; and adiponectin with impaired renal function. Conclusion: We identified that increased serum adiponectin, MDA, and TAS were associated with adverse maternal outcomes.

Differences in the response to iron supplementation on oxidative stress, inflammation, and hematological parameters in nonanemic and anemic pregnant women.

BACKGROUND: Iron supplementation is widely recommended for all pregnant women, irrespective of their iron status. But providing excess iron to nonanemic pregnant women can result in iron overload, which may lead to oxidative stress and inflammation. OBJECTIVES: To assess the differential effect of iron supplementation on hematological parameters, oxidative stress, and inflammation in nonanemic and anemic pregnant women. METHODS: Forty nonanemic and forty anemic pregnant women were recruited at 12 weeks of gestation. The study subjects were supplemented with iron (60 mg/day for nonanemic pregnant women and 120 mg/day for anemic pregnant women). Fasting state blood samples were collected at 12 and 28 weeks of gestation. RESULTS: Malondialdehyde (MDA)/total antioxidant status (TAS) ratio (MDA/TAS) and high-sensitivity C-reactive protein (hsCRP) were significantly higher in anemic pregnant women before iron supplementation. Iron supplementation to the anemic pregnant women resulted in significant improvement in the hematological profile and ferritin levels. Further, the iron supplementation caused a significant reduction in hsCRP levels although the MDA/TAS ratio remained unaltered. Iron supplementation to nonanemic pregnant women resulted in a significant increase in the levels of MDA/TAS ratio and hsCRP, but there were no changes in hematological profile and serum ferritin levels. CONCLUSION: Prophylactic iron supplementation in nonanemic pregnant women increased oxidative stress and inflammation. However, in anemic pregnant women, iron supplementation was found to be beneficial as it improved hematological status and decreased inflammation without affecting oxidative stress.

Increased hepcidin levels in preeclampsia: a protective mechanism against iron overload mediated oxidative stress?

BACKGROUND: Pregnancy is a metabolic state which demands increased iron bioavailability. While in preeclampsia, due to the placental vascular events there is an iron surplus environment along with inflammation and placental hypoxia. Routinely in India iron is supplemented to all pregnant women irrespective of their general physical condition. Hepcidin a regulator of iron metabolism protects the cells from iron mediated cytotoxicity. OBJECTIVE: To find out whether hepcidin gets induced as a protective mechanism in preeclampsia patients in order to combat the environment of iron overload, oxidative stress, and endothelial dysfunction. METHODS: A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients in the gestational age 32 ± 4 weeks were recruited (n = 80). Biochemical analysis to assess the serum levels of the following were carried out (1) indices of iron homeostasis - serum iron, ferritin, transferrin, hepcidin, (2) endothelial dysfunction -serum assymetric dimethyl arginine (ADMA) (3) oxidative stress - Malon di aldehyde (MDA) and ferric reducing ability of plasma (FRAP). Kolmogorov-Smirnov test, Mann-Whitney U test, Spearman's correlation, linear regression and ROCAUC analysis were performed to understand their relationship with each other. RESULTS: Levels of serum iron, ferritin, transferrin saturation, hepcidin, and MDA/FRAP ratio were elevated significantly in preeclampsia patients compared to controls, while serum transferrin levels were significantly decreased in them. Hepcidin levels showed a significant positive correlation with serum ADMA, and MDA/FRAP. Serum hepcidin, transferrin saturationand MDA/FRAP ratio is useful in differentiating pre-eclampsia patients from healthy pregnant women. CONCLUSION: Iron supplementation in preeclampsia patients might have led to a state of iron overload, which might have caused oxidative stress and endothelial dysfunction in preeclampsia patients. The rise in hepcidin levels in this scenario may be viewed as a protective mechanism to combat the iron overload mediated cytotoxicity.

Bowel Arteriovenous Malformation: An Unusual Cause of Lower Gastrointestinal Bleeding in a Child.

In a child, lower gastrointestinal tract bleeding can be attributed to different etiologies. Unusually, the presence of bowel arteriovenous malformations can lead to multiple bouts of painless bright red bleeding per rectum, which develop into severe anemia. The article focuses on the diagnosis and management of bowel arteriovenous malformation in a child.

A hemorragia digestiva baixa nas crianças pode ter diversas etiologias. Invulgarmente, a presença de malformações arteriovenosas no intestino pode levar a múltiplos episódios hemorrágicos, com desenvolvimento de anemia grave. Este artigo aborda o diagnóstico e tratamento de uma malformação arteriovenosa intestinal numa criança.

Clinico-Pathologic Profile and Treatment Outcomes of Patients with Diffuse Large B Cell Lymphoma Based on Cell of Origin Classification.

Diffuse large B cell lymphoma (DLBCLs) constitute 40% of all non-Hodgkin lymphoma and it represent a heterogeneous group of neoplasms rather than a single clinicopathological entity. We analysed the outcomes and clinical features based on the cell of origin in a series of patients with DLBCL from our institute. Medical case records of all newly diagnosed DLBCL treated in our institute from January 2015 to July 2017 were analysed for this study. Cell of origin classification was based on immunohistochemistry using Hans algorithm. Kaplan-Meier curves were used to determine survival. Ninety-five patients were diagnosed to have DLBCL subtype. Immunophenotypic subtyping was available for 71 patients. The median age at diagnosis was 56 years with no difference between Germinal centre B cell (GCB) and non-Germinal centre B cell (non-GCB) subtypes. Approximately 44% of patients had extra-nodal disease, stomach being the commonest site. Forty percent of patients had stage III/IV disease. Bulky disease and extra-nodal presentation was predominantly seen with non-GCB subtype (46% vs 20% and 36% vs 29% respectively). Rituximab was used in 75% of the patients with DLBCL. The 2-year disease-free survival was 70% versus 53% (p = 0.38) in GCB versus non-GCB subtype. This is one of the few data on DLBCL patients reported from India which has described outcomes based on the cell of origin. The disease-free survival in our country appears to be superior in GCB subtype which needs to be confirmed in a larger subset of patients.

Placental Accumulation of Triacylglycerols in Gestational Diabetes Mellitus and Its Association with Altered Fetal Growth are Related to the Differential Expressions of Proteins of Lipid Metabolism.

INTRODUCTION: Gestational diabetes mellitus (GDM) exhibit altered placental lipid metabolism. The molecular basis of this altered metabolism is not clear. Altered placental expression of proteins of lipogenesis and fatty acid oxidation may be involved in the placental accumulation of triacylglycerols (TG). The present study was aimed at investigating the differential expressions of placental proteins related to lipid metabolism among GDM women in comparison with control pregnant women (CPW) and to correlate them with maternal and fetal lipid parameters as well as altered fetal growth. MATERIALS AND METHODS: Maternal blood, cord blood, and placental samples were collected from GDM and CPW. The biochemical parameters, glucose, lipid profile and free fatty acids (FFA) were measured. The placental TG content was measured. Differential placental expressions of proteins; phosphatidylinositol-3-kinase (PI3K) p85α, PI3K p110α,liver X receptor alpha (LXRα), sterol regulatory element binding protein1(SREBP1), fatty acid synthase (FAS), stearyl CoA desaturase1 (SCD1), lipoprotein lipase (LPL),Peroxisome proliferator-activated receptor (PPAR)α and PPARγ were analysed by western blotting and immunohistochemistry. RESULTS: Placental protein expressions of PI3K p110α, LXRα, FAS, SCD1, and LPL were found to be significantly higher, whereas PPARα and PPARγ were lower in GDM women compared with CPW. The placental TG content and cord plasma FFA were increased in GDM women compared with CPW. The placental TG content positively correlated with Ponderal index of GDM new-borns. CONCLUSION: Differential expressions of placental proteins related to lipid metabolism in GDM might have led to placental TG accumulation. This might have contributed to the fetal overgrowth in GDM.

Diagnostic ability of hepcidin in predicting fetal outcome in preeclampsia.

BACKGROUND: Low birth weight and prematurity are the major contributors to neonatal mortality and morbidity. Preeclampsia which is associated with both maternal and fetal mortality and morbidity is a major contributor to such poor fetal outcomes. Hepcidin an acute phase peptide hormone gets elevated in conditions of iron overload, inflammation, infections, and cytotoxicity. Hepcidin levels can get elevated in pregnancies with such pathologies which invariably will be having a poor fetal outcome. OBJECTIVE: To study the role of hepcidin as a diagnostic marker in predicting a poor fetal outcome. MATERIALS AND METHODS: A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients were recruited between the gestational age of 34 ± 4 weeks and followed up till delivery. Serum levels of hepcidin were analyzed for all the participants and comparisons were done between preeclampsia and healthy pregnancies as well as between pregnancies with good and poor fetal outcomes. Fetal outcome variables such as birth weight, gestational age at the time of delivery and NICU admission status of the newborn were collected during the follow-up period. ROC curves were constructed to determine the ability of maternal serum hepcidin levels in predicting poor fetal outcomes with good sensitivity, specificity and likelihood ratios. RESULTS: Maternal hepcidin levels were found to be significantly elevated in preeclampsia patients (p < .001) as well as in mothers with the poor fetal outcome (p < .001). On ROC curve analysis, AUC were 0.686, 0.788, 0.749 and LR + were 2.18, 2.44, 2.14, respectively for predicting low birth weight, preterm delivery and NICU admission status of the newborn. Hepcidin was able to predict the overall poor fetal outcome in our preeclampsia patients above a cut off level of 615 pg/ml. CONCLUSION: Above a cut off level of 615 pg/ml and at the gestational age of 34 ± 4 weeks, maternal hepcidin levels were able to predict poor fetal outcomes such as low birth weight, preterm delivery, and NICU admission.

Clinical Profile and Short Term Outcome of Adult Patients with Acute Myeloid Leukemia.

Acute myeloid leukemia has a poor outcome because of early deaths, high relapse rate and financial constraints. Our hospital provides care free of cost and this study assesses the short term outcome of acute myeloid leukemia in adults. The study was done from September 2013 to May 2015. All patients above 18 years of age were included. Cytarabine infusion 100 mg/m2 daily for 7 days and Daunorubicin 60 mg/m2 daily for 3 days was used for induction chemotherapy followed by three cycles of high dose cytarabine as post-remission therapy. One hundred and two patients were included in the study. 48% were males. The median age was 41 years. There was an intention to treat in 84 patients. 13 patients died before chemotherapy and 71 patients (57 non AML M3) received induction chemotherapy. 82% of them had a Eastern Cooperative Oncology Group performance score of ≤ 2. 28 (of 57 non AML M3) patients were alive after post-remission therapy (with 39% deaths during induction phase) and 15 of them were in remission after a median follow up of nine months. The overall event free survival at the end of the study was 22% (16 out of 71). Altogether, 63 out of 84 patients had died. Sepsis was considered as the cause of death in 46% of the patients, but the isolation of causative organism was limited (20%). The treatment outcomes of AML are poor at our centre and the current standard of care needs a significant improvement.

Increased placental expressions of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes in gestational diabetes: Protective mechanisms against the placental oxidative stress?

OBJECTIVE: Gestational diabetes mellitus is associated with increased oxidative stress. Oxidative stress may contribute to the risk for pregnancy pathologies associated with gestational diabetes mellitus. In this study we investigated the expression of placental nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant enzymes of gestational diabetes mellitus and healthy pregnant women and correlated them with the maternal and cord plasma as well as placental tissue oxidative stress parameters. STUDY DESIGN: A cross sectional study was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty gestational diabetes mellitus patients in the gestational age of 32 ± 4weeks were recruited. Maternal plasma, cord plasma and placental oxidative stress parameters were measured. Placental expression of Nrf2, phospho Nrf2, catalase and superoxide dismutase 1(SOD1) were analyzed by western blotting and immunohistochemistry. RESULTS: Placental expression of Nrf2, catalase and SOD1 were found to be significantly higher in gestational diabetes mellitus. The maternal plasma, cord plasma and placental tissue oxidative stress parameters, total antioxidant status (TAS) levels were significantly lower; whereas MDA (malondialdehyde) and MDA/TAS levels were significantly higher in gestational diabetes mellitus. Placental Nrf2 expression correlated positively with the placental catalase expression and negatively with placental TAS levels in both groups. CONCLUSION: Maternal, fetal and placental oxidative stress was observed in gestational diabetes mellitus. The gestational diabetic placenta had an increased Nrf2 protein expression. The activated placental Nrf2/ antioxidant response element (ARE) pathway might have led to an increased expression of antioxidant enzymes SOD1 and catalase. This may be viewed as a protective mechanism in placenta from the further onslaught of oxidative stress.

Utility of time of onset of hypertension, ADMA and TAS in predicting adverse neonatal outcome in hypertensive disorders of pregnancy.

Background: Limited studies have been conducted to evaluate the utility of indices for the prediction of the adverse neonatal outcomes in hypertensive disorders of pregnancy (HDP).Method: A total of 174 pregnant women with HDP (gestational hypertension, late onset preeclampsia, and early onset preeclampsia) and 49 controls were sampled during the third trimester. Preterm birth, low birth weight, fetal, and infant mortality and low Apgar scores were assessed.Results: Multivariate analysis confirmed systolic blood pressure (SBP), time of onset of hypertension (TOH), and total antioxidant status (TAS) as predictors of preterm births; TOH and diastolic blood pressure (DBP) to be predictors of low birth weight babies; TOH and asymmetric dimethyl arginine (ADMA) as predictors of fetal mortality and babies with low Apgar at 5 min. We found TOH as the single best predictor for adverse neonatal outcomes.Conclusion: This study identified TOH as an important predictor of most of the adverse neonatal outcomes.

Predictive power of tumour budding for lymph node metastasis in colorectal carcinomas: A retrospective study.

Background & objectives: Tumour budding is a feature of epithelial-to-mesenchymal transformation that is characterized histologically within the tumour stroma by the presence of isolated cells or clusters of less than five cells which are different from the other malignant cells. This could be present around the invasive margin of the tumour, called peritumoural budding, or in the bulk of the tumour, called intratumoural budding. The aim of this study was to assess the predictive power of tumour budding for lymph node metastasis and its relationship with other features of tumour progression in colorectal carcinoma (CRC). Methods: Preoperative colonoscopic biopsies and consecutive resection specimens from 80 patients of colorectal cancer were taken. In the biopsy, intratumoural budding was looked for and graded. In the resection, peritumoural budding was seen and graded along with other features such as grade of the tumour, lymphovascular emboli and tumour border configuration. Results: Intratumoural budding was seen in 23 per cent (18/80) and peritumoural in 52 per cent (42/80) of cases. Intratumoural budding was associated with the presence of lymphovascular emboli (P=0.002) and irregular tumour border configuration (P=0.004). Peritumoural budding was also significantly associated with the presence of lymphovascular emboli and irregular margins (P < 0.001). Both intra- and peritumoural budding were not associated with the grade of the tumour. Both intra- and peritumoural budding had a significant association with lymph node metastasis (LNM) (P < 0.001). Interpretation & conclusions: Our findings indicate that tumour budding in preoperative biopsy and resection specimens may predict a possibility of finding LNM in patients with CRC.

Fetal inflammatory response syndrome (FIRS) and outcome of preterm neonates - a prospective analytical study.

OBJECTIVES: To estimate the incidence of fetal inflammatory response syndrome (FIRS) in preterm neonates and correlate it with immediate and one-year neurodevelopmental outcome. MATERIALS AND METHODS: This prospective observational analytical study, in preterm neonates with gestational age between 26 and 34 weeks was conducted from May 2014 to December 2015 in a tertiary care hospital in South India. FIRS was defined as the presence of either elevated levels of interleukin-6 (IL-6) in cord blood ≥11 pg/ml and/or the placental histopathology showing evidence of fetal inflammatory response. One hundred and twenty neonates were recruited. During delivery 2 ml cord blood for interleukin-6 and placenta were collected and stored appropriately. Based on presence/absence of FIRS (IL-6 in cord blood ≥11 pg/ml and or features of placental fetal inflammation), neonates were grouped into two groups. The neonatal and maternal characteristics between two groups were compared. The short-term outcome parameters during NICU stay and neurodevelopmental outcome at one year of corrected age was compared between groups. RESULTS: Among the 120 infants studied, 19 expired. Out of 101 babies discharged, 87 were followed up till corrected 1 year of age. On examination of placenta and cord blood, 50 neonates had evidence of FIRS (41.6%). So there were 50 neonates in FIRS and 70 in NO-FIRS group. The mean gestational age, birth weight, and gender distribution were comparable between the two groups. Mortality [OR: 2.44 (CI: 1.14-5.26)] and early hypotension [OR: 2.13 (CI: 1.1-4.2)] were significantly higher in the FIRS group. The neurodevelopmental assessment at corrected age of 1 year showed that infants with FIRS had lower mean motor developmental quotient by developmental assessment scale for Indian infants (DASII) [87.6 ± 9.15 versus 93.07 ± 9.3, p < .04]. CONCLUSIONS: FIRS has a significant role on survival and neurodevelopmental outcome of preterm infants.

Amla (Emblica officinalis) improves hepatic and renal oxidative stress and the inflammatory response in hypothyroid female wistar rats fed with a high-fat diet.

BACKGROUND: We investigated the protective effects of amla (Emblica officinalis) on the pathogenesis of oxidative stress (OS) and inflammatory response in hypothyroid rats fed with a high-fat diet (HFD) as an experimental model of hypothyroidism (HT) with obesity. METHODS: A total of 80 female wistar rats (5-months-old) were divided into eight different groups. Propylthiouracil (PTU) and HFD were used to induce the experimental HT and obesity, respectively. The euthyroid and hypothyroid rats were fed either normal chow or HFD with and without amla extract (AE, 100 mg/kg bw/day) for 6 weeks. The blood and tissues, liver and kidney OS and inflammatory parameters were studied using appropriate biochemical and molecular techniques. RESULTS: PTU and HFD per se caused OS and inflammatory response as evidenced by increased plasma MDA, TNF-α, CRP and GPx in association with decreased levels of TAS and reduced glutathione (GSH). The proteomic analysis revealed that the expressions of pERK, pP38, TNF-α, IL6, COX2 and NOX-4 were up-regulated in the liver and kidney of these rats. In addition, all these metabolic derangements were further augmented when HT was followed by the addition of HFD. This suggested that there was a synergism between HT and the intake of HFD on the development of OS and inflammatory response. CONCLUSIONS: The treatment with amla fruit extract significantly restored the redox imbalance and inflammatory signaling and ameliorated OS and inflammatory response, suggesting the use of this natural compound as an alternative remedy or adjuvant for the management of metabolic complications concomitant with HT.

Clinico-Histomorphological and Immunohistochemical Profile of Anaplastic Pleomorphic Xanthoastrocytoma: Report of Five Cases and Review of Literature.

Background: Pleomorphic xanthoastrocytoma is a rare tumour of children and young adults, particularly for those with features of anaplasia. Materials and Methods : This retrospective study comprises five cases of anaplastic pleomorphic xanthoastrocytomas diagnosed over a period of 4 years in a tertiary care institute. A detailed clinicopathological and immunohistochemical profile of the tumours were noted from the hospital database. Results: Five cases of anaplastic pleomorphic xanthoastrocytomas were evaluated for their clinicoradiological, histomorphological as well as immunohistochemical findings, which included 3 females and 2 males, with age range of 11-40 years and a mean age at presentation of 22 years. Histologically a solid cystic biphasic tumour with moderate to high cellularity, spindled pleomorphic astrocytes, hyperchromatic nuclei showing moderate to marked atypia, intranuclear inclusions, ≥5 mitoses per 10 high power fields, with evidence of necrosis and atypical mitoses was noted. One of the cases showed transformation into glioblastoma with evidence of spinal metastasis on follow-up. The tumours expressed both glial as well as neuronal markers with expression of CD34 with increased Ki 67 ranging between 5-20%. Conclusion: It was concluded that PXA, a low-grade glioneuronal tumour, can show odd site presentation, marked pleomorphism, increased mitosis, atypical mitoses and increased Ki 67 when associated with features of anaplasia. An appropriate panel of immunohistochemical markers in conjunction with a detailed evaluation of histomorphological features and clinicoradiological information are useful for its diagnosis.

Metabolomic Analysis and Antioxidant Effect of Amla (Emblica officinalis) Extract in Preventing Oxidative Stress-Induced Red Cell Damage and Plasma Protein Alterations: An In Vitro Study.

Amla (Emblica officinalis) has antidiabetic, hypolipidemic, anti-inflammatory, and antioxidant properties, but its effect on free radical induced red cell damage and membrane and plasma protein alterations has not been adequately addressed. The aim of the present study was to evaluate the antioxidant property of amla against oxidative stress-induced red cell damage and plasma protein alterations. Red blood cells (RBCs) were preincubated with different concentrations of amla extract (50, 100, 150, and 200 µg/mL) and then treated with physiological (5 mM) and pathological (50 mM) concentrations of glucose for 24 h. In another in vitro study the plasma was pretreated with different concentrations of amla extract and then incubated with 2, 2'-Azo-Bis (2-methylpropionamidine) dihydrochloride (AAPH) for 2 h. After the incubation RBC-malondialdehyde (MDA), RBC-reduced glutathione (GSH), RBC indices, RBC morphometric study, plasma MDA, protein carbonylation, total protein, and albumin were estimated. The antioxidant property of amla was assessed by DPPH assay. RBC-MDA levels were significantly decreased and RBC-GSH levels were significantly increased with higher concentration of amla extract (150 and 200 µg/mL). Red cell count and its indices were improved with the increasing concentration of amla. In addition, at higher concentration, amla restored the RBC membrane integrity. The plasma in vitro study also showed that amla improved the plasma MDA, protein carbonylation, total protein, and albumin levels. Amla extract effectively protected the RBCs and plasma proteins from the reactive oxygen species induced oxidative damage. Liquid chromatography-mass spectrometry (LC-MS) analysis of the extract revealed the presence of gallic acid, quinic acid, and quercetin as the major constituents in addition to the other flavonoids.