Anjali Rani

Free radicals and antioxidants status in neonates with congenital malformation

Background: Several studies using animal models have shown that oxidative stress during pregnancy may play an important role in causing birth defects. Congenital anomalies affect an estimated 270,000 newborns who die during the first 28 days of life every year from different birth defects. Hence, at present many research works are going on to reduce the infant mortality from congenital anomaly. [1] Objective: The objective was to measure the oxidant and antioxidant level in the serum of newborn babies with the congenital anomaly and compare these levels with age and sex matched normal neonates. This is to identify any role of oxidative stress in the causation of congenital anomaly. Materials and Methods: This case-control study included 159 participants: 106 newborns with the congenital anomaly and 53 healthy newborns. The markers of oxidative stress like serum malondialdehyde (MDA) level, protein carbonyl (PC) level, and the activity of antioxidants such as Vitamin C, glutathione were measured in both cases (neonates with congenital anomaly) and controls (normal healthy neonates). These parameters were statistically compared. Results: MDA levels and PC levels were significantly higher (P < 0.0001), and Vitamin C and reduced glutathione levels were significantly lower (P < 0.0001), in newborns with congenital malformation than in healthy newborns. Conclusions: Increased lipid peroxidation and protein carbonylation might play an important role in the pathogenesis of congenital anomaly. Impairment of the free radical/antioxidant balance is leading to increased free radical damage in neonates with congenital malformation.

Correlation of Oxidative Damage with Pro-Inflammatory Markers (IL-6, TNF-α) in Meningocele.

INTRODUCTION Oxidative damage induces alteration in the status of pro-inflammatory markers like IL-6 and TNF-α in meningocele. The study was performed with estimation of the levels of MDA (Malonyldialdehyde), SOD (Superoxide dismutase) taken as oxidative damage markers and IL-6 (interleukin 6) and TNF-α (Tumour necrosis factor alpha) taken as inflammatory markers, in the serum of meningocele patients and age, sex matched normal neonates. Correlation among the different serum levels of MDA, SOD, IL-6 and TNF-α was determined. MATERIALS AND METHODS It is a case-control study, comprising of 153 participants: 101 newborns with meningocele and 52 healthy newborns. The study was conducted in the Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, in collaboration with the Department of Paediatric Surgery and Department of Obstetrics and Gynecology, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi. The study was conducted during the period of 2012 to 2014. Serum was extracted from blood collected from both groups i.e. meningocele patient group and healthy neonatal control group. The levels of MDA and SOD were determined by spectrophotometric method. IL-6 was determined by the Human IL-6 High Sensitivity ELISA Kit and TNF-α was determined by the Human TNF-α ELISA KIT. RESULTS The levels of MDA, TNF-α and IL-6 were found to be much higher and level of SOD was found lower in the patients with meningocele as compared to the normal healthy neonates. CONCLUSION Increased MDA (oxidative damage product), IL-6, and TNF-α (inflammatory marker) and low level of SOD shows an increased inflammatory response in Meningocele. Our study shows Negative Correlation between MDA and SOD in case & control groups, while a Positive Correlation between TNF alpha and IL-6 in control & case groups.

A novel GLI3c.750delC truncation mutation in a multiplex Greig cephalopolysyndactyly syndrome family with an unusual phenotypic combination in a patient

Greig cephalopolysyndactyly (GCPS) syndrome is an autosomal dominant disorder with high penetrance in majority of cases, characterized by a triad of polysyndactyly, macrocephaly and hypertelorism. GCPS is known to be caused by mutations in the transcription factor GLI3 gene (7p13) which results in functional haploinsufficiency of this gene. The present study reports a large multiplex family having 12 members affected with GCPS in 3 generations and several unaffected members showing autosomal dominant pattern of inheritance with complete penetrance. Interestingly an affected member of the family had unusual features including thumb which is although biphalangeal (confirmed with X-ray) but morphologically looks like finger and a unilateral tiny bony outgrown (externally indistinguishable) on the distal phalanx of the first toe of the left foot. This member also presented with mild ichthyosis. Although it is also possible that one or more of these features are coincidentally present in this member and might not be part of GCPS. Resequencing of the GLI3 gene detected a novel frame-shift mutation c.750delC in heterozygous state transmitting in the family and co-segregating with the disorder suggesting it to be the causal for the GCPS phenotype in the family. In silico analysis suggests that this mutation creates a truncated GLI3 protein resulting in its haploinsufficiency leading to GCPS syndrome. Furthermore, genotype-phenotype correlation is supported by the mutation as it lies in the amino terminal domain of the protein.

Clinicosociodemographic profile of ruptured ectopic pregnancies at a tertiary care centre

Background: Rupture of an ectopic pregnancy remains the most dreaded complication of a pregnancy related event and is the commonest cause of maternal mortality in the first trimester of pregnancy. In the developing countries, the maternal death rate among patients admitted with ectopic pregnancy was found to be as high as one in ten. In addition to high risk for mortality, rupture of an ectopic pregnancy could affect future fertility of a woman. The objectives of this study are to analyse the sociodemographic and clinical characteristics and find out the incidence rate and risk factors associated with ruptured ectopic pregnancies in a tertiary care institution. Methods: This is a retrospective study and was conducted over a period of one year from September 2015 to September 2016 in Department of Obstetrics and Gynecology at Institute of Medical Sciences, BHU, Varanasi, India. It is a tertiary care centre getting referrals not only from nearby cities and hospitals but also from major cities of neighbour states. During this time frame a total of 2601 deliveries have taken place and 57 cases of ruptured ectopic pregnancies were reported. Data were collected in a preconceived format. Results: Total numbers of vaginal deliveries were 2601 during the study period. Out of which 63 (2.42%) were found to be ectopic pregnancies and 57 (1.99%) were diagnosed as ruptured ectopic pregnancies. Maximum number of patients (70.17%) were between 21 and 30 years of age. As far as parity is concerned only 12.29 % of patients were primigravida where as 70.71% patients were multigravida. Previous history of pelvic inflammatory disease was associated among maximum number of cases i.e 50.87% of total number of cases. Among other risk factors, previous abortions, previous ectopic pregnancies and history of infertility treatment were the prime ones. Maximum number of patients were from lower and lower middle class socioeconomic status. Ampullary type of Tubal ectopic pregnancies were found to be the commonest ones. Two cornual pregnancies and two ovarian pregnancies were also found in this series. In 85.97 % of patients the amount of hemoperitoneum was found to be more than 500 ml. Conclusions: There is high incidence rate of ectopic pregnancy and low rate of diagnosis before rupture occurs in developing nations as in our scenario. Pelvic inflammatory disease, Maternal education, socioeconomic status, parity and history of subfertilty are the risk factors associated with ruptured ectopic pregnancy. Effective efforts should be taken to encourage the level of education and improve the rate of diagnosis among health care providers before the occurrence of rupture.

Maternal gene polymorphisms of folate metabolism as genetic risk factor for Down syndrome in North Indian population

Down syndrome (DS), a chromosomal disorder has higher prevalence in population occurring 1 in 700 live births. Recent reports have shown that almost 92% of the DS children are born from young mothers, suggesting that along with advanced maternal age some other risk factors are involved for predisposition of mother to Down child. Polymorphism in genes involved in folate metabolism as well as insufficient folic acid intake could result in genomic instability, DNA hypomethylation and non-disjunction even resulting in trisomy 21. In present study we compared the frequency of Thymidylate Synthase (TYMS) 28 bp repeat polymorphism in 5’UTR region, Cystathionine-Beta-Synthase (CBS) 844ins68bp polymorphism and Solute Carrier (SLC) 19A1 G80A single nucleotide polymorphisms in 80 triads (mother, father and child) and 77 matched control mothers in order to observe whether these variants act as risk factors for DS. A significant association was observed for TYMS 5’UTR 28 bp repeat with odds ratio 2.9 (95% CI 1.2-7.1, p=0.027). An association which is very close to be significant was observed for SLC19A1 G80A with odds 2.01(95% CI 1.04-4.24, p=0.055). Heterozygosity for 68 bp insertion at 844 in CBS showed significant association with odds ratio 10.5 (95% CI 1.29-85.1, p=0.019). Transmission disequilibrium test (TDT) for 28 bp repeat polymorphism in TYMS gene presented more than four times greater preferential transmission of maternal two repeats allele whereas paternal three repeats allele had about 1.5 times higher rate of transmission. TDT for SLC19 A1 G80A SNPs revealed preferential transmission of maternal A allele more than two times greater as compared to G allele whereas paternal alleles transmission didn’t show much difference. The result shows that above three polymorphism are significantly associated as a risk factor for predisposition of mother to DS children in the North Indian population.

Rudimentary Thymus In A Case Of Potter’s Syndrome

Potter syndrome refers to a group of characteristic facial findings associated with lack of amniotic fluid and kidney failure in an unborn infant . It is related to a chain of events that may have different beginnings ( absent kidneys,cystic kidneys,obstructed ureters ),but which all end with the same conclusion ( oligohydramnios ).Rudimentary thymus is a rare finding in Potter syndrome.We report here a case of 20 weeks old male fetus with Potter syndrome, who had polycystic kidneys, hypoplastic lungs, hepatomegaly, intestinal obstruction and most interesting finding was rudimentary thymus which is a rare finding.