Reciprocal Relationship Between HDAC2 and P-Glycoprotein/MRP-1 and Their Role in Steroid Resistance in Childhood Nephrotic Syndrome

Background: Reduced HDACs levels have been reported in steroid resistant chronic obstructive pulmonary disease and bronchial asthma patients. P-glycoprotein (P-gp) over expression in peripheral blood mononuclear cells (PBMCs) has been reported in patients with steroid resistant nephrotic syndrome (NS). Whether and how HDACs and P-gp are linked with each other is not clear, especially in NS patients.Aim: To evaluate mRNA expression of P-gp/MRP-1 and HDAC2 in PBMCs of steroid sensitive (SSNS) and steroid resistant nephrotic syndrome (SRNS) patients, and determine the relationship between expression of HDAC2 and P-gp/ MRP-1in NS patients.Methods: Twenty subjects (10 in each group), SSNS (mean age 7.54 ± 3.5 years), and SRNS (mean age 8.43 ± 3.8 years) were recruited. mRNA expression of HDAC2 and P-gp/MRP-1 was studied by quantitative real time PCR. PBMCs were treated with Theophylline, 1 μM, and Trichostatin A, 0.8 μM, for 48 h for induction and suppression of HDAC2, respectively.Results: At baseline, expression of P-gp (4.79 ± 0.10 vs. 2.13 ± 0.12, p < 0.0001) and MRP-1 (3.99 ± 0.08 vs. 1.99 ±0.11, p < 0.0001) on PBMCs were increased whereas, HDAC2 mRNA levels (2.97 ± 0.15 vs. 6.02 ± 0.13, p < 0.0001) were significantly decreased in SRNS as compared to that of SSNS patients. Compared to baseline, theophylline reduced mRNA expression of P-gp and MRP-1 (fold change 2.65 and 2.21, *p < 0.0001 in SRNS) (fold change 1.25, 1.24, *p < 0.0001 in SSNS), respectively. However, it increased the expression of HDAC2 (fold change 5.67, *p < 0.0001 in SRNS) (fold change 6.93, *p < 0.0001 in SSNS). Compared to baseline, TSA treatment increased mRNA levels of P-gp and MRP-1 (fold change 7.51, 7.31, *p < 0.0001 in SRNS) and (fold change 3.49, 3.35, *p < 0.0001 in SSNS), respectively. It significantly decreased the level of HDAC2 (fold change 1.50, *p < 0.0001 in SRNS) (fold change 2.53, *p < 0.0001 in SSNS) patients.Conclusion: Reduced HDAC2 and increased P-gp/MRP-1 activity may play a role in response to steroids in childhood NS. HDAC2 and P-gp/MRP-1 are in reciprocal relationship with each other

Electrolyte changes in neonates ≥ 35 weeks gestation receiving phototherapy for neonatal jaundice

Introduction: Neonatal hyperbilirubinemia is a common clinical problem encountered during the neonatal period. High serum bilirubin levels can be toxic for central nervous system development and may cause behavioural and neurological impairment (Kernicterus) even in term newborns. Phototherapy is one of the most effective ways available in preventing the neurotoxic complications of indirect hyperbilirubinemia. Methodology: It is a prospective interventional study. Ethical clearance was obtained from institutional ethical committee. Neonates who were born or admitted to a tertiary care centre from September 2020 to August 2021, receiving Light Emitting Diode(LED) phototherapy for unconjugated hyperbilirubinemia after 24 hrs of life without any co-morbidities were involved in the study. Results: A total of 100 neonates were involved of which 55 were males and 45 were females (Figure 1). The mean sodium, potassium and calcium level before therapy were 147.6±5.2, 4.9±0.3, and 9.6±0.6 respectively. After phototherapy the mean sodium, potassium and calcium level were 142.3±5.6, 4.1±0.5 and 8.5±0.7 respectively. There was significant difference in sodium level before and after phototherapy with p-value= 0.02. But, in level of Potassium there But, in level of Potassium there was no significant difference (p=0.31) due to phototherapy before and after. Before phototherapy none of baby had hyponatremia while after phototherapy 8.7% cases had hyponatremia. Similarly, hypocalcaemic was present in 4.2% cases before phototherapy and after phototherapy 28.3% cases had hypocalcaemic which was found significant statistically. Conclusion: Neonatal hyperbilirubinemia can easily pickup on clinical examination however require quick and on the spot treatment. If not treated properly, it leads to many complications. Currently the best treatment option for jaundice is photo therapy

A Study On Risk Factors of Relapses of Nephrotic Syndrome Among Pediatric Patients at a Tertiary Care Center of Bihar

Introduction: Nephrotic syndrome (NS) is 15 times more common in children than in adults. NS affects13/100,000 children<16 years of age . Two-thirds of childhood NS present before the age of 6 years. Therefore, we planned this study with an objective to identify the risk factors for FR in childhood steroid sensitive NS (SSNS). Methodology: A prospective study was conducted by the Department of Pediatrics, Nalanda Medical College &Hospital, Bihar, between February 2020 to January 2021. Cases with the first episode of idiopathic SSNS in the age group of 9 months - 12 years, who followed up for at least 12 months were enrolled in the study. NS was diagnosed in accordance with standard criteria. Results: A total of 100 children with NS were included in the current study based on inclusion criteria during the study period. There was a male preponderance among the study participants. Incidence of infection and hypertension was 34% and 37%, respectively. Incidence of FR was high in 1-8 years age group. The incidence of FR was less in males than in females; but it was not significant. Majority of the children with IFR group responded to steroid therapy in <2 weeks, while the most children with FR showed response after 3-4 weeks. Conclusion: Relapse within first 6 months, associated infections and hypertension were the factors significantly associated with FRs in childhood SSNS. These factors should be kept in mind and should be well documented at the time of initial presentation of NS for the long-term management

Assess the utility of urinary uric acid and creatinine ratio as a marker of neonatal asphyxia: a comparative study

Aim: to assess the utility of urine uric acid creatinine ratio (UA/Cr) as an additional marker of neonatal depression and birth asphyxia and it’s utility as a potential prognostic indicator for the immediate outcome. Material and methods: This prospective observational study was carried out in the department of Pediatrics in Nalanda Medical College and Hospital , Patna Bihar India from November 2019 to April 2020 in this study that included 200 newborns. Newborns with encephalopathy were considered to have an unfavourable outcome. The urine UA/Cr was estimated in both groups. Results: The mean differences of urine UA/Cr were statistically significant in birth asphyxia (3.26±1.37), and controls (2.02± 0.71). Conclusion: The urine UA/Cr is a useful diagnostic and prognostic biomarker in newborns with birth asphyxia. Keywords: UA/Cr, Biomarker, Birth asphyxi

To evaluate the effect of Maternal Vitamin D Deficiency on Increased Risk for Hyperbilirubinemia in Term Newborns: An observational study

Aim: to study the effect of Maternal Vitamin D Deficiency on Increased Risk for Hyperbilirubinemia in Term Newborns. Materials and Methods: This prospective observational study was carried out in the Department of Pediatrics, Nalanda Medical College and Hospital at Patna, Bihar India from July 2019 to march 2020 .Serum 25-hydroxyvitamin D was measured from 200 included pregnant women during birth time. The level of bilirubin was measured in their newborns at 3rd to 5th days of life.  Results: The level of 25-hydroxyvitamin D was low in 190 (95%) pregnant women. Hyperbilirubinemia was detected in 29 (14.5%) newborns at the 3rd to 5th days of life. Maternal vitamin D during pregnancy showed a significant correlation with the levels of bilirubin in newborns(r= - 0.449, P<0.001). Conclusion: The presence of maternal vitamin D deficiency could effectively predict the increased risk for neonatal Hyperbilirubinemia

Biotechnological Interventions in Tomato (<i>Solanum lycopersicum</i>) for Drought Stress Tolerance: Achievements and Future Prospects

Tomato production is severely affected by abiotic stresses (drought, flood, heat, and salt) and causes approximately 70% loss in yield depending on severity and duration of the stress. Drought is the most destructive abiotic stress and tomato is very sensitive to the drought stress, as cultivated tomato lack novel gene(s) for drought stress tolerance. Only 20% of agricultural land worldwide is irrigated, and only 14.51% of that is well-irrigated, while the rest is rain fed. This scenario makes drought very frequent, which restricts the genetically predetermined yield. Primarily, drought disturbs tomato plant physiology by altering plant–water relation and reactive oxygen species (ROS) generation. Many wild tomato species have drought tolerance gene(s); however, their exploitation is very difficult because of high genetic distance and pre- and post-transcriptional barriers for embryo development. To overcome these issues, biotechnological methods, including transgenic technology and CRISPR-Cas, are used to enhance drought tolerance in tomato. Transgenic technology permitted the exploitation of non-host gene/s. On the other hand, CRISPR-Cas9 technology facilitated the editing of host tomato gene(s) for drought stress tolerance. The present review provides updated information on biotechnological intervention in tomato for drought stress management and sustainable agriculture

Long-term outcomes of hepatitis C virus infected renal allograft recipients

Background and Aim: This study aims to study the long-term outcomes of hepatitis C virus (HCV)-infected renal allograft recipients, which is still debatable. Materials and Methods: In this study (study period - January 2003 to December 2013), we studied long-term outcomes of 106 living donor renal allograft recipients - 53 HCV-infected (33 genotype 3 and 20 genotype 1) and 53 age- and gender-matched HCV-noninfected patients. Results: Thirty-nine (73.6%) patients detected HCV positive during dialysis, while 14 (26.4%) before the start of dialysis. Forty (75.5%) patients were positive for both anti-HCV and HCV RNA, while 13 (24.5%) were HCV RNA positive and anti-HCV negative. Twelve and nine patients died among HCV positive and negative groups, respectively. Major cause of death was sepsis in both groups. Hepatic failure contributed to mortality in four HCV-positive patients, two of them also had graft failure. Patient and death noncensored graft survival rates at 1, 5, and 10 years of follow-up in HCV-positive group were 100% and 100%; 79.8% and 70.8%; 58.9% and 37.8%; respectively; and in HCV-negative group were 100% and 100%; 95.9% and 91.8%; 58.9% and 27.4%; respectively. Conclusions: The long-term survival of HCV-positive renal transplant recipients was not inferior to that of HCV-negative recipients

Identification of Novel SNP in Promoter Sequence of TaGW2-6A Associated with Grain Weight and Other Agronomic Traits in Wheat (Triticum aestivum L.).

TaGW2 is an orthologue of rice gene OsGW2, which encodes E3 RING ubiquitin ligase and controls the grain size in rice. In wheat, three copies of TaGW2 have been identified and mapped on wheat homoeologous group 6 viz. TaGW2-6A, TaGW2-6B and TaGW2-6D. In the present study, using as many as 207 Indian wheat genotypes, we identified four SNPs including two novel SNPs (SNP-988 and SNP-494) in the promoter sequence of TaGW2-6A. All the four SNPs were G/A or A/G substitutions (transitions). Out of the four SNPs, SNP-494 was causal, since it was found associated with grain weight. The mean TGW (41.1 g) of genotypes with the allele SNP-494_A was significantly higher than mean TGW (38.6 g) of genotypes with the allele SNP-494_G. SNP-494 also regulates the expression of TaGW2-6A so that the wheat genotypes with SNP-494_G have higher expression and lower TGW and the genotypes with SNP-494_A have lower expression but higher TGW. Besides, SNP-494 was also found associated with grain length-width ratio, awn length, spike length, grain protein content, peduncle length and plant height. This suggested that gene TaGW2-6A not only controls grain size, but also controls other agronomic traits. In the promoter region, SNP-494 was present in 'CGCG' motif that plays an important role in Ca2+/calmodulin mediated regulation of genes. A user-friendly CAPS marker was also developed to identify the desirable allele of causal SNP (SNP-494) for use in marker-assisted selection for improvement of grain weight in wheat. Using four SNPs, five haplotypes were identified; of these, Hap_5 (G_A_G_A) was found to be a desirable haplotype having significantly higher grain weight (41.13g) relative to other four haplotypes (36.33-39.16 g)

Representative gel picture of PCR amplification of promoter region of <i>TaGW2-6A</i> gene in 15 Indian wheat genotypes.

<p>Representative gel picture of PCR amplification of promoter region of <i>TaGW2-6A</i> gene in 15 Indian wheat genotypes.</p

Frequency distribution curve for nine agronomic traits including 1000 grain weight in 207 Indian wheat genotypes used in association mapping study.

<p>Frequency distribution curve for nine agronomic traits including 1000 grain weight in 207 Indian wheat genotypes used in association mapping study.</p