Harshit Singh - Academia.edu (original) (raw)

Papers by Harshit Singh

Journal of Inflammation Research, 2022

Background and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is assoc... more Background and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. Methods: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. Results: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. Conclusion: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.

2022 3rd International Conference on Intelligent Engineering and Management (ICIEM)

Rheumatology

higher in the non-articular group [Table 1]. Th17 cells were lower in group B but did not reach s... more higher in the non-articular group [Table 1]. Th17 cells were lower in group B but did not reach statistical significance [p 0.11]. Th1/Th2 ratio was lower and Th1/Treg and Th17/Treg ratios were higher in sarcoid arthritis [p < 0.05] as opposed to non-articular sarcoidosis. Conclusion: T helper cell axis was skewed towards Th1 and Th17 in sarcoid arthritis when compared to patients without articular involvement. Thus, this difference in T cell subsets may explain to an extent the diversity in the disease manifestations and may have implications on management. It may be worthwhile to study the T cell repertoire in other tissue or body fluids of patients with sarcoidosis with and without arthritis. Disclosures: The authors have declared no conflicts of interest.

2020 IEEE International Conference on Computing, Power and Communication Technologies (GUCON)

A disc-loaded circular radio-frequency interaction structure for its prospective application in a... more A disc-loaded circular radio-frequency interaction structure for its prospective application in a gyro-travelling wave tube amplifier is field analyzed for obtaining dispersion characteristics. The study reveals that a disc-loaded circular radio-frequency interaction structure has a pass-band characteristics. Few azimuthally symmetric transverse electric modes like TE01 and TE02 have been identified. The pass-band characteristics for TE01 and TE02 modes have been obtained using MATLAB simulation and also been verified against CST Microwave Studio. The mathematical and simulation results are in near agreement.

Palaeogeography, Palaeoclimatology, Palaeoecology, 2022

Nephrology Dialysis Transplantation, 2018

INTRODUCTION AND AIMS: Renal transplantation is the best modality of RRT and adequate immunosuppr... more INTRODUCTION AND AIMS: Renal transplantation is the best modality of RRT and adequate immunosuppression is the cornerstone of the success of transplant. is adequate immunosuppression. Tacrolimus (Tac) is one of the most widely used immunosuppressant but there is marked inter individual variations with small therapeutic range of blood Tac level. This inter-individual variations in Tac level may be because off differential expression of P-glycoprotein (P-gp), which is efflux pump expressed on lymphocytes. This study aimed to evaluate the P-gp expression on PBMCs and correlate with Tac trough concentration in renal allograft recipients. Genotype analysis was performed with RFLP. METHODS: Of 54 renal transplant recipients, Group A (n¼15) were higher Tac level (15.2466.45) than target C0 (9-12 ng/ml), Group B (n¼35) were achieved target Tac C0 level (11.5861.15) and Group C (n¼6) were not achieved target C0 (6.1562.26) on day-1 of transplantation at dose of 0.15mg/kg/day. Of the 54 patients, 29 had glomerulonephritis, 19 had interstitial nephropathy, 5 had diabetic nephropathy and 1 had polycystic kidney disease. All patients were on triple immunosuppressive Tac, MMF and prednisolone. Heparinized blood sample were taken for P-gp expression analysis. P-gp expression and functionality were analyzed on flowcytometer. RESULTS: The requirement of Tac (mg/kg/day) was significantly low in group C (0.2360.06) than that of group A (0.09860.03; p¼0.001) and group B (0.14860.02; p¼0.015). Tac C0 to dose ratio (ng/ml per mg/kg/day) was significantly high in group A (149.95656.75) than group B (75.26623.75) and group C (29.45613.14). P-gp positive cell was significantly high in group C than that of group A (p<0.001) and group B (p¼0.004) and significantly high in group B than group A (p¼0.043). The functionality of P-gp was also high in group C than that of group A (p<0.001) and group B (p¼0.021) and significantly high in group B than group A (p¼0.049). There is significant negative correlation between Tac Co with P-gp expression and functionality. We have found significantly high P-gp expression in patients with CC genotype of C3435T SNP. Patients having TTþAA genotype of G2677T/A requires 38% more Tac dose. CONCLUSIONS: Higher P-gp expression lowers the Tac concentration in blood. P-gp monitoring may helpful to predict the initial daily dose needed by individual patients to obtain adequate immunosuppression. Patients with TTþAA genotype of G2677T/A require high Tac dose.

2020 IEEE International Conference on Computing, Power and Communication Technologies (GUCON), 2020

In this paper, electron bunching and power evolution along the axial length of the gyro-TWT ampli... more In this paper, electron bunching and power evolution along the axial length of the gyro-TWT amplifier are explained by making use of an electron flight diagram that shows individual electron trajectories during the entire amplification process. A typical gyro-TWT amplifier operating in TE01 mode at 35 GHz with parameters beam voltage mathrmV0=70textkV\mathrm{V}_{0}=70\text{kV}mathrmV0=70textkV, beam current mathrmI0=15\mathrm{I}_{0}=15mathrmI0=15 Amp, waveguide radius = 5.42 mm, DC magnetic field mathrmB0=1.32mathrmT\mathrm{B}_{0}=1.32\ \mathrm{T}mathrmB0=1.32mathrmT, Hollow beam radius = 2.547 mm, Larmor radius = 0.58 mm resulted in 11.75 kW peak output power. Result obtained from the developed MATLAB code has been benchmarked against the published result and is found to be in good agreement.

2020 IEEE International Conference on Computing, Power and Communication Technologies (GUCON), 2020

Large signal analysis for a circular cylindrical smooth wall gyro-travelling wave tube amplifier ... more Large signal analysis for a circular cylindrical smooth wall gyro-travelling wave tube amplifier has been successfully used to generate the power, and gain plots for a variety of input parameters. The gain versus frequency plots are generated for TE11 mode with the input data as the beam voltage of 100 kV, beam current of 1 Amp., waveguide cut-off frequency of 33.68 GHz and the pitch factor of 1. The gain versus frequency plots are found to be in good agreement with the published data. Additionally, the gain versus axial distance plots are generated at TE11 mode for the frequency of 9 GHz and beam current of 7 Amp. and are also found to be matching with the published data.

Nephrology Dialysis Transplantation, 2018

INTRODUCTION AND AIMS: Fibrosis in the peritoneum is a major cause of ultrafiltration failure in ... more INTRODUCTION AND AIMS: Fibrosis in the peritoneum is a major cause of ultrafiltration failure in continuous ambulatory peritoneal dialysis (CAPD) patients. Transforming growth factor (TGF)-b1 is a major pro-fibrotic cytokine, which is an essential factor in progressive changes in the peritoneal membrane leading to peritoneal fibrosis.To explore anti-fibrotic role of Phosphodiesterase-5 inhibitors, Sildenafil and Zaprinast, respectively in human peritoneal fibroblasts (HPFB) isolated from omentum and parietal peritoneum of CAPD patients. METHODS: Omentum biopsy (OB) of control patients (n¼6) undergone elective abdominal surgery and CAPD patients (n¼2) was incubated in 0.125% trypsin/0.01% EDTA twice for 20 minutes, twice for 40 minutes at 37 C. Parietal peritoneum biopsy (PB) excised during laparotomy was incubated overnight in dispase (2.4 U/mL)/37 C. HPFB appeared within 2 weeks. In disease mimicking strategy, HPFB from OB and PB were incubated with TGF-b1-10ng/ml for 1 hr and later with TGF-b1-10ng/ml and (Sildenafil, Zaprinast-10mM, each) for 24 hr. In second strategy, HPFB from OB and PB were pretreated with (Sildenafil, Zaprinast-10mM, each) for 1 hr and later with only TGF-b1-10ng/ml for 24 hr. Real time qPCR for pro-fibrotic (Col1a1, Col1a2, ACTA2, CTGF and FN1) and anti-fibrotic genes (MMP2/TIMP1) expression was performed. Type I collagen and a-SMA was examined by western blotting. RESULTS: In TGF-b1 stimulated HPFB, upregulated mRNA expression of pro-fibrotic genes (p<0.05) at 24 hr was observed. Pre-treatment of HPFB with Sildenafil and Zaprinast more effectively reduced pro-fibrotic genes expression (p<0.05) than disease mimicking strategies (Figure 1and 2). Ratio of anti-fibrotic mRNA responses (MMP2/ TIMP1) was restored with the pretreatment strategy more efficiently than disease imitating strategy (p<0.05) (Figure 3). Also pre-treatment with Sildenafil and Zaprinast decreased type 1 collagen and a-SMA competently (p<0.05). CONCLUSIONS: Phosphodiesterase-5 inhibitors reduce pro-fibrotic mRNA expression and restore anti-fibrotic mRNA reponses in co-cultured human peritoneal fibroblasts with TGF-b1.

Critical Care Medicine, 2016

Nephrology Dialysis Transplantation, 2018

Nephrology Dialysis Transplantation, 2018

Nephrology Dialysis Transplantation, 2021

Background : - Intravenous administration of radiocontrast media is referred to as contrast-induc... more Background : - Intravenous administration of radiocontrast media is referred to as contrast-induced kidney injury (CI-AKI).CI-AKI is described as the third most common cause of new AKI in hospitalized patients. The occurrence of CI-AKI is reported up to 55% in these high-risk patients.: NGAL (Neutrophil gelatinase-associated Lipocalin)and Cystatin C have been found an early and sensitive marker of acute kidney injury (AKI). Aims To evaluate biomarkers in plasma (P) and urine (U) after intravenous contrast in adult ICU patients. Method Total of 36 patients recruited as per inclusion criteria. ICU patients who were >18 years with radiographic contrast for diagnostic or interventional computed tomography (CT scan), were included. After ethical approval, samples of 5 ml blood and 5 ml urine were collected before contrast exposure and at 4 h, 24 h, and 48 h after contrast exposure. NGAL and Cystatin C assay was done by ELISA, and urinary levels were normalized as per urine creatinine ...

Scientific Reports, 2021

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection fro... more To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil–lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9–86.5) vs. 16% (12.6–23.1) vs. 7.05% (1.4–9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229–1828) vs. 853 (20–968) vs. 99.5 (54.7–140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area u...

Frontiers in Marine Science, 2021

In this study, we presented a high-resolution benthic foraminiferal assemblage record from the we... more In this study, we presented a high-resolution benthic foraminiferal assemblage record from the western Bay of Bengal (BoB) (off Krishna–Godavari Basin) showing millennial-scale variations during the last 45 ka. We studied temporal variations in benthic foraminiferal assemblages (relative abundances of ecologically sensitive groups/species, microhabitat categories, and morphogroups) to infer past changes in sea bottom environment and to understand how monsoon induced primary productivity-driven organic matter export flux and externally sourced deep-water masses impacted the deep-sea environment at the core site. Our records reveal a strong coupling between surface productivity and benthic environment on glacial/interglacial and millennial scale in concert with Northern Hemisphere climate events. Faunal data suggest a relatively oxic environment when the organic matter flux to the sea floor was low due to low primary production during intensified summer monsoon attributing surface wat...

The Pharmacogenomics Journal, 2021

Steroid remains the keystone therapy for Idiopathic Nephrotic Syndrome (NS). Besides genetic fact... more Steroid remains the keystone therapy for Idiopathic Nephrotic Syndrome (NS). Besides genetic factors and histological changes, pharmacogenomic factors also affect the steroid response. The upregulation of P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP-1) modulate the pharmacokinetics of steroids and may contribute to steroid resistance. Flow-cytometric analysis of P-gp, MRP-1 expression and functional activity on peripheral blood mononuclear cells (PBMCs) was carried out in steroid-sensitive nephrotic syndrome (SSNS) (n = 171, male 103, mean age = 8.54 ± 4.3); and steroid-resistant nephrotic syndrome (SRNS) (n = 83, male 43, mean age = 7.43 ± 4.6) patients. The genotypings of MDR-1 gene were carried out using PCR-RFLP. We observed that the percentage expression of P-gp (10.01 ± 2.09 and 3.79 ± 1.13, p < 0.001); and MRP-1 (15.91 ± 3.99 and 7.40 ± 2.33, p < 0.001) on lymphocyte gated population were significantly higher in SRNS than that of SSNS. The functional activity of P-gp and MRP-1 was also significantly escalated in SRNS as compared to SSNS (68.10 ± 13.35 and 28.93 ± 7.57, p < 0.001); (72.13 ± 8.34 and 31.56 ± 8.65, p < 0.001) respectively. AUC-ROC curve analysis revealed that P-gp and MRP-1 expression with a cut-off value of 7.13% and 9.62% predicted SRNS with the sensitivity of 90% and 80.7%; and specificity 90% and 80%, respectively. Moreover, MDR-1 homozygous mutant TT+AA for G2677T/A (rs2032582) was significantly associated with SRNS (p = 0.025, OR = 2.86 CI = 1.14-7.14). The expression of P-gp (9.68 ± 4.99 v/s 5.88 ± 3.38, p = 0.002) was significantly higher in the patients of homozygous mutant alleles compared to wildtype GG. The increased expression and functionality of P-gp and MRP-1 contribute to steroid resistance, and MDR-1 homozygous mutant G2677T/A promotes steroid resistance by inducing P-gp expression in NS.

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Journal of Inflammation Research, 2022

Background and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is assoc... more Background and Aims: Acute-on-chronic liver failure (ACLF) with increasing organ failure is associated with poor outcomes. Severely deranged systemic hemodynamics and decreased effective arterial blood volume contribute to tissue damage and organ failure. Response-guided therapy with albumin, vasoconstrictors, and furosemide may help overcome effective hypovolemia, improve diuresis and impact survival. Methods: In the observation cohort, 230 patients with ACLF (CANONIC criteria) with ascites (≥Grade II) and ACLF ≥Grade I were enrolled. A total of 136 patients (GROUP I) received response-guided (urine sodium >80mmol/day) slow albumin-furosemide infusion ± terlipressin (SAFI ± T), while 94 patients (GROUP II) received standard medical therapy. Twenty-eight-day survival, ascites mobilization (nil or grade 1), and adverse events were noted. In another mechanistic cohort (n = 40), laboratory evidences for improvement in various pathophysiological alterations; gut permeability, endotoxemia, cytokine storm, neutrophil dysfunction, and hemodynamic alterations following SAFI ± T/Noradrenaline (NAdr) were evaluated. Results: Age, gender, CLIF-C-ACLF, SOFA and MELD scores, ACLF grades and urine sodium were not different between the two groups in the observation cohort. Ascites was mobilized in 102/136 in GROUP I (SAFI ± T) and 23/94 in GROUP II (p < 0.05). Twenty-eight-day survival was significantly higher in GROUP I = 103/136 (75.7%) vs GROUP II = 50/94 (53.2%), (P = <0.001). All those who were unable to reach urine sodium >80 mmol/day died. Four patients in GROUP I developed scrotal gangrene. In the mechanistic cohort, 72% of patients survived with significant improvement in gut permeability, endotoxemia, serum cytokines, neutrophil dysfunction, and hemodynamic alterations. Conclusion: Ascitic fluid mobilization by response-guided SAFI ± T/NAdr therapy improves survival by improving splanchnic and systemic hemodynamics, decreasing gut congestion, gut permeability, and endotoxemia, improving neutrophil functions, and reducing pro-inflammatory cytokines in circulation.

2022 3rd International Conference on Intelligent Engineering and Management (ICIEM)

Rheumatology

higher in the non-articular group [Table 1]. Th17 cells were lower in group B but did not reach s... more higher in the non-articular group [Table 1]. Th17 cells were lower in group B but did not reach statistical significance [p 0.11]. Th1/Th2 ratio was lower and Th1/Treg and Th17/Treg ratios were higher in sarcoid arthritis [p < 0.05] as opposed to non-articular sarcoidosis. Conclusion: T helper cell axis was skewed towards Th1 and Th17 in sarcoid arthritis when compared to patients without articular involvement. Thus, this difference in T cell subsets may explain to an extent the diversity in the disease manifestations and may have implications on management. It may be worthwhile to study the T cell repertoire in other tissue or body fluids of patients with sarcoidosis with and without arthritis. Disclosures: The authors have declared no conflicts of interest.

2020 IEEE International Conference on Computing, Power and Communication Technologies (GUCON)

A disc-loaded circular radio-frequency interaction structure for its prospective application in a... more A disc-loaded circular radio-frequency interaction structure for its prospective application in a gyro-travelling wave tube amplifier is field analyzed for obtaining dispersion characteristics. The study reveals that a disc-loaded circular radio-frequency interaction structure has a pass-band characteristics. Few azimuthally symmetric transverse electric modes like TE01 and TE02 have been identified. The pass-band characteristics for TE01 and TE02 modes have been obtained using MATLAB simulation and also been verified against CST Microwave Studio. The mathematical and simulation results are in near agreement.

Palaeogeography, Palaeoclimatology, Palaeoecology, 2022

Nephrology Dialysis Transplantation, 2018

INTRODUCTION AND AIMS: Renal transplantation is the best modality of RRT and adequate immunosuppr... more INTRODUCTION AND AIMS: Renal transplantation is the best modality of RRT and adequate immunosuppression is the cornerstone of the success of transplant. is adequate immunosuppression. Tacrolimus (Tac) is one of the most widely used immunosuppressant but there is marked inter individual variations with small therapeutic range of blood Tac level. This inter-individual variations in Tac level may be because off differential expression of P-glycoprotein (P-gp), which is efflux pump expressed on lymphocytes. This study aimed to evaluate the P-gp expression on PBMCs and correlate with Tac trough concentration in renal allograft recipients. Genotype analysis was performed with RFLP. METHODS: Of 54 renal transplant recipients, Group A (n¼15) were higher Tac level (15.2466.45) than target C0 (9-12 ng/ml), Group B (n¼35) were achieved target Tac C0 level (11.5861.15) and Group C (n¼6) were not achieved target C0 (6.1562.26) on day-1 of transplantation at dose of 0.15mg/kg/day. Of the 54 patients, 29 had glomerulonephritis, 19 had interstitial nephropathy, 5 had diabetic nephropathy and 1 had polycystic kidney disease. All patients were on triple immunosuppressive Tac, MMF and prednisolone. Heparinized blood sample were taken for P-gp expression analysis. P-gp expression and functionality were analyzed on flowcytometer. RESULTS: The requirement of Tac (mg/kg/day) was significantly low in group C (0.2360.06) than that of group A (0.09860.03; p¼0.001) and group B (0.14860.02; p¼0.015). Tac C0 to dose ratio (ng/ml per mg/kg/day) was significantly high in group A (149.95656.75) than group B (75.26623.75) and group C (29.45613.14). P-gp positive cell was significantly high in group C than that of group A (p<0.001) and group B (p¼0.004) and significantly high in group B than group A (p¼0.043). The functionality of P-gp was also high in group C than that of group A (p<0.001) and group B (p¼0.021) and significantly high in group B than group A (p¼0.049). There is significant negative correlation between Tac Co with P-gp expression and functionality. We have found significantly high P-gp expression in patients with CC genotype of C3435T SNP. Patients having TTþAA genotype of G2677T/A requires 38% more Tac dose. CONCLUSIONS: Higher P-gp expression lowers the Tac concentration in blood. P-gp monitoring may helpful to predict the initial daily dose needed by individual patients to obtain adequate immunosuppression. Patients with TTþAA genotype of G2677T/A require high Tac dose.

2020 IEEE International Conference on Computing, Power and Communication Technologies (GUCON), 2020

In this paper, electron bunching and power evolution along the axial length of the gyro-TWT ampli... more In this paper, electron bunching and power evolution along the axial length of the gyro-TWT amplifier are explained by making use of an electron flight diagram that shows individual electron trajectories during the entire amplification process. A typical gyro-TWT amplifier operating in TE01 mode at 35 GHz with parameters beam voltage mathrmV0=70textkV\mathrm{V}_{0}=70\text{kV}mathrmV0=70textkV, beam current mathrmI0=15\mathrm{I}_{0}=15mathrmI0=15 Amp, waveguide radius = 5.42 mm, DC magnetic field mathrmB0=1.32mathrmT\mathrm{B}_{0}=1.32\ \mathrm{T}mathrmB0=1.32mathrmT, Hollow beam radius = 2.547 mm, Larmor radius = 0.58 mm resulted in 11.75 kW peak output power. Result obtained from the developed MATLAB code has been benchmarked against the published result and is found to be in good agreement.

2020 IEEE International Conference on Computing, Power and Communication Technologies (GUCON), 2020

Large signal analysis for a circular cylindrical smooth wall gyro-travelling wave tube amplifier ... more Large signal analysis for a circular cylindrical smooth wall gyro-travelling wave tube amplifier has been successfully used to generate the power, and gain plots for a variety of input parameters. The gain versus frequency plots are generated for TE11 mode with the input data as the beam voltage of 100 kV, beam current of 1 Amp., waveguide cut-off frequency of 33.68 GHz and the pitch factor of 1. The gain versus frequency plots are found to be in good agreement with the published data. Additionally, the gain versus axial distance plots are generated at TE11 mode for the frequency of 9 GHz and beam current of 7 Amp. and are also found to be matching with the published data.

Nephrology Dialysis Transplantation, 2018

INTRODUCTION AND AIMS: Fibrosis in the peritoneum is a major cause of ultrafiltration failure in ... more INTRODUCTION AND AIMS: Fibrosis in the peritoneum is a major cause of ultrafiltration failure in continuous ambulatory peritoneal dialysis (CAPD) patients. Transforming growth factor (TGF)-b1 is a major pro-fibrotic cytokine, which is an essential factor in progressive changes in the peritoneal membrane leading to peritoneal fibrosis.To explore anti-fibrotic role of Phosphodiesterase-5 inhibitors, Sildenafil and Zaprinast, respectively in human peritoneal fibroblasts (HPFB) isolated from omentum and parietal peritoneum of CAPD patients. METHODS: Omentum biopsy (OB) of control patients (n¼6) undergone elective abdominal surgery and CAPD patients (n¼2) was incubated in 0.125% trypsin/0.01% EDTA twice for 20 minutes, twice for 40 minutes at 37 C. Parietal peritoneum biopsy (PB) excised during laparotomy was incubated overnight in dispase (2.4 U/mL)/37 C. HPFB appeared within 2 weeks. In disease mimicking strategy, HPFB from OB and PB were incubated with TGF-b1-10ng/ml for 1 hr and later with TGF-b1-10ng/ml and (Sildenafil, Zaprinast-10mM, each) for 24 hr. In second strategy, HPFB from OB and PB were pretreated with (Sildenafil, Zaprinast-10mM, each) for 1 hr and later with only TGF-b1-10ng/ml for 24 hr. Real time qPCR for pro-fibrotic (Col1a1, Col1a2, ACTA2, CTGF and FN1) and anti-fibrotic genes (MMP2/TIMP1) expression was performed. Type I collagen and a-SMA was examined by western blotting. RESULTS: In TGF-b1 stimulated HPFB, upregulated mRNA expression of pro-fibrotic genes (p<0.05) at 24 hr was observed. Pre-treatment of HPFB with Sildenafil and Zaprinast more effectively reduced pro-fibrotic genes expression (p<0.05) than disease mimicking strategies (Figure 1and 2). Ratio of anti-fibrotic mRNA responses (MMP2/ TIMP1) was restored with the pretreatment strategy more efficiently than disease imitating strategy (p<0.05) (Figure 3). Also pre-treatment with Sildenafil and Zaprinast decreased type 1 collagen and a-SMA competently (p<0.05). CONCLUSIONS: Phosphodiesterase-5 inhibitors reduce pro-fibrotic mRNA expression and restore anti-fibrotic mRNA reponses in co-cultured human peritoneal fibroblasts with TGF-b1.

Critical Care Medicine, 2016

Nephrology Dialysis Transplantation, 2018

Nephrology Dialysis Transplantation, 2018

Nephrology Dialysis Transplantation, 2021

Background : - Intravenous administration of radiocontrast media is referred to as contrast-induc... more Background : - Intravenous administration of radiocontrast media is referred to as contrast-induced kidney injury (CI-AKI).CI-AKI is described as the third most common cause of new AKI in hospitalized patients. The occurrence of CI-AKI is reported up to 55% in these high-risk patients.: NGAL (Neutrophil gelatinase-associated Lipocalin)and Cystatin C have been found an early and sensitive marker of acute kidney injury (AKI). Aims To evaluate biomarkers in plasma (P) and urine (U) after intravenous contrast in adult ICU patients. Method Total of 36 patients recruited as per inclusion criteria. ICU patients who were >18 years with radiographic contrast for diagnostic or interventional computed tomography (CT scan), were included. After ethical approval, samples of 5 ml blood and 5 ml urine were collected before contrast exposure and at 4 h, 24 h, and 48 h after contrast exposure. NGAL and Cystatin C assay was done by ELISA, and urinary levels were normalized as per urine creatinine ...

Scientific Reports, 2021

To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection fro... more To assess utility of neutrophilCD64 (nCD64) expression in differentiating bacterial infection from inflammation in patients with severe alcoholic hepatitis (SAH) fulfilling systemic inflammatory response syndrome criteria. Patients with SAH and infection (n = 58), SAH without infection (n = 70), and healthy controls (n = 20) were included. Neutrophil CD64 expression by flowcytometry, serum Procalcitonin (ELISA) and C-reactive protein (Nephelometry) and neutrophil–lymphocyte ratio (NLR) were studied. Percentage of neutrophils with CD64 expression (nCD64%) was significantly higher in patients with SAH and infection than in those without infection and controls [76.2% (56.9–86.5) vs. 16% (12.6–23.1) vs. 7.05% (1.4–9.5), p < 0.05], as was their mean fluorescence intensity [MFI; 1431 (229–1828) vs. 853 (20–968) vs. 99.5 (54.7–140.7), p < 0.05]. Using a cut-off of 27%, the sensitivity and specificity of nCD64% to diagnose bacterial infection was 94% and 81%, respectively, with area u...

Frontiers in Marine Science, 2021

In this study, we presented a high-resolution benthic foraminiferal assemblage record from the we... more In this study, we presented a high-resolution benthic foraminiferal assemblage record from the western Bay of Bengal (BoB) (off Krishna–Godavari Basin) showing millennial-scale variations during the last 45 ka. We studied temporal variations in benthic foraminiferal assemblages (relative abundances of ecologically sensitive groups/species, microhabitat categories, and morphogroups) to infer past changes in sea bottom environment and to understand how monsoon induced primary productivity-driven organic matter export flux and externally sourced deep-water masses impacted the deep-sea environment at the core site. Our records reveal a strong coupling between surface productivity and benthic environment on glacial/interglacial and millennial scale in concert with Northern Hemisphere climate events. Faunal data suggest a relatively oxic environment when the organic matter flux to the sea floor was low due to low primary production during intensified summer monsoon attributing surface wat...

The Pharmacogenomics Journal, 2021

Steroid remains the keystone therapy for Idiopathic Nephrotic Syndrome (NS). Besides genetic fact... more Steroid remains the keystone therapy for Idiopathic Nephrotic Syndrome (NS). Besides genetic factors and histological changes, pharmacogenomic factors also affect the steroid response. The upregulation of P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP-1) modulate the pharmacokinetics of steroids and may contribute to steroid resistance. Flow-cytometric analysis of P-gp, MRP-1 expression and functional activity on peripheral blood mononuclear cells (PBMCs) was carried out in steroid-sensitive nephrotic syndrome (SSNS) (n = 171, male 103, mean age = 8.54 ± 4.3); and steroid-resistant nephrotic syndrome (SRNS) (n = 83, male 43, mean age = 7.43 ± 4.6) patients. The genotypings of MDR-1 gene were carried out using PCR-RFLP. We observed that the percentage expression of P-gp (10.01 ± 2.09 and 3.79 ± 1.13, p < 0.001); and MRP-1 (15.91 ± 3.99 and 7.40 ± 2.33, p < 0.001) on lymphocyte gated population were significantly higher in SRNS than that of SSNS. The functional activity of P-gp and MRP-1 was also significantly escalated in SRNS as compared to SSNS (68.10 ± 13.35 and 28.93 ± 7.57, p < 0.001); (72.13 ± 8.34 and 31.56 ± 8.65, p < 0.001) respectively. AUC-ROC curve analysis revealed that P-gp and MRP-1 expression with a cut-off value of 7.13% and 9.62% predicted SRNS with the sensitivity of 90% and 80.7%; and specificity 90% and 80%, respectively. Moreover, MDR-1 homozygous mutant TT+AA for G2677T/A (rs2032582) was significantly associated with SRNS (p = 0.025, OR = 2.86 CI = 1.14-7.14). The expression of P-gp (9.68 ± 4.99 v/s 5.88 ± 3.38, p = 0.002) was significantly higher in the patients of homozygous mutant alleles compared to wildtype GG. The increased expression and functionality of P-gp and MRP-1 contribute to steroid resistance, and MDR-1 homozygous mutant G2677T/A promotes steroid resistance by inducing P-gp expression in NS.

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018

Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2018