Multiple Complement Pathway-related Proteins Might Regulate Immunopathogenesis of Major Depressive Disorder

Preethi V. Reddy(Preethi V. Reddy ),Pinku Mani Talukdar(Pinku Mani Talukdar ),Manjula Subbanna(Manjula Subbanna ),Praerna H. Bhargav(Praerna H. Bhargav ),Rashmi Arasappa(Rashmi Arasappa ),Ganesan Venk 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.2

Objective: Exacerbated inflammatory pathway has emerged as a predominant etiological construct of major depressive disorder (MDD). Innate immune molecules like complement proteins induce inflammatory responses and also regulate key neurobiological processes. However, there is a dearth of literature on the impact of critical complement proteins in MDD. Herein, plasma profiling of seven complement proteins was carried out to obtain a better insight into the role of the complement pathway in MDD. Methods: Plasma levels of C1q, C3, C3b/iC3b, C4, Factor B, Factor H, and properdin were assayed in 22 patients with MDD and 27 healthy controls by multiplex suspension assay. The patients with MDD were diagnosed as per DSM IV-TR. Hamilton Depression Rating Scale (HAM-D), Montgomery Depression Rating Scale and Clinical Global Improvement were used for clinical assessments of the patients. The plasma levels of these complement proteins were also correlated with various clinical scores and phenotypes of MDD. Results: The patients with MDD and healthy controls did not differ in terms of age and gender (p > 0.1). The patients with MDD had a mean duration of illness of around 3 years, with average number of depressive episodes being 6 and the mean HAM-D score was 19. Of the seven complement components, the plasma levels of C1q, Factor B, and Factor H (p ≤ 0.05) were significantly elevated in MDD patients compared to healthy controls. However, the plasma levels of these complement proteins were not found to correlate with the clinical profile of MDD patients. Conclusion: Both Factor B and Factor H are crucial in the induction and regulation of the alternative pathway of complement activation. The alternative pathway also plays a critical role in inflammation. These findings suggest an important role of the alternative complement pathway in immuno-inflammation in MDD.

Genetic Algorithm for Satellite Customer Assignment

Kim, S. S.,Kim, H. J.,Mani, V.,Kim, C. H. SPRINGER-VERLAG 2006 Lecture Notes in Computer Science Vol.- No.4234

Parallel Video Processing Using Divisible Load Scheduling Paradigm

S. Suresh,V. Mani,S. N. Omkar,H.J. Kim 한국방송·미디어공학회 2005 방송공학회논문지 Vol.10 No.1

Sensitivity of stabilized a-Se based X-ray photoconductors

M. Zahangir Kabir,M. Yunus,S.O. Kasap,O. Tousignant,H. Mani,P. Gauthier 한국물리학회 2006 Current Applied Physics Vol.6 No.3

A model explaining the ghosting mechanisms in amorphous selenium based X-ray image detectors is described by considering deeptrapping of charge carriers, trapped charges arising from previous exposures, trap lling eects, recombination between drifting andtrapped carriers, generation of X-ray induced new deep trap centers, space charge eects, carrier detrapping, and electric eld dependenttions, and the Poisson’s equation across the photoconductor for a pulse X-ray exposure by the nite dierence method. The numericalresults are compared with Monte Carlo simulations. The relative sensitivity decreases with increasing accumulative X-ray exposure anddecreasing applied electric eld. The sensitivity reduction at negative bias is greater than at positive bias. The theoretical model is tted toexperimental data. The comparison of the model with the experimental data reveals that the recombination between trapped and theoppositely charged drifting carriers, electric eld dependent charge carrier generation and X-ray induced new deep trap centers are mainly responsible for the sensitivity reduction in biased amorphous selenium based X-ray detectors.

Viral Kinetics in Women of Child Bearing Potential with Chronic HBV Following Treatment with Tenofovir Alafenamide or Tenofovir Disoproxil Fumarate

( Brunetto ),( Carla Coffin ),( Audrey Lau ),( Shuyuan Mo ),( John F. Flaherty ),( Anuj Gaggar ),( G Mani Subramanian ),( Mindie H. Nguyen ),( Selim Gurel ),( Alexander Thompson ),( Edward J. Gane ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Suppression of the HBV in women of childbearing potential (WOCBP) has important implications in preventing transmission of HBV from mother to infant. Antiviral therapy that reduces HBV DNA to < 2x105 IU/mL at delivery in mothers can substantially reduce the risk of perinatal transmission. We evaluated the viral kinetics of TAF and TDF in WOCBP. Methods: : In two Phase 3 studies (HBeAg positive and negative patients), 1301 patients (37% female) were randomized (2:1) to receive TAF 25 mg QD or TDF 300 mg QD. All patients were required to have HBV DNA >2x104 IU/mL at screening and serum ALT >2 times AASLD criteria.WOCBP were defined as nonmenopausal females 18 years or older without history of hysterectomy, bilateral oophorectomy, or ovarian failure. For this subanalysis, patients were stratified by baseline HBV DNA levelsand the endpoints were virologic suppression to HBV DNA <29 IU/mL or < 2x105 IU/mL. Results: 365(76%) female were identified as WOCBP with 118 (32%) having HBV DNA >1x108 IU/mL at baseline. Suppression rates were generally similar between TAF and TDF groups and within viral load strata for HBeAg positive and negative patients. After 12 weeks of treatment with TAF or TDF, 77% of WOCBP with baseline HBV DNA <2x105 IU/mL had full suppression to <29 IU/mL compared to 1% of those at the highest baseline viral load (Figure A). By Week 24, 54% of all WOCBP had achieved complete viral suppression. Of WOCBP with baseline viral load ≥2x105 IU/mL (n=305), 76%, 89%, and 93% achieved viral load reduction to <2x105 IU/mL by Weeks 4, 8, and 12, respectively (Figure B). Conclusions: After 12 weeks of treatment the majority of WOCBP had HBV DNA to <2x105 IU/mL. In women with higher baseline viral loads, longer treatment duration may be necessary to achieve viral suppression below recommended thresholds.

SOF/VEL/VOX for 12 Weeks is a Safe and Effective Salvage Regimen for NS5A Inhibitor-experienced Patients with Genotype 1-6 HCV Infection

( Eric Lawitz ),( Michael Manns ),( Marc Bourliere ),( Sooji Lee ),( Nelson Cheinquer ),( Luisa Stamm ),( Robert H. Hyland ),( Liyun Ni ),( Hadas Dvory-sobol ),( Diana Brainard ),( Mani Subramanian ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

Aims: The pangenotypic fixed-dose combination (FDC) of sofosbuvir (SOF), a HCV NS5B inhibitor, velpatasvir (VEL), a HCV NS5A inhibitor, and voxilaprevir (VOX), a HCV NS3/4A protease inhibitor, is an salvage regimen for direct acting antiviral (DAA)-experienced patients based on the safety and efficacy demonstrated in Phase 2 and Phase 3 trials in this population. Methods: This was a retrospective analysis of data from 454 NS5A inhibitor-experienced patients treated with SOF/VEL FDC+VOX or SOF/VEL/VOX FDC in the Phase 2 and Phase 3 trials. Efficacy was assessed by SVR12 and relapse rates. Safety was assessed by treatment-emergent adverse events (AEs) and laboratory abnormalities. Results: Of 454 NS5A inhibitor-experienced patients treated, 77% were male, 41% had compensated cirrhosis, 86% had NS5A and NS3 baseline resistance-associated substitutions (RASs), 74% had genotype 1 HCV infection. Most patients (53%) had previously been exposed to NS5A inhibitor+NS5B inhibitor, with 39% exposed to NS5A inhibitor+NS3/4A protease inhibitor±NS5B inhibitor and 8% exposed to NS5A inhibitor±another DAA. Overall, the SVR12 rate was 97% with a relapse rate of 2%. The SVR12 rate in patients with compensated cirrhosis was 95% and in patients with baseline RASs was 97%. The SVR12 rates by prior regimen were: NS5A inhibitor+NS5B inhibitor 95%; NS5A inhibitor+NS3/4A protease inhibitor±NS5B inhibitor 99%; and NS5A inhibitor±another DAA 100%. Treatment-emergent RASs were uncommon, present in 3 of 10 patients who relapsed. Only 1 patient (0.2%) discontinued treatment due to an AE. No serious adverse events attributed to study medication were reported. Conclusions: Results in over 450 NS5A inhibitor-experienced patients enrolled in Phase 2 or Phase 3 trials demonstrate that the 3-DAA combination of SOF, VEL and VOX for 12 weeks is a safe, well tolerated and effective treatment for patients who previously failed an NS5A inhibitor-containing regimen, irrespective of the other drugs in the prior treatment.