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.

Synthesis of mononuclear copper(II) complexes of acyclic Schiff's base ligands: Spectral, structural, electrochemical, antibacterial, DNA binding and cleavage activity

Jayamani, A.,Thamilarasan, V.,Sengottuvelan, N.,Manisankar, P.,Kang, S.K.,Kim, Y.I.,Ganesan, V. Pergamon 2014 Spectrochimica acta. Part A, Molecular and biomole Vol.122 No.-

The mononuclear copper(II) complexes (1&2) of ligands L<SUP>1</SUP> [N,N'-bis(2-hydroxy-5-methylbenzyl)-1,4-bis(3-iminopropyl)piperazine] or L<SUP>2</SUP> [N,N'-bis(2-hydroxy-5-bromobenzyl)-1,4-bis(3-iminopropyl) piperazine] have been synthesized and characterised. The single crystal X-ray study had shown that ligands L<SUP>1</SUP> and L<SUP>2</SUP> crystallize in a monoclinic crystal system with P2<SUB>1</SUB>/c space group. The mononuclear copper(II) complexes show one quasireversible cyclic voltammetric response near cathodic region (-0.77 to -0.85V) in DMF assignable to the Cu(II)/Cu(I) couple. Binding interaction of the complexes with calf thymus DNA (CT DNA) investigated by absorption studies and fluorescence spectral studies show good binding affinity to CT DNA, which imply both the copper(II) complexes can strongly interact with DNA efficiently. The copper(II) complexes showed efficient oxidative cleavage of plasmid pBR322 DNA in the presence of 3-mercaptopropionic acid as reducing agent through a mechanistic pathway involving formation of singlet oxygen as the reactive species. The Schiff bases and their Cu(II) complexes have been screened for antibacterial activities which indicates that the complexes exhibited higher antimicrobial activity than the free ligands.

Engineering properties of steel fibre reinforced geopolymer concrete

Ganesan, N.,Indira, P.V.,Santhakumar, Anjana Techno-Press 2013 Advances in concrete construction Vol.1 No.4

Engineering properties such as compressive strength, splitting tensile strength, modulus of rupture, modulus of elasticity and Poisson's ratio of geopolymer concrete (GPC) and steel fibre reinforced geopolymer concrete (SFRGPC) have been obtained from standard tests and compared. A total of 15 specimens were tested for determining each property. The grade of concrete used was M 40. The percentages of steel fibres considered include 0.25%, 0.5%, 0.75% and 1%. In general, the addition of fibres improved the mechanical properties of both GPC and SFRGPC. However the increase was found to be nominal in the case of compressive strength (8.51%), significant in the case of splitting tensile strength (61.63%), modulus of rupture (24%), modulus of elasticity (64.92%) and Poisson's ratio (50%) at 1% volume fraction of fibres. An attempt was made to obtain the relation between the various engineering properties with the percentage of fibres added.

High performance fibre reinforced cement concrete slender structural walls

Ganesan, N.,Indira, P.V.,Seena., P. Techno-Press 2014 Advances in concrete construction Vol.2 No.4

In the design of reinforced concrete structural walls, in order to ensure adequate inelastic displacement behaviour and to sustain deformation demands imposed by strong ground motions, special reinforcement is considered while designing. However, these would lead to severe reinforcement congestion and difficulties during construction. Addition of randomly distributed discrete fibres in concrete improves the flexural behaviour of structural elements because of its enhanced tensile properties and this leads to reduction in congestion. This paper deals with effect of addition of steel fibres on the behavior of high performance fibre reinforced cement concrete (HPFRCC) slender structural walls with the different volume fractions of steel fibres. The specimens were subjected to quasi static lateral reverse cyclic loading until failure. The high performance concrete (HPC) used was obtained based on the guidelines given in ACI 211.1 which was further modified by prof.Aitcin (1998). The volume fraction of the fibres used in this study varied from 0 to 1% with an increment of 0.5%. The results were analysed critically and appraised. The study indicates that the addition of steel fibres in the HPC structural walls enhances the first crack load, strength, initial stiffness and energy dissipation capacity.

A Longitudinal Study of Relation between Side-effects and Clinical Improvement in Schizophrenia: Is There a Neuro-metabolic Threshold for Second Generation Antipsychotics?

Ganesan Venkatasubramanian,Naren P. Rao,Rashmi Arasappa,Sunil V. Kalmady,Bangalore N. Gangadhar 대한정신약물학회 2013 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.11 No.1

Objective: Classical studies demonstrated Neuroleptic Induced Extrapyramidal Side-effects (NIES; Neuroleptic threshold) to correlate with the efficacy of first generation antipsychotics. Second generation antipsychotics (SGAs), in addition to the extrapyramidal side effects, are also associated with metabolic side effects. This prospective study on antipsychotic-naïve schizophrenia patients, for the first-time, examined concurrently the relationship between clinical improvement and these side-effects NIES and Neuroleptic Induced Metabolic Side-effects. Methods: Thirty six-antipsychotic-naïve schizophrenia (DSM-IV) patients were examined at baseline and after 5 weeks of treatment with antipsychotics. At baseline and follow-up, we recorded the body mass index (BMI) and assessed psychopathology using Scale for Assessment of Positive-symptoms (SAPS) and Scale for Assessment of Negative-symptoms (SANS), extrapyramidal symptoms using Simpson-Angus Extra Pyramidal Scale (SAEPS) and improvement using Clinical Global Impression Improvement (CGI). Results: After treatment, patients showed significant reduction in SAPS (baseline, 27.97±14.47; follow-up, 14.63±13.25; p<0.001)and SANS total scores (baseline, 63.77±28.96; follow-up, 49.30±28.77; p=0.001) and a significant increase in BMI (baseline,18.5±3.37; follow-up, 19.13±3.17; p<0.001). At follow-up CGI-Improvement score was (2.55±0.65) and SAEPS score was (0.8±1.32). CGI-Improvement score had a significant negative correlation with magnitude of increase in BMI (rs=-0.39; p=0.01)and SAEPS symptom score at follow-up (rs=-0.58; p<0.001). In addition, magnitude of increase in BMI showed positive correlation with the magnitude of reduction in SAPS total score (rs=0.33; p=0.04). Conclusion: The study findings suggest a possible relation between clinical improvement and antipsychotic-induced neuroleptic as well as metabolic side-effects in schizophrenia. Though the mechanism of this relation is yet to be elucidated, insulin signaling pathways and lipid homeostasis are potential mechanisms in addition to the established neurotransmitter hypothesis. Theoretically findings support the novel hypothetical construct of ‘Neuro-Metabolic threshold’ in the treatment of schizophrenia.

Strength and behaviour of reinforced SCC wall panels in one-way action

Ganesan, N.,Indiraa, P.V.,Prasad, S. Rajendra Techno-Press 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.36 No.1

A total of 28 wall panels were cast and tested under uniformly distributed axial load in one-way in-plane action to study the effect of slenderness ratio (SR) and aspect ratio (AR) on the ultimate load. Two concrete formulations, normal concrete (NC) and self compacting concrete (SCC), were used for the casting of wall panels. Out of 28 wall panels, 12 were made of NC and the remaining 16 panels were of SCC. All the 12 NC panels and 12 out of 16 SCC panels were used to study the influence of SR and the remaining 4 SCC panels were tested to study the effect of AR on the ultimate load. A brief review of studies available in literature on the strength and behaviour of reinforced concrete (RC) wall panels is presented. Load-deformation response was recorded and analyzed. The ultimate load of SCC wall panels decreases non-linearly with the increase in SR and decreases linearly with increasing values of AR. Based on this study a method is proposed to predict the ultimate load of reinforced SCC wall panels. The modified method includes the effect of SR, AR and concrete strength.

SFRHPC interior beam-column-slab joints under reverse cyclic loading

Ganesan, N.,Nidhi, M.,Indira, P.V. Techno-Press 2015 Advances in concrete construction Vol.3 No.3

Beam-column joints are highly vulnerable locations which are to be designed for high ductility in order to take care of unexpected lateral forces such as wind and earthquake. Previous investigations reveal that the addition of steel fibres to concrete improves its ductility significantly. Also, due to presence of slab the strength and ductility of the beam increases considerably and ignoring the effect of slab can lead to underestimation of beam capacity and defiance of strong column weak beam concept. The influence of addition of steel fibres on the strength and behaviour of steel fibre reinforced high performance concrete (SFRHPC) interior beam-column-slab joints was investigated experimentally. The specimens were subjected to reverse cyclic loading. The variable considered was the volume fraction of crimped steel fibres i.e., 0%, 0.5% and 1.0%. The results show that the addition of steel fibres improves the first crack load, strength, ductility, energy absorption capacity and initial stiffness of the beam.

Strength and behaviour of bamboo reinforced concrete wall panels under two way in-plane action

Ganesan, N.,Indira, P.V.,Himasree, P.R. Techno-Press 2018 Advances in concrete construction Vol.6 No.1

An experimental investigation has been carried out on the use of an environmentally sustainable material, bamboo, in the construction of precast concrete structural wall panels. The strength and behaviour of three prototype bamboo reinforced concrete wall panel specimens under two-way in-plane action was studied. The specimens with varying aspect ratio and thinness ratio were tested to fail under a uniformly distributed in-plane load applied at an eccentricity of t/6. The aspect ratio of the specimens considered includes 1.667, 1.818 and 2 and the thinness ratio includes 12.5, 13.75 and 15. The influence of aspect ratio and thinness ratio of bamboo reinforced concrete wall panels, on its strength and behaviour was discussed. Varnished and sand blasted bamboo splints of 20 mm width and thickness varying from 8 to 15 mm were used as reinforcement in concrete. Based on the study, an empirical equation was developed considering the geometrical parameters of bamboo reinforced concrete wall panels for predicting its ultimate strength under two way in-plane action.

Effect of hybrid fibers on tension stiffening of reinforced geopolymer concrete

Ganesan, N.,Sahana, R.,Indira, P.V. Techno-Press 2017 Advances in concrete construction Vol.5 No.1

An experimental work was carried out to study the effect of hybrid fiber on the tension stiffening and cracking characteristics of geopolymer concrete (GPC). A total of 24 concentrically reinforced concrete specimens were cast and tested under uniaxial tension. The grade of concrete considered was M40. The variables mainly consist of the volume fraction of crimped steel fibers (0.5 and 1.0%) and basalt fibers (0.1, 0.2 and 0.3%). The load deformation response was recorded using LVDT's. At all the stages of loading after the first cracking, crack width and crack spacing were measured. The addition of fibers in hybrid form significantly improved the tension stiffening effect. In this study, the combination of 0.5% steel fiber and 0.2% basalt fiber gave a better comparison than the other combinations.

RCC frames with ferrocement and fiber reinforced concrete infill panels under reverse cyclic loading

Ganesan, N.,Indira, P.V.,Irshad, P. Techno-Press 2017 Advances in concrete construction Vol.5 No.3

An experimental investigation was carried out to study the strength and behavior of reinforced cement concrete (RCC) frames with ferrocement and fiber reinforced concrete infill panel. Seven numbers of $1/4^{th}$ scaled down model of one bay-three storey frames were tested under reverse cyclic loading. Ferrocement infilled frames and fiber reinforced concrete infilled frames with varying volume fraction of reinforcement in infill panels viz; 0.20%, 0.30%, and 0.40% were tested and compared with the bare frame. The experimental results indicate that the strength, stiffness and energy dissipation capacity of infilled frames were considerably improved when compared with the bare frame. In the case of infilled frames with equal volume fraction of reinforcement in infill panels, the strength and stiffness of frames with fiber reinforced concrete infill panels were slightly higher than those with ferrocement infill panels. Increase in volume fraction of reinforcement in the infill panels exhibited only marginal improvement in the strength and behavior of the infilled frames.