Ototoxicity: A Challenge in Diagnosis and Treatment

Purushothaman Ganesan,Jason Schmiedge,Vinaya Manchaiah,Simham Swapna,Subhashini Dhandayutham,Purushothaman Pavanjur Kothandaraman 대한청각학회 2018 Journal of Audiology & Otology Vol.22 No.2

Ototoxicity is the pharmacological adverse reaction affecting the inner ear or auditory nerve,characterized by cochlear or vestibular dysfunction. The panorama of drug-induced hearingloss has widened over last few decades. Although ototoxic medications play an imperativerole in modern medicine, they have the capacity to cause harm and lead to significant morbidity. Evidence has shown early detection of toxicity through prospective ototoxicity monitoringallows for consideration of treatment modifications to minimize or prevent permanenthearing loss and balance impairment. Although many ototoxicity monitoring protocols exist,their practicality is questionable due to several factors. Even though the existing protocolshave proven to be effective, certain lacunae in practice have been encountered due to discrepanciesamong recommended protocols. Implementation of these protocols is mostlyheld back due to the incapacitated status of the patient. The choice of early ototoxicity identificationtechniques is still debatable due to variables such as high degree of sensitivity,specificity and reliability, less time consumption and less labour-intensive to the patient. Hence, the diagnosis and effective treatment of ototoxicity is challenging, even today. A stringentprotocol with more practicality encompassing all elements aimed at profiling the effectsof ototoxicity is greatly needed. This review describes an efficient application of ototoxicitymonitoring and treatment protocol as an attempt to reduce the challenges in diagnosis andmanagement of ototoxicity.

Effect of Feeding Calcium Salts of Palm Oil Fatty Acids on Performance of Lactating Crossbred Cows

Purushothaman, Sajith,Kumar, Anil,Tiwari, D.P. Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.3

Twenty lactating crossbred cows yielding 10 to 15 litres of milk daily during mid lactation were selected and divided into four groups of five animals to assess the effect of feeding calcium soaps of palm oil fatty acids (bypass fat) on milk yield, milk composition and nutrient utilization in lactating crossbred cows. The animals in groups 1 (control), 2, 3 and 4 were fed concentrate mixture containing 0 (no bypass fat), 2, 4 and 6% bypass fat, respectively. The average daily dry matter consumption in the various groups ranged from 13.1 to 13.6 kg and showed no significant difference among treatment groups. There was no significant difference among different groups in digestibility of DM, OM, CP and CF, however, ether extract digestibility in cows of groups 2 and 4 was significantly (p<0.05) higher than the control group. The average milk yields of the cows in group 3 (4% bypass fat) showed a significantly (p<0.05) higher value than cows of groups 1 and 2. Similarly, a significant (p<0.05) increase in fat yield, 4% FCM yield and SNF yield was observed for the cows in group 3 (4% bypass fat). The milk composition in terms of total solids, fat, lactose, protein, solids-not-fat and ash percentage showed a varying response and bypass fat feeding did not have any effect on milk composition of cows in different groups. The gross and net energetic efficiency of milk production ranged from 23.6 to 27.5% and 37.1 to 44.4%, respectively, and showed no significant difference among different treatment groups. The gross and net efficiency of nitrogen utilization for milk production ranged from 24.0 to 28.7% and 37.2 to 43.5%, respectively, and no significant difference was noted among different treatment groups. The supplementation with calcium salts of palm oil fatty acid reduced the proportion of caproic, caprylic and capric acids and significantly (p<0.01) increased the concentration of palmitic, oleic, stearic, linoleic and linolenic acids in milk fat with increase in level of bypass fat supplementation. It was concluded that incorporation of calcium salts of palm oil fatty acids at a 4% level in the concentrate mixture of lactating crossbred cows improved the milk production and milk quality in terms of polyunsaturated fatty acids without affecting the digestibility of nutrients.

Isolation and Characterization of an Acyclic Isoprenoid from Semecarpus anacardium Linn. and its Antibacterial Potential in vitro - Antimicrobial Activity of Semecarpus anacardium Linn. Seeds -

Purushothaman, Ayyakkannu,Meenatchi, Packirisamy,Saravanan, Nallappan,Karuppaiah, Muthu,Sundaram, Ramalingam KOREAN PHARMACOPUNCTURE INSTITUTE 2017 Journal of pharmacopuncture Vol.20 No.2

Objectives: Semecarpus anacardium Linn. is a plant well-known for its antimicrobial, antidiabetic and anti-arthritic properties in the Ayurvedic and Siddha system of medicine. This has prompted the screening of this plant for antibacterial activity. The main aims of this study were to isolate compounds from the plant's seeds and to evaluate their antibacterial effects on clinical bacterial test strains. Methods: The n-butanolic concentrate of the seed extract was subjected to thin layer chromatography (TLC) and repeated silica gel column chromatography followed by elution with various solvents. The compound was identified based on observed spectral (IR, $^1H$ NMR, $^{13}C$ NMR and high-resolution mass spectrometry) data. The well diffusion method was employed to evaluate the antibacterial activities of the isolated acyclic isoprenoid compound (final concentration: $5-15{\mu}g/mL$) on four test bacterial strains, namely, Staphylococcus aureus (MTCC 96), Bacillus cereus (MTCC 430), Escherichia coli (MTCC 1689) and Acinetobacter baumannii (MTCC 9829). Results: Extensive spectroscopic studies showed the structure of the isolated compound to be an acyclic isoprenoid ($C_{21}H_{32}O$). Moreover, the isoprenoid showed a remarkable inhibition of bacterial growth at a concentration of $15{\mu}g/mL$ compared to the two other doses tested (5 and $10{\mu}g/mL$) and to tetracycline, a commercially available antibiotic that was used as a reference drug. Conclusion: The isolation of an antimicrobial compound from Semecarpus anacardium seeds validates the use of this plant in the treatment of infections. The isolated compound found to be active in this study could be useful for the development of new antimicrobial drugs.

Parameter Optimization of UWB SRR System Performance in Weibull Clutter Environment

Purushothaman Surendran,Jong-Hun Lee,Seok Jun Ko 보안공학연구지원센터 2014 International Journal of Control and Automation Vol.7 No.2

Design, synthesis, and biological evaluation of novel catecholopyrimidine based PDE4 inhibitor for the treatment of atopic dermatitis

Purushothaman, Baskaran,Arumugam, Parthasarathy,Kulsi, Goutam,Song, Joon Myong Elsevier 2018 European journal of medicinal chemistry Vol.145 No.-

<P><B>Abstract</B></P> <P>Selective inhibition of phosphodiesterase (PDE) 4B favorably suppresses the synthesis of inflammatory cytokines and subsequently arrest the development of atopic dermatitis via modulating the intracellular cAMP levels. Considering the side effects of corticosteroids, selective PDE4 inhibition could constitute an effective alternative therapy for the treatment of atopic dermatitis (AD). In this study, a series of novel catechol based compounds bearing pyrimidine as the core have been synthesized and screened for the PDE4 inhibitory properties. The PDE4 selectivity of the active compounds over other PDEs has been investigated. Compound <B>23</B> bearing pyrimidine core functionalized with catechol, pyridine and trifluoromethyl groups can effectively inhibit the PDE4B with IC<SUB>50</SUB> value in nanomolar range (IC<SUB>50</SUB> = 15 ± 0.4 nM). Compound <B>23</B> exhibited seven fold higher selectivity towards PDE4B over PDE4D. Molecular Docking study confirmed its stronger affinity towards catalytic domain of PDE4B. <I>In-vivo</I> analysis confirmed that compound <B>23</B> effectively alleviated the symptoms of atopic dermatitis in DNCB–treated Balb/c mice by suppressing the synthesis of inflammatory mediators such as TNF-α, and Ig-E. Taken together, this study suggested that compound <B>23</B> could be an effective PDE4 inhibitor for the potential treatment of AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A series of novel catecholopyrimidine derivatives was synthesized. </LI> <LI> All compounds showed excellent PDE4B inhibition activity. </LI> <LI> The docking study was performed for the active compound <B>23</B>. </LI> <LI> In-vivo atopic animal study was performed for compound <B>23</B>. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Biotin-conjugated PEGylated porphyrin self-assembled nanoparticles co-targeting mitochondria and lysosomes for advanced chemo-photodynamic combination therapy

Purushothaman, Baskaran,Choi, Jinhyeok,Park, Solji,Lee, Jeongmin,Samson, Annie Agnes Suganya,Hong, Sera,Song, Joon Myong The Royal Society of Chemistry 2019 Journal of Materials Chemistry B Vol.7 No.1

<P>The combination of chemotherapy and photodynamic therapy (chemo-PDT) has been suggested as an alternative therapy for drug-resistant cancers. In this study, biotin-conjugated PEGylated photosensitizer (PS) self-assembled nanoparticles (<I>meso</I>-tetraphenylporphyrin (TPP)-PEG-biotin SANs) were prepared <I>via</I> a self-assembly process to serve as nanocarriers for chemo-drugs as well as PSs. Electron microscopy results reveal the spherical shape of the nanoparticles (NPs). In the NPs, conjugated biotin plays a key role in selective tumor targeting. <I>In vitro</I> cellular experiments revealed the rapid cellular uptake of the TPP-PEG-biotin conjugates by MCF-7 cells that overexpress the biotin receptor, and verified that the conjugates were much more effective PSs than TPPS used as control in the cytotoxicity test. Interestingly, subcellular localization studies showed that the conjugates and their self-assembled NPs were localized mainly in mitochondria and partially in lysosomes, whereas TPPS was localized only in lysosomes. With the exclusive localization in mitochondria, high-content cell based assay showed that the TPP-PEG-biotin SANs induced rapid mitochondrial membrane potential transition (MPT), leading to cellular apoptosis. The chemo-drug doxorubicin (DOX) was successfully encapsulated in the TPP-PEG-biotin SANs (DOX@TPP-PEG-biotin) and had synergistic effects with enhanced cytotoxicity after PDT action. Collectively, the DOX@TPP-PEG-biotin SANs have promising potential as an effective anticancer agent in targeted combination therapy.</P>

A Comparison Study of Four Cervical Disk Arthroplasty Devices Using Finite Element Models

Purushothaman Yuvaraj,Choi Hoon,Yoganandan Narayan,Jebaseelan Davidson,Baisden Jamie,Kurpad Shekar 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.3

Study Design: The study examined and compared four artificial cervical disks using validated finite element models. Purpose: To compare and contrast the biomechanical behavior of four artificial cervical disks by determining the external (range of motion) and internal (facet force and intradiscal pressure) responses following cervical disc arthroplasty (CDA) and to elucidate any device design effects on cervical biomechanics. Overview of Literature: Despite CDA’s increasing popularity most studies compare the CDA procedure with anterior cervical discectomy and fusion. There is little comparative evaluation of different artificial disks and, therefore, little understanding of how varying disk designs may influence spinal biomechanics. Methods: A validated C2–T1 finite element model was subjected to flexion-extension. CDAs were simulated at the C5–C6 level with the Secure-C, Mobi-C, Prestige LP, and Prodisc C prosthetic disks. We used a hybrid loading protocol to apply sagittal moments. Normalized motions at the index and adjacent levels, and intradiscal pressures and facet column loads were also obtained. Results: The ranges of motion at the index level increased after CDA. The Mobi-C prosthesis demonstrated the highest amount of flexion, followed by the Secure-C, Prestige LP, and Prodisc C. The Secure-C demonstrated the highest amount of extension, followed by the Mobi-C, Prodisc C, and Prestige LP. The motion decreased at the rostral and caudal adjacent levels. Facet forces increased at the index level and decreased at the rostral and caudal adjacent levels following CDA. Intradiscal pressures decreased at the adjacent levels for the Mobi-C, Secure-C, and Prodisc C. Conversely, the use of the Prestige LP increased intradiscal pressure at both adjacent levels. Conclusions: While all artificial disks were useful in restoring the index level motion, the Secure-C and Mobi-C translating abilities allowed for lower intradiscal pressures at the adjacent segments and may be the driving mechanism for minimizing adjacent segment degenerative arthritic changes. The facet joint integrity should also be considered in the clinical decision-making process for CDA selection.

Recovery and reuse of TiO2 photocatalyst from aqueous suspension using plant based coagulant - A green approach

Purushothaman Devipriya,Arunkumar Patchaiyappan,Sarangapany Saran 한국화학공학회 2016 Korean Journal of Chemical Engineering Vol.33 No.7

Separation of TiO2 from aqueous suspension is a major constraint in heterogeneous photocatalytic water treatment. As an alternative for existing less effective immobilization techniques, the application of plant based coagulant for the recovery and reuse of TiO2 was investigated for the first time. Aqueous extract derived from seeds of Strychnos potatorum was found to be an effective coagulant for the sedimentation of TiO2. Further, the potential for recovery and reuse of the sedimented photocatalysts TiO2, was investigated by photocatalytic degradation of rhodamine B and terephthalic acid tests. The photocatalytic degradation experiments with recovered catalyst obey pseudo first-order kinetics with enhanced photocatalytic activity than that of the pure TiO2. The investigation of recovered catalysts with XRD, BET, SEM etc., suggests that there is no change in surface and morphological properties when compared with pure TiO2 and the recovered catalysts are highly suitable for recycle and reuse.

Modifying Rhizospheric System for Soil Carbon Sequestration

Purushothaman Chirakkuzhyil Ab 한국토양비료학회 2014 한국토양비료학회 학술발표회 초록집 Vol.2014 No.6

Novel ruthenium(II) triazine complex [Ru(bdpta)(tpy)]²⁺ co-targeting drug resistant GRP78 and subcellular organelles in cancer stem cells

Purushothaman, Baskaran,Arumugam, Parthasarathy,Ju, Hee,Kulsi, Goutam,Samson, Annie Agnes Suganya,Song, Joon Myong Elsevier 2018 European journal of medicinal chemistry Vol.156 No.-

<P><B>Abstract</B></P> <P>Ruthenium(II/III) metal complexes have been widely recognized as the alternative chemotherapeutic agents to overcome the drug resistance and tumor recurrence associated with platinum derivatives. In this work, a novel ruthenium(II) triazine complex namely, <B>1</B> ([Ru(bdpta)(tpy)]<SUP>2+</SUP>) was synthesized and spectroscopically characterized. Drug resistant cancer stem cells (CSCs) were used to evaluate the cytotoxicity of Ru(II) complex <B>1</B>. The complex <B>1</B> showed a greater cytotoxic potential with IC<SUB>50</SUB> values lower than that of cisplatin. The intracellular localization assay confirmed that the complex <B>1</B> was effectively distributed into mitochondria as well as endoplasmic reticulum (ER), and executed a ROS-mediated calcium and Bax/Bak dependent intrinsic apoptosis. Interestingly, direct interaction between complex <B>1</B> and glucose regulated protein 78 (GRP78), a protein associated with drug resistance caused the ROS-mediated ubiquitination of GRP78. Notably, western blot and confocal microscopy analysis confirmed that complex <B>1</B> significantly reduced the protein levels of GRP78. Dose-dependent <I>in vivo</I> antitumor efficacy against CD133+HCT-116 CSCs derived tumor xenograft further validated that complex <B>1</B> could be an effective chemotherapeutic agent.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The novel ruthenium(II) triazine complex <B>1</B> was synthesized and characterized. </LI> <LI> The cytotoxicity study of ruthenium(II) triazine complex <B>1</B> was evaluated against cisplatin in cancer stem cells (CSCs). </LI> <LI> Complex <B>1</B> was mainly accumulated in mitochondria and endoplasmic reticulum (ER). </LI> <LI> Direct interaction between complex <B>1</B> and glucose regulated protein 78 (GRP78), caused ROS mediated ubiquitination of GRP78. </LI> <LI> Dose-dependent <I>in vivo</I> antitumor efficacy of complex <B>1</B> was investigated. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>