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Prevention of aspirin-mediated secondary toxicity by combined treatment of carotenoids in macrophages

Vijay K, Ambedkar R, Sowmya PR, Ramaiah S, Ranga Rao A, Gundamaraju R, et al.

3 Biotech, 2023 Jul;13(7):223.
PMID: 37292139 DOI: 10.1007/s13205-023-03632-w

Upon understanding the boosting role of carotenoids on the endogenous anti-inflammatory system, it is vital to explore their role in reducing the use of high doses of non-steroidal anti-inflammatory drug (NSAIDs), and their mediated secondary toxicity during the treatment of chronic diseases. The current study investigates the carotenoids potential on inhibition of secondary complications induced by NSAIDs, aspirin (ASA) against lipopolysaccharide (LPS) stimulated inflammation. Initially, this study evaluated a minimal cytotoxic dose of ASA and carotenoids (β-carotene, BC/lutein, LUT/astaxanthin, AST/fucoxanthin FUCO) in Raw 264.7, U937, and peripheral blood mononuclear cells (PBMCs). In all three cells, carotenoids + ASA treatment reduced the LDH release, NO, and PGE2 efficiently than an equivalent dose of carotenoid or ASA treated alone. Based on cytotoxicity and sensitivity results, RAW 264.7 cells were selected for further cell-based assay. Among carotenoids, FUCO + ASA exhibited an efficient reduction of LDH release, NO, and PGE2 than the other carotenoids (BC + ASA, LUT + ASA, and AST + ASA) treatment. FUCO + ASA combination decreased LPS/ASA induced oxidative stress, pro-inflammatory mediators (iNOS, COX-2, and NF-κB), and cytokines (IL-6, TNF-α, and IL-1β) efficiently. Further, apoptosis was inhibited by 69.2% in FUCO + ASA, and 46.7% in ASA than LPS treated cells. A drastic decrease in intracellular ROS generation with the increase in GSH was observed in FUCO + ASA compared to LPS/ASA groups. The results documented on the low dose of ASA with a relative physiological concentration of FUCO suggested greater importance for alleviating secondary complications and optimize prolonged chronic disease treatments with NSAID's associated side effects.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-023-03632-w.
Comparison of microparticle transport and deposition in nasal cavity of three different age groups

Valerian Corda J, Shenoy BS, Ahmad KA, Lewis L, K P, Rao A, et al.

Inhal Toxicol, 2024 Jan;36(1):44-56.
PMID: 38343121 DOI: 10.1080/08958378.2024.2312801

Objective: The nasal cavity effectively captures the particles present in inhaled air, thereby preventing harmful and toxic pollutants from reaching the lungs. This filtering ability of the nasal cavity can be effectively utilized for targeted nasal drug delivery applications. This study aims to understand the particle deposition patterns in three age groups: neonate, infant, and adult.Materials and methods: The CT scans are built using MIMICS 21.0, followed by CATIA V6 to generate a patient-specific airway model. Fluid flow is simulated using ANSYS FLUENT 2021 R2. Spherical monodisperse microparticles ranging from 2 to 60 µm and a density of 1100 kg/m3 are simulated at steady-state and sedentary inspiration conditions.Results: The highest nasal valve depositions for the neonate are 25% for 20 µm, for infants, 10% for 50 µm, 15% for adults, and 15% for 15 µm. At mid nasal region, deposition of 15% for 20 µm is observed for infant and 8% for neonate and adult nasal cavities at a particle size of 10 and 20 µm, respectively. The highest particle deposition at the olfactory region is about 2.7% for the adult nasal cavity for 20 µm, and it is <1% for neonate and infant nasal cavities.Discussion and conclusions: The study of preferred nasal depositions during natural sedentary breathing conditions is utilized to determine the size that allows medication particles to be targeted to specific nose regions.
Fulltext One-year follow-up of efficacy and cost of repeated doses versus single larger dose of intra-articular hyaluronic acid for knee osteoarthritis

Suppan VKL, Tew MM, Wong BC, Chan HK, Chew YW, Tan CS, et al.

J Orthop Surg (Hong Kong), 2020 3 5;28(1):2309499019895029.
PMID: 32129141 DOI: 10.1177/2309499019895029

PURPOSE: A recent 3-month randomized, open-label controlled trial found that the intra-articular hyaluronic acid injection (GO-ON®) given as a single dose of 5 mL is as effective and safe as three repeated doses of 2.5 mL in patients with knee osteoarthritis. However, the information on the long-term efficacy and economic implications of the single-dose regimen is still limited. Hence, this follow-up study was designed to compare the effectiveness and costs of the two regimens 12 months following the treatment.
METHODS: All the 127 patients, who received either three repeated doses (n = 64) or a single dose (n = 63) of GO-ON in the previous trial, were followed up in month 12 following the treatment. The effectiveness of both the regimens was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the mean WOMAC scores were compared with those recorded at the baseline and in month 3. Additionally, the total treatment costs of the two regimens, taking account of both direct and indirect costs, were computed and compared.
RESULTS: A total of 125 patients (98.4%) completed the assessment. Despite the reduction of the overall mean WOMAC score from 39.24 to 19.93 (p < 0.001) in the first 3 months following the treatment with GO-ON, no further changes were observed up to month 12 (p > 0.95). In the meantime, the two regimens did not differ in the mean WOMAC scores (p = 0.749) and in the subscale scores for pain (p = 0.970), stiffness (p = 0.526), and physical functioning (p = 0.667) in month 12. The cost for single-dose injection was found to be approximately 30% lower compared to the repeated doses.
CONCLUSION: These findings indicate that the single larger dose of GO-ON is as effective as the repeated doses over 12 months, and yet the total treatment cost is lowered.
Fulltext Randomized controlled trial comparing efficacy of conventional and new single larger dose of intra-articular viscosupplementation in management of knee osteoarthritis

Suppan VKL, Wei CY, Siong TC, Mei TM, Chern WB, Nanta Kumar VK, et al.

J Orthop Surg (Hong Kong), 2017 9 28;25(3):2309499017731627.
PMID: 28946838 DOI: 10.1177/2309499017731627

BACKGROUND: Intra-articular hyaluronic acid (HA) injection is used in management of knee, hand and hip osteoarthritis. While HA injection is included in the list of evaluated therapies, its efficacy and optimum dosing still have no consensus. This study was conducted to explore the possibility of using single injection HA to increase patient convenience while maintaining the therapeutic efficacy.

METHODS: We present a prospective, open label, non-blinded, randomized controlled trial performed in accordance with guidelines in principles of good clinical practice. Block randomization was done for patients to receive either single 5 ml GO-ON injection or the conventional three injections of 2.5 ml GO-ON at weekly interval. Baseline Western Ontario McMaster University Osteoarthritis (WOMAC) scores were evaluated and recorded. All subjects were re-evaluated at 3 months and the WOMAC score recorded again as primary end points. Data analyses were performed with IBM SPSS Statistics for Windows software (version 21.0, IBM Corp, Armonk, New York, USA).

RESULTS: In the cohort of 127 patients, 33 were males and 94 females. The mean age was 59.1 years (standard deviation (SD) = 7.25) in single injection arm and 60.1 years (SD = 7.72) in triple injection arm. The two groups were recorded to have no significant difference in age ( p = 0.46) and Kellgren-Lawrence radiological grade ( p = 0.694). There was significant increase in the WOMAC scores from the baseline (pre-injection) to that recorded 3 months after injection ( p < 0.001) in patients of both groups. However, there was no statistically significant difference noticed in this clinical improvement between the two arms ( p = 0.889).

CONCLUSION: The study shows single 5 ml dose regime comparing well with conventional three doses of 2.5 ml of intra-articular GO-ON HA injected at weekly intervals and confirms good efficacy, tolerability and safety of single larger dose of GO-ON knee intra-articular injection.
Letters about Published Papers

Sinha NK, Bhardwaj A, Sadashiva Rao A, Trivedy PD

J Orthop Surg (Hong Kong), 2019 2 26;27(1):2309499018816450.
PMID: 30798736 DOI: 10.1177/2309499018816450
Letter to the Editor: Minimally invasive plate osteosynthesis for proximal humeral fractures

Sinha N, Rao BS, Trivedy PD, Rao AS

J Orthop Surg (Hong Kong), 2016 04;24(1):139.
PMID: 27122535
Western Lessons/Eastern Perspectives: Combining Neurology and Psychiatry in Preclinical Medical Student Education in Malaysia

Schiess N, Rao A, Mohanraj A, Wiener CM

Acad Psychiatry, 2017 08;41(4):551-555.
PMID: 27738999 DOI: 10.1007/s40596-016-0616-x
Fulltext Separate Belly and Tendon of Flexor Digitorum Superficialis to the Fifth Digit

Rao M, Ashwini LS, Somayaji SN, Mishra S, Guru A, Rao A

Oman Med J, 2011 Nov;26(6):e027.
PMID: 28861181 DOI: 10.5001/omj.2011.120

Variation in the origin of long flexor tendons in the anterior compartment of forearm is common. During routine cadaveric dissection at Melaka Manipal Medical College (Manipal Campus), we observed a separate muscle belly and tendon of flexor digitorum superficialis (FDS) to the fifth digit in the right upper limb of a 60 year-old male cadaver. The anomalous muscle belly originated from the common flexor tendon from the medial epicondyle of the humerus and continued as a thin tendon at the middle of the forearm to get inserted into the middle phalanx of the fifth digit. This can be considered as a case of split flexor digitorum superficialis. Such muscle variations and knowledge of their frequency, appearance, and location can be helpful for surgeons.
Morphine-sparing effect of ketoprofen after abdominal surgery

Rao AS, Cardosa M, Inbasegaran K

Anaesth Intensive Care, 2000 Feb;28(1):22-6.
PMID: 10701031

In a double-blind, placebo-controlled clinical trial (power of 80% to detect a 30% reduction in morphine consumption, P < 0.05), we have determined that the administration of two doses of intravenous ketoprofen 100 mg, one at the end of surgery and the second 12 hours postoperatively, was associated with a significant reduction in morphine consumption at eight (P = 0.028), 12 (P = 0.013) and 24 hours (P = 0.013) but not four hours (P = 0.065) postoperatively, as compared to placebo, when assessed by patient-controlled analgesia. There was no difference between the groups in pain scores or in the incidence of nausea and vomiting. One patient in the placebo group suffered from excessive sedation while one patient from the ketoprofen group suffered from transient oliguric renal failure. There were no other adverse effects. The results of this study show that ketoprofen does provide a morphine-sparing effect in the management of postoperative pain after abdominal surgery.
Fulltext Optimal size selection of laryngeal mask airway in Malaysian female adult population

Rao AS, Yew AEG, Inbasegaran K

Med J Malaysia, 2003 Dec;58(5):717-22.
PMID: 15190658 MyJurnal

The summary of various studies done looking at size selection of the laryngeal mask airway (LMA) in adults is that, selection based on sex is appropriate, and that both sizes 4 or 5 are adequate for adult females. However, in our local population these sizes may be too large especially the size 5 for adult females.
Fulltext Audit on tracheostomies performed at the General Intensive Care Unit, Kuala Lumpur Hospital

Rao AS, Mansor L, Inbasegaran K

Med J Malaysia, 2003 Jun;58(2):213-7.
PMID: 14569741 MyJurnal

During a 6-month period from October 2000 to March 2001, we analysed the indications, methods, waiting period and complications following a tracheostomy at the General Intensive Care Unit (GIGU) of Hospital Kuala Lumpur. There were 49 tracheostomies performed during this period. Thirty of them were performed in the GICU using the percutaneous dilatational method while 19 were performed electively in the Operating Theatre (OT) by the ear, nose and throat (ENT) surgeons. The main indications for a tracheostomy were prolonged mechanical ventilation and airway protection for patients with a poor Glasgow Coma Scale. The average waiting time for a tracheostomy after a decision was made to perform one was 1.34 +/- 0.72 days for a percutaneous tracheostomy and 3.72 +/- 2.52 days for a surgical tracheostomy. This difference was statistically significant (p < 0.001). There was excessive bleeding in 3 patients in the percutaneous tracheostomy group and 1 patient in the surgical tracheostomy group. Percutaneous tracheostomy is now the main method of tracheostomy at the GICU in Hospital Kuala Lumpur. Haemorrhage is the most significant complication of this procedure. However the overall complication rate is comparable with that of a surgical tracheostomy.
Evaluation of hepatoprotective and antioxidant activity of astaxanthin and astaxanthin esters from microalga-Haematococcus pluvialis

Rao AR, Sarada R, Shylaja MD, Ravishankar GA

J Food Sci Technol, 2015 Oct;52(10):6703-10.
PMID: 26396419 DOI: 10.1007/s13197-015-1775-6

Effect of isolated astaxanthin (ASX) and astaxanthin esters (ASXEs) from green microalga-Haematococcus pluvialis on hepatotoxicity and antioxidant activity against carbon tetrachloride (CCl4) induced toxicity in rats was compared with synthetic astaxanthin (SASX). ASX, ASXEs, and SASX, all dissolved in olive oil, fed to rats with 100 and 250 μg/kg b.w for 14 days. They were evaluated for their hepatoprotective and antioxidant activity by measuring appropriate enzymes. Among the treated groups, the SGPT, SGOT and ALP levels were decreased by 2, 2.4, and 1.5 fold in ASXEs treated group at 250 μg/Kg b.w. when compared to toxin group. Further, antioxidant enzymes catalase, glutathione, superoxide dismutase and lipid peroxidase levels were estimated in treated groups, their levels were reduced by 30-50 % in the toxin group, however these levels restored by 136.95 and 238.48 % in ASXEs treated group at 250 μg/kg. The lipid peroxidation was restored by 5.2 and 2.8 fold in ASXEs and ASX treated groups at 250 μg/kg. The total protein, albumin and bilirubin contents were decreased in toxin group, whereas normalized in ASXEs treated group. These results indicates that ASX and ASXEs have better hepatoprotection and antioxidant activity, therefore can be used in pharmaceutical and nutraceutical applications and also extended to use as food colorant.
Fulltext Insights into Disaster Management Scenario among Various Health-Care Students in India: A Multi-Institutional, Multi-Professional Study

Rajesh G, Binnal A, H Pai MB, Nayak SV, Shenoy R, Rao A

Indian J Community Med, 2020 06 02;45(2):220-224.
PMID: 32905107 DOI: 10.4103/ijcm.IJCM_104_19

Background: The frequency of occurrence of disasters is on the rise all over the world. Workforce shortage can be a major impediment toward efficient disaster management. Incorporation of other health-care workers along with conventional medical personnel might be critical for efficient and effective management of disasters.
Objective: The objective of this study was to assess various aspects pertaining to disaster management among various health-care students in India.
Methods: Final-year students pursuing medicine, dentistry, nursing, physiotherapy, pharmacy, Ayurveda, and homeopathy at various institutions in Mangalore, India, were the study participants. Participants' willingness to partake in disaster management and knowledge, attitude, behavior, and perceived effectiveness pertaining to disaster management was ascertained by a questionnaire method. Their previous history of training and familiarity with standard operating procedures was assessed.
Results: A total of 437 students belonging to seven health-care institutions participated in the study. Overall, 98.40% of the participants were willing to partake in disaster management. The mean knowledge, attitude, behavior, and perceived effectiveness scores were 49.19%, 81.75%, 47.28%, and 66.20%, respectively. Step-wise multiple linear regression analysis revealed that course (β = 0.247, P < 0.001), attitude (β = 0.154,P = 0.001), and behavior (β = 0.284, P < 0.001) were significant predictors of perceived effectiveness.
Conclusions: Participants in the present study revealed that they were willing to partake in disaster management. The participants also reported poor behavior and knowledge scores but appropriate attitude scores. The present study highlights the need for curriculum changes and policy implications for effective integration of various sectors for disaster management, particularly in developing nations such as India, which have a definite scarcity of resources.
Erythrocyte indicators of oxidative changes in patients with graded traumatic head injury

Nayak CD, Nayak DM, Raja A, Rao A

Neurol India, 2008 3 4;56(1):31-5.
PMID: 18310834

CONTEXT: Acute oxidative stress following a traumatic head injury (HI) has been implicated in inducing severe secondary brain damage and influencing the clinical outcome of HI patients.
AIMS: This study was performed to evaluate and compare the oxidative changes in patients with varying severity of HI in the early posttraumatic period using erythrocyte indicators.
SETTINGS AND DESIGN: Head injury patients were divided into two groups based on their Glasgow Coma Scale (GCS) scores recorded at admission to the hospital on the day of trauma itself. Accordingly, the study included 30 severe HI (SHI, GCS scores 8 or less) and 25 Mild HI (MHI, GCS scores more than 8) patients. Thirty age and sex-matched healthy individuals were included in this comparative study as controls.
MATERIALS AND METHODS: Blood samples were obtained from controls and HI patients (within 24 h of trauma onset). Erythrocyte oxidative changes were studied by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and glutathione reductase (GR).
RESULTS: Erythrocyte TBARS levels were significantly higher and GSH levels were significantly lower in SHI and MHI patients as compared to controls. The SOD activity was significantly increased only in SHI patients and remained unchanged in MHI patients as compared to controls. As compared to MHI patients, erythrocyte TBARS levels were significantly higher, GSH levels were significantly lower and SOD activity was markedly elevated in SHI patients. Erythrocyte GR activity did not show significant changes in both groups of patients as compared to controls.
CONCLUSION: Oxidative stress is evident in both SHI and MHI patients in the early posttraumatic period as reflected by their erythrocyte indicators, but the severity of oxidative stress has varied relatively with the severity of head injury. The present findings provide indications that early oxidative changes could influence the neurological recovery of HI patients.
Time-relative changes in the erythrocyte antioxidant enzyme activities and their relationship with Glasgow Coma Scale scores in severe head injury patients in the 21-day posttraumatic study period

Nayak CD, Nayak DM, Raja A, Rao A

Indian J Med Sci, 2007 Jul;61(7):381-9.
PMID: 17611343

BACKGROUND: Reactive oxygen species are indicated to play a prime role in the pathophysiology of brain damage following a severe head injury (SHI).
AIM: The current study was designed to understand the time-relative changes and relationship between erythrocyte antioxidant enzyme activities and Glasgow Coma Scale (GCS) scores of SHI patients in the 21-day posttraumatic study period.
SETTINGS AND DESIGN: The study included 24 SHI patients and 25 age- and sex-matched normal controls (NC). Activities of superoxide dismutase (SOD), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) were assayed in these patients and controls. The GCS scores of these patients were also recorded for the comparative study.
MATERIALS AND METHODS: Venous blood samples were collected on day 7 (D7) and D21 from SHI patients and NC for the assay of SOD, GR and GSH-Px activities. These changes were correlated with age and changes in GCS scores of patients.
STATISTICAL ANALYSIS: A one-way analysis of variance (ANOVA) was used to compare mean values of each parameter between group 1 (NC), group 2 (D7 changes in SHI patients) and group 3 (D21 changes in SHI patients). ANOVA was followed by Bonferroni post hoc tests. The Pearson correlation was applied to correlate between the antioxidant parameters and age and GCS scores of these patients.
RESULTS: A significant increase in erythrocyte SOD and GSH-Px activities was observed in group 3 as compared to groups 1 and 2. The increase in GSH-Px activity was significant in group 2 as compared to group 1. Although not significant, there was an increase in mean GR activity in groups 2 and 3 as compared to group 1.
CONCLUSION: These findings indicate that SHI patients have shown significantly enhanced erythrocyte SOD and GSH-Px activities during the 21-day posttraumatic study period.
Relationship between markers of lipid peroxidation, thiol oxidation and Glasgow coma scale scores of moderate head injury patients in the 7 day post-traumatic period

Nayak C, Nayak D, Raja A, Rao A

Neurol Res, 2008 Jun;30(5):461-4.
PMID: 18953735

Epidemiologic works reveal that moderate head injury (MHI) is more frequent and a substantial number of these patients develop complications resulting in neurological disabilities. Reactive oxygen species (ROS) play a major role in post-traumatic neuronal damage following traumatic head injury. Thus, the current study analysed the post-traumatic changes in the erythrocyte markers of oxidative damage and the relationship between these parameters and Glasgow coma scale (GCS) scores of MHI patients during the 7 day study period.
Relationship between neurological outcome and early oxidative changes in erythrocytes in head injury patients

Nayak C, Nayak D, Bhat S, Raja A, Rao A

Clin Chem Lab Med, 2007;45(5):629-33.
PMID: 17484625

Experimental data indicate that destructive oxidative events reach their peak within the first 24 h after trauma in head injury (HI) and that brain damage occurring due to this impact can be the cause of death or irreversible permanent disabilities in affected patients.
Time-level relationship between indicators of oxidative stress and Glasgow Coma Scale scores of severe head injury patients

Nayak C, Nayak D, Raja A, Rao A

Clin Chem Lab Med, 2006;44(4):460-3.
PMID: 16599841

Oxidative stress is said to strongly influence the neurological recovery of patients following a severe head injury. Estimation of the markers of oxidative stress in the blood of such patients can hence aid in predicting the prognosis of head injury.
Variant course of posterior circumflex humeral artery associated with the abnormal origin of radial collateral artery: could it mimic the quadrangular space syndrome?

Mohandas Rao KG, Somayaji SN, Ashwini LS, Ravindra S, Abhinitha P, Rao A, et al.

Acta Med Iran, 2012;50(8):572-6.
PMID: 23109033

Variations in the origin of axillary artery branches are common. But, distinctly abnormal course of its posterior circumflex humeral branch is rare. We are reporting a case of posterior circumflex humeral artery (PCHA) originating from the axillary artery, passing through lower triangular space to reach the scapular region where it accompanied the axillary nerve and posterior circumflex humeral vein to pass around surgical neck of humerus, deep to the fibers of deltoid. Other variations observed in this specimen were the radial collateral artery arising from the PCHA, middle collateral artery arising directly from the brachial artery and absence of profunda brachii artery. PCHA forming a hair pin loop, traversing through lower triangular space instead of quadrangular space taking a long course is being reported for the first time. Further, the clinical and surgical importance of this case especially in relation with quadrangular space syndrome and relevant literature is discussed.
Diagnosis of retinal health in digital fundus images using continuous wavelet transform (CWT) and entropies

Koh JEW, Acharya UR, Hagiwara Y, Raghavendra U, Tan JH, Sree SV, et al.

Comput Biol Med, 2017 05 01;84:89-97.
PMID: 28351716 DOI: 10.1016/j.compbiomed.2017.03.008

Vision is paramount to humans to lead an active personal and professional life. The prevalence of ocular diseases is rising, and diseases such as glaucoma, Diabetic Retinopathy (DR) and Age-related Macular Degeneration (AMD) are the leading causes of blindness in developed countries. Identifying these diseases in mass screening programmes is time-consuming, labor-intensive and the diagnosis can be subjective. The use of an automated computer aided diagnosis system will reduce the time taken for analysis and will also reduce the inter-observer subjective variabilities in image interpretation. In this work, we propose one such system for the automatic classification of normal from abnormal (DR, AMD, glaucoma) images. We had a total of 404 normal and 1082 abnormal fundus images in our database. As the first step, 2D-Continuous Wavelet Transform (CWT) decomposition on the fundus images of two classes was performed. Subsequently, energy features and various entropies namely Yager, Renyi, Kapoor, Shannon, and Fuzzy were extracted from the decomposed images. Then, adaptive synthetic sampling approach was applied to balance the normal and abnormal datasets. Next, the extracted features were ranked according to the significances using Particle Swarm Optimization (PSO). Thereupon, the ranked and selected features were used to train the random forest classifier using stratified 10-fold cross validation. Overall, the proposed system presented a performance rate of 92.48%, and a sensitivity and specificity of 89.37% and 95.58% respectively using 15 features. This novel system shows promise in detecting abnormal fundus images, and hence, could be a valuable adjunct eye health screening tool that could be employed in polyclinics, and thereby reduce the workload of specialists at hospitals.

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