Molecular characterization of lymphocystis disease virus in Indian glass fish: first report from the Andaman Islands.

Here, we report the first detection of lymphocystis disease virus (LCDV) in Indian glass fish in the Andaman Islands, India. Microscopic examination revealed the presence of whitish clusters of nodules on the fish's skin, fins, and eyes. The histopathology of the nodules revealed typical hypertrophied fibroblasts. Molecular characterization of the major capsid protein (MCP) gene of the virus showed a significant resemblance to known LCDV sequences from Korea and Iran, with 98.92% and 97.85% sequence identity, respectively. Phylogenetic analysis confirmed that the MCP gene sequence of the virus belonged to genotype V. This study represents the first documented case of LCDV in finfish from the Andaman Islands, emphasizing the necessity for continued monitoring and research on the health of aquatic species in this fragile ecosystem.

An imbalance between proliferation and differentiation underlies the development of microRNA-defective pineoblastoma.

Mutations in the microRNA processing genes DICER1 and DROSHA drive several cancers that resemble embryonic progenitors. To understand how microRNAs regulate tumorigenesis, we ablated Drosha or Dicer1 in the developing pineal gland to emulate the pathogenesis of pineoblastoma, a brain tumor that resembles undifferentiated precursors of the pineal gland. Accordingly, these mice develop pineal tumors marked by loss of microRNAs, including the let-7/miR-98-5p family, and de-repression of microRNA target genes. Pineal tumors driven by loss of Drosha or Dicer1 mimic tumors driven by Rb1 loss, as they exhibit upregulation of S-phase genes and homeobox transcription factors that regulate pineal development. Blocking proliferation of these tumors facilitates expression of pinealocyte maturation markers, with a concomitant reduction in embryonic markers. Select embryonic markers remain elevated, however, as the microRNAs that normally repress these target genes remain absent. One such microRNA target gene is the oncofetal transcription factor Plagl2, which regulates expression of pro-growth genes, and inhibiting their signaling impairs tumor growth. Thus, we demonstrate that tumors driven by loss of microRNA processing may be therapeutically targeted by inhibiting downstream drivers of proliferation.

Toxicological effect of endocrine disrupting insecticide (deltamethrin) on enzymatical, haematological and histopathological changes in the freshwater iridescent shark, Pangasius hypothalamus.

This study investigated the deltamethrin (DMN) induced harmful effects on Pangasius hypophthalmus using enzymatic activity, haematological, and histopathological changes. LC50 value was 0.021 mg/L at 96 h, and sublethal toxicity was tested for 45 days at two `concentrations (i.e., 1/5th and 1/10th of LC50). Haematological parameters and enzymatic activities significantly changed between DMN-exposed and control groups (p < 0.05). Histopathologically, both DMN doses induced liver hyperemia, hepatic cell rupture, necrosis, hypertrepheoid bile duct, shifting nuclei, vascular haemorrhage, and hepatocyte degeneration, while in gill, secondary lamellae destruction, a fusion of adjacent gill lamellae, hypertrophy, hyperplasia, adhesion, and fusion were noticed. Kidney developed melanomacrophages, increased periglomerular and peritubular space, vacuolation, decreased glomerulus, hyaline droplets in tubular cells, loss of tubular epithelium, distal convoluted segment hypertrophy, and granular layer in brain pyramid and Purkinje cell nucleus. But, limiting pesticide impacts on freshwater fish and their habitat requires a holistic, cradle-to-grave approach and toxicological studies.

Outbreak of hirudiniasis in aquarium-reared albino red-bellied pacu Piaractus brachypomus.

We report hirudiniasis caused by the leech Hemiclepsis marginata asiatica Moore, 1924 in albino red-bellied pacu (pirapitinga) Piaractus brachypomus (Cuvier, 1818), constituting the first documentation of a freshwater fish species being affected in India. The outbreak occurred in a tank of an aquarium-fish retailer; infested fish appeared asphyxiated, unable to swim or swimming upside down, with cloudy eyes and body with thick mucus secretion. The prevalence and mortality was 100%, with a mean intensity of 81 leeches per fish. The histopathology of the morbid fish revealed degenerative necrosis, eosinophilic infiltration in the muscle tissue and haemorrhages in the fin membrane. The leech mitochondrial 18S rDNA and 12S rDNA genes were characterised and submitted to GenBank under accession numbers MN380443 (18S) and MK733282 (12S). A maximum likelihood tree was constructed using 12S rDNA gene sequences to demonstrate the phylogenetic position of Hemiclepsis marginata asiatica among its congeners.

Area efficient folded undecimator based ECG detector.

This paper presents an area-efficient folded wavelet filter-based Electrocardiogram (ECG) detector for cardiac pacemakers. The modified folded undecimator based detector consists of Wavelet Filter Bank, QRS complex detector with Generalized Likelihood Ratio Test (GLRT) block and noise detector. A high-level transformation technique such as folding transformation and Cutset retiming are applied to the GLRT block in order to reduce the silicon area. Folding is a high-level transformation applied at the architectural level to enhance the performance of DSP architectures. It reduces the number of adders, multipliers and delay elements in the architecture. The Cutset retiming reduces clock period of the architecture by changing position of delay elements in the critical path. The folding transformation and cutset retiming implement the functional blocks of the GLRT circuit with minimum hardware. The modified folded ECG detector is tested for short term and long-term MIT-BIH databases. The results show that the modified folded undecimator detector has hardware savings and achieves sensitivity of 99.95%, positive prediction of 99.97% and Detection Error Rate (DER) of 0.061. The folded GLRT block architecture is synthesized with FPGA Zed board XC7Z010CLG484-1. Results show that the device utilization and power consumption are lesser than the conventional GLRT structure.

The Genotoxic and Cytotoxic Effects of CT Scan on Buccal Epithelial Cells.

BACKGROUND: Diagnostic radiation is reported to cause significant damage in buccal cells, while the same effects after natural cell turn over cycle were not checked for in previous studies. The buccal cells were studied in patients exposed to computed tomography (CT) scans for evaluating the cells with micronuclei and cytotoxic changes, namely, pyknotic cells, karyorrhectic cells and karyolytic cells. The pre-exposure counts were compared with postexposure counts on 10 and 20 days corresponding to first and second cell turnover cycles. AIM: The aim of this study is to estimate the counts of micronucleus and cytotoxic changes in buccal cells post-exposure to CT scans and report on variance of the same with first and second buccal cell turnover cycles. MATERIALS AND METHODS: This is an observational study, wherein the buccal smears of patients undergoing CT scans were made before and after CT scan exposures as needed. Papanicolaou (PAP) staining and analysis were performed as per standard criteria for micronuclear and cytotoxic changes, respectively. Statistical test used was paired t-tests. RESULTS: The micronuclear counts revealed 0.4% positive cells before exposure and 1.4% positive cells post 10 days and 20 days of exposure were significant (P < 0.005). The cytotoxic changes showed around 2.5% positive cells before and 5.7% positive cells 10 days after CT exposure (P < 0.005). The cytotoxic cell values from baseline to 20th day were not significant (P < 0.25). CONCLUSION: CT scans have caused genotoxic effects notable after two cell turnover cycles but the cytotoxic changes have significantly decreased naturally after 2nd cell turnover as per our study.

A Randomized Controlled Trial to Compare Preemptive Analgesic Efficacy and Safety of Pregabalin and Gabapentin for Succinylcholine-Induced Myalgia.

BACKGROUND: Succinylcholine is a drug of choice for rapid induction of anesthesia but produces postoperative myalgia. Preemptive analgesia is intended to decrease perception of pain before exposure to painful stimuli. Pregabalin and gabapentin, analogs of the inhibitory neurotransmitter gamma aminobutyric acid, are effective in several models of neuropathic pain, incisional, inflammatory, and formalin-induced injury. However, the data available on their preemptive analgesic efficacy in succinylcholine myalgia are sparse. This study was designed to compare the preemptive analgesic efficacy and safety of pregabalin and gabapentin. MATERIALS AND METHODS: This randomized clinical trial included 120 surgical patients of either sex, between 18 and 70 years, and of American Society of Anesthesiologists-I/II grade. Patients were randomly allocated to control and test groups; received respective treatments 30 min before induction of anesthesia. Myalgia and pain scores were recorded using the myalgia scale and visual analog/facial rating scale at awakening at 6, 12, 18, and 24 h, respectively. Postoperative analgesic requirement over 24 h was recorded. Data were analyzed using OpenEpi (Andrew G. Dean and Kevin M. Sullivan, Atlanta, GA, USA) statistical softwares. RESULTS: Significantly lower pain scores were observed in the pregabalin group at 6, 12, and 24 h, and in gabapentin group at 24 h as compared to control and placebo (P < 0.05). They were however found to be equianalgesic when compared to each other (P > 0.05). Pregabalin-treated patients were more comfortable throughout with significantly less postoperative myalgia and analgesic requirement (P < 0.05). CONCLUSIONS: Results strongly suggest the preemptive analgesic efficacy of a single oral dose of pregabalin and gabapentin over diclofenac in postoperative myalgia and pain management. However, on the basis of safety profile, pregabalin may be preferred over gabapentin in succinylcholine-induced myalgia.

Efficacy Study of Folic Acid Supplementation on Homocysteine Levels in Adolescent Epileptics Taking Antiepileptic Drugs: A Single Blind Randomized Controlled Clinical Trial.

BACKGROUND: Epilepsy is a chronic medical condition that requires long-term therapy with antiepileptic drugs (AEDs). However, long-term employment of AEDs may lead to the onset of hyperhomocysteinemia, which has been found to modulate imperative metabolic mechanisms and induce cardiovascular disorders (CVDs). Therefore, adolescent population that have been diagnosed with epilepsy and utilize AEDs are among the most vulnerable, exhibiting higher risks of developing CVDs. PURPOSE: The present study was designed to explore the effects of folic acid (FA) supplementation on AED-induced hyperhomocysteinemia and CVD risk factors in adolescent epileptics. METHODS: The randomized clinical trial included adolescent epileptics (i.e., 10-19 years of age) of either sex, on antiepileptic therapy for > 6 months with high homocysteine levels (i.e., >10.9 µmol/L). At the time of enrolment, their baseline BP, lipid and homocysteine levels were recorded. Participants were randomly assigned to either treatment or placebo groups and received the respective treatments. At the end of the first month, BP, lipid and homocysteine levels were recorded and compared to determine the effect of FA on these parameters. RESULTS AND CONCLUSION: A significant fall in homocysteine levels was observed with FA supplementation (P < 0.05). However, this fall was significantly high in valproic acid treated epileptic patients. In addition, we observed an improvement in high-density lipoprotein levels, a risk factor for CVDs, but the change was statistically insignificant (P > 0.05). The study results suggest that FA supplementation in epileptic patients receiving AED therapy may minimize AED-induced hyperhomocysteinemia and other CVD risk factors.

Synergistic Protective Effect of Sickle Cell Trait and Blood Group-O on the Risk of Endemic Burkitt's Lymphoma.

BACKGROUND: Previous research strongly suggest that malaria is an important factor in the pathogenesis of endemic Burkitt's lymphoma (eBL). Therefore, genetic factors such as sickle cell trait (SCT) and blood group-O that offer protection against severe malaria would be expected to reduce the risks of eBL. However, previous reports on the protective roles of SCT and blood group-O against the risks of eBL were inconclusive. Hence, the need for further studies on the protective roles of SCT and blood group-O separately, and also to investigate whether or not the combined anti-severe malaria protective roles of SCT and blood group-O have synergistic effects in reducing the risks of eBL. We therefore hypothesize that SCT and blood group-O are independently associated with reduced risks of eBL, and the co-inheritance of both factors (SCT and group-O) would provide greater protection against eBL. If our hypothesis is correct, children who inherited both SCT and blood group-O would have lower risks of eBL than their counterparts who inherited SCT or blood group-O separately. To the best of our knowledge, the possible synergistic relationship between SCT and blood group-O with regards to the risk of eBL has not been previously studied. PATIENTS AND METHODS: We conducted a retrospective logistic regression analysis of the frequencies of Hb phenotypes and ABO blood groups among patients with eBL in order to determine the separate and synergistic protective effects of SCT and blood group-O on the risk of eBL in Nigeria where eBL is among the most common malignant childhood cancers. RESULTS: The Odd Ratios (OR) for the risk of eBL were 0.52 for 'SCT irrespective of ABO blood group'; 0.49 for 'blood group-O irrespective of Hb phenotype'; and 0.23 for 'SCT with blood group-O'. DISCUSSION: These values suggest that both SCT and blood group-O are independently associated with modest reduction in the risk of eBL. However, when SCT with blood group-O was assessed for the risk factor for eBL, we obtained an Odds ratio of 0.23, which was significantly lower than the OR values for SCT (0.52) and blood group-O (0.49) separately. These figures suggest that coinheritance of SCT and blood group-O offers greater reduction in the risk of eBL than that provided by either SCT or blood group-O separately. The greater protection against eBL provided by the coinheritance of SCT and blood group-O is interpreted to be the resultant synergistic effect of the combined anti-malarial attributes of SCT and blood group-O. CONCLUSION: These findings suggest that the combined anti-malarial protective roles of SCT and blood group-O have synergistic effects in reducing the risks of eBL. This study has provided further evidence on the association between malaria-protective genetic polymorphisms and eBL, which is consistent with the aetiologic role of malaria in the pathogenesis of the tumour. Hence, the need for malaria endemic countries to intensify malaria control programs in order to curtail the incidence of eBL.

Design, synthesis and in vitro study of densely functionalized oxindoles as potent α-glucosidase inhibitors.

Diabetes a non-communicable disease occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicated an increase in the trend of people diagnosed with type 2 diabetes mainly due to unhealthy life style. Here in we report a new class of oxindole derivatives 6a-kvia scaffold hopping of known α-glucosidase inhibitors 1-4. When molecular docking was performed against a homology model of α-glucosidase the resulting compound 6d revealed binding interactions comparable to 1-4. The compounds were accessed through a unique condensation-ring opening protocol of pyridofuranone building blocks. Overall the compounds exhibited decent binding to the yeast α-glucosidase, where the most potent compound 6h, inhibited the enzyme with IC50 of 0.6 µM. This was nearly threefold improvement from the original known compounds 1-4, selected to design the newer analogs. The reaction kinetics of 6h indicated competitive inhibition.

Non-invasive in vivo imaging of fluorescence-labeled bacterial distributions in aquatic species.

In vivo imaging is becoming an advanced tool for noninvasive distribution of longitudinal small animals. However, the aquatic species have been limited to the optical imaging of noninvasively tracking on pathogen distribution. The purpose of this study was to develop shell-less fish and shrimp models of non-invasive in vivo imaging technique for visualization of pathogens. This experiment was utilized Escherichia coli, Edwardsiella tarda, Vibrio alginolyticus and Vibrio harveyi labeled with fluorescence probes to imaging bacterial distributions by IVIS Lumina LT system. The study was traced the internal distribution of fluorescence probes labeled bacteria in systemic organs by quantified their fluorescence intensities. The ex vivo organ images were showed more obvious fluorescent signal in catfish intestine, liver, heart, kidney and the shrimp showed heart, hepatopancreas, and colon. Hence, the in vivo imaging methods using fluorescent labeled bacterial distribution were suggested to quantify by fluorescence intensity in whole pre-infected subjects. Therefore, it can offer the information about the localization and distribution of pathogens in the preclinical research, after immersion and injections.

Biochemical changes and tissue distribution of Enterocytozoon hepatopenaei (EHP) in naturally and experimentally EHP-infected whiteleg shrimp, Litopenaeus vannamei (Boone, 1931), in India.

Stunted growth in pond-reared Litopenaeus vannamei was observed in different farms located in Tamil Nadu and Andhra Pradesh, India. No mortality was associated with stunted growth. PCR assay on these samples revealed the presence of Enterocytozoon hepatopenaei (EHP) in stunted shrimp. Tissue distribution of EHP in naturally and experimentally infected shrimp was studied by PCR and histology. Histological examination revealed the presence of EHP in hepatopancreas and gut, but not in other organs. The PCR assay revealed the presence of EHP in all the organs tested in both naturally and experimentally infected shrimp. Healthy shrimp were challenged with E. hepatopenaei by intramuscular injection and oral route, and no mortality was observed in both routes after 30 days post-challenge. Different developmental stages of the microsporidian parasite were observed in the hepatopancreatic epithelial cells. Biochemical parameters such as total protein, albumin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase were measured in the haemolymph of naturally and experimentally EHP-infected shrimp. All biochemical parameters mentioned were found to be significantly higher in EHP-infected shrimp when compared to normal shrimp. This is the first report relating AST and ALT levels to EHP infection in naturally and experimentally infected shrimp.

Comparative pre-emptive analgesic efficacy study of novel antiepileptic agents gabapentin, lamotrigine and topiramate in patients undergoing major surgeries at a tertiary care hospital: a randomized double blind clinical trial.

BACKGROUND: Surgical injury leads to postoperative pain hypersensitivity preceded by central nervous sensitization, due to lowered pain threshold in peripheral nociceptors and increased excitability of the spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen seizing central nervous system sensitization before exposure to painful stimuli. Earlier, few studies support pre-emptive analgesic efficacy of novel antiepileptic agent gabapentin. But topiramate and lamotrigine though proven analgesic in animal models of chronic pain and clinical studies of gabapentin resistant neuropathic pain; literature search revealed scarce data on its pre-emptive analgesic efficacy. The present study is designed to study and compare the pre-emptive analgesic efficacy of lamotrigine, topiramate and gabapentin (as control) in postoperative pain control. METHODS: This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated into control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's score and pain score were recorded using visual analogue scale and facial and behavioral rating scales at awakening and at 1, 2, 4, 6 and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. Data were analyzed using OpenEpi and SciStatCalc statistical softwares. RESULTS: Significantly higher pain scores were observed in the topiramate group postoperatively for 2 h on all pain scales (p<0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p<0.05) postoperative analgesic requirement comparable to gabapentin. CONCLUSIONS: Study results are strongly suggestive of pre-emptive analgesic efficacy of single oral dose lamotrigine comparable to gabapentin and superior to topiramate in postoperative pain control.

Comparative Pre-Emptive Analgesic Efficacy Study of Novel Antiepileptic Agents Lamotrigine and Topiramate in Patients Undergoing Major Surgeries at a Tertiary Care Hospital: A Randomized Double Blind Clinical Trial.

BACKGROUND: Central nervous sensitization, following surgical injury, leads to postoperative pain hypersensitivity due to lowered pain threshold in peripheral nociceptors and increased excitability of spinal neurons. Pre-emptive analgesia is intended to decrease pain perception and overall analgesic need by use of drug regimen, seizing CNS sensitization before exposure to painful stimuli. Few studies support pre-emptive analgesic efficacy of novel antiepileptic agent Gabapentin. Though Topiramate and Lamotrigine have been proven analgesic in animal models of chronic pain and clinical studies of Gabapentin-resistant neuropathic pain, literature search revealed scarce data on its pre-emptive analgesic efficacy. PURPOSE: This study is designed to study and compare the pre-emptive analgesic efficacy of Lamotrigine, Topiramate, and Diclofenac sodium in postoperative pain control. METHODS: This randomized clinical trial included 90 patients of either sex, between 18 and 70 years undergoing major surgeries. Patients were randomly allocated to control and test groups and received respective treatment 30 min before induction of anesthesia. Aldrete's and pain scores were recorded using the Visual Analog Scale, Facial and Behavioral Rating Scale at awakening and at 1, 2, 4, 6, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. RESULTS: Significantly higher pain scores were observed in the Topiramate group postoperatively for 2 h on all pain scales (p < 0.05), whereas in the control group it was significantly higher at 1 h (p < 0.05). Lamotrigine-treated patients were more comfortable throughout the study with significantly less (p < 0.05) postoperative analgesic requirement. CONCLUSIONS: Study results strongly suggest the pre-emptive analgesic efficacy of a single oral dose of Lamotrigine over Diclofenac and Topiramate in postoperative pain control.

A Randomized Double-Blind Placebo-Controlled Study to Compare Preemptive Analgesic Efficacy of Novel Antiepileptic Agent Lamotrigine in Patients Undergoing Major Surgeries.

BACKGROUND: If postoperative acute pain remains unrelieved, it may result in significant morbidity and mortality. Preemptive analgesic initiated before surgery offers premature analgesia even before exposure to an initial noxious stimulus bestowing effective postoperative analgesia. In developed countries, it is regularly practiced as a part of well-defined protocol. In our country however, only a few centers practice it and that too irregularly and with undefined protocol. Few studies support preemptive analgesic efficacy of novel antiepileptic agent gabapentin. Though lamotrigine is a proven analgesic in animal models of chronic pain and clinical studies of gabapentin-resistant neuropathic pain, a literature search revealed scarce data on its preemptive analgesic efficacy. AIMS: The present study is designed to study the preemptive analgesic efficacy of lamotrigine in comparison with diclofenac sodium in postoperative pain control. MATERIALS AND METHODS: This randomized clinical trial included 90 patients of both sexes, between 18 years and 70 years undergoing major surgeries. Patients were randomly allocated into placebo, control, and test groups and received the respective treatment 30 min before the induction of anesthesia. Aldrete score and pain score were recorded using visual analog scale (VAS), facial rating scale (FRS), and behavioral rating scale (BRS) at awakening and at 1 h, 2 h, 4 h, 6 h, and 24 h. Postoperative rescue analgesic consumption for 24 h was recorded. RESULTS: Significantly higher pain scores were observed in the placebo group postoperatively for 2 h on all pain scales (P < 0.05), whereas in the control group it was significantly higher at 1 h (P < 0.05). The test group patients were more comfortable throughout the study and postoperative analgesic requirement was significantly less (P < 0.05). CONCLUSIONS: The study recommends the use of single oral dose lamotrigine as preemptive analgesic for effective postoperative pain control.

Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection.

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death-through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection.

Randomized, double-blind, placebo-controlled study to investigate the pharmacodynamic interaction of 5-HT3 antagonist ondansetron and paracetamol in postoperative patients operated in an ENT department under local anesthesia.

BACKGROUND: The preclinical incision pain models and clinical studies in healthy volunteers have demonstrated the central serotonergic analgesic mechanism, paracetamol analgesia. This has been evidenced by raised serotonin concentrations in the brain following paracetamol administration in a few studies. The inhibition of paracetamol analgesia by 5-HT3 antagonists suggests that this analgesia is 5-HT3 mediated. However, in a few studies, 5-HT3 antagonists themselves exhibited an analgesic action. Various studies in this context stated intricate results. The present study was intended to understand the pharmacodynamic interaction between paracetamol and ondansetron in postoperative patients. METHODS: This randomized clinical trial included 32 postoperative cases of either sex, ages between 18 and 70 years. The patients were randomly allocated into the placebo and test groups and received respective treatment at the end of surgery. The pain score was recorded using Visual Analogue Scale (VAS) and Face, Legs, Activity, Cry, Consolability (FLACC) behavioral scale at awakening and every 30 min for the next 3 h. The postoperative rescue analgesic consumption for 24 h was recorded. The data were analyzed using OpenEpi and SciStatCalc statistical software. RESULTS: A significantly higher pain score was observed in the placebo group postoperatively for 60 min on VAS (p<0.05 and p<0.01), whereas the FLACC behavior scale score was significantly higher at 120 and 150 min (p<0.05). The test group patients were more comfortable throughout the study, and the postoperative analgesic requirement was significantly lesser (p<0.05). CONCLUSIONS: The pharmacodynamic interaction between paracetamol and ondansetron coadministration does not block but instead increase paracetamol analgesia, reduce the postoperative analgesic requirement, and improve the postoperative comfort level.

A comparative study to evaluate the cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients.

BACKGROUND: During the past 2 years, a great deal of evaluation has been accomplished on the cardiovascular (CV) effects of nonsteroidal anti-inflammatory drugs (NSAIDs), nonselective and selective cyclooxygenase-2 inhibitors (COX-2-Is). Clinical trial databases for nonselective and selective COX-2-Is have shown variable effects on CV risk. There is much controversy regarding the CV safety of these selective and nonselective COX inhibitors (COX-Is). This study was therefore conducted to assess and compare the CV risk of COX-Is in arthritic patients over a period of time. METHODS: In this prospective comparative study, adult arthritics of either sex who were freshly diagnosed or taking COX-Is for <3 months were included. Patients were grouped into nonselective and selective COX-2-I groups with reference to the treatment they received, whereas arthritics with no history of COX-I treatment were included as controls. CV risk factors like blood pressure (BP), blood sugar level (BSL), lipid profile, and body mass index (BMI) were assessed and compared; the demography of CV risk factors was also studied. Data obtained were analyzed with Student's t-test using OpenEpi statistical software (Andrew G. Dean and Kevin M. Sullivan, Atlanta, GA, USA). RESULTS: The study clearly revealed that all NSAIDs exhibit potential CV risk; however, selective COX-2-Is were found to exhibit more CV risk. BMI, BP and lipid profile, the potential CV risk factors, showed significant impairment in a selective COX-2-I group: p<0.01, p<0.001 and p<0.05, respectively, vs. baseline and p<0.05 for BMI and triglycerides vs. nonselective COX-Is. CONCLUSIONS: This study depicts the impending CV risk of selective COX-2-Is and confirms and reevaluates the results of earlier studies in this regard.

Association of TLR4 (D299G, T399I), TLR9 -1486T>C, TIRAP S180L and TNF-α promoter (-1031, -863, -857) polymorphisms with risk for systemic lupus erythematosus among South Indians.

The rationale of this case-control study was to explore the association of Toll-like receptor 4 (TLR4) D299G, TLR4 T399I, TLR9 -1486 T>C, TIR-domain-containing adaptor protein (TIRAP) S180 L and tumor necrosis-α (TNF-α) promoter polymorphisms with susceptibility and phenotypic heterogeneity of systemic lupus erythematosus (SLE). PCR-RFLP, real-time PCR was used for the genetic analysis and expression studies and ELISA was used for the determination of specific autoantibodies. TLR4 D299G was associated with the risk for SLE (OR: 1.57, 95% CI: 1.08-2.28), while the TNF-α (-1031, -863, -857) CCC haplotype conferred protection. TLR4 and TIRAP polymorphisms were associated with reduced expression of HLA-DR. The presence of TLR4 and TLR9 polymorphisms increases the MHC2TA expression, while TIRAP polymorphism was associated with reduced expression. TLR4 D299 G showed an inverse association with pulmonary hypertension. TLR 4 T399I and TLR9 -1486 T>C showed a positive association with seizures and photosensitivity, respectively. TIRAP S180 L showed a positive association with alopecia and malar rashes, while an inverse association with psychosis was observed. TLR4 T399I (r = 0.14, p = 0.05) and TIRAP S180 L (r = 0.15, p = 0.03) showed a positive association with anti-Ro antibodies. On the other hand, TLR9 -1486 T>C showed an inverse association with anti-La antibodies (r = -0.20, p = 0.006). To conclude, TLR4 D299G increases the risk for SLE, while TNF-α CCC haplotype reduces the risk for SLE. All these polymorphisms contribute toward phenotypic heterogeneity. TLR4 T399I, TLR9 -1486 T>C and TIRAP S180 L influence specific autoantibody production in SLE.