Publications by authors named "Vishnu Raj"

25 Publications

  • Page 1 of 1

Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor.

Nutrients 2021 Apr 17;13(4). Epub 2021 Apr 17.

Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain PO Box 17666, United Arab Emirates.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in , for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.
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http://dx.doi.org/10.3390/nu13041343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8073634PMC
April 2021

Nerolidol Mitigates Colonic Inflammation: An Experimental Study Using both In Vivo and In Vitro Models.

Nutrients 2020 Jul 8;12(7). Epub 2020 Jul 8.

Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain 17666, UAE.

Nerolidol (NED) is a naturally occurring sesquiterpene alcohol present in various plants with potent anti-inflammatory effects. In the current study, we investigated NED as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were administered 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. Six groups received either vehicle alone or DSS alone or DSS with oral NED (50, 100, and 150 mg/kg body weight/day by oral gavage) or DSS with sulfasalazine. Disease activity index (DAI), colonic histology, and biochemical parameters were measured. TNF-α-treated HT-29 cells were used as in vitro model of colonic inflammation to study NED (25 µM and 50 µM). NED significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue Myeloperoxidase (MPO) concentrations, neutrophil and macrophage mRNA expression (CXCL2 and CCL2), and proinflammatory cytokine content (IL-1β, IL-6, and TNF-α) both at the protein and mRNA level were significantly reduced by NED. The increase in content of the proinflammatory enzymes, COX-2 and iNOS induced by DSS were also significantly inhibited by NED along with tissue nitrate levels. NED promoted Nrf2 nuclear translocation dose dependently. NED significantly increased antioxidant enzymes activity (Superoxide dismutase (SOD) and Catalase (CAT)), Hemeoxygenase-1 (HO-1), and SOD3 mRNA levels. NED treatment in TNF-α-challenged HT-29 cells significantly decreased proinflammatory chemokines (CXCL1, IL-8, CCL2) and COX-2 mRNA levels. NED supplementation attenuates colon inflammation through its potent antioxidant and anti-inflammatory activity both in in vivo and in vitro models of colonic inflammation.
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http://dx.doi.org/10.3390/nu12072032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400891PMC
July 2020

Phytochemical drug candidates for the modulation of peroxisome proliferator-activated receptor γ in inflammatory bowel diseases.

Phytother Res 2020 Jul 3;34(7):1530-1549. Epub 2020 Feb 3.

Department of Physiology, Zayed Bin Sultan Center for Health Sciences, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.

Plant-based compounds or phytochemicals such as alkaloids, glycosides, flavonoids, volatile oils, tannins, resins, and polyphenols have been used extensively in traditional medicine for centuries and more recently in Western alternative medicine. Extensive evidence suggests that consumption of dietary polyphenolic compounds lowers the risk of inflammatory diseases. The anti-inflammatory properties of several phytochemicals are mediated through ligand-inducible peroxisome proliferator-activated receptors (PPARs), particularly the PPARγ transcription factor. Inflammatory bowel disease (IBD) is represented by ulcerative colitis, which occurs in the mucosa of the colon and rectum, and Crohn's disease (CD) that can involve any segment of gastrointestinal tract. Because of the lack of cost-effective pharmaceutical treatment options, many IBD patients seek and use alternative and unconventional therapies to alleviate their symptoms. PPARγ plays a role in the inhibition of inflammatory cytokine expression and activation of anti-inflammatory immune cells. The phytochemicals reported here are ligands that activate PPARγ, which in turn modulates inflammatory responses. PPARγ is highly expressed in the gut making it a potential therapeutic target for IBDs. This review summarizes the effects of the currently published phytochemicals that modulate the PPARγ pathway and reduce or eliminate colonic inflammation.
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http://dx.doi.org/10.1002/ptr.6625DOI Listing
July 2020

Spermine protects alpha-synuclein expressing dopaminergic neurons from manganese-induced degeneration.

Cell Biol Toxicol 2019 04 1;35(2):147-159. Epub 2018 Nov 1.

Division of Molecular Medicine, Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India.

Manganese exposure is among the many environmental risk factors linked to the progression of neurodegenerative diseases, such as manganese-induced parkinsonism. In animal models, chronic exposure to manganese causes loss of cell viability, neurodegeneration, and functional deficits. Polyamines, such as spermine, have been shown to rescue animals from age-induced neurodegeneration in an autophagy-dependent manner; nonetheless, it is not understood whether polyamines can prevent manganese-induced toxicity. In this study, we used two model systems, the Caenorhabditis elegans UA44 strain and SK-MEL-28 cells, both expressing the protein alpha-synuclein (α-syn) to determine whether spermine could ameliorate manganese-induced toxicity. Manganese caused a substantial reduction in the viability of SK-MEL-28 cells and hastened neurodegeneration in the UA44 strain. Spermine protected both the SK-MEL-28 cells and the UA44 strain from manganese-induced toxicity. Spermine also reduced the age-associated neurodegeneration observed in the UA44 strain compared with a control strain without α-syn expression and led to improved avoidance behavior in a functional assay. Treatment with berenil, an inhibitor of polyamine catabolism, which leads to increased intracellular polyamine levels, also showed similar cellular protection against manganese toxicity. While both translation blocker cycloheximide and autophagy blocker chloroquine caused a reduction in the cytoprotective effect of spermine, transcription blocker actinomycin D had no effect. This study provides new insights on the effect of spermine in preventing manganese-induced toxicity, which is most likely via translational regulation of several candidate genes, including those of autophagy. Thus, our results indicate that polyamines positively influence neuronal health, even when exposed to high levels of manganese and α-syn, and supplementing polyamines through diet might delay the onset of diseases involving degeneration of dopaminergic neurons.
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http://dx.doi.org/10.1007/s10565-018-09449-1DOI Listing
April 2019

The National Dental Practice-Based Research Network adult anterior open bite study: A description of the practitioners and patients.

Angle Orthod 2018 Nov 12;88(6):675-683. Epub 2018 Sep 12.

Objectives:: To describe the demographic and practice characteristics of the clinicians enrolled in a large, prospective cohort study examining recommendations and treatment for adult anterior open bite (AOB) and the relationship between these characteristics and practitioners' self-reported treatment preferences. The characteristics of the AOB patients recruited were also described.

Materials And Methods:: Practitioners were recruited from the National Dental Practice-Based Research Network. Participants in the study consisted of practitioners and their adult AOB patients in active treatment. Upon enrollment, practitioners completed questionnaires enquiring about demographics, treatment preferences for adult AOB patients, and treatment recommendations for each patient. Patients completed questionnaires on demographics and factors related to treatment.

Results:: Ninety-one practitioners and 347 patients were recruited. Demographic characteristics of recruited orthodontists were similar to those of American Association of Orthodontists members. The great majority of practitioners reported using fixed appliances and elastics frequently for adult AOB patients. Only a third of practitioners reported using aligners frequently for adult AOB patients, and 10% to 13% frequently recommended temporary anchorage devices (TADs) or orthognathic surgery. Seventy-four percent of the patients were female, and the mean age was 31.4 years. The mean pretreatment overbite was -2.4 mm, and the mean mandibular plane angle was 38.8°. Almost 40% of patients had undergone orthodontic treatment previously.

Conclusions:: This article presents the demographic data for 91 doctors and 347 adult AOB patients, as well as the practitioners' self-reported treatment preferences.
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http://dx.doi.org/10.2319/070118-491.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209525PMC
November 2018

Frondanol, a Nutraceutical Extract from , Attenuates Colonic Inflammation in a DSS-Induced Colitis Model in Mice.

Mar Drugs 2018 Apr 30;16(5). Epub 2018 Apr 30.

Department of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box⁻17666, Al Ain, UAE.

Frondanol is a nutraceutical lipid extract of the intestine of the edible Atlantic sea cucumber, with potent anti-inflammatory effects. In the current study, we investigated Frondanol as a putative anti-inflammatory compound in an experimental model of colonic inflammation. C57BL/6J male black mice (C57BL/6J) were given 3% dextran sodium sulfate (DSS) in drinking water for 7 days to induce colitis. The colitis group received oral Frondanol (100 mg/kg body weight/per day by gavage) and were compared with a control group and the DSS group. Disease activity index (DAI) and colon histology were scored for macroscopic and microscopic changes. Colonic tissue length, myeloperoxidase (MPO) concentration, neutrophil and macrophage marker mRNA, pro-inflammatory cytokine proteins, and their respective mRNAs were measured using ELISA and real-time RT-PCR. The tissue content of leukotriene B4 (LTB4) was also measured using ELISA. Frondanol significantly decreased the DAI and reduced the inflammation-associated changes in colon length as well as macroscopic and microscopic architecture of the colon. Changes in tissue MPO concentrations, neutrophil and macrophage mRNA expression (F4/80 and MIP-2), and pro-inflammatory cytokine content (IL-1β, IL-6 and TNF-α) both at the protein and mRNA level were significantly reduced by Frondanol. The increase in content of the pro-inflammatory mediator leukotriene B4 (LTB4) induced by DSS was also significantly inhibited by Frondanol. It was thus found that Frondanol supplementation attenuates colon inflammation through its potent anti-inflammatory activity.
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http://dx.doi.org/10.3390/md16050148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983279PMC
April 2018

Ellagic acid modulates sodium valproate induced reproductive toxicity in male Wistar rats.

Indian J Physiol Pharmacol 2014 Oct-Dec;58(4):416-22

This study evaluated the protective effect of ellagic acid on sodium valproate-induced sperm abnormalities in male Wistar rats. A total of 30 rats were grouped into five groups, each having 6 animals. Vehicle, sodium valproate (400 mg/kg) and ellagic acid (10, 25, 50 mg/kg) were given orally from day 1 to day 7, and ellagic acid was continued for 3 more days. On day fourteen, animals were sacrificed and the different parameters were recorded. There was a significant decrease in the sperm count and sperm motility after the exposure to sodium valproate. The percentage of abnormal sperms increased in a dose-dependent manner. The histopathological examination revealed that sodium valproate had caused degeneration and desquamation of germinal cells in the epithelium and also showed a decrease in the Johnsen's scoring. Ellagic acid provided partial protection at the doses of 10 and 25 mg/kg and complete protection at 50 mg/kg, against sodium valproate induced testicular and spermatozoal damage.
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August 2015

Proliferation of dinoflagellates in Kochi estuary, Kerala.

J Environ Biol 2014 Sep;35(5):877-82

Phytoplankton community structure and dynamics of Kochi estuary (bar mouth) have been studied seasonally. Three seasonal samplings namely pre-monsoon, monsoon and post-monsoon were made, and a wide variation was observed in phytoplankton community with respect to nutrients and other physicochemical parameters. Contrary to other seasons, dinoflagellate cell density increased during pre-monsoon season though species diversity was less pronounced (D > 0.15). Peridinium oceanicum was the dominant dinoflagellate during pre-monsoon season. Significant fluctuation in three principal nutrients namely total nitrogen, total phosphorous and silicate were observed during pre-monsoon (TP < 1.8 micromol l(-1), TN > 40 micromol l(-1) and SiO4 < 20 micromol l(-1)) season as compared to monsoon season (TP > 3.20 micromol l(-1), TN < 20 micromol l(-1) and SiO4 > 27 micromol l(-1)). Salinity values were also found to be high during pre-monsoon ( > 25 psu). Study suggests that variation in salinity and nutrient concentration during transition of seasons could result in succession of species, thereby causing change in phytoplankton community structure. High salinity and nitrogen values along with low values of silicate and phosphorous resulted in proliferation of dinoflagellates during pre-monsoon season.
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September 2014

Inadequate pain relief for patients with trauma: A cause for concern?

J Pharmacol Pharmacother 2013 Oct;4(4):281-2

Department of Pharmacology, Pondicherry Institute of Medical Sciences, Kalapet, Pondicherry, India.

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http://dx.doi.org/10.4103/0976-500X.119714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3826004PMC
October 2013

Esthetic paradigms in the interdisciplinary management of maxillary anterior dentition-a review.

Authors:
Vishnu Raj

J Esthet Restor Dent 2013 Oct 3;25(5):295-304. Epub 2013 May 3.

Private Practice, Austin, TX, USA.

Unlabelled: This article reviews some commonly used esthetic proportions and paradigms in dentistry. Establishing optimal anterior esthetics frequently entails restorative, orthodontic, and periodontal treatment. Several guidelines have been purported to facilitate an esthetic outcome during the rehabilitation of the maxillary anterior teeth. The golden proportion, recurring esthetic dental proportion, tooth width : height ratios, vertical positioning of the maxillary lateral incisor, and the apparent contact dimension are examples of some such guidelines. Evaluation of these esthetic paradigms including their validity, esthetic significance, perception by laypeople, and the range of tolerance to alterations are very important considerations.

Clinical Significance: This review presents a comprehensive analysis of some selected esthetic dental paradigms and recommendations for their application in the interdisciplinary management of anterior dental esthetics.
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http://dx.doi.org/10.1111/jerd.12028DOI Listing
October 2013

Audit of use of antibiotics and zinc supplement in childhood diarrhea.

J Pharmacol Pharmacother 2013 Jul;4(3):204-5

Department of Pharmacology, Pondicherry Institute of Medical Sciences Kalapet, Puducherry, India.

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http://dx.doi.org/10.4103/0976-500X.114601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746304PMC
July 2013

Involvement of the GABAergic system in the anxiolytic-like effect of the flavonoid ellagic acid in mice.

Eur J Pharmacol 2013 Jun 17;710(1-3):49-58. Epub 2013 Apr 17.

Neuropharmacology Lab, Department of Pharmacology, Pondicherry Institute of Medical Sciences (P.I.M.S.), Kalapet, Puducherry-605 014, India.

Anxiolytic-like effects of dietary flavonoids are relatively well known. Ellagic acid is a naturally occurring flavonoid compound which is abundant in many plants and fruits. The present study was designed to investigate the antianxiety-like effect of ellagic acid in mice using an elevated plus-maze test. The involvement of the GABAergic and serotonergic systems in the antianxiety-like activity of ellagic acid was also studied. Our results showed that ellagic acid treatment (25, 50 and 100 mg/kg, p.o.), produced a significant increase in the percentage of time spent and entry into the open arms, with a profile comparable to that of diazepam (1 mg/kg, p.o.). Unlike diazepam, the anxiolytic doses of ellagic acid did not prolong the duration of sodium thiopental-induced loss of righting reflex, indicating that this flavonoid is non-hypnotic. The anxiolytic effect observed with ellagic acid treatment (25 mg/kg, p.o.) was antagonized by pretreatment with picrotoxin (a non-competitive GABAA receptor antagonist, 1 mg/kg, i.p.) and flumazenil (a benzodiazepine site antagonist, 1 mg/kg, i.p.) but not with p-chlorophenylalanine (a serotonin synthesis inhibitor, 100 mg/kg, i.p.) and pindolol (a β-adrenoceptors blocker/5-HT1A/1B receptor antagonist, 10 mg/kg, i.p.). Taken together, the data demonstrated that acute and chronic administration of ellagic acid to mice has produced antianxiety-like effect when tested in the elevated plus-maze. The experiments with different receptor blockers suggest an involvement of GABAergic system in the anxiolytic action of this bioflavonoid. However, this action is not seems to be mediated through serotonergic system.
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http://dx.doi.org/10.1016/j.ejphar.2013.04.003DOI Listing
June 2013

Evidence for the involvement of the monoaminergic system, but not the opioid system in the antidepressant-like activity of ellagic acid in mice.

Eur J Pharmacol 2012 May 24;682(1-3):118-25. Epub 2012 Feb 24.

Department of Pharmacology, Pondicherry Institute of Medical Sciences (P.I.M.S.), Kalapet, Puducherry-605 014, India.

Dietary flavonoids possess a multiplicity of neuroprotective actions in various central nervous pathophysiological conditions including depression. Ellagic acid is a polyphenolic compound that occurs in plants such as raspberries, nuts and eucalyptus species. The present study was designed to investigate the antidepressant-like effect of ellagic acid in mice using forced swimming test (FST) and tail suspension test (TST). The involvement of the monoaminergic and opioid systems in the antidepressant-like activity of ellagic acid was also studied. Our results showed that ellagic acid when administered acutely or chronically to mice (25, 50 and 100mg/kg, p.o.), produced a significant reduction in the duration of immobility, with a profile comparable to that of fluoxetine (20mg/kg, p.o.). However, ellagic acid treatment had no effect on the locomotor activity of mice when tested in actophotometer. The reduction in immobility time observed with ellagic acid treatment (50mg/kg, p.o.) was prevented by pretreatment with p-chlorophenylalanine (100mg/kg, i.p., a serotonin synthesis inhibitor), pindolol (10mg/kg, i.p., a β-adrenoceptors blocker/5HT(1A/1B) receptor antagonist), ketanserin (5mg/kg, i.p., a 5HT(2A/2B) receptor antagonist), ondansetron (1mg/kg, i.p., a 5HT(3) receptor antagonist), prazosin (1mg/kg, i.p., an α(1)-adrenoceptor antagonist) and yohimbine (1mg/kg, i.p., an α(2)-adrenoceptor antagonist), but not with naloxone (1mg/kg, i.p., an opioid receptor antagonist). Our results suggest that ellagic acid produced an antidepressant-like effect which was unrelated to its locomotor activity. Furthermore, this anti-immobility effect seems most likely to be mediated through an interaction with the monoaminergic system (serotonergic and noradrenergic systems) and not through the opioid system.
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http://dx.doi.org/10.1016/j.ejphar.2012.02.034DOI Listing
May 2012

A fatality due to an accidental methadone substitution in a dental cocktail.

J Anal Toxicol 2011 Sep;35(7):512-5

Analytical Research Laboratories, 840 Research Parkway, Suite 546, Oklahoma City, Oklahoma 73104, USA.

A 6-year-old male child was scheduled for a dental procedure requiring conscious sedation. Prior to the procedure, the child was administered a dental cocktail containing chloral hydrate, hydroxyzine, and methadone. After returning from the dentist, the child appeared groggy and was allowed to sleep. A few hours later, he was found unresponsive, and following resuscitation attempts at a local medical center, he was pronounced dead. Toxicological analyses of femoral blood indicated the presence of hydroxyzine at less than 0.54 μg/mL, trichloroethanol (TCE) at 8.3 μg/mL, and methadone at 0.51 μg/mL. No meperidine was detected. The cause of death was reported to be due to the toxic effects of methadone. The toxicological analysis was corroborated by the analysis of the contents of the dental cocktail, which revealed the presence of hydroxyzine, chloral hydrate, and methadone. Residue from a control sample obtained from the same pharmacy, but administered to a different subject, was found to contain hydroxyzine, chloral hydrate, and meperidine. This report represents the first known fatality due to accidental substitution of methadone in a dental cocktail.
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http://dx.doi.org/10.1093/anatox/35.7.512DOI Listing
September 2011

Analgesic effect of extracts of Alpinia galanga rhizome in mice.

Zhong Xi Yi Jie He Xue Bao 2011 Jan;9(1):100-4

Department of Pharmacology, Kasturba Medical College, Manipal University, Mangalore 575001, Karnataka, India.

Objective: To evaluate the analgesic effect of extracts of Alpinia galanga (AG) rhizome in mice and elucidate the possible mechanism for its analgesic action.

Methods: Analgesic action of extracts of AG rhizome was studied in three experimental models of nociception. Albino mice of both sexes weighing 25 to 30 g were used in this study. For the hot-plate test, mice in the five groups with six in each received three different doses of ethanolic extracts of dried rhizome of AG suspended in 2% gum acacia orally, morphine subcutaneously and 2% gum acacia orally, respectively. Reaction time was observed after administration of vehicle or drugs. For the hot-plate test after naloxone pretreatment, mice in the five groups received naloxone subcutaneously 30 min prior to the administration of vehicle or drugs and reaction time was observed as explained above. In the writhing test, writhes were induced by injecting acetic acid intraperitoneally in another 30 mice which were randomly allocated to five groups of six in each and received three different doses of ethanolic extracts of dried rhizome of AG suspended in 2% gum acacia, aspirin suspended in 2% gum acacia and 2% gum acacia orally, respectively. The mice were observed individually for a period of 15 min and the number of writhes was recorded for each animal.

Results: AG treatment significantly increased the latency period in the hot-plate test at all three doses at 30, 60, 90 and 120 min time intervals compared with control group (P<0.05 or P<0.01). Naloxone pretreatment significantly reduced the latency period in hot-plate test for both AG and morphine groups as compared with corresponding groups that did not receive naloxone pretreatment (P<0.05 or P<0.01). AG at all doses significantly reduced the number of writhes compared with control group (P<0.01).

Conclusion: The study confirmed the analgesic effect of AG rhizome and hence justified its use in ethnomedicine for the treatment of pain due to various causes. The probable mechanism of its analgesic action may be central as well as peripheral.
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http://dx.doi.org/10.3736/jcim20110116DOI Listing
January 2011

The apparent contact dimension and covariates among orthodontically treated and nontreated subjects.

J Esthet Restor Dent 2009 ;21(2):96-111

Department of Orthodontics, School of Dentistry, University of Texas Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

Unlabelled: The apparent contact dimension (ACD), a determinant of dental esthetics, has been purported to exhibit an esthetic relationship termed the "50:40:30" rule, implying that in an esthetic smile, the ACD between the central incisors, central and lateral incisors, and lateral incisor and canine would be 50, 40, and 30% of the height of a central incisor, respectively. This study assessed the existence of this proportion using casts of orthodontically treated (N = 40) and nontreated (N = 27) subjects deemed to possess excellent occlusion. Covariates studied included tooth size, tooth shape, tip, and torque. The average ACD proportions in this study, relative to the height of an ipsilateral central incisor, were found to be 49, 38, and 27% between the central incisors, central and lateral incisors, and the lateral incisor and canine, respectively. The ACD exhibited a positive correlation (p < 0.05) with the height of the clinical crown and a negative correlation (p < 0.05) with the width/height ratios of the corresponding teeth. No statistically significant correlations were evident between the ACD with the shape of the clinical crown, tip, and torque. However, the tip and torque did exhibit a statistically significant (p < 0.05) correlation with the height of the clinical crown. This study is the first to validate the existence and proportions of the ACD.

Clinical Significance: This study validates the existence of the ACD and quantifies the relationship of the ACD with tooth size, tooth shape, mesiodistal crown angulation (tip), and labiolingual crown inclination (torque) among subjects deemed to possess excellent occlusion and alignment. This quantifiable "ideal" and its correlation with the other determinants of dental esthetics may be used in conjunction with various evidence-based paradigms in the esthetic appraisal of the maxillary anterior teeth.
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http://dx.doi.org/10.1111/j.1708-8240.2009.00240.xDOI Listing
September 2009

Quality-control analytical methods: compounding slow-release pharmaceuticals.

Int J Pharm Compd 2009 Mar-Apr;13(2):144-5

Analytical Research Laboratories, Inc., Oklahoma City, Oklahoma.

Slow-release dosage forms are designed to release active drugs at slower rates for prolonging drug effects. These unconventional dosage forms are complex drug delivery systems, which require specialized technical knowledge and skills in their formulation. Verification of the compounding process for slow-release oral dosage forms can be accomplished through quality-control testing of pilot batches to ensure acceptable preparation and patient safety.
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October 2015

Longevity of posterior composite restorations.

J Esthet Restor Dent 2007 ;19(1):3-5

Operative Dentistry Graduate Program, Department of Operative Dentistry, The University of North Carolina, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1111/j.1708-8240.2006.00055.xDOI Listing
August 2007

Longevity of anterior composite restorations.

J Esthet Restor Dent 2006 ;18(6):310-1

Department of Operative Dentistry, University of North Carolina, Chapel Hill, NC, USA.

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http://dx.doi.org/10.1111/j.1708-8240.2006.00042.xDOI Listing
August 2007

Pharmacogenomics for the forensic toxicologist.

J Anal Toxicol 2006 Mar;30(2):65-72

Analytical Research Laboratories, 840 Research Parkway, Suite 546, Oklahoma City, OK 73104, USA.

Pharmacogenomics is the study of the linkage between an individual's genotype and the disposition of drugs in the body. The first association between adverse drug reactions and inherited variations was recognized in the 1950s, and since then, pharmacogenomics has come a long way. The importance of pharmacogenomics is accentuated by the incidence of adverse drug reactions, which may account for hospital expenditures of up to 5.6 billion dollars annually. Interindividual variations in drug metabolism are often the result of genetic variants or genetic polymorphisms, and polymorphisms have been known to alter the relationship between dose and plasma drug concentration. Drug disposition can be affected by polymorphisms in drug metabolizing enzymes, drug transport proteins, and drug targets. The cytochrome P450 (CYP) enzymes are responsible for the metabolism of a large number of drugs. Polymorphisms of the CYP enzymes have been well documented, and CYP2D6 is the most polymorphic CYP enzyme. However, there is a relative dearth of research on the role of transport proteins and drug targets. This review attempts to provide a brief synopsis of the pharmacogenomics of some common drug-metabolizing enzymes, transport proteins, and targets. The examples of tramadol, methadone, and oxycodone are used to illustrate the potential role of pharmacogenomics in forensic toxicology. Pharmacogenomics may present a practicable hypothesis in cases of incongruence between dose and plasma drug concentration, and the possibility of genotype-mediated drug plasma levels needs to be considered.
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http://dx.doi.org/10.1093/jat/30.2.65DOI Listing
March 2006

Fatal seizures due to potential herb-drug interactions with Ginkgo biloba.

J Anal Toxicol 2005 Oct;29(7):755-8

Analytical Research Laboratories, 840 Research Parkway, Suite 546, Oklahoma City, Oklahoma 73104, USA.

Alternative therapy including herbal drugs and complementary medicine is becoming increasingly popular. However, the rise in the incidence of herb-drug interactions is causing concern, especially in the absence of warning labels addressing potential adverse effects. We present the case of a 55-year-old male who suffered a fatal breakthrough seizure, with no evidence of non-compliance with his anticonvulsant medications. The autopsy report revealed subtherapeutic serum levels for both anticonvulsants Depakote and Dilantin. Concomitant with his prescribed medications, the decedent was also self-medicating with a cornucopia of herbal supplements and nutraceuticals, prominent among which was Ginkgo biloba. Ginkgo, an herbal extract from the leaves of the Ginkgo biloba tree, has been used medicinally for centuries and has been touted as a cure for a variety of medical conditions. The induction of Cytochrome P450 enzymes by components of herbal drugs has been known to affect the metabolism of various drugs. Dilantin is primarily metabolized by CYP2C9, and secondarily metabolized by CYP2C19. Valproate metabolism is also modulated in part by CYP2C9 and CYP2C19. A recent study revealed significant inductive effect of ginkgo on CYP2C19 activity. CYP2C19 induction by ginkgo could be a plausible explanation for the subtherapeutic levels of Dilantin and Depakote. Additionally, ginkgo nuts contain a potent neurotoxin, which is known to induce seizure activity. Evidence of other herbal drugs diminishing the efficacy of anticonvulsant medication does exist; however, there has been only one other documented instance of ginkgo potentiating seizure activity in the presence of anticonvulsant therapy. Highlighting the potential adverse effects and drug interactions of ginkgo on the packaging of the drug may help prevent inadvertent use in vulnerable individuals.
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http://dx.doi.org/10.1093/jat/29.7.755DOI Listing
October 2005

Basics of pharmacogenomics for the compounding pharmacist.

Int J Pharm Compd 2005 Jul-Aug;9(4):303-6

DNA Solutions, Analytical Research Laboratories, Oklahoma City, Oklahoma.

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July 2015

A non-fatal case of sodium toxicity.

J Anal Toxicol 2004 Sep;28(6):526-8

Analytical Research Laboratories, 840 Research Parkway, Suite 546, Oklahoma City, Oklahoma 73104, USA.

A non-fatal case of sodium toxicity in a six-year-old boy is presented. Hypernatremia is the clinical term for an excessive concentration of sodium relative to water in the body. The diagnosis of hypernatremia was made at serum sodium (Na(+)) concentrations exceeding 150 mEq/L, and few people have been reported to survive concentrations greater than 160 mEq/L. This case involves a six-year-old boy who was taken to the hospital following a seizure attack, and lab analyses revealed serum sodium (Na(+)) levels of 234 mEq/L and serum chloride (Cl(-)) levels of 205 mEq/L. Clinical tests ruled out diabetes insipidus, dehydration, renal pathology, and other primary causes of hypernatremia. The child's purported history of pica, and the lab results indicating corresponding increases in levels of serum sodium (Na(+)) and serum (Cl(-)), led to a diagnosis of acute sodium toxicity by ingestion of sodium chloride. A search of the boy's house led to the discovery of rock salt in the cabinet and a container of table salt. Extrapolating from the serum sodium (Na(+)) level, it was estimated that the child had ingested approximately four tablespoons of rock salt, leading to the acute toxicity. A literature search revealed that the serum sodium (Na(+)) concentration in the present report was the highest documented level of sodium in a living person.
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http://dx.doi.org/10.1093/jat/28.6.526DOI Listing
September 2004