Medicine and Health Sciences Commons^™

Comprehensive, Evidence-Based, Consensus Guidelines For Prescription Of Opioids For Chronic Non-Cancer Pain From The American Society Of Interventional Pain Physicians (Asipp)., Laxmaiah Manchikanti, Adam M. Kaye, Nebojsa Nick Knezevic, James Giordano, Megan K. Applewhite, Alexander Bautista, Amol Soin, Susan K. Blank, Mahendra R. Sanapati, Jay Karri, Paul J. Christo, Alaa Abd-Elsayed, Alan D. Kaye, Aaron Calodney, Annu Navani, Christopher G. Gharibo, Michael Harned, Mayank Gupta, Mustafa Broachwala, Nalini Sehgal, Andrew Kaufman, Bradley Wargo, Daneshvari R. Solanki, Eric S. Hsu, Gerard Limerick, Allen Dennis, John R. Swicegood, Konstantin Slavin, Lee Snook, Ramarao Pasupuleti, Radomir Kosanovic, Rafael Justiz, Robert Barkin, Sairam Atluri, Shalini Shah, Vidyasagar Pampati, Standiford Helm Ii, Vahid Grami, Vicki Myckowiak, Vincent Galan, Vijay Singh, Vivek Manocha, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate …

Multiomics Characterization Of Preterm Birth In Low- And Middle-Income Countries., Fyezah Jehan, Sunil Sazawal, Abdullah H. Baqui, Muhammad Imran Nisar, Usha Dhingra, Rasheda Khanam, Muhammad Ilyas, Arup Dutta, Dipak K. Mitra, Usma Mehmood, Saikat Deb, Arif Mahmud, Aneeta Hotwani, Said Mohammed Ali, Sayedur Rahman, Ambreen Nizar, Shaali Makame Ame, Mamun Ibne Moin, Sajid Muhammad, Aishwarya Chauhan, Nazma Begum, Waqasuddin Khan, Sayan Das, Salahuddin Ahmed, Tarik Hasan, Javairia Khalid, Syed Jafar Raza Rizvi, Mohammed Hamad Juma, Nabidul Haque Chowdhury, Furqan Kabir, Fahad Aftab, Abdul Quaiyum, Alexander Manu, Sachiyo Yoshida, Rajiv Bahl, Anisur Rahman, Jesmin Pervin, Jennifer Winston, Patrick Musonda, Jeffrey S. A. Stringer, James A. Litch, Mohammad Sajjad Ghaemi, Mira N. Moufarrej, Kévin Contrepois, Songjie Chen, Ina A. Stelzer, Natalie Stanley, Alan L. Chang, Ghaith Bany Hammad, Ronald J. Wong, Candace Liu, Cecele C. Quaintance, Anthony Culos, Camilo Espinosa, Maria Xenochristou, Martin Becker, Ramin Fallahzadeh, Edward Ganio, Amy S. Tsai, Dyani Gaudilliere, Eileen S. Tsai, Xiaoyuan Han, Kazuo Ando, Martha Tingle, Ivana Maric, Paul H. Wise, Virginia D. Winn, Maurice L. Druzin, Ronald S. Gibbs, Gary L. Darmstadt, Jeffrey C. Murray, Gary M. Shaw, David K. Stevenson, Michael P. Snyder, Stephen R. Quake, Martin S. Angst, Brice Gaudilliere, Nima Aghaeepour

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Importance: Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies.

Objective: To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB.

Design, Setting, and Participants: This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in …

Selective Autophagy Maintains The Aryl Hydrocarbon Receptor Levels In Hela Cells: A Mechanism That Is Dependent On The P23 Co-Chaperone, Yujie Yang, William K. Chan

School of Pharmacy Faculty Articles

The aryl hydrocarbon receptor (AHR) is an environmental sensing molecule which impacts diverse cellular functions such as immune responses, cell growth, respiratory function, and hematopoietic stem cell differentiation. It is widely accepted that the degradation of AHR by 26S proteasome occurs after ligand activation. Recently, we discovered that HeLa cells can modulate the AHR levels via protein degradation without exogenous treatment of a ligand, and this degradation is particularly apparent when the p23 content is down-regulated. Inhibition of autophagy by a chemical agent (such as chloroquine, bafilomycin A1, or 3-methyladenine) increases the AHR protein levels in HeLa cells whereas activation …

Bone Marrow Concentrate (Bmc) Therapy In Musculoskeletal Disorders: Evidence-Based Policy Position Statement Of American Society Of Interventional Pain Physicians (Asipp), Laxmaiah Manchikanti, Christopher J. Centeno, Sairam Atluri, Sheri L. Albers, Shane Shapiro, Gerard A. Malanga, Alaa Abd-Elsayed, Mairin Jerome, Joshua A. Hirsch, Alan David Kaye, Steve M. Aydin, Douglas Beall, Don Buford, Joanne Borg-Stein, Ricardo M. Buenaventura, Joseph A. Cabaret, Aaron K. Calodney, Kenneth D. Candido, Cameron Cartier, Richard Latchaw, Sudhir Diwan, Ehren Dodson, Zachary Fausel, Michael Fredericson, Christopher G. Gharibo, Mayank Gupta, Adam M. Kaye, Nebojsa Nick Knezevic, Radomir Kosanovic, Matthew Lucas, Maanasa V. Manchikanti, R. Amadeus Mason, Kenneth Mautner, Samuel Murala, Annu Navani, Vidyasagar Pampati, Sarah Pastoriza, Ramarao Pasupuleti, Cyril Philip, Mahendra R Sanapati, Theodore Sand, Rinoo V Shah, Amol Soin, Ian Stemper, Bradley W Wargo, Philippe Hernigou

School of Pharmacy Faculty Articles

BACKGROUND: The use of bone marrow concentrate (BMC) for treatment of musculoskeletal disorders has become increasingly popular over the last several years, as technology has improved along with the need for better solutions for these pathologies. The use of cellular tissue raises a number of issues regarding the US Food and Drug Administration's (FDA) regulation in classifying these treatments as a drug versus just autologous tissue transplantation. In the case of BMC in musculoskeletal and spine care, this determination will likely hinge on whether BMC is homologous to the musculoskeletal system and spine.

OBJECTIVES: The aim of this review is …

Orofacial Pain And Menstrually Related Migraine, Chisa Nishihara, Keisuke Hatori, Yung-Chu Hsu, Kana Ozasa, Andrew L. Young, Yoshiki Imamura, Noboru Noma

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PURPOSE: Migraine is a common, debilitating, primary headache disorder that can cause and be affected by odontalgia.

CASE REPORT: A 49-year-old woman(Patient 1) presented with pulsating pain in the left maxillary molar area, and a history of unsuccessful root canal treatment. She was ultimately diagnosed with menstrually related migraine without aura and zolmitriptan was prescribed, which reduced her headache and toothache together. A 45-year-old woman (Patient 2) presented with throbbing pain in the right maxillary molar and cheek area. Past repeated endodontic therapy had been unsuccessful. She was then diagnosed with menstrually related migraine without aura, and sumatriptan significantly reduced …

In Vivo Effectiveness And Safety Of Probiotics On Prophylaxis And Treatment Of Oral Candidiasis: A Systematic Review And Meta-Analysis, Lijun Hu, Mimi Zhou, Andrew L. Young, Weiwei Zhao, Zhimin Yan

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BACKGROUND: To systematically review and assess the in vivo effectiveness and safety of probiotics for prophylaxis and treating oral candidiasis.

METHODS: A literature search for studies published in English until August 1, 2018 was conducted in the following databases: PubMed, EMBASE, Cochrane Library, and Web of Science. Randomized controlled clinical trials and experimental mouse animal model studies comparing probiotics (at any dosage and in any form) with control groups (placebo, blank control or other agents) and reporting outcomes of the prophylactic and therapeutic effects were considered for inclusion. A descriptive study and, potentially, a meta-analysis were planned.

RESULTS: Six randomized …

Impact Of High Volume Energy Drink Consumption On Electrocardiographic And Blood Pressure Parameters: A Randomized Trial, Sachin A. Shah, Andy H. Szeto, Raechel Farewell, Allen Shek, Dorothy Fan, Kathy N. Quach, Mouchumi Bhattacharyya, Jasmine Elmiari, Winny Chan, Kate O'Dell, Nancy Nguyen, Tracey J. Mcgaughey, Javed M. Nasir, Sanjay Kaul

School of Pharmacy Faculty Articles

Background Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers. Methods and Results A randomized, double-masked, placebo-controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6-day washout period in between. The primary end point of QT c interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central …

A Rational Approach For Creating Peptides Mimicking Antibody Binding, Sameer Sachdeva, Hyun Joo, Jerry Tsai, Bhaskara Jasti, Xiaoling Li

School of Pharmacy Faculty Articles

This study reports a novel method to design peptides that mimic antibody binding. Using the Knob-Socket model for protein-protein interaction, the interaction surface between Cetuximab and EGFR was mapped. EGFR binding peptides were designed based on geometry and the probability of the mapped knob-sockets pairs. Designed peptides were synthesized and then characterized for binding specificity, affinity, cytotoxicity of drug-peptide conjugate and inhibition of phosphorylation. In cell culture studies, designed peptides specifically bind and internalize to EGFR overexpressing cells with three to four-fold higher uptake compared to control cells that do not overexpress EGFR. The designed peptide, Pep11, bound to EGFR …

Hiv Viral Rebound Due To A Possible Drug-Drug Interaction Between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide And Calcium-Containing Products: Report Of 2 Cases, S. Lena Kang-Birken, Dena El-Sayed, John Prichard

School of Pharmacy Faculty Articles

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a potent fixed-dose, once-daily regimen for HIV-1 treatment and has rare emergence of drug resistance. We report a potential drug-drug interaction in 2 female patients both receiving treatment for HIV and cerebral toxoplasmosis: one case between E/C/F/TAF with calcium carbonate and a second case involving leucovorin as calcium salt. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. To the best of our knowledge, these 2 cases are the first reports of rapid emergence of mutation from coadministration of E/C/F/TAF and calcium.

Responsible, Safe, And Effective Use Of Biologics In The Management Of Low Back Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Annu Navani, Laxmaiah Manchikanti, Sheri L. Albers, Richard E. Latchaw, Jaya Sanapati, Alan David Kaye, Sairam Atluri, Sheldon Jordan, Ashim Gupta, David Cedeno, Alejandro Vallejo, Bert Fellows, Nebojsa Nick Knezevic, Miguel Pappolla, Sudhir Diwan, Andrea M. Trescot, Amol Soin, Adam M. Kaye, Steve M. Aydin, Aaron K. Calodney, Kenneth D. Candido, Sanjay Bakshi, Ramsin M. Benyamin, Ricardo Vallejo, Art Watanabe, Douglas Beall, Todd P. Stitik, Patrick M. Foye, Erik M. Helander, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public …

Vwa Proteins Of Leptospira Interrogans Induce Hemorrhage In Leptospirosis By Competitive Inhibition Of Vwf/Gpib-Mediated Platelet Aggregation., Jia-Qi Fang, Muhammad Imran, Wei-Lin Hu, David M. Ojcius, Yang Li, Yu-Mei Ge, Kai-Xuan Li, Xu'ai Lin, Jie Yan

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BACKGROUD: Leptospira interrogans is the major causative agent of leptospirosis, a worldwide zoonotic disease. Hemorrhage is a typical pathological feature of leptospirosis. Binding of von Willebrand factor (vWF) to platelet glycoprotein-Ibα (GPIbα) is a crucial step in initiation of platelet aggregation. The products of L. interrogans vwa-I and vwa-II genes contain vWF-A domains, but their ability to induce hemorrhage has not been determined.

METHODS: Human (Hu)-platelet- and Hu-GPIbα-binding abilities of the recombinant proteins expressed by L. interrogans strain Lai vwa-I and vwa-II genes (rLep-vWA-I and rLep-vWA-II) were detected by flowcytometry, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Hu-platelet …

A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan

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Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (K

Regulation Of Kv2.1 Channel Inactivation By Phosphatidylinositol 4,5-Bisphosphate., Mayra Delgado-Ramírez, José J De Jesús-Pérez, Iván A Aréchiga-Figueroa, Jorge Arreola, Scott K Adney, Carlos A. Villalba-Galea, Diomedes E Logothetis, Aldo A Rodríguez-Menchaca

School of Pharmacy Faculty Articles

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane phospholipid that regulates the function of multiple ion channels, including some members of the voltage-gated potassium (Kv) channel superfamily. The PIP2 sensitivity of Kv channels is well established for all five members of the Kv7 family and for Kv1.2 channels; however, regulation of other Kv channels by PIP2 remains unclear. Here, we investigate the effects of PIP2 on Kv2.1 channels by applying exogenous PIP2 to the cytoplasmic face of excised membrane patches, activating muscarinic receptors (M1R), or depleting endogenous PIP2 using a rapamycin-translocated 5-phosphatase (FKBP-Inp54p). Exogenous PIP2 rescued Kv2.1 channels from rundown and partially …

Nadph Oxidase 4 Modulates Hepatic Responses To Lipopolysaccharide Mediated By Toll-Like Receptor-4., Anand Singh, Bhargav Koduru, Cameron Carlisle, Hasina Akhter, Rui-Ming Liu, Katrin Schroder, Ralf P. Brandes, David M. Ojcius

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Chronic inflammation plays a key role in development of many liver diseases. Stimulation of Toll-like receptor 4 (TLR4) by bacterial lipopolysaccharide (LPS) initiates inflammation and promotes development of hepatocellular carcinoma and other liver diseases. NADPH oxidases contribute to LPS-induced reactive oxygen species (ROS) production and modulate TLR responses, but whether these enzymes function in TLR4 responses of hepatocytes is unknown. In the present work, we examined the role of NADPH oxidase 4 (Nox4) in LPS-induced TLR4 responses in human hepatoma cells and wildtype and Nox4-deficient mice. We found that LPS increased expression of Nox4, TNF-α, and proliferating cell nuclear antigen …

Bid-Induced Release Of Aif/Endog From Mitochondria Causes Apoptosis Of Macrophages During Infection With, Wei-Lin Hu, Hai-Yan Dong, Yang Li, David M. Ojcius, Shi-Jun Li, Jie Yan

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Leptospirosis is a global zoonotic infectious disease caused by pathogenic Leptospira species. Leptospire-induced macrophage apoptosis through the Fas/FasL-caspase-8/3 pathway plays an important role in the survival and proliferation of the pathogen in hosts. Although, the release of mitochondrial apoptosis-inducing factor (AIF) and endonuclease G (EndoG) in leptospire-infected macrophages has been described, the mechanisms linking caspase and mitochondrion-related host-cell apoptosis has not been determined. Here, we demonstrated that leptospire-infection induced apoptosis through mitochondrial damages in macrophages. Apoptosis was caused by the mitochondrial release and nuclear translocation of AIF and/or EndoG, leading to nuclear DNA fragmentation. However, the mitochondrion-related CytC-caspase-9/3 pathway was …

Mononuclear-Macrophages But Not Neutrophils Act As Major Infiltrating Anti-Leptospiral Phagocytes During Leptospirosis., Xu Chen, Shi-Jun Li, David M. Ojcius, Ai-Hua Sun, Wei-Lin Hu, Xu'ai Lin, Jie Yan

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OBJECTIVE: To identify the major infiltrating phagocytes during leptospirosis and examine the killing mechanism used by the host to eliminate Leptospira interrogans.

METHODS: Major infiltrating phagocytes in Leptospira-infected C3H/HeJ mice were detected by immunohistochemistry. Chemokines and vascular endothelial cell adhesion molecules (VECAMs) of Leptospira-infected mice and leptospirosis patients were detected by microarray and immunohistochemistry. Leptospira-phagocytosing and -killing abilities of human or mouse macrophages and neutrophils, and the roles of intracellular ROS, NO and [Ca2+]i in Leptospira-killing process were evaluated by confocal microscopy and spectrofluorimetry.

RESULTS: Peripheral blood mononuclear-macrophages rather than neutrophils were the main infiltrating phagocytes in the lungs, liver …

Educational Outcomes Of Small-Group Discussion Versus Traditional Lecture Format In Dental Students' Learning And Skills Acquisition., Ana Arias, Raymond Scott, Ove A. Peters, Elizabeth Mcclain, Alan H. Gluskin

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The aim of this prospective quantitative study was to compare the effect of different instructional formats on dental students' skills and knowledge acquisition for access cavity preparation. All first-year dental students were invited to participate in this study conducted during the four consecutive two-week endodontic rotation courses at the University of the Pacific Arthur A. Dugoni School of Dentistry in spring semester 2015. Four alphabetically distributed intact groups of students were randomly allocated to two groups (n=70 each) that participated in either small-group discussion or a traditional lecture on access preparation. The first outcome measure was skill acquisition, measured by …

Retigabine Holds Kv7 Channels Open And Stabilizes The Resting Potential, Aaron Corbin-Leftwich, Sayeed M. Mossadeq, Junghoon Ha, Iwona Ruchala, Audrey Han Ngoc Le, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 …

Biological Markers For Pulpal Inflammation: A Systematic Review., Dan-Krister Rechenberg, Johnah C. Galicia, Ove A. Peters

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BACKGROUND AND OBJECTIVE: Pulpitis is mainly caused by an opportunistic infection of the pulp space with commensal oral microorganisms. Depending on the state of inflammation, different treatment regimes are currently advocated. Predictable vital pulp therapy depends on accurate determination of the pulpal status that will allow repair to occur. The role of several players of the host response in pulpitis is well documented: cytokines, proteases, inflammatory mediators, growth factors, antimicrobial peptides and others contribute to pulpal defense mechanisms; these factors may serve as biomarkers that indicate the status of the pulp. Therefore, the aim of this systematic review was to …

Interrelationships In The Variability Of Root Canal Anatomy Among The Permanent Teeth: A Full-Mouth Approach By Cone-Beam Ct., Paul Monsarrat, Bertrand Arcaute, Ove A. Peters, Elisabeth Maury, Norbert Telmon, Marie Georgelin-Gurgel, Delphine Maret

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OBJECTIVES: In endodontic practice, clinicians should be aware of possible root canal anatomic variations. The aim of this study was to assess using CBCT acquisitions regarding whether one root canal anatomy of a tooth is associated with a specific anatomy of another tooth.

METHODS: A total of 106 CBCT acquisitions were obtained using a CBCT scanner with 200μm voxel size. Numbers of roots and canals of the entire dentition were described. Bivariate analyses and logistic regressions were conducted to explore root canal anatomy on one tooth according to age, gender, jaw, side and the others teeth. Multiple correspondence analysis (MCA) …

Effects Of Periodontal Therapy On White Blood Cell Count And Levels Of Transforming Growth Factor Beta In Serum Of Subjects With Severe Periodontitis, A. C. E. Leite, V. M. A. Carneiro, Ana Carolina Morandini, Erivan Schnaider Ramos-Junior, M. C. M. Guimarães

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This study aimed to investigate the effects of nonsurgical periodontal therapy on white blood cell (WBC) count and levels of transforming growth factor beta (TGF—β) in serum from subjects with severe periodontitis. Serum from 28 subjects with periodontitis (mean age: 34.36±6.24; 32% men) and 27 healthy controls (mean age: 33.18±6.42; 33% men) were collected prior to therapy. Blood samples were obtained from 23 subjects who completed therapy (9—12 months). A well—controlled periodontal treatment protocol was established in three stages: mechanical periodontal therapy (scaling and root planning), reinstrumentation of dental sites, and supportive periodontal therapy. Periodontal and systemic parameters such as …

Functional Local Renin-Angiotensin System In Human And Rat Periodontal Tissue, Carlos Ferreira Santos, Ana Carolina Morandini, Thiago José Dionísio, Flávio A. Faria, Marta C. Lima, Caio M. Figueiredo, Bella L. Colombini-Ishikiriama, Carla Renata Sipert, Rubens P. Maciel, Ana P. Akashi, Gabriela P. Souza, Gustavo P. Garlet, Camila O. Rodini, Sandra L. Amaral, Christiane Becari, Maria C. Salgado, Eduardo B. Oliveira, Isaac Matus, Daniela N. Didier, Andrew S. Greene

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The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression …

A Multidisciplinary Treatment Of Congenitally Missing Maxillary Lateral Incisors: A 14-Year Follow-Up Case Report, Renato Rodrigues De Almeida, Ana Carolina Morandini, Renata Rodrigues De Almeida-Pedrin, Marcio Rodrigues De Almeida, Renata Cristina Faria Ribeiro Castro, Natalia Martins Insabralde

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Absence of the maxillary lateral incisor creates an aesthetic problem which can be managed in various ways. The condition requires careful treatment planning and consideration of the options and outcomes following either space closure or prosthetic replacement. Recent developments in restorative dentistry have warranted a re-evaluation of the approach to this clinical situation. Factors relating both to the patient and the teeth, including the presentation of malocclusion and the effect on the occlusion must be considered. The objective of this study was to describe the etiology, prevalence and alternative treatment modalities for dental agenesis and to present a clinical case …

Neurotrophic Factor Gdnf Promotes Survival Of Salivary Stem Cells, Nan (Tori) Xiao, Yuan Lin, Hongbin Cao, Davud Sirjani, Amato J. Giaccia, Albert C. Koong, Christina S. Kong, Maximilian Diehn, Quynh-Thu Le

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Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland …

Palatal Mucosa Derived Fibroblasts Present An Adaptive Behavior Regarding Cytokine Secretion When Grafted Onto The Gingival Margin, Fabíola Pontes Azevedo, Ana Carolina Morandini, Carla Renata Sipert, Thiago José Dionísio, Carlos Ferreira Santos, Carla Andreotti Damante, Maria Lúcia Rubo De Rezende, Adriana Campos Passanezi Sant'ana, Sebastião Luiz Aguiar Greghi

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BACKGROUND: Considering that grafted gingival tissue might have to be adapted to the receptor area and that fibroblasts have the ability to respond to bacterial stimuli through the release of various cytokines, this study investigated whether fibroblasts from the palatal mucosa behave differently when grafted onto the gingival margin regarding cytokine secretion.

METHODS: Biopsies from the palatal mucosa were collected at the time of free gingival graft surgery, and after four months re-collection was performed upon surgery for root coverage. Fibroblasts were isolated by the explant technique, cultured and stimulated with Porphyromonas gingivalis (Pg) and Escherichia coli (Ec) LPS for …

The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Ccl3 And Cxcl12 Production In Vitro By Dental Pulp Fibroblasts From Permanent And Deciduous Teeth Stimulated By Porphyromonas Gingivalis Lps, Carla Renata Sipert, Ana Carolina Morandini, Karin Cristina Da Silva Modena, Thiago José Dionísio, Maria Aparecida Andrade Moreira Machado, Sandra Helena Penha Oliveira, Ana Paula Campanelli, Carlos Ferreira Santos

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OBJECTIVE: The aim of this study was to compare the production of the chemokines CCL3 and CXCL12 by cultured dental pulp fibroblasts from permanent (PDPF) and deciduous (DDPF) teeth under stimulation by Porphyromonas gingivalis LPS (PgLPS).

MATERIAL AND METHODS: Primary culture of fibroblasts from permanent (n=3) and deciduous (n=2) teeth were established using an explant technique. After the fourth passage, fibroblasts were stimulated by increasing concentrations of PgLPS (0-10 µg/mL) at 1, 6 and 24 h. The cells were tested for viability through MTT assay, and production of the chemokines CCL3 and CXCL12 was determined through ELISA. Comparisons among samples …

Effect Of Voxel Size On The Accuracy Of 3d Reconstructions With Cone Beam Ct., Delphine Maret, Norbert Telmon, Ove A. Peters, B. Lepage, J. Treil, J. M. Inglèse, A. Peyre, Jean-Luc Kahn, Michel Sixou

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OBJECTIVES: The various types of cone beam CT (CBCT) differ in several technical characteristics, notably their spatial resolution, which is defined by the acquisition voxel size. However, data are still lacking on the effects of voxel size on the metric accuracy of three-dimensional (3D) reconstructions. This study was designed to assess the effect of isotropic voxel size on the 3D reconstruction accuracy and reproducibility of CBCT data.

METHODS: The study sample comprised 70 teeth (from the Institut d'Anatomie Normale, Strasbourg, France). The teeth were scanned with a KODAK 9500 3D® CBCT (Carestream Health, Inc., Marne-la-Vallée, France), which has two voxel …

Molecular Mechanism For Depolarization-Induced Modulation Of Kv Channel Closure, Alain J. Labro, Jerome J. Lacroix, Carlos A. Villalba-Galea, Dirk J. Snyders, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the …