• Increased Expression and Activity of 12-Lipoxygenase in Oxygen-Induced Ischemic Retinopathy and Proliferative Diabetic Retinopathy

      Al-Shabrawey, Mohamed; Mussell, Rene; Kahook, Khalid; Tawfik, Amany; Eladl, Mohamed; Sarthy, Vijay; Nussbaum, Julian; El-Marakby, Ahmed; Park, Sun Young; Gurel, Zafer; et al. (2011-01-21)
      OBJECTIVE: Arachidonic acid is metabolized by 12-lipoxygenase (12-LOX) to 12-hydroxyeicosatetraenoic acid (12-HETE) and has an important role in the regulation of angiogenesis and endothelial cell proliferation and migration. The goal of this study was to investigate whether 12-LOX plays a role in retinal neovascularization (NV).
    • Induction of Hemeoxygenase-1 Reduces Renal Oxidative Stress and Inflammation in Diabetic Spontaneously Hypertensive Rats

      Elmarakby, Ahmed A.; Faulkner, Jessica; Baban, Babak; Sullivan, Jennifer C.; Department of Oral Biology; Department of Medicine (2012-02-26)
      The renoprotective mechanisms of hemeoxygenase-1 (HO-1) in diabetic nephropathy remain to be investigated. We hypothesize that HO-1 protects the kidney from diabetic insult via lowering renal oxidative stress and inflammation. We used control and diabetic SHR with or without HO-1 inducer cobalt protoporphyrin (CoPP) treatment for 6 weeks. Urinary albumin excretion levels were significantly elevated in diabetic SHR compared to control and CoPP significantly attenuated albumin excretion. Immuno-histochemical analysis revealed an elevation in TGF-b staining together with increased urinary collagen excretion in diabetic versus control SHR, both of which were reduced with CoPP treatment. Renal oxidative stress markers were greater in diabetic SHR and reduced with CoPP treatment. The increase in renal oxidative stress was associated with an elevation in renal inflammation in diabetic SHR. CoPP treatment also significantly attenuated the markers of renal inflammation in diabetic SHR. In vitro inhibition of HO with stannous mesoporphyrin (SnMP) increased glomerular NADPH oxidase activity and inflammation and blocked the anti-oxidant and anti-inflammatory effects of CoPP. These data suggest that the reduction of renal injury in diabetic SHR upon induction of HO-1 are associated with decreased renal oxidative stress and inflammation, implicating the role of HO-1 induction as a future treatment of diabetic nephropathy.
    • Inflammatory cytokines as predictive markers for early detection and progression of diabetic nephropathy

      Elmarakby, Ahmed A.; Abdelsayed, Rafik; Yao Liu, Jun; Mozaffari, Mahmood S.; Department of Oral Biology (2010-03-13)
      Keywords: Renal disease
    • Innate Lymphoid Cells in Periodontitis: A Novel Therapeutic Modality

      Ghaly, Mira; Emami, Golnaz; Khodadadi, Hesam; Mozaffari, Mahmood; Baban, Babak; Department of Periodontics, Department of Oral Biology and Diagnostic Sciences (Augusta University, 2019)
      To determine the presence of ILCs in human periodontium which are emerging immune cells with the potential to be targeted, via novel therapies, in the treatment of peridontitis.
    • NOMA: A Preventable "Scourge" of African Children

      Ogbureke, Kalu U.E.; Ogbureke, Ezinne I; Department of Oral Biology; Department of Oral Health and Diagnostic Sciences (2010-10-21)
      Noma is a serious orofacial gangrene originating intraorally in the gingival-oral mucosa complex before spreading extraorally to produce a visibly destructive ulcer. Although cases of noma are now rarely reported in the developed countries, it is still prevalent among children in third world countries, notably in sub-Sahara Africa, where poverty, ignorance, malnutrition, and preventable childhood infections are still common. This review summarizes historical, epidemiological, management, and research updates on noma with suggestions for its prevention and ultimate global eradication. The global annual incidence remains high at about 140,000 cases, with a mortality rate exceeding 90% for untreated diseases. Where the patients survive, noma defects result in unsightly facial disfigurement, intense scarring, trismus, oral incompetence, and social alienation. Although the etiology has long been held to be infectious, a definitive causal role between microorganisms cited, and noma has been difficult to establish. The management of noma with active disease requires antibiotics followed by reconstructive surgery. Current research efforts are focused towards a comprehensive understanding of the epidemiology, and further elucidation of the microbiology and pathogenesis of noma.
    • Novel Therapeutic Approaches to Leishmania Infection

      Makala, Levi HC; Baban, Babak; Department of Pediatrics; Department of Oral Biology (InTech, 2014-03-19)
      Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Approximately 1.2 million cases of cutaneous leishmaniasis (CL) and 500,000 cases of visceral leishmaniasis (VL), which is lethal if untreated, occur annually across the globe as per world health organization (WHO) estimates [1-3]. Current statistics and information relevant to leishmaniasis are summarized in Table 1. Leishmaniasis currently affects about 12 million people and it is estimated that approximately 350 million people live in risk of infection [1-3].The number of cases of leishmaniasis is probably underestimated because only 40 of the 88 countries where diseases frequently occur report them on a regular basis [4]. Leishmaniasis, is caused by several leishmania spp., that are obligate intracellular and unicellular kinetoplastid protozoan flagellate that establish themselves within the phagolysosome of host immune competent cells, especially macrophages and dendritic cells (DCs). In 1903, W.B. Leishman and C. Donovan reported this new parasite at the turn of the century [5,6]. Ronald Ross christened the new genus leishmania and the new species donovani in year 1903 [7]. L. major infection (leishmaniasis) in mice is a widely used model of human infection that has yielded critical insights into the immunobiology of leishmaniasis [8-10]. Leishmaniasis as a parasitic disease manifests itself mainly in 3 clinical forms; visceral leishmaniasis (VL), cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL), of which VL is the most severe form of the disease. VL is lethal if untreated and spontaneous cure is extremely rare. Cutaneous leishmaniasis usually has milder course and often results into a self-healing of ulcers. Resolution of leishmanial infection is dependent on the coordinated interactions between components of cell mediated immune response, specifically the activation of targeted T-cell populations for appropriate cytokine production and activation of macrophages. L. major infection of B6 and BALB/c mouse strains drives predominantly TH1 and TH2 responses, respectively [11-14]. In murine model, the development of Th1 response is associated with control of infection, and Th2 response is associated with disease progression. However, Th1 and Th2 dichotomy in the human system is not as distinct as in mice and the murine model does not strictly apply to human leishmaniasis.
    • An ORMOSIL-Containing Orthodontic Acrylic Resin with Concomitant Improvements in Antimicrobial and Fracture Toughness Properties

      Gong, Shi-qiang; Epasinghe, Jeevani; Rueggeberg, Frederick A.; Niu, Li-na; Mettenberg, Donald; Yiu, Cynthia K. Y.; Blizzard, John D.; Wu, Christine D.; Mao, Jing; Drisko, Connie L.; et al. (2012-08-01)
      Global increase in patients seeking orthodontic treatment creates a demand for the use of acrylic resins in removable appliances and retainers. Orthodontic removable appliance wearers have a higher risk of oral infections that are caused by the formation of bacterial and fungal biofilms on the appliance surface. Here, we present the synthetic route for an antibacterial and antifungal organically-modified silicate (ORMOSIL) that has multiple methacryloloxy functionalities attached to a siloxane backbone (quaternary ammonium methacryloxy silicate, or QAMS). By dissolving the water-insoluble, rubbery ORMOSIL in methyl methacrylate, QAMS may be copolymerized with polymethyl methacrylate, and covalently incorporated in the pressure-processed acrylic resin. The latter demonstrated a predominantly contact-killing effect on Streptococcus mutans ATCC 36558 and Actinomyces naselundii ATCC 12104 biofilms, while inhibiting adhesion of Candida albicans ATCC 90028 on the acrylic surface. Apart from its favorable antimicrobial activities, QAMS-containing acrylic resins exhibited decreased water wettability and improved toughness, without adversely affecting the flexural strength and modulus, water sorption and solubility, when compared with QAMS-free acrylic resin. The covalently bound, antimicrobial orthodontic acrylic resin with improved toughness represents advancement over other experimental antimicrobial acrylic resin formulations, in its potential to simultaneously prevent oral infections during appliance wear, and improve the fracture resistance of those appliances.
    • Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma

      Wilson, Justin L.; Duan, Rong; El-Marakby, Ahmed; Alhashim, Abdulmohsin; Lee, Dexter L.; Department of Oral Biology; Department of Pharmacology and Toxicology (2012-07-16)
      The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161 ± 4mmHg versus 145 ± 4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134 ± 7 mmHg). Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30 ± 4 versus 8 ± 2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treatedWT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1,MCP-1 and COX-2 inWT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.
    • Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

      Lee, Dexter L.; Wilson, Justin L.; Duan, Rong; Hudson, Tamaro; El-Marakby, Ahmed; Department of Oral Biology; Department of Pharmacology and Toxicology (2011-12-07)
      Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin- 6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCAsalt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.
    • Phosphorylation of EPS8 Mediates Its Downstream Signaling and Biological Functions

      Shahoumi, Linah; Yeudall, W. Andrew; Department of Oral Biology & Diagnostic Sciences, Georgia Cancer Center (Augusta University, 2019)
      The purpose of this study was to investigate the role of EPS8 phosphorylation in modulating biochemical signaling, cell proliferation and motility in HNSCC.
    • Polymeric-calcium phosphate cement composites-material properties: in vitro and in vivo investigations.

      Khashaba, Rania M.; Moussa, Mervet M; Mettenburg, Donald J; Rueggeberg, Frederick A.; Chutkan, Norman B.; Borke, James L.; Department Oral Biology; Department Orthopedic Surgery; Department of Oral Rehabilitation (2010-09-02)
      New polymeric calcium phosphate cement composites (CPCs) were developed. Cement powder consisting of 60 wt% tetracalcium phosphate, 30 wt% dicalcium phosphate dihydrate, and 10 wt% tricalcium phosphate was combined with either 35% w/w poly methyl vinyl ether maleic acid or polyacrylic acid to obtain CPC-1 and CPC-2. The setting time and compressive and diametral tensile strength of the CPCs were evaluated and compared with that of a commercial hydroxyapatite cement. In vitro cytotoxicity and in vivo biocompatibility of the two CPCs and hydroxyapatite cement were assessed. The setting time of the cements was 5-15 min. CPC-1 and CPC-2 showed significantly higher compressive and diametral strength values compared to hydroxyapatite cement. CPC-1 and CPC-2 were equivalent to Teflon controls after 1 week. CPC-1, CPC-2, and hydroxyapatite cement elicited a moderate to intense inflammatory reaction at 7 days which decreased over time. CPC-1 and CPC-2 show promise for orthopedic applications.
    • The potential role of indoleamine 2,3 dioxygenase (IDO) as a predictive and therapeutic target for diabetes treatment: a mythical truth

      Baban, Babak; Penberthy, W. Todd; Mozaffari, Mahmood S.; Department of Oral Biology (2010-03-19)
      Keywords: Individual tolerance
    • Prediction of diabetic retinopathy: role of oxidative stress and relevance of apoptotic biomarkers

      Al-Shabrawey, Mohamed; Smith, Sylvia B; Department of Oral Biology; Department of Ophthalmology; Vision Discovery Institute; Department of Cellular Biology and Anatomy (2010-03-23)
      Keywords: Diabetic retinopathy
    • Preparation, Physical-Chemical Characterization, and Cytocompatibility of Polymeric Calcium Phosphate Cements

      Khashaba, Rania M.; Moussa, Mervet M; Koch, Christopher; Jurgensen, Arthur R.; Missimer, David M.; Rutherford, Ronny L.; Chutkan, Norman B.; Borke, James L.; Department of Oral Biology; Department of Surgery (2011-09-20)
    • Proliferative Verrucous Leukoplakia (PVL) Expresses High Levels of Toll-Like Receptor 2 (TLR2)

      Koh, Joon; Kurago, Zoya; Georgia Cancer Center (Augusta University, 2019)
      In the current study, we analyzed samples of human oral mucosal PVL and other epithelial disorders to test the possibility that, if TLR2 is involved in early stages of carcinogenesis, then keratinocytes in early-intermediate stages of PVL may express more TLR2 than keratinocytes in non-dysplastic epithelium.