Therapeutic Effects of Melatonin on Alveolar Bone Resorption After Experimental Periodontitis in Rats: A Biochemical and Immunohistochemical Study

Background: The present study aims to investigate the effects of systemic melatonin administration on alveolar bone resorption in experimental periodontitis in rats. Methods: Twenty‐four male Sprague‐Dawley rats were divided into three groups (control, experimental periodontitis [Ped], and experimental periodontitis treated with melatonin [Mel‐Ped]). For periodontitis induction, first molars were ligatured submarginally for 4 weeks. After ligature removal, rats in the Mel‐Ped group were treated with a daily single dose of 10 mg/kg body weight melatonin for 15 consecutive days. At the end of the study, intracardiac blood samples and mandible tissues were obtained for histologic, biochemical, and radiographic analysis. Serum markers related to bone turnover, calcium, phosphorus, bone alkaline phosphatase (b‐ALP), and terminal C telopeptide of collagen Type I (CTX) were analyzed. Myeloperoxidase levels were determined in gingival tissue homogenates, and receptor activator of nuclear factor‐kappa B ligand (RANKL) activation was analyzed in the mandible samples stereologically. Alveolar bone loss was also evaluated radiographically in the mandible samples of each group. Results: Melatonin treatment decreased serum CTX levels and increased b‐ALP levels. Serum calcium and phosphorus levels were not statistically different among groups (P >0.05). Alveolar bone resorption and myeloperoxidase activity were statistically higher in the Ped group compared to the Mel‐Ped group (P <0.05). Immunohistochemical staining of RANKL and osteoclast activity were significantly lower in the Mel‐Ped group compared to the Ped group (P <0.05). Conclusion: This study reveals that melatonin treatment significantly inhibits regional alveolar bone resorption and contributes to periodontal healing in an experimental periodontitis rat model.     

Prevention for Pediatric and Adolescent Migraine

Children and adolescents can experience significant disability from frequent migraine. A number of tools have been developed to help quantify the impact of migraine in this population. Many preventative medications used in adults are routinely used to prevent migraines in children, although there has been less rigorous study. This article reviews the indications and evidence for the use of migraine preventatives, such as antidepressants, antihypertensives, anticonvulsants, antihistamines, and botulinum toxin, in this population.     

How inappropriate high‐pass filters can produce artifactual effects and incorrect conclusions in ERP studies of language and cognition

Although it is widely known that high‐pass filters can reduce the amplitude of slow ERP components, these filters can also introduce artifactual peaks that lead to incorrect conclusions. To demonstrate this and provide evidence about optimal filter settings, we recorded ERPs in a typical language processing paradigm involving syntactic and semantic violations. Unfiltered results showed standard N400 and P600 effects in the semantic and syntactic violation conditions, respectively. However, high‐pass filters with cutoffs at 0.3 Hz and above produced artifactual effects of opposite polarity before the true effect. That is, excessive high‐pass filtering introduced a significant N400 effect preceding the P600 in the syntactic condition, and a significant P2 effect preceding the N400 in the semantic condition. Thus, inappropriate use of high‐pass filters can lead to false conclusions about which components are influenced by a given manipulation. The present results also lead to practical recommendations for high‐pass filter settings that maximize statistical power while minimizing filtering artifacts.     

Infection of Interleukin 17 Receptor A-Deficient C3H Mice with Borrelia burgdorferi Does Not Affect Their Development of Lyme Arthritis and Carditis

Recently, a number of studies have reported the presence of interleukin 17 (IL-17) in patients with Lyme disease, and several murine studies have suggested a role for this cytokine in the development of Lyme arthritis. However, the role of IL-17 has not been studied using the experimental Lyme borreliosis model of infection of C3H mice with Borrelia burgdorferi. In the current study, we investigated the role of IL-17 in the development of experimental Lyme borreliosis by infecting C3H mice devoid of the common IL-17 receptor A subunit (IL-17RA) and thus deficient in most IL-17 signaling. Infection of both C3H and C3H IL-17RA^−/− mice led to the production of high levels of IL-17 in the serum, low levels in the heart tissue, and no detectable IL-17 in the joint tissue. The development and severity of arthritis and carditis in the C3H IL-17RA^−/− mice were similar to what was seen in wild-type C3H mice. In addition, development of antiborrelia antibodies and clearance of spirochetes from tissues were similar for the two mouse strains. These results demonstrate a limited role for IL-17 signaling through IL-17RA in the development of disease following infection of C3H mice with B. burgdorferi.     

Diketo acid inhibitor mechanism and HIV-1 integrase: implications for metal binding in the active site of phosphotransferase enzymes

The process of integrating the reverse-transcribed HIV-1 DNA into the host chromosomal DNA is catalyzed by the virally encoded enzyme integrase (IN). Integration requires two metal-dependent reactions, 3' end processing and strand transfer. Compounds that contain a diketo acid moiety have been shown to selectively inhibit the strand transfer reaction of IN in vitro and in infected cells and are effective as inhibitors of HIV-1 replication. To characterize the molecular basis of inhibition, we used functional assays and binding assays to evaluate a series of structurally related analogs. These studies focused on investigating the role of the conserved carboxylate and metal binding. We demonstrate that an acidic moiety such as a carboxylate or isosteric heterocycle is not required for binding to the enzyme complex but is essential for inhibition and confers distinct metal-dependent properties on the inhibitor. Binding requires divalent metal and resistance is metal dependent with active site mutants displaying resistance only when the enzymes are evaluated in the context of Mg(2+). The mechanism of action of these inhibitors is therefore likely a consequence of the interaction between the acid moiety and metal ion(s) in the IN active site, resulting in a functional sequestration of the critical metal cofactor(s). These studies thus have implications for modeling active site inhibitors of IN, designing and evaluating analogs with improved efficacy, and identifying inhibitors of other metal-dependent phosphotransferases.