Mario Roberto Pontes Lisboa

Pleiotropic effects of statins on the treatment of chronic periodontitis – a systematic review

AIM Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are an important group of hypolipidaemic drugs, widely used in the treatment of hypercholesterolaemia and cardiovascular disease. Some studies have shown that statins are able to modulate inflammation and alveolar bone loss. METHODS In order to evaluate whether statins could influence periodontal treatment, improving the clinical and radiographic parameters in chronic periodontitis, a systematic review was conducted in the databases PUBMED and BIREME, searching for articles in English and Portuguese, published between the years 2004 and 2014, using the combined keywords statin, periodontal disease, periodontitis and alveolar bone. Studies regarding the treatment of chronic periodontitis in humans, blind or double-blind, retrospective cohort or randomized controlled trials that used statins topically or systemically were selected. RESULTS Statins have important anti-inflammatory and immune effects, reducing levels of C-reactive protein and matrix metalloproteinases and their intermediate products, such as tumour necrosis factor-α, and are also able to inhibit the adhesion and extravasation of leukocytes, which block the co-stimulation of T cells. Statins reduce bone resorption by inhibiting osteoclast formation and lead to increased apoptosis of these cells. The effect of statins on bone formation is related to the increased gene expression of bone morphogenetic protein in osteoblasts. CONCLUSION Although we found biological mechanisms and clinical results that show lower alveolar bone loss and reduction of clinical signs of inflammation, further studies are needed to evaluate the clinical applicability of statins in the routine treatment of chronic periodontitis.

Effects of Locally Administered Tiludronic Acid on Experimental Periodontitis in Rats

BACKGROUND It appears there are no studies evaluating the influence of the bisphosphonate tiludronic acid (TIL) on periodontitis. The purpose of this study is to evaluate via microtomographic, histopathologic, histometric, and immunohistochemical analyses the effects of local administration of TIL on ligature-induced periodontitis in rats. METHODS Forty-eight rats were divided into six groups: C (control), EP (experimental periodontitis), EP-Saline, EP-TIL0.1, EP-TIL0.3, and EP-TIL1. In EP, a ligature was placed around maxillary second molars. In EP-TIL0.1, EP-TIL0.3, and EP-TIL1, TIL solutions of 0.1, 0.3, and 1 mg/kg body weight, respectively, were injected into the subperiosteal palatal area adjacent to maxillary second molars every other day. EP-Saline received 0.9% NaCl solution instead. Animals were euthanized at day 11. Bone changes were evaluated by microtomographic and histometric analyses. Histopathologic analysis and immunohistochemical detection of tartrate-resistant acid phosphatase (TRAP) were also performed. Data were statistically analyzed (analysis of variance or Kruskal-Wallis, P <0.05). RESULTS Histometric and microtomographic analyses (at buccal, interproximal, and furcation sites) demonstrated that EP-TIL1 presented less alveolar bone loss (ABL) than EP (P <0.05), whereas EP-TIL0.1 and EP-TIL0.3 did not demonstrate significant differences in alveolar bone level compared to EP (P >0.05). Also, EP-TIL1 showed significantly fewer TRAP-positive multinucleated osteoclasts than EP and EP-Saline (P <0.05). CONCLUSION It can be concluded that locally administered TIL solution (1 mg/kg body weight) reduced alveolar bone loss in experimental periodontitis and the dosage of TIL may influence its anti-inflammatory and antiresorptive properties.

Effects of electroacupuncture on experimental periodontitis in rats

BACKGROUND Acupuncture has shown the capability of modulating the immuno-inflammatory response of the host. This study aims to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats. METHODS Thirty-two animals were divided into four groups: 1) control; 2) experimental periodontitis (EP); 3) sham-treated (EP/EA-sham); and 4) treated with EA (EP/EA). For the EP groups, a ligature was placed around the right mandibular first molars at day 1. Sessions of EA or EA-sham were assigned every other day. For EA treatment, large intestine meridian points LI4 and LI11 and stomach meridian points ST36 and ST44 were used. EA-sham was performed in off-meridian points. Animals were euthanized at day 11. Histomorphometric and microtomographic analyses were performed. Immunolabeling patterns for the receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRAP) were assessed. Expressions of interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, IL-6, and cyclooxygenase (COX)-2 messenger RNAs (mRNAs) were evaluated by quantitative reverse transcription-polymerase chain reaction. Data were analyzed statistically (P <0.05, analysis of variance). RESULTS Histomorphometric and microtomographic analyses demonstrated that group EP/EA presented reduced alveolar bone loss when compared to group EP (P <0.05). Reduced RANKL immunolabeling and fewer TRAP-positive multinucleated cells were observed in the EA-treated group in relation to group EP. No differences were observed in OPG expression among groups. EA treatment decreased the genic expression of IL-1β and MMP-8 (P <0.05), increased the mRNA expression of IL-6 (P <0.05), and did not modify the genic expression of COX-2 in animals with EP (P >0.05). CONCLUSION It can be concluded that EA reduced periodontal tissue breakdown and the expression of some proinflammatory mediators and a proresorptive factor in EP in rats.

Effects of Atorvastatin on Periodontitis of Rats Subjected to Glucocorticoid-Induced Osteoporosis

BACKGROUND Atorvastatin (ATV) has shown pleiotropic effects on bone tissue, and osteoporosis can aggravate periodontitis. Thus, the effects of ATV on experimental periodontitis (EP) in rats subjected to glucocorticoid-induced osteoporosis (GIOP) was assessed. METHODS Male Wistar rats were divided into the following groups: 1) naive; 2) EP; 3) GIOP + EP; and 4) ATV. Groups GIOP + EP and ATV received 7 mg/kg dexamethasone intramuscularly once per week for 5 weeks, and the others received saline (SAL). Groups EP, GIOP + EP, and ATV were submitted to EP by ligature around the maxillary left second molars for 11 days. Group ATV received 27 mg/kg ATV orally, and the others received SAL 30 minutes before EP. Periodontium was analyzed by macroscopy, microtomography, and histopathology; by immunohistochemical examination of receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), wingless (WNT) 10b, dickkopf-related protein 1 (DKK-1), and β-catenin; and by enzyme-linked immunosorbent assay analysis of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-8, IL10, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Leukogram, liver and kidney enzymes, and bone-specific alkaline phosphatase (BALP) serum levels were evaluated. RESULTS ATV decreased bone loss, reduced MPO, TNF-α, IL-1β, IL-6, and IL-8, and increased IL-10, GSH, SOD, and CAT levels. ATV reduced RANKL and DKK-1 and increased OPG, WNT10b, and β-catenin expressions and BALP activity. CONCLUSION ATV reduced inflammation, oxidative stress, and bone loss in rats with EP and GIOP, with participation of the WNT signaling pathway.

Effects of glucocorticoid-induced osteoporosis on bone tissue of rats with experimental periodontitis

OBJECTIVE To evaluate the effects of osteoporosis induced by glucocorticoid (GIOP) on bone tissue of rats with experimental periodontitis (EP). DESIGN 48 male Wistar rats divided into groups: Naïve, EP, GIOP and GIOP+EP. Rats of GIOP and GIOP+EP groups received 7mg/kg of dexamethasone intramuscularly once a week for 5 weeks. Following, EP and GIOP+EP groups were subjected to ligature-induced periodontitis. Naïve group experienced no manipulation. After 11 days, the animals were euthanized and left maxillae collected for macroscopic, radiographic, micro-tomographic and microscopic analysis of alveolar bone loss (ABL). Blood samples were collected for determination of bone-specific alkaline phosphatase (BALP) levels and the right femurs were removed for radiographic and biomechanical analysis. RESULTS EP caused ABL and reduced BALP levels (p<0,05), but it did not change the architecture or biomechanics of femur, compared to Naïve. GIOP did not cause ABL, but it significantly decreased alveolar bone mineral density (ABMD), bone percentage and trabecular thickness (Tb.Th) and increased alveolar bone porosity (p<0.05) and significantly reduced BALP serum levels, as well as radiographic density and Youngs module of femur, compared to Naïve. There was a greater ABL in group GIOP+EP when compared to EP (p<0.05). GIOP+EP caused a greater decrease on ABMD, Tb.Th, bone percentage and increased bone porosity (p<0.05) and also presented a significant reduction in BALP levels (p<0.05), in radiographic density and in Youngs module of femur compared to EP (p<0.05). CONCLUSIONS GIOP can potentiate the destructive effects of EP on alveolar bone and alter the systemic bone loss, by promoting bone resorption and reducing osteoblast activity.

Neurotoxic effect of oxaliplatin: Comparison with its oxalate-free analogue cis-[PtII(1R,2R-DACH)(3-acetoxy-1,1-cyclobutanedicarboxylato)] (LLC-1402) in mice

ABSTRACT Studies suggest that oxalate is involved in the development oxaliplatin‐induced peripheral sensory neuropathy (OPSN). This study aimed to compare the neurotoxic effects of oxaliplatin with its oxalate‐free cytotoxic analogue cis‐[PtII(1R,2R‐DACH)(3‐acetoxy‐1,1‐cyclobutanedicarboxylato)] (LLC‐1402) in mice. Oxaliplatin and LLC‐1402 were intravenously injected in male Swiss mice with a total of nine injections. Oxalate was intraperitoneally injected in other animals. The development of OPSN was evaluated using mechanical and thermal sensitivity tests. Dorsal root ganglia of the mice were removed to evaluate c‐Fos, ATF3 and iNOS expression and a sample of blood was collected for leukocyte count and hepatic and renal biochemical function tests. Oxaliplatin and LLC‐1402 decreased the mechanical and thermal nociceptive threshold, whilst oxalate lead to a partial and later increase in the mechanical sensitivity (P < 0.05). c‐Fos, ATF3 and iNOS expressions were increased in neuronal cells during and after the end of the injections in animals treated with oxaliplatin and LLC‐1402 (P < 0.05), even though oxaliplatin lead to an earlier increase. Only c‐Fos expression was elevated during the period of injections in the oxalate group (P < 0.05), but this expression reduced after the end of the treatment. c‐Fos expression was also shown in glial satellite cells only in the oxaliplatin‐treated animals. Oxaliplatin and LLC‐1402 reduced leukocyte count (P < 0.05), but did not change renal and liver functions. In conclusion, oxalate may contribute to an earlier development of peripheral sensory neuropathy. However, the antitumor cytotoxic mechanism of oxaliplatin seems to be the main responsible by its neurotoxic effect. HighlightsOxaliplatin oxalate‐free analogue induced peripheral sensory neuropathy.Oxaliplatin oxalate‐free analogue seems to lead to neuronal damage.Oxalate may contribute to oxaliplatin‐induced peripheral sensory neuropathy.Oxalate seems to induce increased neuronal activity, but not neuronal damage.

Development and validation of the experimental wound assessment tool (EWAT) for pressure ulcer in laboratory animals

INTRODUCTION In studies with experimental models of pressure ulcer, until date, there is no validated instrument to assess the various visual aspects of the healing process. Measure of wound area is the most used method for this purpose. Thus, we aimed to develop and validate a visual assessment tool for the evaluation of healing in experimental models of pressure ulcer. METHODS The Experimental Wound Assessment Tool (EWAT) was developed based on tools used in clinical practice. The tool was validated using 50 photographs of wound induced by a noninvasive pressure ulcer model in Swiss mice. Five judges performed the Content Validity and 3 raters evaluated the photos by EWAT. Items with the Content Validity Index score lower than 0.8 were modified in accordance to the suggestions of the judges. RESULTS The EWAT showed moderate to high reliability, whilst the Concurrent Validity Test obtained good to high results, demonstrating a significantly strong positive correlation between the analyses of the raters. Moreover, it was shown to have high correlation with the clinical Photographic Wound Assessment Tool. DISCUSSION EWAT showed good/excellent results in all the validation tests, showing it to be a good tool to evaluate wound healing process in animal models of pressure ulcer and being recommended for assessment of wound healing in small experimental animals.

Clinical efficacy of a 1% Matricaria chamomile L. mouthwash and 0.12% chlorhexidine for gingivitis control in patients undergoing orthodontic treatment with fixed appliances.

This pilot study evaluated the clinical efficacy of a mouthwash containing 1% Matricaria chamomilla L. (MTC) extract in reducing gingival inflammation and plaque formation in patients undergoing orthodontic treatment with fixed appliances. This randomized, double-blind, placebo-controlled study enrolled a total of 30 males and females (age, 10-40 years) with fixed orthodontic appliances and a minimum of 20 natural teeth. The participants were allocated to three groups (n = 10 each) and asked to rinse with 15 mL of a placebo, 0.12% chlorhexidine (CHX), or 1% MTC mouthwash, immediately after brushing for 1 min, in the morning and evening, for 15 days. Data (mean ± SD) on visible plaque index (VPI) and gingival bleeding index (GBI) were recorded on days 1 and 15. The placebo group exhibited increases in VPI and GBI (10.2% and 23.1%, respectively) from day 1 to day 15. As compared with placebo, VPI and GBI significantly decreased in the MTC group (-25.6% and -29.9%, respectively) and the CHX group (-39.9% and -32.0%, respectively). In summary, MTC reduced biofilm accumulation and gingival bleeding in patients with gingivitis, probably because of its antimicrobial and anti-inflammatory activities.(J Oral Sci 58, 569-574, 2016).

Local administration of Tiludronic Acid downregulates important mediators involved in periodontal tissue destruction in experimental periodontitis in rats

OBJECTIVE The purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1β, TNF-α, MMP-8 and COX-2 in rats with experimental periodontitis (EP). METHODS Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 μL of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal area adjacent to the maxillary 2nd molar every other day until euthanasia (day 11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL-1β, TNF-α, MMP-8 and COX-2 were assessed by qPCR. IL-1β, TNF-α, MMP-8 and COX-2 were immunohistochemically analyzed. Data were analyzed statistically. RESULTS Group EP-TIL presented reduced alveolar bone loss when compared with group EP (p < 0.05). Group EP-TIL presented decreased mRNA expressions of IL-1β, TNF-α, MMP-8 and COX-2 and reduced immunolabeling of IL-1β, TNF-α and MMP-8 when compared with group EP (p < 0.05). No differences regarding the immunolabeling of COX-2 were found when group EP-TIL was compared with the other groups (p > 0.05). CONCLUSION Within the limits of this study, it can be concluded that local administration of TIL downregulates important mediators involved in periodontal tissue destruction in ligature-induced periodontitis in rats.

Inflammatory pain assessment in the arthritis of the temporomandibular joint in rats: A comparison between two phlogistic agents

Temporomandibular joint (TMJ) disorders are a group of conditions that result in TMJ pain, which frequently limits basic daily activities. Experimental models that allow the study of the mechanisms underlying these inflammatory and pain conditions are of great clinical relevance. The aim of this study was to evaluate nociception, inflammation and participation of the macrophage/microglia cells in the arthritis of the TMJ induced by two phlogistic agents. 84 rats were divided into 2 groups: Zy, which received zymosan intra-articularly, or Cg, which received carrageenan intra-articularly. Mechanical nociception, total leukocyte influx to the synovial fluid and histopathological analyses were evaluated in the TMJ. The participation of macrophage/microglia located in trigeminal ganglia (TG) and in the subnucleus caudalis (V-SnC) was assessed immunohistochemically. Both agents induced mechanical hyperalgesia 6h after the induction, but a more persistent algesic state was perceived in the Cg group, which lasted for 120h. Even though both groups presented increased leukocyte influx, the Zy-group presented a more intense influx. Zymosan recruited resident macrophage in the trigeminal ganglia 24h after the injection. In the V-SnC, the group Cg presented a more prolonged immunolabeling pattern in comparison with the group Zy. It can be concluded that zymosan induced a more intense infiltrate and peripheral nervous changes, while Cg lead to a moderate TMJ inflammation with prominent changes in the V-SnC.