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1.
J Neurosci Res ; 102(1): e25269, 2024 01.
Article in English | MEDLINE | ID: mdl-38284851

ABSTRACT

This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan-induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2 X7 antagonist, a cathepsin S inhibitor or a p-38 mitogen-activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3 CR1 , phospho-p-38 MAPK, ionized calcium-binding adapter molecule-1 (Iba-1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3 CR1 and developed hyperalgesia and up-regulation of phospho-p-38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba-1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p-38 MAPK and reverting morphological alterations in microglia and SGCs.


Subject(s)
Arthritis , Neuralgia , Male , Animals , Rats , Hyperalgesia/drug therapy , Chemokine CX3CL1 , Neuroglia , Neuralgia/drug therapy , Mitogen-Activated Protein Kinases , Protein Kinase Inhibitors , Facial Pain/drug therapy , p38 Mitogen-Activated Protein Kinases
2.
J Biomech ; 157: 111704, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37406602

ABSTRACT

The development and acquisition of mature walking in children is multifactorial, depending among others on foot interaction with the ground, body dynamics and the knowledge of the 'rules' stemming from the gravity field. Indeed, each step the velocity of the centre of mass must be redirected upwards. This redirection may be initiated by the trailing leg, propulsing forward and upward the body before foot contact, or later by the loading limb after the contact with the ground. While it has been suggested that mature walking develops slowly from first independent steps to about 7 years of age, it is still unknown how children acquire the appropriate loading and propulsion forces during the step-to-step transition. To answer that question, twenty-four children (from 3 to 12 years old) and twelve young adults (from 20 to 27 years old) walked on force platforms at different walking speed. The ground reaction forces under each foot were recorded and the vertical velocity of the centre of mass of the body was computed. With decreasing age and increasing velocity (or Froude number), the occurrence of unanticipated transition is higher, related to a different ratio between the vertical support of the front and back leg. The different transition strategy observed in children indicates that body weight transfer from one limb to the other is not fully mature at 12 years old.

3.
Article in Spanish | LILACS | ID: biblio-1384325

ABSTRACT

RESUMEN Los objetivos de este estudio fueron determinar y comparar el riesgo cardiovascular (RCV) en estudiantes de la carrera de preparador físico de las generaciones 2017 y 2019. Las variables medidas fueron peso corporal (PC), estatura (ES), circunferencia de cintura (CC), índice de masa corporal (IMC) e índice de cintura/estatura (ICE). Se utilizó al CC e ICE para la determinación del RCV y su posterior comparación. La metodología utilizada corresponde a un estudio cuantitativo, transversal, descriptivo: con una muestra de 324 participantes (año 2019 = 98 hombres y 62 mujeres; año 2017 = 103 hombres y 61 mujeres). Se utilizó una báscula mecánica con estadímetro marca DETECTO (para PC y ES) y una cintra métrica antropométrica SECA (para CC). Para las diferencias estadísticas se utilizó la prueba de ANOVA de dos vías y comparaciones múltiples de Sidak, se consideró el índice de D Cohen para el tamaño de efecto, con un alfa de 0.05), ni tampoco se clasifican como grupo de riesgo. Se concluye que las mujeres estudiantes tienen características antropométricas diferentes entre ambos años y que la generación del año 2019 presenta RCV.


ABSTRACT The aims of this study were to determine and compare the cardiovascular risk (CVR) in students of the physical trainer career of the 2017 and 2019 generations. The variables measured were body weight (BW), height (HE), waist circumference (WC), body mass index (BMI) and waist to height ratio (WHtR). The WC and WHtR were used to determine the CVR and its subsequent comparison. The methodology used corresponds to a quantitative, cross-sectional, descriptive study: with a sample of 324 participants (year 2017 = 103 men and 61 women; year 2019 = 98 men and 62 women). A mechanical scale with a DETECTO brand stadiometer (for BW and HE) and a SECA anthropometric tape measure (for WC) were used. Sidak's two-way ANOVA test and multiple comparisons were used for statistical differences, the Cohen D index for effect size was considered, with an alpha of 0.05), nor are they classified as a risk group. It is concluded that female students have different anthropometric characteristics between both years and that the generation of 2019 presents CVR.


Subject(s)
Humans , Male , Female , Physical Education and Training , Universities , Heart Disease Risk Factors , Body Mass Index , Chile , Waist Circumference
4.
Neurotox Res ; 39(6): 1782-1799, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34792764

ABSTRACT

Oxaliplatin-induced neurotoxicity is expressed as a dose-limiting peripheral sensory neuropathy (PSN). Cannabinoid substances have been investigated for the analgesic effect. This study aimed to investigate the role of cannabinoid receptors in oxaliplatin-associated PSN. Swiss male mice received nine oxaliplatin injections (2 mg/kg, i.v.). Mechanical and thermal nociceptive tests were performed for 56 days. CB1, CB2, and c-Fos expression were assessed in dorsal root ganglia (DRG), spinal cord (SC), trigeminal ganglia (TG), spinal trigeminal nucleus caudalis (Sp5C), and periaqueductal gray (PAG). Iba-1 expression was assessed in DRG and ATF3 in TG. Cannabidiol (10 mg/kg, p.o.) or a CB1/CB2 non-selective agonist (WIN 55,212-2; 0.5 mg/kg, s.c.) or AM251 (CB1 antagonist) or AM630 (CB2 antagonist) (3 mg/kg, i.p.) were injected before oxaliplatin. Oxaliplatin increased CB1 in DRG, SC, TG, Sp5C, and ventrolateral PAG, with no interference in CB2 expression. Cannabidiol increased CB1 in DRG, reduced mechanical hyperalgesia and c-Fos expression in DRG and SC. Additionally, WIN 55,212-2 increased CB1 in DRG, reduced mechanical hyperalgesia, cold allodynia and c-Fos expression in DRG and SC. CB1 blockage hastened the cold allodynia response, but the CB2 antagonist failed to modulate the oxaliplatin-induced nociceptive behavior. Oxaliplatin also increased Iba-1 in DRG, suggesting immune response modulation which was reduced by cannabidiol and enhanced by AM630. The modulation of the endocannabinoid system, through the CB1 receptor, attenuates the oxaliplatin-associated PNS. The activation of the endocannabinoid system could be considered as a therapeutic target for controlling oxaliplatin-associated neuropathy.


Subject(s)
Endocannabinoids/metabolism , Nociception/drug effects , Oxaliplatin/adverse effects , Peripheral Nervous System Diseases/chemically induced , Receptor, Cannabinoid, CB1/agonists , Animals , Fluorescent Antibody Technique , Ganglia, Spinal/drug effects , Ganglia, Spinal/pathology , Ganglia, Spinal/physiopathology , Male , Mice , Oxaliplatin/antagonists & inhibitors , Pain Measurement , Peripheral Nervous System Diseases/metabolism , Receptor, Cannabinoid, CB1/metabolism , Rotarod Performance Test
5.
Eur J Cancer Care (Engl) ; 30(1): e13360, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33219575

ABSTRACT

OBJECTIVE: There is wide discrepancy on how to perform clinical assessment of oxaliplatin-induced peripheral neuropathy. In this scenario, the Electronic von Frey (EVF), which evaluates pain objectively based upon mechanical pain thresholds (MPTs), may be a valuable tool. The present study aims to quantify hyperalgesia in the hands and feet of patients treated with oxaliplatin and to propose a novel method to classify the degree of neurotoxicity using EVF-derived measures as cut-off points. METHODS: This is a prospective cohort study including 46 patients treated for colorectal cancer with the FLOX regimen. Before each oxaliplatin administration, patients were evaluated with the Acute and Chronic Neuropathy Questionnaire, Oxaliplatin-Specific Neurotoxicity Scale and National Cancer Institute Common Terminology Criteria for Adverse Events scale. Also, objective pain assessment with the EVF was performed. RESULTS: For both upper and lower extremities, EVF was shown to correlate well with patients' symptoms and functional impairment, as assessed by subjective scales. Also, when cut-off MPT variations were determined for diagnosis of neurotoxicity grade 2 or 3, the method showed good sensitivity and specificity. CONCLUSION: Electronic von Frey is a noninvasive and easy-to-perform objective method with potential to supplement the current assessment tools for oxaliplatin-induced peripheral neuropathy, which are mostly subjective.


Subject(s)
Antineoplastic Agents , Peripheral Nervous System Diseases , Antineoplastic Agents/adverse effects , Electronics , Humans , Longitudinal Studies , Oxaliplatin , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/diagnosis , Prospective Studies
6.
Inflammation ; 44(1): 116-128, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32789781

ABSTRACT

Periodontitis and rheumatoid arthritis (RA) are inflammatory diseases characterized by chronic inflammation and bone erosion. Electroacupuncture (EA) shows anti-inflammatory and anti-resorptive effects in experimental periodontitis (EP) and in RA. It is important to investigate whether EA shows these effects in periodontal tissues in the presence of these two inflammatory diseases or not. For this, Wistar rats were divided into six groups: control (C); experimental rheumatoid arthritis (RA; bovine type II collagen-induced (CII)); experimental periodontitis (EP); RA/EP (RA + EP); EP/EA (EP treated with EA); RA/EP/EA (RA + EP treated with EA). EP was induced 21 days after RA induction and EA was performed previously and during the EP induction period, every 3 days until the 36th experimental day. The rats were euthanized on day 39. RA was evaluated by edema and the withdrawal threshold of hind paws. The maxillae were removed, and alveolar bone loss (ABL) and bone radiographic density (BRD) were evaluated. Immunohistochemical analyses for interleukins (IL)-6 and -17 and nuclear factor (NF)-κB were performed. Our results showed that EA reduced only the pain intensity in arthritic rats. Histomorphometric, macroscopic, and radiographic analyses did not show differences between the control and EP/EA groups. EA caused a reduction in ABL and BRD only in the presence of EP. EA caused a reduction in IL-6 and -17 in all groups, but NF-κB was only reduced in the arthritic rats with EP. In conclusion, EA reduced the inflammation related to periodontitis in arthritic rats but did not prevent ABL.


Subject(s)
Alveolar Bone Loss/therapy , Arthritis, Experimental/therapy , Arthritis, Rheumatoid/therapy , Electroacupuncture/methods , Inflammation Mediators/antagonists & inhibitors , Periodontitis/therapy , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/metabolism , Animals , Arthritis, Experimental/diagnostic imaging , Arthritis, Experimental/metabolism , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/metabolism , Inflammation/diagnostic imaging , Inflammation/metabolism , Inflammation/therapy , Inflammation Mediators/metabolism , Periodontitis/diagnostic imaging , Periodontitis/metabolism , Rats , Rats, Wistar
7.
Int J Clin Oncol ; 25(12): 2066-2074, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32761281

ABSTRACT

BACKGROUND: Colorectal carcinoma (CRC) is widely treated by chemotherapy based on an intensely neurotoxic drug: oxaliplatin (OXL). We objective to evaluate prospectively the orofacial neurotoxicity during FLOX (fluorouracil + leucovorin + OXL) chemotherapy. METHODS: So, 46 patients with CRC were prospectively evaluated during FLOX chemotherapy by 3 cycles (C) of 6 weeks (W) each. We weekly applied the orofacial section of the Acute and Chronic Neuropathy Questionnaire of Common Toxicity Criteria for Adverse Events of the National Cancer Institute of the United States of America (Oxaliplatin-specific neurotoxicity scale). Patients were asked the following concerning the severity (scores 0-5) of orofacial symptoms: jaw pain, eyelids drooping, throat discomfort, ear pain, tingling in mouth, difficulty with speech, burning or discomfort of the eyes, loss of any vision, feeling shock/pain down back and problems breathing. We summed the scores (0-50) and evaluated the clinicopathological data. Friedman/Dunn, Chi square and multinomial regression logistic tests were used (SPSS 20.0, p < 0.05). RESULTS: There was a significant increase in sum of orofacial neurotoxicity from baseline to C1.W3, C2.W1 and C3.W5 (p < 0.001) due increase in scores of jaw pain (p < 0.001), eyelids drooping (p = 0.034), throat discomfort (p < 0.001), ear pain (p = 0.034), tingling in mouth (p = 0.015), burning/discomfort of your eyes (p < 0.001), loss of any vision (p < 0.001), feeling shock/pain down back (p < 0.001), problems with breathing (p = 0.045), but not difficulty with speech (p = 0.087). Women (p = 0.021) and young patients (p = 0.027) had significant higher prevalence of orofacial neurotoxicity. CONCLUSIONS: FLOX-related orofacial neurotoxicity begins acutely and remains long term with increased incidence in women and younger patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/drug therapy , Neurotoxicity Syndromes/etiology , Peripheral Nervous System Diseases/chemically induced , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/pathology , Face , Female , Fluorouracil/administration & dosage , Humans , Incidence , Leucovorin/administration & dosage , Longitudinal Studies , Male , Middle Aged , Mouth/drug effects , Neurotoxicity Syndromes/epidemiology , Oxaliplatin/administration & dosage , Peripheral Nervous System Diseases/epidemiology , Prospective Studies
8.
Neurotox Res ; 36(4): 688-699, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31228092

ABSTRACT

The aim of this study was to evaluate the participation of the endothelin ETA and ETB receptors and the effects of bosentan in oxaliplatin-induced peripheral sensory neuropathy (OIN) in mice. Adult male Swiss mice received 1 mg/kg of oxaliplatin intravenously, twice a week for 5 weeks. Dorsal root ganglia (DRG) and spinal cords were removed for evaluation of the endothelin ETA and ETB receptor expression. Afterwards, selective (BQ-123 and BQ-788; 10 nmol in 30 µL, intraplantarly) and non-selective (bosentan, 100 mg/kg, orally) antagonists were administered in order to evaluate the involvement of the endothelin receptors in OIN. Mechanical and thermal nociception tests were performed once a week for 56 days. Oxaliplatin induced mechanical and thermal hypersensitivity and increased the endothelin ETA receptor expression in both the DRG and spinal cord (P < 0.05). Endothelin ETB receptor expression was increased in the DRG (P < 0.05) but not in the spinal cord. Both endothelin ETA and ETB receptor selective antagonists partially prevented mechanical hyperalgesia in mice with OIN (P < 0.05). Moreover, bosentan prevented mechanical and thermal hypersensitivity in oxaliplatin-treated mice (P < 0.05). In conclusion, both endothelin ETA and ETB receptors seem to be involved in the OIN in mice and they should be considered possible targets for the management of this clinical feature.


Subject(s)
Oxaliplatin/toxicity , Peripheral Nervous System Diseases/chemically induced , Receptor, Endothelin A/metabolism , Receptor, Endothelin B/metabolism , Animals , Bosentan/administration & dosage , Endothelin Receptor Antagonists , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Male , Mice , Peripheral Nervous System Diseases/metabolism , Spinal Cord Dorsal Horn/drug effects , Spinal Cord Dorsal Horn/metabolism
9.
Bone ; 127: 59-66, 2019 10.
Article in English | MEDLINE | ID: mdl-31121356

ABSTRACT

This study evaluated the participation of CB1 and CB2 receptors in the antiresorptive effect of electroacupuncture (EA) on an experimental model of inflammatory bone loss in rats. 30 rats were divided into five groups: C (control); EP (experimental periodontitis); EA (C+ EA); EP-EA (EP+ EA in the acupoints LI4, LG11, ST36, ST44); EP - EA-sham (EP+ EA in sham acupoints). 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. Animals were euthanized at day 11. Histometric analysis was performed to evaluate the percentage of bone area in the furcation area. Immunolabeling patterns in the periodontal tissues and immunofluorescent staining in the trigeminal ganglia and in the trigeminal spinal tract for CB1 and CB2 receptors were performed. It was observed increased bone loss in the furcation in the EP and EP-EA-sham groups, in comparison to the other groups (p < 0.05). Enhanced CB2 immunolabeling was observed in the periodontal tissues in the EP-EA group, when compared to the EP and EP-EA-sham groups (p < 0.05). Increased CB1 immunofluorescent staining was observed in the neural tissues in the EA treated group in comparison with the other groups (p < 0.05), while no expression of CB2 was observed in those regions. Our study showed that in the presence of inflammatory bone disease, EA treatment reduced bone erosion and increased the immunoexpression of CB1 in the neural tissues and CB2 in the periodontal tissues.


Subject(s)
Bone Resorption/immunology , Bone Resorption/therapy , Electroacupuncture , Inflammation/pathology , Receptor, Cannabinoid, CB1/immunology , Receptor, Cannabinoid, CB2/immunology , Animals , Male , Periodontium/metabolism , Rats, Wistar , Trigeminal Ganglion/metabolism
10.
Toxicol Appl Pharmacol ; 340: 77-84, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29307816

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.


Subject(s)
Antineoplastic Agents/toxicity , Organoplatinum Compounds/toxicity , Oxalates , Peripheral Nervous System Diseases/chemically induced , Animals , Antineoplastic Agents/chemistry , Male , Mice , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Organoplatinum Compounds/chemistry , Oxaliplatin , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/pathology
11.
Arch Oral Biol ; 88: 1-9, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29335154

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate whether local administration of TIL could influence the expression of the inflammatory mediators IL-1ß, 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-1ß, TNF-α, MMP-8 and COX-2 were assessed by qPCR. IL-1ß, 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-1ß, TNF-α, MMP-8 and COX-2 and reduced immunolabeling of IL-1ß, 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.


Subject(s)
Diphosphonates/administration & dosage , Diphosphonates/pharmacology , Periodontitis/drug therapy , Periodontium/drug effects , Administration, Oral , Alveolar Bone Loss/metabolism , Alveolar Bone Loss/pathology , Animals , Cyclooxygenase 2/metabolism , Disease Models, Animal , Down-Regulation , Immunohistochemistry , Inflammation , Interleukin-1beta/metabolism , Male , Matrix Metalloproteinase 8/metabolism , Periodontitis/metabolism , Periodontitis/pathology , Periodontium/pathology , RNA, Messenger/biosynthesis , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism
12.
Clin Oral Investig ; 22(6): 2175-2185, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29288400

ABSTRACT

OBJECTIVE: The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats. MATERIAL AND METHODS: Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). The gingival tissues were used to quantify the myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1ß (IL-1ß) concentrations by ELISA. Blood samples were collected for leukogram and to evaluate the bone-specific alkaline phosphatase (BALP) activity and serum levels of aspartate and alanine transaminases (AST/ALT). RESULTS: The bone loss induced by 11 days of ligature induced bone loss, reduced levels of BALP, leukocyte infiltration, increased MPO activity, gingival concentrations of TNF-α and IL-1ß, and RANKL while reduced OPG immunoexpressions in the periodontal tissue and leukocytosis. Of the CLO, 90 mg/kg reduced bone loss, neutrophilia, the levels of pro-inflammatory mediators, and RANKL expression, while it increased OPG immunopositive cells and BALP serum levels, when compared to SAL. CLO did not affect either kidney or liver function, indicated by serum AST/ALT levels. CONCLUSION: The present data suggests that CLO reduced inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory properties and its effects on bone metabolism. CLINICAL RELEVANCE: CLO can be a potential therapeutical adjuvant in the treatment of periodontitis.


Subject(s)
Alveolar Bone Loss/drug therapy , Alveolar Bone Loss/metabolism , Calendula , Plant Extracts/pharmacology , Alanine Transaminase/metabolism , Alkaline Phosphatase/metabolism , Animals , Aspartate Aminotransferases/metabolism , Biomarkers/metabolism , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Interleukin-1beta/metabolism , Ligation , Male , Maxilla , Molar , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Rats , Rats, Wistar , Tumor Necrosis Factor-alpha/metabolism
13.
J Periodontol ; 89(1): 105-116, 2018 01.
Article in English | MEDLINE | ID: mdl-28914593

ABSTRACT

BACKGROUND: Tiludronic acid (TIL) presents antiresorptive and anti-inflammatory properties and has not been evaluated in the periodontitis-diabetes mellitus (DM) association to date, to the best knowledge of the authors. This study evaluates effects of local administration of TIL on experimental periodontitis (EP) in rats with streptozotocin-induced DM. METHODS: Thirty-two animals (Rattus norvegicus albinus, Wistar) were divided into groups DM/C (Control), DM/EP, DM/EP/TIL1, and DM/EP/TIL3. In EP groups, a ligature was placed around mandibular first molars. In groups DM/EP/TIL1 and DM/EP/TIL3, TIL solutions (1 and 3 mg/kg, respectively) were injected into the gingival tissue of mandibular molars every other day for 10 days, until euthanasia. Periodontal tissues were analyzed by microcomputed tomography (micro-CT), histomorphometry, immunohistochemistry (tartrate-resistant acid phosphatase [TRAP], receptor activator of nuclear factor-κB ligand [RANKL], osteoprotegerin, cleaved caspase 3), and quantitative reverse transcription-polymerase chain reaction (interleukin [IL]-1ß, vascular endothelial growth factor [VEGF]). RESULTS: In micro-CT analyses, groups DM/EP/TIL1 and DM/EP/TIL3 presented reduced alveolar bone resorption (P < 0.05). Group DM/EP/TIL3 presented decreased attachment loss (P < 0.05). The amount of TRAP-positive multinucleated cells was decreased in TIL groups (P < 0.05). Group DM/EP/TIL3 presented a lower immunolabeling pattern for RANKL (P < 0.05). TIL treatment decreased genic expression of IL-1ß, and in group DM/EP/TIL3, expression of VEGF was increased (P < 0.05). CONCLUSION: Local administration of TIL promoted a protective effect against tissue destruction in EP in diabetic rats, and the dosage of 3 mg/kg of TIL promoted the best results regarding its antiresorptive and anti-inflammatory effects.


Subject(s)
Alveolar Bone Loss , Diabetes Mellitus, Experimental , Periodontitis , Animals , Diphosphonates , RANK Ligand , Rats , Rats, Wistar , Vascular Endothelial Growth Factor A , X-Ray Microtomography
14.
Article in English | MEDLINE | ID: mdl-29100964

ABSTRACT

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.


Subject(s)
Pressure Ulcer/pathology , Wound Healing/physiology , Animals , Animals, Laboratory , Male , Mice , Photography/methods , Reproducibility of Results , Severity of Illness Index
15.
J Pharmacol Toxicol Methods ; 88(Pt 1): 100-108, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28797764

ABSTRACT

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.


Subject(s)
Arthritis/physiopathology , Hyperalgesia/physiopathology , Pain Measurement/methods , Pain/physiopathology , Temporomandibular Joint Disorders/physiopathology , Animals , Arthritis/chemically induced , Arthritis/diagnosis , Arthritis/pathology , Carrageenan/pharmacology , Disease Models, Animal , Hyperalgesia/chemically induced , Hyperalgesia/pathology , Injections, Intra-Articular , Macrophages/drug effects , Macrophages/pathology , Male , Microglia/drug effects , Microglia/pathology , Nociception/drug effects , Nociception/physiology , Pain/chemically induced , Pain/pathology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Temporomandibular Joint Disorders/chemically induced , Temporomandibular Joint Disorders/pathology , Trigeminal Ganglion/cytology , Trigeminal Ganglion/drug effects , Zymosan/pharmacology
16.
Arch Oral Biol ; 77: 55-61, 2017 May.
Article in English | MEDLINE | ID: mdl-28178585

ABSTRACT

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 Young's 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 Young's 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.


Subject(s)
Bone Density/drug effects , Femur/drug effects , Glucocorticoids/toxicity , Osteoporosis/chemically induced , Periodontitis/complications , Alkaline Phosphatase/blood , Animals , Femur/diagnostic imaging , Male , Osteoporosis/diagnostic imaging , Osteoporosis/pathology , Rats , Rats, Wistar
17.
J Oral Sci ; 58(4): 569-574, 2016.
Article in English | MEDLINE | ID: mdl-28025442

ABSTRACT

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).


Subject(s)
Chlorhexidine/administration & dosage , Gingivitis/prevention & control , Matricaria/chemistry , Mouthwashes , Orthodontic Appliances , Plant Extracts/administration & dosage , Adolescent , Adult , Child , Double-Blind Method , Female , Humans , Male , Placebos , Young Adult
18.
J Periodontol ; 87(10): 1206-16, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27240474

ABSTRACT

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 ß-catenin; and by enzyme-linked immunosorbent assay analysis of myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, 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-1ß, 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 ß-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.


Subject(s)
Atorvastatin/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Osteoporosis/drug therapy , Periodontitis/drug therapy , Alveolar Bone Loss , Animals , Gene Expression/drug effects , Glucocorticoids , Male , Osteoporosis/complications , Periodontitis/etiology , Rats , Rats, Wistar
19.
Fortaleza; s.n; 2016. 57 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-972057

ABSTRACT

Tem sido relatado que a acupuntura é capaz de modular a resposta imunoinflamatória dohospedeiro. O objetivo deste estudo foi a avaliar os efeitos da eletroacupuntura (EA) naperiodontite induzida por ligadura em ratos. Trinta e dois animais foram divididos nos gruposC (controle), PE (periodontite experimental), PE/EA-sham e PE/EA. Nos grupos PE, umaligadura foi posicionada ao redor dos 1os molares inferiores direitos. Cinco sessões de EA ouEA-sham foram realizadas a cada dois dias, iniciando-se no dia seguinte à colocação daligadura. Para o tratamento com EA, os acupontos IG4, IG11, E36 e E44 foram utilizados. AEA-sham foi realizada em pontos localizados fora de meridianos. Os animais foramsubmetidos à eutanásia 11 dias após a indução da periodontite. Análises histomorfométrica emicrotomográfica foram realizadas. Expressões dos RNAm de interleucina (IL)-1β,metaloproteinase de matriz (MMP)-8, IL-6, fator de necrose tumoral (TNF)-α e ciclooxigenase(COX)-2 foram avaliadas por meio da reação em cadeia da polimerase datranscrição reversa em tempo real (qRT-PCR). Os dados foram estatisticamente analisados(ANOVA, p0,05). Dentro dos limites do presente estudo, podeser concluído que a EA reduz a destruição tecidual periodontal e a expressão de algunsmediadores pró-inflamatórios na PE em ratos.


Acupuncture has been reported as capable of modulating the host’s immuno-inflammatory response. The purpose of this study was to evaluate the effects of electroacupuncture (EA) on ligature-induced periodontitis in rats.Thirty-two animals were divided into groups C (control), EP (experimental periodontitis), EP/EA-sham and EP/EA. On EP groups, a ligature was placed around right mandibular 1st molars. Five sessions of EA or EA/sham were assigned every other day, starting one day after ligature placement. For EA treatment, acupoints LI4, LI11, ST36 and ST44 were used. EA-sham was performed in off-meridian points.Animals were euthanized 11 days after the induction of periodontitis. Histomorphometric and microtomographic analyses were performed. Expressions of interleukin (IL)-1β, matrix metalloproteinase (MMP)-8, IL-6, tumor necrosis factor (TNF)-αand cyclooxygenase (COX)-2 mRNA were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Data were statistically analyzed (ANOVA, p0.05). Within the limits of the present study, it can be concluded that EA reduces periodontal tissue destruction and the expression of some pro-inflammatory mediators in EP in rats.


Subject(s)
Humans , Electroacupuncture , Periodontitis , Bone Resorption
20.
J Periodontol ; 86(6): 801-11, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25741581

ABSTRACT

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)-1ß, 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-1ß 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.


Subject(s)
Electroacupuncture/methods , Periodontitis/therapy , Acid Phosphatase/analysis , Acupuncture Points , Alveolar Bone Loss/pathology , Alveolar Bone Loss/therapy , Animals , Bone Density/physiology , Cyclooxygenase 2/analysis , Giant Cells/pathology , Image Processing, Computer-Assisted/methods , Interleukin-1beta/analysis , Interleukin-6/analysis , Isoenzymes/analysis , Male , Matrix Metalloproteinase 8/analysis , Osteoprotegerin/analysis , Periodontal Ligament/chemistry , Periodontal Ligament/pathology , Periodontitis/metabolism , Periodontitis/pathology , Rats , Rats, Wistar , Receptor Activator of Nuclear Factor-kappa B/analysis , Tartrate-Resistant Acid Phosphatase , X-Ray Microtomography/methods
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