Anti-inflammatory effect of MAPK phosphatase-1 local gene transfer in inflammatory bone loss

Alveolar bone loss associated with periodontal diseases is the result of osteoclastogenesis induced by bacterial pathogens. The mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) is a critical negative regulator of immune response as a key phosphatase capable of dephosphorylating activated MAPKs. In this study, rat macrophages transduced with recombinant adenovirus (Ad.)MKP-1 specifically dephosphorylated activated MAPKs induced by lipopolysaccharide (LPS) compared with control cells. Bone marrow macrophages from MKP-1 knockout (KO) mice exhibited higher interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, and select chemokine compared with wild-type (WT) mice when stimulated by LPS. In addition, bone marrow cultures from MKP-1 KO mice exhibited significantly more osteoclastogenesis induced by LPS than when compared with WT mice. Importantly, MKP-1 gene transfer in bone marrow cells of MKP-1 KO mice significantly decreased IL-6, IL-10, TNF-α and chemokine levels, and formed fewer osteoclasts induced by LPS than compared with control group of cells. Furthermore, MKP-1 gene transfer in an experimental periodontal disease model attenuated bone resorption induced by LPS. Histological analysis confirmed that periodontal tissues transduced with Ad. MKP-1 exhibited less infiltrated inflammatory cells, less osteoclasts and less IL-6 than compared with rats of control groups. These studies indicate that MKP-1 is a key therapeutic target to control of inflammation-induced bone loss.

Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss

p38 mitogen-activated protein kinases (MAPKs) are critical for innate immune signaling and subsequent cytokine expression in periodontal inflammation and bone destruction. In fact, previous studies show that systemic p38 MAPK inhibitors block periodontal disease progression. However, development of p38 MAPK inhibitors with favorable toxicological profiles is difficult. Here, we report our findings regarding the contribution of the downstream p38 MAPK substrate, mitogen-activated protein kinase-activated protein kinase 2 (MK2 or MAPKAPK-2), in immune response modulation in an experimental model of pathogen-derived lipopolysaccharide (LPS)-induced periodontal bone loss. To determine whether small interfering RNA (siRNA) technology has intraoral applications, we initially validated MK2 siRNA specificity. Then, gingival tissue surrounding maxillary molars of rats was injected with MK2 siRNA or scrambled siRNA at the palatal regions of bone loss. Intraoral tissues treated with MK2 siRNA had significantly less MK2 mRNA expression compared with scrambled siRNA-treated tissues. MK2 siRNA delivery arrested LPS-induced inflammatory bone loss, decreased inflammatory infiltrate, and decreased osteoclastogenesis. This proof-of-concept study suggests a novel target using an intraoral RNA interference strategy to control periodontal inflammation.

Relationship between levels of neuropeptide Substance P in periodontal disease and chronic pain: a literature review

The aim of the current review was to investigate the relationship between levels of neuropeptide Substance P in periodontal disease and chronic pain. Substance P is a neuropeptide that is directly related with pain. In periodontal disease, it is expressed during the inflammatory process, and is one of the factors responsible for bone resorption. Studies have shown that Substance P levels are highest in the gingival crevicular fluid from sites with active periodontal disease and bone loss. The persistence of these substances could be sufficient to stimulate neurogenic inflammation in susceptible tissues, and cause pain. The scientific literature shows that Substance P expressed during periodontal disease can be a risk factor for patients with systemic inflammatory pathologies, such as chronic arthritis or rheumatoid arthritis. Additional research is needed to confirm the participation of this substance in the origin of some types of chronic pain.

Alloxan-Induced Diabetes Causes Morphological and Ultrastructural Changes in Rat Liver that Resemble the Natural History of Chronic Fatty Liver Disease in Humans

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Combining plant and bird data increases the accuracy of an Index of Biotic Integrity to assess conservation levels of tropical forest fragments

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mandibulectomy for treatment of fractures associated with severe periodontal disease

Six cases of mandibular fractures associated with severe periodontal disease that had been treated by mandibulectomy, due to intense bone loss, were evaluated retrospectively. The dogs were mainly older, small breed dogs that had suffered a traumatic event. Four dogs had a bilateral mandibulectomy and 2 a unilateral mandibulectomy.

Androgen receptors and experimental bone loss - an in vivo and in vitro study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of removal of a non-native tree species Mimosa caesalpiniifolia Benth. on the regenerating plant communities in a tropical semideciduous forest under restoration in Brazil

Exotic species are used to trigger facilitation in restoration plantings, but this positive effect may not be permanent and these species may have negative effects later on. Since such species can provide a marketable product (firewood), their harvest may represent an advantageous strategy to achieve both ecological and economic benefits. In this study, we looked at the effect of removal of a non-native tree species (Mimosa caesalpiniifolia) on the understory of a semideciduous forest undergoing restoration. We assessed two 14-year-old plantation systems (modified taungya agroforestry system; and mixed plantation using commercial timber and firewood tree species) established at two sites with contrasting soil properties in São Paulo state, Brazil. The experimental design included randomized blocks with split plots. The natural regeneration of woody species (height ≥0.2 m) was compared between managed (all M. caesalpiniifolia trees removed) and unmanaged plots during the first year after the intervention. The removal of M. caesalpiniifolia increased species diversity but decreased stand basal area. Nevertheless, the basal area loss was recovered after 1 year. The management treatment affected tree species regeneration differently between species groups. The results of this study suggest that removal of M. caesalpiniifolia benefited the understory and possibly accelerated the succession process. Further monitoring studies are needed to evaluate the longer term effects on stand structure and composition. The lack of negative effects of tree removal on the natural regeneration indicates that such interventions can be recommended, especially considering the expectations of economic revenues from tree harvesting in restoration plantings.

Long-term evaluation of oral gavage with periodontopathogens or ligature induction of experimental periodontal disease in mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The genome sequence of the plant pathogen Xylella fastidiosa: The Xylella fastidiosa consortium of the organization for nucleotide sequencing and analysis, Sao Paulo, Brazil

Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range of economically important plant diseases. Here we report the complete genome sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis - a serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305-base-pair (bp) circular chromosome and 'two plasmids of 51,158 bp and 1,285 bp. We can assign putative functions to47% of the 2,904 predicted coding regions. Efficient metabolic functions are predicted, with sugars as the principal energy and carbon source, supporting existence in the nutrient-poor xylem sap. The mechanisms associated with pathogenicity and virulence involve toxins, antibiotics and ion sequestration systems, as well as bacterium-bacterium and bacterium-host interactions mediated by a range of proteins. Orthologues of some of these proteins have only been identified in animal and human pathogens; their presence in X. fastidiosa indicates that the molecular basis for bacterial pathogenicity is both conserved and independent of host. At least 83 genes are bacteriophage-derived and include virulence-associated genes from other bacteria, providing direct evidence of phage-mediated horizontal gene transfer.

Treatment of experimental periodontal disease by antimicrobial photodynamic therapy in nicotine-modified rats

Background The aim of this study was to compare antimicrobial photodynamic therapy (aPDT) as an adjunctive treatment to scaling and root planing (SRP) for induced periodontitis in nicotine-modified rats. Material & Methods A total of 240 rats were evenly divided into two groups: C – saline solution treatment; N – nicotine treatment. Periodontal disease was induced in both groups at the first mandibular molar. After 7 days, the ligature was removed. All animals were submitted to SRP and were divided according to the following treatments: SRP – irrigation with saline solution; Toluidine Blue-O (TBO) – irrigation with phenothiazinium dye (100 μg/ml); LLLT – laser irradiation (660 nm; 0.03 W; 4 J); and aPDT – TBO and laser irradiation. Ten animals in each group/treatment were euthanized at 7, 15 and 30 days. The histometric and immunohistochemical values were statistically analysed. Results Intragroup analysis demonstrated that in both groups the aPDT treatment resulted in lower bone loss (BL) when compared to SRP in all experimental periods. Intergroup analysis demonstrated that aPDT treatment resulted in lower BL in Group N than in Group C treated with SRP in all experimental periods. Conclusion Antimicrobial photodynamic therapy was an effective adjunctive treatment to SRP for induced periodontitis in nicotine-modified rats.

Toxicity and loss of mitochondrial membrane potential induced by Alkyl Gallates in Trypanosoma cruzi

American trypanosomiasis or Chagas disease is a debilitating disease representing an important social problem that affects, approximately, 10 million people in the world. The main aggravating factor of this situation is the lack of an effective drug to treat the different stages of this disease. In this context, the search for trypanocidal substances isolated from plants, synthetic or semi synthetic molecules, is an important strategy. Here, the trypanocidal potential of gallates was assayed in epimastigotes forms of T. cruzi and also, the interference of these substances on the mitochondrial membrane potential of the parasites was assessed, allowing the study of the mechanism of action of the gallates in the T. cruzi organisms. Regarding the preliminary structure-activity relationships, the side chain length of gallates plays crucial role for activity. Nonyl, decyl, undecyl, and dodecyl gallates showed potent antitrypanosomal effect (IC50 from 1.46 to 2.90 μM) in contrast with benznidazole (IC50 = 34.0 μM). Heptyl gallate showed a strong synergistic activity with benznidazole, reducing by 105-fold the IC50 of benznidazole. Loss of mitochondrial membrane potential induced by these esters was revealed. Tetradecyl gallate induced a loss of 53% of the mitochondrial membrane potential, at IC50 value.

Experimental periodontal disease treatment by subgingigval irrigation with tetracycline hidrochloride in rats

Objective: The aim of this study was to compare subgingival irrigation with tetracycline hydrochloride (TTC-HCL) as adjunctive treatment to scaling and root planning (SRP) on induced periodontitis in rats. Material and Methods: In 60 rats, periodontal disease was ligature-induced at the mandibular left first molar. After 7 days, the ligature was removed and all animals were submitted to SRP, and divided into 2 groups according to the following treatment: C (n=30) – subgingival irrigation with 1 mL of saline; T (n=30) – subgingival irrigation with 1 mL of TTC-HCL (50 mg/mL). Ten animals in each group were euthanized at 7, 15 and 30 days posttreatment. The histometric values were statistically analyzed (p<0.05). Results: In the histometric analysis, at 7, 15 and 30 days, Group T (0.72±0.05 mm2, 0.57±0.14 mm2, 0.62±0.07 mm2), showed less bone loss (p<0.05) than Group C (1.35±0.25 mm2; 1.40±0.31 mm2; 1.29±0.27 mm2), respectively. Conclusions: Subgingival irrigation with TTC-HCL was an effective adjunctive treatment for periodontal disease induced in rats.

Endophytic microorganisms isolated from coffee leaves, roots and branches as plant growth promoters and biocontrol agents of coffee leaf rust

Suppression of plant diseases and growth promotion due to the action of endophytic microorganisms has been demonstrated in several pathosystems. Experiments under controlled conditions involving 234 endophytic bacteria and fungi isolated from coffee leaves, roots and branches were conducted with the objective of evaluating the germination inhibition of Hemileia vastatrix urediniospores, the control of coffee leaf rust development in tests with leaf discs and on plastic bags seedling, and to promote growth of coffee seedlings. None of the fungal isolates induced plant growth or reduced disease severity. The bacterial isolates (identified by the fatty acids profile analysis) 85G (Escherichia fergusonii), 161G, 163G, 160G, 150G (Acinetobacter calcoaceticus) and 109G (Salmonella enterica) increased plant growth, the maximum being induced by 85G. This isolate produced in vitro phosphatase and indol acetic acid. In assay to control rust on coffee leaf disc, nine bacterial isolates, 64R, 137G, 3F (Brevibacillus choshinensis), 14F (Salmonella enterica), 36F (Pectobacterium carotovorum), 109G (Bacillus megaterium), 115G (Microbacterium testaceum), 116G and 119G (Cedecea davisae) significantly reduced disease severity, when applied 72 or 24h before challenging with the pathogen. In seedling tests most disease severity reduction was achieved by the isolates 109G and 119G. There was no correspondence between the organisms that promoted seedling growth and those that reduced rust severity on seedlings or leaf discs.

Oncogenic osteomalacia: loss of hypophosphatemia might be the key to avoid misdiagnosis

Diagnosing oncogenic osteomalacia is still a challenge. The disorder is characterized by osteomalacia caused by renal phosphate wasting and low serum concentration of 1,25-dihydroxyvitamin D3 occurring in the presence of a tumor that produces high levels of fibroblast growth factor 23. However, it is possible that the disease is much more misdiagnosed than rare. We present the case of a 42-year-old man with a long-term history of undiagnosed progressive muscle weakness. His laboratory results mainly showed low serum phosphate. Surgical removal of a nasal hemangiopericytoma that had been diagnosed five years earlier, brought him to a symptom-free condition. Even though knowing the underlying etiology would explain his osteomalacia, the patient sought medical help from countless physicians for five consecutive years, and only after adequate treatment a rewarding outcome was achieved.