The present study evaluated bone marrow aspirate (BMA) and low‐level laser therapy (LLLT) on bone healing. It was created critical‐size defects (CSD) of 5 mm diameter in rat calvaria of 64 rats. ...Animals were randomly divided into four groups: Control (blood clot), BMA (coagulated BMA), LLLT (laser irradiation and blood clot), and BMA/LLLT (laser irradiation and coagulated BMA). Euthanasia was performed at 15 or 30 days postoperative. Immunohistochemical reactions were performed to identify vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), runt‐related transcription factor‐2 (Runx2), bone morphogenetic protein‐2 (BMP‐2), osteocalcin (OCN), and osteopontin (OPN). The markers were quantified, and data were statistically analyzed. Groups BMA/LLLT and LLLT presented significantly higher VEGF expression than group control. Group BMA/LLLT presented a significantly higher expression of PCNA than all experimental groups. Groups BMA and BMA/LLLT presented significantly higher expression of BMP‐2 than all experimental groups. Groups LLLT and BMA/LLLT presented significantly higher expression of OPN than groups control and BMA. Groups LLLT, BMA, and BMA/LLLT presented a significantly higher expression of OCN than group control. It can be concluded that the association of BMA and LLLT enhanced bone healing by improving expression of VEGF, PCNA, Runx2, BMP‐2, OPN, and OCN.
Aim
To investigate the relationship between apical periodontitis and atherosclerosis in rats by lipid profile and carotid artery intima tunic measurement, and histological and histometric evaluation ...of periapical lesions.
Methodology
Forty male Wistar rats were allocated into four groups: control (C), with apical periodontitis (AP), with atherosclerosis (AT) and with AP and AT (AP + AT). Atherosclerosis was induced using a high‐lipid diet associated with a surgical ligature in the carotid artery and a super dosage of vitamin D3. AP was induced via pulp exposure to the oral environment. At 45 and 75 days, serum levels of total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C) and low‐density lipoprotein cholesterol (LDL‐C) were measured. The maxillary and mandibular jaws and carotid artery were collected and processed for histological analysis. The Kruskal–Wallis or Mann–Whitney test was performed for nonparametric data, and the Tukey’s or Student’s t‐test was performed for parametric data (P < 0.05).
Results
In nonatherosclerotic animals, the induction of apical periodontitis increased TG levels significantly, from 63.1 ± 11.4 mg dL−1 in group C to 88.2 ± 7.9 mg dL−1 in the AP group (P < 0.05). The induction of AP was associated with a trend for higher TC and LDL‐C levels in atherosclerotic animals (P > 0.05); however, it only significantly increased TG levels, from 93.2 ± 18.0 mg dL−1 in AT group to 121.9 ± 14.5 mg dL−1 in the AP + AT group (P < 0.05). Animals in the AP + AT group had a 36.5% increase in the thickness of the carotid intima tunic when compared with the AT group (P < 0.05). The intensity of the inflammatory infiltrate was significantly larger in the AP + AT group when compared with AP group (P < 0.05). The AP + AT group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 206.4 ± 56.3 × 104 μm2, compared with 151.4 ± 49.1 × 104 μm2 in the AP group (P < 0.05).
Conclusion
Apical periodontitis influenced triglyceride levels, increasing them even in the absence of atherosclerosis, and influenced the increase in the thickness of the carotid artery intima tunic in the presence of atherosclerosis. Atherosclerosis intensified the inflammatory reaction and increased bone resorption in periapical lesions.
The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell ...death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe forms of tuberculosis, disease progression was examined in C57BL/6 and P2X7R-/- mice that were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis strain 1471 of the Beijing genotype family and Mycobacterium bovis strain MP287/03). The low-dose infection of C57BL/6 mice with bacteria of these strains caused the rapid development of extensive granulomatous pneumonia with necrotic areas, intense bacillus dissemination and anticipated animal death. In contrast, in P2X7R-/- mice, the lung pathology presented with moderate infiltrates of mononuclear leukocytes without visible signs of necrosis; the disease attenuation was accompanied by a delay in mortality. In vitro, the hypervirulent mycobacteria grew rapidly inside macrophages and induced death by a P2X7R-dependent mechanism that facilitated the release of bacilli. Furthermore, these bacteria were resistant to the protective mechanisms elicited in macrophages following extracellular ATP stimulation. Based on this study, we propose that the rapid intracellular growth of hypervirulent mycobacteria results in massive macrophage damage. The ATP released by damaged cells engages P2X7R and accelerates the necrotic death of infected macrophages and the release of bacilli. This vicious cycle exacerbates pneumonia and lung necrosis by promoting widespread cell destruction and bacillus dissemination. These findings suggest the use of drugs that have been designed to inhibit the P2X7R as a new therapeutic approach to treat the aggressive forms of tuberculosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
The aim of this study was to verify the suitable use of candidate ‘probiotics’ selected by in vitro tests and the importance of in vivo assays to nominate micro‐organisms as probiotics and ...alternative prophylactic treatments for Salmonella Typhimurium infection.
Methods and Results
Thirty‐three lactic acid bacteria (LAB) isolated from foal's faeces were assessed based on the main desirable functional in vitro criteria. Based on these results, Pediococcus pentosaceus strain 40 was chosen to evaluate its putative probiotic features in a mouse model of Salmonella infection. Daily intragastric doses of Ped. pentosaceus 40 for 10 days before and 10 days after Salmonella challenge (106 CFU of Salm. Typhimurium per mouse) led to a significant aggravation in mouse health by increasing weight loss, worsening clinical symptoms and anticipating the time and the number of deaths by Salmonella. Pediococcus pentosaceus modulated cell‐mediated immune responses by up‐regulation of the gene expression of the proinflammatory cytokines IFN‐γ and TNF‐α in the small intestine.
Conclusion
The usual criteria were used for in vitro screening of a large number of LAB for desirable probiotic functional properties. However, the best candidate probiotic strain identified, Ped. pentosaceus #40, aggravated the experimental disease in mice.
Significance and Impact of the Study
These findings emphasize the need for prophylactic or therapeutic effectiveness to be demonstrated in in vivo models to make precise health claims.
Liver cirrhosis is associated with a wide range of cardiovascular abnormalities including hyperdynamic circulation and cirrhotic cardiomyopathy. The pathogenic mechanisms of these cardiovascular ...changes are multifactorial and include vascular dysregulations.
The present study tested the hypothesis that the systemic vascular hyporesponsiveness in thioacetamide (TAA)-induced liver injury model is dependent on nitric oxide (NO) and cyclooxygenase (COX) derivatives.
Wistar rats were treated with TAA for eight weeks to induce liver injury.
The maximal contractile response in concentration-effect curves to phenylephrine was decreased in aorta from TAA-treated rats, but no differences were found in aorta without endothelium, suggesting an endothelium-dependent mechanism in decreased contractile response. There was no difference in the contractile response with and without L-NAME (N(ω)-nitro-l-arginine methyl ester) in rats with liver injury, showing that the TAA treatment impairs NO synthesis. Pre-incubation of the aorta with indomethacin, a COX-inhibitor, normalized the reduced contractile response to phenylephrine in arteries from TAA group. Also, COX-2 and iNOS (inducible nitric oxide syntase) protein expression was increased in aorta from TAA group compared to control group. Animals submitted to TAA treatment had a reduction in systolic blood pressure. Our findings demonstrated that liver injury induced by TAA caused a decrease in aortic contractile response by a COX-dependent mechanism but not by NO release. Also, it was demonstrated an inflammatory process in the aorta of TAA-treated rats by increased expression of COX-2 and iNOS.
Therefore, there is an essential contribution of COX-2 activation in extra-hepatic vascular dysfunction and inflammation present in cirrhosis induced by TAA.
Cancer‐related fatigue (CRF) is the most stressful and prevalent symptom in paediatric oncology patients. This integrative review aimed to identify, analyse and synthesise the evidence of ...non‐pharmacological intervention studies to manage fatigue and psychological stress in a paediatric population with cancer. Eight electronic databases were used for the search: PubMed, Web of Science, CINAHL, LILACS, EMBASE, SCOPUS, PsycINFO and the Cochrane Library. Initially, 273 articles were found; after the exclusion of repeated articles, reading of the titles, s and the full articles, a final sample of nine articles was obtained. The articles were grouped into five categories: physical exercise, healing touch, music therapy, therapeutic massage, nursing interventions and health education. Among the nine studies, six showed statistical significance regarding the fatigue and/or stress levels, showing that the use of the interventions led to symptoms decrease. The most frequently tested intervention was programmed physical exercises. It is suggested that these interventions are complementary to conventional treatment and that their use can indicate an improvement in CRF and psychological stress.
Coagulase-negative staphylococci (CNS) represent one of the most prevalent microorganisms in nosocomial infections worldwide, nevertheless little is known about their pathogenicity features. Thus, ...our aim was to characterize virulence aspects of CNS isolated from patients with bloodstream infections assisted in hospitals of Belo Horizonte, MG, Brazil. Strains were identified using bioMérieuxVitek® and for biofilm production evaluation, Congo Red Agar (CRA) and polystyrene plates were used. PCR was applied to detect icaA, icaB, icaC, atlE, sea, sec, sed, tsst-1 and agr. For statistical analyses were used hierarchical cluster, chi-square test and correspondence. 59 strains were analyzed, being S. haemolyticus the most prevalent. On CRA, 96.5% were biofilm producer, whereas on polystyrene plate, 100% showed adhesion at different times evaluated. Regarding genotypic analyses, 15.2%, 38.9%, 8.4%, 49.1%, 76.2%, 23.7%, 1.6%, 30.5% and 38.9% were positive for icaA, icaB, icaC, atlE, sea, sec, sed, tsst-1 and agr, respectively. Six clusters were formed and frequency distributions of agr, atlE, icaA, icaB, sea, sec, tsst-1 differed (P < 0.001). In conclusion, all strains were biofilm producer, with high prevalence of atlE, and had potential of toxin production, with high prevalence of sea. According to the group-analyses, icaB showed relationship with the strong adherence in samples.
•Coagulase-negative Staphylococci isolated from bloodstream infections were biofilm producer and atlE gene the most frequent.•This group of microorganisms showed high frequency of genes encoding for toxin production, especially for sea gene.•Statistical analyses showed a relationship between icaB locus and strong adherence in polystyrene plates.
Aim: This study histologically analysed the effect of autogenous platelet‐rich plasma (PRP), prepared according to a new semiautomatic system, on healing of autogenous bone (AB) grafts placed in ...surgically created critical‐size defects (CSD) in rabbit calvaria.
Material and Methods: Sixty rabbits were divided into three groups: C, AB and AB/PRP. A CSD was created in the calvarium of each animal. In Group C (control), the defect was filled by blood clot only. In Group AB (autogenous bone graft), the defect was filled with particulate autogenous bone. In Group AB/PRP (autogenous bone graft with platelet‐rich plasma), it was filled with particulate autogenous bone combined with PRP. All groups were divided into subgroups (n=10) and euthanized at 4 or 12 weeks post‐operatively. Histometric and histologic analyses were performed. Data were statistically analysed (anova, t‐test, p<0.05).
Results: Group C presented significantly less bone formation compared with Group AB and AB/PRP in both periods of analysis (p<0.001). At 4 weeks, Group AB/PRP showed a statistically greater amount of bone formation than Group AB (64.44 ± 15.0%versus 46.88 ± 14.15%; p=0.0181). At 12 weeks, no statistically significant differences were observed between Groups AB and AB/PRP (75.0 ± 8.11%versus 77.90 ± 8.13%; p>0.05). It is notable that the amount of new bone formation in Group AB/PRP at 4 weeks was similar to that of Group AB at 12 weeks (p>0.05).
Conclusion: Within its limitation, the present study has indicated that (i) AB and AB/PRP significantly improved bone formation and (ii) a beneficial effect of PRP was limited to an initial healing period of 4 weeks.
This study aimed to assess diagnosis of Unique Health System (SUS) users profile with regard to herbal medicine. This is a cross-sectional study with observational data collection conducted in the ...city of Marechal Deodoro, through a semi-structured questionnaire with questions related to socioeconomic data, use, and knowledge of medicinal plants and herbal medicines and satisfaction with the use of medicinal herbs (MH) and interactions of phytotherapeutic drugs (PD). Among the topics, 86.89% of users used herbal medicines often, especially lemon balm (Melissa officinalis L.). It was also observed that the plants are generally used as a sedative (21.74%) and as tea (87.84%). 82.32% of respondents claim to have acquired the knowledge of herbal medicine through a family member and 85.36% make use of medicinal plants without having received any information on the use of MH and PD. 61% of the plants described that coincided with the form of use and therapeutic properties found in the literature. With regard to satisfaction by treatment with MH and PD, it was found that 56.67% are satisfied. Therefore, it is necessary to pay attention to this aspect of usage, in order to avoid possible drug interactions or adverse reactions resulting from the incorrect use.
We report on chemistry and cytotoxic studies of four new ruthenium (II) complexes containing uracil derivatives. All compounds are neutral, presenting the formula Ru(PPh3)2(2TU)2 (1), ...Ru(PPh3)2(6m2TU)2 (2), Ru(dppb)(2TU)2 (3) and Ru(dppb)(6m2TU)2 (4), where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane, 2TU = 2-thiouracil and 6m2TU = 6-methyl-2-thiouracil. They were characterized using NMR, UV–vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Furthermore, the crystal structures of 1–4 were determined by single-crystal X-ray diffraction. The coordination of 2-thiouracil derivatives with ruthenium increases regions able to carry out hydrogen bonds with the biological targets, such as DNA. We evaluated the interaction of the complexes with DNA by UV/Vis spectrophotometric titration, and as a result, the values of DNA-binding constants are in the range of 0.8–1.8 × 104 M−1. Moreover, the interaction of the complexes with BSA was investigated. In vitro, activities against B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), HL-60 (human promyelocytic leukemia) and K562 (human chronic myelocytic leukemia) and non-tumor cells: PBMC (human peripheral blood mononuclear cells activated with concanavalin A – human lymphoblast) were carried out. Cytotoxicity assays revealed that complexes (2) and (4) present biological activity against tumor cells comparable with oxaliplatin, the reference platinum drug, revealing that they are promising molecules for developing new antitumor compounds.
Uracil nucleobase analogs were used as key building blocks to form new cytotoxic agents based on Ru(II). These compounds are promising for anticancer treatment. Display omitted
•Synthesis of four Ru(II) complexes with thiouracil•The compounds are bioactives against tumor cells.•The complexes present ability to form strong hydrogen bonds.•The internucleosomal DNA fragmentation and cell cycle distribution was studied.
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