Search

Background: Although Charcot diabetic foot (CDF) is a frequent complication of diabetic neuropathy, less is known about the possibility of its early prevention. Methods: A review of the original articles published in English, using the “biomarkers AND Charcot’s foot” criterion, resulted in 33 articles from the PubMed database and seven articles from the Web of Science database. The five duplicates were eliminated, and two independent reviewers selected the most relevant articles, leaving a total of 21 articles. Results: The biomarkers identified are exhaustively described, related to the system of advanced glycation end products (AGEs) and their soluble receptors (sRAGE), inflammatory cascade, osteoclastogenesis, and, respectively, osteoblastic activity. Conclusions: This article highlights the importance of potential early identifiable biomarkers that can lead to microstructural changes in the affected bones.

Annona muricata Linn. is a common plant found in the warmest regions of South and Central America and its use in traditional medicine has been reported for the treatment of various illnesses. In the current study, we investigate the antioxidant and anti-inflammatory activities of crude extract and fractions from A. muricata L. leaves in isolated murine phagocytic immune cells as well as experimental LPS-induced acute lung injury (ALI). In a luminol-dependent chemiluminescence assay, we showed that ethyl acetate (EtOAc.f) and n-butanol (BuOH.f) fractions—both rich in polyphenols—reduced the generation of reactive oxygen species (ROS) by neutrophils stimulated with opsonized zymosan; similar results were found in culture of bone marrow-derived macrophages (BMDMs). By evaluating anti-inflammatory activity in BMDMs, EtOAc.f and BuOH.f reduced secretion of IL-6 and expression of the co-stimulatory molecule CD40. Furthermore, in LPS-induced ALI, oral administration of EtOAc.f reduced myeloperoxidase (MPO) activity in lung tissue. In addition, on a mechanism dependent on glutathione levels, the oxidative damage was also attenuated. These findings revealed direct antioxidant and anti-inflammatory activities of polyphenols-rich fractions of A. muricata L. leaves on neutrophils and macrophages. Moreover, the reduced oxidative damage and levels of inflammatory markers in experimental ALI suggest that these fractions might be explored for the development of new therapies for inflammatory conditions. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic non-transmittable disease and, alongside periodontal disease, another chronic disease, but with infectious and inflammatory etiology, that have increasing prevalence. The link between the two comorbidities is bidirectional, with common aspects such the inflammatory state, altered immune response and healing process. This link is alimented, also, by oxidative stress, an element that can initiate proinflammatory pathways in both pathologies. Moreover, periodontal disease favors the development of DM complications by a multifactorial mechanism centered on hyperglycemia, that leads to damage of the endothelial vascular cells, characteristic for microvascular complications, while the periodontal bacteria and their waste products, and inflammatory cytokines lead to an increase in systemic inflammation and damage of the vascular walls that aggravates the atherogenic process. The increase of novel cases of type 2 DM or gestational DM in patients with periodontitis has no sufficient data. Dental caries is favored by DM and not by periodontal disease. So, DM is a well-known risk factor for periodontal disease and, on the other hand, periodontitis influences the metabolic control and favors the development of DM complications, but with a link between these conditions that is not fully understood. Other comorbidities, such as missing teeth, depression, osteoporosis are, also, positively associated to higher risk of development for periodontal disease. Patients with DM should be regularly screened for periodontal disease and referred to therapy if necessary, while the patients with periodontal disease should be screened for the presence of DM. [ABSTRACT FROM AUTHOR]

Respiratory infection can be exacerbated by the high glucose concentration in the airway surface liquid (ASL). We investigated the effects of salbutamol and phlorizin on the pulmonary function, oxidative stress levels and SGLT1 activity in lung, pulmonary histopathological damages and survival rates of rats with sepsis. Sepsis was induced by cecal ligation and puncture surgery (CLP). Twenty-four hours after surgery, CLP rats were intranasally treated with saline, salbutamol or phlorizin. After 2 hours, animals were anesthetized and sacrificed. Sepsis promoted atelectasis and bronchial inflammation, and led to increased expression of SGLT1 on cytoplasm of pneumocytes. Salbutamol treatment reduced bronchial inflammation and promoted hyperinsuflation in CLP rats. The interferon-ɤ and Interleucin-1β concentrations in bronchoalveolar lavage (BAL) were closely related to the bronchial inflammation regulation. Salbutamol stimulated SGLT1 in plasma membrane; whereas, phlorizin promoted the increase of SGLT1 in cytoplasm. Phlorizin reduced catalase activity and induced a significant decrease in the survival rate of CLP rats. Taken together, sepsis promoted atelectasis and lung inflammation, which can be associated with SGLT1 inhibition. The loss of function of SGLT1 by phlorizin are related to the augmented disease severity, increased atelectasis, bronchial inflammation and a significant reduction of survival rate of CLP rats. Alternatively salbutamol reduced BAL inflammatory cytokines, bronchial inflammation, atelectasis, and airway damage in sepsis. These data suggest that this selective β2-adrenergic agonist may protect lung of septic acute effects. [ABSTRACT FROM AUTHOR]

In 2017, the International Agency for Research on Cancer classified welding fumes as “carcinogenic to humans” (Group 1). Both mild steel (MS) welding, where fumes lack carcinogenic chromium and nickel, and stainless steel (SS) increase lung cancer risk in welders; therefore, further research to better understand the toxicity of the individual metals is needed. The objectives were to (1) compare the pulmonary toxicity of chromium (as Cr(III) oxide [Cr2O3] and Cr (VI) calcium chromate [CaCrO4]), nickel [II] oxide (NiO), iron [III] oxide (Fe2O3), and gas metal arc welding-SS (GMAW-SS) fume; and (2) determine if these metal oxides can promote lung tumors. Lung tumor susceptible A/J mice (male, 4–5 weeks old) were exposed by oropharyngeal aspiration to vehicle, GMAW-SS fume (1.7 mg), or a low or high dose of surrogate metal oxides based on the respective weight percent of each metal in the fume: Cr2O3 + CaCrO4 (366 + 5 μg and 731 + 11 μg), NiO (141 and 281 μg), or Fe2O3 (1 and 2 mg). Bronchoalveolar lavage, histopathology, and lung/liver qPCR were done at 1, 7, 28, and 84 days post-aspiration. In a two-stage lung carcinogenesis model, mice were initiated with 3-methylcholanthrene (10 μg/g; intraperitoneal; 1x) or corn oil then exposed to metal oxides or vehicle (1 x/week for 5 weeks) by oropharyngeal aspiration. Lung tumors were counted at 30 weeks post-initiation. Results indicate the inflammatory potential of the metal oxides was Fe2O3 > Cr2O3 + CaCrO4 > NiO. Overall, the pneumotoxic effects were negligible for NiO, acute but not persistent for Cr2O3 + CaCrO4, and persistent for the Fe2O3 exposures. Fe2O3, but not Cr2O3 + CaCrO4 or NiO significantly promoted lung tumors. These results provide experimental evidence that Fe2O3 is an important mediator of welding fume toxicity and support epidemiological findings and the IARC classification. [ABSTRACT FROM AUTHOR]

Welding generates a complex aerosol of incidental nanoparticles and cytotoxic metals, such as chromium (Cr), manganese (Mn), nickel (Ni), and iron (Fe). The goal was to use bothin vivoandin vitromethodologies to determine the mechanisms by which different welding fumes may damage the lungs. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with 2.0 mg of gas metal arc-mild steel (GMA-MS) or manual metal arc-stainless steel (MMA-SS) fumes or saline (vehicle control). At 1, 3, and 10 days, bronchoalveolar lavage (BAL) was performed to measure lung toxicity. To assess molecular mechanisms of cytotoxicity, RAW264.7 cells were exposed to both welding fumes for 24 h (0–100 μg/ml). Fume composition was different: MMA-SS (41% Fe, 29% Cr, 17% Mn, 3% Ni) versus GMA-MS (85% Fe, 14% Mn). BAL indicators of lung injury and inflammation were increased by MMA-SS at all time points and by GMA-MS at 3 and 10 days after exposure. RAW264.7 cells exposed to MMA-SS had elevated generation of reactive oxygen species (ROS), protein-HNE (P-HNE) adduct formation, activation of ERK1/2, and expression of cyclooxygenase-2 (COX-2) compared to GMA-MS and control. Increased generation of ROS due to MMA-SS exposure was confirmed by increased expression of Nrf2 and heme oxygenase-1 (HO-1). Results ofin vitrostudies provide evidence that stainless steel welding fume mediate inflammatory responses via activation of ROS/P-HNE/ERK1/2/Nrf2 signaling pathways. These findings were corroborated by elevated expression of COX-2, Nrf2, and HO-1 in homogenized lung tissue collected 1 day afterin vivoexposure. [ABSTRACT FROM PUBLISHER]

The objective of this study is to evaluate the effect of interdisciplinary therapy in the parameters of the oxidative stress and the anti-inflammatory responses of obese adolescents. We selected 57 participants, who were randomly divided into 2 groups: interdisciplinary therapy group and a control group. After 6 months of intervention, 17 participants of the interdisciplinary therapy group and 8 of the control group returned for re-evaluation. The interdisciplinary therapy group participated in a treatment with 4 weekly sessions of exercise, a weekly group therapy session and a weekly nutritional education session. Blood parameters of oxidative stress and anti-inflammatory response were evaluated. The results demonstrated that there were significant increases in the interdisciplinary therapy group for superoxide dismutase activity (6.56 ± 3.22 to 11.40 ± 7.49) and ferric-reducing antioxidant potential concentration (532.91 ± 106.48 to 573.25 ± 112.57), although adiponectin levels did not reduce (40.9 ± 29.34 to 49.05 ± 41.22). A significant decrease in nitrite levels was also found (14.23 ± 8.48 to 11.45 ± 6.05). In the control group, significant reduction was found in adiponectin (31.56 ± 18.88 to 18.01 ± 11.66). This study suggests that interdisciplinary therapy for 6 months was effective in improving the anti-inflammatory responses and the antioxidant defences in obese adolescents. [ABSTRACT FROM PUBLISHER]

Multiple sclerosis (MS) as a chronic neuro-inflammatory and neurodegenerative disease of the central nervous system is frequently associated with severe disability and impairment in quality of life. Early disease-modifying treatment options have mainly focused on inflammatory aspects of the disease. Recently, the neurodegenerative features have received more attention in experimental models, paraclinical assessments and the evaluation of drug effects. Fumaric acid esters (FAEs) as orally available immunomodulatory and neuroprotective compounds have thus advanced to a highly interesting MS treatment option. Here, we will review the pharmaceutical history of FAEs, their immunomodulatory and putative neuroprotective mechanisms of action and clinical trial data in relapsing MS. [ABSTRACT FROM AUTHOR]

Background: Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc -- stainless steel (GMA-SS) welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. Results: The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10). In addition, pulmonary expression of interferon α and β and Irf7 specific pattern recognition receptors (PRR) and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3) were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88) to inhalation of GMA-SS. Conclusion: This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure. [ABSTRACT FROM AUTHOR]

Abstract: Welding results in a unique and complex occupational exposure. Recent epidemiological studies have shown an increased risk of cardiovascular disease following welding fume exposure. In this study, we compared the induction of pulmonary and systemic inflammation following exposure to multiple types of welding fumes. Mice were exposed to 340μg of manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS) by pharyngeal aspiration. Mice were sacrificed at 4 and 24h post-exposure to evaluate various parameters of pulmonary and systemic inflammation. Alterations in pulmonary gene expression by a custom designed TaqMan array showed minimal differences between the fumes at 4h. Conversely at 24h, gene expression changes were further increased by SS but not GMA-MS exposure. These findings were associated with the surrogate marker of systemic inflammation, liver acute phase gene induction. Interestingly, stress response genes in cardiovascular tissues were only increased following MMA-SS exposure. These effects were related to the initial level of pulmonary cytotoxicity, as measured by lactate dehydrogenase activity, which was greatest following MMA-SS exposure. In conclusion, varying types of welding fumes elicit quantitatively different systemic inflammatory and/or stress responses. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to compare the effects of 3 different modalities of exercise on metabolic control, insulin resistance, inflammatory markers, adipocytokines, and tissue expression of insulin receptor substrate (IRS)–1 after 12 weeks of training among patients with type 2 diabetes mellitus. Forty-eight patients with type 2 diabetes mellitus were randomly assigned to 4 groups of training (3 times a week, 60 minutes per session): aerobic group (n = 12), resistance group (n = 12), combined (aerobic and resistance) group (n = 12), and control group (n = 12). Fasting and postprandial blood glucose, glycated hemoglobin, lipid profile, insulin resistance index (homeostasis model assessment of insulin resistance), adipocytokines (adiponectin, visfatin, and resistin), tumor necrosis factor, interleukin, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline and at the end of the study. Patients also underwent a muscle microbiopsy before and after training to quantify IRS-1 expression. All 4 groups displayed decreases in blood pressure, fasting plasma glucose, postprandial plasma glucose, lipid profile, and hs-CRP (P < .05); and there was no difference across the groups. After training, the IRS-1 expression increased by 65% in the resistance group (P < .05) and by 90% in the combined group (P < .01). Exercise training favorably affects glycemic parameters, lipid profile, blood pressure, and hs-CRP. In addition, resistance and combined training can increase IRS-1 expression. [Copyright &y& Elsevier]

Abstract: Epidemiological studies suggest that welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) welding fume exposure. Apolipoprotein E knockout (apoE−/−) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m3 for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE−/− mice. These results complement epidemiological and functional human studies that suggest welding may result in adverse cardiovascular effects. [Copyright &y& Elsevier]

Abstract Welding fumes were reclassified as a Group 1 carcinogen by the International Agency for Research on Cancer in 2017. Gas metal arc welding (GMAW) is a process widely used in industry. Fume generated from GMAW-mild steel (MS) is abundant in iron with some manganese, while GMAW-stainless steel (SS) fume also contains significant amounts of chromium and nickel, known carcinogenic metals. It has been shown that exposure to GMAW-SS fume in A/ J mice promotes lung tumors. The objective was to determine if GMAW-MS fume, which lacks known carcinogenic metals, also promotes lung tumors in mice. Male A/ J mice received a single intraperitoneal injection of corn oil or the initiator 3-methylcholanthrene (MCA; 10 μg/g) and, one week later, were exposed by whole-body inhalation to GMAW-MS aerosols for 4 hours/day x 4 days/week x 8 weeks at a mean concentration of 34.5 mg/m3. Lung nodules were enumerated by gross examination at 30 weeks post-initiation. GMAW-MS fume significantly increased lung tumor multiplicity in mice initiated with MCA (21.86 ± 1.50) compared to MCA/air-exposed mice (8.34 ± 0.59). Histopathological analysis confirmed these findings and also revealed an absence of inflammation. Bronchoalveolar lavage analysis also indicated a lack of lung inflammation and toxicity after short-term inhalation exposure to GMAW-MS fume. In conclusion, this study demonstrates that inhalation of GMAW-MS fume promotes lung tumors in vivo and aligns with epidemiologic evidence that shows MS welders, despite less exposure to carcinogenic metals, are at an increased risk for lung cancer. [ABSTRACT FROM AUTHOR]

Gout is an inflammatory disease characterized by the accumulation of monosodium urate crystals (MSU) in the joints, leading to severe pain and inflammation. Stephalagine is a Brazilian Savanna aporphine alkaloid isolated from Annona crassiflora Mart. Fruit peel, that has been popularly used to treat rheumatism and have been described with antinociceptive properties. However, no studies evaluated the possible therapeutic properties of stephalagine in arthritic pain. To evaluate the possible antinociceptive and anti-inflammatory effects of stephalagine in an acute gout attack in mice. Adult male wild type C57BL/6/J/UFU mice (20–25 g) were used (process number 018/17). The treated group received stephalagine (1 mg/kg, by gavage) and the vehicle group received saline (10 mL/kg, by gavage), both 1 h before the MSU crystals (100 μg/ankle joint) administration. All groups were analyzed for mechanical allodynia, thermal hyperalgesia, overt pain-like behaviors, and edema development at 2, 4, 6 and 24 h after injections. Synovial fluid and the ankle articulation from the injected joint were collected 4 h after administrations for myeloperoxidase enzyme activity, IL-1β measurement, and histological analysis. Stephalagine had a significant antinociceptive effect on mechanical allodynia, when compared to vehicle group at 2–24 h after intra-articular injection of MSU and 2 h for spontaneous and cold thermal sensitivity. Stephalagine was also able to significantly reduce the articular edema (45 ± 1%), the activity of the myeloperoxidase enzyme (37 ± 6%), and IL-1β levels (43 ± 3%). The histological analysis confirms that stephalagine dramatically reduced the number of infiltrating inflammatory cells (75 ± 6%) in MSU injected animals. Also, stephalagine treatment did not alter the uric acid levels, xanthine oxidase activity, AST and ALT activities, urea and creatinine levels, neither cause any macroscopic changes in the mice's weight, deformations, changes in the coat, or feces. Stephalagine may be an alternative for the management of gout, once it was able to induce antinociceptive and anti-inflammatory effects without causing adverse effects on the evaluated parameters. [Display omitted] • Alkaloids are used to treat a variety of painful conditions such as gout. • Stephalagine is an aporphine alkaloid purified from Annona crassiflora mart. • Stephalagine oral treatment has anti-nociceptive and anti-inflammatory effects. • Stephalagine oral treatment does not induce kidney or liver damage in mice. • Stephalagine may be a promising therapeutic option to treat gout. [ABSTRACT FROM AUTHOR]

[Display omitted] Silver nanoparticles (Ag-NPs), silver oxide nanoparticles (AgO-NPs), and zinc oxide nanoparticles (ZnO-NPs) have healing, antibacterial, and antioxidant properties. Furthermore, Ag-NPs and ZnO-NPs also have anti-inflammatory properties. In this study, we synthesized a nanocomposite using Ag-ZnO and AgO-NPs (Ag-ZnO/AgO NPs). The structural and morphological properties of nanocrystals and nanocomposite were investigated by X-ray diffraction and scanning electronics microscopic. The wurtzite crystalline structure of Ag-ZnO and two morphologies for the nanocomposite (nanorods and nanoplatelets) were determined. Topical treatment with 1% Ag-ZnO/AgO NPs was compared to untreated wounds (control group). Wounds were induced in the dorsal region of BALB/c mice and evaluated after 3, 7, 14, and 21 days of treatment. The nanocomposite demonstrated anti-inflammatory and antioxidant capacities. In addition, wounds treated with Ag-ZnO/AgO NPs showed accelerated closure, non-cytotoxicity, especially on keratinocytes and collagen deposition, and increased metalloproteinases 2 and 9 activity. The nanocomposite improved healing by reducing the inflammatory process, protecting tissues from damage caused by free radicals, and increasing collagen deposition in the extracellular matrix. These characteristics contributed to the accelerated wound closure process. Thus, Ag-ZnO/AgO NPs show potential for can be a strategy for topical use in formulations of new drugs to treat wounds. [ABSTRACT FROM AUTHOR]

Sulfadiazine and pyrimethamine are the two drugs used as part of the standard therapy for toxoplasmosis, however; they may cause adverse side effects and fail to prevent relapse in many patients, rendering infected individuals at risk of reactivation upon becoming immunocompromised. Extracts from various parts of Annona muricata have been widely used medicinally for the management, control and/or treatment of several human diseases, acting against parasites that cause diseases in humans. This study was performed to investigate the action of the ethanolic extract of A. muricata (EtOHAm) and its fractions in the control of the apicomplexan parasite Toxoplasma gondii in vitro and in vivo , and the effect of EtOHAm on the inflammatory response and lipid profile alteration induced by in vivo T. gondii infection. The cytotoxicity of EtOHAm and its fractions ethyl acetate (EtOAcAm), n -butanol (BuOHAm), aqueous (H 2 OAm), hexane (HexAm) and dichloromethane (CH 2 Cl 2 Am) was evaluated in NIH/3T3 fibroblasts using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cells were infected with T. gondii , treated with the extracts, and parasite proliferation was analyzed. For the in vivo experiments, C57BL/6 mice were orally infected with T. gondii and, treated with different concentrations of extract fractions that were effective in vitro (EtOHAm, EtOAcAm, HexAm and CH 2 Cl 2 Am). Tissue parasitism, histological alterations, systemic cytokine and lipid profile were investigated. EtOHAm, EtOAcAm, BuOHAm, H 2 OAm presented low cytotoxicity until doses of 200 μg/mL, while HexAm and CH 2 Cl 2 Am presented toxicity from doses of 100μg/mL. EtOHAm, HexAm and CH 2 Cl 2 Am decreased the parasitism in vitro , presenting a therapeutic index of 2.62, 2.44, and 2.96, respectively. In vivo , EtOHAm, HexAm and CH 2 Cl 2 Am improved the survival rate of infected animals, however, only EtOHAm was able to decrease the parasitism in the small intestine and lung. Additionally, EtOHAm decreased the systemic interferon (IFN)-γ and tumor necrosis factor (TNF) systemically in infected mice, and was able to maintain the triglycerides and very-low-density lipoprotein (VLDL) lipid fractions at similar levels to uninfected animals. Although treatment with EtOHAm could not control the inflammation induced by oral infection in the tissues analyzed, it was able to preserve the number of goblet cells in the small intestine. Ethanolic A. muricata leaf extract could be considered as a good candidate for the development of a complementary/alternative therapy against toxoplasmosis, and also as an anti-inflammatory alternative for decreasing TNF and IFN-γ concentrations and lipid fractions in specific diseases. [Display omitted] [ABSTRACT FROM AUTHOR]