Kinins and their receptors have been implicated in a series of pathological alterations, representing attractive pharmacological targets for several diseases. The present review article aims to ...discuss the role of the kinin system in infectious diseases. Literature data provides compelling evidence about the participation of kinins in infections caused by diverse agents, including viral, bacterial, fungal, protozoan, and helminth-related ills. It is tempting to propose that modulation of kinin actions and production might be an adjuvant strategy for management of infection-related complications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Free fatty acid (FFA) receptors FFA1 and FFA4 are omega-3 molecular targets in metabolic diseases; however, their function in cancer cachexia remains unraveled. We assessed the role of FFA1 and FFA4 ...receptors in the mouse model of cachexia induced by Lewis lung carcinoma (LLC) cell implantation. Naturally occurring ligands such as α-linolenic acid (ALA) and docosahexaenoic acid (DHA), the synthetic FFA1/FFA4 agonists GW9508 and TUG891, or the selective FFA1 GW1100 or FFA4 AH7614 antagonists were tested. FFA1 and FFA4 expression and other cachexia-related parameters were evaluated. GW9508 and TUG891 decreased tumor weight in LLC-bearing mice. Regarding cachexia-related end points, ALA, DHA, and the preferential FFA1 agonist GW9508 rescued body weight loss. Skeletal muscle mass was reestablished by ALA treatment, but this was not reflected in the fiber cross-sectional areas (CSA) measurement. Otherwise, TUG891, GW1100, or AH7614 reduced the muscle fiber CSA. Treatments with ALA, GW9508, GW1100, or AH7614 restored white adipose tissue (WAT) depletion. As for inflammatory outcomes, ALA improved anemia, whereas GW9508 reduced splenomegaly. Concerning behavioral impairments, ALA and GW9508 rescued locomotor activity, whereas ALA improved motor coordination. Additionally, DHA improved grip strength. Notably, GW9508 restored abnormal brain glucose metabolism in different brain regions. The GW9508 treatment increased leptin levels, without altering uncoupling protein-1 downregulation in visceral fat. LLC-cachectic mice displayed FFA1 upregulation in subcutaneous fat, but not in visceral fat or gastrocnemius muscle, whereas FFA4 was unaltered. Overall, the present study shed new light on FFA1 and FFA4 receptors' role in metabolic disorders, indicating FFA1 receptor agonism as a promising strategy in mitigating cancer cachexia.
Brief psychodynamic psychotherapy has gained importance in current clinical practice. To achieve brevity, a focus must be established and worked through. Different conceptualizations have emphasized ...the relational patterns and/or conflict foci as central but adopting a mono-schematic approach. However, patients come to treatment with more than one issue that must be addressed. Thus, another focus must be included because of its relevance, i.e., personality functioning. The aims of this study were to identify the presence and depth level of three foci (relational pattern, conflict, and personality functioning) in episodes of change throughout the process, and to evaluate the relationship of each focus with the complexity of patients’ change. Initial OPD foci and the presence and depth of each were evaluated in 13 successful brief psychodynamic therapies. Change episodes of those therapies were analyzed as well. Results showed differences between foci in the initial phase with a higher presence of conflict focus. Throughout the process, only the presence and level of personality functioning improved. Also, complexity of patients’ change was related to conflict focus, specifically on the emergence of competence feelings. The results provide evidence and enrich process research of brief psychodynamic therapies.
Generalized pain and fatigue are both hallmarks of fibromyalgia, a syndrome with an indefinite etiology. The treatment options for fibromyalgia are currently limited, probably because of its ...intricate pathophysiology. Thus, further basic and clinical research on this condition is currently needed. This study investigated the effects of nociceptin/orphanin FQ (N/OFQ) receptor (NOPr) ligands and the modulation of the NOP system in the preclinical mouse model of reserpine-induced fibromyalgia. The effects of administration of the natural agonist N/OFQ and the selective NOPr antagonists (UFP-101 and SB-612111) were evaluated in fibromyalgia-related symptoms in reserpine-treated mice. The expression of prepronociceptin/orphanin FQ and NOPr was assessed in central and peripheral sites at different time points after reserpine administration. Nociceptin/orphanin FQ displayed dual effects in the behavioral changes in the reserpine-elicited fibromyalgia model. The peptide NOPr antagonist UFP-101 produced analgesic and antifatigue effects, by preventing alterations in brain activity and skeletal muscle metabolism, secondary to fibromyalgia induction. The nonpeptide NOPr antagonist SB-612111 mirrored the favorable effects of UFP-101 in painful and fatigue alterations induced by reserpine. A time-related up- or downregulation of prepronociceptin/orphanin FQ and NOPr was observed in supraspinal, spinal, and peripheral sites of reserpine-treated mice. Our data shed new lights on the mechanisms underlying the fibromyalgia pathogenesis, supporting a role for N/OFQ-NOP receptor system in this syndrome.
Purpose
To assess the association between acute disease severity and 1-year quality of life in patients discharged after hospitalisation due to coronavirus disease 2019 (COVID-19).
Methods
We ...conducted a prospective cohort study nested in 5 randomised clinical trials between March 2020 and March 2022 at 84 sites in Brazil. Adult post-hospitalisation COVID-19 patients were followed for 1 year. The primary outcome was the utility score of EuroQol five-dimension three-level (EQ-5D-3L). Secondary outcomes included all-cause mortality, major cardiovascular events, and new disabilities in instrumental activities of daily living. Adjusted generalised estimating equations were used to assess the association between outcomes and acute disease severity according to the highest level on a modified ordinal scale during hospital stay (2: no oxygen therapy; 3: oxygen by mask or nasal prongs; 4: high-flow nasal cannula oxygen therapy or non-invasive ventilation; 5: mechanical ventilation).
Results
1508 COVID-19 survivors were enrolled. Primary outcome data were available for 1156 participants. At 1 year, compared with severity score 2, severity score 5 was associated with lower EQ-5D-3L utility scores (0.7 vs 0.84; adjusted difference, − 0.1 95% CI − 0.15 to − 0.06); and worse results for all-cause mortality (7.9% vs 1.2%; adjusted difference, 7.1% 95% CI 2.5%–11.8%), major cardiovascular events (5.6% vs 2.3%; adjusted difference, 2.6% 95% CI 0.6%–4.6%), and new disabilities (40.4% vs 23.5%; adjusted difference, 15.5% 95% CI 8.5%–22.5). Severity scores 3 and 4 did not differ consistently from score 2.
Conclusions
COVID-19 patients who needed mechanical ventilation during hospitalisation have lower 1-year quality of life than COVID-19 patients who did not need mechanical ventilation during hospitalisation.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
: Qualidade de Vida Relacionada à Saúde e Desfechos em Longo Prazo após COVID-19 Sintomática Leve: Protocolo do Estudo Pós-COVID Brasil 2
Delineamento do estudo Pós-COVID Brasil 2.
Infection and dysbiosis present a close relationship with metabolic diseases although the influence of apical periodontitis (AP) in this context needs further investigation. This study evaluated the ...influence of AP in a rat model of metabolic syndrome induced by 10% fructose supplementation.
Male Wistar rats were used. Animals that received a high-fructose diet (HFD, n = 30) or filtered water (control, n = 30) were subdivided into the following groups:
(1) without induction of AP (no AP, n = 10 each),
(2) with AP induction 2 weeks before euthanasia (AP 14 days, n = 10 each), and
(3) with AP induction 4 weeks before euthanasia (AP 28 days, n = 10 each).
HFD triggered metabolic syndrome, as indicated by the induction of overweight and hyperglycemia, besides polydipsia, regardless of the AP induction. Serum or intestinal tumor necrosis factor, interleukin 1 beta, and interleukin 6 levels were undetectable, regardless of the experimental group. Serum leptin and adiponectin levels were significantly elevated in the HFD group without AP induction. The intestinal levels of leptin were significantly increased in the groups with 28 days of AP induction despite HFD. A significant elevation of liver glutathione levels was observed in animals submitted to HFD and AP for 14 days. AP induction (14 or 28 days) led to pulp and periapical tissue inflammation without any influence of HFD. Either HFD or AP induction led to dysbiosis, as indicated by a significant reduction of fecal A. muciniphila expression.
We provide novel evidence that AP can have systemic impacts on metabolic disorders, likely by modulating intestinal metabolism and microbiota.
•This is the first evidence showing that apical periodontitis (AP) induction alters the intestinal leptin levels.•This is the first experimental evidence showing the influence of AP on fecal Akkermansia muciniphila expression.•AP is able to alter systemic parameters related to metabolic disorders, by showing that AP per se leads to intestinal leptinemia and dysbiosis;•HFD-induced metabolic changes did not appear to modulate AP progression.
BACKGROUNDThe long-term effects of mild COVID-19 on physical, cognitive, and mental health are not yet well understood. OBJECTIVEThe purpose of this paper is to describe the protocol for the ongoing ..."Post-COVID Brazil" study 2, which aims to evaluate the factors associated with health-related quality of life and long-term cardiovascular and non-cardiovascular outcomes one year after a mild episode of symptomatic COVID-19. METHODSThe "Post-COVID Brazil" study 2 is a prospective multicenter study that plans to enroll 1047 patients (NCT05197647). Centralized, structured telephone interviews are conducted at 1, 3, 6, 9, and 12 months after COVID-19 diagnosis. The primary outcome is the health-related quality-of-life utility score, assessed using the EuroQol-5D-3L (EQ-5D-3L) questionnaire at 12 months. Secondary endpoints include the EQ-5D-3L at 3, 6, and 9 months, as well as all-cause mortality, major cardiovascular events, hospitalization, return to work or education, persistent symptoms, new disabilities in instrumental activities of daily living, cognitive impairment, anxiety, depression, and post-traumatic stress symptoms at 3, 6, 9, and 12 months after SARS-CoV-2 infection. A p-value < 0.05 will be considered statistically significant for all analyses. RESULTSThe primary endpoint will be presented as the overall frequency of the EQ-5D-3L domains 12 months after SARS-CoV-2 infection. Main analysis will explore the association of independent variables with the study outcomes. CONCLUSIONThe "Post-COVID Brazil" study 2 aims to clarify the impact of long COVID on the quality of life and cardiovascular and non-cardiovascular outcomes of Brazilian patients who have had mild COVID-19.
Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), ...isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1-3 at concentrations 1-100 µm for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1-3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 Σ fractional inhibitory concentration (FIC) = 0.41, and 2 and 3 (ΣFIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.
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