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OBJECTIVES: To investigate coronavirus disease 2019 (COVID-19)-associated risk of hospitalization and death in RA, AS, PsA, SLE and SSc in comparison with the general population during the first year of the pandemic, and compare their overall mortality with 2019. METHODS: Interlinking nationwide electronic registries, we recorded confirmed COVID-19-associated infections, hospitalizations and deaths, and all-cause deaths between 1 March 2020 and 28 February 2021 in all adults with RA, AS, PsA, SLE and SSc under treatment (n = 74 970, median age 67.5, 51.2, 58.1, 56.2 and 62.2 years, respectively) and in random comparators from the general population matched (1:5) on age, sex and region of domicile. Deaths from all causes during 2019 were also recorded. RESULTS: Compared with the general population, incidence rates (IR) for COVID-19-associated hospitalization were higher in RA [IR ratio (IRR) 1.71(1.50-1.95)], SLE [2.0 (1.4-2.7)] and SSc [2.28 (1.29-3.90)], while COVID-19-associated death rates were higher in RA [1.91 (1.46-2.49)]. When focusing only on severe acute respiratory syndrome coronavirus 2-infected subjects, after adjusting for age and gender, the odds ratio for COVID-19 associated death was higher in RA [1.47 (1.11-1.94)] and SSc [2.92 (1.07-7.99)] compared with the general population. The all-cause mortality rate compared with the general population increased in RA during the first year of the pandemic (IRR 0.71) with reference to 2019 (0.59), and decreased in SSc (IRR 1.94 vs 4.36). CONCLUSION: COVID-19 may have a more severe impact in patients with systemic rheumatic disease than in the general population. COVID-19-related mortality is increased in subgroups of patients with specific rheumatic diseases, underscoring the need for priority vaccination and access to targeted treatments.
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Artrite Psoriásica , Artrite Reumatoide , COVID-19 , Lúpus Eritematoso Sistêmico , Doenças Reumáticas , Adulto , Humanos , Artrite Reumatoide/epidemiologia , Estudos de Coortes , Doenças Reumáticas/epidemiologiaRESUMO
BACKGROUND: Hydroxytyrosol reduces low-density lipoprotein oxidation, contributing to prevention of atherosclerosis progression. METHODS: In a prospective, crossover, double-blind, placebo-controlled trial, 30 chronic coronary artery syndrome (CCAS) patients were randomized to 4 capsules/day, containing 412.5 mg olive oil with 2.5 mg hydroxytyrosol (OOHT) each one or placebo for 1 month and then were crossed over to the alternate treatment (placebo or OOHT). We measured (a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b) flow-mediated dilation (FMD), (c) Coronary Flow Reserve (CFR) and markers of LV diastolic function by Doppler echocardiography, (d) pulse wave velocity (PWV), and (e) oxidative stress, inflammatory biomarkers and blood lipids at baseline and after treatment. RESULTS: Treatment with OOHT improved PBR, FMD, CFR and PWV compared to baseline (1.8 ± .3 vs. 1.7 ± .4 µm, p = .040, 3.7 ± 2.1 vs. 6.5% ± 2.3%, p < .001, 2.3 ± .4 vs. 2.5 ± .4, p = .030 and 11.1 ± 1.8 vs. 11.8 ± 2.3 m/s, p = .002) while there was no effect after placebo (p = NS). No effect of OOHT treatment was observed on blood pressure. There was a parallel improvement of E' of the mitral annulus and deceleration time of the E wave of mitral inflow after OOHT (p < .05) but not after placebo. Compared to baseline, treatment with OOHT reduced malondialdehyde, a marker of lipid peroxidation, oxidized LDL, triglycerides, PCSK9 and CRP blood levels (p < .05) in contrast to placebo. CONCLUSIONS: Hydroxytyrosol-enriched olive oil may have beneficial effects on endothelial, arterial and LV diastolic function likely by reducing oxidative and inflammatory burden in CCAS, though further studies are needed to confirm this mechanism.
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Doença das Coronárias , Cardiopatias , Humanos , Pró-Proteína Convertase 9 , Azeite de Oliva , Análise de Onda de Pulso , Estudos ProspectivosRESUMO
Oral iron supplementation is the cornerstone for the management of iron-deficiency anemia. A new oral formulation of iron conjugated with N-aspartyl-casein (Fe-ASP) (Omalin®, Uni-Pharma) is studied in the ACCESS double-blind, double-dummy randomized clinical trial; 60 patients were randomized to 12-week oral treatment twice every day either with oral ferrous sulfate (FeSO4) delivering 47 mg elementary iron or oral Fe-ASP delivering 40 mg elementary iron. Participants had hemoglobin less than 10 g/dl, decreased red blood cell (RBC) count, and ferritin lower than 30 ng/ml; patients with a medical history of malignancy were excluded. The primary endpoint was the increase of Hb in the first 4 weeks of treatment, and the study was powered for non-inferiority. A new score of global improvement was introduced where all participants were given one point for any at least 10% increase of Hb, RBC, and reticulocytes. At week 4, the mean (SE) change of Hb was 0.76 g/dl in the FeSO4 group and 0.83 g/dl in the Fe-ASP group (p: 0.876). The odds for worse allocation of the global score were 0.35 in the Fe-ASP group compared to the FeSO4 group. Patients in the Fe-ASP group experienced a significant decrease in the number of IDA-related physical signs by week 4. No differences were found between the two groups in any of the patient-reported outcomes of fatigue and of gastrointestinal adverse events either at week 4 or at week 12. ACCESS is the most recent clinical trial showing the non-inferiority of Fe-ASP to FeSO4 for the primary endpoint of the Hb change.
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Anemia Ferropriva , Ferro , Humanos , Ferro/uso terapêutico , Anemia Ferropriva/tratamento farmacológico , Caseínas/uso terapêutico , Ferritinas , Hemoglobinas/análiseRESUMO
Periodontitis is a microbially-induced inflammation of the periodontium that is characterized by the destruction of the periodontal ligament (PDL) and alveolar bone and constitutes the principal cause of teeth loss in adults. Periodontal tissue regeneration can be achieved through guided tissue/bone regeneration (GTR/GBR) membranes that act as a physical barrier preventing epithelial infiltration and providing adequate time and space for PDL cells and osteoblasts to proliferate into the affected area. Electrospun nanofibrous scaffolds, simulating the natural architecture of the extracellular matrix (ECM), have attracted increasing attention in periodontal tissue engineering. Carrageenans are ideal candidates for the development of novel nanofibrous GTR/GBR membranes, since previous studies have highlighted the potential of carrageenans for bone regeneration by promoting the attachment and proliferation of osteoblasts. Herein, we report the development of bi- and tri-layer nanofibrous GTR/GBR membranes based on carrageenans and other biocompatible polymers for the regeneration of periodontal tissue. The fabricated membranes were morphologically characterized, and their thermal and mechanical properties were determined. Their periodontal tissue regeneration potential was investigated through the evaluation of cell attachment, biocompatibility, and osteogenic differentiation of human PDL cells seeded on the prepared membranes.
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Nanofibras , Osteogênese , Adulto , Humanos , Carragenina/farmacologia , Sulfatos , Membranas Artificiais , Periodonto , Regeneração ÓsseaRESUMO
Acute respiratory distress syndrome (ARDS) is a highly morbid inflammatory lung disease with limited pharmacological interventions. The present study aims to evaluate and compare the potential pulmonoprotective effects of natural prolyl oligopeptidase (POP) inhibitors namely rosmarinic acid (RA), chicoric acid (CA), epigallocatechin-3-gallate (EGCG) and gallic acid (GA), against lipopolysaccharide (LPS)-induced ARDS. Cell viability and expression of pro-inflammatory mediators were measured in RAW264.7 cells and in primary murine lung epithelial and bone marrow cells. Nitric oxide (NO) production was also assessed in unstimulated and LPS-stimulated RAW264.7 cells. For subsequent in vivo experiments, the two natural products (NPs) with the most favorable effects, RA and GA, were selected. Protein, cell content and lipid peroxidation levels in bronchoalveolar lavage fluid (BALF), as well as histopathological changes and respiratory parameters were evaluated in LPS-challenged mice. Expression of key mediators involved in ARDS pathophysiology was detected by Western blotting. RA and GA favorably reduced gene expression of pro-inflammatory mediators in vitro, while GA decreased NO production in macrophages. In LPS-challenged mice, RA and GA co-administration improved respiratory parameters, reduced cell and protein content and malondialdehyde (MDA) levels in BALF, decreased vascular cell adhesion molecule-1 (VCAM-1) and the inducible nitric oxide synthase (iNOS) protein expression, activated anti-apoptotic mechanisms and down-regulated POP in the lung. Conclusively, these synergistic pulmonoprotective effects of RA and GA co-administration could render them a promising prophylactic/therapeutic pharmacological intervention against ARDS.
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Produtos Biológicos , Síndrome do Desconforto Respiratório , Animais , Camundongos , Prolil Oligopeptidases , Lipopolissacarídeos/toxicidade , Síndrome do Desconforto Respiratório/tratamento farmacológico , Inibidores Enzimáticos , Ácido Gálico , Mediadores da InflamaçãoRESUMO
Hot flashes are considered the most bothersome complaint during menopause. Although hormone therapy is an effective option to relieve hot flashes, it has been associated with significant side effects. The aim of our study is to suggest a novel combination of different plant extracts with distinct mechanisms of action against hot flashes. We selected the rhizome of Glycyrrhiza glabra L. (Fabaceae), the rhizome of Actaea racemosa L. (Ranunculaceae), the aerial parts of Hypericum perforatum L. (Hypericaceae) to produce extracts rich in bioactive phytochemicals and the seed oil of Oenothera biennis L. (Onagraceae). We investigated their estrogenic and antioxidant potential and their inhibitory effect against prostaglandin D2 receptor 1 (DP1) as a novel mechanistic pathway for vasodilation in hot flashes, alone or in combination. The phytochemical footprint of the extracts was analyzed using HPLC-PDA and UPLC-HRMS. We observed that the tested extracts possess different mechanisms of action. A. racemosa exerts a beneficial activation of the estrogen receptor, H. perforatum possesses the highest antioxidant capacity and the seed oil of O. biennis inhibits the DP1 receptor. The triple combination in the optimal doses pertains to efficacy against all three mechanisms of action, serves as a multitarget plant-based therapy and could serve as a novel strategy for the alleviation of hot flashes in postmenopausal women.
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Fogachos/tratamento farmacológico , Menopausa , Extratos Vegetais/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Linhagem Celular Tumoral , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Estrogênios/química , Estrogênios/farmacologia , Humanos , Menopausa/efeitos dos fármacos , Pessoa de Meia-Idade , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Prostaglandinas/metabolismoRESUMO
AIM: No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. METHODS: Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. RESULTS: During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported. CONCLUSIONS: The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism.
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Acetaminofen/administração & dosagem , Antipiréticos/administração & dosagem , Febre/tratamento farmacológico , Infecções/complicações , Acetaminofen/farmacocinética , Acetaminofen/uso terapêutico , Administração Intravenosa , Adulto , Idoso , Antipiréticos/farmacocinética , Antipiréticos/uso terapêutico , Método Duplo-Cego , Feminino , Febre/etiologia , Seguimentos , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do TratamentoRESUMO
Clinical studies have previously established the role of olive products in cardiovascular disease (CVD) prevention, whilst the identification of the responsible constituents for the beneficial effects is still pending. We sought to assess and compare the cardioprotective potential of oleuropein (OL), hydroxytyrosol (HT), oleocanthal (OC) and oleanolic Acid (OA), regarding Ischemia/Reperfusion Injury (IRI) and CVD risk factors alleviation. The scope of the study was to design a potent and safe combinatorial therapy for high-cardiovascular-risk patients on a bench-to-bedside approach. We evaluated the IRI-limiting potential of 6-weeks treatment with OL, HT, OC or OA at nutritional doses, in healthy and metabolic syndrome (MS)-burdened mice. Three combinatorial regimens were designed and the mixture with preponderant benefits (OL-HT-OC, Combo 2), including infarct sparing and antiglycemic potency, compared to the isolated compounds, was further investigated for its anti-atherosclerotic effects. In vivo experiments revealed that the combination regimen of Combo 2 presented the most favorable effects in limiting infarct size and hyperglycemia, which was selected to be further investigated in the clinical setting in Chronic Coronary Artery Syndrome (CCAS) patients. Cardiac function, inflammation markers and oxidative stress were assessed at baseline and after 4 weeks of treatment with the OL-HT-OC supplement in the clinical study. We found that OL, OC and OA significantly reduced infarct size in vivo compared to Controls. OL exhibited antihyperglycemic properties and OA attenuated hypercholesterolemia. OL-HT-OA, OL-HT-OC and OL-HT-OC-OA combination regimens were cardioprotective, whereas only OL-HT-OC mitigated hyperglycemia. Combo 2 cardioprotection was attributed to apoptosis suppression, enhanced antioxidant effects and upregulation of antioxidant enzymes. Additionally, it reduced atherosclerotic plaque extent in vivo. OL-HT-OC supplement ameliorated cardiac, vascular and endothelial function in the small-scale clinical study. Conclusively, OL-HT-OC combination therapy exerts potent cardioprotective, antihyperglycemic and anti-atherosclerotic properties in vivo, with remarkable and clinically translatable cardiovascular benefits in high-risk patients.
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Hydrogen sulfide (H2S) is an endogenous gasotransmitter with anti-inflammatory actions that also reduces itching. To test whether a combination of an antihistamine with a H2S donor has improved antipruritic efficacy, bifunctional molecules with antihistamine and H2S-releasing pharmacophores were synthesized and tested in vitro and in vivo. H2S release from the hybrid molecules was evaluated with the methylene blue and lead acetate methods, and H1-blocking activity was assessed by determining tissue factor expression inhibition. All new compounds released H2S in a dose-dependent manner and retained histamine blocking activity. Two compounds with the highest potency were evaluated in vivo for their antipruritic as well as sedative action; they proved to possess higher efficacy in inhibiting histamine-induced pruritus and decreased sedative effects compared to the parent compounds (hydroxyzine and cetirizine), suggesting that they exhibit superior antipruritic action and limited side effects that likely arise from the H2S-releasing moiety.
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Antipruriginosos , Sulfeto de Hidrogênio , Humanos , Antipruriginosos/uso terapêutico , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/uso terapêutico , Histamina , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Antagonistas dos Receptores Histamínicos/farmacologia , Antagonistas dos Receptores Histamínicos/uso terapêutico , Prurido/tratamento farmacológico , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/uso terapêuticoRESUMO
Olive is rich in polyphenols such as hydroxytyrosol (HT) that have antioxidative and anti-inflammatory effects. In this study, we examined the short-term effects of olive oil extract (OE) enriched with HT on left atrial function, left ventricular (LV) function, and arterial elastic properties in patients with chronic coronary artery disease (CAD). Sixty-one patients with chronic CAD were enrolled. This randomized study had a two-period, two-sequence crossover (AB/BA) design. Group AB (n = 32) initially received OE capsules (500 mg) enriched with HT (5 mg) (two capsules/day) for 30 days, and after a wash out of 48 h, placebo for another 30 days. The opposite occurred in Group BA (n = 29). Exclusion criteria included age >70 years, diabetes, anemia, hypertension, liver and thyroid disease, malignancy, autoimmune disease, kidney disease, use of corticosteroids, weight loss, excessive exercise dietary intervention, and use of antioxidant vitamins. Patients underwent echocardiography/Doppler and applanation tonometry applied to radial artery at the beginning and end of the study. No significant change regarding Vmax, Vp, Vmin, E wave, A wave, deceleration time, LV ejection fraction, central aortic systolic and pulse pressure, and augmentation index. However, a trend toward improvement of E/e' (P = .062) and pulse wave velocity (P = .091) was observed. Use of OE enriched with HT for a limited time period was associated with a trend toward improvement of LV diastolic function and aortic elastic properties in chronic CAD patients. Studies of longer duration are needed to delineate the effect of this promising agent on cardiovascular function and outcomes in chronic CAD.
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Análise de Onda de Pulso , Disfunção Ventricular Esquerda , Humanos , Idoso , Azeite de Oliva , Função Ventricular Esquerda , Ecocardiografia DopplerRESUMO
Global rates of adolescent obesity have led the World Health Organization to consider the disease a pandemic that needs focus. In search of new anti-obesity agents, Crocus sativus, popularly known as saffron, is a nutraceutical agent, praised for its beneficial effects. The study aimed to investigate the possible effect of Kozanis saffron administration on weight management of obese prediabetic adolescents. Seventy-four obese prediabetic adolescents participated in a double-blind placebo-controlled trial of three arms, randomly assigned to receive either Kozanis saffron (n = 25, 60 mg/day), metformin (n = 25, 1000 mg/day) or a placebo (n = 24), for twelve weeks. Anthropometry, glycemic markers and lipid profiles were investigated at baseline and post-intervention. Saffron supplementation significantly reduced the weight z-score, BMI, BMI z-score and waist circumference (WC) of obese adolescents; however, this reduction was less significant compared to the effect of metformin. Metformin administration offered a significantly more profound improvement in anthropometry compared to saffron administration. Saffron administration also provided significant improvements in weight, weight z-scores, BMI values, BMI z-scores and WCs compared to the placebo. Saffron supplementation failed to change any glycemic marker, but provided a significant reduction in fasting triglyceride levels and also a significant increase in fasting HDL levels. Saffron Kozanis constitutes a promising nutraceutical option for adolescents and children with obesity and prediabetes in need of weight management.
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Lyotropic liquid crystals result from the self-assembly process of amphiphilic molecules, such as lipids, into water, being organized in different mesophases. The non-lamellar formed mesophases, such as bicontinuous cubic (cubosomes) and inverse hexagonal (hexosomes), attract great scientific interest in the field of pharmaceutical nanotechnology. In the present review, an overview of the engineering and characterization of non-lamellar lyotropic liquid crystalline nanosystems (LLCN) is provided, focusing on their advantages as drug delivery nanocarriers and innovative vaccine platforms. It is described that non-lamellar LLCN can be utilized as drug delivery nanosystems, as well as for protein, peptide, and nucleic acid delivery. They exhibit major advantages, including stimuli-responsive properties for the "on demand" drug release delivery and the ability for controlled release by manipulating their internal conformation properties and their administration by different routes. Moreover, non-lamellar LLCN exhibit unique adjuvant properties to activate the immune system, being ideal for the development of novel vaccines. This review outlines the recent advances in lipid-based liquid crystalline technology and highlights the unique features of such systems, with a hopeful scope to contribute to the rational design of future nanosystems.
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The circulation of SARS-CoV-2 omicron BA.4 and BA.5 subvariants with enhanced transmissibility and capacity for immune evasion resulted in a recent pandemic wave that began in April-May of 2022. We performed a statistical phylogeographic study that aimed to define the cross-border transmission patterns of BA.4 and BA.5 at the earliest stages of virus dispersal. Our sample included all BA.4 and BA.5 sequences that were publicly available in the GISAID database through mid-May 2022. Viral dispersal patterns were inferred using maximum likelihood phylogenetic trees with bootstrap support. We identified South Africa as the major source of both BA.4 and BA.5 that migrated to other continents. By contrast, we detected no significant export of these subvariants from Europe. Belgium was identified as a major hub for BA.4 transmission within Europe, while Portugal and Israel were identified as major sources of BA.5. Western and Northern European countries exhibited the highest rates of cross-border transmission, as did several popular tourist destinations in Southern and Central/Western Europe. Our study provides a detailed map of the early dispersal patterns of two highly transmissible SARS-CoV-2 omicron subvariants at a time when there was an overall relaxation of public health measures in Europe.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Filogenia , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , BélgicaRESUMO
BACKGROUND AIM: The Omicron COVID-19 variants BA.1* and BA.2* evade immune system leading to increased transmissibility and breakthrough infections. We aim to test the hypothesis that immunity achieved post COVID-19 infection combined with vaccination (hybrid immunity), is more effective against Omicron infection than vaccination alone in a health-care setting. METHODS: Data on regular pre-emptive PCR testing from all Health-Care Workers (HCWs) at Laiko University Hospital from 29th December 2020, date on which the national COVID-19 immunization program began in Greece, until 24th May 2022, were retrospectively collected and recorded. The infection rate was calculated after December 21st, 2021, when Omicron was the predominant circulating variant in Greece, as the total number of infections (positive PCR COVID-19 test regardless of symptoms) divided by the total person-months at risk. RESULTS: Of 1,305 vaccinated HCWs who were included in the analysis [median age of 47 (IQR: 36, 56) years, 66.7 % women], 13 % and 87 % had received 2 or 3 vaccine doses (full and booster vaccination), respectively. A COVID-19 infection had occurred in 135 of 1,305 of participants prior to Omicron predominance. Of those 135 HCWs with hybrid immunity only 13 (9.6 %) were re-infected. Of the 154 and 1,016 HCWs with full and booster vaccination-induced immunity, respectively, 71 (46.1 %, infection rate 13.4/100 person-months) and 448 (44.1 %, infection rate 12.2/100 person-months) were infected during the follow up period. No association between gender or age and COVID-19 infection was found and none of the participants had a severe infection or died. CONCLUSIONS: Hybrid immunity confers higher protection by almost 5-fold compared to full or booster vaccination for COVID-19 infection with the Omicron variant among HCWs who are at high risk of exposure. This may inform public health policies on how to achieve optimal immunity in terms of the timing and mode of vaccination.
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COVID-19 , Humanos , Feminino , Masculino , COVID-19/prevenção & controle , Estudos Retrospectivos , SARS-CoV-2 , VacinaçãoRESUMO
Tissue hypoxia is one of the main pathophysiologic mechanisms in sepsis and particularly in COVID-19. Microvascular dysfunction, endothelialitis and alterations in red blood cell hemorheology are all implicated in severe COVID-19 hypoxia and multiorgan dysfunction. Tissue hypoxia results in tissue injury and remodeling with re-emergence of fetal programming via hypoxia-inducible factor-1α (HIF-1a)-dependent and -independent pathways. In this context, thyroid hormone (TH), a critical regulator of organ maturation, may be of relevance in preventing fetal-like hypoxia-induced remodeling in COVID-19 sepsis. Acute triiodothyronine (T3) treatment can prevent cardiac remodeling and improve recovery of function in clinical settings of hypoxic injury as acute myocardial infarction and by-pass cardiac surgery. Furthermore, T3 administration prevents tissue hypoxia in experimental sepsis. On the basis of this evidence, the use of T3 treatment was proposed for ICU (Intensive Care Unit) COVID-19 patients (Thy-Support, NCT04348513). The rationale for T3 therapy in severe COVID-19 and preliminary experimental and clinical evidence are discussed in this review.
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Tratamento Farmacológico da COVID-19 , Sepse , Humanos , Hipóxia/metabolismo , Hormônios Tireóideos/metabolismo , Hormônios Tireóideos/uso terapêutico , Tri-Iodotironina/uso terapêuticoRESUMO
Our study aims to describe the global distribution and dispersal patterns of the SARS-CoV-2 Omicron subvariants. Genomic surveillance data were extracted from the CoV-Spectrum platform, searching for BA.1*, BA.2*, BA.3*, BA.4*, and BA.5* variants by geographic region. BA.1* increased in November 2021 in South Africa, with a similar increase across all continents in early December 2021. BA.1* did not reach 100% dominance in all continents. The spread of BA.2*, first described in South Africa, differed greatly by geographic region, in contrast to BA.1*, which followed a similar global expansion, firstly occurring in Asia and subsequently in Africa, Europe, Oceania, and North and South America. BA.4* and BA.5* followed a different pattern, where BA.4* reached high proportions (maximum 60%) only in Africa. BA.5* is currently, by Mid-August 2022, the dominant strain, reaching almost 100% across Europe, which is the first continent aside from Africa to show increasing proportions, and Asia, the Americas, and Oceania are following. The emergence of new variants depends mostly on their selective advantage, translated as enhanced transmissibility and ability to invade people with existing immunity. Describing these patterns is useful for a better understanding of the epidemiology of the VOCs' transmission and for generating hypotheses about the future of emerging variants.
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Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.
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Infecções por Helicobacter , Helicobacter pylori , Probióticos , Antibacterianos/efeitos adversos , Bismuto/farmacologia , Bismuto/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Probióticos/efeitos adversos , Estudos ProspectivosRESUMO
Hydroxytyrosol (HT) is a natural antioxidant found in olive products and characterized by well-documented beneficial effects on human health. Several research studies are ongoing that aim to investigate its potency and molecular mechanism of action. The present study aimed to investigate the potential effect of HT on human obesity through a randomized double-blind prospective design. HT in two different doses (15 and 5 mg/day) and a placebo capsule was administered to 29 women with overweight/obesity for six months and their weight and fat mass were monitored at three time points (baseline, 4, 12 and 24 weeks). Statistically significant weight and visceral fat mass loss (%weight loss: p = 0.012, %visceral fat loss: p = 0.006) were observed in the group receiving the maximum HT dosage versus placebo after 4 weeks of the intervention, with attenuation of these findings at 12 and 24 weeks of the study. Urine samples were collected during the intervention and analyzed via liquid chromatography-high-resolution mass spectrometry for untargeted metabolomic purposes and comparisons between study groups were performed. HT administration was safe and well-tolerated. To the best of our knowledge, this is the first human cohort investigating the effects of HT on obesity for a prolonged study period.
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Metabolômica , Sobrepeso , Peso Corporal , Método Duplo-Cego , Feminino , Humanos , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Estudos ProspectivosRESUMO
Tissue hypoxia occurs in various conditions such as myocardial or brain ischemia and infarction, sepsis, and trauma, and induces cellular damage and tissue remodeling with recapitulation of fetal-like reprogramming, which eventually results in organ failure. Analogies seem to exist between the damaged hypoxic and developing organs, indicating that a regulatory network which drives embryonic organ development may control aspects of heart (or tissue) repair. In this context, thyroid hormone (TH), which is a critical regulator of organ maturation, physiologic angiogenesis, and mitochondrial biogenesis during fetal development, may be of important physiological relevance upon stress (hypoxia)-induced fetal reprogramming. TH signaling has been implicated in hypoxic tissue remodeling after myocardial infarction and T3 prevents remodeling of the postinfarcted heart. Similarly, preliminary experimental evidence suggests that T3 can prevent early tissue hypoxia during sepsis with important physiological consequences. Thus, based on common pathways between different paradigms, we propose a possible role of TH in tissue hypoxia after sepsis with the potential to reduce secondary organ failure.