How long does the biological effect of a red light-emitting diode last on adipose-derived mesenchymal stem cells?

This research investigated the duration of the influence of red light-emitting diodes (LED, 630 nm; output power: 2452.5 mW; laser beam: 163.5 cm2; irradiance: 15 mW/cm2; radiant exposure: 4 J/cm2) on different periods after irradiation (6, 12, 24, 48, and 72 h) on adipose-derived mesenchymal stem cells' (AdMSCs) metabolism and paracrine factors. AdMSCs were irradiated three times every 48 h. Twenty-four hours after the last irradiation, there was a higher MTT absorbance, followed by a decrease after 48 h. The cells' secretome showed increased levels of IL-6 and VEGF after 12 and 24 h, but this was reversed after 48 h. Additionally, LED irradiation resulted in higher levels of nitrite and did not affect oxidative stress markers. LED irradiation had significant effects on AdMSCs after 24 h compared to other groups and its control group.

Effects of phytosterol supplementation on lipoprotein subfractions and LDL particle quality.

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .

Wild-type lytic bacteriophages against Salmonella Heidelberg: Further characterization and effect of prophylactic therapy in broiler chickens.

To characterize wild-type bacteriophages and their effect on Salmonella Heidelberg intestinal colonization in broilers, phages combined in a cocktail were continuously delivered via drinking water since the first day after hatching. After challenge with a field strain, broilers were evaluated at regular intervals for S. Heidelberg and bacteriophages in tissues and cecum, and gross and microscopic lesions in organs. Phages were highly virulent against S. Heidelberg by efficiency of plating. One-step growth curves exhibited eclipse period from 20 to 25 min, whereas the lowest latent period and higher burst size found were 45 min and 54 PFU/cell, respectively. Bacteriophage whole genomic sequencing analyses revealed a lack of genes related to lysogeny, antimicrobial resistance, and virulence factors. Relevant gross or microscopic lesions were absent in tissues analyzed from treated broilers. Although numerically stable bacteriophage concentrations were detected in the cecal contents of treated broilers, no significant difference was found for the S. Heidelberg cecal load in comparison to the untreated group and for the prevalence of positive tissues throughout the evaluated period. The phages produced turbid plaques against some S. Heidelberg re-isolated from treated broilers, suggesting the evolving of a resistant subpopulation. Overall, the results provide new evidence of the safety and in vitro replication of such phages in S. Heidelberg. Nevertheless, continuous administration of the phage suspension most likely induced the development of bacteriophage-resistant mutants, which might have affected the in vivo effect. Therefore, a putative administration protocol should be based on other strategies, such as short-term therapy at pre-harvest age.

Expression of monocyte chemokine receptors in diabetes after non-surgical periodontal treatment: A pilot study.

The aim of this study was to evaluate the effect of non-surgical periodontal treatment in the expression of chemokine receptors, in individuals with Periodontitis, associated or not with Diabetes. Pilot study, which included patients (n = 45) with Periodontitis, associated (n = 25) or not (n = 20) with Diabetes, submitted to the non-surgical periodontal treatment for one month. The expression of chemokine receptors CCR2, CCR5, and CX3CR1 at the mRNA level was evaluated in the peripheral mononuclear cells, as well as the expression of these receptors at the protein level was verified in monocyte subtypes (classical, intermediate, and non-classical monocytes). There was higher expression of CCR2 and CCR5 receptors at the initial visit in the group with Diabetes, with no differences for CX3CR1 (p = 0.002; p = 0.018, and p = 0.896, respectively), without differences after treatment. There was higher expression of CCR2 and CCR5 proteins in the group with Diabetes at the initial visit for classical, intermediate, and nonclassical monocytes, with no differences for CX3CR1 (CCR2: p = 0.004; p = 0.026; p = 0.024; CCR5: 0.045; p = 0.045; p = 0.013; CX3CR1: p = 0.424; p = 0.944; p = 0.392, respectively), without differences after the end of treatment. Concerning each group separately, there were reductions in the expression of CCR2 as well as CCR5 in classical, intermediate, and nonclassical monocytes, and reduction of CX3CR1 in classical monocytes after treatment in the group with Diabetes (p = 0.003; p = 0.006; p = 0.039; p = 0.007; p = 0.006; p = 0.004; p = 0.019, respectively), without differences in the group without Diabetes. The expression of the chemokine receptors CCR2 and CCR5, in patients with Periodontitis associated with Diabetes, is favorably modified after the end of the non-surgical periodontal treatment.

Immunometabolic and Vascular Health Responses among High Endurance Trained Subjects.

In this study, we aimed to examine the impact of high endurance training on vascular health parameters and immune-endocrine responses against modified low-density lipoprotein (LDL) particles. This observational, cross-sectional study included high endurance-trained and healthy non-trained subjects. Vascular ultrasound was used to assess vascular health parameters based on carotid intima-media thickness and endothelial function (flow-mediated dilation). Enzyme-linked immunosorbent assays were used to measure interleukin (IL)-8 and IL-10, autoantibody isotypes anti-oxidized LDL (oxLDL) and anti-apolipoprotein B (ApoB-D) peptide. Plasma levels of the corticosterone and 17 α-hydroxyprogesterone hormones were analyzed by mass spectrometry. This study enrolled 96 subjects, of whom 44 were high endurance trained and 52 were healthy non-trained individuals. Smaller carotid intima-media thickness values were observed in the high-endurance trained than in the healthy non-trained males, while no differences were observed between female groups. Flow-mediated dilation measurements did not differ by training or sex. The humoral immune responses to IgG anti-oxLDL and IgM anti-ApoB-D autoantibodies showed an isotype imbalance between the high-endurance trained and the non-trained groups. Immunoendocrine parameters showed inverse correlations between 17 α-hydroxyprogesterone concentrations and carotid intima-media thickness measurements. Direct correlations were found between IL-10 concentrations and flow-mediated dilation measurements. Chronic high-endurance exercise modulates immune-endocrine and vascular health parameters, in a sex-dependent manner.

Leishmanicidal and healing effects of 3ß,6ß,16ß-trihydroxy lup-20 (29)-ene isolated from Combretum leprosum on Leishmania braziliensis infection in vitro and in vivo.

Treatment of cutaneous leishmaniasis depends on drugs that potentially cause serious side effects and resistance. Thus, topical therapies are attractive alternatives to the drugs currently used. 3ß, 6ß, 16ß-trihydroxylup-20 (29)-ene is a lupane triterpene isolated from Combretum leprosum Mart. leaves (CLF-1), with reports of in vitro antileishmanial effect against L. amazonensis and to promote lesion healing in animal model. Herein, we evaluated the in vitro and in vivo antileishmanial and healing effects of CLF-1 against L. braziliensis. CLF-1 treatment showed low toxicity in macrophages and significantly reduced parasite load in vitro. CLF-1 induced higher IL-12 and TNF-α production and more discrete IL-4 and IL-10 production. For in vivo evaluation, a CLF-1 cream formulation was prepared to treat hamsters infected with L. braziliensis. CLF-1 treatment was able to reduce parasite load of the infected skin and lymph node more efficiently than the conventional treatment. Histopathological analysis indicated a strong inflammatory response accompanied by an important healing response. Data from this study indicate that topical CLF-1 treatment was effective and non-toxic in L. braziliensis infected hamsters suggesting its potential for further development as a future therapeutic intervention.

Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients. / Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos.

BACKGROUND: Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. OBJECTIVE: To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. METHODS: A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. RESULTS: A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. CONCLUSION: High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.

Modulation of monocyte subtypes in diabetes after non-surgical periodontal treatment.

OBJECTIVES: The current study aims to evaluate the effect of non-surgical periodontal treatment on the modulation of monocyte phenotype, in the presence or absence of diabetes. MATERIALS AND METHODS: The identification, quantification, and phenotypic characterization of monocyte subtypes (classical, intermediate, and non-classical) were performed by flow cytometry, at baseline and 1 month after the end of non-surgical periodontal treatment, in patients with periodontitis, associated or not with diabetes. RESULTS: There was an increase in non-classical monocytes after treatment and a reduction in intermediate monocytes, without differences for the classical subtype, regardless of the diabetes status. Furthermore, there was a reduction in intermediate monocytes and an increase in non-classical and classical monocytes after treatment in the diabetes group, while no significant differences were observed for classical, intermediate, and non-classical monocytes in the group without diabetes. Comparisons between the two groups showed significant differences for classical, intermediate, and non-classical monocytes at baseline; these differences were not found one month after treatment. CONCLUSIONS: Non-surgical periodontal treatment leads to modulation of monocytes to a less inflammatory phenotype, especially in individuals with diabetes. CLINICAL RELEVANCE: A better understanding of the role of these biomarkers in the periodontitis contex may constitute a new strategic target for a better treatment of patiens with diabetes associated to periodontitis. CLINICAL TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-RBR-35szwc. Jhefferson Miranda Alves and Danielle Borges Germano contributed equality to this study and should be considered first authors.

A polyvalent virosomal influenza vaccine induces broad cellular and humoral immunity in pigs.

BACKGROUND: Influenza A virus (IAV) is endemic in pigs globally and co-circulation of genetically and antigenically diverse virus lineages of subtypes H1N1, H1N2 and H3N2 is a challenge for the development of effective vaccines. Virosomes are virus-like particles that mimic virus infection and have proven to be a successful vaccine platform against several animal and human viruses. METHODS: This study evaluated the immunogenicity of a virosome-based influenza vaccine containing the surface glycoproteins of H1N1 pandemic, H1N2 and H3N2 in pigs. RESULTS: A robust humoral and cellular immune response was induced against the three IAV subtypes in pigs after two vaccine doses. The influenza virosome vaccine elicited hemagglutinin-specific antibodies and virus-neutralizing activity. Furthermore, it induced a significant maturation of macrophages, and proliferation of B lymphocytes, effector and central memory CD4+ and CD8+ T cells, and CD8+ T lymphocytes producing interferon-γ. Also, the vaccine demonstrated potential to confer long-lasting immunity until the market age of pigs and proved to be safe and non-cytotoxic to pigs. CONCLUSIONS: This virosome platform allows flexibility to adjust the vaccine content to reflect the diversity of circulating IAVs in swine in Brazil. The vaccination of pigs may reduce the impact of the disease on swine production and the risk of swine-to-human transmission.

Immunological profile of mice immunized with a polyvalent virosome-based influenza vaccine.

BACKGROUND: Influenza A virus (IAV) causes respiratory disease in pigs and is a major concern for public health. Vaccination of pigs is the most successful measure to mitigate the impact of the disease in the herds. Influenza-based virosome is an effective immunomodulating carrier that replicates the natural antigen presentation pathway and has tolerability profile due to their purity and biocompatibility. METHODS: This study aimed to develop a polyvalent virosome influenza vaccine containing the hemagglutinin and neuraminidase proteins derived from the swine IAVs (swIAVs) H1N1, H1N2 and H3N2 subtypes, and to investigate its effectiveness in mice as a potential vaccine for swine. Mice were immunized with two vaccine doses (1 and 15 days), intramuscularly and intranasally. At 21 days and eight months later after the second vaccine dose, mice were euthanized. The humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with a polyvalent influenza virosomal vaccine were investigated. RESULTS: Only intramuscular vaccination induced high hemagglutination inhibition (HI) titers. Seroconversion and seroprotection (> 4-fold rise in HI antibody titers, reaching a titer of ≥ 1:40) were achieved in 80% of mice (intramuscularly vaccinated group) at 21 days after booster immunization. Virus-neutralizing antibody titers against IAV were detected at 8 months after vaccination, indicating long-lasting immunity. Overall, mice immunized with the virosome displayed greater ability for B, effector-T and memory-T cells from the spleen to respond to H1N1, H1N2 and H3N2 antigens. CONCLUSIONS: All findings showed an efficient immune response against IAVs in mice vaccinated with a polyvalent virosome-based influenza vaccine.

Persistence of a proinflammatory status after treatment of the acute myocardial infarction.

AIM: To evaluate the lipid-lowering and antiplatelet combined strategies on the expression of the receptors CCR2, CCR5, and CX3CR1 and the percentage of CCR2, CCR5, and CX3CR1 cells in monocyte subtypes after acute myocardial infarction. METHODS: Prospective, randomized, open-label study, with blinded analyses of endpoints (PROBE, ClinicalTrials.gov Identifier: NCT02428374, registration date: April 28, 2015). Participants were treated with rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg. The chemokine receptors CCR2, CCR5, and CX3CR1 were analyzed by real-time polymerase chain reaction as well as the percentages of CCR2, CCR5, and CX3CR1 cells in the monocyte subtypes (classical, intermediate, and non-classical), which were quantified by flow cytometry, at baseline, and after 1 and 6 months of treatment. RESULTS: After comparisons between the three visits, regardless of the treatment arm, there was an increase in CCR2 expression after treatment, as well as an increase in intermediate monocytes CCR2+ and a reduction in non-classical monocytes CCR2+ at the end of treatment. There was also a lower expression of CCR5 after treatment and an increase in classical and non-classical monocytes CCR5+. Concerning CX3CR1, there were no differences in the expression after treatment; however, there were reductions in the percentage of intermediate and non-classical monocytes CX3CR1+ at the end of treatment. CONCLUSIONS: The results suggest the persistence of the inflammatory phenotype, known as trained immunity, even with the highly-effective lipid-lowering and antiplatelet therapies. Geriatr Gerontol Int 2023; 23: 700-707.

Metrics of care and cardiovascular outcomes in patients with ST-elevation myocardial infarction treated with pharmacoinvasive strategy: a decade-long network in a populous city in Brazil.

BACKGROUND: Pharmacoinvasive strategy is an effective myocardial reperfusion therapy when primary percutaneous coronary intervention (p-PCI) cannot be performed in a timely manner. METHODS: Authors sought to evaluate metrics of care and cardiovascular outcomes in a decade-long registry of a pharmacoinvasive strategy network for the treatment of ST-elevation myocardial infarction (STEMI). Data from a local network including patients undergoing fibrinolysis in county hospitals and systematically transferred to the tertiary center were accessed from March 2010 to September 2020. Numerical variables were described as median and interquartile range. Area under the curve (AUC-ROC) was used to analyze the predictive value of TIMI and GRACE scores for in-hospital mortality. RESULTS: A total of 2,710 consecutive STEMI patients aged 59 [51-66] years, 815 women (30.1%) and 837 individuals with diabetes (30.9%) were analyzed. The time from symptom onset to first-medical-contact was 120 [60-210] minutes and the door-to-needle time was 70 [43-115] minutes. Rescue-PCI was required in 929 patients (34.3%), in whom the fibrinolytic-catheterization time was 7.2 [4.9-11.8] hours, compared to 15.7 [6.8-22,7] hours in those who had successful lytic reperfusion. All cause in-hospital mortality occurred in 151 (5.6%) patients, reinfarction in 47 (1.7%) and ischemic stroke in 33 (1.2%). Major bleeding occurred in 73 (2.7%) patients, including 19 (0.7%) cases of intracranial bleeding. C-statistic confirmed that both scores had high predictive values for in-hospital mortality, demonstrated by TIMI AUC-ROC of 0.80 [0,77-0.84] and GRACE AUC-ROC of 0.86 [0.83-0.89]. CONCLUSION: In a real world registry of a decade-long network for the treatment of ST-elevation myocardial infarction based on the pharmacoinvasive strategy, low rates of in-hospital mortality and cardiovascular outcomes were observed, despite prolonged time metrics for both fibrinolytic therapy and rescue-PCI. Register Clinicaltrials.gov NCT02090712 date of first registration 18/03/2014.

Inflammation in Cardiovascular Disease: Current Status and Future Perspectives

Abstract Atherosclerosis has been defined as an inflammatory disease. Three decades of research have pointed to a pivotal role of interleukin 6 for many aspects of cardiovascular disease, not the least of which is atherosclerosis. In this review, experimental and clinical studies are reported on a timeline, exploring mechanisms and possible explanations that form the basis of current knowledge. Some successful clinical trials were proof of concept studies, showing that not only inflammatory biomarkers are related to cardiovascular outcomes, but also that decreasing inflammation can reduce cardiovascular events. Great advances have been made in the management of residual cardiovascular risk due to cholesterol, thrombosis, and metabolic diseases, but the next frontier now seems to be targeting inflammation. In the upcoming years, the importance of inflammation will be evaluated in high-risk patients with chronic kidney disease, after acute coronary heart disease or heart failure with preserved ejection fraction. Inflammation seems to precede the development of cardiovascular risk factors. Moreover, counseling for a heathy lifestyle and, when necessary, the use of cardiometabolic therapies capable of decreasing inflammation, might be important.

Primary Prevention of Cardiovascular Disease at Community Clinics in the State of Sao Paulo, Brazil: Results from the Epidemiological Information Study of Communities.

Background: Primary prevention of cardiovascular disease (CVD) remains a major challenge, especially in communities of low- and middle-income countries with poor medical assistance influenced by distinct local, financial, infrastructural, and resource-related factors. Objective: This a community-based study aimed to determine the proportion and prevalence of uncontrolled cardiovascular risk factors (CRF) in Brazilian communities. Methods: The EPICO study was an observational, cross-sectional, and community clinic-based study. Subjects were living in Brazilian communities and were of both sexes and ≥18 years old, without a history of a stroke or myocardial infarction but presenting at least one of the following cardiovascular risk factors: hypertension, diabetes mellitus and hypercholesterolemia. The study was carried out in Brazil, including 322 basic health units (BHU) in 32 cities. Results: A total of 7,724 subjects with at least one CRF were evaluated, and one clinical visit was performed. Mean age was 59.2 years-old (53.7% were >60 years old). A total of 66.7% were women. Of the total, 96.2% had hypertension, 78.8% had diabetes mellitus type II, 71.1% had dyslipidemia, and 76.6% of patients were overweight/obese. Controlled hypertension (defined by <130/80 mmHg or <140/90 mmHg) was observed in 34.9% and 55.5% patients among respective criteria, the rates of controlled blood glucose in patients taking antidiabetic medications was 29.5%, and among those with documented dyslipidemia who received any lipid-lowering medication, only 13.9% had LDL-c on target. For patients presenting three CRF less than 1.9% had LDL-c < 100 mg/dL once their BP and blood glucose were on target. High education level as associated with blood pressure (BP) target of less than 130 / 80mm Hg. The glucose and LDL-c levels on target were associated with the presence of hypertension and diabetes mellitus. Conclusion: In Brazilian community clinics, regarding most patients in primary prevention, the CRF such as BP, blood glucose, and lipid levels are poorly controlled, with a majority of patients not achieving guidelines/recommendations.

Chest Pain in Acute Myocardial Infarction and Its Association With the Culprit Artery and Fibrotic Segment Identified by Cardiac Magnetic Resonance.

Background: It is still very controversial whether the characteristics of pain in the acute myocardial infarction could be related to the culprit coronary artery. There are no data about associations of pain with the ST-segment elevation myocardial infarction (STEMI) and left ventricular (LV) fibrotic segments. Methods: Data from 328 participants who had STEMI and were included in the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study were analyzed. The culprit artery was identified by coronary angiography and the injured myocardial segments by cardiac magnetic resonance. The statistical significance was established by P value < 0.05. Results: A total of 223 patients (68%) were selected. Association was not observed between chest pain and the culprit artery (P = 0.237), as well as between pain irradiation and the culprit artery (P = 0.473). No significant difference was observed in the pain localization in relation to the segments in the short axis basal, mid, apical, and long axis, except for the mid inferior segment. The data were not considered clinically relevant because this association was observed in only one of 17 segments after multiple comparisons. Conclusions: In patients with STEMI, no associations were observed between the location or irradiation of acute chest pain and/or adjacent areas and the culprit artery, or between pain and segmental myocardial fibrosis in the LV.

Pharmacoinvasive Strategy in Elderly Up to 75 Years or Non-Elderly: Analysis of Biochemical and Cardiac Magnetic Resonance Imaging Parameters. / Estratégia Farmacoinvasiva em Idosos até 75 Anos ou Não Idosos: Análise de Parâmetros Bioquímicos e de Ressonância Nuclear Magnética Cardíaca.

BACKGROUND: Pharmacoinvasive strategy is an alternative when primary percutaneous coronary intervention (PCI) is not feasible. OBJECTIVES: This study aimed to evaluate the effects of early pharmacoinvasive strategy on the infarct size and left ventricular ejection fraction in elderly and non-elderly patients. The role of inflammatory markers was also examined. METHODS: Patients (n=223) with ST segment elevation myocardial infarction (STEMI) were prospectively included and submitted to pharmacological thrombolysis in the first six hours, and underwent coronary angiogram and PCI when necessary, in the first 24 hours. Blood samples were collected in the first day (D1) and after 30 days (D30). Cardiac magnetic resonance imaging (cMRI) was performed at D30. Significance was set at p<0.05. RESULTS: Elderly and non-elderly patients showed similar percentage of infarcted mass (13.7 [6.9-17.0] vs. 14.0 [7.3-26.0], respectively, p=0.13) (median [interquartile range]). However, elderly patients had better left ventricular ejection fraction (53 [45-62] vs. 49 [39-58], p=0.025). Titers of interleukin (IL)1beta, IL-4, IL-6, and IL-10 did not differ between D1 and D30, but elderly patients had higher titers for IL-18 at D1 and D30. Absolute numbers of B and T lymphocytes were similar in both groups at D1 and D30, but elderly patients had higher neutrophil/lymphocyte ratio at D30. Multivariate linear regression analysis of cMRI outcomes in the whole population showed that the independent predictors were not different between elderly and non-elderly patients. CONCLUSION: Pharmacoinvasive strategy in elderly patients was associated with small differences in inflammatory parameters, similar infarct size and better left ventricular function than non-elderly patients.

FUNDAMENTO: A estratégia farmacoinvasiva é uma alternativa na inviabilidade da intervenção coronária percutânea primária (ICP). OBJETIVOS: Este estudo teve como objetivo avaliar os efeitos da estratégia farmacoinvasiva precoce sobre o tamanho da área infartada e a fração de ejeção ventricular esquerda em pacientes idosos e não idosos. O papel dos marcadores inflamatórios também foi avaliado. MÉTODOS: Pacientes (n=223) com infarto do miocárdio com elevação do segmento ST (IAMCSST) foram prospectivamente incluídos e submetidos à trombólise medicamentosa nas primeiras seis horas, e à angiografia coronariana e à ICP, quando necessária, nas primeiras 24 horas. As amostras de sangue foram coletadas no primeiro dia (D1) e 30 dias após (D30). A ressonância magnética cardíaca foi realizada no D30. O nível de significância estatística foi estabelecido em p<0,05. RESULTADOS: Pacientes idosos e não idosos apresentaram porcentagem similares de massa infartada [13,7 (6,9-17,0) vs. 14,0 (7,3-26,0), respectivamente p=0,13)] [mediana (intervalo interquartil)]. No entanto, os pacientes idosos apresentaram maior fração de ejeção ventricular esquerda [53 (45-62) vs. 49 (39-58), p=0,025)]. As concentrações de interleucina (IL)1beta, IL-4, IL-6, e IL-10 não foram diferentes entre D1 e D30, mas pacientes idosos apresentaram níveis mais elevados de IL-18 em D1 e D30. O número absoluto de linfócitos B e T foram similares em ambos os grupos em D1 e D30, porém, pacientes idosos apresentaram uma razão neutrófilo-linfócito mais alta em D30. A análise de regressão linear multivariada dos desfechos de RMC de toda a população do estudo mostrou que os preditores independentes não foram diferentes entre pacientes idosos e não idosos. CONCLUSÃO: A estratégia farmacoinvasiva em pacientes idosos foi associada a pequenas diferenças nos parâmetros inflamatórios, tamanho do infarto similar, e melhor função ventricular esquerda em comparação a pacientes não idosos.

Thermosensitive and mucoadhesive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan for the treatment of oral squamous cell carcinoma.

Buccal drug administration may be chosen as a medication route to treat various diseases for local or systemic effects. This study proposes the development of a thermosensitive hydrogel containing curcumin-loaded lipid-core nanocapsules coated with chitosan to increase mucoadhesion, circumventing several limitations of this route of administration. Hydroxypropylmethylcellulose and Poloxamer® 407 were incorporated for hydrogel production. Physicochemical characterization parameters, such as particle size distribution, mean diameter, polydispersity index, zeta potential, and morphology, were analyzed. Spherical homogeneous particles were obtained with average diameter, of 173 ± 22 nm for LNCc (curcumin lipid-core nanocapsules) and 179 ± 48 nm for CLNCc (chitosan-curcumin lipid-core nanocapsules). A PDI equal to 0.09 ± 0.02 for LNCc and 0.26 ± 0.01 for CLNCc confirmed homogeneity. Tensile analysis and washability test on porcine buccal mucosa indicated higher mucoadhesion for hydrogels in comparison to the nanocapsules in suspension, remaining on the mucous membrane up to 8 h (10.92 ± 3.95 µg of curcumin washed for H-LNCc and 28.41 ± 24.47 µg for H-CLNCc) versus the latter, which remained washed on the membrane for 90 min only (62.60 ± 4.72 µg for LNCc and 52.08 ± 1.63 µg for CLNCc). The irritant potential (IR) of the formulations was evaluated by the hen's egg chorioallantoic membrane test (HET-CAM), with no irritation phenomena observed. Formulations were tested for their efficacy in an in vitro model against oral squamous cancer cell line, showing a significant reduction in cell viability on all tested groups. These findings demonstrated that the proposed nanosystem is mucoadhesive and has potential to deliver buccal treatments.

Relação da Ascensão Matinal da Pressão Arterial com a Hipertrofia Ventricular Esquerda em Hipertensos Obesos / Association between Morning Surge and Left Ventricular Hypertrophy in Obese Hypertensive Patients

Resumo Fundamento O aumento do peso frequentemente desencadeia mecanismos que elevam a pressão arterial. A obesidade causa mudanças estruturais no miocárdio, incluindo aumento da massa ventricular, dilatação atrial, bem como disfunções diastólicas e sistólicas. Além disso, variações pressóricas nos hipertensos obesos, como a ascensão matinal (AM), podem ter relevância clínica na prevenção dos eventos cardiovasculares. A AM da pressão arterial é um fenômeno fisiológico, que quando elevada pode ser considerada um fator de risco independente para eventos cardiovasculares. Objetivo Avaliar valores da elevação da AM e sua associação com a hipertrofia ventricular esquerda (HVE) e com o Descenso do Sono (DS) em obesos e não obesos hipertensos. Métodos Estudo transversal que avaliou medidas pressóricas à monitorização ambulatorial da pressão arterial (MAPA) e a presença de HVE, avaliada pela ecocardiografia, em 203 pacientes hipertensos em tratamento ambulatorial, separados em dois grupos: 109 não obesos e 94 hipertensos obesos. O nível de significância adotado foi de 0,05 em testes bicaudais. Resultados A AM acima de 20 mmHg à MAPA foi detectada em 59,2% dos pacientes do grupo "não obesos" e em 40,6% no grupo "obesos". A HVE foi encontrada em 18,1% no grupo dos não-obesos e em 39,3% no grupo de obesos, p<0,001. No grupo "obesos" foi observado que AM >16 mmHg esteve associada à HVE, com [razão de prevalência: 2,80; IC95% (1,12-6,98), p=0,03]. Para o grupo dos "não obesos", o ponto de corte da AM para essa associação foi >22 mmHg. Conclusão A AM elevada associou-se positivamente com HVE, com comportamento peculiar na população de hipertensos e obesos.

Abstract Background Weight gain can trigger mechanisms that increase blood pressure. Nevertheless, obesity causes structural changes in the myocardium, including increased ventricular mass, atrial dilatation, and diastolic and systolic dysfunction. Additionally, blood pressure variations, like morning surge (MS) in obese hypertensive patients may have clinical relevance in cardiovascular events. Although morning blood pressure surge is a physiological phenomenon, excess MS can be considered an independent risk factor for cardiovascular events. Objective To evaluate MS values and their association with left ventricular hypertrophy (LVH) and nocturnal dipping (ND) in obese and non-obese hypertensive patients. Methods A cross-sectional study that evaluated BP measurements by ambulatory blood pressure monitoring (ABPM) and the presence of LVH by echocardiography in 203 hypertensive outpatients, divided into two groups: 109 non-obese and 94 obese hypertensives patients. The significance level was set at 0.05 in two-tailed tests. Results A MS above 20 mmHg by ABPM was detected in 59.2% of patients in the non-obese group and 40.6% in the obese group. LVH was found in 18.1% and 39.3% of patients in the non-obese and obese groups, respectively, p<0.001. In the "obese group", it was observed that a MS>16 mmHg was associated with LVH, [prevalence ratio: 2.80; 95%CI (1.12-6.98), p=0.03]. For the non-obese group, the cut-off point of MS for this association was >22 mmHg. Conclusion High MS was positively associated with LVH, with a particular behavior in the hypertensive obese group.