Lab-made disposable screen-printed electrochemical sensors and immunosensors modified with Pd nanoparticles for Parkinson's disease diagnostics.

A new conductive ink based on the addition of carbon black to a poly(vinyl alcohol) matrix is developed and investigated for electrochemical sensing and biosensing applications. The produced devices were characterized using morphological and electrochemical techniques and modified with Pd nanoparticles to enhance electrical conductivity and reaction kinetics. With the aid of chemometrics, the parameters for metal deposition were investigated and the sensor was applied to the determination of Parkinson's disease biomarkers, specifically epinephrine and α-synuclein. A linear behavior was obtained in the range 0.75 to 100 µmol L-1 of the neurotransmitter, and the device displayed a limit of detection (LOD) of 0.051 µmol L-1. The three-electrode system was then tested using samples of synthetic cerebrospinal fluid. Afterward, the device was modified with specific antibodies to quantify α-synuclein using electrochemical impedance spectroscopy. In phosphate buffer, a linear range was obtained for α-synuclein concentrations from 1.5 to 15 µg mL-1, with a calculated LOD of 0.13 µg mL-1. The proposed immunosensor was also applied to blood serum samples, and, in this case, the linear range was observed from 6.0 to 100.5 µg mL-1 of α-synuclein, with a LOD = 1.3 µg mL-1. Both linear curves attend the range for the real diagnosis, demonstrating its potential application to complex matrices.

DISTRIBUTION AND ANTIMICROBIAL RESISTANCE OF STAPHYLOCOCCI ISOLATED FROM FREE-LIVING SOUTH AMERICAN COATI (NASUA NASUA) IN AN URBAN PARK IN MINAS GERAIS, BRAZIL.

The scientific information regarding staphylococci in procyonids is scarce. Hence, the aim of this study was to evaluate the frequency, distribution, and pattern of antimicrobial resistance of staphylococcal species isolated from free-roaming coatis (Nasua nasua) in an urban park in Belo Horizonte, Minas Gerais, Brazil. Rectal swabs from 55 free-living coatis were plated onto mannitol salt agar for isolating staphylococci, and species were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, polymerase chain reaction (PCR) of nuc, and sequencing of 16S rRNA and rpoB when needed. Antimicrobial susceptibility was investigated using the disk diffusion method, and the presence of the mecA gene was investigated by PCR. A total of 72.7% of the animals tested positive for staphylococci. Nine different species were identified, and Staphylococcus intermedius (60.4%) and S. delphini (20.9%) were the most frequently isolated species. Most of the isolates were susceptible to most of the antimicrobials evaluated, with a resistance pattern seen for penicillin (13.9%). One isolate was multidrug-resistant (MDR). The present study suggests that coatis are natural hosts of S. intermedius and S. delphini and, despite living in a heavily anthropized environment, the Staphylococcus spp. isolates showed a low incidence of drug resistance.

Bromoditerpenes from the Red Seaweed Sphaerococcus coronopifolius as Potential Cytotoxic Agents and Proteasome Inhibitors and Related Mechanisms of Action.

Seaweeds are a great source of compounds with cytotoxic properties with the potential to be used as anticancer agents. This study evaluated the cytotoxic and proteasome inhibitory activities of 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, and bromosphaerol isolated from Sphaerococcus coronopifolius. The cytotoxicity was evaluated on malignant cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, and SK-MEL-28) using the MTT and LDH assays. The ability of compounds to stimulate the production of hydrogen peroxide (H2O2) and to induce mitochondrial dysfunction, the externalization of phosphatidylserine, Caspase-9 activity, and changes in nuclear morphology was also studied on MCF-7 cells. The ability to induce DNA damage was also studied on L929 fibroblasts. The proteasome inhibitory activity was estimated through molecular docking studies. The compounds exhibited IC50 values between 15.35 and 53.34 µM. 12R-hydroxy-bromosphaerol and 12S-hydroxy-bromosphaerol increased the H2O2 levels on MCF-7 cells, and bromosphaerol induced DNA damage on fibroblasts. All compounds promoted a depolarization of mitochondrial membrane potential, Caspase-9 activity, and nuclear condensation and fragmentation. The compounds have been shown to interact with the chymotrypsin-like catalytic site through molecular docking studies; however, only 12S-hydroxy-bromosphaerol evidenced interaction with ALA20 and SER169, key residues of the proteasome catalytic mechanism. Further studies should be outlined to deeply characterize and understand the potential of those bromoditerpenes for anticancer therapeutics.

The Prospective Use of Brazilian Marine Macroalgae in Schistosomiasis Control.

Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC-MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.

Antioxidant and Neuroprotective Potential of the Brown Seaweed Bifurcaria bifurcata in an in vitro Parkinson's Disease Model.

Bifurcaria bifurcata is a marine brown seaweed mainly found on the Atlantic coast. Herein, we report the antioxidant and neuroprotective activities of seven fractions (F1⁻F7) obtained by normal phase chromatography from the B. bifurcata dichloromethane extract, as well as of its two major isolated diterpenes. Total phenolic content of fractions was determined by the Folin⁻Ciocalteu method, while antioxidant activity was evaluated by the DPPH, ORAC, and FRAP assays. Neuroprotective effects were evaluated in a neurotoxic model induced by 6-hydroxydopamine (6-OHDA) in a human neuroblastoma cell line (SH-SY5Y), while the mechanisms associated to neuroprotection were investigated by the determination of mitochondrial membrane potential, H2O2 production, Caspase-3 activity, and by observation of DNA fragmentation. Fractions F4 and F5 exhibited the best neuroprotective and antioxidant activities, respectively. F4 fraction prevented changes in mitochondrial potential, and induced a reduction of H2O2 levels production and an increase in cell viability, suggesting that it may contain multi-target compounds acting on different pathways. Hence, this fraction was subjected to purification steps, affording the known diterpenes eleganolone and eleganonal. Both compounds exhibited antioxidant potential, being interesting candidates for further neuroprotective studies.

An Insight into Sargassum muticum Cytoprotective Mechanisms against Oxidative Stress on a Human Cell In Vitro Model.

Sargassum muticum is a brown seaweed with strong potential to be used as a functional food ingredient, mainly due to its antioxidant properties. It is widely used in traditional oriental medicine for the treatment of numerous diseases. Nevertheless, few studies have been conducted to add scientific evidence on its effects as well as on the mechanisms of action involved. In this work, the human cell line MCF-7 was used as an in vitro cellular model to evaluate the capability of Sargassum muticum enriched fractions to protect cells on an oxidative stress condition. The concentration of the bioactive compounds was obtained by vacuum liquid chromatography applied on methanol (M) and 1:1 methanol:dichloromethane (MD) crude extracts, resulting in seven enriched fractions from the M extraction (MF2-MF8), and eight fractions from the MD extraction (MDF1-MDF8). All fractions were tested for cytotoxic properties on MCF-7 cells and the nontoxic ones were tested for their capacity to blunt the damaging effects of hydrogen peroxide-induced oxidative stress. The nontoxic effects were also confirmed in 3T3 fibroblast cells as a nontumor cell line. The antioxidant potential of each fraction, as well as changes in the cell's real-time hydrogen peroxide production, in the mitochondrial membrane potential, and in Caspase-9 activity were evaluated. The results suggest that the protective effects evidenced by S. muticum can be related with the inhibition of hydrogen peroxide production and the inhibition of Caspase-9 activity.

Insights on the taxonomy of Haemoproteus parasites infecting cracid birds.

The Haemosporida order is a well-supported clade of heteroxenous parasites transmitted by dipteran insects and frequently found parasitizing wild birds. These parasites have already been reported in all zoogeographic regions of the world, except for Antarctica. One of the potential hosts of haemosporidians is the Cracidae family, which includes approximately 50 species, 22 of which are present in Brazil, classified within nine genera. Data on haemosporidian infecting individuals of the Cracidae family is scarce, with only three Haemoproteus species being recorded in this group of birds. We found Haemoproteus spp. infection in all Penelope obscura bronzina analyzed. Among the parasites found, we observed two lineages of Haemoproteus (PENOBS02 and PENOBS03), which were characterized by morphological, molecular and phylogenetic approaches. The morphological data on cracid haemosporidian parasites, together with our phylogenetic results, allows discussions on the taxonomy of the Haemoproteus parasites that infect birds of the Cracidae family.

Ioxaglate Versus IoDixanol for the Prevention of Contrast-Induced Nephropathy: The IDPC Trial.

BACKGROUND: Despite the potential benefits of percutaneous procedures for the assessment and treatment of coronary artery disease, these interventions require the use of iodine contrast, which might lead to contrast-induced nephropathy (CIN) and increased risk of dialysis and major adverse cardiac events (MACE). AIMS: We sought to compare two different iodine contrasts (low vs. iso-osmolar) for the prevention of CIN among high-risk patients. METHODS: This is a single-center, randomized (1:1) trial comparing consecutive patients at high risk for CIN referred to percutaneous coronary diagnostic and/or therapeutic procedures with low (ioxaglate) vs. iso-osmolarity (iodixanol) iodine contrast. High risk was defined by the presence of at least one of the following conditions: age >70 years, diabetes mellitus, non-dialytic chronic kidney disease, chronic heart failure, cardiogenic shock, and acute coronary syndrome (ACS). The primary endpoint was the occurrence of CIN, defined as a >25% relative increase and/or >0.5 mg/dL absolute increase in creatinine (Cr) levels compared with baseline between the 2nd and 5th day after contrast media administration. RESULTS: A total of 2,268 patients were enrolled. Mean age was 67 years. Diabetes mellitus (53%), non-dialytic chronic kidney disease (31%), and ACS (39%) were highly prevalent. The mean volume of contrast media was 89 ml ± 48.6. CIN occurred in 15% of all patients, with no significant difference regarding the type of contrast used (iso = 15.2% vs. low = 15.1%, P>.99). Differences were not observed in specific subgroups such as diabetics, elderly, and ACS patients. At 30-day follow-up, 13 patients in the iso-osmolarity group and 11 in low-osmolarity group required dialysis (P =.8). There were 37 (3.3%) deaths in the iso-osmolarity cohort vs. 29 (2.6%) in the low-osmolarity group (P =.4). CONCLUSION: Among patients at high risk for CIN, the incidence of this complication was 15%, and independent of the use of low- or iso-osmolar contrast.

Critically ill patients with COVID-19-associated acute kidney injury treated with kidney replacement therapy: Comparison between the first and second pandemic waves in São Paulo, Brazil.

INTRODUCTION: This study aimed to compare the characteristics and outcomes of critically ill patients with COVID-19-associated acute kidney injury (AKI) who were treated with kidney replacement therapy (KRT) in the first and second waves of the pandemic in the megalopolis of Sao Paulo, Brazil. METHODS: A multicenter retrospective study was conducted in 10 intensive care units (ICUs). Patients aged ≥18 years, and treated with KRT due to COVID-19-associated AKI were included. We compared demographic, laboratory and clinical data, KRT parameters and patient outcomes in the first and second COVID-19 waves. RESULTS: We assessed 656 patients (327 in the first wave and 329 in the second one). Second-wave patients were admitted later (7.1±5.0 vs. 5.6±3.9 days after the onset of symptoms, p<0.001), were younger (61.4±13.7 vs. 63.8±13.6 years, p = 0.023), had a lower frequency of diabetes (37.1% vs. 47.1%, p = 0.009) and obesity (29.5% vs. 40.0%, p = 0.007), had a greater need for vasopressors (93.3% vs. 84.6%, p<0.001) and mechanical ventilation (95.7% vs. 87.8%, p<0.001), and had higher lethality (84.8% vs. 72.7%, p<0.001) than first-wave patients. KRT quality markers were independently associated with a reduction in the OR for death in both pandemic waves. CONCLUSIONS: In the Sao Paulo megalopolis, the lethality of critically ill patients with COVID-19-associated AKI treated with KRT was higher in the second wave of the pandemic, despite these patients being younger and having fewer comorbidities. Potential factors related to this poor outcome were difficulties in health care access, lack of intra-hospital resources, delay vaccination and virus variants.

A Case of Recurrent Idiopathic Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a rare chronic neutrophilic dermatosis that can be associated with underlying conditions, such as inflammatory bowel disease and neoplasms, or can be idiopathic. Classically, it presents as painful skin lesions. We present a case of a 54-year-old woman who got a synovial cyst removed from her left hand, which later aggravated into a non-healing wound, and subsequently a painful necrotic ulcer. The histological pattern combined with the clinical features suggested PG. General wound care was performed, associated with topical tacrolimus and oral corticotherapy with a good response. Three similar episodes with lesions scattered over the body followed and required a combination of other pharmacological alternatives. An extensive etiological study was carried out to screen secondary causes without any relevant findings. Therefore, an idiopathic relapsing PG was assumed. PG is poorly understood, underdiagnosed and hard to treat. It has a clear impact on the quality of life of the patient, so high suspicion and timely treatment are essential to minimize complications.

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil.

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge.

The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.

Medusa polyps adherence inhibition: A novel experimental model for antifouling assays.

Although in the last decades significant advances have been made to improve antifouling formulations, the main current options continue to be highly toxic to marine environment, leading to an urgent need for new safer alternatives. For anti-adherence studies, barnacles and mussels are commonly the first choice for experimental purposes. However, the use of these organisms involves a series of laborious and time-consuming stages. In the present work, a new approach for testing antifouling formulations was developed under known formulations and novel proposed options. Due to their high resilience, ability of surviving in hostile environments and high abundance in different ecosystems, medusa polyps present themselves as prospect candidates for antifouling protocols. Thus, a complete protocol to test antifouling formulations using polyps is presented, while the antifouling properties of two invasive seaweeds, Asparagopsis armata and Sargassum muticum, were evaluated within this new test model framework. The use of medusa polyps as model to test antifouling substances revealed to be a reliable alternative to the conventional organisms, presenting several advantages since the protocol is less laborious, less time-consuming and reproductive. The results also show that the seaweeds A. armata and S. muticum produce compounds with anti-adherence properties being therefore potential candidates for the development of new greener antifouling formulations.

Highlighting the Biological Potential of the Brown Seaweed Fucus spiralis for Skin Applications.

Skin aging is a biological process influenced by intrinsic and extrinsic factors. The last ones, mainly exposure to UV radiation, increases reactive oxygen species (ROS) production leading to a loss of extracellular matrix, also enhanced by enzymatic degradation of matrix supporting molecules. Thus, and with the growing demand for eco-friendly skin products, natural compounds extracted from brown seaweeds revealed to be good candidates due to their broad range of bioactivities, especially as antioxidants. The aim of this study was to assess the dermo-cosmetic potential of different fractions obtained from the brown seaweed Fucus spiralis. For this purpose, in vitro antioxidant (Total Phenolic Content (TPC), 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Absorbance Capacity (ORAC)), anti-enzymatic (collagenase, elastase and hyaluronidase), antimicrobial, anti-inflammatory (NO production) and photoprotective (ROS production) capacities were evaluated. Although nearly all fractions evidenced antioxidant effects, fraction F10 demonstrated the highest antioxidant ability (EC50 of 38.5 µg/mL, DPPH assay), and exhibited a strong effect as an inhibitor of collagenase (0.037 µg/mL) and elastase (3.0 µg/mL). Moreover, this fraction was also the most potent on reducing ROS production promoted by H2O2 (IC50 of 41.3 µg/mL) and by UVB (IC50 of 31.3 µg/mL). These bioactivities can be attributed to its high content of phlorotannins, as evaluated by LC-MS analysis, reinforcing the potential of F. spiralis for further dermatological applications.

The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays.

BACKGROUND: Schistosomiasis chemotherapy is largely based on praziquantel (PZQ). Although PZQ is very safe and tolerable, it does not prevent reinfection and emerging resistance is a primary concern. Recent studies have shown that the targeting of epigenetic machinery in Schistosoma mansoni may result in severe alterations in parasite development, leading to death. This new route for drug discovery in schistosomiasis has focused on classes of histone deacetylases (HDACs) and histone acetyltransferases (HATs) as epigenetic drug targets. Schistosoma histone demethylases also seem to be important in the transition of cercariae into schistosomula, as well as sexual differentiation in adult worms. METHODS: The Target-Pathogen database and molecular docking assays were used to prioritize the druggability of S. mansoni histone demethylases. The transcription profile of Smp_03400 was re-analyzed using available databases. The effect of GSK-J4 inhibitor in schistosomula and adult worms' motility/viability/oviposition was assessed by in vitro assays. Ultrastructural analysis was performed on adult worms exposed to GSK-J4 by scanning electron microscopy, while internal structures and muscle fiber integrity was investigated by confocal microscopy after Langeron's carmine or phalloidin staining. RESULTS: The present evaluation of the potential druggability of 14 annotated S. mansoni demethylase enzymes identified the S. mansoni ortholog of human KDM6A/UTX (Smp_034000) as the most suitable druggable target. In silico analysis and molecular modeling indicated the potential for cofactor displacement by the chemical probe GSK-J4. Our re-analysis of transcriptomic data revealed that Smp_034000 expression peaks at 24 h in newly transformed schistosomula and 5-week-old adult worms. Moreover, this gene was highly expressed in the testes of mature male worms compared to the rest of the parasite body. In in vitro schistosome cultures, treatment with GSK-J4 produced striking effects on schistosomula mortality and adult worm motility and mortality, as well as egg oviposition, in a dose- and time-dependent manner. Unexpectedly, western blot assays did not demonstrate overall modulation of H3K27me3 levels in response to GSK-J4. Confocal and scanning electron microscopy revealed the loss of original features in muscle fibers and alterations in cell-cell contact following GSK-J4 treatment. CONCLUSIONS: GSK-J4 presents promising potential for antischistosomal control; however, the underlying mechanisms warrant further investigation.

EMG Pattern Recognition for Persons with Cervical Spinal Cord Injury.

Pattern recognition based myoelectric control has been widely explored in the field of prosthetics, but little work has extended to other patient groups. Individuals with neurological injuries such as spinal cord injury may also benefit from more intuitive control that may facilitate more interactive treatments or improved control of functional electrical stimulation (FES) systems or assistive technologies. This work presents a pilot study with 10 individuals with cervical spinal cord injury between A and C on the American Spinal Injury Association Impairment Scale. Subjects attempted to elicit 10 classes of forearm and hand movements while their electromyogram (EMG) was recorded using a cuff of eight electrodes. Various well-known EMG features were evaluated using a linear discriminant analysis classifier, yielding classification error rates as low as 4.3% ± 3.9 across the 10 classes. Reducing the number of classes to five, those required to control a commercial therapeutic FES device, further reduced the error rates to (2.2% ± 4.4). Results from this study provide evidence supporting continued exploration of EMG pattern recognition techniques for use by high-level spinal cord injured populations as a method of intuitive control over interactive FES systems or assistive devices.

A novel disposable self-adhesive inked paper device for electrochemical sensing of dopamine and serotonin neurotransmitters and biosensing of glucose.

In this work, we detail the progress of a novel electrochemical disposable device, which has a relatively low cost and easy production, with a novel conductive ink, that consists of graphite and automotive varnish mixture, deposited over a self-adhesive paper, granting an easy production with relatively low cost. The electrode surface was characterized by scanning electron microscopy, X-ray powder diffraction and Fourier transforms infrared and Raman, cyclic voltammetry and electrochemical impedance spectroscopies. In addition, the proposed electrode was applied for individual electrochemical determination of dopamine and serotonin. The device achieved a linear response between 30 and 800 µmol L-1 and a limit of detection (LOD) of 0.13 µmol L-1, by square wave voltammetry for dopamine and a linear range from 6.0 to 100 µmol L-1, with a LOD of 0.39 µmol L-1, by differential pulse voltammetry for serotonin. Later, the working electrode was modified with glucose oxidase and dihexadecyl phosphate film in order to obtain a biosensor. At this stage, CV was applied to detect glucose in the range of 1.0-10 µmol L-1 and LOD of 0.21 µmol L-1. By three different techniques and analytes, the sensoring and biosensoring processes presented high reproducibility. The proposed adhesive electrode is easy to prepare, disposable, within non-restrictive nature, which allows an approach of a new device for electrochemical sensing and biosensing.

Effect of Casearia sylvestris on the obliteration of dentinal tubules and the control of dental sensitivity / Efecto de Casearia sylvestris sobre la obliteración de los túbulos dentinarios y el control de la sensibilidad dental

The present study evaluated the efficacy of the mineralizing action of Casearia sylvestris ethanolic extract on bovine dentin blocks in its pure form and in dental paste, through scanning electron microscopy. The dentin blocks were immersed in artificial saliva and incubat ed at 37°C for 7 days. Subsequently, six groups were treated with different test substances and analysed qualitatively and quantitatively at 30 and 60 days. The tests used were Kruskal - Wallis and Dunn's. Shapiro - Wilk and ANOVA. The qualitative analysis at 30 days showed a difference between the groups treated with ethanolic extract and toothpaste. Quantitatively, at 30 days, treatment with ethanolic extract of Casearia showed a greater number of open dentinal tubules. At 60 days, the difference persisted on ly for the blocks treated with toothpaste. The results obtained indicated that there is a positive relationship between the use of Casearia sylvestris and obliteration of dentinal tubules

El presente estudio evaluó la eficacia de la acción mineralizante del extracto etanólico de Casearia sylvestris sobre bloques de dentina bovina en su forma pura y en pasta dental, mediante microscopía electrónica de barrido. Los bloques de dentina se sumergieron en saliva artificial y se incubaron a 37°C durante 7 días. Posteriormente, se trataron seis grupos con diferentes sustancias de ensayo y se analizaron cualitativa y cuantitativamente a los 30 y 60 días. Las p ruebas utilizadas fueron Kruskal - Wallis y Dunn's. Shapiro - Wilk y ANOVA. El análisis cualitativo a los 30 días mostró una diferencia entre los grupos tratados con extracto etanólico y pasta dentífrica. Cuantitativamente, a los 30 días, el tratamiento con ex tracto etanólico de Casearia mostró un mayor número de túbulos dentinarios abiertos. A los 60 días, la diferencia persistió sólo para los bloques tratados con pasta dentífrica. Los resultados obtenidos indicaron que existe una relación positiva entre el us o de Casearia sylvestris y la obliteración de los túbulos dentinarios

De-escalação de inibidores dos receptores P2Y12 após intervenção coronária percutânea / P2Y12 inhibitor de-escalation after percutaneous coronary interventions

Em pacientes que apresentam síndromes coronárias agudas e são tratados com intervenção coronária percutânea, a prescrição do esquema antiplaquetário duplo, composto de ácido acetilsalicílico e um inibidor dos receptores P2Y12, é mandatória, contribuindo para a redução de eventos cardíacos maiores. No entanto, ao mesmo tempo em que previne eventos isquêmicos, essa associação pode precipitar complicações hemorrágicas maiores, o que é mais comumente observado quando são prescritos os medicamentos mais potentes, como o prasugrel ou o ticagrelor. Essas constatações levaram à procura de alternativas terapêuticas capazes de manter a proteção contra eventos isquêmicos e, ao mesmo tempo, prevenir a ocorrência de hemorragias. Uma das estratégias que está em estudo é a de-escalação dos inibidores P2Y12, que consiste no uso dos medicamentos mais potentes numa fase precoce após o procedimento, com substituição deles pelo clopidogrel, após um período de, em geral, 30 dias de evolução; outra possibilidade seria a simples redução da dose do fármaco de maior potência, algo que, até o momento, só pode ser cogitado com o prasugrel. A de-escalação pode ser feita de forma guiada, utilizando testes de mensuração objetiva da agregação plaquetária ou exames para avaliar o perfil genético dos pacientes, ou não guiada, na qual o cardiologista simplesmente faz a substituição ou redução da dose ao fim do período estipulado, sem o auxílio de exames complementares. A literatura contempla ensaios clínicos com essas duas opções de estratégia, os quais são discutidos nesta revisão. Até o momento, nenhuma diretriz médica recomenda de forma explícita o uso regular dessa alternativa terapêutica.

In patients who have acute coronary syndromes and are treated with percutaneous coronary intervention, the prescription of a dual antiplatelet regimen, consisting of acetylsalicylic acid and a P2Y12 receptor inhibitor, is mandatory, contributing to the reduction of major cardiac events. However, while preventing ischemic events, this association may precipitate major bleeding complications, which is more commonly seen when more potent drugs, such as prasugrel or ticagrelor, are prescribed. These findings led to the search for therapeutic alternatives that could maintain the protection against ischemic events and, at the same time, prevent the occurrence of hemorrhages. One of the strategies being studied is de-escalation of P2Y12 inhibitors, which consists of the use of more potent drugs in an early phase after the procedure, replacing them with clopidogrel, after a period of, in general, 30 days of clinical course. Another possibility would be to simply reduce the dose of the most potent drug, which so far can only be considered with prasugrel. De-escalation can be done in a guided way, using objective measuring tests of platelet aggregation or exams to assess the genetic profile of patients, or unguided, in which the cardiologist simply replaces or reduces the dose at the end of the stipulated period, with no ancillary tests. The literature includes clinical trials with these two strategy options, which are discussed in this review. So far, no medical guideline explicitly recommends the regular use of this therapeutic alternative.

Impacto do volume de contraste utilizado após procedimentos coronários percutâneos em pacientes predispostos a desenvolver nefropatia induzida pelo contraste / Impact of contrast volume used after percutaneous coronary procedures in patients predisposed to developing contrast-induced nephropathy

INTRODUÇÃO: A nefropatia induzida por contraste (NIC) é uma complicação dos procedimentos angiográficos que requerem a administração de meios de contraste. Grandes volumes estão associados à NIC. Não está claro se o tipo de contraste interfere nessa diferença. OBJETIVO: Avaliar se o volume de contraste utilizado nos procedimentos percutâneos tem interação com o tipo de contraste (baixa ou isosmolar) no desenvolvimento de NIC. MÉTODOS: A NIC é definida como uma elevação de creatinina sérica de mais de 25% ou ≥0,5 mg/dl da basal após 48 h. Subanálise de estudo randomizado, centro único, incluindo 2268 pacientes consecutivos submetidos a procedimentos coronários diagnósticos e terapêuticos entre 2016 a 2018. Todos os procedimentos foram realizados com contraste de baixa osmolaridade ou iso-osmolar. A amostra foi dividida em 2 grupos em relação ao volume de 150ml de contraste. Análise estatística: para avaliar o efeito do contrate e do volume no NIC, utilizou-se um modelo de regressão logística com efeito de interação. Este modelo foi avaliado também ajustado para síndrome coronária aguda, disfunção ventricular, creatinina basal, sexo e idade. Os dados foram analisados com uso do software R versão 4.1.2. RESULTADOS: População predominantemente masculina, HAS (85%), DM (52%), DRC (31%). Modelo de regressão logística com efeito de interação entre contraste e volume (p>0,999). Modelos aditivos para NIC apresentado na tabela 1 abaixo. CONCLUSÃO: Nesse estudo, mesmos nos casos em que maior quantidade de contraste foi utilizada, o tipo de contraste (iso-osmolar ou de baixa osmolaridade) não foi associado à ocorrência de NIC.