RESUMO

Introduction: This case report presents the intentional periodontal maintenance of two periodontal hopeless lower central incisors with a multidisciplinary approach and 20-year follow-up. Case presentation: A 36-year-old male, in 2001, was diagnosed with aggressive periodontitis, gingival swelling, bleeding, and mandibular central incisors with mobility and poor prognosis. Following periodontal therapy (phase I), root canal treatment, and occlusal adjustment, #31 and #41 were gently extracted to remove the granulation tissues, calculus, and infected cementum from the root surface. Then, tetracycline-HCl was applied for 5 minutes on the root surfaces. The teeth were repositioned into the sockets and splinted with a lingual bar. At 3 months, the bar was removed, and a free gingival autogenous graft was done to improve the local keratinized tissue width. Mobility scores, pocket depths, and clinical attachment levels were recorded, and radiographs were taken at 1, 5, and 20 years. The 5-year follow-up showed that the teeth were clinically and radiographically in function. There was a reduction in probing depth and a gain in clinical attachment and radiographic alveolar bone levels. After 20 years, #41 was stable, but #31 had external root resorption, leading to a new treatment plan (dental implants) and extraction. Conclusion: The clinical result of this case was satisfactory for 20 years. Intentional periodontal maintenance of the teeth may be an alternative treatment, even considering the high level of complexity.

Assuntos

Humanos , Masculino , Adulto , Planejamento de Assistência ao Paciente , Periodontia , Procedimentos Cirúrgicos Operatórios , Tempo , Perda da Inserção Periodontal

RESUMO

As condições fitossanitárias de plantas arbóreas podem ser utilizadas para caracterizar comunidades vegetais, indicando condições de qualidade estrutural do componente vegetal. Assim, ambientes alterados antropicamente podem representar uma ameaça à fitossanidade. O objetivo deste estudo foi averiguar as características fitossanitárias do componente arbóreo em um trecho de 400 metros de extensão ao longo da linha férrea localizada no município de Três Barras, estado de Santa Catarina, Brasil. Foram registradas 33 espécies arbóreas, 29 gêneros e 19 famílias. Os índices ecológicos avaliados foram a abundância, densidade, riqueza e equabilidade. Foram avaliados 190 indivíduos em relação a qualidade da copa, grau de infestação de cipós e sanidade da árvore. Embora a qualidade da copa e a sanidade sejam majoritariamente boas, houve um relativo alto número de infestação de cipós. Tal ocorrência pode ser devido à condição de borda em que as plantas se encontram. Os bons índices ecológicos aliados ao baixo número de espécies arbóreas exóticas também indicam boas condições ecológicas e de fitossanidade local. Contudo, são necessários mais estudos (p. ex. florísticos e fitossociológicos) na área. A arborização urbana das proximidades aliada à formação de corredores ecológicos que liguem os fragmentos à Floresta Nacional de Três Barras pode ser uma medida de conservação e regeneração a ser explorada.

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Phytosanitary conditions of tree plants can be used to characterize plant communities, indicating structural quality conditions of the plant component. Thus, anthropically altered environments may pose a threat to plant health. The objective of this study was to investigate the phytosanitary and ecological condition of the tree component in a stretch of 400 meters along the railway line located in the municipality of Três Barras, Santa Catarina state, Brazil. Thirty-three tree species were recorded, in addition to 54 taxonomically unidentified individuals. The ecological indices evaluated were abundance, density, richness and evenness. 190 individuals were evaluated in terms of crown quality, Abstract degree of liana infestation and tree health. Although canopy quality and health are mostly good, there was a relatively high number of vine infestations. Such an occurrence may be due to the edge condition in which the plants are located. The good ecological indices combined with the low number of exotic tree species also indicate good ecological conditions and local plant health. However, more studies are needed in the area. Urban afforestation, combined with the formation of ecological corridors that connect the fragments to the Três Barras National Forest, can be a conservation and regeneration measure to be explored.

RESUMO

The conceptual expansion, fast development, and general acceptance of flow analysis are consequence of its adherence to the principles of green and white analytical chemistry, and chemical derivatization plays an essential role in this context. Through the flow analysis development, however, some of its potentialities and limitations have been overlooked. This is more evident when the involved modifications in flow rates, timing and/or manifold architecture deteriorate the analytical signals. These aspects have not always been systematically investigated, and are addressed here in relation to flow analyzers with UV-Vis spectrophotometric detection. Novel strategies for solution handling, guidance for dealing with the aforementioned analytical signal deterioration, and an alternative possibility for exploiting differential aspiration are presented. The concept of blank reagent carrier stream is proposed.

RESUMO

Introduction: The morbidity and mortality of acute ischemic hypoxic encephalopathy in newborns have not been dramatically modified over the last 20 years. The purpose of this review is to describe the use of hyperbaric oxygenation therapy (HBOT) in the management of acute ischemic hypoxic encephalopathy in newborns. Methods: A review of the medical literature was conducted on the use of HBOT in the pathophysiology of this condition and its impact on outcomes of patients treated at an early stage. Results: When HBOT is administered promptly, it can promote the survival of the penumbra, modulate the cytokine storm, modify inflammatory cascades, restore mitochondrial function, inhibit apoptosis, reinstate cellular communication and cytoskeleton function, reinstall the functioning of the kinase system, reduce cytotoxic and tissue edema, promote microcirculation, and provide an antioxidant effect. All these secondary mechanisms aid in saving, rescuing, and protecting the marginal tissue. Conclusion: When used promptly, HBOT is a non-invasive adjunct treatment that can preserve the marginal tissue affected by ischemia, hypoxia, meet the metabolic needs of the penumbra, reduce inflammatory cascades, prevent the extension of the damaged tissue, and modulate ischemia-reperfusion injury.

RESUMO

BACKGROUND: Multidrug-resistant bacteria in humans have prompted the search for alternative solutions derived from herbal medicines that can substitute antibiotics in livestock production. Thus, the goal of this study was to evaluate the phytogenic properties of Marrubium vulgare infusion (MVI) on weaned pigs. Thirty animals were randomly divided into five groups of six animals, each receiving a physiological solution, clenbuterol and the infusion extract at doses of 0.01 (MVI 1%), 0.1 (MVI 10%) and 0.2 (MVI 20%) mg kg-1 for 28 days. Biochemical parameters and the liquid chromatographic-electrospray ionization-mass spectrometric (LC-ESI-MS) chemical profiles of the infusion extract and animal serum were studied. RESULTS: The doses MVI 1 and 10% led to weight gain higher than the controls. No significant changes were noted in the biochemical parameters including erythrocytes, hemoglobin, hematocrit, mean corpuscular volume and others. Evaluation of enzymatic levels in blood revealed no significant changes. LC-ESI-MS data of MVI showed the presence of 34 secondary metabolites, and successive chromatographic purification of MVI yielded marrubiin and apigenin as major components. LC-ESI-MS data of animal serum showed the presence of a diterpene, a flavonoid and diverse cholic acid derivatives. CONCLUSION: Results indicated the doses MVI 1 and 10% promote weight gain with no significant alterations in blood biochemicals, and liver and kidney function. © 2024 Society of Chemical Industry.

RESUMO

In this paper, the development of a 3D adaptive probabilistic explicit cracking model for concrete is reported. The contribution offered herein consists in a new adaptive mesh strategy designed to optimize the use of interface elements in probabilistic explicit cracking models. The proposed adaptive mesh procedure is markedly different from other strategies found in the literature, since it takes into account possible influences on the redistribution of stresses after cracking and can also be applied to purely deterministic cracking models. The process of obtaining the most appropriate adaptive mesh procedure involved the development and evaluation of three different adaptivity strategies. Two of these adaptivity strategies were shown to be inappropriate due to issues related to stress redistribution after cracking. The validation results demonstrate that the developed adaptive probabilistic model is capable of predicting the scale effect at a level similar to that experimentally observed, considering the tensile failure of plain concrete specimens. The results also show that different softening levels can be obtained. The proposed adaptive mesh strategy proved to be advantageous, being able to promote significant reductions in the simulation time in comparison with the classical strategy commonly used in probabilistic explicit cracking models.

RESUMO

RATIONALE: Pharmacological treatments for depression are not always effective and produce unwanted side effects. Male and female sexual dysfunction is one of these side effects, which can lead to treatment withdrawal. Combination of two antidepressants with different mechanisms of action, like mirtazapine (MTZ) and venlafaxine (VLF) have been shown to be effective for treatment-resistant depression in humans. Combination of low doses of these drugs may still exert antidepressant-like effects without altering sexual behavior. OBJECTIVES: To investigate the potential antidepressant-like effect of the chronic administration of low doses of MTZ plus VLF combined, as well as its impact on male and female sexual behavior in rats. METHODS: The antidepressant-like effect of a 14-day treatment with combinations of MTZ plus VLF (0/0, 2.5/3.75 or 5/7.5 mg/kg) was assessed in young adult male and female rats in the forced swim test (FST). The 5/7.5 mg/kg MTZ/VLF combination was also tested in the chronic mild stress (CMS) test, in both males and females treated for 21 days. The sexual effects of this last treatment were assessed in sexually experienced males and in gonadally-intact females during proestrus. RESULTS: The 5/7.5 mg/kg MTZ/VLF combination produced an antidepressant-like effect in the FST and reversed the CMS-induced anhedonia in both male and female rats. This combination did not alter male sexual behavior, female proceptive and receptive behaviors or the regularity of the estrous cycle. CONCLUSION: The combination of low doses of MTZ and VLF might be a promising therapeutic alternative to treat depression without affecting the sexual response.

RESUMO

This study assessed the in vitro anthelmintic activity of ethyl acetate extract (Cn-EtOAc) and its bioactive fractions (CnR3 and CnR5) obtained from Chamaecrista nictitans aerial parts against two Haemonchus contortus (Hc) isolates, one resistant (strain HcIVM-R) and another susceptible (strain HcIVM-S) to ivermectin. Ferulic acid and p-coumaric acid were identified in the bioactive fractions; therefore, their commercial standards were also assessed. A colocalization analysis between the ferulic acid commercial standard and eggs of the HcIVM-R strain was performed using confocal laser scanning microscopy and the ImageJ program. The ovicidal effects of the Cn-EtOAc extract, bioactive fractions and commercial compounds were tested through the egg hatching inhibition (EHI) assay on H. contortus isolates HcIVM-R and HcIVM-S. The Cn-EtOAc caused 88 % and 92 % EHI at 5000 µg/mL on HcIVM-R and HcIVM-S, respectively. Fractions CnR3 and CnR5 displayed the highest ovicidal activity against HcIVM-S, with effective concentrations (EC90) of 2134 and 601 µg/mL, respectively. Meanwhile, the commercial standards ferulic acid and p-coumaric acid also resulted in higher effectiveness on the same strain, with EC90 of 57.5 and 51.1 µg/mL. A colocalization analysis of ferulic acid and eggs of HcIVM-R revealed that this compound is localized to the cuticle surface of the embryo inside the egg parasite. The results demonstrated that both ferulic and p-coumaric acids interrupt the egg-hatching processes of the two Hc isolates. Both phenolic acids isolated from C. nictitans and commercial standards exhibited the best anthelmintic effect on HcIVM-S. These findings indicate that the phenolic acids were less effective in egg hatch inhibiting on the HcIVM-R strain compared to the HcIVM-S strain.

Assuntos

Anti-Helmínticos , Ácidos Cumáricos , Haemonchus , Extratos Vegetais , Animais , Haemonchus/efeitos dos fármacos , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Óvulo/efeitos dos fármacos

RESUMO

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

Assuntos

Analgésicos , Antidepressivos , Flavonoides , Morfina , Animais , Morfina/farmacologia , Morfina/uso terapêutico , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/química , Masculino , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Flavonoides/química , Dor/tratamento farmacológico , Manejo da Dor/métodos , Atividade Motora/efeitos dos fármacos

RESUMO

Background: Due to the copious disposal of plastics, marine ecosystems receive a large part of this waste. Microplastics (MPs) are solid particles smaller than 5 millimeters in size. Among the plastic polymers, polystyrene (PS) is one of the most commonly used and discarded. Due to its density being greater than that of water, it accumulates in marine sediments, potentially affecting benthic communities. This study investigated the ingestion of MP and their effect on the meiofauna community of a sandy beach. Meiofauna are an important trophic link between the basal and higher trophic levels of sedimentary food webs and may therefore be substantially involved in trophic transfer of MP and their associated compounds. Methods: We incubated microcosms without addition of MP (controls) and treatments contaminated with PS MP (1-µm) in marine sediments at three nominal concentrations (103, 105, 107particles/mL), for nine days, and sampled for meiofauna with collections every three days. At each sampling time, meiofauna were collected, quantified and identified to higher-taxon level, and ingestion of MP was quantified under an epifluorescence microscope. Results: Except for Tardigrada, all meiofauna taxa (Nematoda, turbellarians, Copepoda, Nauplii, Acari and Gastrotricha) ingested MP. Absorption was strongly dose dependent, being highest at 107 particles/mL, very low at 105 particles/mL and non-demonstrable at 103 particles/mL. Nematodes accumulated MP mainly in the intestine; MP abundance in the intestine increased with increasing incubation time. The total meiofauna density and species richness were significantly lower at the lowest MP concentration, while at the highest concentration these parameters were very similar to the control. In contrast, Shannon-Wiener diversity and evenness were greater in treatments with low MP concentration. However, these results should be interpreted with caution because of the low meiofauna abundances at the lower two MP concentrations. Conclusion: At the highest MP concentration, abundance, taxonomic diversity and community structure of a beach meiofauna community were not significantly affected, suggesting that MP effects on meiofauna are at most subtle. However, lower MP concentrations did cause substantial declines in abundance and diversity, in line with previous studies at the population and community level. While we can only speculate on the underlying mechanism(s) of this counterintuitive response, results suggest that further research is needed to better understand MP effects on marine benthic communities.

Assuntos

Biodiversidade , Microplásticos , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Cadeia Alimentar , Organismos Aquáticos , Poliestirenos , Invertebrados/efeitos dos fármacos , Monitoramento Ambiental/métodos

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), etiological agent for the coronavirus disease 2019 (COVID-19), has resulted in over 775 million global infections. Early diagnosis remains pivotal for effective epidemiological surveillance despite the availability of vaccines. Antigen-based assays are advantageous for early COVID-19 detection due to their simplicity, cost-effectiveness, and suitability for point-of-care testing (PoCT). This study introduces a graphene field-effect transistor-based biosensor designed for high sensitivity and rapid response to the SARS-CoV-2 spike protein. By functionalizing graphene with monoclonal antibodies and applying short-duration gate voltage pulses, we achieve selective detection of the viral spike protein in human serum within 100 µs and at concentrations as low as 1 fg ml-1, equivalent to 8 antigen molecules perµl of blood. Furthermore, the biosensor estimates spike protein concentrations in serum from COVID-19 patients. Our platform demonstrates potential for next-generation PoCT antigen assays, promising fast and sensitive diagnostics for COVID-19 and other infectious diseases.

Assuntos

Técnicas Biossensoriais , COVID-19 , Grafite , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Transistores Eletrônicos , Glicoproteína da Espícula de Coronavírus/análise , Glicoproteína da Espícula de Coronavírus/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Grafite/química , Humanos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/imunologia , COVID-19/diagnóstico , COVID-19/sangue , COVID-19/virologia , Sensibilidade e Especificidade , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química

RESUMO

In this study, we analyzed the hematoimmunological effects of dietary supplementation with immunomodulators (ß-glucans + nucleotides) and different levels of vitamins on Nile tilapia (Oreochromis niloticus) after exposure to physical stress. The following four diet treatments were used: diets with indicated vitamin levels (Vitind), diets with Vitind + immunomodulator (Vitind + Immune), diets with high vitamin content (Vithigh), and those with Vithigh + immunomodulator (Vithigh + Immune). The experiment included 560 fish in 28 tanks (20 fish tank-1), with seven replicates per treatment. After 60 days of supplementation, the water temperature was set at 20 °C, and complete biometrics were performed. The animals were then subjected to physical stress with temperature oscillations of 20 ºC to 30 ºC/30 ºC to 20 ºC/20 ºC to 30 ºC. Hematoimmunological data from 140 animals were collected post-stress. Antimicrobial titer and total plasma protein levels were significantly higher in fish not receiving immunomodulator-supplemented diets (2.88 ± 0.43 log2 and 26.81 ± 4.01 mg∙mL-1, respectively) than in those that did. Conversely, the agglutination titer increased in fish fed with lower vitamin levels (3.33 ± 0.66 log2) compared to those with higher vitamin levels. Increased immunoglobulin levels were observed in fish fed diets co-supplemented with vitamins and immunomodulators, revealing an interaction between immunomodulators and dietary vitamin levels. In summary, the inclusion of immunomodulators in the diet enhanced the animals' resistance to physical stress and improved hematoimmunological parameters. Additionally, a high vitamin content in the diet did not modulate the immune responses in the animals.

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Neste estudo analisamos os efeitos hematoimunológicos da suplementação dietética com imunomoduladores (ß-glucanos+nucleotídeos) e diferentes níveis de vitaminas na tilápia do Nilo (Oreochromis niloticus) após exposição ao estresse físico. Foram utilizados quatro tratamentos: dietas com níveis indicados de vitaminas (Vitind), dietas com Vitind + imunomodulador (Vitind+Immune), dietas com alto teor de vitaminas (Vithigh) e dietas com Vithigh + imunomodulador (Vithigh+Immune). O experimento incluiu 560 peixes em 28 tanques (20 peixes tanques-1), com sete repetições por tratamento. Após 60 dias de suplementação, a temperatura da água foi fixada em 20 °C e realizada biometria completa. Os animais foram submetidos a estresse físico com oscilações de temperatura de 20 ºC a 30 ºC/30 ºC a 20 ºC/20 ºC a 30 ºC. Dados hematoimunológicos de 140 animais foram coletados pós-estresse. O título antimicrobiano e os níveis de proteína plasmática total foram significativamente maiores em peixes que não receberam dietas com imunomodulador (2,88±0,43 log2 e 26,81±4,01 mg∙mL−1) do que naqueles que receberam. Por outro lado, o título de aglutinação aumentou em peixes alimentados com níveis mais baixos de vitaminas (3,33±0,66 log2) comparado àqueles com níveis mais elevados. Níveis aumentados de imunoglobulinas foram observados em peixes alimentados com dietas co-suplementadas com vitaminas e imunomoduladores, revelando interação entre imunomoduladores e níveis de vitaminas na dieta. Em resumo, a inclusão de imunomoduladores na dieta aumentou a resistência dos animais ao estresse físico e melhorou os parâmetros hematoimunológicos. Além disso, o alto teor de vitaminas na dieta não modulou as respostas imunológicas dos animais.

RESUMO

The maternal diet and egg incubation temperature are some of the factors that can influence the embryonic development and performance of the newly chicks at 15 d of age. This study evaluated the effects of adding a blend of organic acids, essential oils, curcumin, tannins, vitamin E, and zinc microencapsulated in to the diet of female quails (Coturnix coturnix japonica) on their productive, reproductive performance and redox parameters of their eggs and the interaction of maternal diet × incubation temperature on embryo (E16 and E18) and chicks development. At 98 d of age, 64 female quails with a mean body weight of 150 g ± 0.5 were distributed into two treatments: a Basal diet or a diet supplemented with blend (Sannimix). The eggs from each female were incubated at 37.5°C (Control) and 38.5°C (High Temperature) throughout the incubation period. After hatching, chicks were distributed in a 2 (maternal diet) × 2 (incubation temperature) factorial design. Female quails supplemented with Sannimix showed better productive and reproductive performance and produced higher-quality embryos. Their offspring had greater weight at hatch and at 15 d of age. The eggs and offspring of supplemented with Sannimix female quails showed better oxidative stability. At E16 and E18, High Temperature increased yolk sac utilization and gene expression of the growth hormone receptor (GHR). At E16, embryos from supplemented with Sannimix female quail had higher expression of insulin-like growth factor type I (IGFI) and heat shock protein 70 kDa genes. At 15 d of age, highest expression of the GHR and IGFI genes was observed in chicks from female quails fed the Sannimix diet, regardless of incubation temperature. Regarding the maternal diet × incubation temperature an improved result was observed for chicks from female quails fed with Sannimix even when eggs are exposed to High Temperature during the incubation. The supplementation of quail diets with blend Sannimix improves productive and reproductive performance, egg quality and their embryos, as well as their offspring quality.

Assuntos

Ração Animal , Coturnix , Curcumina , Dieta , Suplementos Nutricionais , Óleos Voláteis , Vitamina E , Zinco , Animais , Ração Animal/análise , Dieta/veterinária , Feminino , Suplementos Nutricionais/análise , Coturnix/crescimento & desenvolvimento , Óleos Voláteis/administração & dosagem , Vitamina E/administração & dosagem , Zinco/administração & dosagem , Zinco/metabolismo , Curcumina/administração & dosagem , Curcumina/farmacologia , Taninos/administração & dosagem , Temperatura , Reprodução/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos

RESUMO

BACKGROUND & AIMS: The treatment of cardiovascular diseases (CVD) could greatly benefit from using nitric oxide (NO) donors. This study aimed to investigate the mechanisms of action of NONO2P that contribute to the observed responses in the mesenteric artery. The hypothesis was that NONO2P would have similar pharmacological actions to sodium nitroprusside (SNP) and NO. METHODS: Male Wistar rats were euthanized to isolate the superior mesenteric artery for isometric tension recordings. NO levels were measured using the DAF-FM/DA dye, and cyclic guanosine monophosphate (cGMP) levels were determined using a cGMP-ELISA Kit. RESULTS: NONO2P presented a similar maximum efficacy to SNP. The free radical of NO (NO•) scavengers (PTIO; 100 µM and hydroxocobalamin; 30 µM) and nitroxyl anion (NO-) scavenger (L-cysteine; 3 mM) decreased relaxations promoted by NONO2P. The presence of the specific soluble guanylyl cyclase (sGC) inhibitor (ODQ; 10 µM) nearly abolished the vasorelaxation. The cGMP-dependent protein kinase (PKG) inhibition (KT5823; 1 µM) attenuated the NONO2P relaxant effect. The vasorelaxant response was significantly attenuated by blocking inward rectifying K+ channels (Kir), voltage-operated K+ channels (KV), and large conductance Ca2+-activated K+ channels (BKCa). NONO2P-induced relaxation was attenuated by cyclopiazonic acid (10 µM), indicating that sarcoplasmic reticulum Ca2+-ATPase (SERCA) activation is involved in this relaxation. Moreover, NONO2P increased NO levels in endothelial cells and cGMP production. CONCLUSIONS: NONO2P induces vasorelaxation with the same magnitude as SNP, releasing NO• and NO-. Its vasorelaxant effect involves sGC, PKG, K+ channels opening, and SERCA activation, suggesting its potential as a therapeutic option for CVD.

Assuntos

Proteínas Quinases Dependentes de GMP Cíclico , GMP Cíclico , Doadores de Óxido Nítrico , Óxido Nítrico , Canais de Potássio , Ratos Wistar , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Transdução de Sinais , Guanilil Ciclase Solúvel , Vasodilatação , Animais , Masculino , Vasodilatação/efeitos dos fármacos , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico/metabolismo , Guanilil Ciclase Solúvel/metabolismo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Ratos , Canais de Potássio/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiologia , Guanilato Ciclase/metabolismo , Ativação Enzimática/efeitos dos fármacos

RESUMO

Vásquez-Velásquez, Cinthya, Diego Fano-Sizgorich, and Gustavo F Gonzales. Death risk response of high-altitude resident populations to COVID-19 vaccine: Retrospective cohort study. High Alt Med Biol. 00:00-00, 2024. Background: Peru had one of the highest mortality rates caused by the coronavirus disease 2019 (COVID-19) pandemic worldwide. Vaccination significantly reduces mortality. However, the effectiveness of vaccination might differ at different altitudinal levels. The study aimed to evaluate the effect modification of altitude on the association between vaccination and COVID-19 mortality in Peru. Methodology: A retrospective cohort, using open access databases of deaths, COVID-19 cases, hospitalizations, and vaccination was obtained from the Peruvian Ministry of Health. Deaths due to COVID-19 were evaluated in vaccinated and nonvaccinated patients. Crude (RR) and adjusted relative risks (aRR) were calculated using generalized linear models of Poisson family with robust variances. Models were adjusted for age, sex, pandemic wave, and Human Development Index. To evaluate the interaction by altitude, a stratified analysis by this variable was performed. The variable altitude was categorized as, 0-499 m (828,298 cases), 500-1,499 m (64,735 cases), 1,500-2,499 m (106,572 cases), and ≥2,500 m (179,004 cases). The final sample studied included 1,362,350 cases. Results: The vaccine showed a considerable reduction of death risk with the second (aRR: 0.41, 95% confidence interval [CI]: 0.38-0.44) and third doses (aRR: 0.21, 95% CI: 0.20-0.23). In the adjusted and interaction model, it can be observed that medium and high altitude present a higher risk of death compared to sea level (aRR: 2.58 and 2.03, respectively). Likewise, the two doses' group presents an aRR:1.22 for medium altitude (1,500-2,499 m) and 1.6 for high altitude (≥2,500 m), compared with low-altitude population, suggesting that the action of vaccination at high altitude is altered by the effect of the altitude itself. Conclusions: Altitude might modify the protective effect of SARS-CoV-2 vaccine against COVID-19 death.

RESUMO

In response to the steady increase in antimicrobial-resistant strains, the World Health Organisation has emphasised the need to investigate new antimicrobial agents and alternative therapies that improve the spectrum of activity and reduce the dose required, thus improving safety. This study focused on the characterisation of Acanthospermum australe essential oil and green-synthesis silver nanoparticles (AgNP), evaluating their cytotoxicity in human cells, antimicrobial activity and synergistic effect against pathogens causing skin infections. The main components of the essential oil were germacrene A (24.07%), γ-cadinene (21.47%) and trans-caryophyllene (14.97%). Spherical AgNP with a diameter of 15 ± 3 nm were synthesised. The essential oil showed antimicrobial activity against dermatophytes and Malassezia globosa, while AgNP were found to be active against bacteria, yeasts and dermatophytes. Both compounds were found to be primarily non-cytotoxic at the concentrations required to inhibit microbial growth. Furthermore, the combined use of essential oil and AgNP showed a synergistic antimicrobial effect against dermatophytes and M. globosa. In conclusion, the results suggest that the combined use of bioactive compounds from natural sources, such as essential oil and biogenic AgNP, has the potential to improve antimicrobial efficacy against specific skin pathogens, particularly Microsporum canis, Nannizzia gypsea and M. globosa.

RESUMO

This study presents the potential role of deep eutectic solvents (DESs) in a lipase-catalyzed hydrolysis reaction as a co-solvent in an aqueous solution given by a phosphate buffer. Ammonium salts, such as choline chloride, were paired with hydrogen bond donors, such as urea, 1,2,3-propanetriol, and 1,2 propanediol. The hydrolysis of p-nitrophenyl laureate was carried out with the lipase Candida antarctica Lipase B (CALB) as a reaction model to evaluate the solvent effect and tested in different DES/buffer phosphate mixtures at different % w/w. The results showed that two mixtures of different DES at 25 % w/w were the most promising solvents, as this percentage enhanced the activities of CALB, as evidenced by its higher catalytic efficiency (kcatKM). The solvent analysis shows that the enzymatic reaction requires a reaction media rich in water molecules to enable hydrogen-bond formation from the reaction media toward the enzymatic reaction, suggesting a better interaction between the substrate and the enzyme-active site. This interaction could be attributed to high degrees of freedom influencing the enzyme conformation given by the reaction media, suggesting that CALB acquires a more restrictive structure in the presence of DES or the stabilized network given by the hydrogen bond from water molecules in the mixture improves the enzymatic activity, conferring conformational stability by solvent effects. This study offers a promising approach for applications and further perspectives on genuinely green industrial solvents.

Assuntos

Solventes Eutéticos Profundos , Proteínas Fúngicas , Ligação de Hidrogênio , Lipase , Água , Lipase/química , Lipase/metabolismo , Água/química , Solventes Eutéticos Profundos/química , Proteínas Fúngicas/química , Catálise , Hidrólise , Solventes/química , Biocatálise , Cinética

RESUMO

Core-shell micro/nanomotors have garnered significant interest in biomedicine owing to their versatile task-performing capabilities. However, their effectiveness for photothermal therapy (PTT) still faces challenges because of their poor tumor accumulation, lower light-to-heat conversion, and due to the limited penetration of near-infrared (NIR) light. In this study, we present a novel core-shell micromotor that combines magnetic and photothermal properties. It is synthesized via the template-assisted electrodeposition of iron (Fe) and reduced graphene oxide (rGO) on a microtubular pore-shaped membrane. The resulting Fe-rGO micromotor consists of a core of oval-shaped zero-valent iron nanoparticles with large magnetization. At the same time, the outer layer has a uniform reduced graphene oxide (rGO) topography. Combined, these Fe-rGO core-shell micromotors respond to magnetic forces and near-infrared (NIR) light (1064 nm), achieving a remarkable photothermal conversion efficiency of 78% at a concentration of 434 µg mL-1. They can also carry doxorubicin (DOX) and rapidly release it upon NIR irradiation. Additionally, preliminary results regarding the biocompatibility of these micromotors through in vitro tests on a 3D breast cancer model demonstrate low cytotoxicity and strong accumulation. These promising results suggest that such Fe-rGO core-shell micromotors could hold great potential for combined photothermal therapy.

RESUMO

Selective fluorination of the pyrrolidine ring in proline motifs has been found to induce significant conformational changes that impact the structure and biological roles of modified peptides and proteins. Vicinal difluorination of fluoroproline, for example, in (3S,4R)-3,4-difluoroproline, serves to mitigate the inherent conformational bias of the pyrrolidine ring by inducing stereoelectronic effects that attenuate this conformational bias. In this investigation, we present a quantumchemical analysis of the conformational equilibrium and effects that are induced in difluorinated pyrrolidines, with a particular focus on exploring the impact of gauche and anomeric effects on the conformer stabilities of different stereo- and regioisomers. Initially, we conducted a benchmark assessment comparing the optimal density functional theory method with coupled cluster with single and double excitations (CCSD) calculations and crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from nN→σ*CF electron delocalization, is particularly important in modulating the energetics of the α-fluoro isomers and imparts a strong conformational bias. In contrast, the fluorine gauche effect assumes a secondary role, as it is overshadowed by steric and electrostatic interactions, referred to as Lewis interactions from a natural bond orbital perspective.

RESUMO

We examined the antibacterial efficacy of streptomycin, hibiscus acid, and their combination against multidrug-resistant Shiga-toxin-producing Escherichia coli (STEC) and Salmonella Typhimurium in mice. We determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for streptomycin, hibiscus acid, and their combination against STEC and Salmonella. Fifteen sets of six mice in each set were utilised: six groups were orally exposed to 4 log10 colony forming units (CFUs) of S. Typhimurium and another six to STEC, and three acted as the controls. Six hours post-inoculation, specific groups of mice received either oral solutions containing hibiscus acid at 5 and 7 mg/ml; streptomycin at 50 and 450 µg/ml; hibiscus acid/streptomycin (5 mg/ml hibiscus acid and 50 µg/ml streptomycin); or isotonic saline. The study determined the MIC and MBC of 7 mg/ml of hibiscus acid; 300 and 450 µg/ml of streptomycin; and two concentrations of hibiscus/streptomycin (3 mg/ml / 20 µg/ml and 5 mg/ml / 50 µg/ml). Interestingly, the mice that were infected and subsequently treated with hibiscus acid at 7 mg/ml alone or in conjunction with streptomycin did not have either STEC or Salmonella in their faecal samples, and none of the mice died. In contrast, the untreated mice and those exclusively treated with streptomycin had the pathogens present in their stool, leading to the mortality of all the subjects.