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1.
Pediatrics ; 153(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38511227

ABSTRACT

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.


Subject(s)
Intermittent Positive-Pressure Ventilation , Respiratory Distress Syndrome, Newborn , Infant, Newborn , Humans , Continuous Positive Airway Pressure , Infant, Premature , Canada , Gestational Age , Respiratory Distress Syndrome, Newborn/therapy
2.
Res Vet Sci ; 171: 105229, 2024 May.
Article in English | MEDLINE | ID: mdl-38507826

ABSTRACT

This study assessed the pharmacokinetics and pharmacodynamics of low-dose dexmedetomidine after IV bolus in dogs. Six healthy adult dogs (6.8 ± 3.0 kg) received dexmedetomidine (2 µg.kg-1 IV) over 2 min, using an infusion pump. Blood samples were collected totaling 5 h of monitoring. A validated UHPLC-MS/MS method was used to determine the plasma concentration of dexemedetomidine. For pharmacodynamics, HR, RR, oscillometric MBP, Grint END sedation score were evaluated at baseline (T0), every 3 min (T3 to T21), and after 30 (T30) and 60 (T60) minutes, with p < 0.05. T1/2 was 28.28 ± 6.14 min; the area under the curve was 467.44 ± 60.42 ng/mL/min. The total clearance was 5.46 ± 0.41 mL/min/kg, the Vdss was 146.19 ± 21.04 mL/kg, and the C max was 3.13 ± 1.15 ng/mL. HR (bpm) decreased significantly from T6 (79 ± 21) to T21 (78 ± 31) compared to T0 (116 ± 28). RR(mpm) decreased from T3 (43 ± 44) to T60 (41 ± 23), with T0 being 70 ± 48. The MBP (mmHg) increased at T18 (151 ± 34), T21 (152 ± 35), and T30 (140 ± 27), compared to T0 (111 ± 22). Sedation occurred at all times post-bolus, with a maximum peak at T12 (END 8 ± 6). The low dose of dexmedetomidine provided sedation in all animals, characterizing rapid metabolization and elimination. However, cardiovascular effects still may have negative repercussions in dogs with hemodynamic comorbidities, highlighting the caution and individualization of its use in certain patients.


Subject(s)
Dexmedetomidine , Humans , Dogs , Animals , Hypnotics and Sedatives/pharmacology , Tandem Mass Spectrometry/veterinary , Administration, Intravenous/veterinary , Hemodynamics
3.
Early Hum Dev ; 190: 105942, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38306954

ABSTRACT

BACKGROUND: Right ventricular dysfunction, typically qualitatively diagnosed (Q-RVd) in preterm infants, requires echocardiography which is not always acutely available. We aimed to identify clinical indices of Q-RVd in very preterm infants (gestational age, GA <32 weeks) with persistent pulmonary hypertension of newborn (PPHN) and examine the reliability and validity of Q-RVd. METHODS: Forty-seven infants with mean ± SD GA of 26.8 ± 2.7 weeks who had targeted neonatal echocardiography (TNE) ≤72 h old, during PPHN, were retrospectively studied. Three standard TNE clips were reviewed by two blinded assessors, and infants categorized as Q-RVd if moderate-severe RVd was diagnosed on ≥2 clips. Cardiopulmonary clinical indices at TNE and quantitative RV functional markers were compared between Q-RVd vs. no-RVd groups. Potential quantitative RVd definitions examined by classifying each measurement as "low" or "normal" using published data. Inter-rater agreement for Q-RVd assessed using Kappa statistics. RESULTS: Mean age at TNE was 25.3 ± 20.4 h with Q-RVd diagnosed in 19(40 %) infants. Q-RVd group demonstrated higher peak oxygen requirements (96 ± 9 % vs. 84 ± 16 %, p < 0.01); however, no clinical parameters at TNE differentiated the groups. Quantitative measures were lower in Q-RVd patients, confirming classification validity. Among tested quantitative definitions, low RV stroke volume was associated with lower systolic blood pressure (41±7 vs. 47±9 mmHg, p = 0.02) and higher shock index (4.02±0.80 vs. 3.44±0.72, p = 0.02). Kappa for Q-RVd was 0.55 (95%CI 0.32-0.77). CONCLUSIONS: The non-specific nature of clinical markers of RVd in preterm infants with PPHN necessitates echocardiographic diagnosis of RVd. Studies should examine prognostic relevance of RVd and establish outcome-based quantitative definitions in preterm infants.


Subject(s)
Hypertension, Pulmonary , Ventricular Dysfunction, Right , Infant , Humans , Infant, Newborn , Infant, Premature , Hypertension, Pulmonary/diagnostic imaging , Retrospective Studies , Ventricular Dysfunction, Right/diagnostic imaging , Reproducibility of Results
4.
J Pediatr Surg ; 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38413259

ABSTRACT

BACKGROUND: Currently, graft options for pediatric liver transplantation (PLT) include whole (WL) and partial (P) grafts, in the form of either deceased donor transplantation (DD) or living donor liver transplantation (LD). WL transplants from LD are commonly referred to as domino LT. The objective of this manuscript is to compare the outcomes of PLT performed with each of the available graft options. METHODS: Retrospective cohort study from Jan. 2010 to Dec. 2022. The variables included data on the recipients' preoperative clinical status, intraoperative technical aspects, post-operative complications, and survival studies. There were 4 groups: SPLIT (17), DD-WL (55), LD-WL (824), and LD-P (22). RESULTS: The median age and BW of the recipients was smaller in SPLIT, LD-P, and LD-WL compared to DDT-WL groups. HVOO (HR 15.87, 95% CI 1.89-133.06, P = 0.01), retransplantation (HR 7.94, 95% CI 2.63-24.02, P < 0.01), and malignancies (HR 3.08, 95% CI 1.29-7.37, P = 0.01) were independently associated with decreased patient survival. HAT (HR 27.54, 95% CI 10.44-72.68, P < 0.01) and malignancies (HR 2.42, 95% CI 1.10-5.34, P = 0.03) increased the risk of graft loss. The overall survival in this series was 91.4% (mean follow-up of 74.3 months). Patient and graft survival were not different among groups. CONCLUSION: HAT and malignancies were associated with reduced graft survival. Whole liver from living donors with MSUD presented 100% patient survival at 120 months. Even without statistical differences in survival among the studied groups, LD-P and LD-WL recipients presented a trend towards better outcomes. LEVEL OF EVIDENCE: LEVEL III.

5.
Arch Biochem Biophys ; 753: 109884, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38218361

ABSTRACT

The spread of fungi resistant to conventional drugs has become a threatening problem. In this context, antimicrobial peptides (AMPs) have been considered as one of the main alternatives for controlling fungal infections. Here, we report the antifungal and antibiofilm activity and some clues about peptide RQ18's mechanism of action against Candida and Cryptococcus. This peptide inhibited yeast growth from 2.5 µM and killed all Candida tropicalis cells within 2 h incubation. Moreover, it showed a synergistic effect with antifungal agent the amphotericin b. RQ18 reduced biofilm formation and promoted C. tropicalis mature biofilms eradication. RQ18's mechanism of action involves fungal cell membrane damage, which was confirmed by the results of RQ18 in the presence of free ergosterol in the medium and fluorescence microscopy by Sytox green. No toxic effects were observed in murine macrophage cell lines and Galleria mellonella larvae, suggesting fungal target selectivity. Therefore, peptide RQ18 represents a promising strategy as a dual antifungal and antibiofilm agent that contributes to infection control without damaging mammalian cells.


Subject(s)
Amphotericin B , Antifungal Agents , Animals , Mice , Antifungal Agents/pharmacology , Amphotericin B/pharmacology , Peptides/pharmacology , Candida tropicalis , Biofilms , Microbial Sensitivity Tests , Mammals
6.
Plants (Basel) ; 12(19)2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37836163

ABSTRACT

Reflectance hyperspectroscopy is recognised for its potential to elucidate biochemical changes, thereby enhancing the understanding of plant biochemistry. This study used the UV-VIS-NIR-SWIR spectral range to identify the different biochemical constituents in Hibiscus and Geranium plants. Hyperspectral vegetation indices (HVIs), principal component analysis (PCA), and correlation matrices provided in-depth insights into spectral differences. Through the application of advanced algorithms-such as PLS, VIP, iPLS-VIP, GA, RF, and CARS-the most responsive wavelengths were discerned. PLSR models consistently achieved R2 values above 0.75, presenting noteworthy predictions of 0.86 for DPPH and 0.89 for lignin. The red-edge and SWIR bands displayed strong associations with pivotal plant pigments and structural molecules, thus expanding the perspectives on leaf spectral dynamics. These findings highlight the efficacy of spectroscopy coupled with multivariate analysis in evaluating the management of biochemical compounds. A technique was introduced to measure the photosynthetic pigments and structural compounds via hyperspectroscopy across UV-VIS-NIR-SWIR, underpinned by rapid multivariate PLSR. Collectively, our results underscore the burgeoning potential of hyperspectroscopy in precision agriculture. This indicates a promising paradigm shift in plant phenotyping and biochemical evaluation.

7.
Molecules ; 28(19)2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37836787

ABSTRACT

IR-780 is a fluorescent marker, photostable and non-toxic, and is widely used in tumor targeting; however, studies on the impact of IR-780 in animal models of B16-F10 melanoma are scarce in the literature. Therefore, this study aims to analyze behavior of this marker in melanoma cells using in vitro and in vivo analyses with fluorescence microscopy to conduct an analysis of cell culture, and an in vivo imaging system for an analysis of cell culture, tumor targeting on animals, and organ examination. In vitro analysis showed that B16-F10 cells at a concentration of 2 × 105 cells.plate-1 allowed a better visualization using 20 µM of IR-780. Furthermore, the location of IR-780 accumulation was confirmed by its fluorescence microscopy. Through in vivo studies, fluorescence was not observed in subcutaneous nodules, and it was found that animals that received intraperitoneal injection of B16-F10 cells presented ascites and did not absorb IR-780. Additionally, animals exhibiting lung metastasis showed fluorescence in ex vivo lung images. Therefore, use of the IR-780 marker for evaluating the progression of tumor growth did not demonstrate efficiency; however, it was effective in diagnosing pulmonary metastatic tumors. Although this marker presented limitations, results of evaluating pulmonary involvement through ex vivo fluorescence imaging were determined based on intensity of fluorescence.


Subject(s)
Lung Neoplasms , Melanoma, Experimental , Skin Neoplasms , Animals , Mice , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Melanoma, Experimental/diagnostic imaging , Melanoma, Experimental/pathology , Lung/pathology , Mice, Inbred C57BL
8.
Urol Case Rep ; 51: 102545, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37701420

ABSTRACT

Corpus cavernosum abscess is a rare condition that can lead to permanent and debilitating consequences. This case reports a 58-year-old man who developed erectile dysfunction with no response to oral and intracavernous medications after the surgical treatment of a penile abscess.

9.
BrJP ; 6(2): 160-170, Apr.-June 2023. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1513777

ABSTRACT

ABSTRACT BACKGROUND AND OBJECTIVES: Pain is one of the most prevalent causes of disability in the world, and the adverse effects promoted by analgesics can limit therapeutic success. In this context, laser appears as a complementary therapy that can enhance analgesia without increasing the incidence of undesirable adverse events. The aim of this study was to carry out a systematic review on the effectiveness and efficiency of high intensity laser (HIL) in the treatment of pain. CONTENTS: A systematic search was carried out in Medline, LILACS, Pubmed and PEDro, from July 2020 to August 2022. The keywords pain, chronic pain, high intensity laser and treatment were considered. The quality of selected studies was assessed using the PEDro scale. Included systematic reviews were assessed for methodological quality using the AMSTAR tool. The main measure studied was pain intensity. 227 studies were found and, based on the inclusion and exclusion criteria, 32 articles were read in full, whit one being excluded for not assessing pain. Musculoskeletal disorders corresponded to 70,96% of the assessed diseases and the visual analogue scale (VAS) was the only pain measurement tool used in 100% of the studies. Approximately 57% of the studies were of high methodological quality (PEDro=7). In 53,84% of the trials, HIL was used as a single intervention, and in 46,16% it was associated whit exercises. In 96.15% of clinical trials and 100% of systematic reviews there were positive effects of HIL on pain. CONCLUSION: HIL is an effective modality for analgesia by promoting significant pain relief, rapid recovery and improvement in patient's quality of life, in a safe way. The diversity in irradiation parameters (dose, duration, interval and number of sessions) used, indicates the need for further randomized studies to establish its long-term efficiency.


RESUMO JUSTIFICATIVA E OBJETIVOS: A dor é uma das causas mais prevalentes de incapacidade no mundo, e os efeitos adversos promovidos pelos analgésicos podem limitar o sucesso terapêutico. Nesse contexto, surge o laser como terapia complementar que pode potencializar a analgesia, sem aumentar incidência de eventos adversos indesejáveis. O objetivo deste estudo foi realizar uma revisão sistemática sobre a eficácia e a eficiência do laser de alta intensidade (LAI) no tratamento da dor. CONTEÚDO: Foi realizada uma busca sistemática nas plataformas Medline, LILACS, Pubmed e PEDro, de julho de 2020 a agosto de 2022. As palavras chaves dor, dor crônica, laser de alta intensidade e tratamento foram consideradas. A qualidade dos estudos clínicos selecionados foi avaliada utilizando a escala PEDro. As revisões sistemáticas incluídas foram avaliadas quanto à qualidade metodológica através da ferramenta AMSTAR. A principal medida estudada foi a intensidade de dor. Foram encontrados 227 estudos e com base nos critérios de inclusão e exclusão, 32 artigos foram lidos na íntegra, tendo sido excluído um por não avaliar a dor. As desordens musculoesqueléticas corresponderam a 70,96% das doenças avaliadas e a escala analógica visual (EAV) foi a única ferramenta de mensuração da dor utilizada em 100% dos estudos. Aproximadamente 57% dos estudos tinham alta qualidade metodológica (PEDro=7). Em 53,84% dos ensaios o LAI foi utilizado como intervenção única, e em 46,16% foi associado a exercícios. Em 96,15% dos ensaios clínicos e 100% das revisões sistemáticas, o LAI promoveu alívio da dor. CONCLUSÃO: O LAI é uma modalidade eficaz para analgesia ao promover significativo alívio da dor, rápida recuperação e melhora na qualidade de vida dos pacientes de forma segura. A diversidade nos parâmetros de irradiação (dose, duração, intervalo e número de sessões) empregados, indica a necessidade de mais estudos randomizados para estabelecer sua eficiência em longo prazo.

10.
Mem Inst Oswaldo Cruz ; 118: e220144, 2023.
Article in English | MEDLINE | ID: mdl-37018795

ABSTRACT

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans. OBJECTIVES: To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro. METHODS: Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis. FINDINGS: In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells. CONCLUSION: RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.


Subject(s)
COVID-19 , Humans , Animals , Mice , SARS-CoV-2 , RNA, Viral , Microglia/metabolism , Antibodies, Viral , Recombinant Proteins , Macrophages/metabolism
11.
Liver Transpl ; 29(8): 827-835, 2023 08 01.
Article in English | MEDLINE | ID: mdl-36847137

ABSTRACT

Left lateral segment grafts have become a suitable option in pediatric liver transplantation (PLT). The correlation between hepatic vein (HV) reconstruction and outcome is relevant when assessing the safe use of these grafts. We retrospectively reviewed the medical records prospectively collected from a pediatric living donor liver transplantation database and conducted a comparative analysis of the different left lateral segment graft types according to HV reconstruction. Donor, recipient, and intraoperative variables were analyzed. Post-transplant outcomes included vascular complications such as hepatic vein outflow obstruction, early (≤30 d) and late (>30 d) PVT, hepatic artery thrombosis, and graft survival. From February 2017 to August 2021, 303 PLTs were performed. According to venous anatomy, the distribution of the left lateral segment was as follows: single HV (type I) in 174 (57.4%), close HVs, simple venoplasty for reconstruction (type II) in 97 (32.01%), anomalous hepatic vein (AHV) with a distance between the HVs orifices that allowed simple venoplasty (type IIIA) in 25 (8.26%) and AHV with a distance between the HVs orifices requiring homologous venous graft interposition (type IIIB) in 07 (2.31%) grafts. Type IIIB grafts came from male donors ( p =0.04) and had a higher mean donor height ( p =0.008), a higher mean graft weight, and a higher graft-to-recipient weight ratio, both p =0.002. The median follow-up time was 41.4 months. The overall cumulative graft survival was 96.3%, and comparative graft survival showed no difference (log-rank p =0.61). No hepatic vein outflow obstructions were observed in this cohort study. There was no statistically significant difference in the post-transplant outcomes between the graft types. The venous reconstruction of the AHV with homologous venous graft interposition had similar outcomes in the short and long term.


Subject(s)
Liver Transplantation , Humans , Male , Child , Liver Transplantation/adverse effects , Cohort Studies , Retrospective Studies , Living Donors , Hepatic Veins/surgery , Hepatic Veins/anatomy & histology
12.
Toxins (Basel) ; 15(1)2023 01 05.
Article in English | MEDLINE | ID: mdl-36668862

ABSTRACT

In recent years, antimicrobial peptides isolated from amphibian toxins have gained attention as new multifunctional drugs interacting with different molecular targets. We aimed to rationally design a new peptide from temporin-PTa. Hp-MAP3 (NH2-LLKKVLALLKKVL-COOH), net charge (+4), hydrophobicity (0.69), the content of hydrophobic residues (69%), and hydrophobic moment (0.73). For the construction of the analog peptide, the physicochemical characteristics were reorganized into hydrophilic and hydrophobic residues with the addition of lysines and leucines. The minimum inhibitory concentration was 2.7 to 43 µM against the growth of Gram-negative and positive bacteria, and the potential for biofilm eradication was 173.2 µM. Within 20 min, the peptide Hp-MAP3 (10.8 µM) prompted 100% of the damage to E. coli cells. At 43.3 µM, eliminated 100% of S. aureus within 5 min. The effects against yeast species of the Candida genus ranged from 5.4 to 86.6 µM. Hp-MAP3 presents cytotoxic activity against tumor HeLa at a concentration of 21.6 µM with an IC50 of 10.4 µM. Furthermore, the peptide showed hemolytic activity against murine erythrocytes. Structural studies carried out by circular dichroism showed that Hp-MAP3, while in the presence of 50% trifluoroethanol or SDS, an α-helix secondary structure. Finally, Amphipathic Hp-MAP3 building an important model for the design of new multifunctional molecules.


Subject(s)
Amphibian Proteins , Antimicrobial Cationic Peptides , Animals , Humans , Mice , Amino Acid Sequence , Amphibian Proteins/chemistry , Amphibian Proteins/pharmacology , Anti-Bacterial Agents/pharmacology , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Circular Dichroism , Escherichia coli/drug effects , Microbial Sensitivity Tests , Ranidae , Staphylococcus aureus/drug effects
13.
Mem. Inst. Oswaldo Cruz ; 118: e220144, 2023. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1430845

ABSTRACT

BACKGROUND The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can infect common mice inducing significant pathological lung lesions and inflammatory responses. This substantially mimics coronavirus disease 19 (COVID-19) infection and pathogenesis in humans. OBJECTIVES To characterise the effects of recombinant SARS-CoV-2 S1 receptor-binding domain (RBD) peptide in murine macrophage and microglial cells' immune activation compared with classical PAMPs in vitro. METHODS Murine RAW 264.7 macrophages and BV2 microglial cells were exposed to increasing concentrations of the RBD peptide (0.01, 0.05, and 0.1 µg/mL), Lipopolysaccharide (LPS) and Poly(I:C) and evaluated after two and 24 h for significant markers of macrophage activation. We determined the effects of RBD peptide on cell viability, cleaved caspase 3 expressions, and nuclear morphometry analysis. FINDINGS In RAW cells, RBD peptide was cytotoxic, but not for BV2 cells. RAW cells presented increased arginase activity and IL-10 production; however, BV2 cells expressed iNOS and IL-6 after RBD peptide exposure. In addition, RAW cells increased cleaved-caspase-3, apoptosis, and mitotic catastrophe after RBD peptide stimulation but not BV2 cells. CONCLUSION RBD peptide exposure has different effects depending on the cell line, exposure time, and concentration. This study brings new evidence about the immunogenic profile of RBD in macrophage and microglial cells, advancing the understanding of SARS-Cov2 immuno- and neuropathology.

14.
Biochim Biophys Acta Gen Subj ; 1866(12): 130244, 2022 12.
Article in English | MEDLINE | ID: mdl-36162730

ABSTRACT

Antimicrobial peptides (AMPs) are promising tools for developing new antibiotics. We described the design of IKR18, an AMP designed with the aid of computational tools. IKR18 showed antimicrobial activity against Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). CD studies revealed that IKR18 assumes an alpha-helical structure in the membrane-mimetic environment. The action mechanism IKR18 involves damage to the bacteria membrane, as demonstrated by Sytox green uptake. Furthermore, IKR18 displayed synergic and additive effects in combination with antibiotics ciprofloxacin and vancomycin. The peptide showed anti-biofilm activity in concentration and efficiency compared with commercial antibiotics, involving the direct death of bacteria, as confirmed by scanning electron microscopy. The anti-infective activity of IKR18 was demonstrated in the Galleria mellonella model infected with S. aureus, MRSA, and Acinetobacter baumannii. The novel bioinspired peptide, IKR18, proved to be effective in the control of bacterial infection, opening opportunities for the development of further assays, including preclinical models.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Moths , Animals , Antimicrobial Peptides , Staphylococcus aureus , Microbial Sensitivity Tests , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria
15.
Pharmaceuticals (Basel) ; 15(6)2022 Jun 07.
Article in English | MEDLINE | ID: mdl-35745643

ABSTRACT

Nature presents a wide range of biomolecules with pharmacological potential, including venomous animal proteins. Among the protein components from snake venoms, phospholipases (PLA2) are of great importance for the development of new anticancer compounds. Thus, we aimed to evaluate the PLA2 anticancer properties from Bothrops moojeni venom. The crude venom was purified through three chromatographic steps, monitored by enzymatic activity and SDS-PAGE (12%). The purified PLA2 denominated BmPLA2 had its molecular mass and N-terminal sequence identified by mass spectrometry and Edman degradation, respectively. BmPLA2 was assayed against human epithelial colorectal adenocarcinoma cells (Caco-2), human rhabdomyosarcoma cells (RD) and mucoepidermoid carcinoma of the lung (NCI-H292), using human fibroblast cells (MRC-5) and microglia cells (BV-2) as a cytotoxicity control. BmPLA2 presented 13,836 Da and a 24 amino acid-residue homologue with snake PLA2, which showed a 90% similarity with other Bothrops moojeni PLA2. BmPLA2 displayed an IC50 of 0.6 µM against Caco-2, and demonstrated a selectivity index of 1.85 (compared to MRC-5) and 6.33 (compared to BV-2), supporting its selectivity for cancer cells. In conclusion, we describe a new acidic phospholipase, which showed antitumor activity and is a potential candidate in the development of new biotechnological tools.

17.
Oxid Med Cell Longev ; 2022: 3046483, 2022.
Article in English | MEDLINE | ID: mdl-35401919

ABSTRACT

Oxidative stress plays a key role in the initiation and progression of metabolic diseases, including obesity. Preventing the accumulation of reactive oxygen species and oxidative damage to macromolecules is a beneficial strategy for reducing comorbidities associated with obesity. Fruits from the Spondias genus are known for their antioxidant activity, but they are not available year-round due to their seasonality. In this context, we investigated the antioxidant activity and identified the chemical constituents of the aqueous extract of the stem bark of Spondias purpurea L. (EBSp). Additionally, we evaluated the effect of EBSp consumption on metabolic parameters in mice with obesity induced by a high-fat diet. Chemical analyses revealed 19 annotated compounds from EBSp, including flavan-3-ols, proanthocyanidins, methoxylated coumarin, and gallic and ellagic acids, besides other phenolic compounds. In vitro, EBSp showed antioxidant activity through the scavenging of the free radicals and the protection of macromolecules against oxidative damage. Cellular assays revealed that EBSp reduced the levels of malondialdehyde produced by erythrocytes exposed to the oxidizing agent AAPH. Flow cytometry studies showed that EBSp reduced reactive oxygen species levels in human peripheral blood mononuclear cells treated with hydrogen peroxide. Obese mice treated with EBSp (400 mg.kg-1) for 60 days showed reduced levels of malondialdehyde in the heart, liver, kidneys, and nervous system. The total cholesterol levels in mice treated with EBSp reached levels similar to those after treatment with the drug simvastatin. Together, the results show that the combination of the different phenolic compounds in S. purpurea L. bark promotes antioxidant effects in vitro and in vivo, resulting in cytoprotection in the context of oxidative stress associated with obesity and a reduction in hypercholesterolemia. From a clinical perspective, the reduction in oxidative stress in obese individuals contributes to the reduction in the emergence of comorbidities associated with this metabolic syndrome.


Subject(s)
Anacardiaceae , Hypercholesterolemia , Anacardiaceae/chemistry , Animals , Antioxidants/metabolism , Diet, High-Fat/adverse effects , Hypercholesterolemia/drug therapy , Leukocytes, Mononuclear/metabolism , Malondialdehyde/metabolism , Mice , Obesity/drug therapy , Oxidative Stress , Phenols/pharmacology , Plant Bark/chemistry , Plant Extracts/analysis , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Reactive Oxygen Species/metabolism
18.
BMC Sports Sci Med Rehabil ; 14(1): 52, 2022 Mar 29.
Article in English | MEDLINE | ID: mdl-35351196

ABSTRACT

BACKGROUND: Beetroot juice (BJ) and caffeine (CAF) are considered as ergogenic aids among athletes to enhance performance, however, the ergogenic effects of BJ and CAF co-ingestion are unclear during team-sport-specific performance. This study aimed to investigate the acute effects of BJ and CAF co-ingestion on team-sport-specific performance, compared with placebo (PL), BJ, and CAF alone. METHOD: Sixteen semi-professional male soccer players (age: 19.8 ± 2.2 years, body mass: 69.2 ± 6.1 kg, height: 177.3 ± 6.0 cm) completed four experimental trials using a randomized, double-blind study design: BJ + CAF, CAF + PL, BJ + PL, and PL + PL. Countermovement jump with arm swing (CMJAS) performance and cognitive function by Stroop Word-Color test were evaluated before and after the Yo-Yo Intermittent Recovery Test level 1 (YYIR1). Also, rate of perceived exertion (RPE), heart rate, and gastrointestinal (GI) discomfort were measured during each session. RESULTS: No significant differences were shown between test conditions for total distance covered in YYIR1 (BJ + CAF: 1858 ± 455 m, CAF + PL: 1798 ± 422 m, BJ + PL: 1845 ± 408 m, PL + PL 1740 ± 362 m; p = 0.55). Moreover, CMJAS performance, cognitive function, and RPE during the YYIR1 were not significantly different among conditions (p > 0.05). However, the average heart rate during the YYIR1 was higher in CAF + PL compared to PL + PL (by 6 ± 9 beats/min; p < 0.05), and GI distress was greater in BJ + CAF compared to PL + PL (by 2.4 ± 3.6 a.u.; p < 0.05). CONCLUSION: These results suggest, neither acute co-ingestion of BJ + CAF nor BJ or CAF supplementation alone significantly affected team-sport-specific performance compared to the PL treatment.

19.
Eur J Surg Oncol ; 48(4): 727-735, 2022 04.
Article in English | MEDLINE | ID: mdl-34972623

ABSTRACT

BACKGROUND: Autologous fat grating has become increasingly popular as a breast reconstructive procedure. Nevertheless, preclinical studies show that fat transfer to a previous breast cancer site could activate latent cancer cells, creating a favourable environment for disease recurrence. A systematic review and meta-analysis was performed to investigate whether fat grafting increases the risk of locoregional recurrence in patients formerly treated for breast cancer. METHODS: Based on PRISMA guidelines, a systematic review searching for randomised clinical trials and matched cohorts on the topic was performed in the electronic databases Pubmed, Embase, Web of Science, and Cochrane. The date of the last search was July 20, 2021. The meta-analysis assessed the comparison of locoregional recurrence between groups. RESULTS: From a total of 558 publications, data from nine matched cohorts (1.6%) reporting on 4247 subjects (1590 and 2657 subjects, respectively, in lipofilling and control groups) were suitable for inclusion in the meta-analysis. Neither of the outcomes had a statistically significant difference for disease recurrence. For the primary outcome, comparing locoregional recurrence rates between groups, the incidence rate ratio was 0.92 (95% CI: 0.68-1.26; P = 0.620). CONCLUSION: The present meta-analysis, which comprises the outcomes of the individual studies with the best current evidence on the topic so far, strengthens the evidence favouring the oncologic safety of lipofilling for breast reconstruction.


Subject(s)
Breast Neoplasms , Mammaplasty , Adipose Tissue/transplantation , Breast Neoplasms/epidemiology , Female , Humans , Mammaplasty/methods , Mastectomy/methods , Neoplasm Recurrence, Local/surgery , Transplantation, Autologous/adverse effects
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