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1.
Exp Parasitol ; 262: 108771, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38723847

ABSTRACT

Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti-Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent-kaurenoic and ent-polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent-polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii, and this effect can be partially explained by the presence of the isolated compounds ent-kaurenoic and ent-polyalthic acid.

2.
Sci Rep ; 14(1): 11132, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750088

ABSTRACT

Candida species have been responsible for a high number of invasive infections worldwide. In this sense, Rottlerin has demonstrated a wide range of pharmacological activities. Therefore, this study aimed to evaluate the antifungal, antibiofilm and antivirulence activity of Rottlerin in vitro against Candida spp. and its toxicity and antifungal activity in vivo. Rottlerin showed antifungal activity against all yeasts evaluated, presenting Minimum Inhibitory and Fungicidal Concentration (MIC and MFC) values of 7.81 to > 1000 µg/mL. Futhermore, it was able to significantly inhibit biofilm production, presenting Biofilm Inhibitory Concentration (MICB50) values that ranged from 15.62 to 250 µg/mL and inhibition of the cell viability of the biofilm by 50% (IC50) from 2.24 to 12.76 µg/mL. There was a considerable reduction in all hydrolytic enzymes evaluated, with emphasis on hemolysin where Rottlerin showed a reduction of up to 20%. In the scanning electron microscopy (SEM) analysis, Rottlerin was able to completely inhibit filamentation by C. albicans. Regarding in vivo tests, Rottlerin did not demonstrate toxicity at the therapeutic concentrations demonstrated here and was able to increase the survival of C. elegans larvae infected. The results herein presented are innovative and pioneering in terms of Rottlerin's multipotentiality against these fungal infections.


Subject(s)
Acetophenones , Antifungal Agents , Benzopyrans , Biofilms , Microbial Sensitivity Tests , Biofilms/drug effects , Antifungal Agents/pharmacology , Benzopyrans/pharmacology , Animals , Acetophenones/pharmacology , Caenorhabditis elegans/drug effects , Candida/drug effects , Candidiasis/drug therapy , Candida albicans/drug effects
3.
Chem Biodivers ; : e202400680, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748618

ABSTRACT

The study aimed to assess the chemical composition of Miconia ibaguensis leaves extracts and fractions obtained from the ethanolic extract (EE), along with evaluating their antifungal, antibacterial, antidiabetic, and antioxidant activities. The ethyl acetate fraction (EAF) exhibited potent antifungal activity against Candida spp (1.95 - 3.90 µg mL-1) and potent antioxidant activity in the DPPH (1.74 ± 0.07 µg mL-1), FRAP (654.01 ± 42.09 µmol ETrolox/gsample), and ORAC (3698.88 ± 37.28 µmol ETrolox/gsample) methods. The EE displayed inhibition against the α-amylase enzyme (8.42 ± 0.05 µg mL-1). Flavonoids, hydrolysable tannins, triterpenoids, and phenolic acids, identified in the EE and fractions via (-)-HPLC-ESI-MS/MS analysis, were found to contribute to the species' biological activity potentially. These findings suggest promising avenues for further research and potential applications in pharmacology and natural products, offering new possibilities in the fight against global health issues.

4.
Radiol Case Rep ; 19(7): 2891-2894, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38721390

ABSTRACT

Aortic coarctation is a rare cause of secondary hypertension (<1% cases) and can be challenging to detect due to its few clinical manifestations. Early diagnosis and treatment are important because patients with unmanaged aortic coarctation are at increased risk of cardiovascular complications and have a reduced life expectancy. We describe a case of secondary hypertension in a young adult female caused by aortic coarctation, first detected in a general practitioner setting, resulting in the need for a left subclavian-carotid bypass vascular surgery and a descending aortic stent vascular surgery. This case highlights the critical role that proximity medicine in general practice can have in improving the early detection of clinically silent conditions by routinely monitoring blood pressure and other vital parameters, and the increasing importance of medical imaging in assisting early diagnosis and guiding the surgical management of complex cases.

5.
Pharmaceuticals (Basel) ; 17(5)2024 May 14.
Article in English | MEDLINE | ID: mdl-38794203

ABSTRACT

Drug-resistant bacteria constitute a big barrier against current pharmacotherapy. Efforts are urgent to discover antibacterial drugs with novel chemical and biological features. Our work aimed at the synthesis, evaluation of antibacterial effects, and toxicity of licochalcone C (LCC), a naturally occurring chalcone. The synthetic route included six steps, affording a 10% overall yield. LCC showed effects against Gram-positive bacteria (MIC = 6.2-50.0 µg/mL), Mycobacterium species (MIC = 36.2-125 µg/mL), and Helicobacter pylori (MIC = 25 µg/mL). LCC inhibited the biofilm formation of MSSA and MRSA, demonstrating MBIC50 values of 6.25 µg/mL for both strains. The investigations by fluorescence microscopy, using PI and SYTO9 as fluorophores, indicated that LCC was able to disrupt the S. aureus membrane, similarly to nisin. Systemic toxicity assays using Galleria mellonella larvae showed that LCC was not lethal at 100 µg/mL after 80 h treatment. These data suggest new uses for LCC as a compound with potential applications in antibacterial drug discovery and medical device coating.

6.
EJVES Vasc Forum ; 61: 99-103, 2024.
Article in English | MEDLINE | ID: mdl-38560760

ABSTRACT

Introduction: Horseshoe kidney (HK) is an anatomical variant characterised by abnormalities in the position, rotation, and vascular supply of the kidney, with functioning renal masses on both sides of the vertebral column fused together at the isthmus. Due to the altered pattern of kidney vasculature, endovascular aortic repair for aortic abdominal aneurysm (AAA) in the presence of HK requires vascular anatomy specific planning. Report: A 68 year old male, with multiple comorbidities, presented with an asymptomatic AAA and HK. The kidney vasculature was characterised by the presence of three arteries: two arising laterally at the same level and a third polar artery arising from below. The polar artery was 6 mm in diameter and larger than the other two; therefore, in order to preserve this artery, a custom-made device with a single side branch was implanted below the main renal arteries. A balloon expandable covered stent was used to complete the side branch into the polar renal artery. The follow-up computed tomography angiography revealed a successful outcome, with total aneurysm exclusion, branched graft patency, no endoleak, and unchanged renal function. Discussion: This case report shows a possible surgical solution for a case of HK with AAA and the importance of accurate endovascular planning. Large polar arteries, if present, need to be preserved, and custom-made devices in the modern endovascular era permit that. This approach could represent the best option for complicated patients.

7.
Front Med (Lausanne) ; 11: 1273304, 2024.
Article in English | MEDLINE | ID: mdl-38681055

ABSTRACT

Introduction: Anticoagulation is recommended for stroke prevention in patients with atrial fibrillation (AF). The guidelines suggest non-vitamin K antagonist anticoagulants (NOACs) as the primary therapy for anticoagulation in AF. Several patient-related factors increase the risk of thrombotic events: elderly individuals, a previous history of stroke, and chronic kidney disease. This study aims to determine the association between NOACs and other patient variables in AF and the occurrence of thrombotic events. Methods: The database included all adults with the code K78 (ICPC-2 code for AF) who received clinical care in Northern Portugal's Primary Health Care between January 2016 and December 2018 and were dispensed the same NOAC at the pharmacy. Results: The results indicate that 10.2% of AF patients on NOAC anticoagulation experienced a stroke. Furthermore, patients treated with apixaban and dabigatran had higher odds of experiencing a stroke compared to those treated with rivaroxaban. Among patients with the same age, gender, and CHA2DS2Vasc Score, apixaban was significantly associated with a higher likelihood of thrombotic events than rivaroxaban. Discussion: These results have not been previously reported in studies with real-world data; therefore, a more detailed analysis should be conducted to enhance the validity of these findings.

8.
BMJ Open ; 14(4): e076108, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38688672

ABSTRACT

OBJECTIVES: This study aimed to assess the appropriateness of prescribing profiles and intake adherence to non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). DESIGN: Retrospective longitudinal study. SETTING: The study was conducted in the Regional Health Administration of Northern Portugal. PARTICIPANTS: The authors selected a database of 21 854 patients with prescriptions for NOACs between January 2016 and December 2018 and were classified with AF until December 2018. OUTCOME MEASURES: The appropriate dosage of NOAC for patients with AF divided into three categories: contraindicated, inconsistent and consistent, based on the 2020 European Society of Cardiology guidelines for AF. RESULTS: Dabigatran had a lower percentage of guideline-consistent doses (n=1657, 50.1%) than other drugs such as rivaroxaban (n=4737, 81.6%), apixaban (n=3830, 78.7%) and edoxaban (n=436, 82.1%). Most patients with an inconsistent dose were prescribed a lower dose than recommended based on their glomerular filtration rate (GFR). Among patients younger than 75 years with GFR >60 mL/min, 59.8% (n=10 028) had an adequate GFR range, while 27.8% (n=7166) of GFR measurements from patients older than 75 years old and 29.4% (n=913) of GFR measurements from patients younger than 75 years with GFR <60 mL/min were within an adequate time range. Adherence to NOACs varied across different drugs, with 59.1% (n=540) adhering to edoxaban, 56.3% (n=5443) to rivaroxaban, 55.3% (n=3143) to dabigatran and 53.3% (n=4211) to apixaban. CONCLUSIONS: Dabigatran had the lowest percentage of guideline-consistent doses. Patients younger than 75 years with GFR >60 mL/min had the highest percentage with an adequate GFR range, while other groups who require closer GFR monitoring had lower percentages within an adequate GFR range. Adherence to NOACs differed among different drugs, with greater adherence to treatment with edoxaban and less adherence to apixaban.


Subject(s)
Anticoagulants , Atrial Fibrillation , Dabigatran , Pyridones , Rivaroxaban , Humans , Atrial Fibrillation/drug therapy , Aged , Retrospective Studies , Male , Female , Longitudinal Studies , Dabigatran/therapeutic use , Dabigatran/administration & dosage , Rivaroxaban/administration & dosage , Rivaroxaban/therapeutic use , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Middle Aged , Portugal , Pyridones/administration & dosage , Pyridones/therapeutic use , Aged, 80 and over , Administration, Oral , Guideline Adherence/statistics & numerical data , Pyrazoles/therapeutic use , Pyrazoles/administration & dosage , Practice Patterns, Physicians'/statistics & numerical data , Glomerular Filtration Rate , Thiazoles/administration & dosage , Thiazoles/therapeutic use , Pyridines/administration & dosage , Pyridines/therapeutic use , Medication Adherence/statistics & numerical data , Factor Xa Inhibitors/therapeutic use , Factor Xa Inhibitors/administration & dosage
9.
J Pharm Biomed Anal ; 245: 116143, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38678859

ABSTRACT

Centella asiatica (L.) Urb. is a small herbaceous plant belonging to the Apiaceae family that is rich in triterpenes, such as asiaticoside and madecassoside. Centella asiatica finds broad application in promoting wound healing, addressing skin disorders, and boosting both memory and cognitive function. Given its extensive therapeutic potential, this study aimed not only to investigate the Centella asiatica ethanolic extract but also to analyze the biological properties of its organic fractions, such as antioxidant antiglycation capacity, which are little explored. We also identified the main bioactive compounds through spectrometry analysis. The ethanolic extract (EE) was obtained through a static maceration for seven days, while organic fractions (HF: hexane fraction; DF: dichloromethane fraction; EAF: ethyl acetate fraction; BF: n-butanol fraction and HMF: hydromethanolic fraction) were obtained via liquid-liquid fractionation. The concentration of phenolic compounds, flavonoids, and tannins in each sample was quantified. Additionally, the antiglycation (BSA/FRU, BSA/MGO, and ARG/MGO models) and antioxidant (FRAP, ORAC, and DPPH) properties, as well as the ability to inhibit LDL oxidation and hepatic tissue peroxidation were evaluated. The inhibition of enzyme activity was also analyzed (α-amylase, α-glycosidase, acetylcholinesterase, and butyrylcholinesterase). We also evaluated the antimicrobial and cytotoxicity against RAW 264.7 macrophages. The main compounds present in the most bioactive fractions were elucidated through ESI FT-ICR MS and HPLC-ESI-MS/MS analysis. In the assessment of antioxidant capacity (FRAP, ORAC, and DPPH), the EAF and BF fractions exhibited notable results, and as they are the phenolic compounds richest fractions, they also inhibited LDL oxidation, protected the hepatic tissue from peroxidation and inhibited α-amylase activity. Regarding glycation models, the EE, EAF, BF, and HMF fractions demonstrated substantial activity in the BSA/FRU model. However, BF was the only fraction that presented non-cytotoxic activity in RAW 264.7 macrophages at all tested concentrations. In conclusion, this study provides valuable insights into the antioxidant, antiglycation, and enzymatic inhibition capacities of the ethanolic extract and organic fractions of Centella asiatica. The findings suggest that further in vivo studies, particularly focusing on the butanol fraction (BF), may be promising routes for future research and potential therapeutic applications.


Subject(s)
Antioxidants , Centella , Lipoproteins, LDL , Oxidation-Reduction , Plant Extracts , Serum Albumin, Bovine , Triterpenes , alpha-Amylases , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , alpha-Amylases/antagonists & inhibitors , alpha-Amylases/metabolism , Centella/chemistry , Antioxidants/pharmacology , Antioxidants/chemistry , Mice , Oxidation-Reduction/drug effects , Glycosylation/drug effects , Serum Albumin, Bovine/metabolism , Lipoproteins, LDL/metabolism , Triterpenes/pharmacology , Triterpenes/chemistry , RAW 264.7 Cells
10.
Anim Reprod ; 21(1): e20230155, 2024.
Article in English | MEDLINE | ID: mdl-38628495

ABSTRACT

The adnexa fetal tissues are sources of mesenchymal stromal cells (MSCs) due to their noninvasive harvest, with all biological material discarded most of the time. MSCs are a promise regarding to their plasticity, self-renewal, differentiation potentials, immunomodulatory and anti-inflammatory properties, which have made clinical stem cell therapy a reality. The present study aimed to characterize and evaluate the immunomodulation ability of bovine mesenchymal cells collected from bovine amniotic fluid (bAFMSCs) isolated and subjected to sixth consecutive culture passages in vitro. The multilineage properties of the bAFMSCs collections confirmed the ability to undergo adipogenic, chondrogenic and osteogenic differentiation. The mesenchymal gene transcription CD106, CD73, CD29, CD90 and CD166 were detected in bAFMSCs, whereas CD34 and CD45 were not detected. Regarding cytokine mRNA expression, IL2, IL6, INFα, INFß, INFγ, TNFα and TNFß were downregulated, while IL10 was highly regulated in all studied passages. The present study demonstrated the immunological properties and multipotency of in vitro bAFMSCs collections, and thus, they can be tested in cattle pathological treatments or multiplication by nuclear transfer cloning.

11.
J Infect Public Health ; 17(5): 810-818, 2024 May.
Article in English | MEDLINE | ID: mdl-38522155

ABSTRACT

BACKGROUND: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management. METHODS: To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4+ T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period. RESULTS: The subject presented controlled viremia and low CD4+ counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal. CONCLUSION: Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL.


Subject(s)
Coinfection , HIV Infections , Leishmania infantum , Leishmaniasis, Visceral , Phosphorylcholine/analogs & derivatives , Adult , Humans , Portugal , Coinfection/drug therapy , Parasitemia , Viremia , HIV Infections/complications , HIV Infections/drug therapy , Leishmaniasis, Visceral/complications , Leishmaniasis, Visceral/drug therapy
12.
Molecules ; 29(3)2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38338388

ABSTRACT

Antibacterials derived from natural sources represent a fascinating and promising field of research in the quest for effective and sustainable solutions to bacterial infections [...].


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy
13.
MethodsX ; 12: 102575, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38313697

ABSTRACT

The Ordered Weighted Averaging (OWA) operator is a multicriteria method that has conquered space among researchers in the composite indicators field. Typically, OWA operator weights are defined by the decision maker. This type of weighting is highly criticized, as decision-makers are susceptible to errors and bias in judgment. Some methods have been used to define OWA operator weights objectively. However, none of them is concerned about the quality of the composite indicator. This paper introduces a method that defines the weights of the OWA operator based on two quality parameters of the composite indicator: the ability to capture the concept of the multidimensional phenomenon and the informational loss. The method can be implemented in Microsoft Excel Solver and has a high degree of flexibility and applicability in problems of a multidimensional nature and a high degree of appropriation by researchers and practitioners in the area.•Defines weights that maximize the ability of the composite indicator to capture the concept of the multidimensional phenomenon.•Considers restrictions to limit the informational loss of the composite indicator or emphasize positive or negative aspects of the multidimensional phenomenon.•Offers flexibility in setting the objective and constraints of the optimization algorithm.

14.
Toxicon ; 238: 107569, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38122835

ABSTRACT

The present work addressed the abilities of two L-amino acid oxidases isolated from Bothrops moojeni (BmooLAAO-I) and Bothrops jararacussu (BjussuLAAO-II) snake venoms to control the growth and prevent the biofilm formation of clinically relevant bacterial pathogens. Upon S. aureus (ATCC BAA44) and S. aureus (clinical isolates), BmooLAAO-I (MIC = 0.12 and 0.24 µg/mL, respectively) and BjussuLAAO-II (MIC = 0.15 µg/mL) showed a potent bacteriostatic effect. Against E. coli (ATCC BAA198) and E. coli (clinical isolates), BmooLAAO-I (MIC = 15.6 and 62.5 µg/mL, respectively) and BjussuLAAO-II (MIC = 4.88 and 9.76 µg/mL, respectively) presented a lower extent effect. Also, BmooLAAO-I (MICB50 = 0.195 µg/mL) and BjussuLAAO-II (MICB50 = 0.39 µg/mL) inhibited the biofilm formation of S. aureus (clinical isolates) in 88% and 89%, respectively, and in 89% and 53% of E. coli (clinical isolates). Moreover, scanning electron microscopy confirmed that the toxins affected bacterial morphology by increasing the roughness of the cell surface and inhibited the biofilm formation. Furthermore, analysis of the tridimensional structures of the toxins showed that the surface-charge distribution presents a remarkable positive region close to the glycosylation motif, which is more pronounced in BmooLAAO-I than BjussuLAAO-II. This region may assist the interaction with bacterial and biofilm surfaces. Collectively, our findings propose that venom-derived antibiofilm agents are promising biotechnological tools which could provide novel strategies for biofilm-associated infections.


Subject(s)
Bothrops , Crotalid Venoms , Venomous Snakes , Animals , Crotalid Venoms/toxicity , L-Amino Acid Oxidase/pharmacology , L-Amino Acid Oxidase/chemistry , Staphylococcus aureus , Escherichia coli , Snake Venoms/chemistry , Bacteria , Biofilms
15.
J Ethnopharmacol ; 319(Pt 3): 117315, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37852339

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Maytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds-terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. AIMS OF THE STUDY: We aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. MATERIALS AND METHODS: Organic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. RESULTS: HPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 µg/mL and 7.95 µg/mL) compared to acarbose (0.144 µg/mL). Most organic fractions exhibited ∼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. CONCLUSION: This study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.


Subject(s)
Anti-Infective Agents , Celastraceae , Maytenus , Humans , Animals , Rats , Lipid Peroxidation , Acetylcholinesterase , Butyrylcholinesterase , Antioxidants/pharmacology , Maillard Reaction , Magnesium Oxide , Tandem Mass Spectrometry , Phytochemicals , alpha-Amylases , Plant Extracts/pharmacology
16.
Antiviral Res ; 221: 105784, 2024 01.
Article in English | MEDLINE | ID: mdl-38103699

ABSTRACT

African Swine Fever (ASF) is a highly contagious disease caused by a double-stranded DNA virus (ASFV). Despite significant advances made over the last decade, issues such as residual virulence and absence of differentiating infected from vaccinated animals (DIVA) capacity remain an obstacle in the development of live attenuated vaccines (LAVs) against ASFV. It is, therefore, necessary to identify novel strategies to improve vaccine safety, by rational mutagenesis of virulence associated genes and generation of DIVA markers. ASFV encodes a HU (histone-like protein from E. coli strain U93) homolog protein, pA104R, which is involved in viral genome assembly and host immune recognition. A phylogenetic analysis revealed that pA104R is highly conserved among ASFV isolates, suggesting that it can be a good target for vaccine design. Thus, we selectively mutated the ß-strand DNA binding region (BDR) of pA104R to attenuate its enzymatic activity, and identified and mutated several B-cell epitopes present in pA104R to generate a negative marker. Residues K64, K66, and R69 in the BDR were identified as relevant for pA104R activity, with double mutation of the first two showing additive attenuation. pA104R-reactive IgM and IgG epitopes were also identified in the bottom of the BDR, with selective mutagenesis drastically reducing antibody recognition and, when combined with mutations in the arm of the BDR, leading to a further reduction of DNA-binding activity. Interestingly, the immunodominant pA104R-reactive IgG epitope was mainly recognized by IgG1 suggesting that pA104R induces a dominant Th2 response. In sum, the rational mutagenesis can reduce pA104R-DNA binding activity and immune reactivity, providing a rationale for the development of an ASFV pA104R-based DIVA vaccine.


Subject(s)
African Swine Fever Virus , African Swine Fever , Vaccines , Viral Vaccines , Swine , Animals , African Swine Fever/prevention & control , Histones/metabolism , Escherichia coli/genetics , Phylogeny , Protein Conformation, beta-Strand , Mutagenesis , DNA/metabolism , Immunoglobulin G , Vaccines/metabolism , Viral Vaccines/genetics
17.
Nat Prod Res ; : 1-6, 2023 Dec 24.
Article in English | MEDLINE | ID: mdl-38143320

ABSTRACT

Pterodon pubescens Benth is a Brazilian medicinal plant (sucupira, in Brazilian Portuguese). This paper aims to determine the volatile composition and antibacterial activities of hexane extract from P. pubescens seeds (HE-PP). Antibacterial activities were screened by the microdilution broth method in 96-well culture plates and MIC values were expressed as µg/mL. HE-PP was active against several oral bacteria whose MIC values ranged between 12.5 µg/mL and 50 µg/mL and against three mycobacterial strains (MIC = 125 µg/mL and 500 µg/mL). In addition, HE-PP was active against Xanthomonas citri strain (MIC = 100 µg/mL). Cytotoxic activity of the extract was evaluated in human tumour and non-tumour cell lines. HE-PP showed selective cytotoxicity to cervical adenocarcinoma (HeLa cells - IC50 = 53.47 µg/mL). Its major constituents were identified by GC-MS and GC-FID: E-caryophyllene, vouacapane, E-geranylgeraniol and dehydroabietol. Results reinforce the biological potential of HE-PP against a broad spectrum of pathogenic and phytopathogenic bacteria.

18.
Article in English | MEDLINE | ID: mdl-38131740

ABSTRACT

The quality and safety of health care are a priority for health organizations and social institutions to progressively provide people with a higher level of health and well-being. It is in the development of this path that home care currently represents an area of gradual investment and where health care services and the scientific community have shown interest in building circuits and instruments that can respond to needs. The purpose of this article is to identify areas and criteria for quality and safety in home care. The method used was a systematic review registered in PROSPERO (CRD42022380989). The search was systematically carried out in CINAHL Plus with Full Text, MEDLINE with Full Text and Psychology and Behavioral Sciences Collection, using the following criteria: articles published in Portuguese and English, from January 2017 to November 2022. The results of the analysis of the articles showed areas of quality and safety in home care with their respective dimensions and operational criteria. We concluded that there are three areas: the intervention with the patient, with proximity and patient-centered care, which integrates the individual care plan and the proximity of professionals to the patient and family; the intervention of care and service management, with care management and clinical governance that includes the integrated model of health care, goal management, and context management; and the intervention related to training and professional development, where we have the skills and training of professionals.


Subject(s)
Delivery of Health Care , Home Care Services , Humans , Health Facilities
19.
Anim Biotechnol ; 34(9): 5087-5096, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37975200

ABSTRACT

In vitro embryos production from prepubertal heifers can help contribute to breeding programs; however, strategies are necessary to increase their embryo production. The aim of this study was to investigate the effects of two nutritional plans on oocyte recovery, embryo production and growth performance of prepubertal Nelore heifers. Thirty-four Nelore heifers with age of 6.5 months were divided into two feeding treatments (NP1 and NP2). The NP1 diets served as the control and NP2 diets were formulated to contain an average of 1.22-fold more energy than NP1. After 3 months of supplementation, the animals underwent follicular aspiration (ovum pick-up, OPU) every 21 d for 3 months and embryos were produced in vitro. Wither height, chest depth, body weight and subcutaneous fat of animals were measured. The number of retrieved and viable oocytes per OPU were 1.49-fold and 1.42-fold greater in NP2 heifers (p = 0.018 and p = 0.049, respectively) than those in NP1 heifers. Heifers administered NP2 produced 29.7% blastocysts, a percentage higher than NP1 animals that produced 24.40% embryos (p < 0.05). Consequently, females in the NP2 treatment showed improved body development. These results indicate a positive effect of a higher energy diet on assisted reproduction and body development in prepubertal heifers.


Subject(s)
Fertilization in Vitro , Ovarian Follicle , Cattle , Animals , Female , Fertilization in Vitro/veterinary , Embryo Culture Techniques/veterinary , Oocytes , Dietary Supplements
20.
Braz Dent J ; 34(4): 158-168, 2023.
Article in English | MEDLINE | ID: mdl-37909639

ABSTRACT

The objective of this research was to evaluate the effectiveness of using LPL (Low power laser) to reduce pain, edema, and trismus after impacted lower third molar extraction. A split-mouth randomized triple-blind clinical trial was conducted at the Federal University of Ceará. For inclusion criteria, it was necessary that the patient presented a clear indication for removal of both lower third molars, in addition to both molars being in similar positions. The third molars (38 and 48) were randomly allocated to the test group that received the LPL application protocol, and to the placebo group that received a simulation of the protocol, making a total sample of 44 surgeries. Patients in the test group used an average of 50% of the amount of analgesics that was used by the placebo group, however, there was a statistically significant difference only on days four and five. Regarding trismus, the test group presented wide mouth openings, both at 48 hours and at 7 days after surgery compared to the placebo group, but without a statistically significant difference. For edema, we noted an equilibrium between the test group and the placebo group, but no measurement obtained a statistically significant difference. The use of LPL presented better pain and trismus indicators after complex extractions. The use of LPL is thus indicated as a complementary therapy to reduce postoperative discomfort caused by complex tooth extractions.


Subject(s)
Molar, Third , Tooth, Impacted , Humans , Molar, Third/surgery , Trismus/prevention & control , Pain, Postoperative/prevention & control , Pain, Postoperative/drug therapy , Double-Blind Method , Tooth, Impacted/surgery , Tooth, Impacted/complications , Tooth Extraction/adverse effects , Lasers , Edema/prevention & control , Edema/etiology
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