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1.
Toxicol Appl Pharmacol ; 461: 116410, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36738974

ABSTRACT

Different classes of insecticide compounds have been employed to control insects and mosquitoes; Pyrethroids are one of the most common used in both urban and rural household environments. This study investigated the effects of exposure of two doses of commercial transfluthrin-based insecticide (T-BI) on behavior (body bends, pharyngeal pumping rate, and feeding attributes) and biochemical biomarkers (AChE, PolyQ40 aggregations, HSP, antioxidative SOD, CTL, and GST) following three different protocols (transgenerational, neonatal, and lifespan) in Caenorhabditis elegans model system. The relative calculated dose (RCD) and relative calculated half dose (RCHD) of T-BI were compared with those of the control (water). T-BI reduced the health span of worms treated during their whole life and changed biochemical and behavioral patterns due to progenitors' uterine (transgenerational) and neonatal exposures. It was inferred that the effects of T-BI are transgenerational and persistent and can be harmful to non-target species, including humans. In addition, our findings highlight that T-BI contact by progenitors accelerates the establishment of Huntington's disease and causes a cholinergic outbreak in offspring adulthood.


Subject(s)
Caenorhabditis elegans Proteins , Insecticides , Animals , Infant, Newborn , Humans , Adult , Caenorhabditis elegans , Insecticides/pharmacology , Caenorhabditis elegans Proteins/metabolism , Cyclopropanes/toxicity , Cyclopropanes/metabolism
2.
BMC Geriatr ; 23(1): 151, 2023 03 20.
Article in English | MEDLINE | ID: mdl-36941534

ABSTRACT

BACKGROUND: The COVID-19 pandemic primarily impacted long-term care facilities by restricting visiting and circulation of visitors, affecting the quality of life (QoL) of older adults living in these institutions. Volunteer activities, essential for older adults' daily life, were also interrupted and potentially negatively impacted the QoL of older adults, volunteers themselves, and also employees in these institutions. In this context, this study aims to evaluate the impact of the return of volunteer-led activities in a long-term care institution on the QoL of older adult residents, employees, and volunteers. METHODS: This study used a pre-test and post-test design within the same group. The first round of data collection was conducted before volunteer-led activities returned and the second round after 1 month of return. The instrument used to assess QoL was the EUROHIS-QoL-8 scale. This study was conducted within a nursing home in São Paulo, Brazil, created in 1937 by members of the Israeli community living in Brazil. Volunteer-led activities were part of residents' daily life before the COVID-19 pandemic, when these activities were interrupted for about 20 months. A total of 79 individuals participated in both rounds (pre and post), of which: 29 residents, 27 volunteers, and 23 employees of the long-term care institution. RESULTS: Using a Wilcoxon signed-rank test, the analyses indicated improvements after the 1 month return in different QoL aspects for the three groups. Volunteers improved their personal relationships (Z - 2.332, p < .05), residents their overall health (Z - 2.409, p < .05) and employees in their overall QoL perception (Z - 2.714, p < .05). Influencing factors for residents were the number of activities (3 or more), gender (male), and education (undergraduate/graduate). For employees, those who assumed additional activities due to the volunteer-led activities interruption had a significant impact on their overall QoL. CONCLUSIONS: Evidence from this study suggests that volunteers' return positively impacted different QoL aspects for volunteers, residents, and employees.


Subject(s)
COVID-19 , Long-Term Care , Humans , Male , Aged , Quality of Life , Cohort Studies , Pandemics , Brazil , COVID-19/epidemiology , Volunteers
3.
Int J Mol Sci ; 24(5)2023 Feb 24.
Article in English | MEDLINE | ID: mdl-36901954

ABSTRACT

The frequent activation of the PI3K/AKT/mTOR pathway and its crucial role in estrogen receptor-positive (ER+) breast cancer tumorigenesis and drug resistance has made it a highly attractive therapeutic target in this breast cancer subtype. Consequently, the number of new inhibitors in clinical development targeting this pathway has drastically increased. Among these, the PIK3CA isoform-specific inhibitor alpelisib and the pan-AKT inhibitor capivasertib were recently approved in combination with the estrogen receptor degrader fulvestrant for the treatment of ER+ advanced breast cancer after progression on an aromatase inhibitor. Nevertheless, the clinical development of multiple inhibitors of the PI3K/AKT/mTOR pathway, in parallel with the incorporation of CDK4/6 inhibitors into the standard of care treatment in ER+ advanced breast cancer, has led to a multitude of available therapeutic agents and many possible combined strategies which complicate personalizing treatment. Here, we review the role of the PI3K/AKT/mTOR pathway in ER+ advanced breast cancer, highlighting the genomic contexts in which the various inhibitors of this pathway may have superior activity. We also discuss selected trials with agents targeting the PI3K/AKT/mTOR and related pathways as well as the rationale supporting the clinical development of triple combination therapy targeting ER, CDK4/6 and PI3K/AKT/mTOR in ER+ advanced breast cancer.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Receptors, Estrogen/metabolism , TOR Serine-Threonine Kinases/metabolism
4.
Int J Mol Sci ; 23(17)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36077449

ABSTRACT

Triple-negative breast cancer (TNBC) is a heterogeneous disease that accounts for 10-15% of all breast cancer cases. Within TNBC, the treatment of basal B is the most challenging due to its highly invasive potential, and thus treatments to suppress metastasis formation in this subgroup are urgently needed. However, the mechanisms underlying the metastatic ability of TNBC remain unclear. In the present study, we investigated the role of Aurora A and Bcl-xL in regulating basal B cell invasion. We found gene amplification and elevated protein expression in the basal B cells, which also showed increased invasiveness in vitro, compared to basal A cells. Chemical inhibition of Aurora A with alisertib and siRNA-mediated knockdown of BCL2L1 decreased the number of invading cells compared to non-treated cells in basal B cell lines. The analysis of the correlation between AURKA and BCL2L1 expression in TNBC and patient survival revealed significantly decreased relapse-free survival (n = 534, p = 0.012) and distant metastasis-free survival (n = 424, p = 0.017) in patients with primary tumors exhibiting a high combined expression of AURKA and BCL2L1. Together, our findings suggest that high levels of Aurora A and Bcl-xL promote metastasis, and inhibition of these proteins may suppress metastasis and improve patient survival in basal B TNBC.


Subject(s)
Aurora Kinase A/metabolism , Neoplasm Metastasis , Triple Negative Breast Neoplasms , bcl-X Protein/metabolism , Aurora Kinase A/genetics , Cell Line, Tumor , Humans , Neoplasm Recurrence, Local , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , bcl-X Protein/genetics
5.
J Environ Sci Health B ; 57(9): 729-738, 2022.
Article in English | MEDLINE | ID: mdl-35915872

ABSTRACT

Lolium multiflorum Lam. is a winter weed of difficult control found as diploid (2n) and tetraploid plants (4n). Our study aimed to evaluate the responses of antioxidant enzymes and lipid peroxidation, in both diploid and tetraploid ryegrass varieties. Treatments consisted of control plants (without any herbicide application), and four herbicides with different mechanisms of action. Leaf material was collected 36 h after treatment imposition to determine the lipid peroxidation by ferrous oxidation-xylenol (FOX) content, and the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), glutathione-S-transferase (GST), and δ-aminolevulinic acid dehydratase (ALAD). Both ryegrass varieties showed oxidative stress mainly due to a downregulated decreased (>31%) in SOD activity and an increase (>32%) in lipid peroxidation (FOX), mainly in ryegrass genotypes exposed to haloxyfop, glyphosate, and iodosulfuron. On the other hand, clethodim-treated plants had an increase in SOD and APX activities, associated with a reduced ALAD activity in both 2n (32%) and 4n (11%) genotypes. In general, the 2n genotype was more affected than the 4n genotype.


Subject(s)
Herbicides , Lolium , Antioxidants/metabolism , Ascorbate Peroxidases/genetics , Catalase/genetics , Catalase/metabolism , Glutathione , Glutathione Transferase/metabolism , Herbicides/pharmacology , Lipid Peroxidation , Lolium/genetics , Lolium/metabolism , Oxidative Stress , Porphobilinogen Synthase , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Tetraploidy
6.
Breast Cancer Res ; 23(1): 26, 2021 02 18.
Article in English | MEDLINE | ID: mdl-33602273

ABSTRACT

BACKGROUND: Resistance to endocrine treatment in metastatic breast cancer is a major clinical challenge. Clinical tools to predict both drug resistance and possible treatment combination approaches to overcome it are lacking. This unmet need is mainly due to the heterogeneity underlying both the mechanisms involved in resistance development and breast cancer itself. METHODS: To study the complexity of the mechanisms involved in the resistance to the selective estrogen receptor degrader (SERD) fulvestrant, we performed comprehensive biomarker analyses using several in vitro models that recapitulate the heterogeneity of developed resistance. We further corroborated our findings in tissue samples from patients treated with fulvestrant. RESULTS: We found that different in vitro models of fulvestrant resistance show variable stability in their phenotypes, which corresponded with distinct genomic alterations. Notably, the studied models presented adaptation at different cell cycle nodes to facilitate progression through the cell cycle and responded differently to CDK inhibitors. Cyclin E2 overexpression was identified as a biomarker of a persistent fulvestrant-resistant phenotype. Comparison of pre- and post-treatment paired tumor biopsies from patients treated with fulvestrant revealed an upregulation of cyclin E2 upon development of resistance. Moreover, overexpression of this cyclin was found to be a prognostic factor determining resistance to fulvestrant and shorter progression-free survival. CONCLUSIONS: These data highlight the complexity of estrogen receptor positive breast cancer and suggest that the development of diverse resistance mechanisms dictate levels of ER independence and potentially cross-resistance to CDK inhibitors.


Subject(s)
Cyclin-Dependent Kinases/antagonists & inhibitors , Drug Resistance, Neoplasm/drug effects , Estrogen Receptor Antagonists/pharmacology , Fulvestrant/pharmacology , Protein Kinase Inhibitors/pharmacology , Receptors, Estrogen/metabolism , Antineoplastic Agents, Hormonal/pharmacology , Biomarkers, Tumor , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm/genetics , Female , Humans , Mutation , Polymorphism, Single Nucleotide , Signal Transduction
7.
J Dairy Res ; 87(2): 255-258, 2020 May.
Article in English | MEDLINE | ID: mdl-32398181

ABSTRACT

This research communication addresses the impact of the addition of Lactobacillus casei and/or carbonation (CO2) on the chemical composition, physicochemical characteristics, probiotic survival, and sensory acceptance of passion-fruit flavored whey dairy beverages (70% milk/30% whey) during storage (30 d/4°C). The addition of Lactobacillus casei and/or carbonation did not impact on the chemical composition, pH values, and acceptance (flavor and overall impression) of the products, but increased the acidity, and decreased the aroma acceptance. The carbonation process did not affect the probiotic survival but decreased the acidity of the products during storage. It can be concluded that it is possible to develop a probiotic passion-fruit flavored carbonated whey dairy beverage with suitable chemical composition, acidity, sensory acceptance (>6 in 9-point hedonic scale) and probiotic viability (>7 log cfu/ml) that could be refrigerated stored for 30 d. This is the first report considering a probiotic non-fermented carbonated whey dairy beverage.


Subject(s)
Carbonated Beverages/analysis , Carbonated Beverages/microbiology , Lacticaseibacillus casei/physiology , Milk/chemistry , Milk/microbiology , Probiotics/administration & dosage , Animals , Chemical Phenomena , Food Storage/methods , Fruit , Hydrogen-Ion Concentration , Passiflora , Refrigeration , Smell , Whey/chemistry , Whey/microbiology
8.
J Prosthodont ; 28(1): e34-e40, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30028061

ABSTRACT

PURPOSE: To evaluate the influence of age, gender, mandibular bone height, previous experience with prostheses, and methods for denture fabrication on masticatory performance of complete denture (CD) wearers. MATERIALS AND METHODS: For this study, 29 individuals treated with CDs fabricated by simplified or conventional methods had their masticatory performance assessed 4 weeks after the prostheses' adjustment and control, using the sieve method and almonds as a natural food test. Experimental variables related to age, gender, and previous use of complete dentures were collected from dental records. Panoramic digital radiographs were used to determine mandibular bone height according to the criteria described by the American College of Prosthodontists. Data on masticatory performance were assessed using t-test for independent samples to make comparison between simplified and conventional methods, and a multiple linear regression analysis was performed to evaluate the influence of age, gender, previous experience with CDs, and mandibular bone height on masticatory performance using SPSS software with a significance level of 5%. RESULTS: There was no significant influence regarding the method for CD fabrication (p = 0.92), age (p = 0.36), mandibular bone height (p = 0.37), and previous experience with prostheses (p = 0.15) on masticatory performance of CD wearers. Female patients presented lower masticatory performance than male (p = 0.04) patients did. CONCLUSIONS: Considering the limitations of this study, it was concluded that gender might be considered a risk factor for masticatory performance of CD wearers. Female patients demonstrated reduced masticatory performance in comparison to male patients.


Subject(s)
Denture Design , Denture, Complete , Mandible/anatomy & histology , Mastication , Age Factors , Aged , Aged, 80 and over , Denture Design/methods , Female , Humans , Male , Mastication/physiology , Middle Aged , Sex Factors
9.
Breast Cancer Res ; 20(1): 60, 2018 06 19.
Article in English | MEDLINE | ID: mdl-29921289

ABSTRACT

BACKGROUND: Endocrine resistance in estrogen receptor-positive (ER+) breast cancer is a major clinical problem and is associated with accelerated cancer cell growth, increased motility and acquisition of mesenchymal characteristics. However, the specific molecules and pathways involved in these altered features remain to be detailed, and may be promising therapeutic targets to overcome endocrine resistance. METHODS: In the present study, we evaluated altered expression of epithelial-mesenchymal transition (EMT) regulators in ER+ breast cancer cell models of tamoxifen or fulvestrant resistance, by gene expression profiling. We investigated the specific role of increased SNAI2 expression in fulvestrant-resistant cells by gene knockdown and treatment with a SNAIL-p53 binding inhibitor, and evaluated the effect on cell growth, migration and expression of EMT markers. Furthermore, we evaluated SNAI2 expression by immunohistochemical analysis in metastatic samples from two cohorts of patients with breast cancer treated with endocrine therapy in the advanced setting. RESULTS: SNAI2 was found to be significantly upregulated in all endocrine-resistant cells compared to parental cell lines, while no changes were observed in the expression of other EMT-associated transcription factors. SNAI2 knockdown with specific small interfering RNA (siRNA) converted the mesenchymal-like fulvestrant-resistant cells into an epithelial-like phenotype and reduced cell motility. Furthermore, inhibition of SNAI2 with specific siRNA or a SNAIL-p53 binding inhibitor reduced growth of cells resistant to fulvestrant treatment. Clinical evaluation of SNAI2 expression in two independent cohorts of patients with ER+ metastatic breast cancer treated with endocrine therapy in the advanced setting (N = 86 and N = 67) showed that high SNAI2 expression in the metastasis correlated significantly with shorter progression-free survival on endocrine treatment (p = 0.0003 and p = 0.004). CONCLUSIONS: Our results suggest that SNAI2 is a key regulator of the aggressive phenotype observed in endocrine-resistant breast cancer cells, an independent prognostic biomarker in ER+ advanced breast cancer treated with endocrine therapy, and may be a promising therapeutic target in combination with endocrine therapies in ER+ metastatic breast cancer exhibiting high SNAI2 levels.


Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Snail Family Transcription Factors/genetics , Adult , Aged , Antineoplastic Agents, Hormonal/adverse effects , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Epithelial-Mesenchymal Transition/drug effects , Estrogen Receptor alpha/genetics , Female , Fulvestrant/administration & dosage , Fulvestrant/adverse effects , Gene Expression Regulation, Neoplastic/genetics , Humans , MCF-7 Cells , Middle Aged , Neoplasm Metastasis
10.
Langmuir ; 34(41): 12428-12435, 2018 10 16.
Article in English | MEDLINE | ID: mdl-30251859

ABSTRACT

Novel theranostic nanocarriers exhibit a desirable potential to treat diseases based on their ability to achieve targeted therapy while allowing for real-time imaging of the disease site. Development of such theranostic platforms is still quite challenging. Herein, we present the construction of multifunctional dendrimer-based theranostic nanosystem to achieve cancer cell chemotherapy and computed tomography (CT) imaging with targeting specificity. Doxorubicin (DOX), a model anticancer drug, was first covalently linked onto the partially acetylated poly(amidoamine) dendrimers of generation 5 (G5) prefunctionalized with folic acid (FA) through acid-sensitive cis-aconityl linkage to form G5·NHAc-FA-DOX conjugates, which were then entrapped with gold (Au) nanoparticles (NPs) to create dendrimer-entrapped Au NPs (Au DENPs). We demonstrate that the prepared DOX-Au DENPs possess an Au core size of 2.8 nm, have 9.0 DOX moieties conjugated onto each dendrimer, and are colloid stable under different conditions. The formed DOX-Au DENPs exhibit a pH-responsive release profile of DOX because of the cis-aconityl linkage, having a faster DOX release rate under a slightly acidic pH condition than under a physiological pH. Importantly, because of the coexistence of targeting ligand FA and Au core NPs as a CT imaging agent, the multifunctional DOX-loaded Au DENPs afford specific chemotherapy and CT imaging of FA receptor-overexpressing cancer cells. The constructed DOX-conjugated Au DENPs hold a promising potential to be utilized for simultaneous chemotherapy and CT imaging of various types of cancer cells.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Dendrimers/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Antibiotics, Antineoplastic/chemistry , Cell Line, Tumor , Dendrimers/chemical synthesis , Doxorubicin/chemistry , Drug Carriers/chemical synthesis , Drug Liberation , Humans , Hydrogen-Ion Concentration , Theranostic Nanomedicine , Tomography, X-Ray Computed/methods
11.
Nanomedicine ; 14(7): 2407-2420, 2018 10.
Article in English | MEDLINE | ID: mdl-28552649

ABSTRACT

Laponite® is a synthetic smectite clay that already has many important technological applications, which go beyond the conventional uses of clays in pharmaceutics and cosmetics. In biomedical applications, particularly in nanomedicine, this material holds great potential. Laponite® is a 2-dimensional (2D) nanomaterial composed of disk-shaped nanoscale crystals that have a high aspect ratio. These disks can strongly interact with many types of chemical entities (from small molecules or ions, to natural or synthetic polymers, to different inorganic nanoparticles) and are also easily functionalized and readily degraded in the physiological environment giving rise to non-toxic and even bioactive products. This review will highlight the potential of Laponite® as a nanomaterial in the fields of drug delivery, bioimaging, tissue engineering and regenerative medicine. New concepts, as well as novel innovative materials that stand out from the usual ones due to the unique properties of Laponite®, will also be presented and discussed.


Subject(s)
Biomedical Research , Nanomedicine , Nanoparticles/administration & dosage , Regenerative Medicine , Silicates/chemistry , Tissue Engineering , Biocompatible Materials/chemistry , Drug Delivery Systems , Humans , Nanoparticles/chemistry
12.
An Acad Bras Cienc ; 90(2): 1533-1542, 2018.
Article in English | MEDLINE | ID: mdl-29898110

ABSTRACT

Most herbicides applied in crop field, stay in the soil for a period, affecting next crop or even the plants using as green manure. Nowadays, the use of herbicides grow to increase productivity, mainly in the grain producing region north of Rio Grande do Sul state. The objective of this study was to evaluate the effects of herbicides fomesafen and sulfentrazone on antioxidant system in Avena sativa1, Vicia sativa2, Raphanus sativus and Lupinus albus. The plants were exposed to varying concentrations of fomesafen3 (0, 0.125, 0.25 and 0.5 kg ha -1) and sulfentrazone (0, 0.3, 0.6 and 1.2 kg ha-1). For this, the activities of, ascorbat peroxidase, catalase and guaiacol enzymes were analyzed, and the levels of MDA were quantificated. Fomesafen and sulfentrazone promoted alterations in balance of plants generating oxidative stress and elicited the response of the antioxidant system of plants, mainly in the high doses of fomesafen, for the species V. sativa and R. sativus. At the same time, the 1,2 kg ha -1 dose of sulfentrazone generated lipid peroxidation for V. sativa, R. sativus and L. albus. Additionally, A. sativa was the species that demonstrated low alterations on antioxidant system with the exposure to herbicide fomesafen and sulfentrazone. Thus, we can we can suggest that the species present a better response in defense of the oxidative stress generated by the herbicides.


Subject(s)
Benzamides/pharmacology , Crops, Agricultural/drug effects , Herbicides/pharmacology , Oxidative Stress/drug effects , Sulfonamides/pharmacology , Triazoles/pharmacology , Avena/drug effects , Catalase/drug effects , Lupinus/drug effects , Peroxidase/drug effects , Raphanus/drug effects , Species Specificity , Vicia sativa/drug effects
13.
Arch Sex Behav ; 44(2): 357-65, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25318623

ABSTRACT

Combined antiretroviral therapy is now acknowledged for preventing new HIV infections, besides decreasing mortality and morbidity. However, in many Latin America countries the epidemic is still driven by unprotected sexual intercourse. This study aims to describe sexual practices related to HIV/STD and to evaluate factors associated to unprotected sex among men who have sex with women (MSW) and men who have sex with men (MSM) under care at a reference center for HIV in Rio de Janeiro, Brazil. A cross-sectional study, nested in a Brazilian clinical cohort, evaluated the sexual practices of 404 sexually active HIV-positive MSW and men who have MSM. Approximately 30 % of them reported unprotected sexual practices during the 6 months prior to the interview. Most frequent risky practices reported were unprotected vaginal sex among MSW and unprotected receptive anal sex among MSM. Factors increasing the chance of unprotected sexual practices among MSW were the partner's desire of becoming pregnant (OR 2.81; CI 95 %: 1.36-5.95). To have received comments about excessive consumption of alcohol (OR 2.43; CI 95 %: 1.01-5.83), illicit drug use (OR 4.41; CI 95 %: 1.75-11.60) and lived in marital situation (OR 2.10; CI 95 %: 1.09-4.08) were significantly associated with unsafe sexual practices among MSM. The results highlight that health care of men living with HIV, as well as the prevention strategies, must consider the particularities of sexual behavior practiced by people who differ in sexual orientation.


Subject(s)
HIV Seropositivity , Heterosexuality , Homosexuality, Male , Unsafe Sex , Acquired Immunodeficiency Syndrome/prevention & control , Adult , Brazil , Cross-Sectional Studies , Female , HIV Infections/prevention & control , Humans , Logistic Models , Male , Sexual Behavior , Sexual Partners , Urban Population
14.
Phys Ther ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38624192

ABSTRACT

OBJECTIVE: This study aimed to determine the effects of inspiratory muscle training (IMT) on exercise capacity, respiratory muscle strength, length of hospital stay (LOS), and quality of life (QOL) following coronary artery bypass graft surgery. METHODS: The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Cochrane Handbook and included the databases MEDLINE, EMBASE, CINAHL, Scopus, and CENTRAL. The review included randomized controlled trials utilizing IMT during phase 1 or 2 postoperative cardiac rehabilitation (PoCR) versus alternative treatment (active or passive control) in patients following coronary artery bypass graft surgery. RESULTS: Fifteen studies were included (11 phase 1 studies, 4 phase 2 studies) with no reported adverse events. In phase 1 PoCR, IMT reduced the LOS (-1.02 days; 95% CI = -2.00 to -0.03) and increased exercise capacity (6-minute walk distance [6MWD]).(+75.46 m; 95% CI = 52.34 to 98.57), and maximal inspiratory pressure (MIP) (10.46 cm H2O; 95% CI = 2.83 to 18.10), but had no effect on maximal expiratory pressure. In phase 2 PoCR, IMT increased 6MWD (45.84 m; 95% CI = 10.89 to 80.80), MIP (-23.19 cm H2O; 95% CI = -31.31 to -15), maximal expiratory pressure (20.18 cm H2O; 95% CI = 9.60 to 30.76), and QOL (-11.17; 95% CI = -17.98 to -4.36), with no effect on peak oxygen uptake. There was a high risk of bias for MIP (75% of the phase 1 studies) and 6MWT (1 of 4 phase 2 studies). The quality of the evidence ranged from very low to moderate. CONCLUSIONS: IMT significantly improves exercise capacity, respiratory muscle strength, LOS, and QOL in phase 1 and 2 PoCR. IMPACT: IMT may benefit patients during phase 1 and 2 of PoCR, considering the safety, low cost, and potential benefits.

15.
Article in English | MEDLINE | ID: mdl-37172752

ABSTRACT

The use of agrichemical pyrethroid-based insecticides to combat crop infestations and ectoparasites in animals is increasing. In this context, two pyrethroid-based insecticides are widely used, λ-cyhalothrin and Cypermethrin. The mechanism of action of these insecticides is characterized by the opening of ion channels and death by neural hyperexcitability. In this study, we evaluated the toxicological effect of two pyrethroid-based insecticides λ-cyhalothrin and Cypermethrin in C. elegans aiming to evaluate the transgenerational (TG), neonatal (NN) and lifespan (LS) effects of these compounds. At the end of each exposure period, were evaluated behavioral biomarkers of body bends, pharyngeal pumping, and feeding behavior. Furthermore, the fluorescent expression of antioxidant enzymes (superoxide dismutase, catalase, and glutathione-S-transferase) and the fluorescent expression of PolyQ40 aggregates were quantified. Lastly, the activity of the enzyme acetylcholinesterase (AChE) was quantified. Changes in TG were more related to changes in AChE enzyme activity that probably were transferred to the offspring, altering behavioral biomarkers in the adult life of offspring from exposed parents. However, alterations in LS were related to the modulation of ion channels in a chronic way, exerting behavioral effects. In addition, both compounds increased the expression of PolyQ40 muscle aggregates in mutant worms. These proteins are related to the increased probability of the senile incidence of Huntington's Disease in genetically predisposed patients.


Subject(s)
Insecticides , Pyrethrins , Animals , Insecticides/toxicity , Caenorhabditis elegans/metabolism , Acetylcholinesterase/metabolism , Pyrethrins/toxicity , Nitriles , Ion Channels , Biomarkers/metabolism
16.
Sci Rep ; 13(1): 9813, 2023 06 17.
Article in English | MEDLINE | ID: mdl-37330587

ABSTRACT

The use of terpenoid compounds in different neural-related conditions is becoming useful for several illnesses. Another possible activity of these compounds is the reduction of nervous impairment. Cannabis sativa plants are known for their concentration of two important terpenoids, the delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). CBD and THC have central peripheral activities already described and their usage in different brain diseases, such as Alzheimer's and multiple sclerosis. Aluminum (Al) is known as an important neurotoxic compound, the physiological action of Al is not known already, and in high concentrations can lead to intoxication and cause neurotoxicity. Here we evaluated the potential effect of two different doses of CBD- and THC-rich based oils against Al-induced toxicity, in the zebrafish model. We evaluated behavioral biomarkers of the novel tank test (NTT) and social preference test (SPT), and biochemical markers: the activity of the enzyme acetylcholinesterase (AChE) and the antioxidant enzymes-catalase, superoxide dismutase, and glutathione-S-transferase. CBD- and THC-based oils were able to increase the AChE activity helping the cholinergic nervous system actuate against Al toxicity which was reflected by the behavioral biomarkers changes. We concluded that the oils have a protective effect and might be used with proposals for neurological and antioxidant impairment avoidance caused by Al intoxications.


Subject(s)
Cannabidiol , Cannabis , Animals , Cannabis/chemistry , Aluminum , Antioxidants , Acetylcholinesterase , Zebrafish , Cannabidiol/pharmacology , Oils , Dronabinol/pharmacology
17.
Article in English | MEDLINE | ID: mdl-37192702

ABSTRACT

The growing consumption of psychoactive drugs, such as Venlafaxine (VFX), can negatively affect the organisms. Our main hypothesis is to investigate if VFX at human-used doses could exert effects on the behavioral, nervous, and antioxidant systems of two different organisms, zebrafish and C. elegans. We evaluated the effect of acute exposure to VFX at four concentrations (0, 37.5, 75, and 150 mg L-1) using toxicological indicator assessments. We evaluated zebrafish behavior using the novel tank test (NTT), social preference test (SPT), cortisol levels, acetylcholinesterase (AChE) activity, and antioxidant system. In C. elegans, we evaluated body bends, defecation cycles, pharyngeal pumping, AChE activity, and antioxidant system. C. elegans do not show alterations in the behavior analysis of pharyngeal pumping and body bends. Instead, the defecation cycle was increased in the highest dose of VFX. AChE activity also does not have differences compared to the control, the same occurs in lipid peroxidation rates. These results showed that nematodes were more resistant to changes when exposed to VFX. Zebrafish exposed to VFX showed changes in the NTT and SPT test, mainly in the anxiolytic pattern, suggesting that VFX alters this anxiolytic-like behavior. Comparing both organisms, we can observe that zebrafish seems to be more sensitive in this neurotoxicological evaluation.


Subject(s)
Anti-Anxiety Agents , Zebrafish , Animals , Humans , Venlafaxine Hydrochloride/toxicity , Caenorhabditis elegans , Acetylcholinesterase , Antioxidants
18.
Environ Pollut ; 327: 121530, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37004863

ABSTRACT

Pyrethroids prallethrin (P-BI) and transfluthrin (T-BI) are among the most commonly used molecules with insecticide action. These molecules comprise different formulations of insecticides largely used in household, agricultural, and animal production fields. However, the increased use of these molecules has led to concerns regarding their safety in animals and humans. Oxidative stress (OS) is believed to be easily established by xenobiotic contacts, such as pyrethroids. We aimed to evaluate and understand the impact of two household insecticides and two doses applied to different tissues of the antioxidant system of zebrafish (Danio rerio). We observed that the effect on the antioxidant system differed between tissues. The muscle was the most affected tissue in the body, the antioxidant enzymes were activated, and a mechanism of non-enzymatic antioxidants was activated; however, it could still cause cellular damage. The observed effect on muscle may be related to the progression of neurodegenerative conditions. In addition, in the brain, these compounds can inactivate the first line of enzymatic antioxidant defense, which is compensated for by the second line, avoiding cellular damage. Ultimately, the gill tissue did not appear to suffer lipid damage, but heme group formation was largely affected by the compounds.


Subject(s)
Insecticides , Pyrethrins , Animals , Humans , Insecticides/toxicity , Antioxidants/metabolism , Zebrafish/metabolism , Pyrethrins/toxicity , Oxidative Stress , Lipid Peroxidation
19.
Neurotoxicology ; 96: 19-27, 2023 05.
Article in English | MEDLINE | ID: mdl-36868382

ABSTRACT

Pyrethroid-based insecticides are largely used for mosquito control. These compounds have household and agricultural applications with different formulations. Two important compounds used as household insecticides are prallethrin and transfluthrin, both from the pyrethroid chemical group. With the mode of action centered on sodium channels, pyrethroids keep the ionic sodium channels open for a long time causing the death of the insect by nervous hyperexcitability. Given the increased use of household insecticides by humans and the incidence of disease outbreaks with unknown etiology such as autism spectrum disease, schizophrenia, and Parkinson's disease we investigate some physiological inputs of these compounds on zebrafish. In this study, we evaluated the social interaction, shoaling formation, and anxiety-like behavior of zebrafish exposed chronically to transfluthrin- and prallthrin-based insecticides (T-BI and P-BI). In addition, we quantified the activity of the enzyme acetylcholinesterase (AChE) in different brain regions. We observed that both compounds caused anxiolytic behavior and reduced shoaling formation and social interaction. Their behavioral biomarkers indicated a harmful ecological effect on the specie as well as a possible impact of these compounds on autism spectrum disorder (ASD) and schizophrenia (SZP). In addition, the AChE activity would change its activity in different brain regions modulating the anxiety-like behavior and social behavior in zebrafish. We conclude that P-BI and T-BI make us alert about the relationship of these compounds with nervous diseases related to cholinergic signaling.


Subject(s)
Autism Spectrum Disorder , Insecticides , Pyrethrins , Adult , Animals , Humans , Insecticides/toxicity , Zebrafish/metabolism , Acetylcholinesterase/metabolism , Pyrethrins/pharmacology , Brain/metabolism , Cholinergic Agents , Sodium Channels
20.
Rev Bras Parasitol Vet ; 32(4): e012123, 2023.
Article in English | MEDLINE | ID: mdl-38018630

ABSTRACT

The aim of this study was to evaluate the prevalence of endoparasites in domestic cats (Felis catus) in the city of Sousa, state of Paraíba, Northeast Brazil. A total of 207 samples of fresh feces were randomly collected from domestic and semi-domiciled cats. The samples were analyzed by simple centrifugation and centrifuge-flotation in sucrose solution for the diagnosis of helminth eggs and enteric protozoan oocysts and cysts. Epidemiological information was obtained to determine risk factors related to infections. Among the samples collected, 81.6% (169/207; 95% CI: 77.4-83.8) were positive for at least one parasite genus. Ancylostoma spp. was the most prevalent, at 67.1% (139/207), followed by Taenia spp. at 28.5% (59/207), and Spirometra spp. and Platynosomum sp., both at 17.3% (36/207). The variables associated with helminth infection were a historic lack of deworming (Odds ratio = 12.25) and the presence of dry fur (Odds ratio = 2.15). No risk factors were observed for enteric protozoa infection. This study demonstrated a high prevalence of endoparasites in domestic cats in the city of Sousa, state of Paraíba, and associated risk factors, thus establishing an overview of the main helminths and protozoa that affect cats in this region.


Subject(s)
Cat Diseases , Dolphins , Helminths , Parasites , Cats , Animals , Brazil/epidemiology , Feces/parasitology , Cat Diseases/diagnosis , Cat Diseases/epidemiology , Prevalence
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