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1.
PLoS Pathog ; 19(5): e1011369, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37146077

RESUMO

The trematode parasite Schistosoma mansoni causes schistosomiasis, which affects over 200 million people worldwide. Schistosomes are dioecious, with egg laying depending on the females' obligatory pairing with males. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that have been involved in other species with reproduction, stem cell maintenance, and drug resistance. In S. mansoni, we recently showed that the knockdown of one lncRNA affects the pairing status of these parasites. Here, we re-analyzed public RNA-Seq data from paired and unpaired adult male and female worms and their gonads, obtained from mixed-sex or single-sex cercariae infections, and found thousands of differentially expressed pairing-dependent lncRNAs among the 23 biological samples that were compared. The expression levels of selected lncRNAs were validated by RT-qPCR using an in vitro unpairing model. In addition, the in vitro silencing of three selected lncRNAs showed that knockdown of these pairing-dependent lncRNAs reduced cell proliferation in adult worms and their gonads, and are essential for female vitellaria maintenance, reproduction, and/or egg development. Remarkably, in vivo silencing of each of the three selected lncRNAs significantly reduced worm burden in infected mice by 26 to 35%. Whole mount in situ hybridization experiments showed that these pairing-dependent lncRNAs are expressed in reproductive tissues. These results show that lncRNAs are key components intervening in S. mansoni adult worm homeostasis, which affects pairing status and survival in the mammalian host, thus presenting great potential as new therapeutic target candidates.


Assuntos
Parasitos , RNA Longo não Codificante , Esquistossomose mansoni , Masculino , Feminino , Animais , Camundongos , Schistosoma mansoni/genética , RNA Longo não Codificante/genética , Fertilidade/genética , Reprodução , Parasitos/genética , Esquistossomose mansoni/parasitologia , Mamíferos
2.
Am Heart J ; 270: 55-61, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38266665

RESUMO

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.


Assuntos
Benzoatos , Taquicardia Paroxística , Taquicardia Supraventricular , Taquicardia Ventricular , Humanos , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/tratamento farmacológico , Taquicardia Paroxística/diagnóstico , Taquicardia Paroxística/tratamento farmacológico , Adenosina , Taquicardia Ventricular/induzido quimicamente
3.
Cell Mol Life Sci ; 81(1): 11, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117357

RESUMO

Metabolic bone disorders and associated fragility fractures are major causes of disability and mortality worldwide and place an important financial burden on the global health systems. These disorders result from an unbalance between bone anabolic and resorptive processes and are characterized by different pathophysiological mechanisms. Drugs are available to treat bone metabolic pathologies, but they are either poorly effective or associated with undesired side effects that limit their use. The molecular mechanism underlying the most common metabolic bone disorders, and the availability, efficacy, and limitations of therapeutic options currently available are discussed here. A source for the unmet need of novel drugs to treat metabolic bone disorders is marine organisms, which produce natural osteoactive compounds of high pharmaceutical potential. In this review, we have inventoried the marine osteoactive compounds (MOCs) currently identified and spotted the groups of marine organisms with potential for MOC production. Finally, we briefly examine the availability of in vivo screening and validation tools for the study of MOCs.


Assuntos
Produtos Biológicos , Doenças Ósseas Metabólicas , Humanos , Produtos Biológicos/farmacologia
4.
Dysphagia ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958706

RESUMO

Aspiration detected in the fiberoptic endoscopy evaluation of swallowing (FEES) has been inconsistently associated with pneumonia, with no evidence of the risk of pneumonia from other alterations in swallowing safety detected in FEES. We conducted a dynamic, ambidirectional cohort study involving 148 subjects at risk of dysphagia in a tertiary university hospital. Our aim was to determine the risk of pneumonia attributed to alterations in swallowing safety detected during FEES. We used multivariate negative binomial regression models to adjust for potential confounders. The incidence density rate (IR) of pneumonia in patients with tracheal aspiration of any consistency was 26.6/100 people-years (RR 7.25; 95% CI: 3.50-14.98; P < 0.001). The IR was 19.7/100 people-years (RR 7.85; 95% CI: 3.34-18.47; P < 0.001) in those with laryngeal penetration of any consistency and 18.1/100 people-years (RR 6.24; 95% CI: 2.58-15.09; P < 0.001) in those with pharyngeal residue of any consistency. When adjusted for aspiration, the association of residue and penetration with pneumonia disappeared, suggesting that their risk of pneumonia is dependent on the presence of aspiration and that only aspiration is independently associated with pneumonia. This increased risk of pneumonia was significant in uni- and multivariate negative binomial regression models. We found an independently increased risk of pneumonia among patients with dysphagia and aspiration detected during FEES. Alterations in the oral and pharyngeal phases of swallowing, without aspiration, did not increase the risk of pneumonia.

5.
Immunology ; 168(4): 597-609, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36279244

RESUMO

Immunoparalysis is associated with poorer outcomes in the paediatric intensive care unit (PICU) setting. We aimed to determine the group of patients with higher chances of immunoparalysis and correlate this status with increased risks of nosocomial infection and adverse clinical parameters. We conducted an exploratory study with prospective data collection in a university-affiliated tertiary medical, surgical, and cardiac PICU. Fifteen patients with multiple organ dysfunction syndrome were included over a period of 6 months. Monocyte's human leucocyte antigen (HLA)-DR expression and tumour necrosis factor (TNF)-α and interleukin (IL)-6 production were measured by flow-cytometry at three time points (T1 = 1-2 days; T2 = 3-5 days; T3 = 6-8 days). Using the paediatric logistic organ dysfunction-2 score to assess initial disease severity, we established the optimal cut-off values of the evaluated parameters to identify the subset of patients with a higher probability of immunoparalysis. A comparative analysis was performed between them. Sixty per cent were males; the median age was 4.1 years. Considering the presence of two criteria in T1 (classical monocytes mean fluorescence intensity [MFI] for HLA-DR ≤ 1758.5, area under the curve (AUC) = 0.775; and frequency of monocytes producing IL-6 ≤ 68.5%, AUC = 0.905) or in T3 (classical monocytes MFI of HLA-DR ≤ 2587.5, AUC = 0.675; and frequency of monocytes producing TNF-α ≤ 93.5%, AUC = 0.833), a variable to define immunoparalysis was obtained (100% sensitivity, 81.5% specificity). Forty per cent of patients were assigned to the immunoparalysis group. In this: a higher frequency of nosocomial infection (p = 0.011), vasoactive inotropic score (p = 0.014) and length of hospital stay (p = 0.036) was observed. In the subgroup with the diagnosis of sepsis/septic shock (n = 5), patients showed higher percentages of non-classical monocytes (p = 0.004). No mortality was recorded. A reduction in classical monocytes HLA-DR expression with lower frequencies of monocytes producing TNF-α and IL-6 during the first week of critical illness, appears to be a good marker of immunoparalysis; these findings relate to an increased risk of nosocomial infection and deleterious outcomes. The increased frequency of non-classical monocytes in patients with sepsis/septic shock is suggestive of a better prognosis.


Assuntos
Infecção Hospitalar , Sepse , Choque Séptico , Masculino , Humanos , Criança , Pré-Escolar , Feminino , Fator de Necrose Tumoral alfa , Interleucina-6 , Estado Terminal , Antígenos HLA-DR , Monócitos
6.
Microb Pathog ; 185: 106391, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839762

RESUMO

Streptococcus pneumoniae colonizes the human nasopharynx asymptomatically, but it can also cause several diseases, including otitis media, pneumonia, bacteremia, and meningitis. The colonization of the nasopharynx by the bacteria is an essential step for the pneumococcus to invade other sites and cause diseases. Pneumococcal surface protein A (PspA) and Pneumococcal surface Protein C (PspC) are important virulence factors and have been described to play roles in adhesion and immune evasion. In this study, we immunized mice subcutaneously with the recombinant α-helical region of PspA and/or PspC combined with different adjuvants to assess protection against colonization with the serotype 6B strain BHN418. Though high serum levels of specific IgG were detected, none of the formulations led to reduction in the colonization of the nasopharynx. The negative result may be due to the poor induction of IgG2c, which has been previously correlated with protection against pneumococcal colonization in mice. Furthermore, BHN418 pspA and pspC single and double knockouts were evaluated in colonization experiments and no differences in bacterial load were observed. In competition assays with the wild-type strain, borderline to no reduction was observed in the loads of the knockouts. Our results contrast with data from the literature using other pneumococcal strains, showing that the role of PspA and PspC in colonization can vary depending on the background of the knockout strain studied. BHN418 has been selected for its capacity to colonize humans in experimental challenge studies and may have redundant factors that compensate for the lack of PspA and PspC during nasopharyngeal colonization of mice.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Animais , Camundongos , Humanos , Infecções Pneumocócicas/microbiologia , Proteína C/metabolismo , Sorogrupo , Proteínas de Bactérias/metabolismo , Nasofaringe/microbiologia , Proteínas de Membrana/metabolismo , Vacinas Pneumocócicas , Anticorpos Antibacterianos
7.
Virol J ; 20(1): 100, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231481

RESUMO

Dengue has become one of the vector-borne diseases that affect humans worldwide. In Latin American countries, Colombia is historically one of the most affected by epidemics of this flavivirus. The underreporting of signs and symptoms of probable cases of dengue, the lack of characterization of the serotypes of the infection, and the few detailed studies of postmortem necropsies of patients are among other conditions that have delayed progress in the knowledge of the pathogenesis of the disease. This study presents the results of fragment sequencing assays on paraffin-embedded tissue samples from fatal DENV cases during the 2010 epidemic in Colombia. We found that the predominant serotype was DENV-2, with the Asian/American genotype of lineages 1 and 2. This work is one of the few reports of the circulating genotypes of dengue during the 2010 epidemic in Colombia, one of the most lethal dates in the country's history.


Assuntos
Vírus da Dengue , Dengue , Humanos , Vírus da Dengue/genética , Dengue/epidemiologia , Parafina , Genótipo , Filogenia , Sorogrupo
8.
Neurochem Res ; 48(1): 295-304, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36098890

RESUMO

Paclitaxel (PTX) is a frequently used anticancer drug that causes peripheral neuropathy. Transient receptor potential ankyrin 1 (TRPA1), a plasma membrane calcium channel, has been associated with PTX toxicity and with other chemotherapy agents such as oxaliplatin and vincristine. However, the effect of PTX on the functional expression and calcium currents of TRPA1 has not been determined. The present study shows the effect of PTX on TRPA1 activity in a neuronal cell line (SH-SY5Y). The effect of PTX on the expression of TRPA1 was assessed through quantitative PCR and Western blot analyses to determine the relative mRNA and protein expression levels. To assess the effect on calcium flux and currents, cells were exposed to PTX; simultaneously, a specific agonist and antagonist of TRPA1 were added to evaluate the differential response in exposed versus control cells. To assess the effect of PKA, PKC and PI3K on PTX-induced TRPA1 increased activity, selective inhibitors were added to these previous experiments. PTX increased the mRNA and protein expression of TRPA1 as well as the TRPA1-mediated Ca2+ currents and intracellular Ca2+ concentrations. This effect was dependent on AITC (a selective specific agonist) and was abolished with HC-030031 (a selective specific antagonist). The inhibition of PKA and PKC reduced the effect of PTX on the functional expression of TRPA1, whereas the inhibition of PI3K had no effects. PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.


Assuntos
Antineoplásicos , Neuroblastoma , Canais de Potencial de Receptor Transitório , Humanos , Paclitaxel/farmacologia , Canal de Cátion TRPA1/metabolismo , Cálcio/metabolismo , Canais de Potencial de Receptor Transitório/genética , Canais de Potencial de Receptor Transitório/metabolismo , Proteínas do Citoesqueleto/metabolismo , RNA Mensageiro/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo
9.
Inorg Chem ; 62(28): 11016-11027, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37390399

RESUMO

Understanding the fundamental chemistry of soft N,S-donor ligands with actinides across the series is critical for separation science toward sustainable nuclear energy. This task is particularly challenging when the ligands are redox active. We herein report a series of actinyl complexes with a N,S-donor redox-active ligand that stabilizes different oxidation states across the actinide series. These complexes are isolated and characterized in the gas phase, along with high-level electronic structure studies. The redox-active N,S-donor ligand in the products, C5H4NS, acts as a monoanion in [UVIO2(C5H4NS-)]+ but as a neutral radical with unpaired electrons localized on the sulfur atom in [NpVO2(C5H4NS•)]+ and [PuVO2(C5H4NS•)]+, resulting in different oxidation states for uranium and transuranic elements. This is rationalized by considering the relative energy levels of actinyl(VI) 5f orbitals and S 3p lone pair orbitals of the C5H4NS- ligand and the cooperativity between An-N and An-S bonds that provides additional stability for the transuranic elements.

10.
J Math Biol ; 87(1): 9, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37329353

RESUMO

The Kuramoto model was developed to describe the coupling of oscillators, motivated by the natural synchronization phenomena. We are interested in modeling an epileptic seizure considering it as the synchronization of action potentials using and modifying this model. In this article, we propose to modify this model, changing the constant coupling force for a function with logistic growth to simulate the onset and epileptic seizure level in an adult male rat caused by the administration of lithium-pilocarpine. Later, we select some frequencies and their respective amplitude values using an algorithm based on the fast Fourier transform (FFT) from an electroencephalography signal when the rat is in basal conditions. Then, we take these values as the natural frequencies of the oscillators in the modified Kuramoto model, considering every oscillator as a single neuron to simulate the emergence of an epileptic seizure numerically by increasing the synchronization value in the coupling function. Finally, using Dynamic Time Warping algorithm, we compare the simulated signal by the Kuramoto model with an FFT approximation of the epileptic seizure.


Assuntos
Epilepsia , Convulsões , Masculino , Ratos , Animais , Convulsões/diagnóstico , Epilepsia/diagnóstico , Eletroencefalografia , Algoritmos , Neurônios
11.
Metab Brain Dis ; 38(3): 767-782, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36598703

RESUMO

The brain requires a large amount of energy. Its function can be altered when energy demand exceeds supply or during metabolic disturbances such as diabetes mellitus. Diabetes, a chronic disease with a high incidence worldwide, is characterized by high glucose levels (hyperglycemia); however, hypoglycemic states may also occur due to insulin treatment or poor control of the disease. These alterations in glucose levels affect the brain and could cause epileptic seizures and status epilepticus. In addition, it is known that oxidative stress states emerge as diabetes progresses, contributing to the development of diseases secondary to diabetes, including retinopathy, nephropathy, cardiovascular alterations, and alterations in the central nervous system, such as epileptic seizures. Seizures are a complex of transient signs and symptoms resulting from abnormal, simultaneous, and excessive activity of a population of neurons, and they can be both a cause and a consequence of oxidative stress. This review aims to outline studies linking diabetes mellitus and seizures to oxidative stress, a condition that may be relevant to the development of severe seizures in diabetes mellitus patients.


Assuntos
Diabetes Mellitus , Epilepsia , Humanos , Estresse Oxidativo , Convulsões/complicações , Glucose
12.
Anim Biotechnol ; 34(2): 246-252, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34346295

RESUMO

This paper aims to investigate the influence of increasing chitosan doses on the relative proportion and abundance of cellulotytic, amylolytic bacteria, and Archaea transcripts for grazing cattle. Five rumen cannulated crossbread steers [3.6 months and 300 ± 25 kg body LW (live weight), mean ± standard deviation] were used in a 5 × 5 latin square design, randomly assigned to treatment sequence containing chitosan added to 0, 400, 800, 1200, or 1600 mg/kg concentrate. There was the effect of chitosan on the population of Fibrobacter succinogenes, Ruminococcus albus, and Archaea. The lowest population of these bacteria of 576.60 mg/kg DM (dry matter), 1010.40 mg/kg DM, and 634.80 mg/kg DM were noted when chitosan was added at levels of 3.87, 4.16, and 3.52. Except for Ruminococcus albus, which was not affected by increasing chitosan doses, supplementation of this additive in the concentrate quadratically increased the relative abundance of Fibrobacter succinogenes and Archaea Supplemental 740 mg CHI/kg concentrate for grazing steers receiving concentrate at 150 grams/100 kg LW is recommended to promote minimal effect on the relative population and abundance of cellulolytics and amylomatics and to restrict Archaea growth.


Assuntos
Quitosana , Dieta , Bovinos , Animais , Dieta/veterinária , Archaea , Quitosana/farmacologia , Ração Animal/análise , Bactérias
13.
Trop Anim Health Prod ; 55(6): 373, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37874396

RESUMO

This study evaluated the welfare of Saanen, Moxoto, and Anglo-Nubian goats kept in collective or individual pens for a feedlot system, evaluated with infrared thermography. A total of twenty-four goats were used, eight for each breed. Animals were distributed in a completely randomized design, with a 2 × 3 factorial with two fixed effects: housing type (collective or individual pens) and breed (Moxoto, Saanen, and Anglo-Nubian). The surface temperature was evaluated using an infrared thermographic camera, and behavioral analysis was based on the qualitative behavior assessment using a fixed list of descriptors. The breed was not different for all behavior evaluations and surface temperature (p>0.05). There was a difference between the housing types, where the collective pens showed goats more agitated, frustrated, and sociable (p<0.05). There was an influence of agitated, apathetic, frustrated, attentive, and curious behaviors on surface temperatures, in which feet and body temperatures decreased in these goats. (p<0.05). Moxoto, Anglo-Nubian, and Saanen goats showed similar behavior even when kept in collective or individual pens. Individual pens can restrict the goats' social relationships but reduce negative behaviors such as irritation and frustration. The lower foot temperatures of feedlot goats are related to the attention behavior in 86.75% of the observations.


Assuntos
Cabras , Termografia , Animais , Temperatura , Termografia/veterinária
14.
Inorg Chem ; 61(1): 346-356, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34898186

RESUMO

The reaction of [U(κ6-{(t-Bu2ArO)2Me2-cyclam})I][I] (H2{(t-Bu2ArO)2Me2-cyclam} = 1,8-bis(2-hydroxy-3,5-di-tert-butyl)-4,11-dimethyl-1,4,8,11-tetraazacyclotetradecane) with 2 equiv of NaNO2 in acetonitrile results in the isolation of the uranyl complex [UO2{(t-Bu2ArO)2Me2-cyclam}] (3) in 31% yield, which was fully characterized, including by single-crystal X-ray diffraction. Density functional theory (DFT) computations were performed to evaluate and compare the level of covalency within the U═E bonds in 3 and in the analogous trans-bis(imido) [U(κ4-{(t-Bu2ArO)2Me2-cyclam})(NPh)2] (1) and trans-oxido-imido [U(κ4-{(t-Bu2ArO)2Me2-cyclam})(O)(NPh)] (2) complexes. Natural bond orbital (NBO) analysis allowed us to determine the mixing covalency parameter λ, showing that in 2, where both U-Ooxido and U-Nimido bonds are present, the U-Nimido bond registers more covalency with regard to 1, and the opposite is seen for U-Ooxido with respect to 3. However, the covalency driven by orbital overlap in the U-Nimido bond is slightly higher in 1 than in 2. The 15N-labeled complexes [U(κ4-{(t-Bu2ArO)2Me2-cyclam})(15NPh)2] (1-15N) and [U(κ4-{(t-Bu2ArO)2Me2-cyclam})(O)(15NPh)] (2-15N) were prepared and analyzed by solution 15N NMR spectroscopy. The calculated and experimental 15N chemical shifts are in good agreement, displaying the same trend of δN (1-15N) > δN (2-15N) and reveal that the 15N chemical shift may serve as a probe for the covalency of the U═NR bond.

15.
Phys Chem Chem Phys ; 24(23): 14631-14639, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35670365

RESUMO

The gas-phase reactions of noble gas (Ng) cations, namely Kr+ and Xe+, with SF6 were investigated experimentally by Fourier transform ion cyclotron resonance mass spectrometry and computationally using RI-MP2 and BCCD(T) methods. The study revealed a new interaction between Kr+ and neutral SF6 that gave rise to a new cationic, weakly bound complex of Kr, [KrSF5]+, although the major reaction channel was dissociative electron transfer to yield SF5+ and {Kr, F}. Experimental studies examined the formation and stability of the new species and computational studies addressed the energetics of the reaction and indicated that [KrSF5]+ is stable by ca. 1 kcal mol-1. The same computational approach was used to examine the reaction of Xe+ with SF6 and showed it to be thermodynamically unfavourable by ca. 35 kcal mol-1, confirming the non-observation of reaction in the mass spectrometry experiments. An analysis of the bonding in [KrSF5]+ clearly showed that it is a non-covalently bound species, while in its presumed precursor [KrSF6]+ a partially covalent Kr-F bond is present.

16.
Int J Mol Sci ; 23(24)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36555823

RESUMO

The use of Cannabis for medicinal purposes has been documented since ancient times, where one of its principal cannabinoids extracted from Cannabis sativa, cannabidiol (CBD), has emerged over the last few years as a promising molecule with anti-seizure potential. Here, we present an overview of recent literature pointing out CBD's pharmacological profile (solubility, metabolism, drug-drug interactions, etc.,), CBD's interactions with multiple molecular targets as well as advances in preclinical research concerning its anti-seizure effect on both acute seizure models and chronic models of epilepsy. We also highlight the recent attention that has been given to other natural cannabinoids and to synthetic derivatives of CBD as possible compounds with therapeutic anti-seizure potential. All the scientific research reviewed here encourages to continue to investigate the probable therapeutic efficacy of CBD and its related compounds not only in epilepsy but also and specially in drug-resistant epilepsy, since there is a dire need for new and effective drugs to treat this disease.


Assuntos
Canabidiol , Canabinoides , Cannabis , Epilepsia , Humanos , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Canabidiol/metabolismo , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Canabinoides/farmacologia , Canabinoides/uso terapêutico , Cannabis/metabolismo
17.
Int J Mol Sci ; 23(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35563279

RESUMO

One of the main limitations of in vitro studies on lung diseases is the difficulty of maintaining the type II phenotype of alveolar epithelial cells in culture. This fact has previously been related to the translocation of the mechanosensing Yes-associated protein (YAP) to the nuclei and Rho signaling pathway. In this work, we aimed to culture and subculture primary alveolar type II cells on extracellular matrix lung-derived hydrogels to assess their suitability for phenotype maintenance. Cells cultured on lung hydrogels formed monolayers and maintained type II phenotype for a longer time as compared with those conventionally cultured. Interestingly, cells successfully grew when they were subsequently cultured on a dish. Moreover, cells cultured on a plate showed the active form of the YAP protein and the formation of stress fibers and focal adhesions. The results of chemically inhibiting the Rho pathway strongly suggest that this is one of the mechanisms by which the hydrogel promotes type II phenotype maintenance. These results regarding protein expression strongly suggest that the chemical and biophysical properties of the hydrogel have a considerable impact on the transition from ATII to ATI phenotypes. In conclusion, culturing primary alveolar epithelial cells on lung ECM-derived hydrogels may facilitate the prolonged culturing of these cells, and thus help in the research on lung diseases.


Assuntos
Células Epiteliais Alveolares , Pneumopatias , Células Epiteliais Alveolares/metabolismo , Células Cultivadas , Células Epiteliais , Matriz Extracelular , Humanos , Hidrogéis/metabolismo , Hidrogéis/farmacologia , Pulmão , Pneumopatias/metabolismo , Fenótipo
18.
Rev Esp Enferm Dig ; 1162022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36454089

RESUMO

A 49-year-old female presented with a 5-month course of diarrhoea, nocturn abdominal pain, asthenia, and weight loss of 30% of her body mass in three months. The patient had also a four-year medical history of bilateral mechanic gonalgy and arthralgias of the metacarpophalangeal and interphalangeal joints, despite treatment with prednisolone. On examination the patient had hyperpigmentation of the face and thorax, low-grade fever, and a BMI of 15,8 Kg/m2. Diarrhoea was documented with watery stools seven times per day despite loperamide, brownish, with no visible blood or mucous. Since the upper GI endoscopy and colonoscopy had no macroscopic abnormalities, the patient underwent a capsule endoscopy, which revealed continuous mucosal lesion with lymphangiectasia, oedema, villous atrophy and areas of denudation with hematinic punctate from the duodenum to the ileum. Diagnosis of Whipple's Disease was made with typical histology findings in duodenum material and a positive PCR for Tropheryma whipplei.

19.
Trop Anim Health Prod ; 54(1): 36, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34988774

RESUMO

This study aimed to examine the effects of selenium (Se) and vitamin E (vitE) supplementation on blood cell counts and blood metabolite concentrations in goats and their kids. Fifteen Saanen goats (average age 6 years of age; average initial body weight of 70 ± 10 kg) and 21 ½ Saanen × ½ Pardo Alpine crossbred goat kids (average body weight of 3.70 ± 0.64 kg) were used. Animals were distributed in a completely randomized design with five replicates per diet for mother goats and seven for goat kids and randomly assigned into three groups in the following diets: CON, control basal diet; Se, inclusion of 3.2 mg of Se/kg DM; SevitE, inclusion of 3.2 mg Se/kg DM and 1145 IU/day vitE/kg DM. Effects of time were observed on red blood cells, hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin in goats and goat kids. Effects of time were observed on differential counts of leucocytes, lymphocytes, and monocytes in goat kids. Interaction was observed for high-density lipoprotein and total protein in goats and for triglycerides, beta-hydroxybutyrate (BHBA), and gamma-glutamyltransferase (GGT) in goat kids. Effects of time were observed on low-density lipoprotein, triglycerides, glucose, lactate, BHBA, non-esterified fatty acids (NEFA), creatinine, aspartate-aminotransferase, and GGT in goats and all blood metabolites in goat kids. Selenium, vitE, or association in the evaluated levels are not sufficient to change blood cell counts when supplied in diets for goats or goat kids. However, the effect of time or interaction between time and diets change the blood metabolite concentrations in the animals.


Assuntos
Cabras , Selênio , Animais , Dieta/veterinária , Suplementos Nutricionais , Período Periparto , Selênio/farmacologia , Vitamina E
20.
Trop Anim Health Prod ; 54(2): 131, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260924

RESUMO

The current trial was carried out to evaluate the impacts of adding licury cake (Syagrus coronata) in high-concentrate diets for goat kids feedlot-finished on growth performance and metabolic parameters. Forty crossbred non-castrated Boer goat kids with approximately four months and similar initial live weights (20.15 ± 2.79 kg). The experimental design used in this study was a completely randomized, with four diets (0, 10, 20, and 30% of licury cake inclusion in a dry matter basis (DM)). Licury cake inclusion decreased nutrient intake and digestibility (P < 0.05). Times spent in feeding (P < 0.001) and rumination (P = 0.003) activities, number of events in feeding (P < 0.001) and idling (P = 0.015) increased, whereas a linear reduction occurred in feeding and rumination efficiencies of DM and neutral detergent fiber (P < 0.001). Nitrogen (N) intake, retained N (P < 0.001), triglycerides concentrations (P = 0.002), aspartate-aminotransferase, alanine-aminotransferase, and gamma-glutamyltransferase decreased with the licury cake inclusion (P < 0.05). Final body weight (P = 0.008), average daily gain (P = 0.001), and total weight gain (P = 0.001) decreased linearly when licury cake was included in diets. High-concentrate diets containing increasing levels of licury cake decrease intake and apparent digestibility of nutrients and performance when supplied for goat kids feedlot-finished. Therefore, the inclusion of the studied levels of licury cake in goat kids fed high-concentrate diets is not recommended for feedlot-finished systems.


Assuntos
Ração Animal , Cabras , Ração Animal/análise , Animais , Dieta/veterinária , Digestão , Ingestão de Alimentos , Comportamento Alimentar , Cabras/metabolismo , Nitrogênio/metabolismo
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