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1.
Br J Clin Pharmacol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38953404

RESUMO

AIMS: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, ß-adrenoceptor (ß-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant ß2-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD). METHODS: This study evaluated the safety and effects on cerebral activity of the oral, brain-penetrant, ß2-AR agonist clenbuterol (20-160 µg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25 HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1-5 mg), a ß-AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral ß2-AR responses. RESULTS: Significant, dose-dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of -1.7%, 7.3%, 22.9%, 28.4% 3 h after 20, 40, 80 and 160 µg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80 µg clenbuterol were observed both without and with 5 mg nadolol (in hippocampus, 18.6%/13.7% without/with nadolol). Clenbuterol was safe and well-tolerated in all subjects; known side effects of ß2-agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low-dose nadolol. CONCLUSIONS: The effects of clenbuterol on rCBF were evident both in the absence and presence of low-dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful ß2-AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.

2.
J Clin Rheumatol ; 30(5): 200-207, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38809130

RESUMO

BACKGROUND: Rheumatoid arthritis (RA) is a chronic disease that affects different areas of the patient's body. Patient education and health literacy is essential for them to participate actively in follow-up. OBJECTIVES: The aim of this study was to assess differences between clinimetric measurements done by a medical team and patient-reported outcome measures (PROMs) in RA and understand the impact of patient education strategies in order to identify differences between RA assessment methods. METHODS: This is a longitudinal cohort study. It included adult patients with RA and access to digital tools. These were divided into 3 groups by type of education. Group 1 included patients who participated in a multicomponent RA educational program. Group 2 did not have this multicomponent RA education. Group 3 did not receive any education. The 3 groups performed PROMs. Disease activity scales, functional class, and quality of life were measured. Univariate and bivariate analysis (χ 2 and Wilcoxon for paired data) were done. RESULTS: Twenty-eight patients were included in group 1, 26 in group 2, and 37 in group 3. All were women. In group 1, there were no significant differences in clinimetrics between the medical team and patient's PROMs except for fatigue. In group 2 and group 3, significant differences were found. The RAPID3 and PAS variables did not show significant differences when analyzed by intervention subgroups. CONCLUSIONS: This study shows no differences between clinimetrics/PROMs for patients with a high-level education on RA and physicians. On the other hand, when patient did not have any RA education, the clinimetric results differed from physician measurement.


Assuntos
Artrite Reumatoide , Educação de Pacientes como Assunto , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Artrite Reumatoide/terapia , Artrite Reumatoide/diagnóstico , Feminino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Estudos Longitudinais , Masculino , Adulto , Letramento em Saúde/métodos , Letramento em Saúde/estatística & dados numéricos , Idoso , Índice de Gravidade de Doença
3.
Handb Exp Pharmacol ; 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37495851

RESUMO

Adrenoceptors (ARs) throughout the brain are stimulated by noradrenaline originating mostly from neurons of the locus coeruleus, a brainstem nucleus that is ostensibly the earliest to show detectable pathology in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The α1-AR, α2-AR, and ß-AR subtypes expressed in target brain regions and on a range of cell populations define the physiological responses to noradrenaline, which includes activation of cognitive function in addition to modulation of neurometabolism, cerebral blood flow, and neuroinflammation. As these heterocellular functions are critical for maintaining brain homeostasis and neuronal health, combating the loss of noradrenergic tone from locus coeruleus degeneration may therefore be an effective treatment for both cognitive symptoms and disease modification in neurodegenerative indications. Two pharmacologic approaches are receiving attention in recent clinical studies: preserving noradrenaline levels (e.g., via reuptake inhibition) and direct activation of target adrenoceptors. Here, we review the expression and role of adrenoceptors in the brain, the preclinical studies which demonstrate that adrenergic stimulation can support cognitive function and cerebral health by reversing the effects of noradrenaline depletion, and the human data provided by pharmacoepidemiologic analyses and clinical trials which together identify adrenoceptors as promising targets for the treatment of neurodegenerative disease.

4.
Entropy (Basel) ; 25(7)2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37510045

RESUMO

The need to reduce the dependency of chemicals on fossil fuels has recently motivated the adoption of renewable energies in those sectors. In addition, due to a growing population, the treatment and disposition of residual biomass from agricultural processes, such as sugar cane and orange bagasse, or even from human waste, such as sewage sludge, will be a challenge for the next generation. These residual biomasses can be an attractive alternative for the production of environmentally friendly fuels and make the economy more circular and efficient. However, these raw materials have been hitherto widely used as fuel for boilers or disposed of in sanitary landfills, losing their capacity to generate other by-products in addition to contributing to the emissions of gases that promote global warming. For this reason, this work analyzes and optimizes the biomass-based routes of biochemical production (namely, hydrogen and ammonia) using the gasification of residual biomasses. Moreover, the capture of biogenic CO2 aims to reduce the environmental burden, leading to negative emissions in the overall energy system. In this context, the chemical plants were designed, modeled, and simulated using Aspen plus™ software. The energy integration and optimization were performed using the OSMOSE Lua Platform. The exergy destruction, exergy efficiency, and general balance of the CO2 emissions were evaluated. As a result, the irreversibility generated by the gasification unit has a relevant influence on the exergy efficiency of the entire plant. On the other hand, an overall negative emission balance of -5.95 kgCO2/kgH2 in the hydrogen production route and -1.615 kgCO2/kgNH3 in the ammonia production route can be achieved, thus removing from the atmosphere 0.901 tCO2/tbiomass and 1.096 tCO2/tbiomass, respectively.

5.
Int Orthop ; 46(4): 889-895, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35059771

RESUMO

STUDY DESIGN: Case series study. PURPOSE: To describe demographic metrics, and clinical and radiographical outcomes of surgical treatment in patients with ankylosed spine (ASP) such as diffuse idiopathic skeletal hyperostosis (DISH) or ankylosing spondylitis (AS) and non-ankylosed spines (NAS) suffering from hyperextension-distraction spine fractures. METHODS: Patients diagnosed with hyperextension-distraction fractures between 2012 and 2020 were identified. A retrospective analysis of clinical and surgical data was performed. Similarities between patients with ASP and NAS were evaluated by Fisher's exact test. RESULTS: Of the 22 patients, 13 had ASP (10 patients with DISH, 3 AS) and nine NAS. Most of these injuries involved the thoracolumbar spine (45.4%). All patients with NAS presented some sign of spondylosis: facet joint degeneration, intervertebral osteochondrosis, and anterolateral osteophytes. None of the patients with NAS and 30.7% with ASP suffered low-energy mechanisms (p = .11). All the patients with NAS and 61% of the patients with ASP had associated injuries (p = .04). On average, the instrumented levels were four (range, 2-6), achieving a fusion rate of 94.7% in all groups. Most of the ASP and NAS presented post-operative complications respectively (p = .65). CONCLUSION: Hyperextension-distraction spine fractures are not unique in ASP. In patients with spondylosis and high-energy accidents, we should suspect those fractures and rule out associated injuries, fractures in other vertebral segments, and acute spinal cord injury. The four-level instrumentation achieved an effective fusion rate in all patients.


Assuntos
Fraturas Ósseas , Hiperostose Esquelética Difusa Idiopática , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Espondilose , Fraturas Ósseas/complicações , Humanos , Hiperostose Esquelética Difusa Idiopática/complicações , Hiperostose Esquelética Difusa Idiopática/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/cirurgia , Espondilose/complicações
6.
Molecules ; 27(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35897845

RESUMO

The alarming levels of carbon dioxide (CO2) are an environmental problem that affects the economic growth of the world. CO2 emissions represent penalties and restrictions due to the high carbon footprint. Therefore, sustainable strategies are required to reduce the negative impact that occurs. Among the potential systems for CO2 capture are microalgae. These are defined as photosynthetic microorganisms that use CO2 and sunlight to obtain oxygen (O2) and generate value-added products such as biofuels, among others. Despite the advantages that microalgae may present, there are still technical-economic challenges that limit industrial-scale commercialization and the use of biomass in the production of added-value compounds. Therefore, this study reviews the current state of research on CO2 capture with microalgae, for which bibliometric analysis was used to establish the trends of the subject in terms of scientometric parameters. Technological advances in the use of microalgal biomass were also identified. Additionally, it was possible to establish the different cooperation networks between countries, which showed interactions in the search to reduce CO2 concentrations through microalgae.


Assuntos
Microalgas , Bibliometria , Biocombustíveis , Biomassa , Dióxido de Carbono
7.
Emerg Infect Dis ; 26(9): 2287-2290, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32818425

RESUMO

The major toxins of Clostridioides difficile (TcdA, TcdB, CDT) are chromosomally encoded in nearly all known strains. Following up on previous findings, we identified 5 examples of a family of putative conjugative plasmids with tcdB and cdtAB in clinical C. difficile isolates from multilocus sequence typing clades C-I, 2, and 4.


Assuntos
Toxinas Bacterianas , Clostridioides difficile , Proteínas de Bactérias/genética , Toxinas Bacterianas/genética , Clostridioides , Clostridioides difficile/genética , Enterotoxinas , Plasmídeos/genética
8.
Cephalalgia ; 39(1): 100-110, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29783863

RESUMO

OBJECTIVES: The aim of this study was to assess the effects of concomitant administration of erenumab and sumatriptan on resting blood pressure, pharmacokinetics, safety, and tolerability in healthy subjects. METHODS: In this phase 1, parallel-group, one-way crossover, double-blind, placebo-controlled study, healthy adult subjects were randomized (1:2) to receive either intravenous placebo and subcutaneous sumatriptan 12 mg (i.e. two 6-mg injections separated by 1 hour) or intravenous erenumab 140 mg and subcutaneous sumatriptan 12 mg. Blood pressure was measured pre-dose and at prespecified times post-dose. The primary endpoint was individual time-weighted averages of mean arterial pressure, measured from 0 hours to 2.5 hours after the first dose of sumatriptan. Pharmacokinetic parameters for sumatriptan were evaluated by calculating geometric mean ratios (erenumab and sumatriptan/placebo and sumatriptan). Adverse events and anti-erenumab antibodies were also evaluated. RESULTS: A total of 34 subjects were randomized and included in the analysis. Least squares mean (standard error) time-weighted averages of mean arterial pressure were 87.4 (1.0) mmHg for the placebo and sumatriptan group and 87.4 (1.2) mmHg for the erenumab and sumatriptan group. Mean difference in mean arterial pressure between groups was -0.04 mmHg (90% confidence interval: -2.2, 2.1). Geometric mean ratio estimates for maximum plasma concentration of sumatriptan was 0.95 (90% confidence interval: 0.82, 1.09), area under the plasma concentration-time curve (AUC) from time 0 to 6 hours was 0.98 (90% confidence interval: 0.93, 1.03), and AUC from time 0 to infinity was 1.00 (90% confidence interval: 0.96, 1.05). No clinically relevant safety findings for co-administration of sumatriptan and erenumab were identified. CONCLUSION: Co-administration of erenumab and sumatriptan had no additional effect on resting blood pressure or on pharmacokinetics of sumatriptan. Trial registration: ClinicalTrials.gov, NCT02741310.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/farmacologia , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Sumatriptana/farmacologia , Adulto , Estudos Cross-Over , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Voluntários Saudáveis , Humanos , Masculino , Transtornos de Enxaqueca/tratamento farmacológico
9.
Rev Med Chil ; 146(6): 708-716, 2018 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-30148902

RESUMO

BACKGROUND: Recently, five randomized controlled trials confirmed the efficacy and safety of endovascular treatment with or without intravenous thrombolysis in acute ischemic stroke with large-vessel occlusion. AIM: To report patients with ischemic stroke treated with endovascular methods. MATERIAL AND METHODS: Retrospective analysis of 104 patients aged 61 ± 15 years (54% males) with ischemic stroke who received endovascular treatment at a single medical center between 2009 and 2017. RESULTS: Sixty one percent were treated with intravenous thrombolysis plus endovascular procedures and 39% with endovascular procedures alone. The median door-to needle time was 61 minutes and door-to femoral puncture was 135 minutes. The median National Institute of Health Stroke Scale (NIHSS) scores on admission, 24 hours later and at discharge were 12,4 and 1 points, respectively. Middle cerebral artery was occluded in 60% of cases. Other frequent localizations where distal carotid artery in 17% and vertebro-basilar artery in 14%. Thrombolysis in cerebral infarction (TICI) scale flow score after the procedure was 3 or 2b in 58% of cases and significantly correlated with NIHSS scores at 24 hours and discharge. Fifty percent of patients had a mRankin score < = 1 and ten patients died (9.6%). Eight percent had a symptomatic intracerebral hemorrhage. CONCLUSIONS: The clinical improvement of these patients 24 hours after the procedure and at discharge demonstrate the effectiveness of endovascular treatment in ischemic stroke. The presence neurologists able to interpret multimodal images at the emergency room, the use of local guidelines, the availability of an experienced neuro-interventional team engaged with the workflow and the use of stent retrievers are strongly associated with good outcomes.


Assuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/terapia , Terapia Trombolítica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Isquemia Encefálica/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Acidente Vascular Cerebral/diagnóstico por imagem , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-28137804

RESUMO

The antimicrobial resistance (AMR) rates and levels recorded for Clostridium difficile are on the rise. This study reports the nature, levels, diversity, and genomic context of the antimicrobial resistance of human C. difficile isolates of the NAPCR1/RT012/ST54 genotype, which caused an outbreak in 2009 and is endemic in Costa Rican hospitals. To this end, we determined the susceptibilities of 38 NAPCR1 isolates to 10 antibiotics from seven classes using Etests or macrodilution tests and examined 31 NAPCR1 whole-genome sequences to identify single nucleotide polymorphisms (SNPs) and genes that could explain the resistance phenotypes observed. The NAPCR1 isolates were multidrug resistant (MDR) and commonly exhibited very high resistance levels. By sequencing their genomes, we showed that they possessed resistance-associated SNPs in gyrA and rpoB and carried eight to nine acquired antimicrobial resistance (AMR) genes. Most of these genes were located on known or novel mobile genetic elements shared by isolates recovered at different hospitals and at different time points. Metronidazole and vancomycin remain the first-line treatment options for these isolates. Overall, the NAPCR1 lineage showed an enhanced ability to acquire AMR genes through lateral gene transfer. On the basis of this finding, we recommend further vigilance and the adoption of improved control measures to limit the dissemination of this lineage and the emergence of more C. difficile MDR strains.


Assuntos
Clostridioides difficile/genética , Infecções por Clostridium/epidemiologia , Farmacorresistência Bacteriana Múltipla/genética , Doenças Endêmicas , Genoma Bacteriano , Sequências Repetitivas Dispersas , Mutação , Antibacterianos/farmacologia , Clostridioides difficile/classificação , Clostridioides difficile/efeitos dos fármacos , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Infecções por Clostridium/transmissão , Costa Rica/epidemiologia , DNA Girase/genética , DNA Girase/metabolismo , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Expressão Gênica , Transferência Genética Horizontal , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Hospitais , Humanos , Metronidazol/farmacologia , Filogenia , Polimorfismo de Nucleotídeo Único , Vancomicina/farmacologia
11.
Pharm Res ; 34(9): 1784-1795, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28593473

RESUMO

PURPOSE: Capsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy and migraine subjects. METHODS: Repeated capsaicin challenges and DBF measurements were performed and serum erenumab concentrations determined. A population analysis was conducted using a nonlinear mixed-effects modeling approach. Effects of body weight, gender, and age on model parameters were evaluated. RESULTS: Two-compartment target-mediated drug disposition (TMDD) model assuming binding of erenumab in the central compartment best described the nonlinear PK of erenumab. Subcutaneous absorption half-life was 1.6 days and bioavailability was 74%. Erenumab produced a maximum inhibition of 89% (95% confidence interval: 87-91%). Erenumab concentrations required for 50% and 99% of maximum inhibition were 255 ng/mL and 1134 ng/mL, respectively. Increased body weight was associated with increased erenumab clearance but had no effect on the inhibitory effect on CIDBF. CONCLUSIONS: Our results show that erenumab pharmacokinetics was best characterized by a TMDD model and resulted in potent inhibition of CIDBF.


Assuntos
Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/farmacologia , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Capsaicina/farmacologia , Transtornos de Enxaqueca/tratamento farmacológico , Fármacos do Sistema Sensorial/farmacologia , Pele/irrigação sanguínea , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Modelos Biológicos , Adulto Jovem
12.
Trop Anim Health Prod ; 47(6): 1049-54, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25876195

RESUMO

Production of beef cattle is one of the most important economic activities in Mexico. However, anthelmintic resistance (AR) has affected animal productivity. The aim of this study was to determine the presence of AR in gastrointestinal nematodes (GIN) of beef cattle in Candelaria Municipality of Campeche State, Mexico. Sixty-five-month-old beef calves were selected for the faecal egg count reduction test (FECRT) and the inhibition of egg hatch (IEH) assay. These parameters were determined using albendazole (benzimidazole, BZ), ivermectin (IVM, Macrocyclic lactone, ML) and levamisole (LEV, imidazothiazole, IMZ). Allele-specific PCR (AS-PCR) confirmed polymorphisms at codon 200 of isotype 1 of the ß-tubulin gene of Haemonchus placei. The results showed 32 % IVM toxicity by FECRT, indicating problems of AR in the GIN population. In contrast, BZ and LEV showed 95 and 100 % toxicity, respectively, against GIN from infected beef calves. The infective larvae (L3) of Cooperia, Haemonchus and Oesophagostomum were identified before anthelmintic treatment, and Cooperia L3 larvae were identified after treatment with IVM. The IEH assays had lethal dose 50 (LD50) of 187 nM to BZ, confirming the ovicidal effect of BZ. In contrast, the LD50 for LEV and IVM were 3.3 and 0.4 mM, respectively. The results obtained by AS-PCR confirmed two DNA fragments of 250 and 550 bp, corresponding to the resistant and susceptible alleles in the H. placei population. The nematode Cooperia showed AR against IVM, while the toxicity effect of BZ against GIN with both FECRT and IEH was confirmed.


Assuntos
Anti-Helmínticos/farmacologia , Doenças dos Bovinos/epidemiologia , Nematoides/efeitos dos fármacos , Infecções por Nematoides/veterinária , Carne Vermelha , Albendazol/farmacologia , Criação de Animais Domésticos , Animais , Benzimidazóis/farmacologia , Bovinos , Doenças dos Bovinos/parasitologia , Resistência a Medicamentos/efeitos dos fármacos , Fezes/parasitologia , Ivermectina/farmacologia , Levamisol/farmacologia , México/epidemiologia , Infecções por Nematoides/epidemiologia , Contagem de Ovos de Parasitas/veterinária
13.
Biology (Basel) ; 13(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38534468

RESUMO

Microalgae have commercial potential in different sectors of the industry. Specifically in modern agriculture, they can be used because they have the ability to supply nutrients to the soil and produce plant growth hormones, polysaccharides, antimicrobial compounds, and other metabolites that improve agricultural productivity. Therefore, products formulated from microalgae as biofertilizers and biostimulants turn out to be beneficial for agriculture and are positioned as a novel and environmentally friendly strategy. However, these bioproducts present challenges in preparation that affect their shelf life due to the rapid degradation of bioformulated products. Therefore, this work aimed to provide a comprehensive review of biofertilizers and biostimulants from microalgae, for which a bibliometric analysis was carried out to establish trends using scientometric indicators, technological advances were identified in terms of formulation methods, and the global market for these bioproducts was analyzed.

14.
J Clin Pharmacol ; 64(8): 1023-1029, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38651193

RESUMO

Gefapixant (MK-7264, RO4926219, AF-219) is a first-in-class P2X3 antagonists being developed to treat refractory or unexplained chronic cough. The initial single- and multiple-dose safety, tolerability, and pharmacokinetics of gefapixant at doses ranging from 7.5 to 1800 mg were assessed in four clinical trials. Following single-dose administration of 10-450 mg, the pharmacokinetic (PK) profile of gefapixant in plasma and urine demonstrated low inter-subject variability and a dose-proportional exposure. Following administration of multiple doses twice daily, the plasma exposures were dose-proportional at doses ranging from 7.5 to 50 mg and less than dose-proportional at doses ranging from 100 to 1800 mg. The time to mean peak drug concentration ranged from 2 to 3 h post-dose, and steady state was achieved by 7 days after dosing, with an accumulation ratio of approximately 2, comparing data from day 1 to steady state. The mean apparent terminal half-life ranged from 8.2 to 9.6 h. Gefapixant was primarily excreted unmodified in urine. Gefapixant was well tolerated following single-dose administration up to 1800 mg and multiple doses up to 1800 mg twice daily; there were no serious adverse events (AEs) reported. The most common AE reported was dysgeusia. The PK profile supports a twice-daily dosing regimen.


Assuntos
Antagonistas do Receptor Purinérgico P2X , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Adulto Jovem , Antagonistas do Receptor Purinérgico P2X/farmacocinética , Antagonistas do Receptor Purinérgico P2X/administração & dosagem , Antagonistas do Receptor Purinérgico P2X/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Voluntários Saudáveis , Adolescente , Esquema de Medicação , Meia-Vida , Sulfonamidas/farmacocinética , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Pirimidinas/farmacocinética , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Benzenossulfonamidas
15.
Open Access Rheumatol ; 16: 9-20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38249427

RESUMO

Purpose: To determine the value of lung ultrasound (LUS) compared to high-resolution computed tomography (HRCT) in the early diagnosis of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). Patients and Methods: An observational prospective study was performed. Were included patients with respiratory symptoms or/and, patients with crackles in auscultation during medical consultation. All patients underwent to chest X-rays, LUS, HRCT,and respiratory function tests. Results: A total of 192 patients with RA were included. Mean disease duration was 16.8 ± 11.1 years. 72% were positive for rheumatoid factor or anti-citrullinated antibodies. Of the total number of subjects, 54.7% had respiratory symptoms. The other patients did not have respiratory symptoms, but they did have had crackles on pulmonary auscultation. B lines > 11.5 on the ROC curve predicted ILD (AUC 0.63; CI 95%: 0.55-0.71; p < 0.003). A DLCO value of <7.13 significantly predicted the presence of ILD (AUC 0.61; 95% CI: 0.52-0.70; p < 0.028). Conclusion: The findings of this study suggest that LUS is a valuable tool for the early diagnosis of ILD in patients with RA, and together with DLCO, can adequately predict the presence of ILD in this population. LUS also helps to determine which patients with respiratory symptoms and signs suggestive for ILD are undergo to HRCT.

16.
Asian Spine J ; 17(1): 30-36, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35368175

RESUMO

STUDY DESIGN: Case-control study. PURPOSE: Analyze association between imaging factors related to the failure of conservative treatment in isolated subaxial cervical facet fractures. OVERVIEW OF LITERATURE: Facet fracture (F1, F2, and F3 AOSpine) may be stable or unstable depending on clinical and imaging variables, which are not well established. As a result, differences in fracture management lead to differences in surgical or conservative indications, and there is no evidence to predict conservative treatment failure. METHODS: Patients were categorized into two groups: six patients (16.2%) with conservative treatment failure (defined as the appearance of neurological symptoms, listhesis >3.5 mm, kyphotic deformation >11°, and/or non-union), and 31 patients (83.7%) with successful conservative management (defined as complete consolidation confirmed by computed tomography [CT] at the 6-month followup). All participants were fitted with rigid collars of the Miami type, and standardized follow-up was performed until consolidation or failure. CT and magnetic resonance imaging (MRI) was used to examine imaging characteristics. Sagittal balance parameters were assessed using CT, and signs of acute disc injury, prevertebral edema, facet synovitis, and interspinous hyperintense signal were assessed using MRI. RESULTS: Thirty-seven patients were diagnosed with unilateral cervical facet fractures between 2009 and 2020. In this sample, acute disc injury had a significative association to failure of conservative treatment in F2 and F3 AOSpine facet fractures, 100% of the failure group presented with traumatic disc injury compared to 9.7% of the successful group, for the other variables: prevertebral edema, 83.7% vs. 41.9%; facet synovitis, 100% vs. 77.4%; and interspinous hyperintensity, 71.4% vs. 38.7%, respectively. With conservative management, all F1 fractures healed successfully. Conservative treatment failed in 20% of F2 fractures and 50% of F3 fractures, respectively. In terms of cervical sagittal balance parameters, there were no significant differences between groups. CONCLUSIONS: Conservative management was successful in all F1 fractures. In F2 and F3 types, there was a significant association between acute disc injury and conservative treatment failure.

17.
Microorganisms ; 11(11)2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-38004744

RESUMO

Celery (Apium graveolens var. dulce) is affected by several plant diseases, such as Fusarium oxysporum f. sp. apii (Foa). Four Foa races have been found in the US. The goals of this study were to determine which races are present in Costa Rica and to quantify the tolerance of the imported commercial cultivars of celery produced in the country. Isolates from 125 symptomatic celery plants from three different geographical locations were analyzed, 65 of which were selected for phylogenetic analysis. All isolates presented a short sequence of five nucleotides that differentiates Foa race 3 in the IGS rDNA region. Three different haplotypes closely related to race 3 were found, which were highly virulent, produced great losses, and affected all cultivars (resistant to races 2 and 4) of imported commercial celery. Additionally, five different cultivars of celery were evaluated against seven pathogen isolates identified as race 3 in greenhouse conditions. Two of the cultivars showed significantly less chlorosis, wilting, mortality, and higher fresh weight. Most of the Foa isolates significantly increased chlorosis, wilting, and mortality compared to non-inoculated control. Celery producers in Costa Rica lack access to seeds resistant to the Foa race 3 present in the country.

18.
Artigo em Inglês | MEDLINE | ID: mdl-37837597

RESUMO

The increasing emissions of gaseous pollutants of anthropogenic origin, such as carbon dioxide (CO2), which causes global warming, have raised great interest in developing and improving processes that allow their mitigation. Among them, adsorption on porous materials has been proposed as a sustainable alternative. This work presents a study of CO2 equilibrium adsorption at low temperatures (0, 10, and 20 °C) over a wide range of low pressures, on activated carbon derived from Eucalyptus (ES) and Patula pine (PP) forest waste, and carbonaceous material derived from waste tires (WT). The precursors of these materials were previously prepared, and their physicochemical properties were characterized. ES and PP were thermochemically treated with phosphoric acid, and WT was oxidized with nitric acid. Additionally, these materials were used to obtain monoliths using uniaxial compaction techniques and different binding agents, with better results obtained with montmorillonite. A total of six adsorbent solids had their textural and chemical properties characterized and were tested for CO2 adsorption. The highest specific surface area (1405 m2 g-1), and micropore properties were found for activated carbon derived from Eucalyptus whose highest adsorption capacity ranged from 2.27 mmol g-1 (at 0 °C and 100 kPa) to 1.60 mmol g-1 (at 20 °C and 100 kPa). The activated carbon monoliths presented the lowest CO2 adsorption capacities; however, the studied materials showed high potential for CO2 capture and storage applications at high pressures. The isosteric heats of adsorption were also estimated for all the materials and ranged from 16 to 45 kJ mol-1 at very low coverage explained by the energetic heterogeneity and weak repulsive interactions among adsorbed CO2 molecules.

19.
J Transl Autoimmun ; 6: 100187, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654852

RESUMO

Objective: To assess the frequency of polyautoimmunity (PolyA) in a cohort of Colombian patients with systemic lupus erythematosus (SLE) and to identify associated factors. Methods: This is an analytical cross-sectional study in a specialized center., a comprehensive review of the medical records of SLE patients was performed from 2015 to 2020 in order to obtain demographic, clinical data, laboratory, and treatment information. Associations between PolyA, demographic, and characteristics of the disease were explored. Results: A total of 463 patients were included in the analysis. The average age was 47.3 ± 15 years. Most of this population were female (87.4%), whom were diagnosed with SLE in a long-term SLE (10.6 ± 10.1 years). Out of the total patients, 34.7% were diagnosed with PolyA. Among the most frequent clinical criteria for SLICC, arthritis (65%), kidney impairment (39.5%), and alopecia (34.8%) were found. The most frequent SLE-associated PolyA were antiphospholipid syndrome (APS) and Sjögren's syndrome (SS) (16.63% and 10.58%, respectively). PolyA-associated factors were age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis (DVT). In contrast, renal impairment was significantly less frequent in PolyA patients after multivariate analysis. Conclusion: The results have showed associated factors with PolyA like age, xerophthalmia, central nervous system occlusion, and deep vein thrombosis in this cohort. On the other hand, lupus nephritis was less frequent in patients with PolyA. This study provides a spotlight of a specific SLE population as real-life evidence for a better characterization of PolyA in the future.

20.
Toxicon ; 234: 107301, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37741576

RESUMO

Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia.

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