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1.
J Anim Physiol Anim Nutr (Berl) ; 107(3): 907-919, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36245294

RESUMO

Higher long-chain polyunsaturated fatty acids contents in roosters' sperm plasma membrane along with age-related decrease in antioxidant defense make the spermatozoa very susceptible to lipid peroxidation. Ginger root contains abundant amounts of gingerol, shogaols, gingerdiol and other active compounds, which known as antioxidant compounds to enhance semen quality. The goal of the study was to evaluate the effect of dietary supplementation of ginger root on semen quality, blood chemistry, immune response, testicular histology and reproductive performance of Ross-308 breeder roosters from 47 to 60 weeks of age. The feeding of ginger root resulted in an increase in parameters related to sperm forward motility and seminal total antioxidant capacity (TAC), and following there was a tendency to increase and decrease in seminal superoxide dismutase activity and malondialdehyde concentration, respectively; however, sperm concentration was not affected. There was an increase and tendency to increase in blood total protein and TAC in the supplemented group respectively. The roosters fed ginger supplemented diet had a higher spermiation index; and following there was tendency to increase seminal tubes spermatozoids number (p = 0.056) and repopulation index (p = 0.058). Despite the improved seminal antioxidant status and a tendency to lower embryonic mortality in the ginger-received group, the fertility and hatchability rate of roosters were statistically insignificant. Supplementations of ginger root in ageing rooster's diet had a beneficial effect on sperm motility, seminal antioxidant status and testicular spermiation index.


Assuntos
Galinhas , Suplementos Nutricionais , Extratos Vegetais , Zingiber officinale , Animais , Masculino , Antioxidantes/farmacologia , Galinhas/fisiologia , Extratos Vegetais/farmacologia , Plasma/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Reprodução/fisiologia , Análise do Sêmen/veterinária , Motilidade dos Espermatozoides/efeitos dos fármacos , Motilidade dos Espermatozoides/fisiologia , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos
2.
PLoS Pathog ; 16(8): e1008791, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32841299

RESUMO

During antiretroviral therapy (ART) that suppresses HIV replication to below the limit-of-quantification, virions produced during ART can be detected at low frequencies in the plasma, termed residual viremia (RV). We hypothesized that a reservoir of HIV-infected cells actively produce and release virions during ART that are potentially infectious, and that following ART-interruption, these virions can complete full-cycles of replication and contribute to rebound viremia. Therefore, we studied the dynamics of RV sequence variants in 3 participants who initiated ART after ~3 years of infection and were ART-suppressed for >6 years prior to self-initiated ART-interruptions. Longitudinal RV C2V5env sequences were compared to sequences from pre-ART plasma, supernatants of quantitative viral outgrowth assays (QVOA) of cells collected during ART, post-ART-interruption plasma, and ART-re-suppression plasma. Identical, "putatively clonal," RV sequences comprised 8-84% of sequences from each timepoint. The majority of RV sequences were genetically similar to those from plasma collected just prior to ART-initiation, but as the duration of ART-suppression increased, an increasing proportion of RV variants were similar to sequences from earlier in infection. Identical sequences were detected in RV over a median of 3 years (range: 0.3-8.2) of ART-suppression. RV sequences were identical to pre-ART plasma viruses (5%), infectious viruses induced in QVOA (4%) and rebound viruses (5%) (total n = 21/154 (14%) across the 3 participants). RV sequences identical to ART-interruption "rebound" sequences were detected 0.1-7.4 years prior to ART-interruption. RV variant prevalence and persistence were not associated with detection of the variant among rebound sequences. Shortly after ART-re-suppression, variants that had been replicating during ART-interruptions were detected as RV (n = 5). These studies show a dynamic, virion-producing HIV reservoir that contributes to rekindling infection upon ART-interruption. The persistence of identical RV variants over years suggests that a subpopulation of HIV-infected clones frequently or continuously produce virions that may resist immune clearance; this suggests that cure strategies should target this active as well as latent reservoirs.


Assuntos
Antirretrovirais/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Plasma/virologia , Viremia/epidemiologia , Replicação Viral , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Incidência , Plasma/efeitos dos fármacos , Plasma/imunologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Carga Viral , Viremia/virologia , Latência Viral , Suspensão de Tratamento
3.
Am J Physiol Lung Cell Mol Physiol ; 321(6): L1134-L1146, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34704852

RESUMO

Over 40 million people use e-cigarettes worldwide, but the impact of chronic e-cigarette use on health has not been adequately defined. In particular, effects of e-cigarette aerosol inhalation on inflammation and host defenses across the body are not fully understood. We conducted a longitudinal cohort pilot study to explore changes in the inflammatory state and monocyte function of e-cigarette users (n = 20) versus healthy controls (n = 13) and to evaluate effects of e-cigarette use reduction on the same. Saliva, sputum, and blood were obtained from e-cigarette users at baseline and after a 2-wk intervention of decreased e-cigarette use. Overall, across 38 proteins quantified by multiplex, airway samples from e-cigarette users tended to have decreased levels of immunomodulatory proteins relative to healthy controls, whereas levels of cytokines, chemokines, and growth factors in the circulation tended to be elevated. Specifically, e-cigarette users had lower levels of IL-1 receptor antagonist (IL-1Ra) in saliva (P < 0.0001), with higher IL-1Ra and growth-regulated oncogene (GRO) levels in sputum (P < 0.01 and P < 0.05, respectively), and higher levels of both TNFß (P < 0.0001) and VEGF (P < 0.0001) in plasma. Circulating monocytes from e-cigarette users had alterations in their inflammatory phenotype in response to reduced e-cigarette use, with blunted IL-8 and IL-6 release upon challenge with bacterial lipopolysaccharide (P < 0.001 and P < 0.05, respectively), suggesting a decreased ability to appropriately respond to bacterial infection. Based on these findings, chronic inhalation of e-cigarette aerosols alters the inflammatory state of the airways and systemic circulation, raising concern for the development of both inflammatory and infectious diseases in chronic users of e-cigarettes.


Assuntos
Citocinas/metabolismo , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Inflamação/diagnóstico , Sistema Respiratório/imunologia , Fumaça/efeitos adversos , Vaping/efeitos adversos , Adolescente , Adulto , Estudos de Casos e Controles , Citocinas/análise , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Estudos Longitudinais , Masculino , Projetos Piloto , Plasma/efeitos dos fármacos , Plasma/metabolismo , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , Saliva/efeitos dos fármacos , Saliva/metabolismo , Escarro/efeitos dos fármacos , Escarro/metabolismo , Adulto Jovem
4.
Semin Thromb Hemost ; 47(2): 150-160, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33636746

RESUMO

Measurement of direct oral anticoagulants (DOACs) activity is not routinely necessary. Indeed, evaluation of DOACs plasmatic concentration is discouraged for the majority of patients, due to the lack of outcome data supporting this approach. Nevertheless, DOAC measurements may be useful in emergency situations such as serious bleeding events, need for urgent invasive procedures, and acute ischemic stroke or in managing anticoagulation in "special populations" not adequately studied in clinical trials, for example the very elderly or those at the extremes of body weight. The aim of this review is to describe and summarize the methods for DOACs activity evaluation and the settings in which their plasma level measurement may be indicated, analyzing indications from scientific societies and evidence from clinical trials, as well as real world data on the usefulness of DOACs plasma levels "monitoring."


Assuntos
Anticoagulantes/uso terapêutico , Plasma/efeitos dos fármacos , Administração Oral , Anticoagulantes/farmacologia , Humanos , Fatores de Risco
5.
Circ Res ; 125(3): 328-340, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31159652

RESUMO

RATIONALE: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are proposed novel biomarkers of myocardial injury. Their release kinetics have not been explored without confounding by heparin nor has their relationship to myocardial protein biomarkers. OBJECTIVE: To compare ncRNA types in heparinase-treated samples with established and emerging protein biomarkers for myocardial injury. METHODS AND RESULTS: Screening of 158 circRNAs and 21 lncRNAs in human cardiac tissue identified 12 circRNAs and 11 lncRNAs as potential biomarkers with cardiac origin. Eleven miRNAs were included. At low spike-in concentrations of myocardial tissue, significantly higher regression coefficients were observed across ncRNA types compared with cardiac troponins and cMyBP-C (cardiac myosin-binding protein C). Heparinase treatment of serial plasma and serum samples of patients undergoing transcoronary ablation of septal hypertrophy removed spurious correlations between miRNAs in non-heparinase-treated samples. After transcoronary ablation of septal hypertrophy, muscle-enriched miRNAs (miR-1 and miR-133a) showed a steeper and earlier increase than cardiac-enriched miRNAs (miR-499 and miR-208b). Putative cardiac lncRNAs, including LIPCAR (long intergenic noncoding RNA predicting cardiac remodeling and survival), did not rise, refuting a predominant cardiac origin. Cardiac circRNAs remained largely undetectable. In a validation cohort of acute myocardial infarction, receiver operating characteristic curve analysis revealed noninferiority of cardiac-enriched miRNAs, but miRNAs failed to identify cases presenting with low troponin values. cMyBP-C was validated as a biomarker with highly sensitive properties, and the combination of muscle-enriched miRNAs with high-sensitive cardiac troponin T and cMyBP-C returned the highest area under the curve values. CONCLUSIONS: In a comparative assessment of ncRNAs and protein biomarkers for myocardial injury, cMyBP-C showed properties as the most sensitive cardiac biomarker while miRNAs emerged as promising candidates to integrate ncRNAs with protein biomarkers. Sensitivity of current miRNA detection is inferior to cardiac proteins but a multibiomarker combination of muscle-enriched miRNAs with cMyBP-C and cardiac troponins could open a new path of integrating complementary characteristics of different biomarker types.


Assuntos
Biomarcadores/sangue , Cardiomiopatias/sangue , Proteínas de Transporte/sangue , RNA não Traduzido/sangue , Troponina T/sangue , Artefatos , Heparina , Heparina Liase/farmacologia , Humanos , MicroRNAs/sangue , Miocárdio/química , Plasma/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real
6.
Med Mycol ; 59(9): 939-942, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34143187

RESUMO

Coccidioidal meningitis (CM) is a life-threatening infection with limited treatment options. Small series have reported success with isavuconazole; however, limited data exist on cerebrospinal fluid (CSF) penetration. Paired plasma and CSF isavuconazole concentrations were measured. Eleven CSF levels were tested, (7 ventricular, 4 lumbar) in three CM patients. Ventricular CSF levels were undetectable despite detectable plasma levels. All lumbar CSF levels were detectable (mean 1.00 µg/ml). Three pairs of lumbar CSF/plasma concentrations taken within 1 h of each other yielded a mean CSF/plasma ratio of 0.31. Isavuconazole was detectable in lumbar but not ventricular CSF in three patients treated for refractory CM. LAY SUMMARY: Isavuconazole is a triazole antifungal that has been used as salvage therapy in the treatment of coccidioidal meningitis (CM). Few data exist characterizing its concentration in the cerebrospinal fluid (CSF). We report tandem plasma and CSF concentrations of isavuconazole in three patients with CM.


Assuntos
Antifúngicos/uso terapêutico , Líquido Cefalorraquidiano/efeitos dos fármacos , Coccidioidomicose/tratamento farmacológico , Meningite Fúngica/tratamento farmacológico , Plasma/efeitos dos fármacos , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Adulto , Idoso , Antifúngicos/farmacocinética , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Nitrilas/sangue , Nitrilas/líquido cefalorraquidiano , Nitrilas/farmacocinética , Nitrilas/uso terapêutico , Piridinas/sangue , Piridinas/líquido cefalorraquidiano , Resultado do Tratamento , Triazóis/sangue , Triazóis/líquido cefalorraquidiano , Adulto Jovem
7.
Anesth Analg ; 132(1): 110-118, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32118620

RESUMO

BACKGROUND: Propofol can be measured in exhaled gas. Exhaled and plasma propofol concentrations correlate well, but the relationship with tissue concentrations remains unknown. We thus evaluated the relationship between exhaled, plasma, and various tissue propofol concentrations. Because the drug acts in the brain, we focused on the relationship between exhaled and brain tissue propofol concentrations. METHODS: Thirty-six male Sprague-Dawley rats were anesthetized with propofol, ketamine, and rocuronium for 6 hours. Animals were randomly assigned to propofol infusions at 20, 40, or 60 mg·kg·h (n = 12 per group). Exhaled propofol concentrations were measured at 15-minute intervals by multicapillary column-ion mobility spectrometry. Arterial blood samples, 110 µL each, were collected 15, 30, and 45 minutes, and 1, 2, 4, and 6 hours after the propofol infusion started. Propofol concentrations were measured in brain, lung, liver, kidney, muscle, and fat tissue after 6 hours. The last exhaled and plasma concentrations were used for linear regression analyses with tissue concentrations. RESULTS: The correlation of exhaled versus plasma concentrations (R = 0.71) was comparable to the correlation of exhaled versus brain tissue concentrations (R = 0.75) at the end of the study. In contrast, correlations between plasma and lung and between lung and exhaled propofol concentrations were poor. Less than a part-per-thousand of propofol was exhaled over 6 hours. CONCLUSIONS: Exhaled propofol concentrations correlate reasonably well with brain tissue and plasma concentrations in rats, and may thus be useful to estimate anesthetic drug effect. The equilibration between plasma propofol and exhaled gas is apparently independent of lung tissue concentration. Only a tiny fraction of administered propofol is eliminated via the lungs, and exhaled quantities thus have negligible influence on plasma concentrations.


Assuntos
Anestésicos Intravenosos/metabolismo , Encéfalo/metabolismo , Plasma/metabolismo , Propofol/metabolismo , Anestésicos Intravenosos/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Testes Respiratórios/métodos , Expiração/efeitos dos fármacos , Masculino , Plasma/efeitos dos fármacos , Propofol/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
8.
Transfus Med ; 31(2): 136-141, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33686720

RESUMO

OBJECTIVES: Assessment of the impact of pooling five single-donor plasma (SDP) units to obtain six pathogen-reduced therapeutic plasma (PTP) units on standardisation and the retention of labile coagulation factors. BACKGROUND: SDP shows a high inter-donor variability with potential implications for the clinical treatment outcome. Additionally, there is still an existing risk for window-period transmissions of blood borne pathogens including newly emerging pathogens. METHODS/MATERIALS: Five ABO-identical SDP units were pooled, treated with the INTERTCEPT™ Blood System (Cerus Corporation, U.S.A.) and split into six PTP units which were frozen and thawed after 30 days. The variability in volume, labile coagulation factor retention and activity was assessed. RESULTS: The variability of volumes between the PTP units was reduced by 46% compared to SDP units. The variability in coagulation factor content between the PTP units was reduced by 63% compared to SDP units. Moderate, but significant losses of coagulation factors (except for vWF) were observed in PTPs compared to SDPs. CONCLUSION: The pooling of five SDP units to obtain six PTP units significantly increases product standardisation with potential implications for safety, economics as well as transfusion-transmitted pathogen safety, making it an interesting alternative to quarantine SDP (qSDP) and pathogen-reduced SDP.


Assuntos
Preservação de Sangue/métodos , Preservação de Sangue/normas , Furocumarinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Plasma , Raios Ultravioleta , Biomarcadores/análise , Biomarcadores/sangue , Fatores de Coagulação Sanguínea/análise , Fatores de Coagulação Sanguínea/metabolismo , Segurança do Sangue/métodos , Segurança do Sangue/normas , Humanos , Plasma/efeitos dos fármacos , Plasma/metabolismo , Plasma/microbiologia , Reprodutibilidade dos Testes
9.
J Toxicol Environ Health A ; 84(9): 357-388, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33380269

RESUMO

This dermal study tested the potential toxicity of grade 3 (G3) and 4 (G4) organophosphate-containing aircraft engine oils in both new (G3-N, G4-N) and used states (G3-U, G4-U) to alter esterase activities in blood, brain and liver tissues, clinical chemistry parameters, and electrophysiology of hippocampal neurons. A 300 µl volume of undiluted oil was applied in Hill Top Chamber Systems®, then attached to fur-free test sites on backs of male and female Sprague Dawley rats for 6 hr/day, 5 days/week for 21 days. Recovery rats received similar treatments and kept for 14 days post-exposure to screen for reversibility, persistence, or delayed occurrence of toxicity. In brain, both versions of G3 and G4 significantly decreased (32-41%) female acetylcholinesterase (AChE) activity while in males only G3-N and G4-N reduced (33%) AChE activity. Oils did not markedly affect AChE in liver, regardless of gender. In whole blood, G3-U decreased female AChE (29%) which persisted during recovery (32%). G4-N significantly lowered (29%) butyrylcholinesterase (BChE) in male plasma, but this effect was resolved during recovery. For clinical chemistry indices, only globulin levels in female plasma significantly increased following G3-N or G4-N exposure. Preliminary electrophysiology data suggested that effects of both versions of G3 and G4 on hippocampal function may be gender dependent. Aircraft maintenance workers may be at risk if precautions are not taken to minimize long-term aircraft oil exposure.


Assuntos
Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Poluentes Ambientais/efeitos adversos , Enzimas/sangue , Óleos/efeitos adversos , Aeronaves , Animais , Sangue/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Feminino , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Plasma/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
10.
Pharmacology ; 106(3-4): 202-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32998136

RESUMO

BACKGROUND AND OBJECTIVES: With the increasing number of patients with febrile neutropenia (FN), voriconazole (VRC) has been widely used in hospitals for first-line treatment of FN. The study was designed for evaluating the influence of FMO3 mutation on the plasma disposition and adverse reactions of VRC in FN. MATERIALS AND METHODS: A single-center observational study was conducted in the inpatient ward for 4 years. The genotypes of FMO3 and cytochrome P450 (CYP) 2C19 were detected by PCR-restriction fragment length polymorphism. Patients with neutropenia were screened according to the CYP2C19 metabolic phenotype and other inclusion criteria. Five days after empirical administration of VRC, blood concentrations of VRC and nitrogen oxides in patients' blood were determined by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI MS/MS). Serum parameters and clinical adverse reaction symptoms in the medical records were collected and statistically analyzed. RESULTS: A total of 165 patients with neutropenia with the intermediate metabolic phenotype of CYP2C19 were screened. At the initial stage of oral VRC treatment, patients with the FMO3 E308G genotype had a poorer plasma disposal ability to VRC than those with the wide type of FMO3 (WT) genotype (p = 0.0005). Moreover, patients with the FMO3 E308G genotype were more likely to have adverse drug reactions and abnormal serum parameters after receiving VRC treatment. For example, the serum potassium level in the FMO3 E308G genotype group was significantly lower than that in the WT group (p = 0.028), the abnormal level of total bilirubin in the FMO3 E308G genotype group was significantly higher than that in the WT group (p = 0.049), and the aspartate aminotransferase level in the E308G group was significantly higher than that in the WT group (p = 0.05). The incidence of atopic dermatitis and visual impairment in the FMO3 E308G genotype group was 67 and 75%, respectively, and the incidences of peripheral neuroedema, headache, and diarrhea were 57, 50, and 60%, respectively, which were significantly different from those in the WT group. CONCLUSION: FMO3 E308G reduces the activity of the FMO3 enzyme by decreasing the metabolic ability of VRC, which increases the plasma concentration of VRC and may also lead to adverse reactions in patients with FN.


Assuntos
Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Neutropenia Febril/sangue , Neutropenia Febril/tratamento farmacológico , Oxigenases/genética , Voriconazol/efeitos adversos , Voriconazol/farmacocinética , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Citocromo P-450 CYP2C19/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases/metabolismo , Variantes Farmacogenômicos/fisiologia , Fenótipo , Plasma/efeitos dos fármacos , Polimorfismo Genético , Potássio/metabolismo , Estudos Retrospectivos , Soro/efeitos dos fármacos , Distribuição Tecidual , Voriconazol/administração & dosagem , Voriconazol/sangue
11.
Int J Mol Sci ; 22(24)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34948283

RESUMO

The snake genus Daboia (Viperidae: Viperinae; Oppel, 1811) contains five species: D. deserti, D. mauritanica, and D. palaestinae, found in Afro-Arabia, and the Russell's vipers D. russelii and D. siamensis, found in Asia. Russell's vipers are responsible for a major proportion of the medically important snakebites that occur in the regions they inhabit, and their venoms are notorious for their coagulopathic effects. While widely documented, the extent of venom variation within the Russell's vipers is poorly characterised, as is the venom activity of other species within the genus. In this study we investigated variation in the haemotoxic activity of Daboia using twelve venoms from all five species, including multiple variants of D. russelii, D. siamensis, and D. palaestinae. We tested the venoms on human plasma using thromboelastography, dose-response coagulometry analyses, and calibrated automated thrombography, and on human fibrinogen by thromboelastography and fibrinogen gels. We assessed activation of blood factors X and prothrombin by the venoms using fluorometry. Variation in venom activity was evident in all experiments. The Asian species D. russelii and D. siamensis and the African species D. mauritanica possessed procoagulant venom, while D. deserti and D. palaestinae were net-anticoagulant. Of the Russell's vipers, the venom of D. siamensis from Myanmar was most toxic and D. russelli of Sri Lanka the least. Activation of both factor X and prothrombin was evident by all venoms, though at differential levels. Fibrinogenolytic activity varied extensively throughout the genus and followed no phylogenetic trends. This venom variability underpins one of the many challenges facing treatment of Daboia snakebite envenoming. Comprehensive analyses of available antivenoms in neutralising these variable venom activities are therefore of utmost importance.


Assuntos
Hemolíticos/química , Venenos de Víboras/química , Venenos de Víboras/toxicidade , Animais , Antivenenos , Ásia , Fator X/análise , Hemolíticos/análise , Humanos , Plasma/efeitos dos fármacos , Protrombina/análise , Daboia , Mordeduras de Serpentes , Venenos de Víboras/análise , Viperidae
12.
Molecules ; 26(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530389

RESUMO

The Pulmonaria species (lungwort) are edible plants and traditional remedies for different disorders of the respiratory system. Our work covers a comparative study on biological actions in human blood plasma and cyclooxygenase-2 (COX-2) -inhibitory properties of plant extracts (i.e., phenolic-rich fractions) originated from aerial parts of P. obscura Dumort. and P. officinalis L. Phytochemical profiling demonstrated the abundance of phenolic acids and their derivatives (over 80% of the isolated fractions). Danshensu conjugates with caffeic acid, i.e., rosmarinic, lithospermic, salvianolic, monardic, shimobashiric and yunnaneic acids were identified as predominant components. The examined extracts (1-100 µg/mL) partly prevented harmful effects of the peroxynitrite-induced oxidative stress in blood plasma (decreased oxidative damage to blood plasma components and improved its non-enzymatic antioxidant capacity). The cellular safety of the extracts was confirmed in experimental models of blood platelets and peripheral blood mononuclear cells. COX-2 inhibitor screening evidently suggested a stronger activity of P. officinalis (IC50 of 13.28 and 7.24 µg/mL, in reaction with synthetic chromogen and physiological substrate (arachidonic acid), respectively). In silico studies on interactions of main components of the Pulmonaria extracts with the COX-2 demonstrated the abilities of ten compounds to bind with the enzyme, including rosmarinic acid, menisdaurin, globoidnan A and salvianolic acid H.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Ácido Peroxinitroso/efeitos adversos , Fenóis/farmacologia , Plasma/efeitos dos fármacos , Pulmonaria/química , Simulação por Computador , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/química , Humanos , Técnicas In Vitro , Lactatos/química , Lactatos/farmacologia , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Compostos Fitoquímicos , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plasma/química
13.
Transfusion ; 60(5): 1024-1031, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32129478

RESUMO

BACKGROUND: In 2014, passive immunization by transfusion of Ebola convalescent plasma (ECP) was considered for treating patients with acute Ebola virus disease (EVD). Early Ebola virus (EBOV) seroconversion confers a survival advantage in natural infection, hence transfusion of ECP plasma with high levels of neutralizing EBOV antibodies is a potential passive immune therapy. Techniques to reduce the risk of other transfusion-transmitted infections (TTIs) are warranted as recent ECP survivors are ineligible as routine blood donors. As part of an ongoing clinical trial to evaluate the safety and effectiveness of ECP, the impact of amotosalen/UVA pathogen reduction technology (PRT) on EBOV antibody characteristics was examined. STUDY DESIGN AND METHODS: Serum and plasma samples were collected from EVD-recovered subjects at multiple timepoints and evaluated by ELISA for antibodies to recombinant EBOV glycoprotein (GP) and irradiated whole EBOV antigen, as well as for EBOV microneutralization, classic plaque reduction neutralization test (PRNT) and EBOV pseudovirion neutralization assay (PsVNA) activity. RESULTS: Six subjects donated 40 individual ECP units. Substantial antibody titers and neutralizing activity results were demonstrated but were generally lower for the ACD plasma samples compared to the serum samples. Anti-EBOV titers by all assays remained essentially unchanged after PRT. CONCLUSION: Treatment of ECP with PRT to reduce the risk of TTI did not significantly reduce EBOV IgG antibody titers or neutralizing activity. Although ECP was used in the treatment of repatriated patients, no PRT units from this study were transfused to EVD patients. This inventory of PRT-treated ECP is currently available for future clinical evaluation.


Assuntos
Anticorpos Neutralizantes/análise , Doadores de Sangue , Ebolavirus/imunologia , Doença pelo Vírus Ebola/sangue , Imunidade Ativa , Plasma/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Anticorpos Antivirais/uso terapêutico , Chlorocebus aethiops , Convalescença , Ficusina/farmacologia , Doença pelo Vírus Ebola/imunologia , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Imunidade Ativa/fisiologia , Imunização Passiva/métodos , Testes de Neutralização , Plasma/efeitos dos fármacos , Soroconversão/fisiologia , Estados Unidos , Células Vero , Carga Viral/efeitos dos fármacos , Carga Viral/imunologia
14.
Mol Biol Rep ; 47(1): 521-531, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31721019

RESUMO

Diabetic complications are associated with the glycation and formation of advanced glycation end products (AGEs) which leads to structural modifications of biomolecules further affecting cells. Carbonyl compounds such as methylglyoxal and glyceraldehyde-3-phosphate are highly reactive and form an elevated amount of AGEs as compared to glucose and fructose. The investigation of glycation modifications by different compounds may be important to assess the specific pattern of biomolecular and cellular modifications and compare their glycation potential. The present work aims to comprehensively and comparatively examine the effect of glycating agents (glucose, fructose, ribose, methylglyoxal, and glyceraldehyde) on plasma, erythrocytes, platelets, and blood DNA. Glycation of plasma, cells, and DNA was initiated by incubating them with glycating agents for 24-48 h at 37 °C. Negative control samples (without glycating agents) were maintained simultaneously. After treatment, plasma and DNA samples were dialyzed and cell lysate was prepared. Markers of glycation (fructosamine), structural modifications (free amino, ß-amyloid, absorption spectra), antioxidant indices (catalase activity, glutathione) and erythrocyte hemolysis were estimated. In the presence of glycating agents, there was a significant increase in the formation of fructosamine, structural modification markers and depletion in antioxidant indices. Overall results suggest that among all glycating agents; methylglyoxal and glyceraldehyde have more potency of glycation induced structural modifications in plasma and vascular cells. This indicates the specific glycation modifications in plasma and vascular cells by various glycating agents may be investigated further for controlling diabetic pathological changes.


Assuntos
Plaquetas , Eritrócitos , Glicosilação/efeitos dos fármacos , Monossacarídeos/farmacologia , Antioxidantes/análise , Plaquetas/química , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , DNA/química , DNA/efeitos dos fármacos , Eritrócitos/química , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Frutosamina/análise , Hemólise/efeitos dos fármacos , Humanos , Plasma/química , Plasma/efeitos dos fármacos , Aldeído Pirúvico/farmacologia
15.
Anesth Analg ; 130(5): 1435-1444, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31397701

RESUMO

BACKGROUND: Vancomycin is used for antibiotic prophylaxis in pediatric surgical patients without a complete understanding of plasma and soft-tissue pharmacokinetics. Guidelines recommend incision within 60 minutes after administration; however, tissue vancomycin concentrations at that early time may not be therapeutic. We conducted a study of plasma and skin concentrations in pediatric neurosurgical and orthopedic patients to characterize intraoperative vancomycin pharmacokinetics. METHODS: Patients (0.1-18.8 years of age) undergoing posterior spinal fusion (n = 30) or ventriculoperitoneal shunt placement (n = 30) received intravenous vancomycin 15 mg/kg (maximum 1000 mg) over 1 hour. Skin was biopsied at incision and skin closure. Blood samples were collected at incision, at 2 and 4 hours intraoperatively, and at closure. Population pharmacokinetic analysis was performed to characterize pharmacokinetic parameter estimates and to develop a model of intraoperative plasma and skin vancomycin concentrations versus time. RESULTS: Pharmacokinetic analysis included data from 59 subjects, 130 plasma samples, and 107 skin samples. A 2-compartment model, volume of the central (Vc) and volume of the peripheral compartment (V2), proved to have the best fit. Stepwise covariate selection yielded a significant relationship for body surface area on elimination clearance and body weight on V2. Skin vancomycin concentrations rose continuously during surgery. Modeling predicted that equilibration of skin and plasma vancomycin concentrations took ≥5 hours. CONCLUSIONS: Skin vancomycin concentrations immediately after a preoperative dose are relatively low compared with concentrations at the end of surgery. It may be advisable to extend the time between dose and incision if higher skin concentrations are desired at the start of surgery.


Assuntos
Antibacterianos/administração & dosagem , Antibioticoprofilaxia/métodos , Cuidados Pré-Operatórios/métodos , Infecção da Ferida Cirúrgica/metabolismo , Distribuição Tecidual/fisiologia , Vancomicina/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Ortopédicos/efeitos adversos , Plasma/efeitos dos fármacos , Plasma/metabolismo , Infecção da Ferida Cirúrgica/prevenção & controle , Distribuição Tecidual/efeitos dos fármacos
16.
Gen Comp Endocrinol ; 299: 113614, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32950585

RESUMO

Arapaima gigas, one of the world's largest freshwater fish, is considered an emerging species for aquaculture development in Brazil given its high growth rate and meat quality. However, the lack of reproductive control in captivity has limited the expansion of Arapaima farming. This study aimed to test the effects of hormonal induction using mGnRHa implants and size pairing on broodstock reproduction through the analyses of sex steroids. To do so, broodstock of different sizes (large, small or mixed) were paired and implanted. Plasma and cephalic secretion profiles of testosterone (T), 11-ketotestosterone (11-KT) and 17ß-oestradiol (E2) were analysed. Compared to control (non-implanted), implanted broodstock showed a significant increase in plasma 11-KT (large and small males) and T (large and mixed females) post GnRHa implantation. In females, a significant increase in plasma T levels was shown, however, E2 remained unchanged after implantation. Despite the lack of clear spawning induction, this study showed the potency of GnRHa on sex steroid production regardless of pairing groups. Interestingly, significant correlations between blood plasma and cephalic secretion levels of 11-KT in males and T in females were observed, indicating the possible release of pheromones through the cephalic canals of A. gigas.


Assuntos
Hormônios Esteroides Gonadais/análise , Hormônio Liberador de Gonadotropina/farmacologia , Plasma/metabolismo , Reprodução , Animais , Aquicultura , Brasil , Feminino , Peixes , Masculino , Plasma/efeitos dos fármacos
17.
Int J Mol Sci ; 21(5)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32120851

RESUMO

Fish are rich in n-3 long-chain polyunsaturated fatty acids (LC-PUFA) such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Due to the increasing use of vegetable oils (VO), their proportion in diets has lowered, affecting lipid metabolism and fillet composition. Rainbow trout cultured preadipocytes were treated with representative FA found in fish oils (EPA and DHA) or VO (linoleic, LA and alpha-linolenic, ALA acids), while EPA and LA were also orally administered, to evaluate their effects on adipogenesis and lipid metabolism. In vitro, all FA increased lipid internalization, with ALA producing the highest effect, together with upregulating the FA transporter fatp1. In vivo, EPA or LA increased peroxisome proliferator-activated receptors ppara and pparb transcripts abundance in adipose tissue, suggesting elevated ß-oxidation, contrary to the results obtained in liver. Furthermore, the increased expression of FA synthase (fas) and the FA translocase/cluster of differentiation (cd36) in adipose tissue indicated an enhanced uptake of lipids and lipogenesis de novo, whereas stable or low hepatic expression of genes involved in lipid transport and turnover was found. Thus, fish showed a similar tissue metabolic response to the short-term availability of EPA or LA in vivo, while in vitro VO-derived FA demonstrated greater potential inducing fat accumulation.


Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Eicosapentaenoico/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Ácido alfa-Linolênico/administração & dosagem , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Antígenos CD36/genética , Antígenos CD36/metabolismo , Células Cultivadas , Dieta , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/metabolismo , Ácido Eicosapentaenoico/farmacologia , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Fígado/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Plasma/efeitos dos fármacos , Plasma/metabolismo , Ácido alfa-Linolênico/metabolismo , Ácido alfa-Linolênico/farmacologia
18.
Molecules ; 25(3)2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32041370

RESUMO

To explore Auricularia auricula-judae polysaccharides (AAP) as natural anticoagulants for application in the functional food industry, ultrasound assisted extraction (UAE) was optimized for the extraction of AAP by using a response surface methodology (RSM). The maximum extraction yield of crude AAP (14.74 mg/g) was obtained at the optimized extraction parameters as follows: Extraction temperature (74 °C), extraction time (27 min), the ratio of liquid to raw material (103 mL/g), and ultrasound power (198 W). Furthermore, the acidic AAP (aAAP) was precipitated with cetyltrimethylammonium bromide (CTAB) from crude AAP (cAAP). aAAP was further purified using ion exchange chromatography with a DEAE Purose 6 Fast Flow column to obtain aAAP-1. Additionally, according to the HPLC analysis, the aAAP-1 was mainly composed of mannose, glucuronic acid, glucose, galactose, and xylose, with a molar ratio of 80.63:9.88:2.25:1:31.13. Moreover, the results of the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) indicated aAAP-1 had anticoagulant activity, which was a synergic anticoagulant activity by the endogenous and exogenous pathway.


Assuntos
Agaricales/metabolismo , Anticoagulantes/química , Polissacarídeos Fúngicos/química , Plasma/efeitos dos fármacos , Agaricales/química , Anticoagulantes/isolamento & purificação , Anticoagulantes/farmacologia , Polissacarídeos Fúngicos/isolamento & purificação , Polissacarídeos Fúngicos/farmacologia , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Tempo de Trombina
19.
Molecules ; 25(19)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977628

RESUMO

Background: The Paulownia Clone in Vitro 112, known as oxytree or oxygen tree, is a hybrid clone of the species Paulownia elongata and Paulownia fortunei (Paulowniaceae). The oxytree is a fast-growing hybrid cultivar that can adapt to wide variations in edaphic and climate conditions. In this work, Paulownia Clone in Vitro 112 leaves were separated into an extract and four fractions (A-D) differing in chemical content in order to investigate their chemical content using LC-MS analysis. The extract and fractions were also evaluated for their anticoagulant and antioxidant properties in a human plasma in vitro. Results: The Paulownia leaf extract contained mainly phenolic compounds (e.g., verbascoside), small amounts of iridoids (e.g., aucubin or 7-hydroxytometoside) and triterpenoids (e.g., maslinic acid) were also detected. Our results indicate that the extract and fractions have different effects on oxidative stress in human plasma treated with H2O2/Fe in vitro, which could be attributed to differences in their chemical content. For example, the extract and all the fractions, at the two highest concentrations of 10 and 50 µg/mL, significantly inhibited the plasma lipid peroxidation induced by H2O2/Fe. Fractions C and D, at all tested concentrations (1-50 µg/mL) were also found to protect plasma proteins against H2O2/Fe-induced carbonylation. The positive effects of fraction C and D were dependent on the dose. Conclusions: The extract and all four fractions, but particularly fractions C and D, which are rich in phenolic compounds, are novel sources of antioxidants, with an inhibitory effect on oxidative stress in human plasma in vitro. Additionally, the antioxidant potential of fraction D may be associated with triterpenoids.


Assuntos
Antioxidantes/farmacologia , Hemostáticos/farmacologia , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Plasma/efeitos dos fármacos , Antioxidantes/química , Coagulação Sanguínea/efeitos dos fármacos , Hemostáticos/química , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Compostos Fitoquímicos/química , Plasma/metabolismo
20.
Biomacromolecules ; 20(9): 3453-3463, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31329428

RESUMO

Poly(2-alkyl-2-oxazoline)s (PAOx) represent a class of emerging polymers that can substitute or even outperform poly(ethylene oxide) (PEO) standard in various applications. Despite the great advances in PAOx research, there is still a gap in the direct experimental comparison of antifouling properties between PAOx and the golden standard PEO when exposed to blood. Motivated by this, we developed a straightforward protocol for the one-pot PAOx polymerization and surface coating by a "grafting to-" approach. First, we synthesized a library of hydrophilic poly(2-methyl-2-oxazoline)s (PMeOx) and poly(2-ethyl-2-oxazoline)s (PEtOx) with molar mass ranging from 1.5 to 10 kg/mol (DP = 16-115). The PAOx living chains were directly terminated by amine and hydroxyl groups of polydopamine (PDA) anchor layer providing the highest so far reported grafting densities ranging from 0.2 to 2.1 chains/nm2. In parallel, PEO chains providing the same degree of polymerization (molar mass from 1.2 to 5 kg/mol, DP = 28-116) bearing thiol groups were grafted to PDA. The thickness, surface-related parameters, covalent structure, and antifouling properties of the resulting polymer brushes were determined via various surface sensitive techniques. The comparison of the synthesized PAOx and PEO brushes led us to the conclusion that at the same surface-related parameters, PMeOx brushes show significantly better antifouling character when challenged against human blood plasma.


Assuntos
Oxazóis/química , Poliaminas/química , Polímeros/química , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Peso Molecular , Oxazóis/síntese química , Oxazóis/farmacologia , Plasma/efeitos dos fármacos , Poliaminas/síntese química , Poliaminas/farmacologia , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polimerização , Polímeros/síntese química , Polímeros/farmacologia , Propriedades de Superfície/efeitos dos fármacos
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