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1.
Pan Afr Med J ; 40: 43, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795824

RESUMO

INTRODUCTION: an adequate bowel preparation is essential for good mucosal inspection during colonoscopy. This study aims to compare the efficacy of two validated oral lavage solutions for colonoscopy preparation in African patients. METHODS: a prospective observational study of patients undergoing colonoscopy in a referral endoscopy facility in Port Harcourt, Nigeria, using sodium picosulfate magnesium citrate (SPMC) and 4L split-dose polyethylene glycol (PEG). Variables collated were sociodemographic, primary indication, comorbidities, Aronchick bowel preparation scale, polyp/adenoma detection, caecal intubation and outcome. Statistical analysis was performed using IBM SPSS version 20. RESULTS: one hundred and twenty-four patients received PEG prior to colonoscopy and SPMC in 175 patients. The age range was from 22 to 92 years; mean age of 53.8 ± 14.2 years for PEG group and 55.3 ± 13.2 years for SPMC group (p=0.361). There were 215 males and 84 females. An excellent/good bowel preparation scale was recorded in 77 (62%) PEG group and 130 (74.3%) for SPMC group (p=0.592). PEG was predominantly used in the early years of endoscopists practice with the odds ratio (OR) of no polyp detection in the PEG vs SPMC groups as 1.64 (confidence interval CI 1.06-2.55) versus 0.76 (CI 0.62-0.92), respectively (p=0.016). For no adenoma detection, OR was 4.18 (CI 1.12-15.60) versus OR 0.63 (CI 0.52-0.75), respectively (p=0.012). CONCLUSION: there is similar efficacy profile using either split volume PEG or SPMC prior to colonoscopy in these African patients. Polyp and adenoma detection rates are highly dependent on the expertise of the endoscopist.


Assuntos
Catárticos/administração & dosagem , Citratos/administração & dosagem , Colonoscopia/métodos , Compostos Organometálicos/administração & dosagem , Picolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adenoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Estudos Prospectivos , Adulto Jovem
2.
Nutrients ; 13(2)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33572973

RESUMO

Nowadays, obesity is one of the great nutritional problems facing public health. The prevalence of this pathology has increased in a worrying way over recent years, currently reaching epidemic proportions. In this context, nutritional supplements are presented as a therapeutic alternative to which more and more people are turning to. Nutritional supplements to lose weight based on the Garcinia plant, specifically on Garcinia cambogia, are commonly used. The active principle of this plant to which these properties have been attributed, is hydroxycitric acid (HCA). The aim of the present review is to gather reported data concerning the effectiveness of nutritional supplements based on Garcinia extracts on weight loss and their possible negative effects. Contradictory results have been observed regarding the effectiveness of the supplements. While statistically significant weight loss was observed in some studies, no changes were found in others. Regarding safety, although Garcinia supplements have been revealed as safe in the vast majority of the studies carried out in animal models and humans, some cases of hepatotoxicity, serotonin toxicity and mania have been reported. In conclusion, the results suggest that Garcinia-based supplements could be effective in short-term weight loss, although the data are not conclusive. In addition, the safety of the complement should be further studied.


Assuntos
Fármacos Antiobesidade/administração & dosagem , Suplementos Nutricionais , Garcinia cambogia , Obesidade/terapia , Extratos Vegetais/administração & dosagem , Animais , Fármacos Antiobesidade/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citratos/administração & dosagem , Citratos/efeitos adversos , Humanos , Mania/induzido quimicamente , Extratos Vegetais/efeitos adversos , Serotonina/metabolismo , Redução de Peso/efeitos dos fármacos
3.
Am J Perinatol ; 38(10): 1062-1069, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32069484

RESUMO

OBJECTIVE: The aim of this study is to assess the effects of administering 20 mg/kg loading dose of caffeine citrate intravenously on splanchnic oxygenation in preterm infants. STUDY DESIGN: The infants with a gestational age (GA) of <34 weeks who were administered with a 20 mg/kg intravenous loading dose of caffeine citrate within 48 hours after birth were investigated prospectively. Regional splanchnic oxygen saturation (rsSO2) and splanchnic fractional tissue oxygen extraction rate (sFTOE) were measured using near-infrared spectroscopy before caffeine infusion, immediately after caffeine infusion and 1, 2, 3, 4, and 6 hours (h) after dose completion; postdose values were compared with predose values. RESULTS: A total of 41 infants with a mean GA of 29.2 ± 1.6 weeks and birth weight of 1,315 ± 257 g as well as postnatal age of 32.2 ± 10.8 hours were included in the study. rsSO2 significantly reduced from 63.1 to 57.5% immediately after caffeine infusion, 55.1% after 1 hour, and 55.2% after 2 hours with partial recovery at 3-hour postdose. sFTOE increased correspondingly. CONCLUSION: Caffeine reduces splanchnic oxygenation and increases splanchnic oxygen extraction for at least 2 hours with partial recovery to predose levels at 3-hour postdose.


Assuntos
Cafeína/administração & dosagem , Citratos/administração & dosagem , Saturação de Oxigênio/efeitos dos fármacos , Circulação Esplâncnica/efeitos dos fármacos , Cafeína/farmacocinética , Citratos/farmacocinética , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho
4.
Am J Perinatol ; 38(S 01): e116-e122, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32198745

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effects of caffeine on cerebral oxygenation in preterm infants. STUDY DESIGN: This was a prospective study of infants with a gestational age (GA) of < 34 weeks who were treated intravenously with a loading dose of 20 mg/kg caffeine citrate within the first 48 hours of life. Regional cerebral oxygen saturation (rSO2C) and cerebral fractional tissue oxygen extraction (cFTOE) were measured using near-infrared spectroscopy before administering caffeine (baseline), immediately after administering caffeine, and 1, 2, 3, 4, 6, and 12 hours after dose completion; postdose values were compared with the baseline values. RESULTS: A total of 48 infants with a mean GA of 29.0 ± 1.9 weeks, birth weight of 1,286 ± 301 g, and postnatal age of 32.4 ± 11.3 hours were included in the study. rSO2C significantly decreased from 81.3 to 76.7% soon after administering caffeine, to 77.1% at 1 hour, and to 77.8% at 2 hours with recovery at 3 hours postdose. rSO2C was 80.2% at 12 hours postdose. cFTOE increased correspondingly. Although rSO2C values were lower and cFTOE values were higher compared with the baseline values at 3, 4, 6, and 12 hours after caffeine administration, this was not statistically significant. CONCLUSION: A loading dose of caffeine temporarily reduces cerebral oxygenation and increases cerebral tissue oxygen extraction in preterm infants. Most probably these changes reflect a physiological phenomenon without any clinical importance to the cerebral hemodynamics, as the reduction in cerebral oxygenation and increase in cerebral tissue oxygen extraction remain well within acceptable range.


Assuntos
Encéfalo/metabolismo , Cafeína/farmacologia , Citratos/farmacologia , Recém-Nascido Prematuro/metabolismo , Saturação de Oxigênio/efeitos dos fármacos , Oxigênio/sangue , Cafeína/administração & dosagem , Citratos/administração & dosagem , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Doenças do Prematuro/mortalidade , Infusões Intravenosas , Masculino , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho
5.
Blood Purif ; 50(1): 50-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32388506

RESUMO

INTRODUCTION: Patients with cancer admitted to critical care units are at increased risk of being affected with acute kidney injury (AKI) and mortality. Sustained low-efficiency dialysis (SLED) combines the cardiovascular stability of continuous therapy with the operational facility of conventional hemodialysis (HD). Citrate has become an alternative to heparin in anticoagulation because it favors the maintenance of filter patency and reduces bleeding. We analyzed the efficacy and safety of citrate versus heparin use in extended HD for patients with cancer and AKI. METHODS: This retrospective cohort study evaluated patients with cancer and dialytic AKI who received SLED with anticoagulation using citrate versus heparin from January 2014 to June 2017. After stratifying patients by the type of anticoagulation received, we evaluated demographic and clinical data, plus SLED session characteristics. We also analyzed dialysis outcomes, including insufficient session time, hypotension, poor catheter flow, line inversion, and dialysis system coagulation. RESULTS: We identified 423 SLED sessions among 124 patients (41 patients in the heparin group and 83 patients in the citrate group). More sessions with citrate (26.6 vs. 40.9%, p < 0.001) had serum platelet concentrations <50,000/mm3 or <100,000/m3 and ionic calcium (Ca++) values <1.16 mmol/L (33.2 vs. 18.5%, p < 0.001). Dialysis intercurrence occurred in 27% of sessions. The highest odds were associated with heparin sessions (OR 2.88). Compared with the citrate group, the heparin group was subject to more dialysis system coagulation (12.3%), the need for line reversal (9.8%), and insufficient session time (23.9%). CONCLUSION: Citrate represents a safe and effective anticoagulant for SLED for cancer patients with AKI undergoing treatment in the intensive care unit.


Assuntos
Injúria Renal Aguda/terapia , Citratos/administração & dosagem , Heparina/administração & dosagem , Unidades de Terapia Intensiva , Neoplasias/terapia , Diálise Renal , Injúria Renal Aguda/sangue , Idoso , Citratos/efeitos adversos , Feminino , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Estudos Retrospectivos
6.
Ther Apher Dial ; 25(2): 211-217, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32511862

RESUMO

Regional citrate anticoagulation (RCA) is a recommended method for extracorporeal circuit anticoagulation during renal replacement therapy (RRT). Increased risk of citrate accumulation by default of hepatic metabolism limits its use in liver failure patients. A Catot /Caion ratio ≥2.5 is established as an indirect control of plasma citrate poisoning. To investigate the safety of RCA in patients with liver impairment during sustained low-efficiency dialysis (SLED), we conducted a retrospective study of 41 patients with acute or chronic hepatocellular failure requiring RRT between January 2014 and June 2015 in the intensive care unit of the Groupe Hospitalier Sud Ile de France. Sixty-seven SLED sessions were performed. At admission, 32 (78%) patients had acute liver dysfunction and nine (22%) patients had cirrhosis with a median MELD score of 27 (IQR: 18.8, 42.0). Despite a majority of poor prognosis patients (SAPS-II (Simplified Acute Physiology Score II) score 71 [IQR: 58; 87]), with acute liver impairment as a part of multi-organ failure, no dosage of Catot /Caion ratio after SLED sessions exceeded the critical threshold of 2.5. Of the 63 complete sessions, neither dyscalcemia nor major dysnatremia, nor extracorporeal circuit thrombosis were noticed. Observed acid-base disturbances (16.4%) were not significantly correlated with the Catot /Caion ratio (P = .2155). In this retrospective study using RCA during intermittent RRT in ICU patients with severe liver dysfunction, we did not observe any citrate accumulation but monitoring of acid-base status and electrolytes remains necessary to ensure technique safety.


Assuntos
Anticoagulantes/administração & dosagem , Citratos/administração & dosagem , Terapia de Substituição Renal Híbrida/métodos , Hepatopatias/terapia , Idoso , Anticoagulantes/efeitos adversos , Citratos/efeitos adversos , Feminino , França , Humanos , Unidades de Terapia Intensiva , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
7.
Ther Apher Dial ; 25(2): 225-236, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32515160

RESUMO

Extracorporeal albumin dialysis (ECAD) represents a supplemental therapy for patients with liver failure. Most experience was gained with the molecular adsorbent recirculating system (MARS). However, the ADVanced Organ Support (ADVOS) system was recently introduced. This study aims to compare effects of MARS and ADVOS on biochemical and clinical parameters in critically ill patients with liver failure using a retrospective analysis of ECAD at Jena University Hospital. Laboratory parameters, health scoring values, and need for transfusion were recorded before and after treatment. Generalized estimating equations were used to account for repeated measurements of multiple ECAD cycles per patient. Between 2012 and 2017, n = 75 MARS and n = 58 ADVOS cycles were evaluated. Although ADVOS runs significantly longer, both devices provided comparable reduction rates of bilirubin (MARS: -48 [-80.5 to -18.5] µmol/L vs ADVOS: -35 [-87.8 to -2.0] µmol/L, P = .194), a surrogate for detoxification capacity, while urea and lactate levels were more significantly lowered by the ADVOS system. In cycles with similar treatment times, both systems provided comparable reduction rates for bilirubin, renal replacement, coagulation, and metabolic parameters. Citrate was the preferred anticoagulant in case of bleeding. Neither bleeding tendency nor fibrinogen levels or platelets were altered by the type of anticoagulation. No adverse events were reported, but two sessions (one MARS and one ADVOS) were terminated early due to filter clotting. Experience is needed in the application of ADVOS and more prospective trials comparing the detoxification capacity of ECAD devices are needed to support and enlarge the findings of the current evaluation.


Assuntos
Albuminas/metabolismo , Estado Terminal , Falência Hepática/terapia , Diálise Renal/métodos , Adulto , Idoso , Anticoagulantes/administração & dosagem , Citratos/administração & dosagem , Desenho de Equipamento , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/instrumentação , Estudos Retrospectivos , Adulto Jovem
8.
Semin Fetal Neonatal Med ; 25(6): 101178, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33168464

RESUMO

Caffeine is an effective treatment for apnea of prematurity and has several important benefits, including decreasing respiratory morbidity and motor impairment. In this article, we focus on the dose of caffeine. We review the evidence regarding the efficacy and safety of standard caffeine dosing and alternative dosing approaches, including the use of high dose caffeine and routine dose adjustments for age. Current evidence suggests high dose caffeine may provide additional benefit in reducing the risk of bronchopulmonary dysplasia and extubation failure, but may also increase the risk of cerebellar hemorrhage and seizures. Increasing the standard caffeine citrate dose every 1-2 weeks to a goal dose of 8 mg per kilogram every 24 h may help maintain therapeutic effect. We conclude by highlighting the need for additional trials before high dose caffeine is routinely used.


Assuntos
Apneia/tratamento farmacológico , Cafeína/administração & dosagem , Citratos/administração & dosagem , Doenças do Prematuro/tratamento farmacológico , Displasia Broncopulmonar/tratamento farmacológico , Hemorragia Cerebral/prevenção & controle , Relação Dose-Resposta a Droga , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/tratamento farmacológico , Recém-Nascido Prematuro
9.
Int J Mol Sci ; 21(18)2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32957694

RESUMO

Trigeminal nerve injury causes a distinct time window of glial activation in the trigeminal spinal subnucleus caudalis (Vc), which are involved in the initiation and maintenance phases of orofacial neuropathic pain. Microglia-derived factors enable the activation of astrocytes. The complement component C1q, which promotes the activation of astrocytes, is known to be synthesized in microglia. However, it is unclear whether microglia-astrocyte communication via C1q is involved in orofacial neuropathic pain. Here, we analyzed microglia-astrocyte communication in a rat model with infraorbital nerve injury (IONI). The orofacial mechanical hypersensitivity induced by IONI was significantly attenuated by preemptive treatment with minocycline. Immunohistochemical analyses revealed that minocycline inhibited the increase in c-Fos immune-reactive (IR) cells and the fluorescence intensity of both Iba1 and glial fibrillary acidic protein (GFAP) in the Vc following IONI. Intracisternal administration of C1q caused orofacial mechanical hypersensitivity and an increase in the number of c-Fos-IR cells and fluorescence intensity of GFAP. C1q-induced orofacial mechanical hypersensitivity was completely abrogated by intracisternal administration of fluorocitrate. The present findings suggest that the enhancement in the excitability of Vc nociceptive neurons is produced by astrocytic activation via the signaling of C1q released from activated microglia in the Vc following IONI, resulting in persistent orofacial neuropathic pain.


Assuntos
Astrócitos/metabolismo , Complemento C1q/administração & dosagem , Dor Facial/metabolismo , Microglia/metabolismo , Minociclina/administração & dosagem , Neuralgia/metabolismo , Traumatismos do Nervo Trigêmeo/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/metabolismo , Citratos/administração & dosagem , Complemento C1q/metabolismo , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/metabolismo , Masculino , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Minociclina/farmacologia , Nociceptores/metabolismo , Medição da Dor , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley
10.
J Clin Pharm Ther ; 45(6): 1414-1421, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32737938

RESUMO

WHAT IS KNOWN AND OBJECTIVES: Caffeine citrate is a commonly used methylxanthine for pharmacologic treatment of apnea of prematurity. The aim of this study was to develop and verify a population pharmacokinetic (PPK) model, which can provide a reference for individualized caffeine citrate treatment of apnea in Chinese premature infants. METHODS: A total of 88 serum concentration measurements from 46 preterm patients (median gestational age 29 weeks) were retrospectively collected and the relevant clinical data of patients were recorded. The PPK analysis was performed by non-linear mixed-effect modelling method using NONMEM. Allometric scaling was applied in the PPK analysis, and the final model was evaluated by graphic and statistical methods, including goodness-of-fit plots, normalized prediction distribution errors plots and bootstrap procedures. RESULTS: A one-compartment model with first-order elimination was successfully fitted to the data. The typical scaled values for the parameters clearance and volume of distribution (V) were 0.268 L/h and 109 L per 70 kg, respectively. The weight at the time of blood collection (CW) and post-natal age were identified as important predictors for pharmacokinetic parameters of caffeine. The evaluation process showed good stability and predictability of the final PPK model. WHAT IS NEW AND CONCLUSION: This is a complete PPK study of caffeine citrate in Chinese premature infants with apnea, which complements caffeine pharmacokinetic data of the premature from China. A final PPK model was developed which may serve as a beneficial tool for the use of caffeine citrate in the treatment of apnea in Chinese preterm infants.


Assuntos
Apneia/tratamento farmacológico , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/farmacocinética , Citratos/farmacocinética , Modelos Biológicos , Povo Asiático , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Citratos/administração & dosagem , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Masculino , Dinâmica não Linear , Estudos Retrospectivos
11.
Pediatr Pulmonol ; 55(10): 2635-2640, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32639634

RESUMO

BACKGROUND: Caffeine citrate is used to prevent apnea in premature infants and help in extubation of invasive ventilation, but the optimal dose remains undetermined. METHODS: Neonates born at less than 30 weeks gestation who had received invasive ventilation for at least 48 hours and a loading dose of 20 mg/kg caffeine citrate were randomly assigned into high (10 mg/kg daily) or low (5 mg/kg daily) maintenance dose groups. The drug was discontinued if no apnea occurred for 7 consecutive days. RESULTS: A total of 111 infants were assigned into the high (54) or low (57) dose groups. Extubation failure (16.7% vs 36.8%), age of extubation (8.2 ± 2.1 vs 10.7 ± 2.3 day), duration of invasive ventilation (7.2 ± 2.1 vs 8.5 ± 2.4 day), duration of ventilation before extubation (8.0 ± 1.8 vs 10.1 ± 1.9 day), and number of days of apnea (1.8 ± 1.3 vs 3.2 ± 1.1 day) were significantly lower in the high dose group than the low dose group. Difference in time until failure (6.7 ± 1.7d vs 7.0 ± 1.9d) and duration of nasal continuous positive airway pressure(7.8 ± 1.8 vs 8.0 ± 2.2 day) were not significant. Furthermore, no significant differences in the incidence of tachycardia (9.3% vs 12.3%), abdominal distension (16.7% vs 12.3%), feeding intolerance (3.7% vs 5.3%), or irritability (7.4% vs 5.3%) were observed between groups. CONCLUSIONS: A higher maintenance dose of caffeine citrate reduced the incidence of extubation failure and apnea of prematurity without increasing the occurrence of adverse reactions.


Assuntos
Extubação , Apneia/prevenção & controle , Cafeína/administração & dosagem , Citratos/administração & dosagem , Pressão Positiva Contínua nas Vias Aéreas , Recém-Nascido Prematuro , Método Duplo-Cego , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino
13.
Pharmacol Res Perspect ; 8(3): e00596, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32412185

RESUMO

Caffeine is widely used in preterm neonates suffering from apnea of prematurity (AOP), and it has become one of the most frequently prescribed medications in neonatal intensive care units. Goal of this study is to investigate how caffeine citrate treatment affects sleep-wake behavior in preterm neonates. The observational study consists of 64 preterm neonates during their first 5 days of life with gestational age (GA) <32 weeks or very low birthweight of < 1500 g. A total of 52 patients treated with caffeine citrate and 12 patients without caffeine citrate were included. Sleep-wake behavior was scored in three stages: active sleep, quiet sleep, and wakefulness. Individual caffeine concentration of every neonate was simulated with a pharmacokinetic model. In neonates with GA ≥ 28 weeks, wakefulness increased and active sleep decreased with increasing caffeine concentrations, whereas quiet sleep remained unchanged. In neonates with GA < 28 weeks, no clear caffeine effects on sleep-wake behavior could be demonstrated. Caffeine increases fraction of wakefulness, alertness, and most probably also arousability at cost of active but not quiet sleep in preterm neonates. As such, caffeine should therefore not affect time for physical and cerebral regeneration during sleep in preterm neonates.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Citratos/farmacologia , Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos , Cafeína/administração & dosagem , Cafeína/farmacocinética , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estimulantes do Sistema Nervoso Central/farmacocinética , Citratos/administração & dosagem , Citratos/farmacocinética , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Modelos Biológicos
14.
Int J Pharm ; 583: 119319, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32325244

RESUMO

Cancer is one of the leading causes of morbidity and mortality worldwide and nanotechnology has a significant potential to enhance the therapeutic and diagnostic performance of anti-cancer agents. Our work offers a simple and feasible strategy for thiocompound nanomedicines to be used in cancer therapy. Novel gold nanoparticles conjugated with thioabiraterone (AuNP-S-AB) were synthesized and significant new analytical methodologies were developed for their characterization by UV-Vis, TEM, IR, NMR and TGA. Our synthetic approach was based on the ligand exchange of citrates to thioabiraterone on gold nanoparticles. The average particle size of AuNP-S-AB was 14.5 nm with a spherical shape. The identity of thioabiraterone on the gold nanoparticles was proved by NMR and IR spectroscopy. The coverage of the gold nanoparticles with 40.9% (m/m) thioabiraterone was calculated from a TGA analysis. Molecular interactions between the thiol group of thioabiraterone and gold nanoparticles were evaluated through a combined experimental and theoretical study using the density functional theory (DFT). Additionally, an experiment conducted on hepatocytes or human prostate epithelial cells proved that newly synthesized thiol forms of abiraterone, as well as AuNP-S-AB, are more biocompatible than abiraterone. Our proposed idea of delivering abiraterone with our newly designed AuNP-S-AB may constitute a promising and novel prospect in cancer therapy.


Assuntos
Androstenos/química , Citratos/química , Ouro/química , Nanopartículas Metálicas/química , Compostos de Sulfidrila/química , Androstenos/administração & dosagem , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citratos/administração & dosagem , Células Epiteliais/efeitos dos fármacos , Ouro/administração & dosagem , Humanos , Ligantes , Fígado/citologia , Masculino , Nanopartículas Metálicas/administração & dosagem , Próstata/citologia , Neoplasias da Próstata/tratamento farmacológico , Compostos de Sulfidrila/administração & dosagem
15.
Radiat Environ Biophys ; 59(2): 257-263, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32240361

RESUMO

The aim of this work is to determine the effect of chronic immobilization stress on kinetics and dosimetry of 67Ga in a mouse model. A control group (CG) and a stress group (SG), each with 15 mice, were included in the study, and the latter group was subjected to a chronic immobilization stress model 2 h daily for 14 consecutive days. At day 13, 67Ga-citrate was administered intraperitoneally (11.24 ± 0.44 MBq) to each mouse. Then, sets of three mice were obtained sequentially at 24, 36, 48, 60 and 72 h, in which the radionuclide activity was measured with an activity counter. The 67Ga biokinetic data showed a fast blood clearance in the SG, with a mean residence time of 0.06 h. The calculated mean radiation absorbed doses were: liver (2.45 × 10-03 Gy), heart (3.17 × 10-04 Gy) and kidney (1.88 × 10-04 Gy) in the SG. The results show that stress reduced weight gain by approximately 13% and also increased adrenal gland weight by 26%. On the other hand, chronic stress accelerates 67Ga clearance after 24 h compared to normal conditions. It is concluded that murine organisms under chronic immobilization stress have higher gallium-67 clearance rates, decreasing the cumulated activity and absorbed dose in all organs.


Assuntos
Citratos/administração & dosagem , Radioisótopos de Gálio , Gálio/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Restrição Física , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Glândulas Suprarrenais/patologia , Animais , Citratos/farmacocinética , Modelos Animais de Doenças , Gálio/farmacocinética , Masculino , Camundongos , Doses de Radiação , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Aumento de Peso
16.
Sci Rep ; 10(1): 5604, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221332

RESUMO

Bowel cleansing is essential for a successful colonoscopy, but the ideal clearing agent and the volume have yet to be determined. A small-volume cleanser is important for patient compliance. This study aimed to compare the bowel cleansing efficacy, safety, tolerability, and acceptability of a 300-mL small-volume sodium picosulfate/magnesium citrate (PSMC) preparation-Bowklean with one 2-L polyethylene glycol (PEG)/bisacodyl-Klean-Prep/Dulcolax preparation under identical dietary recommendations. This multicenter, randomized, parallel-group, pre-specified noninferiority study enrolled 631 outpatients scheduled to undergo colonoscopy (Bowklean = 316 and Klean-Prep/Dulcolax = 315). After bowel preparation, an independent evaluator blinded to the subject's treatment allocation rated the quality of the colon cleansing. Efficacy was evaluated using the Aronchick Scale and Ottawa Bowel Preparation Scale (OPBS). Safety was assessed by monitoring adverse events. Tolerability and acceptability were measured via a patient questionnaire. Bowklean was non-interior to Klean-Prep/Dulcolax in overall colon cleansing but was associated with significantly better preparation quality. Notably, Bowklean was associated with significantly greater tolerability and acceptability of bowel preparations than Klean-Prep/Dulcolax. Safety profiles did not differ significantly between the groups. Our data indicate that Bowklean is a more effective and better-tolerated bowel cleansing preparation before colonoscopy than Klean-Prep/Dulcolax. Bowklean may therefore increase positive attitudes toward colonoscopies and participation rates.


Assuntos
Bisacodil/administração & dosagem , Citratos/administração & dosagem , Ácido Cítrico/administração & dosagem , Colo/metabolismo , Compostos Organometálicos/administração & dosagem , Picolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Adulto Jovem
17.
Eur J Pharmacol ; 875: 173039, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32119843

RESUMO

Neuropathic pain is a chronic pain characterized by injury to the central or peripheral nervous system and that most often causes disability in individuals. Among the mechanisms involved in central sensitization during neuropathic pain are cytokines and chemokines released by spinal glial cells; however, these mechanisms are not well elucidated. Thus, the present study aimed to investigate the involvement of Chemokine (C-X-C motif) ligand 1 (CXCL1) and glial cells in this process. Male Wistar rats weighing 220-240 g were used and underwent a neuropathic pain model induced by chronic constriction injury (CCI). To investigate the involvement of CXCL1, chemokine receptor type 2 (CXCR2), mitogen-activated protein kinases (MAPK) p38, and microglia and astrocytes, the following drugs were used: SB225002, an CXCR2 antagonist; SML0543, a MAPK p38 inhibitor; minocycline, a microglia inhibitor; fluorocitrate, an astrocytes inhibitor; and recombinant CXCL1. The microglia, astrocytes, CXCL1, and MAPK p38 protein levels was evaluated by a Western blot assay. Furthermore, an immunofluorescence assay was performed to localize microglia and astrocytes immunoreactivity in the spinal cord. The results demonstrated that both CCI and CXCL1 induced nociception, and this effect was reversed by SB225002. In addition, minocycline, fluorocitrate, and SML0543 reversed the mechanical allodynia induced by CCI. Furthermore, there was an increase of spinal CXCL1 and microglial marker Iba1 protein levels , which was reversed by SB225002. This antagonist also reduced the Iba1 immunoreactivity in spinal cord. Thus, the present study suggests that the CXCL1 chemokine participates in neuropathic pain through CXCR2 activation in spinal microglia.


Assuntos
Quimiocina CXCL1/metabolismo , Microglia/metabolismo , Neuralgia/patologia , Nociceptividade/fisiologia , Medula Espinal/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Quimiocina CXCL1/administração & dosagem , Citratos/administração & dosagem , Modelos Animais de Doenças , Humanos , Injeções Espinhais , Masculino , Microglia/efeitos dos fármacos , Minociclina/administração & dosagem , Neuralgia/induzido quimicamente , Nociceptividade/efeitos dos fármacos , Compostos de Fenilureia/administração & dosagem , Ratos , Receptores de Interleucina-8B/antagonistas & inibidores , Receptores de Interleucina-8B/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Eur J Hosp Pharm ; 27(2): 90-94, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32153771

RESUMO

Objectives: To investigate the effect of pH and buffers on the degradation rate of flucloxacillin and to determine if flucloxacillin can be stabilised using a buffered diluent for up to 14 days when stored at 2°C-8°C including a 24-hour infusion period at 32°C in two elastomeric devices (Accufuser and INfusor LV) filled to 240 mL. Testing as per the NHS Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. Methods: A validated stability indicating high-performance liquid chromatography method was used for assessing the stability of flucloxacillin diluted in 0.3% w/v citrate-buffered saline pH 7.0 when stored at 2°C-8°C in two ambulatory devices (Accufuser and INfusor LV). Flucloxacillin at 10 and 50 mg/mL diluted in 0.3% w/v citrate-buffered saline pH 7.0 to a final volume of 240 mL and stored at 2°C-8°C, including 24 hours at 32°C, was tested from two batches in replicate (n=3) at five time points for up to 14 days according to the requirements of the YCD. Results: Greater than 95% of the zero-time concentration of flucloxacillin at 10 and 50 mg/mL remained when stored at 2°C-8°C after 14 days including 24 hours at 32°C in both Accufuser and INfusor LV devices. Conclusions: Flucloxacillin sodium stability was improved, and complied with UK national standards, by using a diluent of 0.3% w/v citrate-buffered saline pH 7 in both Accufuser and INfusor LV ambulatory devices when filled to 240 mL. The data support assigning a shelf-life of up to 14 days (13 days stored at 2°C-8°C and 24 hours at 32°C). Flucloxacillin may now be used appropriately as a continuous 24-hour infusion in outpatient parenteral antimicrobial therapy services, providing further opportunity to avoid or shorten patient hospital stays, as well as support ideal antimicrobial stewardship principles.


Assuntos
Antibacterianos/normas , Citratos/normas , Elastômeros/normas , Floxacilina/normas , Medicina Estatal/normas , Antibacterianos/administração & dosagem , Soluções Tampão , Citratos/administração & dosagem , Embalagem de Medicamentos/métodos , Embalagem de Medicamentos/normas , Estabilidade de Medicamentos , Armazenamento de Medicamentos/métodos , Armazenamento de Medicamentos/normas , Elasticidade , Floxacilina/administração & dosagem , Humanos , Infusões Intravenosas , Soluções Farmacêuticas/administração & dosagem , Soluções Farmacêuticas/normas , Reino Unido/epidemiologia
19.
Korean J Gastroenterol ; 75(2): 65-73, 2020 02 25.
Artigo em Coreano | MEDLINE | ID: mdl-32098459

RESUMO

Optimal bowel preparation is essential for a more accurate, comfortable, and safe colonoscopy. The majority of postcolonoscopy colorectal cancers can be explained by procedural factors, mainly missed polyps or inadequate examination. Therefore the most important goal of optimal bowel preparation is to reduce the incidence of colorectal cancer. Although adequate preparation should be achieved in 85-90% or more of all colonoscopy as a quality indicator, unfortunately 20-30% shows inadequate preparation. Laxatives for oral colonoscopy bowel preparation can be classified into polyethylene glycol (PEG)-electrolyte lavage solution, osmotic laxatives, stimulant laxatives, and divided into high-volume solution (≥3 L) and low-volume solution (<3 L). The updated 2019 European Society of Gastrointestinal Endoscopy (ESGE) guideline is broadly similar to the 2014 American Society for Gastrointestinal Endoscopy (ASGE) recommendations and reaffirms the importance of split-dosing. However, new ESGE guideline, unlike the 2014 ASGE recommendation, suggests the use of high volume or low volume PEG-based regimens as well as that of non-PEG based agents that have been clinically validated for most outpatient scenarios. For effective, safe, and highly adherent bowel preparation, physicians who prescribe and implement colonoscopy should properly know the advantages and limitations, the dosing, and the timing of regimens. Recently many studies have attempted to find the most ideal regimens, and more convenient, effective, and safe regimens have been developed by reducing the dosing volume and improving the taste. The high tolerability and acceptability of the new low-volume regimens suggest us how we should use it to increase the participation of the national colorectal cancer screening program.


Assuntos
Colonoscopia , Laxantes/administração & dosagem , Citratos/administração & dosagem , Citratos/efeitos adversos , Neoplasias Colorretais/diagnóstico , Relação Dose-Resposta a Droga , Humanos , Laxantes/efeitos adversos , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Picolinas/administração & dosagem , Picolinas/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Sulfatos/administração & dosagem , Sulfatos/efeitos adversos , Vômito/etiologia
20.
Ann Nucl Med ; 34(4): 263-271, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32076955

RESUMO

AIM: The main goal in Crohn´s disease (CD) is a sustained suppression of inflammatory activity associated with mucosa healing in endoscopic evaluation. During clinical routine, there are small numbers of good markers to monitor inflammatory activity under treatment. We postulated that Oral 67Gallium Citrate Scintigraphy is able to mark inflammatory disease in mucosa and deep inflammation in CD, when used in oral form. OBJECTIVE: Measure the accuracy of Oral 67Gallium Citrate Scintigraphy in intestinal inflammatory activity of Crohn´s disease. PATIENTS AND METHODS: In a prospective consecutive cross-sectional study from January 2018 to June 2019, the ileocolonic region of 32 patients with CD were studied by dividing into four regions of interest (ROI) from the ileum to the rectum. A total of 128 intestinal segments were analyzed in cluster data. Accuracy values of Oral 67Gallium Scintigraphy and colonoscopy tests were evaluated with the histological reference test. Values of the respective receiver operating characteristic (ROC) curves were obtained  and compared. The reliability between the tests was evaluated by Kappa statistical with the segment-level analyses using variance adjustments. All statistical analyses were performed with a test significance level of 0.05. RESULTS: The study population included 32 patients with CD (10 men, 22 women; average age 39 years). Disease time was five years on average. Anti-TNFs treatment was found in 71%. The most found phenotype of the Montreal classification was L3. Differences in ROC curves for colonoscopy (0.94) and Oral 67Ga Scintigraphy (0.96) did not show significant value (p = 0.32). The sensitivity of scintigraphy to detect intestinal inflammatory activity in CD was 64%, specificity of 96% and accuracy of 84%. A high agreement was found between oral scintigraphy and histological measurements with kappa = 0.64. CONCLUSIONS: Oral 67Ga Scintigraphy had similar accuracy and agreement compared to colonoscopy in the identification of inflammatory activity in Crohn´s Disease. This new approach may be useful and less invasive for long term follow-ups.


Assuntos
Citratos/administração & dosagem , Doença de Crohn/complicações , Radioisótopos de Gálio/administração & dosagem , Gálio/administração & dosagem , Inflamação/diagnóstico por imagem , Cintilografia/métodos , Administração Oral , Adulto , Antineoplásicos/farmacologia , Citratos/química , Estudos Transversais , Feminino , Gálio/química , Radioisótopos de Gálio/química , Humanos , Íleo/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Reto/metabolismo , Reprodutibilidade dos Testes , Medição de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
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