RESUMEN

To study the effect of parecoxib sodium in alleviating inflammation in burned rats and restoring cognitive function in burned rats. 30 SPF grade SD rats were randomly divided into 6 groups: (1) Blank control group (Group C). (2) Sham surgery group (Group Sham). (3) Second-degree burn model (Group B). (4) Low-dose (1 mg/kg/d) parecoxib sodium (Group L+B). (5) Medium-dose (10 mg/kg/d) parecoxib sodium (Group M+B). (6) High-dose (20 mg/kg/d) parecoxib sodium (Group H+B). ELISA measures inflammatory factor IL-2, IL-6, TNF-α and IFN-γ, cognitive function factor NSE, cortisol and S-100ß. Combined with water maze and dark avoidance experiments to further verify the recovery of cognitive function in rats. The contents of IL-2, TNF-α and IL-6 in Group M+B were significantly lower than those in Group Sham (P<0.05), and the content of IFN-γ was significantly lower than that in Group Sham (P<0.05). The cognitive markers NSE, S-100ß and cortisol levels in Group M+B were significantly higher than those in Group Sham at 2h, 1d, 5d and 10d after operation (P<0.05). In the Group M+B dark-avoidance experiment, the number of probes and errors were not significantly different than those in Group Sham and Group C (P>0.05), and the number of times Group M+B found a platform in the water maze experiment and crossed the platform was second only to Group B and Group C. Parecoxib sodium can effectively reduce inflammation in burn rats and promote cognitive recovery in burn rats, and the optimal dose of parecoxib sodium for burn rats is 10 mg/kg.

RESUMEN

This study aimed to assess the effectiveness and optimal dosage of aspirin in preventing preeclampsia in high-risk pregnant women. Traditional and network meta-analyses were conducted on data from 23 randomized controlled trials involving 10 547 pregnant women. The findings demonstrated that aspirin significantly reduced the incidence of preeclampsia (OR = 0.66, 95%CI [0.58, 0.75]), with the best preventive effect observed at a dosage of 80-100 mg/day (OR = 0.51, 95%CI [0.36, 0.72]). No significant differences were found in the occurrence of postpartum hemorrhage (OR = 1.03, 95%CI [0.79, 1.33]), small for gestational age (OR = 0.83, 95%CI [0.50, 1.35]), placental abruption (OR = 0.96, 95%CI [0.53, 1.73]), and intrauterine growth restriction (OR = 0.63, 95%CI [0.45, 1.86]) between women taking aspirin and those taking placebos. Different doses of aspirin showed a reduction in preeclampsia incidence, but there was no significant difference in efficacy between the dosage groups. Side effects did not significantly differ between placebo and different aspirin dosage groups. SUCRA analysis suggested that 80-100 mg/day may be the optimal dosage, prioritizing both effectiveness and minimizing side effects. Sensitivity analysis confirmed the robustness of the findings. However, improvements are needed in addressing issues like loss to follow-up, reporting bias, and publication bias. In conclusion, a dosage of 80-100 mg/day is recommended for preventing preeclampsia in high-risk pregnant women, although individual circumstances should be considered for optimizing the balance between effectiveness and safety.

Asunto(s)

Aspirina , Metaanálisis en Red , Preeclampsia , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Embarazo , Femenino , Preeclampsia/prevención & control , Preeclampsia/epidemiología , Relación Dosis-Respuesta a Droga , Adulto , Embarazo de Alto Riesgo , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Incidencia

RESUMEN

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug.

RESUMEN

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Asunto(s)

Ácido Fólico , Genotipo , Homocisteína , Metilenotetrahidrofolato Reductasa (NADPH2) , Humanos , Ácido Fólico/administración & dosificación , Ácido Fólico/sangre , Homocisteína/sangre , Femenino , Masculino , Método Doble Ciego , Persona de Mediana Edad , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Hipertensión/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Anciano , Enalapril/administración & dosificación , Enalapril/farmacología , Adulto , Hiperhomocisteinemia/tratamiento farmacológico , Hiperhomocisteinemia/sangre

RESUMEN

The anaerobic co-fermentation of iron bound phosphorus (P) compounds (FePs)-bearing sludge with corn gluten meal (CGM) and the underlying mechanisms associated with P release and volatile fatty acids (VFAs) production were investigated. The optimal CGM dosage for P release was 0.6 g chemical oxygen demand (COD)/g total suspended solid (TSS), which resulted in an increase in efficiency from 7 % (control sample) to 39 %. However, the optimal CGM dosage for VFAs production was 0.4 g COD/g TSS, and the yield increased from 37.4 (control sample) to 331.7 mg COD/g volatile suspended solid. The addition of CGM enhanced hydrolysis and acidogenesis by supplying abundant organic substrates to promote the growth of hydrolytic and acidogenic bacteria. A higher VFAs/ammonium-nitrogen ratio resulted in a lower pH, which promoted greater FePs dissolution and P release from the sludge. This study provides novel insights into the effects of CGM on P release and VFAs production.

Asunto(s)

Aguas del Alcantarillado , Zea mays , Fermentación , Aguas del Alcantarillado/microbiología , Anaerobiosis , Glútenes , Fósforo , Concentración de Iones de Hidrógeno , Ácidos Grasos Volátiles

RESUMEN

BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).

Asunto(s)

Retraso en el Despertar Posanestésico , Neostigmina , Bloqueo Neuromuscular , Enfermedades Neuromusculares , Fármacos Neuromusculares no Despolarizantes , Anciano , Humanos , Inhibidores de la Colinesterasa/farmacología , Retraso en el Despertar Posanestésico/inducido químicamente , Neostigmina/administración & dosificación , Neostigmina/farmacología , Bloqueo Neuromuscular/métodos , Náusea y Vómito Posoperatorios/inducido químicamente , Atracurio/toxicidad

RESUMEN

Background: Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury. Objective: To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI. Methods: We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria. Results: Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy. Conclusion: Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.

RESUMEN

Allelochemicals have been shown to inhibit cyanobacterial blooms for several years. In view of the disadvantages of "direct-added" mode, natural and pollution-free tea polyphenolic allelochemicals with good inhibitory effect on cyanobacteria were selected to prepare sustained-release particles by microcapsule technology. Results showed that the encapsulation efficiency of tea polyphenols sustained-release particles (TPSPs) was 50.6% and the particle size ranged from 700 to 970 nm, which reached the nanoscale under optimum preparation condition. Physical and chemical properties of TPSPs were characterized to prove that tea polyphenols were well encapsulated and the particles had good thermal stability. The optimal dosage of TPSPs was determined to be 0.3 g/L, at which the inhibition rate on Microcystis aeruginosa in logarithmic growth period could be maintained above 95%. Simultaneous decrease in algal density and chlorophyll-a content indicated that the photosynthesis of algal cells was affected leading to cell death. Significant changes of antioxidant enzyme activities suggested that Microcystis aeruginosa's antioxidant systems had been disrupted. Furthermore, TPSPs increased the concentration of O2- which led to lipid peroxidation of cell membrane and a subsequent increase in malondialdehyde (MDA) content. Meanwhile, the protein content, nucleic acid content, and electrical conductivity in culture medium rose significantly indicating the cell membrane was irreversibly damaged. This work can provide a basis for the utilization of environmentally friendly algal suppressants.

Asunto(s)

Cianobacterias , Microcystis , Antioxidantes/farmacología , Té , Polifenoles/farmacología , Preparaciones de Acción Retardada , Feromonas/farmacología

RESUMEN

Drug behavior in the bodies of fish is largely influenced by the water temperature. Antimicrobial drugs are needed for the control of bacterial outbreaks in farmed fish including Asian seabass (Lates calcarifer). However, little is known about the temperature effect on appropriate drug uses in this species. The purpose of this study was to investigate the differences in pharmacokinetics (PK), optimal dosages, tissue depletion, and withdrawal time (WDT) of florfenicol (FF) in Asian seabass reared at 25 and 30 °C. In the PK study, the fish were administered with a single oral dose of 10 mg/kg FF. The optimal dosing regimen was determined by the pharmacokinetic-pharmacodynamic (PK-PD) approach. In the tissue depletion and WDT study, FF was administered at the optimal dosages once daily for 5 days and the WDT was determined by linear regression analysis based on the sum of FF and its metabolite florfenicol amine (FFA) in the muscle/skin. When the temperature was increased from 25 to 30 °C, the elimination half-life of FF was significantly decreased from 11.0 to 7.2 h. While the other PK parameters were not changed significantly, the calculated optimal dosages for the target minimum inhibitory concentration (MIC) of 2 µg/mL were 10.9 and 22.0 mg/kg/day, respectively for 25 and 30 °C. The sum of FF + FFA is a preferable marker residue for WDT determination because differential FF metabolism was observed at different temperatures. The depletion half-life of the muscle/skin was shortened from 41.1 to 32.4 h by the 5 °C temperature increase. Despite different absolute amounts of FF given between the two temperature levels, the WDTs were very similar at 6-7 days. Thus, it appears that a single temperature-independent WDT can potentially be assigned when the drug was applied at the optimal dosage.

Asunto(s)

Perciformes , Tianfenicol , Animales , Antibacterianos/análisis , Temperatura , Perciformes/metabolismo

RESUMEN

CONTEXT: In patients with acromegaly on long-term treatment with long-acting somatostatin receptor ligands (SRLs), the time of blood collection for IGF-I measurement after injection is not well defined. OBJECTIVE: We aimed to assess serum IGF-I dynamics and variability in SRL-treated patients compared with surgically cured patients and healthy controls. METHODS: Thirty patients under SRLs considered controlled based on a normal previous IGF-I level, 10 patients cured by pituitary surgery, and 7 healthy subjects underwent 4 weekly IGF-I determinations. RESULTS: In SRL-treated patients, the IGF-I SDS (mean ±â€…SD) was higher just before injection (0.34 ±â€…0.66) than at Day 7 (-0.33 ±â€…0.61; P = 0.0041) and Day 14 (-0.23 ±â€…0.60; P = 0.047) after injection, but it did not significantly vary in cured patients and healthy controls. The IGF-I CV was higher in SRL-treated patients than in cured patients or healthy controls (14.4 ±â€…7.6% vs 7.9 ±â€…4.4% and 8.3 ±â€…3.2%, respectively; P < 0.05 for both). Among SRL-treated patients, IGF-I CV was higher in "nonoptimally controlled patients"-i.e., patients with at least one elevated IGF-I value out of 4 (n = 9) compared with "optimally controlled" patients for whom all 4 IGF-I SDS values were < 2.0 (21.3 ±â€…9.3 vs 11.6 ±â€…6.0%; P = 0.0019). The latter did not differ from surgically cured patients and healthy controls. The measurement at the farthest distance from the SRL injection was the most predictive of patients with nonoptimally controlled disease. CONCLUSION: In patients treated with long-acting SRLs, IGF-I sampling at the farthest distance from SRL injection is the most informative and best predictor of optimal disease control.

Asunto(s)

Acromegalia , Hormona de Crecimiento Humana , Acromegalia/tratamiento farmacológico , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Octreótido , Hipófisis/metabolismo , Receptores de Somatostatina/metabolismo , Somatostatina

RESUMEN

Since all tumors are unique, they may respond differently to the same treatments. Therefore, it is necessary to study their characteristics individually to find their best treatment options. We built a mathematical model for the interactions between the most common chemotherapy drugs and the osteosarcoma microenvironments of three clusters of tumors with unique immune profiles. We then investigated the effects of chemotherapy with different treatment regimens and various treatment start times on the behaviors of immune and cancer cells in each cluster. Saliently, we suggest the optimal drug dosages for the tumors in each cluster. The results show that abundances of dendritic cells and HMGB1 increase when drugs are given and decrease when drugs are absent. Populations of helper T cells, cytotoxic cells, and IFN-γ grow, and populations of cancer cells and other immune cells shrink during treatment. According to the model, the MAP regimen does a good job at killing cancer, and is more effective than doxorubicin and cisplatin combined or methotrexate alone. The results also indicate that it is important to consider the tumor's unique growth rate when deciding the treatment details, as fast growing tumors need early treatment start times and high dosages.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Óseas/tratamiento farmacológico , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Modelos Teóricos , Osteosarcoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Óseas/inmunología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Cisplatino/administración & dosificación , Citotoxicidad Inmunológica/efectos de los fármacos , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Doxorrubicina/administración & dosificación , Esquema de Medicación , Proteína HMGB1/metabolismo , Humanos , Interferón gamma/metabolismo , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Metotrexato/administración & dosificación , Osteosarcoma/inmunología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Selección de Paciente , Medicina de Precisión , Linfocitos T Colaboradores-Inductores/efectos de los fármacos , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Factores de Tiempo , Microambiente Tumoral

RESUMEN

Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 µg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 µg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.

Asunto(s)

Antibacterianos/farmacología , Cefalosporinas/farmacología , Enfermedades de los Caballos/tratamiento farmacológico , Infecciones Estreptocócicas/veterinaria , Streptococcus/efectos de los fármacos , Animales , Antibacterianos/farmacocinética , Cefalosporinas/farmacocinética , Caballos , Inyecciones Intramusculares/veterinaria , Pruebas de Sensibilidad Microbiana/veterinaria , Infecciones Estreptocócicas/tratamiento farmacológico

RESUMEN

BACKGROUND: The suppression of hypothalamic-pituitary-adrenal (HPA) axis is a common complication associated with epidural steroid injections (ESIs). However, the effect of different doses is unknown. OBJECTIVES: The primary objective was to compare the differences in the duration of HPA suppression following treatment with different doses of ESI; triamcinolone acetate (TA) 40 mg and TA 20 mg. The secondary objectives were to compare the extent of salivary cortisol (SC) reduction, the incidence of adrenal insufficiency (AI), and the differences in a numeric rating scale (NRS) depending on the varying levels of TA dose used for ESI. STUDY DESIGN: A double-blind, parallel-group, randomized controlled trial. SETTING: Pain clinics in a university hospital. METHODS: The patients were treated with TA epidurally and divided into 2 groups (T20 and T40) depending on the dose of TA (20 mg and 40 mg). The SC concentration was measured before and after ESI to calculate the duration of HPA axis suppression, the extent of SC concentration reduction, and the SC recovery rate. Additionally, NRS and adrenocorticotropic hormone stimulation tests were used. RESULTS: Thirty patients were analyzed. The T40 group showed longer HPA suppression (19.7 ± 3.1 days) compared with that of the T20 group (8.0 ± 2.4 days). The recovery rate of the T40 group was lower than that of the T20 group (P < 0.015). However, there was no difference in the extent of reduction in SC concentration after ESI, the occurrence of AI, and pain reduction. LIMITATIONS: There were selection bias and no placebo control. CONCLUSIONS: Although the difference in pain relief according to the ESI dose is not significant, the HPA suppression is prolonged with a higher dose than a lower dose, and the recovery is slower. Therefore, the time interval between consecutive ESIs should be adjusted depending on the steroid dose to ameliorate the adverse effects of steroids.

Asunto(s)

Antiinflamatorios/administración & dosificación , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Triamcinolona/administración & dosificación , Insuficiencia Suprarrenal/inducido químicamente , Adulto , Antiinflamatorios/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Hidrocortisona/análisis , Masculino , Persona de Mediana Edad , Dolor/tratamiento farmacológico , Dolor/etiología , Saliva/química , Enfermedades de la Columna Vertebral/complicaciones , Enfermedades de la Columna Vertebral/tratamiento farmacológico , Triamcinolona/efectos adversos

RESUMEN

WHAT IS KNOWN AND OBJECTIVES: Augmented renal clearance (ARC) is characterized by enhanced renal clearance, which leads to insufficient vancomycin exposure and treatment failure. In haematologic malignancy patients, determination of optimal vancomycin dosage is essential because of high stake of life-threatening bacterial infection and increased clearance. The aim of this study was to describe vancomycin pharmacokinetic parameters in haematologic malignancy with augmented renal clearance children and define the appropriate dosing regimen to achieve an AUC0-24h /MIC ≥400. METHODS: Hematologic malignancy with ARC children was enrolled in this retrospective study. The vancomycin PPK model was established by non-linear mixed-effects modelling programme. Goodness-of-fit (GOF) plots, non-parametric bootstrap, normalized prediction distribution error (NPDE) and visual predictive checks (VPCs) were carried out for internal evaluation of the final model. Monte Carlo simulation method was used to stimulate the optimal dosage regimens. RESULTS: Fifty-three patients with 106 samples were included. A one-compartment model with first-order elimination was developed, and the final model was as follows: CL (L/h) = 6.32×（WT/70）0.75  × e0.0467 ; V(L) = 39.6×(WT/70), where WT denotes weight (kg). The internal validation of the model showed a good prediction performance. Monte Carlo simulation results showed that when MIC was 0.5 mg/L or 1 mg/L, the recommended doses to achieve a target of AUC0-24h /MIC ≥400 were 25 to 40 and 50 to 75 mg/kg/d, respectively. With decreasing weight, the recommended dosage to achieve an AUC0-24h /MIC ≥400 increased. WHAT IS NEW AND CONCLUSION: A one-compartment vancomycin PPK model was established in haematologic malignancy with augmented renal clearance children with weight with allometric scaling as a significant covariate. When MIC was 1 mg/L, current recommended paediatric dosages were insufficient in haematologic malignancy with augmented renal clearance children and should be increased.

Asunto(s)

Antibacterianos/administración & dosificación , Neoplasias Hematológicas/patología , Modelos Biológicos , Vancomicina/administración & dosificación , Adolescente , Antibacterianos/farmacocinética , Área Bajo la Curva , Infecciones Bacterianas/tratamiento farmacológico , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Pruebas de Función Renal , Masculino , Pruebas de Sensibilidad Microbiana , Método de Montecarlo , Estudios Retrospectivos , Vancomicina/farmacocinética

RESUMEN

PURPOSE: This review aimed to evaluate the efficacy of intra-articular injections of bone marrow derived mesenchymal stem cells (BM-MSCs) for the treatment of knee osteoarthritis (KOA). METHODS: This narrative review evaluates recent English language clinical data and published research articles between 2014 and 2019. Key word search strings of ((("bone marrow-derived mesenchymal stem cell" OR "bone marrow mesenchymal stromal cell" OR "bone marrow stromal cell")) AND ("osteoarthritis" OR "knee osteoarthritis")) AND ("human" OR "clinical"))) AND "intra-articular injection" were used to identify relevant articles using PMC, Cochrane Library, Web Of Science and Scopus databases. RESULTS: Pre-clinical studies have demonstrated successful, safe and encouraging results for articular cartilage repair and regeneration. This is concluded to be due to the multilineage differential potential, immunosuppressive and self-renewal capabilities of BM-MSCs, which have shown to augment pain and improve functional outcomes. Subsequently, clinical applications of intra-articular injections of BM-MSCs are steadily increasing, with most studies demonstrating a decrease in poor cartilage index, improvements in pain, function and Quality of Life (QoL); with moderate-to-high level evidence regarding safety for therapeutic administration. However, low confidence in clinical efficacy remains due to a plethora of heterogenous methodologies utilised, resulting in challenging study comparisons. A moderate number of cells (40 × 106) were identified as most likely to achieve optimal responses in individuals with grade ≥ 2 KOA. Likewise, significant improvements were reported when using lower (24 × 106) and higher (100 × 106) cell numbers, although adverse effects including persistent pain and swelling were a consequence. CONCLUSION: Overall, the benefits of intra-articular injections of BM-MSCs were deemed to outweigh the adverse effects; thus, this treatment be considered as a future therapy strategy. To realise this, long-term large-scale randomised clinical trials are required to enable improved interpretations, to determine the validity of efficacy in future studies. LEVEL OF EVIDENCE: IV.

Asunto(s)

Cartílago Articular/fisiología , Trasplante de Células Madre Mesenquimatosas , Osteoartritis de la Rodilla/terapia , Regeneración , Células de la Médula Ósea , Humanos , Inyecciones Intraarticulares , Células Madre Mesenquimatosas , Calidad de Vida , Resultado del Tratamiento

RESUMEN

Background and Purpose- Although rivaroxaban 15 mg (R15) was only given to patients with creatinine clearance (CrCl) ≤50 mL/min in the pivotal clinical trial, this dose has been commonly prescribed in Asian patients with nonvalvular atrial fibrillation regardless of renal function. There is a paucity of information on the clinical outcomes of R15 compared with rivaroxaban 20 mg (R20) in patients with CrCl ≥50 mL/min. This study aimed to examine the effectiveness and safety of 2 doses of rivaroxaban in Asian patients with atrial fibrillation and CrCl ≥50 mL/min. Methods- Using the Korean National Health Insurance Service database, patients with atrial fibrillation and normal or mildly impaired renal function (CrCl ≥50 mL/min) and naive to rivaroxaban or warfarin were included from January 2014 to December 2016. Three separate 1:1 propensity score-matched cohorts were conducted: R20 versus warfarin (n=15 584), R15 versus warfarin (n=11 554), and R20 versus R15 (n=10 392). Hazard ratios for ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and composite clinical outcome were analyzed. Results- Compared with warfarin, both R20 and R15 showed significantly lower risk for ischemic stroke, major bleeding (mainly through reduction of intracranial hemorrhage), and all-cause death. Compared with R15, R20 showed better results for the composite clinical outcome (hazard ratio, 0.852; 95% CI, 0.735-0.988). This benefit was consistently observed in patients aged ≥80 years and those <50 kg. R20 was associated with higher risk of major bleeding than R15 in patients with marginal CrCl (50-60 mL/min). Conclusions- Among Asians with atrial fibrillation and CrCl ≥50 mL/min, both R20 and R15 were associated with reduced risk of ischemic stroke, intracranial hemorrhage, major bleeding, and all-cause death without significantly increased risk of gastrointestinal bleeding compared with warfarin. In patients with CrCl ≥50 mL/min, on-label R20 showed better results for the composite clinical outcome compared with off-label R15.

Asunto(s)

Pueblo Asiatico , Fibrilación Atrial/tratamiento farmacológico , Inhibidores del Factor Xa/administración & dosificación , Insuficiencia Renal/tratamiento farmacológico , Rivaroxabán/administración & dosificación , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal/diagnóstico , Insuficiencia Renal/epidemiología , República de Corea/epidemiología , Estudios Retrospectivos

RESUMEN

Environment-friendly algaecides based on allelopathy have been extensively studied to control harmful algal blooms (HABs). The inhibitory effects of linoleic acid (LA) sustained-release microspheres on different cell densities of Microcystis aeruginosa (M. aeruginosa) at different growth phases were studied. The results showed that the growth of M. aeruginosa could be inhibited within 4 days and the constant inhibitory rate with initial algal density of 8 × 105 cells∙mL-1 (exponential phase) was up to 96% compared with control. The chlorophyll-a content in the treatment group had the same change trend with the algal density and declined significantly at day 20th, which suggested that the microspheres could promote the degradation of chlorophyll-a. The activities of superoxide dismutase (SOD) and catalase (CAT) increased gradually within 5 days but then declined sharply, which indicated that LA microspheres could cause oxidative damage to M. aeruginosa during the process of inhibition and reduce the activities of antioxidant enzymes. In addition, the concentration of oxygen free radical (O2-) increased at day 10th and rose constantly, and the content of malodialdehyde (MDA) increased to 2.7 times as much as control at day 20th. Furthermore, the content of protein, nucleic acid and the conductivity in culture solution showed a significant rise. These results showed that algal cell membrane lipid peroxidation occurred and the membrane permeability increased, accompanied by the damage of cell membrane. To sum up, the destruction of algal cell membrane is the main mechanism of LA microspheres inhibiting algal growth.

Asunto(s)

Ácido Linoleico/química , Microcystis/química , Microesferas , Oxidación-Reducción

RESUMEN

Marbofloxacin is a fluoroquinolone antibiotic and highly effective treatment for respiratory diseases. Here we aimed to evaluate the ex vivo activity of marbofloxacin against Streptococcus suis in pig serum, as well as the optimal dosages scheme for avoiding the fluoroquinolone resistance development. A single dose of 8 mg/kg body weight (bw) was administrated orally to healthy pigs and serum samples were collected during the next 72 h. Serum marbofloxacin content was determined by high-performance liquid chromatography. We estimated the Cmax (6.28 µg/ml), AUC0-24 h (60.30 µg.h/ml), AUC0-∞ (88.94 µg.h/ml), T1/2ke, (12.48 h), Tmax (0.75 h) and Clb (0.104 L/h) of marbofloxacin in pigs, as well as the bioavailability of marbofloxacin (94.21%) after a single 8 mg/kg oral administration. We also determined the pharmacodynamic of marbofloxacin against 134 Streptococcus suis strains isolated from Chinese cities in TSB and serum. These isolated strains had a MIC90 of 1 µg/ml. HB2, a virulent, serotype 2 isolate of SS, was selected for having antibacterial activity in TSB and serum to marbofloxacin. We determined the minimum inhibitory concentration (MIC, 1 µg/ml in TSB, 2 µg/ml in serum), minimum bactericidal concentration (MBC, 4 µg/ml in TSB, 4 µg/ml in serum), and mutant prevention concentration (2.56 µg/ml in TSB) for marbofloxacin against Streptococcus suis (HB2). In serum, by inhibitory sigmoid Emax modeling, the AUC0-24h/MIC values for marbofloxacin against HB2 were 25.23 (bacteriostatic), 35.64 (bactericidal), and 39.71 (elimination) h. Based on Monte Carlo simulations, the predicted optimal oral doses of marbofloxacin curing Streptococcus suis were 5.88 (bacteriostatic), 8.34 (bactericidal), and 9.36 (elimination) mg/kg.bw for a 50% target attainment ratio, and 8.16 (bacteriostatic), 11.31 (bactericidal), and 12.35 (elimination) mg/kg.bw for a 90% target attainment ratio. The data presented here provides optimized dosage information for clinical use; however, these predicted dosages should also be validated in clinical practice.

RESUMEN

This study aimed to assess whether traditional initial loading and maintenance doses of teicoplanin were appropriate in endocarditis and renal failure patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and to recommend optimal dosage regimens. Pharmacokinetic parameters and physicochemical properties of teicoplanin were performed to develop pharmacokinetic models using GastroPlusTM. Concentration-time curves of teicoplanin in endocarditis and renal failure patients with MRSA infections were simulated by changing clearance (CL) and volume of distribution of the central compartment (Vc). Different teicoplanin dosage regimens were assessed according to the target trough concentration, and optimal teicoplanin dosage regimens were recommended. Dosage regimen of four teicoplanin doses of 6 mg/kg q12 h followed by 6 mg/kg qd is recommended for renal failure patients infected by MRSA. And optimal dosage regimen is five teicoplanin doses of 15 mg/kg q12 h followed by doses of 12 mg/kg qd for endocarditis patients infected by MRSA.

Asunto(s)

Antibacterianos/farmacocinética , Endocarditis Bacteriana/microbiología , Staphylococcus aureus Resistente a Meticilina , Modelos Teóricos , Insuficiencia Renal/microbiología , Infecciones Estafilocócicas/tratamiento farmacológico , Humanos , Teicoplanina/farmacocinética

RESUMEN

Resumen Diferentes compuestos naturales extraídos de plantas se han usado para el tratamiento de aguas residuales por muchos siglos. Estos en su gran mayoría derivan de semillas, hojas, cortezas o savia, raíces y frutos de árboles y plantas. En este trabajo se evaluó la utilización del polvo de la semilla de la Cassia fístula como coagulante natural en el tratamiento primario de aguas residuales domésticas, estableciendo su dosis óptima mediante la prueba de jarras y determinando los parámetros fisicoquímicos de DBO5, DQO, conductividad, color, turbidez, alcalinidad total, y dureza total. Se utilizó como muestra de estudio agua residual doméstica tomada de una estación de bombeo de la ciudad de Cartagena de Indias (Colombia). Se encontró una dosis óptima del coagulante natural comprendida entre 15-25 mg/L, obteniendo valores finales de 30.25 NTU en la turbidez y 84 UC de color respectivamente. Los valores de pH y alcalinidad total no presentaron mayores variaciones. Los valores de los parámetros turbidez y color, al igual que el pH, alcalinidad total y dureza total se corresponden con los reportados por diferentes autores para este tipo de agua, lo cual demuestra que la C. fistula es un coagulante natural, prometedor y eficaz para la sustitución de coagulantes inorgánicos en el proceso de coagulación de aguas residuales.

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Abstract Different natural compounds extracted from plants have been used for the treatment of wastewater for many centuries. These mostly derived from seeds, leaves, bark or sap, roots and fruits of trees and plants. In this paper the use of seed powder Cassia fistula as a natural coagulant was studied. Establishing optimum dose by jar testing and determining the parameters of DBO5, DQO, conductivity, color, turbidity, total alkalinity and total hardness; using wastewater pumping station of the city of Cartagena de Indias (Colombia). Natural optimal coagulant dose between 15-25 mg/L is found. Obtaining final values of 30.25 NTU turbidity and 84 color UC´s respectively. The values of pH and total alkalinity no major variations. The values of the turbidity and color parameters like pH, total alkalinity and total hardness corresponding with those reported by different authors, which shows that C. fistula is a natural, promising and effective coagulant for the substitution of inorganic coagulants in the process of coagulation of wastewater.

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Resumo Diferentes compostos naturais extraídos de plantas foram utilizados para o tratamento de águas residuais durante muitos séculos. Estes em sua grande maioria derivam de sementes, folhas, cascas ou seiva, raízes e frutos de árvores e plantas. Neste documento, a utilização de pó de sementes de Cassia fístula como um coagulante natural no tratamento primário de águas residuais domésticas foi avaliada estabelecendo a dose óptima mediante o teste de frasco determinando os parâmetros físico-químicos de CBO5, DQO, condutividade, cor, turbidez, alcalinidade total e dureza total. Foi utilizada como amostra de estudo água residual doméstica retirada de uma estação de bombeamento na cidade de Cartagena de Índias (Colômbia. Foi encontrada uma dose ótima do coagulante natural compreendido entre 15-25 mg / L, obtendo valores finais de 30,25 NTU na turbidez e 84 UC de cor, respectivamente. O pH e a alcalinidade total não mostraram maiores variações. Os valores da turbidez e a cor, como o pH, alcalinidade total e dureza total de parâmetros correspondem aos relatados por outros autores para a água, o que mostra que a C. fístula é um coagulante natural, promissora e eficiente para a substituição de coagulantes inorgânicos no processo de floculação de águas residuais.