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Background: Respiratory tract infection (RTI) is associated with a higher risk of kidney failure in patients with chronic kidney disease (CKD), without effective precautions. Self-administered acupressure (SAA) has been shown to potentially prevent RTI, but still lack of clinical evidence in CKD. The present randomized controlled trial assessed the efficacy and safety of SAA in preventing RTI recurrence in patients with CKD. Methods: Participants with CKD who had been diagnosed with RTI on more than 2 occasions in the preceding 12 months were enrolled between November 6, 2017, and August, 6, 2018. They were randomly assigned (1:1) to receive daily SAA combined with usual care (intervention) or usual care alone (control) for 24 months. The primary outcome was time to first RTI. Secondary outcomes were RTI rate, kidney function, proteinuria and serum immune indicators, detected by the clinical laboratory in the hospital. The study would be discontinued if the participant met the criteria of stopping the study. Kaplan-Meier method and multivariable Cox proportional hazards regression were used to compare the primary outcome between the two groups. Results: Among the 540 patients screened, 114 participants were randomly assigned to the intervention group (n=57) or the control group (n=57). The median follow-up duration was 24.4 months. Compared with controls, participants in the intervention group did not have a significantly lower risk of RTI according to Kaplan-Meier analysis, but did have a significantly lower risk of RTI according to competing risk analysis (HR 0.65, 95% CI: 0.42-1.00; P=0.05), when considering endpoint (dialysis or death) and loss to follow-up as competing risks, and had a significantly lower rate of RTI [1.65 vs. 2.19 episodes per patient-year, respectively; incidence rate ratio (IRR) 0.75, 95% CI: 0.62-0.92; P=0.006]. Apart from lower study serum IgG levels in the intervention group at 24 months (mean difference 0.68 g/L; 95% CI: 0.07-1.29; P=0.029), all other secondary outcomes and overall adverse events were comparable between the 2 groups. Conclusions: SAA is a promising effective and safe therapy for preventing RTI in patients with CKD. However, the efficacy of SAA in children and adolescents still needs further study. Trial Registration: Chinese Clinical Trials Registry identifier: ChiCTR-IOR-17012654.
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ETHNOPHARMACOLOGICAL RELEVANCE: Historical literature and pharmacological studies both suggest that Astragalus membranaceus (A. membranaceus) holds potential benefits for diabetic kidney disease (DKD), which is a growing burden with limited proven renal protective options. AIM OF THE STUDY: An updated systematic review was conducted to evaluate the efficacy and safety of A. membranaceus preparations as an adjunctive therapy to conventional therapies for DKD. METHODS: Nine databases and five clinical trial registries were searched for randomized controlled trials (RCTs) of A. membranaceus preparations added to conventional therapies compared with conventional therapies alone for people with DKD. Study screening, data collection, and quality assessment were performed independently by two reviewers. Estimated effects were pooled as mean differences or standardized mean differences with 95% confidence intervals by using a random-effects model. RESULTS: Sixty-six studies, involving 4785 DKD participants, were included. The quality of the included studies was low due to methodological shortfalls. Meta-analysis showed that additional use of A. membranaceus injection reduced more albuminuria (32 RCTs, 2253 participants; SMD: 2.05 [-2.49, -1.61], I2â¯=â¯94%), proteinuria (26 RCTs, 1812 participants; SMD: 1.85 [-2.34, -1.37], I2â¯=â¯95%), and serum creatinine levels (32 RCTs, 2880 participants; -14.78⯵mol/L [-19.22, -10.33], I2â¯=â¯97%) than conventional therapies alone did. An anti-albuminuria effect was also observed in the oral A. membranaceus preparation group (four RCTs, 236 participants; SMD: 1.27 [-1.82, -0.73], I2â¯=â¯73%). Meta-regression suggested that the treatment effect of A. membranaceus injection was associated with the baseline serum creatinine level. The adverse-events profile was similar between the additional A. membranaceus and control groups. CONCLUSION: The low quality of evidence suggested that adjunctive use of A. membranaceus preparations in addition to conventional therapies may be effective and tolerated for short-term reduction of albuminuria, proteinuria, and serum creatinine in DKD patients. The findings should be considered with caution due to the lack of high-quality RCTs and significant heterogeneity and publication bias. Further RCTs are needed to confirm the long-term efficacy and safety of A. membranaceus preparations, especially of the oral form, in patient-important outcomes.
Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Astragalus propinquus , Quimioterapia Adjuvante , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Cubosomes, as biocompatible carriers in drug delivery systems, consist of curved bicontinuous lipid bilayers. With a honeycombed structure divided into two internal aqueous channels, cubosomes could be used for many bioactive ingredients. Achyranthes bidentata polysaccharides (ABPs) are isolated from the roots of Achyranthes bidentata, used in Chinese herbal medicine, and present a noticeable effect as an immunomodulator. This study investigates the optimal preparation of combined cubosome-ABP (Cub-ABP) nanoparticles using response surface methodology and explores their characteristics and stability. The encapsulation efficiency of optimized Cub-ABPs was 72.59%. In-vitro stability studies demonstrated the stability of Cub-ABPs and cubosome nanoparticles without ABPs; both were stable for up to 25days. Safe concentrations of Cub-ABPs and cubosome nanoparticles without ABPs are 104.06µg/mL and 208.13µg/mL with comparatively low cytotoxicity against lymphocytes. Moreover, the feasible immunomodulatory effects of Cub-ABPs were determined by evaluating their proliferation and change of CD4+/CD8+ ratio on splenic lymphocytes in vitro. Proliferation and flow cytometry studies revealed that, compared with free ABPs and blank cubosomes, Cub-ABPs proved more effective in promoting lymphocyte proliferation and in triggering the transformation of T-lymphocytes into Th-cells.
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Amaranthaceae/química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Animais , Composição de Medicamentos , Estabilidade de Medicamentos , Ativação Linfocitária , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Nanopartículas/química , Nanopartículas/ultraestruturaRESUMO
The success of subunit vaccines has been hampered by the problems of weak or short-term immunity and the lack of availability of nontoxic, potent adjuvants. It would be desirable to develop safe and efficient adjuvants with the aim of improving the cellular immune response against the target antigen. In this study, the targeting and sustained release of simple nanoliposomes containing Lycium barbarum polysaccharides (LBP) as an efficacious immune adjuvant to improve immune responses were explored. LBP liposome (LBPL) with high entrapment efficiency (86%) were obtained using a reverse-phase evaporation method and then used to encapsulate the model antigen, ovalbumin (OVA). We demonstrated that the as-synthesized liposome loaded with OVA and LBP (LBPL-OVA) was stable for 45 days and determined the encapsulation stability of OVA at 4°C and 37°C and the release profile of OVA from LBPL-OVA was investigated in pH 7.4 and pH 5.0. Further in vivo investigation showed that the antigen-specific humoral response was correlated with antigen delivery to the draining lymph nodes. The LBPL-OVA were also associated with high levels of uptake by key dendritic cells in the draining lymph nodes and they efficiently stimulated CD4+ and CD8+ T cell proliferation in vivo, further promoting antibody production. These features together elicited a significant humoral and celluar immune response, which was superior to that produced by free antigen alone.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Medicamentos de Ervas Chinesas/administração & dosagem , Imunidade Celular/efeitos dos fármacos , Lipossomos/química , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Medicamentos de Ervas Chinesas/química , Imunidade Humoral/efeitos dos fármacos , Imunidade Humoral/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/administração & dosagem , Nanopartículas/química , Ovalbumina/química , Ovalbumina/imunologia , Ovalbumina/farmacocinética , Fosfolipídeos/química , Glycine max/química , Vacinas/administração & dosagem , Vacinas/imunologiaRESUMO
BACKGROUND: Bispectral index (BIS) is considered very useful to guide anesthesia care in elderly patients, but its use is controversial for the evaluation of the adequacy of analgesia. This study compared the BIS changes in response to loss of consciousness (LOC) and loss of somatic response (LOS) to nociceptive stimuli between elderly and young patients receiving intravenous target-controlled infusion (TCI) of propofol and remifentanil. METHODS: This study was performed on 52 elderly patients (aged 65-78 years) and 52 young patients (aged 25-58 years), American Society of Anesthesiologists physical status I or II. Anesthesia was induced with propofol administered by TCI. A standardized noxious electrical stimulus (transcutaneous electrical nerve stimulation, [TENS]) was applied (50 Hz, 80 mA, 0.25 ms pulses for 4 s) to the ulnar nerve at increasing remifentanil predicted effective-site concentration (Ce) until patients lost somatic response to TENS. Changes in awake, prestimulus, poststimulus BIS, heart rate, mean arterial pressure, pulse oxygen saturation, predicted plasma concentration, Ce of propofol, and remifentanil at both LOC and LOS clinical points were investigated. RESULTS: BISLOCin elderly group was higher than that in young patient group (65.4 ± 9.7 vs. 57.6 ± 12.3) (t = 21.58, P < 0.0001) after TCI propofol, and the propofol Ce at LOC was 1.6 ± 0.3 µg/ml in elderly patients, which was significantly lower than that in young patients (2.3 ± 0.5 µg/ml) (t = 7.474, P < 0.0001). As nociceptive stimulation induced BIS to increase, the mean of BIS maximum values after TENS was significantly higher than that before TENS in both age groups (t = 8.902 and t = 8.019, P < 0.0001). With increasing Ce of remifentanil until patients lost somatic response to TENS, BISLOSwas the same as the BISLOCin elderly patients (65.6 ± 10.7 vs. 65.4 ± 9.7), and there were no marked differences between elderly and young patient groups in BISawake, BISLOS, and Ce of remifentanil required for LOS. CONCLUSION: In elderly patients, BIS can be used as an indicator for hypnotic-analgesic balance and be helpful to guide the optimal administration of propofol and remifentanil individually. TRIAL REGISTRATION: CTRI Reg. No: ChiCTR-OOC-14005629; http://www.chictr.org.cn/showproj.aspx?proj=9875.