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1.
Ocul Surf ; 34: 406-414, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362525

RESUMO

PURPOSE: Neurotrophic keratopathy (NK) is a degenerative corneal condition resulting from corneal nerve injury. Current therapies, including the recombinant human nerve growth factor (rhNGF) therapy, requires continuous administration. This study aims to develop a novel and highly effective gene therapy strategy for the prevention and treatment of NK. METHODS: Adeno-associated virus (AAV) was transduced into corneal stromal cells by intrastromal injection. Three dimensional corneal wholemount imaging with co-immunostaining of ZO-1 and tubulin was utilized to assess the transduction of AAV.rh10. The efficacy of prevention and treatment of NK by a single intrastromal injection of AAV-Ngf was tested using capsaicin mouse model, herpes simplex keratitis (HSK) model, type Ⅱ diabetes model and alkali burn model. rhNGF eye drops served as the positive control. RESULTS: Intrastromal injection of AAV.rh10 efficiently transduced the subepithelial nerve plexus and retrogradely transported to the trigeminal ganglion (TG). A single injection of AAV.rh10-Ngf can significantly promote corneal nerve repair, accelerate corneal epithelial repair, reduce corneal stromal edema, and improve corneal sensitivity across the four NK models. The therapeutic effects were consistent with those achieved by continuous administration of rhNGF drops by 6 times daily. CONCLUSIONS: This proof-of-concept study demonstrates that AAV.rh10-Ngf gene therapy is a promising method for preventing and treating of NK. Our results underline the potential for developing clinical trials to further explore the safety and efficacy of such gene therapy.

2.
Stem Cell Res Ther ; 15(1): 344, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39380037

RESUMO

BACKGROUND: Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. METHODS: To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. RESULTS: Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. CONCLUSION: Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.


Assuntos
Bleomicina , Células-Tronco Embrionárias Humanas , Lesão Pulmonar , Fibrose Pulmonar , Animais , Camundongos , Humanos , Células-Tronco Embrionárias Humanas/citologia , Fibrose Pulmonar/terapia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/induzido quimicamente , Lesão Pulmonar/terapia , Lesão Pulmonar/patologia , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL
3.
Microb Pathog ; 197: 107009, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39395746

RESUMO

Some long-term hospitalized patients with lung infections exhibit pathogen tolerance. To investigate whether long-term chronic infection can induce tolerance, we constructed a mouse model of pneumonia in which mice were infected once, twice, or three times with Acinetobacter baumannii. The results revealed that the inflammatory factor levels decreased in the lung lavage fluid and that pathological damage to the lung tissue was alleviated in the mice infected three times. Flow cytometry and transcriptome analysis of mouse lung tissue revealed that the expression of genes related to T cell activation, differentiation, and regulation and the proportion and number of regulatory T cells and immune suppression-related genes, such as Ctla4, Tigit, Slamf8, ICOS, and IDO1, were increased in mice infected three times. These findings show that repeated A. baumannii infections can induce tolerance, which may be mediated by immune suppression involving regulatory T cells.

4.
Exp Eye Res ; : 110124, 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39396694

RESUMO

Diabetic mellitus causes various complications, including the corneal endothelial dysfunction (CED) that leads to corneal edema and vision loss, especially in the DM patients with intraocular surgeries. However, the pathogenic mechanism of hyperglycemia-caused CED remains incomplete understood. Here we firstly screened and identified the glutamine contents of anterior humor were significantly reduced in both the type 2 diabetic patients and streptozotocin-induced type 1 diabetic mice. To explore the potential therapeutic effects of glutamine supplement on the protection of diabetic corneal endothelial dysfunction, we performed the anterior chamber perfusion with the addition of L-alanyl-L-glutamine (Ala-Gln), and confirmed that Ala-Gln supplement not only accelerated the resolution of corneal edema and recovery of corneal thickness, but also preserved the regular arrangement and barrier-pomp function of corneal. Mechanistically, we revealed that the supplements of Ala-Gln protect corneal endothelial cells from the deleterious effects of high glucose-induced oxidative stress, mitochondrial dysfunction, and cell apoptosis. Overall, these results indicate the glutamine depletion plays an important role in the diabetic corneal endothelial dysfunction, while the Ala-Gln supplement during intraocular surgery provide an effective prevention strategy through regulating the redox homeostasis and mitochondrial function of corneal endothelial cells.

5.
Diabetes ; 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39446568

RESUMO

Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.

6.
Front Pharmacol ; 15: 1469286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39439897

RESUMO

Introduction: Immunosuppression is the main cause of the high mortality rate in patients with sepsis. The decrease in the number and dysfunction of CD4+ T lymphocytes is crucial to the immunosuppressed state of sepsis, in turn affecting the development and prognosis of sepsis. Autophagy has been shown to play an important role in the immune imbalance exhibited during sepsis. Methods: In this study, we modulate the expression of miR-223 in CD4+ T lymphocytes, via the transfection of a mimic or an inhibitor of miR-223 to establish cell models of miR-223 overexpression and knockdown, respectively. Levels of autophagy were monitored using a double-labeled lentivirus (mRFP-GFP-LC3) and electron microscopy, and western blot analysis was used to estimate the levels of autophagy-related proteins and FOXO1 in the two cell models after co-treatment with lipopolysaccharide (LPS) and siRNA against FOXO1. Results: We found that when the expression of miR-223 increased, FOXO1 expression decreased and autophagy decreased; whereas, when FOXO1 expression was inhibited, autophagy decreased significantly in different cell models after LPS induction. Conclusion: Thus, this study proved that miR-223 participate in the regulation of LPS-induced autophagy via the regulation of FOXO1 expression in CD4+ T lymphocytes which shed a new light for the diagnosis and treatment of sepsis.

7.
Front Cell Infect Microbiol ; 14: 1442062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39224703

RESUMO

Background: Klebsiella pneumoniae is a major cause of hospital-acquired infections (HAIs), primarily spread through environmental contamination in hospitals. The effectiveness of current chemical disinfectants is waning due to emerging resistance, which poses environmental hazards and fosters new resistance in pathogens. Developing environmentally friendly and effective disinfectants against multidrug-resistant organisms is increasingly important. Methods: This study developed a bacteriophage cocktail targeting two common carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, ST11 KL47 and ST11 KL64. The cocktail was used as an adjunctive disinfectant in a hospital's respiratory intensive care unit (RICU) via ultrasonic nebulization. Digital PCR was used to quantify CRKP levels post-intervention. The microbial community composition was analyzed via 16S rRNA sequencing to assess the intervention's impact on overall diversity. Results: The phage cocktail significantly reduced CRKP levels within the first 24 hours post-treatment. While a slight increase in pathogen levels was observed after 24 hours, they remained significantly lower than those treated with conventional disinfectants. 16S rRNA sequencing showed a decrease in the target pathogens' relative abundance, while overall species diversity remained stable, confirming that phages selectively target CRKP without disrupting ecological balance. Discussion: The findings highlight the efficacy and safety of phage-based biocleaners as a sustainable alternative to conventional disinfectants. Phages selectively reduce multidrug-resistant pathogens while preserving microbial diversity, making them a promising tool for infection control.


Assuntos
Bacteriófagos , Descontaminação , Unidades de Terapia Intensiva , Klebsiella pneumoniae , RNA Ribossômico 16S , RNA Ribossômico 16S/genética , Klebsiella pneumoniae/virologia , Klebsiella pneumoniae/genética , Descontaminação/métodos , Bacteriófagos/genética , Humanos , Reação em Cadeia da Polimerase/métodos , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologia , Desinfetantes/farmacologia , Infecções por Klebsiella/prevenção & controle , Infecções por Klebsiella/microbiologia , Análise de Sequência de DNA
8.
Int J Biol Macromol ; 280(Pt 2): 135778, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39304050

RESUMO

Limbal stem cell deficiency (LSCD) is a complex disease of the cornea resulting from dysfunction and/or loss of limbal stem cells (LSCs) and their niche. Most patients with LSCD cannot be treated by conventional corneal transplants because the donor tissue lacks the LSCs necessary for corneal epithelial regeneration. Successful treatment of LSCD depends on effective stem cell transplantation to the ocular surface for replenishment of the LSC reservoir. Thus, stem cell therapies employing carrier substrates for LSCs have been widely explored. Hydrogel biomaterials have many favorable characteristics, including hydrophilicity, flexibility, cytocompatibility, and optical properties suitable for the transplantation of LSCs. Therefore, due to these properties, along with the necessary signals for stem cell proliferation and differentiation, hydrogels are ideal carrier substrates for LSCD treatment. This review summarizes the use of different medical-type hydrogels in LSC transplantation from 2001 to 2024. First, a brief background of LSCD is provided. Then, studies that employed various hydrogel scaffolds as LSC carriers are highlighted to provide a multimodal strategic reference for LSCD treatment. Finally, an analysis of prospective future developments and challenges in the field of hydrogels as LSC carriers for treating LSCD is presented.

9.
Research (Wash D C) ; 7: 0426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39109248

RESUMO

Problem: Chest radiography is a crucial tool for diagnosing thoracic disorders, but interpretation errors and a lack of qualified practitioners can cause delays in treatment. Aim: This study aimed to develop a reliable multi-classification artificial intelligence (AI) tool to improve the accuracy and efficiency of chest radiograph diagnosis. Methods: We developed a convolutional neural network (CNN) capable of distinguishing among 26 thoracic diagnoses. The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries. Results: The CNN model achieved an average area under the curve (AUC) of 0.961 across all 26 diagnoses in the testing set. COVID-19 detection achieved perfect accuracy (AUC 1.000, [95% confidence interval {CI}, 1.000 to 1.000]), while effusion or pleural effusion detection showed the lowest accuracy (AUC 0.8453, [95% CI, 0.8417 to 0.8489]). In external validation, the model demonstrated strong reproducibility and generalizability within the local dataset, achieving an AUC of 0.9634 for lung opacity detection (95% CI, 0.9423 to 0.9702). The CNN outperformed both radiologists and nonradiological physicians, particularly in trans-device image recognition. Even for diseases not specifically trained on, such as aortic dissection, the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels (all P < 0.05). Additionally, our model exhibited no gender bias (P > 0.05). Conclusion: The developed AI algorithm, now available as professional web-based software, substantively improves chest radiograph interpretation. This research advances medical imaging and offers substantial diagnostic support in clinical settings.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(4): 793-799, 2024 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-39169999

RESUMO

Ultrasound, a high-frequency mechanical wave with excellent tissue penetration, has been widely applied in medical diagnostic imaging. Furthermore, it has been reported that ultrasound has broad prospects for extensive applications in the field of disease treatment in recent years due to its non-invasiveness and high efficiency. Ultrasound-responsive nanomaterials have the unique advantages of a small size and a high reactivity. Such materials have the capability for precision control of drug release under ultrasound stimulation, which provides a new approach to enhancing the efficiency of drug therapy. Therefore, these materials have attracted the attention of a wide range of scholars. Inflammation is a defensive response produced by organisms to deal with injuries. However, excessive inflammatory response may lead to various tissue damages in organisms and even endanger patients' lives. Many studies have demonstrated that limiting the inflammatory response using ultrasound-responsive nanomaterials is a viable way of treating diseases. Currently, there are still challenges in the application of ultrasound-responsive nanomaterials in anti-inflammatory therapy. The design and synthesis process of nanomaterials is complicated, and further verification of the biocompatibility and safety of these materials is needed. Therefore, in this review, we summarized and classified common ultrasound-responsive nanomaterials in the field of anti-inflammation and systematically introduced the properties of different nanomaterials. In addition, the anti-inflammatory applications of ultrasound-responsive nanomaterials in various diseases, such as bone diseases, skin and muscle diseases, autoimmune diseases, and respiratory diseases, are also described in detail. It is expected that this review will provide insights for further research and clinical applications in the realms of precision treatment, targeted drug delivery, and clinical trial validation of ultrasound-responsive nanomaterials used in anti-inflammatory therapies.


Assuntos
Anti-Inflamatórios , Inflamação , Nanoestruturas , Nanoestruturas/uso terapêutico , Humanos , Anti-Inflamatórios/uso terapêutico , Inflamação/diagnóstico por imagem , Sistemas de Liberação de Medicamentos , Ondas Ultrassônicas , Terapia por Ultrassom/métodos , Animais
13.
Stem Cell Res Ther ; 15(1): 201, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971839

RESUMO

BACKGROUND: Dysfunction or deficiency of corneal epithelium results in vision impairment or blindness in severe cases. The rapid and effective regeneration of corneal epithelial cells relies on the limbal stem cells (LSCs). However, the molecular and functional responses of LSCs and their niche cells to injury remain elusive. METHODS: Single-cell RNA sequencing was performed on corneal tissues from normal mice and corneal epithelium defect models. Bioinformatics analysis was performed to confirm the distinct characteristics and cell fates of LSCs. Knockdown of Creb5 and OSM treatment experiment were performed to determine their roles of in corneal epithelial wound healing. RESULTS: Our data defined the molecular signatures of LSCs and reconstructed the pseudotime trajectory of corneal epithelial cells. Gene network analyses characterized transcriptional landmarks that potentially regulate LSC dynamics, and identified a transcription factor Creb5, that was expressed in LSCs and significantly upregulated after injury. Loss-of-function experiments revealed that silencing Creb5 delayed the corneal epithelial healing and LSC mobilization. Through cell-cell communication analysis, we identified 609 candidate regeneration-associated ligand-receptor interaction pairs between LSCs and distinct niche cells, and discovered a unique subset of Arg1+ macrophages infiltrated after injury, which were present as the source of Oncostatin M (OSM), an IL-6 family cytokine, that were demonstrated to effectively accelerate the corneal epithelial wound healing. CONCLUSIONS: This research provides a valuable single-cell resource and reference for the discovery of mechanisms and potential clinical interventions aimed at ocular surface reconstruction.


Assuntos
Plasticidade Celular , Células-Tronco do Limbo , Limbo da Córnea , Cicatrização , Animais , Camundongos , Epitélio Corneano/metabolismo , Epitélio Corneano/patologia , Epitélio Corneano/lesões , Células-Tronco do Limbo/citologia , Células-Tronco do Limbo/metabolismo , Limbo da Córnea/metabolismo , Limbo da Córnea/citologia , Limbo da Córnea/patologia , Camundongos Endogâmicos C57BL , Nicho de Células-Tronco , Cicatrização/genética
15.
BMC Geriatr ; 24(1): 487, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38831261

RESUMO

BACKGROUND: Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. METHODS: We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. RESULTS: From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8-14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. CONCLUSIONS: Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. TRIAL REGISTRATION: ChiCTR2100046811; 28/05/2021.


Assuntos
Antibacterianos , Relação Dose-Resposta a Droga , Teicoplanina , Humanos , Masculino , Idoso , Feminino , Estudos Prospectivos , Teicoplanina/administração & dosagem , Teicoplanina/efeitos adversos , China/epidemiologia , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
16.
BMC Ophthalmol ; 24(1): 268, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907352

RESUMO

BACKGROUND: Sleep deprivation (SD) is a common public health problem that contributes to various physiological disorders and increases the risk of ocular diseases. However, whether sleep loss can damage corneal endothelial function remains unclear. This study aimed to determine the effect and possible mechanism of SD on the corneal endothelium. METHODS: Male C57BL/6J mice were subjected to establish SD models. After 10 days, quantitative RT-PCR (qRT-PCR) and western blot or immunostaining for the expression levels of zonula occludens-1 (ZO-1), ATPase Na+/K + transporting subunit alpha 1 (Atp1a1), and core clock genes in the corneal endothelium were evaluated. Reactive oxygen species staining and mitochondrial abundance characterized the mitochondrial function. The regulatory role of Bmal1 was confirmed by specifically knocking down or overexpressing basic helix-loop-helix ARNT like 1 protein (Bmal1) in vivo. In vitro, a mitochondrial stress test was conducted on cultured human corneal endothelial cells upon Bmal1 knockdown. RESULTS: SD damaged the barrier and pump functions of mouse corneal endothelium, accompanied by mitochondrial dysfunction. Interestingly, SD dramatically downregulated the core clock gene Bmal1 expression level. Bmal1 knockdown disrupted corneal endothelial function, while overexpression of Bmal1 ameliorated the dysfunction induced by SD. Mitochondrial bioenergetic deficiency mediated by Bmal1 was an underlying mechanism for SD induced corneal endothelial dysfunction. CONCLUSION: The downregulation of Bmal1 expression caused by SD led to corneal endothelial dysfunction via impairing mitochondrial bioenergetics. Our findings offered insight into how SD impairs the physiological function of the corneal endothelium and expanded the understanding of sleep loss leading to ocular diseases.


Assuntos
Fatores de Transcrição ARNTL , Endotélio Corneano , Privação do Sono , Animais , Masculino , Camundongos , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Endotélio Corneano/metabolismo , Endotélio Corneano/patologia , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Privação do Sono/complicações , Privação do Sono/metabolismo , Privação do Sono/fisiopatologia
17.
Immun Ageing ; 21(1): 40, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909272

RESUMO

Sepsis is a dysregulated host response to severe infections, and immune dysfunction plays a crucial role in its pathogenesis. Elderly patients, a special population influenced by immunosenescence, are more susceptible to sepsis and have a worse prognosis. However, the immunopathogenic mechanisms underlying sepsis in elderly patients remain unclear. Here, we performed single-cell RNA sequencing of peripheral blood samples from young and old subjects and patients with sepsis. By exploring the transcriptional profiles of immune cells, we analyzed immune cell compositions, phenotype shifts, expression heterogeneities, and intercellular communication. In elderly patients with sepsis, innate immune cells (e.g., monocytes and DCs) exhibit decreased antigen presentation, presenting an overactive inflammatory and senescent phenotype. However, the immunophenotype of T cells shifted to characterize effector, memory, and exhaustion. Moreover, we identified strong interferon-γ responses of T cells in both aging and sepsis groups and a deranged inflammaging status in elderly sepsis patients. Tregs in elderly patients with sepsis showed increased abundance and enhanced immunosuppressive effects. In addition, metabolism-associated pathways were upregulated in T cells in elderly patients with sepsis, and the lysine metabolism pathway was enriched in Tregs. Cell-cell interaction analysis showed that the expression profile of ligand-receptor pairs was probably associated with aggravated immune dysfunction in elderly patients with sepsis. A novel HLA-KIR interaction was observed between Tregs and CD8 + T cells. These findings illustrate the immunological hallmarks of sepsis in elderly patients, and highlight that immunosuppressive and metabolic regulatory pathways may undergo important alterations in elderly patients with sepsis.

18.
J Antimicrob Chemother ; 79(8): 1938-1950, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38873816

RESUMO

BACKGROUND: The concentrations of linezolid, its optimal regimen and the associated side effects in elderly patients remain unclear. METHODS: In this multicentre, prospective study, elderly patients receiving linezolid at four tertiary hospitals in Beijing between May 2021 and December 2022 were included. Linezolid concentrations and haematological toxicity were monitored dynamically. Risk factors for linezolid overexposure and moderate-to-severe linezolid-induced thrombocytopenia (M/S LIT) were analysed, and a predictive model of M/S LIT was developed. RESULTS: A total of 860 linezolid concentrations were measured in 313 patients. The median trough concentrations of linezolid were 24.4 (15.3, 35.8) mg/L at 36-72 h and 26.1 (17.0, 38.1) mg/L at 5-10 days (P = 0.132). Severe linezolid exposure was independently associated with age, estimated glomerular filtration rate (eGFR) and the worst SOFA score (SOFA1), and we further recommended dose regimens for elderly patients based on these findings. The incidences of linezolid-induced thrombocytopenia(LIT) and M/S LIT were 73.5% and 47.6%, respectively. M/S LIT was independently correlated with treatment duration, average trough concentration (TDMa), baseline platelet count, eGFR and baseline SOFA score (SOFA0). The developed nomogram predicted M/S LIT with an area under the curve of 0.767 (95% CI 0.715-0.820), a sensitivity of 71.1% and a specificity of 73.2%. CONCLUSIONS: Linezolid trough concentrations increased dramatically in the elderly, by about 10 mg/L in patients aged 65-80 years, followed by a further increase of 10 mg/L for every 10 years of age. Therapeutic drug monitoring is recommended in elderly patients receiving linezolid. The developed nomogram may predict M/S LIT and guide dosage adjustments of linezolid. Clinical trial registration number: ChiCTR2100045707.


Assuntos
Antibacterianos , Monitoramento de Medicamentos , Linezolida , Nomogramas , Trombocitopenia , Humanos , Linezolida/efeitos adversos , Linezolida/farmacocinética , Linezolida/administração & dosagem , Idoso , Masculino , Feminino , Estudos Prospectivos , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Antibacterianos/administração & dosagem , Trombocitopenia/induzido quimicamente , Idoso de 80 Anos ou mais , Fatores de Risco , Pessoa de Meia-Idade
19.
Membranes (Basel) ; 14(6)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38921492

RESUMO

The removal of dissolved organic matter (DOM) from seawater before the reverse osmosis (RO) processes is crucial for alleviating organic fouling of RO membranes. However, research is still insufficiently developed in the comparison of the effectiveness of integrating coagulation with ultrafiltration (UF) or sand filtration (SF) in the pretreatment stage of seawater reverse osmosis (SWRO) for the removal of DOM. In this study, we investigated the effect of pretreatment technologies on RO fouling caused by DOM in seawater, including the integration of coagulation and sand filtration (C-S pretreatment) and the integration of coagulation and ultrafiltration (C-U pretreatment). Both integrated pretreatments achieved comparable DOM removal rates (70.2% for C-U and 69.6% for C-S), and C-S exhibited enhanced removal of UV-absorbing compounds. Although C-U was more proficient in reducing the silt density index (below 2) compared to C-S (above 3) and improved the elimination of humic acid-like organics, it left a higher proportion of tyrosine-protein-like organics, soluble microbial by-product-like organics, and finer organics in the effluent, leading to the formation of a dense cake layer on RO membrane and a higher flux decline. Therefore, suitable technologies should be selected according to specific water conditions to efficiently mitigate RO membrane fouling.

20.
Membranes (Basel) ; 14(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38921506

RESUMO

The separation of a toluene/methanol/water ternary mixture is a difficult task due to the toluene/water and toluene/methanol azeotropes. In this article, low-energy pervaporation is proposed for the separation of the ternary azeotrope toluene-methanol-water. This work investigates the effects of feed temperature, feed flow rate, and vacuum on pervaporation and compares the energy consumption of pervaporation with that of distillation. The results showed that at the optimized flow rate of 50 L/h and a permeate side vacuum of 60 kPa at 50 °C, the water and methanol content in the permeate was about 63.2 wt.% and 36.8 wt.%, respectively, the water/ methanol separation factor was 24.04, the permeate flux was 510.7 g/m2·h, the water content in the feed out was reduced from 2.5 wt.% to less than 0.66 wt.%, and the dehydration of toluene methanol could be realized. Without taking into account the energy consumption of pumps and other power equipment, pervaporation requires an energy consumption of 43.53 kW·h to treat 1 ton of raw material, while the energy consumption of distillation to treat 1 ton of raw material is about 261.5 kW·h. Compared to the existing distillation process, the pervaporation process consumes much less energy (about one-sixth of the energy consumption of distillation). There is almost no effect on the surface morphology and chemical composition of the membrane before and after use. The method provides an effective reference for the dehydration of organic solvents from ternary mixtures containing toluene/methanol/water.

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