RESUMEN
Platelet-rich plasma (PRP) has significant potential for various applications and holds clinical value in regenerative medicine. Cryopreservation is used to extend the preservation period of PRP, facilitating its clinical application. However, the potential negative effects of long-term cryopreservation on platelet storage lesion are still uncertain. In this study, PRP was stored at - 30 °C or - 80 °C. Platelet count, apoptosis, reactive oxygen species (ROS) content, and CD62P expression were assessed on the 14th and 28th days. The study also evaluated platelet mitochondria morphology and function, serotonin (5-HT) secretion by platelets, and the inflammatory activating effect of cryopreserved platelets in PRP. The results showed that there were no significant differences in platelet count, the content of 5-HT, and inflammatory effects between fresh PRP and PRP cryopreserved at both - 30 °C and - 80 °C. However, there was an increase in ROS level, apoptosis, and CD62P level after cryopreservation at both temperatures. Additionally, the levels of ROS, apoptosis, and CD62P in platelets were similar after storage at - 30 °C and - 80 °C. The main difference observed was that the morphology and function of mitochondria were severely damaged after storage at - 30 °C, while they were less affected at - 80 °C. Based on these findings, it can be concluded that storing PRP at - 80 °C is more suitable for achieving a better therapeutic effect in clinical applications, but cryopreservation could not replace the current standard.
Asunto(s)
Plasma Rico en Plaquetas , Serotonina , Humanos , Especies Reactivas de Oxígeno , Serotonina/metabolismo , Serotonina/farmacología , Conservación de la Sangre/métodos , Plaquetas/metabolismo , Criopreservación/métodosRESUMEN
BACKGROUND: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE: We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS: Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1ß, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS: We also found significantly higher baseline levels of IL-1ß, IL-6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL-1ß and IL-6 normalized, while TNFα levels declined substantially. CONCLUSION: The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro-inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.
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Emolientes/administración & dosificación , Interleucina-1beta/sangre , Interleucina-1beta/efectos de los fármacos , Interleucina-6/sangre , Fenómenos Fisiológicos de la Piel/efectos de los fármacos , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Emolientes/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
BACKGROUND: Psoriasis is an immune disorder involving numerous cytokines. Recent studies have shown that interleukin (IL)-21 plays an important role in a variety of inflammatory and autoimmune diseases. It is highly expressed in psoriatic plaques and promotes the proliferation of epidermis in mice. It seems that IL-21 plays an important role in the pathogenesis of psoriasis. However, whether or not it is elevated in the peripheral blood of patients with psoriasis and is associated with disease severity is unclear. Therefore, our study focuses on serum IL-21 levels and their correlation with disease severity. OBJECTIVES: To detect serum IL-21 levels in patients with psoriasis and investigate the correlation between these and the Psoriasis Area and Severity Index (PASI) scores. METHODS: Blood samples were collected from patients with plaque psoriasis and from healthy control subjects. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay in 37 patients with psoriasis and 37 healthy controls. The PASI scores of patients with psoriasis and their correlation with serum IL-21 levels were evaluated. RESULTS: Serum IL-21 levels were higher in patients with psoriasis than in healthy controls (P < 0·01). Serum IL-21 levels were positively correlated with PASI scores in the patients with psoriasis (r = 0·471, P < 0·01). CONCLUSIONS: Serum IL-21 levels in patients with psoriasis are elevated and positively correlate with PASI scores. These results indicate that IL-21 may play an important role in the pathogenesis of psoriasis.
Asunto(s)
Interleucinas/sangre , Psoriasis/sangre , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Psoriasis/patología , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Background: Psoriasis is a common chronic inflammatory disease caused by excessive activation of CD4+T cells, including Th17, Th1 and Th22. The role of CD8+T cells in psoriasis pathogenesis remains poorly understood. Aim: To identify the phenotype of CD8+T cells in patients with psoriasis and to investigate its role in the formation of lesions. Methods: The phenotype of CD8+T cells in psoriatic lesions was detected by immunofluorescence staining. Flow cytometry was performed to detect their phenotype in peripheral blood. Thereafter, coculture of CD8αα+T cells with autogenous CD4+T cells was performed to investigate the function of CD8αα+T cells in patients with psoriasis. Finally, pro-inflammatory factors produced by CD8αα+T cells were examined by immunofluorescence staining and flow cytometry. Results: Compared to the CD8αß+T cells, CD8αα+T cell infiltration in psoriatic lesions markedly increased. Moreover, epidermal CD8αα+T cells exhibited tissue-resident memory T cells (TRM) phenotypes and dermal CD8αα+T cells exhibited effector memory (TEM) phenotypes in psoriatic lesions. Additionally, we found that CD8αα+T cells from patients with psoriasis did not express the markers of regulatory T cells and could promote the proliferation of CD4+T effector cells and produce interleukin-17 and interferon-γ. Conclusions: Our findings demonstrate that CD8αα+T cells contribute to the pathogenesis of psoriasis by producing pro-inflammatory factors.
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We present the case of a 21-year-old man admitted to the intensive care unit with multi-organ failure due to multidrug-resistant tuberculosis (TB). TB treatment initially comprised moxifloxacin, ethambutol, linezolid and amikacin administered intravenously. Due to suspected moxifloxacin-induced liver injury, we stopped all fluoroquinolones and switched to bedaquiline (BDQ), which is only available in tablets for oral administration. Since our patient had to be fed through a nasogastric tube (NGT), BDQ was administered after being crushed and dissolved in water; drug pharmacokinetics were studied using repeated blood sampling. Therapeutic drug monitoring showed that BDQ was detectable in blood plasma with a trough concentration above the supposed efficacy threshold, suggesting that this molecule could be administered through NGT.