Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.179
Filtrar
1.
BMC Womens Health ; 24(1): 504, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39261797

RESUMO

BACKGROUND: Menopause significantly impacts the immune system. Postmenopausal women are more susceptible to infection. Nonetheless, the pattern of change in peripheral white blood cell counts around the menopause remains poorly understood. METHODS: We conducted a prospective longitudinal cohort study with repeated measurements using Kailuan cohort study of 3632 Chinese women who participated in the first checkup (2006-2007) and reached their final menstrual period (FMP) by the end of the seventh checkup (2018-2020). Peripheral WBC count indicators included total white blood cells (TWBC), neutrophils (NEUT), lymphocytes (LYM), and monocytes (MON). Multivariable mixed effects regressions fitted piece-wise linear models to repeated measures of WBC count indicators as a function of time before or after the final menstrual period (FMP). Interaction and subgroup analysis were used to explore the effects of age and body mass index (BMI) on changes in WBC indicators around FMP. RESULTS: WBC count indicators decreased before the FMP, and the reduction in TWBC, NEUT, and MON continued for 2 years following the FMP. LYM and NEUT declined during < -1 years and - 4 ∼ + 2 years relative to FMP, respectively. A reduction in MON was observed pre-FMP, extending continuously through the two-year period post-FMP. TWBC declined from - 3 to + 2 years relative to FMP, but both MON and TWBC increased during > + 2 years. The baseline age had an interaction effect on changes in WBC indicators during specific menopausal stages, except for TWBC. Individuals in different age subgroups showed distinct trajectories for NEUT, LYM and MON around the FMP. High baseline BMI had a synergistic effect on changes in specific menopause segments for TWBC, LYM, and MON. The impact of menopause on TWBC and LYM was postponed or counterbalanced in high BMI individuals. Individuals in three BMI subgroups experienced similar MON changes around FMP, and there were slight variations during < -4 years. CONCLUSIONS: Menopause was associated with count changes of peripheral WBC. The trajectories of various WBC types differ around menopause. Age and BMI affected WBC trajectory around menopause. The menopause period may represent a window of opportunity to promote immune health in middle-aged women.


Assuntos
Índice de Massa Corporal , Menopausa , Humanos , Feminino , Contagem de Leucócitos/estatística & dados numéricos , Contagem de Leucócitos/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Menopausa/sangue , Menopausa/fisiologia , Estudos Longitudinais , Adulto , China/epidemiologia , Estudos de Coortes , Neutrófilos
2.
Heliyon ; 10(17): e37011, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39286199

RESUMO

The flounder (Paralichthys olivaceus) is a highly nutritious, cultured bony fish with a high economic value. The health of the fish is closely related to its blood cells, which are critical for oxygen transport, natural defense, and immunity. The microstructures, classification, counting and size of peripheral blood cells in P. olivaceus were observed and measured by Wright-Giemsa staining, and the cytochemical characteristics of peripheral blood cells were investigated by different cytochemical staining methods including periodic acid-Schiff (PAS), Sudan black B (SBB), acid phosphatase (ACP), alkaline phosphatase (ALP), peroxidase (POX), and α-naphthol acetate esterase (NAE). Besides, the ultrastructures of different cells were detected by the transmission electron microscope. The results showed that erythrocytes, thrombocytes, lymphocytes, monocytes, and neutrophils constituted the peripheral blood cells in P. olivaceus. More heterochromatins were found in erythrocytes, thrombocytes and neutrophils; however, more organelles with fewer heterochromatins were found in monocytes. Endoplasmic reticulums and phagocytic vesicles were abundant in neutrophils. Lymphocytes were the most abundant in leukocytes, followed by monocytes and neutrophils. The cytochemical staining results showed that all leukocytes were positive for SBB. Most of the lymphocytes were positive for PAS, and monocytes were positive for PAS, ACP, and POX. As for neutrophils, ACP and POX were positive. Both monocytes and neutrophils showed positive for SBB, ACP and POX, indicating that the two kinds of cells play a vital role in phagocytosis and bactericidal action. Only lymphocytes were positive for ALP, indicating that they were important in inflammation and immune response. Some characteristics similarities in peripheral blood cells were showed in P. olivaceus just as the other fishes.

3.
Curr Res Transl Med ; 72(4): 103463, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39278153

RESUMO

BACKGROUND: The setting of normovolemic anemia is required for a variety of research applications, such as testing of novel medication for anemia treatment. Unfortunately, large animal models using full blood draw and replenishment with balanced electrolyte solution (BES) lead to bleeding complications, as coagulation factors and platelets are also drawn. We therefore aimed to establish a model of selective red blood cell (RBC) depletion to the main endpoint of hemoglobin (Hgb) levels of 4-6 g dL-1 using apheresis in sheep. METHODS: In vitro experiments were performed first to establish the apheresis protocol. In vivo, anesthetized ewes underwent a sham protocol without apheresis (n = 5) or apheresis (n = 4). Both groups were observed for the following six hours at a defined starting point (BE0) to compare Hgb, hematocrit (Hct), coagulation and clinical parameters. For statistical analysis, unpaired t-test with Welch`s correction was used. RESULTS: Hgb levels were effectively decreased by 51 % to mean Hgb of 4.4 g dL-1 in the apheresis group compared to 9.1 g dL-1 in sham (*p < 0.0001). Hct (11.2% vs 25.1 %, *p = 0.01) and RBCs (3.7 vs 8.2 × 106/µl, *p = 0.003) also decreased. The relative number of platelets compared to baseline was different (55.6 ± 10.6% vs. 100 ± 0 %, *p = 0.004), but no hemorrhage was observed. White blood cells (WBCs), lactate, prothrombin ratio and activated partial thromboplastin time (aPTT) remained within similar ranges. CONCLUSIONS: Critical normovolemic anemia without bleeding complications was successfully reached by selective RBC depletion in sheep. Investigations of physiological adaptations to severe anemia and pharmaceutical testing can be performed in large animals with depleted RBCs.

4.
Environ Pollut ; 362: 124921, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39265764

RESUMO

Zinc oxide nanoparticles (ZnO-NPs) are nanomaterials mainly produced and used worldwide. They translocate to circulatory systems from various exposure routes. While blood and endothelial cells are persistently exposed to circulating ZnO-NPs, the potential risks posed by ZnO-NPs to the cardiovascular system are largely unknown. Our study identified the potential risk of thrombosis and disturbance of the blood-brain barrier (BBB) by coagulant activity on red blood cells (RBCs) caused by ZnO-NPs. ZnO-NPs promoted the externalization of phosphatidylserine and the generation of microvesicles through an imbalance of intracellular mechanisms regulating procoagulant activity in human RBCs. The coagulation cascade leading to thrombin generation was promoted in ZnO-NPs-treated human RBCs. Combined with human RBCs, ZnO-NPs caused coagulant activity on isolated rat RBCs and rat venous thrombosis models. We identified the erythrophagocytosis of RBCs into brain endothelial cells via increased PS exposure induced by ZnO-NPs. Excessive erythrophagocytosis contributes to disrupting the BBB function of endothelial cells. ZnO-NPs increased the procoagulant activity of RBCs, causing venous thrombosis. Excessive erythrophagocytosis through ZnO-NPs-treated RBCs resulted in the dysfunction of BBB. Our study will help elucidate the potential risk ZnO-NPs exert on the cardiovascular system.

5.
Ecotoxicol Environ Saf ; 284: 116981, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39232297

RESUMO

Metal exposure has been reported to be associated with metabolic syndrome (MetS), however, the evidence remains inconclusive, particularly in elderly individuals. From May to July 2016, serum levels of 16 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) in 852 elderly individuals (≥65 years) residing in Wuhan, China. Biological detection and disease recognition were based on individual surveys conducted during health check-ups. Spearman's rank correlation analysis was performed to identify the correlation among serum metals. The data were Ln-transformed to fit a normal distribution for further analyses. Linear and logistic regression were applied to explore the associations between metals and diseases. Restricted cubic spline (RCS) analysis was utilized to examine dose-response relationships. The Weighted Quantile Sum (WQS) score was applied to determine the empirical weights of each heavy metal in the context of their combined effect on metabolic diseases. The prevalence of MetS, hypertension, diabetes, and hyperlipidemia were 46.36 %, 68.90 %, 24.65 %, and 21.60 %, respectively. Serum metal mixture was positively associated with the prevalence of MetS (OR = 1.92, 95 % CI: 1.30-2.82), hypertension (OR = 1.50, 95 % CI: 1.01-2.23), and diabetes (OR = 2.18, 95 % CI: 1.48-3.22). In single metal models, we found that serum zinc levels were associated with an increased risk of MetS, while rubidium had a protective effect against MetS. Interestingly, different metals had distinct effects on specific diseases in this study: lithium and barium were more likely to influence blood pressure, while selenium had a more significant effect on blood glucose. Lipids were more susceptible to the effects of zinc, selenium, and strontium. Platelet count (PLT) and lymphocyte count (LYM) mediated the association between selenium exposure and hyperlipidemia, while neutrophil count (NEU) mediated the relationship between serum rubidium exposure and MetS. Our findings offer valuable etiological insights into the relationship between serum heavy metals and the prevalence of MetS, suggesting that peripheral blood cells may play a mediating role in this association.

6.
S Afr Fam Pract (2004) ; 66(1): e1-e8, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39221724

RESUMO

BACKGROUND:  Red blood cell (RBC) transfusion is one of the most critical and expensive lifesaving treatment modalities. A clinical audit is a valuable instrument to determine whether transfusion practices align with the guidelines and identify knowledge deficiencies. The study aimed to evaluate the RBC transfusion practices and patient outcomes at the National District Hospital in Bloemfontein, South Africa, and to determine adherence to transfusion guidelines. METHODS:  A retrospective descriptive study was conducted. All blood transfusion registers in the hospital were used to identify transfusion episodes during the study period. Files were retrieved from the admissions office and information captured on a paper-based datasheet. The appropriateness of the transfusion and adherence to the South African transfusion guidelines were evaluated using specific criteria. RESULTS:  Of the 118 transfusion episodes during the study period, 78 files were retrieved and 76 included in the study. The patients' median age was 47 years (interquartile range [IQR]: 32-66 years), with human immunodeficiency viruses (HIV) (n = 34; 44.7%) being the most common comorbid condition. Pre-transfusion haemoglobin was documented for all patients with a median of 4.6 g/dL (IQR: 3.95 g/dL - 5.5 g/dL). The audit revealed that in 68.4% (n = 52) of the cases, the guidelines were applied appropriately. CONCLUSION:  The study described the blood transfusion practices and identified shortcomings when compared with the standard clinical guidelines.Contribution: The study highlights the importance of applying rationale, caution and consideration of the specific patient profile when performing transfusions.


Assuntos
Auditoria Clínica , Transfusão de Eritrócitos , Fidelidade a Diretrizes , Hospitais de Distrito , Humanos , África do Sul , Transfusão de Eritrócitos/estatística & dados numéricos , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Masculino , Adulto , Idoso , Guias de Prática Clínica como Assunto , Auditoria Médica
7.
J Robot Surg ; 18(1): 337, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39249162

RESUMO

Robotic surgery provides precise control, allowing for optimal dissection and cutting of tissues while minimizing bleeding. However, a significant drop in hemoglobin (Hb) after robot-assisted radical prostatectomy (RARP) is often recorded. The current study aimed to examine the postoperative Hb drop and its predictive factors in prostate cancer (PCa) patients who underwent RARP. From our tertiary care center's prospectively maintained database, all PCa patients who underwent RARP from January 2022 to January 2023 were identified. For each patient, baseline, anesthesiologic, and surgical characteristics, as well as blood samples before and after surgery, were collected. Multivariable linear and logistic regression models were fitted to investigate potential predictive factors of linear Hb drop or Hb drop ≥ 2 g/dl between preoperative and postoperative day (POD) one, after RARP. Overall, 110 RARP patients were enrolled. Considering the Hb, the median preoperative and POD1 values were 14.6 and 12.7 g/dl respectively (∆ = 1.9, p < 0.001); between POD2 and POD3, no statistically significant difference was recorded (12.4 vs 12.5 g/dl, ∆ = 0.1, p = 0.1). After multivariable analyses, age, BMI, prostate volume, nerve-sparing approach, anesthesia time, intraoperative fluids, intraoperative blood loss, and intraoperative diuresis did not show a statistically significant predictive value (all p > 0.05). The current prospective study showed a statistically significant Hb drop until POD1. After that, a quick stabilization of the Hb value was recorded. This reduction was not correlated with pre- and intraoperative variables. These observations might play an important role in postoperative inpatient RARP management, in both large and low-volume centers.


Assuntos
Hemoglobinas , Prostatectomia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Estudos Prospectivos , Hemoglobinas/análise , Hemoglobinas/metabolismo , Pessoa de Meia-Idade , Neoplasias da Próstata/cirurgia , Idoso , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Período Pós-Operatório
8.
Transfus Med ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39243178

RESUMO

BACKGROUND AND OBJECTIVES: Di (2-ethylhexyl) phthalate (DEHP) plasticizer must be removed from polyvinylchloride (PVC) medical devices due to toxicity. DEHP/PVC blood bags were shown to provide stable quality under blood component production and to create good storage conditions for red blood cells concentrate (RBC). It is important that substitution of the DEHP maintains the RBC quality during storage, which should be achieved with Di (isononyl) cyclohexane-1,2-dicarboxylate (DINCH), although substitution of the plasticizer has been challenging. MATERIALS AND METHODS: A DEHP-free Top & Bottom in-line RBC set was validated in a tertiary hospital blood bank facility. Volunteer blood donors were randomly allocated for blood collection into DINCH/PVC or DEHP/PVC set. The groups were additionally divided according to additive solution/filter combination: PAGGS-M + DINCH/PVC filter (only with DINCH/PVC set), and SAG-M + DINCH/PVC filter and SAG-M + DEHP/PVC filter (only with DEHP/PVC set). Processing and storage effects were assessed in all components. RESULTS: RBC concentrates, platelet concentrates and plasma that was processed and stored in DEHP-free set fulfilled European requirements for quality. The cells stored in PAGGS-M after filtration through DEHP-free PVC filter showed the same low haemolysis compared with conventional set at 49 days of storage. Platelets stored in DINCH/PVC bag provided a sufficient quality of platelets after 7 days of storage. Plasma maintained the coagulation factors during 12 months of storage. CONCLUSION: A new DINCH/PVC set allows production of blood components of satisfactory quality in DEHP-free environment.

9.
Biomed J ; : 100787, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39251135

RESUMO

We planned a series of experiments to investigate the possible role of spike protein of different SARS-CoV-2 variants in influencing erythrocyte biology. The values of erythrocyte count, hemoglobin, and mean corpuscular hemoglobin (MHC) did not vary across all samples challenged with both concentrations of the four different SARS-CoV-2 recombinant spike proteins. A significant increase in mean corpuscular volume (MCV) was observed with the recombinant SARS-CoV-2 Alpha and Delta spike proteins at both 2 and 20 ng/mL final concentrations. Red blood cell distribution width (RDW) values increased significantly in samples treated with 20 ng/mL of all SARS-CoV-2 recombinant spike proteins and reached the highest values in samples treated with Omicron recombinant spike protein. Blood smear revision evidenced hemagglutination and rouleaux in samples to which recombinant SARS-CoV-2 spike proteins were added, especially in those with Alpha and Delta variants.

10.
Hepat Med ; 16: 65-77, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247515

RESUMO

Purpose: Both hepatic iron accumulation and hemolysis have been identified as independent prognostic factor in alcohol-related liver disease (ALD); however, the mechanisms still remain poorly understood. We here demonstrate that hepatocytes are able to directly ingest aged and ethanol-primed red blood cells (RBCs), a process termed efferocytosis. Methods: Efferocytosis of RBCs was directly studied in vitro and observed by live microscopy for real-time visualization. RBCs pretreated with either CuSO4 or ethanol following co-incubation with Huh7 cells and murine primary hepatocytes. Heme oxygenase-1 (HO-1) and other targets were measured by q-PCR. Results: As shown by live microscopy, oxidized RBCs, but not intact RBCs, are rapidly ingested by both Huh7 cells and murine primary hepatocytes within 10 minutes. In some cases, more than 10 RBCs were seen within hepatocytes, surrounding the nucleus. RBC efferocytosis also rapidly induces HO1, its upstream regulator Nuclear factor erythroid 2-related factor 2 (Nrf2) and ferritin, indicating efficient heme degradation. Preliminary data further suggest that hepatocyte efferocytosis of oxidized RBCs is, at least in part, mediated by scavenging receptors such as ASGPR1. Of note, pretreatment of RBCs with ethanol but also heme and bilirubin also initiated efferocytosis. In a cohort of heavy human drinkers, a significant correlation of hepatic ASGPR1 with the heme degradation pathway was observed. Conclusion: We here demonstrate that hepatocytes can directly ingest and degrade oxidized RBCs through efferocytosis, a process that can be also triggered by ethanol, heme and bilirubin. Our findings are highly suggestive for a novel mechanism of hepatic iron overload in ALD patients.

11.
Br J Haematol ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39117989

RESUMO

The study of Ellsworth et al. (Br J Haematol, 2024) demonstrated the usefulness of oxygen gradient ektacytometry technique to better identify the physiological parameters that could increase the risk of sickling of red blood cells (RBCs) from sickle cell trait (SCT) carriers. Oxygen gradient ektacytometry combined with pH and osmolality modulations could help in identifying SCT carriers at risk for kidney disorders or exercise-related complications. Other factors than the percentages of haemoglobin S are probably involved in the propensity of RBCs from SCT carriers to sickle during deoxygenation. Commentary on: Ellsworth et al. Hypertonicity and/or acidosis induce marked rheological changes under hypoxic conditions in sickle trait red blood cells. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19669.

12.
Clin Exp Med ; 24(1): 181, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105953

RESUMO

Traditional manual blood smear diagnosis methods are time-consuming and prone to errors, often relying heavily on the experience of clinical laboratory analysts for accuracy. As breakthroughs in key technologies such as neural networks and deep learning continue to drive digital transformation in the medical field, image recognition technology is increasingly being leveraged to enhance existing medical processes. In recent years, advancements in computer technology have led to improved efficiency in the identification of blood cells in blood smears through the use of image recognition technology. This paper provides a comprehensive summary of the methods and steps involved in utilizing image recognition algorithms for diagnosing diseases in blood smears, with a focus on malaria and leukemia. Furthermore, it offers a forward-looking research direction for the development of a comprehensive blood cell pathological detection system.


Assuntos
Células Sanguíneas , Processamento de Imagem Assistida por Computador , Patologia Clínica , Patologia Clínica/métodos , Patologia Clínica/tendências , Células Sanguíneas/microbiologia , Células Sanguíneas/parasitologia , Células Sanguíneas/patologia , Malária/diagnóstico por imagem , Leucemia/diagnóstico por imagem , Algoritmos , Aprendizado de Máquina , Contagem de Células Sanguíneas , Humanos
13.
J Biomed Opt ; 29(8): 085001, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39165858

RESUMO

Significance: Fluorescent organic dyes provide imaging capabilities at cellular and sub-cellular levels. However, a common problem associated with some of the existing dyes such as the US FDA-approved indocyanine green (ICG) is their weak fluorescence emission. Alternative dyes with greater emission characteristics would be useful in various imaging applications. Complementing optical imaging, magnetic resonance (MR) imaging enables deep tissue imaging. Nano-sized delivery systems containing dyes with greater fluorescence emission as well as MR contrast agents present a promising dual-mode platform with high optical sensitivity and deep tissue imaging for image-guided surgical applications. Aim: We have engineered a nano-sized platform, derived from erythrocyte ghosts (EGs), with dual near-infrared fluorescence and MR characteristics by co-encapsulation of a brominated carbocyanine dye and gadobenate dimeglumine (Gd-BOPTA). Approach: We have investigated the use of three brominated carbocyanine dyes (referred to as BrCy106, BrCy111, and BrCy112) with various degrees of bromination, structural symmetry, and acidic modifications for encapsulation by nano-sized EGs (nEGs) and compared their resulting optical characteristics with nEGs containing ICG. Results: We find that asymmetric dyes (BrCy106 and BrCy112) with one dibromobenzene ring offer greater fluorescence emission characteristics. For example, the relative fluorescence quantum yield ( ϕ ) for nEGs fabricated using 100 µ M of BrCy112 is ∼ 41 -fold higher than nEGs fabricated using the same concentrations of ICG. The dual-mode nEGs containing BrCy112 and Gd-BOPTA show a nearly twofold increase in their ϕ as compared with their single optical mode counterpart. Cytotoxicity is not observed upon incubation of SKOV3 cells with nEGs containing BrCy112. Conclusions: Erythrocyte nano-ghosts with dual optical and MR characteristics may ultimately prove useful in various biomedical imaging applications such as image-guided tumor surgery where MR imaging can be used for tumor staging and mapping, and fluorescence imaging can help visualize small tumor nodules for resection.


Assuntos
Carbocianinas , Eritrócitos , Corantes Fluorescentes , Imageamento por Ressonância Magnética , Imagem Óptica , Imageamento por Ressonância Magnética/métodos , Eritrócitos/química , Corantes Fluorescentes/química , Carbocianinas/química , Imagem Óptica/métodos , Humanos , Meios de Contraste/química , Verde de Indocianina/química
14.
Physiol Meas ; 45(8)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39106894

RESUMO

Objective. The widespread adoption of Photoplethysmography (PPG) as a non-invasive method for detecting blood volume variations and deriving vital physiological parameters reflecting health status has surged, primarily due to its accessibility, cost-effectiveness, and non-intrusive nature. This has led to extensive research around this technique in both daily life and clinical applications. Interestingly, despite the existence of contradictory explanations of the underlying mechanism of PPG signals across various applications, a systematic investigation into this crucial matter has not been conducted thus far. This gap in understanding hinders the full exploitation of PPG technology and undermines its accuracy and reliability in numerous applications.Approach. Building upon a comprehensive review of the fundamental principles and technological advancements in PPG, this paper initially attributes the origin of PPG signals to a combination of physical and physiological transmission processes. Furthermore, three distinct models outlining the concerned physiological transmission processes are synthesized, with each model undergoing critical examination based on theoretical underpinnings, empirical evidence, and constraints.Significance. The ultimate objective is to form a fundamental framework for a better understanding of physiological transmission processes in PPG signal generation and to facilitate the development of more reliable technologies for detecting physiological signals.


Assuntos
Fotopletismografia , Processamento de Sinais Assistido por Computador , Fotopletismografia/métodos , Humanos , Volume Sanguíneo/fisiologia
15.
J Control Release ; 374: 425-440, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39103056

RESUMO

For medical emergencies, such as acute ischemic stroke, rapid drug delivery to the target site is essential. For many small molecule drugs, this goal is unachievable due to poor solubility that prevents intravenous administration, and less obviously, by extensive partitioning to plasma proteins and red blood cells (RBCs), which greatly slows delivery to the target. Here we study these effects and how they can be solved by loading into nanoscale drug carriers. We focus on fingolimod, a small molecule drug that is FDA-approved for treatment of multiple sclerosis, which has also shown promise in the treatment of stroke. Unfortunately, fingolimod has poor solubility and very extensive partitioning to plasma proteins and RBCs (in whole blood, 86% partitions to RBCs, 13.96% to plasma proteins, and 0.04% is free). We develop a liposomal formulation that slows the partitioning of fingolimod to RBCs and plasma proteins, enables intravenous delivery, and additionally prevents fingolimod toxicity to RBCs. The liposomal formulation nearly completely prevented fingolimod adsorption to plasma proteins (association with plasma proteins was 98.4 ± 0.4% for the free drug vs. 5.6 ± 0.4% for liposome-loaded drug). When incubated with whole blood in vitro, the liposomal formulation greatly slowed partitioning of fingolimod to RBCs and also eliminated deleterious effects of fingolimod on RBC rigidity, morphology, and hemolysis. In vivo, the liposomal formulation delayed fingolimod partitioning to RBCs for over 30 min, a critical time window for stroke. Fingolimod-loaded liposomes showed improved efficacy in a mouse model of post-stroke neuroinflammation, completely sealing the leaky blood-brain barrier (114 ± 11.5% reduction in albumin leak into the brain for targeted liposomes vs. 38 ± 16.5% reduction for free drug). This effect was only seen for liposomes modified with antibodies to enable targeted delivery to the site of action, and not in unmodified, long-circulating liposomes. Thus, loading fingolimod into liposomes prevented partitioning to RBCs and associated toxicities and enabled targeted delivery. This paradigm can be used for tuning the blood distribution of small molecule drugs for the treatment of acute illnesses requiring rapid pharmacologic intervention.

16.
World Neurosurg ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39182835

RESUMO

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. METHODS: We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic (ROC) curve. RESULTS: Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission CRP levels than those without these complications (P < 0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI and co-occurring CVS and DCI (P < 0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). CONCLUSIONS: Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39183144

RESUMO

BACKGROUND: Emergency transfusion may require the availability of O-negative red blood cell concentrates without pre-transfusion testing. At the Cliniques Universitaires Saint-Luc, the emergency department was used to having access to two decentralized O-negative red blood cell concentrates. This study aims to analyze the consumption of O-negative red blood cell concentrates in emergency situations both before and after the implementation of a novel strategy aiming at optimizing stocks. This strategy provides a combined allocation of one unit of O-positive red blood cell concentrate and one unit of O-negative red blood cell concentrate decentralized in the emergency department and reserve the transfusion of the negative unit only to under 45-year-old women and under 20-year-old men. MATERIALS AND METHODS: A retrospective study was conducted of the transfusion and medical records of all patients who received immediate transfusions in the emergency department without pre-transfusion testing between 2008 and 2022. RESULTS: A total of 193 patients received O red blood cell concentrates without pre-transfusion testing in emergency situations between 2008 and 2022. During the first 24 h of hospitalization, 354 O-negative units were transfused. Mean ratios of number of O-negative bags between 2008 and 2020 was 1.98 unit/patient. After implementation of the new strategy, the ratio in 2021 was 1.46 unit/patient and drastically decreased in 2022 to 0.79 unit/patient. CONCLUSION: In situations of emergency, allocating O-negative units only for women younger than 45 years and men younger than 20 years could have saved 85% of O-negative red blood cell concentrates transfused (303/354) yet balancing the immunological risk. Limiting the number of delocalized units of O-negative red blood cell concentrates in the emergency department seems to lower O-negative consumption. With this strategy, the units spared could have been transfused to patients with greater needs (e.g., sickle cell patients or chronically transfused patients).

18.
J Nucl Med Technol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137978

RESUMO

The early years of nuclear medicine included the development and clinical use of several in vitro or nonimaging procedures. The use of radionuclides as replacements for nonradioactive dyes brought improved accuracies and less subjective measurements to indicator dilution studies of body compartments such as the gastrointestinal system, lungs, urinary system, and vascular space. A popular nuclear medicine procedure was the radionuclide dilution method for quantitation of whole-blood volume or red blood cell volume or mass using 51Cr-labeled red blood cells-an important diagnostic element in patients suspected of having polycythemia vera, congestive heart failure, hypertension, shock, syncope, and other abnormal blood volume disorders. The radionuclide dilution method led to improved evaluation of red blood cell survival, which is important for clinical treatment planning in anemia and confirmation of splenic sequestration of damaged red blood cells. Although it was discovered that 51Cr was a chemically stable radiolabel of red blood cells after binding to intracellular hemoglobin, few nuclear medicine departments offered the clinical study for referring physicians because it required laboratory expertise for technologists, patient coordination, and a time-consuming procedure. The introduction of improved methods that are less time-consuming and have clinically acceptable results, along with the discontinuation of the sodium chromate 51Cr injection radiopharmaceutical by manufacturers, has consigned 51Cr red blood cells for red blood cell volume, mass, or survival evaluation to the list of retired nuclear medicine studies.

19.
Khirurgiia (Mosk) ; (8): 15-20, 2024.
Artigo em Russo | MEDLINE | ID: mdl-39140938

RESUMO

OBJECTIVE: To identify the factors associated with normal leukocyte count and C-reactive protein (CRP) in adults with acute appendicitis. MATERIAL AND METHODS: A retrospective cohort study included patients aged 18-60 years after surgeries for acute appendicitis. Convenience sampling was used to select medical records, and variables such as age, sex, weight, height, origin, self-medication, diabetes (DM2), high blood pressure (HBP), type of appendicitis, duration of illness, preoperative time, type of appendectomy, operative time, and hospital stay were analyzed. Patients were categorized into those with normal and abnormal inflammatory parameters. The SPSS version 28 software was used for analysis. RESULTS: We included 333 patients; 11.11% ones had normal inflammatory parameters. Both groups had mean age of approximately 33 years. Men comprised 56.76% and 57.43%in both groups, respectively. The abnormal group had shorter mean preoperative time, and catarrhal appendicitis was more common in the normal group. Multivariate analysis revealed that rural origin and self-medication were significantly associated with normal inflammatory parameters. CONCLUSION: The prevalence of normal inflammatory parameters in acute appendicitis patients was 11.11%. Rural origin, self-medication, shorter preoperative time, and catarrhal appendicitis were significantly associated with normal inflammatory parameters in this context.


Assuntos
Apendicectomia , Apendicite , Proteína C-Reativa , Humanos , Apendicite/cirurgia , Apendicite/sangue , Apendicite/diagnóstico , Adulto , Masculino , Feminino , Proteína C-Reativa/análise , Contagem de Leucócitos/métodos , Estudos Retrospectivos , Apendicectomia/métodos , Pessoa de Meia-Idade , Doença Aguda , Adolescente , Adulto Jovem
20.
BMC Med Genomics ; 17(1): 212, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143590

RESUMO

Non-coding RNA expression has shown to have cell type-specificity. The regulatory characteristics of these molecules are impacted by changes in their expression levels. We performed next-generation sequencing and examined small RNA-seq data obtained from 6 different types of blood cells separated by fluorescence-activated cell sorting of severe COVID-19 patients and healthy control donors. In addition to examining the behavior of piRNA in the blood cells of severe SARS-CoV-2 infected patients, our aim was to present a distinct piRNA differential expression portrait for each separate cell type. We observed that depending on the type of cell, different sorted control cells (erythrocytes, monocytes, lymphocytes, eosinophils, basophils, and neutrophils) have altering piRNA expression patterns. After analyzing the expression of piRNAs in each set of sorted cells from patients with severe COVID-19, we observed 3 significantly elevated piRNAs - piR-33,123, piR-34,765, piR-43,768 and 9 downregulated piRNAs in erythrocytes. In lymphocytes, all 19 piRNAs were upregulated. Monocytes were presented with a larger amount of statistically significant piRNA, 5 upregulated (piR-49039 piR-31623, piR-37213, piR-44721, piR-44720) and 35 downregulated. It has been previously shown that piR-31,623 has been associated with respiratory syncytial virus infection, and taking in account the major role of piRNA in transposon silencing, we presume that the differential expression patterns which we observed could be a signal of indirect antiviral activity or a specific antiviral cell state. Additionally, in lymphocytes, all 19 piRNAs were upregulated.


Assuntos
COVID-19 , Citometria de Fluxo , RNA Interferente Pequeno , SARS-CoV-2 , Humanos , COVID-19/genética , COVID-19/virologia , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/genética , SARS-CoV-2/genética , Masculino , Feminino , Pessoa de Meia-Idade , Monócitos/metabolismo , Adulto , Células Sanguíneas/metabolismo , RNA de Interação com Piwi
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA