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Inflammatory mediators in the frontal lobe of patients with mixed and vascular dementia.

Vascular dementia (VaD) accounts for about 20% of all dementias, and vascular risk is a key factor in more than 40% of people with Alzheimer's disease (AD). Little is known about inflammatory processes in the brains of these individuals. We have examined inflammatory mediators (interleukin (IL)-1beta, IL-1alpha, IL-6 and tumour necrosis factor alpha) and chemokines (macrophage inflammatory protein 1, monocyte chemo-attractant protein (MCP)-1 and granulocyte macrophage colony-stimulating factor) in brain homogenates from grey and white matter of the frontal cortex (Brodmann area 9) from patient

Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice.

Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood. Previous studies using crude toxin preparations associated ET with subcutaneous edema, and ET-deficient strains of B. anthracis showed a reduction in virulence. We report the first comprehensive study of ET-induced pathology in an animal model. Highly purified ET caused death in BALB/cJ mice at lower doses and more rapidly than previously seen with the other major B. anthracis virulence factor, let

Immunologic characteristics of cytokines in otitis media with effusion.

Levels of cytokines, interleukin (IL)-1 alpha, IL-1 beta, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were investigated in samples of the middle ear effusions (MEEs) from 144 ears with otitis media with effusion (OME) by enzyme-linked immunosorbent assay, followed by cytologic analysis. Middle ear effusions of the acute purulent type contained a significantly higher concentration of cytokines compared with normal control sera (p < .001). Cytokines were observed at lower levels in MEE in adults than in children. Tests of children at the chronic sta

K. pneumoniae and M. smegmatis infect epithelial cells via different strategies.

BACKGROUND: As the first line of defense, epithelial cells play a vital role in the initiation and control of both innate and adaptive immunity, which participate in the development of disease. Despite its therapeutic significance, little is understood about the specific interaction between pathogenic microorganisms and lung epithelial cells. METHODS: In this study, we performed a head-to-head comparison of the virulence and infection mechanisms of Klebsiella pneumoniae (K. pneumoniae) and Mycobacterium smegmatis (M. smegmatis), which represent Gram-negative/positive respiratory pathogens, re

Differential regulation of cytokine and chemokine expression by MK2 and MK3 in airway smooth muscle cells.

BACKGROUND: Airway smooth muscle (ASM) contributes to local inflammation and plays an immunomodulatory role in airway diseases. This is partially regulated by p38 mitogen-activated protein kinase (MAPK), which further activates two closely related isoforms of the MAPK-activated protein kinases (MKs), MK2 and MK3. The MKs have similar substrate specificities but less is known about differences in their functional responses. This study was undertaken to identify differential downstream inflammatory targets of MK2 and MK3 signaling and assess cross-talk between the MAPK pathway and NF-κB signalin

Enhanced prognosis of acute myeloid leukaemia patients with dmCEBPAbZIP -inf mutations: Insights from a multicentre Chinese cohort study.

The 2022 European LeukemiaNet (ELN) recommendation redefined favourable-risk CCAAT/enhancer binding protein alpha (CEBPA)-mutated acute myeloid leukaemia (AML) by in-frame C-terminal basic leucine zipper domain (bZIP) mutations rather than double CEBPA mutations. We analysed 411 CEBPA-mutated AML patients from six Chinese centres, classified as single-mutant CEBPAbZIP-other (smCEBPAbZIP-other; n = 38), smCEBPAbZIP-inf (n = 39), double-mutant CEBPAother (dmCEBPAother; n = 37) and dmCEBPAbZIP-inf (n = 297). DmCEBPAbZIP-inf patients were younger, had more de novo AML and showed distinct co-mutati

Immunotherapy for invasive Candida infections: Translating host-directed strategies into clinical practice.

BACKGROUND: Candida infections are a leading cause of invasive fungal disease (IFD), especially among critically ill and immunocompromised p … ellular approaches. Cytokine-based therapies, including interferon-gamma and granulocyte/macrophage colony-stimulating factors, aim to restore impaired innate immunity and have demonstrated preliminary clinical benefits in selected populations. Immune checkpoint inhibitors represent a novel strategy to reverse T-cell exhaustion, supported by preclinical data but with limite …

Association of social determinants of health and all-cause mortality among individuals across cardiovascular-kidney-metabolic stages 0-4: a nationwide prospective cohort study.

Clozapine remains the antipsychotic of choice for refractory schizophrenia despite its propensity for serious blood disorders. When neutropenia or agranulocytosis occur in people taking clozapine, cessation of treatment is mandated and relapse often results. Because such patients are usually unresponsive to other antipsychotics, many clinicians consider restarting clozapine, despite the risks involved. However, the risks of clozapine rechallenge vary according to the cause and nature of the blood dyscrasia. Neutropenia can arise because of factors unrelated or indirectly related to clozapine t

Efficacy and safety of same-day versus next-day administration of PEG-rhG-CSF for the prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia in patients with breast cancer: a retrospective cohort study.

OBJECTIVES: Polyethylene glycol recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are used to prevent or treat chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). This study aimed to compare the efficacy and safety of same-day versus next-day PEG-rhG-CSF administration following chemotherapy and the effects of 3 mg versus 6 mg dosages. METHODS: We retrospectively analyzed cohort data of patients with breast cancer who underwent chemotherapy and received PEG-rhG-CSF either within 24 h (same-day group) or 24 h (next-day group) after chemotherapy. The incid…

A Multiomic Analysis to Identify Drivers of Subclinical Vascular Disease in Systemic Lupus Erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) increases cardiovascular disease (CVD) risk, and this is not explained by traditional risk factors. Characterization of blood immunologic signatures that associate with subclinical CVD and predict its progression has been challenging and may help identify subgroups at risk. METHODS: Patients with SLE (n = 77) and healthy controls (HCs) (n = 27) underwent assessments of arterial stiffness, vascular wall inflammation, and coronary atherosclerosis burden with cardio-ankle vascular index (CAVI); fluorodeoxyglucose-positron emission tomography/computed

Baseline inflammation indexes and neutrophil-to-LDH ratio for prediction of the first mobilization failure without plerixafor-based regimens in multiple myeloma and lymphoma patients: A single-center retrospective study.

BACKGROUND: Many factors were identified for mobilization failure (MF) in autologous hematopoietic stem-cell transplantation. To our knowledge, this is the first study to investigate the efficacy of baseline inflammation indexes and neutrophil-to-lactate dehydrogenase (LDH) ratio to predict MF in multiple myeloma (MM) and lymphoma. METHODS: A total of 240 patients with lymphoma or MM hospitalized between January 2014 and June 2022 for the first stem cell mobilization were included in this retrospective single-center study. We evaluated the impact of baseline demographic, clinical, and laborat

Changes in Urinary Biomarkers of Organ Damage, Inflammation, Oxidative Stress, and Bone Turnover Following a 3000-m Time Trial.

Strenuous exercise induces organ damage, inflammation, and oxidative stress. Currently, to monitor or investigate physiological conditions, blood biomarkers are frequently used. However, blood sampling is perceived to be an invasive method and may induce stress. Therefore, it is necessary to establish a non-invasive assessment method that reflects physiological conditions. In the present study, we aimed to search for useful biomarkers of organ damage, inflammation, oxidative stress, and bone turnover in urine following exercise. Ten male runners participated in this study and performed a 3000-

Mediators of Neuropathic Pain; Focus on Spinal Microglia, CSF-1, BDNF, CCL21, TNF-α, Wnt Ligands, and Interleukin 1β.

Intractable neuropathic pain is a frequent consequence of nerve injury or disease. When peripheral nerves are injured, damaged axons undergo Wallerian degeneration. Schwann cells, mast cells, fibroblasts, keratinocytes and epithelial cells are activated leading to the generation of an "inflammatory soup" containing cytokines, chemokines and growth factors. These primary mediators sensitize sensory nerve endings, attract macrophages, neutrophils and lymphocytes, alter gene expression, promote post-translational modification of proteins, and alter ion channel function in primary afferent neurons

Impact of the COVID-19 pandemic on health care activities at a Uruguayan mastology unit.

PURPOSE: Health emergency due to COVID-19 started in Uruguay on March 13, 2020; our mastology unit tried to ensure adequate oncological care … djuvant CT, 9 (64.3%) continued with the same regimen with the addition of prophylactic granulocyte-colony-stimulating factors (G-CSF), and 5 (35.7%), who were receiving weekly paclitaxel, continued the treatment with no changes. Of the seven patients that were on palliative CT, 2 (28.5%) continued the treatment with the addition of G-CSF, 3 (42.8%) continued with weekly ca …

Molecular Profile of Barrett's Esophagus and Gastroesophageal Reflux Disease in the Development of Translational Physiological and Pharmacological Studies.

Barrett's esophagus (BE) is a premalignant condition caused by gastroesophageal reflux disease (GERD), where physiological squamous epithelium is replaced by columnar epithelium. Several in vivo and in vitro BE models were developed with questionable translational relevance when implemented separately. Therefore, we aimed to screen Gene Expression Omnibus 2R (GEO2R) databases to establish whether clinical BE molecular profile was comparable with animal and optimized human esophageal squamous cell lines-based in vitro models. The GEO2R tool and selected databases were used to establish human BE

Monocentric Analysis of the Effectiveness and Financial Consequences of the Use of Lenograstim versus Filgrastim for Mobilization of Peripheral Blood Progenitor Cells in Patients with Lymphoma and Myeloma Receiving Chemotherapy and Autologous Stem Cell Transplantation.

PurposeGranulocyte-colony stimulating factors (G-CSFs) are widely used to mobilize CD34+ stem cells and to support the engraftment after hematopoietic stem cell transplantation (HSCT). A budget impact analysis and an incremental cost-effectiveness study of two G-CSFs (Lenograstim and Filgrastim biosimilar), considering engraftment, number of hospitalization days and number of G-CSF vials administered were performed.Patients and methodsBetween 2009 and 2016, 248 patients undergoing autologous HSCT have been evaluated and divided into three groups (100 Leno-Leno, 93 Leno-Fil, 55 Fil-Fil) accordi

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… Introduction In the current clinical practice, dose-intensive chemotherapy followed by peripheral blood stem cell transplantation (PBSCT) is a procedure commonly performed in the treatment of a variety of hematological malignancies. 1 , 2 Use of granulocyte-colony stimulating factor (G-CSF)-mobilized … Concerns about the use of biosimilars granulocyte colony-stimulating factors for the mobilization of stem cells in normal donors position of the World Marrow Donor Association. Haematologica . 2011;96(7):942–947. doi: 10.3324/haematol.2011.045740 16. …

Alterations of multiple peripheral inflammatory cytokine levels after repeated ketamine infusions in major depressive disorder.

Increasing evidence has demonstrated that inflammatory cytokines play an important role in major depressive disorder (MDD) and are associated with treatment outcomes. Few studies have explored the trajectories of multiple inflammatory cytokines after repeated ketamine infusions in MDD. In this study, we conducted a secondary analysis to investigate the impact of ketamine on the modulation of the inflammatory pathway in depression and whether this pathway contributes to the antidepressant properties of ketamine. A total of 60 patients with depression received six ketamine infusions (0.5 mg/kg)

Cervus and cucumis peptides ameliorates bone erosion in experimental arthritis by inhibiting osteoclastogenesis.

OBJECTIVE: Rheumatoid arthritis is an autoimmune disease characterised by inflammation and bone loss, leading to joint destruction and deformity. The cervus and cucumis polypeptide (CCP) injection, one of the traditional Chinese medicine injections combined extracts from deer horn and sweet melon seeds, is widely used to treat arthritis and bone fracture in China. The present study investigated the therapeutic efficacy and mechanism of CCP on pathological immune cells and bone homoeostasis in rodent experimental arthritis. METHODS: The effects of CCP (4 mg/kg and 2 mg/kg) on clinical arthriti

The ratios of pro-inflammatory to anti-inflammatory cytokines in the serum of chronic periodontitis patients with and without type 2 diabetes and/or smoking habit.

OBJECTIVE: This study assessed the impact of chronic periodontitis (CP) and CP associated with type 2 diabetes mellitus (DM) and/or smoking on the serum ratios of pro- to anti-inflammatory cytokines. MATERIALS AND METHODS: Subjects were assigned into one of the following groups: control (n = 25, non-diabetic non-smokers with no history of periodontitis), CP (n = 26, non-diabetic non-smokers with CP), DMCP (n = 30, non-smokers with DM and CP), SCP (n = 27, non-diabetic smokers with CP), and SDMCP (n = 22, smokers with type 2 DM and CP). Serum levels of 18 cytokines were measured using multiple

How should we manage low-dose methotrexate-induced pancytopenia in patients with rheumatoid arthritis?

Low-dose methotrexate (ld-MTX) that is administered during rheumatoid arthritis (RA) treatment has hematological adverse effects such as pancytopenia, although rare. Although well-established and widely used for hematological adverse effects caused by high-dose MTX, leucovorin (folinic acid) treatment does not have an agreed-upon administration for ld-MTX-induced pancytopenia. Here, we aimed to figure out whether there was any difference in response time between the regimens with and without folinic acid prescribed to our patients who developed pancytopenia while on MTX therapy, and to identif