Vitamin D, a crucial hormone in the homeostasis and metabolism of calcium bone, has lately been found to produce effects on other physiological and pathological processes genomically and ...non-genomically, including the cardiovascular system. While lower baseline vitamin D levels have been correlated with atherogenic blood lipid profiles, 25(OH)D supplementation influences the levels of serum lipids in that it lowers the levels of total cholesterol, triglycerides, and LDL-cholesterol and increases the levels of HDL-cholesterol, all of which are known risk factors for cardiovascular disease. Vitamin D is also involved in the development of atherosclerosis at the site of the blood vessels. Deficiency of this vitamin has been found to increase adhesion molecules or endothelial activation and, at the same time, supplementation is linked to the lowering presence of adhesion surrogates. Vitamin D can also influence the vascular tone by increasing endothelial nitric oxide production, as seen in supplementation studies. Deficiency can lead, at the same time, to oxidative stress and an increase in inflammation as well as the expression of particular immune cells that play a pivotal role in the development of atherosclerosis in the intima of the blood vessels, i.e., monocytes and macrophages. Vitamin D is also involved in atherogenesis through inhibition of vascular smooth muscle cell proliferation. Furthermore, vitamin D deficiency is consistently associated with cardiovascular events, such as myocardial infarction, STEMI, NSTEMI, unstable angina, ischemic stroke, cardiovascular death, and increased mortality after acute stroke. Conversely, vitamin D supplementation does not seem to produce beneficial effects in cohorts with intermediate baseline vitamin D levels.
Ongoing research in the field of pediatric oncology has led to an increased number of childhood cancer survivors reaching adulthood. Therefore, ensuring a good quality of life for these patients has ...become a rising priority. Considering this, the following review focuses on summarizing the most recent research in anthracycline-induced cardiac toxicity in children treated for leukemia. For pediatric cancers, anthracyclines are one of the most used anticancer drugs, with over half of the childhood cancer survivors believed to have been exposed to them. Anthracyclines cause irreversible cardiomyocyte loss, leading to chronic, progressive heart failure. The risk of developing cardiotoxicity has been known to increase with the treatment-free interval and total cumulative dose. However, because of individual variations in anthracycline metabolism, it has recently been shown that there is no risk-free dose. Moreover, studies have shown that diagnosing anthracycline-induced cardiomyopathy in the symptomatic phase is associated with poor treatment response and prognosis. Thus, early and systematic evaluation of these patients is crucial to allow optimal therapeutic intervention. Although currently echocardiographic assessment of left ventricle ejection fraction and cardiac biomarker evaluation are being used for cardiac function monitoring in oncologic patients, there is no established follow-up and treatment protocol for these patients, and these methods are neither specific nor sensitive for identifying early cardiac dysfunction. All things considered, the need for ongoing research in the field of pediatric cardiooncology is crucial to offer these patients a chance at a good quality of life as adults.
The use of gentamicin (GM) is limited due to its nephrotoxicity mediated by oxidative stress. This study aimed to evaluate the capacity of a flavonoid-rich extract of
L. elderflower (SN) to inhibit ...lipoperoxidation in GM-induced nephrotoxicity. The HPLC analysis of the SN extract recorded high contents of rutin (463.2 ± 0.0 mg mL
), epicatechin (9.0 ± 1.1 µg mL
), and ferulic (1.5 ± 0.3 µg mL
) and caffeic acid (3.6 ± 0.1 µg mL
). Thirty-two Wistar male rats were randomized into four groups: a control group (C) (no treatment), GM group (100 mg kg
bw day
GM), GM+SN group (100 mg kg
bw day
GM and 1 mL SN extract day
), and SN group (1 mL SN extract day
). Lipid peroxidation, evaluated by malondialdehyde (MDA), and antioxidant enzymes activity-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX)-were recorded in renal tissue after ten days of experimental treatment. The MDA level was significantly higher in the GM group compared to the control group (
< 0.0001), and was significantly reduced by SN in the GM+SN group compared to the GM group (
= 0.021). SN extract failed to improve SOD, CAT, and GPX activity in the GM+SN group compared to the GM group (
> 0.05), and its action was most probably due to the ability of flavonoids (rutin, epicatechin) and ferulic and caffeic acids to inhibit synthesis and neutralize reactive species, to reduce the redox-active iron pool, and to inhibit lipid peroxidation. In this study, we propose an innovative method for counteracting GM nephrotoxicity with a high efficiency and low cost, but with the disadvantage of the multifactorial environmental variability of the content of SN extracts.
The non-steroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in knee OA (osteoarthritis) treatment. Despite their efficiency in pain and inflammation alleviation, NSAIDs accumulate in ...the environment as chemical pollutants and have numerous genetic, morphologic, and functional negative effects on plants and animals. Ultrasound (US) therapy can improve pain, inflammation, and function in knee OA, without impact on environment, and with supplementary metabolic beneficial effects on cartilage compared to NSAIDs. These features recommend US therapy as alternative for NSAIDs use in knee OA treatment.
Wolcott-Rallison syndrome is a rare cause of permanent neonatal diabetes mellitus caused by mutations in the eukaryotic translation initiation factor 2 alpha kinase 3 gene (EIF2AK3). Individuals ...affected by this disorder have severe hyperglycemia, pancreatic failure, and bone abnormalities and are prone to severe and life-threatening episodes of liver failure. This report illustrates the case of a 2-month-old infant with extreme hyperglycemia and severe diabetic ketoacidosis. Acute management was focused on correcting severe acidosis. Further management aimed to obtain stable blood glucose levels, balancing the patient’s need for comfort and lack of distress with the clinicians’ need for adequate information regarding the patient’s glycemic control. Genetic testing of the patient and his parents confirmed the diagnosis. The follow-up for 18 months after diagnosis is detailed, illustrating both the therapeutic success of subcutaneous insulin therapy and the ongoing complications that patients with Wolcott-Rallison syndrome are subject to.
Background: Febrile neutropenia (FN) remains one of the most challenging problems in medical oncology and is a very severe side effect of chemotherapy. Its late consequences, when it is recurrent or ...of a severe grade, are dose reduction and therapy delays. Current guidelines allow the administration of granulocyte-colony-stimulating factors (G-CSF) for profound FN (except for the case when a pegylated form of G-CSF is administrated with prophylactic intention) in addition to antibiotics and supportive care. Methods: This is a prospective study that included 96 patients with confirmed malignancy, treated with chemotherapy, who developed FN during their oncological therapy, and were hospitalized. They received standard treatment plus a dose of G-CSF of 16 µg/Kg/day IV continuous infusion. Results: The gender distribution was almost symmetrical: Male patients made up 48.96% and 51.04% were female patients, with no significance on recovery from FN (p = 1.00). The patients who received prophylactic G-CSF made up 20.21%, but this was not a predictive or prognostic factor for the recovery time from aplasia (p = 0.34). The median chemotherapy line where patients with FN were included was two and the number of previous chemotherapy cycles before FN was three. The median serological number of neutrophils (PMN) was 450/mm3 and leucocytes (WBC) 1875/mm3 at the time of FN. Ten patients possess PMN less than 100/mm3. The median time to recovery was 25.5 h for 96 included patients, with one failure in which the patient possessed grade 5 FN. Predictive factors for shorter recovery time were lower levels of C reactive protein (p < 0.001) and procalcitonin (p = 0.002) upon hospital admission and higher WBC (p = 0.006) and PMN (p < 0.001) at the time of the provoking cycle of chemotherapy for FN. The best chance for a shorter duration of FN was a short history of chemotherapy regarding the number of cycles) (p < 0.0001). Conclusions: Continuous IV administration of G-CSF could be an alternative salvage treatment for patients with profound febrile neutropenia, with a very fast recovery time for neutrophiles.
The aim of the study was to assess the effects of therapeutic ultrasound (US) on oxidative stress (OS)-induced changes in cultured human chondrocytes (HCH). For this, monolayer HCH were randomized in ...three groups: a control group (CG), a group exposed to OS (OS group), and a group exposed to US and OS (US-OS group). US exposure of the chondrocytes was performed prior to OS induction by hydrogen peroxide. Transmission electron microscopy (TEM) was used to assess the chondrocytes ultrastructure. OS and inflammatory markers were recorded. Malondialdehyde (MDA) and tumor necrosis factor (TNF)-α were significantly higher (p < 0.05) in the OS group than in CG. In the US-OS group MDA and TNF-α were significantly lower (p < 0.05) than in the OS group. Finally, in the US-OS group MDA and TNF-α were lower than in CG, but without statistical significance. TEM showed normal chondrocytes in CG. In the OS group TEM showed necrotic chondrocytes and chondrocytes with a high degree of vacuolation and cell organelles damages. In the US-OS group the chondrocytes ultrastructure was well preserved, and autophagosomes were generated. In conclusion, US could protect chondrocytes from biochemical (lipid peroxidation, inflammatory markers synthesis) and ultrastructural changes induced by OS and could stimulate autophagosomes development.
Granulocyte-colony stimulating factor (G-CSF) is a glycoprotein, the second CSF, sharing some common effects with granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin-3 (IL-3) and ...interleukin-5 (IL-5). G-CSF is mainly produced by fibroblasts and endothelial cells from bone marrow stroma and by immunocompetent cells (monocytes, macrophages). The receptor for G-CSF (G-CSFR) is part of the cytokine and hematopoietin receptor superfamily and G-CSFR mutations cause severe congenital neutropenia. The main action of G-CSF - G-CSFR linkage is stimulation of the production, mobilization, survival and chemotaxis of neutrophils, but there are many other G-CSF effects: growth and migration of endothelial cells, decrease of norepinephrine reuptake, increase in osteoclastic activity and decrease in osteoblast activity. In oncology, G-CSF is utilized especially for the primary prophylaxis of chemotherapy-induced neutropenia, but it can be used for hematopoietic stem cell transplantation, it can produce monocytic differentiation of some myeloid leukemias and it can increase some drug resistance. The therapeutic indications of G-CSF are becoming more and more numerous: non neutropenic patients infections, reproductive medicine, neurological disturbances, regeneration therapy after acute myocardial infarction and of skeletal muscle, and hepatitis C therapy.
Bevacizumab or cetuximab represent the standard treatment in association with classical chemotherapy in confirmed metastatic colorectal cancer (mCRC). Bevacizumab could be continued after the first ...disease progression with an overall survival (OS) advantage, compared to chemotherapy alone, but the optimal dose remains a debatable issue.
In a retrospective analysis of mCRC patients treated with bevacizumab, we selected patients with administration beyond progression, and stratified them according to the dose received- same dose bevacizumab (SDB) as first-line chemotherapy or double dose bevacizumab (DDB). For each group we evaluated OS, time to treatment failure (TTF) and progression-free survival in the first-line (PFS1) and in the second-line (PFS2).
In the first-line therapy, oxaliplatin backbone regimen was used in 73% SDB, compared with 22.5% DDB patients, while irinotecan was used in 75% DDB and 27% SDB patients. Second-line oxaliplatin was given to 50% DDB and 29.7% SDB patients, while irinotecan was administered to 47.5% DDB and 70.3% SDB patients. The median values were: OS - 41 months in the DDB group and 25 months in the SDB group (p = 0.01); TTF - 24 months in the DDB group and 19 months in the SDB group (p=0.009); PFS1 - 17 months in the DDB group and 12 months in the SDB group (p=0.008); PFS2 - 9 months in the DDB group and 5 months in the SDB group (p = 0.03).
Doubling the dose of bevacizumab at progression seems to provide OS and PFS advantage for mCRC patients.
The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from ...plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4-6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (
= 0.007 **), miR-146a-5p (
= 0.036 *), miR-221-3p (
= 0.047 *), and miR-484 (
= 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (
= 0.008 **), miR-143-3p (
= 0.009 **), miR-221-3p (
= 0.016 *), and miR-486-5p (
= 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (
= 0.003 **) and miR-486-5p (
= 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.
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