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The American Journal of the Medical... Jan 2023Ischemia-reperfusion injury (IRI), which involves severe inflammation and edema, is an inevitable feature of the lung transplantation process and leads to primary graft...
BACKGROUND
Ischemia-reperfusion injury (IRI), which involves severe inflammation and edema, is an inevitable feature of the lung transplantation process and leads to primary graft dysfunction (PGD). The activation of aquaporin 1 (AQP1) modulates fluid transport in the alveolar space. The current study investigated the role of AQP1 in ischemia-reperfusion (IR)-induced lung injury.
METHODS
A mouse model of lung IR was established by clamping the left lung hilar for 1 h and released for reperfusion for 24 h. The AQP1 inhibitor acetazolamide (AZA) was administered 3 days before lung ischemia with a dose of 100 mg/kg per day via gavage. Lung injury was evaluated using the ratio of wet-to-dry weight, peripheral bronchial epithelial thickness, degree of angioedema, acute lung injury score, neutrophil infiltration, and cytokine concentrations in bronchoalveolar lavage fluid.
RESULTS
Compared with sham treatment, ischemia with no reperfusion (IR 0h) and ischemia with reperfusion for 24 h (IR 24 h) significantly upregulated AQP1 expression, increased the wet/dry weight ratio, angioedema, neutrophil infiltration and cytokine production (interleukin -6 and tumor necrosis factor -α) and thickened the peripheral bronchial epithelium. AZA exacerbated inflammation and pulmonary edema.
CONCLUSION
AQP1 may exert a protective effect against IR-induced lung injury, which could be attributed to alleviating pulmonary edema and inflammation. AQP1 upregulation might be a potential application to alleviate lung IRI and decrease the incidence of PGD.
Topics: Mice; Animals; Aquaporin 1; Pulmonary Edema; Lung; Reperfusion Injury; Acute Lung Injury; Lung Diseases; Cytokines; Ischemia; Inflammation; Tumor Necrosis Factor-alpha; Angioedema
PubMed: 36075463
DOI: 10.1016/j.amjms.2022.08.017 -
European Journal of Pharmacology Jul 2020Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present...
Vitamin D (VD3, cholecalciferol), besides its role on bone calcium homeostasis, has also been shown to present anti-inflammatory actions. The objectives of the present work were to further extend these findings, focusing onVD3action mechanisms at the molecular level and onits central and peripheral effects. For that, VD3 antinociceptive and mainly anti-inflammatory activities were evaluated by acute models of nociception (formalin test) and inflammation (carrageenan-induced paw edema), in mice pretreated orally for 7 days with VD3 (0.5 and 1.0 mg/kg). Afterwards, the edematous paws were evaluated by immunohistochemical assays for TNF-alpha. In addition, brains from mice pretreated with VD3, at the same conditions, were harvested for iNOS andCOX-2 immunohistochemical (IHC) assays. The anti-inflammatory effect of VD3 on human neutrophil degranulation was evaluated by the release of myeloperoxidase (MPO) activity, as well as by the reactive oxygen species production. VD3 significantly reduced the licking time in the formalin test, at the second phase (inflammatory pain). VD3 also reduced the edema volume and the number of polymorphonuclear (PMN) cells, as well as the TNF-alpha expression in the edematous paws, compared with the control group. Furthermore, VD3 significantly decreased iNOS and COX-2 expressions in brain areas, such as hippocampus and prefrontal cortex, and inhibited the degranulation of activated neutrophils by the reduction of ROS production and MPO release. Based in these results, VD3 presents anti-inflammatory and antioxidative effects, manifested at peripheral and central sites as showed in the present work for the first time.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain; Carrageenan; Cyclooxygenase 2; Edema; Formaldehyde; Humans; Male; Mice; Neutrophils; Nitric Oxide Synthase Type II; Pain; Pain Measurement; Peroxidase; Reactive Oxygen Species; Vitamin D; Vitamins
PubMed: 32360837
DOI: 10.1016/j.ejphar.2020.173099 -
International Immunopharmacology Jun 2022Vincristine and paclitaxel are widely used chemotherapeutic drugs for the treatment of brain tumors, breast cancer, leukemia, lymphomas, and malignant solid tumors....
Vincristine and paclitaxel are widely used chemotherapeutic drugs for the treatment of brain tumors, breast cancer, leukemia, lymphomas, and malignant solid tumors. Though, these drugs are associated with some severe adverse effects including peripheral neuropathic pain. The anti-nociceptive and anti-inflammatory properties of the 7-Hydroxyflavone (7HF) were evaluated in the mice using thermally- and chemically-induced nociception, naloxone antagonistic test, and carrageenan-induced paw edema models. Initially, the in-vitro cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitory assays were carried out. Peripheral neuropathic pain was induced in the Sprague Dawley (SD) rats by administration of paclitaxel (4 mg/kg) and vincristine (200 µg/kg) on days 1, 3, 5, 7, and 9, respectively. The protective effect of 7HF was assessed against the chemotherapy-induced peripheral neuropathy in the rats. Moreover, the expression of the inflammatory mediators in the spinal cord was investigated through RT-PCR. In addition, a computational study was performed to find the potential therapeutic targets and the binding mechanism of 7HF. The 7HF caused concentration-dependent inhibition of COX-2 and 5-LOX, it attenuated the nociceptive pain, carrageenan-induced paw edema, and the development of mechanical and cold allodynia, and hyperalgesia dose-dependently without causing motor coordination deficit. Likewise, the 7HF decreased the vincristine-induced increased expression of different inflammatory mediators including COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and nuclear factor-kappa B (NF-κB). The computational study showed the effective interactions of 7HF with the binding sites of NF-κB, COX-2, and 5-LOX, exert its inhibitory activities. These findings reveal that the 7HF has anti-nociceptive, anti-inflammatory, and anti-neuropathic potentials.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Carrageenan; Cyclooxygenase 2; Cytokines; Edema; Flavonoids; Hyperalgesia; Inflammation Mediators; Mice; NF-kappa B; Neuralgia; Paclitaxel; Rats; Rats, Sprague-Dawley; Vincristine
PubMed: 35276461
DOI: 10.1016/j.intimp.2022.108674 -
Pharmacogenomics and Personalized... 2021Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5...
BACKGROUND
Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5 (CYP3A4/5) in the liver. Peripheral edema emerges as the major adverse drug reaction to amlodipine and is the primary reason for discontinuation of amlodipine therapy. However, genetic changes in may lead to changes in the tolerability of amlodipine.
PURPOSE
In this study, we were interested whether variants in CYP3A5 have a role to play in amlodipine-induced peripheral edema.
METHODS
A total number of 240 Chinese Han patients that have experienced hypertension were included in the study. Sixty-four patients had experienced amlodipine-induced peripheral edema, while the remaining 176 patients with no history of edema formed the control group. Twenty-four single-nucleotide polymorphisms (SNPs) of gene were sequenced by targeted region sequencing method. The relationship of these genetic variants with amlodipine-induced peripheral edema risk was assessed using logistic regression.
RESULTS
The allele frequencies of (rs15524), (rs4646453) and (rs776746) were significantly different between cases and controls (<0.05). The (CC) or (AA) carriers showed an increased risk of amlodipine-induced peripheral edema in dominant model. Meanwhile, patients carrying (AC/AA) showed a reduced risk of peripheral edema. Furthermore, we found a strong linkage disequilibrium among rs15524, rs4646453 and rs776746.
CONCLUSION
Our study reveals for the first time that and were associated with amlodipine-induced peripheral edema in Chinese Han patients with hypertension. However, further studies comprising larger number of samples, more related genes and other factors are wanted.
PubMed: 33564260
DOI: 10.2147/PGPM.S291277 -
Acta Informatica Medica : AIM : Journal... Dec 2022Retinitis pigmentosa (RP) is a set of inherited rod-cone degenerative diseases that clinically presents with similar signs and symptoms. Mutations in one of more than 70... (Review)
Review
BACKGROUND
Retinitis pigmentosa (RP) is a set of inherited rod-cone degenerative diseases that clinically presents with similar signs and symptoms. Mutations in one of more than 70 genes are involved. Patients will commonly present with bone-spicule pigment formation, waxy optic nerve pallor, and attenuated blood vessels in the posterior pole.Symptoms often begin with progressive night blindness, mid-peripheral visual field defects, and eventual tunnel vision. Central vision loss will ultimately occur following loss of rod function. Complete blindness is uncommon.
OBJECTIVE
The aim of this article is to present two cases of retinitis pigmentosa (mother and daughter) trough optalmologic exams in our clinic. The next aim it to show how to menage a low vision service and to treat cystoid macular oedema as a complication of retinitis pigmentosa.
METHODS
All medical reports are shown in this article. Every diagnostic tool as well as report is a part from our archived history of the patients and has been throughly analysed. We also reviewed available literature using the key words retinitis pigmentosa, cystoid macular oedema, gene therapy.
CASE PRESENTATION
A 38 year old female patient for a low vision consultation. The patient was legally blind secondary to retinitis pigmentosa, which was diagnosed in her late 20s. She reported gradually progressive hazy central vision and decreasing peripheral vision in both eyes as well as severe night blindness. Other than the diagnosis of retinitis pigmentosa in both eyes,the patient had no other remarkable ocular conditions. Findings at that visit included unaided distance visual acuities VOD: 0,04 VOS: 0,06. Pupils were round with brisk responses. Extraocular muscle motility was full in both eyes. Confrontation methode visual fields were noted as temporal loss in the right eye and superior and temporal loss in the left eye. The perimetry test could not be performed due to the lack of correspondece of the patient even after a couple repetitions of the perimetry. She had normal ocular adnexa and quiet lids, conjunctiva, and sclera in both eyes. Corneas in both eyes were noted as clear epithelium, clear stroma, and clear endothelium. Anterior chambers had normal depth, iris with no pathological findings in both eyes; lens incipient sclerotic. Intraocular pressures were noted as 22 mmHg in both eyes with Icare, 21mmHg and 19 mmHg with aplanation tonometry; pahimetry corretional factor was +1 on both eyes. The vitreous was clear in both eyes. Both optic nerves were measured as 0.4 cup-to-disc ratios with no disc edema, disc hemorrhages, notching, or thinning noted.Waxy disc pallor and attenuated blood vessels were observed in both eyes. The macula in both eyes had retinal pigment epithelium (RPE) changes with no edema or hemorrhages. Bone spicule changes were noted 360 in the periphery of both eyes with no holes or tears(Figure 1a+1b+1c+1d).
CONCLUSION
We presented two cases of retinitis pigmentosa - the mother with diagnosed RP more than 15 years ago in need for low vision rehabilitation service and the daughter that got diagnosed after our initial examination and with complications in visual impairment through cystoid macular oedema.
PubMed: 36467319
DOI: 10.5455/aim.2022.30.329-333 -
Current Cardiology Reports May 2023Heart failure is a highly prevalent condition caused by many different aetiologies and characterised by cardiac dysfunction and congestion. Once developed, congestion... (Review)
Review
PURPOSE OF REVIEW
Heart failure is a highly prevalent condition caused by many different aetiologies and characterised by cardiac dysfunction and congestion. Once developed, congestion leads to signs (peripheral oedema) and symptoms (breathlessness on exertion), adverse cardiac remodelling, and an increased risk of hospitalisation and premature death. This review summarises strategies that could enable early identification and a more objective management of congestion in patients with heart failure.
RECENT FINDINGS
For patients with suspected or diagnosed heart failure, combining an echocardiogram with assessment of great veins, lungs, and kidneys by ultrasound might facilitate recognition and quantification of congestion, the management of which is still difficult and highly subjective. Congestion is a one of the key drivers of morbidity and mortality in patients with heart failure and is often under-recognised. The use of ultrasound allows for a timely, simultaneous identification of cardiac dysfunction and multiorgan congestion; ongoing and future studies will clarify how to tailor diuretic treatments in those with or at risk of heart failure.
Topics: Humans; Diuretics; Heart Failure; Cardiomyopathies; Hospitalization; Lung
PubMed: 37074565
DOI: 10.1007/s11886-023-01865-y -
Kidney International Reports Jan 2024Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and...
INTRODUCTION
Ultracyclists expose themselves to extreme physical challenges. This study aimed to elucidate the effects of ultracycling on electrolyte and fluid balance and investigate the potential occurrence of peripheral edema.
METHODS
A total of 4 clinical visits were performed before, during, and after a 6-day bicycle ride in 13 ultracyclists (5 female, 8 male) including serial laboratory analyses of blood and urine, bioelectrical impedance, and echocardiography. Throughout the ride, participants continuously tracked fluid intake, measured extremity circumferences daily, and self-tested urinary electrolytes using a point-of-care testing device. Portrait photos were judged by 20 physicians for occurrence of facial and eyelid edema.
RESULTS
Participants covered a mean distance of 1205 km and 19,417 vertical meters. From baseline to day 6, body weight remained stable ( = 0.479); however, body composition changed with increasing total body water (TBW) (+1.98 l ± 1.37, = 0.003) and plasma volume (+18.86 % ± 10.7, < 0.001). A significant increase in N-terminal pro brain natriuretic peptide (NT-proBNP) (+297.99 ng/l ± 190.42, < 0.001) until day 6 indicates concomitant cardiac volume overload. Swelling of face and eyelids peaked on day 5 (both ≤ 0.033). On recovery, changes partly resolved. Although urinary sodium concentration showed a nadir on day 4 (-32.18 mmol/l ± 23.88, = 0.022), plasma osmolality (+5.69 mmosmol/kg ± 5.88, = 0.004) and copeptin (+38.28 pg/ml ± 18.90, < 0.001) increased steadily until day 6.
CONCLUSION
Ultracycling over multiple days induces extracellular volume expansion, peripheral edema, and cardiac volume overload. Renal sodium and water retention is likely contributing to this condition.
PubMed: 38312776
DOI: 10.1016/j.ekir.2023.10.025 -
Mediterranean Journal of Hematology and... 2023Gilteritinib (XOSPATA®, Astellas) is a type I oral FLT3 inhibitor, a tyrosine kinase AXL inhibitor, involved in both c-Kit and FMS-like tyrosine kinase 3 (FLT3)...
BACKGROUND AND OBJECTIVES
Gilteritinib (XOSPATA®, Astellas) is a type I oral FLT3 inhibitor, a tyrosine kinase AXL inhibitor, involved in both c-Kit and FMS-like tyrosine kinase 3 (FLT3) resistance. In the phase 3 ADMIRAL trial, gilteritinib was compared with the standard of care in (R/R) acute myeloid leukemia (AML) patients who harbored any FLT3 mutation and showed superior efficacy with regard to response and survival.
OBJECTIVES
This research aimed to investigate the real-life efficacy and safety of gilteritinib in FLT3-positive R/R AML patients who were treated as a part of an early access program held in Turkey in April 2020 (NCT03409081).
RESULTS
The research included 17 R/R AML patients who had received gilteritinib from seven centers. The overall response rate was 100%. The most common adverse events were anemia and hypokalemia (7 patients, 41.2%). Grade 4 thrombocytopenia was observed in one patient only (5.9%), leading to permanent treatment discontinuation. Patients with peripheral edema had a 10.47 (95% CI: 1.64-66.82) times higher risk of death than those without peripheral edema (p<0.05).
CONCLUSION
This research showed that patients with febrile neutropenia and peripheral edema were at a high risk of death when compared to patients without febrile neutropenia and peripheral edema.
PubMed: 37180209
DOI: 10.4084/MJHID.2023.031 -
Frontiers in Cellular Neuroscience 2021Brain edema is a severe stroke complication that is associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral... (Review)
Review
Brain edema is a severe stroke complication that is associated with prolonged hospitalization and poor outcomes. Swollen tissues in the brain compromise cerebral perfusion and may also result in transtentorial herniation. As a physical and biochemical barrier between the peripheral circulation and the central nervous system (CNS), the blood-brain barrier (BBB) plays a vital role in maintaining the stable microenvironment of the CNS. Under pathological conditions, such as ischemic stroke, the dysfunction of the BBB results in increased paracellular permeability, directly contributing to the extravasation of blood components into the brain and causing cerebral vasogenic edema. Recent studies have led to the discovery of the glymphatic system and meningeal lymphatic vessels, which provide a channel for cerebrospinal fluid (CSF) to enter the brain and drain to nearby lymph nodes and communicate with the peripheral immune system, modulating immune surveillance and brain responses. A deeper understanding of the function of the cerebral lymphatic system calls into question the known mechanisms of cerebral edema after stroke. In this review, we first discuss how BBB disruption after stroke can cause or contribute to cerebral edema from the perspective of molecular and cellular pathophysiology. Finally, we discuss how the cerebral lymphatic system participates in the formation of cerebral edema after stroke and summarize the pathophysiological process of cerebral edema formation after stroke from the two directions of the BBB and cerebral lymphatic system.
PubMed: 34483842
DOI: 10.3389/fncel.2021.716825 -
Cureus Oct 2023Heparin, a mixture of sulfated polymorphic polysaccharides (glycosaminoglycan) chains of variable lengths and weights and a natural anticoagulant, is widely used in... (Review)
Review
Heparin, a mixture of sulfated polymorphic polysaccharides (glycosaminoglycan) chains of variable lengths and weights and a natural anticoagulant, is widely used in medical practice to prevent intravascular blood coagulation. Heparin has demonstrated antithrombotic and anti-inflammatory activity, and it is mostly administered systemically (intravenously or subcutaneously) for primary or secondary prevention of venous thromboembolism after surgical interventions, or immobilized patients, or on short-term antithrombotic therapy of patients with atrial fibrillation who must undergo treatment. However, since systemic administration of heparin could be, in certain cases, linked to an increased risk of bleeding, topical heparin is widely used for the prevention and treatment of local symptoms of peripheral vascular disorders, such as venous insufficiency, varicose veins, or superficial thrombophlebitis. This review summarizes the main safety and efficacy characteristics of the topical formulation of Heparin in Gel form (1000 International Units of Heparin/g Gel) currently in use, which has demonstrated an excellent efficacy and tolerability profile in reducing signs and symptoms of peripheral vascular disease, e.g., varicose syndromes and their complications, phlebothrombosis, thrombophlebitis, superficial periphlebitis, varicose ulcers, for post-operative varicophlebitis, sequelae of saphenectomy, for traumas and contusions, local edemas and infiltrates, subcutaneous hematoma and for traumatic affections of musculotendinous and capsuloligamentous apparatuses.
PubMed: 38022089
DOI: 10.7759/cureus.47418