Sheridanbrodersen1374
Neurotoxicity is a common side effect of oxaliplatin; the effect of current drugs such as methylcobalamin and gabapentine is not obvious. Astragaloside IV (AS-IV) is an important active ingredient of
, which can protect the nervous system and inhibit tumor growth to a certain extent. However, whether AS-IV can reduce oxaliplatin neurotoxicity and its molecular mechanism remain unclear.
The network pharmacology method was used to determine the collective targets of AS-IV and oxaliplatin neurotoxicity. The model of neurotoxicity was established by intraperitoneal injection of oxaliplatin in rats. Bodyweight, mechanical withdrawal threshold (MWT), cold allodynia, and nerve conduction velocity (NCV) were examined, pathological changes were observed by hematoxylin-eosin staining, number of Nissl bodies were assessed by Nissl staining, the key collective targets were measured by spectrophotometry and immunohistochemistry.
Through network pharmacological analysis, 25 collective targets of AS-IV and oxaliplatin neurotoxicity were identified, mainly related to inflammation and oxidative stress. AS-IV could increase body weight, elevate MWT, and reduce cold allodynia of model rats, it also raised NCV. Neuropathology was improved and the number of Nissl bodies was increased by AS-IV administration. It reduced TNF-α, IL-6, and IL-1β in the spinal cord of model rats to inhibit inflammation; it also decreased MDA, raised SOD, CAT, and GSH-Px in the spinal cord of model rats to block oxidative stress.
AS-IV improves oxaliplatin neurotoxicity by regulating neuroinflammation and oxidative stress; the results can provide a new perspective for the potential treatment strategy of oxaliplatin neurotoxicity.
AS-IV improves oxaliplatin neurotoxicity by regulating neuroinflammation and oxidative stress; the results can provide a new perspective for the potential treatment strategy of oxaliplatin neurotoxicity.
Cardiotoxicity is an important side effect of the treatment of a malignant tumor with Doxorubicin. Currently, decreasing the dosage of Doxorubicin to alleviate the side effects on cardiac function is the common method to deal with the cardiotoxicity induced by Doxorubicin. The present study aims to investigate the therapeutic effects of Roflumilast on Doxorubicin-induced inflammation and cellular senescence, as well as the potential mechanism in H9c2 myocardial cells.
The injured cardiac cell model was established by incubation with 5 μmol/L Doxorubicin. MTT was used to evaluate the cell viability of treated H9c2 cardiac cells. Sapitinib cell line The expression of 4-HNE was determined using an immunofluorescence assay. The gene expression levels of IL-17, IL-6, TNF-α, IL-4, PAI-1, p21, and SIRT1 were evaluated using qRT-PCR and the protein levels of Gpx4, PAI-1, p21, and SIRT1 were determined using Western blot analysis. Secretions of IL-17, IL-6, TNF-α, IL-4, CK-MB, and cTnI were measured using ELISA. Cellular senescence was assessed using SA-β-Gal staining. Si-RNA technology was used to knockdown the expression of SIRT1 in H9c2 cardiac cells.
Cell viability of H9c2 cardiac cells was significantly inhibited by Doxorubicin but rescued by Roflumilast. The upregulated 4-HNE and downregulated Gpx4 were reversed by Roflumilast. The secretions of IL-6 and IL-17 were promoted by Doxorubicin and suppressed by Roflumilast. The increased SA-β-Gal staining induced by Doxorubicin was inhibited by Roflumilast. P21 and PAI-1 were significantly upregulated and SIRT1 was greatly downregulated by Doxorubicin, all of which were reversed by Roflumilast. The anti-senescent effect of Roflumilast was abolished by knocking down SIRT1.
Roflumilast might attenuate Doxorubicin-induced inflammation and cellular senescence in cardiomyocytes by upregulating SIRT1.
Roflumilast might attenuate Doxorubicin-induced inflammation and cellular senescence in cardiomyocytes by upregulating SIRT1.
The aim of our study was to determine endothelin-1 (ET-1) concentration in chronic idiopathic uveitis in children and adolescents depending on anatomical location and grade of inflammation.
The cross-sectional study was conducted among 17 patients with chronic idiopathic uveitis and 22 healthy controls. Concentration of ET-1 in serum was determined using a commercially available ELISA kit. The concentration of C reactive protein (CRP) in serum was determined by immunoturbidimetric method using CRP4 reagent kit (Roche Diagnostics GmbH, Mannheim, Germany).
Statistically significant difference between ET-1 concentration in patients with chronic idiopathic uveitis and controls was found 1.33 (1.22; 1.48) vs 1.93 (1.1; 3.11),
= 0.008). No correlations were found between ET-1 concentration and age, either in chronic idiopathic uveitis patients or controls. Nine out of 17 patients presented with anterior uveitis, 5 with posterior and 3 with panuveitis. There were no differences in ET-1 concentration between anterior, posterior and panuveitis (
= 0.634), and in terms of grade of inflammation.
ET-1 expression is disturbed in pediatric chronic idiopathic uveitis irrespective of the anatomical location and grade of inflammation. Lower expression of ET-1 plays a crucial role in disturbed vascular tone control and can result in permanent visual impairment in chronic non-infectious uveitis.
ET-1 expression is disturbed in pediatric chronic idiopathic uveitis irrespective of the anatomical location and grade of inflammation. Lower expression of ET-1 plays a crucial role in disturbed vascular tone control and can result in permanent visual impairment in chronic non-infectious uveitis.Palytoxin is one of the most lethal natural toxins ever discovered. This molecule has been isolated from various marine animals, including zoanthid corals. This popular organism is commonly found in many home saltwater aquariums due to its beauty and survivability. As a result of an increase in popularity, an increased number of individuals are at risk for exposure to this potentially deadly toxin. Affected patients may experience various symptoms based on the route of exposure (ie, cutaneous contact, inhalation of aerosolized toxin, ocular exposure, or ingestion). Ocular exposure can occur in various ways (eg, contact with contaminated water, rubbing the eye with a dirtied hand, or direct spraying into the eye), and incidence rates have dramatically risen in recent years. In this review, we discuss a case of systemic toxicity from inhalation and ocular exposure to presumed palytoxin on a zoanthid coral which resulted in an intensive care unit (ICU) stay, and corneal perforation which required a corneal transplant. Additionally, we review what is known about the mechanism of action of this toxin, propose a comprehensive hypothesis of its effects on corneal cells, and discuss the prognosis and clinical management of patients with systemic symptoms secondary to other routes of exposure.
OTX-101 is approved for treatment of keratoconjunctivitis sicca (KCS). We present results of a phase 3 worse-eye efficacy analysis and 1-year safety extension.
During the double-masked treatment phase, patients with bilateral KCS were randomized 11 to 12 weeks OTX-101 or vehicle 1 drop per eye twice daily. Efficacy assessments included Schirmer's test and corneal and conjunctival staining. All patients who completed the treatment phase were eligible for enrollment in the open-label extension and received 1 drop OTX-101 twice daily for up to 52 weeks. Safety endpoints included adverse event (AE) monitoring, Snellen visual acuity (VA), intraocular pressure (IOP), slit-lamp examination (SLE), and dilated fundoscopy.
Overall, 745 and 258 patients enrolled in the treatment and safety extension phases, respectively. At 12 weeks, number (%) of patients with Schirmer's score increase of ≥10 mm from baseline was 76 (20.5%) vs. 42 (11.3%) for OTX-101 vs. vehicle (
=0.0005). OTX-101 significantly improved total conjunctival staining vs. vehicle at week 12 (least squares mean change from baseline -1.65 [0.12] vs. -1.12 [0.12],
=0.0013), and number (%) of patients with clear central corneas vs. vehicle at week 12 (222 [64.0%] vs. 199 [55.3%],
=0.0179). In the 1-year safety extension, AEs were mostly mild; instillation site pain was most common in 59 (22.9%) patients (17 [13.2%] vs. 42 [32.6%] patients receiving prior OTX-101 and vehicle). No safety concerns were raised by VA, IOP, SLE, and fundoscopy.
OTX-101 efficacy was confirmed in the eye with lower baseline Schirmer's score. OTX-101 was well tolerated long term.
Registered at ClinicalTrials.gov on July 27, 2016. NCT02845674 https//clinicaltrials.gov/ct2/show/NCT02845674?term=OTX-101&draw=2&rank=1.
Registered at ClinicalTrials.gov on July 27, 2016. NCT02845674 https//clinicaltrials.gov/ct2/show/NCT02845674?term=OTX-101&draw=2&rank=1.
To describe a new surgical technique for sutureless intrascleral intraocular lens (IOL) fixation with an adapted retinal scraper used as an instrument "the Catcher Pole" to retrieve the IOL haptic through a scleral tunnel.
Public Eye Hospital, Roma, Italy.
Retrospective case series.
Twenty-one eyes from 19 patients who underwent sutureless intrascleral IOL fixation were studied. A standard three-piece posterior chamber IOL (PCIOL) was implanted in aphakia or rescued and fixated in cases of dislocated PCIOL. A 23 to 25 G retinal loop scraper (the "Catcher Pole") was inserted through a 1.5 mm long tunneled sclerotomy performed on the horizontal meridian, to capture, hold and externalize the tip of the haptic of the IOL. A flange created with an handheld cautery on the externalized haptic tip prevents IOL slippage. The best-corrected visual acuity (BCVA), central corneal pachymetry (CCP), IOL tilt and complications were assessed.
In twenty-one eyes of 19 patients, the mean preoperative BCVA was 0.61 logMAR units ±0.05 SD, and the mean postoperative BCVA improved significantly to 0.18 logMAR units at three months ±0.05 SD (
=0.002). The mean preoperative CCP was 610 µ ±17 SD and the mean postoperative CCP 623 µ ±16 SD, (
=0.73). In the subgroup that underwent IOL tilt evaluation, mean IOL tilt was 3.19±2.01. The postoperative complications included iris capture of the IOL in one eye (4,7%) and transient ocular hypertension in two eyes (9,4%).
The "Catcher Pole" sutureless intrascleral IOL fixation technique is easy to perform with reduced anterior chamber manipulations and achieves both anatomical and optical stability.
The "Catcher Pole" sutureless intrascleral IOL fixation technique is easy to perform with reduced anterior chamber manipulations and achieves both anatomical and optical stability.
Botulinum toxin is known to have a powerful chemodenervation effect, and it is a well-established alternative to incisional surgery for strabismus. This study aims to investigate the efficacy of dose increments of botulinum toxin A (BTA) for the treatment of specific ranges of angle deviation.
This was a prospective study that included patients presenting with esotropia to Dhahran Eye Specialist Hospital between 2016 and 2020, who were managed by a single surgeon. Botulinum toxin was given in different dosages (2.5, 5, 7.5, 10 international units (IU)) according to the size of deviation (11-19, 20-29, 30-39, and ≥40 prism diopters (PD)), respectively. A successful outcome was defined as deviation ≤10 PD in the last visit (a minimum of 6 months) following a single injection.
A total of 56 patients with esotropia were included. The mean pre-treatment angle of deviation was 38.6 ± 2.5 PD. BTA injection in a dose of 2.5 IU for the 11-19 PD angle of deviation showed the highest rate of successful outcomes (75%).
