Background: Abdominal adhesions (AAs) are post-traumatic fibrous bands that connect visceral and/or peritoneal surfaces, leading to possible long-term complications. The effect of a novel antifibrotic selective angiotensin II type 2 receptor agonist, compound 21 (C21) on AA formation was assessed in a murine model.
Methods: Female BALB/c mice were laparotomized and the cecum and overlying parietal peritoneum abraded.
Background: Angiotensin II engagement of angiotensin II type 1 receptor (AT1R) is implicated in fibrogenesis, with AT1R blockers used clinically to attenuate cardiac and renal fibrosis. The authors tested the hypothesis that the AT1R blocker losartan could reduce postsurgical cutaneous scarring in rats.
Methods: Human dermal fibroblasts were treated with losartan and assessed for viability, contractile activity, migration, and profibrotic gene transcription by means of calcein, collagen gel, scratch, and quantitative reverse transcriptase polymerase chain reaction assays, respectively.
Background: Cell-assisted lipotransfer involves enrichment of autologous fat with supraphysiologic numbers of adipose-derived stem cells to improve graft take. Adipose-derived stem cells have been shown to promote cancer progression, raising concerns over the safety of adipose-derived stem cells and cell-assisted lipotransfer in postoncologic breast reconstruction. The authors compared the effect of adipose-derived stem cells alone, cell-assisted lipotransfer, and conventional fat grafting on breast cancer growth and metastasis.
View Article and Find Full Text PDFBackground: Although surgical excision and intralesional collagenase injection are mainstays in Dupuytren disease treatment, no effective medical therapy exists for recurrent disease. Compound 21, a selective agonist of the angiotensin II type 2 receptor, has been shown to protect against fibrosis in models of myocardial infarction and stroke. The authors investigated the potential use of compound 21 in the treatment of Dupuytren disease.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
September 2016
Purpose: We previously demonstrated that neural cell adhesion molecule (NCAM) plays an important role in supporting the survival of injured retinal ganglion cells. In the current study, we used light-induced retinal degeneration (LIRD) as a model to investigate whether NCAM plays a functional role in neuroprotection and whether NCAM influences p75NTR signaling in modulating retinal cell survival.
Methods: Retinas from wild-type (WT) and NCAM deficient (-/-) mice were tested by electroretinogram before and after LIRD, and changes in the protein expressions of NCAM, polysialic acid (PSA)-NCAM, p75NTR, and active caspase 3 were measured by immunoblot from 0 to 4 days after light induction.
The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls.
View Article and Find Full Text PDFTumor cells use activated platelets to promote their proliferation and metastatic potential. Because platelet activation is largely mediated through ADP engagement of purinergic P2Y12 receptors on platelets, we investigated the potential of the reversible P2Y12 inhibitor ticagrelor, a clinical agent used in the prevention of cardiovascular and cerebrovascular events, to inhibit tumor adhesion and metastasis. In B16-F10 melanoma intravenous and intrasplenic metastasis models, mice treated with a clinical dose of ticagrelor (10 mg/kg) exhibited marked reductions in lung (84%) and liver (86%) metastases.
View Article and Find Full Text PDFBackground: We wanted to investigate whether heat shock protein (HSP) 27 and HSP 72 are induced in retinal ganglion cells (RGCs) after acute intraocular pressure (IOP)-induced ischaemia.
Methods: Retinal ischaemia was induced by acutely increasing IOP to 100-110 mmHg for 30 or 90 min unilaterally in Sprague Dawley rats. A fluorescent tracer (fluorogold, FG) was applied to the superior colliculi to label RGCs.
The purpose of this study was to determine whether endothelin B (ETB) receptor levels in the optic nerve are related to retinal ganglion cell (RGC) loss in a model of chronic endothelin-1 (ET-1) induced optic neuropathy. RGCs of adult Brown Norway rats were first retrogradely labeled with fluorochrome from the superior colliculi. An osmotic minipump was surgically implanted 7 days later to deliver 10(-11) M (n = 9), 10(-9) M (n = 12) or 10(-7) M (n = 9) ET-1 to the retrobulbar optic nerve for 28 days.
View Article and Find Full Text PDFPurpose: To describe and evaluate a semiquantitative optic nerve grading scheme for assessing axonal loss in endothelin (ET)-1-induced chronic optic neuropathy.
Methods: Optic nerve cross-sections from both eyes of 39 Brown Norway rats unilaterally treated with various concentrations of ET-1 or physiological saline solution via a surgically implanted osmotic minipump were processed for light and transmission electron microscopy (TEM). The optic nerve damage grade, between 0 (no damage) and 10 (total damage), was based on the number of zones of approximately equal damage and the mean percentage of damage within each zone.
In the present study, we compared the in vivo neuroprotective efficacy of intraperitoneally administered tetracycline and minocycline to enhance the survival of retinal ganglion cells (RGCs) following unilateral axotomy of the adult rat optic nerve. We also examined the effects of the tetracycline drugs on the activation of retinal microglia. RGCs in retinal whole-mounts were visualized by retrograde labeling with fluorogold.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2004
Purpose: To describe a model of chronic endothelin (ET)-1 administration to the optic nerve and evaluate its effect on retinal ganglion cell (RGC) and axon survival in rat.
Methods: Osmotic minipumps were surgically implanted in one eye of 113 Brown Norway rats to deliver 0.05, 0.
Purpose: Vasospasm has been associated with glaucoma, but its mechanisms have not been elucidated. The present study was designed to evaluate the role of endothelin (ET)-1, a potent endogenous vasoconstrictor, in the genesis of vasospasm in glaucoma.
Methods: Our sample contained patients with open-angle glaucoma (n = 43) and subjects with normal nonglaucomatous eyes and without acral vasospasm (n = 27).
Purpose: To characterize the effect of intraocular pressure (IOP) on optic disc topography, retinal function, and axonal survival in a model of IOP-induced optic nerve damage in rat.
Methods: Hypertonic (1.75 M) saline was injected into an episcleral vein of one eye of 49 Brown Norway rats, with the fellow untreated eye serving as the control.
Purpose: Topical beta-blockers, such as timolol, have been used extensively in the medical treatment of glaucoma to lower intraocular pressure (IOP). Recently, these drugs have been shown to have effects on the retinal and optic nerve circulation as well as potential neuroprotective properties. In the current study, the concentration of timolol attained in the cornea, iris-ciliary body, retina, vitreous, and plasma was measured after topical or intraperitoneal administration in rats to determine the relative contributions of each route to intraocular timolol concentrations.
View Article and Find Full Text PDFBrain Res
September 1999
The cytochrome P450 enzyme system is a multigene family of enzymes that is modulated in the liver during systemic inflammatory responses or during infection Several forms of the enzyme are expressed in discrete areas of the brain and likely play a critical role in the metabolism of drugs and endogenous chemicals in the central nervous system (CNS). Even though the brain responds to inflammation in a manner different from most tissues, we examined the possible modification of a major cytochrome P450 form (CYP1A) in the brain during inflammation confined to that organ. Total brain CYP1A activity, as measured by ethoxyresorufin dealkylase (EROD), was downregulated 24 and 48 h following the administration of a single dose of lipopolysaccharide (LPS).
View Article and Find Full Text PDFFour groups of monkeys (Callithrix jacchus) were injected with saline or increasing amounts of the immunotoxin, ME20.4 IgG-saporin, directly into the basal nucleus of Meynert via a frontal trajectory which avoided damage to the overlying basal ganglia. ME20.
View Article and Find Full Text PDFThe clearance of sulphamethoxazole (SMX), a compound metabolised primarily by the N-acetyltransferase NAT1, is increased in cystic fibrosis (CF) patients. We assessed the activity and kinetic properties of NAT1 in lysates of peripheral blood mononuclear leukocytes (MNL) from CF (n = 17) and control (n = 22) subjects using SMX and p-aminobenzoic acid (PABA) as test substrates. The Km and Vmax values of both substrates in MNL from CF patients and control subjects were not significantly different.
View Article and Find Full Text PDFThe elimination of cyclosporin A was assessed in eight pediatric renal transplant patients who received calcium channel blockers concomitantly with their immunosuppressive therapy. In three children, verapamil decreased the rate of elimination of cyclosporin A. In five children who received nifedipine, cyclosporin A elimination was also impaired, which contrasts with the reports in adult patients indicating that this calcium channel blocker has no effect on cyclosporin A elimination.
View Article and Find Full Text PDFEighteen healthy Caucasians were evaluated for the systemic acetylation of a caffeine metabolite using the urinary caffeine metabolite ratio 5-acetylamino-6-formylamino-3-methyluracil (AFMU) to 1-methylaxanthine (1X) and for N-acetyltransferase activity in peripheral blood mononuclear leukocytes (MNL) using p-aminobenzoic acid (PABA). These are markers for systemic NAT2 and NAT1 N-acetyltransferase activities, respectively. Fourteen slow acetylators and four fast acetylators (the NAT2 polymorphism) were identified by the caffeine metabolite ratio.
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