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1.
Drug Deliv ; 28(1): 2427-2446, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34763590

ABSTRACT

PURPOSE: To evaluate a new chronic glaucoma model produced by intracameral injection of dexamethasone-loaded poly lactic-co-glycolic acid microspheres (Dex-PLGA-Ms) over six months. METHODS: Healthy rats received two injections (at baseline and Week 4) of Dex-PLGA-Ms into the anterior chamber of the right eye. Clinical signs and intraocular pressure (IOP) were weekly recorded. The structure of the retina and optic nerve was in vivo evaluated using optical coherence tomography (OCT) every two weeks and functionally using dark- and light-adapted electroretinography at 0-12-24 weeks. Histological studies were also performed. RESULTS: IOP progressively increased up to hypertension (23.22 ± 3.63 mmHg) in both eyes but did so later in left eyes. OCT quantified a decrease in full-thickness retina posterior pole (R), retinal-nerve-fiber layer (RNFL), and ganglion-cell layer (GCL) thickness up to 24 weeks. Right eyes showed higher neuroretinal thickness loss up to week 8. RNFL experienced the highest percentage thickness loss at the inferior-superior axis, while in GCL the inner sectors of the horizontal axis (Nasal-Temporal) suffered the greatest decrease in thickness. Retinal ganglion cell, photoreceptor, and intermediate cell functionality decreased over time. Increased deposition of collagen IV was also found in zonular fibers and the ciliary body. CONCLUSIONS: This work shows the usefulness of drug delivery systems, not to treat pathology but to induce it. Only two injections of Dex-PLGA-Ms in the anterior chamber of rat eyes were enough to progressively create ocular hypertension and subsequent functional and structural neuroretinal degeneration, at least over 6 months.


Subject(s)
Dexamethasone/administration & dosage , Dexamethasone/pharmacology , Disease Models, Animal , Glaucoma/chemically induced , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Animals , Chronic Disease , Drug Carriers/chemistry , Drug Liberation , Female , Injections, Intraocular , Intraocular Pressure/drug effects , Male , Microspheres , Optic Nerve/drug effects , Particle Size , Rats , Rats, Long-Evans , Retina/drug effects , Tomography, Optical Coherence
2.
Biomater Sci ; 8(22): 6246-6260, 2020 Nov 21.
Article in English | MEDLINE | ID: mdl-33016285

ABSTRACT

Intravitreal administration is widely used in ophthalmological practice to maintain therapeutic drug levels near the neuroretina and because drug delivery systems are necessary to avoid reinjections and sight-threatening side effects. However, currently there is no intravitreal treatment for glaucoma. The brimonidine-LAPONITE® formulation was created with the aim of treating glaucoma for extended periods with a single intravitreal injection. Glaucoma was induced by producing ocular hypertension in two rat cohorts: [BRI-LAP] and [non-bri], with and without treatment, respectively. Eyes treated with brimonidine-LAPONITE® showed lower ocular pressure levels up to week 8 (p < 0.001), functional neuroprotection explored by scotopic and photopic negative response electroretinography (p = 0.042), and structural protection of the retina, retinal nerve fibre layer and ganglion cell layer (p = 0.038), especially on the superior-inferior axis explored by optical coherence tomography, which was corroborated by a higher retinal ganglion cell count (p = 0.040) using immunohistochemistry (Brn3a antibody) up to the end of the study (week 24). Furthermore, delayed neuroprotection was detected in the contralateral eye. Brimonidine was detected in treated rat eyes for up to 6 months. Brimonidine-LAPONITE® seems to be a potential sustained-delivery intravitreal drug for glaucoma treatment.


Subject(s)
Glaucoma , Neuroprotective Agents , Animals , Brimonidine Tartrate , Follow-Up Studies , Glaucoma/drug therapy , Rats , Silicates
3.
J R Coll Surg Edinb ; 42(5): 355-8, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9354075

ABSTRACT

We report a new case of primary malignant fibrous histiocytoma of the jejunum. Malignant fibrous histiocytoma (MFH) occurs most commonly in the extremities and trunk, but rarely in visceral organs. However, only eight cases of primary tumours involving the small intestine, including the present, have been described. This case report documents the appearance of malignant fibrous histiocytoma as a primary lesion of the intestinal wall in a patient with a 2-month history of dyspepsia, weight loss and unspecific abdominal pain. The final diagnosis was based on the pathological report of the surgical specimen. Emphasis is placed on the clinical signs, radiological studies and pathological findings. The literature on MFH of the jejunum is also reviewed. Malignant fibrous histiocytoma is considered an aggressive tumour, and the treatment of choice is complete surgical excision. Adjuvant chemotherapy or radiation is recommended mainly in those patients in whom there is vascular or lymphatic infiltration.


Subject(s)
Histiocytoma, Benign Fibrous , Jejunal Neoplasms , Combined Modality Therapy , Fatal Outcome , Histiocytoma, Benign Fibrous/pathology , Histiocytoma, Benign Fibrous/therapy , Humans , Jejunal Neoplasms/pathology , Jejunal Neoplasms/therapy , Male , Middle Aged , Neoplasm Metastasis
4.
Hepatogastroenterology ; 43(9): 769-70, 1996.
Article in English | MEDLINE | ID: mdl-8799428

ABSTRACT

Duplications of the digestive tract are very unusual entities that can be located in any other part of the Gastrointestinal tract. However the most frequent location is the jejunoileal one. We report the case of a giant chylous intestinal cyst duplication, located in the ileum, diagnosed in a 41 year-old man.


Subject(s)
Chyle , Cysts/etiology , Ileum/abnormalities , Adult , Congenital Abnormalities/diagnostic imaging , Congenital Abnormalities/surgery , Humans , Male , Radiography
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