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Toxicity Evaluation of Long-Term Topical Application of Recombinant Human Keratinocyte Growth Factor-2 Eye Drops on Macaca Fascicularis.

ABSTRACT: Recombinant human keratinocyte growth factor-2 (rhKGF-2), an effective agent for the regeneration of epithelial tissue, was found to have great potential for use in treatments of corneal diseases that involve corneal epithelial defects. Furthermore, the safety of long-term and high-dose external use of KGF-2 eye drops in rabbits has been well established previously. The aim of this study is to determine the safe dose range and target organs for toxicity of rhKGF-2 eye drops in Macaca fascicularis (M. fascicularis). The M. fascicularis animals were administered with different doses of rhKGF-2 eye drops (125, 500, and 2000 μg/ml) for four consecutive weeks, followed by a 2 week recovery period. No significant differences in weight, electrocardiogram characteristics, blood and urine indexes, pathology, and bone marrow cells were detected among the animals in different groups. The corneas of some animals in the middle- and high-dose groups showed fluorescence when stained with sodium fluorescein, and then the staining disappeared on days 28 and 42. Anti-rhKGF-2 antibodies were detected in a small number of animals in the high-dose group, and their level decreased after rhKGF-2 withdrawal. No neutralizing antibodies were detected. The result demonstrated that there was no obvious adverse reaction when topical application of rhKGF-2 eye drops at the dosage of 125 or 500 μg/ml on the M. fascicularis. This study is of great significance for the future clinical transformation of rhKGF-2 eye drops.

SUBMITTER: Li L

PROVIDER: S-EPMC8490875 | biostudies-literature |

REPOSITORIES: biostudies-literature

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The Effect of Market Competition on the Price of Topical Eye Drops.

Project description:PurposeTo describe the relationship between the number of Federal Drug Administration (FDA)-approved manufacturers and the price change of generic and branded topical eye drops.MethodsRetrospective analysis of topical eye drop medications with formulations listed in the FDA Orange Book and the National Average Drug Acquisition Cost database from 2013 to 2017.ResultsThe most frequently prescribed generic topical drugs were glaucoma medications (34%), antimicrobials (32%), anti-inflammatories (24%), mydriatics (5%), and anesthetics (5%). The most frequently prescribed branded topical drugs were anti-inflammatories (45%), glaucoma medications (32%), antimicrobials (21%) and dry eye medications (3%). From 2013 to 2017, generic eye drops had a median price decrease of 20% (IQR 32%) while branded eye drops had a median price increase of 44% (IQR 28%) (P < .001). A significant inverse association was identified between the price change of generic eye drops and the total number of all manufacturers (r = -.41, P = .010), generic drug manufacturers (r = -.32, P = .0496), and alternative branded drug manufacturers (r = -.57, P = .002). There was no significant association between the price change of branded eye drops and number of manufacturers. Glaucoma (r = -.58, P = .039) and anti-inflammatory (r = -.69, P = .047) eye drops also had significant inverse associations with the number of generic manufacturers.ConclusionFrom 2013 to 2017, the price of generic eye drops decreased whereas the price of branded eye drops increased. Market competition was significantly inversely associated with price changes of generic eye drops but not branded eye drops.

| S-EPMC8478971 | biostudies-literature

Efficacy of topical bevacizumab 0.05% eye drops in dry eye disease: A double-masked, randomized trial.

Project description:The objective of this double-masked, placebo-controlled, randomized trial was to assess the efficacy and safety of bevacizumab 0.05% eye drops in dry eye patients. This study included Dry Eye Workshop Study (DEWS) Grade 3-4 dry eye participants (n = 31) whose tear break-up time (TBUT) was ?5 seconds(s). Participants were randomized to undergo treatment with either bevacizumab 0.05% eye drops (n = 19) or placebo (n = 12). The primary outcome was TBUT, and the proportion of responders (increase of ?3s in TBUT at week 12), ocular surface disease index (OSDI) score, Schirmer test, and Oxford scheme grade were secondary outcomes. All outcomes were measured at 1-, 4- and 12 weeks. TBUT in bevacizumab group differed significantly from TBUT in placebo group within 12 weeks (P = 0.001). Moreover, the improvement of TBUT in bevacizumab group versus placebo group at 4- and 12 weeks differed significantly from that difference at baseline (P = 0.002 and P = 0.003, respectively). The proportion of participants achieving increase of 3 seconds or more of TBUT at week 12 in the bevacizumab group was significantly greater than that in the placebo group (P = 0.02). Oxford scheme grade at 1-, 4- and 12 weeks differed significantly from the values at baseline in bevacizumab group (P = 0.001, P = 0.01, and P = 0.03, respectively). OSDI scores at 1-, 4- and 12-week follow-ups were significantly lower than that at baseline in bevacizumab group (P<0.001 at each follow-up). Schirmer test were not significantly different within or between groups (the lowest P = 0.92). No adverse events occurred in this study. Patients treated with bevacizumab 0.05% eye drops showed significant improvement in tear film stability, corneal staining and symptoms.

| S-EPMC7274382 | biostudies-literature

Topical administration of regorafenib eye drops: phase I dose-escalation study in healthy volunteers.

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Elimination of active trachoma after two topical mass treatments with azithromycin 1.5% eye drops.

Project description:BackgroundFollowing an epidemiological study carried out in 2006 showing a high prevalence of blinding trachoma in the Far North Region of Cameroon, a trachoma elimination programme using the SAFE strategy was initiated: three yearly trachoma mass treatments were to be performed.Methodology/principal findingsThe entire district population (120,000 persons) was treated with azithromycin 1.5% eye drops in February 2008 and January 2009. To assess the effect of treatment on the prevalence of active trachoma, three epidemiological studies were conducted on a representative sample of children aged between 1 and 10 years. The first study was performed just prior to the first treatment, the second just prior to the 2nd treatment and the third one, one year later. The prevalence of active forms of trachoma (TF + TI) dropped from 31.5% (95%CI 26.4-37.5) before treatment to 6.3% (95%CI 4.1-9.6) one year after first treatment; a reduction of nearly 80%. One year after the second treatment, the prevalence decreased to 3.1% (95%CI 2.0-4.9), a total reduction of 90%. Furthermore, there were no more TI cases (only TF). There was no report of serious or systemic side effects. Tolerance was excellent.Conclusions/significanceActive trachoma mass treatment with azithromycin 1.5% eye drops is feasible, well tolerated, and effective.

| S-EPMC2990706 | biostudies-literature

Continental monophyly and molecular divergence of Peninsular Malaysia's Macaca fascicularis fascicularis.

Project description:The phylogenetic relationships of long-tailed macaque (Macaca fascicularis fascicularis) populations distributed in Peninsular Malaysia in relation to other regions remain unknown. The aim of this study was to reveal the phylogeography and population genetics of Peninsular Malaysia's M. f. fascicularis based on the D-loop region of mitochondrial DNA. Sixty-five haplotypes were detected in all populations, with only Vietnam and Cambodia sharing four haplotypes. The minimum-spanning network projected a distant relationship between Peninsular Malaysian and insular populations. Genetic differentiation (F(ST), Nst) results suggested that the gene flow among Peninsular Malaysian and the other populations is very low. Phylogenetic tree reconstructions indicated a monophyletic clade of Malaysia's population with continental populations (NJ = 97%, MP = 76%, and Bayesian = 1.00 posterior probabilities). The results demonstrate that Peninsular Malaysia's M. f. fascicularis belonged to Indochinese populations as opposed to the previously claimed Sundaic populations. M. f. fascicularis groups are estimated to have colonized Peninsular Malaysia ~0.47 million years ago (MYA) directly from Indochina through seaways, by means of natural sea rafting, or through terrestrial radiation during continental shelf emersion. Here, the Isthmus of Kra played a central part as biogeographical barriers that then separated it from the remaining continental populations.

| S-EPMC4124655 | biostudies-literature

TRIMCyp expression in Old World primates Macaca nemestrina and Macaca fascicularis.

Project description:Primates have evolved a variety of restriction factors that prevent retroviral replication. One such factor, TRIM5alpha, mediates a postentry restriction in many Old World primates. Among New World primates, Aotus trivirgatus exerts a similar early restriction mediated by TRIMCyp, a TRIM5-cyclophilin A (CypA) chimera resulting from a CypA retrotransposition between exons 7 and 8 of the TRIM5 gene. Macaca nemestrina do not express TRIM5alpha; therefore, we asked whether these animals and related Old World primates express TRIMCyp. RT-PCR of total RNA from M. nemestrina and Macaca fascicularis yielded three TRIMCyp amplification products, one of which is predicted to encode a TRIMCyp chimera containing a full-length CypA. Unlike A. trivirgatus, genomic sequencing of M. nemestrina and M. fascicularis identifies a CypA retrotransposition in the 3' untranslated region of the TRIM5 locus. There is approximately 78% homology between the predicted protein sequences of Old World and New World primate TRIMCyp, with most of the differences found in the TRIM5-derived sequence. Notably, exon 7 is absent from both M. nemestrina and M. fascicularis TRIMCyp. Neither M. nemestrina nor M. fascicularis TRIMCyp could restrict HIV-1 or simian immunodeficiency virus SIVmac in an in vitro infectivity assay. The discovery of TRIMCyp in both M. nemestrina and M. fascicularis indicates that TRIMCyp expression may be more common among Old World primates than previously believed. Convergent evolution of TRIMCyp in both Old World and New World primates suggests that TRIMCyp may have provided evolutionary advantages.

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Regulation of retinal proteome by topical antiglaucomatous eye drops in an inherited glaucoma rat model.

Project description:Examination of the response of the retinal proteome to elevated intraocular pressure (IOP) and to the pharmacological normalization of IOP is crucial, in order to develop drugs with neuroptorective potential. We used a hereditary rat model of ocular hypertension to lower IOP with travaprost and dorzolamide applied topically on the eye surface, and examine changes of the retinal proteome. Our data demonstrate that elevated IOP causes alterations in the retinal protein profile, in particular in high-mobility-group-protein B1 (HMGB1), calmodulin, heat-shock-protein (HSP) 70 and carbonic anhydrase II expression. The changes of the retinal proteome by dorzolamide or travoprost are different and independent of the IOP lowering effect. This fact suggests that the eye drops exert a direct IOP-independent effect on retinal metabolism. Further investigations are required to elucidate the potential neuroprotective mechanisms signaled through changes of HMGB1, calmodulin, HSP70 and carbonic anhydrase II expression in glaucoma. The data may facilitate development of eye drops that exert neuroprotection through direct pharmacological effect.

| S-EPMC3390333 | biostudies-literature

Bartonella quintana in cynomolgus monkey (Macaca fascicularis).

Project description:We identified a Bartonella quintana strain by polymerase chain reaction amplification, cloning, and sequencing of DNA extracted from lysed erythrocytes and cultured colonies grown from peripheral blood collected from a captive-bred cynomolgus monkey (Macaca fascicularis). This report describes naturally acquired B. quintana infection in a nonhuman primate.

| S-EPMC3367614 | biostudies-literature

Macaca fascicularis GeneChip: Four tissues

Project description:RNA samples from brain, cerebellum, liver, and testis of 3-year-old make Macaca fascicularis was hybridized to the M.fascicularis GeneChip, which was designed by the Laboratory of Genetic Resources, National Institute of Biomedical Innovation. Keywords: Control study

2007-12-18 | GSE8186 | GEO

Labyrinthitis Ossificans in a Cynomolgus Macaque (Macaca fascicularis).

Project description:Labyrinthitis is inflammation of the membranous and bony labyrinth of the inner ear. Typical portals of entry includehematogenous spread from the cochlear vasculature, passage of otitis media pathogens through the round window, and mostcommonly, meningogenic spread from the subarachnoid space. The sequela of chronic inner ear inflammation is labyrinthitisossificans, in which inner ear structures are replaced by fibrous and osseous tissues. Labyrinthitis in humans has been reportedconcurrently with infection due to various viruses (for example, varicella-zoster, measles, mumps) and bacteria (for example,Treponema pallidum, Streptococcus pneumoniae) and may be associated with vertebrobasilar ischemia and meningitis. Profoundsensorineural hearing loss is a common, serious complication of this disease. Here, we report a case of labyrinthitisossificans in a cynomolgus macaque (Macaca fascicularis) with a potential infectious etiology. Historically, this animal hadan indwelling femoral intravenous catheter for more than 4 y. He presented with a right-sided head tilt and incoordinationof 2 mo duration. The macaque was treated with NSAID and antibiotics, which corrected the incoordination but not the headtilt. MRI revealed right-sided labyrinthitis, and euthanasia was elected due to clinical signs that were refractory to treatment.Gross pathology was unremarkable, but histopathology revealed chronic labyrinthitis ossificans with local fibroplasia andvestibuloauditory neuritis. We describe here the clinical features, imaging, and histologic lesions of labyrinthitis in a macaque.

| S-EPMC6008717 | biostudies-literature

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