RESUMO
Matrix metalloproteinases (MMPs) play critical roles in a multiple number of autoimmunity diseases progression and metastasis of solid tumor. Gelatinases including MMP-2 and MMP-9 are extremely overexpressed in multiple pathological processes. MMP-9 and MMP-2 breakdown the extracellular matrix component gelatin very efficaciously. Therefore, designing and expansion of MMPs inhibitors can be an engrossing plan for therapeutic intermediacy. Anyway, a wide range of MMPs inhibitors face failure in several clinical trials. Due to sequence and structural conservation across the various MMPs, achieving specific and selective inhibitors is very demanding. In the current study, a phage-displayed peptide library was screened using active human recombinant MMP-9 protein and evaluated by enzyme-linked immunosorbent assay. Here, we isolate novel peptide sequence from phage display peptide libraries that can be a specific gelatinase inhibitor. Interestingly, in silico molecular docking showed strong interactions between the peptide three-dimensional models and some important residues of the MMP-9 and MMP-2 proteins at the fibronectin domain. A consensus peptide sequence was then synthesized (named as RSH-12) to evaluate its inhibitory potency by in vitro assays. Zymography assay was employed to evaluate the effect of RSH-12 on gelatinolysis activity of MMP-2 and MMP-9 secretion from the HT1080 cells using different concentrations of RSH-12 and inhibiting MMP-9- and MMP-2-driven gelatin proteolysis, measured by fluorescein isothiocyanate-gelatin degradation assay and HT1080 cell invasion assay on Matrigel (gelatinous protein mixture). The negative control peptide (CP) with the irrelevant sequence and no MMP inhibition properties and the positive control compound (GM6001) as a potent inhibitor of MMPs were used to assess the selectivity and specificity of gelatinases inhibition by RSH-12. Therefore, RSH-12 decreased the gelatin degradation by specifically preventing gelatin binding to MMP-9 and MMP-2. Selective gelatinase inhibitors may prove the usefulness of the new peptide discovered in tumor targeting and anticancer and anti-inflammation therapies.
Assuntos
Gelatinases/antagonistas & inibidores , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Peptídeos/química , Peptídeos/farmacologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Fibronectinas/química , Fibronectinas/metabolismo , Fluoresceína-5-Isotiocianato/metabolismo , Gelatina/metabolismo , Gelatinases/metabolismo , Humanos , Metaloproteinase 2 da Matriz/química , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Modelos Moleculares , Simulação de Acoplamento Molecular , Biblioteca de Peptídeos , Peptídeos/metabolismo , Domínios ProteicosRESUMO
PURPOSE: To review the frequency and cause of traumatic enucleation at the University of Wisconsin. METHODS: A 12-year retrospective chart review (2000-2012) from the University of Wisconsin Hospital and Clinics of patients who underwent enucleation following ocular trauma with specimens submitted to the University of Wisconsin Eye Pathology Laboratory. RESULTS: A total of 188 eyes enucleated following ocular trauma were identified between 2000 and 2012. One hundred eleven (59%) cases had an identifiable mechanism of injury recorded in the medical record and were included in the final analysis. The overall median patient age was 41 years with 83.8% male. Assault was the most common reason for enucleation (n=30, 27.0%) of which 15 (13.5%) cases were related to gunshot wounds. Other causes included outdoor or recreational activities (n = 20, 18.0%), fall (n = 14, 12.6%), non-motor vehicle accidents (n = 6, 5.5%), motor vehicle accidents (n = 15, 13.5%), work-related injury (n = 15, 13.5%), and sports-related injury (n = 11, 10%). CONCLUSION: Assault is the most common cause of traumatic ocular injury leading to enucleation. Gunshot and stab wounds were responsible for the majority of these cases. Men were much more likely to undergo enucleation due to ocular trauma with the exception being that caused by falls, where the rate was nearly equal between men and women.
Assuntos
Enucleação Ocular , Traumatismos Oculares/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Traumatismos Oculares/epidemiologia , Traumatismos Oculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Wisconsin/epidemiologiaAssuntos
Córnea/patologia , Doenças da Córnea/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Although osteoma is a common benign tumor of the paranasal sinuses, its orbital extension is not common. Secondary orbital cellulitis has rarely been reported in association with sino-orbital osteoma. CASE: A 30-year-old woman presented with left side proptosis, orbital pain and inflammation. Orbital CT scan showed a well-defined giant osteoma in the superonasal part of the left orbit originating from the left ethmoidal sinus associated with opacity of the ipsilateral ethmoidal sinus and infiltration of orbital soft tissue. After treatment by systemic antibiotics, osteoma was resected with combined external and endoscopic surgery and the patient recovered uneventfully. CONCLUSION: Sino-orbital osteoma may manifest primarily as orbital cellulitis and needs early surgical intervention.
Assuntos
Celulite Orbitária/etiologia , Neoplasias Orbitárias/diagnóstico , Osteoma/diagnóstico , Neoplasias dos Seios Paranasais/diagnóstico , Adulto , Antibacterianos/administração & dosagem , Endoscopia , Seio Etmoidal/patologia , Feminino , Humanos , Órbita/patologia , Celulite Orbitária/terapia , Neoplasias Orbitárias/complicações , Neoplasias Orbitárias/patologia , Neoplasias Orbitárias/cirurgia , Osteoma/complicações , Osteoma/patologia , Osteoma/cirurgia , Neoplasias dos Seios Paranasais/complicações , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Resultado do TratamentoRESUMO
A novel poly(urethane-urea) (PUU) based on poly(glycolide-co-ε-caprolactone) macro-diol with tunable mechanical properties and biodegradation behavior is reported for corneal stromal tissue regeneration. Zn-Al layered double hydroxide (LDH) nanoparticles were synthesized and loaded with vitamin C (VC, VC-LDH) and dispersed in the PUU to control VC release in the cell culturing medium. To mimic the corneal stromal EC, scaffolds of the PUU and its nanocomposites with VC-LDH (PUU-LDH and PUU-VC-LDH) were fabricated via electrospinning. Average diameters of the aligned nanofibers were recorded as 325 ± 168, 343 ± 171, and 414 ± 275 nm for the PUU, PUU-LDH, and PUU-VC-LDH scaffolds, respectively. Results of hydrophilicity and mechanical properties measurements showed increased hydrophobicity and reduced tensile strength and elongation at break upon addition of nanoparticles to the PUU scaffold. VC release studies represented that intercalation of the drug in Zn-Al-LDH controlled the burst release and extended the release period from a few hours to 5 days. Viability and proliferation of stromal keratocyte cells on the scaffolds were investigated via AlamarBlue assay. After 24 h, the cells showed similar viability on the scaffolds and the control. After 1 week, the cells showed some degree of proliferation on the scaffolds, with the highest value recorded for PUU-VC-LDH. SEM images of the scaffolds after 24 h and 1 week confirmed good penetration and attachment of keratocytes on all the scaffolds and the cells oriented with the direction of nanofibers. After 1 week, the PUU-VC-LDH scaffold was fully covered by the cells. Immunocytochemistry assay (ICC) was performed to investigate secretion of vimentin protein, ALDH3A1, and α-SMA by the cells. After 24h and 1 week, remarkably higher levels of vimentin and ALDH3A1 and lower level of α-SMA were secreted by keratocytes on PUU-VC-LDH compared to those on the PUU and PUU-LDH scaffolds and the control. Our results suggest that the aligned PUU-VC-LDH is a promising candidate for corneal stromal tissue engineering due to the presence of zinc and vitamin C.
Assuntos
Ácido Ascórbico , Proliferação de Células/efeitos dos fármacos , Córnea/metabolismo , Queratinócitos/metabolismo , Alicerces Teciduais/química , Vimentina/metabolismo , Animais , Ácido Ascórbico/química , Ácido Ascórbico/farmacologia , Córnea/citologia , Queratinócitos/citologia , Masculino , Nanopartículas/química , Poliuretanos/química , Ratos , Ratos WistarRESUMO
During the planning meeting for the Collaborative Ocular Melanoma Study (COMS) prior to the start of patient recruitment in 1986, there was an interest expressed in determining whether a relationship existed between the presence of uveal melanoma (UM) and asteroid hyalosis (AH). To answer this question, the ophthalmic examination form (unlike the pathology form for enucleated eyes) for each COMS patient asked whether AH was present or not. Though an increased prevalence was not found, this result was never published. A recent unpublished study at the University of Wisconsin School of Veterinary Medicine indicated a higher prevalence of AH in canine eyes with UM when compared to control eyes (without tumor) enucleated for goniodysgenesis. This further increased our interest in revisiting the published literature, clinical records, and histopathology slides of the enucleated eyes from the COMS study, as well as the histopathology slides on file in the University of Wisconsin Eye Pathology Laboratory. While cases with both AH and UM were occasionally encountered in the literature, clinically, we could not find a previous study focusing on these two processes. This study was conducted to explore whether such an association exists.
RESUMO
PURPOSE: The aim of this study was to determine the effect of donor features, including age, death-to-preservation time, preservation-to-surgery time, graft rating, and endothelial cell features, on visual and refractive outcomes and complications occurring after deep anterior lamellar keratoplasty (DALK) in patients with keratoconus. METHODS: In this retrospective study, 290 consecutive keratoconic eyes underwent DALK using donor corneas of different qualities, ranging from fair to excellent. Donor corneas were stored in intermediate-term storage medium. Donor data included age and sex, death-to-preservation time, preservation-to-surgery time, epithelial and stromal status, endothelial cell density and morphology, and graft rating. Postoperative outcomes included visual acuity, refractive error, epithelial problems, suture-related complications, graft rejection, and graft transparency. A multivariate regression analysis was used to assess the correlation between donor characteristics and postoperative outcomes. RESULTS: Mean donor and recipient ages were 33.4 ± 13.1 and 27.7 ± 8.0 years, respectively. The mean follow-up period was 38.2 ± 20.2 months. The presence of epithelial defects on postoperative day 1 had a significant correlation with donor epithelial sloughing (R = 0.26, P < 0.001), preservation-to-surgery time (R = 0.21, P = 0.001), and graft rating (R = -0.17, P = 0.004). Graft stromal edema on postoperative day 1 was significantly correlated with donor epithelial sloughing (R = 0.31, P < 0.001), preservation-to-surgery time (R = 0.24, P < 0.001), and graft rating (R = -0.28, P < 0.001). Suture-related complications, graft rejection episodes, graft clarity, visual acuity, and refractive outcomes at the final follow-up examination were found to have no correlations with any donor factors. CONCLUSIONS: The use of low-quality donors for DALK increased the rate of epithelial defects and stromal edema immediately postoperatively. However, the donor features had no influence on visual and refractive outcomes and complications.
Assuntos
Transplante de Córnea/métodos , Sobrevivência de Enxerto/fisiologia , Refração Ocular/fisiologia , Doadores de Tecidos , Acuidade Visual/fisiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Paquimetria Corneana , Endotélio Corneano/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Preservação de Órgãos/métodos , Soluções para Preservação de Órgãos , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Tempo , Transplantados , Resultado do Tratamento , Adulto JovemRESUMO
IMPORTANCE: To report the clinical and histopathologic findings of ocular adnexal angiolymphoid hyperplasia with eosinophilia, an unusual but often misdiagnosed benign disorder. OBSERVATIONS: The ophthalmologic findings of angiolymphoid hyperplasia with eosinophilia with ocular adnexal involvement are variable and include eyelid swelling, ptosis, proptosis, and loss of vision. Imaging studies typically reveal a well-circumscribed mass in the orbit. The condition may resemble other diseases that involve the orbit and ocular adnexal tissue, such as lymphoma, hemangioma, sarcoidosis, and dermoid cyst. Histopathologic analysis reveals marked vascular proliferation with an accompanying inflammation composed of numerous eosinophils, lymphocytes, and plasma cells. CONCLUSIONS AND RELEVANCE: Angiolymphoid hyperplasia with eosinophilia is a rare disease that can affect the ocular adnexal tissue. The clinical presentation is often nonspecific; therefore, histopathologic studies are essential for diagnosis and subsequent management of this benign condition.
Assuntos
Hiperplasia Angiolinfoide com Eosinofilia/diagnóstico , Doenças Palpebrais/diagnóstico , Órbita/patologia , Doenças Orbitárias/diagnóstico , Adulto , Idoso de 80 Anos ou mais , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órbita/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
The effectiveness of saline injection in reducing the toxicity profile of calcitriol when coadministered in mice was evaluated. Mortality was used as an end point to study the toxic effects of calcitriol; the relative risk of mortality in mice injected with saline was evaluated from our previously published animal experiments. We discovered that coadministration with 0.25 mL normal saline solution injected intraperitoneally is associated with a lower mortality rate than calcitriol given alone. The estimated relative risk of mortality was 0.0789 (95% confidence interval, 0.0051-1.22; z = 1.82; P = 0.070) when saline is administered with calcitriol compared to calcitriol alone. There was a reduction in serum calcium levels in mice that received saline (11.4 ± 0.15 mg/dL) compared to mice that did not receive saline (12.42 ± 1.61 mg/dL). Hydration with saline seems to reduce mortality and toxicity in mice receiving calcitriol. Given the decrease in mortality rates, intraperitoneal injections of saline should be considered in studies involving mice receiving injections of calcitriol.
Assuntos
Calcitriol/efeitos adversos , Neoplasias da Retina/mortalidade , Retinoblastoma/mortalidade , Cloreto de Sódio/uso terapêutico , Vitamina D/efeitos adversos , Animais , Calcitriol/administração & dosagem , Calcitriol/uso terapêutico , Cálcio/sangue , Agonistas dos Canais de Cálcio/administração & dosagem , Agonistas dos Canais de Cálcio/efeitos adversos , Agonistas dos Canais de Cálcio/uso terapêutico , Modelos Animais de Doenças , Combinação de Medicamentos , Injeções Intraperitoneais , Camundongos , Camundongos Nus , Camundongos Transgênicos , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/metabolismo , Retinoblastoma/tratamento farmacológico , Retinoblastoma/metabolismo , Cloreto de Sódio/administração & dosagem , Taxa de Sobrevida , Vitamina D/administração & dosagem , Vitamina D/uso terapêuticoRESUMO
IMPORTANCE: To establish that the intracranial and ophthalmologic findings present in victims of abusive head trauma can also be seen in shaken adults. OBSERVATIONS: We report 2 cases of shaken adults with intracranial and ophthalmologic findings that resulted from repetitive acceleration-deceleration injury. These findings included intracranial hemorrhages, hemorrhages involving the optic nerve sheath, intraretinal and subretinal hemorrhages, and macular folds. CONCLUSIONS AND RELEVANCE: The intracranial and ophthalmologic findings that are characteristic of abusive head trauma--subdural hemorrhages, optic nerve sheath hemorrhages, and retinal hemorrhages--are generally thought to be limited to young children and infants. Adults may also be victims of shaking abuse, and an ophthalmic examination may be beneficial when shaking is suspected.
Assuntos
Hematoma Subdural/etiologia , Traumatismos do Nervo Óptico/etiologia , Hemorragia Retiniana/etiologia , Hemorragia Subaracnoídea Traumática/etiologia , Intoxicação Alcoólica/etiologia , Hematoma Subdural/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Traumatismos do Nervo Óptico/patologia , Hemorragia Retiniana/patologia , Hemorragia Subaracnoídea Traumática/patologia , Inconsciência/etiologiaRESUMO
PURPOSE: To report the clinical features and histopathology of a transplanted cornea that was immediately replaced because of the possible diagnosis of lattice corneal dystrophy in the graft in which histopathologic examination revealed a Zygomycetes infection. METHODS: A 19-year-old patient with keratoconus underwent deep anterior lamellar keratoplasty (DALK) in the right eye. The operation was uneventful, transplanting a corneal graft without Descemet membrane, harvested from a donor with signs of orbital trauma. RESULTS: Three days after keratoplasty, multiple refractile lines involving the entire donor stroma were observed. With the potential diagnosis of lattice dystrophy of the donor cornea, the graft was replaced and sent for histopathologic analysis, which revealed a Zygomycetes graft infection. CONCLUSIONS: This case report introduces Zygomycetes as a cause of donor-to-host infection and also suggests that corneas harvested from donors with signs of orbital trauma may be a risk factor for donor-to-recipient transmission of such fungal infections.