Ocular prosthesis: a brief review and fabrication of an ocular prosthesis for a geriatric patient

Objective: A review of literature for ocular prosthesis is presented along with a case report of a geriatric patient. Review of literature: The evolution of ocular prosthesis, materials and methods, fabrication techniques for custom and stock eye prosthesis, delivery and after care for the ocular prosthesis are reviewed. Case report: A 74‐year‐old female patient who had undergone enucleation of her right eye was restored with a stock ocular prosthesis. Conclusion: The use of stock ocular prosthesis of appropriate contour, size and colour can provide an acceptable aesthetic result.     

Implant-supported palatal lift prosthesis in a patient with velopharyngeal incompetence: a case report

doi: 10.1111/j.1741‐2358.2011.00561.x Implant‐supported palatal lift prosthesis in a patient with velopharyngeal incompetence: a case report Objective: To describe the use of dental implants in the treatment of velopharyngeal incompetence. Background: Velopharyngeal incompetence is characterized by the inability to contract the tissues of the soft palate. The most common causes are neuromuscular problems resulting from concussion and degenerative conditions of the central nervous system. Materials and methods: The treatment using palatal lift prosthesis is well established in the literature; however, reports on the use of osseointegrated implants are scarce. Rehabilitation using only this type of fibromucosal support is difficult in edentulous patients, since the prosthesis has a palatal lift extension. Results: The implants provided retention and stability to the prosthesis, improving swallowing and speech and contributing to improve the patient’s quality of life. Conclusion: This article reports the rehabilitation of a patient with a totally edentulous maxilla with velopharyngeal incompetence using an implant‐retained palatal lift prosthesis.     

Implant‐supported overdenture in an elderly patient with Huntington’s disease

doi:10.1111/j.1741‐2358.2009.00343.x
Implant‐supported overdenture in an elderly patient with Huntington’s disease Huntington’s disease is a hereditary, progressive, neuro‐degenerative disorder characterised by increasingly severe motor impairment, cognitive decline and behavioural manifestations leading to functional disability. Dyskinesia and hyperkinesia of the tongue and the peri‐oral musculature make it impossible for the patient to wear a conventional complete denture, despite an adequate alveolar ridge. The present paper reports on a patient with Huntington’s disease who was rehabilitated with a mandibular overdenture supported by two endosteal implants. One year follow‐up examination showed that the prosthesis was stable and there was considerable improvement in the patient’s masticatory function.     

Accelerated rehabilitation of an edentulous patient with an implant retained dental prosthesis: a case report

This case report details the successful rehabilitation of an edentulous patient using a complete upper prosthesis and a lower implant retained overdenture. The provision of care was split between a specialist centre and a primary care setting. This approach reduced inconvenience to the patient. Modern surgical and prosthodontic techniques also reduced the total delivery time. After initial consultation a new set of complete dentures was prescribed with changes in design to the originals. The patient was also planned for placement of two mandibular implants to stabilise and retain the mandibular denture. The first line of treatment involved provision of a new set of dentures constructed by the patient's general dental practitioner. Dental implants were then placed in a specialist centre and the patient returned to the dental practice for attachment of the lower denture to the dental implants. The benefits and success of mandibular implant retained dentures are well documented. With delivery of the overdenture, the patient reported increased satisfaction with his prostheses which allowed him to eat a greater range of foods and enabled him to feel confident when speaking and socialising.     

The effect of different attachment systems with implant‐retained overdentures on maximum bite force and EMG

doi: 10.1111/j.1741‐2358.2010.00389.x The effect of different attachment systems with implant‐retained overdentures on maximum bite force and EMG Objective: To compare the effect of different attachment systems with implant‐retained overdentures on maximum bite force and muscle activity using electromyography (EMG). Background: Denture retention and stability is of considerable interest in prosthetic dentistry. Materials and methods: Thirty‐five patients were examined: 15 edentulous patients treated with mandibular implant‐retained overdentures (MIRO) and maxillary dentures (MCD) (two implant‐ball attachment) (BC); 10 edentulous patients treated with MIRO and MCD (four implants‐bar attachments) (BRC); 10 patients with edentulous mandibular treated with MIRO and maxillary fixed partial dentures (MFPD) (two implant‐ball attachments) (BF). Before implant placement all patients received new dentures. After using these dentures for 3 months the maximum bite force and electrical activity of masseter muscle were measured. Two or four implants were then inserted into the intraforaminal region. After osseointegration periods, patients were treated with MIRO which duplicated their dentures and after three months the measurements were repeated. The data were collected and statistically analysed. Results: Muscle activity and chewing ability increased in the second period of measurements. Also chewing time was significantly decreased at the first measurements. The highest muscle activity was observed in the group of patients treated with group BF. Conclusion: The EMG values of the masseter muscle significantly increased when an implant attachments was used in the overdenture.     

Ocular prosthesis for a geriatric patient with customised iris: a report of two cases

doi:10.1111/j.1741‐2358.2009.00327.x
Ocular prosthesis for a geriatric patient with customised iris: a report of two cases Objective: An ocular prosthesis is given when trauma or disease may lead to enucleation or evisceration of the eye and the combined efforts of the ophthalmologists and the maxillofacial prosthetist can provide a cosmetically acceptable ocular prosthesis. Methods: An ocular prosthesis is either pre‐fabricated or custom‐made. One of the important factors for achieving a cosmetic result is accurate colour matching of the iris with the contralateral iris. Results: A knowledge of the anatomy of the eye facilitates hand painting of iris and sclera to produce a satisfactory result. Conclusion: The custom‐made ocular prosthesis allows infinite variations during the fabrication.     

The influence of implant number and abutment design on the biomechanical behaviour of bone for an implant-supported fixed prosthesis: a finite element study in the upper anterior region

It is always recommended to use more implants for supporting a prosthesis in the immediate loading condition than in the classical two-stage treatment procedure. By means of the finite element (FE) method, the influence of the number of implants used in immediately loaded fixed partial prosthesis (FPP) on the load distribution was investigated, considering the abutment geometry. Two 3D FE models were studied employing four implants to support a FPP in the premaxilla. One model was designed with straight abutments and the other with 20°-angled abutments. The results concerning implant displacements, stresses and strains were compared with those of two implant-supported FPPs, obtained in a previous study. A noticeable reduction in the determined biomechanical bone loading was observed with the use of more implants in supporting an immediately loaded prosthesis. This study confirms that the use of additional numbers of implants in an immediately loaded prosthesis is highly recommended.     

Crystallographic and activity‐based evidence for thumb flexibility and its relevance in glycoside hydrolase family 11 xylanases

Enzyme intramolecular mobility and conformational changes of loops in particular play a significant role in biocatalysis. In this respect, the highly conserved thumb loop of glycoside hydrolase family (GH) 11 xylanases is an intriguing and characteristic structural element, of which the true dynamic nature and function in catalysis is still unknown. Crystallographic analysis of the structure of a Bacillus subtilis xylanase A mutant, found as a dimer in an asymmetric unit, revealed that the thumb region can adopt an extended conformation, which is stabilized in the crystal lattice through intermolecular contacts. In contrast to the closed thumb conformation of GH11 xylanases and the previously observed small conformational changes upon substrate binding, a relocation of the tip of the thumb of more than 15 Å was observed. Site‐directed mutagenesis of five thumb residues, including putative hinge point residues, and enzyme kinetics assays showed that Arg112, Asn114, and Thr126 play a role in the open‐close thumb movement. Replacement of Arg112 by glycine or proline caused a strong decrease of turnover numbers and elevated Michaelis constants on xylan. Mutant N114P hindered thumb movement, provoking a fourfold decrease of turnover numbers and a sharp rise in Michaelis constants, whereas the proline mutant of Thr126 displayed an increase in specific activity. The observation that extensive thumb opening is possible combined with the kinetic data suggests that the thumb plays a crucial role in both binding of substrate and release of product from the active site. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

MXRA5 is a TGF‐β1‐regulated human protein with anti‐inflammatory and anti‐fibrotic properties

Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling‐associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients. We then explored factors regulating MXRA5 expression and MXRA5 function in cultured human proximal tubular epithelial cells and explored MXRA5 expression in kidney cancer cells and kidney tissue. The fibrogenic cytokine transforming growth factor‐β1 (TGFβ1) up‐regulated MXRA5 mRNA and protein expression. TGFβ1‐induced MXRA5 up‐regulation was prevented by either interference with TGFβ1 activation of the TGFβ receptor 1 (TGFBR1, ALK5) or by the vitamin D receptor agonist paricalcitol. By contrast, the pro‐inflammatory cytokine TWEAK did not modulate MXRA5 expression. MXRA5 siRNA‐induced down‐regulation of constitutive MXRA5 expression resulted in higher TWEAK‐induced expression of chemokines. In addition, MXRA5 down‐regulation resulted in a magnified expression of genes encoding extracellular matrix proteins in response to TGFβ1. Furthermore, in clear cell renal cancer, von Hippel–Lindau (VHL) regulated MXRA5 expression. In conclusion, MXRA5 is a TGFβ1‐ and VHL‐regulated protein and, for the first time, we identify MXRA5 functions as an anti‐inflammatory and anti‐fibrotic molecule. This information may yield clues to design novel therapeutic strategies in diseases characterized by inflammation and fibrosis.     

Evolutionary conservation of a molecular machinery for export and expression of mRNAs with retained introns

Intron retention is one of the least studied forms of alternative splicing. Through the use of retrovirus and other model systems, it was established many years ago that mRNAs with retained introns are subject to restriction both at the level of nucleocytoplasmic export and cytoplasmic expression. It was also demonstrated that specific cis-acting elements in the mRNA could serve to bypass these restrictions. Here we show that one of these elements, the constitutive transport element (CTE), first identified in the retrovirus MPMV and subsequently in the human NXF1 gene, is a highly conserved element. Using GERP analysis, CTEs with strong primary sequence homology, predicted to display identical secondary structure, were identified in NXF genes from >30 mammalian species. CTEs were also identified in the predicted NXF1 genes of zebrafish and coelacanths. The CTE from the zebrafish NXF1 was shown to function efficiently to achieve expression of mRNA with a retained intron in human cells in conjunction with zebrafish Nxf1 and cofactor Nxt proteins. This demonstrates that all essential functional components for expression of mRNA with retained introns have been conserved from fish to man.     

Cast titanium overlay denture for a geriatric patient with a reduced vertical dimension

An older patient reporting to the dental surgery for his/her dental treatment is becoming a common occurrence. Improved oral hygiene has meant that teeth are retained for a longer time, along with the potential problems of attrition, decreased vertical dimension, temporomandibular joint discomfort/strain, and poor aesthetics. The case in question is that of a 65-year-old male patient who had severe attrition in the lower arch, temporomandibular joint pain and reduced vertical dimension. The maxillary arch had previously been restored with a fixed partial prosthesis. For restoration of the lower teeth, a removable cast titanium overlay denture was fabricated incorporating an increased vertical dimension. Porcelain facings were placed to restore the aesthetics of the anterior teeth. The titanium was cast in a semi-automatic electric arc, pressure type casting machine. A titanium overlay denture with porcelain facing on the anterior teeth may provide a means of restoring a patient's concerns regarding aesthetics and function.     

Identification of unique sensitizing targets for anti‐inflammatory CDDO‐Me in metastatic melanoma by a large‐scale synthetic lethal RNAi screening

CDDO‐Me has been shown to exert potent anti‐inflammatory activity for chronic kidney disease and antitumor activity for several tumors, including melanoma, in early clinical trials. To improve CDDO‐Me response in melanoma, we utilized a large‐scale synthetic lethal RNAi screen targeting 6000 human druggable genes to identify targets that would sensitize melanoma cells to CDDO‐Me. Based on screening results, five unique genes (GNPAT, SUMO1, SPINT2, FLI1, and SSX1) significantly potentiated the growth inhibitory effects of CDDO‐Me and induced apoptosis in A375, a BRAF mutated melanoma line (P < 0.001). These five genes were then individually validated as targets to potentiate CDDO‐Me activity, and related downstream signaling pathways of these genes were analyzed. In addition, the levels of phosphorylated Erk1/2, Akt, GSK‐2, and PRAS40 were dramatically decreased by downregulating each of these five genes separately, suggesting a set of common mediators. Our findings indicate that GNPAT, SUMO1, SPINT2, FLI1, and SSX1 play critical roles in synergy with inflammation pathways in modulating melanoma cell survival and could serve as sensitizing targets to enhance CDDO‐Me efficacy in melanoma growth control.     

Purification of anti‐colorectal cancer monoclonal antibody CO17‐1A from insect cell culture using a French press and sonication

Monoclonal antibody (mAb) CO17‐1A binds to GA733, which is a tumor‐associated glycoprotein antigen highly expressed on the colorectal cancer cell surface. Thus, mAb CO17‐1A is considered a useful biomolecule for diagnosis and treatment against colorectal cancer. Previously, we established a baculovirus–insect cell expression system for the production of mAb CO17‐1A. In order to use mAb CO17‐1A as a diagnostic and therapeutic tool, however, the antibody must be properly purified from the insect cells. In this study, our aim was to investigate effective purification processes of mAb CO17‐1A expressed in Spodoptera frugiperda (Sf9) insect cells, using a French press and sonication for cell disruption. SDS‐PAGE confirmed that both mAb CO17‐1A and mAb CO17‐1A fused to the KDEL endoplasmic reticulum (ER) retention signal (mAb CO17‐1AK) were expressed clearly in Sf9 insect cells. Western blot analysis showed that detection levels of mAb CO17‐1A and CO17‐1AK were higher when the insect cells were disrupted two times by the French press and then sonicated, compared to only one French press disruption plus sonication. Optical microscopy confirmed that insect cells treated with both the French press and sonication were properly disrupted. Analysis of gene sequence information on mAb CO17‐1A verified that a signal peptide is present but a transmembrane protein does not exist. These results suggest that cell disruption by the French press twice and sonication once is an effective method for improving purification efficiency.     

Development and scale‐up of a commercial fed batch refolding process for an anti‐CD22 two chain immunotoxin

We describe the development and scale‐up of a novel two chain immunotoxin refolding process. This work provides a case study comparing a clinical manufacturing process and the commercial process developed to replace it. While the clinical process produced high quality material, it suffered from low yield and high yield variability. A systematic approach to process development and understanding led to a number of improvements that were implemented in the commercial process. These include a shorter inclusion body recovery process, limiting the formation of an undesired deamidated species and the implementation of fed batch dilution refolding for increased refold titers. The use of a combination of urea, arginine and DTT for capture column cleaning restored the binding capacity of the capture step column and resulted in consistent capture step yields compared to the clinical process. Scalability is shown with data from 250 L and 950 L scale refolding processes. Compared to the clinical process it replaces, the commercial process demonstrated a greater than fivefold improvement in volumetric productivity at the 950 L refolding scale. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:1380–1389, 2014     

3,4‐dimethoxystilbene,a resveratrol derivative with anti‐angiogenic effect,induces both macroautophagy and apoptosis in endothelial cells

Angiogenesis plays an important role in many pathological processes. Identification of novel anti‐angiogenic agents will provide new insights into the mechanisms for angiogenesis as well as potential lead compounds for developing new drugs. In the present study, a series of resveratrol methylated derivatives have been synthesized and screened. We found trans‐3,4‐dimethoxystilbene (3,4‐DMS) with the fullest potential to develop as an anti‐angiogenic agent. In vitro and in vivo analyses suggested that 3,4‐DMS could effectively inhibit endothelial cell proliferation, migration, tube formation, and endogenous neovascularization. Our results showed that 3,4‐DMS exerted its anti‐angiogenic effect likely through induction of endothelial cell apoptosis via a pathway involving p53, Bax, cytochrome c, and caspase proteases. Moreover, 3,4‐DMS also induced macroautophagy in endothelial cells through activation of AMPK and the downstream inhibition of mTOR signaling pathway. Further studies indicated that intracellular calcium ([Ca²⁺]_i) might bridge the 3,4‐DMS‐induced apoptosis and macroautophagy through modulating reactive oxygen species (ROS) levels in endothelial cells. Combination of 3,4‐DMS with inhibitor of autophagy, such as 3‐methyladenine (3‐MA) and autophagy‐related gene (ATG) 5 small interfering RNA (siRNA), potentiated the pro‐apoptotic and anti‐angiogenic effects of 3,4‐DMS. Our study provides a novel angiogenic inhibitor and a useful tool in exploring the molecular mechanisms for the crosstalk between apoptosis and macroautophagy in endothelial cells. 3,4‐DMS could be served as a potential lead compound for developing a class of new drugs targeting angiogenesis‐related diseases. J. Cell. Biochem. 114: 697–707, 2013. © 2012 Wiley Periodicals, Inc.