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Objectives: to investigate whether baseline mineral distribution modulates the ability of silver diammine fluoride (SDF) to remineralize and stain enamel caries lesions., Methods: This laboratory study followed a 3 [treatment: SDF/fluoride varnish (FV)/deionized water (DIW)] ×3 [lesion protocol: methylcellulose (MeC)/hydroxyethylcellulose (HEC)/Carbopol 907 (C907)] factorial design. Lesions were created in bovine enamel specimens (n = 20). Treatments were applied and lesions remineralized in artificial saliva. Digital transverse microradiography (TMR-D) was used to analyze lesions. Lesion color was monitored spectrophotometrically. The effects of lesion protocol and treatment on changes in lesion depth (ΔLD), mineral loss (ΔΔZ), maximum mineral density at the surface zone (ΔSZ max ), and color changes related to remineralization (ΔL* remin ) were analyzed using two-way ANOVA., Results: The treatment×lesion protocol interaction was significant for ΔΔZ (p < 0.01) and ΔL* remin (p < 0.01), however not for ΔLD (p = 0.23) or ΔSZ max (p = 0.91). There were no differences in ΔΔZ between treatments in HEC and C907 lesions. However, DIW resulted in more remineralization than both SDF (p < 0.01) and FV (p = 0.01) in MeC lesions. Considering changes from lesion baseline after remineralization in MeC lesions, SDF treatment resulted in the highest mineral gain in the surface zone. However, DIW revealed the highest mineral gain after remineralization in the lesion body. SDF stained lesions with the intensity increasing after remineralization in C907 lesions, whereas staining decreased in MeC and HEC lesions., Conclusion: High fluoride treatments can interfere with continuous remineralization of caries lesions due to partial arrest. Baseline lesion mineral distribution affects SDF's ability to enhance remineralization and the staining caused by SDF., Clinical Significance: SDF is being used to arrest active caries lesions extending into dentin and to treat dentin hypersensitivity. This study shed light on SDF's effect on an isolated process in dental caries only, remineralization. It achieved this by examining enamel caries lesions with differing mineral distributions and assessing their staining properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate and compare functional and structural outcomes of accelerated corneal crosslinking (A-CXL) using riboflavin with hydroxypropyl methyl cellulose (HPMC) vs conventional corneal crosslinking (C-CXL) using riboflavin with dextran., Setting: American University of Beirut Medical Center, Beirut, Lebanon., Design: Retrospective analysis., Methods: Retrospective analysis of 83 eyes of 73 patients with mild to moderate keratoconus. First group (n = 44 eyes) underwent C-CXL using a 30-minute riboflavin/dextran soaking between June 2014 and March 2016. Second group (n = 39 eyes) underwent A-CXL using a 20-minute riboflavin/HPMC soaking between April 2016 and December 2017. Patients were evaluated preoperatively and at 1, 3, and 12 months postoperatively. Main outcome measures were simulated keratometry (simK), maximum axial keratometry (Kmax), demarcation line depth, and haze intensity measured using optical coherence tomography-based image analysis software., Results: Demarcation line (DL) was 298.30 ± 64.60 μm and 335.61 ± 99.76 μm for C-CXL and A-CXL groups, respectively ( P = .04). Haze profile was similar for both groups. The mean simK values were reduced from 46.93 ± 3.50 and 46.44 ± 2.93 preoperatively to 46.18 ± 3.65 and 45.54 ± 2.78 at 12 months postoperatively, for C-CXL and A-CXL, respectively ( P = .003 for both groups). The mean Kmax decreased from 52.46 ± 4.82 and 51.50 ± 3.87 preoperatively to 51.30 ± 4.42 and 50.30 ± 3.52 postoperatively, for the C-CXL and A-CXL, respectively ( P < .001 for both groups). There was no difference in the simK and Kmax changes between the C-CXL and A-CXL groups ( P = .814 and P = .913), visual acuity, and refraction between the 2 groups ( P > .05)., Conclusions: A-CXL with a 20-minute riboflavin/HPMC soaking produced deeper DL and similar corneal haze, topographic, refractive, and visual results to C-CXL with a 30-minute riboflavin/dextran soaking., (Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Hypoxic-ischemic encephalopathy (HIE) in newborns is associated with high morbidity and mortality, with many babies suffering long-term neurological deficits. Currently, treatment options are limited to therapeutic hypothermia, which is not appropriate for use in all babies. Previous studies have shown protective effects of increasing the transcription factor-hypoxia-inducible factor-1 (HIF-1) in animal models, by using mild hypoxia or compounds that act as prolyl hydroxylase inhibitors (PHIs). Here, we aimed to examine the neuroprotective actions of an orally active, small molecule PHI, GSK1120360A in a neonatal rat model of hypoxia-ischemia (HI) compared to another PHI, desferrioxamine (DFX). Sprague-Dawley rats underwent HI surgery on postnatal day 7 (P7), where unilateral carotid artery occlusion was performed followed by hypoxia (8% oxygen, 3 h). Initial testing showed that GSK1120360A and erythropoietin levels were detectable in plasma at 6 h following oral exposure to GSK1120360A. For the short-term neuroprotection study, pups were assigned to receive either saline (s.c), desferrioxamine (DFX-200 mg/kg, s.c), methylcellulose (1%, oral) or GSK1120360A (30 mg/kg, oral) immediately after HI. Histological analysis showed that GSK1120360A in this setting reduced brain injury size 7 days after HI, compared to the methylcellulose vehicle control group. DFX had no significant effect on injury size compared to saline group at the same 7 day timepoint. In the long-term neuroprotection study, pups were randomly assigned to be administered methylcellulose (1%, oral) or GSK1120360A (30 mg/kg, oral) immediately after HI. On P42, rats underwent behavioural testing using the forelimb grip strength, grid walking and novel object recognition tasks, and brains were collected for histological analysis. Long-term behavioural deficits were observed in grid walking, grip strength and novel object recognition tests after HI which were not improved in the GSK1120360A treatment group compared to the methylcellulose group. Similarly, there was no improvement in injury size on P42 in the GSK1120360A study group compared to the methylcellulose group. Here, we have shown that GSK1120360A can reduce brain injury at 7 days but that this neuroprotective benefit is not maintained when examined at 5 weeks after HI., (© 2022 The Authors. International Journal of Developmental Neuroscience published by John Wiley & Sons Ltd on behalf of International Society for Developmental Neuroscience.)

Purpose: To compare the effect of corneal collagen cross-linking (CXL) on progressive keratoconus using 0.1% riboflavin with either dextran or methylcellulose as the main supplement., Methods: In a comparative case series, CXL was performed in 40 patients (40 eyes) using a riboflavin solution containing either dextran (dextran-riboflavin; n = 20) or methylcellulose (methylcellulose-riboflavin; n = 20). Changes in central corneal thickness (CCT), Scheimpflug tomography, maximal keratometry reading (K max ), visual acuity (VA) and endothelial cell density (ECD) were recorded. Stromal changes one month after surgery were analysed using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM)., Results: The CCT was significantly higher in the methylcellulose-riboflavin group during the CXL procedure. The IVCM demarcation line depth was 274 ± 80 (SD) μm in the dextran-riboflavin group and 442 ± 80 μm in the methylcellulose-riboflavin group (p < 0.001). Complete absence of keratocytes in the pre-endothelial stroma was found in none of the corneas treated with dextran-riboflavin and in 42% of the corneas treated with methylcellulose-riboflavin. Visibility of the OCT demarcation line was significantly lower in the methylcellulose-riboflavin group. K max and corrected distance visual acuity were improved in the methylcellulose-riboflavin group and stable in the dextran-riboflavin group after 2 years. Endothelial cell density (ECD) was stable in both groups., Conclusion: We found deeper structural changes in the methylcellulose-riboflavin group than in the dextran-riboflavin group. This may be explained by different riboflavin solution properties and raises safety concerns. The study also indicates improved effect using methylcellulose-riboflavin than dextran-riboflavin, possibly explained by deeper stromal CXL effect., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Pharmaceutical applications of three dimensional (3D) printing technology are increasing following the approval of 3D-printed tablets by the U.S. Food and Drug Administration. Semi-solid extrusion-type 3D printers are used to 3D print hydrogel- and paste-based materials. We previously developed tablet formulations for semi-solid extrusion-type 3D bioprinters. In the present study, we extended our study to the preparation of muco-adhesive oral film formulations to 3D bioprint mouth ulcer pharmaceuticals. We focused on hydroxypropyl methylcellulose (HPMC)-based catechin (model drug)-loaded hydrogel formulations and found that the viscosity of a hydrogel formulation is dependent on the HPMC concentration, and that viscosity is important for facile 3D printing. HPMC-based films were prepared using two different drying methods (air drying and freeze drying). The films exhibited different drug dissolution profiles, and increasing the amount of HPMC in the film delayed drug dissolution. The fabrication of HPMC-based catechin-loaded films with different shapes provides a model of individualized, on-demand pharmaceuticals. Our results support the flexible application of 3D bioprinters (semi-solid extrusion-type 3D printers) for preparing film formulations.

Background: Bowel disturbances have been identified as the most important risk factor for fecal incontinence (FI). However, few studies have evaluated the impact of fiber supplementation. Our aim was to assess the correlation between the improvement in stool consistency by fiber supplementation and the changes in urgency and number of FI episodes and in the QoL of patients with FI., Methods: Eighty-three patients who came to our institution with FI and/or fecal urgency associated with loose stools or diarrhea were prospectively included in the study The intervention included dietary advice and methylcellulose 500 mg every 8 h for 6 weeks. All assessments were carried out at baseline and 6 weeks after the start of the intervention, and included a Bristol Stool Scale, a 3-week bowel diary, the St Mark's score, the Fecal Incontinence Quality of Life scale (FIQL) and a bowel satisfaction score., Results: Sixty-one patients completed the study. At baseline 50 reported episodes of urge incontinence, while 11 did not report FI episodes because they rarely left home to avoid leakage. The Bristol score improved to normal stools in 65.6% of patients after treatment. Bowel diaries showed a statistically significant reduction in the number of bowel movements, urge episodes, urge fecal incontinence episodes and soiling per week. The St Mark's score and the bowel satisfaction score significantly improved after methylcellulose and overall deferment time also increased. FIQL significantly improved in two subdomains (lifestyle, coping/behavior). Thirty-one patients (51.7%) were discharged with methylcellulose as the only treatment., Conclusions: FI may significantly improve with methylcellulose in selected cases. Assessment of fecal consistency and initial treatment with methylcellulose could be started at primary care level to reduce the need for specialist referral.

Introduction: HPMC-p, an inert micronized powder form of hydroxy-propyl-methyl-cellulose, when insufflated nasally, provides a natural barrier against pollen allergens and noxious agents. This overview assesses the efficacy and safety of this patented powder product and delivery system without an analogue among the cellulose derivatives. Areas covered: Twenty-six studies with HPMC-p were critically appraised to obtain an updated characteristic of the product. Most studies assessed the efficacy of HPMC-p as a nasal barrier enforcing measure: one experimental setup evaluated its ability to prevent or delay the diffusion of allergen through it, two clinical studies used allergen provocation tests, and the remaining relied on clinical criteria in open real world or placebo controlled designs. Two studies checked if HPMC-p could enhance the efficacy of drugs applied nasally to treat local symptoms. The studies, using either nasal allergen challenge or natural exposure of patients to environmental allergen, support the hypothesis that HPMC-p possesses barrier enforcing properties. Also, acute and clinical experiments indicated that intra-nasal application of HPMC-p following local relief medications enhances their ability to suppress symptoms and reduces their long-term use. Expert commentary: Nasal insufflation of HPMC-p provides a mucosal barrier, reducing the nasal symptoms and enhancing the effects of local relief medications.

Despite the use of modern methods of prevention, at least 10% of patients operated on for ophthalmic indications not develop corneal erosion as the indirect complication of general anesthesia., Objective: To reduce the number of ophthalmic complications of general anesthesia by prophylactic use of new mito- chondria-targeted antioxidants - Vizomitin (eye drops)., Materials and Methods: 70 patients, which was supposed to perform the average duration of operations under general anesthesia were randomized into 3 groups depending on the method specific (pharmacological) prevention of corneal erosions: (1) control (specic (pharmacological) prevention was not carried out), (2), using preparation "natural tear, and (3) "Vizomitin" preparation. Postoperative biomicroscopy was performed to assess the condition of the cornea, tear film stability was measured and the height of the tear meniscus., Results: When using eye drops "Vizomitin" value is an indicator of stability of the tear film on the 3rd day after the operation more than in the control group of patients by 51% (p = 0.012) and patients groups, natural tear by 57% (p = 0.013). Surgical interventions performed under general anesthesia, leading to an increase in the number ofpatients with decreased tear meniscus height index of the control group with 4 to 7 patients (p = 0.30) in the group of natural tear from 3 to 11 patients (p = 0.008) . In the group with drug "Vizomitin" the number of such patients is reduced from 7 to 1 (p = 0.018)., Conclusion: In the surgical procedures under general anesthesia eye drops "Vizomitin" effectively prevents the devel- opment of corneal erosion.

Objective: Wounds that have stalled healing are costly in terms of patient morbidity and increase in use of material and financial resources. A natural polymer beta-glucans has been incorporated into a methylcellulose gel to provide a topical gel designed to accelerate healing in wounds where it has stalled. Although the gel provides an environment conducive to moist wound healing the active agent, beta-glucans, activate the innate immune response., Method: Using a Markov cohort simulation model, data were extrapolated from a double-blind randomised trial to evaluate the economic benefits of the soluble beta-glucan (SBG) gel in the treatment of diabetic foot ulcers (DFUs)., Results: Over an annual budget cycle, SBG gel is expected to heal 94% of wounds compared with 78% when given standard care. It also healed wounds more quickly, with the average expected healed weeks 34.4 in the SBG gel group, compared with 24.7 methylcellulose dressing group. In our model this leads to a cost saving over an annual budget cycle of £503 per patient. Note: healed weeks refers to the number of weeks when the wound has healed during the 12-week period and should not be confused with weeks to healing., Conclusion: The shorter healing time associated with the SBG gel treatment leads to a cost saving because fewer weeks of treatment are required to heal the wound, suggesting this is a promising new cost-effective option for the treatment of DFUs.

Constipation is a common complaint for people of all ages, with prevalence increasing with age and during pregnancy. Women are more likely to be affected than men. Severity of constipation varies from person to person; most people experience short periods of constipation during their lives, including possibly after surgery, while others have constipation as a chronic long-term condition that can significantly affect their quality of life. There are a number of factors that can contribute to developing constipation including diets low in fibre, changes in lifestyle, side effects of certain medications and low fluid intake. People can successfully treat constipation by making changes to their diet and lifestyle. However, medication may be required to manage constipation for some.

The purpose of this study was to improve the operability of calcium silicate cements (CSCs) such as mineral trioxide aggregate (MTA) cement. The flow, working time, and setting time of CSCs with different compositions containing low-viscosity methyl cellulose (MC) or hydroxypropyl cellulose (HPC) additive were examined according to ISO 6876-2012; calcium ion release analysis was also conducted. MTA and low-heat Portland cement (LPC) including 20% fine particle zirconium oxide (ZO group), LPC including zirconium oxide and 2 wt% low-viscosity MC (MC group), and HPC (HPC group) were tested. MC and HPC groups exhibited significantly higher flow values and setting times than other groups ( p < 0.05). Additionally, flow values of these groups were higher than the ISO 6876-2012 reference values; furthermore, working times were over 10 min. Calcium ion release was retarded with ZO, MC, and HPC groups compared with MTA. The concentration of calcium ions was decreased by the addition of the MC or HPC group compared with the ZO group. When low-viscosity MC or HPC was added, the composition of CSCs changed, thus fulfilling the requirements for use as root canal sealer. Calcium ion release by CSCs was affected by changing the CSC composition via the addition of MC or HPC., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Introduction: This article presents the results of an international, multicenter, randomized, double-masked, placebo-controlled clinical study of Visomitin (Mitotech LLC, Moscow, Russian Federation) eye drops in patients with dry eye syndrome (DES). Visomitin is the first registered (in Russia) drug with a mitochondria-targeted antioxidant (SkQ1) as the active ingredient., Methods: In this multicenter (10 sites) study of 240 subjects with DES, study drug (Visomitin or placebo) was self-administered three times daily (TID) for 6 weeks, followed by a 6-week follow-up period. Seven in-office study visits occurred every 2 weeks during both the treatment and follow-up periods. Efficacy measures included Schirmer's test, tear break-up time, fluorescein staining, meniscus height, and visual acuity. Safety measures included adverse events, slit lamp biomicroscopy, tonometry, blood pressure, and heart rate. Tolerability was also evaluated., Results: This clinical study showed the effectiveness of Visomitin eye drops in the treatment of signs and symptoms of DES compared with placebo. The study showed that a 6-week course of TID topical instillation of Visomitin significantly improved the functional state of the cornea; Visomitin increased tear film stability and reduced corneal damage. Significant reduction of dry eye symptoms (such as dryness, burning, grittiness, and blurred vision) was also observed., Conclusion: Based on the results of this study, Visomitin is effective and safe for use in eye patients with DES for protection from corneal damage., Funding: Mitotech LLC.

Oral candidiasis (OC), caused by the fungal pathogen Candida albicans, is the most common opportunistic infection in HIV(+) individuals and other immunocompromised populations. The dramatic increase in resistance to common antifungals has emphasized the importance of identifying unconventional therapeutic options. Antimicrobial peptides have emerged as promising candidates for therapeutic intervention due to their broad antimicrobial properties and lack of toxicity. Histatin-5 (Hst-5) specifically has exhibited potent anticandidal activity indicating its potential as an antifungal agent. To that end, the goal of this study was to design a biocompatible hydrogel delivery system for Hst-5 application. The bioadhesive hydroxypropyl methylcellulose (HPMC) hydrogel formulation was developed for topical oral application against OC. The new formulation was evaluated in vitro for gel viscosity, Hst-5 release rate from the gel, and killing potency and, more importantly, was tested in vivo in our mouse model of OC. The findings demonstrated a controlled sustained release of Hst-5 from the polymer and rapid killing ability. Based on viable C. albicans counts recovered from tongues of treated and untreated mice, three daily applications of the formulation beginning 1 day postinfection with C. albicans were effective in protection against development of OC. Interestingly, in some cases, Hst-5 was able to clear existing lesions as well as associated tissue inflammation. These findings were confirmed by histopathology analysis of tongue tissue. Coupled with the lack of toxicity as well as anti-inflammatory and wound-healing properties of Hst-5, the findings from this study support the progression and commercial feasibility of using this compound as a novel therapeutic agent., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has been suggested as a potential healing therapeutic following glaucoma surgery. Here, we aimed to improve the bioavailability of bevacizumab when used as an adjunct therapy to non-penetrating deep sclerectomy (DS) by using a bevacizumab-methylcellulose mixture (BMM). Ten previously non-operated eyes in ten patients diagnosed with primary open angle glaucoma underwent DS with a subconjunctival injection of 0.3 ml of BMM (bevacizumab 3.75 mg incorporated into 4% methylcellulose) at the surgical site. Bevacizumab release was evaluated in vitro using size-exclusion high performance liquid chromatography (HPLC). Intraocular pressure (IOP), bleb morphology, corneal endothelial cell count (CECC), and complications were evaluated at 6 months after surgery. Using HPLC, bevacizumab was detected in BMM for up to 72 h. Moreover, all surgical blebs remained expanded with hyaline material during the first week. A significant IOP reduction (mean ± SD= -10.3 ± 5.4 mmHg, P<0.001) and diffuse blebs were observed at the final follow-up period. Although CECC was slightly reduced (-7.4%), no complications were observed. In conclusion, bevacizumab was released from BMM, and the use of this innovative mixture yielded good results following DS with no complications. Further studies are required to determine its efficacy prior to establishing BMM as an adjunct treatment for penetrating and non-penetrating glaucoma surgeries.

MMP9-responsive bivalirudin-HPMA copolymers were synthesized for direct, local administration in rat spinal cord contusion injury models. Polymer-conjugated bivalirudin peptides maintained activity while demonstrating enzyme-mediated release upon MMP9 exposure and prolonged release from hyaluronic acid/methylcellulose (HAMC) hydrogels compared to free bivalirudin peptide. Localized administration of bivalirudin copolymers in vivo at the site of rat spinal cord injury decreased cellular proliferation and astrogliosis, suggesting the bivalirudin copolymer and HAMC hydrogel system are a promising therapeutic intervention for reducing immediate inflammatory responses and long term scarring.

Purpose: A pilot investigation to transfer the established corneal collagen crosslinking (CXL) procedure in European eyes into clinically affected African eyes and to optimize the treatment by adapting the riboflavin composition., Materials and Methods: CXL was performed in 15 eyes (11 patients) with advanced stages of keratoconus in the Eye Clinic of Bafoussam in the West Region of Cameroon. The following six riboflavin compositions with different portions of active swelling additives were applied: Solution 1 (0.5% methylhydroxypropylcellulose [MHPC]), solution 2 (1.0% MHPC), solution 3 (1.7% MHPC), solution 4 (5% dextran), solution 5 (10% dextran) and solution 6 (no active swelling ingredient). The central corneal thickness (CCT) was measured by ultrasound pachymetry before and after de-epithelialization and at least every 10 min during CXL., Results: THE APPLICATION OF THE RIBOFLAVIN SOLUTIONS RESULTED IN THE FOLLOWING MEAN FINAL CCT VALUES: 172 ± 15% using solution 1 (60 min/n = 5); 183 ± 8% using solution 2 (60 min/n = 5); 170% using solution 3 (60 min/n = 1); 80% using solution 4 (45 min/n = 1); 99% using solution 5 (45 min/n = 1) and 150 ± 13% using solution 6 (50 min/n = 2)., Conclusions: The combination of riboflavin compositions with swelling and stabilizing effects on the corneal stroma seems necessary in African eyes with advanced keratoconus. Further studies are required to confirm these primary results.

Clinical morphological efficiency of local application of a new biopolymeric film was studied. The film was based on methylcellulose derivatives and contained shikonin (preparation of plant origin) and its esters isolated from Lithospermum erythrorhizon L. cell culture. Combined therapy of 30 patients (34-72 years) with erosive ulcerative lichen planus and leukoplakia of the buccal mucosa was carried out. Local application of the new drug led to more rapid pain relief, epithelialization of the inflammatory destructive foci in the buccal mucosa, and reduced the intensity of morphological signs of lesions in the studied patient population.

Background: Cognitive behavioral therapy (CBT) has been shown to have positive effects on the management of irritable bowel syndrome (IBS) symptoms. A factorial pilot randomized placebo-controlled trial (called MIBS) tested the potential effectiveness of a self-management CBT-based website alongside two medications: methylcellulose and mebeverine, and a placebo. The results showed no significant differences in quality of life or symptom severity measures, but enablement and participant's global assessment of relief was higher in the website groups., Objective: To conduct a qualitative study nested within this trial, in order to explore patients' views and experiences of using the CBT-based website to facilitate self-management of IBS., Methods: Semistructured interviews were carried out with patients who had used the website with one session of nurse support (n=16) or the website alone (n=15) while participating in the MIBS trial. An inductive thematic analysis was conducted., Results: We identified three types of engagement with the CBT-based website. One group of participants, mostly in the website-only condition, had limited or no engagement with the website. One group engaged with the content and advice on practical lifestyle changes. The final group of participants engaged with the content and advice on psychological aspects related to IBS. Similarities and differences between these three groups are explored., Conclusions: Teaching self-management techniques through a Web intervention was received positively by most of the participants. Concepts linked to cognitive aspects of CBT appeared to be harder for participants to engage with. Participants who received nurse support rated the cognitive aspects more positively, suggesting that some therapy support alongside the website should be considered. However, the Web format was preferred by some who favored anonymity as well as those who appreciated the accessibility and ease of use of this type of management. Suggestions on how to encourage engagement with Web interventions are discussed.

The effect of hydroxypropyl methylcellulose (HPMC) on hepatic gene expression was analyzed by exon microarray and real-time PCR from livers of diet-induced obese (DIO) mice fed a high-fat (HF) diet supplemented with either 6% HPMC or 6% microcrystalline cellulose (MCC). HPMC-fed mice exhibited significantly reduced body weight gain (55% lower compared to MCC), liver weight (13%), plasma LDL-cholesterol concentration (45%), and HF diet-increased intestinal permeability (48%). HPMC significantly reduced areas under the curve for 2 h insulin and glucose responses, indicating enhanced insulin sensitivity and glucose metabolism. HPMC up-regulated hepatic genes related to fatty acid oxidation, cholesterol and bile acid synthesis, and cellular activation of glucocorticoid (bile acid recycling) and down-regulated genes related to oxidative stress, triglyceride synthesis, and polyunsaturated fatty acid elongation. In conclusion, HPMC consumption ameliorates the effects of a HF diet on intestinal permeability, insulin resistance, hepatic lipid accumulation, glucocorticoid-related bile acid recycling, oxidative stress, and weight gain in DIO mice.

Background: Many patients with IBS suffer on-going symptoms. The evidence base is poor for IBS drugs but they are widely prescribed and advised in Guidelines. Cognitive Behavioural Therapy (CBT) can be helpful, but availability is poor in the NHS. We developed a web-based CBT self-management programme (Regul8) in partnership with patients and trialled it and common IBS medications in an exploratory factorial RCT to test trial procedures and provide information for a larger trial., Methods: Patients, 16 to 60 years, with IBS symptoms fulfilling Rome III criteria were recruited via GP practices and randomised to over-encapsulated mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 website conditions: Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website., Results: 135 patients recruited from 26 GP practices. Mean IBS SSS score 241.9 (sd 87.7), IBS-QOL 64 (sd 20) at baseline. 91% follow-up at 12 weeks. Mean IBS SSS decreased by 35 points from baseline to 12 weeks. There was no significant difference in IBS SSS or IBS-QOL score between medication or website groups at 12 weeks, or in medication groups at 6 weeks, or IBS-QOL in website groups at 6 weeks. However, IBS SSS at 6 weeks was lower in the No website group than the website groups (IBS SSS no website =162.8 (95% CI 137.4-188.3), website 197.0 (172.4 - 221.7), Website + telephone support 208.0 (183.1-233.0) p = 0.037)., Conclusions: This exploratory study demonstrates feasibility and high follow-up rates and provides information for a larger trial. Primary outcomes (IBS SS and IBS QOL) did not reach significance at 6 or 12 weeks, apart from IBS SSS being lower in the no-website group at 6 weeks - this disappeared by 12 weeks. Improved Enablement suggests patients with access to the Regul8 website felt better able to cope with their symptoms than the non-website group. Improved SGA score in the Regul8 groups may indicate some overall improvement not captured on other measures., Trial Registration: ClinicalTrials.gov Identifier (NCT number): NCT00934973.

Superior limbic keratoconjunctivitis (SLK) is an uncommon, painful inflammation of the ocular surface localized to the superior sectors of the cornea, limbus, and conjunctiva. The clinical course tends to be chronic, with alternating periods of remission and exacerbation. Many patients experience severe ocular discomfort for long periods. Corneal involvement may induce scarring, astigmatism, and ultimately decreased vision. SLK typically occurs in woman between 20 and 60 years of age. Little is known about the features of SLK in young children because the earliest age described in the literature is adolescence. We report the clinical presentation and management of SLK in a 7-year-old boy who responded well to topical steroids and lubricants., (Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Structural and functional abnormalities in the neurovascular unit (NVU) have been recently observed in Alzheimer's disease (AD). Statins, which are used clinically for reducing cholesterol levels, can also exert beneficial vascular actions, improve behavioral memory and reduce senile plaque (SP). Thus, we examined cognitive function, the serum level of lipids, senile plaque (SP), and the protective effects of statins on NVU disturbances in a mouse AD model. Amyloid precursor protein (APP) transgenic (Tg) mice were used as a model of AD. Atorvastatin (30 mg/kg/day, p.o.) or pitavastatin (3mg/kg/day, p.o.) were administered from 5 to 20 months of age. These 2 statins improved behavioral memory and reduced the numbers of SP at 15 and 20 M without affecting serum lipid levels. There was a reduction in immunopositive staining for N-acetyl glucosamine oligomer (NAGO) in the endothelium and in collagen IV in the APP vehicle (APP/Ve) group, with collagen IV staining most weakest near SP. There was also an increase in intensity and numbers of glial fibrillary acidic protein (GFAP) positive astrocytes, particularly around the SP, where MMP-9 was more strongly labeled. Double immunofluorescent analysis showed that astrocytic endfeet had detached from the capillary endothelium in the APP/Ve group. Overall, these data suggest that statins may have therapeutic potential for AD by protecting NVU., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The effect of hydroxyethyl methylcellulose (HEMC) with different viscosities on the glucose metabolism and antioxidative defense system in high fat-fed mice was investigated. The mice were randomly divided into five dietary groups: normal control diet (NC), high fat diet (HF), and high fat diet supplemented with high viscosity (HF-HV), moderate viscosity (HF-MV), and low viscosity (HF-LV) HEMC fibers. After 6 weeks, the HF group showed a marked increase in body weight gain, body fat, blood glucose concentration, insulin level, and erythrocyte lipid peroxidation rate relative to the NC group. However, supplementation of HEMC in the diet suppressed these high fat-induced hyperglycemia and oxidative stress through enhancement of the activities of hepatic glucokinase and antioxidant enzymes. The hypoglycemic and antioxidative effects increased with increased viscosity of the HEMC consumed. These results illustrate that HEMC with high viscosity may be useful in the management of high fat diet-induced hyperglycemia and oxidative stress., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Context: Pediatric cataract surgery is traditionally done with the aid of high-molecular-weight viscoelastics which are expensive. It needs to be determined if low-cost substitutes are just as successful., Aims: The study aims to determine the success rates for anterior and posterior capsulorrhexis and intraocular lens (IOL) implantation in the bag for pediatric cataract surgery performed with the aid of a low-molecular-weight viscoelastic., Settings and Design: Nonrandomized observational study., Materials and Methods: Children less than 6 years of age who underwent cataract surgery with IOL implantation in the period May 2008-May 2009 were included. The surgeries were done by pediatric ophthalmology fellows. A standard procedure of anterior capsulorrhexis, lens aspiration with primary posterior capsulorrhexis, anterior vitrectomy, and IOL implantation was followed. Three parameters were studied: successful completion of anterior and posterior capsulorrhexis and IOL implantation in the bag., Results: 33 eyes of 28 children were studied. The success rate for completion was 66.7% and 88.2 % for anterior and posterior capsulorrhexis, respectively. IOL implantation in the bag was successful in 87.9%., Conclusions: 2% hydroxypropylmethylcellulose is a viable low-cost alternative to more expensive options similar to high-molecular-weight viscoelastics. This is of great relevance to hospitals in developing countries.

Purpose: To compare the efficacies of sodium hyaluronate, hydroxypropyl methylcellulose (HPMC), and a new oil-in-water emulsion (Emustil unidose; SIFI) in the management of lipid-deficient dry eye., Methods: Seventy-five subjects with dry eye were randomly divided into 3 groups. Each was allocated sodium hyaluronate, HPMC, or emulsion eyedrops to be used four times daily for 90 days. Parameters were measured at baseline, 30 days, and 90 days. A compliance visit was performed at days 7 and 60., Results: Significant reduction (P < 0.05) in evaporation and improvement in symptoms in all groups were found. No statistically significant increase in tear turnover rate (TTR) was found with any solution. A significant difference in tear stability and noninvasive tear break-up time (NITBUT) was found in the emulsion and sodium hyaluronate groups but not in the HPMC group (P > 0.05). There was a significant decrease in osmolarity and corneal staining in the emulsion group (P < 0.001) but not in the sodium hyaluronate or HPMC group (P > 0.05)., Conclusions: A significant reduction in evaporation and improvement in symptoms in all therapy groups were found from baseline to 90 days. However, no significant effect was seen on TTR for any group. The emulsion drops were shown to perform best, improving tear stability, and decreasing osmolarity and corneal staining. These results are consistent with improvements in the lipid layer of the tear film as a result of prolonged use of emulsion drops.

We attempted to develop anti-cataract eye drops using disulfiram (DSF) and low-substituted methylcellulose (MC), and evaluated their anti-cataract effect in terms of the lens opacification vs. age-profile curves using a one-exponential equation. The eye drops were prepared using 0.5% DSF and 2% MC (DSF eye drops), and ICR/f rats, a recessive-type hereditary cataractous strain, were used as the experimental model. Gelation of DSF eye drops containing MC was first observed at about 35°C, close to body temperature. In in vivo transcorneal penetration experiments using rabbit corneas, only diethyldithiocarbamate (DDC) was detected in the aqueous humor, while DSF was not detected. The DDC penetration level of DSF eye drops containing MC was approximately 1.3-fold higher than that of DSF eye drops. The opacification rate constant (k) of ICR/f rat instilled with DSF eye drops with or without MC was lower, and the initial time of opacification (τ) was longer than those of ICR/f rats instilled with saline. Furthermore, the k of ICR/f rats instilled with DSF eye drops with MC was lower than that of ICR/f rats instilled with DSF eye drops without MC. In conclusion, the analysis of kinetic parameters including k and τ using a one-exponential equation provided useful information for clarifying the anti-cataract effect of eye drops. ICR/f rats instilled with DSF eye drops using a low-substituted MC-based drug delivery system demonstrated a delay in cataract development, probably resulting from an increase in the retention of DSF eye drops on the cornea.

Purpose: To analyze and compare the postoperative outcomes of eyes with accidental intraoperative inversion of implantable collamer lens (ICL) and viscocannula-assisted reinversion in high myopia., Design: Retrospective observational case comparison., Setting: Institutional practice., Patients: Consecutive eyes with accidental intraoperative inversion of ICL and viscocannula-assisted reinversion from January 2007 to September 2010 were analyzed retrospectively. They were compared with the fellow eyes with normal ICL implantation at 1 month, 6 months, and 2 years., Main Outcome Measures: Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), corneal pachymetry, endothelial cell loss, intraocular pressure, lens transparency, anterior chamber depth, and postoperative uveitis., Results: A total of 206 myopic eyes had ICL implantation. Eight eyes (3.8%) of 8 patients had accidental intraoperative reinversion. Their fellow eyes had normal ICL implantation. There was no significant change (P = .611) in UCVA (reinverted and fellow eyes) at 2 years. There was no significant difference in postoperative UCVA (P = .611) and BCVA (P = .854) between the reinverted and the fellow eyes. The mean endothelial loss at 1 month, 6 months, and 2 years was 0.96% ± 0.5%, 0.92% ± 0.63%, and 0.89% ± 0.52% respectively in the reinverted eyes. There was no significant difference in the endothelial loss between the 2 groups at 1 month (P = .753), 6 months (P = .834), and 2 years (P = .916). One out of 8 eyes with reinversion had postoperative corneal edema, which resolved at 48 hours. None of the eyes reported uveitis or glaucoma. There was no loss of lens transparency., Conclusion: Intraoperative inversion can occur during insertion of ICL and viscocannula-assisted reinversion can be performed without significant complications., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: IBS affects 10-22% of the UK population. Abdominal pain, bloating and altered bowel habit affect quality of life, social functioning and time off work. Current GP treatment relies on a positive diagnosis, reassurance, lifestyle advice and drug therapies, but many suffer ongoing symptoms.A recent Cochrane review highlighted the lack of research evidence for IBS drugs. Neither GPs, nor patients have good evidence to inform prescribing decisions. However, IBS drugs are widely used: In 2005 the NHS costs were nearly £10 million for mebeverine and over £8 million for fibre-based bulking agents. CBT and self-management can be helpful, but poor availability in the NHS restricts their use. We have developed a web-based CBT self-management programme, Regul8, based on an existing evidence based self-management manual and in partnership with patients. This could increase access with minimal increased costs., Methods/design: The aim is to undertake a feasibility factorial RCT to assess the effectiveness of the commonly prescribed medications in UK general practice for IBS: mebeverine (anti-spasmodic) and methylcellulose (bulking-agent) and Regul8, the CBT based self-management website.135 patients aged 16 to 60 years with IBS symptoms fulfilling Rome III criteria, recruited via GP practices, will be randomised to 1 of 3 levels of the drug condition: mebeverine, methylcellulose or placebo for 6 weeks and to 1 of 3 levels of the website condition, Regul8 with a nurse telephone session and email support, Regul8 with minimal email support, or no website, thus creating 9 groups., Outcomes: Irritable bowel symptom severity scale and IBS-QOL will be measured at baseline, 6 and 12 weeks as the primary outcomes. An intention to treat analysis will be undertaken by ANCOVA for a factorial trial., Discussion: This pilot will provide valuable information for a larger trial. Determining the effectiveness of commonly used drug treatments will help patients and doctors make informed treatment decisions regarding drug management of IBS symptoms, enabling better targeting of treatment. A web-based self-management CBT programme for IBS developed in partnership with patients has the potential to benefit large numbers of patients with low cost to the NHS. Assessment of the amount of email or therapist support required for the website will enable economic analysis to be undertaken.

There is no effective treatment for spinal cord injury and clinical drug delivery techniques are limited by the blood-spinal cord barrier. Our lab has developed an injectable drug delivery system consisting of a biopolymer blend of hyaluronan and methylcellulose (HAMC) that can sustain drug release for up to 24h in the intrathecal space. Fibroblast growth factor 2 (FGF2) has great potential for treatment of spinal cord injury due to its angiogenic and trophic effects, but previous studies showed no penetration into spinal cord tissue when delivered locally. Conjugation to poly(ethylene glycol) (PEG) is known to improve penetration of proteins into tissue by reducing clearance and providing immunogenic shielding. We investigated conjugation of PEG to FGF2 and compared its distribution relative to unmodified FGF2 in injured spinal cord tissue when delivered intrathecally from HAMC. Importantly, PEG conjugation nearly doubled the concentration of FGF2 in the injured spinal cord when delivered locally and, contrary to previous reports, we show that some FGF2 penetrated into the injured spinal cord using a more sensitive detection technique. Our results suggest that PEGylation of FGF2 enhanced tissue penetration by reducing its rate of elimination., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: We hypothesised that different solutions for submucosal injection may influence early healing of endoscopic mucosal resection (EMR). The aim of this study was to evaluate histological and immunological changes after EMR in experimental pigs., Materials and Methods: Two parallel EMRs on the anterior and posterior wall of the gastric body were performed by means of the cap technique in 21 female pigs. A glycerol-based solution (anterior EMR) and hydroxypropyl methylcellulose solution (posterior EMR) were applied for submucosal injection. The animals were sacrificed 7 days later, and tissue sections of all EMRs were stained using combined trichrome. Computer image analysis was used for objective evaluation of elastic and collagen fibres content. Two-colour indirect immunophenotyping of blood and gastric samples were performed using mouse anti-pig monoclonal antibodies., Results: The values of collagen fibre content 7 days after EMR were significantly higher in lesions after the use of solution A in comparison with solution B (2.10 +/- 0.25% versus 1.57 +/- 0.25%, p = 0.009). Concordant results were found in elastic fibres (3.23 +/- 0.49% versus 2.93 +/- 0.61%, p = 0.018). No systemic changes in major leukocyte subpopulations were found. In gastric tissue, lymphocyte subsets exhibited only minor changes. CD4(+) T-lymphocytes were increased in the healing tissue after EMR using solution A (17.08 +/- 9.24% versus 9.76 +/- 7.97%, p = 0.011). Significant increase of SWC3(+) leukocytes was observed after EMR using solution B (47.70 +/- 25.41% versus 18.70 +/- 12.16%, p = 0.001)., Conclusions: The use of glycerol-based solution for submucosal injection was associated with more pronounced histological signs of early healing of EMRs compared with hydroxypropyl methylcellulose.

Background/objectives: Consumption of hydroxypropylmethylcellulose (HPMC), a viscous dietary fiber, lowers total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, HPMC had not previously been studied in individuals receiving lipid drug therapy., Subjects/methods: This randomized, double-blind crossover trial examined the lipid effects of HPMC in subjects with hypercholesterolemia on statin therapy. Men (n=5) and women (n=8) with LDL-C> or =2.59 mmol/l after at least 4 weeks of stable-dose statin therapy, and a mean age of 58.6 years, were enrolled. Subjects received twice daily doses of either 2.5 g HPMC or control, delivered in a lemonade beverage for 4 weeks, then crossed over to receive the opposite treatment for an additional 4 weeks., Results: Mean baseline concentrations of TC, non-high-density lipoprotein cholesterol (non-HDL-C), LDL-C, HDL-C, triglyceride (TG), TC/HDL-C ratio and apolipoprotein (Apo) B were 4.95, 3.63, 3.03, 1.33, 1.30 and 3.89 mmol/l and 1.00 g/l, respectively. HPMC consumption resulted in significantly larger reductions (P<0.01 vs control for all) in TC (-10.9 vs -3.5%), non-HDL-C (-12.8 vs -2.9%), LDL-C (-15.7 vs -5.1%), TC/HDL-C ratio (-5.3 vs +1.3%) and Apo B (-8.7 vs -3.9%). There were no differences between treatments for changes in HDL-C (-5.2 vs -4.3%) or TG (+3.9 vs +8.9%)., Conclusions: These results support the view that HPMC is an effective adjunct to statin therapy for further lowering atherogenic lipids and lipoproteins in men and women with primary hypercholesterolemia.

A variety of materials have been used as fillers for soft tissue augmentation. In this study, methylcellulose (MC), a water-soluble derivative of the polysaccharide cellulose, was modified with functional methacrylate groups and photocrosslinked to produce hydrogels for potential application in plastic and reconstructive surgery. Purified macromer (5% theoretical modification, 2.3% actual) was resuspended in 0.05wt.% of the photoinitiator, 2-methyl-1-[4-(hydroxyethoxy)phenyl]-2-methyl-1-propanone, cast into custom molds, and exposed to long-wavelength UV light for 10min to form gels. Photocrosslinked MC hydrogels at varying weight/volume percentages displayed equilibrium weight swelling ratios (wet weight/dry weight) and elastic moduli of 30+/-3 to 17+/-2 and 8.48+/-0.25kPa to 23.21+/-1.55kPa, respectively, demonstrating the formation of stable gels with tunable properties. Human dermal fibroblasts grown in the presence of MC hydrogels in vitro exhibited no significant changes in cell viability after 5days of co-culture, indicating that the materials are non-cytotoxic. Higher weight percentage MC hydrogels (6%) implanted subcutaneously in CD-1 mice maintained their integrity and original dimensions after 80days in vivo, eliciting a mild inflammatory response with no observed inflammatory exudate, minimal vascular infiltration and thin translucent fibrous capsule formation of approximately 50microm in thickness. Taken together, the material and biological properties of photocrosslinked MC hydrogels suggest that they may be of use in soft tissue reconstruction.

Background: Hydroxypropylmethylcellulose (HPMC) is a modified cellulose fiber that creates a viscous solution in the gastrointestinal tract. The present study examined the dose-response characteristics of high-viscosity (HV)-HPMC consumption on postprandial glucose and insulin levels in men and women at increased risk for type 2 diabetes mellitus., Methods: Subjects were a subset of participants in two trials with elevated peak postprandial glucose [>or=7.8 mmol/L (>or=140 mg/dL)] and body mass index (BMI) >or=27 kg/m(2). Subjects (n = 39) consumed breakfast meals containing 75 g of carbohydrate, each of which contained 1, 2, 4, or 8 g of HV-HPMC or a cellulose control in a randomized, double-blind manner. Each subject completed tests with control and two HV-HPMC doses., Results: Peak glucose concentration was lower than control (all P < 0.01) following 2 g (10%), 4 g (18%), and 8 g (20%) of HV-HPMC. Peak insulin was also reduced (P < 0.01) following 2 g (32%), 4 g (35%), and 8 g (46%) of HV-HPMC doses versus control. Incremental areas for glucose from 0 to 120 min were reduced by 8-40% versus control but only reached significance for the 4-g and 8-g conditions, whereas incremental areas under the insulin curves were reduced by 14-53% (P < 0.01 for 2, 4, and 8 g of HV-HPMC)., Conclusions: Among subjects at risk for type 2 diabetes mellitus, 1.0-8.0 g of HV-HPMC blunted postprandial glucose and insulin responses in a dose-dependent manner. Additional research is warranted to assess whether chronic consumption might retard the development or progression of glucose intolerance.

Objective: To determine the cholesterol-lowering efficacy of hydroxypropylmethylcellulose (HPMC) in mildly hypercholesterolemic humans., Subjects: Trial one: entry mean (range) total serum cholesterol values of eight female and four male subjects were 6.48 (5.57-7.51) mmol l(-1) (250 (215-290) mg dl(-1)) and 6.60 (5.57-7.64) mmol l(-1) (255 (215-295) mg dl(-1)), respectively. Trial two: corresponding values for 20 women and 20 men were 5.96 (5.43-6.48) mmol l(-1) 230 (210-250) mg dl(-1)) and 6.05 (5.46-6.63) mmol l(-1) 233 (211-256) mg dl(-1)), respectively., Results: Trial one: HPMC decreased (P< or =0.05) total and LDL-cholesterol 9.3 and 15.3% (medium), 16.9 and 23.5% (high) and 13.8 and 19.4% (ultra-high), respectively, over placebo. Trial two: total and LDL-cholesterol decreased (P< or =0.05) throughout the 8 weeks, with mean (weeks 4-8) reductions of 7 and 8% at 5 g day(-1), and 12 and 15% at 15 g day(-1), respectively, over placebo. Adverse effects were minimal. Trial one: medium, high and ultra-high viscosity HPMC at 15 g day(-1) for 1 week each;1-week wash-out between treatments. Trial two: ultra-high viscosity HPMC at 5 or 15 g day(-1) for 8 weeks., Conclusions: HPMC soluble fiber, especially high-viscosity grades, significantly lowers cholesterol at well-tolerated doses, showing promise as a treatment of hypercholesterolemia.

Objective: To evaluate the efficacy of methylcellulose (Citrucel) and loperamide (Imodium) in managing fecal incontinence by comparing cure rates with expectant management., Design: Prospective controlled study., Setting: Urogynecology clinic in a university hospital., Population: Sixty-nine women with fecal incontinence., Methods: All incontinent women received one heaping tablespoon of methylcellulose twice a day, which was increased to two heaping tablespoons twice a day as needed. If the incontinence persisted after taking the maximum dose of methylcellulose for two weeks, loperamide, one capsule twice a day was added, which was increased to two capsules three times a day as needed. If both fecal urgency and incontinence resolved, the therapy was continued for a three-month treatment period. Women, who declined the proposed treatment and did not undergo any other therapy during the subsequent eight weeks, served as controls. A subject or control was considered cured if she stated that her incontinence was cured, had zero Pescatori incontinence point, resolution of fecal urgency, and her incontinence did not affect her emotional, social, occupational, and physical functions during the three-month treatment or eight-week observation period., Main Outcome Measures: Difference in the cure rate between subjects and controls. Results. Fifty-nine subjects were treated with methylcellulose. Forty (68%) also required loperamide. Ten women served as controls. Women treated with methylcellulose and loperamide had a higher cure rate than those managed expectantly (46% vs. 0%, p<0.01)., Conclusion: Methylcellulose and loperamide are an effective treatment for fecal incontinence, at least on a short-term basis.

Stem cell transplantation is a promising approach for the treatment of traumatic brain injury, although the therapeutic benefits are limited by a high degree of donor cell death. Tissue engineering is a strategy to improve donor cell survival by providing structural and adhesive support. However, optimization prior to clinical implementation requires expensive and time-consuming in vivo studies. Accordingly, we have developed a three-dimensional (3-D) in vitro model of the injured host-transplant interface that can be used as a test bed for high-throughput evaluation of tissue-engineered strategies. The neuronal-astrocytic cocultures in 3-D were subjected to mechanical loading (inducing cell death and specific astrogliotic alterations) or to treatment with transforming growth factor-beta1 (TGF-beta1), inducing astrogliosis without affecting viability. Neural stem cells (NSCs) were then delivered to the cocultures. A sharp increase in the number of TUNEL(+) donor cells was observed in the injured cocultures compared to that in the TGF-beta1-treated and control cocultures, suggesting that factors related to mechanical injury, but not strictly astrogliosis, were detrimental to donor cell survival. We then utilized the mechanically injured cocultures to evaluate a methylcellulose-laminin (MC-LN) scaffold designed to reduce apoptosis. When NSCs were co-delivered with MC alone or MC-LN to the injured cocultures, the number of caspase(+) donor cells significantly decreased compared to that with vehicle delivery (medium). Collectively, these results demonstrate the utility of an in vitro model as a pre-animal test bed and support further investigation of a tissue-engineering approach for chaperoned NSC delivery targeted to improve donor cell survival in neural transplantation., ((c) 2007 Wiley-Liss, Inc.)

Objective: To evaluate efficacy, safety and comfort of a 0.3% hypromellose (HM) eye gel (GenTeal Lubricant Eye Gel), with a sodium perborate preservative system and carbomer gelling agent, in patients with dry eye., Research Design and Methods: Patients with moderate-to-severe dry eye syndrome were enrolled in this open label study and assessed at three visits; a screening consultation (baseline) and two follow-up visits on day 14 (+/- 4 days) and day 28 (+/- 4 days). All screening, evaluation and follow-up visits were carried out at the Tauber Eye Center (formerly the Hunkeler Eye Center), Kansas City. Patients were treated with the product over a 4-week period. They were instructed to use the product at least two times daily, more if necessary, with one drop instilled into the conjunctive sac of both eyes., Main Outcome Measures: Efficacy was measured by ocular symptoms (burning, stinging, foreign body sensation, dryness, pain/soreness and photophobia), ocular signs (eyelid erythema, bulbar conjunctival injection and corneal superficial punctate keratitis score), tear breakup time and global assessment of ocular comfort. Tolerability measures were change from baseline in best corrected Snellen visual acuity and monitoring of adverse events., Results: Thirty-seven patients completed this study. The mean sum symptom score at each visit was significantly lower compared with baseline with approximately 30% reduction in the sum symptom score at 2 weeks and approximately 33% at 4 weeks after treatment initiation (p < 0.001). Mean individual symptom scores for dryness, stinging and foreign body sensation decreased by approximately 40% at the end of the study (p < 0.02). Tear breakup time increased from baseline by 53% and 59% at 2 and 4 weeks, respectively (p < 0.001). The proportion of patients reporting a global evaluation of slightly better or much better was approximately 74% at 2 weeks and 78% at 4 weeks after treatment initiation. The product was well tolerated, with one related adverse event reported., Conclusions: In a small, open-label study, this 0.3% HM eye gel showed statistically significant effects in relieving ocular symptoms and provides a well-tolerated formula that effectively reduced symptoms and improved ocular comfort in patients with dry eye syndrome.

Purpose: To compare the ability of cohesive and dispersive ophthalmic viscoelastic devices (OVDs) to protect the corneal endothelium following in-the-bag phacoemulsification with implantation of a foldable posterior chamber intraocular lens (IOL)., Methods: In a prospective single-masked randomized study, 60 eyes of 60 cataract patients were assigned to three groups of 20 patients each, according to which OVD was used: Celoftal, Vitrax or Healon. The corneal response to surgery was evaluated by measuring the endothelial cell loss, the variation in mean cell area of the endothelial cells (CV), the frequency of hexagonal cells, and the central corneal thickness. Data were recorded preoperatively and 3 months postoperatively., Results: Preoperatively, no significant difference was observed in cell count, CV, hexagonal pattern or pachymetry among groups. Postoperatively, all three groups had a significant decrease in cell count, but the decrease was significantly less in the Vitrax group (6.97%) than in the Celoftal (18.03%) and Healon groups (18.46%). No changes in CV, hexagonality or corneal thickness were observed within any of the three groups or among the groups. There was an equal and significant increase in visual acuity., Conclusions: Phacoemulsification with implantation of a posterior chamber lens is known to affect the density and morphology of corneal endothelial cells. Viscoelastics facilitate cataract surgery and protect the corneal endothelium during the procedure. Choosing a dispersive hyaluronate OVD during the phaco procedure may allow for protection of the endothelial cells while suppressing the formation of free radicals. This may be the reason for the superior protective effect on the corneal endothelial cells of Vitrax compared with Celoftal and Healon.

Purpose: To determine the effect of an oil-in-water emulsion eye drop compared with a conventional dry eye supplement (hypromellose) on tear physiology in dry eye., Methods: A randomized parallel, longitudinal, and investigator-masked study of the efficacy of 1.25% castor oil emulsion and 0.32% hypromellose solution was carried out. A total of 53 patients with mild to moderate dry eye (27 in emulsion group and 26 in hypromellose group) were recruited for the study. Patients were enrolled if they reported at least 2 symptoms on a McMonnies Dry Eye Questionnaire together with 1 of the following screening tests: noninvasive tear breakup time (5-10 seconds) and Schirmer test without anesthesia (2-5 mm in 5 minutes). Patients were instructed to use the test solutions 3 times a day for 30 days. Tear production, evaporation, lipid layer structure, and osmolality were measured before and 30 days after use of the drops., Results: A statistically significant decrease was seen after 1 month in tear evaporation rates with both emulsion (7.25 +/- 5.43 g/m2/h) and hypromellose (2.02 +/- 4.75 g/m2/h). However, the decrease with emulsion was significantly greater than with hypromellose (P < 0.001). Lipid layer structure improved from day 1 to day 30 of the study with the emulsion but not with the hypermellose. No significant changes were seen in tear production and osmolality with either of the drops., Conclusions: The oil-water emulsion was more effective in reducing tear evaporation than hypromellose after repeated application over a 1-month period. This finding signifies the potential of the emulsion in the management of evaporative dry eye.

Aim: To assess the short-term efficacy of hypotonic 0.18% sodium hyaluronate in patients with evaporative tear-sufficient dry eye due to lipid tear deficiency (LTD)., Methods: This was a randomised, double-blind, controlled, exploratory study. A total of 10 patients with dry eye due to LTD were treated as follows: one drop of hypotonic 0.18% sodium hyaluronate in one eye and one drop of isotonic 0.3% hydroxypropyl-methylcellulose (HPMC)/0.1% dextran in the other eye. Non-invasive tear film break-up time (NIBUT) evaluated by using a tear scope with grid pattern and subjective ocular symptoms of dry eye were assessed at 15, 30, 60 and 90 min after instillation., Results: Both sodium hyaluronate and HPMC/dextran caused a significant (p<0.05) improvement in NIBUT and symptoms. Mean (SD) NIBUT in the sodium hyaluronate group was 3.2 (1.0), 6.4 (2.8), 5.5 (1.9), 5.3 (1.3) and 3.9 (1.7) s at 0, 15, 30, 60 and 90 min, respectively, compared with 3.6 (1.9), 5.5 (3.2), 5.0 (1.5), 4.4 (2.2) and 3.5 (1.2) s in the HPMC/dextran group. However, increase in NIBUT was significantly (p<0.05) greater and longer in the sodium hyaluronate group than in the HPMC/dextran group., Conclusion: Treatment with sodium hyaluronate and HPMC/dextran eye drops is useful for treating patients with dry eye due to LTD. However, sodium hyaluronate caused a significantly (p<0.05) greater increase in NIBUT values than HPMC/dextran in such patients.

An easy and convenient method of using a commercially available clear lubricant eye gel for diagnostic and therapeutic contact lens applications at the slit lamp is described. The authors used hydroxypropyl methylcellulose 0.3% as a medium for contact lens applications and compared it to the traditional hydroxypropyl methylcellulose 2.5%. Hydroxypropyl methylcellulose 0.3% as a contact lens solution is clear, viscous, and easy to apply; does not require irrigation after use; and has levels of convenience, safety, and visual recovery superior to the standard 2.5% solution characteristics. The 0.3% gel could be used as an effective and convenient gonioscopic and ophthalmoscopic contact medium.

The poor bioavailability and therapeutic response exhibited by conventional ophthalmic solutions due to rapid pre-corneal elimination of the drug may be overcome by the use of in situ gel-forming systems that are instilled as drops into the eye and then undergo a sol-gel transition in the cul-de-sac. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, gatifloxacin, based on the concept of ion-activated in situ gelation. Alginate (Kelton) was used as the gelling agent in combination with HPMC (Methocel E50Lv) which acted as a viscosity-enhancing agent. The rheological behaviors of all formulations were not affected by the incorporation of gatifloxacin. Both in vitro release studies and in vivo pre-corneal retention studies indicated that the alginate/HPMC solution retained the drug better than the alginate or HPMC E50Lv solutions alone. These results demonstrate that the alginate/HPMC mixture can be used as an in situ gelling vehicle to enhance ocular bioavailability and patient compliance.

Purpose: To examine the change in intraocular pressure (IOP) within 1 week of phacoemulsification and foldable posterior chamber intraocular lens (PC IOL) implantation using Adatocel (hydroxypropyl methylcellulose 2% [HPMC])., Setting: Department of Ophthalmology, University of Sciences, Faculty of Medicine, Pécs, Hungary., Methods: In this prospective study, the IOP in 118 eyes of 118 patients (57 men, 61 women, mean age 68 years +/- 7.8 [SD]) with no history of glaucoma was assessed by Goldmann applanation tonometry 2 to 3, 6 to 8, and 22 to 24 hours and 1 week after uneventful phacoemulsification and PC IOL implantation. The effect of the removal of Adatocel ("partial removal" from the anterior chamber [AC] only versus "complete removal" from behind of the IOL as well), the lens type (Medicontur 601 HP versus Bausch & Lomb Hydroview), and the type of anesthesia (topical versus parabulbar) were compared. Statistical analysis was performed using the Student t test, and P< or =.05 was considered statistically significant., Results: The mean preoperative IOP was 13.83 +/- 2.5 mmHg. There were no significant differences at any time in postoperative IOP measurements between the 2 IOL types and the 2 modes of anesthesia. At 2 to 3 hours, 6 to 8 hours, and 22 to 24 hours, the IOP was significantly higher in the 30 eyes in which the Adatocel was partially removed (from the AC only) than in the 88 eyes in which it was completely removed (from behind the PC IOL as well) (P< or =.05, P< or =.01, and P< or =.001, respectively)., Conclusion: Severe postoperative IOP spikes in nonglaucomatous patients after uneventful phacoemulsification cataract surgery are rare. The type of implanted PC IOL and the mode of anesthesia had no significant effect on postoperative IOP. Total removal of the ophthalmic viscosurgical device, even when using HPMCs such as Adatocel, is necessary to prevent postoperative IOP spikes.

We have previously shown that a novel synthetic hydrogel channel composed of poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (pHEMA-MMA) is biocompatible and supports axonal regeneration after spinal cord injury. Our goal was to improve the number and type of regenerated axons within the spinal cord through the addition of different matrices and growth factors incorporated within the lumen of the channel. After complete spinal cord transection at T8, pHEMA-MMA channels, having an elastic modulus of 263+/-13 kPa were implanted into adult Sprague Dawley rats. The channels were then filled with one of the following matrices: collagen, fibrin, Matrigel, methylcellulose, or smaller pHEMA-MMA tubes placed within a larger pHEMA-MMA channel (called tubes within channels, TWC). We also supplemented selected matrices (collagen and fibrin) with neurotrophic factors, fibroblast growth factor-1 (FGF-1) and neurotrophin-3 (NT-3). After channel implantation, fibrin glue was applied to the cord-channel interface, and a duraplasty was performed with an expanded polytetrafluoroethylene (ePTFE) membrane. Controls included animals that had either complete spinal cord transection and implantation of unfilled pHEMA-MMA channels or complete spinal cord transection. Regeneration was assessed by retrograde axonal tracing with Fluoro-Gold, and immunohistochemistry with NF-200 (for total axon counts) and calcitonin gene related peptide (CGRP, for sensory axon counts) after 8 weeks survival. Fibrin, Matrigel, methylcellulose, collagen with FGF-1, collagen with NT-3, fibrin with FGF-1, and fibrin with NT-3 increased the total axon density within the channel (ANOVA, p<0.05) compared to unfilled channel controls. Only fibrin with FGF-1 decreased the sensory axon density compared to unfilled channel controls (ANOVA, p<0.05). Fibrin promoted the greatest axonal regeneration from reticular neurons, and methylcellulose promoted the greatest regeneration from vestibular and red nucleus neurons. With Matrigel, there was no axonal regeneration from brainstem motor neurons. The addition of FGF-1 increased the axonal regeneration of vestibular neurons, and the addition of NT-3 decreased the total number of axons regenerating from brainstem neurons. The fibrin and TWC showed a consistent improvement in locomotor function at both 7 and 8 weeks. Thus, the present study shows that the presence and type of matrix contained within synthetic hydrogel guidance channels affects the quantity and origin of axons that regenerate after complete spinal cord transection, and can improve functional recovery. Determining the optimum matrices and growth factors for insertion into these guidance channels will improve regeneration of the injured spinal cord.

Aim: To evaluate whether bone formation under Teflon capsules may be enhanced by concomitant implantation of recombinant human platelet-derived growth factor-BB/insulin-like growth factor-I (rhPDGF-BB/IGF-I) incorporated into a methyl cellulose gel., Materials and Methods: Fifty-five male 6-month-old albino rats of the Wistar strain were used in the study. The lateral aspect of the mandibular ramus was exposed on both sides of the jaw. In 70 sites, the periosteum was removed from the ramus, leaving the bone denuded, while in 35 sites, it was preserved. On 10 non-periosteal (P-) sites and five periosteal (P+) sites, an empty rigid teflon capsule (d=7 mm), serving as control, was placed on the ramus. In the 40 test animals, the capsule placed on the one side of the jaw was filled at random with one of three different concentrations (1,200, 600, 150 microg/ml) of rhPDGF-BB/IGF-I gel. The capsules placed on the contralateral side of the jaw contained a placebo methyl cellulose gel. Each growth factor group, defined according to the gel concentration, and the placebo group contained 10 capsules placed on the P- side and five capsules placed on the P+ side. Two months after surgery, all animals were sacrificed., Results: Histologic analysis revealed that in the non-filled control capsules, the amount of new bone including the bone marrow was 29.9% and 39.7% of the capsule area on the P- and P+ sides, respectively. In the test capsules with the growth factor gel and placed on the P-sides, the amounts of new bone ranged from 5.6% to 6.3%, which were similar (p>0.05) to that formed in the capsules filled with the methyl cellulose gel (5.5%). New bone formation was larger in the capsules on the P+ sides than in those on the P- sides but was similar in the capsules with different growth factor concentrations (range 17.9-19.6%) and in those with placebo gel (21.0%). In all groups, the carrier gel was poorly absorbed and occupied most of the capsules., Conclusion: Local application of a methyl cellulose gel obstructed bone formation under Teflon capsules placed adjacent to uninjured cortical bone in the mandibular ramus of rats. These data suggest that another material should be utilized to deliver growth factors under Teflon membranes for guided bone regeneration.

The insertion of an orbital implant in the posterior Tenon's space or in the eviscerated sclera must be smooth, without entrapment or dragging of adjacent soft tissue. Anterior Tenon's fascia and conjunctiva must be closed without undue tension that could lead to subsequent postoperative implant exposure. Current methods to prevent tissue drag include passing the implant via a cut "thumb" from a surgeon's glove, the use of a prepackaged rigid plastic funnel, or a specialized orbital implant introducing forceps, e.g., Carter sphere injector. We recommend also coating the porous implant with an inert semisynthetic viscoelastic polymer, thus enabling easy placement. We illustrate this in a typical case.

We investigated cell proliferation and local insulin-like growth factor-I (IGF-I) expression in ischemic wounds after topical application of IGF-I through different delivery systems. IGF-I dressings were fabricated from an IGF-I containing polyvinyl alcohol film placed on a standard hydrogel dressing. In vitro, the release of IGF-I from this dressing was assessed by enzyme-linked immunosorbent assay. For animal experiments, a standardized ischemic skin flap containing a full-thickness wound was created on the back of male Sprague-Dawley rats. An identical wound outside the flap served as control. We initially investigated intracutaneous pO2 (p(ti)O2), cell proliferation, and local IGF-I expression. In a second setting, wounds were treated either with IGF-I dissolved in methylcellulose gel or with an IGF-I dressing, and ulcer size and cell proliferation were assessed. In vitro, approximately 60% of IGF-I was released from the IGF-I dressing, compared to a 97% release from methylcellulose gel. In vivo, ischemic wounds showed less cell proliferation and decreased IGF-I expression than nonischemic wounds. A lower local p(ti)O2 correlated with larger wound size, less cell proliferation, and decreased IGF-I expression. Ulcer size was reduced after treatment with either IGF-I dressing or methylcellulose gel. However, cell proliferation only increased after treatment with IGF-I dressing, but not after methylcellulose gel treatment. We conclude that IGF-I expression is decreased in ischemic wounds and correlates with low cell proliferation. This can be reversed by local IGF-I application, but the efficacy of treatment depends on the delivery system.