Accelerated corneal crosslinking with 20'-soaking hydroxypropyl methyl cellulose/riboflavin vs conventional crosslinking with 30'-soaking dextran/riboflavin.

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.

The prolyl hydroxylase inhibitor GSK1120360A reduces early brain injury, but protection is not maintained in a neonatal rat model of hypoxic ischaemic encephalopathy.

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.

Fabrication of Muco-Adhesive Oral Films by the 3D Printing of Hydroxypropyl Methylcellulose-Based Catechin-Loaded Formulations.

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.

Superior outcome of corneal collagen cross-linking using riboflavin with methylcellulose than riboflavin with dextran as the main supplement.

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 (Kmax ), 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. Kmax 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.

Conservative treatment of severe defecatory urgency and fecal incontinence: minor strategies with major impact.

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.

Methyl-cellulose powder for prevention and management of nasal symptoms.

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.

The cost-effectiveness of a novel soluble beta-glucan gel.

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.

Assessment and treatment options for patients with constipation.

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.

[MITOCHONDRIA-TARGETED ANTIOXIDANTS IN THE PREVENTION OF THE CORNEA EROSION WHEN PERFORMING SURGERY UNDER GENERAL ANESTHESIA.]

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.

Examination of Calcium Silicate Cements with Low-Viscosity Methyl Cellulose or Hydroxypropyl Cellulose Additive.

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.

Development and In Vivo Evaluation of a Novel Histatin-5 Bioadhesive Hydrogel Formulation against Oral Candidiasis.

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.

Results of a Multicenter, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of Visomitin Eye Drops in Patients with Dry Eye Syndrome.

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.

Safety and feasibility of the use of a bevacizumab-methylcellulose mixture as an adjunct to glaucoma surgery: a pilot study.

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.

Safety and feasibility of the use of a bevacizumab-methylcellulose mixture as an adjunct to glaucoma surgery: a pilot study / Segurança e viabilidade do uso de uma mistura de bevacizumabe-metilcelulose como terapia adjuvante à cirurgia anti-glaucomatosa: um estudo piloto

ABSTRACT 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.

RESUMO O bevacizumabe (um agente anti-fator de crescimento endotelial vascular) tem sido sugerido como potencial modulador cicatricial na cirurgia do glaucoma. Este estudo objetivou melhorar a biodisponibilidade do bevacizumabe, investigando a viabilidade de uma nova mistura de bevacizumabe-metilcelulose (BMM) como terapia adjuvante para a esclerectomia profunda não-penetrante (DS). Dez olhos sem cirurgias prévias de 10 pacientes com glaucoma primário de ângulo aberto foram submetidos à DS associada à uma injeção subconjuntival de 0,3 ml da mistura de bevacizumabe-metilcelulose (bevacizumabe 3,75 mg incorporado em metilcelulose 4%) no sítio cirúrgico. A liberação de bevacizumabe foi avaliada in vitro através de cromatografia líquida de alta performance por exclusão de tamanho (HPLC). A pressão intraocular (PIO), a morfologia da ampola de filtração, a contagem de células endoteliais da córnea (CECC) e as complicações foram estudadas aos seis meses de seguimento. O bevacizumabe foi detectado a partir da mistura de bevacizumabe-metilcelulose por meio do HPLC até 72 horas. Além disso, todas as ampolas cirúrgicas permaneceram expandidas com material hialino durante a primeira semana. Uma redução significativa da pressão intraocular (média ± DP= -10,3 ± 5,4 mmHg, P<0,001) e ampolas difusas foram observadas ao final do período de seguimento. Embora a contagem de células endoteliais da córnea se mostrou discretamente diminuída (-7,4%), nenhuma complicação foi observada. Neste estudo, o bevacizumabe foi liberado da mistura de bevacizumabe-metilcelulose e o uso desta nova mistura se associou com bons resultados cirúrgicos e nenhuma complicação. Estudos futuros serão necessários para determinar sua eficácia, antes de se estabelecer a mistura de bevacizumabe-metilcelulose como um tratamento adjuvante às cirurgias penetrantes e não-penetrantes para o glaucoma.

MMP9-sensitive polymers mediate environmentally-responsive bivalirudin release and thrombin inhibition.

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.

Modulatory effect of different riboflavin compositions on the central corneal thickness of African keratoconus corneas during collagen crosslinking.

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.

Biopolymeric film containing bioactive naphthoquinone (shikonin) in combined therapy of inflammatory destructive lesions in the buccal mucosa.

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.

Exploring patients' views of a cognitive behavioral therapy-based website for the self-management of irritable bowel syndrome symptoms.

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.

Altered hepatic gene expression profiles associated with improved fatty liver, insulin resistance, and intestinal permeability after hydroxypropyl methylcellulose (HPMC) supplementation in diet-induced obese mice.

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.

Management of irritable bowel syndrome in primary care: the results of an exploratory randomised controlled trial of mebeverine, methylcellulose, placebo and a self-management website.

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.