Annular plaques on the back.

Annular lichen planus is a rare clinical variant of the lichen planus presenting with round-oval, red to brown macules and plaques with no central atrophy and slightly raised, nonscaly borders. Histopathological features are indistinguishable from typical lichen planus. Given that the accurate diagnosis relies on both the clinical presentation and typical histological features, it is important to be aware of the clinical spectrum of lichen planus. Click https://wileyhealthlearning.com/#/online-courses/6be3b20c-e9c3-40e9-8f36-bfcda6718a73 for the corresponding questions to this CME article.

AggreRATE-Pred: a mathematical model for the prediction of change in aggregation rate upon point mutation.

MOTIVATION: Protein aggregation is a major unsolved problem in biochemistry with implications for several human diseases, biotechnology and biomaterial sciences. A majority of sequence-structural properties known for their mechanistic roles in protein aggregation do not correlate well with the aggregation kinetics. This limits the practical utility of predictive algorithms. RESULTS: We analyzed experimental data on 183 unique single point mutations that lead to change in aggregation rates for 23 polypeptides and proteins. Our initial mathematical model obtained a correlation coefficient of 0.43 between predicted and experimental change in aggregation rate upon mutation (P-value <0.0001). However, when the dataset was classified based on protein length and conformation at the mutation sites, the average correlation coefficient almost doubled to 0.82 (range: 0.74-0.87; P-value <0.0001). We observed that distinct sequence and structure-based properties determine protein aggregation kinetics in each class. In conclusion, the protein aggregation kinetics are impacted by local factors and not by global ones, such as overall three-dimensional protein fold, or mechanistic factors such as the presence of aggregation-prone regions. AVAILABILITY AND IMPLEMENTATION: The web server is available at http://www.iitm.ac.in/bioinfo/aggrerate-pred/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

AntiHIV-Pred: web-resource for in silico prediction of anti-HIV/AIDS activity.

MOTIVATION: Identification of new molecules promising for treatment of HIV-infection and HIV-associated disorders remains an important task in order to provide safer and more effective therapies. Utilization of prior knowledge by application of computer-aided drug discovery approaches reduces time and financial expenses and increases the chances of positive results in anti-HIV R&D. To provide the scientific community with a tool that allows estimating of potential agents for treatment of HIV-infection and its comorbidities, we have created a freely-available web-resource for prediction of relevant biological activities based on the structural formulae of drug-like molecules. RESULTS: Over 50 000 experimental records for anti-retroviral agents from ChEMBL database were extracted for creating the training sets. After careful examination, about seven thousand molecules inhibiting five HIV-1 proteins were used to develop regression and classification models with the GUSAR software. The average values of R2 = 0.95 and Q2 = 0.72 in validation procedure demonstrated the reasonable accuracy and predictivity of the obtained (Q)SAR models. Prediction of 81 biological activities associated with the treatment of HIV-associated comorbidities with 92% mean accuracy was realized using the PASS program. AVAILABILITY AND IMPLEMENTATION: Freely available on the web at http://www.way2drug.com/hiv/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Generation of Ophthalmic Nanosuspension of Prednisolone Acetate Using a Novel Technology.

PURPOSE: Prednisolone Acetate (PAC) is currently marketed as micronized ophthalmic suspension. The microsuspension has poor dose accuracy and efficacy due to aggregation, slow dissolution rate and limited corneal residence. The ophthalmic nanosuspension of PAC shall show enhanced solubility, dissolution rate and corneal adhesion due to small particle size and increased surface area. METHODS: In the current work, we prepared ophthalmic formulation of PAC using a novel, spray drying based technology. Firstly, PAC nanocrystalline solid dispersions (NCSD) were prepared using Mannitol (MAN) as the crystallization inducing excipient and two separate stabilizers, Polyvinyl Alcohol (PAC_MAN_PVA) and Vitamin E Tocopheryl Polyethylene Glycol Sulphosuccinate (PAC_MAN_TPGS). The NCSD was dispersed in an aqueous vehicle to obtain an ophthalmic nanosuspension. RESULTS: The composition, PAC_MAN_PVA (0.3:0.67:0.03%), was pursued due to absence of crystal growth on storage at 40°C/75%RH for 3 months. The resulting nanosuspension showed crystal size, osmolality and viscosity of 590 ± 165 nm, 297 ± 6 mOsm/L and 11 ± 8cP respectively. In 1%w/v SLS media, the nanosuspension showed rapid and complete dissolution of PAC in 120 s. Ex-vivo goat corneal permeation and adhesion study revealed that in comparison to microsuspension, a higher fraction (6.2 times) of nanosuspension adhered to the cornea. Safety studies performed using corneal histopathology and Hen Egg Test- Chorio Allantoic Membrane (HET-CAM) assay showed no physical change in cornea or capillary damage, respectively. CONCLUSIONS: The NCSD can be explored for generation of ophthalmically acceptable nanosuspensions of poorly soluble drugs.

Modulation of Th17 Proliferation and IL-17A Gene Expression by Acetylated Form of Apigenin in Patients with Multiple Sclerosis.

The presence of Th17 cells in CNS lesion of MS patients due to their inflammatory cytokines secretion is in line with the deterioration of the disease. Currently, the use of natural compounds with anti-inflammatory properties such as flavonoids have been considered to reduce inflammation in these patients, but the remaining issue is how deliver these compounds to the site of inflammation. Acetylation is a way to better uptake compound by cells and cross through cellular layers with tight junctions. This study aimed to investigate the in vitro effects of the Apigenin 3-Acetate on Th17 cells of MS patients and compare its efficacy with Apigenin and Methyl Prednisolone Acetate. IC50 for Apigenin 3-Acetate, and Methyl Prednisolone Acetate were determined using three healthy volunteers. The peripheral blood mononuclear cells (PBMCs) of five MS patients were isolated and co-cultured with a selected dose of Apigenin, Apigenin 3-Acetate, and Methyl Prednisolone Acetate for 48 hr, and then theproliferation of Th17 cells in isolated PBMCs was assessed by flow cytometry. The levels of RAR-related orphan receptor (RORC) and IL-17A expression were also determined by quantitative real-time PCR. The results showed that Apigenin 3-Acetate inhibited Th17 cells proliferation (P value: 0.018) at 80 µM concentration after 48 hr. Additionally, IL-17A gene expression significantly (P value≤ 0.0001) inhibited by Apigenin, Apigenin 3-Acetate and Methyl Prednisolone Acetate in 80 µM, 80 µM and 2.5 µM (selected dose in IC50 determination) respectively These results demonstrate that Acetate increases anti-inflammatory effects of Apigenin on Th17 cells.

MAD2B contributes to parietal epithelial cell activation and crescentic glomerulonephritis via Skp2.

Mitotic spindle assembly checkpoint protein 2 (MAD2B), a well-known anaphase-promoting complex/cyclosome (APC/C) inhibitor and a small subunit of DNA polymerase-ζ, is critical for mitotic control and DNA repair. Previously, we detected a strong increase of MAD2B in the glomeruli from patients with crescentic glomerulonephritis and anti-glomerular basement membrane (anti-GBM) rats, which predominantly originated from activated parietal epithelial cells (PECs). Consistently, in vitro MAD2B was increased in TNF-α-treated PECs, along with cell activation and proliferation, as well as extracellular matrix accumulation, which could be reversed by MAD2B genetic depletion. Furthermore, we found that expression of S phase kinase-associated protein 2 (Skp2), an APC/CCDH1 substrate, was increased in the glomeruli of anti-GBM rats, and TNF-α-stimulated PECs and could be suppressed by MAD2B depletion. Additionally, genetic deletion of Skp2 inhibited TNF-α-induced PEC activation and dysfunction. Finally, TNF-α blockade or glucocorticoid therapy administered to anti-GBM rats could ameliorate MAD2B and Skp2 accumulation as well as weaken PEC activation. Collectively, our data suggest that MAD2B has a pivotal role in the pathogenesis of glomerular PEC activation and crescent formation through induction of Skp2 expression.

i6mA-Pred: identifying DNA N6-methyladenine sites in the rice genome.

MOTIVATION: DNA N6-methyladenine (6mA) is associated with a wide range of biological processes. Since the distribution of 6mA site in the genome is non-random, accurate identification of 6mA sites is crucial for understanding its biological functions. Although experimental methods have been proposed for this regard, they are still cost-ineffective for detecting 6mA site in genome-wide scope. Therefore, it is desirable to develop computational methods to facilitate the identification of 6mA site. RESULTS: In this study, a computational method called i6mA-Pred was developed to identify 6mA sites in the rice genome, in which the optimal nucleotide chemical properties obtained by the using feature selection technique were used to encode the DNA sequences. It was observed that the i6mA-Pred yielded an accuracy of 83.13% in the jackknife test. Meanwhile, the performance of i6mA-Pred was also superior to other methods. AVAILABILITY AND IMPLEMENTATION: A user-friendly web-server, i6mA-Pred is freely accessible at http://lin-group.cn/server/i6mA-Pred.

Herpetic Eye Disease Study: A Controlled Trial of Topical Corticosteroids for Herpes Simplex Stromal Keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-con- trolled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Risk of Cataract Development among Children with Juvenile Idiopathic Arthritis-Related Uveitis Treated with Topical Corticosteroids.

PURPOSE: We sought to investigate the risk of cataract development among patients with juvenile idiopathic arthritis (JIA)-associated uveitis treated with topical corticosteroids. DESIGN: Retrospective cohort study. PARTICIPANTS: We included 75 patients with JIA-associated uveitis observed from July 1984 through August 2005 at a single academic center. METHODS: Clinical data on these patients were collected by chart review and were analyzed. MAIN OUTCOME MEASURES: Incidence of new-onset cataract. Risk factors for cataract development were assessed with attention paid to the use of topical corticosteroids. RESULTS: Over a median follow-up of 4 years, the incidence of new-onset cataract was 0.04/eye-year (EY; 95% confidence interval [CI], 0.02-0.09). Of the 60 eyes in 40 patients who received topical corticosteroid therapy, there was a dose-dependent increase in the rate of cataract development among eyes receiving topical corticosteroids. The incidence of cataract was 0.01/EY for eyes treated with <3 drops daily and 0.16/EY (P = 0.0006 for log-rank test) for eyes treated with >3 drops daily. Among eyes receiving <2 drops daily, the incidence of cataract was 0/EY (95% CI [1 sided], 0.03/EY). Presence of posterior synechiae, active uveitis, and use of topical corticosteroids at presentation were significantly associated with cataract development after controlling for confounding variables. Use of topical corticosteroids was associated with cataract formation independent of uveitis activity. Using longitudinal data analysis and controlling for duration of uveitis, presence and degree of active uveitis, and concomitant use of other forms of corticosteroids in a time-updated fashion, treatment with <3 drops daily of topical corticosteroid was associated with an 87% lower risk of cataract formation compared with eyes treated with >3 drops daily (relative risk, 0.13; 95% CI, 0.02-0.69; P = 0.02). CONCLUSIONS: In our cohort, topical corticosteroid use was associated with an increased risk of cataract formation independent of active uveitis or presence of posterior synechiae. However, chronic use of topical corticosteroids dosed at <3 drops daily seemed to be associated with a lower risk of cataract development relative to eyes receiving higher doses over follow-up in the setting of suppressed uveitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Corticosteroid eyedrops induced blepharoptosis and atrophy of levator muscle.

PURPOSE: The purpose of the study is to analyze the incidence, manifestations, and treatment of blepharoptosis caused by long-term use of corticosteroid eyedrops. METHODS: Retrospective case series include 46 patients with a history of using corticosteroid eyedrops unilaterally for at least 2 months. The palpebral fissure, MRD1, and levator function were evaluated. RESULTS: Among 46 patients, the differences of mean MRD1 (p < 0.0005), palpebral fissure height (p < 0.0005), and levator function (p = 0.003) between eyes with and without corticosteroid eyedrops application were significant. Ptosis existed in 40 out of 46 eyes with corticosteroid; the differences of the mean MRD1 (p < 0.0005) and palpebral fissure height (p = 0.001) between eyes with and without ptosis were significant. Nine patients underwent levator aponeurosis repair surgeries. Pathological examinations revealed mainly vascular fibers and few muscle fibers, as well as apoptosis of levator palpebrae muscle and Muller muscle. CONCLUSION: Blepharoptosis is frequently observed after chronic corticosteroid eyedrops use in Chinese population.

DermaTOP Blue and Antera 3D as methods to assess cosmetic solutions targeting eyelid sagging.

BACKGROUND: As the eye contour ages, the skin on the lid becomes lax often causing a voluminous protrusion where the superior palpebral sulcus begins to sag onto the upper eyelid. This sagging feature may present a novel anti-ageing target for cosmetic products when treating the eye area. A quantitative method to evaluate the volume of this sagging feature has not been previously established. We investigate the use of the DermaTOP fringe projector and Antera 3D Camera to this end. METHODS: Eyelid topographic measurements were collected on 20 female volunteers aged 50-75 years with the DermaTOP and Antera 3D. The DermaTOP and Antera 3D measurements were assessed for reproducibility and product effect detection capabilities. RESULTS: The DermaTOP and Antera 3D successfully measured sagging feature volume, demonstrated reproducibility of measurement and furthermore were suitably sensitive to allow for detection of sagging feature volume reduction after a single application of aqueous tightening serum. DermaTOP parameters were found to moderately correlated with the Antera 3D parameters. CONCLUSION: Both the DermaTOP and Antera 3D allow for quantitative measurement of eyelid sagging feature volume and in-turn permit evaluation of anti-ageing cosmetic preparations targeting the eyelid.

Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment.

Regardless of recent progress, melanoma is very difficult to treat, mainly due to the drug resistance modulated by tumor cells as well as by the tumor microenvironment (TME). Among the immune cells recruited at the tumor site, tumor associated macrophages (TAMs) are the most abundant, promoting important tumorigenic processes: angiogenesis, inflammation and invasiveness. Furthermore, it has been shown that TAMs are involved in mediating the drug resistance of melanoma cells. Thus, in the present study, we used liposomal formulation of prednisolone disodium phosphate (LCL-PLP) to inhibit the protumor function of TAMs with the aim to sensitize the melanoma cells to the cytotoxic drug doxorubicin (DOX) to which human melanoma has intrinsic resistance. Consequently, we evaluated the in vivo effects of the concomitant administration of LCL-PLP and liposomal formulation of DOX (LCL-DOX) on B16.F10 melanoma growth and on the production of key molecular markers for tumor development. Our results demonstrated that the concomitant administration of LCL-PLP and LCL-DOX induced a strong inhibition of tumor growth, primarily by inhibiting TAMs-mediated angiogenesis as well as the tumor production of MMP-2 and AP-1. Moreover, our data suggested that the combined therapy also affected TME as the number of infiltrated macrophages in melanoma microenvironment was reduced significantly.

[Diagnosis and treatment of non-infectious uveitis associated with systemic disease: a guide for internists]. / Prise en charge des uvéites non infectieuses liées à une maladie systémique : guide pour les praticiens.

Uveitis is an inflammation of the eye, resulting from infection or inflammation and is sometimes related to rheumatic and other auto-immune diseases. The condition is classified according to the anatomical site of inflammation: anterior, intermediate, posterior or panuveitis. Uveitis may result in a significant loss of visual acuity, that may however be avoided by controlling the inflammation. Anterior uveitis is the only form that responds to topical therapies (prednisolone acetate and mydriatics). The other forms of inflammatory and non-infectious uveitis often require treatment with systemic corticosteroids, followed by immunosuppressive or biological therapies, which requires close collaboration between the different medical sub-specialties.

Une uvéite est une inflammation oculaire, d'origine infectieuse ou inflammatoire, résultant parfois de maladies autoimmunes ou rhumatismales. Les uvéites sont classées selon leur localisation anatomique : antérieure, intermédiaire, postérieure ou panuvéite. Elles peuvent entraîner une importante baisse de l'acuité visuelle qui peut être évitée par un contrôle de l'inflammation. Seules les uvéites antérieures répondent à un traitement topique de collyres (corticostéroïdes) et à une mydriase médicamenteuse. Les autres uvéites inflammatoires et non infectieuses nécessitent souvent l'utilisation de corticostéroïdes par voie générale relayés par la suite par des traitements immunosuppresseurs ou biologiques qui nécessitent une collaboration étroite entre les différentes disciplines médicales.

Steroid Free Treatment of Autoimmune Hepatitis in Selected Children.

Current guidelines recommend steroids for induction of remission in all children diagnosed with autoimmune hepatitis regardless of the clinical presentation. In this report, we describe our experience in treating selected asymptomatic children with autoimmune hepatitis using a steroid-free regimen; this treatment strategy was safe and effective in inducing remission.

The availability of drug by liposomal drug delivery : Individual kinetics and tissue distribution of encapsulated and released drug in mice after administration of PEGylated liposomal prednisolone phosphate.

Lately, the usefulness of liposomal drug delivery systems has been debated. To better understand the underlying pharmacokinetics of the targeted drug delivery by liposomes, individual encapsulated and non-encapsulated drug concentrations in blood, tumor, liver, spleen and kidneys were quantified after i.v. administration of liposomal prednisolone phosphate in mice. Kinetic analysis shows that the tumor influx of encapsulated drug is not dominant compared to the uptake by the other tissues. Further, from a quantitative point of view, the availability of non-encapsulated drug in the tumor tissue after liposomal delivery is not pronounced as compared to the other tissues studied. However, drug release in the tumor seems more extended than in the other tissues and the non-encapsulated drug concentration decreases more slowly in the tumor than in the liver and spleen. The spleen shows a high affinity for the uptake of encapsulated drug as well as the release of drug from the liposomes. Subsequently, released drug in the spleen, and possibly also in other tissues, is probably quickly redistributed towards the blood and other tissues. This also impairs the drug delivery effect of the liposomes. In contrast to the released drug in the central circulation, liver and spleen, the released drug concentration in the tumor remains at a fairly constant level likely due to the extended release kinetics from the liposomes. These extended release characteristics in the tumor most probably contribute to the beneficial effect. Nevertheless, it should be noted that larger released drug concentrations are formed in healthy tissues.

Impact of topical corticosteroid pretreatment on susceptibility of the injured murine cornea to Pseudomonas aeruginosa colonization and infection.

Research with animal models of Pseudomonas aeruginosa keratitis has shown that use of a topical corticosteroid alone against an established infection can significantly increase the number of colonizing bacteria or worsen clinical disease. Moreover, retrospective analysis has suggested that corticosteroid use in humans is associated with an increased risk of keratitis in eyes with pre-existing disease. Thus, while corticosteroids are often used to reduce ocular inflammation in the absence of infection, the risk of opportunistic infection remains a concern. However, the effect of corticosteroids on the intrinsic barrier function of uninfected corneas is unknown. Here, we tested if short-term topical corticosteroid treatment of an uninfected murine cornea would increase susceptibility to P. aeruginosa colonization or infection after epithelial injury. Topical prednisolone acetate (1%) was administered to one eye of C57BL/6 mice three times a day for 3 days; control eyes were treated with sterile PBS. Prior to inoculation with a cytotoxic P. aeruginosa corneal isolate strain 6206, corneas were subject to superficial-injury by tissue paper blotting, or scratch-injured followed by 12 h of healing. Previously we have shown that blotting renders mouse corneas susceptible to P. aeruginosa adhesion, but not infection, while 12 h healing reduces susceptibility to infection after scratching. Corneas were evaluated at 48 h for bacterial colonization and microbial keratitis (MK). To monitor impact on wound healing, corneal integrity was examined by fluorescein staining immediately after scarification and after 12 h healing. For both the tissue paper blotting and scratch-injury models, there was no significant difference in P. aeruginosa colonization at 48 h between corticosteroid-pretreated eyes and controls. With the blotting model, one case of MK was observed in a control (PBS-pretreated) cornea; none in corticosteroid-pretreated corneas. With the 12 h healing model, MK occurred in 6 of 17 corticosteroid-pretreated eyes versus 2 of 17 controls, a difference not statistically significant. Corticosteroid-pretreated eyes showed greater fluorescein staining 12 h after scarification injury, but this did not coincide with increased colonization or MK. Together, these data show that short-term topical corticosteroid therapy on an uninfected murine cornea does not necessarily enhance its susceptibility to P. aeruginosa colonization or infection after injury, even when it induces fluorescein staining.

Impact of topical anti-fibrotics on corneal nerve regeneration in vivo.

Recent work in vitro has shown that fibroblasts and myofibroblasts have opposing effects on neurite outgrowth by peripheral sensory neurons. Here, we tested a prediction from this work that dampening the fibrotic response in the early phases of corneal wound healing in vivo could enhance reinnervation after a large, deep corneal injury such as that induced by photorefractive keratectomy (PRK). Since topical steroids and Mitomycin C (MMC) are often used clinically for mitigating corneal inflammation and scarring after PRK, they were ideal to test this prediction. Twenty adult cats underwent bilateral, myopic PRK over a 6 mm optical zone followed by either: (1) intraoperative MMC (n = 12 eyes), (2) intraoperative prednisolone acetate (PA) followed by twice daily topical application for 14 days (n = 12 eyes), or (3) no post-operative treatment (n = 16 eyes). Anti-fibrotic effects of MMC and PA were verified optically and histologically. First, optical coherence tomography (OCT) performed pre-operatively and 2, 4 and 12 weeks post-PRK was used to assess changes in corneal backscatter reflectivity. Post-mortem immunohistochemistry was then performed at 2, 4 and 12 weeks post-PRK, using antibodies against α-smooth muscle actin (α-SMA). Finally, immunohistochemistry with antibodies against ßIII-tubulin (Tuj-1) was performed in the same corneas to quantify changes in nerve distribution relative to unoperated, control cat corneas. Two weeks after PRK, untreated corneas exhibited the greatest amount of staining for α-SMA, followed by PA-treated and MMC-treated eyes. This was matched by higher OCT-based stromal reflectivity values in untreated, than PA- and MMC-treated eyes. PA treatment appeared to slow epithelial healing and although normal epithelial thickness was restored by 12 weeks-post-PRK, intra-epithelial nerve length only reached ∼1/6 normal values in PA-treated eyes. Even peripheral cornea (outside the ablation zone) exhibited depressed intra-epithelial nerve densities after PA treatment. Stromal nerves were abundant under the α-SMA zone, but appeared to largely avoid it, creating an area of sub-epithelial stroma devoid of nerve trunks. In turn, this may have led to the lack of sub-basal and intra-epithelial nerves in the ablation zone of PA-treated eyes 4 weeks after PRK, and their continuing paucity 12 weeks after PRK. Intra-operative MMC, which sharply decreased α-SMA staining, was followed by rapid restoration of nerve densities in all corneal layers post-PRK compared to untreated corneas. Curiously, stromal nerves appeared unaffected by the development of large, stromal, acellular zones in MMC-treated corneas. Overall, it appears that post-PRK treatments that were most effective at reducing α-SMA-positive cells in the early post-operative period benefited nerve regeneration the most, resulting in more rapid restoration of nerve densities in all corneal layers of the ablation zone and of the corneal periphery.

Neuronal Intranuclear Inclusion Disease: A Rare Etiology for Rapidly Progressive Dementia.

INTRODUCTION: Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder pathologically characterized by localized neuronal loss, and presence of eosinophilic intranuclear inclusions in neurons and glial cells. CASE REPORT: A 50-year-old man presented with rapidly progressive dementia, behavioral changes, gait disturbances, and incontinence of 3 months duration. His brain magnetic resonance imaging showed diffuse T2/FLAIR hyperintensity of basal ganglia, thalami, cerebral peduncles, ventral pons, and supratentorial white matter with a frontal predominance. Hyperintensity was noted along the corticosubcortical junction on diffusion-weighted images. NIID was suspected and the patient underwent triple biopsy of the sural nerve with adjacent skin and biceps biopsy. Biopsy revealed ubiquitin-positive intranuclear inclusions surrounding the myofibers, and vascular smooth muscles suggestive of NIID. CONCLUSIONS: NIID is a rare neurodegenerative disorder usually diagnosed postmortem. The rectal and skin biopsy had proved helpful in antemortem diagnosis. We have increased the diagnostic armamentarium by showing the presence of intranuclear inclusions in smooth muscle cells of the muscle. Hence, a high degree of suspicion, magnetic resonance imaging features, with nerve/muscle/skin biopsy can help in diagnosis of NIID.

Effect of hyperhydration on the pharmacokinetics and detection of orally administered budesonide in doping control analysis.

The aim of the present study was to investigate if hyperhydration could influence the excretion and subsequent detection of budesonide (BDS) and its main metabolites (6ß-hydroxy-budesonide and 16α-hydroxy-prednisolone) during doping control analysis by leading to concentrations below the WADA reporting level (30 ng/mL). The influence of hyperhydration on the plasma and urinary pharmacokinetic (PK) profiles of BDS and metabolites was also examined. Seven healthy physically active non-smoking Caucasian males participated in a 15-day clinical study. BDS was administered orally at a single dose of 9 mg on Days 1, 7, and 13. Hyperhydration was applied in the morning on two consecutive days, that is, 0 and 24 hours after first fluid ingestion. Water and a commercial sports drink were used as hyperhydration agents (20 mL/kg body weight). Results showed no significant difference (P > 0.05, 95% CI) on plasma or urinary PK parameters under hyperhydration conditions for all the analytes. However, significant differences (P < 0.05, 95% CI) due to hyperhydration were observed on the urinary concentrations of BDS and metabolites. To compensate the dilution effect due to hyperhydration, different adjustment methods were applied based on specific gravity, urinary flow rate, and creatinine. All the applied methods were able to adjust the concentration values close to the baseline ones for each analyte; however, specific gravity was the optimum method in terms of effectiveness and practicability. Furthermore, no masking of the detection sensitivity of BDS or its metabolites was observed due to hyperhydration either in plasma or urine samples.

Acute disseminated encephalomyelitis in children - clinical and MRI decision making in the emergency department.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is an uncommon, treatable, primarily pediatric, immune-mediated disease. Diagnosis of ADEM requires two essential elements: typical clinical presentation and magnetic resonance imaging (MRI) findings. The aim of this study was to evaluate how clinical findings in the initial emergency department (ED) presentation influenced the timing of MRI. METHODS: A retrospective chart review was conducted of children diagnosed with ADEM, over a 12-year period, in a tertiary care pediatric center. Clinical presentation at ED admission was recorded and patients who underwent an MRI as part of their ED evaluation (early MRI) with those who had MRI performed during ward hospitalization (late MRI) were compared. RESULTS: 30 patients were diagnosed with ADEM during the study period. Encephalopathy and polyfocal neurological signs were described in 80% and 50% of patients ED charts, respectively. Seven patients underwent early MRI and polyfocal neurological signs were more common in this group (p = 0.006). Fever was more common in the late MRI group (p = 0.02). Following diagnosis, all patients were treated with immune-modulation therapy, improved clinically, and were discharged. CONCLUSION: 20% of ADEM patients were not encephalopathic at ED presentation. Polyfocal neurological signs and absence of fever at ED presentation were related to earlier MRI utilization and thus earlier diagnosis and treatment. Familiarity with the ADEM constellation of signs, and a high index of suspicion, may help the ED clinician in early diagnosis and treatment of this rare disease.