Hyperbaric Oxygen Therapy-A Novel Treatment Modality in Oral Submucous Fibrosis: A Review.

Oral submucous fibrosis (OSMF) is a chronic, debilitating disease characterized by juxta epithelial fibrosis of the oral cavity and regarded as a potentially malignant disorder. Numerous treatment modalities ranging from various drugs to behavioral therapy have been tried with inconsistent results with varying degrees of success reflecting low predictability, requiring further evaluation and standardization. Novel treatment modality such as Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at increased atmospheric pressure usually ranging between 2.0 and 2.5 atmospheres for periods between 60 and 120 min. HBOT which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve hypoxic environment of OSMF and also possesses potent anti-inflammatory properties. This article enlightens on possible beneficial effects of HBOT in the management of OSMF at cellular and molecular level.

Disrupting SUMOylation enhances transcriptional function and ameliorates polyglutamine androgen receptor-mediated disease.

Expansion of the polyglutamine (polyQ) tract within the androgen receptor (AR) causes neuromuscular degeneration in individuals with spinobulbar muscular atrophy (SBMA). PolyQ AR has diminished transcriptional function and exhibits ligand-dependent proteotoxicity, features that have both been implicated in SBMA; however, the extent to which altered AR transcriptional function contributes to pathogenesis remains controversial. Here, we sought to dissociate effects of diminished AR function from polyQ-mediated proteotoxicity by enhancing the transcriptional activity of polyQ AR. To accomplish this, we bypassed the inhibitory effect of AR SUMOylation (where SUMO indicates small ubiquitin-like modifier) by mutating conserved lysines in the polyQ AR that are sites of SUMOylation. We determined that replacement of these residues by arginine enhances polyQ AR activity as a hormone-dependent transcriptional regulator. In a murine model, disruption of polyQ AR SUMOylation rescued exercise endurance and type I muscle fiber atrophy; it also prolonged survival. These changes occurred without overt alterations in polyQ AR expression or aggregation, revealing the favorable trophic support exerted by the ligand-activated receptor. Our findings demonstrate beneficial effects of enhancing the transcriptional function of the ligand-activated polyQ AR and indicate that the SUMOylation pathway may be a potential target for therapeutic intervention in SBMA.

Smile rejuvenation: A case report.

Mesiodens is the commonly occurring supernumerary tooth seen between the maxillary central incisors which causes compromised aesthetics and malocclusion. Till date orthodontic therapy provides an excellent solution for the management of mesiodens. Recently, Restorative Space Management (RSM) has been used successfully to correct tooth shape, proportions and colour with minimal tooth preparations. This case report describes the successful management of an unaesthetic smile due to presence of a mesiodens in the midline primarily using aesthetic treatment only.

Transcriptional activation of TFEB/ZKSCAN3 target genes underlies enhanced autophagy in spinobulbar muscular atrophy.

Spinobulbar muscular atrophy (SBMA) is an inherited neuromuscular disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract in exon 1 of the androgen receptor (AR) gene. SBMA demonstrates androgen-dependent toxicity due to unfolding and aggregation of the mutant protein. There are currently no disease-modifying therapies, but of increasing interest for therapeutic targeting is autophagy, a highly conserved cellular process mediating protein quality control. We have previously shown that genetic manipulations inhibiting autophagy diminish skeletal muscle atrophy and extend the lifespan of AR113Q knock-in mice. In contrast, manipulations inducing autophagy worsen muscle atrophy, suggesting that chronic, aberrant upregulation of autophagy contributes to pathogenesis. Since the degree to which autophagy is altered in SBMA and the mechanisms responsible for such alterations are incompletely defined, we sought to delineate autophagic status in SBMA using both cellular and mouse models. Here, we confirm that autophagy is induced in cellular and knock-in mouse models of SBMA and show that the transcription factors transcription factor EB (TFEB) and ZKSCAN3 operate in opposing roles to underlie these changes. We demonstrate upregulation of TFEB target genes in skeletal muscle from AR113Q male mice and SBMA patients. Furthermore, we observe a greater response in AR113Q mice to physiological stimulation of autophagy by both nutrient starvation and exercise. Taken together, our results indicate that transcriptional signaling contributes to autophagic dysregulation and provides a mechanistic framework for the pathologic increase of autophagic responsiveness in SBMA.

Outcome of descemet stripping automated endothelial keratoplasty in patients with an anterior chamber intraocular lens.

PURPOSE: To evaluate the outcome of Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with a retained anterior chamber intraocular lens (ACIOL). METHODS: A retrospective review of 11 patients with corneal decompensation and ACIOL who underwent DSAEK was performed. All patients except 1 had open-loop style ACIOLs, and in all cases, there was adequate anterior chamber depth. At the time of surgery, 6 patients had a temporary suture to secure their graft, 2 of which were retained from the insertion method, and the other 4 were placed additionally. Postoperatively, the rate of donor detachment, graft clarity, corneal pachymetry, and visual acuity were noted. RESULTS: There was only 1 graft dislocation postoperatively, which was reattached successfully by air injection. There was 1 primary graft failure (without dislocation) among the 11 patients during the mean follow-up of 12 months (range: 6-25 months); at last follow-up, the visual acuity had improved in all the other 10 patients. CONCLUSIONS: This series demonstrates that DSAEK can be performed successfully in patients with existing ACIOLs. These early outcomes suggest that DSAEK alone may be considered as an alternative to a lens exchange with DSAEK in patients with adequate anterior chamber depth.

Smoothened antagonists for hair inhibition.

A series of aminomethylpyrazoles were prepared and evaluated using cell-based Smoothened beta-lactamase reporter assay and Smoothened binding assay. Potent Smoothened antagonists 10k and 10l were found to inhibit hair growth in vivo in the C3H/HeN mouse hair growth model. The more selective compound 10l was tested negative in the 3T3 NRU assay, indicating a low risk for causing photo-irritation and was efficacious using the C3H/HeN mouse hair growth model although it was slightly less efficacious than that of the reference compound eflornithine (7).

The use of the Fugo Blade in corneal surgery: a preliminary animal study.

PURPOSE: To evaluate the performance of the Fugo Blade in cutting corneal tissue in animals, both in vitro and in vivo. METHODS: Corneal incisions were made on pig eyes using the Fugo Blade. The histologic characteristics of these cuts were then evaluated. Similar cuts were also performed in rabbit corneas in vivo and compared with cuts performed with mechanical blades. The rabbits were euthanized, and the corneas were obtained for histopathologic examination 14 days after surgery. RESULTS: Slit-lamp examinations and histologic findings showed that the Fugo Blade can produce sharp cuts in the cornea with minimal tissue damage beyond the edges of the incisions. It cuts without resistance and permits normal wound healing. CONCLUSIONS: Although the Fugo Blade is currently approved by the Food and Drug Administration for anterior capsulotomy, our study demonstrates that the Fugo Blade can safely and quickly produce resistance-free cuts in corneal tissue in animals, opening additional avenues for use of this device in corneal surgery.

A low-calcemic vitamin D analog (Ro 25-4020) inhibits the growth of LNCaP human prostate cancer cells with increased potency by producing an active 24-oxo metabolite (Ro 29-9970).

In this study, we have characterized a novel less-calcemic vitamin D analog Ro 25-4020 (1alpha, 25 dihydroxy-16-ene-5,6-trans-vitamin D3) and investigated the mechanisms underlying its enhanced growth inhibitory properties. We found that Ro 25-4020 (IC50 = 0.3 nM) exhibited greater inhibitory activity than 1,25(OH)2D3 (IC50 = 1 nM) on LNCaP human prostate cancer cell growth. However, Ro 25-4020 was tenfold less active than 1,25(OH)2D3 in receptor-binding assays, ligand-induced heterodimerization and transactivation assays using VDR. HPLC and GC-MS analyses revealed that 1,25(OH)2D3 is converted to a 24-hydroxy metabolite, which has been shown to be less potent than 1,25(OH)2D3. In contrast, Ro 25-4020 was converted to a major 24-oxo metabolite that was more stable. Ligand-binding assays reveal that both Ro 25-4020 and its 24-oxo metabolite have similar affinity for VDR. Synthetic 24-oxo-Ro 25-4020, however, inhibited LNCaP cell proliferation as potently as 1,25(OH)2D3 and was more potent in transactivation of two out of three vitamin D target genes tested. These results suggest that conversion of Ro 25-4020 into an active and more stable 24-oxo metabolite with longer half-life contributes significantly to its potent antiproliferative actions on the LNCaP cells.

Relationship of contact lenses, pregnancy, and herpes simplex virus.

Herpes simplex virus (HSV) is one of the most common causes of corneal infections in the world, affecting more than 500,000 people in the United States alone. HSV keratitis recurrences can occur with systemic immunosuppression. Pregnancy can resemble a modified state of immunosuppression resulting in an increased risk for HSV keratitis. This type of immunosuppression combined with contact lens wear may have an additive effect and increase the possibility of HSV recurrence. Despite the obvious correlation, there are no reported cases in the literature. A case of bilateral HSV keratitis in a pregnant contact lens wearer is presented with an explanation of the causes and possible treatment methods.