Hyper-proliferation of Glial Tissues Following Autologous Internal Limiting Membrane Transplantation in Idiopathic Large Macular Holes

PURPOSE: To report three cases of glial hyper-proliferation after autologous internal limiting membrane (ILM) transplantation in idiopathic large macular holes. CASE SUMMARY: Three eyes with full thickness macular holes >500 µm underwent autologous ILM transplantation. After surgery, the macular hole was closed and foveal contour was U-shaped. Optical coherence tomography revealed long-lasting proliferation of glial cells in the fovea after the hole closure. This glial proliferation continued for 6 months, with improved visual acuity, and bump-like features of the fovea. CONCLUSIONS: Autologous transplantation of ILM effectively induced long-lasting proliferation of glial cells, thereby achieving the closure of large macular holes. However, an abnormality of the foveal contour may develop after the hole closure in some cases.

Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells

PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.

Comparative effect of dietary borage oil and safflower oil on anti-proliferation and ceramide metabolism in the epidermis of essential fatty acid deficient guinea pigs / 한국영양학회지

PURPOSE: Borage oil (BO) and safflower oil (SO) are efficacious in reversing epidermal hyperproliferation, which is caused by the disruption of epidermal barrier. In this study, we compared the antiproliferative effect of dietary BO and SO. Altered metabolism of ceramide (Cer), the major lipid of epidermal barrier, was further determined by measurement of epidermal levels of individual Cer, glucosylceramide (GlcCer), and sphingomyelin (SM) species, and protein expression of Cer metabolizing enzymes. METHODS: Epidermal hyperproliferation was induced in guinea pigs by a hydrogenated coconut diet (HCO) for 8 weeks. Subsequently, animals were fed diets of either BO (group HCO + BO) or SO (group HCO + SO) for 2 weeks. As controls, animals were fed BO (group BO) or HCO (group HCO) diets for 10 weeks. RESULTS: Epidermal hyperproliferation was reversed in groups HCO + BO (67.6% of group HCO) and HCO + SO (84.5% of group HCO). Epidermal levels of Cer1/2, GlcCer-A/B, and beta-glucocerebrosidase (GCase), an enzyme of GlcCer hydrolysis for Cer generation, were higher in group HCO + BO than in group HCO, and increased to levels similar to those of group BO. In addition, epidermal levels of SM1, serine palmitoyltransferase (SPT), and acidic sphingomyelinase (aSMase), enzymes of de novo Cer synthesis and SM hydrolysis for Cer generation, but not of Cer3-7, were higher in group HCO + BO than in group HCO. Despite an increase of SPT and aSMase in group HCO + SO to levels higher than in group HCO, epidermal levels of Cer1-7, GlcCer-A/B, and GCase were similar in these two groups. Notably, acidic ceramidase, an enzyme of Cer degradation, was highly expressed in group HCO + SO. Epidermal levels of GlcCer-C/D and SM-2/3 did not differ among groups. CONCLUSION: Dietary BO was more prominent for reversing epidermal hyperproliferation by enhancing Cer metabolism with increased levels of Cer1/2, GlcCer-A/B, and SM1 species, and of GCase proteins.

Therapeutic efficacy and safety of propylthiouracil in psoriasis: An open-label study.

Background: Psoriasis is a common hyperproliferative disorder of the skin associated with significant morbidity. Most of the drugs used in psoriasis provide only a temporary relief, whereas they are riddled with potential toxicities and cost concerns. Hence, there is a constant need to explore newer, effective, orally administered, and cost-effective drugs with minimal adverse effects. In this scenario, propylthiouracil (PTU), an antithyroid thioureylene has been shown to be effective in psoriasis which satisfies the above criteria. Aim: The objective of our study is to assess the clinical efficacy of PTU in psoriasis. Methods: A total of 25 patients with plaque psoriasis were treated with oral PTU for 12 weeks. Clinical response was assessed using the "Psoriasis Area and Severity Index" (PASI) score. Routine blood analyses and thyroid function tests were carried out periodically during the study. Results: Oral PTU produced significant clearing of lesions at 6 weeks and 12 weeks of the study period in all patients, as demonstrated by the reduction in PASI scores (33.9% in 6 weeks and 74.1% reduction in 12 weeks). Four patients experienced near complete clearing of the lesions. One patient developed mild elevation of liver enzymes which reversed on withdrawal of PTU. None of the patients had hypothyroidism or cytopenias. Conclusion: PTU significantly clears the lesions in psoriasis with minimal adverse effects. Hence, it can be considered as a therapeutic option in psoriasis, especially when the standard drugs cannot be used due to their toxicities or forbidding cost.

Arctii Fructus is a Prominent Dietary Source of Linoleic Acid for Reversing Epidermal Hyperproliferation of Guinea Pigs

Linoleic acid [LA; 18: 2 (n-6)] is the most abundant polyunsaturated fatty acid in human skin. The exclusion of LA from diet induces epidermal hyperproliferation, which is reversible by the inclusion of LA in diet, and hence, LA is heralded as an essential fatty acid (EFA). Since safflower oil (SO) has been widely recognized as the major dietary source of LA and Arctii Fructus (Arctium lappa L.) is recently reported to contain high level of LA, we compared the antiproliferative effects of SO and Arctii Fructus in this study. Epidermal hyperproliferation was induced in guinea pigs by hydrogenated coconut oil (HCO) diet for 8 wk. During following 2 wk, EFA deficient guinea pigs were fed diets of safflower oil (group HS), water extract of Arctii Fructus (group AW) or organic extract of Arctii Fructus (group AO). Normal control group was fed SO containing diet (group SO) and EFA deficient group was fed HCO containing diet (group HCO) for 10 wk. Epidermal hyperproliferation was reversed in groups AO (55.9% of group HCO) and HS(74.1% of group HCO). However, the thymidine incorporation into epidermal DNA of group HS was greater than of normal control group SO. Epidermal hyperproliferation was not reversed in group AW. The accumulations of LA into phospholipids and ceramides, and of 13-hydroxyoctadecadienoic acid (13-HODE), the potent antiproliferative metabolite of LA in the epidermis of group AO were greater than of group HS. In contrast, the de novo synthesis of ceramides, the major lipids maintaining epidermal barrier, did not differ between all of groups. Together, our data demonstrate that organic extract of Arctii Fructus is more prominent than safflower oil in reversing epidermal hyperproliferation by inducing the higher accumulations of LA and 13-HODE in the epidermis of guinea pigs.

Immunohistochemical Study for Differentiation of Human Middle Ear Cholesteatoma / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Human epidermis is a continuously dividing tissue, in which keratinocytes gradually differentiate and mature while moving from basal cells to suprabasal cell layers. Epidermal homeostasis is maintained by a delicate balance between proliferation and terminal differentiation. Cholesteatoma is characterized by the presence of a squamous epithelium invading the middle ear, which is believed to have hyperproliferative properties. The aim of this study is to determine whether the hyperproliferative character of cholesteatoma is associated with differentiation of basal cell or suprabasal cell layers. MATERIALS AND METHODS: Using immunohistochemical techniques, we investigated the reaction pattern of monoclonal antibody to involucrin and filaggrin as differentiation markers in the cholesteatoma matrices which were harvested during surgery. For the control, the same immunohistochemical study was also done in deep meatal skin and retroauricular skin during the same surgery. RESULTS: The immunostaining intensity of filaggrin at suprabasal cell layers was higher in cholesteatoma than in retroauricular skin and deep meatal skin. The immunostaining intensity of involucrin at suprabasal cell layers was higher in cholesteatoma and deep meatal skin than in retroauricular skin. CONCLUSION: This result represents that the epidermal cells in cholesteatoma at suprabasal layers actively differentiate more than the epidermal cells in retroauricular skin. So this study suggests that hyperkeratinization in cholesteatoma might be due to altered differentiation of suprabasal keratinocytes. Furthermore, this study reveals that the deep meatal skin has unusual hyperproliferative behavior in contrast to the retroauricular skin.

Hyperproliferative Characteristics in Human Deep Meatal Epidermis / 대한이비인후과학회지

In benign hyperproliferative epidermal diseases(eq. warts, psoriasis) and squamous carcinoma, some molecular markers of hyperproliferative keratinocyte such as cytokeratin 16 and PCNA were expressed predominantly. However, all healthy epidermis including the meatal epidermis are nonreactive to those molecular markers except some of thick skin. Recently, there are several reports which show unusal proliferative capacity around the annular region of the ear drum. Our study has concentrated on the characteristics of the differentiation in healthy deep meatal epidermis using immunohistochemistry with cytokeratins and PCNA. Our investigation has demonstrated that the deep meatal epidermis around the annular region in contrast to the other region of the meatus exhibited unusal proliferative capacity. This result suggests a pathology link such as invasion mechanism and hyperkeratinization between the cholesteatoma and deep meatal skin.