Untreated combined persistent fetal vasculature with "coralliform" cataract in a Hispanic 21 year-old male.

Persistent fetal vasculature is a spectrum of ocular abnormalities linked to an incomplete regression of the fetal ocular vasculature. A 21-years old male patient came to the outpatient clinic reporting low vision and strabismus in his left eye since 3 years of age. Ophtalmological examination revealed a normal right eye, while the left eye had a best corrected visual acuity of hand-motion perception, a 30 prism diopters esotropia, a "coralliform" cataract and a vitreous stalk joining the posterior face of the lens and the optic nerve. The coralliform cataract possessed spindle-shaped processes radiating out of its center in an axial direction and was located in the posterior subcapsular area. The patient elected to not undergo vitreoretinal surgery due to the poor visual prognosis. The unusual cataract present in the described patient could be related to his untreated status, as previous authors have reported that untreated cataracts in persistent fetal vasculature may undergo diverse degenerations.

Colonizing microbiota is associated with clinical outcomes in diabetic wound healing.

With the development of society and the improvement of life quality, more than 500 million people are affected by diabetes. More than 10 % of people with diabetes will suffer from diabetic wounds, and 80 % of diabetic wounds will reoccur, so the development of new diabetic wound treatments is of great importance. The development of skin microbe research technology has gradually drawn people's attention to the complex relationship between microbes and diabetic wounds. Many studies have shown that skin microbes are associated with the outcome of diabetic wounds and can even be used as one of the indicators of wound prognosis. Skin microbes have also been found to have the potential to treat diabetic wounds. The wound colonization of different bacteria can exert opposing therapeutic effects. It is necessary to fully understand the skin microbes in diabetic wounds, which can provide valuable guidance for clinical diabetic wound treatment.

Evaluación multimodal de un «micromelanocitoma» del disco óptico: un reporte de caso / Multimodal imaging assessment of a “micro” optic disk melanocytoma: A case report

Un melanocitoma del disco óptico es una lesión neoplásica pigmentada y benigna que en promedio mide 2,00mm de diámetro. Melanocitomas del disco óptico más pequeños son raros y no han sido estudiados con múltiples técnicas de imagen. Un caso de un «micromelanocitoma» del disco óptico con un diámetro de 0,71mm fue estudiado con múltiples estudios de imagen, incluyendo autofluorescencia de fondo de ojo, ultrasonido ocular, campos visuales, tomografía de coherencia óptica (OCT) y angiografía por OCT. Mientras que la exploración con biomicroscopia y la autoflourescencia de fondo de ojo revelan cambios compatibles con los casos de tamaño promedio previamente publicados, la OCT, angiografía por OCT y el ultrasonido revelan cambios que difieren de los artículos previos y que podrían ser útiles para el seguimiento (AU)

An optic disk melanocytoma is a benign pigmented neoplasm of the optic disk measuring 2.00mm of diameter in average. Smaller optic disk melanocytomas are rare and have not been studied with multiple imaging studies. A case of a “micro” optic disk melanocytoma measuring 0.71mm in diameter was studied by multiple imaging modalities, including fundus autofluorescence, ultrasound, visual fields, optical coherence tomography (OCT) and OCT angiography. While clinical appreciation and fundus autofluorescence reveal changes compatible with previously reported cases, OCT, OCT angiography and ultrasound reveal specific changes that could be useful for follow up (AU)

Multimodal imaging assessment of a "micro" optic disk melanocytoma: A case report.

An optic disk melanocytoma is a benign pigmented neoplasm of the optic disk measuring 2.00 mm of diameter in average. Smaller optic disk melanocytomas are rare and have not been studied with multiple imaging studies. A case of a "micro" optic disk melanocytoma measuring 0.71 mm in diameter was studied by multiple imaging modalities, including fundus autofluorescence, ultrasound, visual fields, optical coherence tomography (OCT) and OCT angiography. While clinical appreciation and fundus autofluorescence reveal changes compatible with previously reported cases, OCT, OCT angiography and ultrasound reveal specific changes that could be useful for follow up.

Multimodal imaging assessment of a "micro" optic disk melanocytoma: A case report. / Evaluación multimodal de un «micromelanocitoma¼ del disco óptico: un reporte de caso.

An optic disk melanocytoma is a benign pigmented neoplasm of the optic disk measuring 2.00mm of diameter in average. Smaller optic disk melanocytomas are rare and have not been studied with multiple imaging studies. A case of a "micro" optic disk melanocytoma measuring 0.71mm in diameter was studied by multiple imaging modalities, including fundus autofluorescence, ultrasound, visual fields, optical coherence tomography (OCT) and OCT angiography. While clinical appreciation and fundus autofluorescence reveal changes compatible with previously reported cases, OCT, OCT angiography and ultrasound reveal specific changes that could be useful for follow up.

Specimen Collection for Translational Studies in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.

Improving acne keloidalis nuchae with targeted ultraviolet B treatment: a prospective, randomized, split-scalp comparison study.

BACKGROUND: Acne keloidalis nuchae (AKN) is a chronic scarring folliculitis with fibrotic papules on the occipital scalp. Its treatment is limited and unsatisfactory. OBJECTIVES: To determine whether targeted ultraviolet B (tUVB) phototherapy will (i) improve the clinical appearance of AKN and (ii) induce extracellular matrix remodelling in affected lesions. METHODS: Eleven patients with AKN were enrolled in a prospective, randomized, split-scalp comparison study. One randomly selected side of the scalp was treated with tUVB up to three times weekly for 8 weeks. After week 8, both sides were treated for eight additional weeks. Assessment included lesion counts in two 3 × 3-cm regions of interest (ROIs), one on each side of the scalp (ROI-1: tUVB weeks 0-16, ROI-2: tUVB weeks 9-16), patient self-assessment and analysis of MMP1, MMP9, TGFB1 and COL1A1 mRNA expression by quantitative reverse-transcription polymerase chain reaction. RESULTS: Before treatment, the mean lesion count was similar between tUVB-treated and untreated sides (14·8 vs. 15·0). After 8 weeks of tUVB, the mean lesion count decreased significantly to 9·4 ± 1·2 (P =  0·03), with no change on the untreated side. With continued treatment, the mean lesion count in ROI-1 decreased further to 7 ± 1·5 (P = 0·04) after 16 weeks of tUVB. CONCLUSIONS: tUVB significantly improved the clinical appearance of AKN, led to patient satisfaction and was well tolerated.

Insulin-responsive aminopeptidase trafficking in 3T3-L1 adipocytes.

The insulin-responsive aminopeptidase (IRAP/VP165/gp160) was identified originally in GLUT4-containing vesicles and shown to translocate in response to insulin, much like the glucose transporter 4 (GLUT4). This study characterizes the trafficking and kinetics of IRAP in exocytosis, endocytosis, and recycling to the membrane in 3T3-L1 adipocytes. After exposure of 3T3-L1 adipocytes to insulin, IRAP translocated to the plasma membrane as assessed by either cell fractionation, surface biotinylation, or the plasma membrane sheet assay. The rate of exocytosis closely paralleled that of GLUT4. In the continuous presence of insulin, IRAP was endocytosed with a half-time of about 3-5 min. IRAP endocytosis is inhibited by cytosol acidification, a property of clathrin-mediated endocytosis, but not by the expression of a constitutively active Akt/PKB. Arrival in an LDM fraction derived via subcellular fractionation exhibited a slower time course than disappearance from the cell surface, suggesting additional endocytic intermediates. As assayed by membrane "sheets," GLUT4 and IRAP showed similar internalization rates that are wortmannin-insensitive and occur with a half-time of roughly 5 min. IRAP remaining on the cell surface 10 min following insulin removal was both biotin- and avidin-accessible, implying the absence of thin-necked invaginations. Finally, endocytosed IRAP quickly recycled back to the plasma membrane in a wortmannin-sensitive process. These results demonstrate rapid endocytosis and recycling of IRAP in the presence of insulin and trafficking that matches GLUT4 in rate.

Identification of wortmannin-sensitive targets in 3T3-L1 adipocytes. DissociationoOf insulin-stimulated glucose uptake and glut4 translocation.

The current studies investigated the contribution of phosphatidylinositol 3-kinase (PI3-kinase) isoforms to insulin-stimulated glucose uptake and glucose transporter 4 (GLUT4) translocation. Experiments involving the microinjection of antibodies specific for the p110 catalytic subunit of class I PI3-kinases demonstrated an absolute requirement for this form of the enzyme in GLUT4 translocation. This finding was confirmed by the demonstration that the PI3-kinase antagonist wortmannin inhibits GLUT4 and insulin-responsive aminopeptidase translocation with a dose response identical to that required to inhibit another class I PI3-kinase-dependent event, activation of pp70 S6-kinase. Interestingly, wortmannin inhibited insulin-stimulated glucose uptake at much lower doses, suggesting the existence of a second, higher affinity target of the drug. Subsequent removal of wortmannin from the media shifted this dose-response curve to one resembling that for GLUT4 translocation and pp70 S6-kinase. This is consistent with the lower affinity target being p110, which is irreversibly inhibited by wortmannin. Wortmannin did not reduce glucose uptake in cells stably expressing Myr-Akt, which constitutively induced GLUT4 translocation to the plasma membrane; this demonstrates that wortmannin does not inhibit the transporters directly. In addition to elucidating a second wortmannin-sensitive pathway in 3T3-L1 adipocytes, these studies suggest that the presence of GLUT4 on the plasma membrane is not sufficient for activation of glucose uptake.

Signaling pathways mediating insulin-stimulated glucose transport.

A major action of insulin is to accelerate the rate of uptake of sugar into muscle and adipose cells following a meal. The biochemical mechanism by which this is accomplished has been a subject of intense experimentation, although elucidation of the pathways has remained elusive. In recent years, numerous signaling molecules and cascades modulated by insulin have been identified, although few have been definitively established as important to the metabolic actions of the hormone. An exception to this is the lipid kinase phosphatidylinositide 3'-kinase, which, under many conditions, appears absolutely required for insulin to stimulate hexose uptake into adipocytes. Akt/PKB, a serine/threonine protein kinase activated by insulin in a phosphatidylinositide 3'-kinase-dependent manner, has been implicated as a critical mediator of insulin's actions on metabolism and cell survival. Nonetheless, Akt/PKB's role in many insulin effects, particularly accelerated glucose transport, remains controversial. Interestingly, soluble analogues of ceramide antagonize both insulin's activation of Akt/PKB as well as its stimulation of glucose transport, consistent with a causal relationship between the two.

Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide.

The sphingomyelin derivative ceramide is a signaling molecule implicated in numerous physiological events. Recently published reports indicate that ceramide levels are elevated in insulin-responsive tissues of diabetic animals and that agents which trigger ceramide production inhibit insulin signaling. In the present series of studies, the short-chain ceramide analog C2-ceramide inhibited insulin-stimulated glucose transport by approximately 50% in 3T3-L1 adipocytes, with similar reductions in hormone-stimulated translocation of the insulin-responsive glucose transporter (GLUT4) and insulin-responsive aminopeptidase. C2-ceramide also inhibited phosphorylation and activation of Akt, a molecule proposed to mediate multiple insulin-stimulated metabolic events. C2-ceramide, at concentrations which antagonized activation of both glucose uptake and Akt, had no effect on the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) or the amounts of p85 protein and phosphatidylinositol kinase activity that immunoprecipitated with anti-IRS-1 or antiphosphotyrosine antibodies. Moreover, C2-ceramide also inhibited stimulation of Akt by platelet-derived growth factor, an event that is IRS-1 independent. C2-ceramide did not inhibit insulin-stimulated phosphorylation of mitogen-activated protein kinase or pp70 S6-kinase, and it actually stimulated phosphorylation of the latter in the absence of insulin. Various pharmacological agents, including the immunosuppressant rapamycin, the protein synthesis inhibitor cycloheximide, and several protein kinase C inhibitors, were without effect on ceramide's inhibition of Akt. These studies demonstrate ceramide's capacity to inhibit activation of Akt and imply that this is a mechanism of antagonism of insulin-dependent physiological events, such as the peripheral activation of glucose transport and the suppression of apoptosis.

The effect of monovalent cations on the self-association of cytidylyl-(3-5')-guanosine and guanylyl-(3'5')-cytidine in aqueous solution.

The hydrogen-bonding, base stacking, and formation of extended aggregates has been investigated for salts of guanylyl-3'-5')-cytidine, GpC, and cytidylyl-(3'-5')- guanosine, CpG, in which the cation was Na+, K+, or tetramethylammonium (TMA+). Variable temperature studies were done at 2-70 degrees C on aqueous solutions at pD4 and 8 using 1H NMR and FTIR. At low temperatures it has been found that at pD 8 both GpC and CpG form Watson-Crick dimers which stack upon each other to form larger species. A slight cation effect is observed below 35 degrees C which has the order: TMA+ > Na+ > K+. This order suggests that the cations are interacting with the phosphate and interactions with the bases are unlikely. The 1H NMR spectrum for TMACpG at pD 4 has been assigned and exhibits chemical shift differences from those at pD 8 which are consistent with protonation of the N3 of the cytidine residue. Based on NMR line broadening, CpG at pD 4 has a greater degree of self-association at low temperature than it or GpC have at pD 8. A different type of hydrogen bonding and self-association occur in CpG at pD 4 compared to pD 8, but the structures are uncertain. Due to hemi-protonation of the cytidine N3, parallel G-G/C-C+ base paired dimers or G-tetrads may be forming.

Conformation, hydrogen bonding and aggregate formation of guanosine 5'-monophosphate and guanosine in dimethylsulfoxide.

The tetrabutylammonium salt of guanosine 5'-monophosphate (5'-GMP) dissolves in DMSO-d6 forming aggregated species which exhibit some properties of reverse micelles. 1H NOESY experiments show that the 5'-GMP adopts the syn conformation about the glycosidic bond. Molecular mechanics calculations reveal a stable structure with this conformation in which the phosphate group and the amino group of the base are in close enough proximity to hydrogen bond. In contrast inosine 5'-monophosphate in DMSO-d6, which has no NH2 group for hydrogen bond stabilization of the syn conformation, is shown by NMR to have the anti structure. Guanosine in DMSO-d6 behaves differently from 5'-GMP. Guanosine adopts the anti conformation and forms a symmetric dimer via hydrogen bonding between the N3 and NH2 of the bases.