Lacrimal Puncta Agenesis in Kabuki Syndrome.

Kabuki syndrome (KS) is a rare congenital disorder characterized by multiple systemic anomalies and facial characteristics. Here, the authors present the first case, to the best of the authors' knowledge, of bilateral lacrimal puncta agenesis in a patient with KS.#8232;The proband patient was a 29-year-old woman diagnosed with this syndrome, brought to our office due to recurrent conjunctivitis where agenesia of lacrimal puncta was observed. Therapeutic options were exposed but, as the concomitant medication (topiramate) produced ocular dryness, conservative treatment was decided. Diagnosis of KS is challenging because it is a complex syndrome with many associated findings. The authors recommend taking into account the agenesis of lacrimal points in the differential diagnosis of KS if it is associated with other phenotypic alterations as well as including lacrimal examination in patients with KS diagnosis. The authors emphasize the importance of individualizing treatment since drugs used for the systematic management of these patients can influence tear symptoms.

Gyrate atrophy of the choroid and retina: Update on diagnosis and treatment.

Gyrate atrophy of the choroid and retina (GACR) is a rare autosomal recessive disease characterised by elevated plasma ornithine levels due to deficiency of the enzyme ornithine aminotransferase (OAT). The accumulation of this amino acid in plasma leads to the development of patches of chorioretinal atrophy in the peripheral retina extending into the macular area. Patients usually present with night blindness followed by constriction of the visual field and, finally, decreased central vision and blindness. The disease is diagnosed by the presence of the characteristic clinical picture, the presence of hyperornithinaemia in plasma and the detection of mutations in the OAT enzyme gene. There is currently no effective gene therapy and the most common therapeutic intervention mainly involves dietary modifications with arginine restriction. This article aims to summarise the pathogenesis, clinical and diagnostic findings and treatment options in patients with GACR.

Venous malformations treated with dual wavelength 595 and 1064 nm laser system.

BACKGROUND & OBJECTIVE: Venous malformations (VM) represent a localized error in the embryological development of the venous branch of the circulation. The management of VM is complex and challenging. The aim of this study was to assess the efficacy and safety of combined sequential pulsed dye laser (PDL)-Nd:YAG laser in patients with cutaneous or mucosal VM. METHODS: Thirty patients (age from 8 to 65 years) with cutaneous or mucosal VM treated with dual wavelength PDL-Nd:YAG laser were retrospectively analyzed. Laser parameters were 10 mm spot size with 10 ms pulse and 8-10 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 35-70 J/cm(2); or 7 mm spot size with 10 ms pulse and 5-10.5 J/cm(2) of PDL, followed with a second delay by Nd:YAG with 15 or 20 ms at 50-100 J/cm(2). Laser sessions were repeated approximately every 2-6 months. Air cooling was applied during treatment. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before and after laser treatment (scale from 0 to 4). Differences in the degree of clinical improvement between patients with cutaneous or mucosal VM were also assessed. Adverse events were registered. Patient satisfaction was also assessed in 19 cases (scale from 0 to 10). RESULTS: Mean global improvement was rated as 3.37. Mean improvement in patients with cutaneous VM was 3.35 and 3.38 in patients with mucosal VM. No significant difference between both groups was observed (P = 0.53). Long-lasting side effects included partial epilation of the eyelashes in one patient, ulceration in two patients and permanent scarring in three patients. Mean patient satisfaction was 8.55. CONCLUSIONS: Our study concludes that dual wavelength PDL-Nd:YAG laser was effective for treatment of the superficial component of cutaneous and mucosal VM.

Infantile hemangiomas treated by sequential application of pulsed dye laser and Nd:YAG laser radiation: a retrospective study.

BACKGROUND AND OBJECTIVES: Infantile hemangiomas are the most common benign tumor in children. They have 3 phases of development: a proliferative phase, an involuting phase, and involution. Although active treatment is often not required, it is necessary in some cases. Of the possible treatments for hemangiomas, lasers have been shown to be effective in all phases of development. We report our experience with dual-wavelength sequential pulses from a pulsed dye laser and an Nd:YAG laser. MATERIAL AND METHODS: This was a retrospective, descriptive study of patients with infantile hemangioma in different phases of development treated with pulsed dye laser pulses followed by Nd:YAG laser pulses. Four dermatologists assessed the effectiveness of treatment on a scale of 10 to 0. Adverse effects and incidents related to treatment were recorded. The median and interquartile range were calculated as descriptive statistics. Pretreatment and posttreatment comparisons were performed using the Wilcoxon test. RESULTS: Twenty-two patients with hemangiomas in different phases of development were included. A statistically significant improvement was obtained both for the entire group and for different subgroups. Posttreatment events were reported in 4 patients, and included edema and ulceration, skin atrophy, and hyperpigmentation. CONCLUSIONS: We believe that treatment with dual-wavelength light from a pulsed dye laser and a Nd:YAG laser is a viable treatment option for infantile hemangiomas when first-line therapies are ineffective or contraindicated.

Ablative fractional yttrium-scandium-gallium-garnet laser for scarring residual haemangiomas and scars secondary to their surgical treatment.

BACKGROUND: Infantile haemangiomas are benign self-involuting tumours. They have a characteristic clinical course marked by early proliferation and followed by spontaneous involution. However, residual evidence with scar formation, fibrofatty residua, atrophic wrinkling, yellowish discoloration and telangiectasias is usually seen after involution. OBJECTIVE: The aim of this study was to assess the efficacy and safety of ablative fractional yttrium-scandium-gallium-garnet (YSGG) laser in patients with residual haemangiomas or with scarring after their surgery. METHODS: Twelve patients with atrophic scar or fibrofatty tissue secondary to residual hemangiomas or with scarring after surgery of haemangioma were treated with one or two sessions of ablative fractional YSGG laser at 2.790-nm wavelength. Laser therapy was performed using a spot size of 300 µm, a pulse width of 600 ms, a fluence range between 120 and 200 mJ per microspot and a density level of 3. Treatment with PDL at 595-nm or with combined sequential 595 nm PDL and 1064 nm Nd:YAG was applied if telangiectasias or a residual vascular component were present. Three dermatologists evaluated treatment effectiveness by means of photographs of the patients before starting and 3 months after finishing the therapy; the degree of improvement was rated from 0 to 4. Parents' satisfaction was also assessed (scale from 0 to 10). RESULTS: Improvement was rated as 3 in two patients, 2 in four patients, 1 in five patients and no improvement in only one patient. Mean improvement was 1.58. Degree of parents' satisfaction ranged from 0 to 10. Mean satisfaction was 6.75. A discrete punctuate pattern was seen in three patients as the only long-lasting side-effect. CONCLUSION: We consider that ablative fractional YSGG laser could be an interesting option for the treatment of selected patients with atrophic wrinkling or scarring residual haemangiomas and scars secondary to their surgical treatment.

Keratosis pilaris rubra and keratosis pilaris atrophicans faciei treated with pulsed dye laser: report of 10 cases.

BACKGROUND: Keratosis pilaris rubra (KPR) and keratosis pilaris atrophicans faciei (KPAF) are both keratinization disorders characterized by erythema and keratotic follicular papules usually located on cheeks, forehead, chin and eyebrows. Topical keratolytics, vitamin D3 analogues, antibiotics, topical and oral retinoids have been used with limited results. As this condition can be socially very limiting, the need for an effective treatment has led to the use of other technologies such as pulsed dye laser (PDL) or intense pulsed light. OBJECTIVE: The aim of this study was to assess the efficacy and safety of PDL in patients with KPR or KPAF. METHODS: Ten patients with KPR or KPAF were treated with two to seven sessions of PDL at 595-nm wavelength. Laser therapy was performed using a spot size of 7 or 10mm, a pulse duration of 0.5 or 1.5ms and a fluence from 5 to 9J/cm(2) . Two dermatologists evaluated treatment effectiveness by means of photographs of the patients before starting and after finishing the therapy. RESULTS: Complete resolution of erythema was achieved in three patients; clearance of erythema was >75% in the other seven patients. Transient purpura was present in all patients for about 2weeks and one patient presented postinflammatory hyperpigmentation for 7months. CONCLUSION: We consider that PDL is a good option for the treatment of KPR and KPAF. A marked reduction in erythema is achieved in all patients with a low incidence of side effects.

Discovery of a small molecule insulin mimetic with antidiabetic activity in mice.

Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was selective for insulin receptor versus insulin-like growth factor I (IGFI) receptor and other receptor tyrosine kinases. Oral administration of L-783,281 to two mouse models of diabetes resulted in significant lowering in blood glucose levels. These results demonstrate the feasibility of discovering novel insulin receptor activators that may lead to new therapies for diabetes.

Capillary Malformations Treated With Sequential Pulsed Dye and Nd:YAG Laser Therapy: A Retrospective Study. / Malformaciones capilares tratadas con aplicación secuencial de láser de colorante pulsado y Nd:YAG: estudio retrospectivo.

INTRODUCTION AND OBJECTIVE: Capillary malformations are the most common vascular malformations in childhood. The current treatment of choice is pulsed dye laser (PDL) therapy, but this frequently does not result in complete resolution. The search for alternative treatment strategies thus continues. In this study we describe our experience with the use of sequential dual-wavelength PDL and Nd:YAG laser therapy in patients with capillary malformations. MATERIAL AND METHODS: We conducted a retrospective, descriptive study of patients with capillary malformations treated with dual-wavelength PDL and Nd:YAG laser therapy between 2006 and 2011. Four dermatologists rated the effectiveness of treatment on a scale of 10 to 0. We also investigated the potential value of the following factors as predictors of better treatment response: sex, malformation size and color, and presence of associated hypertrophy. Adverse effects were also analyzed. RESULTS: We studied 71 patients and most of them experienced a statistically significant improvement after treatment. More favorable responses were observed for violaceous malformations, lesions with associated hypertrophy, and smaller lesions. Adverse effects were reported for 26.76% of patients, and the most common effect was the appearance of isolated areas of skin atrophy. CONCLUSIONS: We consider that sequential dual-wavelength PDL and ND:YAG laser therapy is an effective alternative for treating capillary malformations in selected patients.

Determination of ellagic acid in oak leaves and in sheep ruminal fluid by ion-pair RP-HPLC.

An isocratic ion-pair high-performance liquid chromatography (IP-RP-HPLC) method with UV detection was developed to identify and quantify ellagic acid (EA). This phenolic compound is widely distributed in the plants and is often present in the diet of ruminants. The method was validated and validation parameters were: linearity range 5-100 mg/L; correlation coefficient, 0.9995; mean recoveries (99.94 and 101.07%) and detection limit 1.4 mg/L. Method was applied for the determination of ellagic acid in oak leaves and in ruminal fluid from to a vitro ruminal system. The proposed method proved to be rapid and accurate and can be successfully used in ruminant nutrition studies.

The discovery of enfumafungin, a novel antifungal compound produced by an endophytic Hormonema species biological activity and taxonomy of the producing organisms.

In a screening of natural products with antifungal activity derived from endophytic fungi, we detected a potent activity in a culture belonging to the form-genus Hormonema, isolated from leaves of Juniperus communis. The compound is a new triterpene glycoside, showing an antifungal activity highly potent in vitro against Candida and Aspergillus and with moderate efficacy in an in vivo mouse model of disseminated candidiasis. The agent is especially interesting since its antifungal spectrum and its effect on morphology of Aspergillus fumigatus is comparable to that of the glucan synthase inhibitor pneumocandin B,,, the natural precursor of the clinical candidate MK-0991 (caspofungin acetate). An additional search for other Hormonema isolates producing improved titers or derivatives resulted in the isolation of two more strains recovered from the same plant host showing identical activity. The producing isolates were compared with other non-producing Hormonema strains by DNA fingerprinting and sequencing of the rDNA internal transcribed spacers. Comparison of rDNA sequences with other fungal species suggests that the producing fungus could be an undetermined Kabatina species. Kabatina is a coelomycetous genus whose members are known to produce Hormonema-like states in culture.

Discovery of an angiotensin II binding inhibitor from a Cytospora sp. using semi-automated screening procedures.

Cytosporin A, B and C, three antagonists of [125I]-angiotensin II binding to rat adrenal glands were discovered in fermentations of an endophytic Cytospora sp. during routine screening using semi-automated procedures. The most potent of these displayed an IC50 of 1.5-3 microM and was specific for angiotensin II AT2.

Quinoxapeptins: novel chromodepsipeptide inhibitors of HIV-1 and HIV-2 reverse transcriptase. I. The producing organism and biological activity.

Quinoxapeptin A and B are novel chromodepsipeptides which were isolated from a nocardioform actinomycete with indeterminant morphology. Quinoxapeptins A and B are potent inhibitors of HIV-1 and HIV-2 reverse transcriptase and almost equally active against two single mutants forms as well as a double mutant form of HIV-1 reverse transcriptase. Quinoxapeptin A and B are specific inhibitors of HIV-1 and HIV-2 reverse transcriptase because they did not inhibit human DNA polymerase alpha, beta, gamma and delta. Quinoxapeptin A and B are structurally similar to luzopeptin A which was also active against HIV-1 and HIV-2 reverse transcriptase.

Nutritional preferences of a group of Streptosporangium soil isolates.

The nutritional preferences of twelve strains of genus Streptosporangium were studied as a first step in the design of production media to be used in a natural products screening program. The media ingredients included 20 alpha-amino acids, 35 carbon sources (monosaccharides, oligosaccharides, polysaccharides, polyalcohols and others), 22 complex sources (meals, peptones, yeast derivatives, etc.). The growth of these strains in the presence of these culture media ingredients and the production of inhibitory substances against Bacillus subtilis were analyzed in solid-phase cultures. The results show that the isolates studied did not exhibit a common trend in their preference of nutrient sources, either for to support their growth or the production of anti-B. subtilis substances.

Plasma protein binding of an N-pyrrolyl derivative penicillin in several mammalian species.

The extents of protein binding of an N-pyrrolyl derivative penicillin in plasma of different species were determined in vitro by the equilibrium dialysis technique and spectrophotometry determination. The percentage of binding was determined in cows, sheep, pigs and dogs. The percentage of drug that was protein bound was independent of drug concentration for this penicillin within the range studied (5 to 40 micrograms ml-1). The extent of binding was determined at 20 micrograms ml-1. There was a significant difference in the extent of penicillin binding between species (t test P less than 0.005) except for between cows and dogs (t test P less than 0.05) and sheep and pigs (where it was not significantly different). In the species studied the extent of penicillin binding ranged from 41 to 55 per cent.

The comparative stability of different types of penicillin and cephalosporin N-pyrryl derivatives.

The kinetics of the decomposition of potassium salts of 4-thia-1-azabicyclo[3.2.0.]heptane-3,3-dimethyl-6-amino-7-oxo-N- [2(1H-pyrrolyl)acetyl] -2-carboxylic acid (6R, trans), 4-thia-1-azabicyclo[3.2.0]heptane-3,3-dimethyl-6-amino-7-oxo-N-[2-phenyl - 2(1H-pyrrolyl)acetyl]-2-carboxylic acid (6R, trans), 5-thia-1-azabicyclo[4.2.0.]oct-2-ene-3- [(acetyloxy)methyl]-7-amino-8-oxo-N-[2(1H-pyrrolyl)acetyl]-2-ca rbo xylic acid (6R, trans), 5-thia-1-azabicyclo[4.2.0.]oct-2-ene-3- [(acetyloxy)methyl]-7-amino-8-oxo-N-[2-phenyl-2(1H-pyrrolyl)acetyl ]- 2-carboxylic acid (6R, trans), 5-thia-1-azabicyclo[4.2.0.]oct-2-ene-7-amino-3-methyl-8-oxo-N- [2(1H-pyrrolyl)-acetyl]-2-carboxylic acid (6R, trans) and 5-thia-1-azabicyclo[4.2.0.]oct-2-ene-7-amino-3-methyl-8-oxo- N-[2-phenyl-2(1H-pyrrolyl)acetyl]-2-carboxylic acid (6R, trans), in aqueous solution at 37 degrees C and at ionic strength of 0.5 mol.l-1 have been studied over the 2.3-11.5 pH range. In all cases, the hydrolysis of these compounds is subject to acid-base catalysis and, in some instances, to a general catalysis by various species present in the buffer solutions. The experimental results have been analyzed and discussed in relation to the hydrolytic mechanisms.

The discovery of moriniafungin, a novel sordarin derivative produced by Morinia pestalozzioides.

A novel sordarin derivative, moriniafungin (1), containing a 2-hydroxysebacic acid residue linked to C-3' of the sordarose residue of sordarin through a 1,3-dioxolan-4-one ring was isolated from the fungus Morinia pestalozzioides. Isolation of moriniafungin employed a highly specific bioassay consisting of a panel of Saccharomyces cerevisiae strains containing chimeric eEF2 for Candida glabrata, Candida krusei, Candida lusitaniae, Crytpococcus neoformans, and Aspergillus fumigatus as well as wild type and human eEF2. Moriniafungin exhibited an MIC of 6 microg/mL versus Candida albicans and IC(50)'s ranging from 0.9 to 70 microg/mL against a panel of clinically relevant Candida strains. Moriniafungin was shown to inhibit in vitro translation in the chimeric S. cerevisae strains at levels consistent with the observed IC(50). Moriniafungin has the broadest antifungal spectrum and most potent activity of any natural sordarin analog identified to date.