Chronic ulcerative stomatitis

Chronic ulcerative stomatitis (CUS) has recently been described as a new disease entity characterized by chronic ulceration of oral mucosa which responds to treatment with hydroxychloroquine. It has a particular type of stratified epithelium-specific, antinuclear autoantibody as an immunological marker. Twelve cases have been reported in the literature. We present a 40-year-old woman with an 11-year history of chronic oral ulcerations. Other dermatological diseases, including oral lichen planus, pemphigus vulgaris and cicatricial pemphigoid, as well as bullous lupus erythematosus, were excluded. The clinical diagnosis of CUS was confirmed on the grounds of the immunological and ultrastructural findings. The lesions initially responded to high doses of systemic corticosteroids but relapsed promptly after dose reduction. Dapsone was ineffective. Hydroxychloroquine, given at a dosage of 200-400 mg/day, led to a complete and long-lasting remission.     

Actinomycin D, C2 and VII, inhibitors of Grb2-SHC interaction produced by Streptomyces

Actinomycin D, C2 and VII, cyclic peptides, inhibited Grb2 SH2 domain association (IC50 5-7 microM) with a phosphotyrosine containing peptide derived from the Shc protein (pTyr317). Actinomycins are the first examples of nonphosphorylated natural ligands of SH2 domain.     

Stereotactic transcranial magnetic stimulation: correlation with direct electrical cortical stimulation

OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning.     

Chemical sulfonation and anticoagulant activity of acharan sulfate

Acharan sulfate is a glycosaminoglycan prepared from the giant African snail, Achatina fulica. This polysaccharide has a repeating disaccharide structure of -->4)-2-deoxy-2-acetamido-alpha-D-glucopyranose (1-->4)-2-sulfo-alpha-L-idopyranosyluronic acid (1-->). Its structure is related to heparin and heparan sulfate but is distinctly different from all known members of these classes of glycosaminoglycans. Because of its structural similarities to heparin, chemically modified acharan sulfate was studied to understand the chemical structure effected its anticoagulant activity. After de-N-acetylation, acharan sulfate was N-sulfonated using either chlorosulfonic acid-pyridine or sulfur trioxide-trimethylamine complex. The sulfate level in these products ranged from 22 to 24%(w/w), significantly less than that of heparin at 36%. The molecular weight of both N-sulfoacharan sulfates were comparable with that of heparin. In vitro anticoagulant activity assays showed that N-sulfoacharan sulfate derivatives were moderately active for the inhibition of thrombin and neither product showed any measurable anti-factor Xa activity. The differences in the activities of N-sulfoacharan sulfates produced by these two methods are probably ascribable to a small level of concomitant O-sulfonation obtained when using chlorosulfonic acid-pyridine.     

Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system

Vascular endothelial growth factor (VEGF) and its tyrosine kinase receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR) are key mediators of physiological and pathological angiogenesis. They are expressed in most tissues during embryonic development but are down-regulated in the adult, when angiogenesis ceases. Up-regulation of VEGFR-2 and of VEGF are observed in many pathological conditions under which angiogenesis is reinduced. A major regulator of VEGF expression is hypoxia. Although the temporal expression pattern of VEGFR-2 parallels VEGF expression to a high extent, little is known about its regulation. Here, we show that VEGFR-2 is highly expressed in early postnatal mouse brain but is down-regulated commencing at postnatal day 15 (P15) of mouse brain development and is hardly detectable in P30 mouse brain. Using P30 mouse brain slices, we observed that hypoxia up-regulates VEGFR-2 in the slices but not in human umbilical vein endothelial cells, suggesting the presence of a hypoxia-inducible factor in the murine neuroectoderm that up-regulates VEGFR-2. To identify the factors involved, normoxic P30 cerebral slices were cultured with growth factors that are either hypoxia-inducible (e.g., PDGF-BB, erythropoietin, and VEGF) and/or are known to act on endothelial cells (e.g., PDGF-BB, VEGF, and PIGF). Exogenously added recombinant VEGF led to an up-regulation of VEGFR-2 expression, which could be inhibited by preincubation with a neutralizing anti-VEGF antibody. Addition of PDGF-BB, PIGF, and erythropoietin had no effect on VEGFR-2 expression. Our results suggest a differential but synergistic regulation by hypoxia of VEGF and VEGFR-2: a direct induction of VEGF that subsequently up-regulates VEGFR-2 in endothelial cells. This autoenhancing system may represent an important mechanism of tumor angiogenesis.     

Anti asialoglycoprotein receptor antibodies and soluble interleukin-2 receptor levels as marker for inflammation in autoimmune hepatitis

Previous results using an amphibian model showed that systemic and spinal administration of opioids selective for mu, delta and kappa-opioid receptors produce analgesia. It is not known whether non-mammalian vertebrates also contain supraspinal sites mediating opioid analgesia. Thus, opioid agonists selective for mu (morphine; fentanyl), delta (DADLE, [D-Ala2, D-Leu5]-enkephalin; DPDPE, [D-Pen2, D-Pen5]-enkephalin) and kappa (U50488, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methanesulfonate; CI977, (5R)-(544alpha,744alpha,845beta)-N-methyl-N-[7-(1-p yrr olidinyl)-1-oxaspiro[4,5]dec-8yl]-4-benzofuranaceta mide++ + monohydrochloride) opioid receptors were tested for analgesia following i.c.v. administration in the Northern grass frog, Rana pipiens. Morphine, administered at 0.3, 1, 3 and 10 nmol/frog, produced a dose-dependent and long-lasting analgesic effect. Concurrent naltrexone (10 nmol) significantly blocked analgesia produced by i.c.v. morphine (10 nmol). ED50 values for the six opioids ranged from 2.0 for morphine to 63.9 nmol for U50488. The rank order of analgesic potency was morphine > DADLE > DPDPE > CI977 > fentanyl > U50488. These results show that supraspinal sites mediate opioid analgesia in amphibians and suggest that mechanisms of supraspinal opioid analgesia may be common to all vertebrates.     

Folate intake in Europe: recommended, actual and desired intake

OBJECTIVES: To evaluate possible inconsistencies between recommended, actual and desired folate intake in European adult populations. DESIGN: Review of dietary recommendations, of food consumption surveys, and of intervention and observational studies relating folate intake to the risk of neural tube defects and plasma homocysteine levels. RESULTS: In Europe, mean dietary folate intake in adults is 291 micrograms/d (range 197-326) for men and 247 micrograms/d (range 168-320) for women. The recommended intakes vary between 200-300 micrograms/d (men) and 170-300 micrograms/d (women). However, women with a previous pregnancy affected by a neural tube defect (NTD), are recommended to take 4000 micrograms/d of supplemental folic acid when planning a subsequent pregnancy. For those without a history of NTD, the use of 400 micrograms/d of supplemental folic acid is the best option to prevent the occurrence of NTDs. A daily dose of 650 micrograms supplemental folic acid normalises elevated plasma homocysteine levels, which is a risk factor for cardiovascular diseases. A dietary folate intake of at least 350 micrograms/d is desired to prevent an increase in plasma homocysteine levels of the adult population in general. CONCLUSIONS: Mean dietary folate intake in Europe is in line with recommendations, but the desired dietary intake of > 350 micrograms/d is only reached by a small part of studied European populations. It is considered unethical to investigate whether supplements with a dose lower than 400 micrograms/d of folic acid are also protective against NTDs. However, research to establish the lowest effective dose of dietary folate/supplemental folic acid to optimise homocysteine levels and research on the bioavailability of folate is required. This will enable the choice of a strategy to achieve desired folate intakes in the general population. In the meantime, consumption of plant foods like vegetables, fruits, and cereals should be stimulated to reach the desired level of 350 micrograms of dietary folate per day.