The developmentally regulated neural crest-associated glycotope HNK-1 predicts metastasis in cutaneous malignant melanoma

Aberrant glycosylation is a common feature of metastatic sub-clones of malignant tumours and in uveal melanoma in particular, the HNK-1 glycotope has been positively correlated with poor prognosis. So far, no such correlation has been investigated in cutaneous melanoma. In order to do so, HNK-1 expression was evaluated immunohistochemically in 100 primary cutaneous melanomas and correlated with metastasis after up to 10-years' follow-up. Furthermore, HNK-1 expression was analysed in metastatic deposits (19 distant cutaneous metastases and six sentinel lymph node metastases), as well as in benign nevi. Kaplan-Meier analysis revealed a positive association between HNK-1 expression and metastasis (p < 0.005) and multivariate Cox regression analysis adjusted for the standard prognostic markers ulceration and vertical tumour thickness confirmed HNK-1 expression as an independent prognostic marker. HNK-1 expression was preserved in 42% of the distant cutaneous metastases, but metastatic cells in lymph nodes were devoid of HNK-1 immunoreactivity. None of the benign pigmented lesions exhibited HNK-1 immunoreactivity. Expression of the HNK-1 glycotope in cutaneous malignant melanoma is an independent prognostic marker of metastasis. Differential HNK-1 expression at the metastatic sites implies that its expression is modulated by the surrounding environment. As HNK-1 is also transiently expressed during migration of melanocyte precursor cells derived from the neural crest, recapitulation of this transient expression might occur during metastatic spread of cutaneous malignant melanoma.     

Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex

Although loss of cholinergic neurons in the basal forebrain is considered a key initial feature in Alzheimer's disease (AD), changes in other transmitter systems, including serotonin and 5-HT_2A receptors, are also associated with early AD. The aim of this study was to investigate whether elimination of the cholinergic neurons in the basal forebrain directly affects 5-HT_2A receptor levels. For this purpose intraventricular injection of the selective immunotoxin 192 IgG-Saporin was given to rats in doses of either 2.5 or 5 μg. The rats were sacrificed after 1, 2, 4 and 20 weeks. 5-HT_2A protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT_2A receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 IgG-Saporin. Our results show that cholinergic deafferentation leads to decreased frontal cortex and increased hippocampal 5-HT_2A receptor levels. This is probably a consequence of the interaction between the serotonergic and the cholinergic system that may vary depending on the brain region.     

Chemoselective synthesis of multifunctional ferrocene-containing derivatives by the cross Rauhut–Currier reaction

A simple protocol has been developed for the chemoselective synthesis of ferrocene-containing Rauhut–Currier adducts from 1-ferrocenyl-2-nitroethene and vinyl ketones using 20 mol% of triphenylphosphine. Multifunctional ferrocene derivatives were obtained in moderate to high yields (51–92%) by the coupling between the α-position of vinyl ketones and the β-position of the nitroalkene. The study of the Rauhut–Currier reaction under the described conditions showed that the strong electron-donating group at the β-position of nitroalkenes plays a significant role in the reaction outcome due to prevention of polymerization and stabilization of the zwitterionic intermediate. Additionally, a preparative synthesis of 4-ferrocenyl-3-methylene-5-nitropentan-2-one was carried out and its synthetic transformations showed easy conversion to other useful building blocks.

A simple method has been developed for the chemoselective synthesis of ferrocene-containing Rauhut–Currier adducts from 1-ferrocenyl-2-nitroethene and vinyl ketones catalyzed by triphenylphosphine.     

The Churg-Strauss syndrome

Churg-Strauss syndrome (CSS) is medium blood vessels vasculitis with predilection for lungs in patients with bronchial asthma, chronic eosinophilic pneumonia and positive ANCA in the sera in 55-67%. This is a case report of a 60 years old female patient with bronchial asthma, peripherial pulmonary infiltrations, blood eosinophilia, xerophtalmia, tachycardia, chronic rhinosinustis, polyneuropathia and negative imunological tests: CIC (PEG), CRYO, ANA (IIF), RF (aglutination) and ANCA (IFF: pANCA and cANCA; ELISA: proteinase 3, lactoferrin, myeloperoxidase. elastase, cathepsin G). Eosinophilic infiltrates in the tissues tested by skin and salivery gland biopsies were not found. The patient had fulfilled five clinical diagnostic criteria and responded well to imunosuppressive therapy, so this case could be classified as the ANCA negative angiitis and granulomatosis of CSS type.     

Synthesis of some basic 3-(1-acylaminobenzyl)-2H-1-benzopyran-2-ones

The reaction of 3-(1-propanoyloxybenzyl)-2H-1-benzopyran-2-one (2) with the nitriles of 4-dimethylaminobenzoic, 4-diethylaminobenzoic, nicotinic, isonicotinic, and 3-dimethylaminopropionic acid in conc. H₂SO₄ yields the amides 3a-e. 3a-d were converted into hydrochlorides.     

Prevention of tension type headache with topiramate

AIM: The aim of this study was to assess the efficacy of topiramate in the prevention of tension type headache. Tension type headache is the most common primary headache; the 1-year prevalence is 38%. Tension type headache often causes reduced quality of life. SUBJECTS AND METHODS: In this study 51 patients were included; the dose of topiramate was gradually increased to 100 mg and patients were followed up for 6 months. The number of days and decrease in headache intensity were measured by the Visual Analog Scale (VAS) from 1 to 10 before and with therapy. RESULTS: Study results showed a statistically significant decrease in the number of days with headache: the mean number of days before therapy was 13.25 and with therapy 8.65, (p=0,0001). A statistically significant decrease in headache intensity was also observed by VAS scale: before therapy 6.27 and with therapy 3.33 (p=0.0001). CONCLUSION: This study showed topiramate to be efficient in the prevention of tension type headache.     

Posttraumatic stress and alcohol use coping motives among a trauma-exposed community sample: the mediating role of non-judgmental acceptance

The current investigation evaluated (1) the incremental predictive validity of non-judgmental acceptance in terms of alcohol use coping motives and (2) the mediating role of non-judgmental acceptance in the association between posttraumatic stress symptom severity and alcohol use coping motives. Participants included 153 (79 women) adults who reported exposure to at least one DSM-IV PTSD Criterion A traumatic life event and alcohol use in the past month. Non-judgmental acceptance emerged as a significant incremental predictor of alcohol use coping motives. Furthermore, non-judgmental acceptance partially mediated the association between posttraumatic stress symptom severity and alcohol use coping motives. Theoretical and clinical implications of the findings are discussed with regard to better understanding the co-occurrence of posttraumatic stress and alcohol use disorders.     

Marijuana use motives: A confirmatory test and evaluation among young adult marijuana users

The present investigation evaluated the measurement model and construct validity of marijuana use motives as measured by the Marijuana Motives Measure (MMM; [Simons, J., Correia, C. J., Carey, K. B., and Borsari, B. E. (1998). Validating a five-factor marijuana motives measure: Relations with use, problems, and alcohol motives. Journal of Counseling Psychology, 45, 265-273]). Confirmatory factor analysis (CFA) and incremental tests of validity of marijuana use motives were conducted on a sample of young adult marijuana users (n=227, 127 women; M(age)=20.11, SD=4.30 years). As hypothesized, CFA analysis of marijuana use motives, as indexed by the MMM, demonstrated support for a multidimensional measurement model; specifically, a five-factor solution denoting Enhancement, Conformity, Expansion, Coping, and Social motives for marijuana use, each with satisfactory levels of internal consistency. Subsequent tests of incremental validity suggested that only certain motives were uniquely related to current substance use and cognitive-affective factors. Results are discussed in relation to refining the scientific understanding of marijuana use motives.     

Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro

Although aqueous mistletoe extracts are widely used in complementary cancer therapy, the precise mode of action of their main therapeutic agents, the three mistletoe lectins (MLs), is poorly understood as they act both as cytotoxic agents and as immunomodulators due to their cytokine release by mononuclear cells. Thus, this study aims to investigate both the direct and the indirect effects of MLs on the growth of human melanoma cells in vitro. Proliferation of six human melanoma cell lines under ML treatment and additionally under the influence of cytokines induced by them (TNF-alpha, IL-1, IL-6) was assessed by means of the tetrazolium derived reduction (XTT) assay. Furthermore, ML binding patterns were analysed and correlated with the biological effects. All three MLs inhibited melanoma cell proliferation in a dose-dependent manner starting at very low ML concentrations (0.001-100 ng/ml) with ML-I being the most cytotoxic lectin (significant inhibition of ultra-sensitive cell line MV3 at 1 x 10(-13) ng ML-I/ml). Even if applied in a broad concentration range (0.0001-100 ng/ml) cytokines had no influence on cell proliferation at all. For ML-I, no association between binding intensity and cytotoxicity was observed, while for ML-II and -III an association between binding and toxicity was established. In conclusion, this study emphasises the direct anti-proliferative effect of the mistletoe lectins on melanoma cells with ML-I being superior to MLs-II and -III. The observation of an ultra-sensitivity of one cell line towards ML-I toxicity may serve as an explanation for the therapeutic success in anecdotal case reports and needs further investigations.