Ergoline Derivatives as a Probe for Featuring the 5-HT1A Receptor Pharmacophore

A 5-HT_1A pharmacophore has been obtained employing a set of rigid templates encompassing the 5-HT1A structure. The use of rigid templates allowed us to overcome the discrepancy found when flexible structures where the energy of the active conformers are sometimes higher than the global minimum energy are used. On the basis of the results herein reported the three-dimensional requirements necessary for the binding interaction have been defined within this set of molecules. In this study forbidden zones of the receptor have been characterised. The pharmacophore model derived places some agonist/antagonist pharmacophore models appeared in the literature.     

Secreted gelsolin inhibits DNGR-1-dependent cross-presentation and cancer immunity

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Absorption of foliar applied Zn is decreased in Zn deficient sunflower (Helianthus annuus) due to changes in leaf properties

Plant and Soil - Arabidopsis thaliana is the model plant that is mainly used in studying cellulose and hemicellulose (CH) biosynthesis. Unfortunately, A. thaliana does not associate with mycorrhiza...     

Antitumor and antimetastatic effects of dacarbazine combined with cyclophosphamide and interleukin-2 in Lewis lung carcinoma (3LL)

The antitumor and antimetastatic activity of dacarbazine (DTIC) alone or in combination with cyclophosphamide (CY) was tested in C57BL/6 mice bearing Lewis lung carcinoma (3LL). Treatment with both agents significantly reduced tumor growth and the number of metastases. These effects were associated with marked changes of the biochemical and immunological properties of drug-treated 3LL cells, i.e. (a) reduction of 6 integrin expression, (b) increased susceptibility to natural immunity in vivo, as measured in terms of rapid clearance from mouse lungs of prelabeled 3LL cells injected i.v. and (c) increased immunogenicity, as assessed by T-cell-mediated immune responses (i.e. graft rejection by intact syngeneic mice, and frequency of specific CTL precursors recognizing DTIC/CY-treated cancer cells). The immunotherapeutic advantage afforded by increased immunosensitivity and immunogenicity of 3LL cells exposed to DTIC+CY appears to be markedly reduced in vivo by the profound immunodepressive effects of these drugs. Within this context, addition of interleukin-2 was found to increase the antitumor and antimetastatic activity of this chemotherapeutic regimen. The present study shows, for the first time in a solid tumor model, that a biological response modifier increases the antitumor efficacy of drugs that are able to affect the immunological properties of cancer cells.     

Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and Zidovudine (ZDV)

The efficiency of HIV-1 specific transfer factor (TF) administration, combined with Zidovudine (ZDV), in asymptomatic persistent generalised lymphadenopaty, or AIDS related complex (ARC) patients was evaluated. Twenty patients were randomly assigned to receive only ZDV (1st group) or ZDV together with HIV-1-specific TF (2nd group). HIV-1-specific TF was administered orally at 2 × 10⁷ cell equivalent daily for 15 days, and thereafter once a week for up to 6 months. There were no significant differences between the two groups in clinical evolution, red blood cells, haemoglobin, lymphocytes, CD20 subset, transaminases,β-2-microglobulin, p24 antigen. White blood cells, CD8 lymphocytes as well as IL-2 levels increased in the second group, while the CD4 subset increased in the first group. The combination treatment with ZDV and TF appeared to be safe and well tolerated. Furthermore, levels of serum cytokines were investigated in 10 patients (8 asymptomatic and 2 ARC) treated with ZDV, and compared with 5 patients of the 2nd group (3 asymptomatic and 2 ARC) treated with ZDV plus HIV-1-specific TF. Peripheral lymphocytes, CD4, CD8 subsets, IL-2, TNFα, IL-6, p24 antigen, IL-2 soluble lymphocyte receptors (sR), CD4sR, CD8sR and ß-2-microglobulin were evaluated at the baseline and at the 3rd month. The CD4 subset was not significantly different in the two groups, whilst IL-2 increased in the 2nd group receiving ZDV plus TF, suggesting an activation of the Th1 secretion pattern.     

Ragweed (Ambrosia) pollen presence in Livorno,Central Italy: Aerobiological and sensitization data

We have studied Ragweed pollen concentration in the atmosphere of Leghorn (Livorno). where Ragweed is not widespread. Our data, from 1991 to 1995, confirm the presence of Ragweed pollen in the atmosphere of Leghorn in low concentrations (highest value of 11 pollen grains/m³) from August to the end of September. Even if the sensitization level in our area is 6.76%, the clinical significance of Ragweed pollinosis is still very low.     

Regional-dependent increase of sympathetic innervation in rat white adipose tissue during prolonged fasting.

White adipose tissue (WAT) is innervated by the sympathetic nervous system. A role for WAT sympathetic noradrenergic nerves in lipid mobilization has been suggested. To gain insight into the involvement of nerve activity in the delipidation process, WAT nerves were investigated in rat retroperitoneal and epididymal depots after prolonged fasting. A significant increase in tyrosine hydroxylase (TH) content was found in epididymal and, especially, retroperitoneal WAT by Western blotting. Accordingly, an increased immunoreactivity for TH was detected by immunohistochemistry in epididymal and, especially, retroperitoneal vascular and parenchymal noradrenergic nerves. Neuropeptide Y (NPY)-containing nerves were found around arteries and in the parenchyma. Double-staining experiments and confocal microscopy showed that most perivascular and some parenchymal noradrenergic nerves also contained NPY. Detection of protein gene product (PGP) 9.5, a general marker of peripheral nerves, by Western blotting and PGP 9.5-TH by double-staining experiments showed significantly increased noradrenergic nerve density in fasted retroperitoneal, but not epididymal depots, suggesting that formation of new nerves takes place in retroperitoneal WAT in fasting conditions. On the whole, these data confirm the important role of sympathetic noradrenergic nerves in WAT lipid mobilization during fasting but also raise questions about the physiological role of regional-dependent nerve adjustments and their functional significance in relation to white adipocyte secretory products.