Hydroxyl radical generation by the tetracycline antibiotics with free radical damage to DNA, lipids and carbohydrate in the presence of iron and copper salts

Tetracycline antibiotics caused the degradation of carbohydrate in the presence of a ferric salt at pH 7.4. This degradation appeared to involve hydroxyl radicals since the damage was substantially reduced by the presence of catalase, superoxide dismutase, scavengers of the hydroxyl radical and metal chelators. Similarly, the tetracycline antibiotics in the presence of a ferric salt greatly stimulated the peroxidation of liposomal membranes. This damage, which did not implicate the hydroxyl radical, was significantly reduced by the addition of chain-breaking antioxidants and metal chelators. Only copper salts in the presence of tetracycline antibiotics, however, caused substantial damage to linear duplex DNA. Studies with inhibitors suggested that damage to DNA did involve hydroxyl radicals.     

Expression and characterization of human lamin C

We have expressed human lamin C cDNA in E. coli using a modification of the pLcII vector system. Protein produced in this way had seven additional amino acids at its N-terminus, but retained key lamin structural and assembly properties. The modified vector we produced may prove useful when difficulties are encountered in removal of the cII fusion peptide by factor X cleavage in the pLcII system. Shadowed preparations of expressed lamin C showed the presence of 50-nm rod-like particles that closely resembled those observed for native material. Isolated molecules had two globular domains at one end, indicating that they were constructed from two parallel polypeptide chains. The expressed material also formed paracrystals with a characteristic 22.5 nm axial repeat, indicating that its assembly properties had also been retained. We also used site-specific mutagenesis to engineer a lamin fragment that lacked the C-terminal non-helical domain of the molecule. This material formed paracrystals similar to those obtained with the intact molecule, indicating that the large C-terminal non-helical domain did not contain information vital for lamin assembly.     

Risk of Infection with Leishmania spp. in the Canine Population in the Netherlands

The dog is the main reservoir of Leishmania infantum, the causative agent of visceral leishmaniasis (VL) in humans in Southern Europe. In order to identify the risk of dogs from a Leishmania non-endemic area traveling to a Leishmania -endemic area becoming infected and the risk of transmitting infection to humans in non-endemic areas an investigation was performed, in which the results of a questionnaire were combined with the results of a serologic survey.     

Neuropeptide regulation of human dermal microvascular endothelial cell ICAM-1 expression and function

There isincreasing evidence that sensory nerves may participate in cutaneousinflammatory responses by the release of neuropeptides such assubstance P (SP). We examined the direct effect of SP on human dermalmicrovascular endothelial cell (HDMEC) intercellular adhesion molecule1 (ICAM-1) expression and function. Our results indicated that,although cultured HDMEC expressed mRNA for neurokinin receptors 1, 2, and 3 (NK-1R, NK-2R, and NK-3R), SP initiated a rapid increase in HDMECintracellular Ca²⁺ levels,primarily by the activation of NK-1R. Immunohistochemistry studieslikewise demonstrated that HDMEC predominantly expressed NK-1R. Theaddition of SP to HDMEC resulted in a rapid increase in cellular ICAM-1mRNA levels, followed by a fivefold increase in ICAM-1 cell surfaceexpression. This functionally resulted in a threefold increase in⁵¹Cr-labeled binding of J-Ylymphoblastoid cells to HDMEC. In vivo studies demonstrated a markedincrease in microvascular ICAM-1 immunostaining 24 and 48 h afterapplication of capsaicin to the skin. These results indicate thatneuropeptides such as SP are capable of directly activating HDMEC toexpress increased levels of functional ICAM-1 and further support therole of the cutaneous neurological system in modulating inflammatoryprocesses in the skin.

     

Clinical Evaluation of Perhexiline Maleate in Patients with Angina Pectoris

This paper reports a double-blind trial of a new antianginal drug, perhexiline. Fifty-five patients suffering from angina pectoris were studied for periods of 12 or 24 weeks in a cross-over comparison against a placebo in four centres in the United Kingdom and Ireland. Perhexiline was effective in most patients as judged by reducing the number of anginal attacks in 84% and the consumption of glyceryl trinitrate tablets in 64%. The major side effect, dizziness, noted in one-third of the patients, may be dose/body-weight related. Perhexiline is a valuable new agent for the treatment of patients with angina, especially those who do not respond to other antianginal agents.     

Modification of Pattern of Photosynthate Movement within and between Shoots of Vitis vinifera L

During the prebloom and bloom stages, no movement of labeled photosynthates occurred from a shoot of Vitis vinifera L. fed with ¹⁴CO₂, to an adjacent shoot on the same spur. Movement of labeled assimilates into the unfed shoot was induced when this shoot was sprayed with 2.89 × 10⁻³m gibberellic acid during the prebloom stage. During the bloom stage darkening or defoliation of the unfed shoot resulted in the import of labeled photosynthates from the adjacent fed shoot. Similarly, movement of ¹⁴C into an untreated shoot was induced by removing the terminal 7.5 centimeters and deblossoming the fed shoot. During the berry set stage, translocation of labeled photosynthates from a newly exporting leaf was upwards to the shoot tip, but the direction of movement was reversed by removal of the shoot tip or by darkening or removal of the leaves below the fed leaf. Translocation of photosynthates was predominantly basipetal from a fed leaf near the base of the shoot during the berry set stage, but upward movement was induced by darkening or defoliation of the upper part of the shoot.