Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.     

Lecithin vesicles for topical delivery of diclofenac.

Skin penetration of topically applied diclofenac is important for the treatment of rheumatic diseases and actinic keratoses. We have studied the permeation of diclofenac across human cadaver epidermis in-vitro from four lecithin vesicle formulations and a few marketed semi-solid preparations. The lecithin vesicle formulations were prepared by dissolving the lipid contents (lecithin and sodium cholate) in a 1:1 mixture of methanol-chloroform, evaporating the solvents under vacuum, and hydrating the lipid layer with the drug solution in water or 10% ethanol. The vesicles were sonicated for 5 min to reduce the vesicle size and their size and Zeta potential were characterized. The cumulative amount and maximum flux of diclofenac was 69.7+/-40.3 micrograms and 4.77+/-3.16 micrograms/hcm(2) from lecithin vesicles containing sodium cholate and 10% ethanol, and is the highest of all formulations studied. The cumulative amount and mean maximum flux obtained from other formulations were in the range of 2.46+/-1.98-29.9+/-10.1 micrograms and 0.53+/-0.46-3.61+/-0.86 micrograms/hcm(2). Based on the results, lecithin vesicles of diclofenac appear to be advantageous for the topical delivery of diclofenac.     

Reizhusten, Belastungsdyspnoe und zystische Lungenveränderungen bei einem 28jährigen Patienten

Zusammenfassung Eine neu aufgetretene Dyspnoesymptomatik und eine symmetrische, apikal betonte retikulonodul?re Zeichnungsvermehrung im R?ntgen-Thorax bei jungen rauchenden Erwachsenen müssen an das seltene Krankheitsbild der pulmonalen Histiocytosis X denken lassen. Klinischer Befund, laborchemische- und Lungenfunktionsuntersuchungen zeigen unspezifische Befunde. Neue radiologische Verfahren wie die hochaufl?sende Computertomographie (HRCT) leisten bei gezielter Indikationsstellung eine entscheidende differentialdiagnostische Hilfestellung. Dieser Fall verdeutlicht die M?glichkeit einer Diagnosesicherung durch transbronchiale Biopsien unter Verzicht auf offene Lungenbiopsien. Eine ambulante Diagnostik war m?glich, das h?here Risiko eines operativen Eingriffes konnte vermieden werden. Die Indikation zur Therapie ist nicht gesichert und wird daher durch den Grad der subjektiven bzw. funktionellen Einschr?nkung sowie den Verlauf bestimmt.     

A preliminary study of the changes in the direct-acting mutagenicities of several nitropolycyclic aromatic hydrocarbons after exposure under sunlight

Five commercially available nitropolyclyclic aromatic hydrocarbons (nitro-PAH), namely, 4-nitrobiphenyl, 2-nitrofluorene, 9-nitroanthracene, 1-nitropyrene, and 2,7-dinitrofluorene, were exposed under restricted sunlight in the open air. The direct-acting mutagenicities of the samples after an exposure of 45 days were measured in order to compare them with those of the original samples in the Ames Salmonella typhimurium bioassay. It was found that the mutagenicities of some nitro-PAH do not change significantly while the mutagenicities of others increase or decrease after exposure. A preliminary study of nitro-PAH reaction products after exposure using GC, GC/MS, and FT-IR is also reported.     

Hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness

The hereditary characteristics of enzyme deficiency and dermatoglyphics in congenital color blindness (CCB) were studied. We propose that there is a linkage between the two loci on the X-chromosome determining CCB and glucose-6-phosphate dehydrogenase (G6PD), based on our study of a high incidence of G6PD deficiency in 156 male cases with CCB. The CCB gene is closely linked with that of G6PD deficiency from our pedigree investigations. The rise in the frequency of eight or more whorls, the low value of atd angle and the presenting rate of real palmar patterns of the thenar, hypothenar and I, areas presented the hereditary traits of congenital color blindness.     

Electro-oculogram of Retinal Vein Occlusion

Twenty five cases, including 26 eyes with retinal vein occlusion (RVO) were examined by means of the electro-oculogram. The results showed that 23 of the 26 eyes suffering from RVO exhibited abnormalities of the electro-oculogram (EOG). The potential difference and Arden ratio in the RVO eyes were lower than those in the normal eyes (P<0.01). The more the visual acuity of ill eyes was decreased, the higher the abnormal rate of EOG in ill eyes was. 14 eyes had the visual acuity less than 0.1, whose EOGs were abnortmal. Six eyes had the visual acuity from 0. 2 to 0. 4, in which the EOGs of 5 eyes were abnormal. Six eyes had the visual acuity more than 0. 5, a-mong which the EOGs of 4 eyes were abnormal. Based on the above observations, it may be considered that the circulatory disturbance resulting from RVO damages not only the internal layer but also the external layer of the retina. We suggest that EOG is a useful method for distingquishing lesions caused by RVO and may reflect the functional condition