Characterization of membrane melatonin receptor in mouse peritoneal macrophages: inhibition of adenylyl cyclase by a pertussis toxin-sensitive G protein

Melatonin binding sites were characterized in mouse peritoneal macrophages. Binding of 2-[125I]melatonin by macrophages fulfills all criteria for binding to a receptor site. Thus, binding was dependent on time, temperature and cell concentration, stable, reversible, saturable and specific. Stoichiometric studies showed a high-affinity binding site with a Kd of 0.58-0.71 nM. These data are in close agreement with data obtained from kinetic studies (Kd = 0.29 nM). The affinity of these binding sites suggests that they may recognize the physiological concentrations of melatonin in serum. Moreover, binding experiments using macrophage crude membranes showed that melatonin bound specifically to the membranes. Additionally, in competition studies we observed a low-affinity binding site (Kd = 2.02 microM). Melatonin inhibited significantly forskolin-stimulated cyclic AMP accumulation in a dose-dependent manner. This effect was blocked by luzindole, an antagonist of the melatonin membrane receptor. Pretreatment of macrophages with pertussis toxin blocked the inhibitory effect of melatonin. Pertussis toxin ADP-rybosilation and Western blot experiments demonstrated both alpha(i1/2) and alpha(i3/o) G protein subunits expression in mouse peritoneal macrophages membranes. Our results demonstrate the existence of melatonin receptors in mouse peritoneal macrophages, and a pertussis toxin-sensitive melatonin signal transduction pathway that involves the inhibition of adenylyl cyclase.     

Organochlorine residues in tissues of striped dolphins affected by the 1990 mediterranean epizootic: Relationships with the fatty acid composition

A simple and rapid method was developed for the simultaneous determination of fatty acids, organochlorine pesticides, and polychlorinated biphenyl (PCB) congeners in the same sample in order to explore possible connections between levels of contaminants and fatty acid composition. The method was applied to samples of melon, cerebrum, cerebellum, lung, liver, kidneys, and skeletal muscle obtained from 5 male and 5 female striped dolphins (Stenella coeruleoalba) found stranded in 1990 in the northeastern Spanish coasts during the morbillivirus epizootic that affected this cetacean in the Mediterranean Sea. The results indicate that PCBs were dominant in all tissues, with the highest geometric mean concentration being found in melon (903 g g^–1 wet wt); DDTs were also found at high concentrations (111 g g^–1 wet wt, in melon). Statistical analysis indicate that organochlorine concentration was correlated with the fatty acid composition of tissues, although some of these variations can be interpreted as a consequence of a shift in the diet produced in the striped dolphin population. However, other changes such as the negative correlation with arachidonic acid may suggest that the eicosanoid production could have been affected by the extremely high concentrations of PCBs and DDTs.     

Documenting the provision of pharmaceutical care

There is a growing importance and need for the documentation of the clinical work done by the pharmacist in providing pharmaceutical care. The data provided by documentation of care are critical to the effective and efficient transition from a product-based profession to a patient-care, service-based profession, especially during a period of great scrutiny of resource utilization in the hospital industry. Intervention documentation can serve both to document the provision of pharmaceutical care to individual patients and to provide critical information to managers to justify and expand the level of service provided.     

Intravesical oxybutynin: practicalities of clinical use.

Oral anticholinergic therapy, used for the treatment of detrusor overactivity (DO), is limited by systemic side-effects and because of failure to respond. Alternative routes of administration include the intravesical route. We reviewed 11 women who were treated with intravesical oxybutynin (IVO). All had idiopathic DO, their symptoms having been unsuccessfully controlled on oral agents. Seven patients had symptomatic improvement. Six out of the eight patients that completed their voiding diaries showed a reduction in voiding frequency. Five patients found the procedure too inconvenient. Seven patients suffered chemical irritation. One patient complained of voiding difficulties. No patient reported systemic side-effects. The mean duration of treatment was 4-5 weeks; two patients continue to use IVO. IVO can be used successfully in the treatment of DO, but its use is limited due to the inconvenience related to catheterisation. With the advent of Botox and oxybutynin patches, IVO probably has a limited role.