1. Increasing evidence indicates the occurrence of functional interconnections between immune and nervous systems, although data available on the mechanisms of this bi-directional cross-talking are frequently incomplete and not always focussed on their relevance for neuroimmune modulation. 2. Primary (bone marrow and thymus) and secondary (spleen and lymph nodes) lymphoid organs are supplied with an autonomic (mainly sympathetic) efferent innervation and with an afferent sensory innervation. Anatomical studies have revealed origin, pattern of distribution and targets of nerve fibre populations supplying lymphoid organs. 3. Classic (catecholamines and acetylcholine) and peptide transmitters of neural and non-neural origin are released in the lymphoid microenvironment and contribute to neuroimmune modulation. Neuropeptide Y, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide represent the neuropeptides most involved in neuroimmune modulation. 4. Immune cells and immune organs express specific receptors for (neuro)transmitters. These receptors have been shown to respond in vivo and/or in vitro to the neural substances and their manipulation can alter immune responses. Changes in immune function can also influence the distribution of nerves and the expression of neural receptors in lymphoid organs. 5. Data on different populations of nerve fibres supplying immune organs and their role in providing a link between nervous and immune systems are reviewed. Anatomical connections between nervous and immune systems represent the structural support of the complex network of immune responses. A detailed knowledge of interactions between nervous and immune systems may represent an important basis for the development of strategies for treating pathologies in which altered neuroimmune cross-talking may be involved.

This study has investigated, under controlled conditions, peripheral mononuclear cells (PMNC) subset redistribution in a human experimental stress model consisting of cycloergometer activity in healthy male volunteers exposed to a stressful stimulus. After stressful stimuli, leucocyte subpopulations undergo a stereotyped redistribution peculiar for each PMNC cytotype. PMNC subpopulations involved to a greater extent were natural killer (NK) cells and lymphocytes T "memory" cells. The post-stress period was characterized by a decrease of the NK subpopulation. Our findings confirm the view of a sensible functional reduction of immunocompetence in stress conditions. This brings to the opening, even if for a short time, an "immunological window." This window remains open throughout the time of the stimulus, probably representing the basis of the progressive reduction of the competency of immune system. Catecholamines support the acute effects of stress influencing the anatomical redistribution of lymphocyte subpopulation and intermediating acute effects on PMNC. Cortisol, acting for longer time, contributes to create and maintain both the neutrocytosis and lymphopenia in the post-stress period following lymphocytosis.

No abstract

Lovastatin is a lipid-lowering agent indicated for primary hypercholesterolemia. This study has assessed single-dosing pharmacokinetics of lovastatin and of its main metabolite, lovastatin beta-hydroxyacid, and has compared the pharmacokinetics of two formulations of lovastatin, a test lovastatin generic (LVSG), and a reference (mevinacor 40 MSD) preparation. The pharmacokinetics and bioequivalence of the two formulations of lovastatin were evaluated by a two-way cross-over randomized double blinded study, in 36 healthy volunteers after a single oral dose of 2 x 40 mg per subject. On plasma samples, collected at given intervals of time (0-24h), lovastatin and its main active metabolite were assayed by high pressure liquid chromatography with positive turbo ion spray ionization tandem mass spectrometry detection. The pharmacokinetic parameters, area under the curve total (AUC(t)) and to infinity (AUC(inf)), peak plasma concentration (C(max)), time to attain peak (t(max)), and elimination half-life (t(1/2)) were determined and analyzed statistically. Only minor differences in the pharmacokinetics of lovastatin and lovastatin hydroxyacid between LVSG and mevinacor were found. Analysis of variance (ANOVA) did not show any significant difference between the two formulations, and 90% confidence intervals fell within the acceptable range for bioequivalence. The tolerability profile was good and comparable for the two formulations of lovastatin. Our study, which was performed with the largest number of subjects compared with those published in literature, indicates the bioequivalence of LVSG and mevinacor tablets. The high inter-subject variability of parameters investigated indicate the need of appropriate sample size in pharmacokinetics studies with lovastatin.

The bioequivalence of a solution (investigational product) and a tablet (reference product) formulation of the dihydropyridine-type derivative Ca2+ antagonist nicardipine were investigated by measuring plasma levels of the compound after single randomized administration of 20 mg of the two formulations. Drugs were given orally in a single dose to 24 healthy volunteers (12 males and 12 females) at the beginning of the experiment and after a two weeks wash-out. Nicardipine is available in oral and intravenous formulations, the second being used for the short-term treatment of hypertensive crises. Oral formulations of nicardipine most diffused include immediate release (20 or 30 mg, three times a day administration), sustained release (30 mg, 45 mg or 60 mg, twice a day administration) and modified release (80 mg, once a day administration) tablets. A nicardipine solution is available only in Spain, but no published studies on the kinetics of this formulation are available. In the last 15 years, the main efforts were aimed to develop sustained or controlled release formulations of nicardipine to improve patient compliance by reducing the number of doses required each day. However, the use of twice a day or once a day administration of Ca2+ antagonists should be not overemphasized in particular situations like those of possible risk of cerebrovascular and/or coronary steal effect primarily in the elderly. The oral formulation of nicardipine investigated with a bioequivalence range > 70% compared to nicardipine immediate release tablets may represent an additional resource for treating elderly patients with concomitant cerebrovascular or coronary heart disease.