PubMed · 8299469
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C D Saudek. 1993. Future developments in insulin delivery systems.. https://doi.org/10.2337/diacare.16.3.122
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The purpose of this study was to examine the effect of intranasal salmon calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or evening (21:00), on the known circadian variation in biochemical markers of bone turnover. An open, placebo-controlled, randomized, crossover study, with three 24 h studies of blood samples drawn every third hour and urine collected in 3 h aliquots was undertaken. Subjects consisted of nine healthy postmenopausal women, aged 58 +/- 7 years. Urinary CrossLaps (a measure of bone resorption) was measured by ELISA and corrected for creatinine (Cr). Serum osteocalcin (sOC) was measured by radioimmunoassay (RIA). The first 24 h study was performed without intervention. Prior to this control study the participants were randomized to either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were given 4-5 days prior to and during the second study. After a washing-out period of 2 weeks the participants were given 200 IE of sCT at the reverse time of the day 5 days prior to and during the third study. At all timepoints, urinary CrossLaps/Cr exhibited a significant (p < 0.001) circadian rhythm with its zenith in early morning and nadir in late afternoon. Both morning and evening administration of sCT significantly decreased the urinary excretion of CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound effect. sOC did not exhibit a significant circadian variation and was not affected by the calcitonin. The 24 h mean urinary CrossLaps/Cr and sOC remained unchanged. Both morning and evening sCT significantly decreased the urinary excretion of CrossLaps/Cr 3-6 h after administration, with a rebound effect approximately 12 h later. However, the present study does not indicate that neither evening nor twice-daily administration is superior to morning administration.
The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study, the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug L-DOPA were analyzed. By using in vivo microdialysis in the urethane-anesthetized rat, it was found that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore, intranasal administration of L-DOPA, but not of the saline vehicle, also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal L-DOPA on neostriatal dopamine was observed only ipsilaterally but not contralaterally to the side of intranasal drug administration, it can be hypothesized that L-DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse, but may also be useful to target the brain therapeutically, as in the case of neurodegenerative brain disorders.
Mechanisms of protection of mice from Sendai virus, which is exclusively pneumotropic and causes a typical respiratory disease, by immunization with recombinant vaccinia viruses (RVVs) were investigated. Although the RVV carrying a hemagglutinin-neuraminidase gene of Sendai virus (Vac-HN) propagated in the noses and lungs of mice by either intranasal (i.n.) or intraperitoneal (i.p.) inoculation, no vaccinia virus antigens were detected in the mucosal layer of upper and lower airways of the i.p.-inoculated mice. The mice immunized i.n. with Vac-HN or Vac-F (the RVV carrying a fusion protein gene of Sendai virus) demonstrated the strong resistance to Sendai virus challenge both in the lung and in the nose, whereas the i.p.-immunized mice showed almost no resistance in the nose but showed a partial resistance in the lung. Titration of Sendai virus-specific antibodies in the nasal wash (NW), bronchoalveolar lavage (BAL), and serum collected from the Vac-F-immunized mice showed that the NW from the i.n.-immunized mice contained immunoglobulin A (IgA) antibodies but no IgG and the BAL from the mice contained both IgA and IgG antibodies. On the other hand, neither IgA nor IgG antibodies were detected in the NW from the i.p.-immunized mice and only IgG antibodies were detected in the BAL, although both i.n.- and i.p.-immunized mice exhibited similar levels of serum IgG, IgA, and neutralizing antibodies. The resistance to Sendai virus in the noses of i.n.-immunized mice could be abrogated by the intranasal instillation of anti-mouse IgA but not of anti-IgG antiserum, while the resistance in the lung was not significantly abrogated by such treatments. These results demonstrate that IgA is a major mediator for the immunity against Sendai virus induced by the RVVs and IgG is a supplementary one, especially in the lung, and that the RVV should be intranasally inoculated to induce an efficient mucosal immunity even if it has a pantropic nature.