Gender differences in response to intranasal cocaine administration to humans.
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Administration, Intranasal↗
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Repeated intranasal cocaine administration: lack of tolerance to pressor effects.
Three healthy adult male volunteers were allowed to self-administer 96 mg or 4 mg (a dose without measurable effects) of inhaled cocaine approximately once every 35 min during experimental sessions lasting up to 6 h. Heart rate (HR), blood pressure and self-report of drug effects were measured. After inhaling, on average, four doses of 4 mg, subjects voluntarily ended the session. Five out of the six sessions of 96 mg cocaine availability, however, were terminated due to consistent elevated diastolic blood pressure (DP), rather than by subject request. During 96 mg sessions, HR and self-report data either rapidly reached an asymptote or showed a slow rate of increase. Blood pressure, on the other hand, increased throughout the session, generally to the point where the session had to be terminated. These findings suggest the possibility that the rate of development of tolerance to the effects of cocaine may vary as a function of the dependent variable. In addition, the consistent increase in pressor effects may well be a mechanism for the increased cardiovascular toxicity reported for cocaine abusers.
Administration, Intranasal↗
Intranasal capsaicin administration.
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Administration, Intranasal↗
Intranasal insulin administration in insulin dependent diabetes: reproducibility of its absorption and effects.
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Absorption↗
The influence of inadvertent intranasal buserelin administration in early pregnancy.
Buserelin was inadvertently administered during 13 early pregnancies in 12 women with long-standing infertility, who had started the GnRH-agonist for gonadotrophin desensitization prior to ovarian stimulation for IVF. Six women delivered a healthy child and one pregnancy continues uneventfully. Three patients aborted before the sixth week and three women with tubal disease had an ectopic pregnancy. Corpus luteum function was normal in 11 of the 13 pregnancies. Although no evidence of embryotoxic effects of buserelin was observed, barrier contraceptive methods should be advised during the first days of its administration.
Administration, Intranasal↗
Pulmonary edema following phenylephrine intranasal spray administration during the induction of general anesthesia in a child.
Topical phenylephrine, an agent used to facilitate nasotracheal intubation and prevent nasal mucosal bleeding, can cause severe hypertension in some patients, secondary to its stimulation of alpha-adrenergic receptors. Moreover, a high incidence of pulmonary edema is found in patients whose phenylephrine administration is followed by treatment with beta-blocking agents. We report a case of acute pulmonary edema in a pediatric patient who developed severe hypertension after the inadvertent administration of a large dose of topical nasal phenylephrine, followed by beta-adrenergic antagonists (esmolol).
Administration, Intranasal↗
Cholera toxin as a mucosal adjuvant for respiratory antibody responses in mice.
Cholera toxin was investigated as an adjuvant for anti-virus antibody responses in the respiratory mucosa of mice. Two methods of applying cholera toxin were evaluated: oral administration and intranasal administration. Oral immunization with Sendai virus in the presence of cholera toxin effectively primed for respiratory anti-viral antibody responses, whereas oral immunization with Sendai virus alone was ineffective in this respect. In nasal washes, IgA was the predominant anti-viral antibody enhanced by oral cholera toxin; in bronchoalveolar washes, the enhanced anti-viral antibodies included IgG, IgA, and IgM. Effects of direct administration of cholera toxin to the respiratory mucosa on respiratory anti-viral antibody responses depended on the method of anesthesia used during immunization. With inhalation anesthesia (ether), cholera toxin had no adjuvant effect on respiratory antibody responses to coadministered Sendai virus. In contrast, under parenteral anesthesia (i.e., intraperitoneal ketamine), mice which received cholera toxin and Sendai virus via the respiratory tract showed significantly higher anti-viral IgA and IgG antibody titers in nasal washes and IgG antibody in bronchoalveolar washes than mice which received the virus only.
Adjuvants, Immunologic↗
IL-10 is essential for disease protection following intranasal peptide administration in the C57BL/6 model of EAE.
We have shown previously that intranasal administration of encephalitogenic peptides in soluble form to H-2u and H-2s mice affords protection from experimental autoimmune encephalomyelitis (EAE). Here we demonstrate that this method of disease protection can be induced in C57BL/6 mice by administration of the soluble peptide 35-55 from myelin oligodendrocyte glycoprotein. This protective effect was demonstrated by the evaluation of both clinical EAE scores and central nervous system histopathology; the latter showing minimal inflammatory infiltrates in treated mice. The employment of an IL-10-/- congenic strain allowed an appraisal of the involvement of IL-10 in this process. The lack of disease protection in these mice clearly demonstrates the non-redundant role of IL-10 in this process.
Administration, Intranasal↗
Effect of intranasal oxygen administration on arterial blood gas and acid base parameters in spontaneously delivered, term induced and induced premature foals.
The effect of intranasal administration of oxygen at a flow rate of 10 litres per minute for 10 minutes, was studied in a total of 19 foals (thoroughbred and pony) aged between 0.5 and 12 hours. Arterial blood samples were collected before and after oxygen administration for the determination of paO2, paCO2, pHa and base excess. The foals were divided into three groups: five spontaneously delivered thoroughbred and pony foals (group 1), seven term induced thoroughbred foals (group 2) and seven induced premature pony foals (group 3). To examine the effect of duration of oxygen administration on blood gas values, three foals aged five to seven days received intranasal oxygen for 40 minutes and serial arterial blood samples were collected. Significant increases in paO2 values were found in group 1 and group 2 foals in response to intranasal oxygen. When the groups were compared, groups 1 and 2 had significantly higher paO2 values than group 3 foals, whether breathing air or oxygen. The duration of administration of intranasal oxygen had no significant effect on blood gas values.
Administration, Intranasal↗
Protective activity of recombinant cytokines against Sendai virus and herpes simplex virus (HSV) infections in mice.
The efficacy of recombinant cytokines such as murine interferon-gamma (IFN-gamma), human granulocyte colony-stimulating factor (G-CSF), mouse granulocytic-macrophage colony-stimulating factor (GM-CSF) and human interleukin-1 beta (IL-1 beta) has been examined for augmentation of host resistance against Sendai virus and herpes simplex virus (HSV) infections. All four cytokines were found to protect mice against Sendai virus infection. IFN-gamma afforded protection when administered intranasally but not intravenously several days before the infection. Intranasal administration of G-CSF one day before the infection was the most effective administration route and timing. Intranasal administration of GM-CSF was found to afford protection 1 or 3 days before the infection. IL-1 beta demonstrated therapeutic activity against Sendai virus infection after intranasal administration on the same day as the infection. When each of the cytokines was administered subcutaneously four times daily into cyclophosphamide-treated mice before intravenous infection with HSV, only GM-CSF revealed any protective activity.
Administration, Intranasal↗
[Aerodiol: the efficacy and tolerability of intranasal estrogen administration. An overview].
UNLABELLED: Estrogen supplementation, given mainly by oral or transdermal route has been shown to decrease climacteric symptoms, bone turnover, prevent postmenopausal bone loss, and significantly reduce fracture risk in both early and late postmenopausal women. Estrogens exert their principal biological effects through the actions on 2 different intracellular estrogen receptor (ER) proteins, ERa and ERb. These receptors, are completely distinct in their action. However, regardless the type of receptor involved, the response induced through the action of ER induction can be dependent also on the total dose exposure rather than estradiol concentrations at subsaturating levels. The nasal route is an effective and well-established route of drug delivery. Nasal administration produces a pulsed profile of plasma estradiol, with plasma levels rising rapidly and returning to pre-administration levels within 12 h (fall to 10% of their peak level within approximately 2 h). As a consequence, daily intranasal administration results in a pulse-like estrogen profile, rather than the relatively sustained serum levels attained with both oral and transdermal administration. In addition, exposure obtained with a single dose is compared with the exposure obtained with the same total dose given as 2 divided doses administered 12 h apart. It's known that different route of administration exert different biological and clinical RESULTS: In the years, several clinical studies have demonstrated the efficacy and safety of intranasal estradiol in the treatment of climacteric symptoms, compared with other routes of estrogen administration. Interestingly, intranasal therapy also showed a lower tendency to stimulate endometrial proliferation than the oral route, with a high incidence of atrophic endometrium maintained during the long-term study. The reduced level of stimulation of the reproductive organs produced by Aerodiol compared with oral estradiol therapy of equivalent efficacy on climacteric symptoms may be related to the pulsed kinetic profile of estradiol exposure that occurs with the intranasal route. Improvement of climacteric symptoms observed with nasal estradiol administration is comparable to that seen with transdermal or oral estrogens. A similar reduction in Kupperman Index or in the number of hot flushes was reported over a 6-month period with results similar to those of several studies performed with transdermal patches delivering estradiol or with conjugated equine estrogen. Different routes of administration may exert different results in terms of compliance, biological and clinical effects even if long term clinical trials are needed for demonstrating it. The pulsed kinetics of Aerodiol may exert less side effects in terms of coagulation cascade activation and a favourable lipid profile with less mammary tissue stimulation. These aspects became of paramount importance since the recent publication of 2 trials, Women Health Initiative (WHI) and Heart and Estrogen/Progestin Replacement Study (HERS), regardless their important population selection bias and uncertain results, left important consequences in terms of HRT indication and use for both women and clinicians. In conclusion, Aerodiol introduces the new concept of pulsed estrogen therapy. Pulsed estrogen therapy is safe, well accepted and highly efficient in alleviating postmenopausal symptoms and prevent postmenopausal bone loss. Aerodiol therapy demonstrated also a lower stimulation of reproductive tissues (endometrium, breast) compared with the equivalent oral therapy, with important repercussion for future HRT strategies.
Administration, Intranasal↗
Rates of endometriosis recurrence and pregnancy 1 year after treatment with intranasal buserelin acetate (Suprecur) (a prospective study).
OBJECTIVES: This multicenter prospective study of buserelin acetate (Suprecur) therapy for endometriosis was performed in order to examine pregnancy rates and the recurrence of endometriosis 1 year after the end of intranasal administration. METHODS: This study was conducted at 349 institutions, including university hospitals and major hospitals in Japan, and 1,284 patients were recruited as participants. Recurrence of symptoms was followed for 1 year after the end of administration of buserelin acetate in patients whose condition as a whole was evaluated as "improved" or better at the end of administration. Furthermore, the pregnancy rate was similarly followed in patients who complained of sterility at the commencement of the administration. Recurrence was defined as either a case in which all of the main symptoms observed before administration returned to the pretreatment state, or a case in which at least one symptom deteriorated compared to the pretreatment state. Kaplan-Meier's method was used for statistical analysis. RESULTS: Among 459 patients who could be evaluated for recurrence of symptoms, the cumulative recurrence rate was 17.8% 1 year after the end of administration. Among 156 patients who could be evaluated for pregnancy, the pregnancy rate was 23.3% 1 year after the end of administration. CONCLUSION: Intranasal buserelin acetate therapy exhibited not only transient clinical effects during administration or immediately after the end of administration, but also exhibited specific continuing effects after the end of administration.
Administration, Intranasal↗
Biodegradable microparticles with different release profiles: effect on the immune response after a single administration via intranasal and intramuscular routes.
In the development of single-dose microparticulate vaccines, identification of the type of protein release profile required to elicit high and sustainable immune responses is important. Microparticles exhibiting different protein release profiles (continuous, pulsatile and plateau) were made by solvent evaporation or solvent extraction methods from biodegradable polymers encapsulating the model antigen, bovine serum albumin (BSA). The immune responses obtained after a single intranasal or intramuscular administration of microparticles were determined, and also after a subcutaneous boost after 11 months. Microparticles were manufactured with acceptable protein loading and average volume size ranging from 1 to 10 microm. The integrity of BSA extracted and released from microparticles after 2 months incubation was retained. Microparticulate preparations administered by either intranasal or intramuscular routes, evoked rapid, high titre and long-lived (up to 11 months after priming) specific serum IgG responses which were significantly greater than for free BSA. The type of protein release from microparticles had no significant effect on the systemic immune responses. Interestingly, a formulation exhibiting a plateau-release profile was the only microparticulate system capable of inducing significantly greater IgA responses than free BSA after intranasal immunization. This study shows the benefit of microencapsulation in inducing high and long-lasting systemic immune responses after a single dose by both parenteral and mucosal delivery. We conclude that of the microparticles tested, the longevity and magnitude of humoral responses was not effected by the type of in-vitro protein release profile.
Administration, Intranasal↗
Desmopressin (DDAVP) for treatment of disorders of hemostasis.
At a time when the acquired immunodeficiency syndrome as well as hepatitis and other blood-borne diseases are a threat to patients with bleeding disorders who need treatment with blood products, it is rewarding to realize that a number of these patients can be safely and effectively treated with their own desmopressin-stimulated F.VIII:C and vWF. Desmopressin is clinically useful for treatment of patients with moderate and mild hemophilia. The limits of the clinical indications are established by the nature of the bleeding episode, the resting factor level, the level that must be achieved, and the length of time the level must be maintained to manage any given bleeding episode. In von Willebrand disease, desmopressin can be used more extensively to raise F.VIII:C levels than in classic hemophilia, because fewer of the patients have the severe form of the disease that is unresponsive to desmopressin. Increases in the level of F.VIII:C of about four times the resting value can be expected both in hemophilia and von Willebrand disease, but it must be borne in mind that the range of individual responses is large. Even though it is not easy to correct the prolonged bleeding time, particularly in patients with dysfunctional vWF, this drawback is of clinical relevance only in a minority of cases. A role for the use of desmopressin in acquired diseases of primary hemostasis has been proposed more recently, and experience is more limited than in congenital bleeding disorders. Uremia is probably the most firmly established indication because it has been shown that the bleeding time is often dramatically shortened by desmopressin, and hemorrhages can be stopped or prevented before surgical procedures. The indications for use of the compound in liver cirrhosis and congenital and acquired platelet dysfunctions are promising but much less established from a clinical standpoint. The bulk of available clinical experience is based on intravenous administration. Intranasal and subcutaneous administration have been successfully attempted and might be more convenient in selected circumstances, such as home treatment and the stimulation of blood donors to provide more abundant supplies of F.VIII:C and vWF. However, the responses after intranasal administration are less predictable and consistent than after intravenous administration. Desmopressin has few troublesome side-effects. Mild facial flushing, a small increase in heart rate, and, more rarely, mild headache can occur transiently during infusion. Signs of hyponatremia or cerebral edema are extremely rare, providing that excessive fluid intake is avoided.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Cutaneous↗
The immunostimulating complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses.
ISCOM is an efficient mucosal delivery system for RSV envelope proteins as measured by antibody responses in respiratory tract secretions and in sera of mice following two intranasal (i.n.) administrations. Intranasally administered RSV ISCOMs induced high levels of IgA antibodies both in the upper respiratory tract and in the lungs. In the lungs, a prominent and long-lasting IgA response was recorded, which still persisted 22 weeks after the second i.n. immunization when the experiment ended. Subcutaneous (s.c.) immunization only induced low IgA titres in the upper respiratory tract and no measurable response to RSV was found in the lungs. Differences were also noticed in serum between the i.n. and s.c. modes of immunization. ISCOMs given intranasally induced earlier, higher and longer lasting IgM and IgG1 serum anti-RSV antibody responses than those induced by the s.c. mode of administration. A low serum IgE response was only detectable at 2 weeks after i.n. immunization with ISCOMs and after s.c. immunization with an inactivated virus, but no IgE response was detectable after s.c. injection of ISCOMs. The serum IgA response was more pronounced following s.c. injection of inactivated virus than after i.n. application of ISCOMs, and a clear-cut booster effect was obtained with a second immunization. Virtually no serum IgA response was detected after the s.c. administration of ISCOMs. In conclusion, the high immune responses induced by RSV ISCOMs in the respiratory tract and serum after i.n. administration indicate prominent mucosal delivery and adjuvant properties of the ISCOMs, warranting further studies.
Administration, Intranasal↗
Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging.
The function of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis is reduced in aging, although the secretory capacity of somatotrope cells is preserved. Previous studies have suggested that continuous administration of GH-releasing peptides (GHRPs) results in homologous desensitization to the GH-releasing effect of the peptides. In the present study we have studied whether healthy elderly subjects would remain responsive to short-term, intermittent treatment with Hexarelin (HEX), a GHRP, and whether this treatment would result in an increase in serum IGF-I. In study I, the effect of an 8-day treatment with intranasal administration of 1.25 mg (about 18 micrograms/kg) t.i.d. HEX on the acute GH response to the hexapeptide and on serum IGF-I, IGF binding protein 3 (IGFBP-3), prolactin and cortisol levels was studied in seven elderly subjects (four males and three females, aged 67-80 years). In study II, the same parameters were studied before and after a 15-day treatment with oral administration of 20 mg (about 300 micrograms/kg) t.i.d. HEX in seven elderly women (aged 63-80 years). The GH response to the intranasal HEX administration was not significantly higher than that induced by 1 microgram/kg iv GHRH (229.4 +/- 35.9 vs 145.8 +/- 26.9 micrograms.l-1.h-1) and was maintained with a trend towards increase after an 8-day treatment with the peptide (342.5 +/- 199.3 micrograms.l-1.h-1). On the other hand, HEX treatment did not significantly modify IGF-I (138.7 +/- 11.1 vs 122.4 +/- 14.1 micrograms/l) but increased IGFBP-3 levels (2.4 +/- 0.2 vs 1.6 +/- 0.2 mg/l, p < 0.02). The GH response to the oral HEX administration was also not significantly higher than that to iv GHRH (257.6 +/- 72.0 vs 179.0 +/- 42.8 micrograms.l-1.h-1) and did not change after a 15-day treatment with the peptide (237.8 +/- 42.8 micrograms.l-1.h-1). Both IGF-I and IGFBP-3 levels were slightly but significantly increased by oral HEX treatment (156.0 +/- 10.7 vs 141.6 +/- 13.6 micrograms/l, p < 0.03, 3.4 +/- 0.2 vs 3.1 +/- 0.2 mg/l, p < 0.03, respectively). Neither intranasal nor oral HEX treatment modified PRL or cortisol levels and did not induce any side effect. In conclusion, these results indicate that chronic but intermittent treatment with HEX, administered either by intranasal or oral route, does not desensitize the GH response to the peptide. Moreover, after HEX treatment a trend towards increase was shown for IGF-I and IGFBP-3 levels. Thus, our findings strengthen the hypothesis that prolonged treatment with HEX may restore the reduced GH release in aging.
Administration, Intranasal↗
[Neuroactivating mechanism of action of the new trophinotropic drug cerebral].
The new drug cerebral, as well as its low-molecular-weight (LMW) fraction (MW, < or = 500 Da) separated from a ready-to-use commercial form of this new neutrotropic drug, increases the level of synthesis and secretion of the nerve growth factor (NGF) in rats under conditions of experimental hemorrhagic stroke (HS), while not influencing the NGF synthesis and secretion in intact animals. This neuroactivating effect of the trophinotropic drug cerebral and its LMW fraction in the acute HS development stage was observed upon intranasal administration. In comparison with parenteral (intraperitoneal) administration, the intranasal introduction provides for the optimum drug delivery to the CNS bypassing the blood-brain barrier. Trophinotropic agents are a new class of drugs with neuroactivating mechanism of action upon the NGF synthesis and secretion under HS conditions.
Administration, Intranasal↗
Comparison of intranasal inoculation of influenza HA vaccine combined with cholera toxin B subunit with oral or parenteral vaccination.
The antibody responses to influenza virus A/PR/8/34 HA vaccine and protection against virus challenge in mice given the vaccine together with the B subunit of cholera toxin (CTB) intranasally were compared with those in mice given the vaccine with CTB perorally, intraperitoneally or subcutaneously. Intranasal vaccination induced remarkably higher levels of antiviral IgA antibodies in both respiratory washings and serum than did other routes of vaccination. The titres of antiviral IgG antibodies in respiratory washings and serum, and haemagglutination-inhibiting (HI) antibodies in serum, were similar after intranasal and parenteral vaccination. Oral vaccination, however, induced low levels of antiviral IgG antibodies but no detectable HI antibodies. Moreover, intranasal immunization elicited significantly higher titres of antiviral IgA antibodies in intestinal secretions in comparison with oral immunization. In contrast, parenteral immunization failed to induce these IgA antibodies. In virus challenge studies, a greater protective effect was seen after intranasal and intraperitoneal vaccination than after other routes of vaccination. These results suggest that intranasal inoculation of combined HA vaccine and CTB is superior to oral or parenteral inoculation in protecting mice. Furthermore, the intestinal antiviral IgA responses suggest that intranasal administration of CTB-combined vaccines could be effective not only against respiratory pathogens but also against enteropathogens.
Administration, Intranasal↗