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Results for “Administration, Intranasal”

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PubMed1985

Effects of intravenous, subcutaneous, and intranasal administration of growth hormone (GH)-releasing hormone-40 on serum GH concentrations in normal men.

In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.003, 0.01, 0.03, and 0.1 micrograms/kg; n = 10), sc (1, 3.3, and 10 micrograms/kg; n = 8), or in (3, 10, 30, and 100 micrograms/kg; n = 5). No subject had any symptoms after administration of vehicle or GHRH-40. During the 2-h period after iv administration of GHRH-40, the maximal increment in serum GH levels above basal (nanograms per ml; mean +/- SD) after the 0.1 micrograms/kg dose was 15.5 +/- 10.4 compared to 2.4 +/- 4.1 after vehicle (P = 0.0017). During the 3-h period after sc administration, when compared to the maximal increment in serum GH above basal after vehicle alone (10.2 +/- 12.9), the maximal increments above basal in serum GH were increased after both the 3.3 micrograms/kg (26.2 +/- 23.1; P = 0.022) and 10 micrograms/kg (63.6 +/- 53.5; P = 0.0003) doses. During the 3-h period after in administration, when compared to the maximal increment in serum GH above basal after vehicle alone (2.8 +/- 6.4), the maximal increments above basal in GH were higher after both the 30 micrograms/kg (18.5 +/- 10.4; P = 0.0053) and 100 micrograms/kg (21.7 +/- 8.1; P = 0.0028) doses. In addition, significant dose-response relationships were documented between the maximal increments above basal in serum GH and GHRH-40 administered by all routes. The mean (+/- SEM) peak plasma level of IR-GHRH (nanograms per ml) achieved after administration of 10 micrograms/kg GHRH-40, iv, as reported previously (66.6 +/- 17.6), was approximately 60- and 500-fold higher than the mean levels in the current study after administration of the same dose sc (1.11 +/- 0.39) or in (0.14 +/- 0.02), respectively. In summary, although GHRH-40 stimulates GH release when administered iv, sc, or in, significantly higher doses were required using the sc and in routes to achieve responses comparable to those obtained with iv administration.

Administration, Intranasal↗

PubMed2002

Excitotoxic neurodegeneration induced by intranasal administration of kainic acid in C57BL/6 mice.

Glutamate excitotoxicity plays a key role in inducing neuronal cell death in many neurological diseases. In mice, administration of kainic acid, an analogue of the excitotoxin glutamate, results in hippocampal cell death and seizures. Kainic-acid-induced seizures in mice provide a well-characterized model for studies of human neurodegenerative diseases. However, C57BL/6 mice, which are often used for genetic analyses and transgenic and knockout studies, are resistant to excitotoxicity induced by subcutaneous administration of kainic acid. In the present study, kainic acid administered by the intranasal route was shown to result in continuous tonic-clonic seizures in C57BL/6 mice. These seizures continued for 1-5 h and successfully induced selective lesions in area CA3 of the hippocampus. The survival rate was high even after mice experienced severe seizures. The hippocampal lesions were associated with a high level of cyclooxygenase-2 production as well as astrogliosis. Administration of kainic acid also altered behavioral responses, with mice showing a significant increase in locomotion and rearing activity as indicated by an open-field test. This animal model could provide a valuable tool for exploring the role of excitotoxicity in neuropathological conditions and should be further evaluated in gene-targeting studies of neurodegenerative diseases.

Administration, Intranasal↗

PubMed2006

Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein.

BACKGROUND: We investigated the lipid core peptide (LCP) system for mucosal vaccine delivery against infection with group A streptococcus (GAS)--the causative pathogen of rheumatic fever and rheumatic heart disease. METHODS: An LCP vaccine formulation containing 2 different peptide epitopes of the antiphagocytic M protein of GAS--a conformational epitope from the carboxyterminal conserved C-repeat region and an aminoterminal serotypic epitope--was intranasally administered to mice with cholera toxin B subunit or without additional adjuvant. RESULTS: Our data demonstrate that the LCP vaccine formulation induced the elicitation of antigen-specific systemic immunoglobulin G responses when administered with or without cholera toxin B subunit, whereas cholera toxin B subunit was required for the induction of antigen-specific mucosal immunoglobulin A responses. Immune serum samples from vaccinated mice were capable of opsonization of a homologous GAS strain, as well as opsonization of a heterologous GAS strain. Furthermore, mice were protected from GAS challenge following immunization with the LCP vaccine formulation, even in the absence of additional adjuvant. CONCLUSIONS: These data support the potential of the LCP system in the development of a self-adjuvanting, synthetic, peptide-based mucosal GAS vaccine for the prevention of diseases caused by GAS.

Adjuvants, Immunologic↗

PubMed2001

Intranasal administration of insulin-like growth factor-I bypasses the blood-brain barrier and protects against focal cerebral ischemic damage.

BACKGROUND: Insulin-like growth factor-I (IGF-I) has been shown to protect against stroke in rats when administered intracerebroventricularly. However, this invasive method of administration is not practical for the large number of individuals who require treatment for stroke. Intranasal (IN) delivery offers a noninvasive method of bypassing the blood-brain barrier (BBB) to deliver IGF-I and other neurotrophic factors to the brain. Here, we demonstrate for the first time the therapeutic benefit of IN IGF-1 in rats following middle cerebral artery occlusion (MCAO). METHODS: A blinded, vehicle-controlled study of IN IGF-I was performed using the intraluminal suture occlusion model. Rats were randomly divided into vehicle-control, 37.5 and 150 microg IGF-I-treated groups. Treatments occurred at 10 min after onset of 2 h of MCAO, and then 24 and 48 h later. Four neurologic behavioral tests were performed 4, 24, 48 and 72 h after the onset of MCAO. Corrected infarct volumes were evaluated 72 h after the onset of MCAO. RESULTS: Treatment with the 150 microg IGF-I significantly reduced the infarct volume by 63% vs. control (p=0.004), and improved all the neurologic deficit tests of motor, sensory, reflex and vestibulomotor functions (p<0.01). However, the 37.5 microg dose of IGF-I was ineffective. CONCLUSION: While IGF-I does not cross the BBB efficiently, it can be delivered to the brain directly from the nasal cavity following IN administration, bypassing the BBB. IN IGF-I markedly reduced infarct volume and improved neurologic function following focal cerebral ischemia. This noninvasive, simple and cost-effective method is a potential treatment for stroke.

Administration, Intranasal↗

PubMed1985

Effect of intranasal administration of norethisterone and progesterone on pituitary and gonadal function in adult male and female bonnet monkeys (Macaca radiata).

The effect of intranasal spray of norethisterone (NET) and progesterone (P) on serum testosterone (T) and total sperm count in adult male bonnet monkeys and the effect of NET spray on the menstrual cycle in female monkeys has been studied. Whereas NET spray resulted in a drastic decrease in serum T levels and sperm count, P spray caused a decrease in total sperm count only. Intranasal spray of NET in adult cycling female monkeys between days 5 and 14 resulted in shortening of the menstrual cycle; this could be ascribed to a decrease in serum follicle-stimulating hormone, luteinizing hormone, 17 beta-estradiol, and P levels. Nasal spray of only solvent in male or female monkeys, however, had no effect on any of the parameters tested.

Administration, Intranasal↗

PubMed1998

Efficacy of intranasal administration of formalin-killed Pasteurella haemolytica A2 against intratracheal challenge in goats.

A trial was conducted to compare the efficacy of intranasal vaccination in protecting goats against pneumonic pasteurellosis with intramuscular vaccination using an oil adjuvant vaccine, and a combination of the two methods. Forty goats were divided into four equal groups. Group 1 was vaccinated twice intranasally with formalin-killed Pasteurella haemolytica A2, group 2 was vaccinated twice intramuscularly with an oil adjuvant vaccine containing P haemolytica A7, and group 3 was initially vaccinated intranasally with the formalin-killed P haemolytica A2 followed by intramuscular vaccination with the oil adjuvant vaccine. In each group the two vaccinations were carried out four weeks apart. Group 4 was the unvaccinated control group. All goats were challenged intratracheally with 4 ml of an inoculum containing live P haemolytica A2 at a concentration of 1.3 x 10(7) colony forming units/ml two weeks after the last vaccination and were killed 14 days after the challenge. Although group 2 showed the highest clinical score following the challenge, deaths were observed only in group 3. Three goats in group 1 had pneumonic lung lesions, compared with six goats in group 2 and all the goats in groups 3 and 4. The lung lesions in group 1 were significantly (P < 0.05) less severe than in groups 3 and 4. Similarly, the lesions in group 2 were markedly less severe than in groups 3 and 4, although the differences were not significant. The difference between the extent of the lung lesions in the goats in groups 1 and 2 was not significant. Antibody against P haemolytica A2 in group 1 reached peak levels and was significantly (P < 0.01) higher than in the control group one week after the second vaccination, before declining.

Administration, Intranasal↗

PubMed1996

[The effect of midazolam after intranasal administration on spontaneous respiration and respiratory control in young children].

AIM: The aim of this study was to investigate the influence of intranasally administered midazolam in different doses on spontaneous respiration in children. METHODS: 40 children received in randomised order 0.2, 0.4 or 0.6 mg/kg b.w. midazolam intranasally or NaCl 0.9% as control. 10 minutes later, anaesthesia was induced by inhalation of halothane, nitrous oxide and oxygen. The children were breathing spontaneously at a PEEP of 5 cm H2O on a circle system with a fresh gas flow of 61/min (FIO2 = 0.33). Intubation was performed in deep anaesthesia without muscle relaxant. Halothane concentration was reduced to an endtidal concentration of 0.4 Vol%. With a baby pneumotachograph, minute ventilation, tidal volume, peak inspiratory and expiratory flow and respiratory rate were recorded during quiet breathing. Endtidal pCO2 was measured. Ventilation was then stimulated with 0.2 and 0.41/min CO2 and the same parameters were recorded. Regression analysis was performed for minute ventilation and endtidal pCO2 to obtain the slope which is a parameter for the sensitivity of the chemoreceptor mediated control of ventilation. RESULTS: The tidal volume and peak inspiratory flow were significantly reduced for a dose of 0.6 mg/kg compared to the control group. No statistical difference could be found for any other parameter between the control and study groups. CONCLUSION: We conclude that nasally administered midazolam reduces tidal volume and inspiratory peak flow in spontaneously breathing children at a dose of 0.6 mg/kg b.w. compared to control during halothane--nitrous oxide--oxygen anaesthesia. The CO2 mediated control of respiration under this condition is preserved.

Administration, Intranasal↗

PubMed1999

Intravenous or intranasal administration of gliadin is able to down-regulate the specific immune response in mice.

The mucosal lesion in coeliac disease (CD) represents an immunologically mediated injury triggered by gliadin and is restricted by a particular assortment of major histocompatibility complex (MHC) class II genes. Therefore, immunomodulatory strategies to tolerize gliadin-specific, class II-restricted T-cell responses could represent an alternative to current treatments of CD, which are based on a gluten-free diet. In this study, BALB/c mice derived from a gluten-free diet colony were tolerized by either intranasal (i.n.) or intravenous (i.v.) administration of single or multiple doses of gliadin. While a single dose failed to induce tolerance, a significant decrease in gliadin-specific T-cell proliferation was detected (P < 0.001) after multiple i.n. or i.v. administrations. No significant difference in antibody titre was detected for antigen-specific immunoglobulin G (IgG) or the IgG1 subclass, but a lower IgG2a-specific titre was observed. Both interferon-gamma (IFN-gamma) and interleukin (IL)-2 expression, measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), were reduced on antigen administration, both i.v. and i.n. Neither regimen showed a regulatory effect on IL-4 production. As T helper 1 (Th1) cytokines seem to be important in the pathogenesis of CD, our data therefore highlight the potential of i.n. and i.v. routes for the design of useful immunomodulatory strategies for CD.

Administration, Intranasal↗

PubMed2004

Intranasal administration of an Escherichia coli-expressed codon-optimized rotavirus VP6 protein induces protection in mice.

We are developing rotavirus vaccines based on the VP6 protein of the human G1P[8] [corrected] [J. Virol. 73 (1999) 7574] CJN strain of rotavirus. One prototype candidate consisting of MBP::VP6::His6, a chimeric protein of maltose-binding protein, VP6 and hexahistidine, was expressed mainly as truncated polypeptides in Escherichia coli BL21(DE3) cells. A possible reason for this extensive truncation is the high frequencies of rare bacterial codons within the rotavirus VP6 gene. Expression of truncated recombinant VP6 was found to be reduced, and expression of complete VP6 protein was simultaneously increased, when the protein was expressed in Rosetta(DE3)pLacI E. coli cells that contain increased amounts of transfer RNAs for a selection of rare codons. The same observation was made when a synthetic codon-optimized CJN-VP6 gene was expressed in E. coli BL21 or Rosetta cells. To increase protein recovery, recombinant E. coli cells were treated with 8M urea. Denatured, full-length MBP::VP6::His6 protein was then purified and used for intranasal vaccination of BALB/c mice (2 doses administered with E. coli heat-labile toxin LT(R192G) as adjuvant). Following oral challenge with the G3P[16] [corrected] [J. Virol. 76 (2002) 560] EDIM strain of murine rotavirus, protection levels against fecal rotavirus shedding were comparable (P>0.05) between groups of mice immunized with denatured codon-optimized or native (not codon-optimized) immunogen with values ranging from 87 to 99%. These protection levels were also comparable to those found after immunization with non-denatured CJN VP6. Thus, expression of complete rotavirus VP6 protein was greatly enhanced by codon optimization, and the protection elicited was not affected by denaturation of recombinant VP6.

Administration, Intranasal↗

PubMed1991

Assessment of the biological activity of synthetic salmon calcitonin by intranasal administration in healthy volunteers.

The authors conducted an open crossover trial of the biological activity of single-dose salmon calcitonin (sCT) 100 I.U. by nasal spray versus single-dose sCT 50 I.U. by intramuscular route in six healthy volunteers. The biological activity of the hormone was assessed on the changes in the blood levels of calcium, cAMP and osteocalcin recorded in the 4 h following administration. The increase in plasma cAMP shows that the hormone acts effectively by the nasal route. Further, the lack of statistically significant differences between the two modes of administration in any of the parameters considered demonstrates the bioequivalence of 50 I.U. of sCT i.m. and 100 I.U. of sCT intranasally.

Administration, Intranasal↗

PubMed1988

[Bioavailability of dalargin and its metabolism during intranasal administration to rats].

Bioavailability and metabolism of a peptide drug Dalargin with a chemical structure Tyr-D-Ala-Gly-Phe-Leu-Arg have been examined. Dalargin is applied for the treatment of gastric and duodenal ulcers. Bioavailability was estimated following intramuscular (i/m) and intranasal (i/n) routes of administration of 3H-dalargin in anesthetized dogs. The highest dalargin concentration was achieved about 10 min after i/m and i/n administration. Absolute dalargin bioavailability was 15% and 8%, while its elimination half-life was 23.2 min and 21.3 min, respectively. Tyrosine, N-terminated tetra- and pentapeptides were the main metabolites detected in the blood. The intranasal route of dalargin administration is concluded to be possible in the clinical practice.

Administration, Intranasal↗

PubMed1999

Subacute onset of oculogyric crises and generalized dystonia following intranasal administration of heroin.

A case is reported of a patient who experienced sudden onset of severe respiratory failure, shock and coma after first-time intranasal heroin abuse. During the following days full consciousness was restored, revealing persistent oculogyric crises, axial retropulsive dystonia and ataxia. Initially computer tomography (CT) scans of the brain were normal and cerebral spinal fluid examination showed a slight elevation of lactate. Magnetic resonance imaging (MRI) scans of the brain demonstrated diffuse bilateral subcortical white matter hyperintensities, with sparing of the U-fibers, symmetric bilateral hyperintensities of the globus pallidum and very hyperintensive subcortical foci in the right hemisphere. Differential diagnostic assessment, treatment, clinical and MRI course of a 6-month follow-up are discussed.

Administration, Intranasal↗

PubMed2004

Glycol chitosan improves the efficacy of intranasally administrated replication defective human adenovirus type 5 expressing glycoprotein D of bovine herpesvirus 1.

The ability of two soluble formulations, namely chitosan and glycol chitosan, when used as an intranasal adjuvant, to improve the immunogenicity of an intranasal human adenovirus type 5 replication defective expressing bovine herpesvirus 1 (BoHV-1) glycoprotein D based vaccine, was investigated in cattle. Their adjuvant effects on immune response by increasing clinical and especially virological protection against an intranasal BoHV-1 challenge were then evaluated. The best virological protection was obtained in calves immunized with the vaccine vector adjuvanted with glycol chitosan which decreased the challenge BoHV-1 virus excretion titres by 0.5-1.5 log when compared to those obtained in calves immunized with the vaccine vector alone or adjuvanted with chitosan. A slight difference in clinical scores was observed in calves immunized with the adjuvanted vaccine vector compared to calves immunized with the vaccine vector alone. The obtained data suggest that the tested soluble formulation of glycol chitosan has promising potential use as an intranasal adjuvant for recombinant viral vector vaccines in cattle.

Adenoviridae↗

PubMed1977

Hyposensitization of patients with allergic rhinitis by intranasal administration of chemically modified grass pollen allergen. A pilot study.

In a pilot study, five adult patients with allergic rhinitis due to grass pollen underwent local intranasal hyposensitization with a chemically modified grass pollen extract--a so-called allergoid. Local hyposensitization during a pre-seasonal period resulted in an increased serum level of timothy-specific IgE antibodies in all patients, indicating that the allergoid had immunogenic properties. In four of the patients the clinical effect during the grass pollen season was judged satisfactory. Pre- and post-seasonal provocation test in these four patients also showed a reduction of the nasal sensitivity during this period. All patients tolerated the treatment well without any marked side effects. These promising preliminary results motivate further investigation into this form of therapy.

Administration, Intranasal↗

PubMed1992

Intranasal administration of estradiol in combination with progesterone to oophorectomized women: a pilot study.

A pilot study was done to investigate the pharmacokinetics and acceptability of an intranasal 17 beta-estradiol/progesterone formulation. This formulation contained dimethyl-beta-cyclodextrin as a solubilizer and absorption enhancer of the steroid hormones. The study was performed in four oophorectomized and hysterectomized patients. After nasal delivery of 0.34 mg estradiol and 0.85 mg progesterone, concentration-time curves of progesterone, estradiol and its metabolite estrone were established. Rapid absorption of progesterone and estradiol was demonstrated. Progesterone peak-levels (3.9-6.7 nmol/l) exceeded the levels which are found in the follicular phase of the menstrual cycle, but did not reach the levels of the luteal phase. Comparison with an earlier reported study in which only estradiol was administered shows that the addition of progesterone does not alter the absorption and pharmacokinetics of estradiol. The nasal formulation was well accepted by the four patients and no adverse effects were noted.

Administration, Intranasal↗

PubMed1996

[Comparison of calcitonin tolerance after intramuscular or intranasal administration in treatment for postmenopausal osteoporosis].

The aim of the study was to compare the tolerance of synthetic salmon calcitonin applied in two different ways, intramuscularly or intranasally, in 50 patients with postmenopausal osteoporosis with bone fractures. Thirty patients were treated with calcitonin in intramuscular or subcutaneous injections, whereas in 20 cases calcitonin was applied in nasal spray. In the first group several side effects were observed, like nausea, vomiting, abdominal pains, skin rush, headaches, dropping blood pressure, symptoms of bronchial spasm. Finally in 13 cases it was necessary to stop calcitonin therapy. On the other hand the patients receiving calcitonin in nasal spray did not manifest any severe side effects.

Abdominal Pain↗

PubMed1984

Intranasal administration of RA 27/3 rubella virus vaccine. A clinical trial in young adults.

Of the vaccines and inoculation routes studied for the prevention of rubella, only the RA27/3 vaccine, administered intranasally, has the ability to stimulate a humoral antibody pattern very similar to that evoked by wild rubella infection. Because information about intranasal (IN) vaccination has only been obtained using the RA 27/3 vaccine manufactured in Europe, we conducted a trial of IN vaccination among young adults using Meruvax II which is manufactured in the USA. Of 597 family planning clinic patients screened in 1980-1981, 71 (11.9%) were susceptible to rubella; forty-one subjects were randomly assigned to receive IN or subcutaneous (SC) vaccine. All 20 SC vaccinees, but only 8/21 (38%) IN vaccinees, were successfully immunized. We conclude that standard doses of commercially available RA 27/3 vaccine are insufficient for IN immunization against rubella. Additional study of the dose-response relationship is needed if IN vaccination is to be recommended.

Administration, Intranasal↗

PubMed1995

Comparison of rectal to intranasal administration of midazolam for premedication of children.

Sixty children aged 3 to 9, undergoing minor surgical procedures, were studied to compare 0.5 mg/kg intranasal with 0.5 mg/kg rectal midazolam as a premedication. The children were evaluated for their ability to tolerate the medication, preanesthetic sedation, and alertness after anesthesia. Both premedication routes were equally effective in sedating the children. In both groups, a significant loss of effectiveness was noted if induction of the anesthesia began more than 30 minutes after administration of the medication (p < 0.0003). Rectal midazolam was much better tolerated by the children than the intranasal route (30 versus 3, p < 0.0001). We advocate the rectal over the intranasal route for premedication with midazolam in children, and anesthetic induction should occur no more than 30 minutes after administration of premedication.

Administration, Intranasal↗