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Results for “Administration, Intranasal”

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PubMed1979

[Effect of an autovaccine on the course of an experimental staphylococcal infection].

The effect of autovaccine on the state of cellular immunity in mice with staphylococcal infection was studied. The maximum decrease of staphylococcal dissemination in internal organs, espeically in the lungs, as well as an increase in the intensity of phagocytosis by peritoneal macrophages were observed after the administration of the vaccine by the method of inhalation. The intranasal administration of the vaccine also proved to be more effective than subcutaneous injection. The cumulation of immune response was more pronounced after the aerosol administration of autovaccine, especially in cases of pathological processes in the respiratory organs.

Animals↗

PubMed2003

Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens.

Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139-151 (PLP(139-151)). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP(72-85) significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP(72-85) fused to the marker enzyme beta-glucuronidase (beta-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis.

Administration, Intranasal↗

PubMed1974

Specific immunoglobulin responses in serum and nasal secretions after the administration of attenuated rubella vaccine.

The indirect immunofluorescent technique has been used to study the specific immunoglobulin responses in the sera of 63 non-immune adult women who received either Cendehill rubella vaccine subcutaneously, RA27/3 rubella vaccine subcutaneously, or RA27/3 vaccine intranasally. IgG, IgA and IgM antibodies increased virtually simultaneously, starting about 2 weeks after vaccination. IgG antibody appeared in all subjects and reached maximum titres 4-6 weeks after vaccination. The mean IgG titres elicited by the three different methods of vaccination did not differ significantly. IgA and IgM antibodies reached their highest titres between 21 and 28 days after vaccination and then declined to low or undetectable titres within about 9 weeks. The maximum IgA titres observed after intranasal administration of RA27/3 vaccine were significantly higher than those which occurred when the same vaccine was given subcutaneously, but no significant difference in IgM titres was observed. When unfractionated sera were examined IgA antibody was detected in 57 cases (91%) and IgM in 51 (81%). Fluorescent examination of fractions obtained by centrifugation on sucrose density gradients frequently revealed small amounts of IgA and IgM antibody which could not be detected by staining unfractionated serum, and with the inclusion of these results IgA antibody was detected in 61 cases (97%) and IgM in 59 (94%).When 39 adults with pre-existing serum antibody were challenged with vaccine a definite IgA response was detected in only one subject and in no case was there any evidence of the appearance of IgM antibody.Nasal antibody, consisting of IgG or IgA or both, was detected in 17 out of 23 non-immune subjects (74%) who received RA27/3 vaccine, either subcutaneously or intranasally. Titres were much lower than those which occur in the natural disease and there was no evidence that nasal antibody was elicited more readily by intranasal than by subcutaneous vaccination.

Administration, Intranasal↗

PubMed1988

[Paradoxical correlations of the effectiveness of the intranasal and intraperitoneal administration of dermorphins in rats].

The analgetic activity of dermorphin and its analogue A-2 was assessed by the tail-flick test. Following intraperitoneal administration at doses 5 mg/kg and above the peptides showed significant effects. After intranasal application of the peptides a significant effect was observed in the range of low doses 0.001-0.1 mg/kg. After intranasal application of high dermorphin doses (1 or 5 mg/kg) the analgetic activity decreased. The effect of analogue A-2 lasted longer after intranasal, than after intraperitoneal administration. It is assumed that the neurophysiological mechanisms of the analgetic activity of dermorphins depend on the route of their administration.

Administration, Intranasal↗

PubMed1998

Mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in mice.

It has been shown previously that recombinant virus-like particles (VLPs) of papillomavirus can induce VLP-specific humoral and cellular immune responses following parenteral administration. To test whether mucosal administration of bovine papillomavirus type 1 (BPV1) VLPs could produce mucosal as well as systemic immune responses to VLPs, 50 micrograms chimeric BPV1 VLPs containing an HPV16 E7 CTL epitope (BPVL1/E7 VLP) was administered intranasally to mice. After two immunisations, L1-specific serum IgG and IgA were observed. L1-specific IgG and IgA were also found in respiratory and vaginal secretions. Both serum and mucosal antibody inhibited papillomavirus VLP-induced agglutination of RBC, indicating that the antibody induced by mucosal immunisation may recognize conformational determinants associated with virus neutralisation. For comparison, VLPs were given intramuscularly, and systemic and mucosal immune responses were generally comparable following systemic or mucosal delivery. However, intranasal administration of VLP induced significantly higher local IgA response in lung, suggesting that mucosally delivered HPV VLP may be more effective for mediating local mucosal immune responses. Intranasal immunisation with HPV6b L1 VLP produced VLP-specific T proliferative responses in splenocytes, and immunisation with BPVL1 VLP containing an HPV16 E7 CTL epitope induced E7-specific CTL responses. We conclude that immunisation with papillomavirus VLPs via mucosal and intramuscular routes, without adjuvant, can elicit specific antibody at mucosal surfaces and also systemic VLP epitope specific T cell responses. These findings suggest that mucosally delivered VLPs may offer an alternative HPV VLP vaccine strategy for inducing protective humoral immunity to anogenital HPV infection, together with cell-mediated immune responses to eliminate any cells which become infected.

Administration, Intranasal↗

PubMed2003

Optimization of route of administration for coexposure to ovalbumin and particle matter to induce adjuvant activity in respiratory allergy in the mouse.

Epidemiological and experimental studies have not only shown that air pollution induces increased pulmonary morbidity, and mortality, but also that air pollution components may potentiate allergic responses. The respiratory allergy model to ovalbumin in the mouse has been shown a useful tool to characterize the adjuvant potency of air pollution components. However, the choice for the most effective route of administration for testing small amounts of air pollution component is hampered by the diversity of routes of administration used. To test the adjuvant activity of airborne particles (Ottawa dust EHC-93), we studied the optimal route of respiratory administration: intranasally (in) and aerosol (aero) in comparison with responses observed by intraperitoneal (ip) with diesel exhaust particles (DEP) as a positive control. Our results show that the combination of in/aero with ovalbumin caused almost similar immunoglobulin (Ig)E and inflammatory responses compared to the ip/aero. In/in application induced less responses for IgE, less inflammation in the lung, and less increased numbers of eosinophils in the bronchoalveolar lavage (BAL). This response increased dramatically when ovalbumin was coadministered with DEP. Subsequently, EHC-93, which is made up of airborne particles, was tested via the in/in route of administration. EHC-93 induced similar IgE responses, inflammation, and eosinophilic response in BAL compared to DEP. In addition, EHC-93 increased the airway responsiveness of the ovalbumin-sensitized mice measured in unrestrained condition and not in nonsensitized control mice. It is concluded that intranasal sensitization with intranasal challenge with airborne particles (EHC-93) is an effective route of administration to show potency of adjuvant activity of airborne particles.

Administration, Intranasal↗

PubMed1990

Survival after intramuscular or inhalation administration of gentamicin in neutropenic guinea pigs infected by Klebsiella pneumoniae.

Guinea pigs were infected by intranasal administration of Klebsiella pneumoniae on day 7 after irradiation with a dose of 4 Gy and treated on days 8-10 by gentamicin 4 mg/kg bd im or by inhalation leading to estimated systemically absorbed doses of 5.9 mg/kg/day. All animals died; however, gentamicin treatment significantly (P less than 0.05, Fisher's exact test) delayed death in the specific time intervals: 7-13 days (with the exception of day 11) and 12-26 days after im and inhalation administration respectively. Comparison of the two treatments by Fisher's exact test showed a significant advantage (P less than 0.05) for im vs inhalation treatment on days 9 and 10 only. The log rank test gave somewhat different results in that the delay of death after im administration was highly significantly (P less than 0.002) different from control whereas results after inhalation were not significantly different from control (P = 0.06). Moreover, according to the log rank test, im administration delayed death significantly (P = 0.04) better than inhalation. In conclusion these data do not show any advantage of inhalation over im administration for treatment of experimental pneumonia, indeed they are compatible with im administration being marginally more effective.

Administration, Inhalation↗

PubMed2004

A trial of intranasal ACTH(1-24) administration to a patient with isolated ACTH deficiency.

BACKGROUND: Isolated adrenocorticotropic hormone (ACTH) deficiency is a rare cause of secondary adrenocortical insufficiency. Normally it could be used therapeutically as an alternative to glucocorticoid treatment in these patients. We investigated the possibility of therapeutic approach as intranasal ACTH replacement therapy in patients with ACTH deficiency. CASE REPORT: A 32-year-old woman with general fatigue, weakness of legs and loss of consciousness due to severe hyponatremia was admitted to our hospital. Endocrinological studies showed low levels of plasma ACTH and serum cortisol with the loss of circadian rhythm. Plasma ACTH and serum cortisol levels failed to respond after intravenous injection of human corticotropin releasing hormone (hCRH), however, serum cortisol showed a blunted response to ACTH(1-24) stimulation test. She was diagnosed isolated ACTH deficiency. We performed continuous intranasal administration of ACTH(1-24) to the patient. There were no cortisol, aldosterone and dehydroepiandrosterone (DHEA) responses to a single intranasal ACTH(1-24) administration while these levels increased 6 days after intranasal treatment of ACTH(1-24). CONCLUSIONS: These data demonstrate that adrenocortical steroids production are stimulated by intranasal administration of ACTH(1-24) in this patient with isolated ACTH deficiency. We suggest that intranasal administration of ACTH offers a therapeutic approach as ACTH replacement therapy in patients with ACTH deficiency. The latter may be more physiologic than glucocorticoid replacement.

Administration, Intranasal↗

PubMed2000

Suppression of specific IgE antibody responses by liposome-conjugated ovalbumin in mice sensitized with ovalbumin via the respiratory tract.

BACKGROUND: Previously we have shown that intranasal administration of ovalbumin (OVA) together with cholera toxin (CT) abrogates nasal tolerance to OVA, resulting in the induction of specific IgE antibody (Ab) responses, and that intraperitoneal injection of OVA coupled with liposomes (OVA-liposomes) induces a selective suppression of IgE Ab responses to OVA. Whether OVA-liposomes suppress anti-OVA IgE Ab responses in mice sensitized with CT-combined OVA via the respiratory tract remains to be clarified. METHODS: In some experiments, mice were given OVA, liposomes or OVA-liposomes with or without CT intranasally three times, at 2-week intervals (weeks 0, 2 and 4). In other experiments, mice were given OVA-liposomes intranasally 2 days before or 1 and 3 weeks after CT-combined OVA (week 0), which was administered intranasally three times, at 2-week intervals (weeks 0, 2 and 4). Two weeks after the third administration of CT-combined OVA (week 0), nasal wash and serum IgA, IgG and IgE Ab responses were assayed. RESULTS: Pretreatment with OVA-liposomes suppressed IgE Ab responses to CT-combined OVA, with a significantly high production of both nasal IgA and serum IgG Abs. Moreover, treatment with OVA-liposomes 1 and 3 weeks after CT-combined OVA administration also suppressed IgE Ab responses. The suppression of anti-OVA IgE Ab production by OVA-liposomes was accompanied by a simultaneous enhancement of specific IgA and IgG (IgG1, and especially IgG2a) Ab production. CONCLUSIONS: Postimmunization treatment with OVA-liposomes, as well as preimmunization treatment, suppressed specific IgE Ab responses in mice sensitized intranasally with CT-combined OVA. Allergens conjugated to liposomes may be appropriate for preventing the development of allergies to inhaled or dietary antigens in humans.

Administration, Intranasal↗

PubMed1994

Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man.

We evaluated the GH-releasing activity of hexarelin, a new synthetic hexapeptide, after i.v. (1 and 2 micrograms/kg), sc (1.5 and 3 micrograms/kg), intranasal (20 micrograms/kg), and oral (po; 20 and 40 mg) administration to 12 healthy young volunteers. Reference treatments were i.v. saline and GH-releasing hormone (GHRH; 1 microgram/kg). GH release (mean +/- SEM) after the i.v. dose of 1 microgram/kg hexarelin [area under the curve (AUC), 3175 +/- 506 micrograms/min.L] was about 2 times higher than that induced by 1 microgram/kg GHRH (AUC, 1544 +/- 161 micrograms/min.L; P < 0.001). Hexarelin (2 micrograms/kg, i.v.) elicited a further increase in GH levels (AUC, 4422 +/- 626 micrograms/min.L) compared to the 1 microgram/kg dose. The GH response to 2 micrograms/kg hexarelin, i.v., was very reproducible (AUC, 4016 +/- 563 vs. 3959 +/- 803 micrograms/min.L). The sc administration of hexarelin produced a dose-dependent GH response (AUC, 3180 +/- 392 and 4459 +/- 566 micrograms.min.L with 1.5 and 3 micrograms/kg, respectively). Intranasal administration of 20 micrograms/kg hexarelin induced GH release (AUC, 2642 +/- 452 micrograms/min.L) similar to that caused by 1 microgram/kg, i.v. Twenty and 40 mg hexarelin, po, produced a dose-related increase in GH levels (AUC, 2278 +/- 442 and 4079 +/- 514 micrograms/min.L). Biological bioavailabilities were 77.0 +/- 10.5%, 4.8 +/- 0.9%, and 0.3 +/- 0.1% for the sc, intranasal, and po routes, respectively. This study shows that the GH response to hexarelin administered by the i.v. route has a limited variability and is superior to the response to GHRH. The GH-releasing activity appeared to be dose dependent. Thus, hexarelin could be clinically useful to stimulate GH secretion in humans.

Administration, Intranasal↗

PubMed2005

Correction of changes in ADP-induced platelet aggregation with vasopressin analogue desglycinamide-arginine-vasopressin.

We studied the effect of vasopressin analogue desglycinamide-arginine-vasopressin on changes in platelet hemostasis produced by intragastric administration of Ticlid or clopidogrel (inhibitors of ADP-induced platelet aggregation). Intranasal administration of the peptide under conditions of hemorrhagic diathesis produced a hemostatic effect and normalized some parameters of blood coagulation.

Adenosine Diphosphate↗

PubMedDate not supplied

Role of integrative pharmacokinetic and pharmacodynamic optimization strategy in the management of Parkinson"s disease patients experiencing motor fluctuations with levodopa.

Parkinson's disease is a progressively debilitating motor neuron disease that affects the dopaminergic neurons within the nigral-striatal and surrounding pathways and which is characterized clinically by rigidity, resting tremor and bradykinesia with or without postural imbalance. Levodopa is the "gold standard" for the treatment and management of Parkinson's disease worldwide. However, following prolonged use of the drug, the "honey-moon" which was once enjoyed by patients on levodopa begins to wane. The clinical as well as the socio-economic costs associated with such failure in response to levodopa is enormous. Various approaches in the management of Parkinson's disease patients experiencing motor fluctuations with levodopa treatment have been suggested and include both pharmacologic and non-pharmacologic strategies involving invasive surgical intervention. Currently, the non-pharmacological approach, which is invasive, remains to be fully perfected and is associated with high morbidity and mortality. The use of the non-invasive, pharmacological approach is currently the most widely accepted approach but would require a review of all possible drug regimens used. This entails evaluating the pharmacokinetics and pharmacodynamic actions of the drug regimens used and possibly, dosage form and route of administration of the drugs. The use of levodopa formulated for transdermal or intranasal administration might help improve the ease of use and compliance. Controversy abounds as to the role of plasma pharmacokinetics of levodopa in the management of Parkinson's patients, vis a vis its dynamics at the central nerve terminal and its receptor site. However, it is worthy of mention that an integrated optimal pharmacological approach involving the peripheral, and central pharmacokinetics of levodopa as well as its central pharmacodynamics would ensure better treatment and management of this disease. In addition, the choice of alternate formulations and routes of administration will not only improve on the bioavailability and overall pharmacokinetics of levodopa, but also increase compliance. Furthermore, monitoring of both plasma and central concentrations of levodopa and its metabolites might play a major role in individualization of pharmacotherapy in special Parkinsonian patients experiencing motor fluctuations with levodopa.

Antiparkinson Agents↗

PubMed1995

Safety, efficacy, and duration of immunity induced in swine by use of an avirulent live Salmonella choleraesuis-containing vaccine.

An avirulent live Salmonella choleraesuis culture (SC-54) was evaluated for use as an effective vaccine in preventing salmonellosis caused by S. choleraesuis in pigs. Eighty-two pigs, 3 to 4 weeks old, were randomly assigned to 1 of 2 treatment groups, which were designated as either vaccinates or controls. After vaccination, all pigs were examined for fecal shedding of S choleraesuis, rectal temperature, and 10 clinical variables. Significant difference was not detected between vaccinated and nonvaccinated pigs for 14 days (phase I) after intranasal administration of the vaccine. Efficacy and duration of immunity were examined by intranasally challenge exposing respective pigs from either treatment group with a virulent field isolate of S choleraesuis at 2, 8, or 20 weeks after vaccination (phases II-IV). Pigs were again evaluated for 14 days after challenge exposure, and 10 clinical variables and rectal temperature were monitored. Surviving pigs were euthanatized and evaluated for gross lesions, and samples of 7 organs were collected. These organs samples were homogenized, and level of S choleraesuis infection was determined. After virulent challenge exposure during phases II-IV, the clinical status of the SC-54 vaccinates was significantly (P < 0.05) superior to that of nonvaccinates for rectal temperature, feces consistency, behavior, appetite, body condition, and mean score for the 10 clinical variables. Quantitative bacteriologic culture of the tonsil, lung, liver, spleen, mesenteric lymph nodes, ileum, and colon samples indicated consistent reduction of organ colonization in vaccinates; bacteria numbers in the mesenteric lymph nodes, lungs, and ileum were significantly (P < 0.05) reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1984

Changes in plasma thyrotrophin-releasing hormone, thyrotrophin, prolactin and thyroid hormone levels after intravenous, intranasal or rectal administration of synthetic thyrotrophin-releasing hormone in man.

Changes in plasma thyrotrophin-releasing hormone (TRH), thyrotrophin (TSH), prolactin and thyroid hormone levels after iv, intranasal, or rectal administration of synthetic TRH were studied in man. The plasma TRH concentration increased with all three routes, but remained at higher levels for a longer time after intranasal or rectal administration, in contrast to the rapid decrease after iv administration. Plasma TSH, prolactin and thyroid hormone levels increased significantly after intranasal or rectal administration and also remained elevated for a longer period than iv administration. These findings suggest that TRH administered intranasally or rectally enters the blood stream and stimulates TSH, prolactin and thyroid hormone release in man.

Administration, Intranasal↗

PubMed1992

Comparison of intranasal and intratracheal oxygen administration in healthy awake dogs.

Intranasal (IN) and intratracheal (IT) oxygen administration techniques were compared by measuring inspired oxygen concentrations (FIO2) and partial pressures of arterial oxygen (PaO2) in 5 healthy dogs at various IN (50, 100, 150, and 200 ml/kg of body weight/min) and IT (10, 25, 50, 100, 150, 200, and 250 ml/kg/min) oxygen flow rates. Intratracheal administration of oxygen permitted lower oxygen flow rates than IN administration. Each IT oxygen flow rate produced significantly higher FIO2 and PaO2 than the corresponding IN flow rate. An IT oxygen flow rate of 25 ml/kg/min produced FIO2 and PaO2 values equivalent to those produced by an IN oxygen flow rate of 50 ml/kg/min. An IT oxygen flow rate of 50 ml/kg/min produced FIO2 and PaO2 values equivalent to those produced by IN oxygen flow rates of 100 and 150 ml/kg/min. All IT oxygen flow rates greater than or equal to 100 ml/kg/min produced FIO2 and PaO2 values that were greater than FIO2 and PaO2 values produced by IN oxygen flow rates of 200 ml/kg/min. The lowest flow rates studied (50 ml/kg/min, IN, and 10 ml/kg/min, IT) produced PaO2 capable of maintaining 97% hemoglobin saturation, which should be adequate for most clinical situations. Arterial blood gas analysis and FIO2 measurements are necessary to accurately guide oxygen flow adjustments to achieve the desired PaO2 and to prevent oxygen toxicity produced by excessive FIO2.

Administration, Intranasal↗

PubMed1991

Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration.

Twelve children 1-5 y old were randomly assigned to receive midazolam 0.2 mg.kg-1 either by the intravenous (IV) or intranasal (IN) routes. After IN administration the rapid onset of absorption was observed (tmax 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration. The results are consistent with an estimated mean bioavailability of 55%.

Administration, Intranasal↗

PubMed1987

Analysis of immunoglobulin G antibody responses after administration of live and inactivated influenza A vaccine indicates that nasal wash immunoglobulin G is a transudate from serum.

Following intranasal administration of live influenza A virus vaccine or parenteral inoculation of inactivated influenza virus vaccine, immunoglobulin antibody to the influenza virus hemagglutinin was detected in nasal wash specimens from adult volunteers. Several observations supported the suggestion that this immunoglobulin G hemagglutinin nasal wash antibody appeared to be mainly derived from the serum by a process of passive transudation.

Adult↗

PubMed1982

Protective effect of different mouse interferons in mice infected with encephalomyocarditis (EMC).

Antiviral activity of various preparations of mouse interferons (Mu-IFN) administered prophylactically by the intranasal route 4 h before intranasal infection of mice with EMC virus was studied. In spite of the same activity of Mu-IFN preparations in vitro, their antiviral effect in vivo displayed differences. The "alveolar" Mu-IFN induced with NDV obtained in the upper respiratory tract, appeared to be the most effective interferon preparation in the prophylaxis of viral infection in mice. Several-fold intranasal administration of "alveolar" interferon at 4-day intervals markedly increased the survival of animals intranasally infected with EMC.

Animals↗