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Results for “Administration, Intranasal”

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PubMed2003

Role for IL-10 in suppression mediated by peptide-induced regulatory T cells in vivo.

Regulatory CD4(+) T cells were induced in the Tg4 TCR transgenic mouse specific for the N-terminal peptide (Ac1-9) of myelin basic protein by intranasal administration of a high-affinity MHC-binding analog (Ac1-9[4Y]). Peptide-induced tolerant cells (PItol) were anergic, failed to produce IL-2, but responded to Ag by secretion of IL-10. PItol cells were predominantly CD25(-) and CTLA-4(+) and their anergic state was reversed by addition of IL-2 in vitro. PItol cells suppressed the response of naive Tg4 cells both in vitro and in vivo. The in vitro suppression mediated by these cells was not reversed by cytokine neutralization and was cell-cell contact-dependent. However, suppression of proliferation and IL-2 production by PItol cells in vivo was abrogated by neutralization of IL-10. These results emphasize an important role for IL-10 in the function of peptide-induced regulatory T cells in vivo and highlight the caution required in extrapolating mechanisms of T regulatory cell function from in vitro studies.

Administration, Intranasal↗

PubMed2004

The cholera toxin-derived CTA1-DD vaccine adjuvant administered intranasally does not cause inflammation or accumulate in the nervous tissues.

Although highly effective, the use of GM1-receptor binding holotoxins as nasal mucosal adjuvants has recently been cautioned due to the risk for their accumulation in the brain and other nervous tissues. Therefore we have explored the efficacy of the CTA1-DD adjuvant for its ability to enhance nasal immune responses in mice. We found that despite the lack of a mucosal binding element, the B cell-targeted CTA1-DD molecule was an equally strong adjuvant as cholera toxin (CT). The potency of CTA1-DD was not a result of endotoxin contamination because more than a 50-fold higher dose of LPS was needed to achieve a similar enhancement. Moreover, the adjuvant effect was TLR4-independent and absent in mutant CTA1-E112K-DD, lacking enzymatic activity. The CTA1-DD adjuvant augmented germinal center formations and T cell priming in the draining lymph nodes, and contrary to CT, promoted a balanced Th1/Th2 response with little effect on IgE Ab production. CTA1-DD did not induce inflammatory changes in the nasal mucosa, and most importantly did not bind to or accumulate in the nervous tissues of the olfactory bulb, whereas CT bound avidly to the nervous tissues. We believe that the nontoxic CTA1-DD adjuvant is an attractive solution to the current dilemma between efficacy and toxicity encountered in CT-holotoxin adjuvant or Escherichia coli heat-labile toxin-holotoxin adjuvant strategies and provides a safe and promising candidate to be included in future vaccines for intranasal administration.

Administration, Intranasal↗

PubMed2000

[Expression in vivo of the lacZ gene, delivered to mouse lungs using synthetic microspheres].

A capacity of MF-2 synthetic microspheres to serve as the vehicle for transfer of the marker LacZ gene to mouse lung epithelial cells was studied after a single intranasal administration of the MF-2/gene complex. Two types of plasmids carrying marker gene LacZ were used in the experiments: with cytoplasmic (pCMV-LacZ) and nuclear (pCMV-nlsLacZ) localization of the gene product (beta-galactosidase). As early as 7 days after the complexes MF-2/pCMV-LacZ and MF-2/pCMV-nlsLacZ were administered, specific staining for beta-galactosidase revealed this enzyme activity in the epithelial cells of bronchi, bronchioli, and alveoli. The maximum in vivo of the marker gene in the MF-2/pCMV-LacZ complex was observed at day 14 to 21 after administration and the corresponding gene product was detected during the following two months. The MF-2-mediated gene transfer led to a twofold increase in beta-galactosidase activity relative to the case when the "unbound" pCMV-LacZ plasmid was administered. These results suggest that the synthetic microsphere-mediated transfer of alien genes to the lung of experimental animals is promising. Microspheres may be used in gene therapy for pulmonary affections, in particular cystic fibrosis.

Administration, Intranasal↗

PubMedDate not supplied

Neutralizing influenza antibodies, IgA and total protein in the nasopharyngeal secretions of subjects vaccinated by nasal route with the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology.

Intranasal administration of two doses of the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was followed by rises in the level of neutralizing secretory influenza antibodies in 82% of the cases. The concomitant study of secretory antibody, IgA and total protein levels, as well as of the serum HAI influenza antibodies demonstrated that their evolution was parallel only in 23% of the vaccinees. The percentage of secretory antibody conversion was similar to the rate of protection conferred by the vaccine.

Administration, Intranasal↗

PubMed1975

Immune response to combined live influenza virus vaccines administered intranasally.

The immune responses in volunteers vaccinated intranasally with a live influenza virus vaccine containing attenuated A and B strains have been studied. The hemagglutination-inhibiting antibody titers for both components were determined a few weeks after vaccination. They demonstrated that a good antibody response had been induced in a high percentage of volunteers. The hemagglutination inhibiting titers and percentage of seroconversion for both components were comparable to the results obtained after the intranasal administration of each component separately.

Administration, Intranasal↗

PubMed2002

[Neuropeptide induction of compensatory processes at aphasias].

Dynamic changes of speech function were studied in patients with persistence aphatic disorders after stroke under the conditions of application of V2 vasopressin receptor agonist (1-desamino-8-D-arginin-vasopressin). A course of intranasal administration of the medical drug by using the double blind control showed a reliable reduction of frustration severity of expressive and impressive speech in patients with aphasias of different forms and degrees. A correlation of positive influence of vasopressin on speech, verbal memory and attention was found at efferent motor aphasias. The achieved effects preserved during a two-year catamnestic observation period. A repeated course of therapy resulted in an additional improvement of speech. Neuropeptide restored initially, in patients with aphasias, relatively simple forms of speech and later--complicated ones. This resulted in an improvement of speech functions which are regulated by both cerebral hemispheres. Supposedly, neuropeptide optimized the activity of both the right and left cerebral hemispheres. The stability of the obtained effects is explained by induction, due to vasopressin, of compensatory processes leading to reorganization of intercentral connections.

Administration, Intranasal↗

PubMedDate not supplied

[Modification of rat behavioral reactions by peptides secreted by olfactory cortex cells upon their tetanization].

We studied neurotrophic properties of neuropeptide extracts from tetanized slices of the rat olfactory cortex. Two types of the extracts were studied, EP and ED, obtained from perfusates of the tetanized slices after long-term potentiation and from the slices after long-term depression, respectively. The effects of these two extracts were tested on rats using the open field and passive avoidance tests upon intranasal administration of the extracts (ca. 1 ng total protein). EP showed a neurotropic effect combined with a moderate sedative-hypnotic effect, while EP had obvious neurotropic and nootropic properties, affecting mainly the mechanisms of memory consolidation, and had an activating effect combined with a minor, delayed sedative effect. The functional significance of the secreted endogenous neuropeptides and the mechanisms of their effects are discussed.

Administration, Intranasal↗

PubMed1976

Immunity studies in calves vaccinated with a multivalent live respiratory vaccine composed of I.B.R., parainfluenza 3 and bovine adenovirus type 3.

The persistence of systemic and local antibodies was studied after two intranasal administrations of the vaccine, six weeks apart. Systemic antibodies to I.B.R. and adenovirus 3 evoked by the vaccine were still present 21 weeks following the second dose of the vaccine. Inconslusive results were obtained regarding the persistence of systemic and local PI-3 antibodies because of an intercurrent natureal PI-3 infection occurring during the observation period. Local antibodies to adenovirus type 3 were found in a high percentage of vaccinated animals 21 weeks after the second dose of the vaccine, whereas local antibodies to I.B.R. remained detectable in 50% of the animals eight weeks after thesecond dose. The results of a challenge study 21 weeks after revaccination show that the presence of local and systemic antibodies prevent the multiplication of PI-3 and BAV-3 in the upper respiratory tract. Protection against I.B.R. was achieved in the absence of detectable local antibodies.

Adenoviridae↗

PubMed1991

[Diabetes insipidus in sarcoidosis].

Sarcoidosis is a generalized disorder which involves the central nervous system in 5 per cent of patients presenting with the disease. We describe the case of a 22-year-old man who developed central diabetes insipidus with a daily urine production of 14,81 seven weeks after diagnosis of pulmonary sarcoidosis and parotid gland enlargement. Computed tomography showed a contrast enhancement of pituitary gland and stalk, no other intracranial manifestations were demonstrated. Intranasal administration of synthetic antidiuretic hormone (ADH) reduced urine volume to normal levels immediately. After discontinuation of 15 months therapy with corticosteroids and administration of ADH for 29 months spontaneous urine volume didn't exceed 31. The patient has been free of symptoms since discontinuation of therapy.

Administration, Intranasal↗

PubMedDate not supplied

[Comparison of intramuscular and intranasal premedication with midazolam in children].

The study involved 40 children ASA I to II type who were randomly divided into two groups of 20 patients with comparable age and sex profile. Premedication consisting of 0.2 mg/kg of midazolam (Dormicum, Roche) and 0.015 mg/kg of atropine was administered 30 to 40 min before surgical intervention by intramuscular way in one group and by intranasal in the other one. In the operating room a peripheral vein was cannulated and general anesthesia was induced with thiopental sodium and succinylcholine. Arterial blood oxygen saturation, heart rate, arterial blood pressure and respiratory rate were measured at baseline, beginning of sedation (closing eyes), and arrival at the operating room. The time at the onset of sedation, the degree of sedation at the operating room, and the reaction to the venopuncture were also measured. In both groups of patients heart rate and systolic arterial blood pressure measured at the arrival to the operating room were significantly higher than those recorded at baseline and at the onset of sedation. Diastolic blood pressure in patients with intranasal premedication increased on arrival to the operating room with respect to the sedation values. Arterial oxygen saturation significantly decreased from the baseline values in both groups at the onset of sedation and on arrival at the operating room. There were no significant changes in respiratory rate. None of the alterations had clinical consequences. There were no significant differences in the onset of sedation (12.42 +/- 4.07 min in the intramuscular group and 15.26 +/- 7.99 min in the intranasal administration), degree of sedation and response to venopunction in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMedDate not supplied

[The incidence of influenzal, para-influenzal and adenoviral antigens in keratoconjunctivitis patients during immunization with NIVGRIP vaccine].

Repeated intranasal administrations of NIVGRIP, influenza inactivated vaccine, to patients with chronic recurrent keratoconjunctivitis, led to a significant reduction of respiratory virus incidence, as revealed by the immunofluorescence test in the conjunctive epithelial cells. The effect is probably due to endogenous interferon stimulation by the vaccine, at the nasopharyngeal level.

Adenoviruses, Human↗

PubMed1990

Absorption of peptides and proteins from the respiratory tract and the potential for development of locally administered vaccine.

Since the appearance of the first therapeutic active peptides and proteins produced by genetic engineering, there has been an ever-increasing demand to be able to deliver these drugs by routes other than the parenteral. For most drugs the need for alternative delivery systems is due to short-half lives in the bloodstream, large extents of first pass metabolism, or the possibility of obtaining endogenous-like plasma profiles. A wide variety of drugs have now been tested for bioavailability after respiratory, especially intranasal, administration. A small range of drugs (such as propranolol and progesterone) appears to be absorbed effectively via the nasal route and shows bioavailabilities comparable to the intravenous route. However, most drugs shows a much lower degree of absorption. The present review discusses the critical steps that have to be considered when attempting to deliver drugs effectively via the nasal and pulmonary routes and how it is possible by suitable formulation of delivery systems to overcome some of the most important barriers to drug absorption. Furthermore, the immunological responses to respiratory absorption of exogenous peptides and proteins and the potential for development of locally administered vaccines are reviewed.

Absorption↗

PubMed1988

Nasal response to substance P and methacholine in subjects with and without allergic rhinitis.

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.

Administration, Intranasal↗

PubMed1986

[Neuropeptides in the treatment of alcoholism and alcoholic psychoses].

The intranasal administration of the hypothalamic peptide hormones vasopressin and corticotropin was used in the therapy of alcohol abstinence syndrome, acute and chronic alcoholic psychoses and in the conditioned reflex therapy of alcoholism. The proposed methods of therapy were fairly effective and free of complications and marked side effects.

Administration, Intranasal↗

PubMed1988

Intranasal nitroglycerin and intraocular pressure during general anesthesia.

Two separate studies of the effects of nitroglycerin (NTG) on intraocular pressure (IOP) were conducted. In study I, 12 healthy adults received 3 ml NTG solution (2 mg/3 ml) intranasally during steady-state anesthesia. This resulted in a significant decrease in IOP along with decreases in arterial blood pressure and central venous pressure. In study II, 30 patients, classified randomly into two equal groups, received either normal saline (3 ml) or NTG solution (2 mg/3 ml) intranasally, in a double-blind manner, 2 minutes before anesthetic induction with thiopental followed by succinylcholine (1.5 mg/kg). In patients given saline, IOP increased significantly above the preinduction levels after succinylcholine. Tracheal intubation increased it further. In the NTG group, increases in IOP after succinylcholine and after tracheal intubation were significantly less than in the control (saline) group. It is concluded that intranasal administration of NTG decreases IOP in anesthetized patients and, when employed as pretreatment, allows the use of succinylcholine to facilitate tracheal intubation without an increase in IOP above preinduction levels.

Administration, Intranasal↗

PubMed1988

[Effect of detergent and glycerin on the efficacy of nasal immunotherapy with allergens and on the level of the lymphocyte subpopulation in the organs of local immunity].

Experimental mixed allergy to staphylococcal antigens in guinea pigs was treated by the intranasal administration of a staphylococcal allergen with a surfactant or glycerin added. The treatment was found to produce a hyposensitizing effect with respect to immediate and delayed hypersensitivity. The addition of glycerine enhanced this effect. At the same time the level of T-lymphocytes in the lungs and the lymph nodes of the respiratory tract returned to normal. Detergent used at a concentration of 2% abolished the hyposensitizing effect of the allergen, stimulated T-lymphocytes in the lymph nodes of the respiratory tract and the lungs; the number of T-suppressors decreased.

Administration, Intranasal↗

PubMed1987

Granulomatous lung disease by Thermoactinomyces vulgaris antigen in C5 deficient and sufficient mice.

Hypersensitivity pneumonitis (HP) is a granulomatous lung disease with pulmonary lymphocytic infiltration supposed to be caused by type III and type IV allergic mechanisms. In type III allergy, compliment activation plays an important role. In this study, we adopted the intranasal administration of the ultrasonified Thermoactinomyces vulgaris(Tv) antigen to mice, which causes granulomatous lung lesions. We used C5 (the fifth component of compliment) deficient B10D2/oSnJ mice and C5 sufficient B10D2/nSn control mice for the above murine model of HP to see if late components of compliment (C5-9) are concerned in the granuloma formation of HP. The result was that both C5 deficient and sufficient mice formed histologically similar granulomatous lung lesions with lymphocytic infiltration. Our data indicate that C5 is not necessary for the granulomatous lung lesions of HP by the Tv antigen.

Actinomyces↗

PubMed1977

Hypotensive action of an intra-nasally applied angiotensin II-antagonist.

Intranasal administration of the specific angiotensin II-antagonist (1-NSuc-5-Val-8-Phg) A II was investigated in anaesthetized rats with different forms of experimentally elevated blood pressure. Renin- or angiotensin II-induced blood pressure increases were markedly reversed by the angiotensin II-antagonist applied intra-nasally. In rats with acute accelerated elevation of blood pressure the analogue induced also a significant decrease. No change could be observed in rats with chronic renal hypertension.

Administration, Intranasal↗