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At least 793 records · Page 44Linked to original sources
PubMed2006

[Fluticasone propionate aqueous nasal spray for the treatment of chronic sinusitis with eosinophil].

Chronic sinusitis with eosinophils easily recurs after endoscopic sinus surgery. The condition is usually complicated by asthma, and many eosinophils are present in the sinus mucosa. One conservative treatment method is the administration of glucocorticoids locally or systematically. To evaluate the efficacy and tolerability of intranasal fluticasone propionate for the treatment of chronic sinusitis with eosinophils, seven patients with chronic sinusitis with eosinophils were treated over a 12-week period using a fluticasone propionate aqueous nasal spray (800 microg per day in each nostrilz). The Symptons of 7 patients, especially nasal discharge and nasal obstructions, improved and an expanded air space was observed on paranasal CT images. The percent of drug systemically available after intranasal administration varied by less than 1% for intranasal fluticasone propionate. Therefore, even if intranasal fluticasone propionate is administerved at double the usual dose, it is unlikely to cause systemic side effects. Fluticasone propionate aqueous nasal spray at double the usual dose is effective for the treatment of chronic sinusitis with eosinophils.

Administration, Intranasal↗
PubMed1997

Synthesis and biological evaluation of potent, selective, hexapeptide CCK-A agonist anorectic agents.

Cholecystokinin (CCK) is a 33-amino acid peptide with multiple functions in both the central nervous system (via CCK-B receptors) and the periphery (via CCK-A receptors). CCK mediation of satiety via the A-receptor subtype suggest a role for CCK in the management of obesity. The carboxy terminal octapeptide (CCK-8) is fully active in this regard, but is lacking in receptor selectivity, metabolic stability, and oral bioavailability. Inversion of the chirality of Asp7 in conjunction with N-methylation of Phe8 produces compound 5 which exhibits high affinity and 2100-fold selectivity for CCK-A receptors. Compound 6 (Hpa(SO3H)-Nle-Gly-Trp-Nle-MeAsp-Phe-NH2), derived from moving the N-methyl group from Phe to Asp, decreased CCK-B affinity substantially without affecting CCK-A affinity, giving a compound with 6600-fold selectivity for CCK-A receptors. These compounds inhibit food intake with nanomolar potency following intraperitoneal administration in fasted rats. In addition to greater potency, compound 6 produces weight loss in rats when administered over nine consecutive days. Intranasal administration of 6 potently inhibits feeding in beagle dogs. Compound 6 produces potent anorectic activity via the CCK-A receptor system.

Administration, Intranasal↗
PubMed1998

[Anxiety-inducing and -inhibiting agents: differential effect of pentagastrins on the white rat behavior].

Parenteral administration of des-BOC-Pentagastrin induced the anxiety and fear manifestations, depressing also explorative behaviour in open field experiments in rats. Intranasal administration evoked similar effects, whereas pentagastrin reduced the anxiety level, increasing explorative behaviour. Pentagastrin and des-BOC-Pentagastrin displayed antagonism at the receptor level.

Administration, Intranasal↗
PubMed2001

Intranasal immunization with SAG1 and nontoxic mutant heat-labile enterotoxins protects mice against Toxoplasma gondii.

Effective protection against intestinal pathogens requires both mucosal and systemic immune responses. Intranasal administration of antigens induces these responses but generally fails to trigger a strong protective immunity. Mucosal adjuvants can significantly enhance the immunogenicities of intranasally administered antigens. Cholera toxin (CT) and heat-labile enterotoxin (LT) are strong mucosal adjuvants with a variety of antigens. Moreover, the toxicities of CT and LT do not permit their use in humans. Two nontoxic mutant LTs, LTR72 and LTK63, were tested with Toxoplasma gondii SAG1 protein in intranasal vaccination of CBA/J mice. Vaccination with SAG1 plus LTR72 or LTK63 induced strong systemic (immunoglobulin G [IgG]) and mucosal (IgA) humoral responses. Splenocytes and mesenteric lymph node cells from mice immunized with LTR72 plus SAG1, but not those from mice immunized with LTK63 plus SAG1, responded to restimulation with a T. gondii lysate antigen in vitro. Gamma interferon and interleukin 2 (IL-2) production by splenocytes and IL-2 production by mesenteric lymph node cells were observed in vitro after antigen restimulation, underlying a Th1-like response. High-level protection as assessed by the decreased load of cerebral cysts after a challenge with the 76K strain of T. gondii was obtained in the group immunized with LTR72 plus SAG1 and LTK63 plus SAG1. They were as well protected as the mice immunized with the antigen plus native toxins. This is the first report showing protection against a parasite by using combinations of nontoxic mutant LTs and SAG1 antigen. These nontoxic mutant LTs are now attractive candidates for the development of mucosally delivered vaccines.

Adjuvants, Immunologic↗
PubMed2002

Growth hormone-releasing hormone facilitates hypoglycemia-induced release of cortisol.

Early sleep in humans is characterized by a distinct suppression of pituitary-adrenal activity coinciding with enhanced activity of the somatotropic axis. Here, we tested in awake humans the hypothesis of an inhibiting influence of hypothalamic growth hormone-releasing hormone (GHRH) on pituitary-adrenal activity. For this purpose, pituitary-adrenal activity was stimulated in 10 men through a standard insulin-hypoglycemia-test (IHT) and in another 10 men through combined administration of CRH/vasopressin. Stimulation was performed in each man on three conditions following pretreatment with Placebo and GHRH administered intravenously (50 microg) or intranasally (300 microg) 1 h before. GH, ACTH and cortisol as well as blood pressure and heart rate were measured repeatedly. Contrary to expectations, pretreatment with GHRH did not suppress but enhanced secretion of cortisol upon insulin-induced hypoglycemia regardless of the route of GHRH pretreatment (p<0.05). In contrast, GHRH did not facilitate cortisol release after stimulation with CRH/vasopressin. Changes in ACTH remained inconsistent. Plasma levels of GH increased significantly after i.v. GHRH application, but remained unchanged after the intranasal administration. Blood pressure and heart rate were not influenced by the treatments. Results indicate facilitating effects of GHRH mediated at a suprapituitary (i.e. hypothalamic) level as suggested by restriction of the effect to the hypoglycemia-induced cortisol release with no effects after pituitary stimulation with CRH/vasopressin.

Administration, Intranasal↗
PubMed1998

Evaluation of drug disappearance from nasal cavity by the deposit method.

In order to evaluate antiallergic intranasal formulations, the rates of drug disappearance from rat nasal cavity were estimated by the deposit and perfusion methods. The deposit method, which estimates changes in the amount of residual drug in the nasal cavity following washout of the deposited drug over time after application, yielded a good correlation between apparent disappearance rate constant and the combination of lipophilicity and molecular weight. Since the deposit method can be used only with delivery of small amounts of drug to the nasal cavity, the physiological characteristics of the nasal membrane readily affect drug disposition in tests performed with it, and adsorptive drugs such as parabens exhibited rapid disappearance. Doses used clinically for intranasal administration are usually small, and in the case of antiallergic formulations, it is important to maintain the drug concentration in the nasal mucous membrane. The deposit method should be useful for evaluating intranasal antiallergic drug formulations.

Administration, Intranasal↗
PubMed2005

Induction of dendritic cell-mediated immune responses against HIV-1 by antigen-capturing nanospheres in mice.

Prophylactic vaccines, designed to elicit potent humoral and cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens in mucosa, are the important approach to the protection of individuals against HIV-1 infection, since HIV-1 transmission is largely a result of sexual contact. In this study, a novel strategy has been developed to induce HIV-1-specific immune responses, which involves inactivated HIV-1-caputring concanavalin A (Con A)-immobilized nanospheres (HIV-NS) and their interaction with bone marrow (BM)-derived dendritic cells. HIV-NS were taken up by dendritic cells via cytoskeleton-dependent but mannose-binding site-independent phagocytosis. Serial stimulations to unprimed T-cells with HIV-1 gp120-capturing NS-pulsed dendritic cells could induce antigen-specific T-cell response. Intranasal administration of fluorescein isothiocyanate-labeled nanospheres (NS) in mice proved that the particles were taken up into pulmonary dendritic cells. Analysis of mice receiving intranasal immunizations with HIV-NS revealed that the mice efficiently induced the antibodies against HIV-1 in the genital tract and specific cytotoxic T-cells in the spleen. These results suggest that the use of HIV-1-NS may provide a novel and promising approach for the induction of humoral and cellular immune responses to HIV-1.

AIDS Vaccines↗
PubMed2005

Insulin gel as an alternate to parenteral insulin: formulation, preclinical, and clinical studies.

The objective of the present study was to formulate insulin gel for intranasal administration and to evaluate with respect to in vitro release studies and hypoglycemic activity in animal model and healthy human volunteers. The insulin gel was formulated using the combination of carbopol and hydroxypropyl methylcellulose as gelling agent. The in vivo efficacy of insulin gel administered intranasally was assessed by measuring the blood glucose levels and serum insulin levels at specified time intervals in rats and humans. The use of bioadhesive nasal gel containing insulin not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity but also facilitated direct absorption of medicament through the nasal mucosa. Absorption of the drug through the nasal mucosa was high in the first 0.5 to 1.5 hours of the study with a sharp decline in blood sugar and rise in insulin values corresponding to that decline in blood sugar. This study further demonstrates that administration of insulin intranasally in gel form is a pleasant and painless alternative to injectable insulin.

Administration, Intranasal↗
PubMed2004

Potent, long lasting systemic antibody levels and mixed Th1/Th2 immune response after nasal immunization with malaria antigen loaded PLGA microparticles.

The immunogenicity of the synthetic malaria vaccine SPf66 has been recently improved by the application of new adjuvants as QS-21 saponin or poly-D,L-lactide-co-glycolide (PLGA) polymers. The search for less invasive administration routes made us test the immunogenicity of SPf66-loaded microparticles by the nasal route in Balb/c mice. We report here that the intranasal administration of the adequate PLGA vaccine formulations greatly improves and maintains higher antibody levels compared to the conventional alum adjuvant and to the administration of the particles by other routes (subcutaneous, oral). Systemic immune responses were characterized as mixed Th1/Th2-type: IFN-gamma and IgG2a isotype were found as signs of Th1 activation, whilst IgE and IgG1 secretions indicate Th2 response. Since both types of response have been associated to protective immunity in malaria, we postulate that this new approach supposes an advantage over the traditional adjuvants and routes.

Administration, Intranasal↗
PubMed2005

Transient overexpression of gamma interferon promotes Aspergillus clearance in invasive pulmonary aspergillosis.

Cytokines are critical molecules necessary for normal lung pathogen host defences. Gamma interferon (IFN-gamma) and T1-phenotype immune responses are important components of host defence against Aspergillus. Therefore, we hypothesized that transient overexpression of IFN-gamma within the lung could augment host immunity against Aspergillus. Here it was showed that intranasal administration of 5 x 10(7) colony-forming units (CFU) of Aspergillus fumigatus (Af ) induced the expression of IFN-gamma. Mice were intranasally (i.n) administrated with 5 x 10(8) PFU of a recombinant adenovirus vector containing the murine IFN-gamma cDNA (AdmIFN-gamma), and challenged 24 h later with Af. We observed that i.n. administration of AdmIFN-gamma resulted in about a fourfold increase in levels of IFN-gamma and IL-12 within the lung, about a 75% reduction in lung fungal contents at day 2 and a more than threefold higher survival rate in the AdmIFN-gamma-treated group compared to the controls (P < 0.01). This protection effect was not found when AdmIFN-gamma was i.p. administrated. Alveolar macrophages and lung leucocytes isolated from i.n. AdmIFN-gamma-treated animals displayed enhanced killing of intracellular Aspergillus organisms ex vivo. These results demonstrate that transient overexpression of IFN-gamma could augment host defence against Aspergillus.

Adenoviridae↗
PubMed1990

Safety and efficacy of a thymidine kinase negative equine herpesvirus-1 vaccine in young horses.

A drug induced equine herpesvirus-1 (EHV-1) mutant lacking thymidine kinase inducing activity was developed and evaluated as a vaccine. The safety and effectiveness of the vaccine to protect against experimentally induced EHV-1 respiratory disease were evaluated in weanling horses free of EHV-1 neutralizing antibody. The vaccine was safe when administered either intramuscularly or intravenously, and EHV-1 was not shed intranasally during the 12 days following administration. Intranasal challenge with virulent EHV-1 was used to evaluate vaccine efficacy. Following challenge, there was a significantly (p less than 0.05) greater increase in peak body temperatures and duration of nasal virus shedding in the nonvaccinates, and a significant (p less than 0.05) increase in serum neutralizing antibody titers in the vaccinates.

Animals↗
PubMed2002

A comparison of patient-controlled analgesia administered by the intravenous or intranasal route during the early postoperative period.

Intranasal administration of lipophilic opioids has been shown to be an effective method of administration which is devoid of major side-effects. Whether it is as effective as intravenous administration for patient-controlled analgesia (PCA) has been investigated for fentanyl and pethidine, but not for diamorphine. This study reports a randomised controlled trial designed to compare the effectiveness of diamorphine administered as PCA utilising either the intranasal or intravenous routes. We investigated 52 consecutive patients undergoing primary lower limb joint replacement surgery. Patients were randomly allocated to receive PCA diamorphine, administered either intravenously (0.5 mg bolus, 3 min lockout) or intranasally (1.0 mg bolus, 3 min lockout). Pain was assessed using a Visual Analogue Score (VAS) at rest and on movement on five occasions over the first 36 h postoperatively. The results demonstrated that patients in the intranasal PCA group had significantly higher VAS scores than the intravenous group, both at rest (intranasal median 35.5 vs. intravenous median 20; p = 0.030) and on movement (intranasal median 64 vs. intravenous median 50; p = 0.016). However, significantly fewer patients in the intranasal group compared with the intravenous group suffered episodes of vomiting (intranasal 0/24 vs. intravenous 6/24 patients; p = 0.022). We suggest that if a maximal reduction in pain score is considered the goal of PCA management, the intravenous route is preferable to the intranasal route.

Administration, Intranasal↗
PubMed2002

Nasal immunization with homogenate and peptide antigens induces protective immunity against Trichinella spiralis.

Mice were successfully immunized against the intestinal nematode Trichinella spiralis by intranasal administration of a 30-mer peptide antigen with cholera toxin B. Immunized mice developed antigen-specific serum immunoglobulin G1, intestinal immunoglobulin A, and a type 2-biased cytokine response. Intranasal immunization therefore generates the Th2-mediated responses required for immunity against intestinal parasites.

Administration, Intranasal↗
PubMed1994

Activation of systemic and mucosal immune response following nasal administration of liposomes.

Adjuvant effects of liposomes on systemic and mucosal immune response were investigated following nasal administration to Balb/c mice. Bovine serum albumin (BSA)-specific serum IgG and salivary IgA levels were significantly elevated when BSA-associated liposomes were administered intranasally twice at 4-week intervals. Systemic immune response was activated only by negatively charged liposomes, while activation of mucosal immune response was independent of liposomal charge. Antigen localization in liposomes affected immune adjuvant effect; the mucosal immune response could be activated only by liposomes to whose surface BSA was attached, but the systemic immune response was activated by both liposomes to which antigens were attached and in which the encapsulating antigens occurred. The results suggest that the contribution of antigen-presenting cells in activation of systemic and mucosal immunity following intranasal administration is different.

Adjuvants, Immunologic↗
PubMed2006

Adjuvant effects of adenylate cyclase toxin of Bordetella pertussis after intranasal immunisation of mice.

This study examined the ability of the adenylate cyclase toxin (CyaA) of Bordetella pertussis to act as a mucosal adjuvant for other antigens when co-administered by the intranasal route in mice. Two forms of CyaA were used: the cell-invasive, enzymically active form and a cell-invasive toxin lacking adenylate cyclase enzymic activity (CyaA*). Co-administration intranasally (i/n) of CyaA or CyaA* with ovalbumin (Ova) significantly enhanced (P<0.05) anti-Ova IgG and IgA antibody responses in the serum and anti-Ova IgA responses in lung and nasal secretions compared to those generated by immunisation i/n with Ova alone. The effects were greater with CyaA*. Administration of CyaA* with Ova induced priming of Ova-specific T cells in vivo to a greater extent than that obtained after immunisation with Ova alone. Co-administration of CyaA or CyaA* with pertactin (Prn) significantly enhanced (P<0.05) the serum anti-Prn IgG responses and immunisation with Prn and CyaA* significantly increased the anti-Prn IgA responses in the lungs compared with responses after immunisation with Prn alone. Immunisation i/n with Prn alone partially protected mice (P<0.05) against challenge i/n with B. pertussis. Co-administration of CyaA or CyaA* with pertactin (Prn) significantly increased protection (P<0.05) against challenge compared to that obtained with Prn alone. These effects were particularly apparent with CyaA* as the adjuvant.

Adenylate Cyclase Toxin↗
PubMed2002

Persistent infection of influenza virus in irradiated mice and its prevention by intranasal vaccination.

Effects of intranasal administration of influenza vaccine on persistent viral infection in gamma-ray irradiated mice were examined. BALB/c mice were exposed to a sub-lethal dose of gamma-ray (7Gy) and infected intranasally with non-lethal A/PR/8/34 (PR8, H1N1) viruses. The mice irradiated on days 0 or +2 of infection showed a significant weight loss with a slight decrease in survival rate 3 weeks after infection. These mice kept infective viruses in the nasal and/or lung sites even 3 weeks after infection (persistent viral infection) without IgA or IgG antibodies (Abs), although non-irradiated infected mice cleared the virus completely within 2 weeks. On the other hand, the pretreatment with the nasal adjuvant-combined vaccine (3 days before irradiation) prevented the persistent viral infection with the Abs. These results demonstrate that the exacerbation of influenza is induced by the irradiation during early days of infection (0-2 days) and that the exacerbation is prevented by the intranasal vaccination at least 3 days before irradiation.

Administration, Intranasal↗
PubMed1996

Attenuation of allergen-evoked nasal responses by local pretreatment with exogenous neuropeptide Y in atopic patients.

BACKGROUND: Nasal obstruction and rhinorrhea present in allergic rhinitis are at least partly influenced by neuropeptides released from sensory, parasympathetic, and sympathetic nerves. Neuropeptide Y (NPY) is co-localized with norepinephrine in sympathetic perivascular nerves. NPY is released with norepinephrine on sympathetic nerve stimulation and produces long-lasting vasoconstriction of the nasal vascular bed. In addition to vasoconstriction, there is evidence to suggest that NPY modulates the release of transmitters originating from parasympathetic and sensory nerves by acting on prejunctional receptors. Putative therapeutic application of NPY in rhinitis has been recently suggested because intranasal administration of exogenous NPY in human beings reduces nasal airway resistance and vascular permeability without affecting submucosal gland secretion. OBJECTIVE: The aim of this study was to determine whether intranasal pretreatment with exogenous NPY could influence the functional responses to subsequent allergen challenge. METHODS: A randomized double-blind, three-way, crossover, placebo-controlled study was performed in 13 patients with allergic rhinitis. Pretreatments with NPY (20 nmol), oxymetazoline hydrochloride (20 nmol), or saline solution (NaCl 0.9%) were administered in one nostril 5 minutes before nasal challenge with grass pollen allergen (10,000 standardized quality units). The number of sneezes and the subjective evaluation of nasal itching obstruction, and rhinorrhea were recorded. Nasal airway resistance was measured by anterior rhinomanometry, and nasal secretions were weighed. Mean arterial pressure and heart rate were recorded by noninvasive methods. RESULTS: The number of sneezes, nasal itching, and subjective rhinorrhea evoked by the allergen were similar after the three pretreatments. Subjective and objective increases in nasal airway resistance and mucus production induced by the allergen were significantly (p < 0.01) reduced after NPY pretreatment when compared with saline solution or oxymetazoline pretreatment. Mean arterial pressure and heart rate were not changed. CONCLUSIONS: Local pretreatment with exogenous NPY reduces nasal obstruction and mucus secretion evoked by allergen challenge in allergic patients without modification of local itching and number of sneezes.

Administration, Intranasal↗