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Biomedical subjects

S Gizurarson

Publications and source records attributed to S Gizurarson.

At least 19 recordsLinked to original sources
PubMed2001

Serum amyloid P component inhibits influenza A virus infections: in vitro and in vivo studies.

Serum amyloid P component (SAP) binds in vitro Ca(2+)-dependently to several ligands including oligosaccharides with terminal mannose and galactose. We have earlier reported that SAP binds to human influenza A virus strains, inhibiting hemagglutinin (HA) activity and virus infectivity in vitro. These studies were extended to comprise five mouse-adapted influenza A strains, two swine influenza A strains, a mink influenza A virus, a ferret influenza A reassortant virus, a influenza B virus and a parainfluenza 3 virus. The HA activity of all these viruses was inhibited by SAP. Western blotting showed that SAP bound to HA trimers, monomers and HA1 and HA2 subunits of influenza A virus. Binding studies indicated that galactose, mannose and fucose moieties contributed to the SAP reacting site(s). Intranasal administration of human SAP to mice induced no demonstrable toxic reactions, and circulating antibodies against SAP were not detected. Preincubation of virus (A/Japan/57) with SAP prevented primary infection of mice and development of antiviral antibodies. After a single intranasal administration of SAP (40 microg) 1 h before primary infection with virus (2LD(50)), nine out of 10 mice survived on day 10 and these mice approached normal body weight, whereas control mice (one out of five surviving on day 10) died. The data provide evidence of the potential of intranasally administered SAP for prophylactic treatment of influenza A virus infections in humans.

Animals↗
PubMed2001

Electroencephalographic effects and serum concentrations after intranasal and intravenous administration of diazepam to healthy volunteers.

AIMS: To evaluate the electroencephalographic (EEG) effects, blood concentrations, vehicle irritation and dose-effect relationships for diazepam administered nasally. METHODS: The study had a cross-over design with eight healthy volunteers (one drop out). It consisted of four legs with four different administrations: intranasal (i.n.) placebo, 4 mg diazepam i.n., 7 mg diazepam i.n. and 5 mg intravenous (i.v.) diazepam. Polyethylene glycol 300 (PEG300) was used as a vehicle in the nasal formulations to solubilize a clinically relevant dose of diazepam. Changes in N100, P200 and P300 brain event-related potentials (ERP) elicited by auditory stimulation and electroencephalographic beta-activity were used to assess effects on neurological activity. RESULTS: The mean [95% confidence intervals] differences between before and after drug administration values of P300-N100 amplitude differences were -0.9 [-6.5, 4.7], -6.4 [-10.1, -2,7], -8.6 [-11.4, -5.8] and -9.6 [-12.1, -7.1] for placebo, 4 mg i.n., 7 mg i.n. and 5 mg i.v. diazepam, respectively, indicating statistically significant drug induced effects. The bioavailabilities of 4 and 7 mg i.n. formulations, were found to be similar, 45% [32, 58] and 42% [22, 62], respectively. CONCLUSION: The present study indicates that it is possible to deliver a clinically effective nasal dose of diazepam for the acute treatment of epilepsy, using PEG300 as a solubilizer.

Administration, Intranasal↗
PubMed2001

[Attitude of the Icelandic population towards performing cardiopulmonary resuscitation on strangers in the pre-hospital setting.].

OBJECTIVE: Initiation of bystander cardiopulmonary resuscitation (CPR) is directly linked to the outcome of cardiac arrest in the community. Recent reports have indicated a reluctance among witnesses to perform CPR on strangers especially mouth to mouth ventilation. The status of this in Iceland is unknown. The objective of this study was to assess the attitude of Icelanders towards bystander CPR. MATERIAL AND METHODS: A telephone survey was conducted on 1200 randomly selected Icelanders, aged 16-75 years, with regard to their attitude towards pre-hospital CPR on strangers. A total of 804 (70.1%) chose to participate. RESULTS: A large number had received some kind of training in CPR (73%), wheras only 6% had actually participated in CPR. In accordance, 50% thought they would be able to perform chest compressions adequately and 55% mouth to mouth ventilation. A total of 491 (65%) would likely volunteer to perform chest compressions on a stranger, while 178 (24%) would not and 84 (11%) were undecided. Similarly, 473 (64%) would likely volunteer to perform mouth to mouth ventilation on a stranger. One hundred seventy seven (24%) would not and 93 (12%) were unsure. An overwhelming majority, 620 (81%) said it would not make any difference regarding their participation in CPR if the procedure was simplified and included only chest compressions but not mouth to mouth ventilation. CONCLUSIONS: Icelanders have a very positive attitude towards bystander CPR, over two thirds have had some kind of CPR instruction and a large majority has no aversion towards performing mouth to mouth ventilation on strangers. These results are in contrast to similar data from the United States.

English Abstract↗
PubMed2000

Intranasal absorption of buprenorphine--in vivo bioavailability study in sheep.

The bioavailability of buprenorphine, HCl (BPP) in sheep after nasal administration of two formulations has been studied. 0.9 mg BPP in 150 microl was administered nasally and compared to 0.6 mg i.v. The test solutions were formulated with 30% polyethylene glycol 300 (PEG 300) and 5% dextrose, respectively. The bioavailability for PEG 300 was 70% (S.D.+/-27%, n=6), whereas the bioavailability for 5% dextrose was 89% (S.D.+/-23%, n=6). A two-compartment model with initial and terminal serum half-lives of 10 and 23 min, respectively, may describe the pharmacokinetics. The rate of absorption for both nasal formulations was very fast (t(max)=10 min). The C(max) was 37 ng/ml (S.D.+/-17) and 48 (S.D.+/-10) for PEG 300 and dextrose, respectively. No significant difference was found between the two formulations, but PEG 300 has advantages in relation to freezing point depression and solubility, which may be considered if further studies are going to be initiated. The high nasal bioavailability and short time to maximal plasma concentration suggests that it is possible to make a clinically relevant nasal formulation of BPP for the treatment of pain.

Administration, Intranasal↗
PubMed1999

Intranasal immunization with pneumococcal polysaccharide conjugate vaccines protects mice against invasive pneumococcal infections.

Host defenses against Streptococcus pneumoniae depend largely on opsonophagocytosis mediated by antibodies and complement. Since pneumococcus is a respiratory pathogen, mucosal immune responses may play a significant role in the defense against pneumococcal infections. Thus, mucosal vaccination may be an alternative approach to current immunization strategies, but effective adjuvants are required. Protein antigens induce significant mucosal immunoglobulin A (IgA) and systemic IgG responses when administered intranasally (i. n.) with the glyceride-polysorbate based adjuvant RhinoVax (RV) both in experimental animals and humans. The immunogenicity and efficacy of pneumococcal polysaccharide conjugate vaccines (PNC) of serotypes 1 and 3 was studied in mice after i.n. immunization with RV. Antibodies were measured in serum (IgM, IgG, and IgA) and saliva (IgA) and compared to antibody titers induced by parenteral immunization. The PNCs induced significant systemic IgG and IgA antibodies after i.n. immunization only when given with RV and, for serotype 1, serum IgG titers were comparable to titers induced by subcutaneous immunization. In addition, i.n. immunization with PNC-1 in RV elicited detectable mucosal IgA. These results demonstrate that RV is a potent mucosal adjuvant for polysaccharides conjugated to proteins. A majority of the PNC-1-immunized mice were protected against both bacteremia and pneumonia after i.n. challenge with a lethal dose of serotype 1 pneumococci, and protection correlated significantly with the serum IgG titers. Similarly, the survival of mice immunized i.n. with PNC-3 in RV was significantly prolonged. These results indicate that mucosal vaccination with PNC and adjuvants may be an alternative strategy for prevention against pneumococcal infections.

Administration, Intranasal↗
PubMed1999

Single- and repeated-dose local toxicity in the nasal cavity of rabbits after intranasal administration of different glycols for formulations containing benzodiazepines.

To furnish a systemic effect after intranasal administration, a formulation must contain the therapeutic dose in no more than 150 L, the maximum volume that can be applied as a single administration in one nostril in man. The objectives of these studies were to examine the local toxicity of formulations containing benzodiazepines and to document the effects to support clinical trials in man. After stability, pharmacological and pharmacokinetic studies of several benzodiazepine formulations, we studied nasal toxicity after single and repeated administration to rabbits of poly(ethylene glycol) 200, tetra(ethylene glycol), glycofurolum and mixtures of these vehicles both with and without benzodiazepines. Single-dose studies with examinations 5 or 10min after application were undertaken with poly(ethylene glycol), tetra(ethylene glycol), glycofurolum and tetra(ethylene glycol)-glycofurolum in the ratio 95:5; the reactions were similar to that after physiological saline. A 14-day repeated-dose study was conducted with diazepam, lorazepam and flunitrazepam formulations in poly(ethylene glycol), and flunitrazepam in poly(ethylene glycol)-glycofurolum in the ratio 70:30; the two vehicles without any benzodiazepine were also examined. Microscopic study revealed mild changes only in the treated groups. A final four-week study was conducted with repeated administration of clonazepam formulated in tetra(ethylene glycol)-glycofurolum in the ratio 95:5; microscopy revealed mild changes after three 150-microL doses daily, but no abnormalities after one or three 100-microL doses daily. It was concluded that these three solvents individually or as mixtures resulted in only mild local toxicity and might be acceptable as vehicles in nasal preparations of benzodiazepines and other non-irritating drugs for short-term use in man.

Administration, Intranasal↗
PubMed1999

Intranasal administration of diazepam aiming at the treatment of acute seizures: clinical trials in healthy volunteers.

Intranasal administration of diazepam may be a practical alternative to the conventional acute medication of seizures, such as status epilepticus. Nine healthy students participated in an open crossover study on intranasal versus intravenous administration of diazepam (2 mg). Blood samples were collected, pharmacodynamic tests were performed, and the volunteers filled out questionnaire. Peak concentration was achieved after 18+/-11 min and the bioavailability was 50.4+/-23.3%. A pharmacodynamic effect was observed after about 5 min, but the dose, even for i.v. administration, was too low to generate a strong measurable effect. The results indicate that intranasally administered diazepam may be an effective alternative to i.v. administration in relief of seizures, e.g. in an acute situation when a physician or nurse is not available on location.

Administration, Intranasal↗
PubMed1998

Selective augmentation of antibodies in various mucosal regions, after intranasal immunization with diphtheria in mice.

The kinetics of antibody responses were analyzed in various mucosal membranes as well as in the blood and the spleen after intranasal vaccination of mice with diphtheria toxoid. The results show a selective increase in antibody response in the respiratory area and the vagina followed by the gastrointestinal tract, but not in the spleen. IgG and IgM showed an increase 7 days after revaccination, followed by a rapid decline. However, IgA peaked 3 days after revaccination and did not decline throughout the study.

Administration, Intranasal↗
PubMed1998

Intranasal vaccination: pharmaceutical evaluation of the vaccine delivery system and immunokinetic characteristics of the immune responses.

The purpose of this study was to analyze the effect of some pharmaceutical excipients when used for mucosal vaccine formulations and to characterize the achieved immune response. After conducting various pharmaceutical evaluations of the formulations, immunokinetic studies were performed in mice, guinea pigs, and rabbits. The kinetics and the characteristics (antibody isotypes, etc.) of the immune response were studied, as well as the induced level of toxin neutralizing IgG antibodies, which are usually used as the only measures of the potency of vaccines. Results in mice show that intranasal vaccination results in a potent and rapid immune response, similar to that seen after subcutaneous immunization. In guinea pigs and rabbits, however, the subcutaneous immunization produced significantly stronger response than did intranasal vaccination. The most promising excipients were found to be either Polysorbate 20 or Cremophor EL in an aqueous mixture together with caprylic/capric glyceride. The results indicate that nontoxic and pharmaceutically acceptable excipients can be used for mucosal vaccination, providing an interesting alternative to parenteral vaccination.

Administration, Intranasal↗
PubMed1997

Intranasal booster vaccination against diphtheria and tetanus in man.

The booster responses of three different formulations of intranasal (i.n.) diphtheria-tetanus (D-T) vaccines were determined in military recruits and compared with a conventional subcutaneous D-T vaccine. The vaccines for mucosal delivery were sprayed into one nostril and contained D and T toxoids in an enhancer mixture of polysorbate and caprylic/capric glycerides. All of the vaccines gave rise mainly to a systemic IgG response. Among 51 persons with anti-D antibody concentrations in serum below a protective level of 0.01 international units (IU ml-1) before vaccination, all except two attained protective antibody concentrations 4 weeks after vaccination. The median increase in anti-D antibody concentration was 113-fold with the most efficient i.n. formulation. The median increase in anti-T antibody level was 2.4-fold, however, the pre-vaccination levels for this antigen were very high. Within the examined levels, the booster response depended mainly on the dose of the antigen in the vaccine rather than on the concentration of the vehicle mixture. Compared with the parenteral D-T vaccine containing aluminium hydroxide as an adjuvant, all of the tested i.n. formulations showed somewhat lower immunogenicity in man as well as in pre-clinical guinea-pig studies. Among 215 persons immunized i.n., 61% preferred this route of administration rather than a parenteral injection, although the formulations were all associated with varying local symptoms, frequently stinging and pronounced, nasal secretion.

Administration, Intranasal↗
PubMed1997

Pharmacokinetic and pharmacodynamic response after intranasal administration of diazepam to rabbits.

Nasal application of drugs might be an alternative to intravenous administration in acute situations such as epileptic or fever seizures. In the search for a nasal formulation leading to a peak plasma concentration of diazepam at a tmax < or = 5 min bioavailability in rabbits has been studied after intranasal administration of the drug in ten vehicles of different polarity. The animals were dosed with 3 mg diazepam, dissolved in 100 microL vehicle, the solution being administered into both nostrils. The bioavailability, measured during the first 30 min, because periods after this are not relevant for acute treatment, was found to be between 49 and 62% for the four most promising vehicles, pure glycofurol 75, tetraethyleneglycol, poly(ethylene glycol) 200 and 30% glycofurol in tetraethyleneglycol. The tmax for these vehicles was achieved after 5 min, and they induced a very rapid pharmacodynamic response after 1.5 to 3.5 min. The bioavailability was reduced when more polar liquids such as ethanol and tween 20, or lipid oils, e.g. vegetable oil and miglyol 840 were added to the glycofurol. There was a good correlation between tmax and the induction of pharmacodynamic response. These results suggest that nasal application of diazepam in a water-free low-molecular-weight glycol might be of clinical importance as an alternative to intravenous injection, especially in acute situations.

Administration, Intranasal↗
PubMed1996

Evaluation of local toxicity after repeated intranasal vaccination of guinea-pigs.

In intranasal vaccination it is important that the adjuvant does not have any toxic effect on the sensitive nasal mucosa. In this study a histological and clinical evaluation of the effects of two different adjuvants in a vaccine containing detoxified diphtheria (DT) and tetanus toxoid (TT) in guinea pigs was done. The guinea pigs were divided in four groups and treated daily for 14 days with different formulations. Group I with saline, Groups 2 and 3 with the vaccines in a non-ionic surfactant formulation containing glycerides and Group 4 with tetraethyleneglycol formulation containing glycofurol. The guinea pigs in Groups 1, 2 and 4 were sacrificed on day 15 and Group 3, 1 week later and the tissues processed for histological examination. The animals remained healthy during the treatment and minor clinical signs, such as nose-blowing, decreased with time. The histological appearance, including the development of lymphoid tissue, was comparable in all groups. A specific toxic effect on the nasal mucosa by the different vaccine and adjuvant formulations was not observed.

Adjuvants, Immunologic↗
PubMed1995

Intranasal administration of diphtheria toxoid. Selecting antibody isotypes using formulations having various lipophilic characteristics.

Non-ionic excipients, having different lipophilicity, were compared for their selection of immunological response in different organs and biological fluids. In order to express the lipophilicity of the formulation, the balance between the size and strength of the hydrophilic and lipophilic groups was used, called the hydrophile-lipophile balance (HLB) value. Mice were immunized and boosted intranasally with diphtheria toxoid, and samples were taken from the blood, spleen, nasal wash, lungs, saliva, stomach, duodenum, jejunum and the skin. In general, formulations which were highly hydrophilic and highly lipophilic were not able to augment the immunological response markedly (except for IgA). Formulations having intermediate HLB values, e.g. around 9.0, stimulated both IgG1 and IgG2a production, where the HLB = 5.5 formulation seemed to stimulate mainly IgG2b and IgG3 antibody production. On the other hand, comparing the IgA concentration in various samples with respective IgG level, increasing HLB value seems to augment the production of mainly IgA antibodies. The results indicate that the antibody isotypes may be controlled, using variations in the hydrophile-lipophile balance value.

Administration, Intranasal↗
PubMed1992

Stimulation of the transepithelial flux of influenza HA vaccine by cholera toxin B subunit.

Secretory antibodies in mucosal surfaces are known to play an essential role in protection against various infectious diseases. To enhance the production of such antibodies, influenza HA vaccine was inoculated intranasally into rabbits, together with cholera toxin B subunit (CTB) which is known to augment antibody response to an unrelated antigen. This combination resulted in high levels of serum IgG antibody responses against HA and CTB molecules, 3-4 weeks after inoculation, compared with the inoculation of HA vaccine alone. The adjuvant mechanism for CTB was studied by using Ussing chambers, in which nasal mucosa from rabbits were mounted. CTB was found to enhance the transepithelial flux of HA vaccine, from the mucosal side (lumen) into the serosal side (lamina propria), indicating that the permeability of the membrane was changed by CTB. Moreover, to achieve effective flux of HA vaccines, some interactions between the vaccine and CTB across the membrane were found, which may effect the effectiveness of the vaccine formulation. The results suggest that one of the mechanisms by which CTB enhances the production of mucosal antibody response is to enhance the transepithelial influx of vaccine into the nasal mucosa, where the cells involved in the antibody production are located. CTB may be used as a potent adjuvant to induce antibody response, by nasal vaccination, against pathogens impinging on mucosal surfaces.

Adjuvants, Immunologic↗
PubMed1991

Intranasal administration of insulin to humans.

The purpose of this review is to summarize the information and experience at present available on the intranasal administration of insulin to human subjects and to describe some of the anatomical, physiological, pharmaceutical and technological factors which can affect the absorption of insulin. An overview is given of those absorption promoters which have been used in clinical insulin studies, and the possible absorption-promoting mechanisms are discussed. This review shows that the nasal route offers a promising alternative to parenteral administration. The easier administration and the acceptance by the patients is encouraging the development of new intranasal insulin preparations.

Absorption↗