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Improvements in the selective perception and training of rats using an original analog of the C-terminal fragment of vasopressin.

This report presents studies on the effects of intranasal administration of five doses (0.001, 0.01, 0.1, 1, and 10 microg/kg) of a new analog of arginine-vasopressin fragment AVP(6-9), i.e., D-MPRG, on the learning ability of rats with positive and negative reinforcement. All doses of the peptide improved learning. The most effective dose was 0.01 microg/kg, at which the peptide accelerated the acquisition of a conditioned active avoidance reflex both when given 1 h before and when given immediately after training sessions. The peptide had greater effects when animals were trained with negative reinforcement. Analysis of the results suggests that the action of D-MPRG is mainly on perception processes, i.e., extraction of the conditioned stimulus from the environmental surroundings and evaluation and enhancement of its biological significance. In addition, this peptide prevented extinction of the acquired habit and improved the processes of consolidation, though this effect was weaker than its effect on perception.

Administration, Intranasal↗

Intranasal absorption of salmon calcitonin.

Eight normal subjects and 4 children with osteogenesis imperfecta were administered salmon calcitonin (S-CT) intranasally, and the pharmacokinetics of S-CT were studied. In the normal subjects, the plasma S-CT concentration showed a dose-dependent increase over a dosage range of 200-400 IU. Maximal plasma concentrations were reached 20-60 min after intranasal administration of S-CT. The plasma calcium concentration was significantly decreased 60 min after the administration. In the children, S-CT was also absorbed through the nasal mucosa. This suggests that nasal spraying may be an efficient method for administration of S-CT.

Administration, Intranasal↗

Premedication with nasal s-ketamine and midazolam provides good conditions for induction of anesthesia in preschool children.

PURPOSE: To evaluate the efficacy and safety of intranasally administered s-ketamine and midazolam for premedication in pediatric patients. METHODS: Ninety children were randomly allocated to receive intranasally administered s-ketamine 1 mg.kg(-1) and midazolam 0.2 mg.kg(-1) (Group K1, n = 30), s-ketamine 2 mg.kg(-1) and midazolam 0.2 mg.kg(-1) (Group K2, n = 30), or midazolam 0.2 mg.kg(-1) (Group M, n = 30) as premedicants, using a double-blind study design. Sedation and anxiolysis were evaluated using a sedation and cooperation scale and recorded at several time points. RESULTS: Acceptable conditions (K1: 23; K2: 26, M: 19) for parental separation were not different between groups. Induction conditions were acceptable in 26 patients in K2 (P < 0.05 vs M) (K1: 23; M: 19). Compared to baseline values individual conditions significantly improved in groups K1 and K2 from 2.5 min after premedication until induction of anesthesia (P < 0.003), in group M conditions improved only five minutes after premedication (P < 0.05). Adverse effects observed in this series were within an acceptable range and similar for the three groups. CONCLUSION: Intranasal administration of s-ketamine and midazolam is an appropriate premedication in preschool children.

Adjuvants, Anesthesia↗

[Body weight regulation through the central nervous system. The development of a pathogenetically based adiposity therapy].

The last decade witnessed a dramatic increase in knowledge concerning regulation of body weight and obesity. According to recent concepts constancy of body weight is a side product of regulatory events which ensure constant glucose fluxes to the brain. Within these control systems glucocorticoids and melanocortins play a fundamental role at several sites. The melanocortin neurons in the arcuate nucleus of the hypothalamus are important mediators of the feedback effects of leptin and insulin. Glucocorticoid and mineralocorticoid receptors in hippocampal neurons are crucial, as they define the balance between glucose allocation processes and food intake. Thereby, the hippocampal structures determine the setpoint for body weight regulation. A modulation of these brain structures by intranasal administration of melanocortin and inhisulin has been shown to reduce body weight and body fat mass in humans. So the manipulation of weight-regulating centers in the brain opens a novel approach to a pathogenetically based treatment of obesity.

Administration, Intranasal↗

The anti-inflammatory effect of fusafungine during experimentally induced rhinosinusitis in the rabbit.

The short-term effects of local intranasal administration of fusafungine were studied for its anti-inflammatory and antimicrobial properties against experimentally induced bacterial rhinosinusitis. The maxillary sinuses of 20 rabbits were infected with encapsulated Streptococcus pneumoniae after mechanical occlusion of each animal's anatomic ostium. Either fusafungine solution or placebo was administered as a nasal spray through the nostrils twice daily for 10 days. Histopathological grading of inflammation, biochemical assay of inflammatory mediators, and the number of bacterial species isolated from the nasal cavities all showed significant recovery from inflammation after fusafungine treatment. The beneficial effects of fusafungine on inflamed sinus mucosa may possibly also be attributable to an initial alleviation of inflammation in the nasal cavity, which permitted entry of the drug to the sinus cavity through a partially reopened ostium. A reciprocal relationship between nasal and sinus reactivity involving generalization of inflammation and recovery was also thought to be of importance. The present findings indicate that local applications of fusafungine may effectively improve clinical conditions producing rhinitis and sinusitis.

Administration, Intranasal↗

Attenuation of a human H9N2 influenza virus in mammalian host by reassortment with an avian influenza virus.

In order to develop a surrogate virus strain for production of an inactivated influenza vaccine against a human H9N2 virus, A/Hong Kong/1073/99 (HK1073: H9N2) was co-infected in embryonated chicken eggs with an apathogenic avian influenza virus, A/Duck/Czechoslovakia/56 (Dk/Cz: H4N6), for gene segment reassortment. Multiple-gene reassortants obtained were examined for replication in mammalian hosts in vitro and in vivo by infecting MDCK cells and by intranasal administration to hamsters, respectively. A 2-6 gene reassortant with both surface glycoproteins of HK1073 origin and the rest of Dk/Cz origin, HK/CZ-13, was shown to replicate poorly in the mammalian hosts both in vivo and in vitro comparing with HK1073, although this reassortant replicated as efficiently as each parental strain in embryonated eggs. No sequence difference was observed in the HA1 region between HK1073 and HK/CZ-13, indicating that the reassortant would be equivalent in its immunogenicity to the parental HK1073 strain when it is used as an inactivated vaccine. A virus strain with attenuation in mammalian hosts is preferable for production of an H9 vaccine, since it should reduce the risk of manufacturing-related infections of employees during the vaccine production. HK/CZ-13 can therefore be a surrogate strain for production of an inactivated vaccine as well as diagnostic antigens in case of a possible future pandemic caused by an HK1073-like H9 influenza virus.

Administration, Intranasal↗

Effects of semax against the background of dopaminergic receptor blockade with haloperidol.

We studied the neurotropic effects of ACTH(4-10) analog semax against the background of dopaminergic receptors blockade with haloperidol. Intranasal administration of semax (0.05, 0.2, and 0.6 mg/kg) produced virtually no effect on disturbances of orientation and exploratory reactions and motor activity caused by intraperitoneal injection of 0.2 mg/kg haloperidol. By contrast, preliminary administration of 0.05 mg/kg semax prevented haloperidol-induced disturbances in active avoidance conditioning.

Administration, Intranasal↗

Hydrolysis of leucine enkephalin in the nasal cavity of the rat--a possible factor in the low bioavailability of nasally administered peptides.

In order to investigate the utility of intranasal administration of peptides for systemic medication, the nasal absorption of the model peptide, leucine enkephalin (Tyr-Gly-Gly-Phe-Leu), was studied in the rat. At a concentration of 60 micrograms/ml in Ringer's buffer the pentapeptide was found to undergo, extensive hydrolysis in the nasal cavity. The hydrolysis rather than the polarity of the pentapeptide appears responsible for limiting the nasal absorption of this model compound. In the presence of dipeptides, the hydrolysis of leucine enkephalin was significantly inhibited. These results suggest that the nasal administration of peptides may become an important route for drug administration provided that the peptidases in the nasal mucosa can be transiently inhibited via coadministration of pharmacologically inactive peptidase substrates.

Absorption↗

Cocaine: peak time of action on isolation-induced fighting.

Cocaine (35 mg/kg i.p.) produced a peak increase in fighting duration in isolated male ICR mice at 30 minutes. However, the crest of this peak ranged from 15--45 minutes. During the offset period (45--120 min.), fight duration remained elevated, but at a lower level. At 240 and 360 minutes, fighting had essentially returned to control levels. The results coincide with peak effects reported by others for locomotor activity, stereotypy, and other cocaine-induced behaviors in animals but later than physiological and subjective parameters measured in human volunteers (cocaine addicts) after intravenous and intranasal administration of the drug.

Administration, Intranasal↗

Clinical evaluation of intranasal topical flunisolide therapy in allergic rhinitis.

A double-blind, vehicle control, parallel clinical trial evaluated the effectiveness and safety of the local application of flunisolide, a potent new topical steroid, in the treatment of ragweed hay fever. Fifty patients with well-defined, poorly controlled ragweed allergy were studied during the 1974 ragweed season. Analysis of the data showed that the active drug group had a significant decrease in individual symptoms of sneezing, nasal stuffiness, and nasal secretions, compared with the placebo group. Antihistamine usage was statistically decreased in the active drug over placebo group. There was no evidence of adrenal suppression. This study indicates that intranasal administration of flunisolide in adult patients is both efficacious and safe in the treatment of seasonal allergic rhinitis.

Administration, Intranasal↗

The significance of nasal carriage of Staphylococcus aureus and the incidence of postoperative wound infection.

Staphylococcus aureus infections are associated with considerable morbidity and, in certain situations, mortality. The association between the nasal carriage of S. aureus and subsequent infection has been comprehensively established in a variety of clinical settings, in particular, patients undergoing haemodialysis and continuous ambulatory peritoneal dialysis (CAPD), and in patients undergoing surgery. Postoperative wound infections are associated with a high degree of morbidity and represent an important medical issue. Until recently, eradication of S. aureus nasal carriage by various topical and systemic agents had proved unsuccessful. Mupirocin is a novel topical antibiotic with excellent antibacterial activity against staphylococci. Recent studies have demonstrated that intranasal administration of mupirocin is effective in eradicating the nasal carriage of S. aureus and in reducing the incidence of S. aureus infections in haemodialysis and CAPD patients. It has been suggested that sufficient evidence now exists to test the hypothesis that eradication of the carrier state in surgical patients preoperatively may reduce the incidence of S. aureus postoperative wound infections.

Administration, Intranasal↗

Effect of muramyl dipeptide and its stearoyl derivatives on resistance to Sendai virus infection in mice.

The efficacy of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), 6-O-stearoyl-MDP (L18-MDP), N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine (MDP-Lys-L18) and N-stearoylmuramyl-L-alanyl-D-isoglutamine (2N-L18-MDP) for augmenting host-resistance to viral infection was examined in Sendai virus infected mice. L18-MDP and MDP-Lys-L18 augmented the non-specific host-resistance to infection with Sendai virus. MDP showed a slight enhancement of host-resistance to this infection but 2N-L18-MDP was ineffective. The protective effect of MDP-Lys-L18 was seen only when the drug was administered a few days before the virus challenge. The intranasal administration of MDP-Lys-L18 was effective at 1 microgram but only slight activity was observed in mice treated intravenously or intraperitoneally even at the 100 microgram dose level. MDP-Lys-L18 treatment preceding infection augmented interferon production in the lung of the mice but MDP-Lys-L18 treatment alone induced no interferon.

Acetylmuramyl-Alanyl-Isoglutamine↗

Influenza vaccine: enhancement of immune response by application of carboxy-vinylpolymer.

We evaluated the possibility of application of carboxy vinylpolymer (CVP) to influenza vaccine for the improvement of immune response. Our result shows that CVP induces good immune responses after inoculation of vaccines to mice both subcutaneously, intraperitoneally, and intranasally. Considering the efficacy and safety, intranasal administration of the CVP-coupled vaccine may be the best route of immunization.

Administration, Intranasal↗

Immune responses and protection against Bordetella pertussis infection after intranasal immunization of mice with filamentous haemagglutinin in solution or incorporated in biodegradable microparticles.

The intranasal (i.n.) immunization of mice with Bordetella pertussis filamentous haemagglutinin (FHA) either as a solution or incorporated in biodegradable microparticles induced very similar immune responses. Both resulted in strong systemic IgG responses to FHA and good levels of anti-FHA IgG and IgA in the lungs of immunized mice. In comparison, the intraperitoneal (i.p.) immunization of mice with FHA, as a solution, engendered anti-FHA antibody responses which were stronger for serum IgG, similar for lung IgG and lower for lung IgA. The anti-FHA antibody levels, as measured by immunosorbent assay, were shown to correlate with their functional activity in the blocking of B. pertussis adhesion to HeLa tissue-culture cells. All three forms of immunization appeared to stimulate T-cell responses as assessed by in vitro antigen-specific spleen cell proliferation and IL-2 secretion indicative of a Th1 type response, however, cells from i.p. immunized mice only secreted low levels of IL-5. All three methods of FHA immunization provided mice with significant protection against subsequent aerosol challenge with virulent B. pertussis. Mice which had been immunized intra-nasally eliminated the bacteria from their lungs slightly more rapidly than i.p. immunized mice, demonstrating the efficacy of intranasal administration of FHA in solution and in the more practical biodegradable microparticle form.

Administration, Intranasal↗

Effects of lysine-vasopressin and 1-deamino-8-D-arginine-vasopressin on memory in healthy individuals and diabetes insipidus patients.

Central diabetes insipidus (DI) patients showed impairments in short- and long-term memory functions, but not in attention and concentration, as compared to healthy individuals. A single i.m. injection or sub-chronic intranasal administration of either lysine-vasopressin (LVP) or 1-deamino-8-D-arginine-vasopressin (DDAVP) normalized the disturbed memory functions in DI patients. These peptides also improved memory functions in healthy individuals.

Administration, Intranasal↗

Contribution of Haemophilus influenzae type b lipopolysaccharide to pathogenesis of infection.

The mechanism(s) by which the lipopolysaccharide (LPS) of Haemophilus influenzae type b may contribute to the virulence of this organism is unclear. Purified LPS of Haemophilus influenzae type b or phosphate buffered saline was administered intranasally to infant rats prior to the intranasal instillation of approximately 2-20 x 10(6) cfu of Hib two or three times per day for three consecutive days. The preadministration of 2.0 micrograms Hib LPS resulted in a significantly greater incidence of bacteremia (P = 0.0006) than PBS 30 min after the completion of the intranasal inoculation. Four days following completion of intranasal Hib inoculation the incidence of bacteremia was greater (P = 0.017) in the animals pretreated with LPS at 2.0 micrograms compared to the PBS pretreated animals. Preadministration of 0.2 micrograms LPS had no effect on the incidence of bacteremia or meningitis. There were no differences in the histology of the nasal cavities or turbinates of infant rats inoculated intranasally only with LPS or PBS. There were no differences in the frequency or density of bacteremia following intranasal administration of LPS from either Hib or E. coli. Although the mechanism is unknown, our findings suggest that the LPS of Hib may contribute to the ability of H. influenzae type b to invade the nasal mucosa in this infant rat model.

Administration, Intranasal↗

Oxytocin improves "mind-reading" in humans.

BACKGROUND: The ability to "read the mind" of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals. METHODS: In a double-blind, placebo-controlled, within-subject design, 30 healthy male volunteers were tested for their ability to infer the affective mental state of others using the Reading the Mind in the Eyes Test (RMET) after intranasal administration of 24 IU oxytocin. RESULTS: Oxytocin improved performance on the RMET compared with placebo. This effect was pronounced for difficult compared with easy items. CONCLUSIONS: Our data suggest that oxytocin improves the ability to infer the mental state of others from social cues of the eye region. Oxytocin might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.

Administration, Intranasal↗