• Biomolecules & Therapeutics
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• v.27 no.5
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• pp.450-456
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• 2019

Taurine has a number of beneficial pharmacological actions in the brain such as anxiolytic and neuroprotective actions. We explored to test whether taurine could be transported to the central nervous system through the intranasal route. Following intranasal administration of taurine in mice, elevated plus maze test, activity cage test and rota rod test were carried out to verify taurine's effect on anxiety. For the characterization of potential mechanism of taurine's anti-anxiety action, mouse convulsion tests with strychnine, picrotoxin, yohimbine, and isoniazid were employed. A significant increase in the time spent in the open arms was observed when taurine was administered through the nasal route in the elevated plus maze test. In addition, vertical and horizontal activities of mice treated with taurine via intranasal route were considerably diminished. These results support the hypothesis that taurine can be transported to the brain through intranasal route, thereby inducing anti-anxiety activity. Taurine's anti-anxiety action may be mediated by the strychnine-sensitive glycine receptor as evidenced by the inhibition of strychnine-induced convulsion.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.4
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• pp.772-781
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• 1998

The purpose of this study was to assess the sedative effect of intranasal spray with midazolam for management of the uncooperative 20 children aged from 24 months to 92 months who required extensive treatment. The patients were given randomly a dose of 0.2mg/kg of intranasal placebo, intranasal spray with midazolam, and intranasal drop with midazolam. All the children were restrained in a pediwrap and were monitored with pulse oximeter for assessing the pulse rate and peripheral oxygen saturation. According to Fukuta's behavior rating scale, behavior was checked for evaluation of the clinical sedative effect. The obtained results were as follows: 1. Behavior score of intranasal spray with midazolam was lower than intranasal drop with midazolam(P<0.01). 2. Pulse rate was a significant change as a function of dental procedure(P<0.001), however the peripheral oxygen saturation was not influenced significantly by either adiministration route of drug or dental procedure. Clinically, intranasal spray with midazolam were safe and effective sedation in young children undergoing pediatric dental procedures.

• Journal of The Korean Dental Society of Anesthesiology
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• v.12 no.4
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• pp.223-227
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• 2012

Autism patients in general have bad oral hygiene. It is hard for autism patients to get dental treatment as poor communication. Therefore, they may have to be treated by deep sedation or general anesthesia in numerous cases. However, this process requires induction with mask, so it is not easy to do for disobliging autism patient. Midazolam is a water-soluble benzodiazepine, has been used in pediatric dentistry or dentistry for the handicapped because of rapid onset. Midazolam can be administered through oral, rectal, intramuscular,intravenous, and intranasal (IN) routes. IN route of midazolam may be considered as effective way to allay for uncooperative autism patients before general anesthesia. In this case report, two autism patients required dental treatment. Intranasal spray of midazolam before general anesthesia was safe and effective procedure of behavioral management.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.149-157
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• 2017

The interleukin-1 receptor antagonist (IL-1RA) is a potential stroke treatment candidate. Intranasal delivery is a novel method thereby a therapeutic protein can be penetrated into the brain parenchyma by bypassing the blood-brain barrier. Thus, this study tested whether intranasal IL-1RA can provide neuroprotection and brain penetration in transient cerebral ischemia. In male Sprague-Dawley rats, focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1 h. The rats simultaneously received 50 mg/kg human IL-1RA through the intranasal (IN group) or intraperitoneal route (IP group). The other rats were given 0.5 mL/kg normal saline (EC group). Neurobehavioral function, infarct size, and the concentration of the administered human IL-1RA in the brain tissue were assessed. In addition, the cellular distribution of intranasal IL-1RA in the brain and its effect on proinflammatory cytokines expression were evaluated. Intranasal IL-1RA improved neurological deficit and reduced infarct size until 7 days after MCAO (p<0.05). The concentrations of the human IL-1RA in the brain tissue 24 h after MCAO were significantly greater in the IN group than in the IP group (p<0.05). The human IL-1RA was confirmed to be co-localized with neuron and microglia. Furthermore, the IN group had lower expression of $interleukin-1{\beta}$ and tumor necrosis $factor-{\alpha}$ at 6 h after MCAO than the EC group (p<0.05). These results suggest that intranasal IL-1RA can reach the brain parenchyma more efficiently and provide superior neuroprotection in the transient focal cerebral ischemia.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.4
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• pp.782-787
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• 1998

The treatment for pediatric dental patient has become more complex than the previous, because patients of pediatric dentistry, younger than the previous, and they were often combined with systemic disease. And, the importnace of conscious sedation has been increased by this time for this reason. In a variety of CNS depressants, newly developed imidazobenzodiazepine (midazolam) is well known as a safe and effective medicament. It has a rapid onset, minimized cardiovascular depression and various possible administering, route, so it is commonly used for the conscious sedation of pediatric dental patients. Recently, "intranasal drop-in method" draws attention for its safety, but discomfort during administration and posterior dripping through pharynx diminish its popularity. Now more advanced method for intranasal administration is introduced for conscious sedation for pediatric dental patients, it is "intranasal spray" with aerosol form of medicament. With this method, we can achieve some benefits as belows : 1. Diminished discomfort during intranasal spray than nitranasal drop-in. 2. Rapid osnet and reduction than intranasal drop-in. 3. Eliminatin of adverse reaction, such as rhinorrhea. 4. More improved behavior rating scale.

• Parasites, Hosts and Diseases
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• v.58 no.2
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• pp.185-189
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• 2020

Immunogenicity of dendritic cell-derived exosomes stimulated with Toxoplasma gondii lysates (TLA exo), mixed with cholera toxin as an adjuvant, was investigated in mice immunized via 2 mucosal routes (ocular vs intranasal). BALB/c mice were injected 3 times with TLA exo vaccine at 2 week interval, and the levels of IgG in serum and IgA in tear, saliva, feces, and vaginal wash were measured. To observe the expression of T. gondii-specific B1 gene, mice infected with ME49 T. gondii cysts were immunized with TLA exo or PBS exo (not stimulated with TLA), and their brain tissues were examined. The mice vaccinated via intranasal route elicited significantly higher humoral and mucosal immune responses compared with mice treated with PBS alone. Also, mice immunized via ocular route (by eyedrop) induced significantly higher T. gondii-specific IgG in serum and IgA in tear and feces in comparison with PBS controls. B1 gene expression was significantly lower in TLA exo vaccinated mice than in PBS or PBS exo vaccinated mice. These results demonstrated that ocular immunization of mice with TLA exo vaccine has the potential to stimulate systemic or local antibody responses. This study also highlighted an advantage of an eyedrop vaccine as an alternative for T. gondii intranasal vaccines.

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.2
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• pp.159-167
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• 2002

The purpose of this study was to evaluate the efficacy and safety depending on the route of flumazenil, as an antagonist against midazolam. The subjects of this study were 15 volunteers of $22{\sim}24$ years old. They were sedated with midazolam 0.2mg/Kg intranasal spray, and then 40 minutes after midazolam administration, they were given flumazenil 0.2mg intranasal spray for their reversal. For evaluation of the efficacy and safety of intranasal spray for flumazenil, they were monitored with pulse-oxymeter(Nellcor symphony N-3000, Nellcor Puritan CO. USA) and electric sphygmomanometer (Heartcare 200, National CO. Japan), and were assessed themselves using visual analogue scale(VAS) for tranquilization, sleep, fatigue and attitude. All of these subjects were reduced completely without any undesired situations. The results from this study can be summarized as follows ; 1. Nasaly administered flumazenil using spray device produced much more rapid reduction than intravenously administered flumazenil, but soon after fell in more deep sedated state than intravenously administered flumazenil. 2. There were no considerable side effects or bad influence on vital signs of both nasaly administered flumazenil and intravenously administered flumazenil. These results suggested that the flumazenil administered nasaly using spray device for reversal, we could treat patients safely and effectively under conscious sedation using midazolam administration. But, We will have to research about its optimal dosages for flumazenil, used as intranasal spray for reversal agents against the midazolam by evaluating the blood plasma concentration of midazolam and flumazenil.

• Journal of the korean academy of Pediatric Dentistry
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• v.31 no.3
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• pp.412-420
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• 2004

The purpose of this study was to assess the anterograde amnesic effect of Midazolam administrated by intranasal and oral route. Fifteen healthy volunteers(ASA I) were administrated with placebo, oral Midazolam(15mg), intranasal Midazolam(0.25mg/kg) every 2 weeks. First picture cards were shown to volunteers before medication. At 15, 30, 45 minutes, other picture cards were shown to volunteers. BP, $SpO_2$ and sedation scores were measured. After 24 hours, the volunteers were questioned about their memory of pictures. To assess amnesic effect, recall and recognition test were performed using a series of picture cards designed for this purpose. The obtained results were as follows; 1. Compared to placebo, Midazolam group(oral and intranasal) experienced a significant anterograde amnesic effect(P<0.01) 2. There was no difference between oral and intranasal Midazolam(P>0.01). 3. Anterograde amnesic effect of oral and intranasal Midazolam group began at 15minutes. It became increasingly, oral Midazolam group experienced extremely amnesic effect at 45minutes, intranasal Midazolam group was at 30minutes. 4. After 30minutes of Midazolam administration, anterograde amnesia of oral Midazolam group is more effective than intranasal Midazolam group.

• Journal of Microbiology
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• v.40 no.1
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• pp.11-19
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• 2002

Mice immunized with equine herpesvirus type-1(EHV-1) L-particles skewed a significant increase (p<7.75) in serum antibody titers. Upon a booster dose four weeks lateral antibody titers increased significantly. Interestingly, immunization via intravenous or intramuscular route induced significantly higher (p<0.75) antibody titers. However, mice iummunized with UV-treated L-particles, visions or immunization via intranasal route induced lower antibody titers. Upon challenge inoculation with wildtype EHV-1, our data showed there was a poor correlation between antibody titers and protection against virus replication. Therefore, the role of cell-mediated immunity Inwards protection was investigated. As predicted, the strongest cell-mediated immunity, as measured by delayed-hypersensitivity test, was detected in mice immunized with live virus particles. The magnitude of cell-mediated immune response correlated with the efficacy of L-particles as immunizing agent. The highest efficacy, as indicated in mice immunized via intranasal routed was highly correlated with cell-mediated immunity. A similar phenomenon was also demonstrated in mice immunized intranasally with UV-treated L-particles. However, the degree of protection was reduced when mice immunized intravenously or intramuscularly with UV-treated L-particles. In conclusion, protection conferred in these animals was highly implicated by immune cells and the least by antibodies. The route of immunization and the nature of the antigen also contributed to the efficacy of L-particles as immunizing agent. In contrast to that of herpes simplex virus type 1, our data showed EHV-1 non-infectious L-particles are highly suitable for immunization of the host against EHV-1 disease.

• Journal of the korean academy of Pediatric Dentistry
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• v.32 no.3
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• pp.499-508
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• 2005

The purpose of this study were to evaluate the effect on the reversion of sedation induced by midazolam with flumazenil and to determine the plasma concentration of flumazenil according to the method of administration. Intranasal and intravenous flumazenil were administered to sedated health volunteers aged from 23 to 25 years, in doses typical of those used clinically to induce sedation with midazolam and for reversal with flumazenil. Objective assessment for degree of sedation and vital signs, plasma concentration were made for 2 hours period. 1. Systolic and diastolic blood pressure, $SpO_2$ were not changed by adminstration of flumazenil in sedated subject with midazolam, but pulse rate was increased temporarily. 2. Flumazenil showed the reversal of the sedative effect induced by midazolam regardless of administration methods. But intravenous administration showed more effect on the degree and the duration of reversion than intranasal administration with the exception of on set time. 3. Peak plasma concentration of flumazenil administered by intranasal route reached after 2 min and that of flumazenil administered by intravenous route was 4 min. Thus uptake of flumazenil did not showed any difference in accordance with the adminstration route. 4. Administration of flumazenil resulted in the temporary increase of midazolam plasma concentration.