• Clinical and Experimental Pediatrics
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• v.60 no.9
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• pp.273-281
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• 2017

To date, preterm infants with respiratory distress syndrome (RDS) after birth have been managed with a combination of endotracheal intubation, surfactant instillation, and mechanical ventilation. It is now recognized that noninvasive ventilation (NIV) such as nasal continuous positive airway pressure (CPAP) in preterm infants is a reasonable alternative to elective intubation after birth. Recently, a meta-analysis of large controlled trials comparing conventional methods and nasal CPAP suggested that CPAP decreased the risk of the combined outcome of bronchopulmonary dysplasia or death. Since then, the use of NIV as primary therapy for preterm infants has increased, but when and how to give exogenous surfactant remains unclear. Overcoming this problem, minimally invasive surfactant therapy (MIST) allows spontaneously breathing neonates to remain on CPAP in the first week after birth. MIST has included administration of exogenous surfactant by intrapharyngeal instillation, nebulization, a laryngeal mask, and a thin catheter. In recent clinical trials, surfactant delivery via a thin catheter was found to reduce the need for subsequent endotracheal intubation and mechanical ventilation, and improves short-term respiratory outcomes. There is also growing evidence for MIST as an alternative to the INSURE (intubation-surfactant-extubation) procedure in spontaneously breathing preterm infants with RDS. In conclusion, MIST is gentle, safe, feasible, and effective in preterm infants, and is widely used for surfactant administration with noninvasive respiratory support by neonatologists. However, further studies are needed to resolve uncertainties in the MIST method, including infant selection, optimal surfactant dosage and administration method, and need for sedation.

• Journal of Environmental Health Sciences
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• v.39 no.1
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• pp.48-55
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• 2013

Objective: The use of nanoparticle products is expected to present a potential harmful effect on consumers. Also, the lack of information regarding inhaled nanoparticles may pose a serious problem. In this study, we addressed this issue by studying pulmonary toxicity after nasal instillation of Al-NPs in SD rats. Methods: The animals were exposed to Al-NPs at 1 mg/kg body weight (low dose), 20 mg/kg body weight (medium dose) and 40 mg/kg body weight (high dose). To determine pulmonary toxicity, bronchoalveolar lavage (ts.AnBAL) fluid analysis and histopathological examination were conducted in rats. In addition, cell viability was investigated at 24 hours after the treatment with Al-NPs. Results: BAL fluid analysis showed that total cells (TC) count and total protein (TP) concentrations increased significantly in all treatment groups, approximately two to three times. Also, lactate dehydrogenase (LDH) and cytokines such as TNF-alpha and IL-6 dose-dependently increased following nasal instillation of Al-NPs. However, polymorphonuclear leukocytes (PMNs) levels showed no significant changes in a dose dependant manner in BAL fluid. In the cytotoxicity analysis, the treatment of Al-NPs significantly and dose-dependently induced cell viability loss (20 to 30%) and damage of cell membrane (5 to 10%) in rat normal lung epithelial cells (L2). Conclusions: Our results suggest that inhaled Al-NPs in the lungs may be removed quickly by alveolar macrophages with minimal inflammatory reaction, but Al-NPs have the potential to affect lung permeability. Therefore, extensive toxicity evaluations of Al-NPs are required prior to their practical application as consumer products.

• Toxicological Research
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• v.29 no.3
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• pp.181-185
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• 2013

Aluminum nanoparticles (Al-NPs) are one of the most widely used nanomaterial in cosmetics and medical materials. For this reason, Al-NP exposure is very likely to occur via inhalation in the environment and the workplace. Nevertheless, little is known about the mechanism of Al-NP neurotoxicity via inhalation exposure. In this study, we investigated the effect AL-NPs on the brain. Rats were exposed to Al-NPs by nasal instillation at 1 mg/kg body weight (low exposure group), 20 mg/kg body weight (moderate exposure group), and 40 mg/kg body weight (high exposure group), for a total of 3 times, with a 24-hr interval after each exposure. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that the presence of aluminum was increased in a dose-dependent manner in the olfactory bulb (OFB) and the brain. In microarray analysis, the regulation of mitogen-activated protein kinases (MAPK) activity (GO: 0043405), including Ptprc, P2rx7, Map2k4, Trib3, Trib1, and Fgd4 was significantly over-expressed in the treated mice than in the controls (p = 0.0027). Moreover, Al-NPs induced the activation of ERK1 and p38 MAPK protein expression in the brain, but did not alter the protein expression of JNK, when compared to the control. These data demonstrate that the nasal exposure of Al-NPs can permeate the brain via the olfactory bulb and modulate the gene and protein expression of MAPK and its activity.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.59-66
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• 1994

The objective of this study was to determine the influence of drug lipophilicity on the extent of ocular and systemic absorption following topical solution instillation in the pigmented rabbit. ${\beta}-Blockers$ of various lipophilicity were chosen as model drugs, $25\;{\mu}l$ of a 15 mM drug solution in isotonic pH 7.4 buffer was instilled, and ocular tissue and plasma drug concentrations were monitored. Ocular absorption was apparently increased in all eye tissues, but non-corneal absorption ratio was decreased by increasing of drug lipophilicity. Systemic bioavailability was ranged from 61% for atenolol to 100% for timolol, and at least 50% of the systemically absorbed drug reached the blood stream from the nasal mucosa. Occluding the nasolacrimal duct for 5 min reduced the extent of systemic absorption of timolol and levobunolol, but did not do so for atenolol and betaxolol. Taken together, the ocular absorption of topically applied ophthalmic drugs would be modest for lipophilic drugs. By contrast, the systemic bioavailability would be modest for drugs at the extremes of lipophilicity, and the nasal contribution to systemically absorbed drug diminished with increasing of drug lipophilicity.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.20-35
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• 2008

Objective : This study was designed to investigate the effects of Curcuma longa Rhizoma(CLR) on asthma. Methods : Detecting splenocyte proliferation rates, cytokines and antigen specific antibody isotypes in bronchoalveolar lavage fluid (BALF). In addition, the present author I also investigated changes in spleen and histopathological changes of lung tissues. Results : Oral administration of CLR lowered spleen weight and splenocyte proliferation rates. In addition, levels of IL-4, IL-17A and Granulocyte/Macrophage Colony-Stimulating Factor(GM-CSF), Th2 driven cytokines, were lowered respectively and IFN-g, and Th1 driven cytokine, were elevated by CLR. Levels of Ovalbumin(OVA) specific IgE and IgGl in BALF were also lowered by oral administration of CLR too. Conclusion : CLR is useful to treat patients with asthma and the mechanisms are related to the in suppression of Th2 skewing reactions.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.1
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• pp.38-54
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• 2008

Objective : This study was designed to investigated effects of Pinelliae Rizoma (PR) on asthma Methods : Detecting antigen specific antibody isotypes, cytokines in serum and bronchoalveolar lavage fluid (BALF). In addition, the present author also investigated changes in weight of spleen and proliferation rates of splenocytes. Finally, histopathological observation of the lung tissue was also investigated. Results : Oral administration of PR lowered OVA specific IgE levels in serum, IgG1 levels in serum and BALF. PR also decreased production levels of IL-4 in BALF. In addition, total cells in BALF were decreased by oral administration of PR effectively. In histapathological observation, PR group showed downward tendency of inflammatory cell infiltration around small vessels. Conclusion : PR is useful to treat patients with asthma and the mechanisms are related in suppression of Th2 skewing reactions.

• Korean Journal of Veterinary Research
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• v.37 no.4
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• pp.793-807
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• 1997

We tried to develop detection system of porcine reproductive and respiratory syndrome virus(PRRSV) by in situ hybridization(ISH) in the piglets experimentally infected with KPRRS-2, the Korean isolate(12 piglets) or Mn-1b, the American isolate(4 piglets), and in the natural infection suspected 6 piglets. Twelve 30-days-old piglets(two pigs per each inoculated group) were inoculated by nasal instillation of KPRRS-2 virus(total dose $10^{4.5}TCID_{50}$), Six piglets(one pig per each group) were induced contact infection with inoculated piglets, during the experiment, and two piglets were used as control. Inoculated or contacted piglets were euthanized at 1, 3, 5, 7, 14 and 21 days postinoculation(DPI). The respiratory signs such as coughing and nasal discharge were observed on day 3 DPI, and ear cyanosis were on day 5 DPI, including contacted piglets. Through the necropsy, purple discolorization of dorsal part of lung, and hypertrophy of local lymph nodes were observed. The histopathological lesions of lung were interstitial pneumonia characterized by type 2 pneumocyte hyperplasia. We prepared the probe for ISH by RNA isolation from KPRRS-2, RT-PCR, and biotin labeling. We performed the ISH within only 1~2 hours using $Microprobe^{TM}$ capillary action system. As the results, the strong red specific positive signals, means PRRSV distribution, was mainly observed in the cytoplasm of alveolar macrophages. And also signals were detected in some type 2 pneumocytes and bronchiolar epithelium of lung, myocardium, liver, kidney, tonsil, spleen, gastrointestinal mucosa, testis and lymph nodes.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.36-51
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• 2008

Objective : This study investigated the effects of PR(Pinelliae Rhizoma) on gene expression of lung tissue resected from asthma induced mice using intra-nasal instillation. Methods : Gene expression levels were measured using a microarray technique, and a functional analysis on these genes was conducted. Results : A total of 3270 genes were up-regulated or down-regulated, 860 genes which were lowered by induction of asthma were restored to those of naive animals, Furthermore hand, 1235 genes were lowered to normal levels, which were elevated by induction of asthma. Most of changed genes were involved in signalling pathways. Genes in which expression levels were restored by oral administration of PR were involved in MAPK pathway, focal adhesion, and regulation of actin cytoskeleton etc. Genes of which expression levels were lowered by oral administration of PR were involved in rhodopsin-like receptor activity, zinc ion binding and ATP binding. These genes were also involved in neuroactive ligand receptor interaction, the JAK-STAT signaling pathway and also the T-cell receptor signaling pathway. Conclusion : These results demonstrate the strong possibility that the mechanisms of PR on asthma are involved in neuroactive ligand receptor interaction pathway or related molecules.