• The Korean Journal of Pain
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• 제19권2호
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• pp.137-141
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• 2006

Background: It has been known that melatonin is involved in the modulation of nociceptive transmission. However, the effect of melatonin administered spinally has not been examined. Therefore, we examined the effect of melatonin on the formalin-induced or thermal-induced nociception at the spinal level. Methods: Intrathecal catheter was inserted into the subarachnoid space of male Sprague-Dawley rats. Pain was assessed by formalin test (induced by injection of $50{\mu}l$ of a 5% formalin solution to the hindpaw) or Hot-Box test (induced by radiant heat application to the hindpaw). The effect of intrathecal melatonin was examined on flinching behavior in the formalin test or withdrawal response in Hot-Box test. Results: Intrathecal melatonin produced a limited, but dose-dependent reduction of the flinching response during phase 1 and 2 in the formalin test. In addition, melatonin delivered at evening also decreased the flinching response in both phases of the formalin test. Melatonin restrictively increased the withdrawal latency in Hot-Box test. Conclusions: These results suggest that melatonin is active against the formalin- and thermal-induced nocicpetion at the spinal level, but the effect is limited.

• 한국어업기술학회:학술대회논문집
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• 한국어업기술학회 2000년도 춘계수산관련학회 공동학술대회발표요지집
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• pp.233-234
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• 2000

Formalin, 37% formaldehyde, has been employed as a chemical for controlling ectoparasites and aquatic fungi responsible for infectious fish of diseases in hatcheries and culture facilities (Roberts, 1978; Schnick, 1991; Rach et al., 1997). Regarding the commercial usage of formaldehyde in the aquaculture industry, the U.S. Food and Drug Administration (FDA) approved three commercial products as parasiticides in a species-specific manner: Paracide-F and Formalin-F for bluegill, catfish, largemouth bass, salmon, and trout and Parasite-S for all finfish (FDA, 1998). Withdrawal time for these products was legally zero when used as permitted under the regulations. With the increased production of cultured fish in Korea, such as olive Hounder Paralichthys olivaceus and black rockfish Sebastes schlegeli, application of formalin to diseased fish has become more frequent. Moreover, there is still some concern about environmental exposures caused by effluents from fish culture facilities. The purpose of the present study was to evaluate residues in fish resulting from therapeutic usage of formalin in the aquaculture industry and to document the rate of disappearance of formaldehyde in seawater treated with formalin. (omitted)

• 한국어병학회지
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• 제10권1호
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• pp.53-63
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• 1997

본 실험에서는 두 온도 조건(15, $25^{\circ}C$)하에서 포르말린과 중성 포르말린(0, 50, 100, 150, 200, 300 ppm)으로 약욕한 넙치(Paralichthys olivaceus)의 회복에 필요한 시간을 알아보기 위해 아가미와 신장의 병리 조직학적인 관찰과 혈액내 변형 적혈구율이 조사되었다. 모든 실험구에서 포르말린이 중성 포르말린보다 독성이 강하게 나타났고, 낮은 농도(50~100 ppm)에서는 병변이 아중증까지 진행되지 않았다. 예상대로, 약욕 농도와 온도가 증가할수록 회복시간이 길어졌다. 약욕에 의한 아가미의 병변은 부종, 2차 새변의 뒤틀림, 상피세포의 박리, 혈전 증상이 나타나고 신장에서는 부종, 수증성 퇴행성 병변, 초자적 변성이 일어났다. 대표적으로, 포르말린과 중성 포르말린 300 ppm에 침지된 어류의 아가미 조직 회복시간은 $25^{\circ}C$조건의 포르말린에서는 약 120시간, 중성 포르말린에서는 72시간과 $15^{\circ}C$조건의 포르말린에서는 72시간, 중성 포르말린에서는 48시간 정도였다. 신장 조직의 회복은 $25^{\circ}C$조건 포르말린에서는 72시간, 중성 포르말린에서는 48시간 정도였고 $15^{\circ}C$조건의 포르말린과 중성 포르말린에서는 다같이 48시간 정도였다. 혈액내 변형적혈구율의 최대 수치는 $25^{\circ}C$ 수온조건, 포르말린 300 ppm 구에서 27.84%로 나타났다. 변형적혈구율의 감소 추세는 조직의 회복과 비슷한 양상을 보였다.

• Journal of Yeungnam Medical Science
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• 제4권2호
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• pp.113-120
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• 1987

백서에서 formalin의 방광점막하주사가 상피의 탈락을 일으키는지의 여부와 기타 방광벽에 나타나는 변화를 알아보기 위하여 건강한 Sprague-Dawley 수컷 흰쥐(체중 350gm 내외) 36마리를 3군으로 나누어 Nembutal 복강내 마취하에 방광을 노출한 다음 생리적 식염수, 10% formalin과 4% formalin을 각각 0.01ml씩 각군 동물의 방광점막하에 주사한 후 1일, 2일, 3일, 1주, 2주 그리고 4주째에 방광을 적출하여 방광벽에 나타나는 육안적, 병리조직학적 소견을 관찰하여 다음과 같은 결과를 얻었다. 1. 10% formalin 주사군에서는 제 1주부터 4% formalin 주사군과 생리적 식염수 주사군에서는 제 2주부터 방광결석 형성을 볼 수 있었다. 2. 10% formalin 주사군과 4% formalin 주사군에 있어서 조직학적 소견의 차이는 없었다. 3. Formalin 주사군에서는 점막궤양 또는 현저한 정막붕괴가 24시간째에 나타나고 점막재생은 제 2일부터 시작하여 제 3일에 현저하였고 제 1주에는 거의 정상적인 상피화를 보였다. 4. 상피하 부종, 혈판확장 및 염증반응은 24시간 째에 현저하였고, 상피하 부종은 제 1주까지, 혈판확장과 염증반응은 제4주까지 중등도로 지속되었다. 섬유아세포증식은 제2일부터 나타나 제4주까지 중등도로 지속되었다. 5. 본 실험중 동물이 죽거나 방광천공을 일으킨 예는 없었다. 이상의 결과로 미루어보아 formalin의 방광점막하 주사는 이로 인해 파괴되는 조직의 범위와 그 재생과의 관계가 보다 명백히 규명되면 재발성 표재성 방광암 환자의 선별적인 예의 치료에 응용해, 볼 가치가 있을 것으로 생각된다.

• The Korean Journal of Pain
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• 제14권1호
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• pp.1-6
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• 2001

Background: Subcutaneous injection of 5% formalin into the hind paw of the rat produces a biphasic nociceptive response. The second phase depends on changes in the dorsal horn cell function that occur shortly after an initial C-fiber discharge, spinal sensitization, or windup phenomenon. This study was performed to investigate the role of glutamate during spinal sensitization. Methods: Sprague-Dawley rats weighing 200 to 250 g were used for this study. Under light anesthesia (0.5% isoflurane) the rats were segregated in a specially designed cage and $50{\mu}l$ 0.5% formalin was injected subcutaneously in the foot dorsum of right hindlimb. Forty minutes after the formalin injection, the rat was quickly decapitated and spinal cord was removed. The spinal segments at the level of L3 (largest area) was collected and stored in a deep freezer ($-70^{\circ}C$). The mRNA gene expression of N-methyl-D-aspartate receptor (NMDAR) and the metabotropic glutamate receptor subtype 5 (mGluR5) were determined by the polymerase chain reaction. Results: The number of flinches was $19.8{\pm}2.3/min$. at one minute after formalin injection and decreased to zero after then. The second peak appeared at 35 and 40 minutes after formalin injection. The values were $17.8{\pm}2.2$ and $17.2{\pm}3.0/min$. The mRNA gene expressions of NMDAR and mGluR5 were increased by $459.0{\pm}46.8%$ (P < 0.01) and $111.1{\pm}4.8%$ (P > 0.05) respectively at 40 minutes after formalin injection. The increased rate of NMDAR was significantly higher than that of mGluR5 (P < 0.01). Conclusions: From these results it suggested that NMDAR partly contributed to the mechanism of central sensitization after the formalin test but mGluR5 did not.

• The Korean Journal of Pain
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• 제24권3호
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• pp.131-136
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• 2011

Background: Pregabalin is an anticonvulsant and analgesic agent that interacts selectively with the voltage-sensitive-$Ca^{2+}$-channel alpha-2-delta subunit. The aim of this study was to evaluate whether the analgesic action of intrathecal (IT) pregabalin is associated with KATP channels in the rat formalin test. Methods: IT PE-10 catheters were implanted in male Sprague-Dawley rats (250.300 g) under inhalation anesthesia using enflurane. Nociceptive behavior was defined as the number of hind paw flinches during 60 min after formalin injection. Ten min before formalin injection, IT drug treatments were divided into 3 groups: normal saline (NS) $20\;{\mu}l$ (CON group); pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $10\;{\mu}l$ (PGB group); glibenclamide $100\;{\mu}g$ in DMSO $5\;{\mu}l$ with pregabalin 0.3, 1, 3 and $10\;{\mu}g$ in NS $5\;{\mu}l$ (GBC group). All the drugs were flushed with NS $10\;{\mu}l$. Immunohistochemistry for the $K_{ATP}$ channel was done with a different set of rats divided into naive, NS and PGB groups. Results: IT pregabalin dose-dependently decreased the flinching number only in phase 2 of formalin test. The log dose response curve of the GBC group shifted to the right with respect to that of the PGB group. Immunohistochemistry for the $K_{ATP}$ channel expression on the spinal cord dorsal horn showed no difference among the groups 1 hr after the formalin test. Conclusions: The antinociceptive effect of pregabalin in the rat formalin test was associated with the activation of the $K_{ATP}$ channel. However, pregabalin did not induce $K_{ATP}$ channel expression in the spinal cord dorsal horn.

• 한국수산과학회지
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• 제46권6호
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• pp.923-929
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• 2013

Black seabream juveniles Acanthopagrus schlegelii held at $20^{\circ}C$ were exposed to formalin at concentrations of 50 to 400 ppm, and tolerance values were determined by calculating median lethal concentration values (LC50) through probit analysis. The 12-, 24, 48, 72- and 96-h LC50 values for formalin were 297, 233, 171, 162 and 157 ppm, respectively. The histological effects of formalin on gill and liver tissues in this fish were determined. No histological effects were observed in the control group. The intensity of cell damage increased with the concentration of, and duration of exposure to, formalin. Hyperplasia, separation and epithelial necrosis, epithelial lifting, lamellar synechiae and collapsed lamellae were observed in gill tissues exposed to formalin. Hepatic lesions in liver tissues of fishes exposed to formalin were characterized by cloudy swelling of hepatocytes, necrosis, cytoplasmic vacuolization, deposition of pigments, spongiosis hepatis, nuclear hypertrophy, dilation of sinusoids and bile stagnation. The LC50 values and histological results obtained in this study will aid in designing treatment regimens to minimize toxic side effects and increase efficacy.

• International Journal of Oral Biology
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• 제41권4호
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• pp.191-197
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• 2016

The present study was to evaluate effects of vitamin E on intravenous administration of lidocaine-induced antinociception. Experiments were carried out using male Sprague-Dawley rats. Orofacial formalin-induced nociceptive behavioral responses were used as the orofacial animal pain model. Subcutaneous injection of formalin produced significant nociceptive scratching behavior. Intraperitoneal injection of 5 and 10 mg/kg of lidocaine attenuated formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. Intraperitoneal injection of 1 g/kg of vitamin E also attenuated the formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. However, low dose of vitamin E (0.5 g/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. The present study also investigated effects of intraperitoneal injection of both vitamin E and lidocaine on orofacial formalin-induced behavioral responses. Vehicle treatment affected neither formalin-induced behavioral responses nor lidocaine-induced antinociceptive effects. However, intraperitoneal injection of 0.5 g/kg of vitamin E enhanced the lidocaine-induced antinociceptive effects in the 2nd phase compared to the vehicle-treated group. Intraperitoneal injection of naloxone, an opioid receptor antagonist, did not affect antinociception produced by intraperitoneal injections of both vitamin E and lidocaine. These results suggest that treatment with vitamin E enhances the systemic treatment with lidocaine-induced antinociception and reduces side effects when systemically treated with lidocaine. Therefore, the combined treatment with vitamin E and lidocaine is a potential therapeutic for chronic orofacial pain.

• 한국양식학회지
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• 제19권2호
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• pp.90-94
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• 2006

The effects of formalin on mixed function oxygenase (MFO) system and stress-response were investigated in olive flounder (Paralichthys olivaceus). Olive flounder was exposed to formalin at the concentration of 300 ppm for 1, 2, 4 and 16 h. Levels of stress-response enzymes together with total protein, glucose and osmolality were quantitatively determined in blood, and the activities of phase I (cytochrome P450, ethoxyresorufin deethylase) and phase II (glutathione S-transferase) hepatic enzymes were also determined. Since the formalin-exposure for 16 h resulted no significant changes in aspartate aminotransferase and alanine aminotransferase, specific enzymes for liver damage, it was thought that it did not cause hepatic tissue damage at the concentration of 300 ppm. However, hepatic MFO system was induced at 1 to 4 h, and stress response was induced after 16 h of exposure. Moreover, it is considered that the depression of MFO activity after 16 h of exposure may not be adaptation to formalin, but toxic response. These results suggest that low concentration of formalin does not cause hepatic tissue damage of fish, but could induce MFO and stress response.

• Archives of Pharmacal Research
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• 제28권2호
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• pp.227-231
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• 2005

We examined the effect of the subcutaneous (s.c.) pretreatment of formalin into both hind paws of mice on the antinociception induced by the intracerebroventricularly (i.c.v.) or intrathecally (i.t.) administration of ${\beta}$-endorphin using the tail-flick test. Pretreatment with formalin ($5\%$) for 5 h had no affect on the i.c.v. administered ${\beta}$-endorphin-induced tail-flick response. However, pretreatment with formalin for 40 h attenuated the tail-flick inhibition induced by i.c.v. administered ${\beta}$-endorphin. This antinociceptive tolerance to i.c.v. ${\beta}$-endorphin continued up to 1 week, but to a lesser extent. Pretreatment with formalin for 5 and 40 h significantly reduced the i.t. ${\beta}$-endorphin-induced inhibition of the tail-flick response, which continued up to 1 week. The s.c. formalin treatment increased the hypothalamic pro-opiomelanocortin (POMC) mRNA level at 2 h, but this returned to the basal level after 40 h. Our results suggest that the increase in the POMC mRNA level in the hypothalamus appears to be involved in the supraspinal or spinal ${\beta}$-endorphin-induced antinociceptive tolerance in formalin-induced inflammatory pain.