• Archives of Pharmacal Research
• /
• 제17권4호
• /
• pp.263-268
• /
• 1994

This study was conducted to characterize the in vivo pharmacology of KR-30988, KR-30992 and losartan, new AT antagonists, given as i.v. cumulative doses, in two antimal models of high renin, conscious renal artery-ligated hypertensinve rats (RHRs) and nomotensive rats anesthetized with urethane (90 mg/kg, i.p.) and .alpha.-chloralose (90 mg/kg, i.p.), with a special emphasis on the phamacological characterization of the latter model. In conscious RHRs, KR-30988, KR-30992, losartan and captopril caused a dose-dependent decrease in blood pressure, their relative potencise ($ED_{20}$) being 0.057, 0.028, 0164 and 0.018 mg/kg, i.v., repectively. In anesthetized rats, 2 hours after anesthesia, plasma renin activity was increased from 7.31 tp 34.07 ng/ml/h, the level approximately 1.5 times greater than the highest level in RHRs. In anesthtized rats, the $ED_{20}$s for all four compounds were 0.004 mg/kg i.v., respectively. By comparison, $ED_{20}$sfrom anesthetized rats were 4 to 5 times smaller than those from conscious RHRs, with a good correlation (.gamma. = 0.999) noted between thetized rats to the hypotensive activity of the compounds and the same order of potencies intwo models. These results suggest that, in addition to PHRs, the normotensive rats anesthetized as above can serve as a suitable model for the rapid phamacological evaluation of $AT_1$ receptor antagonists.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4071-4075
• /
• 2013

Expression changes of somatostatin receptor subtypes (SSTRs) including SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5 in the development of gallbladder cancer were assessed with attention to relationships with clinical pathological characteristics. SSTRs in 29 gallbladder cancer and 25 normal gallbladder tissue specimens were examined by immunohistochemical staining. Differences between SSTRs expressions and clinical pathological parameters were analyzed by chi-square test. The five subtypes of SSTR were all expressed in gallbladder cancer tissues and SSTR3 presented the highest expression. SSTR5 expression was increased significantly in gallbladder cancer (P<0.05) compared with that in normal gallbladder tissue. SSTR3 expression in highly and moderately differentiated gallbladder cancer was significantly higher than that in poorly differentiated lesions (P<0.05). SSTR4 expression was lower in gallbladder cancer with lymph node metastasis than that in gallbladder cancer without lymph node metastasis (P<0.05). Therfore, these results indicated that SSRT5, SSTR3 and SSTR4 may play important roles in the formation and development of gallbladder cancer.

• 대한약리학회지
• /
• 제22권2호
• /
• pp.88-95
• /
• 1986

백서에서 열판법을 이용하여 과민동통을 일으키는 약물로 알려진 phenobarbital의 동통에 대한 효과를 재검토하고 그 기전을 알고저 phenobarbital 단기 또는 장기처리에 의한 뇌내 ${\beta}-endorphin$함량, opiate 수용체 및 시험관내 실험으로 functional opiate 수용체의 변동유무를 검토하여 다음과 같은 결과를 얻었다. 1) 마취에 미달하는 용량의 phenobarbital 1회 복강내 투여는 일시적인 HPL단축에 이어 이를 지연시켰고 phenobarbital 장기 처리는 HPL을 현저히 지연시켰다. 2) Naloxone 자체는 HPL을 현저히 단축시켰고, naloxone처리는 phenobarbital의 HPL 지연 효과를 억제하였다. 3) Phenobarbital 1회 복강내 투여는 뇌내 ${\beta}-endorphin$ 함량에 영향을 미치지 못하였으나 phenobarbital 장기처리는 이를 현저히 증가시켰다. 4) Phenobarbital 1회 복강내 투여는 [3H]-morphine binding에 영향을 미치지 못하였으나, phenobarbital 장기처리는 Kd치와는 달리 Bmax를 현저히 감소시켰다. 5) Phenobarbital 장기처리에 의한 HPL변동, 뇌내 ${\beta}-endorphin$함량변동 그리고 opiate receptor Bmax변동 삼자간에는 유의한 상관관계가 있었다. 6) 적출vas deferens 표본에서 phenobarbital 장기처리는 morphine의 ID50은 증가시키고 maximum effect는 감소시키나 naloxone에 대한 $pA_2 $치에는 영향을 미치지 못하였다. 이상의 실험성적은 phenobarbital이 일시적인 과민동통 효과에 이어 진통효과를 갖고 있으며, phenobarbital의 진통효과는 뇌내 ${\beta}-endorphin$함량 증가와 이로 인한 functional opiate 수용체의 숫적 변동에 기인함을 시사하였다.

• Clinical and Experimental Reproductive Medicine
• /
• 제47권2호
• /
• pp.122-129
• /
• 2020

Objective: The survival of a semi-allogeneic fetus depends on several immunological mechanisms, and it has been suggested that recurrent pregnancy loss (RPL) could develop as a result of one or more immunological abnormalities. Methods: Compatibility between partners for human leukocyte antigen (HLA) genotypes and the relationships between maternal killer-cell immunoglobulin-like receptor (KIR) and paternal HLA-Bw4/Bw6 and HLA-C1/C2 supra-groups were investigated in 25 couples with RPL in comparison to healthy couples with children. HLA and KIR genotyping was performed using polymerase chain reaction with sequence-specific primers and/or sequence-specific oligonucleotides. Results: HLA class I incompatibility between partners, especially in HLA-B alleles, was more common in the RPL group (p= 0.01). HLA-C2 homozygosity was more frequent in the male partners of RPL couples than in other groups (p= 0.03). The KIR2DL5 gene frequency was significantly higher in both the female and male partners of RPL couples, whereas the KIR2DS3 gene frequency in male partners of RPL couples was significantly reduced (p= 0.03). The presence of KIR2DL3 in women with RPL was correlated with the presence of HLA-C2 alleles in their spouses (p= 0.03). Conclusion: Our data from a Turkish population suggest that male HLA-C2 homozygosity may play an important role in RPL. Additionally, an incidental match between male HLA-C2 and female HLA-C1 ligand KIR receptors might perturb the balance between activatory and inhibitory KIR-ligand interactions during pregnancy in couples affected by RPL. The roles of orphan KIR2DL5 and orphan KIR2DS3 in RPL remain obscure.

• 약학회지
• /
• 제58권2호
• /
• pp.141-149
• /
• 2014

Background: Oriental lifestyle for treating diseases has been developed and well-accepted for a long time among Koreans. Sasang Constitution theory, originated from Korean traditional medicine, suggests that medication treatment should be differentiated by each patient's body classification (So-yang [SY], So-eum [SE], Tae-yang [TY], and Tae-eum [TE]), in contrary to western medicine's theory that medication should be applied equally by disease indication without such classification. However, the pharmacotherapeutic outcomes of these theories have not been compared to date. In this study, we aimed to compare the two theories by evaluating blood pressure (BP), which is lowered as a therapeutic outcome, among hypertensive patients taking angiotensin II receptor blockers (ARBs) or calcium channel blockers (CCBs), two most commonly used antihypertensive classes in Korea. Methods: From April 2006 to June 2012, we retrospectively collected data on hypertensive patients with Sasang Constitution classification at Kyunghee University Hospital at Gangdong, one of the East-West collaborative medical centers in Korea. We collected information on age, gender, underlying diseases, antihypertensive drugs (ARB, CCB, ARB+CCB), and BP by reviewing the electronic medical records. We excluded patients with missing blood pressure at baseline or follow-up, or those who had a change in their antihypertensive drug class during follow-up. Results: We selected a total of 573 patients (SY: 165, SE: 158, TY: 0, TE: 250). Baseline BPs were on average 139.0/82.0 mmHg for SY, 137.8/78.5 mmHg for SE, and 138.7/79.2 mmHg for TE. In all three groups, CCBs were the most prescribed, followed by combination therapy with ARB+CCB, then ARBs. BP reduction after 1 month of initial medication was significantly different among the drug classes, but not in Sasang constitutional classification (ARB [SY: -12.4/-4.7, SE: -12.3/-2.5, TE: -8.6/-1.8], CCB [SY: -12.3/-5.4, SE: -13.0/-2.3, TE: -10.8/-6.0], ARB+CCB [SY: -15.6/-6.7, SE: -18.4/-8.1, TE: -20.2/-6.7], drug [$P{\leq}0.05$/P>0.05], constitutional type [P>0.05/P>0.05]). Conclusion: We observed significant differences in reduction of blood pressure by classes of drugs (ARB+CCB>CCB>ARB) but not by Sasang constitutional classification. Therefore, current approach of antihypertensive pharmacotherapy assisted by Western medicine is appropriate for treatment of hypertension. However, further larger scale or prospective studies are required in order to confirm these results.

• Bulletin of the Korean Chemical Society
• /
• 제29권2호
• /
• pp.417-421
• /
• 2008

The efficient synthesis of four mesitylene-based receptors 1-4 and their potentiometric response characteristics to alkali metal, alkaline earth metal, and transition metal ions, under various pH conditions are outlined. Receptor 1-based electrode exhibited more sensitive response to Ag+ ion (49 mV/decade of range from 10-6 to 10-2 M) than the 2-based electrode (47 mV/decade of range from 3 ´ 10-5 to 10-2 M), while the 3- and 4-based ones revealed sub-Nernstian below 40 mV/pAg+. All electrodes showed substantial responses to Ag+ ion under acidic condition, but there was almost nil-response to other transition metal ions (Fe2+, Co2+, Zn2+, Ni2+, Pb2+, Cd2+, Cu2+ and Hg2+). The association constant of receptor 1 toward Ag+ ion, measured by 1H NMR titration, showed the largest value (200 M-1) among the tested receptors. The results were interpreted with semi empirically-modeled structures.

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

• 한국안광학회지
• /
• 제5권2호
• /
• pp.157-161
• /
• 2000

광원의 세기가 다른 조건하에서 눈의 시감효율은 추상체와 간상체에 의해 파장에 따라 2개의 함수로 이루어진다. 광자에 대한 추상체-간상체의 반응확률을 이용하여 $P({\lambda})=A{\cdot}e^{-({\lambda}-{\lambda}_0)^2/2W^2}$의 분포함수 수식을 유도하였다. 이 식은 파장에 따른 CIE의 눈의 시감효율 곡선에 잘 적용되며 상대 시감효율의 경우 photopic의 경우 A=106.4, ${\lambda}_0=559.2$, W=83.5이고 scotopic의 경우 A=99.3, ${\lambda}_0=502.6$, W=79.5의 값을 얻었다. 1m/W의 단위를 사용하는 시감효능 곡선에서는 photopic의 경우 $A=7.2{\times}10^4$, ${\lambda}_0=559.2$, W=86.5이고 scotopic의 경우 $A=1.6{\times}10^5$, ${\lambda}_0=502.6$, W=79.5의 값을 얻었다.

• The Korean Journal of Physiology and Pharmacology
• /
• 제7권2호
• /
• pp.59-63
• /
• 2003

The medial vestibular nucleus (MVN) neurons are controlled by excitatory synaptic transmission from the vestibular afferent and commissural projections, and by inhibitory transmission from interneurons. Spontaneous synaptic currents of MVN neurons were studied using whole cell patch clamp recording in slices prepared from 13- to 17-day-old rats. The spontaneous inhibitory postsynaptic currents (sIPSCs) were significantly reduced by the $GABA_A$ antagonist bicuculline ($20{\mu}M$), but were not affected by the glycine antagonist strychnine ($1{\mu}M$). The frequency, amplitude, and decay time constant of sIPSCs were $4.3{\pm}0.9$ Hz, $18.1{\pm}2.0$ pA, and $8.9{\pm}0.4$ ms, respectively. Spontaneous excitatory postsynaptic currents (sEPSCs) were mediated by non-NMDA and NMDA receptors. The specific AMPA receptor antagonist GYKI-52466 ($50{\mu}M$) completely blocked the non-NMDA mediated sEPSCs, indicating that they are mediated by an AMPA-preferring receptor. The AMPA mediated sEPSCs were characterized by low frequency ($1.5{\pm}0.4$ Hz), small amplitude ($13.9{\pm}1.9$ pA), and rapid decay kinetics ($2.8{\pm}0.2$ ms). The majority (15/21) displayed linear I-V relationships, suggesting the presence of GluR2-containing AMPA receptors. Only 35% of recorded MVN neurons showed NMDA mediated currents, which were characterized by small amplitude and low frequency. These results suggest that the MVN neurons receive excitatory inputs mediated by AMPA, but not kainate, and NMDA receptors, and inhibitory transmission mediated by $GABA_A$ receptors in neonatal rats.

• 생물정신의학
• /
• 제3권1호
• /
• pp.51-56
• /
• 1996

The effects of 3 week treatment with haloperidol(2mg/kg/day, i.p.) on dopamine(DA) D2 receptor and DA metabolism in rat striata were studied at various time points after withdrawal from the drug treatment. Striatal DA D2 receptors were characterized with the radioligand 0.5nM [$^3H$]Spiperone. Dopamine(DA), homovanillic acid(HVA), 3,4-dihydroxyphenyl acetic acid(DOPAC) in rat striatum were measured with the high performance liquid chromatography. Drug withdrawal for 1 week induced significant increase in the number of D2 receptor in striatum after withdrawal for 1 week(p<0.05), and then this change was restored to control level during the withdrawal time of 2 and 4 weeks. There was no difference in striatal concentrations of DA and its metabolites among the groups. In conclusion, one-week withdrawal from chronic haloperidol treatment induced DA D2 receptor supersensitivity in the striatum, and that was normalized rapidly. Though this adaptive change in DA receptors, it may not affect the metabolism of DA in striatum.