• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.168-175
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• 2023

Tramadol is an opioid analog used to treat chronic and acute pain. Intradermal injections of tramadol at hundreds of millimoles have been shown to produce a local anesthetic effect. We used the whole-cell patch-clamp technique in this study to investigate whether tramadol blocks the sodium current in HEK293 cells, which stably express the pain threshold sodium channel Na_v1.7 or the cardiac sodium channel Na_v1.5. The half-maximal inhibitory concentration of tramadol was 0.73 mM for Na_v1.7 and 0.43 mM for Na_v1.5 at a holding potential of -100 mV. The blocking effects of tramadol were completely reversible. Tramadol shifted the steady-state inactivation curves of Na_v1.7 and Na_v1.5 toward hyperpolarization. Tramadol also slowed the recovery rate from the inactivation of Na_v1.7 and Na_v1.5 and induced stronger use-dependent inhibition. Because the mean plasma concentration of tramadol upon oral administration is lower than its mean blocking concentration of sodium channels in this study, it is unlikely that tramadol in plasma will have an analgesic effect by blocking Na_v1.7 or show cardiotoxicity by blocking Na_v1.5. However, tramadol could act as a local anesthetic when used at a concentration of several hundred millimoles by intradermal injection and as an antiarrhythmic when injected intravenously at a similar dose, as does lidocaine.

• The Korean Journal of Pain
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• v.36 no.4
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• pp.450-457
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• 2023

Background: Genicular nerve neurolysis with phenol and radiofrequency ablation (RFA) are two interventional techniques for treating chronic refractory knee osteoarthritis (KOA) pain. This study aimed to compare the efficacy and adverse effects of both techniques. Methods: Sixty-four patients responding to diagnostic blockade of the superior medial, superior lateral, and inferior medial genicular nerve under ultrasound guidance were randomly divided into two groups: Group P (2 mL phenol for each genicular nerve) and Group R (RFA 80℃ for 60 seconds for each genicular nerve). The numeric rating scale (NRS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to evaluate the effectiveness of the interventions. Results: RFA and phenol neurolysis of the genicular nerves provided effective analgesia within groups at 1 week, 1 month, and 3 months compared to baseline. There was no significant difference between the groups in terms of NRS and WOMAC scores at all measurement times. At the 3rd month follow-up, 50% or more pain relief was observed in 53.1% of patients in Group P and 50% of patients in Group R. The rate of transient paresthesia was 34.4% in Group P and 6.3% in Group R, and this was significantly higher in Group P. Conclusions: Neurolysis of the genicular nerves with both RFA and phenol is effective in the management of KOA pain. Phenol may be a good alternative to RFA. Further studies are needed on issues such as dose adjustment to prevent transient paresthesia response.

• Journal of Dental Anesthesia and Pain Medicine
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• v.23 no.3
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• pp.153-162
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• 2023

Background: Recent animal studies have suggested the role of GABA type A (GABA-_A) receptors in salivation, showing that GABA-_A receptor agonists inhibit salivary secretion. This study aimed to evaluate the effects of propofol (a GABA-_A agonist) on salivary secretions from the submandibular, sublingual, and labial glands during intravenous sedation in healthy volunteers. Methods: Twenty healthy male volunteers participated in the study. They received a loading dose of propofol 6 mg/kg/h for 10 min, followed by 3 mg/kg/h for 15 min. Salivary flow rates in the submandibular, sublingual, and labial glands were measured before, during, and after propofol infusion, and amylase activity was measured in the saliva from the submandibular and sublingual glands. Results: We found that the salivary flow rates in the submandibular, sublingual, and labial glands significantly decreased during intravenous sedation with propofol (P < 0.01). Similarly, amylase activity in the saliva from the submandibular and sublingual glands was significantly decreased (P < 0.01). Conclusion: It can be concluded that intravenous sedation with propofol decreases salivary secretion in the submandibular, sublingual, and labial glands via the GABA-_A receptor. These results may be useful for dental treatment when desalivation is necessary.

• Journal of Korean Medicine for Obesity Research
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• v.23 no.1
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• pp.28-41
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• 2023

Objectives: This study was aimed to evaluate the hemodynamic feasibility using pulse parameters as a way to establish safe dose guidelines for herbal prescription containing Ephedra herb (Ephedra intermedia Schrenk & C.A.Mey) on weight loss, and to provide a foundation for developing evidence-based guidelines for clinical use. Methods: Forty-two volunteers were recruited to participate in a study examining the changes in pulse wave characteristics following the ingestion of Gambi-hwan, a herbal prescription containing ephedra, over a period of 4 weeks, and pulse wave measurements were taken before and after the administration. Pulse wave parameters were measured in this study using a 3-dimensional radial pulse tonometry device (DMP-Lifeplus). In addition, questionnaire, blood pressure, temperature, and body composition were also measured as secondary measures. Results: Fifteen minutes after administration of Gambi-hwan, the non-adverse event group (non-AE) exhibited a statistically significant increase in several power and pressure-related parameters, including h1, h5, systolic area, pulse area, and pulse width, while the AE group showed a trend of decreasing stroke volume and increasing Radial Augmentation Index (RAI), w, and w/t. After 4 weeks of administration, both groups exhibited significant changes in pulse rate, w/t, RAI, t3/t, stroke volume (SV), and stroke volume Index (SVI). Notably, there are significant differences between AE group and non-AE group in w/t, SV, and SVI. Conclusions: These findings suggest that pulse parameters may be a useful way to establish safe dosing guidelines for weight loss herbal prescription containing ephedra. Further research is needed to confirm these results and to develop evidence-based guidelines for clinical use.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.167-176
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• 2023

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E₂) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E₂ expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.

• Structural Engineering and Mechanics
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• v.88 no.5
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• pp.481-492
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• 2023

The past earthquakes revealed the importance of the design of moment-resisting reinforced concrete framed structures with ductile behavior. Due to seismic activity, failures in framed structures are widespread in beam-column joints. Hence, the joints must be designed to possess sufficient strength and stiffness. This paper investigates the effects of fibers on the ductility of hybrid fiber reinforced self-compacting concrete (HFRSCC) when subjected to seismic actions; overcoming bottlenecks at the beam-column joints has been studied by adding low modulus sisal fiber and high modulus steel fiber. For this, the optimized dose of hooked end steel fiber content (1.5%) was kept constant, and the sisal fiber content was varied at the rate of 0.1%, up to 0.3%. The seismic performance parameters, such as load-displacement behavior, ductility, energy absorption capacity, stiffness degradation, and energy dissipation capacity, were studied. The ductility factor and the cumulative energy dissipation capacity of the hybrid fiber (steel fiber, 1.5% and sisal fiber, 0.2%) added beam-column joint specimen is 100% and 121% greater than the control specimen, respectively. And also the stiffness of the hybrid fiber reinforced specimen is 100% higher than the control specimen. Thus, the test results showed that adding hybrid fibers instead of mono fibers could significantly enhance the seismic performance parameters. Therefore, the hybrid fiber reinforced concrete with 1.5% steel and 0.2% sisal fiber can be effectively used to design structures in seismic-prone areas.

• CELLMED
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• v.13 no.14
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• pp.18.1-18.13
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• 2023

Background and objectives: Bacterial vaginosis (BV) is recognized as the most prevalent type of vaginal infection, impacting approximately 19-24% of women in their reproductive years. The recurrence rate of BV is significant, negatively impacting the well-being of affected women. This study aimed to compare the therapeutic effects of a polyherbal Unani formulation and metronidazole in treating bacterial vaginosis. Methodology: In this prospective patient blinded standard controlled trial, a total of 40 individuals with a clinical diagnosis of bacterial vaginosis were randomly assigned to receive either an active control treatment (n = 20) or a test drug (n = 20). In the test drug combination of Acacia catechu, Azadirachta indica and Quercus infectoria in tablet (1g) form in the dose of 2 tablets orally twice daily with water was administered for 3 weeks. In the active control standard drug, metronidazole 400 mg tablet, orally twice daily was given for one week. The primary outcome measure was clinical cure; H. negative Amsel's criteria and a reduction in subjective symptoms, while the secondary outcome measure was an improvement in SF-36 quality of life (QOL). Results and conclusion: Both the experimental treatment and the metronidazole demonstrated a significant clinical cure for bacterial vaginosis as well as an increase in health-related quality of life. Based on these findings, it appears that the test medication is a potent Unani formulation for the treatment of bacterial vaginosis. A well conducted trial with a bigger sample size is required to corroborate these findings.

• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.634-643
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• 2024

Juglans mandshurica Maxim. walnut (JMW) is well-known for the treatment of dermatosis, cancer, gastritis, diarrhea, and leukorrhea in Korea. However, the molecular mechanism underlying its antiobesity activity remains unknown. In the current study, we aimed to determine whether JMW can influence adipogenesis in 3T3-L1 preadipocytes and high-fat diet rats and determine the antioxidant activity. The 20% ethanol extract of JMW (JMWE) had a total polyphenol content of 133.33 ± 2.60 mg GAE/g. Considering the antioxidant capacity, the ABTS and DPPH values of 200 ㎍/ml of JMWE were 95.69 ± 0.94 and 79.38 ± 1.55%, respectively. To assess the anti-obesity activity of JMWE, we analyzed the cell viability, fat accumulation, and adipogenesis-related factors, including CCAAT-enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). We found that total lipid accumulation and triglyceride levels were reduced, and the fat accumulation rate decreased in a dose-dependent manner. Furthermore, JMWE suppressed adipogenesis-related factors C/EBPα, PPARγ, and SREBP1c, as well as FAS and ACC, both related to lipogenesis. Moreover, animal experiments revealed that JMWE could be employed to prevent and treat obesity-related diseases. Hence, JMWE could be developed as a healthy functional food and further explored as an anti-obesity drug.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.263-272
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• 1994

Since it was been reported that the depolarization-induced ACh release is inhibited by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus, a large body of experimental data on the post-receptor mechanism of this process has been accumulated. But, the post-receptor mechanism of presynaptic $A_1-adenosine$ receptor on the ACh release has not been clearly elucidated yet. Therefore, it was attempted to clarify the post-receptor mechanisms of the $A_1-adenosine$ receptor-mediated control of ACh release in this study. Slices from rat hippocampus were equilibrated with $^3H-choline$ and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 $VCm^{-1}$, 2ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Adenosine, in concentrations ranging from $0.3{\sim}300\;{\mu}M$, decreased the ACh release in a dose-dependent manner, without affecting the basal rate of release. The adenosine effects were significantly inhibited by $DPCPX\;(2\;{\mu}M)$, a selective $A_1-receptor$ antagonist. The responses to N-ethylmaleimide $(10&30{\mu}M)$, a SH-alkylating agent of G-protein, were characterized by increments of the evoked ACh-release and the basal release, and the adenosine effects were completely abolished by NEM pretreatment. PDB $(1{\sim}10\;{\mu}M)$, a specific protein kinase C (PKC) activator, increased, whereas PMB $(0.03{\sim}1\;mg)$, a PKC inhibitor, decreased the evoked ACh-release, and the adenosine effects were not affected by these agents. Nifedipine $(1\;{\mu}M)$, a $Ca^{2+}\;-channel$ blocker of dihydropyridine analogue, significantly inhibited the adenosine effect, but glibenclamide, a $K^+-channel$ blocker, did not. Finally, 8-bromo cyclic AMP $(100\;&\;300{\mu}M)$, a membrane-permeable analogue of cAMP, did not alter the ACh release, but adenosine effects were inhibited by pretreatment with large dose of 8-br-cAMP $(300\;{\mu}M)$. These results indicate that the decrement of the evoked ACh-release by $A_1-adenosine$ receptor is mediated by the G-protein, and nifedipine-sensitive $Ca^{2+}-channel$ and adenylate cyclase system are coupled partly to this effect, and that protein kinase C and glibenclamide-sensitive $K{^+}-channel$ are not involved in this process.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.2
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• pp.111-119
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• 2009

Objective: The aim of this study was to compare the clinical efficacy of clomiphene citrate (CC) and letrozole combined with gonadotropins for controlled ovarian stimulation (COS) in patients with CC-induced thin endometrium Methods: Fifty-one intrauterine insemination cycles performed in patients who previously had a thin endometrium (<8 mm) to ovulation induction using CC were included in this study. A CC 100 mg/day (CC+gonadotropin group, n=26) or letrozole 2.5 or 5 mg/day (letrozole+gonadotropin group, n=25) was administered on day 3~7 of the menstrual cycle, combined with gonadotropins at dose 75~150 IU every other day starting on day 5~7. We compared total dose of gonadotropin used, endometrial thickness, endometrial pattern, number of follicles ${\geq}14\;mm$ on hCG day, pregnancy rate and multiple pregnancy rate between the two groups, which were statistically analyzed using Mann-Whitney U test or Fisher's exact test, where appropriate. Results: There were no significant differences in clinical characteristics such as age, duration of infertility, number of previous IUI cycles, basal serum hormone levels and cause of infertility between the two groups. In both groups, the endometrium was significantly thicker than that of previous ovulation induction cycles using CC. No significant differences were found in the total dose of gonadotropin used, day of hCG administration, the rate of triple endometrium and pregnancy rate. The number of follicles ${\geq}14\;mm$ was significantly lower ($3.7{\pm}1.7$ vs. $2.8{\pm}1.7$, p=0.03) and the endometrium on hCG day was significantly thicker ($7.7{\pm}1.5$ vs. $9.1{\pm}1.7$, p=0.001) in letrozole+gonadotropin group compared to CC+gonadotropin group. Conclusion: The clomiphene citrate and letrozole combined with gonadotropins appear to avoid the undesirable effects on the endometrium frequently seen with CC for ovulation induction. However, in terms of adequate endometrial development or optimal follicular growth, letrozole may be more beneficial than CC for gonadotropin-combined COS in patients with CC-induced thin endometrium. Further prospective randomized controlled studies in a larger scale will be necessary to confirm our findings.